bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Ligament Z-Plasty and Conventional Surgery for the Treatment of Carpal Tunnel Syndrome: A Randomized Clinical Trial
Authors: Calzado-Alvarez Irene , Camacho-Sanchez Maria R. , Carpintero-Lluch Rocio , Muñoz-Luna Francisco , Lopez-Medina Clementina , Minarro Jose Carlos , Izquierdo-Fernandez Alberto 
Published: August 2024

Background:
Conventional surgery performed to treat carpal tunnel syndrome (CTS) is associated with complications such as pillar pain or loss of strength. This study aimed to compare the incidence of pillar pain between 2 techniques at the 3-week and 6-month follow-up and to determine differences in the recovery of grip strength (GS), pinch strength (PS), and Boston Carpal Tunnel Questionnaire scores.

Methods:
This randomized clinical trial included 109 patients, 55 of whom underwent ligament Z-plasty and 54, conventional surgery (longitudinal section of the transverse carpal ligament without posterior closure). GS, PS, pillar pain, and Boston Carpal Tunnel Questionnaire scores were assessed preoperatively and 3 weeks and 6 months after surgery.

Results:
The incidence of pillar pain 3 weeks after surgery was lower in patients undergoing Z-plasty than in those undergoing conventional surgery (25.5% versus 44.4%; P = 0.04). Moreover, the absolute change in PS 3 weeks after surgery (P = 0.01) and GS 6 months after surgery (P = 0.05) and the absolute and relative changes in PS after 6 months (P = 0.008 and P = 0.01, respectively) were significantly higher in the Z-plasty group than in the conventional surgery group.

Conclusions:
Z-plasty is a valid surgical procedure for treating CTS. It is associated with a lower incidence of pillar pain and better recovery of postoperative strength compared with the conventional surgical technique, with both techniques showing similar results in CTS recovery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
Missing genetic diversity impacts variant prioritisation for rare disorders
Authors: Tallman Sam , Moutsianas Loukas , Nguyen Thuy , Cho Yoonsu , Mackintosh Maxine , Kasperaviciute Dalia , Brown Matthew A , Ellingford Jamie , Kuchenbaecker Karoline , Silver Matt J 
Published: August 2024

AbstractWhole genome sequencing identifies millions of genetic variants per individual. When applied to rare disease diagnosis, potentially pathogenic variants are prioritised for clinical interpretation, a process that may be influenced by an individual’s genetic ancestry. We analysed millions of rare protein-altering variants prioritised in 29,425 participants with rare disease from the UK 100,000 Genomes Project. We observed disparities in the number of variants prioritised across genetic ancestry groups, with an up to 3-fold increase in participants with African compared to European ancestries. Variants prioritised in participants with non-European ancestries were less likely to be assessed as pathogenic. Leveraging a cohort of 34,701 diverse genomes from the UK, we identified thousands of candidate variants that were ultra-rare or unobserved across populations in gnomAD but common among ancestry-matched individuals. Our findings highlight the importance of using reference databases that reflect patient genetic diversity when prioritising variants for rare disease diagnosis.
Impending Heart Failure : An Artificial Intellectual Reality
Authors: Ray Abhijit 
Published: August 2024

AbstractBackgroundHaving a prevalence of almost 64 million patients globally, Heart Failure (HF) remains a leading cause of cardiac death with high morbidity and mortality rates despite constant updates in diagnostic and therapeutic measures. One of the main reasons behind this might be a delay in initiating treatment.PurposeTo obtain a method of screening patients for Heart Failure even before they develop symptoms.MethodsAn Artificial Intelligence-based algorithm, named Heart Failure Predictor (HFP), born from mathematical calculations of a patented formula, came up with a cutting-edge solution that can predict the chances of HF in patients not suffering from any symptoms of Heart Failure. HFP was applied to data from the Framingham Heart Study as a retrospective analysis. LVEF and NT pro-BNP levels were used as a method of correlation. Asymptomatic patients who had been followed up extensively for at-least 24 months were included, while patients already diagnosed with HF were excluded.ResultsData from 20896 patients were analysed.17 out of 1230 were false positive while 31 out of 19660 were false negative.Thus, HFP has a Positive Predictive Value of 98.6% and a Specificity of 99.9%.DiscussionEarly screening and detection may lead to vast improvements in HF treatment efficacy. HFP fills this need with a new classification of HF, “Impending Heart Failure”, and synonymously “Ray’s Disease”.Apart from screening HF patients, HFP can also be used for continuous monitoring of LVEF in cardiac beds, bringing about a revolution in the cardiac space.
The Aryl Hydrocarbon Receptor Controls IFNγ-Induced Immune Checkpoints PD-L1 and IDO via the JAK/STAT Pathway in Lung Adenocarcinoma
Authors: Snyder Megan , Wang Zhongyan , Lara Brian , Fimbres Jocelyn , Pichardo Tachira , Mazzilli Sarah , Khan Mohammed Muzamil , Duggineni Vinay K. , Monti Stefano , Sherr David H. 
Published: August 2024

AbstractWhile immunotherapy has shown efficacy in lung adenocarcinoma (LUAD) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of immune checkpoint regulation. Here, we investigated a possible link between an environmental chemical receptor implicated in lung cancer and immune regulation,(the aryl hydrocarbon receptor/AhR), a known but counterintuitive mediator of immunosuppression (IFNγ), and regulation of two immune checkpoints (PD-L1 and IDO). AhR gene-edited LUAD cell lines, a syngeneic LUAD mouse model, bulk- and scRNA sequencing of LUADs and tumor-infiltrating leukocytes were used to map out a signaling pathway leading from IFNγ through the AhR to JAK/STAT, PD-L1, IDO, and tumor-mediated immunosuppression. The data demonstrate that:1)IFNγ activation of the JAK/STAT pathway leading to PD-L1 and IDO1 upregulation is mediated by the AhR in murine and human LUAD cells,2)AhR-driven IDO1 induction results in the production of Kynurenine (Kyn), an AhR ligand, which likely mediates an AhR➔IDO1➔Kyn➔AhR amplification loop,3)transplantation of AhR-knockout LUAD cells results in long-term tumor immunity in most recipients.4)The 23% of AhR-knockout tumors that do grow do so at a much slower pace than controls and exhibit higher densities of CD8+T cells expressing markers of immunocompetence, increased activity, and increased cell-cell communication. The data definitively link the AhR to IFNγ-induced JAK/STAT pathway and immune checkpoint-mediated immunosuppression and support the targeting of the AhR in the context of LUAD.
Thalamus normalisation improves detectability of hypoperfusion via arterial spin labelling in an Alzheimer’s disease cohort
Authors: Zhang Logan X. , Kirk Thomas F. , Craig Martin S. , Chappell Michael A. 
Published: August 2024

AbstractData normalisation is an important approach to reduce inter-subject variability in group studies, but care must be taken when choosing a normalisation strategy to not introduce further confounds or artefacts into the data. Normalisation of arterial spin labelling perfusion measurements remains challenging, especially in the context of Alzheimer’s disease, where there may be global hypoperfusion present. We propose that using the thalamus as a reference region for normalisation could improve the detectability of hypoperfusion in Alzheimer’s disease and alleviate the pseudo-hyperperfusion artefacts caused by the commonly-used strategy of normalisation using global mean perfusion. Evaluation on an Alzheimer’s disease dataset found this strategy was able to reduce coefficient of variation in perfusion measurements by around 60% and yield increases in statistical power of comparisons against healthy controls.
A variant of the autophagic receptor NDP52 counteracts phospho-TAU accumulation and emerges as a protective factor for Alzheimer Disease
Authors: Mattioni Anna , Carsetti Claudia , Bruqi Krenare , Caputo Valerio , Cianfanelli Valentina , Bacalini Maria Giulia , Casa Mariella , Gabelli Carlo , Giardina Emiliano , Cestra Gianluca , Strappazzon Flavie 
Published: August 2024

ABSTRACTSelective elimination of early pathological TAU species may be a promising therapeutic strategy to reduce TAU accumulation that contributes to neurodegeneration and hallmarks Alzheimer disease (AD). By performing a genetic analysis of a cohort of 435 patients with AD, we defined the NDP52GEvariant (rs550510) of the autophagic receptor NDP52 (also known as CALCOCO2) as a protective factor for AD. We provide evidence that inin vitrosystems and in aDrosophila melanogastermodel of TAU-induced AD, NDP52 reduces the accumulation of pathological forms of TAU through the autophagic process and rescues typical neurodegenerative phenotypes induced by hTAU-toxicity. More importantly, we showed that the NDP52GEvariant is much more effective in this respect than NDP52WT. Mechanistically, we showed that NDP52 directly binds pathological phospho-TAU, and that NDP52WTand NDP52GEbind them with comparable efficiency. On the contrary, we showed that NDP52GEbinds the autophagic machinery (LC3C and LC3B) more efficiently than NDP52WT. We also showed for the first time that NDP52 is a direct target of protein phosphatase 2A (PP2A)in vitro, opening the way to the possibility that this phosphatase may fine-tune the autophagic function of NDP52 in AD. Finally, we found a positive correlation between the worldwide distribution of the allele encoding NDP52GEand the incidence or prevalence of AD. Overall, our work highlights the variant NDP52GEas a resilience factor in AD that shows a robust effectiveness to drive pathological TAU degradation.
Dual Metrics of Obesity: Evaluating BMI and Central Obesity as Indicators of Cardiometabolic Risk in Rural India
Authors: Prasad Raghav , Sagiraju Manogna , Chatterjee Priya , Sahadevan Pravin , Pradhan Hitesh , Sundarakumar Jonas S ,   SANSCOG Team
Published: August 2024

AbstractPurposeIndians face a higher risk of cardiometabolic diseases (CMDs) at the same BMI compared to Caucasians. This study explored the use of the Dual Metric Obesity Criteria (DMOC), combining central obesity (CO) indices with BMI, to assess sex-specific associations with CMDs in rural Indians.MethodsBaseline cross-sectional data from 3,397 participants aged ≥45 from the Centre for Brain Research-Srinivaspura Aging, Neuro Senescence and COGnition (CBR-SANSCOG) study were analysed. Five obesity indices were examined: BMI, Waist Circumference, Waist-Hip Ratio (WHR), Waist-Height Ratio (WHtR), and Visceral Fat Percentage. Cohen’s Kappa assessed the agreement between BMI and CO indices. Participants were classified based on BMI and CO status: NWNC (Normal Weight No CO), AWNC (Abnormal Weight No CO), NWCO (Normal Weight CO), and AWCO (Abnormal Weight CO). Multinomial logistic regression models evaluated associations between DMOC groups and CMDs. Interaction analyses explored CO and CMD relationships across sex, BMI categories, and age groups. The mediation effect of CO indices on the relationship between BMI and cardiometabolic risk factors was investigated.ResultsBMI showed a slight to fair agreement with WHR and moderate agreement with WHtR. Individuals with AWCO had the highest odds for all CMDs (p<0.001). Males with NWCO had a 3.51 (2.14,6.04) times increased odds times for diabetes and 2.04 (1.22,3.37) times odds for dyslipidemia. Individuals < 58 years and males had stronger associations with CMDs.ConclusionCombining CO indices with BMI effectively identifies high-risk CMD groups in rural Indians, including those with NWCO a previously overlooked group.
“I wanted to be a responsible public health professional”: applying serious games for deep learning in global health courses
Authors: Smith Julia , Gooderham Ellie , Piper Julianne 
Published: August 2024

ABSTRACTSerious games, including simulations, are increasingly used in university teaching, including medical and humanitarian studies as well as political science and international relations. There is less evidence of application in global health pedagogy. This article reports and reflects on the application of a simulation of negotiations around a global pandemic treaty in a Master of Public Health class on Global Health and International Affairs. Through participant observation and thematic analysis of students’ reflective essays we find that the simulation enabled deep learning in line with the assignment objectives (to apply learning from past health crisis, engage with key concepts, and experience global health cooperation and challenges), as well as prompted critical reflections on moral dilemmas related to global health cooperation and decolonizing global health. The simulation provided an opportunity for students to engage with the wicked problems embedded within global health by drawing on multiple perspectives and approaches. While the students failed in negotiating a successful pandemic treaty, it was these failures that provided opportunities for deep learning and critical reflection as they questioned constraints on their underlying motivations and actions. This experience suggests simulations can serve as a particularly apt approach for teaching interdisciplinary approaches to global health as they enable to students to apply different sets of knowledge to a particular problem, explore unfamiliar concepts and critically asses their assumptions.
CarD-T: Interpreting Carcinomic Lexicon via Transformers
Authors: O’Neill Jamey , Reddy Gudur Ashrith , Dhillon Nermeeta , Tripathi Osika , Alexandrov Ludmil , Katira Parag 
Published: August 2024

AbstractThe identification and classification of carcinogens is critical in cancer epidemiology, necessitating updated methodologies to manage the burgeoning biomedical literature. Current systems, like those run by the International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP), face challenges due to manual vetting and disparities in carcinogen classification spurred by the volume of emerging data. To address these issues, we introduced the Carcinogen Detection via Transformers (CarD-T) framework, a text analytics approach that combines transformer-based machine learning with probabilistic statistical analysis to efficiently nominate carcinogens from scientific texts. CarD-T uses Named Entity Recognition (NER) trained on PubMed abstracts featuring known carcinogens from IARC groups and includes a context classifier to enhance accuracy and manage computational demands. Using this method, journal publication data indexed with carcinogenicity & carcinogenesis Medical Subject Headings (MeSH) terms from the last 25 years was analyzed, identifying potential carcinogens. Training CarD-T on 60% of established carcinogens (Group 1 and 2A carcinogens, IARC designation), CarD-T correctly to identifies all of the remaining Group 1 and 2A designated carcinogens from the analyzed text. In addition, CarD-T nominates roughly 1500 more entities as potential carcinogens that have at least two publications citing evidence of carcinogenicity. Comparative assessment of CarD-T against GPT-4 model reveals a high recall (0.857 vs 0.705) and F1 score (0.875 vs 0.792), and comparable precision (0.894 vs 0.903). Additionally, CarD-T highlights 554 entities that show disputing evidence for carcinogenicity. These are further analyzed using Bayesian temporal Probabilistic Carcinogenic Denomination (PCarD) to provide probabilistic evaluations of their carcinogenic status based on evolving evidence. Our findings underscore that the CarD-T framework is not only robust and effective in identifying and nominating potential carcinogens within vast biomedical literature but also efficient on consumer GPUs. This integration of advanced NLP capabilities with vital epidemiological analysis significantly enhances the agility of public health responses to carcinogen identification, thereby setting a new benchmark for automated, scalable toxicological investigations.
Porcine Nasal Organoids as a model to study the interactions between the swine nasal microbiota and the host
Authors: Bonillo-Lopez Laura , Carmona-Vicente Noelia , Tarrés-Freixas Ferran , Kochanowski Karl , Martínez Jorge , Perez Mònica , Sibila Marina , Correa-Fiz Florencia , Aragon Virginia 
Published: August 2024

SUMMARYInteractions between the nasal epithelium, commensal nasal microbiota, and respiratory pathogens play a key role in respiratory infections. Currently there is a lack of experimental models to study such interactions under definedin vitroconditions. Here, we developed a Porcine Nasal Organoid (PNO) system from nasal tissue of pigs as well as from cytological brushes. PNOs exhibited similar structure and cell types than the nasal mucosa, as evaluated by immunostaining. PNOs were inoculated with porcine commensal strains ofMoraxella pluranimalium, Rothia nasimuriumand the pathobiontGlaesserella parasuisfor examining host-commensal-pathogen interactions. All strains adhered to the PNOs, although at different levels.M. pluranimaliumandG. parasuisstrains stimulated the production of proinflammatory cytokines, whereasR. nasimuriuminduced the production of IFNγ and diminished the proinflammatory effect of the other strains. Overall, PNOs mimic thein vivonasal mucosa and can be useful to perform host-microbe interaction studies.In briefInteractions between nasal epithelium, commensal nasal microbiota, and respiratory pathogens play a key role in respiratory infections. We developed porcine nasal organoids to mimic the nasal mucosa and use as a model to study those interactions. Additionally, this development supports the reduction of the number of animals for animal experimentation.HighlightsFirst generation of Porcine Nasal Organoids (PNOs) from nasal turbinates and swabsPNOs recapitulate features ofin vivotissue and maintain self-renewal capacityHost-microbe interactions can be studied using the PNO systemRothia nasimuriuminhibits the inflammation induced by other bacteria
APEX: Automated Protein EXpression inEscherichia coli
Authors: Kasprzyk Martyna , Herrera Michael A. , Stracquadanio Giovanni 
Published: August 2024

AbstractHeterologous protein expression is an indispensable strategy to generate significant amounts of recombinant proteins. To this end,Escherichia coli(E. coli) is one the most used microbial host for recombinant protein production due to its rapid growth, well-characterised genetics, and ability to produce recombinant proteins in high yields using modern recombinant DNA technology. However, while there is a plethora of robust protein expression protocols forE. coli, these methods are often unsuitable for high-throughput screening due to their significant resource and time consumption; these protocols are also susceptible to operator error and inconsistency.To address these challenges, we have developed APEX, a robust and automated protocol for recombinant protein production inE. coli. APEX leverages the accessible, open-source Opentrons OT-2 platform to automate microbial handling and protein expression with high precision and repro-ducibility. APEX can be configured to perform heat shock transformation, colony selection, colony sampling, inoculation, subculturing and protein expression using a low-cost, minimal OT-2 hardware setup. We further demonstrate the efficacy of our automated transformation workflows using a variety of plasmids (2.7-17.7 kb), and exemplify the automated heterologous expression of a diverse array of proteins (27-222 kDa). Designed with customization, modularity and user-friendliness in mind, APEX can be easily adapted to the operator’s needs without requiring any coding expertise.APEX is available athttps://github.com/stracquadaniolab/apex-nfunder the AGPL3 license.
A Light Sensitive Hyaluronic Acid-based Hydrogel for 3D Culturing, Differentiation, and Harvesting of Mesenchymal Stromal Cells
Authors: Palmieri Francesco , Gueye Marieme , Vicario del Rio Lucia , Bunschuh Saskia , Chopra Pradeep , Mihăilă Silvia , Vermonden Tina , Levato Riccardo , Boons Geert-Jan 
Published: August 2024

ABSTRACTHydrogels derived from natural sources are commonly used for 3D cell culturing due to their favourable interactions with cells. However, these biomaterials (e.g. Matrigel) suffer from variations in composition, limited mechanical tunability, the presence of xenogenic components and difficulties of cell retrieval. Semi-synthetic hydrogels are emerging to address these limitations, making these attractive for drug delivery and tissue engineering. Here, we describe a hydrogel platform based on hyaluronic acid (HA) modified by (1R,8S,9S)-bicycle[6.1.0]non-4-yn-9-ylmethanol (BCN) and a cross-linker composed of light sensitiveo-nitrobenzyl moieties and polyethylene glycol (PEG) chains terminating in azides. The two components can undergo strain-promoted azide-alkyne cycloaddition (SPAAC) resulting in rapid gel formation. The stiffness of the hydrogel can be modulated by varying the crosslinker ratio and multi-functionalizing is possible by the incorporation of chemical cues modified by an azide. The fast hydrogelation enables easy encapsulation of cells and harvesting with preservation of viability is possible be short exposure to UV light. Moreover, it is demonstrated that visible light (405 nm) can soften the hydrogel resulting in phenotypical changes of human Mesenchymal Stromal Cells (hMSCs) co-cultured with endothelial colony-forming cells (ECFCs) with high viability. Our findings highlight that the photosensitive HA-based hydrogel provides a versatile and biocompatible platform for cell culture and tissue engineering applications, offering advantages over traditional 3D cell culturing platforms.
An extra-glycolytic function for hexokinase 2 as an RNA-binding protein regulatingSOX10mRNA translation in melanoma
Authors: Dian Ana Luisa , Moya-Plana Antoine , Claps Giuseppina , Labbé Céline M. , Quidville Virginie , Baille Dorothée , Roy Séverine , Raynal Virginie , Baulande Sylvain , Robert Caroline , Vagner Stéphan 
Published: August 2024

ABSTRACTSeveral studies have reported the importance of aerobic glycolysis in melanoma development. Although metabolic benefits of glycolysis have been extensively described in tumor cells, the extra-metabolic functions linked to this energetic pathway in melanoma growth and proliferation have not been clearly established yet. Recently, some key glycolytic enzymes, such as GAPDH and PKM2, were reported to regulate mRNA translation. Translational control of gene expression is considered as a critical effector in cancer biology, representing a highly promising area of research. Here, we report that Hexokinase 2 (HK2), a glucose kinase that catalyzes the first step of glycolysis, is an RNA binding protein (RBP) that regulates mRNA translation in melanoma. We show that siRNA-mediated HK2 depletion changes the translational landscape of melanoma cells. Polysome profiling experiments and RNA-Seq indicate that the translational regulation exerted by HK2 is partly independent of the metabolic status or the glycolytic pathway. We found that HK2 specifically regulates the translation of the mRNA encoding SOX10, a transcription factor implicated in the regulation of tumor initiation, maintenance and progression in melanoma. RNA-protein interaction assays, including crosslinking immunoprecipitation (CLIP), indicate that HK2 is an RBP whose interaction with RNA is independent of its hexokinase activity or subcellular localization. We also show that HK2 specifically associates with the 5’ untranslated region (5’UTR) of theSOX10mRNA, and that several deletions in this region decreases both HK2-SOX10mRNA association andSOX105’ UTR-mediated translation. We further show that HK2-dependent SOX10 translational regulation is involved in melanoma cell proliferation and colony formation. Collectively, our data highlight a non-metabolic function of HK2, indicating that melanoma cells may enhance glycolysis for purposes beyond simple anabolism.