bluuebunny/crossref_metadata_2025_split huggingface dataset:
AI as an intervention: improving clinical outcomes relies on a causal approach to AI development and validation
Authors: Joshi Shalmali , Urteaga Iñigo , van Amsterdam Wouter A C , Hripcsak George , Elias Pierre , Recht Benjamin , Elhadad Noémie , Fackler James , Sendak Mark P , Wiens Jenna , Deshpande Kaivalya , Wald Yoav , Fiterau Madalina , Lipton Zachary , Malinsky Daniel , Nayan Madhur , Namkoong Hongseok , Park Soojin , Vogt Julia E , Ranganath Rajesh 
Published: January 2025

Abstract
The primary practice of healthcare artificial intelligence (AI) starts with model development, often using state-of-the-art AI, retrospectively evaluated using metrics lifted from the AI literature like AUROC and DICE score. However, good performance on these metrics may not translate to improved clinical outcomes. Instead, we argue for a better development pipeline constructed by working backward from the end goal of positively impacting clinically relevant outcomes using AI, leading to considerations of causality in model development and validation, and subsequently a better development pipeline. Healthcare AI should be “actionable,” and the change in actions induced by AI should improve outcomes. Quantifying the effect of changes in actions on outcomes is causal inference. The development, evaluation, and validation of healthcare AI should therefore account for the causal effect of intervening with the AI on clinically relevant outcomes. Using a causal lens, we make recommendations for key stakeholders at various stages of the healthcare AI pipeline. Our recommendations aim to increase the positive impact of AI on clinical outcomes.
On Being Simultaneously Arab and “Modern”: Saloua Raouda Choucair’s Design Between Science and Sufism
Authors: Taan Yasmine Nachabe 
Published: January 2025

Abstract
This article discusses Saloua Raouda Choucair’s commitment to design through her combined interest in science and Sufism. Her artistic and design accomplishments portray her as a resolute and determined woman who actively pursued education, independence, and progress throughout her career. By looking into Saloua’s engagement with science, technology, and mysticism, this study seeks to unravel the nuanced intersections between tradition and modernity, craftsmanship, and technology in the realm of design production. The aim is to illuminate how her utilization of scientific knowledge and Sufism shaped her design thinking, challenging prevailing norms and contributing to a broader understanding of the dynamic relationship between gender, education, and design practice in Lebanon. This research aims to interrogate the intricacies of design production by challenging the conventional dichotomy that juxtaposes tradition against modernity and craftsmanship against technology.
Effects of Metarhizium anisopliae on lethality, transfer, behavior, and physiology in Eucryptorrhynchus scrobiculatus and E. brandti (Coleoptera: Curculionidae)
Authors: Sun Xuewen , Wen Chao , Yang Danhui , Zhang Genzhuang , Zhang Bohan , Wen Junbao 
Published: January 2025

Abstract
Eucryptorrhynchus scrobiculatus (Motschulsky) and E. brandti (Harold) are 2 serious pests inflicting damage on Ailanthus altissima (Mill.) Swingle. In the field, these species exhibit aggregation behavior. We hypothesized that this behavior facilitated the contact and horizontal transfer of Metarhizium anisopliae (Metschn.) Sorokin in weevil species. Little or no mortality in both E. scrobiculatus and E. brandti adult individuals exposed to low concentrations M. anisopliae (1 × 105, 1 × 106 conidia/ml). A mortality rate of 100% was observed in both E. scrobiculatus and E. brandti adults after 3 and 5 d of treatment with M. anisopliae at concentrations of 1 × 109 and 1 × 108 conidia/ml. The aggregation behavior of E. scrobiculatus and E. brandti adults was unaffected by M. anisopliae. In the transfer test of M. anisopliae, the mortality rate of recipients mixed with donors treated with M. anisopliae conidia was significantly higher compared to untreated donors and control recipients in laboratory and field experiments. Furthermore, the mortality of secondary recipients in both E. scrobiculatus and E. brandti was significantly higher than that of the control group. The findings suggested that horizontal transfer of M. anisopliae occurred in both species, which was further supported by microscopy observation and the activity of immune-related enzymes in the donor, recipient, and secondary recipient. Our findings demonstrated a specific method for improving pest control by combining aggregation behavior with the use of biopesticides, thereby enhancing the understanding of biological management strategies.
Remaking trade for a sustainable future
Authors: Trachtman Joel , Remy Jan Yves , Esty Daniel C 
Published: January 2025

Abstract
The articles in this Special Feature have been developed as part of the Remaking Trade for a Sustainable Future Project and are a part of the research and analysis that formed the background for the Villars Framework 2.0 report prepared through that project to develop a vision for reform of the international trade system in order to promote sustainable development.
Fisheries subsidies, the WTO, and sustainability
Authors: De Gama Mustaqeem 
Published: January 2025

Abstract
This article analyses the World Trade Organization (WTO) fisheries subsidies mandate and the outcomes of the 12th and 13th Ministerial Conferences. It assesses the relative merits of outcomes under the various pillars of negotiations and recommends a greater focus on addressing issues such as special and differential treatment, overfishing, and overcapacity. In order to address overfishing and overcapacity, WTO members that subsidize long-range fishing must drastically reduce such subsidies due to their deleterious impact on fish stocks, the marine environment, and the livelihoods of millions of low resource fishers.
Topical review: sleep regulation as a novel target for treating preschool-aged children with attention-deficit/hyperactivity disorder symptoms
Authors: Lunsford-Avery Jessica R , Wu Jade Q , French Alexis , Davis Naomi O 
Published: January 2025

Abstract

Objective
Elevated attention-deficit/hyperactivity disorder (ADHD) symptoms in preschoolers are a risk factor for poorer psychiatric health, cognitive deficits, and social and academic impairment across the lifespan. The first-line treatment for these preschoolers, behavioral parent training (BPT), reduces children’s disruptive behaviors and parenting stress, yet its impact on core ADHD symptoms is inconsistent. Early interventions targeting biological mechanisms linked to core ADHD pathophysiology are critically needed.

Methods
This topical review explores sleep dysregulation as a potential key target for early intervention for ADHD symptoms among preschoolers.

Results
Sleep dysregulation is common in school-aged children with ADHD, and treating sleep improves core ADHD symptoms in older children. Cross-sectional and prospective research with preschoolers offers compelling evidence that sleep dysregulation and ADHD symptoms are closely linked over the course of early development. BPT and behavioral sleep medicine (BSM) interventions share an underlying theoretical framework and could be streamlined to target sleep in addition to daytime behaviors.

Conclusions
Novel early interventions targeting underlying biological mechanisms linked to core ADHD pathophysiology are critically needed to improve the trajectories of ADHD symptoms, comorbidity, and functional deficits for preschoolers with elevated ADHD symptoms. Sleep regulation is a promising mechanistic treatment target for this population, and future interventions may draw from the shared behavioral principles of BPT and BSM to target behaviors across the 24-hr period and employ scalable formats to optimize the number of families who can benefit from parent-based interventions targeting ADHD symptoms and sleep in early development.
Persistent ascending mesocolon: an unexpected content in a giant and complex paraumbilical hernia of a 48-year-old obese woman
Authors: Naabo Nuhu N , Maalman Raymond S , Adamu Aishah F , Naabo Mohammed N , Mensah Samuel 
Published: January 2025

Abstract
Persistent ascending mesocolon (PAM) is a rare congenital anomaly in ⁓2%–4% of individuals. PAM is associated with various complications, including volvulus of the colon and caecum, bowel perforation, intestinal obstruction, and adhesions. This case is reported on a 48-year-old woman who reported to the Ho Teaching Hospital specialist clinic with a 13-year history of initial painless and reducible paraumbilical swelling. Management was based on a surgical approach. The content of the hernia sac was unusual with a viable appendix, caecum, ascending and transverse colons inclusive, and ascending mesocolon was persistent. The repair was done through an anterior component separation technique. An onlay mesh repair was fashioned with a 30 cm × 30 cm polypropylene mesh. This case report highlights the complexities of managing a giant paraumbilical hernia in a morbidly obese patient with a PAM, a rare congenital anomaly.
Increased burstiness at high redshift in multiphysics models combining supernova feedback, radiative transfer, and cosmic rays
Authors: Dome Tibor , Martin-Alvarez Sergio , Tacchella Sandro , Yuan Yuxuan , Sijacki Debora 
Published: January 2025

ABSTRACT
We study star formation variability, or burstiness, as a method to constrain and compare different galaxy formation models at high redshift using the azahar simulation suite. The models range from magnetohydrodynamics with turbulence-driven star formation to more sophisticated set-ups incorporating radiative transfer and cosmic ray physics. Analysing a sample of galaxies at redshifts $z=4-10$, we find that including both radiative transfer and cosmic rays results in more regular star formation periodicity, as revealed by the Lomb–Scargle periodogram. While both radiative transfer and cosmic rays amplify star formation stochasticity, their combination leads to the largest scatter in burst intensity and the most pronounced deviations from the star-forming main sequence. To compare this comprehensive model against observations, we generate a mock spectrum of a low-mass galaxy during a mini-quenching event at $z=7.5$. The resulting spectrum aligns well with the low-mass quiescent galaxy JADES-GS-z7-01-QU observed at $z=7.3$, though discrepancies attributed to stellar metallicity suggest it may have a composite nature. Our findings highlight the importance of including complex physical processes like cosmic rays and radiative transfer in simulations to accurately capture the bursty nature of star formation in early galaxy formation. Future JWST observations, particularly of the scatter around the star-forming main sequence, might provide critical constraints for numerical models of galaxy formation at high redshift.
Selection Can Favor a Recombination Landscape That Limits Polygenic Adaptation
Authors: Parée Tom , Noble Luke , Roze Denis , Teotónio Henrique 
Published: January 2025

Abstract
Modifiers of recombination rates have been described but the selective pressures acting on them and their effect on adaptation to novel environments remain unclear. We performed experimental evolution in the nematode Caenorhabditis elegans using alternative rec-1 alleles modifying the position of meiotic crossovers along chromosomes without detectable direct fitness effects. We show that adaptation to a novel environment is impaired by the allele that decreases recombination rates in the genomic regions containing fitness variation. However, the allele that impairs adaptation is indirectly favored by selection, because it increases recombination rates and reduces the associations among beneficial and deleterious variation located in its chromosomal vicinity. These results validate theoretical expectations about the evolution of recombination but suggest that genome-wide polygenic adaptation is of little consequence to indirect selection on recombination rate modifiers.
Interplay between the Xer recombination system and the dissemination of antibioresistance in Acinetobacter baumannii
Authors: Blanchais Corentin , Pages Carine , Campos Manuel , Boubekeur Kenza , Contarin Rachel , Orlando Mathias , Siguier Patricia , Laaberki Maria-Halima , Cornet François , Charpentier Xavier , Rousseau Philippe 
Published: January 2025

Abstract
Antibiotic-resistant infections are a pressing clinical challenge. Plasmids are known to accelerate the emergence of resistance by facilitating horizontal gene transfer of antibiotic resistance genes between bacteria. We explore this question in Acinetobacter baumannii, a globally emerging nosocomial pathogen responsible for a wide range of infections with a worrying accumulation of resistance, particularly involving plasmids. In this species, plasmids of the Rep_3 family harbor antibiotic resistance genes within variable regions flanked by potential site-specific recombination sites recognized by the XerCD recombinase. We first show that the Xer system of A. baumannii functions as described in Escherichia coli, resolving chromosome dimers at the dif site and recombining plasmid-carried sites. However, the multiple Xer recombination sites found in Rep_3 plasmids do not allow excision of plasmid fragments. Rather, they recombine to cointegrate plasmids, which could then evolve to exchange genes. Cointegrates represent a significant fraction of the plasmid population and their formation is controlled by the sequence of recombination sites, which determines the compatibility between recombination sites. We conclude that plasmids in A. baumannii frequently recombine by Xer recombination, allowing a high level of yet controlled plasticity in the acquisition and combination of antibiotic resistance genes.
SProtFP: a machine learning-based method for functional classification of small ORFs in prokaryotes
Authors: Khanduja Akshay , Mohanty Debasisa 
Published: January 2025

Abstract
Small proteins (≤100 amino acids) play important roles across all life forms, ranging from unicellular bacteria to higher organisms. In this study, we have developed SProtFP which is a machine learning-based method for functional annotation of prokaryotic small proteins into selected functional categories. SProtFP uses independent artificial neural networks (ANNs) trained using a combination of physicochemical descriptors for classifying small proteins into antitoxin type 2, bacteriocin, DNA-binding, metal-binding, ribosomal protein, RNA-binding, type 1 toxin and type 2 toxin proteins. We have also trained a model for identification of small open reading frame (smORF)-encoded antimicrobial peptides (AMPs). Comprehensive benchmarking of SProtFP revealed an average area under the receiver operator curve (ROC-AUC) of 0.92 during 10-fold cross-validation and an ROC-AUC of 0.94 and 0.93 on held-out balanced and imbalanced test sets. Utilizing our method to annotate bacterial isolates from the human gut microbiome, we could identify thousands of remote homologs of known small protein families and assign putative functions to uncharacterized proteins. This highlights the utility of SProtFP for large-scale functional annotation of microbiome datasets, especially in cases where sequence homology is low. SProtFP is freely available at http://www.nii.ac.in/sprotfp.html and can be combined with genome annotation tools such as ProsmORF-pred to uncover the functional repertoire of novel small proteins in bacteria.
Long-read structural and epigenetic profiling of a kidney tumor-matched sample with nanopore sequencing and optical genome mapping
Authors: Margalit Sapir , Tulpová Zuzana , Detinis Zur Tahir , Michaeli Yael , Deek Jasline , Nifker Gil , Haldar Rita , Gnatek Yehudit , Omer Dorit , Dekel Benjamin , Baris Feldman Hagit , Grunwald Assaf , Ebenstein Yuval 
Published: January 2025

Abstract
Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural variants (SVs) and copy number variations (CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing [Oxford Nanopore Technologies (ONT)] bridge this resolution gap and offer enhanced performance for cytogenetic applications. Additionally, both methods can capture epigenetic information as they profile native, individual DNA molecules. We compared the effectiveness of the two methods in characterizing the structural, copy number and epigenetic landscape of a clear cell renal cell carcinoma tumor. Both methods provided comparable results for basic karyotyping and CNVs, but differed in their ability to detect SVs of different sizes and types. ONT outperformed OGM in detecting small SVs, while OGM excelled in detecting larger SVs, including translocations. Differences were also observed among various ONT SV callers. Additionally, both methods provided insights into the tumor’s methylome and hydroxymethylome. While ONT was superior in methylation calling, hydroxymethylation reports can be further optimized. Our findings underscore the importance of carefully selecting the most appropriate platform based on specific research questions.
Mapping glioma’s impact on cognition: Insights from macrostructure, microstructure, and beyond
Authors: Cayuela Nuria , Izquierdo Cristina , Vaquero Lucía , Càmara Estela , Bruna Jordi , Simó Marta 
Published: January 2025

Abstract

Background
Cognitive impairment (CI) significantly impacts the quality of life of glioma patients. The main contributing risk factors include tumor characteristics, treatment-related factors, and their complex interplay. This review explores the role of advanced structural neuroimaging techniques in understanding CI in glioma patients.

Methods
A literature search was conducted in PubMed, PsycINFO, and ISI Web of Knowledge using specific keywords. We included studies with advanced magnetic resonance imaging techniques and objective neuropsychological exams.

Results
At diagnosis, during the pre-surgery phase, associations between glioma characteristics and cognitive outcomes have been described. Specifically, patients with isocitrate dehydrogenase (IDH)-wild-type gliomas exhibit more adverse cognitive outcomes, accompanied by disruptions in gray (GM) and white matter (WM) networks when compared to IDH-mutant. In addition, pre- and post-surgery imaging analyses highlight the importance of preserving specific WM tracts, such as the inferior longitudinal and arcuate fasciculus, in mitigating verbal memory and language processing decline. Furthermore, examining gliomas in perisylvian regions emphasizes deleterious effects on various cognitive domains. Additionally, it has been suggested that neuroplastic reorganization could serve as a compensatory mechanism against CI. Lastly, a limited number of studies suggest long-term CI linked to GM atrophy and leukoencephalopathy induced by radiotherapy ± chemotherapy in glioma survivors, highlighting the need for improving treatment approaches, particularly for patients with extended survival expectations.

Conclusion
This review underscores the need for nuanced understanding and an individual approach in the management of glioma patients. Neuroplastic insights offer clinicians valuable guidance in surgical decision-making and personalized therapeutic approaches thus improving patient outcomes in neuro-oncology.
Construction of the Gene Tagging and Knock Out system for reliable genetic analysis of nuclear genes in Cyanidioschyzon merolae
Authors: Bora Prerna , Tanaka Kan 
Published: January 2025

Abstract
The unicellular red alga Cyanidioschyzon merolae is a eukaryotic photosynthetic model organism used for basic and applied cell biology studies. Its nuclear genome can be modified by homologous recombination with exogenously introduced DNA. The comparison of mutants with isogenic strains is critical for reliable genetic analyses; however, this has been impossible thus far. Strain construction and genetic complementation studies take a long time and give rise to unstable phenotypes. In this study, we modified the pMKT vector system described in Takemura et al. (Takemura, T., Imamura, S., Kobayashi, Y. and Tanaka, K. (2018) Construction of a selectable marker recycling system and the use in epitope tagging of multiple nuclear genes in the unicellular red alga Cyanidioschyzon merolae. Plant Cell Physiol. 59: 2308–2316.) by adding an upstream sequence of the target gene, after the URA5.3 T marker, to create a double sandwich of repeat elements at the target gene genomic loci after transformation. 5-Fluoroorotic acid selection-based DNA excision yields two mutants simultaneously: an epitope-tagged mutant with only the URA5.3 marker eliminated and a knockout mutant with both URA5.3 T and the target gene’s open reading frame eliminated. This system can provide multiple sets of isogenic controls in parallel, and further reveal the essentialness of a gene. Here, we introduce the multifunctional mutant design system Gene Tagging and Knock Out (GTKO), and demonstrate its utility by creating GTKO mutants of the CmBTB1 and CmBTB2 genes in C. merolae.
Genetic insights into visceral obesity with health conditions, from disease susceptibility to therapeutic intervention
Authors: Zhang Genshan , Han Baolin , Chen Yanghui , Jiang Wei , Fu Jie , Xu Xiangshang , Luo Xuelai , Cao Zhixin 
Published: January 2025

Abstract

Purpose
This study aimed to investigate the relationship between visceral obesity and various disease traits, as well as to identify potential safe targets for the prevention and treatment of visceral obesity.

Study Design
Univariable and multivariable Mendelian randomization (MR) analyses were performed to examine the associations between visceral obesity and 1883 disease traits. Furthermore, we assessed the potential effect of 1684 protein expressions on visceral obesity using the available quantitative trait locus data for plasma proteins. To evaluate the potential safety profiles associated with biomarker intervention, we conducted phenome-wide MR using 1883 outcomes, focusing on the significant biomarkers.

Results
Visceral obesity was significantly associated with elevated risks of 183 disease traits across multiple systems, such as endocrine, cardiovascular, respiratory, digestive, musculoskeletal, and genitourinary systems. Higher genetically predicted levels of GCKR, CYB5A, ITPKA, and ENTPD6 were found to increase the risk of visceral obesity, while 1433B, SEMA3G, FOXO3, and HAPLN4 were associated with a decreased risk of visceral obesity. The results of the phenome-wide MR analysis indicate that CYB5A, ENTPD6, 1433B, and HAPLN4 can potentially be safe and effective drug targets for visceral obesity treatment.

Conclusions
This study indicates visceral obesity is associated with an increased risk of diseases within various physiological systems, such as cardiovascular, respiratory, and endocrine systems. The circulatory proteome reveals eight novel biomarkers for visceral obesity intervention, with CYB5A, ENTPD6, 1433B, and HAPLN4 displaying particular potential as safe and effective drug targets.