bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinically actionable hypertrophic cardiomyopathy genes in South Asian Indians
Authors: Rao Vinay J , Sairam Thiagarajan , Rathinavel Andiappan , Mohanan Kurukkanparampil Sreedharan , Ahamed Hisham , Shenthar Jayaprakash , Dhandapany Perundurai S
Published: February 2025

Background

Primary hypertrophic cardiomyopathy (HCM) is predominantly a genetic disease causing left ventricular hypertrophy in the absence of other cardiac and systemic metabolic diseases. Currently, limited data exists on the prevalence of clinically actionable gene variants for primary HCM in South Asian Indians (SAI), that is necessary for minimizing disparities in interpreting ancestry-specific variants.

Objectives

The ClinGen Hereditary Cardiovascular Disorders (HCVD) Gene Curation Expert Panel categorized HCM-causing genes into five categories according to their clinical relevance: definitive, strong, moderate, limited, and disputed. However, comprehensive studies examining this classification in SAI are lacking.

Methods

Whole-exome sequencing was performed for 335 primary SAI-HCM patients, including all known cardiovascular genes and clinically actionable gene categories to determine their allele frequencies.

Results

SAI-HCM exomes revealed a total of 194 P/LP and VUS across 26 clinically actionable genes in 119 (35.52%) of the 335 cases. The SAI-HCM cohort exhibited significantly fewer variants in the 12 definitive category genes compared to other global HCM cohorts (17.33% vs. 41.21%, P = 0.0003). For the five strong/moderate genes, no significant difference was observed between the SAI-HCM cohort and other global HCM cohorts (2.59% vs. 2.49%, P = 1). Among the 21 limited and disputed genes,MYH6showed a significantly higher prevalence of variants in the SAI-HCM cohort than in the other global HCM cohorts (5.07% vs. 1.67%, P = 0.0408).

Conclusions

The clinically actionable gene variants in SAI-HCM cohort differed significantly from other global HCM cohorts, specificallyMYBPC3,MYH7, andMYH6.
Immune, metabolic, anatomical, and functional features of people after successful tuberculosis treatment: an exploratory analysis
Authors: Webber Tariq , Macdonald Candice , Tameris Michele , Tredoux Nicolette , Bierman Anandi , Gutschmidt Andrea , Tönsing Susanne , Hiemstra Andriëtte , Noor Firdows , Snyders Candice , Richardson Tracy , Fransman Bernadine , Allwood Brian , Hatherill Mark , Kleynhans Leanie , Loxton André G. , Walzl Gerhard , Chegou Novel , du Plessis Nelita , Shaw Jane A , Malherbe Stephanus T.
Published: February 2025

Background

We explored the underlying mechanisms that may drive Post-tuberculosis (TB) lung disease, a multifactorial, heterogenous, and prevalent disease.

Methods

Extensive clinical phenotyping through fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) scans, pulmonary function testing, and symptom and quality of life questionnaires, was performed on a cohort of 48 adults who completed TB treatment within 6 months prior. Immunological characteristics of paired blood- and bronchoalveolar lavage fluid (BALF)-derived immune cells were assessed by multiplex bead-based immunoassay, ELISA and flow cytometry.

Results

There was agreement between measures of inflammation on PET, the severity of anatomical abnormalities on CT, and pulmonary function testing. However, of these, only PET was associated with exercise tolerance and symptom scores. Measures of radiologic extent (total glycolytic activity and SUVmax on PET, and segments involved on CT) also correlated with proteins detected in blood that implicate Type 1 (IFN-γ, TNFα, IL-12) and Type 2 (IL-4, IL-33) responses, ongoing remodelling of lung tissue (MMPs), airways and vasculature (VEGF), as well as subsets of activated CD8+and CD4+T-cells.

Conclusion

The radiologic extent of structural post-TB lung involvement is associated with a range of impaired lung function measures and immunological dysregulation. Our findings suggest that obstructive and restrictive lung pathology due to pulmonary tuberculosis do not occur in opposition but rather point towards a mixed pathology in most TB survivors.
Longitudinal associations between parental bonding and child preschool social-emotional problems: The unique and combined role of mothers and fathers
Authors: Hatakka Enni , Flykt Marjo , Rusanen Erja , Kylliäinen Anneli , Paavonen E. Juulia , Kiviruusu Olli
Published: February 2025

Research is currently limited on the impact of maternal and especially paternal postpartum bonding on child social-emotional development. This study is part of the nationally representative CHILD-SLEEP -sample (n = 710 families), where postpartum bonding was assessed with Postpartum Bonding Questionnaire (PBQ) at the child age of eight months, and child social-emotional problems were assessed with the Five to Fifteen (FTF) and the Strengths and Difficulties Questionnaire (SDQ) at child age of five years. Both maternal and paternal postpartum bonding difficulties at eight months were associated with child externalizing, internalizing and peer problems at five years. When parental depressive symptoms were controlled, the association remained significant only with internalizing problems. When investigating joint maternal and paternal bonding, we found both cumulative and mother-driven effects with child internalizing problems. The results emphasize the role of early parental bonding for later child mental health, highlighting the importance of early parental support.
Sentiment analysis of employees and COVID-19 vaccine hesitancy at workplace
Authors: Akpan Ikpe Justice , Warner Teai , Peters Mbuotidem
Published: February 2025

Vaccination is a potent means to combat the spread of infectious disease epidemics or pandemics, such as the COVID-19 pandemic. However, getting sufficient people to accept the vaccine and achieve herd immunity remains a significant challenge. This study evaluates preschool workers’ sentiments and challenges during in-person schooling amidst the COVID-19 pandemic and attitudes toward COVID-19 vaccination through a survey. The study surveyed preschool workers as part of a consulting project. Workers’ sentiments are analyzed using Azure Machine Learning (AML) data analytic method, statistical analysis, and theoretical evaluation. The results show that no association exists between employee job category (teachers versus support staff) and COVID-19 vaccine hesitancy. However, fewer teaching staff were hesitant to take the COVID-19 vaccine than the support staff (46% < 50%), but the difference was not significant [Chi-Square (χ2) = 0.009; p>0.05]. The overall sentiments of all preschool workers showed 46%, indicating low neutrality, implying hesitancy toward the COVID-19 vaccine. Preschool workers who felt optimistic about the vaccine’s potency cited scientific reasons; those with neutral sentiments needed further information and assurances about the side effects, indicating that appropriate health education can sway more people positively towards accepting the vaccine; people with negative sentiments displayed distrust, fear, personal beliefs, and misinformation. The results also highlight the need to educate all workers on vaccine potency despite the levels of education. Regardless of academic qualifications, any uninformed person can fall prey to misinformation and conspiracy theories. Proper health education helps people make informed decisions.
A Hybrid Data-Driven Approach For Analyzing And Predicting Inpatient Length Of Stay In Health Centre
Authors: Chowdhury Tasfia Noor , Mou Sanjida Afrin , Rahman Kazi Naimur
Published: February 2025

Patient length of stay (LoS) is a critical metric for evaluating the efficacy of hospital management. The primary objectives encompass to improve efficiency and reduce costs while enhancing patient outcomes and hospital capacity within the patient journey. By seamlessly merging data-driven techniques with simulation methodologies, the study proposes an all-encompassing framework for the optimization of patient flow. Using a comprehensive dataset of 2.3 million de-identified patient records, we analyzed demographics, diagnoses, treatments, services, costs, and charges with machine learning models (Decision Tree, Logistic Regression, Random Forest, Adaboost, LightGBM) and Python tools (Spark, AWS clusters, dimensionality reduction). Our model predicts patient length of stay (LoS) upon admission using supervised learning algorithms. This hybrid approach enables the identification of key factors influencing LoS, offering a robust framework for hospitals to streamline patient flow and resource utilization. The research focuses on patient flow corroborates the efficacy of the approach, illustrating decreased patient length of stay within a real healthcare environment. The findings underscore the potential of hybrid data-driven models in transforming hospital management practices. This innovative methodology provides generally flexible decision-making, training, and patient flow enhancement; such a system could have huge implications for healthcare administration and overall satisfaction with healthcare.
Discovery and optimization of a guanylhydrazone-based small molecule to replace bFGF for cell culture applications
Authors: Feofanov Mikhail , Daubner Gerrit Martin , Saltalamacchia Andrea , Köhler Karsten , Schulz Christine , Henry Clare Elizabeth , Ziegler Michael Josef , Benabderrahmane Mohammed , Hiault Florence Andrée Suzanne , Decker Tim-Michael , Shen Mei-Chun , Pahl Jürgen , Lambertz Sophie , Noori Hamid R.
Published: February 2025

Replacing growth factors with a synthetic alternative molecule is an attractive opportunity to increase consistency, scalability and cost-effectiveness of cell-based products. Herein, we describe the discovery of a chemical class of FGFR1 agonists mimicking the action of basic fibroblast growth factor (bFGF), an essential component of cell-culture media. The guanylhydrazone-based molecule, TCB-32, was identified via structure-based virtual screening on the orthosteric binding site of FGFR1. It was shown to significantly increase cell proliferation by activating the FGFR1 signalling pathway like bFGF and exhibited enhanced thermostability over bFGF by containing activity over the course of several days. After extensive structure-activity relationship studies it was possible to increase potency and efficacy leading to three highly potent agonists. This finding has the potential to remove current bottlenecks in large-scale cell production as required for applications like cultivated meat or cell therapy.

GRAPHICAL ABSTRACT

HIGHLIGHTS

Discovery of a highly potent small molecule to replace bFGF in serum-free medium

Activation of proliferation through the FGFR1-signalling pathway

Enhanced thermal stability over bFGF

SAR led to three small molecules with decreased EC50, named TCB-494, TCB-541 and TCB-621
BlueBerry: Closed-loop wireless optogenetic manipulation in freely moving animals
Authors: Nourizonoz Ali , Girard Benoit , Guyoton Maëlle , Galiñanes Gregorio , Thurnherr Raphael , Pellat Sebastien , Bellone Camilla , Huber Daniel
Published: February 2025

Optogenetics is a powerful tool for neuroscientists, enabling manipulations of neuronal activity to explore their effects on behavior. Recent advances in wireless technology enabled the development of novel remotely controlled optogenetic devices, thereby promising to facilitate the study of more complex behaviors, including social interactions. Yet, studying such behaviors in real time and automated manner in large scale naturalistic settings or with multiple animals remains challenging. In addition, many published devices can only be reproduced in labs having specific engineering skills and fabrication facilities and are thus not accessible for the larger neuroscience community. Here we introduce BlueBerry, an open-source, multi-channel optogenetic device that can be assembled with off the shelf components. The lightweight (1.4 g) design and robust long-range communication makes Blueberry an ideal tool for behavior-triggered optogenetic studies with multiple animals interacting freely in a large-scale setting. We show how BlueBerry can be used to guide decision making during spatial navigation and demonstrate for the first time that social dynamics can be rapidly altered in groups of mice by triggering specific social behavior with closed-loop optogenetics.
Improving American chestnut resistance to two invasive pathogens through genome-enabled breeding
Authors: Westbrook Jared W , Malukiewicz Joanna , Sreedasyam Avinash , Jenkins Jerry W , Zhang Qian , Lakoba Vasiliy , Fitzsimmons Sara F. , Van Clief Jamie , Collins Kendra , Hoy Stephen , Stark Cassie , Grabowski Lake , Jenkins Eric , Saielli Thomas , Jarrett Benjamin T. , Wigfield Lucinda , Kerwien Lauren M. , Wilbur Ciera , Sandercock Alexander , Craddock James Hill , Zannini Paola , Kerio Susanna , Zhebentyayeva Tatyana , Fan Shenghua , Thomas Austin , Abbott Albert , Nelson Charles Dana , Xia Xiaoxia , Williams Melissa , Boston LoriBeth , Plott Christopher , Carle Florian , Swatt Jack , Ostroff Jack , Jeffers Steven , Mckeever Kathleen , Smith Erica , Ellis Thomas J , James Joseph B , Sisco Paul , Newhouse Andrew E , Carlson Erik , Powell William A , Hebard Frederick V , Scrivani John , Heverly Caragh , Cipollini Martin , Clark Brian , Evans Eric , Levine Bruce , Carlson John , Goodstein David M , Grimwood Jane M , Schmutz Jeremy , Holliday Jason , Lovell John T
Published: February 2025

Over a century after two introduced pathogens decimated American chestnut populations, breeding programs continue to incorporate resistance from Chinese chestnut to recover self-sustaining populations. Due to complex genetics of chestnut blight resistance, it is challenging to obtain trees with sufficient resistance and competitive growth. We developed high quality reference genomes for Chinese and American chestnut and leveraged large disease phenotype and genotype datasets to develop accurate genomic selection. Inoculation and simulation results indicate that resistance may be substantially increased in trees that inherited 70% to 100% of their genome from American chestnut. To facilitate gene editing, we integrated multiple lines of evidence to discover candidate alleles for blight resistance and susceptibility. These genomic resources provide a strong foundation to accelerate restoration of this iconic tree.
A Bayesian decision-making model of implicit motor learning from internal and external errors
Authors: Kim Hyosub E. , Chua Romeo , Hu Davin
Published: February 2025

A key challenge for the sensorimotor system is deciding which errors to learn from and which to ignore. Recent work has shown that humans are remarkably precise in parsing movement errors into internally- and externally-generated components for this purpose: Participants automatically ignore internally-generated reaching errors caused by motor noise, yet implicitly adapt to size-matched externally-generated errors caused by visuomotor rotations (Ranjan & Smith 2018, 2022). Following replication of these results with 16 neurotypical adults, we formalized our understanding of this behavior with a novel Bayesian decision-making model. The Parsing of Internal and External Causes of Error (PIECE) model frames adaptation as a process of causal inference regarding the source of error, with the magnitude of motor corrections reflecting a combination of state estimation and the observer’s degree-of-belief that their movement was externally perturbed. Thus, PIECE presents a challenge to a class of computational models that frames adaptation as a process of re-aligning the perceived hand position with the movement goal. We show that only PIECE can capture the precise parsing of internal versus external errors observed. Combined, this work provides a normative explanation of how the nervous system discounts intrinsic motor noise and adapts to perturbations, keeping movements finely-calibrated.
InfEHR: Resolving Clinical Uncertainty through Deep Geometric Learning on Electronic Health Records
Authors: Kauffman Justin , Holmes Emma , Vaid Akhil , Charney Alexander W , Kovatch Patricia , Lampert Joshua , Sakhuja Ankit , Zitnik Marinka , Glicksberg Benjamin S , Hofer Ira , Nadkarni Girish N
Published: February 2025

Electronic health records (EHRs) contain multimodal data that can inform diagnostic and prognostic clinical decisions but are often unsuited for advanced machine learning (ML)–based patient-specific analyses. ML models and clinical heuristics learn generalizable relationships from predefined factors, yet many patients may not benefit if those factors are missing in the EHR or differ—however subtly—from typical training populations. Clinical heuristics are limited to low complexity, often linear, relationships and patterns between clinical variables. ML approaches in EHRs significantly expand pattern sophistication but require large, labeled datasets, which are often unattainable especially in low prevalence diseases and are limited by sources of random and non-random variation in EHRs. Deep learning (DL), in contrast with ML and clinical heuristics, learns features without predefinition but requires even greater label access for predictions. While DL can construct unsupervised EHR representations, the patterns and characteristics of less prevalent examples are poorly resolved, and downstream clinical applications still require labels. We present Inf-EHR, a framework to automatically compute clinical likelihoods from whole EHRs of patients from diverse clinical settings without need of large volumes of labeled training data. We apply deep geometric learning to EHRs through a novel procedure that converts whole EHRs to temporal graphs. These graphs naturally capture phenotypic temporal dynamics leading to unbiased representations. Using only a few labeled examples, InfEHR computes and automatically revises likelihoods leading to highly performant inferences especially in low prevalence diseases which are often the most clinically ambiguous. To demonstrate utility, we use EHRs from the Mount Sinai Health System and The University of California, Irvine Medical Center and test its performance compared to physician-provided clinical heuristics across two diseases with no clinical or epidemiological overlap: a rare disease (neonatal culture-negative sepsis) with prevalence of 2% in neonates, and a more common disease (adult post-operative acute kidney injury) with prevalence of 22%. We show that Inf-EHR is superior to existing clinical heuristics both for culture-negative sepsis (sensitivity: 0.65 vs .041, specificity: 0.99 vs.0.98) and post-operative acute kidney injury (sensitivity: 0.72 vs 0.20, specificity: 0.91 vs 0.97). We present the first application of geometric deep learning in EHRs that can be used in real world clinical settings at scale, for improving phenotype identification and resolving clinical uncertainty.
Stakeholder Networks and Systems for Health Equity: Accessibility of Newly Commissioned District Hospitals in Ghana
Authors: Frimpong Felix , Peprah Charles , Owusu-Addo Ebenezer
Published: February 2025

Equitable access to healthcare necessitates the establishment of resilient stakeholder networks and comprehensive systemic integration to address the multifaceted needs of heterogeneous populations effectively. This research critically assesses the significance of stakeholder engagement in the planning and the provision of newly commissioned district hospitals in Ghana’s Ashanti Region, examining the extent to which their contributions influenced dimensions of accessibility and the uptake of services.

A convergent parallel mixed-method design was employed, incorporating qualitative methods (indepth interviews) with stakeholders such as healthcare providers, community leaders, and local officials, and quantitative data was collected from healthcare seekers. The study applied an accessibility framework—availability, affordability, accommodation, geographical access, and acceptability—to assess the impact of systemic and stakeholder-driven initiatives.

Stakeholder networks played a crucial role in the strategic planning and provision of the newly commissioned district hospital services. The collaborative decision-making process facilitated the key dimensions of access to healthcare to be prioritized. Nevertheless, the issue of affordability surfaced as a systemic limitation that critically impacted service utilization, particularly among economically disadvantaged populations. The research findings indicated that demographic groups characterized by female gender, advanced age, and higher educational attainment derived greater benefits from the stakeholder-oriented planning methodologies, whereas rural populations and those belonging to socio-economically disadvantaged backgrounds encountered substantial obstacles.

The findings underscore the critical role of stakeholder networks in health promotion. Their engagement ensured alignment between systemic goals and community needs, fostering service uptake and reducing disparities. The study emphasizes the importance of leveraging multi-level connections between policy, health systems, and community networks to achieve Universal Health Coverage and Sustainable Development Goal 3
Psychosis-linked Symptoms and Structural Brain Patterns in Cognitive Subgroups among Familial High-Risk Children in the ABCD Study
Authors: Türközer Halide Bilge , Karcher Nicole R. , Clauss Jacqueline , Nordentoft Merete , Lewandowski Kathryn E. , Roffman Joshua L. , Öngür Dost
Published: February 2025

Objective

Children at familial high risk for psychosis (FHR) are at substantially increased risk for psychotic disorders and other serious mental illnesses. Identifying risk subgroups within FHR youth may enhance prediction models to identify children at greatest risk for potential intervention. This study investigated psychosis-linked symptoms and structural brain patterns in neurocognitive subgroups among FHR children in the Adolescent Brain Cognitive Development (ABCD) Study using baseline, 2-year, and 4-year follow-up data.

Methods

Among children with first- and second-degree family history of psychosis, neurocognitive subgroups were defined using NIH Toolbox Cognitive Battery baseline age-corrected total scores: children with low (FHR-LC, 0-33%, n=234), moderate (FHR-MC, 33-66%, n=261), and high (FHR-HC, 66-100%, n=277) cognitive performance. Psychiatric symptoms were assessed using Prodromal Questionnaire-Brief Child Version (PQ-BC) and Childhood Behavior Checklist (CBCL). Regional vulnerability indices (SSD-RVIs), which quantify the similarity of participants’ structural brain patterns to the patterns found in adults with schizophrenia spectrum disorders, were calculated using cortical thickness measures following rigorous quality control.

Results

At baseline, FHR-LC had significantly higher PQ-BC and CBCL scores, and trend-level higher SSD-RVIs compared to FHR-HC. Longitudinally, PQ-BC and CBCL scores decreased with age across all FHR participants, while SSD-RVIs remained stable. No longitudinal cognitive subgroup-by-age interactions were observed, indicating that subgroup differences persisted over time.

Conclusion

Children at FHR who have concurrent poor cognitive performance exhibit elevated and stable clinical and imaging psychosis risk markers. This suggests that they may represent a risk subgroup with elevated vulnerability, presenting an opportunity for early identification and intervention.
Prognostic implications of splenomegaly in BCMA-directed CAR T-Cell therapy for relapsed myeloma
Authors: Wiemers Thomas , Ferle Maximilian , Ader Jonas , Sotikova Veronika , Fandrei David , Grieb Nora , Fischer Luise , Born Patrick , Weidner Heike , Wang Song Yau , Jentzsch Madlen , Franke Georg-Nikolaus , Herling Carmen , Metzeler Klaus , Herling Marco , Heyn Simone , Denecke Timm , Reiche Kristin , Platzbecker Uwe , Vucinic Vladan , Meyer Hans-Jonas , Neumuth Thomas , Merz Maximilian
Published: February 2025

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has shown promise for patients with relapsed or refractory multiple myeloma (RRMM), yet its use is often complicated by adverse events such as cytokine release syndrome and hematologic toxicities. This study evaluates the prognostic significance of spleen size, measured via computed tomography (CT), in predicting clinical outcomes for RRMM patients undergoing CAR T-cell therapy. We retrospectively analyzed data from patients treated with Idecabtagene vicleucel or Ciltacabtagen autoleucel (N=73) and show that enlarged spleen size is associated with severe and prolonged thrombocytopenia, higher metabolic tumor volumes, and elevated soluble BCMA (sBCMA) levels. Our findings indicate that splenomegaly (>340 cm³) is an independent prognostic marker for both progression-free and overall survival, outperforming markers such as sBCMA levels, EASIX, and CAR- Hematotox scores. These results suggest that spleen size could enhance risk stratification in CAR T-cell therapy for RRMM patients, offering a readily accessible tool for guiding monitoring strategies and healthcare resource management.
Peripheral Venous Pressure Accurately Evaluates Congestion in Constrictive pericarditis
Authors: Xia Xue , Zhou Jianzhong
Published: February 2025

Background

The primary clinical characteristic of initial constrictive pericarditis(CP) is a cardiac decreased diastolic function, which results in venous congestion, limitation of venous return, and elevated central venous pressure(CVP).

Objective was to evaluate the relationship between peripheral venous pressure (PVP) and CVP with the aim to assess the diagnostic value of PVP in CP.

Methods

Subjects underwent invasive haemodynamic and low invasive peripheral venous pressure assessment and also underwent physical examination, biochemical indices to assess venous congestion and echocardiography to assess cardiac structure and function. Patients were divided into 2 groups by CVP > 22 cmH2O(Modal 1 defined as CVP > 22 cmH2O; Modal 2 defined as CVP≦22cmH2O).

Results

Of the 36 patients, PVP and CVP had a significant positive association (Pearson’s = 0.831; P < 0.0001), with CVP = 0.962 + 0.907PVP as the regression equation.PVP was negatively correlated with FIB-4 (Pearson’s = −0.425; P=0.01), while it was not statistically significantly correlated with Pro-BNP, albumin, serum Na, hematocrit, hemoglobin, total bilirubin, direct bilirubin, or ARPI. Modal 1 and 2 groups were separated based on CVP > 22 cmH2O. By comparing the area under the curve (AUC) of the participants’ working mass, it was definitively established that 24 cmH2O was the ideal PVP threshold for the diagnosis of CP.

Conclusions

In Constrictive Pericarditis, PVP is a reliable, minimally invasive, and accurate technique for calculating CVP, which is remarkably positively correlated with CVP. Measurement of PVP is therefore important in the assessment of congestion and helps in the early diagnosis of Constrictive Pericarditis when PVP is greater than 24 cmH2O.
Two cowpea Rubisco activase isoforms for crop thermotolerance
Authors: Gjindali Armida , Page Rhiannon , Ashton Catherine J. , Robertson Ingrid , Page Mike T. , Bloemers Duncan , Gould Peter D. , Worrall Dawn , Orr Douglas J. , Carmo-Silva Elizabete
Published: February 2025

A vital crop for sub-Saharan Africa, cowpea productivity is threatened by climate change, including increased heatwave intensity, duration, and frequency. Rubisco activase (Rca) is a key molecular chaperone that maintains Rubisco activity and due to its thermal sensitivity is a key target for improving crop climate resilience.

We identified and characterised four Rca isoforms inVigna unguiculata(L.) Walp. cv. IT97K-499-35in vitro: Rca1β, Rca8α, Rca10α and Rca10β. Cowpea leaf and plant growth traits were also investigated during a 5-day +10 °C heatwave that included assessment of Rubisco and Rca activity in leaf extracts, and relative changes in the abundance of the four Rca isoforms.

Cowpea Rca10α and Rca10β had higher thermal maxima, broader thermal optima and higher rates of ATP hydrolysis and Rubisco reactivationin vitro. In the absence of water deficit, the heatwave caused only mild effects, including increases in leaf temperature and expression ofRca10, small decreases in Rubisco activity and activation state, and unaltered temperature response of Rubisco activation by Rca.

The superior Rca10α and Rca10β isoforms offer the prospect of enhancing the thermotolerance of cowpea and other crops in anticipation of more extreme future heatwaves.
Multiple fertility restorer loci for cytoplasmic male sterility caused byorf137in tomato
Authors: Iki Yurie , Harada Issei , Ezura Kentaro , Mashita Seira , Kuwabara Kosuke , Takei Hitomi , Toyoda Atsushi , Shirasawa Kenta , Ariizumi Tohru
Published: February 2025

Cytoplasmic male sterility (CMS) in plants is caused by incompatibility between nuclear and cytoplasmic genetic information. Fertility can be restored through the action of fertility restoration (RF) genes, which are usually present in the nucleus. CMS lines of tomato (Solanum lycopersicum) have been developed from asymmetric cell fusions, in these lines, cultivated tomato served as a nuclear donor and its wild relative,S. acaule, as a cytoplasm donor. AlthoughRFgenes are present in wild relatives of tomato, no genetic or genomic information on the RF genes is yet available. This study reports anRFgenetic locus,RF1, on chromosome 1 ofS. pimpinellifoliumLA1670 andS. lycopersicumvar.cerasiformeLA1673 that was revealed by bulked segregant analysis and sequencing. An additionalRFlocus,RF2, was identified on chromosome 2 of LA1670. A transgenic approach identified two other candidate genes that also restored fertility. The genomic sequence ofS. cheesmaniaeLA0166 was assembled using high-fidelity, long-read sequencing technology. Sequence comparisons identified further candidateRFgenes on chromosome 1 ofS. cheesmaniaeLA0166. These results suggested that multiple gene loci control the fertility restoration trait in wild relatives of tomato.
Polarizing SNPs without outgroup
Authors: Liang Jinyang , Dutheil Julien Y.
Published: February 2025

Asserting which allele is ancestral or derived, known as polarization, is a prerequisite of many population and quantitative genetic methods. In particular, it allows inference of the unfolded site-frequency spectrum (uSFS). The most widely used approaches are based on outgroup data. However, for studies on species for which closely related outgroups are difficult to obtain, information on many sites of interest may be missed due to alignment problems. Here, we present PolarBEAR (Polarization By Estimation of the Ancestral recombination graph), a method that uses the local genealogies from the ancestral recombination graph (ARG) to infer ancestral states. We show that PolarBEAR can reach high accuracy in polarization and uSFS estimation using simulations under several scenarios. This accuracy, however, heavily depends on the ARG used as input. It is maximal when the true ARGs is used, but can be very low depending on the ARG reconstruction method employed. We also applied our method to human population data and compared it with the outgroup-based method est-sfs. Although our method could not infer the ancestral state with high confidence at certain positions, it obtained results for positions that est-sfs could not polarize due to missing outgroup data. The polarization results of the two methods were highly consistent at positions inferred by both methods. The two methods inferred similar uSFS, with PolarBEAR estimating slightly fewer high-frequency derived alleles. Furthermore, we demonstrate that PolarBEAR is robust to the mutation model used, while est-sfs exhibits a bias in the presence of heterogeneous base composition. PolarBEAR can complement outgroup-based methods, or replace them when no appropriate outgroup sequence is available.
Listeria monocytogenescell-to-cell spread bypasses nutrient limitation for replicating intracellular bacteria
Authors: Radhakrishnan Prathima , Theriot Julie A.
Published: February 2025

Listeria monocytogenesis an intracellular bacterial pathogen that obtains nutrients from the mammalian host cell to fuel its replication in cytosol. Sparse infection of epithelial monolayers byL. monocytogenesresults in the formation of distinct infectious foci, where each focus originates from the initial infection of a single host cell followed by multiple rounds of active bacterial cell-to-cell spread into neighboring host cells in the monolayer. We used time-lapse microscopy to measure changes in bacterial growth rate in individual foci over time and found that intracellular bacteria initially replicate exponentially, but then bacterial growth rate slows later in infection, particularly in the center of the infectious focus. We found that the intracellular replication rate ofL. monocytogenesis measurably decreased by limiting host cell glucose availability, by decreasing the rate of intracellular bacterial oligopeptide import, and, most interestingly, by alterations in host cell junctional proteins that limit bacterial spread into neighboring cells without directly affecting bacterial growth or metabolism. By measuring the carrying capacity of individual host cells, we found that the nutritional density of cytoplasm is comparable to rich medium. Taken together, our results indicate that the rate of intracellularL. monocytogenesreplication is governed by a balance of the rate of nutrient depletion by the bacteria, the rate of nutrient replenishment by the metabolically active host cells, and the rate of bacterial cell-to-cell spread which enables the bacteria to seek out “greener pastures” before nutrient availability in a single host cell becomes limiting.

SIGNIFICANCE

Listeria monocytogenesis a foodborne pathogen that is capable of facultative intracellular growth in a wide variety of mammalian cell types. It uses actin-based motility to spread directly from the cytoplasm of one infected host cell into another. After initially infecting cells in the small intestine,L. monocytogenescan circulate inside of infected macrophages, and subsequently spread to cells of distal organs, where it can cause spontaneous abortions in pregnant women and meningitis in immunocompromised individuals. In addition to facilitating body-wide dissemination, the actin-based cell-to-cell spread ofL. monocytogenescontributes to the ability of the pathogen to evade the cell-mediated arm of the immune system. In this work, we find that cell-to-cell spread also benefits the bacteria in a third way, by enabling the bacteria to overcome the nutrient limitation they would face if they remained confined to a single host cell, such that they never enter stationary phase.
Generative latent diffusion language modeling yields anti-infective synthetic peptides
Authors: Torres Marcelo D. T. , Chen Tianlai , Wan Fangping , Chatterjee Pranam , de la Fuente-Nunez Cesar
Published: February 2025

Generative artificial intelligence (AI) offers a powerful avenue for peptide design, yet this process remains challenging due to the vast sequence space, complex structure–activity relationships, and the need to balance antimicrobial potency with low toxicity. Traditional approaches often rely on trial-and-error screening and fail to efficiently navigate the immense diversity of potential sequences. Here, we introduce AMP-Diffusion, a novel latent diffusion model fine-tuned on antimicrobial peptide (AMP) sequences using embeddings from protein language models. By systematically exploring sequence space, AMP-Diffusion enables the rapid discovery of promising antibiotic candidates. We generated 50,000 candidate sequences, which were subsequently filtered and ranked using our APEX predictor model. From these, 46 top candidates were synthesized and experimentally validated. The resulting AMP-Diffusion peptides demonstrated broad-spectrum antibacterial activity, targeting clinically relevant pathogens—including multidrug-resistant strains—while exhibiting low cytotoxicity in human cell assays. Mechanistic studies revealed bacterial killing via membrane permeabilization and depolarization, and the peptides showed favorable physicochemical profiles. In preclinical mouse models of infection, lead peptides effectively reduced bacterial burdens, displaying efficacy comparable to polymyxin B and levofloxacin, with no detectable adverse effects. This study highlights the potential of AMP-Diffusion as a robust generative platform for designing novel antibiotics and bioactive peptides, offering a promising strategy to address the escalating challenge of antimicrobial resistance.
Pica in childhood: concurrent and sequential psychiatric comorbidity
Authors: Rubino Laura , Bulik Cynthia , Chawner Samuel JRA , Micali Nadia
Published: February 2025

Objective:Pica is the persistent eating of non-nutritive, nonfood substances and is associated with serious medical consequences. There has been a lack of research into the psychiatric comorbidities of pica, despite being important for informing clinical care. The current study examines psychiatric comorbidities of pica in childhood and the longitudinal relationship between childhood pica and adolescent eating disorders.Methods:We analyzed data from the Avon Longitudinal Study of Parents and Children study. Pica and psychopathology, assessed with the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire, were assessed at about 7- and 10-years of age, reported eating disorders (ED) at 14-, 16-, and 18-years of age. We conducted linear and logistic regression models, adjusting for covariates, to identify concurrent psychiatric comorbidities, as well as risk for later EDs.Results. Pica was associated with increased odds of any psychiatric disorder and behavioral disorders in early childhood [OR = 7.30,p< .001 and OR = 5.65,p< .001, respectively] and mid-childhood [OR = 5.75,p< .001 and OR = 10.66,p< .001, respectively], and greater concurrent hyperactivity, conduct problems, peer problems, prosocial and emotional difficulties (p<.01 across analyses). We did not find evidence pica presence increased odds for concurrent emotional disorders nor for later ED risk.Discussion: The association between pica and psychiatric and behavioral disorders, indicates a likely shared aetiology. Our findings provide insight into the psychiatric characteristics of children with pica and highlight they may require complex behavioral support beyond their eating difficulties. [250]

Public Significance (for IJED)

This study investigated the relationship between pica (the eating of non-food substances) and mental health conditions in childhood. We found that in childhood, pica was associated with increased odds of having behavioral disorders (e.g., ADHD and conduct disorder) and mental disorder (e.g., anxiety or ADHD) but not emotional disorders (e.g., OCD and depression). Our findings suggest children with pica may require complex behavioral support beyond their eating difficulties.
The yeast phosphofructokinase β-subunit has ATP-dependent RNA unwinding activity and modulates cell cycle progression
Authors: Albihlal Waleed S. , Matia-González Ana M. , Schmidt Tobias , Mayer Wieland , Bushell Martin , Niessing Dierk , Barberis Matteo , Schmidt Alexander , Heinisch Jürgen J. , Gerber André P.
Published: February 2025

Phosphofructokinase (PFK) is a rate-limiting glycolytic enzyme that also possesses an unexplored RNA binding activity. Here, we show that the α- and β-subunits of yeast PFK, encoded byPFK1andPFK2, respectively, bind hundreds of mRNAs in cells, including one’s coding for proteins involved in regulation of mitotic cell cycle. Pkf2p directly binds in a Mg-ATP-dependent manner to short GA-, UC-, AU- and U-rich motifs overrepresented in its mRNA targets. Strikingly, Pfk2p displays directional 5’ - 3’ double-stranded RNA unwinding activity not seen with Pfk1p. Furthermore, Pfk2p dynamically associates with ribosomes and promotes translation of cell cycle genes. Consequently,pfk2Δ,but notpfk1Δ,mutant cells show severely delayed G1/S phase transition which is independent of the enzyme’s glycolytic activity. Our results uncovered a hidden function for the Pfk2 subunit as a translational activator of mitotic cell cycle gene transcripts possibly through energy-dependent RNA unwinding activity.
Multilingual Computational Models Reveal Shared Brain Responses to 21 Languages
Authors: de Varda Andrea Gregor , Malik-Moraleda Saima , Tuckute Greta , Fedorenko Evelina
Published: February 2025

At the heart of language neuroscience lies a fundamental question: How does the human brain process the rich variety of languages? Recent developments in Natural Language Processing, particularly in multilingual neural network language models, offer a promising avenue to answer this question by providing a theory-agnostic way of representing linguistic content across languages. Our study leverages these advances to ask how the brains of native speakers of 21 languages respond to linguistic stimuli, and to what extent linguistic representations are similar across languages. We combined existing (12 languages across 4 language families; n=24 participants) and newly collected fMRI data (9 languages across 4 language families; n=27 participants) to evaluate a series of encoding models predicting brain activity in the language network based on representations from diverse multilingual language models (20 models across 8 model classes). We found evidence of cross-lingual robustness in the alignment between language representations in artificial and biological neural networks. Critically, we showed that the encoding models can be transferred zero-shot across languages, so that a model trained to predict brain activity in a set of languages can account for brain responses in a held-out language, even across language families. These results imply a shared component in the processing of different languages, plausibly related to a shared meaning space.
SVCFit: Inferring structural variant cellular fraction in tumors
Authors: Liu Yunzhou , Lai Jiaying , Wood Laura D. , Karchin Rachel
Published: February 2025

Many tumors evolve through cellular mutation and selection, where subpopulations of cells (subclones) with shared ancestry compete for dominance. Introduction of next generation sequencing enables subclone identification using small somatic. However, there are several advantages to marking subclones with structural variants: they have greater functional impact, play a crucial role in late-stage tumors, and provide a more complete view of genomic instability driving tumor evolution. Here, we present SVCFit, a scalable method to estimate the cellular prevalence of somatic deletions, duplications and inversions. We demonstrate that cellular prevalence estimation can be improved by incorporating distinct read patterns for each structural variant type. Additionally, this improvement is achieved without prior knowledge of tumor purity, which is often inaccurate. Using a combination of simulated data and patient-derived metastatic samples with known mixture proportions, we show that our algorithm achieves significantly greater accuracy than state-of-the-art in estimating the structural variants cellular prevalence (p<0.05). The speed of SVCFit estimation from cost-effective bulk whole-genome sequencing (WGS) makes it well-suited for analyzing large cohorts of sequenced tumor samples, enhancing the accessibility of SV-based clonal reconstruction.
Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring
Authors: Macartney Erin L , Senior Alistair M , Crean Angela J , Small Lewin , Pulpitel Tamara J , Nobrega Marcelo A , Barrès Romain , Simpson Stephen J
Published: February 2025

Brown adipose tissue (BAT) dissipates energy as heat, not only under cold exposure but also in the dissipation of excess ingested energy. Therefore, enhancing BAT activity is a potential avenue to combat weight gain. Dietary macronutrient composition influences BAT size and has recently been shown to influence BAT size of daughters through the patriline of C57BL/6J mice. However, the effects of macronutrient composition and any paternal effects on BAT function have yet to be characterised. Using the Geometric Framework for Nutrition, we investigated the effects of macronutrient composition on the BAT proteome in male mice and intergenerational effects in their offspring. In fathers, >50% of the proteome was affected by macronutrient composition, with distinct clusters of proteins that responded in similar ways. We identified two clusters with inverse patterns that correlated with BAT mass. Notably, UCP1 was reduced on low fat diets that promoted increased BAT mass, while there were increased levels of proteins involved in protein turnover on those same diets. The same diets also led to a reduction in proteins involved in purine biosynthesis (often UCP1 inhibitors). We did not find any effects of paternal diet on the BAT proteome in sons, but paternal protein intake negatively affected basigin expression in daughters - a protein that regulates UCP1 transcription. Our results highlight that dietary macronutrient composition in males remodels the protein expression landscape of BAT, and pre-conceptionally reprograms BAT expression profiles of female offspring.
Optimal membrane fluidity modulates biofilm formation inEscherichia coli
Authors: Hong Yaoqin , Qin Jilong , Totsika Makrina
Published: February 2025

Changes in membrane composition govern the fitness and survival of bacteria in response to environmental stresses. One critical parameter is membrane fluidity, which dictates overall membrane integrity, adaptability to environmental fluctuations (e.g., temperature changes), and the functionality and interactions between integral and peripheral membrane proteins. In recent years, substantial evidence has shown that membrane fluidity is finely tuned for biofilm formation. While high membrane fluidity promotes robust biofilm formation in Klebsiella pneumoniae, this is challenged by reports from multiple species indicating that biofilms are enriched in saturated fatty acids (i.e., reduced fluidity). We hypothesize that this paradox arises from the complex relationship between lipid composition and biofilm formation. Our findings demonstrate that an optimal balance of lipid fluidity is required for biofilm formation. We propose that the precise fluidity required for biofilm growth, relative to that required for planktonic growth, may differ between species, and is readily adjusted during lifestyle transitions.