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https://www.readbyqxmd.com/read/29050646/worldwide-incidence-and-prevalence-of-inflammatory-bowel-disease-in-the-21st-century-a-systematic-review-of-population-based-studies
#1
Siew C Ng, Hai Yun Shi, Nima Hamidi, Fox E Underwood, Whitney Tang, Eric I Benchimol, Remo Panaccione, Subrata Ghosh, Justin C Y Wu, Francis K L Chan, Joseph J Y Sung, Gilaad G Kaplan
BACKGROUND: Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. METHODS: We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area...
October 13, 2017: Lancet
https://www.readbyqxmd.com/read/29044160/eosinophilia-and-clinical-outcome-of-chronic-obstructive-pulmonary-disease-a-meta-analysis
#2
Jeffery Ho, Wajia He, Matthew T V Chan, Gary Tse, Tong Liu, Sunny H Wong, Czarina C H Leung, Wai T Wong, Sharon Tsang, Lin Zhang, Rose Y P Chan, Tony Gin, Joseph Leung, Benson W M Lau, William K K Wu, Shirley P C Ngai
Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting. We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients. We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016. Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030344/cell-type-specific-chromatin-signatures-underline-regulatory-dna-elements-in-human-induced-pluripotent-stem-cells-and-somatic-cells
#3
Mingtao Zhao, Ning-Yi Shao, Shijun Hu, Ning Ma, Rajini Srinivasan, Fereshteh Jahanbani, Jaecheol Lee, Sophia L Zhang, Michael P Snyder, Joseph C Wu
Rationale: Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is a mystery how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. Objective: We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression...
October 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/28992430/human-induced-pluripotent-stem-cell-hipsc-derived-cells-to-assess-drug-cardiotoxicity-opportunities-and-problems
#4
Tarek Magdy, Adam J T Schuldt, Joseph C Wu, Daniel Bernstein, Paul W Burridge
Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular safety concerns, and several lead molecules that pass the early safety screening make it to market but are later withdrawn owing to severe cardiac side effects. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28991855/cancer-risk-in-2621-chinese-patients-with-inflammatory-bowel-disease-a-population-based-cohort-study
#5
Jacqueline So, Whitney Tang, Wai Keung Leung, Michael Li, Fu Hang Lo, Marc T L Wong, Alex Shun Fung Sze, Chi Man Leung, Steven Woon Choy Tsang, Edwin Hok Shing Shan, Kam Hon Chan, Belsy C Y Lam, Aric J Hui, Wai Hung Chow, Tsz Yiu Lam, Vernon Lam, Tsz Wai Lee, Harris Ho Him Lo, Ching Man Tang, Cheuk Lau Wong, Justin C Y Wu, Francis K L Chan, Joseph J Y Sung, Marcus Harbord, Siew C Ng
BACKGROUND: Studies on cancer risk in inflammatory bowel disease (IBD) have yielded inconsistent results. We conducted a population-based study to determine the risk of cancer in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Using a territory-wide IBD registry in Hong Kong, we identified 2621 patients with IBD and no history of cancer from 1990 to 2016. We followed them from diagnosis until either September 2016, cancer development, proctocolectomy, or death...
November 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28977353/incremental-value-of-right-heart-metrics-and-exercise-performance-to-well-validated-risk-scores-in-dilated-cardiomyopathy
#6
Kegan J Moneghetti, Genevieve Giraldeau, Matthew T Wheeler, Yukari Kobayashi, Bojan Vrtovec, David Boulate, Tatiana Kuznetsova, Ingela Schnittger, Joseph C Wu, Jonathan Myers, Euan Ashley, Francois Haddad
Aims: Risk stratification in heart failure (HF) relies on several established clinical risk scores, however, myocardial deformation, right heart metrics, and exercise performance have not usually been considered. This study sought to assess the incremental value of advanced echocardiographic and cardiopulmonary exercise testing (CPX) parameters to validated risk scores in HF. Methods and results: The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) scores were applied to 208 ambulatory patients with dilated cardiomyopathy (DCM) who completed echocardiography in conjunction with CPX as part of the Stanford Exercise Testing registry...
July 21, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/28974735/control-of-western-corn-rootworm-diabrotica-virgifera-virgifera-reproduction-through-plant-mediated-rna-interference
#7
Xiping Niu, Adane Kassa, Xu Hu, Jonathan Robeson, Mollie McMahon, Nina M Richtman, Joseph P Steimel, Bliss M Kernodle, Virginia C Crane, Gary Sandahl, Julie L Ritland, James K Presnail, Albert L Lu, Gusui Wu
RNA interference (RNAi) in transgenic maize has recently emerged as an alternative mode of action for western corn rootworm (Diabrotica virgifera virgifera) control which can be combined with protein-based rootworm control options for improved root protection and resistance management. Currently, transgenic RNAi-based control has focused on suppression of genes that when silenced lead to larval mortality. We investigated control of western corn rootworm reproduction through RNAi by targeting two reproductive genes, dvvgr and dvbol, with the goal of reducing insect fecundity as a new tool for pest management...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28961760/endoscopic-and-histologic-mucosal-healing-in-ulcerative-colitis-in-the-first-year-of-diagnosis-results-from-a-population-based-inception-cohort-from-six-countries-in-asia
#8
Choy May Leung, Whitney Tang, Kyaw Moe, Gani Niamul, Satimai Aniwan, Julajak Limsrivilai, Yu-Fang Wang, Qin Ouyang, Marcellus Simadibrata, Murdani Abdullah, David E Ong, Hon Ho Yu, Jinwen Zhang, Jessica Ching, Justin C Wu, Francis K Chan, Joseph J Y Sung, Siew C Ng
Background and Aims: Mucosal healing is associated with improved long-term clinical outcomes in patients with ulcerative colitis. This population-based study assessed endoscopic and histologic mucosal healing within the first year of diagnosis. Methods: Consecutive patients diagnosed with ulcerative colitis from 6 countries in Asia were prospectively enrolled. Clinical demographics, blood markers and inflammatory activity were assessed at baseline. Mayo score and Nancy index were used to assess endoscopic and histologic activities, respectively...
July 26, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28957668/aldosterone-sensing-neurons-in-the-nts-exhibit-state-dependent-pacemaker-activity-and-drive-sodium-appetite-via-synergy-with-angiotensin-ii-signaling
#9
Jon M Resch, Henning Fenselau, Joseph C Madara, Chen Wu, John N Campbell, Anna Lyubetskaya, Brian A Dawes, Linus T Tsai, Monica M Li, Yoav Livneh, Qingen Ke, Peter M Kang, Géza Fejes-Tóth, Anikó Náray-Fejes-Tóth, Joel C Geerling, Bradford B Lowell
Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS(HSD2) neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS(HSD2) neuron activation, identify the circuit by which NTS(HSD2) neurons drive appetite, and uncover an interaction between the NTS(HSD2) circuit and ATII signaling...
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28930010/disease-burden-of-clostridium-difficile-infections-in-adults-hong-kong-china-2006-2014
#10
Jeffery Ho, Rudin Z W Dai, Thomas N Y Kwong, Xiansong Wang, Lin Zhang, Margaret Ip, Raphael Chan, Peter M K Hawkey, Kelvin L Y Lam, Martin C S Wong, Gary Tse, Matthew T V Chan, Francis K L Chan, Jun Yu, Siew C Ng, Nelson Lee, Justin C Y Wu, Joseph J Y Sung, William K K Wu, Sunny H Wong
Cross-sectional studies suggest an increasing trend in incidence and relatively low recurrence rates of Clostridium difficile infections in Asia than in Europe and North America. The temporal trend of C. difficile infection in Asia is not completely understood. We conducted a territory-wide population-based observational study to investigate the burden and clinical outcomes in Hong Kong, China, over a 9-year period. A total of 15,753 cases were identified, including 14,402 (91.4%) healthcare-associated cases and 817 (5...
October 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28920457/implementing-a-tiered-approach-to-bioanalytical-method-validation-for-large-molecule-ligand-binding-assay-methods-in-pharmacokinetic-assessments
#11
Rebecca G Watson, Adrienne Clements-Egan, Allen Schantz, Mark Ware, Bonnie Wu, Tong-Yuan Yang, Gopi Shankar, Joseph C Marini
Bioanalytical methods must enable the delivery of data that meet sound, scientifically justified, fit-for-purpose criteria. At early phases of biotherapeutic drug development, suitable criteria of a ligand-binding assay could be met for pharmacokinetic (PK) in-study sample testing without a full validation defined by regulatory guidelines. To ensure fit-for-purpose methods support PK testing through all phases of biotherapeutic development, three tiers of method validation - regulatory, scientific and research validations - are proposed...
September 18, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28881876/accuracy-of-faecal-immunochemical-test-to-predict-endoscopic-and-histological-healing-in-ulcerative-colitis-a-prospective-study-based-on-validated-histological-scores
#12
Hai Yun Shi, Francis K L Chan, Anthony W H Chan, Akira Higashimori, Moe Kyaw, Jessica Y L Ching, Arthur K C Luk, Sunny H Wong, Justin C Y Wu, Joseph J Y Sung, Siew C Ng
Background and Aims: Endoscopic and histological healing are associated with improved clinical outcomes in ulcerative colitis [UC]. We aimed to investigate the predictive value of faecal immunochemical test [FIT] for endoscopic and histological healing in UC. Methods: We measured quantitative FIT and faecal calprotectin [FC] in 140 consecutive UC patients who underwent colonoscopy. We assessed the diagnostic accuracy of FIT for predicting endoscopic healing using the Mayo endoscopic subscore [MES 0/1] and for histological healing using the Geboes score [< 2...
September 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28875984/multiscale-technologies-for-treatment-of-ischemic-cardiomyopathy
#13
REVIEW
Morteza Mahmoudi, Mikyung Yu, Vahid Serpooshan, Joseph C Wu, Robert Langer, Richard T Lee, Jeffrey M Karp, Omid C Farokhzad
The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease...
September 6, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#14
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28859893/predictors-of-long-term-survival-after-renal-cancer-surgery
#15
Joseph Zabell, Sevag Demirjian, Brian R Lane, Ithaar H Derweesh, Sudhir Isharwal, Chalairat Suk-Ouichai, Jitao Wu, Diego Aguilar Palacios, Steven C Campbell
PURPOSE: Renal cancer surgery (RCS) can adversely impact long-term function and survival. We evaluate predictors of chronic kidney disease (CKD) at 5-years and non-renal cancer mortality (NRCM) 10-years after RCS. MATERIALS AND METHODS: We analyzed 4,283 patients undergoing RCS (1997-2008). Radical nephrectomy (RN) and partial nephrectomy (PN) were performed in 46%/54% of patients, respectively. Cumulative probability ordinal modeling was used to predict CKD status 5-years after surgery and multivariable logistic regression for predicting NRCM at 10-years...
August 28, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28852707/design-and-rationale-for-examining-neuroimaging-genetics-in-ischemic-stroke-the-mri-genie-study
#16
Anne-Katrin Giese, Markus D Schirmer, Kathleen L Donahue, Lisa Cloonan, Robert Irie, Stefan Winzeck, Mark J R J Bouts, Elissa C McIntosh, Steven J Mocking, Adrian V Dalca, Ramesh Sridharan, Huichun Xu, Petrea Frid, Eva Giralt-Steinhauer, Lukas Holmegaard, Jaume Roquer, Johan Wasselius, John W Cole, Patrick F McArdle, Joseph P Broderick, Jordi Jimenez-Conde, Christina Jern, Brett M Kissela, Dawn O Kleindorfer, Robin Lemmens, Arne Lindgren, James F Meschia, Tatjana Rundek, Ralph L Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Vincent Thijs, Daniel Woo, Bradford B Worrall, Steven J Kittner, Braxton D Mitchell, Jonathan Rosand, Polina Golland, Ona Wu, Natalia S Rost
OBJECTIVE: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI-GENetics Interface Exploration (MRI-GENIE) study. METHODS: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributed MRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants...
October 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28841599/treating-breast-conservation-therapy-defects-with-brava-and-fat-grafting-technique-outcomes-and-safety-profile
#17
Michael N Mirzabeigi, Michael Lanni, Catherine S Chang, Ran Y Stark, Stephen J Kovach, Liza C Wu, Joseph M Serletti, Louis P Bucky
BACKGROUND: Fat grafting has been demonstrated as a means of reconstructing breast conservation therapy defects. However, there is continued uncertainty regarding its clinical efficacy and oncologic safety. Furthermore, the role of external preexpansion (i.e., with the Brava device) remains unclear in this setting. The purpose of this study was to examine the safety and clinical outcomes of Brava/fat grafting following breast conservation therapy. METHODS: A retrospective chart review was performed on all patients undergoing fat grafting following breast conservation therapy...
September 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28834758/alloimmune-responses-of-humanized-mice-to-human-pluripotent-stem-cell-therapeutics
#18
Nigel G Kooreman, Patricia E de Almeida, Jonathan P Stack, Raman V Nelakanti, Sebastian Diecke, Ning-Yi Shao, Rutger-Jan Swijnenburg, Veronica Sanchez-Freire, Elena Matsa, Chun Liu, Andrew J Connolly, Jaap F Hamming, Paul H A Quax, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Joseph C Wu
There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28815832/targeting-the-genome-stability-hub-ctf4-by-stapled-peptide-design
#19
Yuteng Wu, Fabrizio Villa, Joseph Maman, Yu Heng Lau, Lina Dobnikar, Aline C Simon, Karim Labib, David R Spring, Luca Pellegrini
The exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the synthetic lethality approach. Herein, we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28783718/integrative-clinical-genomics-of-metastatic-cancer
#20
Dan R Robinson, Yi-Mi Wu, Robert J Lonigro, Pankaj Vats, Erin Cobain, Jessica Everett, Xuhong Cao, Erica Rabban, Chandan Kumar-Sinha, Victoria Raymond, Scott Schuetze, Ajjai Alva, Javed Siddiqui, Rashmi Chugh, Francis Worden, Mark M Zalupski, Jeffrey Innis, Rajen J Mody, Scott A Tomlins, David Lucas, Laurence H Baker, Nithya Ramnath, Ann F Schott, Daniel F Hayes, Joseph Vijai, Kenneth Offit, Elena M Stoffel, J Scott Roberts, David C Smith, Lakshmi P Kunju, Moshe Talpaz, Marcin Cieślik, Arul M Chinnaiyan
Metastasis is the primary cause of cancer-related deaths. Although The Cancer Genome Atlas has sequenced primary tumour types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here we perform whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1...
August 17, 2017: Nature
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