bluuebunny/crossref_metadata_2025_split huggingface dataset:
Menopause and mental health
Authors: Horst Karen , Cirino Nicole , Adams Karen E. 
Published: February 2025

Purpose of review
This review discusses mental health changes commonly experienced by individuals during the menopause transition (MT). The pathophysiology of the MT, the chronology and type of mental health symptoms arising from this pathophysiology, and evidence-based options for treating midlife patients are discussed. This review concludes with treatment options to enable clinicians to more effectively counsel, recognize and treat symptoms during the MT.

Recent findings
The MT begins earlier than previously understood with mood and cognitive issues as common initial mental health symptoms significantly impacting quality of life. These symptoms are due to profound changes in the brain’s structure, connectivity, energy metabolism, and inflammation linked to perimenopausal hormone shifts. Hormone therapy, psychiatric medication, psychotherapy, and lifestyle adjustments all play a role in the management of mental health symptoms arising during the MT. Lack of both obstetrician and gynecologist and mental health clinician awareness can leave patients undertreated and vulnerable to nonevidence-based approaches.

Summary
Patients in the MT are at increased risk for mental health issues, both preexisting and new onset. The OB/GYN clinician plays a key role in recognizing and addressing these conditions to improve health outcomes in midlife women.
Deep immune profiling of intrahepatic cholangiocarcinoma with CODEX multiplexed imaging
Authors: Baretti Marina , Shekhar Soumya , Sahai Vaibhav , Shu Daniel , Howe Kathryn , Gunchick Valerie , Assarzadegan Naziheh , Kartalia Emma , Zhu Qingfeng , Hallab Elsa , Sheth-Shah Archit , Kondo Aya , Azad Nilofer S. , Yarchoan Mark 
Published: February 2025

Background:
Intrahepatic cholangiocarcinoma (iCCA) may be genomically subclassified by the presence of potentially actionable molecular aberrations, of which pathogenic alterations in isocitrate dehydrogenase (IDH)1 and fibroblast growth factor receptor (FGFR)2 are the most frequently observed. The impact of these molecular alterations on the tumor immune microenvironment remains incompletely understood.

Methods:
We performed a high-parameter spatial immune phenotyping of iCCA samples with pathogenic FGFR2 or IDH1 alterations and FGFR2/IDH1 wild-type controls at the single-cell level using CO-Detection by indEXing.

Results:﻿
A total of 24 tumors were examined. Tumors with FGFR2 alterations were characterized by fewer CD8+ T cells and “M2-like” macrophages but higher levels of polymorphonuclear myeloid-derived suppressor cells as compared to FGFR2 wild-type tumors. Spatial relationships between polymorphonuclear myeloid-derived suppressor cells and multiple other cell types in the tumor microenvironment (including tumor cells, CD4+, and CD8+ T cells) were enriched in tumors with FGFR2 alterations. Tumors with IDH1 mutations had a trend toward more fibroblasts and were characterized by a closer proximity of tumor cells to CD4+ T cells, and between macrophages and multiple structural tumor microenvironment components as compared to other subtypes.

Conclusions:
iCCAs with pathogenic FGFR2 fusions/rearrangements and IDH1 mutations have distinct immunophenotypes. Tailoring immunotherapeutic approaches to specific molecular subsets could improve treatment outcomes across the divergent molecularly defined iCCA subtypes.
Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study
Authors: Smith Helen T. , Das Sugato , Fettiplace James , von Maltzahn Robyn , Troke Philip J.F. , McLaughlin Megan M. , Jones David E. , Kremer Andreas E. 
Published: February 2025

Background:
Pruritus affects up to 80% of patients with primary biliary cholangitis (PBC) and reduces health-related quality of life (HRQoL). GLIMMER (NCT02966834) was a randomized, placebo-controlled phase IIb study of linerixibat in patients with PBC and pruritus. Using patient-reported outcome data from GLIMMER, we characterize the impact of pruritus in PBC.

Methods:
To objectively assess HRQoL impact, EQ-5D-5L data from GLIMMER (0–1 scale; 0 = death, 1 = perfect health) were analyzed post-hoc across pruritus severities. Inter-relationships between pruritus severity (0–10 numerical rating scale [NRS]), depression (Beck Depression Inventory-II, post-hoc), and sleep interference (0–10 NRS) and their impact on HRQoL were explored.

Results:
In patients with PBC (n = 147), severe pruritus was associated with worse HRQoL. EQ-5D-5L scores were lower in those with severe pruritus (≥7–10 NRS) versus mild/moderate pruritus (mean [SD]: 0.49 [0.28] and 0.75 [0.17]/0.76 [0.17], respectively). Among patients with severe pruritus, 31% had severe depression, versus 9/3% with mild/moderate pruritus. Patients with both severe pruritus and depression had a mean EQ-5D-5L score of 0.30. In those with severe pruritus, 54% reported severe sleep interference. Improvements in pruritus were accompanied by stepwise improvements in EQ-5D-5L scores.

Conclusions:
This analysis of patients in the largest investigational trial of cholestatic pruritus to date shows a clear association between pruritus and impaired HRQoL. Patients with severe pruritus had HRQoL comparable to patients with severe Parkinson’s disease. Severe pruritus alongside depression was associated with extremely poor HRQoL, indicating the importance of evaluating itch and managing depression. Sleep interference appears to be a major cofactor for reduced HRQoL. For each 1-point improvement in NRS HRQoL improved, clinicians should offer appropriate and timely intervention.
Reduced short-term survival following liver transplant in patients with acute-on-chronic liver failure: Reevaluating OPTN data
Authors: Tanaka Tomohiro , Roberts Emily K. , Platt Jonathan 
Published: February 2025

Background:
Prior studies show severe acute-on-chronic liver failure (ACLF) at liver transplantation (LT) negatively impacts short-term, but not long-term, post-LT outcomes. However, not accounting for ACLF’s time-varying effect on the waitlist may underappreciate its dynamic nature. Moreover, excluding those who died or dropped off the waitlist raises concerns about selection bias.

Methods:
This US nationwide retrospective cohort study estimated the effect of severe ACLF (grade 3) (ACLF-3) on post-LT outcomes, including adult, first-time deceased donor LT candidates listed from June 2013 to May 2023. A marginal structural model (MSM) to address selection bias and time-varying exposure (ACLF-3) was applied, with extended Cox proportional hazard models using a Heaviside step function to assess the hazard of death after LT.

Results:
Among 31,267 eligible candidates for LT (baseline cohort), 11.3% (n = 3518) had ACLF-3 at listing; 13.6% (n = 4243) died or dropped out while on the LT waitlist. Of the 27,024 patients who received LT (transplanted cohort), 12.3% (n = 3333) had ACLF-3 at LT. ACLF-3 at LT (but not at waitlisting) was associated with a higher hazard of death, with the hazard ratio of 1.80 (95% CI: 1.09–2.97) within 1 year after LT but not thereafter. This marginal structural model effect size was 9% higher than conventional multivariable Cox proportional hazard models. Sensitivity analyses corroborated these findings.

Conclusions:
Compared to previous studies, ACLF-3 at LT in our marginal structural model was associated with a discernible increase in short-term mortality after transplant, presumably due to our addressing of selection bias, while long-term survival was similar to those without severe ACLF at LT. However, potential vulnerability to posttransplant complications warrants further investigation.
Implementing Strengths-Based, Positive Approaches Within Rheumatology Fellowship Training
Authors: Kumar Bharat , Feng Alick , Thoene Patricia Bruffey , Sigwarth Erica , Cobb Kristina , Swee Melissa , Suneja Manish 
Published: February 2025

Objective
Appreciative Inquiry (AIn) is a strengths-based organizational framework to promote engagement and change. It has shown promise in graduate medical education settings, but how, why, and for whom AIn may drive educational outcomes is underexplored. This realist evaluation examines the causal relationships between contexts, mechanisms, and outcomes at a rheumatology fellowship program in a large tertiary care center that implemented a set of AIn-based interventions. We generate recommendations for leaders in rheumatology fellowship programs on the implementation of AIn-based interventions.

Methods
The realist evaluation was conducted in 3 phases. In phase 1, a scoping review informed the initial program theory. In phase 2, realist interviews were conducted to identify and refine causal relationships between contexts, mechanisms, and outcomes, yielding a final program theory. In phase 3, the final program theory was utilized to generate recommendations for implementation.

Results
The final program theory identified 15 contexts, 10 mechanisms, and 10 outcomes along with 43 context-mechanism-outcome configurations. Through analysis of the final program theory, 3 recommendations were generated: (1) programs must first create permission structures for critical self-reflection through strengths-based feedback, (2) programs must consistently and synergistically apply AIn principles at multiple levels, and (3) programs can sustain AIn-based interventions through the deliberate co-design of virtuous cycles.

Conclusions
This realist evaluation has generated a theory on how AIn may be implemented into rheumatology fellowship programs to drive educational outcomes. Because of the intricate causal relationships, leaders are well-advised to tailor AIn-based interventions based on the context of their training programs.
The causal association of Cardiometabolic diseases and Sepsis-related outcomes: A Mendelian randomization and population study
Authors: Qi Mengmeng , Wei Jin , Zhang Meng , Jiao Chucheng , He Chang , Sui Liutao , Ma Shiyin , Mao Zhi , Pan Xudong , Zhu Xiaoyan 
Published: February 2025

Abstract

Objective
The causality between CMD and sepsis has remained largely unknown. To elucidate this, we conducted a Mendelian randomization (MR) and population study.

Methods
Firstly, we used univariable and multivariable MR analyses to investigate causal associations between CMD and sepsis-related outcomes. We obtained Genome-wide association study summary from both the MRC Integrative Epidemiology Unit and the FinnGen consortium. Subsequently, a two-step mediation MR analysis was performed to explore mediators. Afterward, we conducted an observational study using the MIMIC-IV database, in which multivariable logistic regression models were utilized to examine the relationship between CMD and sepsis-related outcomes.

Results
In the MR study, type 2 diabetes mellitus (T2DM) (OR = 1.058, 95%CI = 1.017-1.100, p = 0.005), obesity (OR = 1.113, 95%CI = 1.057-1.172, p < 0.001) and heart failure (HF) (OR = 1.178, 95% CI = 1.063-1.305, p = 0.002) were independently causally related to sepsis. Obesity (OR = 1.215, 95% CI = 1.027-1.437, p = 0.023) and HF (OR = 1.494, 95% CI = 1.080-2.065, p = 0.015) also showed independent causal associations with sepsis critical care admission. Mediation MR analysis identified 23 blood metabolites potentially causally linked to sepsis (p < 0.05), yet none mediated the relationship between CMD and sepsis. In the observational study, we found associations between sepsis and several conditions including T2DM, obesity, hypertension, stroke, HF, and hyperlipidemia after adjusting for confounding factors. Moreover, hypertension, stroke, HF, coronary artery disease, and hyperlipidemia were linked to sepsis critical care admission.

Conclusion
This study has, for the first time, revealed indicative evidence of a causal relationship between CMD and sepsis through observational and genetic evidence. Taken together, clinical attention to sepsis may be warranted among patients with CMD.
AKAP1-stabilized TIMP-4 attenuates Ang-II-induced oxidative stress and inflammation in vascular smooth muscle cells by inactivating the NF-κB signaling
Authors: Han Yongxin , Wu Xuejun , Shi Xin , Zhang Guoliang , Wang Xiaohan , Wang Chuanle , Zhou Hua 
Published: February 2025

Abstract

Background
Oxidative stress and inflammation are key factors contributing to the complex pathogenesis of abdominal aortic aneurysm (AAA). Tissue inhibitor of metalloproteinases-4 (TIMP-4) expression is reduced in AAA patients. In this study, we investigated the impact of TIMP-4 on the phenotype alterations induced by angiotensin II (Ang-II) in human vascular smooth muscle cells (VSMCs).

Methods
The expression profiling of TIMP-4 and A-kinase anchoring protein (AKAP1) in AAA samples was analyzed using the GSE7084 and GSE140947 datasets. Levels of TIMP-4 and AKAP1 in Ang-II-exposed VSMCs and AAA tissues and serum samples were detected. RNA immunoprecipitation (RIP) experiment and mRNA stability analysis were used to examine the interaction between AKAP1 and TIMP-4 mRNA. The impact of the AKAP1/TIMP-4 cascade on Ang-II-induced VSMC phenotype alterations was determined by evaluating cell viability, apoptosis, oxidative stress, and inflammation.

Results
TIMP-4 and AKAP1 levels were decreased in Ang-II-exposed VSMCs. Increased TIMP-4 expression protected VSMCs against Ang-II-evoked growth impairment in vitro. Moreover, TIMP-4 upregulation diminished Ang-II-evoked oxidative stress and inflammation in VSMCs. Mechanistically, RNA binding protein (RBP) AKAP1 stabilized TIMP-4 mRNA to elevate TIMP-4 expression. TIMP-4 reduction partially abrogated AKAP1-driven suppression on oxidative stress, inflammation, matrix metalloproteinase (MMP9) expression, and nuclear factor kappa B (NF-κB) pathway activation in Ang-II-exposed VSMCs. Additionally, TIMP-4 and AKAP1 levels were downregulated in AAA patients in their AAA tissues and serum samples. TIMP-4 and AKAP1 had good diagnostic values for AAA with high Area under the ROC curve (AUC).

Conclusion
Our study provides evidence for the role of the AKAP1/TIMP-4/NF-κB pathway in Ang-II-induced VSMC inflammation and oxidative stress.
Evaluation of Prognostic Risk Models Based on Age and Comorbidity in Septic Patients: Insights from Machine Learning and Traditional Methods in a Large-Scale, Multicenter, Retrospective Study
Authors: Liu Guoxiang , Shang Zhaoming , Ning Ning , Li Juan , Sun Wenwu , Fan Yiwen , Guo Yiran , Ye Jiawei , Zhou Wenzhen , Qian Junwei , Ma Chaoping , Zhang Jiyuan , Jiang Xiaofei , Zhu Changqin , Mao Enqiang , Chen Mingquan , Gao Chengjin 
Published: February 2025

ABSTRACT

Background
Age and comorbidity significantly impact the prognosis of septic patients and inform treatment decisions. To provide clinicians with effective tools for identifying high-risk patients, this study assesses the predictive value of the age-adjusted Charlson Comorbidity Index (ACCI) and its simplified version, the quick ACCI (qACCI), for mortality in septic patients.

Methods
This retrospective study included septic patients from four Chinese medical centers. The internal validation cohort comprised patients from Xinhua Hospital, Ruijin Hospital, and Huashan Hospital, while participants from Renji Hospital served as the external validation cohort. Machine learning models identified ACCI's feature importance. Restricted cubic spline regression and subgroup analysis assess the correlation between ACCI and mortality risk. The qACCI, derived from the ACCI components, was also evaluated for predictive reliability.

Results
A total of 3,287 septic patients were included: 2,974 in the internal cohort (mean age 67.96 years; 37.5% male) and 313 in the external cohort (mean age 67.90 years; 48.2% male). Machine learning models identified ACCI as a key predictor of in-hospital mortality. A linear correlation was confirmed between ACCI and risks of in-hospital, 30-day, and ICU mortality. Sensitivity analysis revealed consistent results across subgroups, demonstrating significantly higher mortality risks in the moderate- (HR 2.18, 95% CI 1.77-2.70) and high-ACCI (HR 3.72, 95% CI 2.99-4.65) groups compared to the low-ACCI group (HR 1, Reference). The ACCI achieved an AUC of 0.788 for in-hospital mortality, outperforming the SOFA in gastrointestinal (0.831 vs. 0.794) and central nervous system infections (0.803 vs. 0.739). The qACCI showed moderate predictive performance in both the internal (AUC, 0.734) and external (AUC, 0.758) cohorts.

Conclusions
As composite indicators of age and comorbidity, ACCI and qACCI provide valuable and reliable tools for clinicians to identify high-risk patients early.
Plasma Utilization Exacerbates Renal Cortex Inflammation in a Rodent Model of Hemorrhagic Shock and Resuscitation
Authors: Risinger William B. , Matheson Paul J. , Franklin Marisa E. , Hammond Victoria R. , Lakshmanan Jaganathan , Pushpakumar Sathnur , Li Yan , Volk Emily E. , Harbrecht Brian G. , Smith Jason W. 
Published: February 2025

ABSTRACT

Background and Hypothesis
Resuscitation strategies incorporating fresh frozen plasma have become the standard of care in the management of traumatic hemorrhagic shock. While plasma resuscitation has been shown to augment the circulation and reduce inflammation within the splanchnic and pulmonary circulation, its global effect on the kidney remains unknown. We hypothesized that plasma would improve intra-renal blood flow and reduce parenchymal inflammation when compared to resuscitation with lactated ringer’s.

Methods
Animals were randomized into four groups (n = 8): a) baseline, b) hemorrhagic shock alone, c) lactated ringer’s resuscitation, and d) fresh frozen plasma resuscitation. Multiplex immunoassays were used to evaluate cytokine and chemokine signaling within the renal cortex and immunohistochemistry was used to identify leukocyte infiltration. Doppler ultrasonography was used to evaluate changes in blood flow and maximum kidney diameter during hemorrhagic shock and resuscitation.

Results
While no difference in resistive index (surrogate for blood flow) within the renal artery or parenchymal vessels was observed between resuscitation strategies, plasma resulted in increased transverse kidney diameter. Plasma administration promoted cytokine/chemokine signaling, resulting in increased infiltration of leukocytes within the renal cortex when compared to lactated ringer’s.

Conclusion
Although the clinical benefits of plasma resuscitation mandate its utilization, our current findings highlight the complexities of plasma resuscitation. While the increase in renal diameter may be related to augmentation of the microcirculation, plasma resuscitation did not enhance macro-circulatory blood flow. Furthermore, plasma resuscitation appears to exacerbate inflammation within the renal cortex after hemorrhage. The downstream physiologic implications of plasma-induced inflammation warrant further exploration.
Assessing Job Satisfaction and Associated Factors Among Female Married Nurses: A Descriptive Cross-sectional Study
Authors: Amarasinghe M. G. N. M. , Erandika S. G. R. , Sandamali A. W. G. , Kalhari W. M. , Sriyani K.A. , De Silva D.K.M. 
Published: February 2025

ABSTRACTObjectiveTo assess the job satisfaction and personal, work-related, and socio-economic factors influencing the job satisfaction of married female nurses working at a District General Hospital in the Southern Province of Sri Lanka.Method and analysisA descriptive cross-sectional design was utilized to assess job satisfaction among married female nurses who worked in a District General Hospital in Sri Lanka. 278 nurses were selected using simple random sampling. Data collection was done with a self-report questionnaire that had demographic data and measurement of job satisfaction through the validated Nurse Job Satisfaction Scale (ESET). Descriptive statistics were applied to analyze the data using SPSS software version 26, t-tests, ANOVA, and linear regression. The threshold for significance was set as p<0.05.ResultsThe study found overall nurses’ job satisfaction was high (132.07±20.64) with the highest satisfaction in terms of professional recognition (3.9±0.66) and the lowest satisfaction in terms of recognition and remuneration (3.00±0.85). Age (p=0.031), unit of workplace (p=0.001), and educational level (p=0.010) were significantly associated with job satisfaction. However, multiple regression analysis could not find any significant predictors (p=0.190, R² = 0.024), which implies that job satisfaction is caused by many unmeasured variables.ConclusionThe study identified high overall job satisfaction among nurses, with professional recognition as the highest and remuneration as the lowest. Job satisfaction was associated with several factors including age, work unit, and education level. However, no strong predictors were found, which implies job satisfaction is driven by several unmeasured factors.STRENGTHS AND LIMITATIONSThe study used the reliable Nurse Job Satisfaction Scale (ESET) with strong internal consistency (Cronbach’s alpha = 0.92).The questionnaire covered multiple dimensions of job satisfaction, providing a holistic understanding of influencing factors.The study was conducted in a single hospital, restricting the applicability of findings to other regions or healthcare settings.Self-reported data may introduce bias due to social desirability or subjective perceptions.
Estimation of the global burden of autosomal recessive rare inborn errors of metabolism
Authors: Mondal Soumyajit , Goswami Kalyan , Dutta Atanu Kumar 
Published: February 2025

AbstractWhile many Rare Inborn Errors of Metabolism are treatable conditions their optimal diagnosis and treatment is a challenge for nations with low resources. Moreover, the population prevalence of these conditions is largely unknown. The availability of large genomic datasets brings the opportunity to estimate population carrier frequency of autosomal recessive IEMs. This would help to generate diseases burden statistics for better allocation of resources. In the current work we estimated the gene specific combined minor allele frequency of pathogenic variants from the gnomAD dataset for 235 genes associated with IEM phenotypes in OMIM. As per our estimation almost one third of the Global population is carrier for a pathogenic variant responsible for rare autosomal recessive inborn error of metabolism with the highest carrier frequency in the Ashkenazi Jews. Globally per thousand live births approximately five children are born with an ARIEM. European Finnish have the highest burden of nine out of 10,000 live births. With 25 million live births per year India is expected to have at least 8,025 newborns with an ARIEM. Since many of these diseases are treatable early newborn screening holds the key to ensure optimal management of these children.