bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Epigenetic Age and Everyday Discrimination With Longitudinal Trajectories of Chronic Health Conditions in Older Adults
Authors: Mutambudzi Miriam , Brown Maria T , Chen Nai-Wei 
Published: January 2024

Abstract
We investigated the strength of the association between baseline epigenetic age, everyday discrimination, and trajectories of chronic health conditions (CHCs) across 3 study waves, among adults 50 years of age and older. We used 2016–2020 data from the Health and Retirement Study (HRS). Data for the PhenoAge and DNAm GrimAge second-generation epigenetic clocks were from the 2016 HRS Venous Blood Study. CHC trajectories were constructed using latent class growth curve models. Multinomial logistic regression models assessed the strength of the association between accelerated epigenetic age, everyday discrimination, and the newly constructed CHC trajectories for participants with complete data (n = 2 893). In the fully adjusted model, accelerated PhenoAge (relative risk ratios [RRR] = 2.53, 95% confidence interval [95% CI] = 1.81, 3.55) and DNAm GrimAge (RRR = 2.79, 95% CI = 1.95, 4.00) were associated with classification into the high CHC trajectory class. Racial disparities were evident, with increased risk of classification into the high trajectory class for Black (PhenoAge: RRR = 1.69, 95% CI = 1.07, 2.68) and reduced risk for Hispanic (PhenoAge: RRR = 0.32, 95% CI = 0.16, 0.64; DNAm GrimAge: RRR = 0.34, 95% CI = 0.17, 0.68), relative to White participants. Everyday discrimination was associated with classification into the medium-high (RRR = 1.28, 95% CI = 1.00, 1.64) and high (RRR = 1.52, 95% CI = 1.07, 2.16) trajectory classes in models assessing DNAm GrimAge. More research is needed to better understand the longitudinal health outcomes of accelerated aging and adverse social exposures. Such research may provide insights into vulnerable adults who may need varied welfare supports earlier than the mandated chronological age for access to federal and state resources.
The ethics of engaged scholarship in a complex world
Authors: Avant Deborah , Barma Naazneen H , Demartino George F , Grabel Ilene 
Published: January 2024

Abstract
Social scientists must grapple with how to pursue knowledge about an uncertain and complex world. This challenge is accentuated when scholars wish to engage responsibly with policy-makers and the public in the interests of social betterment. In this article, we use the scholarly literature on uncertainty and complexity to examine how these issues complicate the practice of engaged scholarship. We ground our analysis in interviews with publicly engaged scholars on the ethical challenges they have faced and how they have navigated uncertainties and complexities in their applied work in peace and security. We identify four broad ethical dilemmas associated with publicly engaged scholarship and propose ways that scholars might begin to navigate these challenges. Our analysis urges greater acceptance of uncertainty and complexity in the social science community and associated epistemic humility in collective scholarship, pedagogy and public engagement.
What do we talk about when we talk about the ‘return’ of geopolitics?
Authors: Nickel Carsten 
Published: January 2024

Abstract
Western public and academic debates stipulate a ‘return’ of geopolitics, but confusion reigns over its substantial meaning. Recent scholarship has increasingly equated the term with the imperialist context in which ‘classical’ geopolitics first emerged, unmasking its spatial determinism but also losing sight of its geographic dimension. Today, geopolitics vaguely combines notions of systemic power competition in a neo-realist sense with constructivist ideas about spatially expansive authoritarianism. To address the resulting confusion, the article conducts interpretive process tracing and analyses how, throughout the twentieth century, classical geopolitics spatially substantiated systemic dynamics of shifting international power balances and broader political programmes such as imperialism, especially via competition on and over the Eurasian landmass. The article examines how, amid renewed competition with Russia and China over Eurasia—as well as doubts over the leanings of European and Asian middle powers in this contest—these traditional concerns reverberate even in contemporary western geopolitical debates characterized by vaguer definitions. This approach helps differentiate geopolitics from standard theories of International Relations and highlights how our unease with spatial arguments under liberal universalism drives today's largely metaphorical use of the term. American Cold War geopolitics, leveraged in defence of domestic democracy, emerges as a thought-provoking contrast.
Unstable environmental conditions constrain the fine-tune between opsin sensitivity and underwater light in an Amazon forest stream fish
Authors: de Almeida Borghezan Elio , da Silva Pires Tiago Henrique , Zuanon Jansen , Sugiura Hideki , Kohshima Shiro , Kishida Takushi 
Published: January 2024

Abstract
Visual adaptations can stem from variations in amino acid composition, chromophore utilization, and differential opsin gene expression levels, enabling individuals to adjust their light sensitivity to environmental lighting conditions. In stable environments, adaptations often involve amino acid substitutions, whereas in unstable conditions, differential gene expression may be a more relevant mechanism. Amazon forest streams present diverse underwater lighting conditions and experience short-term water colour fluctuations. In these environments, it is less likely for genetic and amino acid sequences to undergo modifications that tailor opsin proteins to the prevailing lighting conditions, particularly in species having several copies of the same gene. The sailfin tetra, Crenuchus spilurus, inhabits black and clear water Amazon forest streams. The long-wavelength sensitivity (LWS) is an important component for foraging and courtship. Here, we investigated LWS opsin genes in the sailfin tetra. Three copies of LWS1 and two copies of LWS2 genes were found. The maximum absorbance wavelength (λmax) estimated from the amino acid sequences of LWS1 genes exhibited variation among the different copies. In contrast, the copies of LWS2 genes showed identical expected λmax values. Although the amino acid positions affecting λmax varied among LWS genes, they remained consistent among populations living in different water colours. The relative expression levels of LWS genes differed between gene copies. While not formally tested, our results suggest that in fluctuating environments, visual adaptations may primarily stem from alterations in gene expression profiles and/or chromophore usage rather than precise genetic tuning of protein light sensitivity to environmental lighting conditions.
Ca2+ signatures in symbiosis: another level of dynamism for this key messenger
Authors: Dong Xiaoxu , Gifford Miriam L , Su Chao 
Published: January 2024

This article comments on:
Binci F, Offer E, Crosino A, Sciascia I, Kleine-Vehn J, Genre A, Giovannetti M, Navazio L. 2024. Spatially and temporally distinct Ca2+ changes in Lotus japonicus roots orient fungal-triggered signalling pathways towards symbiosis or immunity. Journal of Experimental Botany 75,605–619.
Clinical Relevance of Human Immunodeficiency Virus Low-level Viremia in the Dolutegravir era: Data From the Viral Load Cohort North-East Lesotho (VICONEL)
Authors: Kohler Maurus , Brown Jennifer A , Tschumi Nadine , Lerotholi Malebanye , Motaboli Lipontso , Mokete Moliehi , Chammartin Frédérique , Labhardt Niklaus D 
Published: January 2024

Abstract

Background
Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however.

Methods
We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (&lt;50 copies/mL) and low- and high-range LLV (50–199 and 200–999 copies/mL, respectively) with virological failure (≥1000 copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group.

Results
Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4–51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4–2.4 and dolutegravir: 2.1; 1.3–3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1–5.7 and 4.4; 2.4–7.9).

Conclusions
In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL.
Mutation of AtPME2, a pH-Dependent Pectin Methylesterase, Affects Cell Wall Structure and Hypocotyl Elongation
Authors: Hocq Ludivine , Habrylo Olivier , Sénéchal Fabien , Voxeur Aline , Pau-Roblot Corinne , Safran Josip , Fournet Françoise , Bassard Solène , Battu Virginie , Demailly Hervé , Tovar José C , Pilard Serge , Marcelo Paulo , Savary Brett J , Mercadante Davide , Njo Maria Fransiska , Beeckman Tom , Boudaoud Arezki , Gutierrez Laurent , Pelloux Jérôme , Lefebvre Valérie 
Published: January 2024

Abstract
Pectin methylesterases (PMEs) modify homogalacturonan’s chemistry and play a key role in regulating primary cell wall mechanical properties. Here, we report on Arabidopsis AtPME2, which we found to be highly expressed during lateral root emergence and dark-grown hypocotyl elongation. We showed that dark-grown hypocotyl elongation was reduced in knock-out mutant lines as compared to the control. The latter was related to the decreased total PME activity as well as increased stiffness of the cell wall in the apical part of the hypocotyl. To relate phenotypic analyses to the biochemical specificity of the enzyme, we produced the mature active enzyme using heterologous expression in Pichia pastoris and characterized it through the use of a generic plant PME antiserum. AtPME2 is more active at neutral compared to acidic pH, on pectins with a degree of 55–70% methylesterification. We further showed that the mode of action of AtPME2 can vary according to pH, from high processivity (at pH8) to low processivity (at pH5), and relate these observations to the differences in electrostatic potential of the protein. Our study brings insights into how the pH-dependent regulation by PME activity could affect the pectin structure and associated cell wall mechanical properties.
Beyond 2D: A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue
Authors: Yamada Hiroyuki , Makino Shin-ichi , Okunaga Issei , Miyake Takafumi , Yamamoto-Nonaka Kanae , Oliva Trejo Juan Alejandro , Tominaga Takahiro , Empitu Maulana A , Kadariswantiningsih Ika N , Kerever Aurelien , Komiya Akira , Ichikawa Tomohiko , Arikawa-Hirasawa Eri , Yanagita Motoko , Asanuma Katsuhiko 
Published: January 2024

Abstract
The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-μm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.
Multiple sclerosis and hypogonadism: is there a relationship?
Authors: Hammad Muhammed A M , Rush Adriana , Loeb Charles A , Banton Jasmin , Abou Chawareb Elia , Khanmammadova Narmina , Gevorkyan Rafael R , Barham David W , Yafi Faysal A , Jenkins Lawrence C 
Published: January 2024

Abstract

Introduction
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is widely recognized as a disease primarily affecting women. The relationship between MS and hypogonadism is complex and not fully understood, with recent evidence showing that hypogonadism may have a significant impact on the quality of life and disease progression of patients with MS.

Objectives
This review aims to provide an overview of the current knowledge regarding the relationship between MS and hypogonadism, including the mechanisms underlying this relationship; the effects of hypogonadism on patients with MS; and the potential benefits and drawbacks of testosterone replacement therapy for patients with MS and hypogonadism.

Methods
This scientific review analyzed 19 articles that investigated the potential relationship among MS, testosterone levels, and hypogonadism. The articles were published between November 2008 and March 2022 and were identified through a comprehensive search of the PubMed database. The search terms used included “multiple sclerosis,” “testosterone,” “hypogonadism,” and “MS and testosterone levels.”

Results
Of the 19 articles reviewed, 11 described a positive correlation between low testosterone levels and dysfunction within the hypothalamic-pituitary-gonadal axis in individuals with MS. These findings suggest that low testosterone levels may contribute to dysfunction within the hypothalamus-pituitary-gonadal axis, which plays a crucial role in regulating testosterone production. The results also showed a relationship between sexual dysfunction and low testosterone levels, as well as a positive correlative relationship between these factors.

Conclusion
The reviewed articles indicate a complex relationship among MS, testosterone levels, and the hypothalamic-pituitary-gonadal axis, with low testosterone levels potentially contributing to dysfunction in this axis and to sexual dysfunction. Further research is needed to better understand the effects of testosterone therapy on MS and sexual dysfunction in patients with MS.
Deep Learning and Likelihood Approaches for Viral Phylogeography Converge on the Same Answers Whether the Inference Model Is Right or Wrong
Authors: Thompson Ammon , Liebeskind Benjamin J , Scully Erik J , Landis Michael J 
Published: January 2024

Abstract
Analysis of phylogenetic trees has become an essential tool in epidemiology. Likelihood-based methods fit models to phylogenies to draw inferences about the phylodynamics and history of viral transmission. However, these methods are often computationally expensive, which limits the complexity and realism of phylodynamic models and makes them ill-suited for informing policy decisions in real-time during rapidly developing outbreaks. Likelihood-free methods using deep learning are pushing the boundaries of inference beyond these constraints. In this paper, we extend, compare, and contrast a recently developed deep learning method for likelihood-free inference from trees. We trained multiple deep neural networks using phylogenies from simulated outbreaks that spread among 5 locations and found they achieve close to the same levels of accuracy as Bayesian inference under the true simulation model. We compared robustness to model misspecification of a trained neural network to that of a Bayesian method. We found that both models had comparable performance, converging on similar biases. We also implemented a method of uncertainty quantification called conformalized quantile regression that we demonstrate has similar patterns of sensitivity to model misspecification as Bayesian highest posterior density (HPD) and greatly overlap with HPDs, but have lower precision (more conservative). Finally, we trained and tested a neural network against phylogeographic data from a recent study of the SARS-Cov-2 pandemic in Europe and obtained similar estimates of region-specific epidemiological parameters and the location of the common ancestor in Europe. Along with being as accurate and robust as likelihood-based methods, our trained neural networks are on average over 3 orders of magnitude faster after training. Our results support the notion that neural networks can be trained with simulated data to accurately mimic the good and bad statistical properties of the likelihood functions of generative phylogenetic models.
Crime and Gender Segregation: Evidence from the Bogota “Pico y Genero” Lockdown
Authors: Knight Brian , Ponce de Leon Maria Mercedes , Tribin Ana 
Published: January 2024

Abstract
The city of Bogota implemented a lockdown during the pandemic under which only men were allowed out on odd days and only women were allowed out on even days. Crime rates in Bogota increased, relative to a synthetic Bogota and relative to the pre-period, during this gender-based lockdown. Moreover, this increase is driven by more crime on men-only days and, more specifically, more robberies with male victims on men-only days. There is no evidence that higher crime rates on men-only days are offset by lower crime rates on women-only days. In fact, there is evidence of some increases in crimes with female victims on women-only days. In particular, there was an increase in robberies involving female victims on women-only days during the second half of the lockdown, when some restrictions were eased and more men, and thus more potential perpetrators, were on the streets. Overall, the gender-based lockdown, if anything, increased crime.
Patterns of work and retirement in a pension system with a flexible old-age retirement age: a register study of Finnish employees and self-employed persons born in 1949
Authors: Polvinen Anu , Riekhoff Aart-Jan , Nivalainen Satu , Kuivalainen Susan 
Published: January 2024

Abstract
The aims of this study were to explore patterns of work and retirement of Finnish employees and self-employed persons in a pension system with a flexible old-age retirement age and how income develops in these patterns. We used individual-level register data from Statistics Finland of the total Finnish birth cohort born in 1949. The cohort was 62–70 years old over the study period 2011–2019. Sequence and cluster analyses were used to identify typical trajectories of individuals’ transitions in and out of salaried work and self-employment and work in old-age retirement. Our analysis yielded a ten-cluster solution: four clusters were found for employees who did not continue working in retirement (62%), four clusters for those employees who continued working in retirement (26%), and two clusters for the self-employed (12%). The clusters differed by the timing of retirement. The results showed that employees who retired earlier on an old-age pension and who were not working afterwards had lower incomes. Their incomes also decreased after old-age retirement. Employees who worked for several years in retirement had higher incomes which remained stable between the ages of 62 and 70. We found two types of self-employed persons: those who continued working in retirement with high incomes and those who stopped working earlier and had lower incomes. The results indicate that inequalities between lower and higher income groups might become exacerbated in a flexible retirement system.
The first fossil record of an aquatic caecilian (Gymnophiona: Typhlonectidae)
Authors: Santos Rodolfo Otávio , Wilkinson Mark , do Couto Ribeiro Graziella , Carvalho Alberto B , Zaher Hussam 
Published: January 2024

Abstract
The lissamphibian clade Gymnophiona includes approximately 220 recognized modern species known by the English vernacular as caecilians and characterized by their elongated and annulated bodies, without girdles or limbs. Fossils of caecilians are particularly rare and mostly limited to isolated vertebrae. Until now, only four bona fide Gymnophionomorpha species have been named based on fossils. Only one of these (Apodops pricei) is a crown-group caecilian, but its affinities with modern caecilians are uncertain because the material is limited to one damaged vertebra and is currently lost. Here we describe a new genus and species of caecilian from the Oligocene Tremembé Formation, Brazil, based on a partially preserved fossil skeleton (including elements of the skull and postcranium) that is damaged but still partly articulated. We investigated the fossil caecilian’s anatomy using high-resolution microcomputed tomography, and then compared it to the osteology of modern species. We interpret the fossil as a member of Typhlonectidae, a family of caecilians well known for their aquatic and semi-aquatic lifestyles. This new record represents the first record for caecilians from the Oligocene and also the first fossil species confidently assigned to an extant caecilian family.