tbuckley/cabot-search huggingface dataset:
Diastolic Blood Pressure Does Not Influence Cardiovascular Outcomes in Type 2 Diabetes; or Does It?
Authors: Pantelis Sarafidis, George Bakris
Journal: Diabetes Care (2020)

Hypertension and diabetes are prominent cardiovascular (CV) risk factors and major issues of public health (1,2). The common coexistence of hypertension and type 2 diabetes is long-established and represents a “deadly” combination: diabetes increases CV risk threefold at any level of systolic blood pressure (SBP), while the presence of hypertension in patients with diabetes increases CV risk by fourfold (3,4).

The optimal level of blood pressure (BP) in patients with diabetes has been a matter of debate for many years (5–7). Following older observational evidence and interventional data from the UK Prospective Diabetes Study (UKPDS) 38 and Hypertension Optimal Treatment (HOT) study, which showed CV benefits with diastolic blood pressure (DBP) of  15% 10-year CV risk) with type 2 diabetes to a target SBP of <120 mmHg or <140 mmHg. After 4.7 years of follow-up, the two groups had no differences in the primary outcome (nonfatal myocardial infarction, nonfatal stroke, death from CV causes) (hazard ratio [HR] 0.88, 95% CI 0.73–1.06; P = 0.20), CV mortality, and all-cause mortality; those in the intensive group had fewer stroke events (HR 0.59, 95% CI 0.39–0.89) but a higher incidence of serious adverse events (3.3% vs. 1.3%, P < 0.001), including hypotension, syncope, arrhythmias, hyperkalemia, angioedema, and renal failure.

The ACCORD BP findings were considered by many as conclusive evidence against the <130 mmHg …
First clinical experience with RNA interference [RNAI]-based triple combination therapy in chronic hepatitis B (CHB): JNJ-73763989 (JNJ-3989), JNJ-56136379 (JNJ-6379) and a nucleos(t)ide analogue (NA)
Authors: Rmf Yuen, S Locarnini, B Given, T Schluep, J Hamilton, M Biermer, R Kalmeijer, M Beumont-Mauviel, O Lenz, G Cloherty, K Jackson, C Ferrari, CL Lai, Shk Liu, LY Mak, Dkh Wong, WP To, KL Ko, RG Gish
Journal: Hepatology (2019)
Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial
Authors: Chamara Basnayake, Michael A Kamm, Annalise Stanley, Amy Wilson-O'Brien, Kathryn Burrell, Isabella Lees-Trinca, Angela Khera, Jim Kantidakis, Olivia Wong, Kate Fox, Nicholas J Talley, Danny Liew, Michael R Salzberg, Alexander J Thompson
Journal: The Lancet. Gastroenterology & hepatology (2020)
Abstract 15822: Are Angiotensin - (1-7) and Alamandine Biomarkers of Heart Ischemia?
Authors: Anna C Stein, Luiz Henrique Santana, Bruno Lauda, Barbara de Paula, Diana Russo, Charles Stefani, Paulo R Schvartzman, Milton Kalil, David Saitovitch, Mauricio Lutzky, Renato Eick, Daniel Sganzerl, Kátia De Angelis, Robson A Santos, Maria Claudia C Irigoyen
Journal: Circulation (2019)

Introduction: The renin-angiotensin system (RAS) is recognized as a clinical pathway to induce myocardial ischemia and renal dysfunction. On the other hand, the recent identification of novel compo...
Efficacy and safety of oral immunotherapy with AR101 in European children with a peanut allergy (ARTEMIS): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial
Authors: Jonathan O'B Hourihane, Kirsten Beyer, Allyah Abbas, Montserrat Fernández-Rivas, Paul J Turner, Katharina Blumchen, Caroline Nilsson, Maria D Ibáñez, Antoine Deschildre, Antonella Muraro, Vibha Sharma, Michel Erlewyn-Lajeunesse, José Manuel Zubeldia, Frederic De Blay, Christine D Sauvage, Aideen Byrne, John Chapman, Franck Boralevi, Audrey DunnGalvin, Charmaine O'Neill, David Norval, Andrea Vereda, Ben Skeel, Daniel C Adelman, George du Toit
Journal: The Lancet Child & Adolescent Health (2020)
Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease
Authors: Jamshid Maddahi, Joel Lazewatsky, James E. Udelson, Daniel S. Berman, Rob S.B. Beanlands, Gary V. Heller, Timothy M. Bateman, Juhani Knuuti, Cesare Orlandi
Journal: Journal of the American College of Cardiology (2020)
Genome-Wide Association Analysis Identifies a Genetic Basis of Infectivity in a Model Bacterial Pathogen
Authors: Jason P Andras, Peter D Fields, Louis Du Pasquier, Maridel Fredericksen, Dieter Ebert
Journal: Molecular Biology and Evolution (2020)

Knowledge of the genetic architecture of pathogen infectivity and host resistance is essential for a mechanistic understanding of coevolutionary processes, yet the genetic basis of these interacting traits remains unknown for most host-pathogen systems. We used a comparative genomic approach to explore the genetic basis of infectivity in Pasteuria ramosa, a Gram-positive bacterial pathogen of planktonic crustaceans that has been established as a model for studies of Red Queen host-pathogen coevolution. We sequenced the genomes of a geographically, phenotypically, and genetically diverse collection of P. ramosa strains and performed a genome-wide association study to identify genetic correlates of infection phenotype. We found multiple polymorphisms within a single gene, Pcl7, that correlate perfectly with one common and widespread infection phenotype. We then confirmed this perfect association via Sanger sequencing in a large and diverse sample set of P. ramosa clones. Pcl7 codes for a collagen-like protein, a class of adhesion proteins known or suspected to be involved in the infection mechanisms of a number of important bacterial pathogens. Consistent with expectations under Red Queen coevolution, sequence variation of Pcl7 shows evidence of balancing selection, including extraordinarily high diversity and absence of geographic structure. Based on structural homology with a collagen-like protein of Bacillus anthracis, we propose a hypothesis for the structure of Pcl7 and the physical location of the phenotype-associated polymorphisms. Our results offer strong evidence for a gene governing infectivity and provide a molecular basis for further study of Red Queen dynamics in this model host-pathogen system.
Chemotherapy and Venetoclax in Elderly Acute Myeloid Leukemia Trial (CAVEAT): A Phase Ib Dose-Escalation Study of Venetoclax Combined With Modified Intensive Chemotherapy
Authors: Chong Chyn Chua, Andrew W. Roberts, John Reynolds, Chun Yew Fong, Stephen B. Ting, Jessica M. Salmon, Sarah MacRaild, Adam Ivey, Ing Soo Tiong, Shaun Fleming, Fiona C. Brown, Sun Loo, Ian J. Majewski, Stefan K. Bohlander, Andrew H. Wei
Journal: Journal of Clinical Oncology (2020)

PURPOSE The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax has an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with hypomethylating agents or low-dose cytarabine in older patients. The tolerability and efficacy of venetoclax in combination with intensive chemotherapy in AML is unknown. PATIENTS AND METHODS Patients with AML who were ≥ 65 years (≥ 60 years if monosomal karyotype) and fit for intensive chemotherapy were allocated to venetoclax dose-escalation cohorts (range, 50-600 mg). Venetoclax was administered orally for 14 days each cycle. During induction, a 7-day prephase/dose ramp-up (days −6 to 0) was followed by an additional 7 days of venetoclax combined with infusional cytarabine 100 mg/m 2 on days 1-5 and idarubicin 12 mg/m 2 intravenously on days 2-3 (ie, 5 + 2). Consolidation (4 cycles) included 14 days of venetoclax (days −6 to 7) combined with cytarabine (days 1-2) and idarubicin (day 1). Maintenance venetoclax was permitted (7 cycles). The primary objective was to assess the optimal dose schedule of venetoclax with 5 + 2. RESULTS Fifty-one patients with a median age of 72 years (range, 63-80 years) were included. The maximum tolerated dose was not reached with venetoclax 600 mg/day. The main grade ≥ 3 nonhematologic toxicities during induction were febrile neutropenia (55%) and sepsis (35%). In contrast to induction, platelet recovery was notably delayed during consolidation cycles. The overall response rate (complete remission [CR]/CR with incomplete count recovery) was 72%; it was 97% in de novo AML and was 43% in secondary AML. During the venetoclax prephase, marrow blast reductions (≥ 50%) were noted in NPM1-, IDH2-, and SRSF2-mutant AML. CONCLUSION Venetoclax combined with 5 + 2 induction chemotherapy was safe and tolerable in fit older patients with AML. Although the optimal postremission therapy remains to be determined, the high remission rate in de novo AML warrants additional investigation (ANZ Clinical Trial Registry No. ACTRN12616000445471).
Somalier: rapid relatedness estimation for cancer and germline studies using efficient genome sketches
Authors: Brent S. Pedersen, Preetida J. Bhetariya, Joe Brown, Stephanie N. Kravitz, Gabor Marth, Randy L. Jensen, Mary P. Bronner, Hunter R. Underhill, Aaron R. Quinlan
Journal: Genome Medicine (2020)

Abstract Background When interpreting sequencing data from multiple spatial or longitudinal biopsies, detecting sample mix-ups is essential, yet more difficult than in studies of germline variation. In most genomic studies of tumors, genetic variation is detected through pairwise comparisons of the tumor and a matched normal tissue from the sample donor. In many cases, only somatic variants are reported, which hinders the use of existing tools that detect sample swaps solely based on genotypes of inherited variants. To address this problem, we have developed Somalier, a tool that operates directly on alignments and does not require jointly called germline variants. Instead, Somalier extracts a small sketch of informative genetic variation for each sample. Sketches from hundreds of germline or somatic samples can then be compared in under a second, making Somalier a useful tool for measuring relatedness in large cohorts. Somalier produces both text output and an interactive visual report that facilitates the detection and correction of sample swaps using multiple relatedness metrics. Results We introduce the tool and demonstrate its utility on a cohort of five glioma samples each with a normal, tumor, and cell-free DNA sample. Applying Somalier to high-coverage sequence data from the 1000 Genomes Project also identifies several related samples. We also demonstrate that it can distinguish pairs of whole-genome and RNA-seq samples from the same individuals in the Genotype-Tissue Expression (GTEx) project. Conclusions Somalier is a tool that can rapidly evaluate relatedness from sequencing data. It can be applied to diverse sequencing data types and genome builds and is available under an MIT license at github.com/brentp/somalier .
Caring for vulnerable patients during the pandemic: the consultant ophthalmologist
Authors: Helen Jones
Journal: BMJ (2020)

Covid-19 has had a huge impact on the work of Kin Sheng Lim, who is clinical lead in the glaucoma service at Guy's and St Thomas' NHS Foundation Hospital Trust."A lot of my patients are elderly and we really don't want to bring them into hospital unless we have to," Lim says, "But at the same time, glaucoma is one of those conditions where you have to physically see patients and measure pressure in the eye-there are no shortcuts for that."
Dose-dependant protective effect of lactation against breast cancer in ever-lactated women in Korea
Authors: Maddalena Barba, Susan E. McCann, Paolo Muti, Saverio Stranges, Barbara Fuhrman, Maurizio Trevisan, Jo L. Freudenheim
Journal: Cancer Research (2005)

3220  For the last twenty years in Korea, breast cancer has been steadily increasing and it became the most frequent female neoplasm from 2002. Rapid changes in westernized dietary habits and reproductive behaviors may contribute to the extraordinary increase of breast cancer incidence in Korean women. Among the risk factors, lactation might have a crucial role in the recent changes of breast cancer in Korea. National Health and Nutrition survey reported the proportion of women who had experienced breastfeeding has changed from 19.2% in 1995 to 7.4% in 2002. This hospital-based case-control analysis was performed to evaluate whether lactation associate with breast cancer risk among ever-lactated women in Korea. Of the 5 major eligible university hospitals, women who had previous cancer, benign breast tumor, ovarian removal, other severe systematic conditions and missing information on breast feeding were excluded. Finally, 541 histologically confirmed incident cases and 541 age-hospital-matched controls were analyzed using conditional logistic regression models. Family history, body mass index, age at menopause, age at first full-term pregnancy, and the number of live births showed clear significant trends in the risk of breast cancer, as known by other investigations. Among ever-lactated women, breast cancer risk significantly decreased according to the number of breastfed children (p for trend=0.004). Women who had ever lactated for 3 or more children showed the lowest risk of breast cancer (OR=0.42, 95% CI=0.23-0.77). The trend of decreasing risk with increasing average months of breast feeding was statistically significant (p for trend=0.01). Particularly noteworthy was that the decreasing trend in the breast cancer risk was apparent when analysis was restricted to the first breastfed child. This study reconfirms a dose-dependent protective effect of lactation against breast cancer in Korean women. The role of breastfeeding of the first child should be pursued in further investigations.
Society of Homoeopaths is investigated over claims that standards chief promoted anti-vaccination material
Authors: Clare Dyer
Journal: BMJ (2020)

The Professional Standards Authority (PSA) is to review the accreditation of the Society of Homoeopaths after the society’s professional standards chief was accused of having promoted anti-vaccination messages online.

The PSA renewed the society’s accreditation in February, imposing a condition requiring it to make clear that registered homoeopaths, whether acting in a professional or a public capacity, are not allowed “to provide advice on vaccination or offer or provide homeopathy as an alternative to vaccination for the prevention of serious infectious diseases.”

The condition averted a judicial review which the Good Thinking Society, a charity that promotes rational thinking, had …
Cancer cell CCR2 orchestrates suppression of the adaptive immune response
Authors: Miriam R. Fein, Xue-Yan He, Ana S. Almeida, Emilis Bružas, Arnaud Pommier, Ran Yan, Anaïs Eberhardt, Douglas T. Fearon, Linda Van Aelst, John Erby Wilkinson, Camila O. dos Santos, Mikala Egeblad
Journal: The Journal of Experimental Medicine (2020)

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2−/− cancer cells did not induce immune suppression in Batf3−/− mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.
Expression of CXCR4 Receptors in Refractory Atypical Mediastinal Carcinoid
Authors: Venkata Subramanian Krishnaraju, Swayamjeet Satapathy, Ashwani Sood, Chandan Krushna Das, Debajyoti Chatterjee, Jaya Shukla, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2020)

Abstract Primary neuroendocrine tumor of the mediastinum is a relatively rare entity. In metastatic/inoperable disease, therapeutic options are limited to cytotoxic chemotherapy in poorly differentiated tumors and peptide receptor radionuclide therapy in case of well-differentiated tumors. We present the case of a 52-year-old man with mediastinal atypical carcinoid (grade II) neuroendocrine tumor showing mild somatostatin receptor expression and intense FDG avidity with progressive disease on chemotherapy. Chemokine receptor targeted PET/CT with CXCR4 ( 68 Ga-CXCR4) showed tracer avidity in tumor sites higher than the physiological sites, which may pave the way for CXCR4-targeted radionuclide therapy in this subgroup of patients.
G4C2 Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS/FTD
Authors: Alyssa N. Coyne, Benjamin L. Zaepfel, Lindsey Hayes, Boris Fitchman, Yuval Salzberg, En-Ching Luo, Kelly Bowen, Hannah Trost, Stefan Aigner, Frank Rigo, Gene W. Yeo, Amnon Harel, Clive N. Svendsen, Dhruv Sareen, Jeffrey D. Rothstein
Journal: Neuron (2020)
Aberrant venous anatomy as a risk factor for thromboembolic events in patients with Klippel-Trénaunay syndrome: Case-control study within a cohort study
Authors: Lilly Geertruida Johanna Maria Zwerink, D. Maroeska W.M. te Loo, Richard Praster, Bas H. Verhoeven, Carine J.M. van der Vleuten
Journal: Journal of the American Academy of Dermatology (2020)
Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study
Authors: Luke W Meredith, William L Hamilton, Ben Warne, Charlotte J Houldcroft, Myra Hosmillo, Aminu S Jahun, Martin D Curran, Surendra Parmar, Laura G Caller, Sarah L Caddy, Fahad A Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Sally Forrest, Sushmita Sridhar, Michael P Weekes, Stephen Baker, Nicholas Brown, Elinor Moore, Ashley Popay, Iain Roddick, Mark Reacher, Theodore Gouliouris, Sharon J Peacock, Gordon Dougan, M Estée Török, Ian Goodfellow
Journal: The Lancet Infectious Diseases (2020)

The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.
Covid-19: lack of guidance on PPE for hearing impaired doctors
Authors: Isabelle J M Williams
Journal: BMJ (2020)

Given the likely ongoing need for personal protective equipment (PPE) in healthcare settings, I question whether facemasks alone are satisfactory in the long term.Alternatives, such as visor-like facial coverings, could provide better communication in low risk settings for all, none more so than healthcare workers and patients with impaired hearing who rely on lip reading. 1 Masks, with their ear loops, are not ideal for hearing aid wearers.Visors are sturdier, attach around the head, and allow lip reading.They are less claustrophobic for all users and more appealing to patients who rely on non-verbal cues, as the authors of this article allude to. 1 Yet because they lack a good facial seal peripherally, face shields cannot be used as primary protection for preventing respiratory disease transmission. 2Innovation is needed.
Abstract PR15: Acting at a distance: Medulloblastoma-secreted ligands disrupt normal neural stem cell function
Authors: Alexander Gont, Jaclin V. Simonetta, Jenna Park, Alice R. Shan, Michael J. Borrett, Michael D. Taylor, Freda D. Miller, David R. Kaplan
Journal: Cancer Research (2020)

Abstract Long-term cognitive impairments are common in pediatric brain cancer survivors. While these impairments are thought to arise following radiation treatment, recent reports suggest a link to tumor-specific mechanisms. We therefore hypothesized that pediatric brain tumors, more specifically medulloblastoma (MB), can directly affect neural stem and precursor cell function in the forebrain stem cell niche—the subventricular zone (V-SVZ) —by secreting bioactive factors. Mice harboring subcutaneous flank MB tumors had fewer proliferating neural precursor cells in the V-SVZ than controls as well as decreased olfactory bulb neurogenesis and white matter oligodendrogenesis. To assess the effects of the MB secretome in the brain, concentrated conditioned media from MB cell lines (MB-CM) was injected intracerebroventricular (ICV) into mouse pups. ICV injection of MB-CM decreased neural precursor cell proliferation as well as decreased numbers of V-SVZ neurospheres in culture. MB-CM from multiple cell lines decreased V-SVZ neurosphere number and promoted astrocyte differentiation in culture. To identify the ligands contributing to the phenotype, an interaction model was developed extracting ligands from MB microarray data, networking them to receptors on NSCs. Of the predicted ligands, IL6-family cytokine expression and secretion was validated in MB cells. When added in culture, recombinant IL6, IL11, and CT1 decreased neurosphere number and ICV injection of IL11 into mouse pups decreased V-SVZ neural precursor cell proliferation. Overall, this work demonstrates that medulloblastoma secretes bioactive compounds that perturb neural stem cell function and the circuity involved in normal cognitive function. This abstract is also being presented as Poster B64. Citation Format: Alexander Gont, Jaclin V. Simonetta, Jenna Park, Alice R. Shan, Michael J. Borrett, Michael D. Taylor, Freda D. Miller, David R. Kaplan. Acting at a distance: Medulloblastoma-secreted ligands disrupt normal neural stem cell function [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR15.