bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-6 Levels During Normothermic Machine Perfusion Impact Postreperfusion Hemodynamics of Liver Graft Recipients: A Prospective Single-center Observational Study
Authors: Mathis Simon , Weissenbacher Annemarie , Putzer Gabriel , Gasteiger Lukas , Cardini Benno , Hell Tobias , Schlosser Lisa , Oberhuber Rupert , Schneeberger Stefan , Martini Judith 
Published: November 2023

Background.
Hemodynamic instability after liver graft reperfusion increases recipient morbidity after liver transplantation. The etiologies of hemodynamic disturbances appear to be multifactorial and are poorly understood. Normothermic machine perfusion (NMP) provides an opportunity to analyze graft quality prior to transplantation. In the present study, we aim to investigate the influence of interleukin-6 (IL-6) levels during NMP on postreperfusion hemodynamics of the recipient.

Methods.
Consecutive NMP-liver transplants at a single-center were prospectively analyzed. Perfusate samples were collected at the beginning, after 6 h, and at the end of perfusion and analyzed for IL-6 levels. Mean arterial pressure (MAP) and catecholamine consumption during surgery were recorded. IL-6 levels at the end of NMP were correlated to donor and perfusion characteristics as well as changes in MAP and catecholamine requirements during the anhepatic and reperfusion phase.

Results.
IL-6 perfusate measurements were assessed in 77 livers undergoing NMP and transplantation. Donor age, sex, cold ischemic time, and NMP time did not correlate with IL-6 levels. Perfusates of donation after circulatory death grafts showed higher IL-6 levels at the end of NMP than donation after brain death grafts. However, IL-6 levels at the end of NMP correlated with catecholamine requirements and MAP in the reperfusion phase. Per log10 increase in IL-6 levels, an increase of 42% points in administered catecholamine dose was observed, despite MAP being decreased by 3.6% points compared to baseline values.

Conclusions.
IL-6 levels may be a predictor for recipient hemodynamic instability during liver reperfusion. Larger studies are needed to confirm this finding.
Visual Snow Syndrome Improves With Modulation of Resting-State Functional MRI Connectivity After Mindfulness-Based Cognitive Therapy: An Open-Label Feasibility Study
Authors: Wong Sui H. , Pontillo Giuseppe , Kanber Baris , Prados Ferran , Wingrove Janet , Yiannakas Marios , Davagnanam Indran , Gandini Wheeler-Kingshott Claudia A. M. , Toosy Ahmed T. 
Published: November 2023

Background:
Visual snow syndrome (VSS) is associated with functional connectivity (FC) dysregulation of visual networks (VNs). We hypothesized that mindfulness-based cognitive therapy, customized for visual symptoms (MBCT-vision), can treat VSS and modulate dysfunctional VNs.

Methods:
An open-label feasibility study for an 8-week MBCT-vision treatment program was conducted. Primary (symptom severity; impact on daily life) and secondary (WHO-5; CORE-10) outcomes at Week 9 and Week 20 were compared with baseline. Secondary MRI outcomes in a subcohort compared resting-state functional and diffusion MRI between baseline and Week 20.

Results:
Twenty-one participants (14 male participants, median 30 years, range 22–56 years) recruited from January 2020 to October 2021. Two (9.5%) dropped out. Self-rated symptom severity (0–10) improved: baseline (median [interquartile range (IQR)] 7 [6–8]) vs Week 9 (5.5 [3–7], P = 0.015) and Week 20 (4 [3–6], P < 0.001), respectively. Self-rated impact of symptoms on daily life (0–10) improved: baseline (6 [5–8]) vs Week 9 (4 [2–5], P = 0.003) and Week 20 (2 [1–3], P < 0.001), respectively. WHO-5 Wellbeing (0–100) improved: baseline (median [IQR] 52 [36–56]) vs Week 9 (median 64 [47–80], P = 0.001) and Week 20 (68 [48–76], P < 0.001), respectively. CORE-10 Distress (0–40) improved: baseline (15 [12–20]) vs Week 9 (12.5 [11–16.5], P = 0.003) and Week 20 (11 [10–14], P = 0.003), respectively. Within-subject fMRI analysis found reductions between baseline and Week 20, within VN-related FC in the i) left lateral occipital cortex (size = 82 mL, familywise error [FWE]-corrected P value = 0.006) and ii) left cerebellar lobules VIIb/VIII (size = 65 mL, FWE-corrected P value = 0.02), and increases within VN-related FC in the precuneus/posterior cingulate cortex (size = 69 mL, cluster-level FWE-corrected P value = 0.02).

Conclusions:
MBCT-vision was a feasible treatment for VSS, improved symptoms and modulated FC of VNs. This study also showed proof-of-concept for intensive mindfulness interventions in the treatment of neurological conditions.
Soil seed bank richness, abundance and density across spatial scales and global biomes
Authors: Auffret Alistair G. , Ladouceur Emma , Haussmann Natalie S. , Keil Petr , Daouti Eirini , Elumeeva Tatiana G. , Kačergytė Ineta , Knape Jonas , Kotowska Dorota , Low Matthew , Onipchenko Vladimir G. , Paquet Matthieu , Rubene Diana , Plue Jan 
Published: November 2023

AbstractSoil seed banks are an important component of plant population and community dynamics. As a functional strategy that has evolved in response to abiotic disturbance regimes, they are likely to play a key role in determining biodiversity responses to global change. However, like all aspects of biodiversity, patterns in soil seed banks are likely to be scale-dependent. Here, we investigate components of diversity in the soil seed bank across global biomes, accounting for sampled soil area and geographic extent. Species richness increases with spatial scale at a similar rate across terrestrial biomes, but with differences in the slope (beta diversity). At small scales (0.01 m2), mediterranean systems exhibited the highest seed bank richness, while at larger scales (15 m2) it was tropical forests. Seed density m-2in the soil was highest in arable systems, followed by tropical and temperate grasslands. Lower densities were found in both high-diversity tropical biomes that are characterised by short-lived seeds, and low-diversity boreal/tundra biomes with more stable established vegetation. Our synthesis shows how a combination of spatial scale and the environmental conditions of different biomes shape global patterns of the multiple components of biodiversity in the soil seed bank.
Study protocol of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA)
Authors: Bankó Éva M. , Weiss Béla , Hevesi István , Manga Annamária , Vakli Pál , Havadi-Nagy Menta , Kelemen Rebeka , Somogyi Eszter , Homolya István , Bihari Adél , Simon Ádám , Nárai Ádám , Tóth Krisztina , Báthori Noémi , Tomacsek Vivien , Kamondi Anita , Racsmány Mihály , Dénes Ádám , Simor Péter , Kovács Tibor , Hermann Petra , Vidnyánszky Zoltán 
Published: November 2023

ABSTRACTBackgroundNeurocognitive aging and the associated brain diseases impose a major social and economic burden. Therefore, substantial efforts have been put into revealing the lifestyle, neurobiological and genetic underpinnings of healthy neurocognitive aging. However, these studies take place almost exclusively in a limited number of highly-developed countries. Thus, it is an important open question to what extent their findings may generalize to neurocognitive aging in other, not yet investigated regions.PurposeThe purpose of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA) is to collect multi-modal longitudinal data on healthy neurocognitive aging to address the data gap in this field in Central and Eastern Europe.MethodsWe adapted the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging1study protocol to local circumstances and will collect demographic, lifestyle, mental and physical health, medication and medical history related information as well as record a series of magnetic resonance imaging (MRI) data. In addition, participants will also be offered to participate in the collection of blood samples to assess circulating inflammatory biomarkers as well as a sleep study aimed at evaluating the general sleep quality based on multi-day collection of subjective sleep questionnaires and whole-night electroencephalographic (EEG) data.Results & DiscussionData collection will be longitudinal with 18 months between measurements and at least three sessions are intended. The collected data might reveal specific local trends or could also indicate the generalizability of previous findings. Moreover, as the HuBA protocol also offers a sleep study designed for thorough characterization of participants’ sleep quality and related factors, our extended multi-modal dataset might provide a base for incorporating these measures into healthy and clinical aging research.ConclusionBesides its straightforward national benefits in terms of health expenditure, we hope that this Hungarian initiative could provide results valid for the whole Central and Eastern European region and could also promote aging and Alzheimer’s disease research in these countries.
ProkBERT Family: Genomic Language Models for Microbiome Applications
Authors: Ligeti Balázs , Szepesi-Nagy István , Bodnár Babett , Ligeti-Nagy Noémi , Juhász János 
Published: November 2023

ABSTRACTMachine learning offers transformative capabilities in microbiology and microbiome analysis, deciphering intricate microbial interactions, predicting functionalities, and unveiling novel patterns in vast datasets. This enriches our comprehension of microbial ecosystems and their influence on health and disease. However, the integration of machine learning in these fields contends with issues like the scarcity of labeled datasets, the immense volume and complexity of microbial data, and the subtle interactions within microbial communities. Addressing these challenges, we introduce the ProkBERT model family. Built on transfer learning and self-supervised methodologies, ProkBERT models capitalize on the abundant available data, demonstrating adaptability across diverse scenarios. The models’ learned representations align with established biological understanding, shedding light on phylogenetic relationships. With the novel Local Context-Aware (LCA) tokenization, the ProkBERT family overcomes the context size limitations of traditional transformer models without sacrificing performance or the information rich local context. In bioinformatics tasks like promoter prediction and phage identification, ProkBERT models excel. For promoter predictions, the best performing model achieved an MCC of 0.74 forE. coliand 0.62 in mixed-species contexts. In phage identification, they all consistently outperformed tools like VirSorter2 and DeepVirFinder, registering an MCC of 0.85. Compact yet powerful, the ProkBERT models are efficient, generalizable, and swift. They cater to both supervised and unsupervised tasks, providing an accessible tool for the community. The models are available on GitHub and HuggingFace.
Sleep Disruption in a Mouse Model of Chronic Traumatic Brain Injury
Authors: Morris Andrew R. , Gudenschwager Basso Erwin K. , Gutierrez-Monreal Miguel A. , Arja Rawad Daniel , Kobeissy Firas H. , Janus Christopher G. , Wang Kevin K. W. , Zhu Jiepei , Liu Andrew C. 
Published: November 2023

AbstractChronic sleep/wake disturbances are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong sleep/wake disturbances. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in four months old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. The sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at three months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Furthermore, TBI mice showed extensive brain tissue loss and increased GFAP and IBA1 levels in the hypothalamus and the vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes following TBI early in life.
Methyl-TWAS: A powerful method forin silicotranscriptome-wide association studies (TWAS) using long-range DNA methylation
Authors: Kim Soyeon , Qin Yidi , Park Hyun Jung , Yue Molin , Xu Zhongli , Forno Erick , Chen Wei , Celedón Juan C. 
Published: November 2023

ABSTRACTIn silicotranscriptome-wide association studies (TWAS) are commonly used to test whether expression of specific genes is linked to a complex trait. However, genotype-basedin silicoTWAS such as PrediXcan, exhibit low prediction accuracy for a majority of genes because genotypic data lack tissue- and disease-specificity and are not affected by the environment. Because methylation is tissue-specific and, like gene expression, can be modified by environment or disease status, methylation should predict gene expression with more accuracy than SNPs. Therefore, we propose Methyl-TWAS, the first approach that utilizes long-range methylation markers to impute gene expression forin silicoTWAS through penalized regression. Methyl-TWAS 1) predicts epigenetically regulated/associated expression (eGReX), which incorporates tissue-specific expression and both genetically- (GReX) and environmentally-regulated expression to identify differentially expressed genes (DEGs) that could not be identified by genotype-based methods; and 2) incorporates bothcis-andtrans-CpGs, including various regulatory regions to identify DEGs that would be missed usingcis-methylation only. Methyl-TWAS outperforms PrediXcan and two other methods in imputing gene expression in the nasal epithelium, particularly for immunity-related genes and DEGs in atopic asthma. Methyl-TWAS identified 3,681 (85.2%) of the 4,316 DEGs identified in a previous TWAS of atopic asthma using measured expression, while PrediXcan could not identify any gene. Methyl-TWAS also outperforms PrediXcan for expression imputation as well asin silicoTWAS in white blood cells. Methyl-TWAS is a valuable tool forin silicoTWAS, leveraging a growing body of publicly available genome-wide DNA methylation data for a variety of human tissues.
Thein vitrofunctional profiles of fentanyl and nitazene analogs at the µ-opioid receptor - high efficacy is dangerous regardless of signaling bias
Authors: Tsai Meng-Hua M. , Chen Li , Baumann Michael H. , Canals Meritxell , Javitch Jonathan A. , Lane J. Robert , Shi Lei 
Published: November 2023

AbstractNovel synthetic opioids (NSOs), including both fentanyl and non-fentanyl analogs that act as the μ-opioid receptor (MOR) agonists, are associated with serious intoxication and fatal overdose. Previous studies proposed that G protein biased MOR agonists are safer pain medications, while other evidence indicates that low intrinsic efficacy at MOR better explains reduced opioid side effects. Here, we characterized thein vitrofunctional profiles of various NSOs at MOR using adenylate cyclase inhibition and β-arrestin2 recruitment assays, in conjunction with the application of the receptor depletion approach. By fitting the concentration-response data to the operational model of agonism, we deduced the intrinsic efficacy and affinity for each opioid in the Gi protein signaling and β-arrestin2 recruitment pathways. Compared to the reference agonist DAMGO, we found that several fentanyl analogs were more efficacious at inhibiting cAMP production, whereas all fentanyl analogs were less efficacious at recruiting β-arrestin2. In contrast, the non-fentanyl 2-benzylbenzimidazole (i.e., nitazene) analogs were highly efficacious and potent in both the cAMP and β-arrestin2 assays. Our findings suggest that the high intrinsic efficacy of the NSOs in Gi protein signaling is a common property that may underlie their high risk of intoxication and overdose, highlighting the limitation of usingin vitrofunctional bias to predict the adverse effects of opioids. Instead, our results show that, regardless of bias, opioids with sufficiently high intrinsic efficacy can be lethal, especially given the extremely high potency of many of these compounds that are now pervading the illicit drug market.
Hybrid-hybrid correction of errors in long reads with HERO
Authors: Kang Xiongbin , Xu Jialu , Luo Xiao , Schönhuth Alexander 
Published: November 2023

AbstractAlthough generally superior, hybrid approaches for correcting errors in third-generation sequencing (TGS) reads, using next-generation sequencing (NGS) reads, mistake haplotype-specific variants for errors in polyploid and mixed samples. We suggest HERO, as the first “hybrid-hybrid” approach, to make use of both de Bruijn graphs and overlap graphs for optimal catering to the particular strengths of NGS and TGS reads. Extensive benchmarking experiments demonstrate that HERO improves indel and mismatch error rates by on average 65% (27 95%) and 20% (4 61%). Using HERO prior to genome assembly significantly improves the assemblies in the majority of the relevant categories.
Scaling deep identifiable models enables zero-shot characterization of single-cell biological states
Authors: Dong Mingze , Agrawal Kriti , Fan Rong , Sefik Esen , Flavell Richard A. , Kluger Yuval 
Published: November 2023

AbstractHow to identify true biological differences across samples while overcoming batch effects has been a persistent challenge in single-cell RNA-seq data analysis, hindering analyses across datasets for transferable biological findings. In this work, we show that scaling up deep identifiable models leads to a surprisingly effective solution for this challenging task. We developed scShift, a deep variational inference framework with theoretical support in disentangling batch-dependent and independent variations. By training the model with compendiums of scRNA-seq atlases, scShift shows remarkablezero-shotcapabilities in revealing representations of cell types and biological states in single-cell data while overcoming batch effects. We employed scShift to systematically compare lung fibrosis states across different datasets, tissues and experimental systems. scShift uniquely extrapolates lung fibrosis states to previously unseen post-COVID-19 fibrosis, characterizing universal myeloid-fibrosis signatures, potential repurposing drug targets and fibrosis-associated cell interactions. Evaluations of over 200 trained scShift models demonstrate emergent zero-shot capabilities and a scaling law beyond a transition threshold, with respect to dataset diversity. With its scaling performance on massive single-cell compendiums and exceptional zero-shot capabilities, scShift represents an important advance toward next-generation computational models for single-cell analysis.
Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model
Authors: Whyte-Fagundes P , Vance A , Carroll A , Figueroa F , Manukyan C , Baraban S.C. 
Published: November 2023

AbstractDravet syndrome (DS) is a severe genetic epilepsy primarily caused byde novomutations in a voltage-activated sodium channel gene (SCN1A). Patients face life-threatening seizures that are largely resistant to available anti-seizure medications (ASM). Preclinical DS animal models are a valuable tool to identify candidate ASMs for these patients. Among these,scn1labmutant zebrafish exhibiting spontaneous seizure-like activity are particularly amenable to large-scale drug screening. Prior screening in ascn1labmutant zebrafish line generated using N-ethyl-N-nitrosourea (ENU) identified valproate, stiripentol, and fenfluramine e.g., Federal Drug Administration (FDA) approved drugs with clinical application in the DS population. Successful phenotypic screening inscn1labmutant zebrafish consists of two stages: (i) a locomotion-based assay measuring high-velocity convulsive swim behavior and (ii) an electrophysiology-based assay, usingin vivolocal field potential (LFP) recordings, to quantify electrographic seizure-like events. Using this strategy more than 3000 drug candidates have been screened inscn1labzebrafish mutants. Here, we curated a list of nine additional anti-seizure drug candidates recently identified in preclinical models: 1-EBIO, AA43279, chlorzoxazone, donepezil, lisuride, mifepristone, pargyline, soticlestat and vorinostat. First-stage locomotion-based assays inscn1labmutant zebrafish identified only 1-EBIO, chlorzoxazone and lisuride. However, second-stage LFP recording assays did not show significant suppression of spontaneous electrographic seizure activity for any of the nine anti-seizure drug candidates. Surprisingly, soticlestat induced frank electrographic seizure-like discharges in wild-type control zebrafish. Taken together, our results failed to replicate clear anti-seizure efficacy for these drug candidates highlighting a necessity for strict scientific standards in preclinical identification of ASMs.
Photobody formation spatially segregates two opposing phytochrome B signaling actions to titrate plant environmental responses
Authors: Kim Ruth Jean Ae , Fan De , He Jiangman , Kim Keunhwa , Du Juan , Chen Meng 
Published: November 2023

ABSTRACTPhotoactivation of the plant photoreceptor and thermosensor phytochrome B (PHYB) triggers its condensation into subnuclear photobodies (PBs). However, the function of PBs remains frustratingly elusive. Here, we found that PHYB recruits PHYTOCHROME-INTERACTING FACTOR5 (PIF5) to PBs. Surprisingly, PHYB exerts opposing roles in degrading and stabilizing PIF5. Perturbing PB size by overproducing PHYB provoked a biphasic PIF5 response: while a moderate increase in PHYB enhanced PIF5 degradation, further elevating the PHYB level stabilized PIF5 by retaining more of it in enlarged PBs. These results reveal a PB-mediated light and temperature sensing mechanism, in which PHYB condensation confers the co-occurrence and competition of two antagonistic phase-separated PHYB signaling actions—PIF5 stabilization in PBs and PIF5 degradation in the surrounding nucleoplasm— thereby enabling an environmentally-sensitive counterbalancing mechanism to titrate nucleoplasmic PIF5 and its transcriptional output. This PB-enabled signaling mechanism provides a framework for regulating a plethora of PHYB-interacting signaling molecules in diverse plant environmental responses.