bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gretl—variation GRaph Evaluation TooLkit
Authors: Vorbrugg Sebastian , Bezrukov Ilja , Bao Zhigui , Weigel Detlef 
Published: December 2024

Abstract

Motivation
As genome graphs are powerful data structures for representing the genetic diversity within populations, they can help identify genomic variations that traditional linear references miss, but their complexity and size makes the analysis of genome graphs challenging. We sought to develop a genome graph analysis tool that helps these analyses to become more accessible by addressing the limitations of existing tools. Specifically, we improve scalability and user-friendliness, and we provide many new statistics tailored to variation graphs for graph evaluation, including sample-specific features.

Results
We developed an efficient, comprehensive, and integrated tool, gretl, to analyze genome graphs and gain insights into their structure and composition by providing a wide range of statistics. gretl can be utilized to evaluate different graphs, compare the output of graph construction pipelines with different parameters, as well as perform an in-depth analysis of individual graphs, including sample-specific analysis. With the assistance of gretl, novel patterns of genetic variation and potential regions of interest can be identified, for later, more detailed inspection. We demonstrate that gretl outperforms other tools in terms of speed, particularly for larger genome graphs.

Availability and implementation
Commented Rust source code and documentation is available under MIT license at https://github.com/MoinSebi/gretl together with Python scripts and step-by-step usage examples. The package is available at Bioconda for easy installation.
Assessing gene flow between Dicranum scoparium Hedw. and D. bonjeanii De Not. (Dicranaceae) using single nucleotide polymorphisms (SNPs)
Authors: Klink Jan M A , Cronberg N , Lang A S , Stech M 
Published: December 2024

Abstract
While hybridisation in vascular plants has received considerable attention, hybridisation in bryophytes is still relatively understudied. Here we investigate hybridisation between two species from the moss genus Dicranum Hedw. Dicranum scoparium Hedw. and D. bonjeanii De Not. are two moss species of the D. scoparium species complex with partially overlapping morphology and habitat ranges. This study aimed to investigate a potential hybridisation pathway between the two species by using single nucleotide polymorphisms (SNP), morphologically identifying the sex of the specimens and analysing potential sex-specific SNP markers, focusing on southern Sweden. The species differ by D. scoparium being polymorphic and D. bonjeanii monomorphic for the used SNP markers. The SNP markers genetically separate D. scoparium and D. bonjeanii specimens, although admixture between the species was observed on a limited scale. This admixture appears to originate from unidirectional fertilisation of D. bonjeanii by D. scoparium (with a genome skewed towards D. scoparium as a result), possibly followed by back-crossing of first-generation hybrids with D. scoparium. Male expressing specimens were completely absent in the D. bonjeanii samples, making a fertilisation of D. bonjeanii by males of D. scoparium more likely. No sex-specificity was observed in the used SNP markers.
De-escalating and discontinuing disease-modifying therapies in multiple sclerosis
Authors: Androdias Géraldine , Lünemann Jan D , Maillart Elisabeth , Amato Maria Pia , Audoin Bertrand , Bruijstens Arlette L , Bsteh Gabriel , Butzkueven Helmut , Ciccarelli Olga , Cobo-Calvo Alvaro , Derfuss Tobias , Di Pauli Franziska , Edan Gilles , Enzinger Christian , Geraldes Ruth , Granziera Cristina , Hacohen Yael , Hartung Hans-Peter , Hynes Sinéad , Inglese Matilde , Kappos Ludwig , Kuusisto Hanna , Langer-Gould Annette , Magyari Melinda , Marignier Romain , Montalban Xavier , Mycko Marcin P , Nourbakhsh Bardia , Oh Jiwon , Oreja-Guevara Celia , Piehl Fredrik , Prosperini Luca , Sastre-Garriga Jaume , Sellebjerg Finn , Selmaj Krzysztof , Siva Aksel , Tallantyre Emma , van Pesch Vincent , Vukusic Sandra , Weinstock-Guttman Bianca , Zipp Frauke , Tintoré Mar , Iacobaeus Ellen , Stankoff Bruno 
Published: December 2024

Abstract
The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical. This topic was discussed during an international focused workshop organized by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in 2023. The aim was to review the current evidence on the rationale for, but also the potential pitfalls of, treatment de-escalation in MS. Several clinical scenarios emerged, mainly driven by a change in the benefit-risk ratio of DMTs over the course of the disease and with aging. The workshop also addressed the issue of de-escalation by the type of DMT used and in specific situations including pregnancy and paediatric onset MS. Finally, we provide practical guidelines for selecting appropriate patients, defining de-escalation and monitoring modalities, and outline unmet needs in this field.
Synergistic effect of teclistamab with PD-1 inhibition: a case of acute interstitial nephritis with dual immunotherapy
Authors: Mohan Arjunmohan , Barbir Elena-Bianca , Hernandez Loren Herrera , Leung Nelson , Herrmann Sandra M 
Published: December 2024

ABSTRACT
We report a case of acute interstitial nephritis (AIN) in a 68-year-old male with squamous cell carcinoma (SCC) and relapsed/refractory multiple myeloma (RRMM) who developed acute kidney injury (AKI) shortly after starting teclistamab for RRMM. Despite stable renal function on immune checkpoint inhibitor (ICI) therapy for SCC, proton pump inhibitors and trimethoprim-sulfamethoxazole for 3 years, AKI only occurred post-teclistamab initiation. Biopsy-confirmed AIN with serum creatinine improved only after pulse-dose steroids. This case highlights a potential synergistic nephrotoxic effect of teclistamab and ICIs, warranting further investigation into teclistamab's renal safety.
Moderately elevated ambient temperature is associated with mortality in dialysis patients, but not in transplant patients
Authors: Couchoud Cécile , Lobbedez Thierry , Bayat Sahar , Glowacki François , Brunet Philippe , Frimat Luc 
Published: December 2024

ABSTRACT

Background
In many parts of the world, heat waves have been associated with excess morbidity and mortality in the general population. Studies on the effects of high-temperature exposure in kidney transplantation are lacking and are scare in dialysis patients. The aim of this study was to investigate the association between high temperatures and mortality for chronic kidney disease (CKD) stage 5 patients treated with dialysis or with a kidney graft in France using various definition of elevated temperature.

Methods
In this retrospective cohort study, the association between temperature indicators and mortality was analysed with Poisson models taking into account the trend over time and seasonality and possible confounding factors. Models were compared by their AIC. All patients treated with RRT between 2012 and 2022 in France were extracted from the national REIN registry. Various definitions of elevated temperatures were explored based on all temperature measured at one station per district per hour and per day, from June to September during the years 2012–2022 in Metropolitan France.

Results
Between June and September, over the years 2012–2022, temperatures varied from 6.7 to 45.4°C. During this period, 20 174 deaths were recorded among 116 808 dialysis patients and 3340 among 64 531 transplanted patients. A maximum temperature &gt;32.5°C was associated with mortality and an incidence ratio (IR) of 1.09 (1.04–1.15) in the dialysed population. No association was found among transplanted patients.

Conclusions
Further analyses are needed to confirm these results and better understand the biological and clinical impact of heat intensity and the cumulative effect with other environmental factors such as air pollution. More detailed studies on reasons for hospitalizations and causes of death are also planned.
MiCK: a database of gut microbial genes linked with chemoresistance in cancer patients
Authors: Shahzaib Muhammad , Muaz Muhammad , Zubair Muhammad Hasnain , Kayani Masood Ur Rehman 
Published: December 2024

Abstract
Cancer remains a global health challenge, with significant morbidity and mortality rates. In 2020, cancer caused nearly 10 million deaths, making it the second leading cause of death worldwide. The emergence of chemoresistance has become a major hurdle in successfully treating cancer patients. Recently, human gut microbes have been recognized for their role in modulating drug efficacy through their metabolites, ultimately leading to chemoresistance. The currently available databases are limited to knowledge regarding the interactions between gut microbiome and drugs. However, a database containing the human gut microbial gene sequences, and their effect on the efficacy of chemotherapy for cancer patients has not yet been developed. To address this challenge, we present the Microbial Chemoresistance Knowledgebase (MiCK), a comprehensive database that catalogs microbial gene sequences associated with chemoresistance. MiCK contains 1.6 million sequences of 29 gene types linked to chemoresistance and drug metabolism, curated manually from recent literature and sequence databases. The database can support downstream analysis as it provides a user-friendly web interface for sequence search and download functionalities. MiCK aims to facilitate the understanding and mitigation of chemoresistance in cancers by serving as a valuable resource for researchers.
Database URL: https://microbialchemreskb.com/
Air pollution exposure is associated with gene expression in children
Authors: Das Siddhartha , Rundblad Amanda , Marques Irene Fontes , Soares Ana Goncalves , Jaddoe Vincent W , Vrijheid Martine , Nieuwenhuijsen Mark , Verlouw Joost , Matthews Jason , Holven Kirsten B , Thoresen Magne , Timpson Nicholas J , Felix Janine F , Ulven Stine M 
Published: December 2024

Abstract
Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter &lt;2.5 (PM2.5) and &lt; 10 (PM10) micrometers, nitrogen dioxide, green spaces, and blue space, with whole-blood gene expression were explored in children from the Dutch Generation R Study (n = 172). Analyses were adjusted for age, sex, batch, maternal education, and area socioeconomic status. Follow-up analysis was carried out using lymphoblastoid cell line gene expression in children from the ALSPAC Study (n = 946). Gene set enrichment analysis (GSEA) using hallmark and immune gene sets from the molecular signature database was carried out to identify significantly over-represented gene sets for insights into biological mechanisms Exposure to PM2.5 was associated with expression of 86 genes in discovery analyses in the Generation R Study [false discovery rate (FDR)-adjusted P-value &lt; .25]. Of these, PM2.5 was also associated with GNG11 expression in the same direction in follow-up analysis (FDR-adjusted P-value &lt; .05). The remaining exposures showed much fewer associations in the discovery analyses. GSEA using PM2.5 association results for both cohorts indicated suppression of gene sets related to interferon response and response to bacterial and viral exposure. In conclusion, gene expression analysis performed in two independent cohorts suggests that PM2.5 exposure in children may be involved in interferon and microbial infection responses.
To Defer or to Differ: Experimental Evidence on the Role of Cash Transfers in Nigerian Couples’ Decision–Making
Authors: Bakhtiar M Mehrab , Fafchamps Marcel , Goldstein Markus , Leonard Kenneth L , Papineni Sreelakshmi 
Published: December 2024

Abstract
We conduct an original lab-in-the-field experiment on the decision–making process of married couples over the allocation of rival and non-rival household goods. The experiment measures individual preferences over allocations and traces the process of deferral, consultation, communication and accommodation by which couples implement these preferences. We find few differences in individual preferences over allocations of goods. However, wives and husbands have strong preferences over process: women prefer to defer decisions to their husbands even when deferral is costly and is not observed by the husband; men rarely defer under any condition. Our study follows a randomised controlled trial that ended a year earlier and gave large cash transfers over eighteen months to half of the women in the study. We estimate the effect of treatment on the demand for agency among women and find that the receipt of cash transfers does not change women’s bargaining process except in a secret condition when the decision to defer is shrouded from her husband. This suggests that the cash transfer to women increases their demand for agency but does not change the intra-household balance of power enough to allow them to express it publicly.
Digital quantification of somatostatin receptor subtypes 2 and 5 in growth hormone–secreting pituitary tumors
Authors: Campana Claudia , Amarù Jessica , Milioto Angelo , Nista Federica , van Koetsveld Peter M , Iyer Anand , Arvigo Marica , Ferone Diego , Hofland Leo J , Gatto Federico 
Published: December 2024

Abstract
Immunohistochemistry (IHC) of somatostatin receptor subtype 2 can predict response to first-generation somatostatin receptor ligands (fg-SRLs) in acromegaly. Recently, we validated an open-source digital image analysis (DIA) to quantify somatostatin receptor subtype 2 (SSTR2) expression. We aimed to validate the DIA also on somatostatin receptor subtype 5 (SSTR5) in a new cohort of growth hormone (GH)-secreting pituitary tumors, with IHC performed in a different laboratory, and to correlate fg-SRL response with SSTs expression. Somatostatin receptor subtype 2 and SSTR5 were assessed in 42 GH-secreting pituitary tumors, using a semiquantitative immunoreactivity score (IRS) and the DIA by use of the open-access software CellProfiler. The DIA calculates the staining intensity and the percentage of positive cells (%PC). We found a good correlation between IRS and DIA for both SSTR2 and SSTR5 (P &lt; .001), demonstrating the reliability of the DIA in this setting. Response to fg-SRL treatment correlated with SSTR2, but not SSTR5, expression. Somatostatin receptor subtype 2 expression predicted response to fg-SRL. In particular, the identified cut-offs were IRS ≥ 5 (area under the curve [AUC] 0.763; sensitivity 77%; specificity 83%); intensity/area ≥0.106 (AUC 0.833; sensitivity 92%; specificity 83%); and %PC-DIA ≥63.7% (AUC 0.917; sensitivity 92%; specificity 83%). The SSTR2 %PC correlated with treatment response only when evaluated using the DIA, showing a better performance of this method.
Opinion of Polish doctors on the use of futile therapy
Authors: Damps Maria , Gajda Maksymilian , Wiktor Łukasz , Byrska-Maciejasz Elżbieta , Rybojad Beata , Kowalska Małgorzata , Bartkowska-Śniatkowska Alicja , Paprocka-Lipińska Anna , Kucewicz-Czech Ewa 
Published: December 2024

Abstract
The discontinuation of futile therapy is increasingly discussed in Polish clinical practice. Given the need to ensure patient well-being, it is essential to consider whether all clinical options resulting from medical progress should be used for every patient and on what grounds decisions to limit therapy should be based. The aim of our study was to determine the opinions of Polish medical doctors on this topic. We anonymously surveyed physicians across various specialties. An analysis of the collected data was carried out using descriptive and analytical methods. A total of 323 physicians participated in the study; 93% of them were aware of the problem of futile therapy in adults, with intensivists being significantly more aware (P = 0.002). Additionally, 95% of respondents supported the idea of discontinuing futile therapy, and over 68% used the therapy discontinuation protocol. Among the most common reasons for undertaking futile therapy, respondents cited fear of legal liability (93.5%), as well as fear of being accused of unethical behavior (62.2%) and fear before talking to the patient/patient’s family and their reactions (57.9%). Respondents also identified factors that would facilitate making decisions about limiting futile therapy, including precise qualification criteria for limiting therapy and education in this area (95.3%), the patient’s declaration of will (87.5%), and a clear legal act (81.3%). The majority of study participants supported the idea of limiting futile therapy, and this issue is well known among Polish physicians.
Long-sperm precedence and other cryptic female choices in Drosophila melanogaster
Authors: Peckenpaugh Brooke , Yew Joanne Y , Moyle Leonie C 
Published: December 2024

Abstract
Females that mate multiply make postmating choices about which sperm fertilize their eggs (cryptic female choice); however, the male characteristics they use to make such choices remain unclear. In this study, we sought to understand female sperm use patterns by evaluating whether Drosophila melanogaster females adjust sperm use (second male paternity) in response to 4 main factors: male genotype, male courtship effort, male pheromone alteration, and male postmating reproductive morphology. Our experiment was replicated across 4 different D. melanogaster lines, in a full factorial design, including a pheromone manipulation in which second males were perfumed to resemble heterospecific (Drosophila yakuba) males. We found that females prefer longer sperm—regardless of mating order—in almost all contexts; this observed pattern of “long-sperm precedence” is consistent with female postmating choice of high-fitness male traits. Nonetheless, we also found that this general preference can be plastically altered by females in response to effects including perfuming treatment; this differential female sperm use is between otherwise identical males, and therefore solely female-mediated. Furthermore, our finding that females exercise choice using diverse criteria suggests a possible mechanism for the maintenance of variation in sexually selected male traits.
Large-scale remote sensing reveals that tree mortality in Germany appears to be greater than previously expected
Authors: Schiefer Felix , Schmidtlein Sebastian , Hartmann Henrik , Schnabel Florian , Kattenborn Teja 
Published: December 2024

Abstract
Global warming poses a major threat to forests and events of increased tree mortality are observed globally. Studying tree mortality often relies on local-level observations of dieback while large-scale analyses are lacking. Satellite remote sensing provides the spatial coverage and sufficiently high temporal and spatial resolution needed to investigate tree mortality at landscape-scale. However, adequate reference data for training satellite-based models are scarce. In this study, we employed the first maps of standing deadwood in Germany for the years 2018–2022 with 10 m spatial resolution that were created by using tree mortality observations spotted in hundreds of drone images as the reference. We use these maps to study spatial and temporal patterns of tree mortality in Germany and analyse their biotic and abiotic environmental drivers using random forest regression. In 2019, the second consecutive hotter drought year in a row, standing deadwood increased steeply to 334 ± 189 kilohectar (kha) which corresponds to 2.5 ± 1.4% of the total forested area in Germany. Picea abies, Pinus sylvestris, and Fagus sylvatica showed highest shares of standing deadwood. During 2018–2021 978 ± 529 kha (7.9 ± 4.4%) of standing dead trees accumulated. The higher mortality estimates that we report compared to other surveys (such as the ground-based forest condition survey) can be partially attributed to the fact that remote sensing captures mortality from a bird’s eye perspective and that the high spatial detail (10 m) in this study also captures scattered occurrences of tree mortality. Atmospheric drought (i.e. climatic water balance and vapor pressure deficit) and temperature extremes (i.e. number of hot days and frosts after vegetation onset) were the most important predictors of tree mortality. We found increased tree mortality for smaller and younger stands and on less productive sites. Monospecific stands were generally not more affected by mortality than average, but only when interactions with damaging insects (e.g. bark beetles) occurred. Because excess tree mortality rates threaten many forests across the globe, similar analyses of tree mortality are warranted and technically feasible at the global scale. We encourage the international scientific community to share and compile local data on deadwood occurrences (see example: www.deadtrees.earth) as such a collaborative effort is required to help understand mortality events on a global scale.
Multiple DNA repair pathways prevent acetaldehyde-induced mutagenesis in yeast
Authors: Porcher Latarsha , Vijayraghavan Sriram , Patel Yashvi , Becker Samuel , Blouin Thomas , McCollum James , Mieczkowski Piotr A , Saini Natalie 
Published: December 2024

Abstract
Acetaldehyde is the primary metabolite of alcohol and is present in many environmental sources including tobacco smoke. Acetaldehyde is genotoxic, whereby it can form DNA adducts and lead to mutagenesis. Individuals with defects in acetaldehyde clearance pathways have increased susceptibility to alcohol-associated cancers. Moreover, a mutation signature specific to acetaldehyde exposure is widespread in alcohol and smoking-associated cancers. However, the pathways that repair acetaldehyde-induced DNA damage and thus prevent mutagenesis are vaguely understood. Here, we used Saccharomyces cerevisiae to delete genes in each of the major DNA repair pathways to identify those that alter acetaldehyde-induced mutagenesis. We observed that loss of functional nucleotide excision repair (NER) had the largest effect on acetaldehyde mutagenesis. In addition, base excision repair (BER), as well as DNA protein crosslink (DPC) repair pathways were involved in modulating acetaldehyde mutagenesis, while mismatch repair (MMR), homologous recombination (HR) and post replication repair are dispensable for acetaldehyde mutagenesis. Acetaldehyde-induced mutations in an NER-deficient (Δrad1) background were dependent on translesion synthesis as well as DNA inter-strand crosslink (ICL) repair. Moreover, whole genome sequencing of the mutated isolates demonstrated an increase in C→A changes coupled with an enrichment of gCn→A changes which is diagnostic of acetaldehyde exposure in yeast and in human cancers. Finally, downregulation of the leading strand replicative polymerase Pol epsilon, but not the lagging strand polymerase, resulted in increased acetaldehyde mutagenesis, indicating that lesions are likely formed on the leading strand. Our findings demonstrate that multiple DNA repair pathways coordinate to prevent acetaldehyde-induced mutagenesis.