tbuckley/cabot-search huggingface dataset:
Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I
Authors: K.N. Moore, A.M. Oza, N. Colombo, A. Oaknin, G. Scambia, D. Lorusso, G.E. Konecny, S. Banerjee, C.G. Murphy, J.L. Tanyi, H. Hirte, J.A. Konner, P.C. Lim, M. Prasad-Hayes, B.J. Monk, P. Pautier, J. Wang, A. Berkenblit, I. Vergote, M.J. Birrer
Journal: Annals of Oncology (2021)

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population.A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.
Blood Transcriptomics Predicts Progression of Pulmonary Fibrosis and Associated Natural Killer Cells
Authors: Yong Huang, Justin M. Oldham, Shwu-Fan Ma, Avraham Unterman, Shu-Yi Liao, Andrew J. Barros, Catherine A. Bonham, John S. Kim, Rekha Vij, Ayodeji Adegunsoye, Mary E. Strek, Philip L. Molyneaux, Toby M. Maher, Jose D. Herazo-Maya, Naftali Kaminski, Bethany B. Moore, Fernando J. Martinez, Imre Noth
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Disease activity in idiopathic pulmonary fibrosis (IPF) remains highly variable, poorly understood, and difficult to predict. Objectives: To identify a predictor using short-term longitudinal changes in gene expression that forecasts future FVC decline and to characterize involved pathways and cell types. Methods: Seventy-four patients from COMET (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in IPF) cohort were dichotomized as progressors (≥10% FVC decline) or stable. Blood gene-expression changes within individuals were calculated between baseline and 4 months and regressed with future FVC status, allowing determination of expression variations, sample size, and statistical power. Pathway analyses were conducted to predict downstream effects and identify new targets. An FVC predictor for progression was constructed in COMET and validated using independent cohorts. Peripheral blood mononuclear single-cell RNA-sequencing data from healthy control subjects were used as references to characterize cell type compositions from bulk peripheral blood mononuclear RNA-sequencing data that were associated with FVC decline. Measurements and Main Results: The longitudinal model reduced gene-expression variations within stable and progressor groups, resulting in increased statistical power when compared with a cross-sectional model. The FVC predictor for progression anticipated patients with future FVC decline with 78% sensitivity and 86% specificity across independent IPF cohorts. Pattern recognition receptor pathways and mTOR pathways were downregulated and upregulated, respectively. Cellular deconvolution using single-cell RNA-sequencing data identified natural killer cells as significantly correlated with progression. Conclusions: Serial transcriptomic change predicts future FVC decline. An analysis of cell types involved in the progressor signature supports the novel involvement of natural killer cells in IPF progression.
Government faces legal action over £23m deal involving patient data
Authors: Clare Dyer
Journal: BMJ (2021)

NHS England is facing a legal challenge against its decision to award a two year £23m (€27m; $32m) contract in December to the US data mining firm Palantir Technologies.

The independent media platform openDemocracy, which is bringing the legal action, claims that NHS England failed to carry out the required data protection impact assessment to ensure that health information was adequately protected before awarding the contract to build a software platform to handle patient data.1

The case is the latest challenge to the handling of contracts involving millions of dollars of taxpayers’ money during the pandemic. The High …
Pro-osteogenesis and in vivo tracking investigation of a dental implantation system comprising novel mTi implant and HYH-Fe particles
Authors: Xiyu Li, Juan Wu, Danxue Li, Qin Zou, Yi Man, Ling Zou, Wei Li
Journal: Bioactive Materials (2021)

Insufficient early osteogenesis seriously affects the later stage osteogenic quality and osseointegration of dental implants. To promote early osteogenesis, we first designed a Ti dental implant with a built-in magnet (mTi) to produce a local static magnetic field (SMF). Then, a dental implantation system comprising the mTi implant and the superparamagnetic hydroxyapatite (HA:Yb/Ho–Fe, named HYH-Fe) particles was implanted into the alveolar bone of beagles. The results showed that the mTi + HYH-Fe group displayed better early osteogenesis and later stage osseointegration than the Ti + HA and mTi + HA groups. A combination of the local SMF (mTi) and superparamagnetic HYH-Fe particles had a positive effect on the pro-osteogenesis of Ti implants. The results also indicated that week 10 could be adopted as the key time point to evaluate the early osteogenic effect of the mTi + HYH-Fe implantation system, which would be a promising prospect for promotion of osteogenesis, in vivo tracking investigation of material-bone relationships, and clinical applications.
Abstract 12862: Prevalence and Outcomes Associated With Advanced Respiratory Support in Contemporary Cardiac Intensive Care Units: A Critical Care Cardiology Trials Network (CCCTN) Registry Study
Authors: Thomas S Metkus, Khalil Ibrahim, Jason N Katz, Erin A Bohula, Jeong-Gun Park, Sean F van Diepen, Steven P Schulman, David A Morrow
Journal: Circulation (2019)

Introduction: The illness severity of patients in the modern cardiac intensive care units (CICUs) is increasing, yet little is known about the epidemiology and outcomes of respiratory failure in th...
THE TREATMENT OF ASIATIC CHOLERA.
Authors: Elmer Lee
Journal: JAMA (1893)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Human reading versus computer-automated reading of chest radiographs in a tuberculosis screening programme in Romania
Authors: Gerard de Vries, Dan Gainaru, Sytze Keizer, Beatrice Mahler, Ileana Radulescu, Marina Zamfirescu, Ibrahim Abubakar
Journal: European Respiratory Journal (2021)

<b>Automated reading of chest radiographs in a tuberculosis screening programme can reduce human reading to less than 20% of the chest radiographs, avoiding unnecessary TB examinations while maintaining high sensitivity</b>https://bit.ly/3kCFWmq
NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 2.2021
Authors: David S. Ettinger, Douglas E. Wood, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Thomas A. D’Amico, Thomas J. Dilling, Jonathan Dowell, Scott Gettinger, Matthew A. Gubens, Aparna Hegde, Mark Hennon, Rudy P. Lackner, Michael Lanuti, Ticiana A. Leal, Jules Lin, Billy W. Loo Jr, Christine M. Lovly, Renato G. Martins, Erminia Massarelli, Daniel Morgensztern, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Aditi P. Singh, James Stevenson, Alda Tam, Jane Yanagawa, Stephen C. Yang, Kristina M. Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
Abstract LT013: Endocrine-exocrine signaling is a driver of obesity-associated pancreatic ductal adenocarcinoma
Authors: Cathy Garcia, Jaffarguriqbal Singh, Lauren Lawres, Sherry Agabiti, Daniel B. Burkhardt, Alexander Tong, Rebecca Cardone, Richard G. Kibbey, Smita Krishnaswamy, Mandar D. Muzumdar
Journal: Cancer Research (2021)

Abstract Obesity is a major modifiable host risk factor for pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer death in the United States and a major cause of morbidity and mortality worldwide. Despite the rapid rise in the prevalence of obesity, surprisingly little is known about how it drives tumor progression. Therefore, deciphering these mechanisms is not only a societal imperative but also represents a key untapped target to develop novel strategies for PDAC prevention and therapy. Motivated by this gap in knowledge, we developed a rapid and reversible autochthonous mouse model of obesity-associated PDAC that recapitulates the genetic and histologic features of the human disease. We showed that obesity accelerates pancreatic tumorigenesis, while genetic or dietary weight loss intercepts tumor development, consistent with a causal and reversible role for obesity in early PDAC progression. By analyzing human and murine biospecimens, we defined obesity-driven microenvironmental alterations that foster tumorigenesis rather than new driver mutations, including significant inflammation, fibrosis, and islet adaptation. Specifically, we identified aberrant pancreatic beta cell expression of the hormone cholecystokinin (CCK) in response to obesity and showed that islet CCK itself promotes oncogenic Kras-driven pancreatic cancer. We further observed that CCK expression and tumor progression correlated with hyperglycemia, beta cell dysfunction, and reduced insulin secretion, suggesting that islet adaptations apart from insulin may drive tumorigenesis in obesity. By performing single-cell RNA-sequencing of islets from genetic and diet-induced obesity models, we have further nominated molecular mechanisms of CCK induction in beta cells and are testing their functional role in PDAC progression. Together, our findings argue that PDAC development is driven by local obesity-associated alterations in the tumor microenvironment, implicate a previously unappreciated endocrine-exocrine signaling axis beyond insulin in this process, and highlight the possibility of targeting the endocrine pancreas as a novel approach to intercept pancreatic exocrine tumorigenesis. Citation Format: Cathy Garcia, Jaffarguriqbal Singh, Lauren Lawres, Sherry Agabiti, Daniel B. Burkhardt, Alexander Tong, Rebecca Cardone, Richard G. Kibbey, Smita Krishnaswamy, Mandar D. Muzumdar. Endocrine-exocrine signaling is a driver of obesity-associated pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT013.
Development of a novel RNAi therapy: Engineered miR-31 exosomes promoted the healing of diabetic wounds
Authors: Jinghuan Huang, Muyu Yu, Wenjing Yin, Bo Liang, Ang Li, Jingfeng Li, Xiaolin Li, Shichang Zhao, Fang Liu
Journal: Bioactive Materials (2021)

Rationale: Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment. Exosome therapy is an extension of stem cell therapy, and RNA interference (RNAi)-based therapy is a type of advanced precision therapy. Based on the discovery of chronic wound-related genes in diabetes, we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds. Methods: We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach. Results: First, chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds, and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro. Second, bioinformatics analysis, luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis, fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1 (HIF1AN, also named FIH) and epithelial membrane protein-1 (EMP-1). Third, engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent. In vivo, the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis, fibrogenesis and reepithelization. Conclusion: Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.
Cellular heterogeneity and plasticity in liver cancer
Authors: Lo-Kong Chan, Yu-Man Tsui, Daniel Wai-Hung Ho, Irene Oi-Lin Ng
Journal: Seminars in Cancer Biology (2021)

Hepatocarcinogenesis involves complex genetic and cellular dysregulations which drive the formation of hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, with extensive heterogeneity. In contrast to the broad spectrum of molecularly driven therapies available for defined patient groups in certain cancer types, unfortunately the treatment options for HCC are highly limited. The lack of representative molecular and cellular signatures in the heterogeneous HCC tumors that can effectively guide the choice of the most appropriate treatment among the patients unavoidably limits the treatment outcome. Advancement and wide availability of the next-generation sequencing technologies have empowered us to examine and capture not only the detailed genetic alterations of the HCC cells but also the precise composition of different cell types within the tumor microenvironment and their interactions with the HCC cells at an unprecedented level. The information generated has provided new insight and better defined the inter-patient intertumoral heterogeneity, intra-patient intratumoral heterogeneity as well as the plasticity of HCC cells. These collectively provide a robust scientific basis in guiding the development and use of targeted therapy and immunotherapy. To complement, liquid biopsy coupled with high-sensitivity sequencing could potentially be adopted as a more practical and safer approach to detect and reflect the tumor heterogeneity in HCC patients in guiding the choice of treatment and monitoring disease progression.
Corrigendum to: “Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort”☆ (J Hepatol [2020] 505–515)
Authors: Quentin M. Anstee, Rebecca Darlay, Simon Cockell, Marica Meroni, Olivier Govaere, Dina Tiniakos, Alastair D. Burt, Pierre Bedossa, Jeremy Palmer, Yang-Lin Liu, Guruprasad P. Aithal, Michael Allison, Hannele Yki-Järvinen, Michele Vacca, Jean-Francois Dufour, Pietro Invernizzi, Daniele Prati, Mattias Ekstedt, Stergios Kechagias, Sven Francque, Salvatore Petta, Elisabetta Bugianesi, Karine Clement, Vlad Ratziu, Jörn M. Schattenberg, Luca Valenti, Christopher P. Day, Heather J. Cordell, Ann K. Daly
Journal: Journal of Hepatology (2021)
DUOX2 variants associate with preclinical disturbances in microbiota-immune homeostasis and increased inflammatory bowel disease risk
Authors: Helmut Grasberger, Andrew T. Magis, Elisa Sheng, Matthew P. Conomos, Min Zhang, Lea S. Garzotto, Guoqing Hou, Shrinivas Bishu, Hiroko Nagao-Kitamoto, Mohamad El-Zaatari, Sho Kitamoto, Nobuhiko Kamada, Ryan W. Stidham, Yasutada Akiba, Jonathan Kaunitz, Yael Haberman, Subra Kugathasan, Lee A. Denson, Gilbert S. Omenn, John Y. Kao
Journal: Journal of Clinical Investigation (2021)

A primordial gut-epithelial innate defense response is the release of hydrogen peroxide by dual NADPH oxidase (DUOX). In inflammatory bowel disease (IBD), a condition characterized by an imbalanced gut microbiota-immune homeostasis, DUOX2 isoenzyme is the highest induced gene. Performing multiomic analyses using 2872 human participants of a wellness program, we detected a substantial burden of rare protein-altering DUOX2 gene variants of unknown physiologic significance. We identified a significant association between these rare loss-of-function variants and increased plasma levels of interleukin-17C, which is induced also in mucosal biopsies of patients with IBD. DUOX2-deficient mice replicated increased IL-17C induction in the intestine, with outlier high Il17c expression linked to the mucosal expansion of specific Proteobacteria pathobionts. Integrated microbiota/host gene expression analyses in patients with IBD corroborated IL-17C as a marker for epithelial activation by gram-negative bacteria. Finally, the impact of DUOX2 variants on IL-17C induction provided a rationale for variant stratification in case control studies that substantiated DUOX2 as an IBD risk gene. Thus, our study identifies an association of deleterious DUOX2 variants with a preclinical hallmark of disturbed microbiota-immune homeostasis that appears to precede the manifestation of IBD.
Attributes and predictors of long COVID
Authors: Carole H. Sudre, Benjamin Murray, Thomas Varsavsky, Mark S. Graham, Rose S. Penfold, Ruth C. Bowyer, Joan Capdevila Pujol, Kerstin Klaser, Michela Antonelli, Liane S. Canas, Erika Molteni, Marc Modat, M. Jorge Cardoso, Anna May, Sajaysurya Ganesh, Richard Davies, Long H. Nguyen, David A. Drew, Christina M. Astley, Amit D. Joshi, Jordi Merino, Neli Tsereteli, Tove Fall, Maria F. Gomez, Emma L. Duncan, Cristina Menni, Frances M. K. Williams, Paul W. Franks, Andrew T. Chan, Jonathan Wolf, Sebastien Ourselin, Tim Spector, Claire J. Steves
Journal: Nature Medicine (2021)
Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel
Authors: Lu Qin, Haiyang Wu, Enyu Xu, Xin Zhang, Jian Guan, Ruizhi Zhao, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Most biopharmaceutics classification system (BCS) class IV drugs, with poor solubility and inferior permeability, are also substrates of P-glycoprotein (P-gp) and cytochrome P450 (CYP450), leading to their low oral bioavailability. The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles (PLHNs) to enhance the oral absorption of BCS IV drugs. In this paper, taking paclitaxel (PTX) as a drug model, PTX-loaded PLHNs were prepared by a self-assembly method. Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability. Three P-gp inhibitors (D-α-tocopherol polyethylene glycol 1000 succinate, pluronic P123 and SolutolⓇ HS15) were incorporated into selected PLHNs, and a CYP450 inhibitor (the extract of VBRB, BC0) was utilized to jointly promote the drug absorption. Properties of all the PLHNs were characterized systemically, including particle size, zeta potential, encapsulation efficiency, morphology, stability, in vitro drug release, mucoadhesion, in situ intestinal permeability and in vivo systemic exposure. It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested, with absolute bioavailability 21.95%. P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%, 8-fold increase compared with that of PTX itself (4.75%). Taken together, our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption, especially for BCS IV drugs.
Ocular Findings in Infants with Congenital Toxoplasmosis after a Toxoplasmosis Outbreak
Authors: Aline Reetz Conceição, Deisi Nara Belucik, Lilian Missio, Luiz Gustavo Brenner, Matheus Henrique Monteiro, Kleber Silva Ribeiro, Deise Fialho Costa, Maria Clara da Silva Valadão, Alessandra Gonçalves Commodaro, João Rafael de Oliveira Dias, Rubens Belfort
Journal: Ophthalmology (2021)