bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the Glycan-Binding Specificity and Structure ofCucumis meloAgglutinin, a New R-Type Lectin
Authors: Lundstrøm Jon , Gillon Emilie , Chazalet Valérie , Kerekes Nicole , Di Maio Antonio , Liu Yan , Feizi Ten , Varrot Annabelle , Bojar Daniel 
Published: December 2023

AbstractPlant lectins have garnered attention for their roles as laboratory probes and potential therapeutics. Here, we report the discovery and characterization ofCucumis meloagglutinin (CMA1), a new R-type lectin from melon. Our findings reveal CMA1’s unique glycan-binding profile, mechanistically explained by its 3D structure, augmenting our understanding of R-type lectins. We expressed CMA1 recombinantly and assessed its binding specificity using multiple glycan arrays, covering 1,046 unique sequences. This resulted in a complex binding profile, strongly preferring C2-substituted, beta-linked galactose (both GalNAc and Fuca1-2Gal), which we contrasted with the established R-type RCA1 lectin. We also report binding of specific glycosaminoglycan subtypes and a general enhancement of binding by sulfation. Further validation using agglutination, thermal shift assays, and surface plasmon resonance confirmed and quantified this binding specificity in solution. Finally, we solved the high-resolution structure of the CMA1 N-terminal domain using X-ray crystallography, supporting our functional findings at the molecular level. Our study provides a comprehensive understanding of CMA1, laying the groundwork for further exploration of its biological and therapeutic potential.
Impact of disruptions in antigen processing and presentation machinery on sarcoma
Authors: Renne Salvatore Lorenzo , Sama’ Laura , Kumar Sonia , Mintemur Omer , Ruspi Laura , Santori Ilaria , Sicoli Federico , Bertuzzi Alexia , Laffi Alice , Bonometti Arturo , Colombo Piergiuseppe , D’amato Vittoria , Bressan Alessandra , Scorsetti Marta , Terracciano Luigi , Navarria Pierina , D’incalci Maurizio , Quagliuolo Vittorio , Pasqualini Fabio , Grizzi Fabio , Cananzi Ferdinando Carlo Maria 
Published: December 2023

AbstractBackgroundThe antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. The status of the APM in sarcomas is not well characterized.MethodsWe investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.ResultsAll investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.ConclusionSarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.
Divergent trends in the incidence and mortality of coronary events, especially in women. Evidence from Finland in 1996-2021
Authors: Kallström Atte , Holopainen Ida , Kambur Oleg , Perola Markus , Salomaa Veikko , Havulinna Aki S. , Ramste Markus , Sinisalo Juha 
Published: December 2023

AbstractObjectiveAcute coronary syndrome (ACS) incidence and case fatality (CF) have declined in the past decades, but some studies have suggested a potential stagnation in this decline. We examined how the ACS burden has evolved among persons aged 35-74 in Finland from 1996 to 2021.MethodsWe used Finnish country-wide Hospital Discharge- and Causes of Death-Registers covering first non-fatal and fatal ACS events, totaling 69 906 442 person-years at risk. We analyzed incidence, mortality, and 28-day CF, and their trends using negative binomial, Poisson, segmented, and logistic regression adjusting for age and sex.ResultsAltogether, the analysis consisted of 186 489 non-fatal and 72 907 fatal ACS events. ACS incidence declined in men (annual percentage change (APC) −2.0% [95% CI −2.2 to −1.8]) and in older women (APC of 55-64 year old −1.5% [−1.7 to −1.2] and 65-74 year old −3.3% [−3.4 to −3.2]), but the incidence decline slowed down over the last decade. In younger women aged 35-54, incidence was unchanged during the study period. ACS mortality and CF declined (APC of the mortality in men - 4.4% [−4.6 to −4.2] and in women −5.0% [−5.2 to −4.7]. APC of CF in men −2.7% [−2.8 to −2.6] and in women −3.3% [−3.6 to −3.1]).ConclusionsACS mortality declined in all groups, but the decline in ACS incidence slowed down and even halted in women. In women aged 35-54, the incidence was unchanged during the study period. These results emphasize the need of intensified cardiovascular prevention, particularly in women.Key messagesWhat is already known on this topicDuring the last decades coronary artery disease treatment and prevention have improved worldwide which has led to a decline in ACS mortality and case fatality. However, recent studies from several countries suggest, that incidence decline has stagnated or even turned to increase, especially in younger age cohorts.What this study addsThis study showed that incidence has ceased its decline in women aged 35-54 and has slowed down in older age groups. Together with declining mortality this results in a growing number of patients living with cardiovascular disease leading to increased healthcare costs.How this study might affect research, practice, or policyThe alarming results of this study underline the importance of intensifying prevention, focusing especially on young and middle-aged women.
Assessment of transparency indicators in Space Medicine
Authors: Bellomo Rosa Katia , Zavalis Emmanuel A. , Ioannidis John P. A. 
Published: December 2023

ABSTRACTSpace medicine is a vital discipline with often time-intensive and costly projects and constrained opportunities for studying various elements such as space missions, astronauts, and simulated environments. Moreover, private interests gain increasing influence in this discipline. In scientific disciplines with these features, transparent and rigorous methods are essential. Here, we undertook an evaluation of transparency indicators in publications within the field of space medicine. A meta-epidemiological assessment of PubMed Central Open Access (PMC OA) eligible articles within the field of space medicine was performed for prevalence of code sharing, data sharing, pre-registration, conflicts of interest, and funding. Text mining was performed with the rtransparent text mining algorithms with manual validation of 200 random articles to obtain corrected estimates. Across 1215 included articles, 39 (3%) shared code, 258 (21%) shared data, 10 (1%) were registered, 110 (90%) contained a conflict-of-interest statement, and 1141 (93%) included a funding statement. After manual validation, the corrected estimates for code sharing, data sharing, and registration were 5%, 27%, and 1%, respectively. Data sharing was 32% when limited to original articles and highest in space/parabolic flights (46%). Overall, across space medicine we observed modest rates of data sharing, rare sharing of code and almost non-existent protocol registration. Enhancing transparency in space medicine research is imperative for safeguarding its scientific rigor and reproducibility.
Classification of virologic trajectories during nucleos/tide analogue treatment of hepatitis B virus (HBV) infection
Authors: Wang Tingyan , Campbell Cori , Stockdale Alexander J , Todd Stacy , McIntyre Karl , Frankland Andrew , Jaworski Jakub , Glampson Ben , Papadimitriou Dimitri , Mercuri Luca , Jones Christopher R , Salih Hizni , Roadknight Gail , Little Stephanie , Noble Theresa , Várnai Kinga A , Davis Cai , Heinson Ashley I , George Michael , Borca Florina , English Louise , Romão Luis , Ramlakhan David ,   NIHR HIC Viral Hepatitis and Liver Disease Consortium, Woods Kerrie , Davies Jim , Nastouli Eleni , Khakoo Salim I , Gelson William , Cooke Graham S , Barnes Eleanor , Matthews Philippa C 
Published: December 2023

AbstractBackground & AimsThe dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos/tide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.MethodsUtilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase (ALT), and with liver fibrosis/cirrhosis.ResultsWe retrieved data from 1885 adults on NA treatment (median follow-up 6.2 years, interquartile range (IQR) 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n=1367, discrimination: 0.93, entropy: 0.90): class 1 ‘long term suppression’ (n=827, 60.5%), class 2 ‘timely virological suppression’ (n=254, 18.6%), class 3 ‘persistent moderate viraemia’ (n=140, 10.2%), class 4 ‘persistent high-level viraemia’ (n=44, 3.2%), and class 5 ‘slow virological suppression’ (n=102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n=518). ALT decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p<0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had 2-fold increased hazards of fibrosis/cirrhosis compared to class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02).ConclusionsHeterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression.
Antimicrobial resistance landscape in a metropolitan city context using open drain wastewater-based metagenomic analysis
Authors: Madhukar Manas Kumar , Singh Nirupama , Rajesh Iyer V , Sowpati Divya Tej , Tallapaka Karthik Bharadwaj , Mishra Rakesh Kumar , Moharir Shivranjani Chandrashekhar 
Published: December 2023

AbstractThe One Health concept recognizes the inextricable interactions of the diverse ecosystems and their subsequent effect on human, animal and plant health. Antimicrobial resistance (AMR) is a major One Health concern and is predicted to cause catastrophes if appropriate measures are not implemented. In this study, to understand the AMR landscape in metropolitan city context, we performed metagenomic analysis of open drain wastewater samples. We analysed 17 samples from open drains that receive influx from human, animal, agricultural and industrial wastes. Our data suggests that macrolide antibiotics have developed the highest resistance in the city through mutations in the 23S rRNA gene, which is present in multiple pathogens includingEscherichia coli, Campylobacter jejuni, Acinetobacter baumannii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Klebsiella pneumoniaeandHelicobacter pylori. Except for a few geographical locations, most other locations show a similar landscape for AMR. Considering human mobility and other similar anthropogenic activities, we suggest that such an AMR landscape may be common across other regions.
Analysis of the Cross-Study Replicability of Tuberculosis Gene Signatures Using 49 Curated Transcriptomic Datasets
Authors: Wang Xutao , Harper Katie , Sinha Pranay , Johnson W. Evan , Patil Prasad 
Published: December 2023

BackgroundTuberculosis (TB) is the leading cause of infectious disease mortality worldwide. Numerous blood-based gene expression signatures have been proposed in the literature as alternative tools for diagnosing TB infection. Ongoing efforts are actively focused on developing additional signatures in other TB-related contexts. However, the generalizability of these signatures to different patient contexts is not well-characterized. There is a pressing need for a well-curated database of TB gene expression studies for the systematic assessment of existing and newly developed TB gene signatures.ResultsWe built the curatedTBData, a manually-curated database of 49 TB transcriptomic studies. This data resource is freely available through GitHub and as an R Bioconductor package that allows users to validate new and existing biomarkers without the challenges of harmonizing heterogeneous studies. We also demonstrate the use of this data resource with cross-study comparisons for 72 TB gene signatures. For the comparison of subjects with active TB from healthy controls, 19 gene signatures had weighted mean AUC of 0.90 or greater, with the highest result of 0.94. In active TB disease versus latent TB infection, 7 gene signatures had weighted mean AUC of 0.90 or greater, with a maximum of 0.93. We also explore ensembling methods for averaging predictions from multiple gene signatures to significantly improve diagnostic ability beyond any single signature.ConclusionsThe curatedTBData data package offers a comprehensive resource of curated gene expression and clinically annotated data. It could be used to identify robust new TB gene signatures, to perform comparative analysis of existing TB gene signatures, and to develop alternative gene set scoring or ensembling methods, among other things. This resource will also facilitate the development of new signatures that are generalizable across cohorts or more applicable to specific subsets of patients (e.g. with rare comorbid conditions, etc.). We demonstrated that these blood-based gene signatures could distinguish patients with distinct TB outcomes; moreover, the combination of multiple gene signatures could improve the overall predictive accuracy in differentiating these subtypes, which point out an important aspect for the translation of genomics to clinical implementation.
A mitochondrial quality control mechanism reverses the phagosome maturation arrest caused byMycobacterium tuberculosis
Authors: Verma Surbhi , Das Mrinmoy , Sharma Raman D. , Yadav Vikas , Thakur Shweta , Sharma Priya , Marzuki Mardiana , Foo Shihui , Piperno Giulia M. , Khan Mehak Z. , Mathew Babu , Bajpai Meenu , Maras Jaswinder Singh , Howland Shanshan , Sarkar Sovan , Benvenuti Federica , Singh Amit , Nandicoori Vinay , Singhal Amit , Kumar Dhiraj 
Published: December 2023

AbstractPhagosome maturation arrest (PMA) imposed byMycobacterium tuberculosis(Mtb) is a classic tool that helpsMtbevade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, fromMtb-phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA. CRISPR-mediated p62/SQSTM1 depletion (p62KD) blocks mitophagy flux without impacting mitochondrial quality. Inp62KDcells,Mtbgrowth and survival are diminished, mainly through witnessing an increasingly oxidative environment and increased lysosomal targeting. The lysosomal targeting ofMtbis facilitated by enhanced TOM20+mitochondria-derived vesicles (MDVs) biogenesis, a key MQC mechanism. Inp62KDcells, TOM20+-MDVs biogenesis is MIRO1/MIRO2-dependent and delivered to lysosomes for degradation in a RAB7-dependent manner. Upon infection inp62KDcells, TOM20+-MDVs get extensively targeted toMtb-phagosomes, inadvertently facilitating RAB7 recruitment, PMA reversal and lysosomal targeting ofMtb. Triggering MQC collapse inp62KDcells further diminishesMtbsurvival signifying cooperation between redox- and lysosome-mediated mechanisms. The MQC-anti-bacterial pathway crosstalk could be exploited for host-directed anti-tuberculosis therapies.
High-throughput Microfluidic 3D Outer Blood-Retinal Barrier Model in a 96-Well Format: Analysis of Cellular Interactions and Barrier Function in Retinal Health and Disease
Authors: Kim Jiho , Song Youngsook , Jolly Amber L. , Hwang Taeseon , Kim Suryong , Lee Byungjun , Jang Jinhwan , Jo Dong Hyun , Baek Kyusuk , Liu Tsung-Li , Yoo Sanghee , Jeon Noo Li 
Published: December 2023

AbstractNumerous diseases, including AMD (age-related macular degeneration), arise from the blood-retinal barrier and blood vessel abnormalities in the eye; unfortunately, there is a lack of reliable in-vitro models for their systematic study. This study describes a high-throughput microphysiological system (MPS) designed to model the outer Blood-Retinal Barrier (oBRB). The MPS platform is engineered to integrate seamlessly with high-content screening technologies, utilizing a design with a single oBRB model incorporating RPE (retina pigment epithelial cells) and endothelial cell co-culture to fit within a single 96-well. Arranged in the standard 96-well plate format, the platform allows high-throughput assessment of barrier integrity through 3D confocal imaging (ZO-1 staining), Trans Epithelial Electrical Resistance (TEER), and permeability measurements.The oBRB model enables the investigation of crosstalk among different cell types in co-culture. This includes assessing changes in the barrier integrity of the Retinal Pigment Epithelium (RPE) monolayer and investigating neovascularization events resulting from endothelial cell remodeling. The platform is positioned for utility in drug discovery and development efforts targeting diseases involving oBRB damage and choroidal neovascularization, such as age-related macular degeneration (AMD).
Biosensors Characterization: Formal methods from the Perspective of Proteome Fractions
Authors: Vaccari Nicolás A. , Zevallos-Aliaga Dahlin , Peeters Tom , Guerra Daniel G. 
Published: December 2023

AbstractMany studies characterize transcription factors and other regulatory elements to control the expression of heterologous genes in recombinant systems. However, most lack a formal approach to analyse the parameters and context-specific variations of these regulatory components. This study addresses this gap by establishing formal and convenient methods for characterising regulatory circuits. We model the bacterial cell as a collection of a small number of proteome fractions. Then, we derive the proteome fraction over time and obtain a general theorem describing its change as a function of its expression fraction, which represents a specific portion of the total biosynthesis flux of the cell. Formal deduction reveals that when the proteome fraction reaches a maximum, it becomes equivalent to its expression fraction. This equation enables the reliable measurement of the expression fraction through direct protein quantification. In addition, experimental data demonstrate a linear correlation between protein production rate and specific growth rate over a significant time period. This suggests a constant expression fraction within this window. The expression fractions estimated from the slopes of these intervals and those obtained from maximum protein amount points can both be independently fitted to a Hill function. In the case of an IPTG biosensor, in five cellular contexts, expression fractions determined by the maximum method and the slope method produced similar dose-response parameters. Additionally, by analysing two more biosensors, for mercury and cumate detection, we demonstrate that the slope method can be effectively applied to various systems, generating reliable Hill function parameters.
Caveolin scaffolding domain (CSD) peptide LTI-2355 modulates the phagocytic and synthetic activity of lung derived myeloid cells in Idiopathic Pulmonary Fibrosis (IPF) and Post-acute sequelae of COVID-fibrosis (PASC-F)
Authors: Creyns Brecht , MacKenzie BreAnne , Sa Yago , Coelho Ana Lucia , Christensen Dale , Parimon Tanyalak , Windsor Brian , Hogaboam Cory M. 
Published: December 2023

AbstractRationaleThe role of the innate immune system in Idiopathic Pulmonary Fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, and to mediate innate immune responses against pathogens. Aberrant macrophage activity has been described in patients with Post-acute sequelae of COVID fibrosis (PASC-F). Therefore, we examined the functional and synthetic properties of myeloid cells isolated from normal donor lung and lung explant tissue from both IPF and PASC-F patients and explored the effect of LTI-2355, a Caveolin Scaffolding Domain (CSD) peptide, on these cells.Methods & ResultsCD45+myeloid cells isolated from lung explant tissue from IPF and PASC-F patients exhibited an impaired capacity to clear autologous dead cells and cellular debris. Uptake of pathogen-coated bioparticles was impaired in myeloid cells from both fibrotic patient groups independent of type of pathogen highlighting a cell intrinsic functional impairment. LTI-2355 improved the phagocytic activity of both IPF and PASC-F myeloid cells, and this improvement was paired with decreased pro-inflammatory and pro-fibrotic synthetic activity. LTI-2355 was also shown to primarily target CD206-expressing IPF and PASC-F myeloid cells.ConclusionsPrimary myeloid cells from IPF and PASC-F patients exhibit dysfunctional phagocytic and synthetic properties that are reversed by LTI-2355. Thus, these studies highlight an additional mechanism of action of a CSD peptide in the treatment of IPF and progressive fibrotic lung disease.