bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smartphone Postural Sway and Pronator Drift tests as Measures of Neurological Disability
Authors: Calcagni Michael , Kosa Peter , Bielekova Bibi 
Published: November 2024

AbstractThe COVID-19 pandemic and increased demands for neurologists have inspired the creation of remote, digitalized tests of neurological functions. This study investigates two tests from the Neurological Functional Tests Suite (NeuFun-TS) smartphone application, the “Postural Sway” and “Pronator Drift” tests. These tests capture different domains of postural control and motoric dysfunction in healthy volunteers (n=13) and people with neurological disorders (n=68 relapsing-remitting multiple sclerosis [MS]; n=21 secondary progressive MS; n=23 primary progressive MS; n=13 other inflammatory neurological diseases; n=21 non-inflammatory neurological diseases; n=4 clinically isolated syndrome; n=1 radiologically isolated syndrome). Smartphone accelerometer data was transformed into digital biomarkers, which were filtered in the training cohort (∼80% of subjects) for test-retest reproducibility and correlations with subdomains of neurological examinations and validated imaging biomarkers. The independent validation cohort (∼20%) determined whether biomarker models outperformed the best single digital biomarkers. Postural sway acceleration magnitude in the eyes closed and feet together stance demonstrated the highest reliability (ICC=.706), strongest correlations with age (Pearson r<=.82) and clinical and imaging outcomes (r<=.65, p<0.001) and stronger predictive value for sway-relevant neurological disability outcomes than models that aggregated multiple biomarkers (coefficient of determination R2=.46 vs .38). The pronator drift test only captured cerebellar dysfunction, had less reproducible biomarkers, but provided additive value when combined with postural sway biomarkers into models predicting global scales of neurological disability. In conclusion, a simple 1-minute postural sway test accurately measures body oscillations that increase with natural aging and differentiates them from abnormally increased body oscillations in people with neurological disabilities.
Evaluation of a commercial Multiplex Real-Time PCR Assay for orthopoxvirus and monkeypox virus detection, and simultaneous subclade Ib identification
Authors: Wawina-Bokalanga Tony , Haesler Michael , Akil-Bandali Prince , Ola-Mpumbe Rilia , Kinganda-Lusamaki Eddy , Makangara-Cigolo Jean-Claude , Pukuta-Simbu Elisabeth , Cikaya-Kankolongo Fiston , Mapenzi-Kashali Nelson , Ponga-Museme Ange , de Block Tessa , Lumembe-Numbi Raphaël , Amuri-Aziza Adrienne , Luakanda Gradi , Jansen Daan , Vercauteren Koen , Ahuka-Mundeke Steve , Schuchmann Kai , Mbala-Kingebeni Placide , Muyembe-Tamfum Jean-Jacques 
Published: November 2024

AbstractSeveral mpox outbreaks, caused by subclades Ia and Ib monkeypox virus (MPXV), are ongoing in the Democratic Republic of the Congo. The World Health Organization declared the ongoing mpox outbreak a Public Health Emergency of International Concern due to the geographic expansion of subclade Ib. We assessed the performance of a novel multiplex real-time PCR assay designed for MPXV detection and simultaneous subclade Ib identification. This assay demonstrates high accuracy and specificity, underscoring its use for the current mpox outbreak.
Engineering assembloids to mimic graft-host skeletal muscle interaction
Authors: Rossi Lucia , Auletta Beatrice , Placa Marco La , Cecconi Giada , Chiolerio Pietro , Maghin Edoardo , Angiolillo Silvia , Carraro Eugenia , Gagliano Onelia , Laterza Cecilia , Elvassore Nicola , Piccoli Martina , Urciuolo Anna 
Published: November 2024

AbstractSkeletal muscle (SkM) tissue engineering aims to generate in vitro three-dimensional (3D) products that can be implanted in patients to replace or repair damaged muscles. Having a humanized in vitro model able to mimic the interaction between the innervated recipient and the engineered SkMs at a functional level would greatly help in the evaluation of the graft potential.Here we developed a 3D in vitro model that allowed to investigate the function, stability, and adaptability of the human NM system in response to an engineered SkM construct. To achieved this, we used decellularized SkMs (dSkM)-based constructs as engineered SkM and human neuromuscular organoids (NMOs) as the recipient-like NM system to create graft-host SkM assembloids.We observed migration of myogenic cells and invasion of neural axons from the NMO to the engineered SkM construct in the assembloids, with the generation of functional neuromuscular junctions (NMJs). Finally, we showed that assembloids were able to regenerate following acute damage, with SkM regeneration and functional recovery.Despite limited by the absence of immunocompetent cells and vasculature, our data showed that our assembloid represents a useful tool to evaluate in vitro the response of the human innervated SkM to a potential tissue-engineered SkM graft.
Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation
Authors: Guha Tuhin K. , Esplin Edward D. , Horning Aaron M. , Chiu Roxanne , Paul Kristina , Weimer Annika K. , Becker Winston R. , Laquindanum Rozelle , Mills Meredith A. , Esplin D. Glen , Shen Jeanne , Monte Emma , White Shannon , Karathanos Thomas V. , Cotter Daniel , Bi Joanna , Ladabaum Uri , Longacre Teri A. , Curtis Christina , Greenleaf William J. , Ford James M. , Snyder Michael P. 
Published: November 2024

AbstractColorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Familial adenomatous polyposis (FAP) is a hereditary syndrome that raises the risk of developing CRC, with total colectomy as the only effective prevention. Even though FAP is rare (0.5% of all CRC cases), this disease model is well suited for studying the early stages of malignant transformation as patients form many polyps reflective of pre-cancer states. In order to spatially profile and analyze the pre-cancer and tumor microenvironment, we have performed single-cell multiplexed imaging for 52 samples: 12 normal mucosa,16 FAP mucosa,18 FAP polyps, 2 FAP adenocarcinoma, and 4 sporadic colorectal cancer (CRCs) using Co-detection by Indexing (CODEX) imaging platform. The data revealed significant changes in cell type composition occurring in early stage polyps and during the malignant transformation of polyps to CRC. We observe a decrease in CD4+/CD8+ T cell ratio and M1/M2 macrophage ratio along the FAP disease continuum. Advanced dysplastic polyps show a higher population of cancer associated fibroblasts (CAFs), which likely alter the pre-cancer microenvironment. Within polyps and CRCs, we observe strong nuclear expression of beta-catenin and higher number neo-angiogenesis events, unlike FAP mucosa and normal colon counterparts. We identify an increase in cancer stem cells (CSCs) within the glandular crypts of the FAP polyps and also detect Tregs, tumor associated macrophages (TAMs) and vascular endothelial cells supporting CSC survival and proliferation. We detect a potential immunosuppressive microenvironment within the tumor ‘nest’ of FAP adenocarcinoma samples, where tumor cells tend to segregate and remain distant from the invading immune cells. TAMs were found to infiltrate the tumor area, along with angiogenesis and tumor proliferation. CAFs were found to be enriched near the inflammatory region within polyps and CRCs and may have several roles in supporting tumor growth. Neighborhood analyses between adjacent FAP mucosa and FAP polyps show significant differences in spatial location of cells based on functionality. For example, in FAP mucosa, naive CD4+ T cells alone tend to localize near the fibroblast within the stromal compartment. However, in FAP polyp, CD4+T cells colocalize with the macrophages for T cell activation. Our data are expected to serve as a useful resource for understanding the early stages of neogenesis and the pre-cancer microenvironment, which may benefit early detection, therapeutic intervention and future prevention.
Automated identification of small molecules in cryo-electron microscopy data with density- and energy-guided evaluation
Authors: Muenks Andrew , Farrell Daniel P. , Zhou Guangfeng , DiMaio Frank 
Published: November 2024

SUMMARYMethodological improvements in cryo-electron microscopy (cryoEM) have made it a useful tool in ligand-bound structure determination for biology and drug design. However, determining the conformation and identity of bound ligands is still challenging at the resolutions typical for cry-oEM. Automated methods can aid in ligand conformational modeling, but current ligand identification tools — developed for X-ray crystallography data — perform poorly at resolutions common for cryoEM. Here, we present EMERALD-ID, a method capable of docking and evaluating small molecule conformations for ligand identification. EMERALD-ID identifies 43% of common ligands exactly and identifies closely related ligands in 66% of cases. We then use this tool to discover possible ligand identification errors, as well as previously unidentified ligands. Furthermore, we show EMERALD-ID is capable of identifying ligands from custom ligand libraries of various small molecule types, including human metabolites and drug fragments. Our method provides a valuable addition to cryoEM modeling tools to improve small molecule model accuracy and quality.
Coagulative Granular Hydrogels with an Enzyme Catalyzed Fibrin Network for Endogenous Tissue Regeneration
Authors: Deng Zhipeng , Tovani Camila B. , Bianco Simona , Comandini Gianni , Elghajiji Aya , Adams Dave J. , Scarpa Fabrizio , Whitehouse Michael R. , Seddon Annela M. , Armstrong James P. K. 
Published: November 2024

AbstractGranular hydrogels, composed of densely packed microgels, are an emerging class of injectable microporous scaffolds that provide interstitial porosity for endogenous cell recruitment and tissue repair. However, weak bonding interactions between constituent microgels compromises the mechanical integrity of these biomaterials, limiting their scope and effectiveness forin vivoapplication where structural support is required. To address this challenge, we introduce a new bioinspired stabilization method and a novel class of regenerative biomaterial:coagulative granular hydrogels, assembled from thrombin-functionalized gelatin methacryloyl microgels. The surface-bound thrombin is enzymatically active and catalyzes the conversion of fibrinogen into a fibrin hydrogel that extends throughout the interstitial voids of the granular hydrogel. This secondary network acts as a biological glue to stabilize the granular hydrogel, yielding shear and compressive properties comparable to bulk hydrogel controls. Furthermore, the interstitial fibrin network provides a favorable microenvironment for the adhesion, proliferation, and invasion of endothelial cells, highlighting the potential of the biomaterial to support endogenous tissue repair. This innovative stabilization mechanism provides a responsive biomaterial system, and future studies will seek to explore how the biomaterial is annealedin vivoby the presence of blood plasma fibrinogen.
Wind Tunnel Study of the Forces Due to Drafting in Dolphin Mother-Calf pairs
Authors: Weihs D. , Ringel M. 
Published: November 2024

AbstractCetacean calves can get assistance in rapid swimming by drafting with the mothers. The hydrodynamic forces produced have been predicted to enable reducing the drag on the calf Using models in a wind tunnel, the similarity between motion in the air and submerged swimming is used to produce quantitative data on the reduction of drag due to drafting in accordance with the theoretical predictions.
Signaling downstream of tumor-stroma interaction regulates mucinous colorectal adenocarcinoma apicobasal polarity
Authors: Pasquier Nicolas , Isomursu Aleksi , Hamidi Hellyeh , Mathieu Jacques R.R. , Härkönen Jouni , Follain Gautier , Desterke Christophe , Fusilier Zoé , Solis Junel , Belaya Irina , Kankaanpää Pasi , Barresi Valeria , Cartry Jérôme , Bedja Sabrina , Jaulin Fanny , Ivaska Johanna 
Published: November 2024

AbstractMucinous colorectal carcinoma (MUC CRC) dissemination into the tumor stroma and metastasis to multiple organs, including the peritoneum, is associated with poor prognosis. Disseminating MUC CRCs exhibit either a conventional ‘apical-in’ or an inverted ‘apical-out’ polarity phenotype that influence patient outcome. Identifying the mechanisms controlling MUC CRC polarity is critical to understand disease progression. Here, we analyze patient-derived MUC CRC xenografts, with apical-in or apical-out polarity, ex vivo or within collagen gels to mimic the peritumoral stroma. Single-cell analyses reveal α2β1-integrin as a key collagen-binding receptor in these models. Collagen–α2β1-integrin interaction activates Src and ERK/MAPK signaling and upregulates the expression of SorLA, an endosomal sorting receptor. SorLA supports apical-in polarity and carcinoma-stroma interactions by promoting integrin recycling to the plasma membrane and HER2/HER3 expression through a positive feedback mechanism. Accordingly, we observe positive correlation between HER2, HER3 and SorLA in patient samples with the highest HER2 expression in apical-in-presenting tissues. Treatment of tumor spheres with clinically relevant HER2/HER3-targeting antibodies reverts sphere polarity and impedes collagen remodeling and adhesion to mouse peritoneum. This SorLA—integrin—HER2/HER3 signaling axis may represent a basis for MUC CRC-patient stratification and shed light on other carcinomas with similar apical-out phenotypes.
Assessing the performance of current strain resolution tools on long-read metagenomes
Authors: Afolayan Ayorinde O. , Montaño Stefany Ayala , Akintayo Ifeoluwa J. , Duarte dos Santos Leonardo , Reuter Sandra 
Published: November 2024

AbstractRecent advances in long-read sequencing-based methods have greatly enhanced genomics and public health applications. However, the challenge of effectively distinguishing strains within microbial communities from clinical samples using these technologies restricts their widespread use. We assessed the strain resolution capabilities of three currently available bioinformatics tools—TRACS, Strainy, and Strainberry—using both mock communities and authentic metagenomic datasets.Following sample preparation and long-read sequencing using the GridION sequencing platform, raw reads were processed using TRACS, aligning them to a custom reference database, while Strainberry and Strainy mapped reads to metagenome assemblies for strain resolution. Performance on mock microbial community was assessed by comparing predicted microbiota composition to the expected composition, and on both mock and authentic datasets by evaluating strain-resolved genome assemblies. Computational efficiency was measured in terms of task execution time, single-core CPU usage, and physical memory usage.TRACS demonstrated substantial agreement with the known composition, achieving a median score of 86.7% forEscherichia coli-dominant communities and 94.7% forKlebsiella pneumoniae-dominant communities. Strainberry and Strainy exhibited improved concordance after excluding strains with a genome size below 1 Mb, thus showcasing comparable performance metrics to TRACS. In mock and real metagenomic datasets, TRACS demonstrated the highest haplotype completeness compared to the other two tools, while Strainy demonstrated the highest haplotype accuracy. All tools were able to allocate strains to their respective transmission clusters (< 20 SNPs), albeit with varying degrees of success. Except for single core CPU usage, TRACS outperformed Strainy and Strainberry in terms of speed and computational efficiency.Our study underscores the utility of TRACS, Strainy, and Strainberry in resolving strains within microbial communities from clinical samples. TRACS stands out for its better haplotype completeness and computational efficiency, suggesting its potential to streamline advanced genomic analyses and public health initiatives.
Aphid effectors suppress plant immunity via recruiting defence proteins to processing bodies
Authors: Liu Qun , Neefjes Anna C. M. , Kobylinska Roksolana , Mugford Sam T. , Marzo Mar , Canham James , Schuster Mariana , van der Hoorn Renier A. L. , Chen Yazhou , Hogenhout Saskia A. 
Published: November 2024

AbstractAphids are small insects that have developed specialized mouthparts and effector proteins to establish long-term relationships with plants. The peach-potato aphid,Myzus persicae, is a generalist, feeding on many plant species and capable of transmitting numerous pathogens. This study reveals how host-responsive cathepsins B (CathB) in the oral secretions ofM. persicaefacilitate aphid survival by modulating plant immune responses. Aphid CathB localize to processing bodies (p-bodies) and recruit key immune regulators EDS1, PAD4, and ADR1 to these bodies, suppressing plant defenses. A plant protein, Acd28.9 (Hsp20 family), counteracts this CathB activity and contributes to plant resistance to aphids. These findings highlight a novel role for p-bodies in plant immunity and uncover a plant resistance mechanism to aphid infestation.
BAZ1A, an Imitation Switch (ISWI) protein, interacts and facilitates the recruitment of E2F1 to activate the E2F transcription program
Authors: Prajapati Bidisha , Chowdhury Abhishek , Prasasvi Kaval Reddy , Garg Lakshay , Somasundaram Kumaravel 
Published: November 2024

AbstractISWI (ImitationSwitch) family of chromatin remodeling complexes mobilize nucleosomes to regulate DNA-template associated functions. Analysis of glioblastoma (GBM) transcriptome datasets revealed that BAZ1A (BromodomainAdjacent toZinc Finger Domain1A) is a highly expressed ISWI family member. RNAi-based depletion or inhibition by a small molecule inhibited the survival/migration of glioma cells and glioma stem-like cells (GSCs), sensitized glioma cells to Temozolomide but did not affect normal astrocytes. BAZ1A-silencing arrested cells in the G1 phase and induced apoptosis. While GO analysis of BAZ1A regulated transcriptome showed enrichment of “cell cycle” related terms, GSEA showed a depletion of the “HALLMARK_E2F_TARGETS” gene set with the highest significance, indicating a nonfunctional E2F transcription program. BAZ1A silencing and overexpression experiments confirmed the requirement of BAZ1A for the E2F transcription program by identifying E2F1 as the primary target. ChIP experiments revealed that BAZ1A and E2F1 bind to the E2F1 promoter. ChIP-ReChIP demonstrated that BAZ1A-bound chromatin fragments are enriched for E2F1 protein on the E2F1 promoter at specific sites. SMARCA1/5, ATPase subunits of the ISWI family, also exhibited binding to the E2F1 promoter. BAZ1A depletion decreased the DNaseI sensitivity of E2F1 binding regions of the E2F1 promoter. Co-immunoprecipitation experiments revealed an interaction between BAZ1A and E2F1 and the presence of an E2F1-BAZ1A-SMARCA1/5 complex. Finally, BAZ1A silencing inhibited glioma tumor growth in an orthotopic xenograft mouse model. Our results demonstrate that BAZ1A containing ISWI complex recruits E2F1 to activate the E2F transcription program, thus promoting G1-S progression and highlighting BAZ1A as a potential therapeutic target.
Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-λR1) and IFN-λ Signaling in Influenza A Virus (IAV) Infection
Authors: Yang Alina X. , Ramos-Rodriguez Lisa , Sorkhdini Parand , Yang Dongqin , Norbrun Carmelissa , Majid Sonoor , Zhang Yong , Holtzman Michael J. , Boyd David F. , Zhou Yang 
Published: November 2024

ABSTRACTPhospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, the exact mechanisms of anti-flu activity of PLSCR1 in relation to its expression compartment and enzymatic activity, and the molecular and cellular mechanisms involved have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections. We hypothesize that PLSCR1 protects hosts against IAV infection by regulating type 3 interferon (IFN-λ) signaling pathways. Our results showed that Plscr1 expression was highly induced by IAV infectionin vivoand in epithelial cells treated with IFN-λ. We found thatPlscr1knockout (KO) mice exhibited exacerbated body weight loss, decreased survival rates, heightened viral replication, and increased lung damage. Interestingly, transcriptomic analyses demonstrated that Plscr1 was required for type 3 interferon receptor (Ifn-λr1) expression, and impaired expression of Ifn-λr1 and downstream ISGs may be responsible for delayed viral clearance in Plscr1 KO mice. In addition, Plscr1 interacted with Ifn-λr1 within the epithelial compartment following IAV infection, suggesting Plscr1 may modulate IFN-λ signaling via protein-protein interactions. Finally, single-cell RNA sequencing data indicated thatPlscr1expression was significantly upregulated in ciliated airway epithelial cells in mice following IAV infection. Consistently,Plscr1floxStopFoxj1-Cre+mice with ciliated epithelial cell-specific Plscr1 overexpression showed reduced susceptibility, less inflammation and enhanced Ifn-λr1 expression in IAV infection. Our research will elucidate virus-host interactions and pave the way for the development of novel anti-influenza drugs that target human elements like PLSCR1, thereby mitigating the emergence of drug-resistant IAV strains.