bluuebunny/crossref_metadata_2025_split huggingface dataset:
A perfusion-independent high-throughput method to isolate liver sinusoidal endothelial cells
Authors: Babin-Ebell Gonçalves Anna , Mao Yifang , Baljkas Tinja , Wiedmann Felix , Pilz Franziska , Winkler Manuel , Kürschner-Zacharias Sina W. , Hoffarth Marlene , Schmidt Constanze , Goerdt Sergij , Reiners-Koch Philipp-Sebastian , Singhal Mahak 
Published: March 2024

SummaryLiver sinusoidal endothelial cells (LSECs) critically regulate homeostatic liver function and liver pathogenesis. However, the isolation of LSECs remains a major technological bottleneck in studying molecular mechanisms governing LSEC functions. Current techniques to isolate LSECs, relying on perfusion-dependent liver digestion, are cumbersome with limited throughput. We here describe a perfusion-independent high-throughput procedure to isolate LSECs with high purity. Indifferently from previous perfusion-independent approaches, chopped liver tissue was incubated in the digestion mix for 30 minutes with intermittent mixing with a serological pipette. This led to the safeguarding of LSEC integrity and yielded 10 ± 1.0 million LSECs per adult mouse liver, which is far higher than previous perfusion-independent protocols and comparable yield to established perfusion-dependent protocols for isolating LSECs. Combining magnetic and fluorescence-activated cell sorting (FACS), LSECs from different zones of the hepatic sinusoid can now be isolated in high numbers in less than two hours for downstream applications including proteomics. Our protocol enabled the isolation of LSECs from fibrotic liver tissues from mice and healthy liver tissues from higher vertebrate species (pigs), where traditional perfusion-based digestion protocols have very limited application. In conclusion, these technical advancements reduce post-mortem changes in the LSEC state and aid in reliable investigation of LSEC functions.
Stiffness regulates dendritic cell and macrophage subtype development and increased stiffness induces a tumor-associated macrophage phenotype in cancer co-cultures
Authors: Guenther Carla 
Published: March 2024

AbstractMechanical properties of tissues including their stiffness change throughout our lives, during both healthy development but also during chronic diseases like cancer (1-4). How changes to stiffness, occurring during cancer progression, impact leukocytes is unknown. To address this, myeloid phenotypes resulting from mono- and cancer co-cultures of primary murine and human myeloid cells on 2D and 3D hydrogels with varying stiffnesses were analyzed. On soft hydrogels, conventional DCs (cDCs) developed, whereas on stiff hydrogels plasmacytoid DCs (pDCs) developed. Cell populations expressing macrophage markers CD14, Ly6C, and CD16 also increased on stiff hydrogels. In cancer co-cultures, CD86+populations decreased on higher stiffnesses across four different cancer types. High stiffness also led to increased vascular endothelial growth factor A (VEGFA), matrix metalloproteinases (MMP) and CD206 expression; ‘M2’ markers expressed by tumour-associated macrophages (TAMs) (5). Indeed, the majority of CD11c+cells expressed CD206 across human cancer models. Targeting the PI3K/Akt pathway led to a decrease in CD206+cells in murine cultures only, while human CD86+cells increased.Increased stiffness in cancer could, thus, lead to the dysregulation of infiltrating myeloid cells and shift their phenotypes towards a M2-like TAM phenotype, thereby actively enabling tumor progression. Additionally, stiffness-dependent signaling appears species-dependent, potentially contributing to the high failure rate of clinical trials (6).
Subject-Agnostic Transformer-Based Neural Speech Decoding from Surface and Depth Electrode Signals
Authors: Chen Junbo , Chen Xupeng , Wang Ran , Le Chenqian , Khalilian-Gourtani Amirhossein , Jensen Erika , Dugan Patricia , Doyle Werner , Devinsky Orrin , Friedman Daniel , Flinker Adeen , Wang Yao 
Published: March 2024

AbstractObjectiveThis study investigates speech decoding from neural signals captured by intracranial electrodes. Most prior works can only work with electrodes on a 2D grid (i.e., Electrocorticographic or ECoG array) and data from a single patient. We aim to design a deep-learning model architecture that can accommodate both surface (ECoG) and depth (stereotactic EEG or sEEG) electrodes. The architecture should allow training on data from multiple participants with large variability in electrode placements and the trained model should perform well on participants unseen during training.ApproachWe propose a novel transformer-based model architecture named SwinTW that can work with arbitrarily positioned electrodes by leveraging their 3D locations on the cortex rather than their positions on a 2D grid. We train subject-specific models using data from a single participant and multi-patient models exploiting data from multiple participants.Main ResultsThe subject-specific models using only low-density 8×8 ECoG data achieved high decoding Pearson Correlation Coefficient with ground truth spectrogram (PCC=0.817), over N=43 participants, outperforming our prior convolutional ResNet model and the 3D Swin transformer model. Incorporating additional strip, depth, and grid electrodes available in each participant (N=39) led to further improvement (PCC=0.838). For participants with only sEEG electrodes (N=9), subject-specific models still enjoy comparable performance with an average PCC=0.798. The multi-subject models achieved high performance on unseen participants, with an average PCC=0.765 in leave-one-out cross-validation.SignificanceThe proposed SwinTW decoder enables future speech neuropros-theses to utilize any electrode placement that is clinically optimal or feasible for a particular participant, including using only depth electrodes, which are more routinely implanted in chronic neurosurgical procedures. Importantly, the generalizability of the multi-patient models suggests that such a model can be applied to new patients that do not have paired acoustic and neural data, providing an advance in neuroprostheses for people with speech disability, where acoustic-neural training data is not feasible.
Treatment Outcomes of Doxycycline Use for Musculoskeletal Infections: A Systematic Review and Meta-Analysis
Authors: Aljadani Rawabi , Bravo Carolina Gonzalez , Bojang Matida , Carvour Martha L. 
Published: March 2024

ABSTRACTDoxycycline is among the most commonly used antibiotics for the treatment and long-term suppression of musculoskeletal infections such as osteomyelitis and periprosthetic joint infection. We systematically reviewed clinical trials and cohort studies that examined outcomes of musculoskeletal infections treated with doxycycline. Eligible studies were published in Medline or Embase in English before March 2, 2021. Eleven reports were included; eight addressed medical/non-dental infections, and three addressed dental infections.Brucellawas the most frequently studied organism in the non-dental studies. Random-effects meta-analyses showed no significant difference inBrucellarelapse risk after six weeks of treatment with 200 mg doxycycline compared to 400 mg ofloxacin daily (pool risk ratio: 0.94, 95% confidence interval: 0.2 - 4.45, I2=L0%). Despite a large number of case reports, case series, and cross- sectional studies on this topic, few studies investigated doxycycline treatment outcomes; and evidence was largely limited to rare infections such asBrucella.
SCAPE-APA: a package for estimating alternative polyadenylation events from scRNA-seq data
Authors: Cheng Guangzhao , Le Tien , Zhou Ran , Cheng Lu 
Published: March 2024

AbstractSummarySCAPE is a package we previously developed to estimate alternative polyadenylation events from single cell RNA-seq (scRNA-seq) data, which is composed of ad-hoc python scripts and has speed issues when handling large scRNA-seq data. To suit the needs of analyzing large scRNA-seq datasets, we present SCAPE-APA, which is a re-implementation of SCAPE with substantial changes. We made the following updates to the package (1) we binned similar reads together to accelerate the estimation (2) we re-derived the mixture model to tailor it for binned reads (3) we implemented the inference algorithm using Taichi language for acceleration (4) we re-implemented the untranslated region (UTR) annotation extraction script using the professional package gffutils for better maintenance (5) we wrote a script to detect spurious alternative polyadenylation sites generated due to junction reads and (6) we made a formal python package and uploaded it to the Python Package Index website (Pypi).Availability and ImplementationScape-apa is freely available athttps://github.com/chengl7-lab/scapeand can be easily installed using pip.Contactlu.cheng.ac@gmail.com
TheMycobacterium tuberculosiscomplex pangenome is small and driven by sub-lineage-specific regions of difference
Authors: Behruznia Mahboobeh , Marin Maximillian , Farhat Maha , Thomas Jonathan C , Domingo-Sananes Maria Rosa , Meehan Conor J 
Published: March 2024

AbstractTheMycobacterium tuberculosiscomplex (MTBC) is a group of bacteria causing tuberculosis (TB) in humans and animals. Understanding MTBC genetic diversity is crucial for insights into its adaptation and traits related to survival, virulence, and antibiotic resistance. While it is known that within MTBC diversity is characterised by large lineage-specific deletions (regions of difference [RD]), a comprehensive pangenomic analysis incorporating both coding and non-coding regions remains unexplored. We utilised a curated dataset representing various MTBC genomes, including under-represented lineages to quantify the true diversity of the MTBC pangenome. The MTBC was found to have a small, closed pangenome with distinct genomic features and RDs both between lineages (as previously known) and between sub-lineages. The accessory genome was identified to be a product of genome reduction, showing both lineage-specific and independent deletions. This variation has implications for traits like virulence, drug resistance, and metabolism. The study provides a comprehensive understanding of the MTBC pangenome, highlighting the importance of genome reduction in its evolution and showing that within-lineage genome content diversity is present. The findings underline the significance of genomic variations in determining the pathogenic traits of different MTBC lineages.
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Authors: Hermosilla-Trespaderne Marina , Hu-Yang Mark Xinchen , Dannoura Abeer , Frey Andrew M. , George Amy L. , Trost Matthias , Marín-Rubio José Luis 
Published: March 2024

ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukaemia (CML) cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilising CDK4/6 and downregulating cell cycle-related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the non-small cell lung carcinoma cell line (NSCLC), A549. These findings highlight trilaciclib’s potential as a therapeutic option for haematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in CML treatment, as well as in NSCLC.ABSTRACT GRAPHIC
The GC-content at the 5’ends of human protein-coding genes is undergoing mutational decay
Authors: Qiu Yi , Kang Yoon Mo , Korfmann Christopher , Pouyet Fanny , Eckford Andrew , Palazzo Alexander F. 
Published: March 2024

AbstractIn vertebrates, most protein-coding genes have a peak of GC-content near their 5’ transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation of mRNAs. Despite the importance of GC-content for RNA metabolism, its general features, origin, and maintenance remain mysterious. We investigated the evolutionary forces shaping GC-content at the transcriptional start site (TSS) of genes through both comparative genomic analysis of nucleotide substitution rates between different species and by examining humande novomutations. Our data suggests that GC-peaks at TSSs were present in the last vertebrate common ancestor and are largely dictated by recombination patterns. We observe that in primates and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at protein-coding gene TSSs is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at protein-coding gene TSSs is increasing. These patterns extend into the open reading frame affecting protein-coding regions, and we show that changes in GC-content due to recombination affect synonymous codon position choices at the start of the open reading frame. Our results indicate that although high GC-content in protein-coding genes may be shaped by selective pressures to enhance expression, the dynamics of GC-content in mammals are largely shaped by patterns of recombination.
Reliability of brain metrics derived from a Time-Domain Functional Near-Infrared Spectroscopy System
Authors: Dubois Julien , Field Ryan M. , Jawhar Sami , Koch Erin M. , Aghajan Zahra M. , Miller Naomi , Perdue Katherine L. , Taylor Moriah 
Published: March 2024

AbstractWith the growing interest in establishing brain-based biomarkers for precision medicine, there is a need for noninvasive, scalable neuroimaging devices that yield valid and reliable metrics. Kernel’s second-generation Flow2 Time-Domain Functional Near-Infrared Spectroscopy (TD-fNIRS) system meets the requirements of noninvasive and scalable neuroimaging, and uses a validated modality to measure brain function. In this work, we investigate the test-retest reliability (TRR) of a set of metrics derived from the Flow2 recordings. We adopted a repeated-measures design with 49 healthy participants, and quantified TRR over multiple time points and different headsets—in different experimental conditions including a resting state, a sensory, and a cognitive task. Results demonstrated high reliability in resting state features including hemoglobin concentrations, head tissue light attenuation, amplitude of low frequency fluctuations, and functional connectivity. Additionally, passive auditory and Go/No-Go inhibitory control tasks each exhibited similar activation patterns across days. Notably, areas with the highest reliability were in auditory regions during the auditory task, and right prefrontal regions during the Go/No-Go task, consistent with prior literature. This study underscores the reliability of Flow2-derived metrics, supporting its potential to actualize the vision of using brain-based biomarkers for diagnosis, treatment selection and treatment monitoring of neuropsychiatric and neurocognitive disorders.
A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring
Authors: Dowrey Todd W. , Cranston Samuel F. , Skvir Nicholas , Lok Yvonne , Gould Brian , Petrowitz Bradley , Villar Daniel , Shan Jidong , James Marianne , Dodge Mark , Belkina Anna C. , Giadone Richard M. , Sebastiani Paola , Perls Thomas T. , Andersen Stacy L. , Murphy George J. 
Published: March 2024

ABSTRACTCentenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models ofhumanaging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 50 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.
Divergent marine anaerobic ciliates harbor closely relatedMethanocorpusculumendosymbionts
Authors: Schrecengost Anna , Rotterová Johana , Poláková Kateřina , Čepička Ivan , Beinart Roxanne 
Published: March 2024

ABSTRACTCiliates are a diverse group of protists known for their ability to establish various partnerships and thrive in a wide variety of oxygen-depleted environments. Most anaerobic ciliates harbor methanogens, one of the few known archaea living intracellularly. These methanogens increase the metabolic efficiency of host fermentation via syntrophic use of host end-product in methanogenesis. Despite the ubiquity of these symbioses in anoxic habitats, patterns of symbiont specificity and fidelity are not well known. We surveyed two unrelated, commonly found groups of anaerobic ciliates, the Plagiopylea and Metopida, isolated from anoxic marine sediments. We sequenced host 18S rRNA and symbiont 16S rRNA marker genes as well as the symbiont ITS region from our cultured ciliates to identify hosts and their associated methanogenic symbionts. We found that marine ciliates from both of these co-occurring, divergent groups harbor closely related yet distinct intracellular archaea within theMethanocorpusculumgenus. The symbionts appear to be stable at the host species level, but at higher taxonomic levels, there is evidence that symbiont replacements have occurred. Gaining insight into this unique association will deepen our understanding of the complex transmission modes of marine microbial symbionts, and the mutualistic microbial interactions occurring across domains of life.
Transcriptional and neurochemical signatures of cerebral blood flow alterations in schizophrenia and the clinical high-risk state for psychosis
Authors: Knight S.R. , Abbasova L. , Zeighami Y. , Hansen J.Y. , Martins D. , Zelaya F. , Dipasquale O. , Liu T. , Shin D. , Bossong M.G. , Azis M. , Antoniades M. , Howes O. , Bonoldi I. , Egerton A. , Allen P. , O’Daly O. , McGuire P. , Modinos G. 
Published: March 2024

ABSTRACTThe brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behaviour, and understanding the relationships between these layers may be fundamental to advancing our understanding of how the brain works in health and disease. Recent neuroimaging research has shown that alterations in brain function that are associated with schizophrenia spectrum disorders (SSD) are already present in young adults at clinical high-risk for psychosis (CHR-P), yet the cellular and molecular determinants of these alterations are not well understood. Here, combining regional cerebral blood flow (rCBF) data with existing transcriptomic and neurotransmitter data, we show that cell-types involved in stress response and inflammation, as well as the dopamine, acetylcholine, GABAA and NMDA receptor systems, align as shared and distinct cellular and neurochemical signatures of rCBF phenotypes in people with SSD and those at CHR-P. Decoding the biological pathways involved in neuroimaging-based psychosis phenotypes may provide a basis for the development of novel interventions.
Stem rot affects the structure of rhizosphere microbiome in Berseem Clover (Trifolium alexandrinum)
Authors: Mukhtar Salma , Ahmad Zain , Khan Noor , John Michael , Aiysha Dalaq 
Published: March 2024

AbstractRhizosphere microbiome plays an essential role in maintaining plant health and productivity. Fungal and bacterial diseases may affect the rhizosphere-associated microbial communities and overall structure of plant microbiome. Here, we studied the effect of stem rot of berseem clover on the bacterial and fungal communities associated with the rhizosphere. We analyzed the rhizosphere-associated bacterial and fungal microbiome from healthy and infected berseem clover collected from three sampling sites by using 16S rRNA and ITS based Illumina sequencing metabarcoding approach. Microbiome analysis showed that healthy plants had higher bacterial and fungal diversity as compared to stem rot infected plants. At the genus level, bacterial generaRhizobiumandComamonaswere more abundant in healthy plants whilePantoeawas more abundant in infected plants and fungal generaSclerotinia,FusariumandCladorrhinumwere more abundant in infected plants whileMicrodochiumandCladosporiumwere distinctively abundant in healthy Berseem. Functional characterization of bacterial and fungal microbiomes revealed that bacterial communities from infected plants showed more abundance of bacteria with functions replication and repair, enzyme families and biosynthesis of other secondary metabolites as compared to healthy plant microbiome and decreased in fungal groups including arbuscular mycorrhiza and soil saprotrophs and an increase in plant saprotrophs and fungal parasite-plant pathogens. This study provides comprehensive information about the structure and composition of bacterial and fungal communities associated with the berseem clover rhizosphere that could be utilized for future research on the control of stem rot of berseem clover.