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https://www.readbyqxmd.com/read/28088938/clinical-analysis-of-54-cases-of-large-area-soft-tissue-avulsion-in-the-lower-limb
#1
Yu Chen, Lei Liu
OBJECTIVE: To assess the clinical curative effect of different treatment methods for large area avulsion injury in the lower limb. METHODS: Between January 2010 and December 2013, 54 patients with large area avulsion injury in the lower limb were treated in the trauma center of our hospital, including 34 males and 20 females with a mean age of 35.7 years (range, 16-65 years). The injury mechanism was traffic accident in 44 cases, hitting by heavy objects in 8 cases, and fall from height in 2 cases, involving 31 thighs, 19 legs and 4 feet involved...
December 1, 2016: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
https://www.readbyqxmd.com/read/28072524/common-hits-approach-combining-pharmacophore-modeling-and-molecular-dynamics-simulations
#2
Marcus Wieder, Arthur Garon, Ugo Perricone, Stefan Boresch, Thomas Seidel, Anna Maria Almerico, Thierry Langer
We present a new approach that incorporates flexibility based on extensive MD simulations of protein-ligand complexes into structure based pharmacophore modeling and virtual screening. The approach uses the multiple coordinate sets saved during the MD simulations and generates for each frame a pharmacophore model. Pharmacophore models with the same pharmacophore features are pooled. In this way the high number of pharmacophore models that results from the MD simulation is reduced to only a few hundred representative pharmacophore models...
January 10, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28059695/a-systematic-scoping-review-of-the-domains-and-innovations-in-secondary-uses-of-digitised-health-related-data
#3
Ann R R Robertson, Ulugbek Nurmatov, Harpreet S Sood, Kathrin Cresswell, Pam Smith, Aziz Sheikh
BACKGROUND: Substantial investments are being made in health -information -technology (HIT) based on assumptions that these systems will save costs through increased quality, safety and efficiency of care provision. Whilst -short-term -benefits have often proven difficult to demonstrate, there is increasing interest in achieving benefits in the medium and long term through secondary uses of -HIT-derived data. AIMS: We aimed to describe the range of secondary uses of HIT-derived data in the international literature and identify innovative developments of particular relevance to UK policymakers and managers...
November 10, 2016: Journal of Innovation in Health Informatics
https://www.readbyqxmd.com/read/28057719/structure-and-inhibitor-specificity-of-the-pctaire-family-kinase-cdk16
#4
Sarah E Dixon-Clarke, Saifeldin N Shehata, Tobias Krojer, Timothy D Sharpe, Frank von Delft, Kei Sakamoto, Alex N Bullock
CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent protein kinase (CDK) family that has emerged as a key regulator of neurite outgrowth, vesicle trafficking and cancer cell proliferation. CDK16 is activated through binding to cyclin Y via a phosphorylation-dependent 14-3-3 interaction and has an unique consensus substrate phosphorylation motif compared to conventional CDKs. To elucidate the structure and inhibitor binding properties of this atypical CDK we screened the CDK16 kinase domain against different inhibitor libraries and determined the co-structures of identified hits...
January 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28031390/methylphenidate-cognition-and-epilepsy-a-double-blind-placebo-controlled-single-dose-study
#5
Jesse Adams, Valerie Alipio-Jocson, Katherine Inoyama, Victoria Bartlett, Saira Sandhu, Jemima Oso, John J Barry, David W Loring, Kimford Meador
OBJECTIVE: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. METHODS: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test...
December 28, 2016: Neurology
https://www.readbyqxmd.com/read/28029775/combining-a-ru-ii-building-block-and-rapid-screening-approach-to-identify-dna-structure-selective-light-switch-compounds
#6
Erin Wachter, Diego Moyá, Edith C Glazer
A chemically reactive Ru(II) "building block", able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent "light switch" dipyrido-[3,2-a:2',3'-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA...
December 28, 2016: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28005139/-heparin-induced-thrombocytopenia-type%C3%A2-ii-hit%C3%A2-ii-a%C3%A2-medical-economic-view
#7
R Riedel, A Schmieder, A Koster, S Kim, G Baumgarten, J C Schewe
BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered...
December 22, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/27984258/incidental-learning-a-brief-valid-measure-of-memory-based-on-the-wais-iv-vocabulary-and-similarities-subtests
#8
Robert J Spencer, Jaclyn Reckow, Lauren L Drag, Linas A Bieliauskas
OBJECTIVE: We assessed the validity of a brief incidental learning measure based on the Similarities and Vocabulary subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). BACKGROUND: Most neuropsychological assessments for memory require intentional learning, but incidental learning occurs without explicit instruction. Incidental memory tests such as the WAIS-III Symbol Digit Coding subtest have existed for many years, but few memory studies have used a semantically processed incidental learning model...
December 2016: Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology
https://www.readbyqxmd.com/read/27981900/pharmacophore-and-docking-guided-virtual-screening-study-for-discovery-of-type-i-inhibitors-of-vegfr-2-kinase
#9
Heena R Bhojwani, Urmila J Joshi
BACKGROUND: Kinase domain of VEGFR-2 displays conformational flexibility which leads to existence of two kinds of inhibitors viz. type I and type II inhibitors. They exhibit different binding modes and this necessitates the development of separate pharmacophore models for them. METHODS: The virtual screening study for discovery of type I inhibitors of VEGFR-2 kinase was done by using combined pharmacophore (generated using PHASE and validated by 3D-QSAR) and docking (Glide) based approach...
December 14, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27980108/dual-hdac-and-pi3k-inhibitor-cudc-907-downregulates-myc-and-suppresses-growth-of-myc-dependent-cancers
#10
Kaiming Sun, Ruzanna Atoyan, Mylissa A Borek, Steven DellaRocca, Maria Elena S Samson, Anna W Ma, Guang-Xin Xu, Troy Patterson, David P Tuck, Jaye L Viner, Ali Fattaey, Jing Wang
Upregulation of MYC is a common driver event in human cancers, and some tumors depend on MYC to maintain transcriptional programs that promote cell growth and proliferation. Preclinical studies have suggested that individually targeting upstream regulators of MYC, such as histone deacetylases (HDACs) and phosphoinositide 3-kinases (PI3Ks), can reduce MYC protein levels and suppress the growth of MYC-driven cancers. Synergy between HDAC and PI3K inhibition in inducing cancer cell death has also been reported, but the involvement of MYC regulation is unclear...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27966652/effectiveness-and-safety-of-transcatheter-patent-foramen-ovale-closure-for-migraine-eastform-trial
#11
Ying-Qi Xing, Yu-Zhu Guo, Yong-Sheng Gao, Zhen-Ni Guo, Peng-Peng Niu, Yi Yang
We evaluated the safety and effectiveness of transcatheter patent foramen ovale (PFO) closure for the treatment of migraine in a Chinese population. This non-randomized clinical trial enrolled 258 consecutive substantial or severe migraineurs with a right-to-left shunt (RLS) (grade II-IV) and grouped subjects according to their election or refusal of PFO closure. Migraine was diagnosed according to the International Classification of Headache Disorders III-beta and evaluated using the Headache Impact Test-6 (HIT-6)...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891692/smarce1-mutation-screening-in-classification-of-clear-cell-meningiomas
#12
Miriam J Smith, Soomin Ahn, Jung-Il Lee, Michael Bulman, Daniel du Plessis, Yeon-Lim Suh
AIMS: Clear cell meningioma is a rare subtype of meningioma and shows not only unusual histology, but also unique clinical features. Recently, SMARCE1 mutations have been shown to cause spinal and cranial clear cell meningiomas. We present 12 cases which were diagnosed with a clear cell meningioma in a single institution between 1997 and 2014, and investigate their SMARCE1 mutation status. METHODS AND RESULTS: To investigate the SMARCE1 mutation status of these tumours, we used a combination of Sanger sequencing and multiplex ligation dependent probe amplification analysis and also performed SMARCE1 immunohistochemical staining...
November 28, 2016: Histopathology
https://www.readbyqxmd.com/read/27881076/clustering-of-disulfide-rich-peptides-provides-scaffolds-for-hit-discovery-by-phage-display-application-to-interleukin-23
#13
David T Barkan, Xiao-Li Cheng, Herodion Celino, Tran T Tran, Ashok Bhandari, Charles S Craik, Andrej Sali, Mark L Smythe
BACKGROUND: Disulfide-rich peptides (DRPs) are found throughout nature. They are suitable scaffolds for drug development due to their small cores, whose disulfide bonds impart extraordinary chemical and biological stability. A challenge in developing a DRP therapeutic is to engineer binding to a specific target. This challenge can be overcome by (i) sampling the large sequence space of a given scaffold through a phage display library and by (ii) panning multiple libraries encoding structurally distinct scaffolds...
November 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27872081/novel-effects-of-lapatinib-revealed-in-the-african-trypanosome-using-hypothesis-generating-proteomics-and-chemical-biology-strategies
#14
Paul J Guyett, Ranjan Behera, Yuko Ogata, Michael Pollastri, Kojo Mensa-Wilmot
Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei Lapatinib, a human epidermal growth factor receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases associate with lapatinib, suggesting the drug may be a multi-targeted inhibitor of phosphoprotein signaling in the bloodstream trypanosome. Phosphoprotein signaling pathways in T. brucei have diverged significantly from those in humans...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27871234/a-genome-wide-bac-end-sequence-survey-provides-first-insights-into-sweetpotato-ipomoea-batatas-l-lam-genome-composition
#15
Zengzhi Si, Bing Du, Jinxi Huo, Shaozhen He, Qingchang Liu, Hong Zhai
BACKGROUND: Sweetpotato, Ipomoea batatas (L.) Lam., is an important food crop widely grown in the world. However, little is known about the genome of this species because it is a highly heterozygous hexaploid. Gaining a more in-depth knowledge of sweetpotato genome is therefore necessary and imperative. In this study, the first bacterial artificial chromosome (BAC) library of sweetpotato was constructed. Clones from the BAC library were end-sequenced and analyzed to provide genome-wide information about this species...
November 21, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27853960/phase-ii-study-of-tivozanib-an-oral-vegfr-inhibitor-in-patients-with-recurrent-glioblastoma
#16
Jayashree Kalpathy-Cramer, Vyshak Chandra, Xiao Da, Yangming Ou, Kyrre E Emblem, Alona Muzikansky, Xuezhu Cai, Linda Douw, John G Evans, Jorg Dietrich, Andrew S Chi, Patrick Y Wen, Stephen Stufflebeam, Bruce Rosen, Dan G Duda, Rakesh K Jain, Tracy T Batchelor, Elizabeth R Gerstner
Targeting tumor angiogenesis is a potential therapeutic strategy for glioblastoma because of its high vascularization. Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. We conducted a phase II study to test the effectiveness of tivozanib in patients with recurrent glioblastoma. Ten adult patients were enrolled and treated with tivozanib 1.5 mg daily, 3 weeks on/1 week off in 28-day cycles. Brain MRI and blood biomarkers of angiogenesis were performed at baseline, within 24-72 h of treatment initiation, and monthly thereafter...
November 16, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27831568/arqiv-hts-a-versatile-whole-organism-screening-platform-enabling-in-vivo-drug-discovery-at-high-throughput-rates
#17
David T White, Arife Unal Eroglu, Guohua Wang, Liyun Zhang, Sumitra Sengupta, Ding Ding, Surendra K Rajpurohit, Steven L Walker, Hongkai Ji, Jiang Qian, Jeff S Mumm
The zebrafish has emerged as an important model for whole-organism small-molecule screening. However, most zebrafish-based chemical screens have achieved only mid-throughput rates. Here we describe a versatile whole-organism drug discovery platform that can achieve true high-throughput screening (HTS) capacities. This system combines our automated reporter quantification in vivo (ARQiv) system with customized robotics, and is termed 'ARQiv-HTS'. We detail the process of establishing and implementing ARQiv-HTS: (i) assay design and optimization, (ii) calculation of sample size and hit criteria, (iii) large-scale egg production, (iv) automated compound titration, (v) dispensing of embryos into microtiter plates, and (vi) reporter quantification...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27806312/systematic-approach-identifies-rhoa-as-a-potential-biomarker-therapeutic-target-for-asian-gastric-cancer
#18
Hae Ryung Chang, Seungyoon Nam, Jinhyuk Lee, Jin-Hee Kim, Hae Rim Jung, Hee Seo Park, Sungjin Park, Young Zoo Ahn, Iksoo Huh, Curt Balch, Ja-Lok Ku, Garth Powis, Taesung Park, Jin-Hyun Jeong, Yon Hui Kim
Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27788488/serum-exosomal-mir-4772-3p-is-a-predictor-of-tumor-recurrence-in-stage-ii-and-iii-colon-cancer
#19
Chang Liu, Cathy Eng, Jianjun Shen, Yue Lu, Yoko Takata, Amir Mehdizadeh, George J Chang, Miguel A Rodriguez-Bigas, Yanan Li, Ping Chang, Yixiang Mao, Manal M Hassan, Fangyu Wang, Donghui Li
PURPOSE: The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer. RESULTS: 145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0...
24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27759029/a-cross-ethnic-survey-of-cfb-and-slc44a4-indian-ulcerative-colitis-gwas-hits-underscores-their-potential-role-in-disease-susceptibility
#20
Aditi Gupta, Garima Juyal, Ajit Sood, Vandana Midha, Keiko Yamazaki, Arnau Vich Vila, Motohiro Esaki, Toshiyuki Matsui, Atsushi Takahashi, Michiaki Kubo, Rinse K Weersma, B K Thelma
The first ever genome-wide association study (GWAS) of ulcerative colitis in genetically distinct north Indian population identified two novel genes namely CFB and SLC44A4. Considering their biological relevance, we investigated allelic/genetic heterogeneity in these genes among ulcerative colitis cohorts of north Indian, Japanese and Dutch origin using high-density ImmunoChip case-control genotype data. Comparative linkage disequilibrium profiling and test of association were performed. Of the 28 CFB SNPs, similar strength of association was observed for rs4151657 (novel ulcerative colitis GWAS SNP) in north Indians (P=1...
January 2016: European Journal of Human Genetics: EJHG
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