tbuckley/cabot-search huggingface dataset:
The NCI-nature pathway interaction database: An authoritative collection of human cell signaling pathways
Authors: Kira Anthony, Shiva Krupa, Jeffrey Buchoff, Matthew Day, Timo Hannay, Carl Schaefer
Journal: Cancer Research (2008)

786  With more than 300,000 citations in PubMed containing the search term signal(l)ing, signal transduction represents a vital and ever-growing field of research. The NCI-Nature Pathway Interaction Database (PID, http://pid.nci.nih.gov) is an open access resource of cell signaling information with the goal of comprehensively assemblingpathways in a computationally accessible format from this vast amount of literature. The PID pathways are manually curated and reviewed by experts. They are constructedfrom data in primary research publications and depict the molecular interactions and key biological processes that take place in human cells. Pathways are prioritized for curation based on potential drug targets, recommendations made by expert reviewers and users, and other molecules known to be of interest to the cell signaling community. Users of the PID are provided with the necessary tools to facilitate pathway exploration. They can browse and view the complete set of pathways, create interaction network maps centered on a single molecule of interest, and generate advanced query results incorporating, for example, biological process search terms from the Gene Ontology (GO) or NCI Thesaurus controlled vocabularies. In addition, theBatch query tool allows users to upload extensive list(s) of molecules, such as those derived from microarray experiments, and visualize the resulting molecular connectivitymap. Users can also download molecule lists, citation lists and complete database content in extensible markup language (XML) or Biological Pathways Exchange (BioPAX) Level 2 format. As of November 2007, the database contained 59 pathways, encompassing 3309 molecular interactions, 2035 proteins, 119 small molecules, 1422 complexes and 2152 peer-reviewed publications, thus providing the cell signaling community with a wealth of data for forming novel insights and enabling hypothesis development.
A multitranscript blood neuroendocrine tumor molecular signature to identify treatment efficacy and disease progress.
Authors: Irvin M. Modlin, Ignat Drozdov, Mark S. Kidd
Journal: Journal of Clinical Oncology (2013)

4137 Background: Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) or NETs (also called “carcinoids”) are problematic since they present with advanced disease and have limited treatment options. Imaging has proved to be insensitive in identifying treatment effect. Similarly, the currently used biomarker, a neurosectory peptide, Chromogranin A (CgA) is of limited value as a predictor of treatment efficacy. We have developed a multi-transcript (n=51 genes) molecular signature for PCR-based blood analysis which exhibits a high sensitivity (85-98%), specificity (93-97%), positive predictive value (95-96%) and negative predictive value (87-98%) for the identification of GEP-NENs. This test significantly outperforms (p&lt;0005) plasma CgA (measured by ELISA). Methods: The candidate gene signature was examined by a 2-step PCR method in a training set of 130 blood samples (GEP-NENs: n=63, treatment-naïve (n=28)) and validated in an independent set ([n=182, GEP-NENs: n=133, including complete remission (n=4), clinically stable disease (n=82) and non-responders/clinically progressive disease (n=47). Results: The PCR score was significantly elevated (p&lt;0.0001) in the treatment-naïve group compared to treated GEP-NENs, while levels were significantly reduced (p&lt;0.004) in 11 matched samples (pre- and post-treatment – surgical removal (n=10), RFA (n=1)). In the independent set, the scores for complete remission were not different to controls (0.5±0.25 vs. 0.4±0.16), while scores for stable disease (0.63±0.12) were significantly lower than for non-responders (5.85±0.34, p&lt;0.002). Stable disease could be differentiated from clinically progressive disease since the latter exhibited a high score (85% vs. 10%, p&lt;0.0001). The performance metrics for differentiation were: sensitivity (91%), specificity (91%), PPV (86%), NPV (95%). Conclusions: This study demonstrated that the multi-transcript molecular signature is both sensitive and specific for the detection of neuroendocrine tumor disease and is capable of differentiating clinically stable from progressive disease. It therefore has potential utility as a measure for monitoring treatment efficacy for GEP-NENs.
Immunoproteomics of ticks from two geographical regions reveal IgE reactivity to the same alpha-Gal containing proteins
Authors: D Apostolovic, S Commins, M Starkhammar, J Grunstrom, N Bigdeli, Tanja Cirkovic Velickovic, T Platts-Mills, C Hamsten, M van Hage
Journal: Allergy (2016)
In high-risk type 1 diabetes, insulin pumps with suspend-before-low technology reduced hypoglycemic events
Authors: Omar M. El Kawkgi, Victor M. Montori
Journal: Annals of Internal Medicine (2019)

Source Citation Bosi E, Choudhary P, de Valk HW, et al; SMILE Study Group. Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7:462-72. 31047902
Richard Frank Ciezak
Authors: Dorothy Crowther
Journal: BMJ (2019)

Richard (“Dick”) Frank Ciezak’s parents were Polish; they chose to relocate to the UK at the end of the second world war. His father had fought in the allied army and took part in the D Day landings. Dick was bilingual and was always very proud of his father and of his Polish roots.

He qualified from St Mary’s Hospital Medical School and followed this with vocational training for general practice in Swindon. He joined …
Q fever in Bulgaria: Laboratory and epidemiological findings on human cases and outbreaks, 2011 to 2017
Authors: Petia Genova-Kalou, Nadezhda Vladimirova, Savina Stoitsova, Stefka Krumova, Anna Kurchatova, Todor Kantardjiev
Journal: Eurosurveillance (2019)

Background Q fever is a zoonosis, included in category B of particularly dangerous infectious agents and as such merits careful surveillance and regular updating of the information about its distribution. Aim This observational retrospective study aimed to provide an overview of Q fever incidence in Bulgaria in the period 2011 to 2017. Methods Aggregated surveillance data from Bulgaria’s mandatory surveillance system, laboratory data on individual samples received at the National Reference Laboratory Rickettsiae and Cell Cultures and outbreak reports sent by the regional health authorities to the National Centre of Infectious and Parasitic Diseases, were used in this analysis. Cases were described by year, region, age group and most commonly identified risk behaviours. Results A total of 139 confirmed cases were reported in the study period (average annual incidence: 0.27 cases/100,000 inhabitants). No seasonality or trend in reported cases was observed. Cases were mostly sporadic, with two small outbreaks in 2017. Identified risk behaviours among cases were occupational exposure and consumption of milk and dairy products, although exposure data were incomplete. The male/female ratio was 1.4. The identification and resolution of the two rural outbreaks in 2017 with a total of 18 cases involved good practices: active case finding and collaboration between public health and veterinary authorities. Conclusion Between 2011 and 2017, Bulgaria retained low Q fever incidence, mostly sporadic cases and two small outbreaks. Occupational exposure and consumption of milk and dairy products were the most often reported likely exposures among cases. The outbreak investigations demonstrate the application of good control practices.
Abstract 3072: GFH018, a novel TGF-βRI inhibitor, for the treatment of advanced solid tumors
Authors: Gang Hu, Rong Zhao, Fusheng Zhou, Jiong Lan, Biao Zheng, Qiang LU, Jianyu Lu, Lifang Wu, Fei Sun, Lihong Hu, Shuhua Han, Haijun Tong, Yuanfeng Xia, Wei Li, Liping Ma, Ying Chen, Charles Ding, Chichung Chan, Shuhui Chen
Journal: Cancer Research (2019)

Abstract Background: The transforming growth factor-β (TGF-β) signaling pathway has been shown to play an important role in various cellular processes including growth inhibition, cell migration, tumor invasion, epithelial-mesenchymal transition, and immune-suppression. TGF-βs are often overexpressed in various types of cancers, and the anti-TGF-β therapy has been pursued intensively for cancer treatment. Results: GFH018 is a potent, selective inhibitor of TGF-βRI with a kinase inhibition activity IC50 of 70.5 nM. Our studies demonstrated that GFH018 could inhibit TGF-β-induced SMAD phosphorylation and migration of tumor cells. GFH018 is a potent immune regulator in that it could inhibit in vitro Treg cell induction and reverse M2 phenotype to M1, leading to increased pro-inflammatory cytokine production. In addition, GFH018 exhibited a significant inhibitory effect on in vitro angiogenesis formation assay. Importantly, GFH018 has shown promising anti-tumor efficacy in multiple in vivo mouse syngeneic models as a monotherapy as well as in combination with an anti-PD-(L)1 antibody. Following oral administration, GFH018 demonstrated fast absorption, and high oral bioavailability in preclinical animal species including mouse, rat, and dog. Results from the toxicology studies in rat and dog have also supported further development of GFH018. Conclusion: GFH018 has the potential to be developed as a monotherapy or combinational therapy with checkpoint inhibitors for advanced solid tumor patients. The first-in-human clinical trial is scheduled in 2019. Citation Format: Gang Hu, Rong Zhao, Fusheng Zhou, Jiong Lan, Biao Zheng, Qiang LU, Jianyu Lu, Lifang Wu, Fei Sun, Lihong Hu, Shuhua Han, Haijun Tong, Yuanfeng Xia, Wei Li, Liping Ma, Ying Chen, Charles Ding, Chichung Chan, Shuhui Chen. GFH018, a novel TGF-βRI inhibitor, for the treatment of advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3072.
Michael Harrison: clinical neurologist and stroke researcher
Authors: Matthew Limb
Journal: BMJ (2019)

Neurologist Michael Harrison is best known for his research into stroke and the neurological complications of HIV/AIDS. He is a former director of the Reta Lila Weston Institute for Neurological Studies at the Middlesex Hospital in London.

Aside from his academic achievements, he was also regarded as “one of the best clinical neurologists of his generation,” says Hadi Manji, who was his houseman at the Middlesex in 1982 and later HIV research registrar.

Another former colleague, Andrew Lees, professor of neurology at the National Hospital for Neurology and Neurosurgery, at Queen Square, London, says: “What is remarkable in looking back over his contributions to neurology is the breadth of his curiosity in an era of increasing specialisation, and his determination to maintain his physician status. He was an inspirational teacher for both medical students and his junior staff.”

Harrison produced numerous “clinically relevant” papers on cerebrovascular disease in the 1970s and was one of the first doctors to investigate the effects of aspirin in reducing transient ischaemic attacks. He was the epitome of the “physician neurologist”—now viewed as something of a rare breed—and conscious of the importance of preserving neurology’s links with general medicine.

He won an open scholarship to Magdalen College, Oxford, from where he graduated with …
Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges
Authors: Richard A. Bryant
Journal: World Psychiatry (2019)

Post‐traumatic stress disorder (PTSD) is arguably the most common psychiatric disorder to arise after exposure to a traumatic event. Since its formal introduction in the DSM‐III in 1980, knowledge has grown significantly regarding its causes, maintaining mechanisms and treatments. Despite this increased understanding, however, the actual definition of the disorder remains controversial. The DSM‐5 and ICD‐11 define the disorder differently, reflecting disagreements in the field about whether the construct of PTSD should encompass a broad array of psychological manifestations that arise after trauma or should be focused more specifically on trauma memory phenomena. This controversy over clarifying the phenotype of PTSD has limited the capacity to identify biomarkers and specific mechanisms of traumatic stress. This review provides an up‐to‐date outline of the current definitions of PTSD, its known prevalence and risk factors, the main models to explain the disorder, and evidence‐supported treatments. A major conclusion is that, although trauma‐focused cognitive behavior therapy is the best‐validated treatment for PTSD, it has stagnated over recent decades, and only two‐thirds of PTSD patients respond adequately to this intervention. Moreover, most people with PTSD do not access evidence‐based treatment, and this situation is much worse in low‐ and middle‐income countries. Identifying processes that can overcome these major barriers to better management of people with PTSD remains an outstanding challenge.
Blood Pressure Control and Stroke or Bleeding Risk in Patients with Atrial Fibrillation: Results from the ROCKET AF Trial
Authors: Sreekanth Vemulapalli, Anne S. Hellkamp, W. Schuyler Jones, Jonathan P. Piccini, Kenneth W. Mahaffey, Richard C. Becker, Graeme J. Hankey, Scott D. Berkowitz, Guenter Breithardt, Daniel E. Singer, Keith A. Fox, Robert M. Califf, Manesh R. Patel
Journal: Circulation (2014)
A Trans-amplifying RNA Vaccine Strategy for Induction of Potent Protective Immunity
Authors: Tim Beissert, Mario Perkovic, Annette Vogel, Stephanie Erbar, Kerstin C. Walzer, Tina Hempel, Silke Brill, Erik Haefner, René Becker, Özlem Türeci, Ugur Sahin
Journal: Molecular Therapy (2019)
Prognostic significance of presence of any mucinous component in curatively resected stage II and III colorectal cancer patients who received adjuvant treatments: Data from a single tertiary center.
Authors: Faysal Dane, Mehmet Akif Ozturk, Perran Fulden Yumuk, Muharrem Kocar, Mehmet Besiroglu, Beste Melek Atasoy, Ferhat Telli, Metin Kanitez, Bilge Aktas, Nazim S. Turhal
Journal: Journal of Clinical Oncology (2013)

e14660 Background: Mucinous adenocarcinoma colorectal cancer (CRC) is defined as presence of more than 50% mucinous component and its prognostic significance is debatable. We analyzed the prognostic importance of positivity of any mucinous component in early stage adenocarcinoma patients who were operated and received adjuvant treatments in a single tertiary cancer center. Methods: Data from charts of early stage CRC patients curatively treated between January 1998-December 2009 in our clinic was retrospectively analyzed. Cases with any degree of mucine presence in final pathology reports were noted (including mucinous adenocarcinomas). Adjuvant treatments were either 5-FU or oxaliplatin based regimens. All rectal carcinoma patients received postoperative radiotherapy. Survival analyses were made by Kaplan-Meier estimator, and independent factors of survival were tested with Cox regression test. Survival data of subgroups were compared with log-rank test. Results: 532 patients (45% female) were analyzed. Median follow-up was 36 months. Median age at diagnosis was 62 years (24-84). Fifty-four percent of patients had rectal primary (n=292). Presence of any mucinous component was found in 94 patients (17.7%). There was a close relation between mucine presence and T stage (p=0.0001) or tumor grade (p=0.0001). There was no statistical relation between presence of mucine and lymphatic invasion, vascular invasion, or perineural invasion. Five-year disease-free survival for mucine (+) and mucine (-) tumors were, 45.7% and 61.4%, respectively (p=0.031). Five -year overall survival of mucine (+) tumors was worse than mucine (-) tumors (65% vs. 74%, p=0.004). Conclusions: Presence of any mucinous component in early stage CRC appears to be an important bad prognostic feature in our patient group, which was not previously reported in the literature to our knowledge. This “context specific prognostic property” of presence of any mucinous component might serve as a stratification factor for further adjuvant CRC studies.
Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
Authors: Leena George, Adam R. Taylor, Anna Esteve‐Codina, María Soler Artigas, Gian Andri Thun, Stewart Bates, Stelios Pavlidis, Scott Wagers, Anne Boland, Antje Prasse, Piera Boschetto, David G. Parr, Adam Nowinski, Imre Barta, Jens Hohlfeld, Timm Greulich, Maarten van den Berge, Pieter S. Hiemstra, Wim Timens, Timothy Hinks, Sally Wenzel, Salman Siddiqui, Matthew Richardson, Per Venge, Simon Heath, Ivo Gut, Martin D. Tobin, Lindsay Edwards, John H. Riley, Ratko Djukanovic, Charles Auffray, Bertrand De‐Meulder, Sven Erik‐Dahlen, Ian M. Adcock, Kian Fan Chung, Loems Ziegler‐Heitbrock, Peter J. Sterk, Dave Singh, Christopher E. Brightling
Journal: Allergy (2019)

Abstract Background Whether the clinical or pathophysiologic significance of the “treatable trait” high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma. Methods Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U‐BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U‐BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil &gt; 200 cells/μL as a cut‐off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values). Results There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U‐BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. Conclusion Despite shared “treatable traits” between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.
Trends Associated With Large-scale Expansion of Peritoneal Dialysis Within an Integrated Care Delivery Model
Authors: Leonid V. Pravoverov, Sijie Zheng, Rishi Parikh, Thida C. Tan, Neelam Bhalla, Chitra Reddy, Joanna Mroz, Tracy Y. Jonelis, Alan S. Go
Journal: JAMA Internal Medicine (2019)

Despite favorable national trends in the incidence of end-stage renal disease (ESRD) from 2008 to 2011, ESRD incidence has been increasing recently, and less than 10% of patients with ESRD start renal replacement therapy with peritoneal dialysis (PD) in the United States. Given known and potential advantages of PD over hemodialysis, the Kaiser Permanente Northern California integrated health care delivery system implemented a program to expand use of PD.To describe the system-level approach to expansion of PD use and temporal trends in initiation and persistence of PD and its associated mortality.This retrospective cohort study included adult members of a large integrated health care delivery system in Northern California who initiated chronic dialysis therapy from January 1, 2008, through December 31, 2018. Data were analyzed from March 1, 2018, through May 31, 2019.From 2008 to 2018, Kaiser Permanente Northern California implemented a multidisciplinary, system-wide approach to increase use of PD that included patient and caregiver education, education and support tools for health care professionals, streamlined system-level processes, monitoring, and continuous quality improvement.Temporal trends in the proportion of patients starting chronic dialysis with PD vs hemodialysis compared with national trends. Secondary outcomes included persistence of PD at 1 year in those initiating it and standardized 1-year mortality rates in those initiating PD or hemodialysis.Among 13 500 eligible health plan members in the study population (7840 men [58.1%] and 5660 women [41.9%]; mean [SD] age, 64.3 [14.4] years), initiation of PD increased from 165 of 1089 all new dialysis patients (15.2%) in 2008 to 486 of 1438 (33.8%) in 2018, which was substantially higher than national trends (6.1% in 2008 and 9.7% in 2016). Among the 2974 patients who initiated PD from 2008 to 2017, 2387 (80.3%) continued PD at 1 year after initiation, with a significant increase in age-, sex-, and race-standardized rates from 2008 (69.1%) to 2017 (84.2%). Age-, sex-, and race-standardized 1-year mortality for patients receiving PD and hemodialysis did not change significantly across this 10-year period (17.3% to 15.5% for hemodialysis, P = 0.89 for trend; and 5.5% to 7.3% for PD, P = 0.12 for trend).This study suggests that large-scale expansion of PD is feasible using a multidisciplinary, integrated, coordinated care approach; we believe these findings represent a national opportunity to improve outcomes for patients with advanced kidney disease.
Enabling Web-scale data integration in biomedicine through Linked Open Data
Authors: Maulik R. Kamdar, Javier D. Fernández, Axel Polleres, Tania Tudorache, Mark A. Musen
Journal: npj Digital Medicine (2019)

Abstract The biomedical data landscape is fragmented with several isolated, heterogeneous data and knowledge sources, which use varying formats, syntaxes, schemas, and entity notations, existing on the Web. Biomedical researchers face severe logistical and technical challenges to query, integrate, analyze, and visualize data from multiple diverse sources in the context of available biomedical knowledge. Semantic Web technologies and Linked Data principles may aid toward Web-scale semantic processing and data integration in biomedicine. The biomedical research community has been one of the earliest adopters of these technologies and principles to publish data and knowledge on the Web as linked graphs and ontologies, hence creating the Life Sciences Linked Open Data (LSLOD) cloud. In this paper, we provide our perspective on some opportunities proffered by the use of LSLOD to integrate biomedical data and knowledge in three domains: (1) pharmacology, (2) cancer research, and (3) infectious diseases. We will discuss some of the major challenges that hinder the wide-spread use and consumption of LSLOD by the biomedical research community. Finally, we provide a few technical solutions and insights that can address these challenges. Eventually, LSLOD can enable the development of scalable, intelligent infrastructures that support artificial intelligence methods for augmenting human intelligence to achieve better clinical outcomes for patients, to enhance the quality of biomedical research, and to improve our understanding of living systems.