bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stratification along tropical forest succession enhances pollinator diversity via functionally unique canopies
Authors: Diniz Ugo Mendes , Böttger Dennis , Brehm Gunnar , Lalama Sabine Fernanda Viteri , Frühholz Kilian , Pitz Maximilian , Windl Julia , Rasmussen Claus , Keller Alexander , Leonhardt Sara Diana 
Published: January 2025

ABSTRACTVertical stratification is among the main drivers of biodiversity in forests. Canopies are a key spatial component for primary consumers due to a higher concentration of resources, but methodological constraints impair a proper assessment of canopy communities. Therefore, the occupancy of key animal groups along the forest’s vertical axis and the role of stratification in forest succession remains little understood. In this work, we investigated the stratification of pollinator abundance, (functional) diversity, and composition along a succession chronosequence in a lowland rainforest ecosystem. Moths, social diurnal bees, and nocturnal bees were more abundant and diverse in canopies, while orchid bees showed an inverse trend across parameters, suggesting taxa-specific responses. Late successional and old-growth forests were similarly diverse, suggesting that stratification establishes fast. Moreover, canopy- bearing successional and old-growth forests were more diverse than early successional plots across all groups. For moths and partially for bees, stratification enhanced diversity in old-growth and late-successional forests via species turnover between canopy and understory. Plot isolation, elevation, and canopy height had overall little effect on the variance between canopy and understory, potentially indicating a more prominent role of resource composition than environmental and local plot variables. Moreover, canopies harbored different pollinator compositions than understories. In particular, smaller, shorter-tongued, slower-flying, light-colored bees, and cryptic moths were associated with the canopy, suggesting that the relative role of interaction, dispersal and response traits in pollinator stratification is also group-dependent. Our study underlines the importance of stratification in leveraging diversity along forest succession, with a trait-driven, group-specific divergence of pollinator communities between forest strata. These results highlight the importance of considering canopies to improve sampling completeness and fully assess ecosystem biodiversity.
Reprogramming of alveolar macrophages by intestinal segmented filamentous bacteria protects mice from lethal bacterial pneumoniae following influenza infection
Authors: Ngo Vu L. , Lieber Carolin M. , Abo Hirohito , Kuczma Michal , Plemper Richard K. , Gewirtz Andrew T. 
Published: January 2025

SUMMARYThe most severe outcomes of respiratory viral infection (RVI) result from secondary bacterial infection, which RVI promotes via depletion of alveolar macrophages (AM). Colonization of the intestine by the common but non-ubiquitous commensal, segmented filamentous bacteria (SFB), reprograms AM to resist RVI-induced depletion. Hence, we examined if SFB against secondary infection byS. pneumoniae,H. influenzae, orS. aureus,following primary infection by influenza virus (IAV). Indeed, SFB colonization conferred strong post-IAV protection against these lethal bacterial pathogens. AM depletion and transplant studies indicated that SFB reprogramming these cells was necessary and sufficient for such protection. Assay of AM,ex vivo, from SFB-colonized mice argued their protection against secondary bacterial infection was not only due to their withstanding IAV-induced depletion. Rather, AM from SFB-colonized mice displayed complement-dependent increases in phagocytosis and killing of these bacteria. Furthermore, AM from SFB-colonized mice stably held their enhanced anti-bacterial phenotype even when transplanted into an inflamed interferon-rich post IAV-environment. Thus, SFB, and perhaps gut microbiota composition in general influences proneness to bacterial pneumonia, especially post-RVI.One Sentence summarySFB colonization stably changed the phenotype of alveolar macrophages resulting in sustained clearance of bacterial pathogens even amidst an inflamed interferon-rich immune suppressed lung.
Sleep in People Experiencing Homelessness Under Different Conditions and Seasons
Authors: Rice Alicia , Casiraghi Leandro P. , Gildee Cristina , Almquist Zack W. , Hagopian Amy , Martin Melanie A. , de la Iglesia Horacio O. 
Published: January 2025

AbstractPoor sleep represents a central health disparity for people experiencing homelessness, and any intervention to alleviate the impacts of homelessness should aim to improve sleep. We measured actimetry-based sleep in homeless adults spending their nights in four types of shelters in Seattle, WA, during the summer and winter. Homeless participants experienced more sleepless nights than housed participants in both seasons. During the summer sleeping nights, homeless participants experienced sleep patterns similar to housed subjects, but during the winter, their sleep duration was up to 1.5 hours shorter. Similarly, sleep quality, determined through sleep variability index, activity during the night, and intraindividual variability of sleep parameters, was poorer during the winter in homeless than in housed participants. Our study demonstrates the feasibility of using objectively measured sleep as a proxy for assessing the value of specific interventions to improve living conditions in people experiencing homelessness. Given the bidirectional relationship between sleep and both physical and mental health, our study reveals the health inequities of chronic sleep disparity for those living outdoors.Significance statementSleep disparities are central to the poor physical and mental health experienced by houseless people. Here we show that measured sleep through wrist actigraphy captures different aspects of this sleep disparity and represents a useful, objective metric of the impact of interventions to improve living conditions among people experiencing homelessness.
γδ T cells are the prime anti-tumoral T cells in pediatric neuroblastoma
Authors: Castenmiller Suzanne M. , Borst Anne L. , Wardak Leyma , Molenaar Jan J. , Papadopoulou Maria , de Krijger Ronald R. , van der Steeg Alida F. W. , Vermijlen David , de Groot Rosa , Wienke Judith , Wolkers Monika C. 
Published: January 2025

ABSTRACTHigh-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New treatment options are thus required. Even though HLA expression in neuroblastoma is low and immune cell infiltrates are limited, the presence of tumor infiltrating lymphocytes (TILs) is indicative for better patient survival. Here, we show that most tumor lesions contain viable immune cell infiltrates after induction chemotherapy, with high percentages of CD3+T cells. We therefore expanded the TILs and tested their anti-tumoral activity. With sufficient starting material, TIL expansion was as efficient as for adult solid tumors. However, whereas TIL products from adult tumors almost exclusively contained αβ T cells, in neuroblastoma-derived TILs, γδ T cells expanded with similar efficacy as αβ T cells. Importantly, the anti-tumor responses in response to autologous tumor digest primarily originated from (Vδ1- and Vδ3-expressing) γδ T cells, and not from αβ T cells. In conclusion, this finding creates a window of opportunity for immunotherapy for neuroblastoma patients, with γδ T cells as potential prime responders.
Germline-restricted chromosome of songbirds has different centromere compared to regular chromosomes
Authors: Rídl Jakub , Dedukh Dmitrij , Halenková Zuzana , Schlebusch Stephen A , Beneš Vladimír , Lopez Mireia Osuna , Osiejuk Tomasz S. , Ruiz-Ruano Francisco J , Suh Alexander , Albrecht Tomáš , Reif Jiří , Reifová Radka 
Published: January 2025

AbstractCentromeres are an important part of chromosomes which direct chromosome segregation during cell division. Their modifications can therefore explain the unusual mitotic and meiotic behaviour of certain chromosomes, such as the germline-restricted chromosome (GRC) of songbirds. This chromosome is eliminated from somatic cells during early embryogenesis and later also from male germ cells during spermatogenesis. Although the mechanism of elimination is not yet known, it is possible that it involves a modification of the centromeric sequence on the GRC, resulting in problems with the attachment of this chromosome to the mitotic or meiotic spindle and its lagging during anaphase, which eventually leads to its elimination from the nucleus. However, the repetitive nature and rapid evolution of centromeres make their identification and comparative analysis across species and chromosomes challenging. Here, we used a combination of cytogenetic and genomic approaches to identify the centromeric sequence of two closely related songbird species, the common nightingale (Luscinia megarhynchos) and the thrush nightingale (L. luscinia). We found a 436-bp satellite repeat present in the centromeric regions of all regular chromosomes, making it a strong candidate for the centromeric repeat. This centromeric repeat was highly similar between the two nightingale species. Interestingly, hybridization of the probe to this satellite repeat on meiotic spreads suggested that this repeat is missing on the GRC. Our results indicate that the change of the centromeric sequence may underlie the unusual inheritance and programmed DNA elimination of the GRC in songbirds.
Ensemble docking for intrinsically disordered proteins
Authors: Dhar Anjali , Sisk Thomas R. , Robustelli Paul 
Published: January 2025

AbstractIntrinsically disordered proteins (IDPs) are implicated in many human diseases and are increasingly being pursued as drug targets. Conventional structure-based drug design methods that rely on well-defined binding sites are however, largely unsuitable for IDPs. Here, we present computationally efficient ensemble docking approaches to predict the relative affinities of small molecules to IDPs and characterize their dynamic, heterogenous binding mechanisms at atomic resolution. We demonstrate that these ensemble docking protocols accurately predict the relative binding affinities of small molecule α-synuclein ligands measured by NMR spectroscopy and generate conformational ensembles of ligand binding modes in remarkable agreement with experimentally validated long-timescale molecular dynamics simulations. Our results display the potential of ensemble docking approaches for predicting small molecule binding to IDPs and suggest that these methods may be valuable tools for IDP drug discovery campaigns.
Human Genome Book:Words,Sentences and Paragraphs
Authors: Liang Wang 
Published: January 2025

AbstractSince the completion of the human genome sequencing project in 2001, significant progress has been made in areas such as gene regulation editing and protein structure prediction. However, given the vast amount of genomic data, the segments that can be fully annotated and understood remain relatively limited. If we consider the genome as a book, constructing its equivalents of words, sentences, and paragraphs has been a long-standing and popular research direction. Recently, studies on transfer learning in large language models have provided a novel approach to this challenge. Multilingual transfer ability, which assesses how well models fine-tuned on a source language can be applied to other languages, has been extensively studied in multilingual pre-trained models. Similarly, the transfer of natural language capabilities to “DNA language” has also been validated. Building upon these findings, we first trained a foundational model capable of transferring linguistic capabilities from English to DNA sequences. Using this model, we constructed a vocabulary of DNA words and mapped DNA words to their English equivalents. Subsequently, we fine-tuned this model using English datasets for paragraphing and sentence segmentation to develop models capable of segmenting DNA sequences into sentences and paragraphs. Leveraging these models, we processed the GRCh38.p14 human genome by segmenting, tokenizing, and organizing it into a “book” comprised of genomic “words,” “sentences,” and “paragraphs.” Additionally, based on the DNA-to-English vocabulary mapping, we created an “English version” of the genomic book. This study offers a novel perspective for understanding the genome and provides exciting possibilities for developing innovative tools for DNA search, generation, and analysis.
Individual dopaminergic neurons induce unique, yet overlapping combinations of behavioural modulations including safety learning, memory retrieval and acute locomotion
Authors: Toshima Naoko , Behrad Arman , Behnke Franziska , Kaushik Gauri , Weiglein Aliće , Strauch Martin , Thoener Juliane , Kobler Oliver , Wang Maia Lisandra M. , Dörr Markus , Schleyer Michael 
Published: January 2025

AbstractTwo evolutionary highly conserved functions of dopamine are to carry “teaching” signals during associative learning and to control movement. In mammals and humans these functions are generally thought to be produced by different populations of neurons. Here, we investigated in the larva ofDrosophila melanogasterwhether both these functions can be induced by the same individual dopaminergic neurons in the central brain. Focusing on the dopaminergic neurons of the DL1-cluster, we asked whether the optogenetic activation of individual neurons established associative punishment and/or safety memories, controlled the retrieval of the established memories, and acutely modulated locomotion. We found that each neuron had a unique, yet overlapping set of behavioural effects. Several individual neurons both established a memory and modulated acute locomotion by increasing the animals’ bending and decreasing its velocity. Our results demonstrate that individual dopaminergic neurons can fulfil a surprisingly broad range of functions in different behavioural contexts. Given the highly conserved roles of the dopaminergic system across the animal kingdom, this study raises the question whether a similarly diverse functionality can be found also in other animals, including humans.
Metabolic alterations in human post-mortem frontal cortex and cerebrospinal fluid associated with high levels of nicotine metabolite cotinine
Authors: Masvosva Wadzanai , Lehtonen Marko , Martiskainen Mika , Tiihonen Jari , Karhunen Pekka J. , Hanhineva Kati , Rysä Jaana , Kok Eloise , Kärkkäinen Olli 
Published: January 2025

AbstractCigarette smoking is the single most significant cause of preventable death in the world. Tobacco smoking causes exposure to thousands of chemicals and disrupts biological pathways. It impacts several organs, including the brain, where its effects are mediated by nicotinic acetylcholine receptors. Women seem to be more susceptible to the negative health effects of smoking. In this study we focused on the changes in the metabolic profile of human postmortem frontal cortex and cerebrospinal fluid samples associated with high levels of the nicotine metabolite cotinine. We used non-targeted metabolomics to analyze post-mortem frontal cortex and cerebrospinal fluid (CSF) samples from the Tampere Sudden Death Study cohort. We identified 137 cases (24 females) with high cotinine levels, indicating nicotine exposure. For controls, we identified 82 subjects (20 females) with no cotinine in the frontal cortex or CSF samples and no known history of smoking based on medical records and autopsy reports. Cases had significantly higher levels of 1-methylhistamine (Cohen’s d=0.66, p<0.0001) and N-acetylputrescine (d=0.84, p<0.0001), and lower levels of aspartic acid (d=-0.53, p<0.001), 3-methylhistidine (d=-0.58, p=0.0004), and taurine (d=-0.47, p=0.0002) in the frontal cortex compared to controls. Compared to the frontal cortex, differences between cases and controls were smaller in the CSF samples. Most of the observed differences were similar in both sexes, with a few exceptions like low ergothioneine levels, observed especially in female cases. In conclusion, smoking or nicotine exposure is associated with alterations in metabolites linked to increased oxidative stress and neuroinflammation, as well as reduced neurotransmitter levels in the frontal cortex.
Binge Eating and Psychological Distress: Investigating Relationships with Depression, Anxiety, and Stress
Authors: Soares Marinho Ana Carolina , da Costa Julio Cezar Albuquerque , Fernandes Sheyla C.S 
Published: January 2025

AbstractBinge eating (BE) involves the consumption of a greater amount of food than most people would under similar conditions, within a specified period and may be associated with various psychiatric disorders. This study aimed to compare the variables of Depression, Anxiety, and Stress among groups defined by the severity of binge eating symptoms. Participants were recruited through social media advertisements and responded online to the Depression, Anxiety, and Stress Scale (DASS-21) and the Binge Eating Scale (BES). It was observed that individuals with medium-high depressive symptoms showed a higher presence of binge eating symptoms, while those with moderate, severe, and extremely severe anxiety symptoms exhibited an increased occurrence of binge eating. The findings suggest a need for interventions addressing binge eating with comorbidities such as depression and anxiety, or binge eating as a comorbidity of these conditions.
Improving the accuracy of Respiratory Syncytial Virus (RSV) incidence among hospitalised adults in Bristol, UK
Authors: Lihou Katie , Challen Robert , Chatzilena Anastasia , Qian George , Oben Glenda , King Jade , McGuinness Serena , Morales-Aza Begonia , Duale Kaltun , Rodriguez Pereira Ainhoa , Healy William , Oliver Jennifer , Maskell Nick , Finn Adam , Danon Leon , Hyams Catherine 
Published: January 2025

ABSTRACTRespiratory Syncytial Virus (RSV) burden in adults is of interest due to recently-licensed vaccines, however, estimates are affected by test characteristics.We conducted a prospective cohort study of adults with acute lower respiratory tract disease (aLRTD) hospitalised in Bristol from April 2022–March 2023. RSV was detected by RT-PCR at standard-of-care and by additional nasopharyngeal, saliva, and sputum samples. Latent class analysis quantified and adjusted for test error and multiple testing.6906/11445 aLRTD cases (60%) were tested and 251 were positive (3.6%). Test-positivity peaked in December (7.9-12.7%). Among cases, 43% had pneumonia and 55% had non-pneumonic infection. Due to low positivity-rates and imperfect specificity, test-positivity (3.6%) overestimated true prevalence (2.3%). Adjusted adult population incidence/1000-person-years was 0.33 (0.21-0.49), and 2.02 (1.10-3.06) in ≥75-year-olds.RSV vaccines could reduce morbidity of hospitalised adult aLRTD, including non-pneumonic infection. Adult RSV burden accuracy is improved by adjustment for test characteristics, particularly estimates out-of-season.
Mapping obesity-related traits with regional white matter microstructure highlights the importance of brainstem tracts and sex-related differences
Authors: Gurholt Tiril P. , Beck Dani , Voldsbekk Irene , Parker Nadine , Askeland-Gjerde Daniel E. , de Lange Ann-Marie G. , van der Meer Dennis , Tamnes Christian K. , Thompson Paul M. , Sønderby Ida E. , Maximov Ivan I. , Westlye Lars T. , Andreassen Ole A. 
Published: January 2025

AbstractBackground and aimsThe relationships between obesity-related traits and the brain’s white matter characteristics and the context of sex- and age-related differences, remain unclear. This study aims to elucidate these body-brain connections using a large-scale dataset.MethodsWe analyzed data from 40,040 participants from the UK Biobank (52.2% female; ages 44-83 years) using multiple linear regression to evaluate associations between obesity-related traits (obesity, body anthropometrics) and white matter diffusion tensor imaging (DTI) metrics (fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity). We also examined interactions with age and sex.ResultsOur analyses revealed significant associations between obesity-related traits and DTI metrics with partial correlation coefficient |r| effect sizes ranging from 0.02 to 0.20 for most regions of interest with largest effects in brainstem tracts. We observed more widespread sex-by-obesity-related than age-by-obesity-related interaction effects on DTI metrics.ConclusionsOur results link obesity-related traits and white matter phenotypes, suggesting that shared body fat-related pathways linking physical and brain health that may vary based on sex and age. Understanding these relationships could enhance the development and evaluation of targeted, individualized, treatment strategies for conditions that co-occur with obesity, although further longitudinal studies are needed to map the dynamics of these associations.
A real-world cohort study of immune-related adverse events in patients receiving immune checkpoint inhibitors
Authors: Wang Yanfei , Guo Yi , Tan Aik Choon , Zhao Lili , Shi Xu , Chen Yong , Sun Ramon C , Liu Mei , Su Jing , George Thomas J , Bian Jiang , Song Qianqian 
Published: January 2025

ABSTRACTBackgroundImmune checkpoint inhibitors (ICIs) have significantly improved patient survival outcomes across various cancer types. However, their use is often associated with immune-related adverse events (irAEs), posing challenges in clinical management. Understanding the incidence, severity, and risk factors of irAEs is critical for optimizing ICI therapy and minimizing adverse outcomes.ObjectiveThis study aimed to identify and evaluate risk factors for immune-related adverse events (irAEs) among patients receiving ICIs, focusing on patient demographics, comorbidities, cancer types, and ICI regimens. Additionally, we sought to examine the incidence, severity, and organ-specific patterns of irAEs to guide personalized management strategies.MethodsThis retrospective cohort study utilized real-world data from the OneFlorida+ Clinical Research Network, including 9,193 adult patients who received ICIs between January 2018 and December 2022. Patients were categorized based on whether they developed irAEs within one year of initiating ICI therapy. Multivariable logistic regression was employed to identify risk factors for irAEs, adjusting for key covariates such as age, sex, cancer type, smoking status, and comorbidities. Kaplan-Meier survival analysis and cumulative incidence functions were applied to evaluate time to irAE event and overall incidence, stratified by irAE severity, cancer type, and ICI regimens.ResultsOf the 6,526 patients included in the final analysis, 56.2% developed irAEs within one year of ICI treatment, including 284 severe cases. Female and younger patients (ages 18-29) were at higher risk of developing irAEs, while comorbidities such as myocardial infarction, congestive heart failure, and renal disease significantly increased irAE risk. In contrast, dementia was associated with a reduced risk of irAEs. Patients treated with combined CTLA4+PD(L)1 inhibitors exhibited a 35% higher risk of irAEs compared to PD-1 inhibitors alone (OR: 1.35, 95% CI: 1.14–1.60, P < 0.001). Cancer type also influenced irAE risk, with breast cancer (OR: 2.36, 95% CI: 1.57–3.60, P < 0.001) and hematological cancer (OR: 2.61, 95% CI: 1.40–5.14, P = 0.004) associated with higher risk compared to melanoma, whereas brain cancer had a reduced risk (OR: 0.55, 95% CI: 0.32–0.92, P = 0.025). Survival analysis revealed that irAE severity significantly impacts both the timing of irAE onset (P = 0.038) and overall survival (P < 0.0001). While treatment regimens significantly influenced irAE-free survival in multi-site cancers (P = 0.02) and overall survival in kidney cancer (P = 0.0011), their effects were less pronounced in other cancer types.