tbuckley/cabot-search huggingface dataset:
Travel-Associated and Locally Acquired Dengue Cases — United States, 2010–2017
Authors: Aidsa Rivera, Laura E. Adams, Tyler M. Sharp, Jennifer A. Lehman, Stephen H. Waterman, Gabriela Paz-Bailey
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Dengue is a potentially fatal acute febrile illness caused by any of four mosquito-transmitted dengue viruses (DENV-1 to DENV-4) belonging to the family Flaviviridae and endemic throughout the tropics. Competent mosquito vectors of DENV are present in approximately one half of all U.S. counties. To describe epidemiologic trends in travel-associated and locally acquired dengue cases in the United States, CDC analyzed cases reported from the 50 states and District of Columbia to the national arboviral surveillance system (ArboNET). Cases are confirmed by detection of 1) virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in any body fluid or tissue, 2) DENV antigen in tissue by a validated assay, 3) DENV nonstructural protein 1 (NS1) antigen, or 4) immunoglobulin M (IgM) anti-DENV antibody if the patient did not report travel to an area with other circulating flaviviruses. When travel to an area with other flaviviruses was reported, IgM-positive cases were defined as probable. During 2010-2017, totals of 5,009 (93%) travel-associated and 378 (7%) locally acquired confirmed or probable dengue cases were reported to ArboNET. Cases were equally distributed between males and females, and median age was 41 years. Eighteen (three per 1,000) fatal cases were reported, all among travelers. Travelers should review country-specific recommendations (https://wwwnc.cdc.gov/travel/notices/watch/dengue-asia) for reducing their risk for DENV infection, including using insect repellent and staying in residences with air conditioning or screens on windows and doors.
The DNA Cytosine Deaminase APOBEC3B is a Molecular Determinant of Platinum Responsiveness in Clear Cell Ovarian Cancer
Authors: Artur A. Serebrenik, Prokopios P. Argyris, Matthew C. Jarvis, William L. Brown, Martina Bazzaro, Rachel I. Vogel, Britt K. Erickson, Sun-Hee Lee, Krista M. Goergen, Matthew J. Maurer, Ethan P. Heinzen, Ann L. Oberg, Yajue Huang, Xiaonan Hou, S. John Weroha, Scott H. Kaufmann, Reuben S. Harris
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify a new biomarker for detection and intervention. Experimental Designs: APOBEC3 expression was analyzed by IHC and qRT-PCR in a pilot set of CCOC specimens (n = 9 tumors). The IHC analysis of APOBEC3B was extended to a larger cohort to identify clinical correlates (n = 48). Dose-response experiments with platinum-based drugs in CCOC cell lines and carboplatin treatment of patient-derived xenografts (PDXs) were done to address mechanistic linkages. Results: One DNA deaminase, APOBEC3B, is overexpressed in a formidable subset of CCOC tumors and is low or absent in normal ovarian and fallopian tube epithelial tissues. High APOBEC3B expression associates with improved progression-free survival (P = 0.026) and moderately with overall survival (P = 0.057). Cell-based studies link APOBEC3B activity and subsequent uracil processing to sensitivity to cisplatin and carboplatin. PDX studies extend this mechanistic relationship to CCOC tissues. Conclusions: These studies demonstrate that APOBEC3B is overexpressed in a subset of CCOC and, contrary to initial expectations, associated with improved (not worse) clinical outcomes. A likely molecular explanation is that APOBEC3B-induced DNA damage sensitizes cells to additional genotoxic stress by cisplatin. Thus, APOBEC3B is a molecular determinant and a candidate predictive biomarker of the therapeutic response to platinum-based chemotherapy. These findings may have broader translational relevance, as APOBEC3B is overexpressed in many different cancer types.
Outbreak of Listeriosis in South Africa Associated with Processed Meat
Authors: Juno Thomas, Nevashan Govender, Kerrigan M. McCarthy, Linda K. Erasmus, Timothy J. Doyle, Mushal Allam, Arshad Ismail, Ntsieni Ramalwa, Phuti Sekwadi, Genevie Ntshoe, Andronica Shonhiwa, Vivien Essel, Nomsa Tau, Shannon Smouse, Hlengiwe M. Ngomane, Bolele Disenyeng, Nicola A. Page, Nelesh P. Govender, Adriano G. Duse, Rob Stewart, Teena Thomas, Deon Mahoney, Mathieu Tourdjman, Olivier Disson, Pierre Thouvenot, Mylène M. Maury, Alexandre Leclercq, Marc Lecuit, Anthony M. Smith, Lucille H. Blumberg
Journal: New England Journal of Medicine (2020)

We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018.
The Lung: Radiologic-pathologic Correlations
Journal: Thorax (1985)

The wide diversity of the T and B Ag receptor repertoires becomes even more extensive postneonatally due to the activity of TdT, which adds nontemplated N nucleotides to Ig and TCR coding ends during V(D)J recombination. In addition, complementarity-determining region 3 sequences formed in the absence of TdT are more uniform due to the use of short sequence homologies between the V, D, and J genes. Thus, the action of TdT produces an adult repertoire that is both different from, and much larger than, the repertoire of the neonate. We have generated TdT-deficient nonobese diabetic (NOD) and MRL-<i>Fas</i><sup><i>lpr</i></sup> mice, and observed a decrease in the incidence of autoimmune disease, including absence of diabetes and decreased pancreatic infiltration in NOD TdT<sup>−/−</sup> mice, and reduced glomerulonephritis and increased life span in MRL-<i>Fas</i><sup><i>lpr</i></sup> TdT<sup>−/−</sup> mice. Using tetramer staining, TdT<sup>−/−</sup> and TdT<sup>+/+</sup> NOD mice showed similar frequencies of the diabetogenic BDC 2.5 CD4<sup>+</sup> T cells. We found no increase in CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cells in NOD TdT<sup>−/−</sup> mice. Thus, TdT deficiency ameliorates the severity of disease in both lupus and diabetes, two very disparate autoimmune diseases that affect different organs, with damage conducted by different effector cell types. The neonatal repertoire appears to be deficient in autoreactive T and/or B cells with high enough affinities to induce end-stage disease. We suggest that the paucity of autoreactive specificities created in the N region-lacking repertoire, and the resultant protection afforded to the newborn, may be the reason that TdT expression is delayed in ontogeny.
In community-acquired bacterial pneumonia, lefamulin was noninferior to moxifloxacin at 96 h after the first dose
Authors: Debra Powell, Anthony Donato
Journal: Annals of Internal Medicine (2020)

Source Citation Alexander E, Goldberg L, Das AF, et al. Oral lefamulin vs moxifloxacin for early clinical response among adults with community-acquired bacterial pneumonia: the LEAP 2 randomized clinical trial. JAMA. 2019;322:1661-71. 31560372
Annals Consult Guys - Bridging Anticoagulation for Patients With Valvular Heart Disease
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Consult Guys - Bridging Anticoagulation for Patients With Valvular Heart DiseaseFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0035 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, and Howard H. Weitz, MD, report that they have no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: CG1KeywordsCardiovascular therapyDiagnostic techniquesDisclosure ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Trends in Incidence of Type 1 and Type 2 Diabetes Among Youths — Selected Counties and Indian Reservations, United States, 2002–2015
Authors: Jasmin Divers, Elizabeth J. Mayer-Davis, Jean M. Lawrence, Scott Isom, Dana Dabelea, Lawrence Dolan, Giuseppina Imperatore, Santica Marcovina, David J Pettitt, Catherine Pihoker, Richard F. Hamman, Sharon Saydah, Lynne E. Wagenknecht
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change [APC] = 1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC = 4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.
A hypermethylation strategy utilized by enhancer-bound CARM1 to promote estrogen receptor α-dependent transcriptional activation and breast carcinogenesis
Authors: Bing-ling Peng, Wen-juan Li, Jian-cheng Ding, Yao-hui He, Ting Ran, Bing-lan Xie, Zi-rui Wang, Hai-feng Shen, Rong-quan Xiao, Wei-wei Gao, Tian-yi Ye, Xiang Gao, Wen Liu
Journal: Theranostics (2020)

While protein arginine methyltransferases (PRMTs) and PRMT-catalyzed protein methylation have been well-known to be involved in a myriad of biological processes, their functions and the underlying molecular mechanisms in cancers, particularly in estrogen receptor alpha (ERα)-positive breast cancers, remain incompletely understood.Here we focused on investigating PRMT4 (also called coactivator associated arginine methyltransferase 1, CARM1) in ERα-positive breast cancers due to its high expression and the associated poor prognosis.Methods: ChIP-seq and RNA-seq were employed to identify the chromatin-binding landscape and transcriptional targets of CARM1, respectively, in the presence of estrogen in ERα-positive MCF7 breast cancer cells.High-resolution mass spectrometry analysis of enriched peptides from anti-monomethyland anti-asymmetric dimethyl-arginine antibodies in SILAC labeled wild-type and CARM1 knockout cells were performed to globally map CARM1 methylation substrates.Cell viability was measured by MTS and colony formation assay, and cell cycle was measured by FACS analysis.Cell migration and invasion capacities were examined by wound-healing and trans-well assay, respectively.Xenograft assay was used to analyze tumor growth in vivo.Results: CARM1 was found to be predominantly and specifically recruited to ERα-bound active enhancers and essential for the transcriptional activation of cognate estrogen-induced genes in response to estrogen treatment.Global mapping of CARM1 substrates revealed that CARM1 methylated a large cohort of proteins with diverse biological functions, including regulation of intracellular estrogen receptor-mediated signaling, chromatin organization and chromatin remodeling.A large number of CARM1 substrates were found to be exclusively hypermethylated by CARM1 on a cluster of arginine residues.Exemplified by MED12, hypermethylation of these proteins by CARM1 served as a molecular beacon for recruiting coactivator protein, tudor-domain-containing protein 3 (TDRD3), to CARM1-bound active enhancers to activate estrogen/ERα-target genes.In consistent with its critical role in estrogen/ERα-induced gene transcriptional activation, CARM1 was found to promote cell proliferation of ERα-positive breast cancer cells in vitro and tumor growth in mice.Conclusions: our study uncovered a "hypermethylation" strategy utilized by enhancer-bound CARM1 in gene transcriptional regulation, and suggested that CARM1 can server as a therapeutic target for breast cancer treatment.
5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-Mediated Apoptosis
Authors: Sha Jin, Dan Cojocari, Julie J. Purkal, Relja Popovic, Nari N. Talaty, Yu Xiao, Larry R. Solomon, Erwin R. Boghaert, Joel D. Leverson, Darren C. Phillips
Journal: Clinical Cancer Research (2020)

Patients with acute myeloid leukemia (AML) frequently do not respond to conventional therapies. Leukemic cell survival and treatment resistance have been attributed to the overexpression of B-cell lymphoma 2 (BCL-2) and aberrant DNA hypermethylation. In a phase Ib study in elderly patients with AML, combining the BCL-2 selective inhibitor venetoclax with hypomethylating agents 5-azacitidine (5-Aza) or decitabine resulted in 67% overall response rate; however, the underlying mechanism for this activity is unknown.We studied the consequences of combining two therapeutic agents, venetoclax and 5-Aza, in AML preclinical models and primary patient samples. We measured expression changes in the integrated stress response (ISR) and the BCL-2 family by Western blot and qPCR. Subsequently, we engineered PMAIP1 (NOXA)- and BBC3 (PUMA)-deficient AML cell lines using CRISPR-Cas9 methods to understand their respective roles in driving the venetoclax/5-Aza combinatorial activity.In this study, we demonstrate that venetoclax and 5-Aza act synergistically to kill AML cells in vitro and display combinatorial antitumor activity in vivo. We uncover a novel nonepigenetic mechanism for 5-Aza-induced apoptosis in AML cells through transcriptional induction of the proapoptotic BH3-only protein NOXA. This induction occurred within hours of treatment and was mediated by the ISR pathway. NOXA was detected in complex with antiapoptotic proteins, suggesting that 5-Aza may be "priming" the AML cells for venetoclax-induced apoptosis. PMAIP1 knockout confirmed its major role in driving venetoclax and 5-Aza synergy.These data provide a novel nonepigenetic mechanism of action for 5-Aza and its combinatorial activity with venetoclax through the ISR-mediated induction of PMAIP1.
Distributional Validity and Prognostic Power of the National Institutes of Health Stroke Scale in US Administrative Claims Data
Authors: Hamidreza Saber, Jeffrey L. Saver
Journal: JAMA Neurology (2020)

Comparative assessment of acute ischemic stroke care quality provided by hospitals in the United States has been hampered by the unavailability of the National Institutes of Health Stroke Scale (NIHSS) in administrative data sets, preventing adequate adjustment for variations in patient case-mix risk. In response to stakeholder concerns, the US Centers for Medicare & Medicaid Services in 2016 implemented optional reporting of NIHSS scores.To analyze the distributional, convergent, and predictive validity of nationally submitted NIHSS values in the National Inpatient Sample.This population-based retrospective cross-sectional study took place from October 1 to December 31, 2016. The nationally representative sample included US adults who had ischemic stroke hospitalizations during the first calendar quarter in which optional NIHSS reporting was implemented. Analysis began September 2019.Distribution of NIHSS scores, functional independence at discharge, inpatient mortality, and administrative reporting of NIHSS.Among 154 165 ischemic stroke hospitalizations during the first 3 months of the reporting policy, NIHSS scores were reported in 21 685 patients (14%) (10 925 women [50.4%]; median [interquartile range] age, 72 [61-82] years). Median (interquartile range) NIHSS score was 4 (2-11), and frequency of severity categories included absent (NIHSS score, 0) in 2080 patients (9.6%), minor (NIHSS score, 1-4) in 8760 patients (40.4%), and severe (NIHSS score, 21-42) in 1930 patients (8.9%). National Institutes of Health Stroke Scale score of 10 or more, an indicator of possible large vessel occlusions, was present in 6290 patients (29%). Presenting NIHSS score was higher in very elderly patients (age ≥80 y) and women and also in patients receiving endovascular thrombectomy vs intravenous thrombolysis alone vs no reperfusion therapy (median [interquartile range], 17 [12-22] vs 6 [4-12] vs 4 [2-9], respectively) (P < .001). National Institutes of Health Stroke Scale scores were similarly higher for discharge outcomes of mortality vs discharge to skilled nursing facility vs discharge home (median [interquartile range], 19 [12-25] vs 7 [3-15] vs 2 [1-5], respectively) (P < .001). Likelihood of NIHSS scores being reported independently increased with interfacility transfer, receipt of acute reperfusion therapies, larger hospital size, academic centers, and region other than the West.In the initial national optional reporting period in the United States, NIHSS scores were reported in nearly 1 in 7 ischemic stroke hospitalizations. The distribution of NIHSS scores was similar to that from narrow population-based studies and registries, and NIHSS scores were powerfully associated with discharge outcome, supporting the validity and potential to aid care quality assessment.
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Authors: Daixi Ren, Yuze Hua, Boyao Yu, Xin Ye, Ziheng He, Chunwei Li, Jie Wang, Yongzhen Mo, Xiaoxu Wei, Yunhua Chen, Yujuan Zhou, Qianjin Liao, Hui Wang, Bo Xiang, Ming Zhou, Xiaoling Li, Guiyuan Li, Yong Li, Zhaoyang Zeng, Wei Xiong
Journal: Molecular Cancer (2020)

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.
Abstract P2-10-11: Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications
Authors: Samer Al Hadidi, Martha Mims, Courtney Miller-Chism, Rammurti Kamble
Journal: Cancer Research (2020)

Abstract BACKGROUND African Americans comprise 12% of the total United States population. Lifetime probability of developing cancer in African Americans is 37.55%. Lifetime probability of developing breast cancer in African Americans is 11.1%. African Americans have higher lifetime probability of dying because of breast cancer compared to Caucasians (3.3% versus 2.7%). Concerns exist that African Americans are underrepresented in trials of breast cancer medications. We sought to examine African Americans participation for pivotal breast cancer medications trials submitted to the U.S. Food and Drug Administration (FDA) supporting marketing applications. METHODS On the basis of publicly available FDA reviews, the authors assessed enrollment of African Americans in trials supporting 9 drug approvals from 2014 to 2018. Those trials resulted in approval of medications to treat breast cancer. Prevalence-corrected estimates for the participation of African Americans were calculated as the percentage of African Americans among trial participants divided by the percentage of African Americans in the disease population (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting similar representation of African Americans in the trial and disease population. RESULTS A total of 22,075 patients enrolled in clinical trials, which resulted in subsequent FDA approval. The proportion of African Americans enrolled in the clinical trials that led to breast cancer medication approval in the 5-year period was 6.83%. The calculated PPR for participation of African Americans in clinical trials that led to drug approval for breast cancer was 0.29. CONCLUSIONS African Americans were under represented in trials of drugs for breast cancer. Efforts should be made to increase the proportion of participation of African Americans in clinical trials. Citation Format: Samer Al Hadidi, Martha Mims, Courtney Miller-Chism, Rammurti Kamble. Participation of African Americans in clinical trials supporting FDA approval of breast cancer medications [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-11.
Coronary Revascularization in the United States—Patient Characteristics and Outcomes in 2020
Authors: Debabrata Mukherjee
Journal: JAMA Network Open (2020)

Mohamad Alkhouli, MD; Fahad Alqahtani, MD; Ankur Kalra, MD; Sameer Gafoor, MD; Mohamed Alhajji, MD; Mohammed Alreshidan, MD; David R. Holmes, MD; Amir Lerman, MD