tbuckley/cabot-search huggingface dataset:
Exposure to Low Levels of Lead <i>in Utero</i> and Umbilical Cord Blood DNA Methylation in Project Viva: An Epigenome-Wide Association Study
Authors: Shaowei Wu, Marie-France Hivert, Andres Cardenas, Jia Zhong, Sheryl L. Rifas-Shiman, Golareh Agha, Elena Colicino, Allan C. Just, Chitra Amarasiriwardena, Xihong Lin, Augusto A. Litonjua, Dawn L. DeMeo, Matthew W. Gillman, Robert O. Wright, Emily Oken, Andrea A. Baccarelli
Journal: Environmental Health Perspectives (2017)

Background: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. Objectives: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure. Methods: Among 268 mother–infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal blood samples, and using HumanMethylation450 Bead Chips, we measured genome-wide methylation levels at 482,397 CpG loci in umbilical cord blood and retained 394,460 loci after quality control. After adjustment for batch effects, cell types, and covariates, we used robust linear regression models to examine associations of prenatal lead exposure with DNA methylation in cord blood at epigenome-wide significance level [false discovery rate (FDR)<0.05]. Results: The mean [standard deviation (SD)] maternal RBC lead level was 1.22 (0.63) μg/dL. CpG cg10773601 showed an epigenome-wide significant negative association with prenatal lead exposure (−1.4% per doubling increase in lead exposure; p=2.3×10−7) and was annotated to C-Type Lectin Domain Family 11, Member A (CLEC11A), which functions as a growth factor for primitive hematopoietic progenitor cells. In sex-specific analyses, we identified more CpGs with FDR<0.05 among female infants (n=38) than among male infants (n=2). One CpG (cg24637308), which showed a strong negative association with prenatal lead exposure among female infants (−4.3% per doubling increase in lead exposure; p=1.1×10−06), was annotated to Dynein Heavy Chain Domain 1 gene (DNHD1) which is highly expressed in human brain. Interestingly, there were strong correlations between blood and brain methylation for CpG (cg24637308) based on another independent set of samples with a high proportion of female participants. Conclusion: Prenatal low-level lead exposure was associated with newborn DNA methylation, particularly in female infants. https://doi.org/10.1289/EHP1246
可溶性CD40リガンドではなくてP‐セレクチンおよびTIMP‐2の腹部大動脈りゅう破裂の予測の可能性
Authors: Shinmyo Takafumi, Negoro Nobuyuki, Hazui Hiroshi, Kohbayashi Eiko, Muraoka Hideyuki, Murai Motonobu, Takeda Yoshihiro, Yasuda Hajime, Hoshiga Masaaki, Ishihara Tadashi, Hanafusa Toshiaki
Journal: Circulation (2006)
Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study
Authors: Sana R Mostaghim, Joshua J Gagne, Aaron S Kesselheim
Journal: BMJ (2017)

Objective To determine if drugs approved through the Food and Drug Administration's expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways.Design Retrospective cohort study.Setting FDA public records, January 1997 to April 2016.Participants 382 FDA approved drugs.Main outcome measures The number of times a particular safety section of a label (boxed warning, contraindication, warning, precaution, or adverse reaction) was changed during a drug's time on the market. The relative rate of safety related label changes per year for expedited pathway and non-expedited pathway drugs was compared by forming matched pairs of drugs in the same therapeutic class that were approved within three years of each other.Results Among the 382 eligible new drugs, 135 (35%) were associated with an expedited development or review pathway, and matches were available for 96 (71%). The matched pairs were associated with a total of 1710 safety related label changes during the study period. Expedited pathway drugs were characterized by a rate of 0.94 safety related label changes for each drug per year, compared with 0.68 safety related label changes per year for non-expedited pathway drugs (rate ratio 1.38, 95% confidence interval 1.25 to 1.52). Compared with non-expedited pathway drugs, expedited pathway drugs had a 48% higher rate of changes to boxed warnings and contraindications, the two most clinically important categories of safety warnings (1.48, 95% confidence interval 1.07 to 2.06). A qualitative review of changes to the boxed warning sections revealed that less than 5% (3/67) were changed to describe reduced risks for patients.Conclusions Expedited development and regulatory review pathways can accelerate the availability of new drugs, but drugs approved through these pathways are associated with increased safety related label changes after approval, particularly for the types of changes representing the highest risk warnings. To inform appropriate policy interventions, additional research should explore the causal factors contributing to these different rates.
Heart failure oral therapies at discharge are associated with better outcome in acute heart failure: a propensity‐score matched study
Authors: Etienne Gayat, Mattia Arrigo, Simona Littnerova, Naoki Sato, Jiri Parenica, Shiro Ishihara, Jindrich Spinar, Christian Müller, Veli‐Pekka Harjola, Johan Lassus, Òscar Miró, Aldo P. Maggioni, Khalid F. AlHabib, Dong‐Ju Choi, Jin Joo Park, Yuhui Zhang, Jian Zhang, James L. Januzzi, Katsuya Kajimoto, Alain Cohen‐Solal, Alexandre Mebazaa
Journal: European Journal of Heart Failure (2017)
Association of the Presence of Anti–Carbamylated Protein Antibodies in Early Arthritis With a Poorer Clinical and Radiologic Outcome
Authors: Marie‐Elise Truchetet, Stéphanie Dublanc, Thomas Barnetche, Olivier Vittecoq, Xavier Mariette, Christophe Richez, Patrick Blanco, Michael Mahler, Cécile Contin‐Bordes, Thierry Schaeverbeke
Journal: Arthritis & Rheumatology (2017)

To assess the prevalence of anti-carbamylated protein (anti-CarP) antibodies in a French cohort of patients with early arthritis and to investigate their association with clinical features, final diagnosis, prognosis, and comorbidities.The presence of anti-CarP antibodies among patients with early arthritis in the French Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (n = 720) was determined using enzyme-linked immunosorbent assay. We investigated the prevalence of anti-CarP antibodies in different patient subgroups stratified according to anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) status. Diagnostic and prognostic values of the test were evaluated in this population.Anti-CarP antibodies were present in approximately one-third of the patients (32.6%) and in 23.6% of the patients who were seronegative for both RF and ACPA. Anti-CarP positivity was associated with a more active disease status at baseline and over time. Anti-CarP-positive patients had a significantly higher Disease Activity Score in 28 joints using the erythrocyte sedimentation rate at month 36 than anti-CarP-negative patients (3.1 ± 0.11 versus 2.8 ± 0.06; P = 0.03). Anti-CarP-positive early arthritis was associated with a higher risk of developing erosions after 96 months of follow-up (55.6% of anti-CarP-positive patients versus 37.3% of anti-CarP-negative patients) (odds ratio 2.1 [95% CI 1.2-3.6]; P = 0.009). This association was particularly true when anti-CarP was associated with ACPA positivity. Moreover, ACPA positivity alone in early arthritis was not associated with a higher risk of erosive evolution.Our findings indicate that anti-CarP antibodies are present in one-third of patients with early arthritis and in one-fourth of the RF-negative and ACPA-negative patients. They are particularly associated with a more severe radiographic outcome. Anti-CarP antibody positivity may help to accurately identify those at risk of erosive evolution in an early arthritis population.
Prevention of carboplatin-induced resistance in human ovarian tumor xenografts
Authors: Gerald D. Frenkel, Paula B. Caffrey
Journal: Cancer Research (2005)

1497  The development of drug resistance is a major problem in cancer chemotherapy. Most attempts to circumvent resistance have involved the use of agents to reverse resistance after it has arisen. We have suggested an alternative approach: the use of agents to prevent the development of resistance during chemotherapy, and we have been investigating the use of selenium compounds as preventive agents [Frenkel, G.D. and Caffrey, P.B., A prevention strategy for circumventing drug resistance in cancer chemotherapy. Current Pharmaceutical Design 7: 1595-1614 (2001)]. The prevention approach is particularly relevant in ovarian cancer where the majority of tumors are chemosensitive at diagnosis, but treatment often fails nevertheless, due to the development of resistance during initial chemotherapy. Since platinum-based chemotherapy is the treatment of choice for ovarian cancer, we have examined the ability of selenite to prevent the induction of drug resistance by carboplatin in human ovarian tumor xenografts (derived from A2780 cells). The sensitivity/resistance of a tumor to platinum compounds was determined by measuring tumor growth after a single high dose of carboplatin (50 mg/kg ip) or cisplatin (5.2 mg/kg ip). The growth of control tumors was completely (although temporarily) stopped by these doses; however, pre-treatment with a single low dose of carboplatin (15 mg/kg ip) resulted in the rapid development of resistance to these high doses. Pre-treatment with selenite (3 x 1.5 mg/kg ip) prevented this carboplatin-induced resistance. We also have examined the effectiveness of selenite in combination with these platinum compounds in inhibiting tumor growth during a 3-week course of treatment. The combinations of selenite (1.5 mg/kg, 3 x weekly) with cisplatin (5.2 mg/kg, 2 x weekly) or with carboplatin (20 mg/kg, 2 x weekly) were significantly more effective than either platinum drug alone, despite the fact that selenite itself had no effect on tumor growth. These findings have led to the initiation of a clinical trial on the prevention of carboplatin-induced resistance by selenite and its effect on the chemotherapy of ovarian cancer. The current status of this ongoing Phase I trial at the Cancer Institute of New Jersey is described in another presentation [Gounder, M. et al] at this meeting. This research was supported in part by a grant from the New Jersey Commission on Cancer Research.
NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome
Authors: Kyoko Hayakawa, Anthony M. Formica, Yan Zhou, Daiju Ichikawa, Masanao Asano, Yue-Sheng Li, Susan A. Shinton, Joni Brill-Dashoff, Gabriel Núñez, Richard R. Hardy
Journal: The Journal of Experimental Medicine (2017)

Although B cell development requires expression of the B cell antigen receptor (BCR), it remains unclear whether engagement of self-antigen provides a positive impact for most B cells. Here, we show that BCR engagement by self-ligand during development in vivo results in up-regulation of the Nod-like receptor member Nod1, which recognizes the products of intestinal commensal bacteria. In anti-thymocyte/Thy-1 autoreactive BCR knock-in mice lacking self–Thy-1 ligand, immunoglobulin light chain editing occurred, generating B cells with up-regulated Nod1, including follicular and marginal zone B cells with natural autoreactivity. This BCR editing with increased Nod1 resulted in preferential survival. In normal adult mice, most mature B cells are enriched for Nod1 up-regulated cells, and signaling through Nod1 promotes competitive survival of mature B cells. These findings demonstrate a role for microbial products in promoting survival of mature B cells through up-regulated Nod1, providing a positive effect of BCR engagement on development of most B cells.
Incidence of Primary Immune Thrombocytopenia (ITP) in Adults in One Region of Russia
Authors: Anait L. Melikyan, Elena I Pustovaya, Elena M. Volodicheva, Tamara I Kolosheinova, Marina V Kalinina, Ekaterina N Zotina, Ilya N Kontievskiy, Irina I Zotova, Valentina L Ivanova, Yulia V Gubina, Olga M Bekker, Nadezhda V Kurkina, Irina S Sokolova, Tatiana N Babaeva, Tatiana M Sycheva, Marina T Savinova, Yulia A Sedlova, Naida D Baigisheva, Varvara S Bogova, Elena A Borisenkova, Ekaterina I Kuzub, Ekaterina Yu Kalinovskaya, Michail A Rusinov, Sergei M Kulikov, Valeriy G. Savchenko
Journal: Blood (2016)
骨指向は骨腫瘍の光熱治療のためのペプチド介在骨標的化【Powered by NICT】
Authors: Wang Yitong, Yang Jian, Liu Hongmei, Wang Xinyu, Zhou Zhengjie, Huang Quan, Song Dianwen, Cai Xiaopan, Li Lin, Lin Kaili, Xiao Jianru, Liu Peifeng, Zhang Qiang, Cheng Yiyun
Journal: Biomaterials (2017)
Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic — China, October 1, 2016–August 7, 2017
Authors: James C. Kile, Ruiqi Ren, Liqi Liu, Carolyn M. Greene, Katherine Roguski, A. Danielle Iuliano, Yunho Jang, Joyce Jones, Sharmi Thor, Ying Song, Suizan Zhou, Susan C. Trock, Vivien Dugan, David E. Wentworth, Min Z. Levine, Timothy M. Uyeki, Jacqueline M. Katz, Daniel B Jernigan, Sonja J. Olsen, Alicia M. Fry, Eduardo Azziz-Baumgartner, C. Todd Davis
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Among all influenza viruses assessed using CDC's Influenza Risk Assessment Tool (IRAT), the Asian lineage avian influenza A(H7N9) virus (Asian H7N9), first reported in China in March 2013,* is ranked as the influenza virus with the highest potential pandemic risk (1). During October 1, 2016-August 7, 2017, the National Health and Family Planning Commission of China; CDC, Taiwan; the Hong Kong Centre for Health Protection; and the Macao CDC reported 759 human infections with Asian H7N9 viruses, including 281 deaths, to the World Health Organization (WHO), making this the largest of the five epidemics of Asian H7N9 infections that have occurred since 2013 (Figure 1). This report summarizes new viral and epidemiologic features identified during the fifth epidemic of Asian H7N9 in China and summarizes ongoing measures to enhance pandemic preparedness. Infections in humans and poultry were reported from most areas of China, including provinces bordering other countries, indicating extensive, ongoing geographic spread. The risk to the general public is very low and most human infections were, and continue to be, associated with poultry exposure, especially at live bird markets in mainland China. Throughout the first four epidemics of Asian H7N9 infections, only low pathogenic avian influenza (LPAI) viruses were detected among human, poultry, and environmental specimens and samples. During the fifth epidemic, mutations were detected among some Asian H7N9 viruses, identifying the emergence of high pathogenic avian influenza (HPAI) viruses as well as viruses with reduced susceptibility to influenza antiviral medications recommended for treatment. Furthermore, the fifth-epidemic viruses diverged genetically into two separate lineages (Pearl River Delta lineage and Yangtze River Delta lineage), with Yangtze River Delta lineage viruses emerging as antigenically different compared with those from earlier epidemics. Because of its pandemic potential, candidate vaccine viruses (CVV) were produced in 2013 that have been used to make vaccines against Asian H7N9 viruses circulating at that time. CDC is working with partners to enhance surveillance for Asian H7N9 viruses in humans and poultry, to improve laboratory capability to detect and characterize H7N9 viruses, and to develop, test and distribute new CVV that could be used for vaccine production if a vaccine is needed.
Association of Guideline Adherence for Serial Evaluations With Survival and Adverse Clinical Events in Patients With Asymptomatic Severe Aortic Stenosis
Authors: Aisha Ahmed, Paul Sorajja, Ross F. Garberich, R. Saeid Farivar, Kevin M. Harris, Mario Gössl
Journal: JAMA Cardiology (2017)

For patients with asymptomatic severe aortic stenosis and normal left ventricular function, current practice guidelines empirically recommend serial evaluations every 6 to 12 months. The benefit of this clinical monitoring is unknown.To determine the association of guideline adherence with clinical outcomes in patients with asymptomatic severe aortic stenosis.This retrospective cohort study involved 300 patients with asymptomatic severe aortic stenosis who were seen in the ambulatory Minneapolis Heart Institute at Abbott Northwestern Hospital. Rates of survival and adverse clinical events, including myocardial infarction, stroke, and heart failure hospitalization, were compared between patients who adhered to serial evaluation guidance and those who did not. Medical records were reviewed from July 25, 2007, to December 6, 2012. Data analysis took place from February 4, 2017, to July 10, 2017.All-cause mortality, heart failure hospitalization, and major adverse clinical events during follow-up.The study population of 300 comprised 143 men (47.7%) and had a mean (SD) age of 78.6 (11.5) years. There were no differences in age, race/ethnicity, sex, comorbidities, insurance status, left ventricular function, and aortic stenosis severity between patients with (n = 202) and patients without (n = 98) guideline adherence. Aortic valve replacement (surgical or catheter based) was performed more frequently (54.0% vs 19.4%; P < .001) and the median (interquartile range) time for this performance was earlier (2.2 [1.2-3.6] years vs 3.5 [2.0-5.8] years; P < .001) in patients with guideline adherence. All-cause mortality was higher for nonadherent patients (hazard ratio [HR], 1.57; 95% CI, 1.07-2.30; P < .001), and these patients also had a higher rate of hospital admission for heart failure decompensation in follow-up (HR, 1.66; 95% CI, 1.27-2.18; P < .001). Four-year survival that is free from death and heart failure hospitalization was higher for adherent patients than for nonadherent patients (38.7% vs 23.3%; P < .001), and this difference remained significant in models adjusted for baseline variables (adjusted HR, 1.54; 95% CI, 1.04-2.29; P = .03).The findings of this study support the need for close monitoring of patients with asymptomatic severe aortic stenosis and help to validate current guidelines for serial evaluations. These findings also support initiatives to improve guideline adherence in clinical practice.
新生血管標的化ナノ粒子パクリタキセルによるメトロノーム化学療法を用いた腫瘍プライミング【Powered by NICT】
Authors: Luan Xin, Guan Ying-Yun, F Lovell Jonathan, Zhao Mei, Lu Qin, Liu Ya-Rong, Liu Hai-Jun, Gao Yun-Ge, Dong Xiao, Yang Si-Cong, Zheng Lin, Sun Peng, Fang Chao, Chen Hong-Zhuan
Journal: Biomaterials (2016)
Investigation of a gene signature to predict response to immunomodulatory derivatives for patients with multiple myeloma: an exploratory, retrospective study using microarray datasets from prospective clinical trials
Authors: Manisha Bhutani, Qing Zhang, Reed Friend, Peter M Voorhees, Lawrence J Druhan, Bart Barlogie, Pieter Sonneveld, Gareth J Morgan, James T Symanowski, Belinda R Avalos, Edward A Copelan, Saad Z Usmani
Journal: The Lancet Haematology (2017)
The pathway of PI3K/AKT/mTOR in pulmonary carcinoids.
Authors: Zixuan Zhang, Mengzhao Wang
Journal: Journal of Clinical Oncology (2014)

e22185 Background: We tested some exons’ sequences of genes in PI3K/AKT/mTOR pathway, expected to guide the clinical treatment for pulmonary carcinoid. Methods: We enrolled 17 typical carcinoid patients, 8 atypical carcinoid patients, 17 large cell neuroendocrine carcinoma patients and 12 small cell lung cancer patients in all. Their postoperative specimens were analyzed by nest PCR and Immunohistochemistry simultaneously. Results: We found four missense mutations in pulmonary carcinoid tumors, including 48 exon of mTOR (c.6667C>T), 21 exon of TSC1 (c.2765G>A), 12 exon (c.1265C>T) and 19 exon (c.2148C>C/T) of TSC2. One TSC2 mutation site we found was reported in tuberous sclerosis syndrome (TSC) (c.2148_2149insGAGTCCC, p.Leu717Glufs*6) and the other one was on SNPs (dbSNP: rs137854238; position: chr16:2112505-2112506; c.1265_1266delCC). In addition, the 48 exon mutation in mTOR and 12 exon mutation in TSC2 were occurred in an atypical patients, whose mTOR immunohistochemistry results was weekly positive. Other mutations were occurred in different patients, but their mTOR expressions were all strong positive. However, we did not found same mutations in SCLC and LCNEC. Conclusions: We found new mutations in mTOR, TSC1 and TSC2 in bronchial carcinoid patients and these patients may be benefit from mTOR inhibitors. But large-scale clinical trials still need to verify this result.
Hen's egg allergen in house and bed dust is significantly increased after hen's egg consumption—A pilot study
Authors: V. Trendelenburg, S. Tschirner, B. Niggemann, K. Beyer
Journal: Allergy (2017)

Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty-eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.
薬剤溶出ステント留置後のステント破損による再狭窄に対する経皮的冠動脈インターベンション:de novo病変とステント内再狭窄病変の比較
Authors: Ohtsuru Suguru, Kadota Kazushige, Matsushita Kazuki, Hata Leo, Iwasaki Keiichiro, Miyawaki Hiroshi, Misao Ayumi, Kuwayama Akimune, Miura Katsuya, Ohya Masanobu, Shimada Takenobu, Izawa Yu, Amano Hidewo, Hyodo Yusuke, Hasegawa Daiji, Habara Seiji, Tada Takeshi, Tanaka Hiroyuki, Fuku Yasushi, Gotoh Tsuyoshi, Mitsudo Kazuaki
Journal: Circulation (2016)
Obesity-induced vascular dysfunction and arterial stiffening requires endothelial cell arginase 1
Authors: Anil Bhatta, Lin Yao, Zhimin Xu, Haroldo A. Toque, Jijun Chen, Reem T. Atawia, Abdelrahman Y. Fouda, Zsolt Bagi, Rudolf Lucas, Ruth B. Caldwell, Robert W. Caldwell
Journal: Cardiovascular Research (2017)

Elevation of arginase activity has been linked to vascular dysfunction in diabetes and hypertension by a mechanism involving decreased nitric oxide (NO) bioavailability due to L-arginine depletion. Excessive arginase activity also can drive L-arginine metabolism towards the production of ornithine, polyamines, and proline, promoting proliferation of vascular smooth muscle cells and collagen formation, leading to perivascular fibrosis. We hypothesized that there is a specific involvement of arginase 1 expression within the vascular endothelial cells in this pathology.