tbuckley/cabot-search huggingface dataset:
Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomised, phase 2 trial
Authors: Ynke Larivière, Trésor Zola Matuvanga, Bernard Isekah Osang'ir, Solange Milolo, Rachel Meta, Primo Kimbulu, Cynthia Robinson, Michael Katwere, Chelsea McLean, Gwen Lemey, Junior Matangila, Vivi Maketa, Patrick Mitashi, Jean-Pierre Van geertruyden, Pierre Van Damme, Hypolite Muhindo-Mavoko
Journal: The Lancet Infectious Diseases (2024)
High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial
Authors: Rovina Ruslami, Federica Fregonese, Lika Apriani, Leila Barss, Nancy Bedingfield, Victor Chiang, Victoria J Cook, Dina Fisher, Eri Flores, Greg J Fox, James Johnston, Rachel K Lim, Richard Long, Catherine Paulsen, Thu Anh Nguyen, Nguyen Viet Nhung, Diana Gibson, Chantal Valiquette, Andrea Benedetti, Dick Menzies
Journal: The Lancet Respiratory Medicine (2024)
Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study
Authors: Torsten P Vahl, Vinod H Thourani, Raj R Makkar, Nadira Hamid, Omar K Khalique, David Daniels, James M McCabe, Lowell Satler, Mark Russo, Wen Cheng, Isaac George, Gabriel Aldea, Brett Sheridan, Dean Kereiakes, Harsh Golwala, Firas Zahr, Stanley Chetcuti, Pradeep Yadav, Susheel K Kodali, Hendrik Treede, Stephan Baldus, Nicholas Amoroso, Lauren S Ranard, Duane S Pinto, Martin B Leon
Journal: The Lancet (2024)
The Lancet Psychiatry Commission: transforming mental health implementation research
Authors: Emma E McGinty, Margarita Alegria, Rinad S Beidas, Jeffrey Braithwaite, Lola Kola, Douglas L Leslie, Nathalie Moise, Bernardo Mueller, Harold A Pincus, Rahul Shidhaye, Kosali Simon, Sara J Singer, Elizabeth A Stuart, Matthew D Eisenberg
Journal: The Lancet Psychiatry (2024)
Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study
Authors: Ayse Bahar Ercan, Melyssa Aronson, Nicholas R Fernandez, Yuan Chang, Adrian Levine, Zhihui Amy Liu, Logine Negm, Melissa Edwards, Vanessa Bianchi, Lucie Stengs, Jiil Chung, Abeer Al-Battashi, Agnes Reschke, Alex Lion, Alia Ahmad, Alvaro Lassaletta, Alyssa T Reddy, Amir F Al-Darraji, Amish C Shah, An Van Damme, Anne Bendel, Aqeela Rashid, Ashley S Margol, Bethany L Kelly, Bojana Pencheva, Brandie Heald, Brianna Lemieux-Anglin, Bruce Crooks, Carl Koschmann, Catherine Gilpin, Christopher C Porter, David Gass, David Samuel, David S Ziegler, Deborah T Blumenthal, Dennis John Kuo, Dima Hamideh, Donald Basel, Dong-Anh Khuong-Quang, Duncan Stearns, Enrico Opocher, Fernando Carceller, Hagit Baris Feldman, Helen Toledano, Ira Winer, Isabelle Scheers, Ivana Fedorakova, Jack M Su, Jaime Vengoechea, Jaroslav Sterba, Jeffrey Knipstein, Jordan R Hansford, Julieta Rita Gonzales-Santos, Kanika Bhatia, Kevin J Bielamowicz, Khurram Minhas, Kim E Nichols, Kristina A Cole, Lynette Penney, Magnus Aasved Hjort, Magnus Sabel, Maria Joao Gil-da-Costa, Matthew J Murray, Matthew Miller, Maude L Blundell, Maura Massimino, Maysa Al-Hussaini, Mazin F Al-Jadiry, Melanie A Comito, Michael Osborn, Michael P Link, Michal Zapotocky, Mithra Ghalibafian, Najma Shaheen, Naureen Mushtaq, Nicolas Waespe, Nobuko Hijiya, Noemi Fuentes-Bolanos, Olfat Ahmad, Omar Chamdine, Paromita Roy, Pavel N Pichurin, Per Nyman, Rachel Pearlman, Rebecca C Auer, Reghu K Sukumaran, Rejin Kebudi, Rina Dvir, Robert Raphael, Ronit Elhasid, Rose B McGee, Rose Chami, Ryan Noss, Ryuma Tanaka, Salmo Raskin, Santanu Sen, Scott Lindhorst, Sebastien Perreault, Shani Caspi, Shazia Riaz, Shlomi Constantini, Sophie Albert, Stanley Chaleff, Stefan Bielack, Stefano Chiaravalli, Stuart Louis Cramer, Sumita Roy, Suzanne Cahn, Suzanne Penna, Syed Ahmer Hamid, Tariq Ghafoor, Uzma Imam, Valerie Larouche, Vanan Magimairajan Issai, William D Foulkes, Yi Yen Lee, Paul C Nathan, Yosef E Maruvka, Mary-Louise C Greer, Carol Durno, Adam Shlien, Birgit Ertl-Wagner, Anita Villani, David Malkin, Cynthia Hawkins, Eric Bouffet, Anirban Das, Uri Tabori
Journal: The Lancet Oncology (2024)
Metformin boosts antitumor immunity and improves prognosis in upfront resected pancreatic cancer: an observational study
Authors: Casper W F van Eijck, Disha Vadgama, Casper H J van Eijck, Johanna W Wilmink, Daan J Lips, Erwin van der Harst, Geert Kazemier, Gijs A Patijn, Ignace H de Hingh, Jan H Wijsman, Joris I Erdmann, Sebastiaan Festen, Bas Groot Koerkamp, J Sven D Mieog, Marcel den Dulk, Martijn W J Stommel, Olivier R Busch, Roeland F de Wilde, Vincent E de Meijer, Wouter te Riele, I Quintus Molenaar, Werner Draaisma, Eric Manusama, Kishan R D Lutchman, Susan van Dieren, Anniek Vlijm, Bert A Bonsing, C Yung Nio, Derik-Jan de Groot, Elske C Gootjes, Eran van Veldhuisen, Fenny Wit, Freek Daams, Geert Cirkel, Geertjan van Tienhoven, Irene E G van Hellemond, Johanna W Wilmink, Judith de Vos-Geelen, Koop Bosscha, Leonie J Mekenkamp, Maarten W Nijkamp, Maartje Los, Marion B van der Kolk, Marjolein Homs, Mark Ramaekers, Mike S Liem, Miriam L Wumkes, Nynke Michiels, Ronald van Dam, Rutger T Theijse, Saskia Luelmo, Thomas L Bollen, Ulf Neumann, Vincent Nieuwenhuijs
Journal: JNCI Journal of the National Cancer Institute (2024)

Beyond demographic and immune factors, metabolic considerations, particularly metformin's recognized impact in oncology, warrant exploration in treating pancreatic cancer. This study aimed to investigate the influence of metformin on patient survival and its potential correlation with distinct immune profiles in pancreatic ductal adenocarcinoma (PDAC) tumors.
Effects of Tirzepatide Versus Basal Insulins in People With Type 2 Diabetes and Different Baseline Glycemic Patterns: Post Hoc Analyses of the SURPASS-3 and SURPASS-4 Trials
Authors: Francesco Giorgino, Denise R. Franco, Claudia Nicolay, Andrea Hemmingway, Ángel Rodríguez, Russell J. Wiese
Journal: Diabetes Care (2024)

OBJECTIVE This post hoc analysis assessed change from baseline to week 52 in glycemic parameters for tirzepatide (5, 10, 15 mg) versus insulin degludec (SURPASS-3 trial) and glargine (SURPASS-4 trial) in people with type 2 diabetes and different baseline glycemic patterns, based on fasting serum glucose (FSG) and postprandial glucose (PPG) values. RESEARCH DESIGN AND METHODS Participant subgroups with low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG were defined according to the median values of these measures. RESULTS All tirzepatide doses and basal insulins were associated with decreased HbA1c, FSG, and PPG values from baseline to week 52 in all subgroups (P &amp;lt; 0.05). Within each subgroup, HbA1c and PPG decreases were greater with tirzepatide than insulin (P &amp;lt; 0.05). FSG decreases were generally similar. There were no differential treatment effects by FSG/PPG subgroup. CONCLUSIONS In this post hoc analysis, tirzepatide was associated with superior glycemic control compared with insulin, irrespective of baseline glycemic pattern.
Interferon-induced MXB protein restricts vimentin-dependent viral infection
Authors: Dongrong Yi, Ni An, Quanjie Li, Qian Liu, Huihan Shao, Rui Zhou, Jing Wang, Yongxin Zhang, Ling Ma, Fei Guo, Xiaoyu Li, Zhenlong Liu, Shan Cen
Journal: Acta Pharmaceutica Sinica B (2024)

Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses. Here, we find that IFN alters the subcellular localization of hundreds of host proteins, and this IFN effect is partially lost upon MXB depletion. The results of our mechanistic study reveal that MXB recognizes vimentin (VIM) and recruits protein kinase B (AKT) to phosphorylate VIM at amino acid S38, which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes, hence causing a restriction of virus infection. These results highlight a new function of MXB in modulating VIM-mediated trafficking, which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.
DermSynth3D: Synthesis of in-the-wild annotated dermatology images
Authors: Ashish Sinha, Jeremy Kawahara, Arezou Pakzad, Kumar Abhishek, Matthieu Ruthven, Enjie Ghorbel, Anis Kacem, Djamila Aouada, Ghassan Hamarneh
Journal: Medical Image Analysis (2024)
Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins
Authors: Ze Jin, Taehyun Hwang, Daehoon Kim, Byounghyun Lim, Oh-Seok Kwon, Sangbin Kim, Moon-Hyun Kim, Je-Wook Park, Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: npj Digital Medicine (2024)

Abstract Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm ( p &lt; 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p &lt; 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.
Bioactive Nanofiber‐Hydrogel Composite Regulates Regenerative Microenvironment for Skeletal Muscle Regeneration after Volumetric Muscle Loss
Authors: Wei Yu, Xiangqi Zhang, Muge Gu, Jiayu Wang, Yihui Zhang, Wenkai Zhang, Wei‐En Yuan
Journal: Advanced Healthcare Materials (2024)

Abstract Volumetric muscle loss (VML) is a severe form of muscle trauma that exceeds the regenerative capacity of skeletal muscle tissue, leading to substantial functional impairment. The abnormal immune response and excessive reactive oxygen species (ROS) accumulation hinder muscle regeneration following VML. Here, an interfacial cross‐linked hydrogel‐poly(ε‐caprolactone) nanofiber composite, that incorporates both biophysical and biochemical cues to modulate the immune and ROS microenvironment for enhanced VML repair, is engineered. The interfacial cross‐linking is achieved through a Michael addition between catechol and thiol groups. The resultant composite exhibits enhanced mechanical strength without sacrificing porosity. Moreover, it mitigates oxidative stress and promotes macrophage polarization toward a pro‐regenerative phenotype, both in vitro and in a mouse VML model. 4 weeks post‐implantation, mice implanted with the composite show improved grip strength and walking performance, along with increased muscle fiber diameter, enhanced angiogenesis, and more nerve innervation compared to control mice. Collectively, these results suggest that the interfacial cross‐linked nanofiber‐hydrogel composite could serve as a cell‐free and drug‐free strategy for augmenting muscle regeneration by modulating the oxidative stress and immune microenvironment at the VML site.
Validation and incorporation of digital entheses into a preliminary GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis
Authors: Esperanza Naredo, Maria Antonietta D'Agostino, Lene Terslev, Carlos Pineda, M Isabel Miguel, Joan Blasi, George A Bruyn, Marion C Kortekaas, Peter Mandl, Rodina Nestorova, Marcin Szkudlarek, Plamen Todorov, Violeta Vlad, Priscilla Wong, Catherine Bakewell, Emilio Filippucci, Alen Zabotti, Mihaela Micu, Florentin Vreju, Mohamed Mortada, José Alexandre Mendonça, Carlos A Guillen-Astete, Otto Olivas-Vergara, Annamaria Iagnocco, Petra Hanova, Ilaria Tinazzi, Peter V Balint, Sibel Zehra Aydin, David Kane, Helen Keen, Gurjit S Kaeley, Ingrid Möller
Journal: Annals of the Rheumatic Diseases (2024)

Objectives The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system. Methods The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis. Results 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39–0.71) and intraobserver reliability good to excellent (κ 0.80–0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes). Conclusions We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.
Author Correction: 2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease
Authors: Joselyn Rwebembera, James Marangou, Julius Chacha Mwita, Ana Olga Mocumbi, Cleonice Mota, Emmy Okello, Bruno Nascimento, Lene Thorup, Andrea Beaton, Joseph Kado, Alexander Kaethner, Raman Krishna Kumar, John Lawrenson, Eloi Marijon, Mariana Mirabel, Maria Carmo Pereira Nunes, Daniel Piñeiro, Fausto Pinto, Kate Ralston, Craig Sable, Amy Sanyahumbi, Anita Saxena, Karen Sliwa, Andrew Steer, Satupaitea Viali, Gavin Wheaton, Nigel Wilson, Liesl Zühlke, Bo Reményi
Journal: Nature Reviews Cardiology (2024)
Rab35 Is Required for Embryonic Development and Kidney and Ureter Homeostasis through Regulation of Epithelial Cell Junctions
Authors: Kelsey R. Clearman, Napassawon Timpratoom, Dharti Patel, Addison B. Rains, Courtney J. Haycraft, Mandy J. Croyle, Jeremy F. Reiter, Bradley K. Yoder
Journal: Journal of the American Society of Nephrology (2024)

Key Points Loss of Rab35 leads to nonobstructive hydronephrosis because of loss of ureter epithelium. Rab35 regulates kidney and ureter epithelial cell adhesion and polarity. Rab35 is required for embryonic development. Background Rab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. In addition, sea urchin Rab35 regulates actin organization and is required for gastrulation. In mice, loss of Rab35 in the central nervous system disrupts hippocampal development and neuronal organization. Outside of the central nervous system, the functions of mammalian Rab35 in vivo are unknown. Methods We generated and analyzed the consequences of both congenital and conditional null Rab35 mutations in mice. Using a LacZ reporter allele, we assessed Rab35 expression during development and postnatally. We assessed Rab35 loss in the kidney and ureter using histology, immunofluorescence microscopy, and western blotting. Results Congenital Rab35 loss of function caused embryonic lethality: homozygous mutants arrested at E7.5 with cardiac edema. Conditional loss of Rab35, either during gestation or postnatally, caused hydronephrosis. The kidney and ureter phenotype were associated with disrupted actin cytoskeletal architecture, altered Arf6 epithelial polarity, reduced adherens junctions, loss of tight junction formation, defects in epithelial growth factor receptor expression and localization, disrupted cell differentiation, and shortened primary cilia. Conclusions Rab35 may be essential for mammalian development and the maintenance of kidney and ureter architecture. Loss of Rab35 leads to nonobstructive hydronephrosis, making the Rab35 mutant mouse a novel mammalian model to study mechanisms underlying this disease.
IgG hexamers initiate complement-dependent acute lung injury
Authors: Simon J. Cleary, Yurim Seo, Jennifer J. Tian, Nicholas Kwaan, David P. Bulkley, Arthur E.H. Bentlage, Gestur Vidarsson, Éric Boilard, Rolf Spirig, James C. Zimring, Mark R. Looney
Journal: Journal of Clinical Investigation (2024)

Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful antibodies often activate the complement cascade. A model for how IgG antibodies trigger complement activation involves interactions between IgG Fc domains driving assembly of IgG hexamer structures that activate C1 complexes. The importance of IgG hexamers in initiating injury responses was unclear, so we tested their relevance in a mouse model of alloantibody and complement-mediated acute lung injury. We used three approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from Staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer 'decoy' therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate an in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles
Authors: Peter Ruzanov, Valentina Evdokimova, Manideep C. Pachva, Alon Minkovich, Zhenbo Zhang, Sofya Langman, Hendrik Gassmann, Uwe Thiel, Marija Orlic-Milacic, Syed H. Zaidi, Vanya Peltekova, Lawrence E. Heisler, Manju Sharma, Michael E. Cox, Trevor D. McKee, Mark Zaidi, Eve Lapouble, John D. McPherson, Olivier Delattre, Laszlo Radvanyi, Stefan E.G. Burdach, Lincoln D. Stein, Poul H. Sorensen
Journal: Journal of Clinical Investigation (2024)

Aberrant expression of ETS transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS::FLI1 and EWS::ERG fusions in Ewing sarcoma (EwS) and TMPRSS2::ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both EWS::FLI1 and ERG bind and transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 and HSAT3 RNAs, together with LINE, SINE, ERV and other repeat transcripts, are expressed in EwS and PCa tumors, secreted in extracellular vesicles (EVs) and are highly elevated in plasma of EwS patients with metastatic disease. High HSAT2,3 levels in EWS::FLI1 or ERG expressing cells and tumors were associated with induction of G2/M checkpoint, mitotic spindle and DNA damage programs. These programs were also activated in EwS EV-treated fibroblasts, coincident with accumulation of HSAT2,3 RNAs, proinflammatory responses, mitotic defects, and senescence. Mechanistically, HSAT2,3-enriched cancer EVs induced cGAS-TBK1 innate immune signaling and formation of cytosolic granules positive for double-strand RNAs, RNA-DNA and cGAS. Hence, aberrantly expressed ETS proteins derepress pericentromeric heterochromatin, yielding pathogenic RNAs which transmit genotoxic stress and inflammation to local and distant sites. Monitoring HSAT2,3 plasma levels and preventing their dissemination may thus improve therapeutic strategies and blood-based diagnostics.
Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort
Authors: Xiumei Hong, Kari Nadeau, Guoying Wang, Ben Larman, Kellie N. Smith, Colleen Pearson, Hongkai Ji, Pamela Frischmeyer-Guerrerio, Liming Liang, Frank B. Hu, Xiaobin Wang
Journal: Journal of Allergy and Clinical Immunology (2024)