bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats
Authors: Floris Gabriele , Dabrowski Konrad R. , Zanda Mary Tresa , Daws Stephanie E. 
Published: October 2024

AbstractPreclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT2AR), a well-documented target for modulation of drug seeking, and evidence suggests 5-HT2AR agonists may dampen motivation for opioids. We sought to investigate the therapeutic efficacy of psilocybin in mediating cessation of opioid use and maintenance of long-lasting abstinence from opioid seeking behavior in a rat model of heroin self-administration (SA). Psilocybin or 5-HT2AR antagonists ketanserin and volinanserin were administered systemically to rats prior to SA of 0.075 mg/kg/infusion of heroin, or relapse following forced abstinence. Psilocybin did not alter heroin taking, but a single exposure to 3.0 mg/kg psilocybin 4–24 h prior to a relapse test blunted cue-induced heroin seeking. Conversely, 5-HT2AR antagonists exacerbated heroin relapse. To begin to elucidate mechanisms of psilocybin, drug-naïve rats received psilocybin and/or ketanserin, and tissue was collected from the prefrontal cortex (PFC), a region critical for drug seeking and responsive to psilocybin, 24 h later for RNA-sequencing. 3.0 mg/kg psilocybin regulated ~2-fold more genes in the PFC than 1.0 mg/kg, including genes involved in the cytoskeleton and cytokine signaling. Ketanserin blocked >90% of psilocybin-regulated genes, including the IL-17a cytokine receptor, Il17ra. Psychedelic compounds have reported anti-inflammatory properties, and therefore we performed a gene expression array to measure chemokine/cytokine molecules in the PFC of animals that displayed psilocybin-mediated inhibition of heroin seeking. Psilocybin regulated 4 genes, including Il17a, and a subset of genes correlated with relapse behavior. Selective inhibition of PFC IL-17a was sufficient to reduce heroin relapse. We conclude that psilocybin reduces heroin relapse and highlight IL-17a signaling as a potential downstream pathway of psilocybin that also reduces heroin seeking.
The relationships between resilience and child health behaviors in a national dataset
Authors: McMahon Ellen L. , Wallace Shelby , Samuels Lauren R. , Heerman William J. 
Published: October 2024

Abstract
Background
Resilience mechanisms at the individual, family, and environmental levels may improve health outcomes despite potentially harmful stress exposure partly through the practice of positive health behaviors.

Methods
We performed a secondary analysis of 2016–2021 National Survey of Children’s Health data to assess the relationships between three resilience domains – child, family, neighborhood – and six health behaviors using multiple regression models adjusted for the other resilience domain(s) and potential confounders.

Results
Analysis revealed significant associations between each resilience domain and multiple health behaviors in a total weighted analytic sample of 70,156,540 children. For each outcome, the odds of better health behaviors were highest with high resilience in all possible domains. For example, among children ages 0–5 years, the adjusted odds of having “good quality” vs. “poor quality” sleep for those with “high” resilience in all domains were 2.21 times higher (95% CI 1.78, 2.63) than for those with “low” resilience in all domains.

Conclusions
This line of research may help to inform the design of resilience and health behavior promotion interventions by targeting multiple socio-ecological domains of influence to improve health and development outcomes in children exposed to experiences or sources of potential stress.

Impact

This study assessed the associations between three socio-ecological resilience domains (child, family, and neighborhood) and six child and family health behaviors in a national dataset.

Resilience exists within multiple socio-ecological levels and supports healthy functioning despite experiencing stress. Studies in adults and limited pediatric sub-populations show associations between resilience and health behaviors, which in turn influence numerous health outcomes.

Resilience at three levels of socio-ecological levels was found to be associated with the performance of multiple child and family health behaviors in a nationally representative general pediatric population. These findings have important implications for child and family health promotion efforts.
Corynebacterium parakroppenstedtii secretes a novel glycolipid to promote the development of granulomatous lobular mastitis
Authors: Liu Ran , Luo Zixuan , Dai Chong , Wei Yuchen , Yan Shuqing , Kuang Xinwen , Qi Kuan , Fu Aisi , Li Yinxin , Fu Shuai , Ma Zhengning , Dai Wen , Xiao Xiao , Wu Qing , Zhou Haokui , Rao Yan , Yuan Jingping , Shi Ting , Deng Zixin , Chen Chuang , Liu Tiangang 
Published: October 2024

AbstractGranulomatous lobular mastitis (GLM) is a chronic idiopathic granulomatous mastitis of the mammary gland characterized by significant pain and a high propensity for recurrence, the incidence rate has gradually increased, and has become a serious breast disease that should not be ignored. GLM is highly suspected relative to microbial infections, especially those of Corynebacterium species; however, the mechanisms involved are unclear, and prevention and treatment are difficult. In this study, we demonstrated the pathogenicity of Corynebacterium parakroppenstedtii in GLM using Koch’s postulates. Based on the drug sensitization results of C. parakroppenstedtii, and utilizing a retrospective study in conjunction with a comprehensive literature review, we suggested an efficacious, targeted antibiotic treatment strategy for GLM. Subsequently, we identified the pathogenic factor as a new type of glycolipid (named corynekropbactins) secreted by C. parakroppenstedtii. Corynekropbactins may chelate iron, cause the death of mammary cells and other mammary -gland-colonizing bacteria, and increase the levels of inflammatory cytokines. We further analyzed the prevalence of C. parakroppenstedtii infection in patients with GLM. Finally, we suggested that the lipophilicity of C. parakroppenstedtii may be associated with its infection route and proposed a possible model for the development of GLM. This research holds significant implications for the clinical diagnosis and therapeutic management of GLM, offering new insights into targeted treatment approaches.
Identification of KW-2449 as a dual inhibitor of ferroptosis and necroptosis reveals that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis
Authors: Zhao Yaxing , Wang Qingsong , Zhu Jing , Cai Jin , Feng Xiaona , Song Qianqian , Jiang Hui , Ren Wenqing , He Yuan , Wang Ping , Feng Du , Yu Jianqiang , Liu Yue , Wu Qihui , Siriporn Jitkaew , Cai Zhenyu 
Published: October 2024

AbstractNecroptosis and ferroptosis are two distinct forms of necrotic-like cell death in terms of their morphological features and regulatory mechanisms. These two types of cell death can coexist in disease and contribute to pathological processes. Inhibition of both necroptosis and ferroptosis has been shown to enhance therapeutic effects in treating complex necrosis-related diseases. However, targeting both necroptosis and ferroptosis by a single compound can be challenging, as these two forms of cell death involve distinct molecular pathways. In this study, we discovered that KW-2449, a previously described necroptosis inhibitor, also prevented ferroptosis both in vitro and in vivo. Mechanistically, KW-2449 inhibited ferroptosis by targeting the autophagy pathway. We further identified that KW-2449 functioned as a ULK1 (Unc-51-like kinase 1) inhibitor to block ULK1 kinase activity in autophagy. Remarkably, we found that Necrostatin-1, a classic necroptosis inhibitor that has been shown to prevent ferroptosis, also targets the autophagy pathway to suppress ferroptosis. This study provides the first understanding of how necroptosis inhibitors can prevent ferroptosis and suggests that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis. Therefore, the identification and design of pharmaceutical molecules that target the autophagy pathway from necroptosis inhibitors is a promising strategy to develop dual inhibitors of necroptosis and ferroptosis in clinical application.
Kinetochore dynein is sufficient to biorient chromosomes and remodel the outer kinetochore
Authors: Prevo Bram , Cheerambathur Dhanya K. , Earnshaw William C. , Desai Arshad 
Published: October 2024

AbstractMultiple microtubule-directed activities concentrate on mitotic chromosomes to ensure their faithful segregation. These include couplers and dynamics regulators localized at the kinetochore, the microtubule interface built on centromeric chromatin, as well as motor proteins recruited to kinetochores and chromatin. Here, we describe an in vivo approach in the C. elegans one-cell embryo in which removal of the major microtubule-directed activities on mitotic chromosomes is compared to the selective presence of individual activities. Our approach reveals that the kinetochore dynein module, comprised of cytoplasmic dynein and its kinetochore-specific adapters, is sufficient to biorient chromosomes; by contrast, this module is unable to support congression. In coordination with orientation, the dynein module directs removal of outermost kinetochore components, including dynein itself, independently of the other microtubule-directed activities and kinetochore-localized protein phosphatase 1. These observations indicate that the kinetochore dynein module is sufficient to biorient chromosomes and to direct remodeling of the outer kinetochore in a microtubule attachment state-sensitive manner.
Cancer treatment monitoring using cell-free DNA fragmentomes
Authors: van ’t Erve Iris , Alipanahi Bahar , Lumbard Keith , Skidmore Zachary L. , Rinaldi Lorenzo , Millberg Laurel K. , Carey Jacob , Chesnick Bryan , Cristiano Stephen , Portwood Carter , Wu Tony , Peters Erica , Bolhuis Karen , Punt Cornelis J. A. , Tom Jennifer , Bach Peter B. , Dracopoli Nicholas C. , Meijer Gerrit A. , Scharpf Robert B. , Velculescu Victor E. , Fijneman Remond J. A. , Leal Alessandro 
Published: October 2024

AbstractCirculating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.90, p < 0.0001, Pearson correlation) even in cases where mutations are undetectable. DELFI-TF scores prior to therapy initiation are associated with clinical response and are independent predictors of overall survival (HR = 9.84, 95% CI = 1.72-56.10, p < 0.0001). Patients with lower DELFI-TF scores during treatment have longer overall survival (62.8 vs 29.1 months, HR = 3.12, 95% CI 1.62-6.00, p < 0.001) and the approach predicts clinical outcomes more accurately than imaging. These results demonstrate the potential of using cfDNA fragmentomes to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.
Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging
Authors: Din Misbahud , Paul Souvik , Ullah Sana , Yang Haoyi , Xu Rong-Guang , Abidin Nurul Aisha Zainal , Sun Allan , Chen Yiyao Catherine , Gao Rui , Chowdhury Bari , Zhou Fangyuan , Rogers Stephenie , Miller Mariel , Biswas Atreyee , Hu Liang , Fan Zhichao , Zahner Christopher , Fan Jing , Chen Zi , Berman Megan , Xue Lingzhou , Ju Lining Arnold , Chen Yunfeng 
Published: October 2024

AbstractArterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor–ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin αIIbβ3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient’s pathological profile.
Developmental mouse brain common coordinate framework
Authors: Kronman Fae N. , Liwang Josephine K. , Betty Rebecca , Vanselow Daniel J. , Wu Yuan-Ting , Tustison Nicholas J. , Bhandiwad Ashwin , Manjila Steffy B. , Minteer Jennifer A. , Shin Donghui , Lee Choong Heon , Patil Rohan , Duda Jeffrey T. , Xue Jian , Lin Yingxi , Cheng Keith C. , Puelles Luis , Gee James C. , Zhang Jiangyang , Ng Lydia , Kim Yongsoo 
Published: October 2024

Abstract3D brain atlases are key resources to understand the brain’s spatial organization and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of developing mouse brain 3D reference atlases hinders advancements in understanding brain development. Here, we present a 3D developmental common coordinate framework (DevCCF) spanning embryonic day (E)11.5, E13.5, E15.5, E18.5, and postnatal day (P)4, P14, and P56, featuring undistorted morphologically averaged atlas templates created from magnetic resonance imaging and co-registered high-resolution light sheet fluorescence microscopy templates. The DevCCF with 3D anatomical segmentations can be downloaded or explored via an interactive 3D web-visualizer. As a use case, we utilize the DevCCF to unveil GABAergic neuron emergence in embryonic brains. Moreover, we map the Allen CCFv3 and spatial transcriptome cell-type data to our stereotaxic P56 atlas. In summary, the DevCCF is an openly accessible resource for multi-study data integration to advance our understanding of brain development.
Confidence control for efficient behaviour in dynamic environments
Authors: Balsdon Tarryn , Philiastides Marios G. 
Published: October 2024

AbstractSignatures of confidence emerge during decision-making, implying confidence may be of functional importance to decision processes themselves. We formulate an extension of sequential sampling models of decision-making in which confidence is used online to actively moderate the quality and quantity of evidence accumulated for decisions. The benefit of this model is that it can respond to dynamic changes in sensory evidence quality. We highlight this feature by designing a dynamic sensory environment where evidence quality can be smoothly adapted within the timeframe of a single decision. Our model with confidence control offers a superior description of human behaviour in this environment, compared to sequential sampling models without confidence control. Using multivariate decoding of electroencephalography (EEG), we uncover EEG correlates of the model’s latent processes, and show stronger EEG-derived confidence control is associated with faster, more accurate decisions. These results support a neurobiologically plausible framework featuring confidence as an active control mechanism for improving behavioural efficiency.
Ethane-oxidising archaea couple CO2 generation to F420 reduction
Authors: Lemaire Olivier N. , Wegener Gunter , Wagner Tristan 
Published: October 2024

AbstractThe anaerobic oxidation of alkanes is a microbial process that mitigates the flux of hydrocarbon seeps into the oceans. In marine archaea, the process depends on sulphate-reducing bacterial partners to exhaust electrons, and it is generally assumed that the archaeal CO2-forming enzymes (CO dehydrogenase and formylmethanofuran dehydrogenase) are coupled to ferredoxin reduction. Here, we study the molecular basis of the CO2-generating steps of anaerobic ethane oxidation by characterising native enzymes of the thermophile Candidatus Ethanoperedens thermophilum obtained from microbial enrichment. We perform biochemical assays and solve crystal structures of the CO dehydrogenase and formylmethanofuran dehydrogenase complexes, showing that both enzymes deliver electrons to the F420 cofactor. Both multi-metalloenzyme harbour electronic bridges connecting CO and formylmethanofuran oxidation centres to a bound flavin-dependent F420 reductase. Accordingly, both systems exhibit robust coupled F420-reductase activities, which are not detected in the cell extract of related methanogens and anaerobic methane oxidisers. Based on the crystal structures, enzymatic activities, and metagenome mining, we propose a model in which the catabolic oxidising steps would wire electron delivery to F420 in this organism. Via this specific adaptation, the indirect electron transfer from reduced F420 to the sulphate-reducing partner would fuel energy conservation and represent the driving force of ethanotrophy.
Direct and lagged climate change effects intensified the 2022 European drought
Authors: Bevacqua Emanuele , Rakovec Oldrich , Schumacher Dominik L. , Kumar Rohini , Thober Stephan , Samaniego Luis , Seneviratne Sonia I. , Zscheischler Jakob 
Published: October 2024

AbstractIn 2022, Europe faced an extensive summer drought with severe socioeconomic consequences. Quantifying the influence of human-induced climate change on such an extreme event can help prepare for future droughts. Here, by combining observations and climate model outputs with hydrological and land-surface simulations, we show that Central and Southern Europe experienced the highest observed total water storage deficit since satellite observations began in 2002, probably representing the highest and most widespread soil moisture deficit in the past six decades. While precipitation deficits primarily drove the soil moisture drought, human-induced global warming contributed to over 30% of the drought intensity and its spatial extent via enhanced evaporation. We identify that 14–41% of the climate change contribution was mediated by the warming-driven drying of the soil that occurred before the hydrological year of 2022, indicating the importance of considering lagged climate change effects to avoid underestimating associated risks. Human-induced climate change had qualitatively similar effects on the extremely low observed river discharges. These results highlight that global warming effects on droughts are already underway, widespread and long lasting, and that drought risk may escalate with further human-induced warming in the future.
Fight or flight alternative mating tactics may explain the iconic male polymorphism of the European stag beetle
Authors: Giannetti Daniele , Schifani Enrico , Rolli Enrico , Fior Emanuele , Pasquali Benedetta , Campanaro Alessandro , Grasso Donato A. 
Published: October 2024

AbstractThe existence of different male morphologies within a single species is associated with alternative mating tactics across different animal groups, offering textbook examples of evolutionary biology. The European stag beetle Lucanus cervus is a flagship species which has long fascinated naturalists for its charismatic appearance and behavior, with males possessing large mandibles used in ritualized ground fights for females. Males are polymorphic, with larger males possessing disproportionately larger mandibles and being better fighters, while smaller males require less food to develop and may have better chances to escape predation. We discovered an alternative mating tactic that opens a new interpretation on the evolution of the smaller males, based on aggregations of flying males competing to catch flying females in mid-air. Flight aggregations occur earlier in the season and in sites with sparser canopy cover as compared to ground fight aggregations, but most importantly, smaller males tend to prevail due to their greater agility in flight. Competition between males is crucial for reproductive success in this species, and alternative mating tactics involving flight were unknown in beetles, advocating for further research on the ecology and evolution of the iconic male polymorphism of stag beetles.
Predictive machine learning models for anticipating loss to follow-up in tuberculosis patients throughout anti-TB treatment journey
Authors: Chen Jingfang , Jiang Youli , Li Zhihuan , Zhang Mingshu , Liu Linlin , Li Ao , Lu Hongzhou 
Published: October 2024

AbstractLoss to follow-up (LTFU) in tuberculosis (TB) management increases morbidity and mortality, challenging effective control strategies. This study aims to develop and evaluate machine learning models to predict loss to follow-up in TB patients, improving treatment adherence and outcomes. Retrospective data encompassing tuberculosis patients who underwent treatment or registration at the National Center for Clinical Medical Research on Infectious Diseases from January 2017 to December 2021 were compiled. Employing machine learning techniques, namely SVM, RF, XGBoost, and logistic regression, the study aimed to prognosticate LTFU. A comprehensive cohort of 24,265 tuberculosis patients underwent scrutiny, revealing a LTFU prevalence of 12.51% (n = 3036). Education level, history of hospitalization, alcohol consumption, outpatient admission, and prior tuberculosis history emerged as precursors for pre-treatment LTFU. Employment status, outpatient admission, presence of chronic hepatitis/cirrhosis, drug adverse reactions, alternative contact availability, and health insurance coverage exerted substantial influence on treatment-phase LTFU. XGBoost consistently surpassed alternative models, boasting superior discriminative ability with an average AUC of 0.921 for pre-treatment LTFU and 0.825 for in-treatment LTFU. Our study demonstrates that the XGBoost model provides superior predictive performance in identifying LTFU risk among tuberculosis patients. The identification of key risk factors highlights the importance of targeted interventions, which could lead to significant improvements in treatment adherence and patient outcomes.