tbuckley/cabot-search huggingface dataset:
Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration
Authors: Liang Zhou, Feng Cai, Hongyi Zhu, Yichang Xu, Jincheng Tang, Wei Wang, Ziang Li, Jie Wu, Zhouye Ding, Kun Xi, Liang Chen, Yong Gu
Journal: Bioactive Materials (2024)

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.
Retraction remedy: a resource for transparent science
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2024)

Open science and Artificial intelligence (AI) tools have led to improving scientific discourse in an unexpected way. With the help of AI, last month a research misconduct sleuth, Sholto David, found inconsistencies in 58 studies authored by influential scientists at the Dana-Farber Cancer Institute, resulting in retractions of six papers, and corrections in 31 manuscripts. Retractions resulting from image or data fabrications are on the rise and could be heightened at times of global emergency. During the COVID-19 pandemic, suspected data fabrication resulted in a number of retracted studies, bringing into question the veracity of data in research, at a time when research integrity was key for maintaining public trust.
Use of a meningococcal group B vaccine (4CMenB) in populations at high risk of gonorrhoea in the UK
Authors: Shamez N Ladhani, Peter J White, Helen Campbell, Sema Mandal, Ray Borrow, Nick Andrews, Sunil Bhopal, John Saunders, Hamish Mohammed, Lana Drisdale-Gordon, Emma Callan, Katy Sinka, Kate Folkard, Helen Fifer, Mary E Ramsay
Journal: The Lancet Infectious Diseases (2024)
NHS funding for a secure future
Authors: John Appleby, Gillian Leng, Martin Marshall
Journal: BMJ (2024)

Worries about the sustainability of NHS funding have a long history.Just five years after the NHS opened its doors, amid concern about escalating spending on the NHS, the then Conservative government set up an independent commission led by Claude Guillebaud to examine the costs of the NHS.That inquiry found that spending remained sustainable even though it had increased, and actually recommended that extra investment was needed in hospitals and community services.
Cost‐effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction: A pooled analysis of <scp>DAPA‐HF</scp> and <scp>DELIVER</scp> data
Authors: Jason A. Davis, David Booth, Phil McEwan, Scott D. Solomon, John J.V. McMurray, Rudolf A. de Boer, Josep Comin‐Colet, Erasmus Bachus, Jieling Chen
Journal: European Journal of Heart Failure (2024)

To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF).
Design of a Novel Delivery Efficiency Feedback System for Biphasic Dissolving Microarray Patches Based on Poly(Lactic Acid) and Moisture‐Indicating Silica
Authors: Huanhuan Li, Qonita Kurnia Anjani, Aaron R. J. Hutton, Juan Luis Paris, Natalia Moreno‐Castellanos, Achmad Himawan, Eneko Larrañeta, Ryan F. Donnelly
Journal: Advanced Healthcare Materials (2024)

Dissolving microarray patches (DMAPs) represent an innovative approach to minimally invasive transdermal drug delivery, demonstrating efficacy in delivering both small and large therapeutic molecules. However, concerns raised in end-user surveys have hindered their commercialization efforts. One prevalent issue highlighted in these surveys is the lack of clear indicators for successful patch insertion and removal time. To address this challenge, a color-change-based feedback system is devised, which confirms the insertion and dissolution of DMAPs, aiming to mitigate the aforementioned problems. The approach combines hydrophilic needles containing model drugs (fluorescein sodium and fluorescein isothiocyanate (FITC)-dextran) with a hydrophobic poly(lactic acid) baseplate infused with moisture-sensitive silica gel particles. The successful insertion and subsequent complete dissolution of the needle shaft are indicated by the progressive color change of crystal violet encapsulated in the silica. Notably, distinct color alterations on the baseplate, observed 30 min and 1 h after insertion for FITC-dextran and fluorescein sodium DMAPs respectively, signal the full dissolution of the needles, confirming the complete cargo delivery and enabling timely patch removal. This innovative feedback system offers a practical solution for addressing end-user concerns and may significantly contribute to the successful commercialization of DMAPs by providing a visualized drug delivery method.
BMP9 is a key player in endothelial identity and its loss is sufficient to induce arteriovenous malformations
Authors: Agnes Desroches-Castan, Dzenis Koca, Hequn Liu, Caroline Roelants, Léa Resmini, Nicolas Ricard, Claire Bouvard, Nicolas Chaumontel, Pierre-Louis Tharaux, Emmanuelle Tillet, Christophe Battail, Olivia Lenoir, Sabine Bailly
Journal: Cardiovascular Research (2024)

BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder hereditary hemorrhagic telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms downstream of BMP9 to better characterize its role in vascular homeostasis in different organs.
ARF4-mediated retrograde trafficking as a driver of chemoresistance in GBM
Authors: Shreya Budhiraja, Graysen McManus, Shivani Baisiwala, Ella N Perrault, Sia Cho, Miranda Saathoff, Li Chen, Cheol H Park, Hasaan A Kazi, Crismita Dmello, Peiyu Lin, C David James, Adam M Sonabend, Dieter H Heiland, Atique U Ahmed
Journal: Neuro-Oncology (2024)

Abstract Background Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear. Methods To identify genetic drivers of TMZ resistance, we conducted comprehensive CRISPR-knockout screening, revealing ADP-ribosylation factor 4 (ARF4), a regulator of retrograde trafficking, as a major contributor. Results Suppressing ARF4 significantly enhanced TMZ sensitivity in GBM patient-derived xenograft (PDX) models, leading to improved survival rates (P &amp;lt; .01) in both primary and recurrent lines. We also observed that TMZ exposure stimulates ARF4-mediated retrograde trafficking. Proteomics analysis of GBM cells with varying levels of ARF4 unveiled the influence of this pathway on EGFR signaling, with increased nuclear trafficking of EGFR observed in cells with ARF4 overexpression and TMZ treatment. Additionally, spatially resolved RNA-sequencing of GBM patient tissues revealed substantial correlations between ARF4 and crucial nuclear EGFR (nEGFR) downstream targets, such as MYC, STAT1, and DNA-PK. Decreased activity of DNA-PK, a DNA repair protein downstream of nEGFR signaling that contributes to TMZ resistance, was observed in cells with suppressed ARF4 levels. Notably, treatment with DNA-PK inhibitor, KU-57788, in mice with a recurrent PDX line resulted in prolonged survival (P &amp;lt; .01), highlighting the promising therapeutic implications of targeting proteins reliant on ARF4-mediated retrograde trafficking. Conclusions Our findings demonstrate that ARF4-mediated retrograde trafficking contributes to the development of TMZ resistance, cementing this pathway as a viable strategy to overcome chemoresistance in GBM.
Muscle Strength Identification based on Isokinetic Testing and Spine Musculoskeletal Modeling
Authors: Zuming Xiao, Chang Li, Xin Wang, Jianqiao Guo, Qiang Tian
Journal: Cyborg and Bionic Systems (2024)

Subject-specific spinal musculoskeletal modeling can help understand the spinal loading mechanism during human locomotion. However, existing literature lacks methods to identify the maximum isometric strength of individual spinal muscles. In this study, a muscle strength identification method combining isokinetic testing and musculoskeletal simulations was proposed, and the influence of muscle synergy and intra-abdominal pressure (IAP) on identified spinal muscle strength was further discussed. A multibody dynamic model of the spinal musculoskeletal system was established and controlled by a feedback controller. Muscle strength parameters were adjusted based on the measured isokinetic moments, and muscle synergy vectors and the IAP piston model were further introduced. The results of five healthy subjects showed that the proposed method successfully identified the subject-specific spinal flexor/extensor strength. Considering the synergistic activations of antagonist muscles improved the correlation between the simulated and measured spinal moments, and the introduction of IAP slightly increased the identified spinal extensor strength. The established method is beneficial for understanding spinal loading distributions for athletes and patients with sarcopenia.
scalepopgen: Bioinformatic Workflow Resources Implemented in Nextflow for Comprehensive Population Genomic Analyses
Authors: Maulik Upadhyay, Neža Pogorevc, Ivica Medugorac
Journal: Molecular Biology and Evolution (2024)

Population genomic analyses such as inference of population structure and identifying signatures of selection usually involve the application of a plethora of tools. The installation of tools and their dependencies, data transformation, or series of data preprocessing in a particular order sometimes makes the analyses challenging. While the usage of container-based technologies has significantly resolved the problems associated with the installation of tools and their dependencies, population genomic analyses requiring multistep pipelines or complex data transformation can greatly be facilitated by the application of workflow management systems such as Nextflow and Snakemake. Here, we present scalepopgen, a collection of fully automated workflows that can carry out widely used population genomic analyses on the biallelic single nucleotide polymorphism data stored in either variant calling format files or the plink-generated binary files. scalepopgen is developed in Nextflow and can be run locally or on high-performance computing systems using either Conda, Singularity, or Docker. The automated workflow includes procedures such as (i) filtering of individuals and genotypes; (ii) principal component analysis, admixture with identifying optimal K-values; (iii) running TreeMix analysis with or without bootstrapping and migration edges, followed by identification of an optimal number of migration edges; (iv) implementing single-population and pair-wise population comparison-based procedures to identify genomic signatures of selection. The pipeline uses various open-source tools; additionally, several Python and R scripts are also provided to collect and visualize the results. The tool is freely available at https://github.com/Popgen48/scalepopgen.
Mimicking clinical trials with synthetic acute myeloid leukemia patients using generative artificial intelligence
Authors: Jan-Niklas Eckardt, Waldemar Hahn, Christoph Röllig, Sebastian Stasik, Uwe Platzbecker, Carsten Müller-Tidow, Hubert Serve, Claudia D. Baldus, Christoph Schliemann, Kerstin Schäfer-Eckart, Maher Hanoun, Martin Kaufmann, Andreas Burchert, Christian Thiede, Johannes Schetelig, Martin Sedlmayr, Martin Bornhäuser, Markus Wolfien, Jan Moritz Middeke
Journal: npj Digital Medicine (2024)

Clinical research relies on high-quality patient data, however, obtaining big data sets is costly and access to existing data is often hindered by privacy and regulatory concerns. Synthetic data generation holds the promise of effectively bypassing these boundaries allowing for simplified data accessibility and the prospect of synthetic control cohorts. We employed two different methodologies of generative artificial intelligence - CTAB-GAN+ and normalizing flows (NFlow) - to synthesize patient data derived from 1606 patients with acute myeloid leukemia, a heterogeneous hematological malignancy, that were treated within four multicenter clinical trials. Both generative models accurately captured distributions of demographic, laboratory, molecular and cytogenetic variables, as well as patient outcomes yielding high performance scores regarding fidelity and usability of both synthetic cohorts (n = 1606 each). Survival analysis demonstrated close resemblance of survival curves between original and synthetic cohorts. Inter-variable relationships were preserved in univariable outcome analysis enabling explorative analysis in our synthetic data. Additionally, training sample privacy is safeguarded mitigating possible patient re-identification, which we quantified using Hamming distances. We provide not only a proof-of-concept for synthetic data generation in multimodal clinical data for rare diseases, but also full public access to synthetic data sets to foster further research.
Platelet-derived microparticles and their cargos: The past, present and future
Authors: Jingwen Guo, Bufeng Cui, Jie Zheng, Chang Yu, Xuran Zheng, Lixin Yi, Simeng Zhang, Keke Wang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.
The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for Revisions of the “T” Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma
Authors: Ritu R. Gill, Anna K. Nowak, Dorothy J. Giroux, Megan Eisele, Adam Rosenthal, Hedy Kindler, Andrea Wolf, Robert T. Ripley, Andre Billé, David Rice, Isabelle Opitz, Andreas Rimner, Marc de Perrot, Harvey I. Pass, Valerie W. Rusch
Journal: Journal of Thoracic Oncology (2024)
Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure
Authors: Georg Semmler, Sonia Alonso López, Monica Pons, Sabela Lens, Elton Dajti, Marie Griemsmann, Alberto Zanetto, Lukas Burghart, Stefanie Hametner-Schreil, Lukas Hartl, Marisa Manzano, Sergio Rodriguez-Tajes, Paola Zanaga, Michael Schwarz, María Luisa Gutierrez, Mathias Jachs, Anna Pocurull, Benjamín Polo, Dominik Ecker, Beatriz Mateos, Sonia Izquierdo, Yolanda Real, Adriana Ahumada, David Josef Maria Bauer, Jim Benjamin Mauz, Michelle Casanova-Cabral, Michael Gschwantler, Francesco Paolo Russo, Francesco Azzaroli, Benjamin Maasoumy, Thomas Reiberger, Xavier Forns, Joan Genesca, Rafael Bañares, Mattias Mandorfer, Sofia Maria Agostini, Lorenz Balcar, Sara Battistella, David Chromy, Markus Cornberg, Katja Deterding, Inmaculada Fernandez, Conrado Fernandez-Rodriguez, Francisco Gea, Fiona Koeck, Julia Krawanja, Daniela Neumayer, Daniel Riado, Diego Rincón, Philipp Schwabl, Benedikt Simbrunner, Michael Trauner, Clara Uson, Heiner Wedemeyer
Journal: Journal of Hepatology (2024)

Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints.
A pledge for a better care and consideration of patients with vitiligo
Authors: Thierry Passeron
Journal: British Journal of Dermatology (2024)

Journal Article Corrected proof A pledge for a better care and consideration of patients with vitiligo Get access Thierry Passeron Thierry Passeron Conceptualization, Writing - original draft, Writing - review & editing Université Côte d'Azur, CHU Nice, Department of DermatologyUniversité Côte d'Azur, INSERM, U1065, C3 M, Nice, France Correspondence: Thierry Passeron. Email: passeron@unice.fr https://orcid.org/0000-0002-0797-6570 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae083, https://doi.org/10.1093/bjd/ljae083 Published: 21 March 2024 Article history Received: 14 February 2024 Accepted: 20 February 2024 Corrected and typeset: 21 March 2024 Published: 21 March 2024
Multiple Genomic Landscapes of Recombination and Genomic Divergence in Wild Populations of House Mice—The Role of Chromosomal Fusions and Prdm9
Authors: Cristina Marín-García, Lucía Álvarez-González, Laia Marín-Gual, Sònia Casillas, Judith Picón, Keren Yam, María Magdalena Garcias-Ramis, Covadonga Vara, Jacint Ventura, Aurora Ruiz-Herrera
Journal: Molecular Biology and Evolution (2024)

Abstract Chromosomal fusions represent one of the most common types of chromosomal rearrangements found in nature. Yet, their role in shaping the genomic landscape of recombination and hence genome evolution remains largely unexplored. Here, we take advantage of wild mice populations with chromosomal fusions to evaluate the effect of this type of structural variant on genomic landscapes of recombination and divergence. To this aim, we combined cytological analysis of meiotic crossovers in primary spermatocytes with inferred analysis of recombination rates based on linkage disequilibrium using single nucleotide polymorphisms. Our results suggest the presence of a combined effect of Robertsonian fusions and Prdm9 allelic background, a gene involved in the formation of meiotic double strand breaks and postzygotic reproductive isolation, in reshaping genomic landscapes of recombination. We detected a chromosomal redistribution of meiotic recombination toward telomeric regions in metacentric chromosomes in mice with Robertsonian fusions when compared to nonfused mice. This repatterning was accompanied by increased levels of crossover interference and reduced levels of estimated recombination rates between populations, together with high levels of genomic divergence. Interestingly, we detected that Prdm9 allelic background was a major determinant of recombination rates at the population level, whereas Robertsonian fusions showed limited effects, restricted to centromeric regions of fused chromosomes. Altogether, our results provide new insights into the effect of Robertsonian fusions and Prdm9 background on meiotic recombination.
Transplant benefit-based offering of deceased donor livers in the United Kingdom
Authors: Elisa Allen, Rhiannon Taylor, Alexander Gimson, Douglas Thorburn
Journal: Journal of Hepatology (2024)

The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant.
Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients
Authors: Becky M. Ma, Naama Elefant, Martina Tedesco, Kelsie Bogyo, Natalie Vena, Sarath K. Murthy, Shiraz A. Bheda, Sandy Yang, Nikita Tomar, Jun Y. Zhang, Syed Ali Husain, Sumit Mohan, Krzysztof Kiryluk, Hila Milo Rasouly, Ali G. Gharavi
Journal: Kidney International (2024)

Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.
Prevention of allergic reactions during oxaliplatin desensitization through inhibition of Bruton tyrosine kinase
Authors: Kristin A. Erickson, James E. Norton, Jennifer Law, Nicole Soriano, Malgorzata Strojny, Nicole Gentry, Morgan Fried, Bruce S. Bochner, Sheetal Kircher, Whitney W. Stevens
Journal: Journal of Allergy and Clinical Immunology (2024)