bluuebunny/crossref_metadata_2025_split huggingface dataset:
edgeR v4: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets
Authors: Chen Yunshun , Chen Lizhong , Lun Aaron T L , Baldoni Pedro L , Smyth Gordon K 
Published: January 2025

Abstract
edgeR is an R/Bioconductor software package for differential analyses of sequencing data in the form of read counts for genes or genomic features. Over the past 15 years, edgeR has been a popular choice for statistical analysis of data from sequencing technologies such as RNA-seq or ChIP-seq. edgeR pioneered the use of the negative binomial distribution to model read count data with replicates and the use of generalized linear models to analyze complex experimental designs. edgeR implements empirical Bayes moderation methods to allow reliable inference when the number of replicates is small. This article announces edgeR version 4, which includes new developments across a range of application areas. Infrastructure improvements include support for fractional counts, implementation of model fitting in C and a new statistical treatment of the quasi-likelihood pipeline that improves accuracy for small counts. The revised package has new functionality for differential methylation analysis, differential transcript expression, differential transcript and exon usage, testing relative to a fold-change threshold and pathway analysis. This article reviews the statistical framework and computational implementation of edgeR, briefly summarizing all the existing features and functionalities but with special attention to new features and those that have not been described previously.
Digital health intervention reconnects war-affected people living with HIV to healthcare: Ukraine case study
Authors: Aleksandrenko Hlib , Shevchenko Maryna , Chervak Olga 
Published: January 2025

Abstract
The unprovoked full-scale invasion of Ukraine in February 2022 severely damaged the national health system, disconnecting thousands of people living with human immunodeficiency virus (PLHIV) from essential health services. Digital health interventions (DHIs) offer the potential to reconnect war-affected PLHIV to healthcare and improve health system resilience in case of emergencies. This study aimed to present a comprehensive case study of the implementation and lessons learned from a DHI aimed at reconnecting Ukrainian PLHIV to healthcare in the context of war. A DHI called ‘#ARTporuch’ was implemented in Ukraine in response to the war-related challenges for PLHIV. The case study methodology was used to present the DHI’s life cycle, from creation to maintenance. Usage and geographic coverage data were analyzed descriptively. The multi-component DHI, consisting of a website, chatbot, database and information campaign, was implemented. The case study yielded pivotal insights into the DHI lifecycle, including rapid conceptualization, security considerations, agile implementation and continuous adaptation. The online advertising generated &gt;10 million impressions within the information campaign. The website attracted 20 619 visitors, while the chatbot was activated by 2950 users. This case study underscores the potential of DHI as a crisis-response component to reconnect PLHIV to healthcare during wartime. While quantitative evidence of effectiveness is limited due to wartime constraints, the study provides insights into the implementation of DHI in conflict-affected or resource-constrained settings, contributing to the ongoing efforts to achieve universal health coverage and enhance health system resilience planning.
What Constitutes an American Racial Institutional Order? Review Article on America's New Racial Battle Lines: Protect Versus Repair
Authors: Hochschild Jennifer 
Published: January 2025

Abstract
Following up on their 2011 book, Still a House Divided, Rogers M. Smith and Desmond King argue in America's New Racial Battle Lines: Protect versus Repair, that the United States has recently entered a new racial institutional order. Its battle lines are organized around two alliances, each with social networks, control of some institutions, core political and ideological commitments, and specific policy goals. One alliance seeks to protect the historical and continuing hierarchy in which white people enjoy social, economic, and political dominance; the other seeks to repair American society so that Black people and other people of color become fully equal citizens and participants.
In this review, I describe their analysis and then examine two questions emerging from it: what distinguishes an institutional order from a less fundamental and perhaps less durable political contest or social movement? And does an analysis centered on the Black-white binary sufficiently capture the complex nature of the United States' history and practice involving Native Americans, European immigrants, Latinos, Asian Americans, and other groups? I suggest how the protect versus repair battle lines might shift if a majority of Latinos move toward racialization or toward whiteness, or whether “racial” categories should be understood predominantly as varying intersections of race and class.
Effect of gamma dose rate on the public from soil samples collected from industrial areas of Tamil Nadu
Authors: Karthikayini Seenuvasan , Chandrasekaran Ananthanarayanan , Sathish Vilvanathan , Musthafa Mohamed Saiyad 
Published: January 2025

Abstract
The present work is the first and foremost radiological study of soil samples collected from industrial estates in Tamil Nadu. The magnetic susceptibility measurement revealed that 74.19% of the samples have medium %χFD, which denotes a commixture of coarser grains or the SP grains with a size of &lt;0.005 μm. The range of measured activities of 210Po and 210Pb were 3 ± 0.3–38 ± 2.6 Bq kg−1 and 16 ± 1.5–48 ± 2.9 Bq kg−1. The mean activity concentrations of 238U (33 Bq kg−1) and 40K (467 Bq kg−1) marginally exceeded the Indian recommended values of 28.67 and 400 Bq kg−1, respectively, whereas 232Th (47 Bq kg−1) did not exceed 63.83 Bq kg−1. The 238U and 232Th are the significant contributors to the production of radiogenic heat in the study area. Pearson correlation analysis confirmed the prime role of 232Th in radiation hazards and the insignificant relation between magnetic minerals and natural radioactivity.
Plasma Metabolic Characteristics and Potential Biomarker Combinations in Schizophrenia Patients With Tardive Dyskinesia
Authors: Lu Chenghao , Dong Yeqing , Qi Dan , Liu Nannan , Li Yanzhe , Chi Jinghui , Wang Xinxu , Zeng Min , Liu Feng , Li Shen , Li Jie 
Published: January 2025

Abstract

Background and Hypothesis
The pathogenesis of tardive dyskinesia (TD) remains unclear, involving multiple biological pathways. This study aimed to explore biomarkers of TD through untargeted metabolomics for the early identification of TD.

Study Design
This study recruited 84 schizophrenia (SZ) patients with TD and 160 SZ patients without TD. TD diagnosis was based on the Schooler–Kane criteria, and the severity of TD and psychiatric symptoms were assessed using the Abnormal Involuntary Movement Scale and the Positive and Negative Syndrome Scale. Fasting blood samples were collected from all patients and subjected to untargeted metabolomics analysis using Ultra-high-performance liquid chromatography-high resolution mass spectrometry, allowing for the quantification and profiling of 699 metabolites. Data were analyzed with orthogonal partial least squares discriminant analysis, and receiver-operating characteristic curves.

Study Results
In TD, 57 metabolites exhibited significant changes (variable importance of projection &gt; 1, false discovery rate-adjusted P &lt; .05), primarily involving amino acids and lipids. These changes predominantly affected the phenylalanine, tyrosine, and tryptophan pathway (impact = 0.5, P = .0252), as well as the phenylalanine metabolism pathway (impact = 0.36, P = .0498). N-Acetyl-l-phenylalanine (B = 2.249, t = 4.56, P &lt; .001, 95% CI, 1.302–3.286) and Succinylcarnitine (AcCa(4:0-DC)) (B = 1.009, t = 3.07, P = .002, 95% CI, 0.362–1.656) are negatively related to the total abnormal involuntary movement scale score. Additionally, 5 differential metabolites had area under the curve (AUC) values greater than 0.7 for diagnosing TD, with the combined diagnostic capability exceeding 0.8 (AUC = 0.817, 95% CI, 0.759–0.875).

Conclusions
In TD, disruptions in amino acid and lipid metabolism were predominantly observed. Amino acids and lipid metabolites may be involved in the development of TD. Additionally, a biomarker panel composed of amino acids and lipids can be used for the differential diagnosis of TD.
Evaluating UCE Data Adequacy and Integrating Uncertainty in a Comprehensive Phylogeny of Ants
Authors: Borowiec Marek L , Zhang Y Miles , Neves Karen , Ramalho Manuela O , Fisher Brian L , Lucky Andrea , Moreau Corrie S 
Published: January 2025

Abstract
While some relationships in phylogenomic studies have remained stable since the Sanger sequencing era, many challenging nodes remain, even with genome-scale data. Incongruence or lack of resolution in the phylogenomic era is frequently attributed to inadequate data modeling and analytical issues that lead to systematic biases. However, few studies investigate the potential for random error or establish expectations for the level of resolution achievable with a given empirical dataset and integrate uncertainties across methods when faced with conflicting results.
Ants are the most species-rich lineage of social insects and one of the most ecologically important terrestrial animals. Consequently, ants have garnered significant research attention, including their systematics. Despite this, there has been no comprehensive genus-level phylogeny of the ants inferred using genomic data that thoroughly evaluates both signal strength and incongruence. In this study, we provide insight into and quantify uncertainty across the ant tree of life by utilizing the most taxonomically comprehensive Ultraconserved Elements dataset of ants to date, including 277 (81%) of recognized ant genera from all 16 extant subfamilies, and representing over 98% of described species. We use simulations to establish expectations for resolution, identify branches with less-than-expected concordance, and dissect the effects of data and model selection on recalcitrant nodes.
Simulations show that hundreds of loci are needed to resolve recalcitrant nodes on our genus-level ant phylogeny. This demonstrates the continued role of random error in phylogenomic studies. Our analyses provide a comprehensive picture of support and incongruence across the ant phylogeny, while offering a more nuanced depiction of uncertainty and significantly expanding generic sampling. We use a consensus approach to integrate uncertainty across different analyses and find that assumptions about root age exert substantial influence on divergence dating. Our results suggest that advancing the understanding of ant phylogeny will require not only more data but also more refined phylogenetic models. We also provide a workflow for identifying under-supported nodes in concatenation analyses, outline a pragmatic way to reconcile conflicting results in phylogenomics, and introduce a user-friendly locus selection tool for divergence dating.
Stakeholder-informed refinement of a behavioral sleep/circadian intervention for gynecologic cancer survivors: an application of the MOST preparation phase
Authors: Fox Rina S , Brandon Krista , Badger Terry A , Gaumond Julia S , Morales Ana Acuña , Ong Jason C , Parthasarathy Sairam , Rini Christine , Zee Phyllis C , Tanner Edward J , Ancoli-Israel Sonia , Penedo Frank J , Siddique Juned , Wu Lisa M , Reid Kathryn J , Kaiser Karen 
Published: January 2025

Abstract

Background
Sleep disturbance is among the most frequent and distressing symptoms reported by gynecologic cancer survivors. Existing evidence-based behavioral sleep interventions are limited by implementation burden, which can decrease adherence.

Purpose
As part of the preparation phase of the multiphase optimization strategy (MOST), this study solicited stakeholder feedback to maximize adherence in a planned behavioral sleep/circadian intervention optimization trial.

Methods
Thirteen post-treatment survivors of early-stage gynecologic cancer completed the protocol for the planned optimization trial, including simultaneous receipt of all candidate intervention components. This included six weeks of combined sleep restriction, stimulus control, and systematic exposure to morning bright light. Participants then completed a semi-structured interview to provide feedback on their experience. We used a rapid analytic approach to quickly identify actionable feedback from de-identified transcripts.

Results
Participants generally reacted positively to the intervention components. Actionable feedback identified recommended protocol modifications and was categorized into four overarching themes: (i) remove barriers to engagement; (ii) revise for clarity; (iii) augment content; and (iv) consider individual circumstances.

Conclusions
Rapid qualitative analysis enabled us to effectively modify our planned study protocol on an expedited timeline. This approach is consistent with the core principles of MOST and can be incorporated into the Preparation phase to enhance optimization efforts.
An eco-physiological model of forest photosynthesis and transpiration under combined nitrogen and water limitation
Authors: Fransson Peter , Lim Hyungwoo , Zhao Peng , Tor-ngern Pantana , Peichl Matthias , Laudon Hjalmar , Henriksson Nils , Näsholm Torgny , Franklin Oskar 
Published: January 2025

Abstract
Although the separate effects of water and nitrogen (N) limitations on forest growth are well known, the question of how to predict their combined effects remains a challenge for modeling of climate change impacts on forests. Here, we address this challenge by developing a new eco-physiological model that accounts for plasticity in stomatal conductance and leaf N concentration. Based on optimality principle, our model determines stomatal conductance and leaf N concentration by balancing carbon uptake maximization, hydraulic risk and cost of maintaining photosynthetic capacity. We demonstrate the accuracy of the model predictions by comparing them against gross primary production estimates from eddy covariance flux measurements and sap-flow measurement scaled canopy transpiration in a long-term fertilized and an unfertilized Scots pine (Pinus sylvestris L.) forest in northern Sweden. The model also explains the response to N fertilization as a consequence of (i) reduced carbon cost of N uptake and (ii) increased leaf area per hydraulic conductance. The results suggest that leaves optimally coordinate N concentration and stomatal conductance both on short (weekly) time scales in response to weather conditions and on longer time scales in response to soil water and N availabilities.
Sepsis‐induced NET formation requires MYD88 but is independent of GSDMD and PAD4
Authors: Englert Hanna , Rangaswamy Chandini , Kullik Giuliano A. , Divivier Mylène , Göbel Josephine , Hermans‐Borgmeyer Irm , Borgmeyer Uwe , Mowen Kerri A. , Beerens Manu , Frye Maike , Mailer Reiner K. , Gelderblom Mathias , Stavrou Evi X. , Preston Roger J. S. , Schneider Stefan W. , Fuchs Tobias A. , Renné Thomas 
Published: January 2025

AbstractNeutrophils are peripheral blood‐circulating leukocytes that play a pivotal role in host defense against bacterial pathogens which upon activation, they release web‐like chromatin structures called neutrophil extracellular traps (NETs). Here, we analyzed and compared the importance of myeloid differentiation factor 88 (MYD88), peptidyl arginine deiminase 4 (PAD4), and gasdermin D (GSDMD) for NET formation in vivo following sepsis and neutrophilia challenge. Injection of lipopolysaccharide (LPS)/E. coli or the transgenic expression of granulocyte colony‐stimulating factor (G‐CSF), each induced NET‐mediated lethal vascular occlusions in mice with combined genetic deficiency in Dnase1 and Dnase1l3 (D1/D1l3−/−). In accordance with the signaling of toll‐like receptors, Myd88/D1/D1l3−/− animals were protected from the formation of lethal intravascular NETs during septic conditions. However, this protection was not observed during neutrophilia. It was unexpected to find that both Gsdmd/D1/D1l3−/− and Pad4/D1/D1l3−/− mice were fully capable of forming NETs upon LPS/E.coli challenge. Sepsis equally triggered a similar inflammatory response in these mice characterized by formation of DNA‐rich thrombi, vessel occlusions, and mortality from pulmonary embolism, compared to D1/D1l3−/− mice. Pharmacologic GSDMD inhibitors did not reduce PMA‐stimulated NET formation in ex vivo models either. Similarly, neither Pad4 nor GSDMD deficiency affected intravascular occlusive NET formation upon neutrophilia challenge. The magnitude of NET production, multi‐organ damage, and lethality were comparable to those observed in challenged control mice. In conclusion, our data indicate that NET formation during experimental sepsis and neutrophilia is regulated by distinct stimulus‐dependent pathways that may be independent of canonical PAD4 and GSDMD.
Reliability and Validity of the Turkish Version of Early-Onset Scoliosis Self-Report Questionnaire
Authors: Goker Barlas , Beydemir Ataberk , Yavuz Yasemin , Kinikli Gizem Irem , Ramazanov Rafik , Anderson Kayla Erin , Olgun Zeynep Deniz , Demirkiran Halil Gokhan , Yazici Muharrem 
Published: January 2025

Objective:
Early-Onset Scoliosis Self-Report Questionnaire (EOSQ-SELF) is a recently developed self-reported questionnaire based on the widely adopted Early-Onset Scoliosis Questionnaire and evaluates health-related quality of life in children with early-onset scoliosis over 8 years of age. To date, the questionnaire does not have a validated version in Turkish. The aim of this study was to translate EOSQ-SELF into Turkish and evaluate its reliability and validity.

Methods:
Content validity was assessed through the item (I-CVI) and scale (S-CVI) content validity indices. The distribution of survey responses was analyzed and ceiling and floor effects were calculated with descriptive statistics. Internal consistency was measured with the Cronbach alpha coefficient. Construct validity was evaluated by comparing the responses between EOSQ-SELF and Scoliosis Research Society questionnaire-22 revised.

Results:
Eighty-five patients (30 males and 55 females) diagnosed with early-onset scoliosis completed the EOSQ-SELF questionnaire. The I-CVI for the relevance of 30 questions was found to be 0.875 for 3 questions and 1.0 for the remaining questions, whereas the S-CVI was 0.9875. The I-CVI for the clarity of 30 questions was found 0.500 for 1 question, 0.875 for 3 questions, and 1.0 for the remaining questions. The S-CVI value for clarity was 0.97083. The Cronbach alpha coefficient for the total score of the Turkish EOSQ-SELF was recorded at 0.942. Common domains were significantly correlated with the Scoliosis Research Society questionnaire-22 revised.

Conclusions:
We found excellent internal consistency in our study and were able to demonstrate the reliability as well as the validity of EOSQ-SELF in Turkish.

Level of Evidence:
Level I—diagnostic.
Pharmacokinetic Boosting of Calcineurin Inhibitors in Transplantation: Pros, Cons, and Perspectives
Authors: Pattanaik Smita , Monchaud Caroline 
Published: January 2025

Abstract:
The concept of pharmacokinetic (PK) boosting of calcineurin inhibitors (CNI) emerged after the FDA approval of cyclosporine-A. Several studies followed, and the proof of concept was well established by the late 1990s. This also continued for the next blockbuster immunosuppressant, tacrolimus. The driver for such research was an endeavor to save costs, as both drugs were expensive due to patent protection. Two CYP inhibitors, ketoconazole and diltiazem, have been extensively studied in this context and continue to be prescribed off-label along with the CNI. It has been observed that using ketoconazole reduces the dose requirement of tacrolimus by about 50% and 30% with diltiazem, which is in conformity with their pharmacological actions. Off-label co-prescription of these drugs with CNI is often encountered in low and middle-income countries. The foremost reason cited is economic. This article collates the evidence from the clinical studies that evaluate the PK-boosting effects of CNI and also reviews the gaps in the current evidence base. The current knowledge prevents the transplant community from making meaningful inferences about the risks and benefits of such strategies. Although the PK-boosting strategy can lead to serious adverse events, emerging evidence suggests that it may be advantageous for individuals with high CNI dose requirements. Hence, PK boosting may be an unmet need in the therapeutics of CNI. Nevertheless, there are several unanswered questions surrounding such use, and therefore, this merits testing in well-designed clinical studies. Moreover, drugs with better safer profiles and a history of successful PK boosting may be considered for evaluation with CNI.
Rho(D) immune globulin shortage and fetal Rh(D) screening with cell-free DNA
Authors: Grace Matthew R. , Goodhue Brighton , Vora Neeta L. 
Published: January 2025

Purpose of review
Despite the availability of Rh(D) immune globulin (RhIg) to prevent alloimmunization in Rh(D)-negative pregnant patients, anti-Rh(D) alloimmunization remains a prevalent cause of hemolytic disease of the fetus and newborn (HDFN). Recent RhIg shortages have caused clinicians and professional societies to identify methods to prioritize RhIg administration. New cell-free DNA (cfDNA) tests to predict fetal red blood cell antigen genotypes have been proposed as an option to prioritize the administration of RhIg to Rh(D)-negative pregnant people.

Recent findings
Commercial laboratories offer fetal Rh(D) genotype testing as part of cfDNA screening for fetal aneuploidy. Studies indicate that these tests have a high sensitivity and specificity for the detection of fetal Rh(D) status. Considering the current RhIg shortage, the American College of Obstetricians & Gynecologists (ACOG) suggests that utilizing cfDNA tests to determine fetal Rh(D) status is a reasonable approach to prioritize RhIg administration when supply is limited.

Summary
cfDNA screening for fetal Rh(D) status is a reasonable approach to triage the administration of RhIg in the setting of the current RhIg shortage. Utilization of cfDNA screening for fetal Rh(D) and other red blood cell antigen status is likely to increase in routine care. Research, professional society guidance, and education are necessary to ensure well tolerated and equitable utilization.