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A Mann-Whitney U test was conducted to examine differences in PWB dimensions between employed women and homemakers (n = 308). The analysis revealed that five of the six dimensions showed no statistically significant differences between the two groups (Table 5 ). However, a significant difference was found in self-acceptance scores between employed women and homemakers , indicating that employment status may influence individuals' level of self-acceptance.
|
PMC11698264_p25
|
PMC11698264
|
Results
| 2.415349 |
biomedical
|
Study
|
[
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[
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en
| 0.999997 |
Table 6 presents the results of MANOVA comparing six domains of PWB between homemakers and employed women. Prior to the main analysis, Box's M test was conducted to examine the assumption of homogeneity of variance-covariance matrices. Box's M test indicated that the assumption of homogeneity of variance-covariance matrices was violated (M = 69.174, F = 3.22, p < 0.001). Given the relatively large and balanced sample sizes, we proceeded with MANOVA using Pillai's Trace as the test statistic due to its robustness to assumption violations. MANOVA revealed a significant multivariate effect of employment status on PWB domains (Pillai's Trace = 0.071, F (6, 301) = 3.827, p = 0.001, partial η² = 0.071). This result indicates that there are significant differences in PWB profiles between employed women and homemakers, though the effect size suggests these differences are modest in magnitude.
|
PMC11698264_p26
|
PMC11698264
|
Results
| 4.006819 |
biomedical
|
Study
|
[
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0.0008208799990825355,
0.14242064952850342
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[
0.9992454051971436,
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0.0002542397996876389,
0.00003638544512796216
] |
en
| 0.999998 |
Subsequent univariate analyses were conducted to examine differences between homemakers and employed women across six domains of PWB. The results revealed significant differences in two domains: self-acceptance and autonomy. Self-acceptance demonstrated the most robust difference between groups (p = 0.001, partial η² = 0.048), with homemakers reporting higher levels compared to employed women. The effect size indicates that group membership accounted for 4.8% of the variance in self-acceptance scores. Autonomy showed a marginally significant difference (p = 0.050, partial η² = 0.012), with employed women scoring higher than homemakers. The remaining four domains did not exhibit statistically significant differences between groups. The effect sizes for these non-significant domains were notably small, ranging from 0.001 to 0.007, suggesting minimal practical differences between the groups in these aspects of PWB.
|
PMC11698264_p27
|
PMC11698264
|
Results
| 3.504761 |
other
|
Study
|
[
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[
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en
| 0.999997 |
The present study provides valuable insights into the PWB of homemakers and employed women in the Perambalur district, Tamil Nadu, revealing complex patterns in both overall well-being and specific psychological domains. The findings contribute to our understanding of how occupational status influences women's mental health in the Indian sociocultural context.
|
PMC11698264_p28
|
PMC11698264
|
Discussion
| 2.122373 |
other
|
Study
|
[
0.44041305780410767,
0.0012032331433147192,
0.5583837032318115
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[
0.9922693967819214,
0.007200310938060284,
0.00037003873148933053,
0.00016024229989852756
] |
en
| 0.999998 |
Our analysis revealed that homemakers demonstrated slightly higher overall PWB scores (69.35 ± 6.595) compared to employed women (68.21 ± 6.046), though this difference was not statistically significant (p = 0.121). This finding aligns with research by Choudhary and Ahmad, who reported similar patterns in their study of women in North Bihar . The lack of significant differences in overall scores suggests that employment status alone may not be the primary determinant of women's PWB, supporting Sinha's assertion that multiple roles and their successful management are more crucial for psychological health than employment status per se .
|
PMC11698264_p29
|
PMC11698264
|
Discussion
| 3.553864 |
biomedical
|
Study
|
[
0.8737635612487793,
0.0008706778171472251,
0.12536582350730896
] |
[
0.9991815686225891,
0.0005183801404200494,
0.0002622717001941055,
0.00003771776027861051
] |
en
| 0.999996 |
The multivariate analysis revealed significant differences in PWB profiles between the groups (Pillai's Trace = 0.071, p = 0.001), particularly in the self-acceptance and autonomy domains. The higher self-acceptance scores among homemakers (p = 0.001, partial η² = 0.048) suggest that these women may have developed a stronger sense of identity and satisfaction within their chosen role. This finding resonates with research by Chaudhry and Chhajer, who emphasized the importance of role satisfaction in PWB .
|
PMC11698264_p30
|
PMC11698264
|
Discussion
| 3.750062 |
biomedical
|
Study
|
[
0.8711422085762024,
0.0011257071746513247,
0.1277320683002472
] |
[
0.9990524649620056,
0.0005206723581068218,
0.00038137295632623136,
0.00004549250297714025
] |
en
| 0.999998 |
Employed women demonstrated marginally higher autonomy scores (p = 0.050, partial η² = 0.012), consistent with findings by De-Juanas et al. regarding the relationship between autonomy and PWB . This increased autonomy might be attributed to financial independence and workplace empowerment, as suggested by Houston et al. in their comparative study of employed women and homemakers .
|
PMC11698264_p31
|
PMC11698264
|
Discussion
| 2.396673 |
biomedical
|
Study
|
[
0.5578632354736328,
0.001250493573024869,
0.4408862590789795
] |
[
0.9968396425247192,
0.002565936651080847,
0.0004985592677257955,
0.00009592896094545722
] |
en
| 0.999997 |
The sociodemographic analysis revealed important patterns that may influence PWB. The higher prevalence of homemakers in rural areas (146,72.3%) and employed women in urban areas (80, 75.5%) reflects broader sociocultural and economic factors affecting women's employment choices. This geographic distribution pattern aligns with findings by Maeda et al., who identified significant associations between domestic work stress and psychological health outcomes across different residential settings .
|
PMC11698264_p32
|
PMC11698264
|
Discussion
| 2.380237 |
biomedical
|
Study
|
[
0.8238667249679565,
0.0014695334248244762,
0.17466366291046143
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[
0.9970224499702454,
0.00256347400136292,
0.0003276495262980461,
0.00008642377360956743
] |
en
| 0.999997 |
The concentration of employed women in higher socioeconomic classes (n = 31, 73.8% in Class 1 and n = 49, 69% in Class 2) suggests that economic status and educational attainment significantly influence women's occupational choices. This observation supports research by Bramhankar et al., who found strong correlations between socioeconomic status and life satisfaction among Indian adults .
|
PMC11698264_p33
|
PMC11698264
|
Discussion
| 1.46849 |
other
|
Study
|
[
0.08328791707754135,
0.000611551629845053,
0.9161005616188049
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[
0.8641168475151062,
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0.0007017355528660119
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en
| 0.999996 |
The absence of significant differences in environmental mastery, personal growth, positive relations, and purpose in life between groups is particularly noteworthy. This finding suggests that both homemakers and employed women can achieve similar levels of fulfillment in these domains through different pathways, supporting Ryff and Keyes' conceptualization of PWB as a multidimensional construct .
|
PMC11698264_p34
|
PMC11698264
|
Discussion
| 1.337932 |
other
|
Study
|
[
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0.0004293910460546613,
0.9827978610992432
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[
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0.003035999834537506,
0.0012046798365190625
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en
| 0.999998 |
Recent research by Beulah suggests that the relationship between employment status and PWB is mediated by various factors, including social support, family dynamics, and personal aspirations . This may explain why both groups showed comparable scores in several domains despite different daily experiences and challenges.
|
PMC11698264_p35
|
PMC11698264
|
Discussion
| 1.801629 |
biomedical
|
Study
|
[
0.6649811267852783,
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0.3331001400947571
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[
0.6925367712974548,
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0.010707280598580837,
0.0011626073392108083
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en
| 0.999997 |
The similar scores in positive relations across both groups indicate that women can develop and maintain meaningful social connections regardless of their occupational status. This finding aligns with research by Arcos-Romero and Calvillo, who emphasized the importance of social relationships in women's overall well-being, regardless of their professional status .
|
PMC11698264_p36
|
PMC11698264
|
Discussion
| 1.394619 |
other
|
Study
|
[
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[
0.5880658626556396,
0.4049862325191498,
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en
| 0.999997 |
The marginally higher environmental mastery scores among homemakers (mean: 9.53 ± 3.879) compared to employed women (mean: 8.88 ± 3.703) suggest that managing household responsibilities may enhance women's sense of control over their immediate environment. This finding corresponds with research by Parmar, who found that homemakers often develop strong organizational and management skills through their domestic responsibilities .
|
PMC11698264_p37
|
PMC11698264
|
Discussion
| 1.609874 |
other
|
Study
|
[
0.054771892726421356,
0.0006814603111706674,
0.9445466995239258
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[
0.972233235836029,
0.026618976145982742,
0.0007447274983860552,
0.0004030735872220248
] |
en
| 0.999998 |
The slightly higher personal growth scores among homemakers challenge the common assumption that professional employment is necessary for personal development. This finding supports research by Chaurasia and Kumari, who found that both employed and non-employed women can experience significant personal growth through different life experiences and responsibilities .
|
PMC11698264_p38
|
PMC11698264
|
Discussion
| 1.124962 |
other
|
Other
|
[
0.007377888076007366,
0.0003852277877740562,
0.9922369122505188
] |
[
0.28698408603668213,
0.706739604473114,
0.004346001893281937,
0.0019303273875266314
] |
en
| 0.999997 |
The socioeconomic distribution pattern in our study, with employed women predominantly in higher classes, raises important questions about access to employment opportunities and its relationship with PWB. This observation aligns with findings by Dhanabhakyam and Sarath, who identified socioeconomic status as a significant moderator of PWB among women .
|
PMC11698264_p39
|
PMC11698264
|
Discussion
| 1.950269 |
biomedical
|
Study
|
[
0.8114291429519653,
0.001680254121311009,
0.1868906021118164
] |
[
0.9878379106521606,
0.010931005701422691,
0.0010127890855073929,
0.00021836547239217907
] |
en
| 0.999997 |
The findings of this study have significant implications for developing targeted mental health interventions and support systems for women across different occupational statuses. The identification of distinct PWB profiles between homemakers and employed women suggests the need for tailored mental health promotion strategies . For instance, the higher autonomy scores among employed women indicate that workplace mental health programs should focus on maintaining and enhancing this strength while addressing potential challenges in self-acceptance. Conversely, community-based mental health initiatives for homemakers could focus on enhancing autonomy while building upon their stronger self-acceptance .
|
PMC11698264_p40
|
PMC11698264
|
Discussion
| 3.458219 |
biomedical
|
Study
|
[
0.9123764634132385,
0.0007357117137871683,
0.08688782900571823
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[
0.993869423866272,
0.005210993345826864,
0.0008385785040445626,
0.00008096978126559407
] |
en
| 0.999996 |
The socioeconomic disparities observed in our study, particularly the concentration of employed women in higher socioeconomic classes, highlight the need for public health policies that address barriers to employment and mental health support for women in lower socioeconomic groups . Additionally, the similar scores in positive relations and purpose in life across both groups suggest that community-based support networks and social engagement programs could be equally effective for both homemakers and employed women, potentially serving as a cost-effective public health intervention strategy. Healthcare providers and public health practitioners should consider these findings when designing preventive mental health services and wellness programs, ensuring that interventions are culturally sensitive and address the specific psychological needs of both homemakers and employed women in different socioeconomic contexts .
|
PMC11698264_p41
|
PMC11698264
|
Discussion
| 4.048487 |
biomedical
|
Study
|
[
0.9924852252006531,
0.0007719665882177651,
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[
0.986659049987793,
0.005379469599574804,
0.007851663045585155,
0.00010980053048115224
] |
en
| 0.999998 |
Strengths of the study
|
PMC11698264_p42
|
PMC11698264
|
Discussion
| 2.058209 |
biomedical
|
Other
|
[
0.9714938998222351,
0.0015183181967586279,
0.026987770572304726
] |
[
0.4269254803657532,
0.5569177865982056,
0.014762169681489468,
0.001394562772475183
] |
en
| 0.999997 |
The study demonstrated several notable strengths in its approach and execution. The research utilized the validated Ryff's PWBS-18, providing a comprehensive assessment of both overall and domain-specific well-being. The methodology was strengthened by relatively balanced sample sizes between groups and the application of appropriate statistical analyses, including MANOVA and Mann-Whitney U tests. The study's robustness was further enhanced by using Pillai's Trace to address violated assumptions in statistical analysis. Additionally, the research incorporated a detailed examination of socio-demographic variables, including various family-related factors such as family type, size, and spouse addiction, as well as health and financial considerations like chronic illness and debts. This comprehensive approach provided a rich context for understanding the relationship between occupational status and PWB.
|
PMC11698264_p43
|
PMC11698264
|
Discussion
| 4.120613 |
biomedical
|
Study
|
[
0.9902931451797485,
0.0005787977133877575,
0.009127994067966938
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[
0.9993851184844971,
0.0001583127013873309,
0.0004222890129312873,
0.00003420814755372703
] |
en
| 0.999998 |
Limitations
|
PMC11698264_p44
|
PMC11698264
|
Discussion
| 1.55944 |
biomedical
|
Other
|
[
0.8676750063896179,
0.006674593314528465,
0.12565049529075623
] |
[
0.4818660616874695,
0.5091313123703003,
0.006395956967025995,
0.0026066452264785767
] |
it
| 0.857138 |
Several limitations should be considered when interpreting the study's findings. The cross-sectional design inherently limits causal inference, and the focus on a single geographic location (Perambalur district) may affect the generalizability of results to other populations. The study's measurement approach faced some challenges, including relatively low internal consistency (Cronbach's α = 0.682) and the use of a shortened version of the PWBS, which might not capture the full complexity of the PWB construct. There were also analytical limitations, such as the violation of the homogeneity assumption in MANOVA and limited control for potential confounding variables. The absence of analysis regarding interaction effects between demographic variables represents another limitation of the study's scope.
|
PMC11698264_p45
|
PMC11698264
|
Discussion
| 3.954471 |
biomedical
|
Study
|
[
0.9889497756958008,
0.0004099136858712882,
0.010640381835401058
] |
[
0.9993810653686523,
0.00021988320804666728,
0.00036620860919356346,
0.00003281379758846015
] |
en
| 0.999997 |
This study provides valuable insights into the complex relationship between women's occupational status and PWB in the Perambalur district of Tamil Nadu. While the overall PWB scores were comparable between both groups, the study revealed significant domain-specific differences. Homemakers demonstrated higher self-acceptance, suggesting a more stable self-concept and greater acceptance of their life choices, while employed women showed higher autonomy, reflecting increased independence and decision-making opportunities. The absence of significant differences in environmental mastery, personal growth, positive relations, and purpose in life domains indicates that both groups find distinct ways to fulfill these aspects of PWB. These findings challenge common assumptions about the relative advantages of employment versus staying at home and suggest that PWB is more nuanced than previously understood, influenced by factors such as family support, personal choice, and social circumstances.
|
PMC11698264_p46
|
PMC11698264
|
Conclusions
| 3.717561 |
biomedical
|
Study
|
[
0.5427451133728027,
0.0012741349637508392,
0.45598074793815613
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[
0.9985858201980591,
0.0008278183522634208,
0.0005197892896831036,
0.00006662794476142153
] |
en
| 0.999996 |
Future research should prioritize longitudinal studies across diverse geographical and socioeconomic contexts to better understand the temporal dynamics of PWB among women. Healthcare providers and policymakers should develop targeted mental health interventions addressing the specific needs of both homemakers and employed women while implementing community support programs that validate women's occupational choices. Establishing support groups and counseling services, along with educational initiatives focusing on coping strategies, would benefit both groups. Workplace policies should be designed to promote work-life balance, while community awareness programs should focus on destigmatizing and supporting women's choices regarding employment and domestic roles.
|
PMC11698264_p47
|
PMC11698264
|
Conclusions
| 3.193158 |
biomedical
|
Other
|
[
0.6895682215690613,
0.0029750564135611057,
0.3074566423892975
] |
[
0.029300887137651443,
0.9520536065101624,
0.018329540267586708,
0.00031595988548360765
] |
en
| 0.999996 |
Pristane, a tetramethylpentadecane hydrocarbon oil, is well known for inducing in mice features of systemic lupus erythematosus (SLE) as autoantibodies, arthritis, peritonitis, and glomerulonephritis [ 1 – 4 ].
|
39752468_p0
|
39752468
|
Introduction
| 3.168016 |
biomedical
|
Study
|
[
0.9989897608757019,
0.00024152954574674368,
0.0007686752360314131
] |
[
0.7292957901954651,
0.24986208975315094,
0.0192289836704731,
0.0016131959855556488
] |
en
| 0.999998 |
Neutrophils are innate immune first-line effector cells defense against invading pathogens [ 5 – 8 ]. They are produced by the bone marrow and are activated by a series of different PAMPs and DAMPs . The CD11b and the Ly6G are neutrophil receptors responsible for: 1- cell migration, 2- making permanent connection with the endothelium, and 3- characterizing its phenotypic expressions . CD11b is present on human and animal neutrophils, while Ly6G is merely observed in mice . Notably, CD11b expression increases after neutrophils activation . Both qualitative and quantitative alterations are observed in neutrophils from patients with autoimmune diseases as SLE [ 5 , 10 , 12 – 14 ]. These alterations include increased number of activated neutrophils , reduced phagocytosis capacity with lesser removal of apoptotic material [ 15 – 17 ], increased release of neutrophil extracellular traps (NETs), and increased number of low-density granulocytes (LDGs) [ 18 – 21 ].
|
39752468_p1
|
39752468
|
Introduction
| 4.338437 |
biomedical
|
Study
|
[
0.9995613694190979,
0.00022688732133246958,
0.00021180072508286685
] |
[
0.9892327785491943,
0.00050536630442366,
0.010118064470589161,
0.00014377075422089547
] |
en
| 0.999998 |
LDGs are a subset of neutrophils, morphologically different, with a less segmented nuclei and a more lobular shape . LDGs are characterized by INF type 1 secretion, pro-inflammatory activity, and enhanced spontaneous NETs release [ 18 – 22 ]. LDGs express neutrophil markers as CD15, and monocyte markers as CD14, suggesting these cells are immature neutrophils . However, some authors believe LDGs arise from mature neutrophils that undergo degranulation after activation and, this way, are less dense . Therefore, LDGs are considered a heterogeneous population of mature and immature neutrophils with a still discordant surface marker pattern . During acute inflammation, activated neutrophils and LDGs were observed in primary and secondary lymphoid organs, and peripheral blood of SLE patients . Increased amounts of LDGs in SLE patients have been related to disease activity and cutaneous involvement [ 18 – 21 , 23 ].
|
39752468_p2
|
39752468
|
Introduction
| 4.285951 |
biomedical
|
Study
|
[
0.9996422529220581,
0.0001752070675138384,
0.00018261496734339744
] |
[
0.9967852830886841,
0.0003384833107702434,
0.002784193493425846,
0.00009207948460243642
] |
en
| 0.999996 |
Our research group recently observed that the pristane-induced lupus mice model show increased number of activated T lymphocytes and reduced number of regulatory T cells (Treg) . However, the innate immune response in this lupus model needs to be better understood.
|
39752468_p3
|
39752468
|
Introduction
| 2.704884 |
biomedical
|
Study
|
[
0.9983213543891907,
0.000281805288977921,
0.001396867330186069
] |
[
0.927996039390564,
0.06827457994222641,
0.002974114613607526,
0.0007553253672085702
] |
en
| 0.999997 |
Therefore, we hypothesize whether the pristane-induced lupus mice model show early activation of neutrophils, the presence of LDGs, and NETs release which could contribute to the development of a lupus phenotype.
|
39752468_p4
|
39752468
|
Introduction
| 3.886334 |
biomedical
|
Study
|
[
0.9996242523193359,
0.00016106713155750185,
0.000214665342355147
] |
[
0.9978255033493042,
0.001703949528746307,
0.0003694423066917807,
0.00010111059964401647
] |
en
| 0.999997 |
Twelve female wild-type Balb/c mice, 8 to 10 weeks old, were provided by the Multidisciplinary Center for Biological Research–CEMIB/UNICAMP (Campinas, Brazil), and they were maintained in the Rheumatology Division, University of São Paulo School of Medicine—Brazil. All animal protocols were approved by the Institutional Animal Care and Research Advisory Committee , and conducted according to the U.S. National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. Mice were kept in an acclimatized facility with an automatic dark side cycle ( http://www.biot.fm.usp.br/ ) and food and water were available ad libitum. After the acclimatization period, at 10 to 12 weeks of age, and 12 days before the intraperitoneal injection, the time required for recovery of the leukocyte pool, a peripheral blood sample was collected from all animals. This blood sample was used as the normal or basal number of activated neutrophils, LDGs, and NETs released by both the former cells. Mice used in the experiments weighed 20 to 25g, and they received a single intraperitoneal injection of 0.5 ml of pristane (TMPD-tetramethylpentadecane Sigma Chemical Co., St. Louis, MO) (n = 6; pristane group), as we previously used for SLE induction , or an equal volume of 0.9% saline (n = 6; control group). Five days after pristane or saline was intraperitoneally injected, that is, the shortest period ever analyzed according to our literature review [ 1 – 4 ], and before the disappearance of neutrophils after the inflammation induction, samples of blood, peritoneal lavage, bone marrow, and spleen were collected from both mice groups for flow cytometry analysis. The Balb/c mice were then sacrificed with anesthetic overdose, a mixture of ketamine hydrochloride (Ketalar—300 mg/kg body weight) and xylazine hydrochloride (Rompum—30 mg/kg body weight).
|
39752468_p5
|
39752468
|
Mice
| 4.145471 |
biomedical
|
Study
|
[
0.9994476437568665,
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[
0.9993496537208557,
0.00028523741639219224,
0.0002932236238848418,
0.00007190922042354941
] |
en
| 0.999995 |
Immediately after collecting, 200 μL of peripheral blood from the caudal vein 12 days before the intraperitoneal injection, and 500 μL of blood from the inferior vena cava five days after pristane or saline injection, red blood cells were lysed by incubating samples with FACSTM Lysing Solution (Becton Dickinson New Jersey NJ USA). After that, samples were centrifuged (800 g for 10 min at 4°C), the cells pellet washed, and it was suspended in RPMI medium 1640 (Gibco BRL U.S.A), containing 5% fetal bovine serum (FBS)—Gibco BRL U.S.A. The hemolysis method was chosen as it has simple steps and preserves all types of white blood cells (granulocytes, monocytes and lymphocytes). Cell suspensions were promptly analyzed by flow cytometry Guava EasyCyteTM HT (Millipore Minneapolis, NM, USA).
|
39752468_p6
|
39752468
|
Blood samples
| 4.111613 |
biomedical
|
Study
|
[
0.9995645880699158,
0.00025627409922890365,
0.00017905666027218103
] |
[
0.9983239769935608,
0.0012292817700654268,
0.00035486937849782407,
0.00009178590698866174
] |
en
| 0.999995 |
Five days after pristane or saline injection, mice were euthanized with anesthetic overdose, 2 mL of RPMI were intraperitoneally injected, and the cell suspension recovered. The peritoneal lavage was centrifuged (800 g for 10 min at 4°C), the cells pellet washed, and it was suspended in RPMI containing 5% FBS. The cell suspension, containing all types of white cells was counted in a Neubauer chamber ( Labor Optik UK) using trypan blue (Thermo Fisher Scientific Oregon USA) (1:1) to ensure a differential count of at least 1x10 6 polymorphonuclear and mononuclear cells.
|
39752468_p7
|
39752468
|
Peritoneal lavage sample
| 4.123058 |
biomedical
|
Study
|
[
0.9994655251502991,
0.0003710642922669649,
0.00016348088684026152
] |
[
0.9980225563049316,
0.0014521147822961211,
0.0003952658735215664,
0.0001301137963309884
] |
en
| 0.999997 |
Immediately after mice were euthanized, femurs and tibias were obtained and the bone marrow was washed with Hank’s balanced salt solution with EDTA (Thermo Fisher Scientific Oregon USA). The recovered suspension was centrifuged (800 g for 10 min at 4°C), the cells pellet washed, and it was suspended in RPMI containing 5% FBS. The bone marrow cell suspension was promptly analyzed by flow cytometry.
|
39752468_p8
|
39752468
|
Bone marrow sample
| 4.095534 |
biomedical
|
Study
|
[
0.9996143579483032,
0.0002168847859138623,
0.00016879070608410984
] |
[
0.9978523254394531,
0.0016210662433877587,
0.00042049665353260934,
0.00010607948206597939
] |
en
| 0.999995 |
After mice euthanasia, the spleen was removed, chopped, and crushed in a plate with RPMI medium. The cell suspension was transferred to a tube (Becton Dickson New Jersey NJ USA), which stood for approximately 2 min for precipitation of larger tissue samples. Red blood cells were lysed by incubating samples with lysing solution. Samples were then centrifuged (800 g for 10 min at 4°C), and the cell pellet was washed twice and suspended in RPMI containing 5% FBS. The cell suspension was counted in the Neubauer chamber to obtain at least 1x10 6 polymorphonuclear and mononuclear cells.
|
39752468_p9
|
39752468
|
Spleen sample
| 4.148999 |
biomedical
|
Study
|
[
0.9994034767150879,
0.00042139942524954677,
0.00017510628094896674
] |
[
0.9897738099098206,
0.009206874296069145,
0.0007365502533502877,
0.00028288920293562114
] |
en
| 0.999996 |
The following anti-mouse monoclonal antibodies (BD Biosciences New Jersey NJ USA) were used: Ly6G PE-Cy7 (clone:1A8), Ly6G PE (clone:1A8), CD14 PE (clone:mC5-3), CD11b APC-Cy7, (clone:M1/70), and Anti-SSEA-1 APC-Cy5.5 CD15 (clone:MC480). Sytox Green (Invitrogen by Thermo Fisher Scientific Oregon USA) was also used. Isotypic controls were used according to the company’s protocols.
|
39752468_p10
|
39752468
|
Monoclonal antibodies
| 3.081489 |
biomedical
|
Study
|
[
0.9984381794929504,
0.0003166995302308351,
0.0012451219372451305
] |
[
0.725214958190918,
0.272596150636673,
0.0013506230898201466,
0.00083825399633497
] |
en
| 0.999995 |
NETs released by activated neutrophils (Ly6G+CD11b+) and LDGs (CD15+CD14low) were quantitatively measured by flow cytometry . NETs release was detected by staining the cells with the fluorescent dye for DNA Sytox Green, which does not permeate the cell membrane, and bind to pendant-DNA . The number of activated neutrophils and LDGs in NETosis was determined by flow cytometry using triple staining (Ly6G+CD11b+Sytox+ and CD15+CD14lowSytox+, respectively). Additionally, NETs released by neutrophils were qualitatively demonstrated by the high-content screening technique (Invitrogen by Thermo Fisher Scientific Oregon USA). Sytox Green is reliable for detection of NETs by both flow cytometry and fluorescent staining .
|
39752468_p11
|
39752468
|
NETs release assays
| 4.138174 |
biomedical
|
Study
|
[
0.9995850920677185,
0.00022854514827486128,
0.00018639423069544137
] |
[
0.9992191791534424,
0.0003837780677713454,
0.00033580767922103405,
0.00006128666427684948
] |
en
| 0.999997 |
Cells from blood, peritoneal lavage, bone marrow, and spleen were stained with the Ly6G, CD11b, CD15, and CD14 monoclonal antibodies in the dark for 30 min at 4 to 8°C. After this period, phosphate-buffered saline (PBS) + FBS was added, and cells were centrifuged (800g for 5 min at room temperature). The supernatant was discarded, cells were suspended with Sytox Green+PBS+FBS, and incubated (Nuare US auto Flow USA) in a CO2 ambient for 30 min at 37°C. The multiparameter flow cytometry assays were carried out using Guava EasyCyteTM HT, and the analyses were conducted using InCyte software (Millipore). Based on forward, side scatter and isotypic controls, we determined the (R1) region containing the neutrophil and monocyte populations. Within the R1 region, activated neutrophils were detected by monoclonal antibodies Ly6G and CD11b double-positive (R2) region. Within the R2 region, Sytox Green-positive activated neutrophils were quantified for NETs release. In (R2), we isolated positive activated neutrophil labeled with Sytox Green to quantify the release of NETs (R3) . In another tube containing the population of neutrophils and monocytes was analyzed with the same parameters, within the (R1) region, LDGs were detected marked with positive monoclonal antibodies of CD15 and CD14low (R2) region, they are the surface markers most related to autoimmune diseases in the literature . Within the (R2) region, Sytox Green-positive LDGs (NETs) were quantified (R3).
|
39752468_p12
|
39752468
|
Flow cytometry assays
| 4.169046 |
biomedical
|
Study
|
[
0.9995531439781189,
0.0002768458507489413,
0.00017002547974698246
] |
[
0.9990894794464111,
0.0004930209834128618,
0.00034463140764273703,
0.00007283872400876135
] |
en
| 0.999997 |
Cell suspensions of blood, peritoneal lavage, bone marrow, and spleen were diluted with 3 mL of PBS containing 0.5% bovine albumin. Each diluted suspension was submitted to the Ficoll-Hypaque 1.077 and 1.119 gradient technique. After collecting the interface between gradients, 1x104 neutrophils were distributed on a plate, and they were stained with Ly6G monoclonal antibody which colored them in red. Cell suspension was then stained with Sytox Green which highlights NETs in green. Finally, the plate was stained with Hoechst dye (Invitrogen by Thermo Fisher Scientific Oregon USA), which colored nuclei in blue.
|
39752468_p13
|
39752468
|
High-content screening assay
| 4.139927 |
biomedical
|
Study
|
[
0.9994580149650574,
0.00032498949440196157,
0.0002169998042518273
] |
[
0.9786157608032227,
0.020054074004292488,
0.0010133918840438128,
0.0003167118411511183
] |
en
| 0.999998 |
The statistical analysis was completed by the software IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. or GraphPad Prism version 8.0 (GraphPad software Inc., La Jolla, CA, United States of America). The data normality was analyzed using the Shapiro-Wilk’s test. The results were analyzing by Kruskal-wallis’ test, followed by Mann-Whitney U test was used to compare 2 groups of nonparametric data. Data are expressed as mean ± SD as well as median, minimum, and maximum. P values ≤ 0.05 were considered statistically significant. GraphPad Prism software was used for drawing figures.
|
39752468_p14
|
39752468
|
Statistical analysis
| 2.779444 |
biomedical
|
Study
|
[
0.9964122176170349,
0.00030995148699730635,
0.003277907846495509
] |
[
0.7130476236343384,
0.2847430109977722,
0.0014994717203080654,
0.0007099080830812454
] |
en
| 0.999998 |
The pristane-induced mice group had a significantly increased number of activated neutrophils (Ly6G+CD11b+) of blood compared to both the saline-injected mice group (control) (4,120.2 ± 2,648.5 vs 1,149 ± 183.8, p < 0.001) as well as the basal value (the sample collected 12 days before the pristane injection) of activated neutrophils (4,120.2 ± 2,648.5 vs 660.6 ± 478.3, p < 0.001). An increased number of activated neutrophils was also observed in the pristane group compared to the saline group for the samples of peritoneal lavage (4,953 ± 797 vs 569.7 ± 538.4, p < 0.023), bone marrow (6,222.8 ± 515.3 vs 302.3 ± 48.3, p <0.023), and spleen (2,119.7 ± 638.6 vs 1,739 ± 102.5, p < 0.38), as shown in Fig 1 .
|
39752468_p15
|
39752468
|
The pristane-induced mice model shows an increased number of activated neutrophils
| 4.119956 |
biomedical
|
Study
|
[
0.9995225667953491,
0.00027867782046087086,
0.00019876663282047957
] |
[
0.9994214773178101,
0.00019923083891626447,
0.000320334336720407,
0.000059004112699767575
] |
en
| 0.999997 |
The pristane group had a significantly increased number of LDGs of blood compared to both the saline group (1,998.3 ± 1,012.4 vs 418 ± 36.8, p < 0.001) and the basal value of LDGs (1,998.3 ± 1,012.4 vs 38.8 ± 37.7, p < 0.001). An increased number of LDGs was also observed in the pristane group compared to the saline group for the samples of peritoneal lavage (2,813 ± 1,032.8 vs 448.3 ± 141.5, p < 0.023), bone marrow (2,483.5 ± 372.2 vs 168.7 ± 25.9, p < 0.023), and spleen (929.2 ± 182.7 vs 802 ± 65.2, p < 0.29), as shown in Fig 1 .
|
39752468_p16
|
39752468
|
The pristane-induced mice model shows an increased number of LDGs
| 4.103538 |
biomedical
|
Study
|
[
0.9994785189628601,
0.0002885166322812438,
0.00023296571453101933
] |
[
0.9994674324989319,
0.00021459197159856558,
0.00026380011695437133,
0.0000541462613909971
] |
en
| 0.999997 |
The pristane group had a significantly increased NETs release by activated neutrophils of blood compared to the saline group (3,371.5 ± 2,162.9 vs 393 ± 49.5, p < 0.001), and the basal value of NETs release (3,371.5 ± 2,162.9 vs 383.2 ± 423.7, p < 0.001). An increased NETs release by activated neutrophils was also observed in the pristane group compared to the saline group for the samples of peritoneal lavage (2,035.5 ± 636.1 vs 308.7 ± 285.9, p < 0.02), bone marrow (1,735 ± 639.7 vs 154 ± 29.1, p < 0.023), and spleen (1,179 ± 299 vs 432.7 ± 113.8, p < 0.035), as shown in Fig 2 . Representative images of the high-content screening immunostaining of NETs release by activated neutrophils in all evaluated sites as shown in Fig 3 .
|
39752468_p17
|
39752468
|
The pristane-induced mice model shows an increased NETs release by activated neutrophils
| 4.115148 |
biomedical
|
Study
|
[
0.9994792342185974,
0.0003172980505041778,
0.00020354519074317068
] |
[
0.9994144439697266,
0.00019923892978113145,
0.00032599965925328434,
0.00006033476529410109
] |
en
| 0.999998 |
The pristane group had significantly increased NETs release by LDGs of blood compared to the saline group (1,623.3 ± 824.3 vs 178 ± 29.7, p < 0.001), and the basal value of NETs released by LDGs (1,623.3 ± 824.3 vs 5.7 ± 6.8, p < 0.001). An increased NETs release by LDGs was also observed in the pristane group compared to the saline group for the samples of peritoneal lavage (1,011 ± 387.5 vs 186.7 ± 42.2, p < 0.02), bone marrow (744.5 ± 275 vs 93 ± 20.1, p < 0.023), and spleen (534 ± 106.4 vs 209.7 ± 52.4, p < 0.035), as shown in Fig 2 . Results are also summarized in the S1 Table .
|
39752468_p18
|
39752468
|
The pristane-induced mice model shows an increased NETs release by LDGs
| 4.110085 |
biomedical
|
Study
|
[
0.9994990825653076,
0.0002877586812246591,
0.0002132132212864235
] |
[
0.9994400143623352,
0.00019050510309170932,
0.000311590323690325,
0.00005795390825369395
] |
en
| 0.999998 |
This study shows that the pristane-induced mice model present as early as five days increased number of activated neutrophils and LDGs (except spleen), accompanied by increased NETs release by these cells in all the sites evaluated namely, blood, peritoneum, bone marrow and spleen, corroborating the role of the innate immune system in the development of lupus.
|
39752468_p19
|
39752468
|
Discussion
| 4.088874 |
biomedical
|
Study
|
[
0.9996123909950256,
0.00023973411589395255,
0.00014792046567890793
] |
[
0.9992250204086304,
0.0002598189457785338,
0.0004349771188572049,
0.00008011390309548005
] |
en
| 0.999996 |
In human lupus, it has been shown that large amounts of intracellular debris exposed during the acute inflammatory process by neutrophils act as the major source of autoantigens [ 10 , 12 , 13 , 18 , 27 – 29 ]. In addition, LDGs are present in increased amounts and related to disease activity [ 18 – 21 , 23 ] and cutaneous involvement . Recently, the inhibitory action of gasdermin D on LDGs from patients and the pristane-induced mice model was demonstrated, since disease severity was reduced with this treatment . In this regard, our study shows that not only an increased number of LDGs occur in lupus, but also increased NETs released by these cells. This study also shows that the former alterations occur not only in blood, but also in the peritoneum, and the lymphoid organs such as bone marrow and spleen. In the spleen, there is an increased in NETs and not the number of LDGs.
|
39752468_p20
|
39752468
|
Discussion
| 4.187501 |
biomedical
|
Study
|
[
0.9995359182357788,
0.00027463011792860925,
0.00018944896874018013
] |
[
0.9993552565574646,
0.000187367491889745,
0.0003822157741524279,
0.00007515738252550364
] |
en
| 0.999998 |
NETs are rich in DNA and histones and participate in the presentation of autoantigens, inducing increased production of pro-inflammatory cytokines during the immune response . In patients with SLE, increased amounts of NETs in peripheral blood have also been described, similar to our findings in mice . Furthermore, impaired clearance of NETs results in increased anti-NET and anti-dsDNA autoantibodies, and the development of kidney damage . It is important to emphasize that in SLE patients, neutrophils and LDGs have a great propensity to release NETs and undergo an accelerated process of apoptosis in vitro , as observed herein . Thus, our results indicate that the primary and initial event for the autoantibodies production may be the early NETs release, as observed five days after the pristane injection. Therefore, the search for factors and procedures that block NETs release may be a way to prevent the development of lupus.
|
39752468_p21
|
39752468
|
Discussion
| 4.250049 |
biomedical
|
Study
|
[
0.9996633529663086,
0.0002262820489704609,
0.00011039439414162189
] |
[
0.9973679184913635,
0.00047635106602683663,
0.002021295018494129,
0.00013445928925648332
] |
en
| 0.999998 |
Lupus pictures are established in mice models in a median of 90 days after pristane injection and show massive autoreactive infiltration and cell death overwhelming the clearance process . We observed an increased amount of activated T lymphocytes (CD4+CD69+) in peripheral blood and spleen . However, it was remarkable that no T lymphocytes were found in the peritoneum, possibly due to cell migration from the application area to blood and other organs . On the other hand, in this study, we observed an increased number of activated neutrophils and LDGs in the blood, peritoneum and bone marrow except spleen. We suggest that this may have occurred because these populations expelled their chromatin. These findings highlight the role of the innate immune system, neutrophils, and LDGs, with subsequent NETs release, as possible early alterations involved in the etiopathogenesis of lupus [ 17 – 21 , 23 , 24 ]. Few studies have analyzed NETs and LDGs in different animal models (BALB/cJ, galectin-3 deficient mice, wild-type C57BL/6, PAD4, LysMCre-PAD4, pristane-induced, Gsdmd -/- mice, WT, and rats) and periods (seven, fourteen days, three and seven months) but no research at an early period and with so many different anatomic sites as in this study. It is interesting to note that five days after pristane injection the immune response is reasoned on activated neutrophils and not on the acquired immune system producing antibodies. Lymphocytes will be induced to produce autoantibodies late in the process of lupus disease. NETs release is an extreme action of neutrophils against invaders due to the huge stimulus loaded by PAMPs . This data appears to accompany the increase in the number of LDGs, which may represent activated neutrophils that have already released their cytoplasmic granules, and as already activated cells, due to possible pre-exposure to PAMPs, their next action can only be NETs release . Again, this data shows that the beginning of the lupus induction process passes through the innate immune system and only later reaches the acquired immune system.
|
39752468_p22
|
39752468
|
Discussion
| 4.434286 |
biomedical
|
Study
|
[
0.9993699193000793,
0.000395023642340675,
0.00023502409749198705
] |
[
0.9987401366233826,
0.0003031427040696144,
0.0008300444460473955,
0.00012665776011999696
] |
en
| 0.999997 |
Another relevant aspect identified in this study is the fact that the immune response is systemic, that is, after a local injection of pristane into the peritoneum, activated neutrophils, LDGs, and NETs release were identified not only locally, but also in blood, bone marrow, and NETs in spleen. This systemic behavior corresponds to infectious processes that evolve into sepsis, a systemic condition . It is relevant to note that lupus patients have a systemic condition with the impairment of several organs due to autoimmune activity .
|
39752468_p23
|
39752468
|
Discussion
| 4.100295 |
biomedical
|
Study
|
[
0.9995883107185364,
0.0002322118089068681,
0.00017943493730854243
] |
[
0.9992886781692505,
0.00025445022038184106,
0.0003941095492336899,
0.00006280916568357497
] |
en
| 0.999998 |
To the best of our knowledge, this is the first study to analyze, in mice model, the pristane induction effects at the bone marrow, the primary site of immune cell production. Similar to what happens in the peritoneum, an acute increase in the number of activated neutrophils and LDGs, as well as an enhanced NETs release by these cells were demonstrated in the bone marrow.
|
39752468_p24
|
39752468
|
Discussion
| 4.070136 |
biomedical
|
Study
|
[
0.9995754361152649,
0.00023839567438699305,
0.0001861639611888677
] |
[
0.9994345307350159,
0.00025530214770697057,
0.00024709972785785794,
0.00006298678636085242
] |
en
| 0.999997 |
The strong points of present study were: 1- the use of fresh cells labeled right after their isolation which avoids any spontaneous activation or NETs release in contrast to studies that used frozen cells; 2- neutrophils and LDGs changes were analyzed right after the breakdown of the immune tolerance (five days after pristane injection); 3- NETs release was assessed in both neutrophils and LDGs; 4- neutrophils and LDGs changes were evaluated at different anatomic sites including the primary injury site (peritoneum), the circulation (blood) and the lymphoid organs (bone marrow and spleen).
|
39752468_p25
|
39752468
|
Discussion
| 4.079786 |
biomedical
|
Study
|
[
0.9995348453521729,
0.00023313976998906583,
0.00023196876281872392
] |
[
0.9995043277740479,
0.0001837631716625765,
0.00026569367037154734,
0.0000462311327282805
] |
en
| 0.999998 |
This study limitations were: 1- the small number of samples analyzed; 2- the lack of evaluating the behavior of neutrophils and LDGs over different periods; and 3- not distinguishing the LDGs subsets.
|
39752468_p26
|
39752468
|
Discussion
| 2.234289 |
biomedical
|
Study
|
[
0.9977490305900574,
0.000530440709553659,
0.0017204817850142717
] |
[
0.9852448105812073,
0.013355747796595097,
0.000992436776868999,
0.00040701215039007366
] |
en
| 0.999999 |
In conclusion, we demonstrated early changes in the innate immune response such as an increased number of activated neutrophils and LDGs and mainly increased NETosis in the pristane-induced mice model which may be considered as the primary event triggering lupus development.
|
39752468_p27
|
39752468
|
Discussion
| 4.094145 |
biomedical
|
Study
|
[
0.9996238946914673,
0.00023317922023124993,
0.0001428693503839895
] |
[
0.9988849759101868,
0.00036986437044106424,
0.0006497922004200518,
0.00009532698459224775
] |
en
| 0.999997 |
Gestational diabetes mellitus (GDM) is a glucose intolerance disease that is onset or first diagnosed during pregnancy. However, GDM does not meet the diagnostic criteria for diabetes in the general population . Over the last couple of years, there has been a steady rise in the prevalence of GDM, ranging from 9.3% to 25.5%, potentially affecting 20 million newborns per year worldwide . GDM poses various risks and complications for both the pregnant woman and the fetus. Generally, GDM increases the risk of preeclampsia, large-for-gestational-age newborns, shoulder dystocia, birth trauma, and neonatal hypoglycemia . Mothers with GDM and their infants are more susceptible to developing obesity, cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and other conditions . Moreover, the diagnostic criteria for GDM vary worldwide and at different time nodes. Currently, the main international diagnostic criteria for GDM are the one- and two-step methods performed at 24–28 weeks of gestation . The International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization (WHO) support the one-step method, which has also received significant endorsement from multiple international organizations [ 6 – 8 ]. However, the American College of Obstetricians and Gynecologists (ACOG) prefers the two-step method, considering the potential increase in healthcare costs and the understanding that no particular screening strategy has been proven optimal . However, a recent study found that GDM treatment during early pregnancy (< 20 weeks) effectively prevented the associated adverse outcomes . Consequently, early identification of pregnancies at risk of GDM is crucial for preventing adverse pregnancy outcomes and intergenerational transmission of metabolic dysregulation.
|
39752447_p0
|
39752447
|
Introduction
| 4.339829 |
biomedical
|
Review
|
[
0.9920547008514404,
0.004541371949017048,
0.0034039593301713467
] |
[
0.010842413641512394,
0.0016803633188828826,
0.9870083928108215,
0.00046885214396752417
] |
en
| 0.999997 |
Abnormal serum lipid metabolism is a risk factor for GDM development. However, dyslipidemia during pregnancy can be a normal physiological phenomenon . It has been demonstrated that insulin resistance (IR) and estrogen stimulation during pregnancy can result in maternal hyperlipidemia . Excessive eating and increased fat production result in the accumulation of maternal fat, generally occurring during the initial two trimesters. The process of fat storage is inhibited during the final trimester of pregnancy. This is due to increased activity of lipolytic enzymes and decreased lipoprotein lipase (LPL) activity in adipose tissue. This shift to a catabolic state favors the maternal use of lipids as an energy source and provides glucose and amino acids to the fetus. Therefore, it is unclear whether these changes in lipid metabolism are specific to pregnancy or can contribute to the emergence of future diseases. Due to the multifactorial etiology of GDM, its pathogenesis remains unclear . However, the IR caused by obesity, inflammation, and oxidative stress is currently considered the primary pathogenic mechanism of GDM . Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol (HDL-C) are the two important metabolic abnormalities associated with IR .
|
39752447_p1
|
39752447
|
Introduction
| 4.520234 |
biomedical
|
Study
|
[
0.9990229606628418,
0.0005992931546643376,
0.00037773666554130614
] |
[
0.712740957736969,
0.0019949900452047586,
0.28450316190719604,
0.0007608197629451752
] |
en
| 0.999995 |
Traditionally, HDL-C has been considered a lipid parameter against atherosclerosis (AS). Various studies indicate that HDL-C is closely associated with metabolic diseases . Multiple studies suggest that women with GDM have higher levels of circulating triglycerides (TG) and lower levels of HDL-C as compared to women without GDM . However, few studies have reported that the HDL-C concentration did not differ for women with and without GDM during pregnancy, and the relevant conclusions remain controversial . The clinical application of serum TG and its increase in GDM have been extensively investigated . A new lipid marker—residual cholesterol (RC)—has recently been linked to CVD and other related disorders. Besides, the onset and progression of RC, diabetes mellitus (DM), CVD secondary to DM, and nonalcoholic fatty liver disease (NAFLD) have been investigated [ 24 – 26 ]. In the RC, lipoprotein cholesterol levels are normally determined by intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) remnants in the fasting state (hepatocyte origin) and chylomicron (CM) remnants in the non-fasting state (intestinal origin) . As the cholesterol content of partially lipolyzed triglyceride-rich lipoproteins (TRLs), RC may be more representative of circulating TG. Moreover, RC has been indicated to be more associated with IR than TG . Meanwhile, RC, possibly as the most cholesterol-containing lipoprotein, may have a greater toxic effect on pancreatic beta cells (PBC) and promote their apoptosis . Recently, the relationship between RC and GDM has been explored. However, related studies are limited .
|
39752447_p2
|
39752447
|
Introduction
| 4.283965 |
biomedical
|
Study
|
[
0.9990454316139221,
0.00047452159924432635,
0.0004800308670382947
] |
[
0.6525495648384094,
0.0012770495377480984,
0.34563836455345154,
0.000535006111022085
] |
en
| 0.999996 |
The RC/HDL-C ratio, as an emerging indicator of IR, has not been extensively studied, with previous investigations primarily focusing on its association with metabolic diseases. However, a relationship between the RC/HDL-C ratio and the risk of GDM has never been investigated. Based on the above related studies, we hypothesized that the RC/HDL-C ratio in early pregnancy may be correlated with the diagnosis of GDM. Given the similar IR pathway between GDM and T2DM, we conducted a secondary analysis based on published research to evaluate the relationship between early pregnancy RC/HDL-C ratio and the possibility of developing GDM in Korean women in this study.
|
39752447_p3
|
39752447
|
Introduction
| 4.047951 |
biomedical
|
Study
|
[
0.9995219707489014,
0.00025362835731357336,
0.00022439325402956456
] |
[
0.9995226860046387,
0.00021224384545348585,
0.00021567851945292205,
0.000049463302275398746
] |
en
| 0.999994 |
The primary data utilized in this study were freely accessed from the article titled "Nonalcoholic Fatty Liver Disease is a Risk Factor for Large-for-Gestational-Age Birthweight" by Lee SM et al., published in PLoS ONE (available at https://journals.plos.org/plosone ) . The publicly available primary data has been disseminated under the Creative Commons Attribution License, permitting unlimited use, distribution, and replication in any medium, provided that due acknowledgment is accorded to the author and the original source. We extend our sincere appreciation to the contributors of this invaluable data. The analysis included all the relevant data from November 2014 to July 2016.
|
39752447_p4
|
39752447
|
Data source
| 1.281863 |
biomedical
|
Other
|
[
0.9161827564239502,
0.0015167564852163196,
0.082300566136837
] |
[
0.23374968767166138,
0.7617937922477722,
0.003408050863072276,
0.0010485268430784345
] |
en
| 0.999997 |
Seoul Metropolitan Government Seoul National University Boramae Medical Center and Incheon Seoul Women’s Hospital recruited 663 singleton pregnant women with less than 14 weeks of pregnancy. Data collection for the ongoing ’Fatty Liver in Pregnancy’ registry was conducted from November 2014 to July 2016 . Before participating, all individuals provided written consent as required by the original study. To ensure privacy protection, the researchers employed untraceable codes instead of identifiable participant information. The Institutional Review Board of the Seoul Metropolitan Government, Seoul National University Boramae Medical Center, and the Public Institutional Review Board of the Ministry of Health and Welfare of Korea approved the study . This secondary analysis was based on a previously approved ethical framework; therefore, no additional ethical clearance was required. Moreover, the primary research was conducted following the Helsinki Declaration.
|
39752447_p5
|
39752447
|
Study population
| 2.666172 |
biomedical
|
Study
|
[
0.9960579872131348,
0.002088162349537015,
0.0018539064330980182
] |
[
0.9948423504829407,
0.004717555362731218,
0.00019967184925917536,
0.00024040526477620006
] |
en
| 0.999997 |
In the final analysis, patients with chronic liver disease, excessive alcohol consumption, and pre-gestational diabetes were excluded. Additionally, individuals who were lost to follow-up or experienced preterm birth before 34 weeks of gestation were excluded. Consequently, the preliminary investigation encompassed a cohort of 623 participants. In the present study, we eliminated missing data for total cholesterol (TC), TG, HDL-C, low-density lipoprotein cholesterol (LDL-C), insulin, pre-pregnancy body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), aspartate aminotransferase (AST), and fasting plasma glucose (FPG) in 28 cases and incomplete information regarding GDM in 13 cases. Ultimately, the current investigation encompassed a total of 582 eligible participants, as depicted in Fig 1 .
|
39752447_p6
|
39752447
|
Study population
| 4.037383 |
biomedical
|
Study
|
[
0.9991254210472107,
0.0006000878056511283,
0.00027455869712866843
] |
[
0.9994605183601379,
0.00030500502907671034,
0.00016148720169439912,
0.00007301170262508094
] |
en
| 0.999996 |
The variables for the investigation were selected based on a comprehensive review of the initial investigation, clinical experience, and previous investigations into the risk factors associated with GDM. Due to this, we included the following covariates in our analysis: (1) categorical variables, such as parity and hepatic steatosis; (2) continuous variables, such as age, pre-pregnancy BMI, FPG, insulin levels, HOMA-IR (determined using the formula [insulin (IU/mL) × FPG (mmol/L)/22.5]), AST, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), adiponectin levels, LDL-C, HDL-C, TG, and TC. The severity of hepatic steatosis was determined using a previously validated semiquantitative grading system, ranging from grades 0 to 3 . Between the 10th and 14th weeks of gestation, a venous blood sample was obtained following a minimum fasting period of 8 h. The samples were centrifuged, aliquoted, and stored at –70°C for future analysis to evaluate hematological markers. FBG, routine lipid profiles, and liver enzyme concentrations were quantified using an enzymatic method (Glucose HK; Roche Diagnostics, Indianapolis, IN, USA) with a Roche/Hitachi 911 chemistry analyzer (Roche Diagnostics). Serum insulin concentrations were determined through an immunometric assay (IRMA) in duplicate using the same batch of a kit (INS-IRMA; DIAsource ImmunoAssays, Louvain-la-Neuve, Belgium). Adiponectin concentrations were quantified using an enzyme-linked immunosorbent assay (R&D Systems, United States).
|
39752447_p7
|
39752447
|
Variables
| 4.11095 |
biomedical
|
Study
|
[
0.9994220733642578,
0.0003915444540325552,
0.00018647618708200753
] |
[
0.9991437196731567,
0.00020648374629672617,
0.0005781229119747877,
0.00007167820876929909
] |
en
| 0.999998 |
During the gestational period of 10 to 14 weeks, venous blood samples were analyzed for HDL-C and RC using a computerized analyzer after a minimum fasting period of 8 h. To obtain the RC/HDL-C ratio, the RC (mg/dL) was divided by HDL-C (mg/dL). RC (mg/dL) was calculated as follows: TC (mg/dL) ˗ HDL-C (mg/dL) ˗ LDL-C (mg/dL), as previously reported.
|
39752447_p8
|
39752447
|
Ratio of RC to HDL-C
| 4.058877 |
biomedical
|
Study
|
[
0.999549925327301,
0.00029131548944860697,
0.00015872312360443175
] |
[
0.9988728165626526,
0.0007779484149068594,
0.00026923822588287294,
0.0000799914778326638
] |
en
| 0.999996 |
All participants underwent a two-step screening for GDM between 24 and 28 weeks of gestation, as recommended by the ACOG . In non-fasting scenarios, pregnant women undergo a glucose challenge test (GCT) by ingesting a 50-gram oral glucose solution, after which serum glucose levels are assessed. A serum glucose level of 7.8 mmol/L or higher indicates a positive GCT. Individuals with a positive GCT underwent testing in the form of a 100-gram OGTT. For the diagnosis of GDM, at least two increased blood glucose levels must be confirmed: Fasting glucose level ≥ 5.3 mmol/L, 1 h postprandial level ≥ 10 mmol/L, 2 h postprandial level ≥ 8.6 mmol/L, and 3 h postprandial level ≥ 7.8 mmol/L.
|
39752447_p9
|
39752447
|
Diagnosis of GDM
| 4.041736 |
biomedical
|
Study
|
[
0.9800839424133301,
0.019504912197589874,
0.00041113252518698573
] |
[
0.9140036106109619,
0.07872442901134491,
0.004171363078057766,
0.0031006874050945044
] |
en
| 0.999996 |
We partitioned the baseline data into three equal segments based on the RC/HDL-C ratio to evaluate its distribution. Continuous variables are represented as mean ± standard deviation or median (interquartile range), while categorical variables are presented as frequencies and percentages. Overall group differences were evaluated using either one-way analysis of variance for normally distributed data or the Kruskal–Wallis H test for non-normally distributed data.
|
39752447_p10
|
39752447
|
Data analysis
| 3.971268 |
biomedical
|
Study
|
[
0.9994986057281494,
0.00029571237973868847,
0.00020561055862344801
] |
[
0.9990299940109253,
0.0006203120574355125,
0.0002931683848146349,
0.00005652647450915538
] |
en
| 0.999998 |
Models of univariate and multivariate logistic regression were constructed in our study. For the non-adjusted model, no covariates were adjusted. The model I was adjusted for variables such as age, pre-pregnancy BMI, and parity. Adjusted model II incorporated variables such as age, pre-pregnancy BMI, parity, hepatic steatosis, levels of AST, GGT, ALT, adiponectin, and HOMA-IR. With corresponding 95% confidence intervals (CIs), the odds ratios (ORs) were adjusted to evaluate the GDM risk. Covariate adjustments were made based on a criterion where the inclusion of a covariate resulted in an OR change of at least 10%, which indicated its necessity for adjustment in the model.
|
39752447_p11
|
39752447
|
Data analysis
| 4.063386 |
biomedical
|
Study
|
[
0.9995054006576538,
0.0002751966821961105,
0.0002193956752307713
] |
[
0.9994266033172607,
0.0002185516495956108,
0.0003012436500284821,
0.000053724386816611513
] |
en
| 0.999997 |
This investigation utilized a sensitivity analysis to assess the robustness of the findings. To evaluate the correlation between the RC/HDL-C ratio and diverse factors and investigate possible non-linear relationships, we divided the RC/HDL-C ratio into three equal portions and computed the trend p -values. It is crucial to understand the interrelationships between obesity, NAFLD, and T2DM. To evaluate the correlation between the RC/HDL-C ratio and GDM, we excluded participants with hepatic steatosis grading greater than 0 or a pre-pregnancy BMI greater than 25 kg/m 2 .
|
39752447_p12
|
39752447
|
Data analysis
| 4.016119 |
biomedical
|
Study
|
[
0.9994831085205078,
0.0002928921894636005,
0.00022396423446480185
] |
[
0.9995521903038025,
0.00019570597214624286,
0.00020009381114505231,
0.000051983181037940085
] |
en
| 0.999998 |
To analyze subgroups, stratified logistic regression models were used in different subgroups, such as nulliparity, hepatic steatosis, age, pre-pregnancy BMI, and HOMA-IR. Clinical findings were used as cutoff points for categorical variables, while continuous variables were transformed into categorical variables based on median values or recognized clinical findings (age: below 35 or 35 years or above; pre-pregnancy BMI: below 25 or 25 kg/m 2 or above; HOMA-IR: up to 2 or greater than 2). A stratification analysis was performed, with each stratum adjusted for all aforementioned factors, excluding the stratification factor itself. Furthermore, a log-likelihood ratio was used to determine heterogeneity in subgroup associations.
|
39752447_p13
|
39752447
|
Data analysis
| 4.045075 |
biomedical
|
Study
|
[
0.9994797110557556,
0.0003008579951710999,
0.00021947643836028874
] |
[
0.9993682503700256,
0.00020345795201137662,
0.000373125629266724,
0.00005516708915820345
] |
en
| 0.999999 |
Moreover, a receiver operating characteristic (ROC) analysis was performed to assess the predictive capacity of the RC/HDL-C ratio, RC, TC, TG, LDL-C, HDL-C, and HOMA-IR for GDM. Subsequently, the sensitivity and specificity of a variable were evaluated through ROC analysis to determine its optimal threshold. R software (version 4.1.2) was used for statistical analysis. A two-tailed test was used to evaluate statistical significance, where results were considered statistically significant if p -values were below 0.05.
|
39752447_p14
|
39752447
|
Data analysis
| 4.018312 |
biomedical
|
Study
|
[
0.9995768666267395,
0.00022102720686234534,
0.0002021273539867252
] |
[
0.9992576241493225,
0.00027017135289497674,
0.0004143889236729592,
0.00005779856655863114
] |
en
| 0.999997 |
The demographic and clinical characteristics of the study participants are provided in Table 1 . The average age observed was 32.07 ± 3.78 years. Among the participants, 278 individuals (47.77%) had multiparous status, while 472 individuals (81.10%) were free from fatty liver disease. GDM was diagnosed in 35 (6.01%) pregnant women. Participants were classified into three categories based on their levels of the RC/HDL-C ratio. The highest tertile group exhibited significantly higher levels of pre-pregnancy BMI, TG, GGT, LDL-C, RC, and HOMA-IR levels than the lowest. Conversely, HDL-C and adipokines demonstrated an inverse trend. The distribution of RC/HDL-C ratio displayed a positively skewed pattern, with a median value of 0.33 (interquartile range: 0.26–0.47), as depicted in Fig 2 .
|
39752447_p15
|
39752447
|
Baseline characteristics
| 4.065158 |
biomedical
|
Study
|
[
0.9991627931594849,
0.0006142769707366824,
0.00022292218636721373
] |
[
0.9995088577270508,
0.00017566517635714263,
0.0002321544016012922,
0.00008332417928613722
] |
en
| 0.999996 |
The results of the univariate logistic analysis are presented in Table 2 . These results indicated a positive correlation between pre-pregnancy BMI, liver steatosis grade, TC levels, TG levels, ALT levels, GGT levels, FPG levels, insulin levels, HOMA-IR index, and RC/HDL-C ratio, and the occurrence of GDM. Additionally, GDM incidence exhibited a negative correlation with HDL-C levels.
|
39752447_p16
|
39752447
|
The outcomes of univariate analyses
| 4.052073 |
biomedical
|
Study
|
[
0.9994032382965088,
0.0003884641919285059,
0.00020830638823099434
] |
[
0.9993496537208557,
0.00019339761638548225,
0.00038278085412457585,
0.00007420085603371263
] |
en
| 0.999997 |
A multivariate logistic regression model was used to determine the association between the RC/HDL-C ratio and the incidence of GDM ( Table 3 ). The OR of the unadjusted model was 57.47, with a 95% CI of 13.32 to 248.01 ( P < 0.001). In Model I, the results consistently exhibited stable outcomes without significant variations (OR: 41.24, 95% CI: 8.63–197.16, P < 0.001). Furthermore, even in Model II, there was a statistically significant association between the RC/HDL-C ratio and the incidence of GDM (OR: 21.78, 95% CI: 3.55–133.73, P < 0.001). The adjustment factors incorporated in each of Model I and Model II are expressed in the data analysis section above and can be seen in the table notes.
|
39752447_p17
|
39752447
|
The outcomes of multivariate analyses
| 4.087246 |
biomedical
|
Study
|
[
0.9994686245918274,
0.00034574404708109796,
0.0001856846793089062
] |
[
0.9993250370025635,
0.00023231410887092352,
0.00036790696321986616,
0.00007475687743863091
] |
en
| 0.999997 |
As presented in Table 4 , supplementary sensitivity analyses were performed specifically on participants with a BMI less than 25 kg/m 2 . When controlling for confounding variables, a significant positive correlation was found between RC/HDL-C ratio and the incidence of GDM (OR = 22.13, 95% CI: 1.51–324.71). Furthermore, we conducted sensitivity analyses by including individuals without any signs of hepatic steatosis (grade 0). After adjusting for covariates, including age, parity, pre-pregnancy BMI, AST, GGT, ALT, HOMA-IR, and adiponectin, the findings consistently indicated an association between the RC/HDL-C ratio and GDM incidence (OR = 32.28, 95% CI: 2.08–500.67). Sensitivity analysis revealed robust and reliable results.
|
39752447_p18
|
39752447
|
Sensitive analysis
| 4.070864 |
biomedical
|
Study
|
[
0.9994528889656067,
0.0003402041329536587,
0.00020693507394753397
] |
[
0.9994485974311829,
0.00017553217185195535,
0.0003130542463622987,
0.00006273504550335929
] |
en
| 0.999997 |
To investigate the potential factors that could affect the association between the RC/HDL-C ratio and the incidence of GDM, we performed a subgroup analysis, as demonstrated in Fig 3 . Pre-pregnancy BMI, hepatic steatosis, age, parity, and HOMA-IR were stratified. Even after accounting for the potential confounders listed previously, the robust association between the RC/HDL-C ratio and GDM risk remained evident. Furthermore, the robustness of our results was validated through subgroup analysis.
|
39752447_p19
|
39752447
|
Subgroup analysis
| 4.026561 |
biomedical
|
Study
|
[
0.9994897842407227,
0.00030480840359814465,
0.00020544155267998576
] |
[
0.9994391798973083,
0.00017108279280364513,
0.0003292170586064458,
0.00006052407843526453
] |
en
| 0.999997 |
ROC curve analysis was used to evaluate the prognostic efficacy of the RC/HDL-C ratio in the prediction of GDM. The findings indicated that the area under the curve (AUC) for the RC/HDL-C ratio was 0.795 (95% CI: 0.723–0.868), as detailed in Table 5 and displayed in Fig 4 . Generally, the RC/HDL-C ratio exhibits superior predictive accuracy for GDM compared to other biomarkers, including TG, TC, HDL-C, LDL-C, RC, and HOMA-IR, with an anticipated higher AUC. An analysis utilizing Youden’s index identified a threshold of 0.45 for the RC/HDL-C ratio, yielding optimal specificity and sensitivity values of 71.4% and 75.3%, respectively, GDM prediction.
|
39752447_p20
|
39752447
|
ROC analysis
| 4.105677 |
biomedical
|
Study
|
[
0.9994626641273499,
0.0003596397873479873,
0.00017779799236450344
] |
[
0.9990940093994141,
0.00023710528330411762,
0.0005884675774723291,
0.00008044483547564596
] |
en
| 0.999997 |
According to a secondary analysis of Korean prospective data, the RC/HDL-C ratio was independently associated with the risk of GDM in the second trimester. Moreover, a sensitivity analysis confirmed the stable association between the RC/HDL-C ratio and GDM risk. Furthermore, the RC/HDL-C ratio can predict GDM with an AUC of 0.795 (95% CI: 0.723–0.868), a sensitivity of 71.4%, and a specificity of 75.3% when the cutoff value is 0.45. The RC/HDL-C ratio has greater predictive power than conventional lipid indices, including TG, LDL-C, HDL-C, and the emerging RC lipid index for GDM in early pregnancy. Therefore, this new marker may be a straightforward and non-invasive diagnostic index of GDM and useful for early diagnosis, treatment, and prognosis.
|
39752447_p21
|
39752447
|
Discussion
| 4.104372 |
biomedical
|
Study
|
[
0.9995262622833252,
0.0003377827233634889,
0.00013592439063359052
] |
[
0.9977226853370667,
0.0004003914655186236,
0.0017732445849105716,
0.0001036606845445931
] |
en
| 0.999997 |
GDM is fundamentally a heterogeneous disease that develops during pregnancy. According to previous studies, there is a linear relationship between increased blood glucose levels during 24–28 weeks of gestation and adverse perinatal outcomes . However, an unclear inflection point suggests we should focus on blood glucose levels in early pregnancy. According to the WHO diagnostic criteria for GDM , women diagnosed with diabetes in early pregnancy are more likely to have adverse outcomes and require insulin or other glucose-lowering medications than those generally diagnosed at 24–28 weeks of gestation . A meta-analysis revealed that, with and only in the first trimester of pregnancy, intervention can be effective in treating GDM . A large randomized controlled trial in an Australian population, published in the latest New England Journal of Medicine , reported that treating GDM immediately before 20 weeks’ gestation resulted in a slightly lower combined incidence of poor neonatal prognosis than that if no treatment was administered, making early diagnosis urgent. However, according to the diagnosis of GDM based on blood glucose in early pregnancy, the highest rate of positive GDM in the second trimester is only about 50%, which suggests a possibility of excessive diagnosis and treatment . Consequently, it is imperative to find an efficient and stable economic surveillance indicator to diagnose GDM despite uncertainty about the benefits and harms of early intervention.
|
39752447_p22
|
39752447
|
Discussion
| 4.219837 |
biomedical
|
Review
|
[
0.996268630027771,
0.00216902163811028,
0.0015623979270458221
] |
[
0.06158319115638733,
0.0012568775564432144,
0.9367382526397705,
0.000421679113060236
] |
en
| 0.999998 |
Traditional lipid indicators are extensively used in clinical practice. Studies have shown that non-traditional lipid parameters, including the atherosclerotic index (AIP), RC, and non-high-density lipoprotein cholesterol (non-HDL-C), have higher predictive value in identifying abnormal glucose metabolism in patients with GDM . The advantage of these non-traditional parameters is their ability to provide a more comprehensive assessment of metabolic status, especially during pregnancy, when physiological changes in women can affect the accuracy of traditional indicators. The progress of lipidomics provides a new perspective on understanding the pathophysiological mechanisms of GDM. In prospective studies, multiple fatty acids, phospholipids, lipoproteins, certain glycerolipids, and cholesterol have been reported to be associated with incident GDM . The elevation of certain lipid species, including TG and cholesteryl esters, is closely associated with GDM . Moreover, lipidomics studies have indicated that the lipid profiles of patients with GDM are associated with the risk of developing T2DM in the future, suggesting that abnormalities in lipid metabolism can play an important role in GDM pathophysiology . However, different lipidomics platforms result in difficulties in external validation and expensive assays, which pose limitations for the field of lipidomics.
|
39752447_p23
|
39752447
|
Discussion
| 4.350476 |
biomedical
|
Review
|
[
0.9971932768821716,
0.001610392238944769,
0.0011963037541136146
] |
[
0.11333665251731873,
0.001354895648546517,
0.884687602519989,
0.0006208869745023549
] |
en
| 0.999998 |
Reducing serum LDL-C levels is the primary therapeutic target for the primary and secondary prevention of CVD. Nevertheless, patients with substantial decreases in LDL-C levels have a considerable risk of CVD, namely residual risk. Accordingly, high levels of RC can partially explain residual risk and are independent of the conventional lipid profile. Numerous epidemiological studies indicated that the RC concentration is positively associated with the occurrence of cardiovascular events such as AS. Furthermore, RC has stronger all-cause mortality in ischemic heart disease than the conventional lipid profile . Related mechanisms can include the following: (1) Through the LPL-mediated (and, to a lesser extent, hepatic lipase-mediated) removal of TG and cholesteryl ester transfer protein-mediated cholesterol exchange in the LDL and HDL, RC particles contain more cholesterol than the nascent CM or VLDL, and RC is larger than LDL-C particles and carries more cholesterol (possibly 5–20 times more than LDL) . Cholesterol is considered the primary component of AS. (2) Unlike LDL, RC is absorbed by macrophages and smooth muscle cells. (3) RC can rapidly enter the subendothelial space, with RC efflux being slow compared to the rate at which they enter, increasing the chance of macrophage internalization and foam cell formation . (4) As with adipocytes and cardiomyocytes, atherosclerotic lesional macrophages can produce large amounts of LPL. The LPL-mediated release of free fatty acids from the accumulated RC can induce the production of pro-inflammatory mediators (cytokines, interleukins, and adhesion molecules); therefore, accelerating the recruitment of leukocytes to areas of inflammation. Simultaneously, we discovered that increased RC levels were linked to reduced inflammation and ischemic heart disease, suggesting that RC causes atherosclerotic with inflammatory components . Several Mendelian randomization analyses have been published, providing a genetic basis for the causal role of TRLs (RC precursors) in AS . Concurrently, more studies have focused on RC, NAFLD, and T2DM metabolic diseases. NAFLD is a hepatic manifestation of the metabolic syndrome. Conventional dyslipidemia, characterized by elevated serum TG and LDL-C levels and decreased HDL-C levels, has been identified as a risk factor for NAFLD . Decreased LPL activity results in insufficient clearance of TRLs. The activation of LPL has been confirmed to reduce the severity of hepatic steatosis effectively . Second, low-grade systemic inflammation, which plays a key role in NAFLD pathogenesis, can be involved in RC and NAFLD. In the second trimester, NAFLD is predictive of GDM, indicating that RC may be involved in the pathogenesis of NAFLD to GDM and that IR may be a significant mechanism . Similarly, diabetic dyslipidemia contributes to the progression of diabetes at an early stage. With the finding that statins do not control diabetic dyslipidemia , the focus of research has shifted from traditional lipid profiles such as LDL-C to TRLs. Moreover, the fact that RC has reportedly been associated with the risk of residual CVD in diabetes sidesteps this point . The RC is the cholesterol content of TRLs. Although plasma TG can be used as a surrogate marker for clinical RC, it represents different types of lipid disorders. RC can promote IR more directly than TG, while the toxic effect of cholesterol on PBC leads to the structural changes of insulin-containing granules . A study with a large sample in China reported that RC transcends LDL-C and is associated with diabetes, which can be mediated by IR and proinflammatory status . Moreover, diabetes is more likely to develop in women exposed to RC, which can be associated with different dietary profiles, estrogen, and cholesterol metabolism. At the genomic level, GDM and T2DM have a genetic correlation. Several studies have indicated that the genetics of GDM risk can be classified into two groups: one is T2DM risk, and the other is the main factor specific to GDM. The GDM-specific mechanism can be associated with islet cells, central glucose homeostasis, steroidogenesis, and placental expression . It suggests that GDM and T2DM seek differences in gene mechanisms.
|
39752447_p24
|
39752447
|
Discussion
| 4.946834 |
biomedical
|
Study
|
[
0.9977598190307617,
0.0014152888907119632,
0.0008248928934335709
] |
[
0.8801771998405457,
0.002220079768449068,
0.11611344665288925,
0.0014892115723341703
] |
en
| 0.999996 |
Research indicates maternal lipid profiles, particularly TG and RC, can significantly influence fetal growth and metabolic outcomes. For instance, a study found that higher maternal TG and RC levels were associated with increased fetal head circumference and abdominal circumference growth rates, suggesting a direct impact on fetal development. Furthermore, these lipid levels were positively correlated with the risk of large-for-gestational-age infants, suggesting that dysregulated lipid metabolism can affect maternal and fetal health . The future of lipid components other than TG in GDM is evolving and controversial [ 56 – 58 ]. Currently, there is limited research on the relationship between RC and GDM. Moreover, the relevant literature is quite scarce, and the metabolic mechanisms need further investigation. Weiming Wang et al. conducted a prospective study on the relationship between GDM and RC using the RC calculation method. Additionally, the experiment was nested and measured relevant parameters in Chinese women in the first trimester (12–14 weeks), which demonstrated that increased RC levels were associated with an increased risk of GDM despite traditional risk factors. Pregnant women with elevated BMI, TG, and RC had a significantly increased risk of GDM. Our study found that RC can be correlated with GDM risk. Additionally, further analysis indicated that RC/HDL-C ratio was an independent risk factor for GDM, which persisted even after adjusting for insulin, fasting glucose, and hepatic steatosis. However, the study by Weiming Wang et al. did not incorporate any of these metrics to explore. The mechanisms by which RC affects GDM may involve inflammatory pathways and endothelial dysfunction. Increased RC can lead to the activation of pro-inflammatory pathways, which can exacerbate IR and contribute to the pathophysiology of GDM. Additionally, maternal dyslipidemia, characterized by elevated cholesterol levels, has been associated with impaired vascular function in the placenta, potentially affecting nutrient delivery to the fetus and leading to adverse outcomes . Moreover, studies utilizing Mendelian randomization have provided causal evidence supporting the role of RC in in GDM development. These analyses suggest that genetically predicted elevated RC levels are associated with an increased risk of GDM, highlighting the importance of lipid management during pregnancy . In summary, the interplay between RC and GDM involves metabolic, inflammatory, and vascular mechanisms.
|
39752447_p25
|
39752447
|
Discussion
| 4.453157 |
biomedical
|
Study
|
[
0.9991579055786133,
0.0005685050855390728,
0.0002735339803621173
] |
[
0.9583122134208679,
0.0007725174655206501,
0.0405234768986702,
0.0003918007423635572
] |
en
| 0.999998 |
Ethnic differences in lipid metabolism and GDM risk are critical areas of research that highlight how genetic, environmental, and lifestyle factors interact to influence metabolic health across diverse populations. Research indicates that South Asian women tend to have a higher prevalence of GDM compared to their White European counterparts, which can be attributed to differences in body fat distribution and insulin sensitivity at a given BMI level . This ethnic disparity is further complicated by the fact that South Asians often exhibit a more adverse lipid profile, including higher levels of TG and lower levels of HDL-C, which are risk factors for metabolic diseases . Moreover, genetic factors significantly influence lipid metabolism and GDM risk. Variants in genes associated with lipid metabolism, including the cholesteryl ester transfer protein and LPL, have been shown to influence lipid levels differently across ethnic groups. Studies have demonstrated that black South African women exhibit a more favorable lipid profile than their white counterparts, a phenomenon that is associated with particular genetic polymorphisms . Besides, a study on the Korean population reported that the variants in KCNQ1 were associated with a risk for GDM and decreased insulin secretion capacity . Insufficient insulin secretion can enhance lipolysis, resulting in elevated concentrations of TG and cholesterol in the bloodstream. This suggests that genetic predisposition can contribute to the observed ethnic differences in lipid metabolism and the associated risk of GDM. In conclusion, understanding the ethnic differences in lipid metabolism and their implications for GDM risk is essential for developing targeted prevention and treatment strategies.
|
39752447_p26
|
39752447
|
Discussion
| 4.433927 |
biomedical
|
Review
|
[
0.9983516931533813,
0.0009275574702769518,
0.0007207845919765532
] |
[
0.4447213411331177,
0.001548851141706109,
0.5530206561088562,
0.000709055457264185
] |
en
| 0.999996 |
HDL-C is involved in the reverse transport of cholesterol in the human body, where it can "remove" cholesterol from the atherosclerotic vessel wall and transport it to the liver for metabolic clearance. Generally, HDL-C reduction is a characteristic dyslipidemia of T2DM . Researchers reported that a low HDL-C level affects glucose homeostasis by decreasing insulin secretion, insulin sensitivity, and adenosine monophosphate-activated protein kinase (AMPK) activity . With further studies of HDL, several additional functional features were identified, including antioxidant and anti-inflammatory properties . The anti-inflammatory effect of HDL plays a role in preventing T2DM . Reactive oxygen species can directly damage PBC, interfere with the normal function of the insulin signaling pathway, and reduce cell responsiveness to insulin, leading to increased blood glucose levels. The HDL-associated antioxidant enzyme paraoxonase 1 (PON1) enhances the scavenging of lipid hydroperoxides, thereby reducing oxidative stress. According to experimental evidence, this increases insulin secretion in mice and cellular models .
|
39752447_p27
|
39752447
|
Discussion
| 4.641898 |
biomedical
|
Study
|
[
0.9986767172813416,
0.0008187777712009847,
0.0005044182180427015
] |
[
0.6696736216545105,
0.0019118484342470765,
0.32743197679519653,
0.0009826291352510452
] |
en
| 0.999996 |
Generally, a normal increase in HDL-C content is observed from the first trimester through the second trimester. However, a decrease is observed in the third trimester. HDL-C concentrations were lower throughout GDM . There is evidence that moderate increases in HDL-C concentration can protect against GDM, and HDL-C levels are inversely correlated with GDM risk . According to Jin et al. , relatively low maternal HDL-C was associated with an increased risk of both GDM and macrosomia, while high HDL-C was protective. However, we observed that HDL-C was low in GDM. Moreover, univariate analysis exhibited a negative correlation with the occurrence of GDM. HDL-C is involved in modulating insulin sensitivity. Lower levels of HDL-C are associated with increased IR, a key factor in GDM development. This relationship can arise from HDL-C’s role in influencing peripheral glucose uptake, promoting beneficial signaling pathways that enhance insulin action . First, oxidative stress and inflammation are elevated during pregnancy, and these factors are further exacerbated in GDM. HDL-C has anti-inflammatory and antioxidant properties that can reduce these conditions. Studies have indicated that HDL-C can influence the activity of PON1, an enzyme associated with antioxidant properties. In GDM, decreased PON1 activity correlates with lower HDL-C levels, indicating a disturbance in antioxidative mechanisms that may contribute to IR development . Second, HDL-C is crucial for cholesterol efflux and lipid homeostasis. Impairments in these functions can result in the accumulation of lipotoxic intermediates, further exacerbating IR and promoting PBC dysfunction—both critical in GDM pathogenesis . Furthermore, HDL-C plays a role in maintaining endothelial function and vascular health. Reduced HDL-C levels can compromise endothelial integrity, affecting placental blood flow and glucose transport and contributing to GDM pathophysiology . The relationship between HDL-C and GDM is complex and involves lipid metabolism, inflammatory responses, and oxidative stress.
|
39752447_p28
|
39752447
|
Discussion
| 4.605464 |
biomedical
|
Study
|
[
0.9992361068725586,
0.0005054249195381999,
0.00025854443083517253
] |
[
0.9911502599716187,
0.0007239818223752081,
0.007840471342206001,
0.0002853348560165614
] |
en
| 0.999997 |
Given the preceding positive correlation of RC with the occurrence of related diseases and the negative correlation of HDL-C, this study investigates whether the combination of RC and HDL-C (RC/HDL-C ratio) can improve the predictive power for GDM. Currently, RC/HDL-C ratio-based studies in related diseases are limited. Reportedly, the RC/HDL-C ratio contributes to and mediates the risk of BMI-related NAFLD and contributes more to the mediation effect than conventional lipid markers . The same results have been studied and verified in the Japanese population . Meanwhile, the RC/HDL-C ratio can reflect the balance between potential pro-atherogenic lipoprotein particles and is a useful independent predictor of myocardial damage in some patients with DM .
|
39752447_p29
|
39752447
|
Discussion
| 4.068347 |
biomedical
|
Study
|
[
0.9995588660240173,
0.0002629696682561189,
0.0001781722530722618
] |
[
0.9990948438644409,
0.00022158233332447708,
0.0006125116487964988,
0.00007099366484908387
] |
en
| 0.999998 |
Our study is the first prospective study on the relationship between RC/HDL-C ratio and GDM. We found a positive correlation between the RC/HDL-C ratio and GDM risk. The risk remained significant after adjustment for the confounding variables. Furthermore, our study revealed that the RC/HDL-C ratio is the best predictor of GDM risk compared with conventional lipid profile TG, TC, LDL-C, HDL-C, and non-conventional lipid index RC. Meanwhile, through sensitivity analyses, we noticed that the RC/HDL-C ratio was associated with GDM risk among Korean women with a BMI < 25 kg/m 2 or without hepatic steatosis. Several variables were considered to identify potential confounders that can affect the relationship between RC/HDL-C ratio and GDM events, including age, pre-pregnancy BMI, parity, hepatic steatosis, and HOMA-IR. The results revealed that RC/HDL-C ratio and GDM risk were unaffected by the aforementioned confounding variables, suggesting the robustness of our results.
|
39752447_p30
|
39752447
|
Discussion
| 4.100321 |
biomedical
|
Study
|
[
0.9994303584098816,
0.00036890493356622756,
0.00020079713431186974
] |
[
0.9993022680282593,
0.00017785256204660982,
0.0004419207980390638,
0.00007790727249812335
] |
en
| 0.999996 |
Conclusively, the mechanism that links the RC/HDL-C ratio to GDM development is unclear and can take several forms. (1) Common pathway of metabolic diseases: RC carries a large amount of cholesterol toxic to PBC, inducing apoptosis and affecting insulin formation and secretion; HDL has cholesterol efflux capacity; RC and HDL-C participate in IR via opposing inflammatory effects. (2) Previous studies reported that the TG/HDL-C ratio is a valid surrogate marker for IR, with good IR prediction performance . Additionally, most laboratories utilize enzymatic methods to detect TG levels, which not only measure the TG in the aforementioned lipoproteins but also free glycerol. Therefore, we cannot directly replace RC with TG. Abnormalities in TRLs (mostly RC-carrying lipoproteins) carried by apolipoprotein B in T2DM may precede IR . Moreover, it has been indicated that RC particle diameter is associated with hemoglobin A1C. Similarly, RC was negatively correlated with HDL-C levels , suggesting that low HDL-C can be a biomarker for increased TG and RC levels. Therefore, selecting the RC/HDL-C ratio may be more favorable. (3) Sex-specific: Pregnancy increases circulating pregnancy hormones (including human placental lactogen, progesterone, and estrogen), which change normal homeostatic glucose pathways in the brain and pancreas, leading to impaired insulin sensitivity in maternal peripheral tissues . Estrogen secretion during pregnancy promotes atherosclerotic lipid abnormalities, visceral weight gain, and IR, which increase the risk of liver disease and cardiometabolic disease . Moreover, the human placenta plays a crucial role in transforming cholesterol into steroids. The production of these hormones is vital for sustaining pregnancy and supporting the embryo’s growth. During the second half of pregnancy, IR status can be triggered by placental hormones , which potentially explains the role of RC in GDM development. (4) HDL participates in the reverse remnant-cholesterol transport. An earlier version of this hypothesis explained the adverse relationship between plasma HDL-C and CVD (free cholesterol transfer is impaired at low and very high triglyceride lipoproteins) . Generally, a steady-state concentration of HDL-C can serve as a biomarker for cholesterol removal from TRLs in plasma. Some of the RC were lipolysis products (apolipoprotein A-I (apoA-I) and cholesterol), which generated HDL-C in plasma (50% of their species). This pathway originates from the intestine, with apoA-I produced via RC lipolysis and cholesterol and subsequently transported to the plasma via lymph. Accordingly, the plasma concentration of HDL-C represents an imperfect static measure of cholesterol flux through this dynamic pathway. Therefore, high plasma HDL concentrations may be both a result and a cause of the effective clearance of plasma RC. It is suggested that the RC/HDL-C ratio can reflect the dynamic process of this pathway, indicating a mechanism by which HDL facilitates the clearance of RC particles from the bloodstream, thereby contributing to overall lipid homeostasis. This clearance is crucial because RC particles, if accumulated, can have atherogenic and pro-inflammatory effects . All these need to be demonstrated through our further research.
|
39752447_p31
|
39752447
|
Discussion
| 4.701646 |
biomedical
|
Study
|
[
0.9990921020507812,
0.0005629709339700639,
0.00034494863939471543
] |
[
0.9823287129402161,
0.0008089382317848504,
0.016521306708455086,
0.0003410219505894929
] |
en
| 0.999995 |
The present study has some advantages. Firstly, the relationship between the RC/HDL-C ratio and GDM has been demonstrated for the first time, not only in terms of the IR mechanism to explain it, but also in the direction of the reverse remnant-cholesterol transport doctrine to try to explain the dynamics of the partial transformation between RC and HDL-C. Secondly, it explains to some extent the similar but independent mechanisms of GDM and T2DM, which of course has been claimed at the genetic level. Furthermore, Mendelian randomization studies have revealed that apolipoprotein B is more dynamically representative of the association of TRLs and LDL-C and coronary heart disease (CHD). Besides, RC and HDL-C contain a wide range of apolipoproteins with different compositions and contents, suggesting that apolipoproteins can be the direction of our future research.
|
39752447_p32
|
39752447
|
Discussion
| 4.114816 |
biomedical
|
Study
|
[
0.9995285272598267,
0.00024274286988656968,
0.00022872975387144834
] |
[
0.9994708895683289,
0.00019217116641812027,
0.0002846499264705926,
0.00005234283526078798
] |
en
| 0.999997 |
This study has certain limitations. First, the sample size was small, and the sampling population also had limitations, necessitating its validation in different populations. Second, this is a secondary analysis of a prospective cohort study based in Korea, which has inherent limitations, including a lack of control over the design and data collection of the original study in the context of secondary data analysis. Insufficient life and clinical information, including participant’s dietary intake and physical activity levels, can be confounding factors affecting the experiment’s outcome. Additionally, standardization of specimen collection and quality control during laboratory testing reflects the challenges of this study. Furthermore, excluding participants with a BMI ≥ 25 and hepatic steatosis strengthened the robustness of our study results but also presented potential limitations. Primarily, excluding relevant participants can limit the generalizability of our findings to broader populations where overweight, obesity, and hepatic steatosis are common. Excluding such participants could overlook the complex interplay of these metabolic factors and their impact on GDM risk. Moreover, given the rising incidence of obesity and related metabolic conditions globally, our criteria can underrepresent a significant demographic at risk of GDM. Moreover, RC measurement adopts a calculation method. Although the calculation method strongly correlates with the homogeneous reagent method, the detection result can be high because some intermediate products are counted, and the detection results are unreliable when the TG content is high . Accordingly, the direct methods of measuring RC can give different results, which could affect the study results. Meanwhile, in this experiment, the two-step OGTT method was employed to diagnose GDM in the Korean population, which differs from the diagnostic criteria of the one-step OGTT method recommended by the IADPSG in other parts of Asia (including China). The database referenced in this article used the ACOG diagnostic criteria for GDM 2013, which solely confirmed the presence of GDM without specifying individual blood glucose values for the two-step testing method. Therefore, redefining GDM in this study using the updated 2018 ACOG diagnostic criteria poses a challenge. However, the minor discrepancies between the 2013 and 2018 criteria likely exert minimal influence on the study’s outcomes. Consequently, the results can differ, which requires further categorization and exploration in the future. Additionally, insulin secretion is limited in Asians compared with Caucasians, and PBC dysfunction is a significant risk factor for GDM in Korean females . Furthermore, there is no dynamic monitoring of the entire gestational cycle to learn about the dynamic changes in this indicator during pregnancy. Finally, some studies have found that compared with patients with GDM having normal glucose tolerance, women with insulin sensitivity defects had higher fasting blood glucose and greater birth weight (thereby a higher probability of adverse events), whereas women with insulin secretion defects were less different from normal pregnant women . Considering the heterogeneity in content and components between fasting and postprandial in RC, the role of the emerging lipid marker RC/HDL-C ratio in GDM and its metabolic subtypes deserves further exploration.
|
39752447_p33
|
39752447
|
Discussion
| 4.260926 |
biomedical
|
Study
|
[
0.999234676361084,
0.0005003749975003302,
0.00026492855977267027
] |
[
0.9988827109336853,
0.00022924299992155284,
0.0007816422148607671,
0.00010645895235938951
] |
en
| 0.999996 |
This research emphasizes the initial demonstration of RC/HDL-C ratio’s efficacy during early pregnancy for predicting the development of GDM during the second trimester. Consequently, the RC/HDL-C ratio can be used as a useful tool for early screening and included in regular obstetric clinical evaluations. Prevention of at-risk pregnancies based on the RC/HDL-C ratio early in pregnancy has the potential to reduce the incidence of GDM and improve pregnancy outcomes. This study has the potential to reduce the burden of care at a medical level and the economic burden at a social level for patients with GDM, and can be effective in improving adverse maternal and neonatal outcomes in the long term.
|
39752447_p34
|
39752447
|
Conclusion
| 4.058869 |
biomedical
|
Study
|
[
0.9993910789489746,
0.0004690280184149742,
0.00013989796570967883
] |
[
0.9973485469818115,
0.0005261015612632036,
0.001993251731619239,
0.00013213741476647556
] |
en
| 0.999997 |
Erythrodermic psoriasis (EP) is a rare and severe form of psoriasis vulgaris, with a 1-2.25% prevalence among psoriatic patients . It is defined by considerable erythema that covers at least 80-90% of the body surface and is frequently associated with fever, chills, headache, and general discomfort . EP often mimics a burn-like appearance of the skin due to the intense inflammation, and the associated systemic symptoms can make it difficult to differentiate from other severe skin conditions.
|
PMC11698379_p0
|
PMC11698379
|
Introduction
| 3.93657 |
biomedical
|
Other
|
[
0.9974520802497864,
0.0020637442357838154,
0.0004841532208956778
] |
[
0.0607772022485733,
0.5473515391349792,
0.38464269042015076,
0.007228576112538576
] |
en
| 0.999998 |
The onset might be abrupt or gradual and can be triggered by a range of factors, such as mental stress, infections, or new medications . The pathophysiology of EP requires additional research; however, certain immunological biomarkers, like interleukin-4, interleukin-10, IgE antibodies, and T-helper 2 lymphocytes, are suspected to be implicated. EP is a medical emergency because it disrupts the skin’s normal barrier functions, which are crucial for regulating body temperature, preventing infections, and maintaining fluid and electrolyte balance. The loss of these protective functions can lead to severe fluid loss, multiorgan failure, and an increased risk of infections. The management of EP can be very challenging, and if left untreated, the patient could be at risk of experiencing multi-system organ failure and high-output heart failure due to cutaneous volume loss .
|
PMC11698379_p1
|
PMC11698379
|
Introduction
| 4.090506 |
biomedical
|
Other
|
[
0.9839550256729126,
0.015715964138507843,
0.00032904199906624854
] |
[
0.21954597532749176,
0.5891958475112915,
0.16758663952350616,
0.02367153950035572
] |
en
| 0.999999 |
We present a case where EP is evident in a patient, serving as a manifestation of recent psychological stress on a background of multiple treatment failures. The extent of the disease in this report was measured using the Dermatology Life Quality Index (DLQI). DLQI is a questionnaire comprising 10 questions aimed at assessing the influence of skin conditions on an individual's quality of life. Each question receives a score between 0 and 3, resulting in a total score range from 0 (indicating no effect of the skin condition on quality of life) to 30 (suggesting the highest impact on quality of life) .
|
PMC11698379_p2
|
PMC11698379
|
Introduction
| 3.888388 |
clinical
|
Clinical case
|
[
0.48483940958976746,
0.5122115612030029,
0.0029489893931895494
] |
[
0.01617254503071308,
0.02228376641869545,
0.003615501569584012,
0.9579281210899353
] |
en
| 0.999994 |
A 76-year-old woman with poorly controlled psoriasis (DLQI 28) was referred to the medical expected unit after experiencing generalized weakness with limited movement, fever, tachycardia, leg swelling associated with pain and redness, decreased appetite, and a reduced level of consciousness. The patient had recently visited her general practitioner for leg cellulitis, for which she was given oral antibiotics that were ineffective.
|
PMC11698379_p3
|
PMC11698379
|
Case presentation
| 2.858345 |
clinical
|
Clinical case
|
[
0.07229616492986679,
0.9203532934188843,
0.007350590080022812
] |
[
0.0017076825024560094,
0.005599432624876499,
0.002185563324019313,
0.9905072450637817
] |
en
| 0.999997 |
She has been struggling with psoriasis and psoriatic arthritis for about 30 years, for which she was under both dermatology and rheumatology specialists. She had tried various disease-modifying anti-rheumatic drugs, notably sulfasalazine, leflunomide, and cyclosporin, which provided marginal benefits. The patient is presently undergoing treatment with 25 milligrams (mg) of subcutaneous methotrexate administered weekly. Additionally, it has been observed that she recently experienced the loss of her daughter, an event that may have exerted a psychosocial impact on her.
|
PMC11698379_p4
|
PMC11698379
|
Case presentation
| 2.275101 |
clinical
|
Clinical case
|
[
0.0674118623137474,
0.9251297116279602,
0.0074584647081792355
] |
[
0.0016872892156243324,
0.014153406955301762,
0.0020362166687846184,
0.982123076915741
] |
en
| 0.999998 |
During the clinical assessment, psoriasis was observed to involve the entire body surface area, accompanied by a low-grade fever. The skin was warm to touch, dry, and thickened with prominent silvery-white scaling . Notably, there was substantial edema in the lower extremities with localized cellulitis, resulting in restricted mobility . In the hospital setting, the patient was initially treated with intravenous clindamycin at a dose of 600 mg four times daily for two days, after which therapy was switched to oral clindamycin, and the patient subsequently remained afebrile. Methotrexate was withheld while treating the acute infection, and the patient was started on adalimumab following a short course of intravenous hydrocortisone. The results of the blood tests during admission indicated an improvement in C-reactive protein and normalization of serum creatinine following fluid management (Table 1 ). Mild thrombophilia had also improved after discharge from the hospital, and neutrophilia was observed to be related to steroid initiation.
|
PMC11698379_p5
|
PMC11698379
|
Case presentation
| 3.878731 |
clinical
|
Clinical case
|
[
0.06327320635318756,
0.9336168169975281,
0.0031099712941795588
] |
[
0.007549612782895565,
0.008892030455172062,
0.004417170770466328,
0.9791411757469177
] |
en
| 0.999996 |
The effectiveness of adalimumab was re-evaluated after a period of six weeks. Notable improvement in the skin symptoms was observed. Nevertheless, the patient continued to exhibit some visible signs of the disease, and hence, another assessment of adalimumab's efficacy will be conducted at 16 weeks.
|
PMC11698379_p6
|
PMC11698379
|
Case presentation
| 1.767366 |
clinical
|
Clinical case
|
[
0.3981468379497528,
0.5960093140602112,
0.005843819584697485
] |
[
0.08013559877872467,
0.31003713607788086,
0.005093842279165983,
0.604733407497406
] |
en
| 0.999995 |
Photography
|
PMC11698379_p7
|
PMC11698379
|
Case presentation
| 0.926969 |
biomedical
|
Other
|
[
0.585479199886322,
0.01565660536289215,
0.3988642394542694
] |
[
0.00923518743366003,
0.9802674055099487,
0.006710190325975418,
0.003787222784012556
] |
en
| 0.999998 |
Photography of this patient was quite restricted due to her condition and lack of mobility. However, with nursing help and patient compliance, a variety of different views were obtained to illustrate the condition. There was plenty of natural light available in the room, so an ISO (film speed) of 3200 was used with some additional fill-in-flash to enhance the texture and detail of the condition within the images .
|
PMC11698379_p8
|
PMC11698379
|
Case presentation
| 1.607897 |
clinical
|
Other
|
[
0.36549922823905945,
0.5904781818389893,
0.044022563844919205
] |
[
0.014435214921832085,
0.5096497535705566,
0.0038073204923421144,
0.4721077084541321
] |
en
| 0.999997 |
Psoriasis (psoriasis vulgaris) is a chronic (long-term) autoimmune condition characterized by extensive scaling caused by epidermal cell hyperproliferation. It typically presents with large oval-circular plaques over the scalp, trunk, and extensor body surface . More commonly, EP arises as a complication of psoriasis vulgaris .
|
PMC11698379_p9
|
PMC11698379
|
Discussion
| 3.68191 |
biomedical
|
Other
|
[
0.996839165687561,
0.002557146828621626,
0.0006036291015334427
] |
[
0.020295219495892525,
0.9425214529037476,
0.0330335758626461,
0.004149723332375288
] |
en
| 0.999996 |
Although EP is classified as a subtype of psoriasis, the pathogenic processes are distinct from those seen in plaque psoriasis , IL36RN mutations have been linked to pustular psoriasis, and the class I antigens HLA-Cw6, HLA-B57, HLA-B13, and HLA-B17 have been linked to psoriasis vulgaris. However, very little is known about the genetic foundation of EP . Several studies suggest that the disease is associated with a predominantly T-helper 2 phenotype.
|
PMC11698379_p10
|
PMC11698379
|
Discussion
| 4.065632 |
biomedical
|
Study
|
[
0.9996016621589661,
0.0001983566617127508,
0.00020000124641228467
] |
[
0.9260936379432678,
0.002441782271489501,
0.07113444805145264,
0.0003300905809737742
] |
en
| 0.999997 |
In this report, the patient’s symptoms were classic EP, including widespread erythema, desquamation, and systemic involvement. Notably, the patient also developed cellulitis of the lower limbs . Given the severity of the infection, the cellulitis was treated with antibiotics to prevent further complications, such as sepsis, which can occur if left untreated. The co-occurrence of an infection with EP underscores the delicate nature of the skin’s integrity in this condition.
|
PMC11698379_p11
|
PMC11698379
|
Discussion
| 3.682749 |
clinical
|
Clinical case
|
[
0.3678233325481415,
0.6293997168540955,
0.0027769168373197317
] |
[
0.010161101818084717,
0.023117410019040108,
0.002804078860208392,
0.9639174342155457
] |
en
| 0.999999 |
A contributing factor to the relapse of EP in this patient might have been the psychological stress related to a significant life event that the patient described. Stress is well-known to trigger or exacerbate psoriasis by altering immune system activity and increasing inflammation.
|
PMC11698379_p12
|
PMC11698379
|
Discussion
| 2.638458 |
biomedical
|
Other
|
[
0.9859920144081116,
0.012946635484695435,
0.0010614250786602497
] |
[
0.09746444225311279,
0.8313973546028137,
0.006297299172729254,
0.0648408904671669
] |
en
| 0.999996 |
The mechanism by which psychological stress contributes to the onset or worsening of psoriasis is not yet fully understood. Psychological stress activates the hypothalamic-pituitary-adrenal axis, leading to the release of stress hormones (cortisol, adrenaline, and noradrenaline) that interfere with immune regulation and amplify inflammatory responses, fostering a pro-inflammatory environment . Although cortisol typically exerts anti-inflammatory effects, prolonged stress may diminish its regulatory capacity, allowing unopposed inflammatory pathways .
|
PMC11698379_p13
|
PMC11698379
|
Discussion
| 4.085594 |
biomedical
|
Study
|
[
0.9994663596153259,
0.0003142862697131932,
0.00021928877686150372
] |
[
0.8088816404342651,
0.021769335493445396,
0.16860754787921906,
0.0007414214196614921
] |
en
| 0.999996 |
Subsets and Splits
SQL Console for rntc/test-pp-aa
The query retrieves a sample of documents that are clinical cases with an educational score above 3, providing limited analytical value.
Clinical Cases Sample
Returns a sample of 100 clinical case documents, providing a basic overview of the document type's content.