tbuckley/cabot-search huggingface dataset:
A bipartite graph-based expected networks approach identifies DDR genes not associated with TMB yet predictive of immune checkpoint blockade response
Authors: William H. Weir, Peter J. Mucha, William Y. Kim
Journal: Cell Reports Medicine (2022)

Immune checkpoint blockade (ICB) has had remarkable success for treatment of solid tumors. However, as only a subset of patients exhibit responses, there is a continued need for biomarker development. Numerous reports have shown a link between tumor mutational burden (TMB) and ICB response, while others have identified a link between ICB response and mutation in DNA damage repair (DDR) genes. However, it remains unclear to what extent mutations in DDR genes hold predictive value above and beyond their association with TMB. Herein, we present a networks-based test and bipartite graph-based expected TMB score (BiG-BETS) with higher specificity for discriminating DDR genes and pathways that are associated with elevated TMB. Moreover, we find that mutations in certain DDR genes that are not associated with elevated TMB (low BiG-BETS) are nevertheless predictive of ICB benefit in high TMB patients, demonstrating that their inactivation contributes to ICB response in a TMB-independent manner.
The complex karyotype in hematological malignancies: a comprehensive overview by the Francophone Group of Hematological Cytogenetics (GFCH)
Authors: F. Nguyen-Khac, A. Bidet, A. Daudignon, M. Lafage-Pochitaloff, G. Ameye, C. Bilhou-Nabéra, E. Chapiro, M. A. Collonge-Rame, W. Cuccuini, N. Douet-Guilbert, V. Eclache, I. Luquet, L. Michaux, N. Nadal, D. Penther, B. Quilichini, C. Terre, C. Lefebvre, M.-B. Troadec, L. Véronèse
Journal: Leukemia (2022)
A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model
Authors: Menghuan Tang, Kai Lin, Mythili Ramachandran, Longmeng Li, Hongye Zou, Huzhi Zheng, Zhao Ma, Yuanpei Li
Journal: Acta Pharmaceutica Sinica B (2022)

Hybrid lipid‒nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles. Here we developed a kind of lipid-small molecule hybrid nanoparticles (LPHNPs) for imaging and treatment in an orthotopic glioma model. LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a‒quinolinium conjugate (PQC), a mitochondria-targeting small molecule. Compared with the pure nanofiber self-assembled by PQC, LPHNPs not only preserve the comparable antiproliferative potency, but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection. Also, this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes. By integrating the advantages from liposome and PQC molecule, LPHNPs have minimal system toxicity, enhanced potency of photodynamic therapy (PDT) and visualization capacities of drug biodistribution and tumor imaging. The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma. The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.
Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection
Authors: Paul B. Eckburg, Lori Muir, Ian A. Critchley, Susannah Walpole, Hanna Kwak, Anne-Marie Phelan, Gary Moore, Akash Jain, Tim Keutzer, Aaron Dane, David Melnick, Angela K. Talley
Journal: New England Journal of Medicine (2022)

There is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase–producing and fluoroquinolone-resistant strains.
Admission Serum Metabolites and Thyroxine Predict Advanced Hepatic Encephalopathy in a Multicenter Inpatient Cirrhosis Cohort
Authors: Jasmohan S. Bajaj, Puneeta Tandon, Jacqueline G. O’Leary, K. Rajender Reddy, Guadalupe Garcia-Tsao, Paul Thuluvath, Jennifer C. Lai, Ram M. Subramanian, Hugo E. Vargas, Florence Wong, Andrew Fagan, Sara McGeorge, Leroy R. Thacker, Patrick S. Kamath
Journal: Clinical Gastroenterology and Hepatology (2022)
First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results
Authors: Christoph Königs, Margareth C. Ozelo, Amy Dunn, Roshni Kulkarni, Beatrice Nolan, Simon A. Brown, Michele Schiavulli, Sriya Gunawardena, Sutirtha Mukhopadhyay, Deepthi Jayawardene, Bent Winding, Manuel Carcao
Journal: Blood (2022)

PUPs A-LONG evaluated the safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously untreated patients (PUPs) with hemophilia A. This open-label, phase 3 study enrolled male PUPs (<6 years) with severe hemophilia A to receive rFVIIIFc. The primary endpoint was the occurrence of inhibitor development. Secondary endpoints included annualized bleed rate (ABR). Of 103 subjects receiving ≥1 dose of rFVIIIFc, 80 (78%) were aged <1 year at the study start, 20 (19%) had a family history of inhibitors, and 82 (80%) had high-risk F8 mutations. Twenty subjects began on prophylaxis, while 81 began an on-demand regimen (69 later switched to prophylaxis). Eighty-seven (81%) subjects completed the study. Inhibitor incidence was 31.1% (95% confidence interval [CI], 21.8% to 41.7%) in subjects with ≥10 exposure days (or inhibitor); high-titer inhibitor incidence was 15.6% (95% CI, 8.8% to 24.7%). The median (range) time to high-titer inhibitor development was 9 (4-14) exposure days. Twenty-eight (27%) subjects experienced 32 rFVIIIFc treatment-related adverse events; most were inhibitor development. There was 1 nontreatment-related death due to intracranial hemorrhage (onset before the first rFVIIIFc dose). The overall median (interquartile range [IQR]) ABR was 1.49 (0.00-4.40) for subjects on variable prophylaxis dosing regimens. In this study of rFVIIIFc in pediatric PUPs with severe hemophilia A, overall inhibitor development was within the expected range, although high-titer inhibitor development was on the low end of the range reported in the literature. rFVIIIFc was well-tolerated and effective for prophylaxis and treatment of bleeds. This trial is registered at www.clinicaltrials.gov (NCT02234323).
Regulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma
Authors: Jiao Li, Jian‐Kang Zhou, Xiaoyu Mu, Shu Shen, Xiaomin Xu, Yao Luo, Yuxin Luo, Yue Ming, Yuangang Wu, Yong Peng
Journal: MedComm (2022)

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre-miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl-prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55β subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55β-containing PP2A in miRNA expression and may shed light on HCC pathogenesis.
Intense 68Ga-FAPI Uptake in a Patient With Myositis Ossificans
Authors: Weidong Gong, Si Chen, Lei He, Wei Liu, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract A 72-year-old man presented with right hip pain, difficulty in walking, and a mass in his right hip for 3 months. CT suggested osteonecrosis of the right femoral head and a mass in the right hip with calcification. A malignancy was suspected, and the patient was subsequently enrolled in the clinical trial of 68 Ga-FAPI. 68 Ga-FAPI PET/CT showed a mass in his right hip with intense FAPI activity. It was also highly suggestive of malignancy. The pathological examination after right-hip surgery confirmed the diagnosis of myositis ossificans.
Think Pragmatically: Investigators’ Obligations to Patient-Subjects When Research is Embedded in Care
Authors: Stephanie Morain, Emily Largent
Journal: The American Journal of Bioethics (2022)

Growing interest in embedded research approaches—where research is incorporated into clinical care—has spurred numerous studies to generate knowledge relevant to the real-world needs of patients and other stakeholders. However, it also has presented ethical challenges. An emerging challenge is how to understand the nature and extent of investigators' obligations to patient-subjects. Prior scholarship on investigator duties has generally been grounded upon the premise that research and clinical care are distinct activities, bearing distinct duties. Yet this premise—and its corresponding implications—are challenged when research and clinical care are deliberately integrated. After presenting three case studies from recent pragmatic clinical trials, we identify six differences between explanatory trials and embedded research that limit the application of existing scholarship for ascertaining investigator duties. We suggest that these limitations indicate a need to account for the implications of usual care and to move beyond a narrow focus on the investigator-subject dyad, one that better reflects the team- and institution-based nature of contemporary health systems.
Outcome of COVID-19 in Patients With Mantle Cell Lymphoma—Report From the European MCL Registry
Authors: Marie-Kristin Tilch, Carlo Visco, Sandra Kinda, Olivier Hermine, Milena Kohn, Caroline Besson, Sylvain Lamure, Rémy Duléry, Simone Ragaini, Toby A. Eyre, Tom Van Meerten, Anke Ohler, Steffen Eckerle, Martin Dreyling, Georg Hess, Eva Giné, Maria Gomes da Silva
Journal: HemaSphere (2022)

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44-84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.
Reduction of mtDNA heteroplasmy in mitochondrial replacement therapy by inducing forced mitophagy
Authors: Xiao-Yan Fan, Lei Guo, Lei-Ning Chen, Shen Yin, Jiarong Wen, Sen Li, Jun-Yu Ma, Tao Jing, Man-Xi Jiang, Xiao-Hong Sun, Meilan Chen, Feng Wang, Zhen-Bo Wang, Chang-Fa Zhang, Xing-Hua Wang, Zhao-Jia Ge, Chun Hu, Lizhang Zeng, Wei Shen, Qing-Yuan Sun, Xiang-Hong Ou, Shi-Ming Luo
Journal: Nature Biomedical Engineering (2022)
The tendon microenvironment: Engineered in vitro models to study cellular crosstalk
Authors: Manuel Gomez-Florit, Claudia J. Labrador-Rached, Rui M.A. Domingues, Manuela E. Gomes
Journal: Advanced Drug Delivery Reviews (2022)

Tendinopathy is a multi-faceted pathology characterized by alterations in tendon microstructure, cellularity and collagen composition. Challenged by the possibility of regenerating pathological or ruptured tendons, the healing mechanisms of this tissue have been widely researched over the past decades. However, so far, most of the cellular players and processes influencing tendon repair remain unknown, which emphasizes the need for developing relevant in vitro models enabling to study the complex multicellular crosstalk occurring in tendon microenvironments. In this review, we critically discuss the insights on the interaction between tenocytes and the other tendon resident cells that have been devised through different types of existing in vitro models. Building on the generated knowledge, we stress the need for advanced models able to mimic the hierarchical architecture, cellularity and physiological signaling of tendon niche under dynamic culture conditions, along with the recreation of the integrated gradients of its tissue interfaces. In a forward-looking vision of the field, we discuss how the convergence of multiple bioengineering technologies can be leveraged as potential platforms to develop the next generation of relevant in vitro models that can contribute for a deeper fundamental knowledge to develop more effective treatments.
Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression—Reply
Authors: Olivia I. Okereke, David Mischoulon, JoAnn E. Manson
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Blood Biomarkers May Have Found a New Frontier in Spaceflight
Authors: Taylor R. Zuidema, Megan E. Huibregtse, Keisuke Kawata
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
A SARS-CoV-2 omicron (B.1.1.529) variant outbreak in a primary school in Geneva, Switzerland
Authors: Elsa Lorthe, Mathilde Bellon, Julie Berthelot, Grégoire Michielin, Arnaud G L'Huillier, Klara M Posfay-Barbe, Andrew S Azman, Idris Guessous, Sebastian J Maerkl, Isabella Eckerle, Silvia Stringhini
Journal: The Lancet Infectious Diseases (2022)
Cardiac Resident Macrophage-Derived Legumain Improves Cardiac Repair by Promoting Clearance and Degradation of Apoptotic Cardiomyocytes After Myocardial Infarction
Authors: Daile Jia, Siqin Chen, Peiyuan Bai, Chentao Luo, Jin Liu, Aijun Sun, Junbo Ge
Journal: Circulation (2022)

Cardiac resident macrophages are self-maintaining and originate from embryonic hematopoiesis. After myocardial infarction, cardiac resident macrophages are responsible for the efficient clearance and degradation of apoptotic cardiomyocytes (efferocytosis). This process is required for inflammation resolution and tissue repair; however, the underlying molecular mechanisms remain unknown. Therefore, we aimed to identify the mechanisms of the continued clearance and degradation of phagolysosomal cargo by cardiac resident macrophages during myocardial infarction. Multiple transgenic mice such as Lgmn-/-, LgmnF/F; LysMCre, LgmnF/F; Cx3cr1CreER, LgmnF/F; LyveCre, and cardiac macrophage Lgmn overexpression by adenovirus gene transfer were used to determine the functional significance of Lgmn in myocardial infarction. Immune cell filtration and inflammation were examined by flow cytometry and quantitative real-time polymerase chain reaction. Moreover, legumain (Lgmn) expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction in the cardiac tissues of patients with ischemic cardiomyopathy and healthy control subjects. We identified Lgmn as a gene specifically expressed by cardiac resident macrophages. Lgmn deficiency resulted in a considerable exacerbation in cardiac function, accompanied by the accumulation of apoptotic cardiomyocytes and a reduced index of in vivo efferocytosis in the border area. It also led to decreased cytosolic calcium attributable to defective intracellular calcium mobilization. Furthermore, the formation of LC3-II-dependent phagosome around secondary-encountered apoptotic cardiomyocytes was disabled. In addition, Lgmn deficiency increased infiltration of MHC-IIhigh CCR2+ macrophages and the enhanced recruitment of MHC-IIlow CCR2+ monocytes with downregulation of the anti-inflammatory mediators, interleukin-10, and transforming growth factor-β and upregulationof the proinflammatory mediators interleukin-1β, tumor necrosis factor-α, interleukin-6, and interferon-γ. Our results directly link efferocytosis to wound healing in the heart and identify Lgmn as a significant link between acute inflammation resolution and organ function.
Blood Biomarkers May Have Found a New Frontier in Spaceflight—Reply
Authors: Peter zu Eulenburg
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Humoral immune-response to a SARS-CoV-2-BNT162b2 booster in inflammatory arthritis patients who received an inactivated virus vaccine
Authors: Josefina Durán, Paula Isabel Burgos, Nicole Le Corre, Cinthya Ruiz Tagle, Constanza Martinez-Valdebenito, Mauricio Castro, Valentina Metcalfe, Paula Niemann, M Elvira Balcells
Journal: Annals of the Rheumatic Diseases (2022)
Transcatheter Mitral Valve Edge-to-Edge Repair Versus Transapical Mitral Valve Replacement in Patients With LV Dysfunction
Authors: Sara L. Hungerford, Nicole K. Bart, Ning Song, Paul Jansz, Gry Dahle, Alison Duncan, Christopher Hayward, David W.M. Muller
Journal: JACC. Cardiovascular imaging (2022)
JHEP at a glance (May 2022)
Authors: Olivier Govaere, Kragh Petersen, Nuria Martinez-Lopez, Quentin Anstee, Matthias Trost, Anetta Härtlova, Jerome Boursier, Hannes Hagström, Mattias Ekstedt, Jeremie Riou, Aldo Trylesinski, Manuel Romero-Gomez, Fanny Petermann-Rocha, Stuart Gray, Ewan Forrest, Carlos Celis-Morales, Frederick Ho, Jill Pell, Brian Lee, Giuseppe Cullaro, Aidan Vosooghi, David Goldberg, Norah Terrault, Nadim Mahmud
Journal: Journal of Hepatology (2022)
Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years
Authors: Nicklas Brustad, Sina Yousef, Jakob Stokholm, Klaus Bønnelykke, Hans Bisgaard, Bo Lund Chawes
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described. <h3>Objective</h3> To systematically assess the risk of adverse events after high-dose supplementation with vitamin D reported in published randomized clinical trials. <h3>Data Sources</h3> PubMed and ClinicalTrials.gov were searched through August 24, 2021. <h3>Study Selection</h3> Randomized clinical trials of high-dose vitamin D supplementation in children aged 0 to 6 years, defined as greater than 1000 IU/d for infants (aged 0-1 year) and greater than 2000 IU/d for children aged 1 to 6 years. <h3>Data Extraction and Synthesis</h3> Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 reviewers independently extracted the data from the eligible studies. Summary risk ratio (RR), 95% CI, and<i>P</i>values were derived from random-effects meta-analysis. <h3>Main Outcomes and Measures</h3> Adverse events, serious adverse events (SAEs), and/or levels of 25-hydroxyvitamin D, calcium, alkaline phosphatase, phosphate, parathyroid hormone, and/or the ratio of urine calcium to creatinine levels. <h3>Results</h3> A total of 32 randomized clinical trials with 8400 unique participants were included. Different clinical outcomes of children receiving high-dose vitamin D supplements ranging from 1200 to 10 000 IU/d and bolus doses from 30 000 IU/week to a single dose of 600 000 IU were evaluated. Eight studies with 4612 participants were eligible for meta-analysis using a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo when investigating the risk of SAEs such as hospitalization or death. No overall increased risk of SAEs in the high-dose vitamin D vs control groups was found (RR, 1.01 [95% CI, 0.73-1.39];<i>P</i> = .89,<i>I</i><sup>2</sup> = 0%). In addition, risk of hypercalcemia (n = 726) was not increased (RR, 1.18 [95% CI, 0.72-1.93];<i>P</i> = .51). Clinical adverse events potentially related to the vitamin D supplementation reported in the studies were rare. <h3>Conclusions and Relevance</h3> This meta-analysis and systematic review found that high-dose vitamin D supplementation was not associated with an increased risk of SAEs in children aged 0 to 6 years, and that clinical adverse events potentially related to the supplementation were rare. These findings suggest that vitamin D supplementation in the dose ranges of 1200 to 10 000 IU/d and bolus doses to 600 000 IU to young children may be well tolerated.