bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy and reliability of data extraction for systematic reviews using large language models: A protocol for a prospective study
Authors: Oami Takehiko , Okada Yohei , Nakada Taka-aki 
Published: May 2024

AbstractBackgroundSystematic reviews require extensive time and effort to manually extract and synthesize data from numerous screened studies. This study aims to investigate the ability of large language models (LLMs) to automate data extraction with high accuracy and minimal bias, using clinical questions (CQs) of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG) 2024. the study will evaluate the accuracy of three LLMs and optimize their command prompts to enhance accuracy.MethodsThis prospective study will objectively evaluate the accuracy and reliability of the extracted data from selected literature in the systematic review process in J-SSCG 2024 using three LLMs (GPT-4 Turbo, Claude 3, and Gemini 1.5 Pro). Detailed assessment of errors will be determined according to the predefined criteria for further improvement. Additionally, the time to complete each task will be measured and compared among the three LLMs. Following the primary analysis, we will optimize the original command with integration of prompt engineering techniques in the secondary analysis.Trial registrationThis research is submitted with the University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN000054461].Conflicts of interestAll authors declare no conflicts of interest to have.
Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses
Authors: Conner Tonia L. , Goguet Emilie , Haines-Hull Hannah , Segard Allison , Darcey Emily S. , Kobi Priscilla , Balogun Bolatito , Olsen Cara , Esposito Dominic , Jones Milissa , Burgess Timothy H. , O’Connell Robert J. , Broder Christopher C. , Saunders David , Pollett Simon , Laing Eric D. , Mitre Edward 
Published: May 2024

SUMMARYThis study characterized antibody responses induced by COVID-19 mRNA vaccination and SARS-CoV-2 infection in saliva. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, and secretory IgA in 1,224 saliva samples collected from healthcare workers in the Prospective Assessment of SARS-CoV-2 Seroconversion study between August of 2020 through December of 2022. By spring of 2022, most individuals had detectable spike-specific antibodies in saliva. Longitudinal measurements of saliva anti-SARS-CoV-2 nucleocapsid IgG revealed that most spike-specific IgA and secretory IgA detected in saliva was driven by subclinical and clinically-evident infections, rather than by vaccination alone. In contrast, saliva anti-SARS-CoV-2 spike IgG was strongly induced by vaccination and exhibited improved durability with hybrid immunity. Baseline levels of saliva antibodies to the endemic human coronaviruses positively correlated with post-vaccination anti-SARS-CoV-2 spike IgG levels. This study provides insights for development of vaccines that generate mucosal antibodies to respiratory pathogens.HIGHLIGHTSSaliva anti-spike antibodies were present in > 90% of participants by spring 2022Saliva anti-spike IgA was driven by subclinical and clinically evident infectionsCOVID-19 mRNA vaccination alone was a weak inducer of saliva IgA antibodiesHCoV immunity correlates with post-vaccine anti-spike saliva antibody levels
Discordance between a deep learning model and clinical-grade variant pathogenicity classification in a rare disease cohort
Authors: Kong Sek Won , Lee In-Hee , Collen Lauren V. , Manrai Arjun K. , Snapper Scott B. , Mandl Kenneth D. 
Published: May 2024

AbstractGenetic testing has become an essential component in the diagnosis and management of a wide range of clinical conditions, from cancer to developmental disorders, especially in rare Mendelian diseases. Efforts to identify rare phenotype-associated variants have predominantly focused on protein-truncating variants, while the interpretation of missense variants presents a considerable challenge. Deep learning algorithms excel in various applications across biomedical tasks1,2, yet accurately distinguishing between pathogenic and benign genetic variants remains an elusive goal3-5. Specifically, even the most sophisticated models encounter difficulties in accurately assessing the pathogenicity of missense variants of uncertain significance (VUS). Our investigation of AlphaMissense (AM)5, the latest iteration of deep learning methods for predicting the potential functional impact of missense variants and assessing gene essentiality, reveals important limitations in its ability to identify pathogenic missense variants within a rare disease cohort. Indeed, AM struggles to accurately assess the pathogenicity of variants in intrinsically disordered regions (IDRs), leading to unreliable gene-level essentiality scores for certain genes containing IDRs. This limitation highlights the challenges in applying AM faces in the context of clinical genetics6.
Optimized Time-segmented Acquisition Expands Peptide and Protein Identification in TIMS-TOF Pro Mass Spectrometry
Authors: Zhang Huoming , Bensaddek Dalila 
Published: May 2024

AbstractWe introduce here a novel approach, termed time-segmented acquisition (Seg), to enhance the identification of peptides and proteins in trapped ion mobility spectrometry (TIMS)-Time of flight (TOF) mass spectrometry. Our method exploits the positive correlation between ion mobility values and liquid chromatography (LC) retention time to improve ion separation and resolution. By dividing the LC retention time into multiple segments and applying a segment-specific narrower ion mobility range within the TIMS tunnel, we achieved better separation and higher resolution of ion mobility. This resulted in a substantial increase in peptide identification. In comparison to conventional TIMS methods, which typically scan a static ion mobility range (either from 0.6 to 1.6 or from 0.85 to 1.3), the Seg method significantly enhances the identification of peptides, proteins and average sequence coverage per protein. These findings highlight the potential of the Seg method in expanding the capabilities of TIMS-TOF mass spectrometry, especially for peptide-focused analysis such as post-translational modifications and peptidomics.
reCRAC: A Stringent Method for Precise Mapping of Protein-RNA Interactions in Yeast
Authors: Ristova Michaela , Shchepachev Vadim , Tollervey David 
Published: May 2024

AbstractIntricate interactions between RNA-binding proteins (RBPs) and RNA play pivotal roles in cellular homeostasis, impacting a spectrum of biological processes vital for survival. UV crosslinking methods to study protein-RNA interactions have been instrumental in elucidating their interactions but can be limited by degradation of target proteins during the process, low signal-to-noise ratios, and non-specific interactions. Addressing these limitations, we describe reCRAC (reverse CRAC), a novel adaptation of the CRAC (crosslinking and analysis of cDNA) technique, optimized for yeastSaccharomyces cerevisiae. Like CRAC, reCRAC applies tandem affinity purification to yield highly enriched protein preparations. However, reCRAC is redesigned to work with unstable proteins. This is achieved by lysing the cells directly into highly denaturing buffer conditions, followed by stringent purification steps. The reCRAC method was successfully applied to the easily degraded yeast protein Pin4, allowing identification of precise binding sites at base-pair resolution with greatly reduced target protein degradation and improved signal-to-noise ratios.
Spatial Profiling of Metals through Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging
Authors: Stopka Sylwia A. , Bodineau Clément , Baquer Gerard , Lin Jia-Ren , Hossain Md Amin , Regan Michael S. , Ruiz Daniela , Fletcher Stecia-Marie , Pourquié Olivier , Lutsenko Svetlana , Payne Connor N. , Agar Jeffrey N. , Mazitschek Ralph , McDannold Nathan J. , Sorger Peter K. , Santagata Sandro , Agar Nathalie Y. R. 
Published: May 2024

AbstractThe spatial-omic analysis of biomolecules such as nucleic acids, lipids, metabolites, and proteins is advancing the study of biological systems and processes in a physio-pathological context. Here, we describe an innovative matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) method to detect metals within biological tissues using instrumentation that is widely available in research and clinical laboratories. We characterize the spatial distribution of metals in diverse settings including mouse embryogenesis, genetic disorders leading to abnormal metal accumulation, and preclinical testing for improved platinum-based chemotherapy delivery through focused ultrasound across the blood-brain barrier. Spatial metal profiling will advance research studies and the clinical analysis of metal-related diseases, enabling more precise use of metal-based therapies and advances in diverse scientific fields beyond biomedicine.One-Sentence SummarySpatial metallomic profiling maps native metals or those coordinated to xenobiotics, antibodies, and biomolecules in tissues.
Tau pathology leads to lonely non-traveling slow waves that mediate human memory impairment
Authors: Sharon Omer , Chen Xi , Dude Jason , Shah Vyoma D. , Ju Yo-El S. , Jagust Willam J. , Walker Matthew P 
Published: May 2024

AbstractMemory markedly declines with age, exaggerated in those with Alzheimer’s disease, yet the mechanisms are still not resolved. Here, we show that frontal lobe tau pathology in humans leads to impaired en masse unity and cortical traveling propagation of NREM slow waves, consequentially impairing memory retention. We elucidate these findings using PET tau brain imaging, and then replicate and extend them using AD pathology markers derived from lumbar puncture CSF in an independent clinical cohort. Thus, tau-associated memory deficits are not wholly direct, but indirectly mediated through consequential “lonely”, non-traveling slow-wave events.
Gene deletion as a possible strategy adopted by New WorldLeishmania infantumto maximize geographic dispersion
Authors: Florêncio Monique , Chagas Marne Coimbra , Guimarães-Costa Anderson , Oliveira Jullyanna , Waclawiak Ingrid , Oliveira Thamara K. F. , Saraiva Elvira Maria , Freitas-Mesquita Anita Leocadio , Meyer-Fernandes José Roberto , Aragão-Farias Laura , Trindade Camilly Enes , Escobar Patricia Cuervo , Nascimento Renata Azevedo do , Moreira Otacilio C. , Ribeiro-Gomes Flávia Lima , Traub-Csekö Yara M. , Telleria Erich Loza , Vaselek Slavica , Leštinová Tereza , Volf Petr , Späth Gerald F. , Cupolillo Elisa , Boité Mariana C. 
Published: May 2024

AbstractBackgroundThe present study investigates implications of a sub-chromosomal deletion inLeishmania infantumstrains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3’-nucleotidase/nuclease enzyme (3’NU/NT), impacting parasite virulence, pathogenicity, and drug susceptibility. The potential factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the New World (NW) are discussed under the generated data.MethodsWe conducted phenotypic analyses of the parasites showing the sub- chromosomal deletion by applyingin vitroassays of 3’NU/NT activity, metacyclic enrichment, and relative quantitation of transcripts abundance on axenic parasites. We further performed experimental infections in bothin vitroandin vivomodels of vertebrate and invertebrate hosts using geographically diverse mutant field isolates.ResultsVirulence assays, poorer ability to survive neutrophil traps (NETs) and murine model infection revealed reduced pathogenicity in vertebrate hosts by the DEL strains. Conversely, these parasites exhibit enhanced metacyclogenesis and colonization rates in sand flies, potentially facilitating transmission. This combination may represent a more efficient way to maintain and disperse the transmission cycle of DEL strains.ConclusionsPhenotypic assessments reveal altered parasite fitness, with enhanced transmissibility at the population level. Reduced susceptibility of DEL strains to miltefosine, a key drug in VL treatment, further complicates control efforts. Our study underscores the importance of typing parasite genomes for surveillance and control and proposes the sub-chromosomal deletion as a molecular marker in AVL management.
Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain
Authors: Dias Caroline , Mo Alisa , Cai Chunhui , Sun Liang , Cabral Kristen , Brownstein Catherine A. , Rockowitz Shira , Walsh Christopher A. 
Published: May 2024

AbstractRecurrent copy number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder (ASD). Duplication of 15q11.2-13.1 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of ASD by over 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown. To identify the cell-type-specific transcriptional and epigenetic effects of dup15q in the human frontal cortex we conducted single-nucleus RNA-sequencing and multi-omic sequencing on dup15q cases (n=6) as well as non-dup15q ASD (n=7) and neurotypical controls (n=7). Cell-type-specific differential expression analysis identified significantly regulated genes, critical biological pathways, and differentially accessible genomic regions. Although there was overall increased gene expression across the duplicated genomic region, cellular identity represented an important factor mediating gene expression changes. Neuronal subtypes, showed greater upregulation of gene expression across a critical region within the duplication as compared to other cell types. Genes within the duplicated region that had high baseline expression in control individuals showed only modest changes in dup15q, regardless of cell type. Of note, dup15q and ASD had largely distinct signatures of chromatin accessibility, but shared the majority of transcriptional regulatory motifs, suggesting convergent biological pathways. However, the transcriptional binding factor motifs implicated in each condition implicated distinct biological mechanisms; neuronal JUN/FOS networks in ASD vs. an inflammatory transcriptional network in dup15q microglia. This work provides a cell-type-specific analysis of how dup15q changes gene expression and chromatin accessibility in the human brain and finds evidence of marked cell-type-specific effects of this genetic driver. These findings have implications for guiding therapeutic development in dup15q syndrome, as well as understanding the functional effects CNVs more broadly in neurodevelopmental disorders.
VesselBoost: A Python Toolbox for Small Blood Vessel Segmentation in Human Magnetic Resonance Angiography Data
Authors: Xu Marshall , Ribeiro Fernanda L. , Barth Markus , Bernier Michaël , Bollmann Steffen , Chatterjee Soumick , Cognolato Francesco , Gulban Omer Faruk , Itkyal Vaibhavi , Liu Siyu , Mattern Hendrik , Polimeni Jonathan R. , Shaw Thomas B. , Speck Oliver , Bollmann Saskia 
Published: May 2024

AbstractMagnetic resonance angiography (MRA) performed at ultra-high magnetic field provides a unique opportunity to study the arteries of the living human brain at the mesoscopic level. From this, we can gain new insights into the brain’s blood supply and vascular disease affecting small vessels. However, for quantitative characterization and precise representation of human angioarchitecture to, for example, inform blood-flow simulations, detailed segmentations of the smallest vessels are required. Given the success of deep learning-based methods in many segmentation tasks, we here explore their application to high-resolution MRA data, and address the difficulty of obtaining large data sets of correctly and comprehensively labelled data. We introduceVesselBoost, a vessel segmentation package, which utilizes deep learning and imperfect training labels for accurate vasculature segmentation. Combined with an innovative data augmentation technique, which leverages the resemblance of vascular structures,VesselBoostenables detailed vascular segmentations.
A single amino acid substitution in the Borna disease virus glycoprotein enhances the infectivity titer of vesicular stomatitis virus pseudotyped virus by altering membrane fusion activity
Authors: Akiba Yusa , Matsugo Hiromichi , Kanda Takehiro , Sakai Modoka , Makino Akiko , Tomonaga Keizo 
Published: May 2024

AbstractBorna disease virus 1 (BoDV-1) causes acute fatal encephalitis in mammals, including humans. Despite its importance, research on BoDV-1 cell entry has been hindered by low viral particle production in cells and the lack of cytopathic effects. To address these issues, we developed a method to efficiently produce vesicular stomatitis virus (VSV) pseudotyped with glycoprotein (G) of the genusOrthobornavirus, including BoDV-1. We discovered that optimal G expression is required to obtain a high infectivity titer of the VSV pseudotyped virus. Remarkably, the infectivity of the VSV pseudotyped virus with G from the BoDV-1 strain huP2br was significantly higher than that of the VSV pseudotyped virus with G from the He/80 strain. Mutational analysis demonstrated that the BoDV-1-G residue 307 determines the infectivity titer of VSV pseudotyped with BoDV-1-G (VSV-BoDV-1-G). A cell‒cell fusion assay indicated that this residue plays a pivotal role in membrane fusion, thus suggesting that high membrane fusion activity and a broad pH range for membrane fusion are crucial for achieving a high infectivity titer of VSV-BoDV-1-G. This finding may be extended to increase the infectivity titer of VSV pseudotyped virus with other orthobornavirus G. Our study also contributes to identifying functional domains of BoDV-1-G and provides insight into G-mediated cell entry.
Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics
Authors: Zheng Xiang , Mund Andreas , Mann Matthias 
Published: May 2024

SummaryDeciphering the intricate tumor-immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we developed a novel approach integrating highly multiplexed imaging, laser microdissection, and deep visual proteomics (DVP) to spatially profile the proteomes of 21 distinct cell populations in human colorectal and tonsil cancers with high sensitivity. We selected colorectal tumor as an example of a cold tumor, uncovering an immunosuppressive macrophage barrier impeding T cell infiltration and regionally altering lymphocyte proteomes. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In tonsil cancer - a hot tumor, we identified significant heterogeneity of cell proteomes influenced by proximity to cytotoxic T cell subtypes. Tumor-infiltrating T cells exhibited metabolic adaptations and enhanced stress resilience, enabling migration into hypoxic regions. Our spatially-resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, with implications for identifying new immunotherapy targets and signatures.HighlightsNovel approach integrates multiplexed imaging and deep proteomics to profile the tumor microenvironmentIdentified 21 distinct cell populations and thousands of proteins from single cell typesMacrophage barrier impedes T cell tumor infiltration and T cells adapt to hypoxiaSpatial insights may guide new immunotherapy targets and personalized oncology
Bread and hummus: trait connectance and correlation pleiades in grain crops
Authors: Sadras Victor O. 
Published: May 2024

AbstractPhenotypic integration has been investigated from multiple perspectives. From a developmental perspective, connectance has been defined as the level of linkage between traits. Correlation pleiades,i.e., correlations between some traits and, simultaneously, lack of correlations between these and other traits have been interpreted as the independence of certain developmental processes with respect to other processes within the organism, and as the outcome from the discrepancy between the agencies participating in the formation of the trait and the selective forces influencing its function. Here, I use two published data sets to test the variation in connectance with both trait and genotype and the existence and meaning of correlation pleiades in wheat and chickpea. Connectance varied from 0.09 to 4.2 in wheat and from 0.06 to 22.8 in chickpea, and cluster analyses revealed correlation pleiades. The frequency distribution of connectance conformed to a power law with similar slopes = −1.665 ± 0.222 for wheat and −1.555 ± 0.126 for chickpea, consistent with developmental self-organisation. Connectance was lower for traits with higher heritability such as seed weight, which together with the negative association between heritability and phenotypic plasticity completes a relational triangle: high connectance ⇔ low heritability ⇔ high phenotypic plasticity.
Ca2+Regulation of Myosin II and Myosin VI during Rupture of theShigella-Containing Vacuole
Authors: Bonnet Mariette , Sun Chun Hui , Enninga Jost , Houdusse Anne , Tran Van Nhieu Guy 
Published: May 2024

AbstractShigella, the causative agent of bacillary dysentery, invades epithelial cells to colonize the intestinal mucosa. Following invasion,Shigellais enclosed in a vacuole that needs to rupture for bacterial intra-cytosolic replication. We show here that rupture of theShigellavacuole requires Ca2+influx leading to long lasting local Ca2+increases that regulate actin dynamics affecting theShigellavacuole integrity. These Ca2+increases promote vacuolar rupture by activating myosin II associated with actin filaments in membrane ruffles distant from the vacuole, while tethering myosin VI at the actin coat-surrounded vacuole. Ca2+depletion and myosin II inhibition impair formation of the actin coat and vacuole rupture. Inhibition of myosin VI also delays rupture of vacuoles but lead to their tumbling. These findings highlight a role for Ca2+in coordinating actin–based forces and constraints during early rupture steps of bacterial vacuole, that pull on vacuolar membranes and tether them to the actin cortex via myosin II and VI, respectively, a process relevant to intracellular pathogen and endomembrane trafficking.