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https://www.readbyqxmd.com/read/28941407/targeted-neurogenesis-pathway-based-gene-analysis-identifies-adora2a-associated-with-hippocampal-volume-in-mild-cognitive-impairment-and-alzheimer-s-disease
#1
Emrin Horgusluoglu-Moloch, Kwangsik Nho, Shannon L Risacher, Sungeun Kim, Tatiana Foroud, Leslie M Shaw, John Q Trojanowski, Paul S Aisen, Ronald C Petersen, Clifford R Jack, Simon Lovestone, Andrew Simmons, Michael W Weiner, Andrew J Saykin
Alzheimer's disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in 2 regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the subventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD, and many of the molecular players in AD are also modulators of adult neurogenesis. However, the genetic mechanisms underlying adult neurogenesis in AD have been underexplored...
August 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28941377/guiding-principles-of-value-creation-through-collaborative-innovation-in-pharmaceutical-research
#2
Liang Schweizer, Jeff He
Open innovation has become the main trend in pharmaceutical research. Potential obstacles and pitfalls of collaborations often lead to missed opportunities and/or poorly executed partnerships. This paper aims to provide a framework that facilitates the execution of successful collaborations. We start by mapping out three checkpoints onto early-stage collaborative partnerships: inception, ignition and implementation. Different value types and value drivers are then laid out for each stage of the partnership...
September 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28941361/hepatitis-c-virus-testing-for-case-identification-in-persons-born-during-1945-1965-results-from-three-randomized-controlled-trials
#3
Anthony K Yartel, David B Rein, Kimberly Ann Brown, Katherine Krauskopf, Omar I Massoud, Cynthia Jordan, Natalie Kil, Alex D Federman, David R Nerenz, Joanne E Brady, Danielle L Kruger, Bryce D Smith
CDC and U.S. Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born during 1945-1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions to usual care using an independently-designed randomized controlled trial...
September 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28938744/an-improved-ivm-method-for-cumulus-oocyte-complexes-from-small-follicles-in-polycystic-ovary-syndrome-patients-enhances-oocyte-competence-and-embryo-yield
#4
F Sánchez, F Lolicato, S Romero, M De Vos, H Van Ranst, G Verheyen, E Anckaert, J E J Smitz
STUDY QUESTION: Are meiotic and developmental competence of human oocytes from small (2-8 mm) antral follicles improved by applying an optimized IVM method involving a prematuration step in presence of C-Type Natriuretic Peptide (CNP) followed by a maturation step in presence of FSH and Amphiregulin (AREG)? SUMMARY ANSWER: A strategy involving prematuration culture (PMC) in the presence of CNP followed by IVM using FSH + AREG increases oocyte maturation potential leading to a higher availability of Day 3 embryos and good-quality blastocysts for single embryo transfer...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938715/the-harm-done-to-reproducibility-by-the-culture-of-null-hypothesis-significance-testing
#5
Timothy L Lash
In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated...
September 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28938686/incidence-and-clearance-of-oral-human-papillomavirus-infection-a-population-based-cohort-study-in-rural-china
#6
Chaoting Zhang, Fangfang Liu, Yaqi Pan, Qiuju Deng, Xiang Li, Zhonghu He, Mengfei Liu, Tao Ning, Chuanhai Guo, Yongmei Liang, Ruiping Xu, Lixin Zhang, Hong Cai, Yang Ke
The natural history of oral human papillomavirus (HPV) infection which is linked with the increased incidence of oropharyngeal squamous cell cancer (OPSCC) has been incompletely studied. Oral swab specimens and questionnaire data were obtained bi-annually for up to 6 visits from 4314 healthy adults aged 25-69 in rural Anyang, China. HPV infection status was evaluated with PCR-based sequencing. Participants with at least two consecutive valid HPV results within the study period were included in the incidence and clearance analysis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938662/meta-analysis-of-the-association-between-the-inflammatory-potential-of-diet-and-colorectal-cancer-risk
#7
Yu Fan, Xin Jin, Changfeng Man, Zhenjun Gao, Xiaoyan Wang
OBJECTIVES: The inflammatory potential of diet has been inconsistently linked to colorectal cancer (CRC) risk. This meta-analysis aimed to evaluate the association of the inflammatory potential of diet, as estimated by the dietary inflammatory index (DII) score, with CRC risk. MATERIALS AND METHODS: The PubMed and Embase databases were searched for relevant studies from inception to February 2017. All cohort and case-control studies investigating the association of the DII score with CRC risk were selected...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938573/iatc-mhyb-a-hybrid-multi-label-classifier-for-predicting-the-classification-of-anatomical-therapeutic-chemicals
#8
Xiang Cheng, Shu-Guang Zhao, Xuan Xiao, Kuo-Chen Chou
Recommended by the World Health Organization (WHO), drug compounds have been classified into 14 main ATC (Anatomical Therapeutic Chemical) classes according to their therapeutic and chemical characteristics. Given an uncharacterized compound, can we develop a computational method to fast identify which ATC class or classes it belongs to? The information thus obtained will timely help adjusting our focus and selection, significantly speeding up the drug development process. But this problem is by no means an easy one since some drug compounds may belong to two or more than two ATC classes...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938542/the-immune-checkpoint-molecule-v-set-ig-domain-containing-4-is-an-independent-prognostic-factor-for-multiple-myeloma
#9
Jin Roh, Youkyoung Jeon, A-Neum Lee, Sang Min Lee, YeonMee Kim, Chang Ohk Sung, Chan-Jeoung Park, Jung Yong Hong, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Inhak Choi, Chan-Sik Park
Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938500/acceptability-of-two-colorectal-cancer-screening-tests-pain-as-a-key-determinant-in-sigmoidoscopy
#10
Benedicte Kirkøen, Paula Berstad, Edoardo Botteri, Eirin Dalén, Jens Aksel Nilsen, Geir Hoff, Thomas de Lange, Tomm Bernklev
Background Participants' experience with a screening test can influence adherence, and therefore the efficacy of screening programs. We compared screening with unsedated flexible sigmoidoscopy and fecal immunochemical testing (FIT) for participants' satisfaction with the decision and for willingness to repeat colorectal cancer screening. Methods In a prospective, randomized trial 3257 individuals (50 - 74 years) were invited to either flexible sigmoidoscopy or FIT (1:1), of whom 1650 took up the offer (52...
September 22, 2017: Endoscopy
https://www.readbyqxmd.com/read/28938478/roux-en-y-gastric-bypass-surgery-has-unique-effects-on-postprandial-fgf21-but-not-fgf19-secretion
#11
Lydia-Ann L S Harris, Gordon I Smith, Bettina Mittendorfer, J Christopher Eagon, Adewole L Okunade, Bruce W Patterson, Samuel Klein
Context: Fibroblast growth factors (FGF) 19 and FGF21 are secreted by the intestine and liver in response to macronutrient intake. Intestinal resection and reconstruction via bariatric surgery may alter their regulation. Objective: We tested the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery, but not matched weight loss induced by laparoscopic adjustable gastric banding (LAGB), increases postprandial plasma FGF19 and FGF21 concentrations...
August 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938471/low-vitamin-b12-in-pregnancy-is-associated-with-adipose-derived-circulating-mirs-targeting-ppar%C3%AE-and-insulin-resistance
#12
Antonysunil Adaikalakoteswari, Manu Vatish, Mohammad Tauqeer Alam, Sascha Ott, Sudhesh Kumar, Ponnusamy Saravanan
Context: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance(IR) and gestational diabetes(GDM). B12 is a key co-factor in 1-carbon metabolism. Objective: We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs(miRs) during adipocyte differentiation and results in an adverse metabolic phenotype. Design, settings and main-outcome measure: Human pre-adipocyte cell-line(Chub-S7) were differentiated in various B12 concentrations: Control(500nM), LowB12(0...
September 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938435/the-role-of-sequential-bmp-signaling-in-directing-human-embryonic-stem-cells-to-bipotential-gonadal-cells
#13
Kirsi Sepponen, Karolina Lundin, Katri Knuus, Pia Väyrynen, Taneli Raivio, Juha S Tapanainen, Timo Tuuri
Context: Human gonads arise as a pair of epithelial ridges on the surface of intermediate mesoderm (IM)-derived mesonephros. Toxic environmental factors and mutations in various genes are known to disturb normal gonadal development, but due to a lack of suitable in vitro models, detailed studies characterizing the molecular basis of the observed defects have not been performed. Objective: Our objective was to establish an in vitro method for studying differentiation of bipotential gonadal progenitors using human embryonic stem cells (hESCs), and to investigate the role of bone morphogenetic protein (BMP) in gonadal differentiation...
August 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938431/association-of-thyroid-function-with-maternal-and-neonatal-homocysteine-concentrations
#14
Mirjana Barjaktarovic, Eric A P Steegers, Vincent W V Jaddoe, Yolanda B de Rijke, Theo J Visser, Tim I M Korevaar, Robin P Peeters
Context: High homocysteine concentrations are associated with maternal pregnancy complications and low birth weight, jaundice and cerebrovascular accidents in neonates. Thyroid hormone may interfere with homocysteine metabolism via stimulation of vitamin B12- and folate-dependent processes and via effects on enzymes of the re-methylation pathway. Objective: Investigating the associations of maternal and neonatal thyroid function with homocysteine during pregnancy and after delivery, respectively...
September 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938429/effect-of-preconception-impaired-glucose-tolerance-on-pregnancy-outcomes-in-women-with-polycystic-ovary-syndrome
#15
Daimin Wei, Bo Zhang, Yuhua Shi, Lin Zhang, Shigang Zhao, Yanzhi Du, Lizhen Xu, Richard S Legro, Heping Zhang, Zi-Jiang Chen
Context: Women with polycystic ovary syndrome (PCOS) commonly have intrinsic insulin resistance and are recommended to undergo an oral glucose tolerance test (OGTT) for diabetes screening. However, the effect of preconception impaired glucose tolerance (IGT) on pregnancy is still unclear. Objective: To prospectively assess the effect of preconception IGT on pregnancy outcomes. Design, Setting, Patients, Intervention(s) and Main Outcome Measure(s): This was a secondary analysis of a multicenter randomized trial in 1508 women with PCOS comparing live birth and obstetric complications between fresh and frozen embryo transfer...
August 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938406/ct-derived-body-fat-distribution-and-incident-cardiovascular-disease-the-multi-ethnic-study-of-atherosclerosis
#16
Morgana L Mongraw-Chaffin, Matthew A Allison, Gregory L Burke, Michael H Criqui, Kunihiro Matsushita, Pamela Ouyang, Ravi V Shah, Christina M Shay, Cheryl A M Anderson
Background: Visceral fat has been shown to be associated with increased cardiometabolic risk, but the role of subcutaneous fat remains unclear, and evidence from diverse populations is lacking. We hypothesized that visceral, but not subcutaneous fat, would be independently associated with incident cardiovascular disease and all-cause mortality. Methods: Among 1,910 participants from the Multi-Ethnic Study of Atherosclerosis with abdominal fat measurements from computed tomography (CT) scans and followed for an average of 9...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938403/change-in-weight-and-body-mass-index-associated-with-all-cause-mortality-in-korea-a-nationwide-longitudinal-study
#17
Yang-Hyun Kim, Seon Mee Kim, Kyung-do Han, Jang-Won Son, Seong-Su Lee, Sang Woo Oh, Won-Young Lee, Soon Jib Yoo
Background: Many studies have reported conflicting evidence on the association between weight change and mortality. Objective: We investigated the association between weight change and subsequent all-cause mortality, using a large-scale population-based cohort from the National Health Insurance System health checkup data between 2005 and 2015. Methods: A total of 11,524,763 subjects aged over 20 years were included. Weight was measured every two years and weight change over 4 years was divided into eight categories, from weight loss ≥15% to weight gain ≥20%, for every 5% of weight change...
August 24, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938401/n-glycomic-profiling-of-pheochromocytomas-and-paragangliomas-separates-metastatic-and-non-metastatic-disease
#18
Helena Leijon, Tuomas Kaprio, Annamari Heiskanen, Tero Satomaa, Jukka O Hiltunen, Markku M Miettinen, Johanna Arola, Caj Haglund
Context: No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a new diagnostic tool. Objective: To identify differences in N-glycomic profiles of primary metastasized and non-metastasized pheochromocytomas and paragangliomas...
August 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938338/mortality-implications-of-lower-dbp-with-lower-achieved-systolic-pressures-in-coronary-artery-disease-long-term-mortality-results-from-the-international-verapamil-trandolapril-study-us-cohort
#19
Anita Wokhlu, Steven M Smith, Yan Gong, Eileen M Handberg, Islam Y Elgendy, Anthony A Bavry, Rhonda M Cooper-DeHoff, Carl J Pepine
OBJECTIVES: A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort. METHODS: We categorized 17 131 hypertensive patients from the INternational VErapamil-trandolapril STudy US cohort, aged at least 50 years with CAD, by mean achieved SBP (<120, 120 to <130, 130 to <140, and ≥140 mmHg) and DBP tertiles (low, middle, and high per SBP category) during active follow-up...
September 21, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28938266/identification-of-an-optimal-cut-off-for-drain-fluid-amylase-on-postoperative-day-1-for-predicting-clinically-relevant-fistula-after-distal-pancreatectomy-a-multi-institutional-analysis-and-external-validation
#20
Laura Maggino, Giuseppe Malleo, Claudio Bassi, Valentina Allegrini, Joal D Beane, Ross M Beckman, Bofeng Chen, Euan J Dickson, Jeffrey A Drebin, Brett L Ecker, Douglas L Fraker, Michael G House, Nigel B Jamieson, Ammar A Javed, Stacy J Kowalsky, Major K Lee, Matthew T McMillan, Robert E Roses, Roberto Salvia, Vicente Valero, Lavanniya K P Velu, Christopher L Wolfgang, Amer H Zureikat, Charles M Vollmer
OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016)...
September 21, 2017: Annals of Surgery
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