tbuckley/cabot-search huggingface dataset:
No-deal Brexit may worsen drug shortages, pharmacists warn
Authors: Abi Rimmer, Gareth Iacobucci, Elisabeth Mahase
Journal: BMJ (2019)

The Royal Pharmaceutical Society has expressed concern about drug shortages in a no-deal Brexit despite the government’s “multi-layered approach” to mitigate risks.

Documents compiled this month by the Cabinet Office under the codename Operation Yellowhammer, which were leaked to the Sunday Times on 18 August, set out the likely effect of Britain leaving the European Union without a deal.12

They said that, because three quarters of medicines come to the UK through the main Channel crossing between the UK and France—where disruption is expected to last as long as six months after a no-deal Brexit—these medicines were particularly vulnerable to severe delays.

“While some products can be stockpiled, others cannot because of short shelf lives. It will not be practical to stockpile six months’ supplies,” the documents said.

They added that the Department for Health and Social Care was developing …
New biological treatments for asthma and skin allergies
Authors: Stefanie Eyerich, Martin Metz, Apostolos Bossios, Kilian Eyerich
Journal: Allergy (2019)

Abstract Allergies are typically endemic, complex and heterogeneous diseases with a high impact at quality of life. Mechanistically, type 2 immune responses involving eosinophil and basophil granulocytes, mast cells and humoral factors such as IgE are key drivers of allergic diseases. Fighting allergic diseases knows three strategies: prevention, symptomatic and causative therapy. While remarkable progress was made in understanding molecular events in allergies as a prerequisite for effective prevention and desensitization, this review article focuses on the most efficient symptomatic treatments—that is using more and more specific antibodies neutralizing particular immune pathways. We highlight and classify recent and upcoming developments in the three prototype chronic allergic diseases allergic asthma, chronic spontaneous urticaria and atopic eczema. In all three examples, biologics such as dupilumab or omalizumab become reliable and efficient therapeutic options. Finally, we give an outlook how a diagnostic and therapeutic workflow might look like in the near future for these three major burdens of society.
Type 1 Diabetes Advances Could Pave Way for Prevention
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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
Gut microbiota and osteoarthritis management: An expert consensus of the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO)
Authors: Emmanuel Biver, Francis Berenbaum, Ana M. Valdes, Islene Araujo de Carvalho, Laure B. Bindels, Maria Luisa Brandi, Philip C. Calder, Vincenzo Castronovo, Etienne Cavalier, Antonio Cherubini, Cyrus Cooper, Elaine Dennison, Claudio Franceschi, Nicholas Fuggle, Andrea Laslop, Pierre Miossec, Thierry Thomas, Sansin Tuzun, Nicola Veronese, Mila Vlaskovska, Jean-Yves Reginster, René Rizzoli
Journal: Ageing Research Reviews (2019)

The prevalence of osteoarthritis (OA) increases not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and diets low in fiber and rich in sugar and saturated fats, which promote chronic low-grade inflammation and obesity. Adverse alterations of the gut microbiota (GMB) composition, called microbial dysbiosis, may favor metabolic syndrome and inflammaging, two important components of OA onset and evolution. Considering the burden of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA, an expert working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) to review the potential contribution of GMB to OA. Such a contribution is supported by observational or dietary intervention studies in animal models of OA and in humans. In addition, several well-recognized risk factors of OA interact with GMB. Lastly, GMB is a critical determinant of drug metabolism and bioavailability and may influence the response to OA medications. Further research targeting GMB or its metabolites is needed to move the field of OA from symptomatic management to individualized interventions targeting its pathogenesis.
Dysregulated balance of lung macrophage populations in idiopathic pulmonary fibrosis revealed by single-cell RNA seq: an unstable “ménage-à-trois”
Authors: Bernard Mari, Bruno Crestani
Journal: European Respiratory Journal (2019)

<b>Using single-cell RNA sequencing, Morse and co-workers have identified profound modifications within pulmonary macrophage populations during the course of idiopathic pulmonary fibrosis and propose a new therapeutic strategy against this deadly disease</b>http://bit.ly/30Hb0Gl
Keeping silent at GMC hearings could draw “adverse inferences,” says High Court
Authors: Clare Dyer
Journal: BMJ (2019)

A longstanding belief that doctors could safely remain silent at medical practitioners tribunal hearings and that the panel would not draw negative conclusions from their decision not to give evidence has been overturned by the High Court.

The court has ruled for the first time that there is no “right to silence” at tribunals and that panels are free to draw “adverse inferences” from the fact that a doctor declines to give evidence.1

Barrister Christopher Geering, writing on the website of 2 Hare Court chambers, described it as “a dramatic new development.” Solicitors Claire Raftery and Chris Dunn of the law firm Clyde & Co wrote in a blog, “This will have immediate implications for …
Antibody targeting tumor-derived soluble NKG2D ligand sMIC provides dual co-stimulation of CD8 T cells and enables sMIC+ tumors respond to PD1/PD-L1 blockade therapy
Authors: Jinyu Zhang, Pablo Saenz-lopez Larrocha, Bin Zhang, Derek Wainwright, Payal Dhar, Jennifer D. Wu
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Insufficient co-stimulation accounts for a great deal of the suboptimal activation of cytotoxic CD8 T cells (CTLs) and presumably unsatisfactory clinical expectation of PD1/PD-L1 therapy. Tumor-derived soluble NKG2D ligands are associated with poor clinical response to PD1/PD-L1 blockade therapy in cancer patients. One of the mostly occurring tumor-derived soluble NKG2D ligands, the soluble MHC I chain related molecule (sMIC) can impair co-stimulation to CD8 T cells. We investigated whether co-targeting sMIC can provide optimal co-stimulation to CTLs and enhance the therapeutic effect of PD1/PD-L1 blockades. <h3>Methods</h3> Single agent therapy of a PD1/PD-L1 blockade antibody or a sMIC-targeting non-blocking antibody or a combination therapy of the two antibodies were implied to well-characterized pre-clinical MIC/sMIC<sup>+</sup> tumor models that closely resemble the NKG2D-mediated oncoimmune dynamics of MIC<sup>+</sup> cancer patients. Therapeutic efficacy and associated effector mechanisms were evaluated. <h3>Results</h3> We show that antibody co-targeting sMIC enables or enhances the response of sMIC<sup>+</sup> tumors to PD1/PD-L1 blockade therapy. The therapy response of the combination therapy was associated with enhanced antigen-specific CD8 T cell enrichment and function in tumors. We show that co-targeting sMIC with a nonblocking antibody provides antigen-specific CD8 T cells with NKG2D and CD28 dual co-stimulation, in addition to elimination of inhibitory signals, and thus amplifies antigen-specific CD8 T cell anti-tumor responses. <h3>Conclusion</h3> Our findings provide the proof-of-concept rationale and previously undiscovered mechanisms for co-targeting sMIC to enable and enhance the response to PD1/PD-L1 blockade therapy in sMIC<sup>+</sup> cancer patients.
Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake
Authors: Alice E. Adriaenssens, Emma K. Biggs, Tamana Darwish, John Tadross, Tanmay Sukthankar, Milind Girish, Joseph Polex-Wolf, Brain Y. Lam, Ilona Zvetkova, Warren Pan, Davide Chiarugi, Giles S.H. Yeo, Clemence Blouet, Fiona M. Gribble, Frank Reimann
Journal: Cell Metabolism (2019)
gFACs: Gene Filtering, Analysis, and Conversion to Unify Genome Annotations Across Alignment and Gene Prediction Frameworks
Authors: Madison Caballero, Jill Wegrzyn
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Published genomes frequently contain erroneous gene models that represent issues associated with identification of open reading frames, start sites, splice sites, and related structural features. The source of these inconsistencies is often traced back to integration across text file formats designed to describe long read alignments and predicted gene structures. In addition, the majority of gene prediction frameworks do not provide robust downstream filtering to remove problematic gene annotations, nor do they represent these annotations in a format consistent with current file standards. These frameworks also lack consideration for functional attributes, such as the presence or absence of protein domains that can be used for gene model validation. To provide oversight to the increasing number of published genome annotations, we present a software package, the Gene Filtering, Analysis, and Conversion (gFACs), to filter, analyze, and convert predicted gene models and alignments. The software operates across a wide range of alignment, analysis, and gene prediction files with a flexible framework for defining gene models with reliable structural and functional attributes. gFACs supports common downstream applications, including genome browsers, and generates extensive details on the filtering process, including distributions that can be visualized to further assess the proposed gene space. gFACs is freely available and implemented in Perl with support from BioPerl libraries at https://gitlab.com/PlantGenomicsLab/gFACs.
Variation in Colonoscopy Performance Measures According to Procedure Indication
Authors: Carolina Mangas-Sanjuan, Enrique Santana, Joaquín Cubiella, Elena Rodríguez-Camacho, Agustín Seoane, Marco Antonio Alvarez-Gonzalez, Adolfo Suárez, Verónica Álvarez-García, Natalia González, Alberto Luè, Lucía Cid-Gomez, Marta Ponce, Luis Bujanda, Isabel Portillo, María Pellisé, Pilar Díez-Redondo, Maite Herráiz, Akiko Ono, Ángeles Pizarro, Pedro Zapater, Rodrigo Jover, Rodrigo Jover, Carolina Mangas-Sanjuan, Enrique Santana, Juan A. Casellas, Francisco A. Ruíz-Gómez, Eva Serrano, Cristina Mira, Adolfo Suárez, Verónica Álvarez-García, Olegario Castaño, Lorena Blanco, Natalia González, Javier Lara, Enrique Quintero, H. Clínic, María Pellisé, Liseth Rivero, Josep Llach, Henry Cordova, Isis Araujo, Ariadna Sánchez, Ingrid Ordas, Karina Lisette, H. del Mar, Agustín Seoane, Marco Antonio Álvarez-González, Laura Carot, Inés Ana Ibáñez, Faust Riu, Miguel Pantaleón, Josep María Dedeu, Luis Eugenio Barranco, Akiko Ono, Joaquín Cubiella, Elena Rodríguez-Camacho, Franco Baiocchi, Coral Tejido, Luis Bujanda, Isabel Portillo, Isabel Idígoras, Isabel Bilbao, Maite Herráiz, Cristina Carretero, Maite Betés, Ángeles Pizarro, Marta Ponce, Marco Bustamante, Vicente Pons, Lidia Argüello, Carla Satorres, Pilar Díez-Redondo, Henar Núñez, Victoria Busto, Lucía Cid-Gómez, Vicent Hernández, Luisa de Castro, Nereida Fernández-Fernández, Alfonso Martínez-Turnes, Beatriz Romero-Mosquera, Romina Fernández-Poceiro, Alberto Lué, Ángel Lanas, Angel Ferrández, Pilar Roncales
Journal: Clinical Gastroenterology and Hepatology (2019)
Treating Hypercholesterolemia in Older Adults—Reply
Authors: Neil Skolnik
Journal: JAMA (2019)

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
Translating clinical trial results into personalized recommendations by considering multiple outcomes and subjective views
Authors: Noa Dagan, Chandra J. Cohen-Stavi, Meytal Avgil Tsadok, Morton Leibowitz, Moshe Hoshen, Tomas Karpati, Amichay Akriv, Ilan Gofer, Harel Gilutz, Eduardo Podjarny, Eitan Bachmat, Ran D. Balicer
Journal: npj Digital Medicine (2019)

Currently, clinicians rely mostly on population-level treatment effects from RCTs, usually considering the treatment's benefits. This study proposes a process, focused on practical usability, for translating RCT data into personalized treatment recommendations that weighs benefits against harms and integrates subjective perceptions of relative severity. Intensive blood pressure treatment (IBPT) was selected as the test case to demonstrate the suggested process, which was divided into three phases: (1) Prediction models were developed using the Systolic Blood-Pressure Intervention Trial (SPRINT) data for benefits and adverse events of IBPT. The models were externally validated using retrospective Clalit Health Services (CHS) data; (2) Predicted risk reductions and increases from these models were used to create a yes/no IBPT recommendation by calculating a severity-weighted benefit-to-harm ratio; (3) Analysis outputs were summarized in a decision support tool. Based on the individual benefit-to-harm ratios, 62 and 84% of the SPRINT and CHS populations, respectively, would theoretically be recommended IBPT. The original SPRINT trial results of significant decrease in cardiovascular outcomes following IBPT persisted only in the group that received a "yes-treatment" recommendation by the suggested process, while the rate of serious adverse events was slightly higher in the "no-treatment" recommendation group. This process can be used to translate RCT data into individualized recommendations by identifying patients for whom the treatment's benefits outweigh the harms, while considering subjective views of perceived severity of the different outcomes. The proposed approach emphasizes clinical practicality by mimicking physicians' clinical decision-making process and integrating all recommendation outputs into a usable decision support tool.
Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features
Authors: Joyce E. Karlinsey, Taylor A. Stepien, Matthew Mayho, Larissa A. Singletary, Lacey K. Bingham-Ramos, Michael A. Brehm, Dale L. Greiner, Leonard D. Shultz, Larry A. Gallagher, Matt Bawn, Robert A. Kingsley, Stephen J. Libby, Ferric C. Fang
Journal: Cell Host & Microbe (2019)
Abstract 15138: GWAS Identifies GPC6 as a Novel Predictor of Arrhythmia in Heart Failure
Authors: Haider Mehdi, Ryan L Boudreau, Rebecca Gutmann, Patrick Breheny, Gina M Morgan, Alexander M Greiner, Heather L Bloom, Alaa Shalaby, Raul Weiss, Samuel C Dudley, Samir Saba, Dennis M McNamara, Madhurmeet Singh, Steven A Lubitz, Patrick T Ellinor, Barry London
Journal: Circulation (2017)

Background: Arrhythmias and sudden cardiac death (SCD) remain a major cause of mortality in heart failure (HF) patients. A prior genome-wide association study (GWAS) and candidate gene studies have...
Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma
Authors: Ajai Chari, Dan T. Vogl, Maria Gavriatopoulou, Ajay K. Nooka, Andrew J. Yee, Carol A. Huff, Philippe Moreau, David Dingli, Craig Cole, Sagar Lonial, Meletios Dimopoulos, A. Keith Stewart, Joshua Richter, Ravi Vij, Sascha Tuchman, Marc S. Raab, Katja C. Weisel, Michel Delforge, Robert F. Cornell, David Kaminetzky, James E. Hoffman, Luciano J. Costa, Terri L. Parker, Moshe Levy, Martin Schreder, Nathalie Meuleman, Laurent Frenzel, Mohamad Mohty, Sylvain Choquet, Gary Schiller, Raymond L. Comenzo, Monika Engelhardt, Thomas Illmer, Philip Vlummens, Chantal Doyen, Thierry Facon, Lionel Karlin, Aurore Perrot, Klaus Podar, Michael G. Kauffman, Sharon Shacham, Lingling Li, Shijie Tang, Carla Picklesimer, Jean-Richard Saint-Martin, Marsha Crochiere, Hua Chang, Samir Parekh, Yosef Landesman, Jatin Shah, Paul G. Richardson, Sundar Jagannath
Journal: New England Journal of Medicine (2019)

Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point.A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients.Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).
Lumen-apposing metal stent creating jejuno-jejunostomy for blind pouch syndrome in patients with esophago-jejunostomy after gastrectomy: a novel technique
Authors: Helwig V. Wundsam, Viktoria Kertesz, Franziska Bräuer, Ines Fischer, Johannes Zacherl, Reinhold Függer, Georg O. Spaun
Journal: Endoscopy (2019)

Blind pouch syndrome is characterized by a vicious circle of incomplete pouch clearance and subsequent dilation of the jejunal blind pouch segment in patients with esophago-jejunostomy after total gastrectomy. It manifests as regurgitation, diarrhea, and weight loss. As patients mostly present in a weak general condition and poor nutritional state, surgical revision [1] [2] is not always possible.
Dynamic CD138 surface expression regulates switch between myeloma growth and dissemination
Authors: Ilseyar Akhmetzyanova, Mark J. McCarron, Samir Parekh, Marta Chesi, P. Leif Bergsagel, David R. Fooksman
Journal: Leukemia (2019)

Abstract The canonical plasma cell marker CD138 (syndecan-1) is highly expressed on the myeloma cell surface, but its functional role in vivo is unclear, as well as the ontogeny of CD138-high and CD138-negative (neg) myeloma cells. In this study we used an in vivo murine Vk*MYC myeloma model where CD138 is heterogeneously expressed depending on tumor size. We find that in comparison to CD138-neg myeloma cells, the CD138-high subset of myeloma cells is highly proliferative, less apoptotic, and enhanced IL-6R signaling, which is known to promote survival. In addition CD138-high myeloma engrafts better than its CD138-neg counterpart. In contrast, CD138-neg cells are more motile both in vitro and in vivo, and more readily disseminate and spread to other bones in vivo than CD138-high subset. Neutralizing CD138 rapidly triggers migration of myeloma cells in vivo and leads to intravasation, which results in increased dissemination to other bones. Both murine and human myeloma cells can rapidly recycle CD138 surface expression through endocytic trafficking, in response to serum levels. Blocking CD138 enhances myeloma sensitivity to bortezomib chemotherapy and significantly reduces tumor size compared to bortezomib treatment alone. Thus, our data show that CD138 surface expression dynamically regulates a switch between growth vs. dissemination for myeloma, in response to nutrient conditions.
Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment
Authors: Xinyu Tian, Han Shen, Zhiyang Li, Tingting Wang, Shengjun Wang
Journal: Journal of Hematology & Oncology (2019)

Plenty of immune cells infiltrate into the tumor microenvironment (TME) during tumor progression, in which myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with immunosuppressive activity. Tumor cells and stromal cells facilitate the activation and expansion of MDSCs in TME via intercellular communication, and expanded MDSCs suppress anti-tumor immune responses through direct and indirect mechanisms. Currently, exosomes, which are a kind of extracellular vesicles (EVs) that can convey functional components, are demonstrated to participate in the local and distal intercellular communication between cells. Numerous studies have supposed that tumor-derived exosomes (TEXs), whose assembly and release can be modulated by TME, are capable of modulating the cell biology of MDSCs, including facilitating their activation, promoting the expansion, and enhancing the immunosuppressive function. Therefore, in this review, we mainly focus on the role of TEXs in the cell-cell communication between tumor cells and MDSCs, and discuss their clinical applications.