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Kenneth Wang

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https://www.readbyqxmd.com/read/29655979/discovery-of-chiral-dihydropyridopyrimidinones-as-potent-selective-and-orally-bioavailable-inhibitors-of-akt
#1
Saravanan Parthasarathy, Kenneth Henry, Huaxing Pei, Josh Clayton, Mark Rempala, Deidre Johns, Oscar De Frutos, Pablo Garcia, Carlos Mateos, Sehila Pleite, Yong Wang, Stephanie Stout, Bradley Condon, Sheela Ashok, Zhohai Lu, William Ehlhardt, Tom Raub, Mei Lai, Sandaruwan Geeganage, Timothy P Burkholder
During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK2 . A key challenge in this program was the poor physicochemical properties of the initial lead compound 5. Integration of structure-based drug design and physical properties-based design resulted in replacement of a highly hydrophobic poly fluorinated aryl ring by a simple trifluoromethyl that led to identification of compound 6 with much improved physicochemical properties...
April 2, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29650408/normothermic-ex-vivo-preservation-with-the-portable-organ-care-system-lung-device-for-bilateral-lung-transplantation-inspire-a-randomised-open-label-non-inferiority-phase-3-study
#2
Gregor Warnecke, Dirk Van Raemdonck, Michael A Smith, Gilbert Massard, Jasleen Kukreja, Federico Rea, Gabriel Loor, Fabio De Robertis, Jayan Nagendran, Kumud K Dhital, Francisco Javier Moradiellos Díez, Christoph Knosalla, Christian A Bermudez, Steven Tsui, Kenneth McCurry, I-Wen Wang, Tobias Deuse, Guy Lesèche, Pascal Thomas, Igor Tudorache, Christian Kühn, Murat Avsar, Bettina Wiegmann, Wiebke Sommer, Arne Neyrinck, Marco Schiavon, Fiorella Calebrese, Nichola Santelmo, Anne Olland, Pierre-Emanuel Falcoz, Andre R Simon, Andres Varela, Joren C Madsen, Marshall Hertz, Axel Haverich, Abbas Ardehali
BACKGROUND: Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. METHODS: In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates...
April 9, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29629122/luminescent-zero-dimensional-organic-metal-halide-hybrids-with-near-unity-quantum-efficiency
#3
Chenkun Zhou, Haoran Lin, Yu Tian, Zhao Yuan, Ronald Clark, Banghao Chen, Lambertus J van de Burgt, Jamie C Wang, Yan Zhou, Kenneth Hanson, Quinton J Meisner, Jennifer Neu, Tiglet Besara, Theo Siegrist, Eric Lambers, Peter Djurovich, Biwu Ma
Single crystalline zero-dimensional (0D) organic-inorganic hybrid materials with perfect host-guest structures have been developed as a new generation of highly efficient light emitters. Here we report a series of lead-free organic metal halide hybrids with a 0D structure, (C4 N2 H14 X)4 SnX6 (X = Br, I) and (C9 NH20 )2 SbX5 (X = Cl), in which the individual metal halide octahedra (SnX6 4- ) and quadrangular pyramids (SbX5 2- ) are completely isolated from each other and surrounded by the organic ligands C4 N2 H14 X+ and C9 NH20 + , respectively...
January 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29622466/comparative-molecular-analysis-of-gastrointestinal-adenocarcinomas
#4
Yang Liu, Nilay S Sethi, Toshinori Hinoue, Barbara G Schneider, Andrew D Cherniack, Francisco Sanchez-Vega, Jose A Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, Jaegil Kim, Walid Chatila, Rehan Akbani, Rupa S Kanchi, Charles S Rabkin, Joseph E Willis, Kenneth K Wang, Shannon J McCall, Lopa Mishra, Akinyemi I Ojesina, Susan Bullman, Chandra Sekhar Pedamallu, Alexander J Lazar, Ryo Sakai, Vésteinn Thorsson, Adam J Bass, Peter W Laird
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE...
April 2, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29617660/genomic-pathway-network-and-immunologic-features-distinguishing-squamous-carcinomas
#5
Joshua D Campbell, Christina Yau, Reanne Bowlby, Yuexin Liu, Kevin Brennan, Huihui Fan, Alison M Taylor, Chen Wang, Vonn Walter, Rehan Akbani, Lauren Averett Byers, Chad J Creighton, Cristian Coarfa, Juliann Shih, Andrew D Cherniack, Olivier Gevaert, Marcos Prunello, Hui Shen, Pavana Anur, Jianhong Chen, Hui Cheng, D Neil Hayes, Susan Bullman, Chandra Sekhar Pedamallu, Akinyemi I Ojesina, Sara Sadeghi, Karen L Mungall, A Gordon Robertson, Christopher Benz, Andre Schultz, Rupa S Kanchi, Carl M Gay, Apurva Hegde, Lixia Diao, Jing Wang, Wencai Ma, Pavel Sumazin, Hua-Sheng Chiu, Ting-Wen Chen, Preethi Gunaratne, Larry Donehower, Janet S Rader, Rosemary Zuna, Hikmat Al-Ahmadie, Alexander J Lazar, Elsa R Flores, Kenneth Y Tsai, Jane H Zhou, Anil K Rustgi, Esther Drill, Ronglei Shen, Christopher K Wong, Joshua M Stuart, Peter W Laird, Katherine A Hoadley, John N Weinstein, Myron Peto, Curtis R Pickering, Zhong Chen, Carter Van Waes
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29616661/shell-feature-a-new-radiomics-descriptor-for-predicting-distant-failure-after-radiotherapy-in-non-small-cell-lung-cancer-and-cervix-cancer
#6
Hongxia Hao, Zhiguo Zhou, Shulong Li, Genevieve Maquilan, Michael R Folkert, Puneeth Iyengar, Kenneth D Westover, Kevin Albuquerque, Fang Liu, Hak Choy, Robert D Timmerman, Lin Yang, Jing Wang
Distant failure is the main cause for human cancer-related mortalities. To develop a model for predicting distant failure in non-small cell lung cancer (NSCLC) and cervix caner (CC) patients, a shell feature, consisting of outer voxels around the tumor boundary, was constructed using pre-treatment positron emission tomography (PET) images from 48 NSCLC patients received stereotactic body radiation therapy (SBRT) and 52 CC patients underwent external beam radiation therapy and concurrent chemotherapy followed with high-dose-rate intracavitary brachytherapy...
April 4, 2018: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29608452/barrett-esophagus-length-nodularity-and-low-grade-dysplasia-are-predictive-of-progression-to-esophageal-adenocarcinoma
#7
Dipesh Solanky, Rajesh Krishnamoorthi, Nicholas Crews, Michele Johnson, Kenneth Wang, Herbert Wolfsen, David Fleischer, Francisco C Ramirez, David Katzka, Navtej Buttar, Prasad G Iyer
GOALS: To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. BACKGROUND: Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned...
March 30, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29593015/an-apoo-pseudogene-on-chromosome-5q-is-associated-with-ldl-c-levels
#8
May E Montasser, Elizabeth A O'Hare, Xiaochun Wang, Alicia D Howard, Rebecca McFarland, James A Perry, Kathleen A Ryan, Kenneth Rice, Cashell E Jaquish, Alan R Shuldiner, Michael Miller, Braxton D Mitchell, Norann A Zaghloul, Yen-Pei C Chang
Background -Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for CVD via its contribution to the development and progression of atherosclerotic lesions. While the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ~20% of the variation in LDL-C levels. Methods -Through an array-based association analysis in 1,102 Amish subjects, we identified a variant strongly associated with LDL-C levels. Using a combination of genetic analyses, zebrafish models, and in in vitro experiments, we sought to identify the causal gene driving this association...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29571807/cumulative-effective-dose-and-cancer-risk-for-pediatric-population-in-repetitive-full-spine-follow-up-imaging-how-micro-dose-is-the-eos-microdose-protocol
#9
Martin Law, Wang-Kei Ma, Damian Lau, Kenneth Cheung, Janice Ip, Lawrance Yip, Wendy Lam
OBJECTIVE: To evaluate and to obtain analytic formulation for the calculation of the effective dose and associated cancer risk using the EOS microdose protocol for scoliotic pediatric patients undergoing full spine imaging at different age of exposure; to demonstrate the microdose protocol capable of delivering lesser radiation dose and hence of further reducing cancer risk induction when compared with the EOS low dose protocol; to obtain cumulative effective dose and cancer risk for both genders scoliotic pediatrics of US and Hong Kong population using the microdose protocol...
April 2018: European Journal of Radiology
https://www.readbyqxmd.com/read/29569716/genetic-and-clonal-dissection-of-osteosarcoma-progression-and-lung-metastasis
#10
Huaiyuan Xu, Xiaojun Zhu, Hua Bao, Tony Wh Shek, Zongwen Huang, Yongqian Wang, Xue Wu, Yong Wu, Zhili Chang, Shuyu Wu, Qinglian Tang, Huizhong Zhang, Anjia Han, Kenneth Mc Cheung, Changye Zou, Raymond Yau, Wai-Yip Ho, Gang Huang, Sellma Batalha, Jinchang Lu, Guohui Song, Yao Kang, Yang W Shao, Ying Lee Lam, Jingnan Shen, Jin Wang
Osteosarcoma is a primary malignant bone tumor that has a high potential to metastasize to lungs. Little is known about the mechanisms underlying the dissemination of OS cancer cells to lungs. We performed whole exome sequencing of 13 OS primary tumors, with matched lung metastases and normal tissues. Phylogenetic analyses revealed that lung metastatic tumors often harbor clones that are nonexistent or rare in the matched primary OS tumors. Spatially and temporally separated lung metastases were from parallel seeding events with a polyphyletic pattern...
March 23, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29563323/evaluation-of-liquid-from-the-papanicolaou-test-and-other-liquid-biopsies-for-the-detection-of-endometrial-and-ovarian-cancers
#11
Yuxuan Wang, Lu Li, Christopher Douville, Joshua D Cohen, Ting-Tai Yen, Isaac Kinde, Karin Sundfelt, Susanne K Kjær, Ralph H Hruban, Ie-Ming Shih, Tian-Li Wang, Robert J Kurman, Simeon Springer, Janine Ptak, Maria Popoli, Joy Schaefer, Natalie Silliman, Lisa Dobbyn, Edward J Tanner, Ana Angarita, Maria Lycke, Kirsten Jochumsen, Bahman Afsari, Ludmila Danilova, Douglas A Levine, Kris Jardon, Xing Zeng, Jocelyne Arseneau, Lili Fu, Luis A Diaz, Rachel Karchin, Cristian Tomasetti, Kenneth W Kinzler, Bert Vogelstein, Amanda N Fader, Lucy Gilbert, Nickolas Papadopoulos
We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease...
March 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29559475/germline-mutations-in-lysine-specific-demethylase-1-lsd1-kdm1a-confer-susceptibility-to-multiple-myeloma
#12
Xiaomu Wei, M Nieves Calvo-Vidal, Siwei Chen, Gang Wu, Maria V Revuelta, Jian Sun, Jinghui Zhang, Michael F Walsh, Kim E Nichols, Vijai Joseph, Carrie Snyder, Celine M Vachon, James D McKay, Shu-Ping Wang, David S Jayabalan, Lauren M Jacobs, Dina Becirovic, Rosalie G Waller, Mykyta Artomov, Agnes Viale, Jayeshkumar Patel, Jude M Phillip, Selina Chen-Kiang, Karen Curtin, Mohamed Salama, Djordje Atanackovic, Ruben Niesvizky, Ola Landgren, Susan L Slager, Lucy A Godley, Jane Churpek, Judy E Garber, Kenneth C Anderson, Mark J Daly, Robert G Roeder, Charles Dumontet, Henry T Lynch, Charles G Mullighan, Nicola J Camp, Kenneth Offit, Robert J Klein, Haiyuan Yu, Leandro Cerchietti, Steven M Lipkin
Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal...
March 20, 2018: Cancer Research
https://www.readbyqxmd.com/read/29554404/relationship-between-dysarthria-and-oral-oropharyngeal-dysphagia-the-current-evidence
#13
Brandon J Wang, Felicia L Carter, Kenneth W Altman
There is a high prevalence of dysphagia among patients with neuromuscular diseases and cerebrovascular diseases, and its consequences can be profound. However, the correlation between dysarthria and oral-oropharyngeal dysphagia remains unclear. We conducted a literature review to define the clinical presentation of both dysarthria and dysphagia in patients with neuromuscular and cerebrovascular diseases. We performed a systematic PubMed search of the English-language literature since 1995. Objective and subjective outcomes instruments were identified for both dysarthria and dysphagia...
March 2018: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/29551072/discovery-and-optimization-of-phosphopantetheine-adenylyltransferase-inhibitors-with-gram-negative-antibacterial-activity
#14
Colin K Skepper, Robert J Moreau, Brent A Appleton, Bret M Benton, Joseph E Drumm, Brian Y Feng, Mei Geng, Andreas Lingel, Yipin Lu, Mulugeta Mamo, Wosenu Mergo, Mina Mostafavi, Christopher M Rath, Micah Steffek, Kenneth T Takeoka, Kyoko Uehara, Lisha Wang, Jun-Rong Wei, Lili Xie, Wenjian Xu, Qiong Zhang, Cindy Li, Javier de Vicente
In the preceding manuscript we described a successful fragment-based lead discovery (FBLD) strategy for discovery of bacterial phosphopantetheine adenylyltransferase inhibitors (PPAT, CoaD). Following several rounds of optimization two promising lead compounds were identified: triazolopyrimidinone 3 and 4-azabenzimidazole 4. Here we disclose our efforts to further optimize these two leads for on-target potency and Gram-negative cellular activity. Enabled by a robust X-ray crystallography system, our structure-based inhibitor design approach delivered compounds with biochemical potencies 4-5 orders of magnitude greater than their respective fragment starting points...
March 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29540821/chain-breakage-in-the-supercooled-liquid-liquid-transition-and-re-entry-of-the-%C3%AE-transition-in-sulfur
#15
Linji Zhang, Yang Ren, Xiuru Liu, Fei Han, Kenneth Evans-Lutterodt, Hongyan Wang, Yali He, Junlong Wang, Yong Zhao, Wenge Yang
Amorphous sulfur was prepared by rapid compression of liquid sulfur at temperatures above the λ-transition for to preserve the high-temperature liquid structure. We conducted synchrotron high-energy X-ray diffraction and Raman spectroscopy to diagnose the structural evolution of amorphous sulfur from room temperature to post-λ-transition temperature. Discontinuous changes of the first and second peaks in atomic pair-distribution-function, g(r), were observed during the transition from amorphous to liquid sulfur...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29537832/model-for-predicting-toxicities-of-metals-and-metalloids-in-coastal-marine-environments-worldwide
#16
Yunsong Mu, Zhen Wang, Fengchang Wu, Buqing Zhong, Mingru Yang, Fuhong Sun, Chenglian Feng, Xiaowei Jin, Kenneth M Y Leung, John P Giesy
Metals can pose hazards to marine species and can adversely affect structures and functions of communities of marine species. However, little is known about how structural properties of metal atoms combined with current geographical and climatic conditions affect their toxic potencies. A mathematical model, based on quantitative structure-activity relationships and species sensitivity distributions (QSAR-SSD) was developed by use of acute toxicities of six metals (Cd, Cr, Cu, Hg, Ni, and Zn) to eight marine species and accessory environmental conditions...
March 14, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29534318/molecular-level-hybridization-of-nafion-with-quantum-dots-for-highly-enhanced-proton-conduction
#17
Wenjia Wu, Yifan Li, Jindun Liu, Jingtao Wang, Yakun He, Kenneth Davey, Shi-Zhang Qiao
Nanophase-separated membranes hold promise for fast molecule or ion transfer. However, development and practical application are significantly hindered by both the difficulty of chemical modification and nanophase instability. This can be addressed by organic-inorganic hybridization of functional fillers with a precise distribution in specific nanophase. Here, a molecular-level hybridization for nanophase-separated Nafion using 2-5 nm quantum dots (QDs) as a new smart filler is demonstrated. Two kinds of QDs are prepared and used: hydrophilic polymer-like QDs (PQDs) and hydrophobic graphene oxide QDs (GQDs)...
March 13, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29533785/systematic-functional-annotation-of-somatic-mutations-in-cancer
#18
Patrick Kwok-Shing Ng, Jun Li, Kang Jin Jeong, Shan Shao, Hu Chen, Yiu Huen Tsang, Sohini Sengupta, Zixing Wang, Venkata Hemanjani Bhavana, Richard Tran, Stephanie Soewito, Darlan Conterno Minussi, Daniela Moreno, Kathleen Kong, Turgut Dogruluk, Hengyu Lu, Jianjiong Gao, Collin Tokheim, Daniel Cui Zhou, Amber M Johnson, Jia Zeng, Carman Ka Man Ip, Zhenlin Ju, Matthew Wester, Shuangxing Yu, Yongsheng Li, Christopher P Vellano, Nikolaus Schultz, Rachel Karchin, Li Ding, Yiling Lu, Lydia Wai Ting Cheung, Ken Chen, Kenna R Shaw, Funda Meric-Bernstam, Kenneth L Scott, Song Yi, Nidhi Sahni, Han Liang, Gordon B Mills
The functional impact of the vast majority of cancer somatic mutations remains unknown, representing a critical knowledge gap for implementing precision oncology. Here, we report the development of a moderate-throughput functional genomic platform consisting of efficient mutant generation, sensitive viability assays using two growth factor-dependent cell models, and functional proteomic profiling of signaling effects for select aberrations. We apply the platform to annotate >1,000 genomic aberrations, including gene amplifications, point mutations, indels, and gene fusions, potentially doubling the number of driver mutations characterized in clinically actionable genes...
March 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29530886/hyperacute-monocyte-gene-response-patterns-are-associated-with-lower-extremity-vein-bypass-graft-failure
#19
Jonathan P Rehfuss, Kenneth M DeSart, Jared M Rozowsky, Kerri A O'Malley, Lyle L Moldawer, Henry V Baker, Yaqun Wang, Rongling Wu, Peter R Nelson, Scott A Berceli
BACKGROUND: Despite being the definitive treatment for lower extremity peripheral arterial disease, vein bypass grafts fail in half of all cases. Early repair mechanisms after implantation, governed largely by the immune environment, contribute significantly to long-term outcomes. The current study investigates the early response patterns of circulating monocytes as a determinant of graft outcome. METHODS: In 48 patients undergoing infrainguinal vein bypass grafting, the transcriptomes of circulating monocytes were analyzed preoperatively and at 1, 7, and 28 days post-operation...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29520796/application-of-statistical-and-computational-methodology-to-predict-brainstem-dosimetry-for-trigeminal-neuralgia-stereotactic-radiosurgery
#20
Qian Du, Chi Zhang, Xiaofeng Zhu, Xiaoying Liang, Chi Zhang, Vivek Verma, Kenneth Follet, Shuo Wang, Qiyong Fan, Rongtao Ma, Sumin Zhou, Dandan Zheng
OBJECTIVES: To apply advanced statistical and computational methodology in evaluating the impact of anatomical and technical variables on normal tissue dosimetry of trigeminal neuralgia (TN) stereotactic radiosurgery (SRS). METHODS: Forty patients treated with LINAC-based TN SRS with 90 Gy maximum dose were randomly selected for the study. Parameters extracted from the treatment plans for the study included three dosimetric output variables: the maximum dose to the brainstem (BSmax), the volume of brainstem that received at least 10 Gy (V10BS), and the volume of normal brain that received at least 12 Gy (V12)...
March 9, 2018: Medical Physics
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