bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeostasis After Injury: How Intertwined Inference and Control Underpin Post-Injury Pain and Behaviour
Authors: Mahajan Pranav , Dayan Peter , Seymour Ben 
Published: February 2025

AbstractInjuries are an unfortunate but inevitable fact of life, leading to an evolutionary mandate for powerful homeostatic processes of recovery and recuperation. The physiological responses of the body and the immune system must be coordinated with behaviour to allow protected time for this to happen, and to prevent further damage to the affected bodily parts. Reacting appropriately requires an internal control system that represents the nature and state of the injury and specifies and withholds actions accordingly. We bring the formal uncertainties embodied in this system into the framework of a partially observable Markov decision process (POMDP). We discuss nociceptive phenomena in light of this analysis, noting particularly the paradoxical behaviours associated with injury investigation, and the propensity for transitions from normative, tonic, to pathological, chronic, pain states. Importantly, these simulation results provide a quantitative account and enable us to sketch a much needed roadmap for future theoretical and experimental studies on injury, tonic pain, and transition to chronic pain. Ultimately, we seek novel ways to target chronic pain.
Computational detection, characterization, and clustering of microglial cells in a mouse model of fat-induced postprandial hypothalamic inflammation
Authors: Sanchez Clara , Nadal Morgane , Cansell Céline , Laroui Sarah , Descombes Xavier , Rovère Carole , Debreuve Éric 
Published: February 2025

AbstractObesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hour of high-fat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight. Understanding more precisely the kinetics of glial activation of two major brain cells (astrocytes and microglia) and their impact on eating behavior could prevent obesity and offer new prospects for therapeutic treatments. To understand the mechanisms pertaining to obesity-related neuroinflammation, we developed a fully automated algorithm, NutriMorph. Although some algorithms were developed in the past decade to detect and segment cells, they are highly specific, not fully automatic, and do not provide the desired morphological analysis. Our algorithm cope with these issues and performs the analysis of cells images (here, microglia of the hypothalamic arcuate nucleus), and the morphological clustering of these cells through statistical analysis and machine learning. Using the k-Means algorithm, it clusters the microglia of the control condition (healthy mice) and the different states of neuroinflammation induced by high-fat diets (obese mice) into subpopulations. This paper is an extension and re-analysis of a first published paper showing that microglial reactivity can already be seen after few hours of high-fat diet (Cansell et al., 2021). Thanks to NutriMorph algorithm, we unravel the presence of different hypothalamic microglial subpopulations (based on morphology) subject to proportion changes in response to already few hours of high-fat diet in mice.
Universal bacterial clade dynamics dominate under predation despite altered phenotypes and mutation targets
Authors: Kičiatovas Dovydas , Cairns Johannes , Partanen Veera , Hoffmann Julius , Becks Lutz , Hiltunen Teppo , Mustonen Ville 
Published: February 2025

AbstractRecent studies have revealed bacterial genome-wide evolution to be complex and dynamic even in a constant environment. The evolution is characterized by the emergence of new clades competing or temporarily coexisting as each clade continues to undergo evolutionary change. Previous studies on predator-prey dynamics tracking simple ecological and phenotypic metrics have shown predation to fundamentally alter prey evolution, often giving rise to defense evolution followed by frequency dependent selection between defended and undefended prey genotypes as well as coevolution. Moreover, these dynamics can differ between prey species depending, for example, on mutation rate and the physiological and fitness effects of the mutations available. Here we sought to consolidate these fields by examining genome-wide evolution in five bacterial prey species separately subjected to long-term evolution under ciliate predation. For all species, we found mutational signals of prey defense evolution, with phenotypic data demonstrating change in phenotypic composition for defense trait over time. Mutational targets and dynamics also differed between prey species. Intriguingly, however, overall temporal molecular dynamics across the prey species were strikingly similar to those of bacteria evolving alone, with constant emergence, competition and quasi-stable coexistence of clades. This makes molecular evolution more interesting and less predictable than we might expect based on existing coevolutionary theories.
IGLV3-21R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia
Authors: Fischer Claudia , Stücheli Simon , Chen Shih-Shih , Nimmerfroh Johanna , Schultheiß Christoph , Widmer Corinne , Heim Dominik , Kasenda Benjamin , Passweg Jakob , Kobold Sebastian , Egli Lukas , Coianiz Nicolò , Chijioke Obinna , Chiorazzi Nicholas , Follo Marie , Läubli Heinz , Peipp Matthias , Binder Mascha 
Published: February 2025

ABSTRACTWe previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to either an anti-IGLV3-21R110Fab or an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors. R110-bsAb spared polyclonal human B cells (as opposed to CD19-targeting Blinatumomab) as well as CD34+human stem cells. Yet, R110-bsAb induced lower T cell activation than Blinatumomab with primary CLL cells likely due to lower expression of target antigen. In vivo, R110-bsAb specifically killed IGLV3-21R110-expressing cell lines and CLL cells while sparing peripheral blood mononuclear cells. These findings highlight bispecific antibodies as a promising, off-the-shelf immunotherapy for high-risk CLL patients, offering selective targeting while preserving healthy B cells.
Molecular insights into electroreceptor ribbon synapses from differential gene expression in sturgeon lateral line organs
Authors: Campbell Alexander S. , Minařík Martin , Buckley David , Anand Tanmay , Gela David , Pšenička Martin , Baker Clare V. H. 
Published: February 2025

AbstractIn fishes and aquatic-stage amphibians, mechanosensory neuromasts are arranged in characteristic lines in the skin of the head and trunk, with afferent innervation from anterior or posterior lateral line nerves. In electroreceptive non-teleost jawed fishes and amphibians, fields of electrosensory ampullary organs flank some or all of the cranial neuromast lines, innervated by the anterior lateral line nerve. Like the mechanosensory hair cells found in neuromasts and the inner ear, electroreceptor cells in ampullary organs form specialised ribbon synapses with afferent nerve terminals. Ribbon synapses in hair cells are distinct from other glutamatergic synapses, including the ribbon synapses in photoreceptors: otoferlin is the Ca2+sensor for synaptic vesicle exocytosis and synaptic vesicles are loaded with glutamate by vGlut3. We previously showed that the genes encoding otoferlin and vGlut3 are expressed by ampullary organs as well as neuromasts in a chondrostean ray-finned fish, the Mississippi paddlefish (Polyodon spathula), suggesting that electroreceptor ribbon synapses are very similar to those in hair cells. In this study, we selected seven additional synapse-related candidate genes from our previously published dataset of putatively lateral line organ-enriched genes from late-larval paddlefish, and examined their expression in developing lateral line organs in a related chondrostean, the sterlet sturgeon (Acipenser ruthenus). We found that genes encoding the presynaptic cell adhesion molecule Nrxn3, the calcium-independent synaptotagmin Syt14, the high-affinity glutamate re-uptake transporter EAAT1 (GLAST), calmodulin regulator protein PCP4 (PEP-19) and cell adhesion molecule DSCAML1 were expressed in both neuromasts and ampullary organs. In contrast,Cbln18, encoding a secreted trans-synaptic scaffolding protein, was only expressed in neuromasts andTulp1, encoding tubby-related protein 1 (required for the development and function of photoreceptor ribbon synapses), was only expressed in ampullary organs. Our results support electroreceptor ribbon synapses being glutamatergic and suggest further commonalities, but also some differences, with hair cell ribbon synapses.
Regional heterothermy inMegasoma gyasis not related to active heat dissipation by the horns
Authors: Giacometti Danilo , Lima Silva Luiz Henrique , Gomes Guilherme , de Carvalho José Eduardo , Palaoro Alexandre V. 
Published: February 2025

AbstractAnimals rely on physiological and behavioral processes to maintain thermal balance. Some animals, however, bear structures that help dissipate excess heat when body temperatures rise. Although widespread in animals, animal weapons—exaggerated morphological structures with multiple characteristics that can make them good at dissipating heat—have rarely been studied in the context of thermoregulation. Here, we investigated whether the horns of the Rhinoceros Beetle (Megasoma gyas) acted as a thermal window. We heated live and dead beetles to 30ºC and allowed them to cool to 20ºC while measuring surface temperature changes in four body regions: the cephalic and thoracic horns, the scutellum, and the abdomen. If horns actively dissipated heat, they would show the lowest cooling rate among body regions. Contrary to this expectation, we found that the cephalic horn had the highest cooling rate, followed by the abdomen, thoracic horn, and scutellum, respectively. This suggests that the horns are not used for active heat dissipation inM. gyas. The low cooling rate of the scutellum can be explained by the presence of large flight muscles in the thorax, which play a role in heat generation, but could also aid in heat dissipation by pumping hemolymph across tagmata or through the low-insulated cuticle to prevent thoracic overheating. We also demonstrate that beetles show regional heterothermy even in the absence of exercise or stress. As such, we propose that regional heterothermy may result from both active (control of hemolymph flow) and passive (heat dissipation through poorly insulated structures) processes within individuals.
Comprehensive phylogenetic reconstructions support ancestral omnivory in the ecologically diverse bat family Phyllostomidae
Authors: Yi Xueling , Kontopoulos Dimitrios-Georgios , Hiller Michael 
Published: February 2025

AbstractAdaptive radiations often occur with an early burst of ecological diversification, which requires not only various available niches but also a generalist ancestor with wide ecological niche breadths. However, ancestral generalism remains hard to test in empirical cases. The New World leaf-nosed bats (family Phyllostomidae) represent an unparalleled mammalian adaptive radiation with diverse dietary niches including arthropods, blood, terrestrial vertebrates, nectar, and fruits. However, when and how often phyllostomid bats transitioned from insectivory to fruit or nectar feeding remains unclear. Here we tested the hypotheses of ancestral insectivory versus ancestral omnivory in Phyllostomidae (141 species) using improved trait reconstructions based on multi-response phylogenetic threshold models, while explicitly accounting for phylogenetic uncertainty. Our results indicate that complementary fruit feeding has fully evolved at the early burst of the phyllostomid radiation and started to evolve in the most recent common ancestor of the family, supporting the ancestral omnivory hypothesis. In addition, fruit feeding probably evolved before nectar eating in Phyllostomidae, in contrast to the claims of previous studies. Extending this analysis to all bat families (621 species) reveals independent evolution of ancestral fruit feeding in four families, namely the Pteropodidae (Old World fruit bats) and three families from the Noctilionoidea superfamily. Despite the ancestral omnivory of these fruit-eating families, only Phyllostomidae and Pteropodidae show high species diversity and evolved predominant and strict fruit feeding. Therefore, our results reveal that ancestral generalism (i.e., omnivory) may be a precondition of but does not necessarily lead to adaptive radiations which also require subsequent niche partitioning and speciation.
DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication
Authors: Feng Fei , Chen Jiannan , Li Rong , Zhu Yunkai , Ma Yanlong , Wang Ziqiao , Wang Yuyan , Gao Zhichao , Yang Lulu , Yu Yin , Liu Yanfeng , Sun Yingjie , Liao Ying , Huang Xinxin , Zhang Qisheng , Huang Yongheng , Qiu Lin , Wu Jiayu , Zhao Jingxian , Liu Chao , Ding Qiang , Xie Youhua , Yuan Zhenghong , Hong Yue , Zhang Ping , Sun Jing , Zhao Jincun , Zhang Rong 
Published: February 2025

ABSTRACTThe SARS-CoV-2 pandemic and the emergence of novel variants underscore the need to understand host-virus interactions and identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen to identify host restriction factors for SARS-CoV-2, revealing DAZAP2 as a potent antiviral gene. DAZAP2, previously implicated in SARS-CoV-2 restriction, is found to inhibit viral entry by blocking virion fusion with both endolysosomal and plasma membranes. Additionally, DAZAP2 suppresses genomic RNA replication without affecting the primary translation of viral replicases. We demonstrate that DAZAP2 functions as a pan-coronavirus restriction factor across four genera of coronaviruses. Importantly, knockout ofDAZAP2enhances SARS-CoV-2 infection in mouse models and in human primary airway epithelial cells, confirming its physiological relevance. Mechanistically, antiviral activity of DAZAP2 appears to be indirect, potentially through the regulation of host gene expression, as it primarily localizes to the nucleus. Our findings provide new insights into the host defense system against coronaviruses and highlight DAZAP2 as a potential target for host-directed antiviral therapies.IMPORTANCEDuring viral infection, the host defense response is mediated by a variety of host factors through distinct mechanisms that have yet to be fully elucidated. AlthoughDAZAP2was previously implicated in SARS-CoV-2 restriction, its mechanisms of action andin vivorelevance remain unclear. In this study, we identify the DAZAP2 as a potent pan-coronavirus restriction factor that inhibits viral infection through dual mechanisms: blocking virion fusion with both endolysosomal and plasma membranes, and suppressing genomic RNA replication. We confirm its physiological relevance in host defense using mouse models and primary cell cultures. This study advances our understanding of host-pathogen interactions. Targeting DAZAP2 or its regulatory pathways could provide a new approach to enhance host defense against current and future coronavirus threats.
Do you really want to see a 2-year-old suffer? Understanding people’s views on the relative value of health gains by age
Authors: De Silva Ashwini , Bailey Cate , Devlin Nancy , Norman Richard , Pan Tianxin , Peasgood Tessa 
Published: February 2025

AbstractObjectivesStandard economic evaluation methods assume that quality-adjusted life years (QALYs) have equal social value, regardless of recipient. However, evidence suggests that people place greater social value on health gains for children. This study examines the factors driving age-related preferences for health gains.MethodsThink-aloud, semi-structured interviews were conducted with Australian adolescents (n=7), non-parents (n=11), parents with healthy children (n=8) and parents of children with health conditions (n=15). Participants completed Person Trade-Off (PTO) and attitudinal questions about resource allocation for improvements in life extension, mental health, mobility, and pain/discomfort choosing between interventions for adults (ages 40 or 55) and younger people (ages one month to 24).ResultsEleven themes emerged, illustrating participants’ complex reasoning. They considered differences in the impact of health loss at various ages, with difficulty envisaging mental health impacts for very young children. Emotional responses were strongest around children in pain. Adolescents tended to prioritize younger people, while parents often emphasized adults’ caregiving role. Most participants prioritized based on age in PTO questions, though some adults objected to prioritizing healthcare based on age.ConclusionChoices were shaped by perceptions of the impact of the health states. These findings provide insight into interpreting quantitative results from PTO tasks.
Maternal-antenatal attachment is higher in young pregnant women with more social support, mentors, and lower fear of childbirth
Authors: Alavala Vishnupriya , De Genna Natacha M. 
Published: February 2025

AbstractThe goal of this study was to examine correlates of maternal-fetal attachment in a diverse sample of young pregnant mothers. Although studies have looked at social determinants of health and maternal-fetal attachment, none have examined correlates that may be more prevalent in younger populations including prenatal drug use or fear of childbirth. We analyzed data from a prospective cohort of 154 pregnant adolescents and young adults (75.5% Black/African American, 15.6% white, 7.5% biracial, 1.4% other) ranging from 14-21 years old. Participants were recruited early in pregnancy and completed online surveys during each trimester of pregnancy. Maternal fetal attachment was measured with the Maternal Antenatal Attachment Scale (MAAS) between 30-36 weeks gestation. A linear regression model was constructed to determine the independent contributions of demographic variables (age, race, sexual minority status), maternal mental health, substance use, and social support to maternal-fetal attachment. Third trimester social support, presence of a natural mentor, not having a younger partner, and lower fear of childbirth were associated with higher MAAS scores, and therefore greater maternal fetal attachment, accounting for 32% of the variance in MAAS scores. Maternal age, substance use, and psychological symptoms were not significantly related to maternal fetal attachment in this sample. Social support and patient education to lessen fear of childbirth should be the target of interventions to improve maternal-fetal attachment in adolescent and young adult women. Fostering and supporting mentorship may also be a promising avenue to improve maternal-fetal bonding in younger patients. More research is needed to better understand the impact of perceived health, body dissatisfaction, physical fitness, healthcare access, pre-existing OB/GYN conditions, fear of breastfeeding, history of emotional neglect, and future child rearing support to address gaps in knowledge within this field.
Global, Regional, and National Burden of Non-Rheumatic Calcified Aortic Valve Disease from 1990 to 2021 and Projections to 2050
Authors: Wang Zhenglong , Li Hao , Wei Hongwei , Chen Ming , Liu Xiaobo 
Published: February 2025

AbstractBackgroundnon-rheumatic calcific aortic valve disease (nrCAVD) is a valvular disease characterized by progressive calcification of the aortic valve that can lead to progressive left heart failure and death. This study reports on the global burden of CAVD, utilizing all available data and using the Global Burden of Disease (GBD) study methodology to understand the epidemiology of this widely prevalent disease.MethodsPrior to the current effort, the burden of CAVD was included in GBD as a non-specific contributor to “valvular heart disease” burden. In this study, CAVD was distinguished as its own cause of death and disability in GBD, producing comparable and consistent estimates of CAVD burden. We used epidemiological and vital registry data to estimate the non-fatal and fatal burden of CAVD in 204 countries and 21 territories from 1990 to 2021 using standard GBD modelling approaches.ResultsIn 2021, there were an estimated 13,320,896.13 (95% uncertainty interval [UI] 11,422,539.18 to 15,249,410.95) prevalent cases of CAVD globally. Of these, 6,018,666.77 (5,139,855.53 to 6,897,468.51) were in females (45%) and 7,302,229.37 (6,260,246.93 to 8,340,870.42) in males (55%). The age-standardised prevalence was 158.35 cases per 100 000 population (95% UI 135.92 – 181.00). Prevalence increased with age such that the highest prevalence was among individuals aged 90–94 years. In 2021, there were 142,205.00 例 (120,674.91 – 155,574.74) attributed to PAH globally, with an age-standardised mortality rate of 1.83 deaths from CAVD per 100 000 population (1.54 – 2.00). The burden of disease appears to be improving over time.
Impact of Aspirin Therapy on Progression of Thoracic and Abdominal Aortic Aneurysms
Authors: Mohammadmoradi Shayan , Heier Kory , Driehaus Elizabeth R. , Alfar Hammodah R. , Tyagi Sam , McQuerry Kristen , Whiteheart Sidney W. 
Published: February 2025

AbstractBackground and ObjectiveAortic aneurysms, including abdominal (AAA) and thoracic (TAA), pose significant challenges due to their rupture risk and complex pathophysiology. While aspirin has been proposed to manage aneurysm progression, evidence remains limited. This retrospective, single-center study used AI-driven methods to examine the association between aspirin therapy and aneurysm growth.MethodsThe study, at the University of Kentucky Healthcare, utilized de-identified electronic health record data from 2010 to 2023. To evaluate platelet counts changes, Cohort 1 included patients with AAA or TAA and matched healthy controls. Cohort 2 included AAA or TAA patients who had at least two imaging studies. Extraction of aortic diameters utilized an advanced AI-based natural language processing (NLP) algorithm to identify and extract relevant text strings related to aortic dimensions. Multivariable-adjusted linear regression analyses assessed the impact of aspirin on aneurysm progression.ResultsCohort 1 included 11,538 participants: 5,774 controls, 3,439 with AAA, and 2,325 with TAA. Platelet counts were significantly lower in patients with aortic aneurysms compared to controls, though they were not considered thrombocytopenic. Cohort 2 included 302 AAA and 141 TAA patients. Subgroup analysis revealed that aspirin use was associated with increased AAA progression in females with small aneurysms (<50 mm). Further, aspirin therapy showed no significant impact on the annualized change in aneurysm diameter for TAA or for males with AAA.ConclusionOur findings suggest aspirin’s effectiveness varies by sex and potentially aneurysm size, underscoring the need for further research to refine antiplatelet therapy guidelines for aortic aneurysms.