bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moral distress among maternal-fetal medicine fellows: a national survey study
Authors: Ding Jia Jennifer , Vu Thi , Stammler Suzanne , Murray Peter , Epstein Elizabeth , Cross Sarah N. 
Published: February 2025

Abstract

Background
Moral distress, or the inability to carry out what one believes to be ethically appropriate because of constraints or barriers, is understudied in obstetrics and gynecology. We sought to characterize moral distress among Maternal-Fetal Medicine (MFM) fellows using a standardized survey.

Methods
We disseminated a national anonymized survey study of MFM fellows electronically regarding moral distress using a validated questionnaire with supplemental questions pertaining to specific challenges within MFM clinical care. Multivariable linear regression modeling was used to examine the association between abortion restrictions, maternal mortality, and moral distress, controlling for demographic variables. Thematic analysis was performed for the free text responses elaborating upon moral distress and grouped by thematic elements. We hypothesized that training in states with more abortion restrictions and higher maternal mortality would be associated with higher moral distress scores.

Results
Among 245 total responses (61% response rate), 177 complete responses (44% complete response rate) were included for analysis. Most of our respondents identified as female (78.5%), White (71.8%), and training in urban programs (83.1%). 37.9% of respondents reported training in the Northeast, with the remainder of respondents evenly distributed across the United States. The mean score for the validated questions was 85.9 ± 48.8, with female gender identity associated with higher measures of moral distress on the validated portion of the questionnaire as compared to male gender identity (90.1 ± 49.2 vs. 70.4 ± 44.7, p < 0.05), whereas more advanced training was associated with higher measures of moral distress on the supplemental questions as compared to those less advanced in training (20.9 ± 11.8 vs. 28.5 ± 15.9 vs. 25.9 ± 15.6 for PGY-5 vs. PGY-6 vs. PGY-7 and PGY-8 combined, respectively, p < 0.05). After adjustment, higher measure of moral distress on the validated questionnaire was associated with training in states designated “Abortion restrictive” as compared to “Abortion most protective” (beta estimate 27.80 and p < 0.01). Of 34 free responses, 65% referred to limitations on abortion access and reproductive justice as causes of significant moral distress.

Conclusion
MFM fellows who identify as female reported higher measures of moral distress, as well as those training in states with more abortion restrictions. Among free text respondents, abortion restrictions underlie a significant proportion of moral distress.
Short- and long-term comparative effectiveness of nirmatrelvir/ritonavir and molnupiravir in asthma patients: a cohort study
Authors: Lin Guozhang , Wei Yuchen , Guo Zihao , Wang Huwen , Chan Kate Ching Ching , Chan Renee Wan Yi , Hung Chi Tim , Jiang Xiaoting , Li Conglu , Yam Carrie Ho Kwan , Chow Tsz Yu , Wang Yawen , Zhao Shi , Li Kehang , Yang Aimin , Mok Chris Ka Pun , Hui David S. C. , Yeoh Eng Kiong , Chong Ka Chun 
Published: February 2025

Abstract

Background
Few studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.

Methods
This is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication. Outcomes included acute and post-acute mortality, post-acute all-cause hospitalization, and cause-specific hospitalization.

Results
1,745 patients were eligible for this study, with a median follow-up time of 365 days (IQR: 335–365). Patients in the nirmatrelvir/ritonavir group had significantly lower risks of acute inpatient death (HR, 0·27 [95% CI, 0·12 to 0·59]; p = 0·0011), post-acute inpatient death (HR, 0·49 [95% CI, 0·28 to 0·85]; p = 0·011), all-cause hospitalization (HR, 0·72 [95% CI, 0·58 to 0·89]; p = 0·0020), and myocardial infarction (HR, 0·10 [95% CI, 0·01 to 0·92]; p = 0·042) than patients in the control group. The risk of all-cause hospitalization was significantly lower in the nirmatrelvir/ritonavir group compared to the molnupiravir group (HR, 0·65 [95% CI, 0·52 to 0·81]; p = 0·00012). Among patients who were prescribed medium-/ high-dose inhaled corticosteroids, the nirmatrelvir/ritonavir group had a lower hazard of asthma exacerbation than the molnupiravir group (HR, 0·58 [95% CI, 0·35 to 0·95]; p = 0.030).

Conclusion
Compared with molnupiravir, nirmatrelvir/ritonavir may offer more benefits in reducing the risk of post-acute sequelae of COVID-19 among asthma patients. In addition, the post-acute benefits of the antivirals were also demonstrated in patients with mild asthma, which have not been generally recommended in existing clinical management guidelines.
Comprehensive evaluation of diabetes subtypes in a European cohort reveals stronger differences of lifestyle, education and psychosocial parameters compared to metabolic or inflammatory factors
Authors: Rohmann Nathalie , Epe Johannes , Geisler Corinna , Schlicht Kristina , Türk Kathrin , Hartmann Katharina , Kruse Lucy , Koppenhagen Julia , Kohestani Ahmad Yusuf , Adam Tanja , Bang Corinna , Franke Andre , Schulte Dominik M. , Hollstein Tim , Laudes Matthias 
Published: February 2025

Abstract

Background
The traditional binary classification of diabetes into Type 1 and Type 2 fails to capture the heterogeneity among diabetes patients. This study aims to identify and characterize diabetes subtypes within the German FoCus cohort, using the ANDIS cohort's classification framework, and to explore subtype-specific variations in metabolic markers, gut microbiota, lifestyle, social factors, and comorbidities.

Methods
We utilized data from 416 participants (208 with diabetes and 208 matched metabolically healthy controls) from the German FoCus cohort. Participants were classified into five subtypes: severe autoimmune diabetes (SAID)-like, severe insulin-deficient diabetes (SIDD)-like, severe insulin-resistant diabetes (SIRD)-like, mild obesity-related diabetes (MOD)-like, and mild age-related diabetes (MARD)-like. Comprehensive characterization included anthropometric measurements, dietary and physical activity questionnaires, blood biomarker analysis, and gut microbiota profiling.

Results
The subtype distribution in the FoCus cohort accounted to SAID-like: 2.84%, SIDD-like: 30.81%, SIRD-like: 32.23%, MOD-like: 17.54%, MARD-like: 16.59%. Of interest, inflammatory markers (C-reactive protein (CRP) and Interleukin-6 (IL-6)) and glucagon-like peptide-1 (GLP-1) levels were similarly elevated across all subtypes compared to controls, indicating common aspects in Type 2 diabetes molecular pathology despite different clinical phenotypes. While the gut microbiota and dietary patterns only showed minor differences, smoking status, sleep duration, physical activity and psychological aspects varied significantly between the subtypes. In addition, we observed a lower educational status especially for SIDD-like and SIRD-like groups, which should be considered in establishing future diabetes-related patient education programs. In respect to the development of cardio-metabolic comorbidities, we observe not only significant differences in the presence of the diseases but also for their age-of onset, highlighting the need for early preventive intervention strategies.

Conclusions
The study validates the ANDIS classification framework's applicability not only at the time point of manifestation but also in cohorts with pre-existing diabetes. While we did not find major differences regarding the classical metabolic, microbial and nutritional parameters, we identified several significant associations with lifestyle factors. Our findings underscore the importance of personalized, subtype-specific therapies not solely focusing on anthropometric and laboratory markers but comprehensively addressing the patient’s own personality and situation of life.
A qualitative study of benzodiazepine/z-drug and opioid co-use patterns and overdose risk
Authors: Family Hannah E. , Vojt Gabriele , Poulter Hannah , Bailey Chris P. , Abdala Sheikh Ana Paula , Cavallo Damiana , Karimi Sara , Booth Nick , Da Silva Peter , Aitken Louise , Stewart Samantha , Hickman Matthew , Henderson Graeme , Scott Jenny , Kesten Joanna M. 
Published: February 2025

Abstract

Background
Co-use of benzodiazepines and/or ‘z-drugs’ along with opioids is linked to the rise in drug related deaths (DRD) in the UK. Understanding patterns of co-use could inform harm reduction strategies for reducing DRDs. This study explored how people co-use, including dosages, timings, methods of administration, use of other substances and desired effects sought.

Methods
Forty-eight semi-structured interviews across Glasgow in Scotland (n = 28), Bristol (n = 10) and Teesside (n = 10) in England with individuals who co-use illicit and/or prescribed opioids and benzodiazepines/z-drugs were conducted. Eighteen interviews were co-facilitated with qualitatively trained local peer researchers. Interviews were analysed using the Framework method.

Results
Six co-use patterns were generated: (1) co-use to aid sleep or come down, (2) curated co-use, opioid agonist therapy (OAT) only (3) morning and evening benzodiazepine doses with opioids throughout the day (4) co-use binges (5) co-use throughout the day, (6) benzodiazepine use throughout the day plus OAT. Patterns one to three reflected more controlled co-use with a focus on self-medicating to give confidence, manage anxiety, promote sleep and come-down from cocaine/ketamine. Patterns four to six involved greater poly-drug use, and less controlled co-use with a focus on seeking euphoria (“warm glow”, “gouching out”) or oblivion (to escape untreated mental health conditions and trauma). Patterns two, three, five and six involved daily co-use. People switched between patterns depending on available resources (e.g. finances) or changes to prescriptions (opioids or benzodiazepines). Near-fatal overdoses were reported by participants across all co-use patterns. Patterns four to six were conceptualised as presenting greater overdose risk due to less controlled co-use and more extensive polydrug use.

Conclusions
The patterns identified provide opportunities for future harm reduction strategies, tailoring advice to patterns of use, updated prescribing guidance and policies, and the need for better access to mental health care, for people who co-use benzodiazepines and opioids to reduce DRDs.
The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway
Authors: Mukherjee Srimoyee , Barua Atish , Wang Luyang , Tian Bin , Moore Claire L. 
Published: February 2025

Abstract

Background
Macrophages are required for development and tissue repair and protect against microbial attacks. In response to external signals, monocytes differentiate into macrophages, but our knowledge of changes that promote this transition at the level of mRNA processing, in particular mRNA polyadenylation, needs advancement if it is to inform new disease treatments. Here, we identify CFIm25, a well-documented regulator of poly(A) site choice, as a novel mediator of macrophage differentiation.

Methods
CFIm25 expression was analyzed in differentiating primary human monocytes and monocytic cell lines. Overexpression and depletion experiments were performed to assess CFIm25’s role in differentiation, NF-κB signaling, and alternative polyadenylation (APA). mRNA 3’ end-focused sequencing was conducted to identify changes in poly(A) site use of genes involved in macrophage differentiation and function. Cell cycle markers, NF-κB pathway components, and their targets were examined. The role of CFIm25 in NF-κB signaling was further evaluated through chemical inhibition and knockdown of pathway regulators.

Results
CFIm25 showed a striking increase upon macrophage differentiation, suggesting it promotes this process. Indeed, CFIm25 overexpression during differentiation amplified the acquisition of macrophage characteristics and caused an earlier slowing of the cell cycle, a hallmark of this transition, along with APA-mediated downregulation of cyclin D1. The NF-κB signaling pathway plays a major role in maturation of monocytes to macrophages, and the mRNAs of null, TBL1XR1, and NFKB1, all positive regulators of NF-κB signaling, underwent 3’UTR shortening, coupled with an increase in the corresponding proteins. CFIm25 overexpression also elevated phosphorylation of the NF-κB-p65 transcription activator, produced an earlier increase in the NF-κB targets p21, Bcl-XL, ICAM1 and TNF-α, and resulted in greater resistance to NF-κB chemical inhibition. Knockdown of Tables 2 and TBL1XR1 in CFIm25-overexpressing cells attenuated these effects, reinforcing the mechanistic link between CFIm25-regulated APA and NF-κB activation. Conversely, depletion of CFIm25 hindered differentiation and led to lengthening of NFKB1, TAB2, and TBL1XR1 3’ UTRs.

Conclusions
Our study establishes CFIm25 as a key mediator of macrophage differentiation that operates through a coordinated control of cell cycle progression and NF-κB signaling. This linkage of mRNA processing and immune cell function also expands our understanding of the role of alternative polyadenylation in regulating cell signaling.
Salidroside protects against myocardial infarction via activating MIF-mediated mitochondrial quality control
Authors: You Baiyang , Zhang Jie , Yang Chuyan , Dun Yaoshan , Qi Dake , Long Yuqiong , Cheng Jing , Lin Yuan , Zhou Nanjiang , Zeng Tanghao , Dong Jie , Liu Suixin 
Published: February 2025

Abstract

Background
Salidroside is a potential therapeutic agent for myocardial infarction (MI), exerting therapeutic effects on macrophage migration inhibitory factor (MIF)-regulated mitochondrial quality control. Our aim was to explore the mechanism through which the MIF pathway regulates salidroside-mediated resistance to hypoxia-induced cardiomyocyte apoptosis.

Methods
Ligation surgery of the left anterior descending branch of the coronary artery was employed to establish a myocardial infarction mouse model. Salidroside at low and high doses was administered to the mice for 4 weeks after the surgery. Cardiac function was evaluated via echocardiography. Morphological changes, apoptosis, and mitochondrial damage in the myocardium were examined. For the cell experiments, cardiomyocytes were treated with salidroside under oxygen‒glucose deprivation (OGD) conditions and were either treated with recombinant MIF (rMIF) or transfected with Mif-siRNA. Subsequently, mitochondrial quality control and apoptosis were assessed.

Results
Salidroside enhanced mitochondrial quality control in MI model mice, mitigated apoptosis and improved cardiac dysfunction. Transmission electron microscopy indicated that there were fewer damaged mitochondria in the salidroside-treated mice compared with the control mice. MIF and downstream mitochondrial quality control pathways were activated in the mice treated with salidroside. Consistently, the cell experiments demonstrated that salidroside and rMIF alleviated apoptosis, improved impaired mitochondrial quality control in OGD-induced cells and activated MIF signaling in OGD-induced cells. However, these effects of salidroside were partially blocked by Mif-siRNA transfection.

Conclusion
Salidroside alleviated myocardial apoptosis and ameliorated cardiac dysfunction in MI model mice through the MIF pathway and downstream mitochondrial quality control.
Clinical and economic burden of achondroplasia in the United States: results from a retrospective, observational study
Authors: Merchant Nadia , Alvir Jose , Ericksen Paulette Negron , Loftus Jane , Cara Jose Francisco , Slade Alison , Wajnrajch Michael P. , Baker Christine L. 
Published: February 2025

Abstract

Background
Achondroplasia, a disease characterized by disproportionate short stature and increased morbidity, affects daily function and quality of life over the lifetime of the individual. However, data are limited on its economic impact, especially related to healthcare resource utilization (HCRU) and associated costs. This study aimed to characterize the clinical and economic impact of achondroplasia in the US relative to matched non-achondroplasia controls stratified by pediatric and adult populations.

Methods
This retrospective study used data from the IQVIA PharMetrics Plus national claims database from January 2008 to December 2021. Individuals diagnosed with achondroplasia (index event) between July 2008 and December 2020 were matched on age and sex (1:2 ratio) to non-achondroplasia controls. General comorbidities were evaluated in the pediatric and adult populations. All-cause HCRU and direct medical costs were determined for the 12-month post-index period; out-of-pocket (OOP) costs were also determined. Study variables were analyzed using descriptive statistics.

Results
A total of 530 individuals with achondroplasia (47.7% pediatric and 52.3% adults) were matched with 1,060 controls. Individuals in the achondroplasia cohort had higher overall comorbidity burdens than controls. HCRU was higher in the achondroplasia cohort relative to controls, with outpatient visits the most frequently used resource. Inpatient visits were the primary driver of mean (SD) total costs, which were 14-fold higher than controls ($28,386 [$259,858] vs $2,031 [$5,418]) in pediatric individuals, and 4-fold higher in adults $21,579 [$58,817] vs $4,951 [$13,020]); prescriptions accounted for 4.7% and 7.4% of total costs in the pediatric and adult achondroplasia cohorts, respectively. The OOP costs were approximately 3-fold higher in both pediatric and adult individuals with achondroplasia relative to controls.

Conclusions
Individuals with achondroplasia are characterized by a higher comorbidity burden and substantially higher HCRU and related costs relative to matched controls. The results also suggest that despite high HCRU and costs, individuals with achondroplasia likely are not seen by providers early enough nor are they necessarily seen by appropriate specialists, indicating a need for improved care and disease management.
TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients
Authors: Vodnjov Nina , Cerar Andraž , Maver Aleš , Peterlin Borut , Writzl Karin 
Published: February 2025

Abstract

Background
Titin truncating variants (TTNtv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare TTNtv-s in the constitutively expressed exons of the A-band of the protein titin are associated with DCM according to the guidelines, however, studies in large cohorts of patients with DCM suggest that the region where TTNtv-s are associated with DCM is wider, extending at least into the I-band. The aim of this study was to describe the molecular pathology of TTNtv-s in Slovenian patients with cardiomyopathy and to clinically characterise the most recurrent TTNtv.

Results
We collected all TTNtv-s identified in patients with cardiomyopathy using next-generation sequencing genetic testing between 2010 and July 2024, resulting in 42 unique variants identified in 54 patients. The TTN:c.12478del variant, affecting not the A-band but the proximal I-band, specifically the cardiac-specific N2Bus region, was found to be the most recurrent variant, present in seven (11.6%) probands with DCM. Genetic characterisation revealed a probable founder origin of the variant. Clinical characterisation of these probands revealed a phenotype consistent with DCM and severely reduced left ventricular ejection fraction in all probands. Three (43%) of the probands had atrial fibrillation and/or non-sustained ventricular tachycardia. Based on literature reports and evidence supporting the pathogenicity of the TTN:c.12478del variant affecting the proximal I-band, we classified all rare TTNtv-s in constitutively expressed exons of the I-band as (likely) pathogenic. Therefore, 33 (78.6%) TTNtv-s were classified as (likely) pathogenic (13 in the I-band, affecting 19 probands and 20 in the A-band affecting 25 probands), meaning that TTNtv-s were identified in 44 genotype-positive Slovenian probands with DCM, explaining 73.3% of the molecular pathology of DCM.

Conclusion
We report an almost threefold higher diagnostic yield of TTNtv-s in probands with DCM compared to previously reported findings in cohorts of patients with DCM from other populations. We also highlight the need for screening for rare TTNtv-s in the constitutively expressed exons of the I-band and for TTN:c.12478del in patients with DCM in this geographical region.
Methods for assessing exercise fidelity in unsupervised home-based cardiovascular rehabilitation: a scoping review
Authors: Jarallah Mohammad , Withers Thomas M , Rosewilliam Sheeba , Stathi Afroditi , Greaves Colin J 
Published: February 2025

Abstract

Background
Home-based cardiac rehabilitation is increasingly popular for patients with cardiovascular diseases. However, this mode of rehabilitation involves unsupervised exercise, making it challenging to assess, correct, and monitor exercise fidelity (the extent to which the patient performs the exercise intended by the intervention provider). This review aimed to identify the range, validity, and acceptability of measures for assessing exercise fidelity in unsupervised, home-based cardiovascular rehabilitation.

Methods
We searched PubMed, Embase, CINAHL, Medline, and PsycINFO for studies published between 2000 and 2024 to identify observational studies, trials, and protocols published in English with a home-based cardiovascular rehabilitation intervention and at least one measure of exercise fidelity (e.g., adherence to the intended frequency, intensity, time, type, safety, progression/regression). Two reviewers selected eligible studies and extracted data, including study characteristics, exercise components, adherence definition, adherence measures, and data on measurement validity or acceptability. We conducted a narrative synthesis using a comprehensive definition of exercise fidelity, which evolved as the analysis progressed.

Results
Forty-six articles describing 41 studies were included. Exercise intensity was the most commonly measured fidelity component (38/41 studies), followed by exercise frequency (32/41 studies). Exercise intensity was mostly assessed by wearable devices (28/41 studies). Frequency of exercise was most commonly assessed subjectively using a self-reported exercise log or diary, but also (objectively) using wearable devices. Exercise quantity was most commonly assessed (in terms of time or duration) by self-reported exercise logs, diaries and wearable devices, or (in terms of steps or distance) mostly by wearable devices (pedometers, other step activity monitors). Safety was only assessed in 12/41 studies. No studies assessed progression or regression of exercise, quality of exercise (accuracy of movement) or the appropriateness of progression or regression.

Conclusions
Most studies to date have conceptualised exercise fidelity or adherence narrowly, ignoring important elements of the initial exercise prescription and many have relied on non-validated self-report measures. We present a comprehensive framework for assessing exercise fidelity, which may be useful for designing more robust assessments of exercise fidelity in home-based rehabilitation programmes.