tbuckley/cabot-search huggingface dataset:
In older men, 5α-reductase inhibitors were linked to increased risk for self-harm and depression but not suicide
Authors: Clifford C. Dacso
Journal: Annals of Internal Medicine (2017)

ACP Journal Club18 July 2017In older men, 5α-reductase inhibitors were linked to increased risk for self-harm and depression but not suicideClifford C. Dacso, MD, MPH, MBAClifford C. Dacso, MD, MPH, MBABaylor College of Medicine, Houston, Texas, USA (C.C.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-167-2-009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWelk B, McArthur E, Ordon M, et al. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177:683-91. https://pubmed.ncbi.nlm.nih.gov/28319231Clinical Impact RatingsGIM/FP/GP: Mental Health: Geriatrics: Reference1 Center for Drug Evaluation and Research. Approval package for application number: NDA 20-788/S-017. March 11, 2011. www.accessdata.fda.gov/drugsatfda_docs/nda/2011/020788Orig1s017.pdf (accessed 15 May 2017). Google Scholar Author, Article, and Disclosure InformationAffiliations: Baylor College of Medicine, Houston, Texas, USA (C.C.D.)This article was published at Annals.org on 4 July 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 July 2017Volume 167, Issue 2Page: JC9KeywordsCohort studiesDatabasesDrug therapyDrugsEmergency departmentHazard ratioHealth careHospitalizationsPsychiatry and mental healthSuicide ePublished: 18 July 2017 Issue Published: 18 July 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Egg Albumen as a Fast and Strong Medical Adhesive Glue
Authors: Kaige Xu, Yuqing Liu, Shousan Bu, Tianyi Wu, Qiang Chang, Gurankit Singh, Xiaojian Cao, Chuang Deng, Bingyun Li, Gaoxing Luo, Malcolm Xing
Journal: Advanced Healthcare Materials (2017)

Abstract Sutures penetrate tissues to close wounds. This process leads to inflammatory responses, prolongs healing time, and increases operation complexity. It becomes even worse when sutures are applied to stress‐sensitive and fragile tissues. By bonding tissues via forming covalent bonds, some medical adhesives are not convenient to be used by surgeons and have side effects to the tissues. Here egg albumen adhesive (EAA) is reported with ultrahigh adhesive strength to bond various types of materials and can be easily used without any chemical and physical modifications. Compared with several commercial medical glues, EAA exhibits stronger adhesive property on porcine skin, glass, polydimethylsiloxane. The EAA also shows exceptional underwater adhesive strength. Finally, wound closure using EAA on poly(caprolactone) nanofibrous sheet and general sutures is investigated and compared in a rat wound model. EAA also does not show strong long‐term inflammatory response, suggesting that EAA has potential as a medical glue, considering its abundant source, simple fabrication process, inherent nontoxicity, and low cost.
Disruption of Wnt/β-Catenin Signaling Exerts Antileukemia Activity and Sensitizes with Tyrosine Kinase Inhibitors in FLT3 Mutated AML In Vivo
Authors: Xuejie Jiang, Po Yee Mak, Hong Mu, Duncan Mak, Qi Zhang, Marina Konopleva, Michael Andreeff, Bing Z Carter
Journal: Blood (2016)
PRESENCE OF ABNORMAL FINDINGS WITHIN SPORTS PRE-PARTICIPATION CARDIOVASCULAR SCREENING
Authors: João Freitas, Renato Andrade, Rogério Pereira, Ana Leal, Cátia Saavedra, Nuno Pais, Diana Marques, Isabel Lopes, Nuno Loureiro, Paulo Maia, Ovídio Costa, João Espregueira-Mendes
Journal: British Journal of Sports Medicine (2017)

Background Sports pre-participation cardiovascular screening remains a challenging topic, without consensus amongst the scientific community. Sports pre-participation cardiovascular screening with electrocardiogram (ECG) is not systematically included in the United States of America. However, in some European countries both ECG and echocardiogram are requested. These asymmetric proceedings are related with the ongoing discussion on health-related benefits effectiveness and costs. Objective Define the proportion of cardiovascular screening exams which require complementary cardiovascular exams in addition to the routine electrocardiogram performed by the athletes. Moreover, it was intended to analyze the influence of the complementary cardiovascular exams results' in the decision making for medical clearance. Design Retrospective cohort study. Setting Nonprofessional to elite athletes. Patients (or Participants) Between 2014 and 2015, a total of 862 athletes performed sports pre-participation cardiovascular screening. Interventions (or Assessment of Risk Factors) All the athletes underwent a cardiovascular screening, including medical history, physical examination and 12-lead electrocardiogram. In case of cardiovascular diseases suspicion, complementary cardiovascular exams (echocardiogram and cardiac stress test) were solicited. Main Outcome Measurements As main outcomes were considered the need for complementary cardiovascular exams according the Seattle criteria (%), presence of abnormalities in these complementary cardiovascular exams (%) and decision for medical clearance (%). Results From the 862 athletes, 54 (6%) required complementary cardiovascular exams, of which 8 (0.9%) showed abnormal cardiovascular findings. Three athletes (0.3%) did not get medical clearance to participate in sports. Conclusions The sports pre-participation cardiovascular screening with ECG required complementary cardiovascular exams in 6% of the cases and 0.3% were not cleared to participate in sports. The decision was based in the most up-to-date knowledge of life threatening cardiac clinical conditions and supports a life-preventive measure to 3 young persons over an approximate cost of 12000€.
The Disease Risk Index Is a Robust Tool for Allogeneic Hematopoietic Stem Cell Transplantation Risk Stratification: An Independent Validation Study on a Large Cohort of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Roni Shouval, Joshua Fein, Myriam Labopin, Nicolaus Kroger, Rafael F. Duarte, Peter Bader, Chiara Bonini, Peter Dreger, Carlo DuFour, Andrew Gennery, Jurgen Kuball, Francesco Lanza, Silvia Montoto, Emmanuelle Polge, John A Snowden, Jan Styczynski, Anna Sureda, Mohamad Mohty, Arnon Nagler
Journal: Blood (2016)
Using a gene-environment interaction study to evaluate risk for lung cancer.
Authors: Travis John Osterman, Lisa Bastarache, Wei-Qi Wei, Jonathan David Mosley, Josh Charles Denny
Journal: Journal of Clinical Oncology (2016)

1524 Background: Lung cancer is known be associated with over 20 germline single nucleotide polymorphisms (SNPs). Tobacco exposure is a known risk factor for developing lung cancer. Genotype by environment interaction (GxE) studies provide a framework to assess whether genomic and environmental effects are additive or whether there is an additional interaction. We describe here a GxE study to investigate associations between tobacco exposure, genetic risk, and lung cancer risk. Methods: Patients were identified from Vanderbilt University Medical Center's (VUMC) de-identified DNA biobank (BioVU), which is linked to electronic medical record data. Approximately 15,000 individuals of European ancestry who had Illumina exome array data were selected for this analysis. Tobacco exposure was ascertained by a novel natural language processing algorithm. Lung cancer diagnoses were determined by International Classification of Disease 9 (ICD-9) codes. We attempt to replicate 25 SNPs associated with lung cancer previously reported in the NHGRI catalog using a logistic regression with age and gender as covariates. To test for interactions between smoking and known lung cancer association SNPs, we modeled the data using logistic regression with age, gender, pack years, SNP, and pack years x SNP terms. We also used a two degree of freedom (2df) joint test of the SNP and the interaction term, controlling for the main effects of the remaining covariates. Results: Lung cancer-associated ICD-9 codes were found in 803 individuals. Smoking was strongly associated with risk of developing lung cancer across all SNPs. We replicated 5 of the 25 previously reported SNPs associated with lung cancer (p < 0.05). Five SNPs (below) showed interaction with tobacco exposure (p < 0.05).Conclusions: This study explores the relationship between genetic and environmental risk for lung cancer. Five of the SNPs showed a non-additive interaction with smoking. Individuals with these mutations may be more sensitive to tobacco exposure than those without the SNP. SNP Chromosome SNP-lung cancer p-value SNP-smoking interaction p-value rs402710 5 0.01 0.01 rs7626795 3 0.24 0.001 rs3117582 6 0.40 0.004 rs16951095 18 0.48 0.009 rs1209950 21 0.76 0.03
Clinical and biologic covariates of outcomes in ZUMA-1: A pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL).
Authors: Frederick Lundry Locke, Sattva Swarup Neelapu, Nancy L. Bartlett, Lazaros J. Lekakis, David Bernard Miklos, Caron Alyce Jacobson, Ira Braunschweig, Olalekan O. Oluwole, Tanya Siddiqi, Yi Lin, John Timmerman, Patrick Michael Reagan, Adrian Bot, John Rossi, Lynn Navale, Yizhou Jiang, Jeff Aycock, Meg Elias, Jeffrey S. Wiezorek, William Y. Go
Journal: Journal of Clinical Oncology (2017)

7512 Background: Outcomes in activated B cell subtype diffuse large B cell lymphoma (ABC-DLBCL) and r-NHL are poor (Sehn Blood 2015, Crump ASCO 2016). ZUMA-1 is the first, multicenter trial of anti-CD19 chimeric antigen receptor (CAR) T cells, axi-cel, in r-NHL. Methods: Dosing and eligibility were per Neelapu ASH 2016. The primary endpoint was objective response rate (ORR); secondary endpoints were duration of response (DOR), overall survival (OS), and safety. Cell of origin (COO) and CD19 status were assessed centrally using Lymphoma Subtyping Test NanoString (Wallden JCO 2015) and a validated immunohistochemistry assay, respectively. Results: As of Jan 27, 2017, 111 patients (pts) were enrolled; the manufacturing success rate was 99% with an average 17-d turnaround time; 101 pts (modified intent-to-treat [mITT] population) received axi-cel. In the mITT population, the ORR was 82% (complete response [CR], 54%). With 8.7 m median follow-up, 44% remain in response and 39% in CR. The median DOR was 8.1 m and not reached (NR) for pts with CR. Median OS was NR. Results for clinical and biologic covariates are listed in the table. In pts who received tocilizumab (n = 43) and/or steroids (n = 27) for cytokine release syndrome (CRS) and/or neurologic events (NE), ORR was 84% and 78%, respectively. Most common grade ≥3 adverse events (AEs) were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), thrombocytopenia (24%), and encephalopathy (21%). Rates of grade ≥3 CRS and NE were 13% and 28%, respectively. There were 3 grade 5 AEs (Neelapu ASH 2016). Conclusions: Axi-cel induced an ORR of 82% in pts with r-NHL, response is ongoing in 44% of pts at 8.7 m. Similar clinical responses were observed in pts with r-ABC-DLBCL. AEs were manageable and the use of tocilizumab/steroids did not appear to impact ORR. Drs Locke and Neelapu contributed equally. Funding source: Kite Pharma and Leukemia &amp; Lymphoma Society Therapy Acceleration Program Clinical trial information: NCT02348216. [Table: see text]
Abstract 216: Genetic Deletion of Cardiomyocyte Mineralocorticoid Receptors Prevents Cardiac Dysfunction and Premature Death in Mice Lacking Glucocorticoid Receptors in the Heart
Authors: Robert H Oakley, Diana Cruz-Topete, Julie F Foley, Page H Myers, Pierre Chambon, Monte S Willis, John A Cidlowski
Journal: Circulation Research (2015)

Heart failure is one of the leading causes of death in the Western world, and stress is increasingly associated with adverse cardiac outcomes. Glucocorticoids are primary stress hormones, but their direct role in heart physiology and pathology is poorly understood. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR); however, in cardiomyocytes glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed glucocorticoid response. To elucidate the in vivo function of glucocorticoid signaling in the heart, we generated mice with cardiomyocyte-specific deletion of GR (cardioGRKO). The cardioGRKO mice spontaneously develop cardiac hypertrophy by 2 months of age and left ventricular systolic dysfunction and dilatation between 3-6 months of age, and they die prematurely from heart failure. The mean survival age of the cardioGRKO mice was 9.3 months, and 97% (38 of 39) of the mice died prior to reaching 12 months of age. Loss of GR in the heart was not accompanied by an increase in fibrosis. To investigate whether cardiomyocyte MR signaling contributes to the pathology in the cardioGRKO mice, we generated for the first time mice lacking both GR and MR in the heart (cardioGRMRKO). Despite showing increased expression of classic hypertrophic marker genes, the cardioGRMRKO mice were protected from the development of cardiac hypertrophy, and no major alterations were observed in the function and chamber size of the left ventricle. Moreover, the cardioGRMRKO mice were protected from premature death as 94% (15 of 16) of the mice survived past the 13 month study endpoint. Microarray analysis revealed marked differences in gene expression profiles between the cardioGRKO and cardioGRMRKO hearts. These findings reveal that cardiomyocyte MR signaling, when unopposed by GR signaling, plays a major role in the progression of cardiac disease. Moreover, they suggest that combining GR agonists with MR antagonists may represent an improved therapeutic approach for treating heart failure.
Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia
Authors: Jianbiao Zhou, Chonglei Bi, Ying Qing Ching, Jing-Yuan Chooi, Xiao Lu, Jessie Yiying Quah, Sabrina Hui-Min Toh, Zit-Liang Chan, Tuan Zea Tan, Phyllis SY Chong, Wee-Joo Chng
Journal: Journal of Hematology & Oncology (2017)

Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML. However, the molecular mechanism by which LIN28B contributes to the development of AML remains largely elusive.We modulated LIN28B expression in AML and non-leukemic cells and investigated functional consequences in cell proliferation, cell cycle, and colony-forming assays. We performed a microarray-based analysis for LIN28B-silencing cells and interrogated gene expression data with different bioinformatic tools. AML mouse xenograft model was used to examine the in vivo function of LIN28B.We demonstrated that targeting LIN28B in AML cells resulted in cell cycle arrest, inhibition of cell proliferation and colony formation, which was induced by de-repression of let-7a miRNA. On the other hand, overexpression of LIN28B promoted cell proliferation. Data point to a mechanism where that inhibition of LIN28B induces metabolic changes in AML cells. IGF2BP1 was confirmed to be a novel downstream target of LIN28B via let-7 miRNA in AML. Notably, ectopic expression of LIN28B increased tumorigenicity, while silencing LIN28B led to slow tumor growth in vivo.In sum, these results uncover a novel mechanism of an important regulatory signaling, LIN28B/let-7/IGF2BP1, in leukemogenesis and provide a rationale to target this pathway as effective therapeutic strategy.
Checking HER2 rates in breast cancer: A 4 year-experience with a nationwide database containing 105,717 records—HER-France.
Authors: Marie-Pierre Chenard, Eric Anger, Marie-Helene Bizollon, Jerome Chetritt, Jean Kapfer, Magali Lacroix, Catherine Lefebvre, Eve Lefort, Elisabeth Luporsi-Gely, Gaetan mac Grogan, Julien Palasse, Thomas Petit, Bruno Poulet, Vincent Rouleau, Emmanuel Watkin, Caroline Egele, Jean-Pierre Bellocq
Journal: Journal of Clinical Oncology (2016)

e12089 Background: AFAQAP (French national quality control association in histopathology) has developed HER-France, a website tool collecting data concerning breast cancer characterization updated by pathologists. The aim of HER-France is to collect, analyze and provide consolidated data to monitor at a national and individual laboratory level the HER2 rate, and also other usual predictive and prognostic factors. It allows every participating lab to compare its own data with the national data (obtained by aggregation of data of all participating labs) to detect possible deviations from reference conditions and amend their practice if necessary. The use of HER-France is cost-free and available to all French Pathology Laboratories (FPL) on a voluntary basis since October 2011. Anonymity of the participants is protected. Roche supports AFAQAP to realize statistical analysis on HER-France database. Methods: Collected data include type of sample (core-biopsy [CB] vs lumpectomy/mastectomy), tumor type and grade, percentage of positive tumor cells for ER, PR and Ki67, mean staining intensity for ER and PR, HER2 score by immunohistochemistry (IHC) and amplification status by in situ hybridization (ISH). Results: Up to October 2015, 124 public and private FPL used HER-France and 105,717 data on specimens have been collected, among which 55,199 on CB. In order to avoid possible bias in the IHC/ISH results due to adverse pre-analytical conditions, focus was made on 45,785 untreated primitive CB of primary tumors and 2,382 metastases. The HER2 overexpression rate average since 2011 is 12.0% on primary tumors and 14.6% on metastases. Most labs that initially were outliers came gradually closer to this average. Regarding primary tumors, HER2 positivity rate was 13.5%, 4.0%, 5.0% and 0.6% for No Special Type (NST), lobular, mucinous and tubular carcinoma respectively. HER2 positivity rate for NST and lobular carcinoma was 2.8%, 11.6% and 26.6% for grade 1, 2 and 3 respectively. Conclusions: HER-France produces indicators to monitor quality of prognostic/predictive factors in breast cancer. It permits FPL to follow their own HER2 overexpression rate and compare their results to the mean national rate.
Outpatient Hematopoietic Grafting in Patients with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells: A Feasibility Study
Authors: Guillermo J. Ruiz-Arguelles, Andrés León-Peña, Emilio Medina-Ceballos, Alejandro Ruiz-Arguelles, Manuel A Ruiz-Delgado, Rodrigo J Ruiz-Delgado, Guillermo Ruiz-Reyes, Manuel Priesca-Marin, Guillermo J Ruiz-Delgado
Journal: Blood (2015)
An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility
Authors: Samuel Lessard, Emily Stern Gatof, Mélissa Beaudoin, Patrick G. Schupp, Falak Sher, Adnan Ali, Sukhpal Prehar, Ryo Kurita, Yukio Nakamura, Esther Baena, Jonathan Ledoux, Delvac Oceandy, Daniel E. Bauer, Guillaume Lettre
Journal: Journal of Clinical Investigation (2017)

The lack of mechanistic explanations for many genotype-phenotype associations identified by GWAS precludes thorough assessment of their impact on human health. Here, we conducted an expression quantitative trait locus (eQTL) mapping analysis in erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (rbc). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4–/– mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine mapped the genetic signal to an erythroid-specific enhancer of ATP2B4. Erythroid cells with a deletion of the ATP2B4 enhancer had abnormally high intracellular calcium levels. These results illustrate the power of combined transcriptomic, epigenomic, and genome-editing approaches in characterizing noncoding regulatory elements in phenotype-relevant cells. Our study supports ATP2B4 as a potential target for modulating rbc hydration in erythroid disorders and malaria infection.
Measuring treatment-induced peripheral neuropathy in patients with cancer.
Authors: Tito R. Mendoza, Loretta A. Williams, Qiuling Shi, Xin Shelley Wang, Shireen Haq, Nazim N Ali, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2016)

e21674 Background: Peripheral neuropathy (PN) is a common complication of cancer treatment. Measurement of PN is necessary for prevention and effective management. An important aspect of PN measurement is patient report. Our objective was to develop a valid, reliable, and brief patient-reported outcome (PRO) measure for PN. Methods: Subjects reported PN from bortezomib, oxaliplatin, or taxane therapies. Qualitative interviews with patients were descriptively analyzed to develop the conceptual framework and generate items for the Treatment-Induced Peripheral Neuropathy Scale (TNAS). A separate cohort of patients completed the EORTC CIPN20 once and the proposed TNAS twice one day apart (test and retest) for item reduction and determination of preliminary validity and reliability using standard psychometric and descriptive analyses. Results: Analysis of 30 patient interviews defined two PN burden domains: sensations and interference. After sixty patients completed the five sensation items and five interference items of the TNAS, a strongly gender-biased interference item (trouble finding/wearing shoes – males: m [mean]=0.64, standard deviation [sd]= 1.646; females: M=3.46, sd=3.758) was dropped, leaving 9 items. The most severe sensation was numbness (M=4.88, sd=2.811) and the greatest interference was with walking (M=3.62, sd=3.232). Reliability testing was acceptable for sensation and interference items (Table). Correlation of the TNAS with the CIPN20 established concurrent validity (Table). Conclusions: The TNAS is a brief, valid, reliable PRO measure of cancer therapy-induced PN for research and practice. Further study on the sensitivity of the TNAS to the development of PN and to defining clinically meaningful differences is planned. Selected TNAS Descriptive and Psychometric Analyses Results Cronbach’s α Sensation Items Interference Items All Items Test 0.78 0.83 0.88 Retest 0.86 0.80 0.90 Interclass Correlations Test-Retest 0.952 0.971 0.967 Pearson Correlations CIPN20- Sensory CIPN20- Motor CIPN20- Autonomic Significance Sensation Items 0.717a 0.631 a 0.243 a0.01 Interference Items 0.551a 0.672a 0.365a a0.01 All Items 0.686a 0.699a 0.327b a0.01, b0.05