bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five-leaf Generalizations of the D-statistic Reveal the Directionality of Admixture
Authors: Leppälä Kalle , da Silva Coelho Flavio Augusto , Richter Michaela , Albert Victor A , Lindqvist Charlotte 
Published: September 2024

Abstract
Over the past 15 years, the D-statistic, a four-taxon test for organismal admixture (hybridization, or introgression) which incorporates single nucleotide polymorphism data with allelic patterns ABBA and BABA, has seen considerable use. This statistic seeks to discern significant deviation from either a given species tree assumption, or from the balanced incomplete lineage sorting that could otherwise defy this species tree. However, while the D-statistic can successfully discriminate admixture from incomplete lineage sorting, it is not a simple matter to determine the directionality of admixture using only four-leaf tree models. As such, methods have been developed that use five leaves to evaluate admixture. Among these, the DFOIL method (“FOIL”, a mnemonic for “First-Outer-Inner-Last”), which tests allelic patterns on the “symmetric” tree S=(((1,2),(3,4)),5), succeeds in finding admixture direction for many five-taxon examples. However, DFOIL does not make full use of all symmetry, nor can DFOIL function properly when ancient samples are included because of the reliance on singleton patterns (such as BAAAA and ABAAA). Here, we take inspiration from DFOIL to develop a new and completely general family of five-leaf admixture tests, dubbed Δ-statistics, that can either incorporate or exclude the singleton allelic patterns depending on individual taxon and age sampling choices. We describe two new shapes that are also fully testable, namely the “asymmetric” tree A=((((1,2),3),4),5) and the “quasisymmetric” tree Q=(((1,2),3),(4,5)), which can considerably supplement the “symmetric” S=(((1,2),(3,4)),5) model used by DFOIL. We demonstrate the consistency of Δ-statistics under various simulated scenarios, and provide empirical examples using data from black, brown and polar bears, the latter also including two ancient polar bear samples from previous studies. Recently, DFOIL and one of these ancient samples was used to argue for a dominant polar bear → brown bear introgression direction. However, we find, using both this ancient polar bear and our own, that by far the strongest signal using both DFOIL and Δ-statistics on tree S is actually bidirectional gene flow of indistinguishable direction. Further experiments on trees A and Q instead highlight what were likely two phases of admixture: one with stronger brown bear → polar bear introgression in ancient times, and a more recent phase with predominant polar bear → brown bear directionality.
Elderly-onset inflammatory myopathy associated with Sjögren’s syndrome following SARS-CoV-2 vaccination
Authors: Komori Yuta , Kobayashi Satomi , Hatano Keiko , Saito Yuko , Arai Tomio , Kubo Kanae 
Published: September 2024

ABSTRACT
As vaccination against SARS-CoV-2 has progressed, various autoimmune diseases, including inflammatory myopathies, have been reported to develop after vaccination. Sjögren’s syndrome (SS) sometimes presents as extra-glandular manifestations including inflammatory myopathy. In this report, we describe a case of inflammatory myopathy associated with SS that occurred in an atypically elderly patient after receiving the first dose of the SARS-CoV-2 mRNA vaccine (BNT162b2). The inflammatory myopathy was pathologically classified into non-specific myositis and characterised by predominant infiltration of the B cell lineage in this case. Combined treatment with glucocorticoid, intravenous immunoglobulin, and immunosuppressant resulted in an improvement in swallowing function and muscle strength. While we recognise the efficacy and safety of SARS-CoV-2 vaccines, we also emphasise the importance of recognising that individuals with an immunogenetic predisposition such as positivity of anti SS-A antibody may show disease activity including inflammatory myopathy following vaccination in SS, even at an atypically old age.
The Added Value of Data Protection within the Framework of Digital Constitutionalism in Europe
Authors: De Hert Paul , Cocito Cristina 
Published: September 2024

Abstract
This chapter discusses the contribution(s) of data protection law within the framework of digital constitutionalism in the European Union. The rise of the welfare state and of the surveillance state has challenged the focus of modern constitutionalism on limiting and balancing the power of the three branches of states. Because of increasing new power players and their agendas within state governance, the project of constitutionalism has progressively shifted from one primarily focused on setting the constitutional limits of power to one also concerned with guiding and channelling legitimate powers. Rights of a due process nature enshrined in the EU Charter of Fundamental Rights, such as the right to data protection, are emblematic of this development. These legal tools shifted the constitutional attention to procedures of power implementation and decision-making. This chapter examines the added value of the right to data protection and the role of independent data protection authorities within the context of digital constitutionalism in Europe. The due process nature of data protection supports the objectives of constitutionalism in the digital. Moreover, by applying both to public and private actors, data protection contributes to move beyond the public-private divide in line with the precepts of digital constitutionalism. As independent oversight institutions, data protection authorities offer another system of check and balance and layer of accountability in addition to traditional ones.
Implicit commitments of instrumental acceptance: A case study
Authors: Castaldo Luca , Głowacki Maciej 
Published: September 2024

Abstract
When accepting an axiomatic theory S, we are implicitly committed to various statements that are independent of its axioms. Examples of such implicit commitments include consistency statements and reflection principles for S. While foundational acceptance has received considerable attention in this context, the study of implicit commitments triggered by weaker notions remains underdeveloped. This article extends the analysis investigating implicit commitments inherent in instrumental acceptance, comparing them with the implicit commitments involved in foundational acceptance. Concentrating on Reinhardt’s instrumentalism vis-à-vis Kripke–Feferman theory of truth as a case study, we present a number of formal theories of acceptance motivated by Reinhardt’s program and we analyze their properties. We argue that, under reasonable assumptions, instrumental acceptance does entail non-trivial implicit commitments, yet weaker than those associated with foundational acceptance.
The impact of COVID-19 restrictions on crime and its implications for public health: a case study from a small developing country
Authors: Dookeram Navin , Pooransingh Shalini , Mohammed Asad , Dialsingh Isaac 
Published: September 2024

Abstract

Background
Crime has been described as a public health issue in Trinidad and Tobago, a small developing nation. COVID-19 restrictions, aimed at maintaining public health safety by limiting disease spread, may have negatively impacted crime rates due to an alteration of social and economic conditions. This study evaluates the implications of these restrictions on crime dynamics and hence their impacts on overall public health.

Methods
Employing interrupted time series analysis with seasonal autoregressive integrated moving average with exogenous factor (Seasonal Autoregressive Integrated Moving Average with Exogenous Variables) models, monthly data on murders, sexual offences, and motor vehicle larcenies from January 2013 to June 2023 were analysed.

Results
The study found a decrease in murders and motor vehicle larcenies with the onset of restrictions, followed by an inverse trend correlating with the easing of measures. Sexual offences showed no significant change in response to the restrictions.

Conclusions
While COVID-19 restrictions initially influenced certain crime rates, the effect varied across crime types. Policy interventions based on lessons learned from the COVID-19 pandemic must be done to strategically reduce and prevent crime without having the negative side effects of the pandemic.
Neural dynamics underlying the illusion of control during reward processing
Authors: Zheng Ya , Yang Canming , Jiang Huiping , Gao Bo 
Published: September 2024

Abstract
The illusion of control refers to a behavioral bias in which people believe they have greater control over completely stochastic events than they actually do, leading to an inflated estimate of reward probability than objective probability warrants. In this study, we examined how reward system is modulated by the illusion of control through the lens of neural dynamics. Participants in a behavioral task exhibited a classical illusion of control, assigning a higher value to the gambling wheels they picked themselves than to those given randomly. An event-related potential study of the same task revealed that this behavioral bias is associated with reduced reward anticipation, as indexed by the stimulus-preceding negativity, diminished positive prediction error signals, as reflected by the reward positivity, and enhanced motivational salience, as revealed by the P300. Our findings offer a mechanistic understanding of the illusion of control in terms of reward dynamics.
Effects of therapeutically approved individual bile acids on the development of metabolic dysfunction-associated steatohepatitis a low bile acid mouse model
Authors: Taylor Rulaiha , Basaly Veronia , Kong Bo , Yang Ill , Brinker Anita M , Capece Gina , Bhattacharya Anisha , Henry Zakiyah R , Otersen Katherine , Yang Zhenning , Meadows Vik , Mera Stephanie , Joseph Laurie B , Zhou Peihong , Aleksunes Lauren M , Roepke Troy , Buckley Brian , Guo Grace L 
Published: September 2024

Abstract
Bile acid (BA) signaling dysregulation is an important etiology for the development of metabolic dysfunction-associated steatotic liver disease (MASLD). As diverse signaling molecules synthesized in the liver by pathways initiated with CYP7A1 and CYP27A1, BAs are endogenous modulators of farnesoid x receptor (FXR). FXR activation is crucial in maintaining BA homeostasis, regulating lipid metabolism, and suppressing inflammation. Additionally, BAs interact with membrane receptors and gut microbiota to regulate energy expenditure and intestinal health. Complex modulation of BAs in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs, especially during MASLD development. Previously, we determined that acute feeding of individual BAs differentially affects lipid, inflammation, and oxidative stress pathways in a low-BA mouse model, Cyp7a1/Cyp27a1 double knockout (DKO) mice. Currently, we investigated to what degree cholic acid (CA), deoxycholic acid (DCA), or ursodeoxycholic acid (UDCA) at physiological concentrations impact MASLD development in DKO mice. The results showed that these 3 BAs varied in the ability to activate hepatic and intestinal FXR, disrupt lipid homeostasis, and modulate inflammation and fibrosis. Additionally, UDCA activated intestinal FXR in these low-BA mice. Significant alterations in lipid uptake and metabolism in DKO mice following CA and DCA feeding indicate differences in cholesterol and lipid handling across genotypes. Overall, the DKO were less susceptible to weight gain, but more susceptible to MASH diet induced inflammation and fibrosis on CA and DCA supplements, whereas WT mice were more vulnerable to CA-induced fibrosis on the control diet.
Comprehensive genotoxicity and carcinogenicity assessment of molnupiravir
Authors: Escobar Patricia A , Sobol Zhanna , Miller Randy R , Ferry-Martin Sandrine , Stermer Angela , Jacob Binod , Muniappa Nagaraja , Sanchez Rosa I , Blanchard Kerry T , Galijatovic-Idrizbegovic Alema , Amin Rupesh P , Troth Sean P 
Published: September 2024

Abstract
Molnupiravir is registered or authorized in several countries as a 5-d oral coronavirus disease 2019 treatment for adults. Molnupiravir is a prodrug of the antiviral ribonucleoside β-D-N4-hydroxycytidine (NHC) that distributes into cells, where it is phosphorylated to its pharmacologically active ribonucleoside triphosphate (NHC-TP) form. NHC-TP incorporates into severe acute respiratory syndrome coronavirus 2 RNA by the viral RNA-dependent RNA polymerase, resulting in an accumulation of errors in the viral genome, leading to inhibition of viral replication and loss of infectivity. The potential of molnupiravir to induce genomic mutations and DNA damage was comprehensively assessed in several in vitro and in vivo genotoxicity assays and a carcinogenicity study, in accordance with international guideline recommendations and expert opinion. Molnupiravir and NHC induced mutations in vitro in bacteria and mammalian cells but did not induce chromosome damage in in vitro or in vivo assays. The in vivo mutagenic and carcinogenic potential of molnupiravir was tested in a series of in vivo mutagenicity studies in somatic and germ cells (Pig-a Assay and Big Blue® TGR Mutation Assay) and in a carcinogenicity study (transgenic rasH2-Tg mouse), using durations of exposure and doses exceeding those used in clinical therapy. In vitro genotoxicity results are superseded by robustly conducted in vivo studies. Molnupiravir did not increase mutations in somatic or germ cells in the in vivo animal studies and was negative in the carcinogenicity study. The interpretation criteria for each study followed established regulatory guidelines. Taken together, these data indicate that molnupiravir use does not present a genotoxicity or carcinogenicity risk for patients.
Development of machine learning-based quantitative structure–activity relationship models for predicting plasma half-lives of drugs in six common food animal species
Authors: Wu Pei-Yu , Chou Wei-Chun , Wu Xue , Kamineni Venkata N , Kuchimanchi Yashas , Tell Lisa A , Maunsell Fiona P , Lin Zhoumeng 
Published: September 2024

Abstract
Plasma half-life is a crucial pharmacokinetic parameter for estimating extralabel withdrawal intervals of drugs to ensure the safety of food products derived from animals. This study focuses on developing a quantitative structure–activity relationship (QSAR) model incorporating multiple machine learning and artificial intelligence algorithms, and aims to predict the plasma half-lives of drugs in 6 food animals, including cattle, chickens, goats, sheep, swine, and turkeys. By integrating 4 machine learning algorithms with 5 molecular descriptor types, 20 QSAR models were developed using data from the Food Animal Residue Avoidance Databank (FARAD) Comparative Pharmacokinetic Database. The deep neural network (DNN) algorithm demonstrated the best prediction ability of plasma half-lives. The DNN model with all descriptors achieved superior performance with a high coefficient of determination (R2) of 0.82 ± 0.19 in 5-fold cross-validation on the training sets and an R2 of 0.67 on the independent test set, indicating accurate predictions and good generalizability. The final model was converted to a user-friendly web dashboard to facilitate its wide application by the scientific community. This machine learning-based QSAR model serves as a valuable tool for predicting drug plasma half-lives and extralabel withdrawal intervals in 6 common food animals based on physicochemical properties. It also provides a foundation to develop more advanced models to predict the tissue half-life of drugs in food animals.
Ohio Farmworkers and Heat-Related Illness Prevention
Authors: Edgerly Ashley , Gillespie Gordon Lee , Bhattacharya Amit , Hittle Beverly M. 
Published: September 2024

Objective
The aim of the study is to understand farmworkers’ knowledge of heat-related illness prevention and behavioral and cultural factors related to heat-related illness (HRI) prevention.

Methods
The theory of planned behavior and an ethnographic study design were used. Data collection consisted of observations and interviews. Recorded interviews were conducted with participants and transcribed verbatim. Transcribed interviews were analyzed using thematic analysis.

Results
Overall, 14 interviews were conducted, and four themes emerged: acquisition and interpretation, perception, interoception, and action. Other findings included an insufficiency of formal training and the absence of knowledge of a protocol for acclimatization.

Conclusions
Better education and training are needed in this occupation, especially regarding acclimatization. Occupational health professionals must lead efforts to develop HRI plans and measures to ensure acclimatization protocols are adopted in the workforce.
Topical Ophthalmic Administration of VIAN-c4551 Antiangiogenic Peptide for Diabetic Macular Edema: Preclinical Efficacy and Ocular Pharmacokinetics
Authors: Adán-Castro Elva , Zamora Magdalena , Granados-Carrasco Daniela , Siqueiros-Márquez Lourdes , García-Rodrigo Jose F. , Bertsch Thomas , Triebel Jakob , Martínez de la Escalera Gonzalo , Robles Juan Pablo , Clapp Carmen 
Published: September 2024

AbstractVIAN-c4551 is a cyclic antiangiogenic peptide that stands as a potent and stable inhibitor of vascular endothelial cell growth factor (VEGF), the major vasopermeability and angiogenic factor in diabetic macular edema and diabetic retinopathy. Intravitreal injections of inhibitors of VEGF are a first-line therapy, but the invasiveness, risk, and low adherence of frequent intravitreal injections interfere with the needed long-term treatments and successful outcomes. Eye drops are non-invasive and favor compliance. Here, we evaluated the preclinical efficacy, permeability, and ocular pharmacokinetics of VIAN-c4551 delivered in eye drops. VIAN-c4551 demonstrated high potency (IC50= 137 pM) to inhibit the permeability of human umbilical vein endothelial cell monolayers induced by VEGF. VIAN-c4551 eye drops potently (0.005% minimum effective dose) prevented the retinal vascular leakage induced by VEGF injected intravitreally for up to 24 hours and reversed the increase in retinal vascular permeability due to streptozotocin-induced diabetes in rats and mice. VIAN-c4551 exhibited high permeability across MDCK epithelium and, after a single topical ocular instillation in rabbits, reached the retina-choroid in micromolar concentrations several orders of magnitude above its IC50(Cmax= 51 µM at 6 hours) that lasted at least 24 hours. In conclusion, VIAN-c4551 eye drops reach the back of the eye at therapeutic concentrations, providing a potential, once-a-day, non-invasive intervention for preventing and reversing retinal vascular leakage in diabetic macular edema, diabetic retinopathy, and other vascular retinopathies and preserving sight.
Spatial microenvironments tune immune response dynamics in theDrosophilalarval fat body
Authors: Schlomann Brandon H. , Pai Ting-Wei , Sandhu Jazmin , Imbert Genesis Ferrer , Graham Thomas G.W. , Garcia Hernan G. 
Published: September 2024

AbstractImmune responses in tissues display intricate patterns of gene expression that vary across space and time. While such patterns have been increasingly linked to disease outcomes, the mechanisms that generate them and the logic behind them remain poorly understood. As a tractable model of spatial immune responses, we investigated heterogeneous expression of antimicrobial peptides in the larval fly fat body, an organ functionally analogous to the liver. To capture the dynamics of immune response across the full tissue at single-cell resolution, we established live light sheet fluorescence microscopy of whole larvae. We discovered that expression of antimicrobial peptides occurs in a reproducible spatial pattern, with enhanced expression in the anterior and posterior lobes of the fat body. This pattern correlates with microbial localization via blood flow but is not caused by it: loss of heartbeat suppresses microbial transport but leaves the expression pattern unchanged. This result suggests that regions of the tissue most likely to encounter microbes via blood flow are primed to produce antimicrobials. Spatial transcriptomics revealed that these immune microenvironments are defined by genes spanning multiple biological processes, including lipid-binding proteins that regulate host cell death by the immune system. In sum, the larval fly fat body exhibits spatial compartmentalization of immune activity that resembles the strategic positioning of immune cells in mammals, such as in the liver, gut, and lymph nodes. This finding suggests that tissues may share a conserved spatial organization that optimizes immune responses for antimicrobial efficacy while preventing excessive self-damage.
Optimal transport reveals dynamic gene regulatory networks via gene velocity estimation
Authors: Zhao Wenjun , Larschan Erica , Sandstede Björn , Singh Ritambhara 
Published: September 2024

AbstractInferring gene regulatory networks from gene expression data is an important and challenging problem in the biology community. We propose OTVelo, a methodology that takes time-stamped single-cell gene expression data as input and predicts gene regulation across two time points. It is known that the rate of change of gene expression, which we will refer to as gene velocity, provides crucial information that enhances such inference; however, this information is not always available due to the limitations in sequencing depth. Our algorithm overcomes this limitation by estimating gene velocities using optimal transport. We then infer gene regulation using time-lagged correlation and Granger causality via regularized linear regression. Instead of providing an aggregated network across all time points, our method uncovers the underlying dynamical mechanism across time points. We validate our algorithm on 13 simulated datasets with both synthetic and curated networks and demonstrate its efficacy on 4 experimental data sets.Author summaryUnderstanding how genes interact to regulate cellular functions is crucial for advancing our knowledge of biology and disease. We present OTVelo, a method that uses single-cell gene expression data collected at different time points to infer gene regulatory networks. OTVelo offers a dynamic view of how gene interactions change over time, providing deeper insights into cellular processes. Unlike traditional methods, OTVelo captures temporal information through ancestor-descendant transitions without assuming a specific underlying regulatory model. We validate our approach using both simulated and real-world data, demonstrating its effectiveness in revealing complex gene regulation patterns. This method could lead to new discoveries in understanding biological systems and developing disease treatments.