bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe hypophosphatemia induced by excessive production of FGF23 in acute hepatitis: from bedside to bench
Authors: Hamroun Aghiles , Boukrout Nihad , Cauffiez Christelle , Fellah Sandy , Van der Hauwaert Cynthia , Pottier Nicolas , Mentaverri Romuald , Zaworski Jeremy , Gnemmi Viviane , Gibier Jean-Baptiste , Letavernier Emmanuel , Louvet Alexandre , Provôt François , Lenain Rémi , Maanaoui Mehdi , Glowacki François , Lionet Arnaud 
Published: October 2024

ABSTRACT

Background
Although hepatic production of FGF23 has been suggested in chronic settings, there are no data indicating hypophosphatemia resulting from acute hepatic FGF23 production. Based on two clinical observations of profound hypophosphatemia in the setting of acute hepatitis, our study investigates the hypothesis of acute FGF23 liver expression.

Methods
Retrospective analyses were conducted to estimate FGF23 liver expression both qualitatively (in situ hybridization) and quantitatively (relative FGF23 gene expression and protein production) on histological specimens of human and murine acute hepatitis livers, compared with controls of hepatic fibrosis or healthy liver.

Results
The index clinical case involves acute alcoholic hepatitis complicated by profound hypophosphatemia due to phosphate diabetes, revealing a major production of both FGF23 C-terminal fraction (cFGF23) and bio-intact form (iFGF23, 39 751 RU/mL, N: 21–91; and 228.6 pg/mL, N: 22.7–93.1, respectively). A second case of acute hepatitis related to erythrocytic protoporphyria also exhibited comparable abnormalities. In both cases, no other cause of renal phosphate wasting was identified, and the hydroelectrolytic disorders disappeared in parallel with normalization of the liver balance and FGF23 levels. Histological data of acute hepatitis compared with cirrhosis and healthy liver confirmed our hypothesis of hepatic FGF23 overproduction. Furthermore, mouse models showed a significant increase in FGF23 mRNA relative liver expression in acute hepatitis and a moderate increase in cirrhosis, compared with healthy liver (respectively 60.55 ± 16.75 and 3.70 ± 0.87 vs 1.00 ± 0.65, both P &lt; .05). These findings were also confirmed at the protein level.

Conclusion
This translational study raises the hypothesis of renal phosphate wasting induced by excessive hepatic production of FGF23 in case of acute hepatitis.
Evolutionary Modes of wtf Meiotic Driver Genes in Schizosaccharomyces pombe
Authors: Xu Yan-Hui , Suo Fang , Zhang Xiao-Ran , Du Tong-Yang , Hua Yu , Jia Guo-Song , Zheng Jin-Xin , Du Li-Lin 
Published: October 2024

Abstract
Killer meiotic drivers are a class of selfish genetic elements that bias inheritance in their favor by destroying meiotic progeny that do not carry them. How killer meiotic drivers evolve is not well understood. In the fission yeast, Schizosaccharomyces pombe, the largest gene family, known as the wtf genes, is a killer meiotic driver family that causes intraspecific hybrid sterility. Here, we investigate how wtf genes evolve using long-read–based genome assemblies of 31 distinct S. pombe natural isolates, which encompass the known genetic diversity of S. pombe. Our analysis, involving nearly 1,000 wtf genes in these isolates, yields a comprehensive portrayal of the intraspecific diversity of wtf genes. Leveraging single-nucleotide polymorphisms in adjacent unique sequences, we pinpoint wtf gene-containing loci that have recently undergone gene conversion events and infer their ancestral state. These events include the revival of wtf pseudogenes, lending support to the notion that gene conversion plays a role in preserving this gene family from extinction. Moreover, our investigation reveals that solo long terminal repeats of retrotransposons, frequently found near wtf genes, can act as recombination arms, influencing the upstream regulatory sequences of wtf genes. Additionally, our exploration of the outer boundaries of wtf genes uncovers a previously unrecognized type of directly oriented repeats flanking wtf genes. These repeats may have facilitated the early expansion of the wtf gene family in S. pombe. Our findings enhance the understanding of the mechanisms influencing the evolution of this killer meiotic driver gene family.
Loneliness Trajectories in U.S. Military Veterans: A 3-Year Longitudinal Study of Risk and Protective Factors
Authors: Ong Anthony D , Cintron Dakota W , Rottenberg Jonathan , Panaite Vanessa , Fischer Ian C , Na Peter J , Jeste Dilip V , Pietrzak Robert H 
Published: October 2024

Abstract

Objectives
Loneliness is a significant public health concern associated with adverse mental and physical health outcomes in older adults. This study examined the nature and correlates of predominant loneliness trajectories in a nationally representative sample of older U.S. military veterans.

Methods
Participants included 2,441 veterans (mean age = 63, 8% female, 80% White) from the National Health and Resilience in Veterans Study, a 3-year longitudinal cohort study. Growth mixture modeling (GMM) was used to identify distinct trajectory classes of loneliness based on self-reported ratings. Multinomial logistic 3-step regression analyses examined potential psychosocial risk and protective factors associated with loneliness trajectories.

Results
GMM revealed 3 distinct loneliness trajectories: low-decreasing loneliness (61.2%), moderate-increasing loneliness (31.6%), and high-increasing loneliness (7.2%). Being married/partnered and perceiving a greater purpose in life emerged as protective factors against elevated levels of loneliness. Worse cognitive functioning was a risk factor for the moderate-increasing loneliness trajectory, while greater psychological distress and more adverse childhood experiences were risk factors for the high-increasing loneliness trajectory.

Discussion
Nearly 40% of older U.S. veterans exhibited trajectories characterized by moderate to high levels of loneliness, with both groups showing increases over time. Targeted interventions that promote social connectedness, enhance purpose in life, and address mental health concerns and early life adversities may help mitigate the negative health consequences associated with chronic loneliness in this vulnerable population.
Gender Selectively Mediates the Association Between Sex and Memory in Cognitively Normal Older Adults
Authors: Bohn Linzy , Han Astrid Y , McFall G Peggy , Drouin Shannon M , Pettersen Jacqueline A , Rajah M Natasha , Einstein Gillian , Anstey Kaarin J , Dixon Roger A 
Published: October 2024

Abstract

Background and Objectives
Sex and gender are important topics of increasing interest in aging and dementia research. Few studies have jointly examined sex (as a biological attribute) and gender (as a sociocultural and behavioral characteristic) within a single study. We explored a novel data mining approach to include both sex and gender as potentially related influences in memory aging research.

Research Design and Methods
Participants were 746 cognitively normal older adults from the Victoria Longitudinal Study. First, we adapted the Gender Outcomes INternational Group: To Further Well-being Development (GOING-FWD) framework—which is informed by gender dimensions of the Women’s Health Research Network—to identify, extract, and operationalize gender-related variables in the database. Second, we applied principal component analysis (PCA) to a pool of potential gender variables for creating empirically derived gender-related components. Third, we verified the expected pattern of sex differences in memory performance and evaluated each gender-related component as a potential mediator of the observed sex–memory association.

Results
Systematic data mining produced a roster of potential gender-related variables, 56 of which corresponded to gender dimensions represented in the GOING-FWD framework. The PCA revealed 6 gender-related components (n indicators = 37): Manual Non-Routine Household Tasks, Subjective Memory Beliefs, Leisure Free Time, Social and Routine Household Management, Health Perceptions and Practices, and Brain Games. We observed sex differences in latent memory performance whereby females outperformed males. Sex differences in memory performance were mediated by Manual Non-Routine Household Tasks, Social and Routine Household Management, and Brain Games. Follow-up analyses showed that education also mediated the sex–memory association.

Discussion and Implications
We show that (i) data mining can identify and operationalize gender-related variables in archival aging and dementia databases, (ii) these variables can be examined for associations with sex, and (iii) sex differences in memory performance are mediated by selected facets of gender.
What Characteristics Modify the Relation of Neighborhood Walkability and Walking Behavior in Older Adults?
Authors: Rosso Andrea L , Moored Kyle D , Harding Alyson B , Studenski Stephanie , Bear Todd , Acharya Geeta , Rosano Caterina 
Published: October 2024

Abstract

Background and Objectives
Neighborhood walkability can influence walking behaviors in older adults. However, its associations of walkability with walking may differ by demographic, socioeconomic, health, social, and residential characteristics due to factors such as increased vulnerability to environmental factors or increased resilience.

Research Design and Methods
In a sample of older adults (n = 493, median age = 82 [range 78–89], 56% female, 31% Black), a walkability index was derived from audits of Google Street View images of participants’ immediate neighborhoods. Walking was self-reported in the past week. Effect modifiers by demographic (age, race, gender, marital status), socioeconomic (education, income), health (gait speed, falls, knee pain, depressive symptoms, cognitive status, perceived energy), social (driving status, social engagement), and residential/neighborhood (residence type, neighborhood socioeconomic status [SES], population density) characteristics were assessed by interaction terms in logistic regression models, adjusted for gender, race, gait speed, prior falls, high depressive symptoms, currently driving, and cognitive status. When effect modification was suggested (p for interaction &lt;.1), adjusted analyses of walkability with walking stratified on the effect modifier were conducted.

Results
In this sample, 59% walked in the past week and greater walkability was associated with greater odds of walking (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.01–1.34). This association (p for interaction range 0.002–0.07) was present for those who were not currently married (OR = 1.35, 95% CI: 1.17–1.56), who reported knee pain (OR = 1.40, 95% CI: 1.14–1.72) or high depressive symptoms (OR = 1.30, 95% CI: 1.06–1.60), or who had declining cognitive function (OR = 1.30, 95% CI: 1.09–1.55).

Discussion and Implications
High walkability may influence physical activity, particularly for those with vulnerabilities related to social, pain, and brain health characteristics. These results should inform neighborhood planning and targeted interventions for vulnerable older adults.
Home Health Care and Place of Death in Medicare Beneficiaries With and Without Dementia
Authors: Kim Hyosin (Dawn) , Duberstein Paul R , Zafar Anum , Wu Bei , Lin Haiqun , Jarrín Olga F 
Published: October 2024

Abstract

Background and Objectives
Home health care supports patient goals for aging in place. Our objective was to determine if home health care use in the last 3 years of life reduces the risk of inpatient death without hospice.

Research Design and Methods
We analyzed the characteristics of 2,065,300 Medicare beneficiaries who died in 2019 and conducted multinomial logistic regression analyses to evaluate the association between the use and timing of home health care, dementia diagnosis, and place of death.

Results
Receiving any home health care in the last 3 years of life was associated with a lower probability of inpatient death without hospice (Pr 23.3% vs 31.5%, p &lt; .001), and this effect was stronger when home health care began prior to versus during the last year of life (Pr 22.5% vs 24.3%, p &lt; .001). Among all decedents, the probability of death at home with hospice compared to inpatient death with hospice was greater when any home health care was used (Pr 46.0% vs 36.5%, p &lt; .001), and this association was strongest among beneficiaries with dementia who started home health care at least 1 year prior to death (Pr 55.6%, p &lt; .001).

Discussion and Implications
Use of home health care during the last 3 years of life was associated with reduced rates of inpatient death without hospice, and increased rates of home death with hospice. Increasing affordable access to home health care can positively affect end-of-life care outcomes for older Americans and their family caregivers, especially those with dementia.
Deepdefense: annotation of immune systems in prokaryotes using deep learning
Authors: Hauns Sven , Alkhnbashi Omer S , Backofen Rolf 
Published: October 2024

Abstract

Background
Due to a constant evolutionary arms race, archaea and bacteria have evolved an abundance and diversity of immune responses to protect themselves against phages. Since the discovery and application of CRISPR-Cas adaptive immune systems, numerous novel candidates for immune systems have been identified. Previous approaches to identifying these new immune systems rely on hidden Markov model (HMM)–based homolog searches or use labor-intensive and costly wet-lab experiments. To aid in finding and classifying immune systems genomes, we use machine learning to classify already known immune system proteins and discover potential candidates in the genome. Neural networks have shown promising results in classifying and predicting protein functionality in recent years. However, these methods often operate under the closed-world assumption, where it is presumed that all potential outcomes or classes are already known and included in the training dataset. This assumption does not always hold true in real-world scenarios, such as in genomics, where new samples can emerge that were not previously accounted for in the training phase.

Results
In this work, we explore neural networks for immune protein classification, deal with different methods for rejecting unrelated proteins in a genome-wide search, and establish a benchmark. Then, we optimize our approach for accuracy. Based on this, we develop an algorithm called Deepdefense to predict immune cassette classes based on a genome. This design facilitates the differentiation between immune system–related and unrelated proteins by analyzing variations in model-predicted confidence values, aiding in the identification of both known and potentially novel immune system proteins. Finally, we test our approach for detecting immune systems in the genome against an HMM-based method.

Conclusions
Deepdefense can automatically detect genes and define cassette annotations and classifications using 2 model classifications. This is achieved by creating an optimized deep learning model to annotate immune systems, in combination with calibration methods, and a second model to enable the scanning of an entire genome.
Regional Approach to Boosting Local Pharmaceutical Manufacturing Capacity: A Critique of the East African Community Pharmaceutical Manufacturing Plan of Action
Authors: Olatunji Olugbenga Ajani 
Published: October 2024

Abstract
The East African Community (EAC) has had a chequered history, evidenced by multiple changes of names and objectives, and a hiatus lasting more than two decades following a collapse in 1977. It was resuscitated in 1999 by its founding members (Uganda, Tanzania, and Kenya). That four other partner states have since joined is a clear testament to the effectiveness of its overhaul. The community is regulated by the EAC Treaty which promotes collective actions in several areas of mutual interests. Plagued by an ongoing access-to-medicines conundrum, EAC governments have considered collective action as recommended by the Treaty. This effort began around the 2010s when policy measures aimed at exploring collective solutions were adopted with a view to replacing reliance on importation and external drug donation with a gradually developed regional pharmaceutical production capacity. EAC policies such as the Policy/Protocol on TRIPS Flexibilities, the Medicines Registration Harmonisation Initiative, the Draft Anti-Counterfeit Policy, and a Pharmaceutical Manufacturing Plan of Action (EAC PMP) have since been developed to achieve this ambitious goal. Using both doctrinal and empirical (semi-structured interviews) methods, this paper examines the EAC PMP – the ‘be all’ of the policies. The priority actions outlined under the plan’s six pillars and presented as a bankable pathway to self-sufficiency in pharmaceutical production are critiqued. The paper finds considerable implementation of the drug harmonisation theme, while the others (leveraging TRIPS flexibilities, ensuring coherence, and boosting research and development and technology transfer) remain largely unimplemented.
Collective Bargaining for the ‘New’ Working Class: Putting ‘Personal Work Relations’ to Work for Street Vendors
Authors: Von Broembsen Marlese 
Published: October 2024

Abstract
Robert Hale’s famous proposition is that the propertyless man needs to eat and in order to eat, he exchanges his labour for access to property. Indeed, labour law is constituted by these property relations. Historically, most of the workforce (in the global North) has accessed property for livelihood purposes through an employment contract. However, in developing countries, most of the workforce is structurally unable to access property for livelihood purposes by means of an employment contract. These worker-citizens nevertheless need access to property to eat; street vendors need access to public space to trade. The question is whether the scope of labour law, particularly the institution of collective bargaining, can expand to include informal self-employed workers? The article discusses the capability, regulatory, human rights and personal work relations theories; it shows that Freedland and Kountouris’ theory of ‘labour law as personal work relations’ could incorporate informal self-employed workers and illustrates how it might be operationalized to realise collective bargaining laws for street vendors. Informal self-employed workers challenge labour law to examine its assumptions of how property relations are constituted; and to re-theorise property relations to account for workers accessing property by means of an employment contract as well as accessing property based on worker-citizens making rights-based claims.
Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia
Authors: Williams Derek J , Gautam Shruti , Creech C Buddy , Jimenez Natalia , Anderson Evan J , Bosinger Steven E , Grimes Tyler , Arnold Sandra R , McCullers Jonathan A , Goll Johannes , Edwards Kathryn M , Ramilo Octavio ,   for the 16-0036 Study Team, Anderson Julie , Johnson Gayle , Phillips Shanda , Sokolow Katherine , Yoder Sandra , Myers Deborah , Adkisson Robert , Jain Seema , Ampofo Krow , Pavia Andy , Cockcroft Jody , Kleinhenz Dean , Huston Hannah , Rouphael Nadine , McCullough Michele Paine 
Published: October 2024

Abstract

Background
Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches.

Methods
Using whole blood RNA sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed (DE) genes that best identified children according to detected microbial pathogens (viral only vs bacterial only and typical vs atypical bacterial [with or without [±] viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe).

Results
Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial detections (± viral co-detections), and 26 (12%) had atypical bacterial detections (± viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (± viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including 4 genes also identified in the viral-only versus bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and 4 genes from the typical versus atypical bacterial model (PRSS23, IFI27, OLFM4, ABO).

Conclusions
We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.
Causal Evidence for Theories of Contagious Civil Unrest
Authors: Fyfe Rebekah , Desmarais Bruce 
Published: October 2024

Abstract
Many types of civil unrest, including protest, violent conflict, and rebellion, have been found to be subject to both inter- and intra-state contagion. These spillover effects are conventionally tested through the application of parametric structural models that are estimated using observational data. Drawing on research in methods for network analysis, we note important challenges in conducting causal inference on contagion effects in observational data. We review a recently developed non-parametric test—the “split-halves test”—that is robust to confounding and apply the test to replication data from several recent studies in which researchers tested for contagion in civil unrest. We find that about half the time findings in the published literature fail to replicate with the split-halves test. Across ten total replications, we do not see strong patterns in terms of which results do and do not replicate. We do, however, find evidence for general contagion in six of the replications, indicating that contagion is a prevalent phenomenon in civil unrest. As such, we recommend that researchers (1) use the split-halves test as a general-purpose robustness check for parametric models of contagion in the study of civil unrest, and (2) consider modeling contagion in research on civil unrest.
Preferential Trade Agreements and Leaders’ Business Experience
Authors: Nones Nicola 
Published: October 2024

Abstract
Many theories attempt to explain the determinants of preferential trade agreements (PTAs) and their design. Existing accounts, however, focus almost exclusively on structural or domestic factors and ignore individual leaders. In this paper, I develop and test novel theoretical claims regarding executive leaders’ prior career in business and their trade cooperation policy once in office. I construct a new dataset on the heads of the executive’s business managerial experience and test my main claims in a time-series-cross-sectional setting covering 185 countries from 1948 to 2009. To establish causality, I rely on an instrumental variable strategy and leverage exogenous transitions due to sudden deaths or terminal illness in office. The results show that businesspersons-turned-politicians are more likely to enter PTAs and are more likely to sign deeper PTAs. The relationship is further investigated in an illustrative case study of the 1988—Canada trade deal. The substantive effect of business experience is comparable to that of established factors in the literature, such as regime type, and is robust to numerous tests, specifications, subsamples, and measurements of business experience.