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https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#1
Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Helen Toledano, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Michael Weintraub, Mony Benifla
Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study...
November 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29129539/leptospirosis-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#2
REVIEW
Juan Ignacio Silesky Jiménez, Jorge Luis Hidalgo Marroquin, Guy A Richards, Pravin Amin
Leptospirosis is a zoonosis caused by a gram negative aerobic spirochete of the genus Leptospira. It is acquired by contact with urine or reproductive fluids from infected animals, or by inoculation from contaminated water or soil. The disease has a global distribution, mainly in tropical and subtropical regions that have a humid, rainy climate and is also common in travelers returning from these regions. Clinical suspicion is critical for the diagnosis and it should be included in the differential diagnosis of any patient with a febrile hepatorenal syndrome in, or returning from endemic regions...
November 9, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/29127533/a-phase-2-study-of-ontuxizumab-a-monoclonal-antibody-targeting-endosialin-in-metastatic-melanoma
#3
Sandra P D'Angelo, Omid A Hamid, Ahmad Tarhini, Dirk Schadendorf, Bartosz Chmielowski, Frances A Collichio, Anna C Pavlick, Karl D Lewis, Susan C Weil, John Heyburn, Charles Schweizer, Daniel J O'Shannessy, Richard D Carvajal
Objectives Ontuxizumab (MORAB-004) is a first-in-class monoclonal antibody that interferes with endosialin function, which is important in tumor stromal cell function, angiogenesis, and tumor growth. This Phase 2 study evaluated the 24-week progression-free survival (PFS) value, pharmacokinetics, and tolerability of 2 doses of ontuxizumab in patients with metastatic melanoma. Patients and methods Patients with metastatic melanoma and disease progression after receiving at least 1 prior systemic treatment were randomized to receive ontuxizumab (2 or 4 mg/kg) weekly, without dose change, until disease progression...
November 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29083324/protein-kinase-a-determines-platelet-life-span-and-survival-by-regulating-apoptosis
#4
Lili Zhao, Jun Liu, Chunyan He, Rong Yan, Kangxi Zhou, Qingya Cui, Xingjun Meng, Xiaodong Li, Yang Zhang, Yumei Nie, Yang Zhang, Renping Hu, Yancai Liu, Lian Zhao, Mengxing Chen, Weiling Xiao, Jingluan Tian, Yunxiao Zhao, Lijuan Cao, Ling Zhou, Anning Lin, Changgeng Ruan, Kesheng Dai
Apoptosis delimits platelet life span in the circulation and leads to storage lesion, which severely limits the shelf life of stored platelets. Moreover, accumulating evidence indicates that platelet apoptosis provoked by various pathological stimuli results in thrombocytopenia in many common diseases. However, little is known about how platelet apoptosis is initiated or regulated. Here, we show that PKA activity is markedly reduced in platelets aged in vitro, stored platelets, and platelets from patients with immune thrombocytopenia (ITP), diabetes, and bacterial infections...
October 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29054530/a-molecular-morphometric-approach-to-diabetic%C3%A2-kidney-disease-can-link-structure-to%C3%A2-function-and-outcome
#5
Viji Nair, Claudiu V Komorowsky, E Jennifer Weil, Berne Yee, Jeffrey Hodgin, Jennifer L Harder, Bradley Godfrey, Wenjun Ju, Carine M Boustany-Kari, Margrit Schwarz, Kevin V Lemley, Peter J Nelson, Robert G Nelson, Matthias Kretzler
Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes. Tissue obtained from protocol kidney biopsies underwent genome-wide compartment-specific gene expression profiling and quantitative morphometric analysis. The ultrastructural lesion most strongly associated with transcriptional regulation was cortical interstitial fractional volume (VvInt), an index of tubule-interstitial damage...
October 18, 2017: Kidney International
https://www.readbyqxmd.com/read/29053804/reply-mri-findings-of-visual-system-alterations-in-parkinson-s-disease
#6
Rimona S Weil, Peter McColgan, Anette E Schrag, Jason D Warren, Sebastian J Crutch, Andrew J Lees, Huw R Morris
No abstract text is available yet for this article.
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29036709/deep-learning-of-the-splicing-epi-genetic-code-reveals-a-novel-candidate-mechanism-linking-histone-modifications-to-esc-fate-decision
#7
Yungang Xu, Yongcui Wang, Jiesi Luo, Weiling Zhao, Xiaobo Zhou
Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA processing to increase transcriptome and proteome diversity. Comprehensively decoding these regulatory mechanisms holds promise in getting deeper insights into a variety of biological contexts involving in AS, such as development and diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic stem cell (hESC) differentiation by integrating heterogeneous features of genomic sequences, 16 histone modifications with a multi-label deep neural network...
September 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28992267/white-blood-cell-fractions-correlate-with-lesions-of-diabetic-kidney-disease-and-predict-loss-of-kidney-function-in-type-2-diabetes
#8
Kevin M Wheelock, Pierre-Jean Saulnier, Stephanie K Tanamas, Pavithra Vijayakumar, E Jennifer Weil, Helen C Looker, Robert L Hanson, Kevin V Lemley, Berne Yee, William C Knowler, Samy Hadjadj, Bezhad Najafian, Michael Mauer, Robert G Nelson
Background: Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study. Methods: Associations of WBC variables with morphometric parameters were assessed by linear regression...
July 18, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28954630/multi-disciplinary-patient-centered-model-for-the-expedited-provision-of-costly-therapies-in-community-settings-the-case-of-new-medication-for-hepatitis-c
#9
Nitzan Avisar, Yael Heller, Clara Weil, Aviva Ben-Baruch, Shani Potesman-Yona, Ran Oren, Gabriel Chodick, Varda Shalev, Nachman Ash
BACKGROUND: In January 2015, the first interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection was approved for inclusion in Israel's national basket of health services. During 2015, HCV genotype 1 patients with advanced liver fibrosis (stage F3-F4) were eligible for treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir (OMB/PTV/r + DSV) provided through the four national health plans. As all health plans committed to identifying eligible patients nationwide, risk-sharing agreements created an additional incentive to develop an innovative model for rapid treatment delivery...
September 28, 2017: Israel Journal of Health Policy Research
https://www.readbyqxmd.com/read/28950010/gastric-precancerous-diseases-classification-using-cnn-with-a-concise-model
#10
Xu Zhang, Weiling Hu, Fei Chen, Jiquan Liu, Yuanhang Yang, Liangjing Wang, Huilong Duan, Jianmin Si
Gastric precancerous diseases (GPD) may deteriorate into early gastric cancer if misdiagnosed, so it is important to help doctors recognize GPD accurately and quickly. In this paper, we realize the classification of 3-class GPD, namely, polyp, erosion, and ulcer using convolutional neural networks (CNN) with a concise model called the Gastric Precancerous Disease Network (GPDNet). GPDNet introduces fire modules from SqueezeNet to reduce the model size and parameters about 10 times while improving speed for quick classification...
2017: PloS One
https://www.readbyqxmd.com/read/28928962/current-concepts-and-controversies-in-the-pathogenesis-of-parkinson-s-disease-dementia-and-dementia-with-lewy-bodies
#11
REVIEW
Rimona S Weil, Tammaryn L Lashley, Jose Bras, Anette E Schrag, Jonathan M Schott
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are relentlessly progressive neurodegenerative disorders that are likely to represent two ends of a disease spectrum. It is well established that both are characterised pathologically by widespread cortical Lewy body deposition. However, until recently, the pathophysiological mechanisms leading to neuronal damage were not known. It was also not understood why some cells are particularly vulnerable in PDD/DLB, nor why some individuals show more aggressive and rapid dementia than others...
2017: F1000Research
https://www.readbyqxmd.com/read/28928300/zoonotic-surveillance-for-rickettsiae-in-rodents-and-mapping-of-vectors-of-rickettsial-diseases-in-india-a-multi-centric-study
#12
Rina Tilak, Rajesh Kunwar, P K Tyagi, Anurag Khera, R K Joshi, Urmila B Wankhade
BACKGROUND: The global resurgence of rickettsial diseases and their potential to impact the fitness of military personnel and inflict widespread casualties amongst civil populations has emerged as a major cause of public health concern. Absence of surveillance system, lack of awareness amongst medical fraternity to rickettsial activity along with the difficulty in diagnosis because of their protean clinical manifestations are reasons for the outbreaks of these diseases. OBJECTIVES: To determine rickettsial activity amongst rodents and study vector diversity, abundance and their distribution to enable mapping of rickettsial hotspots...
July 2017: Indian Journal of Public Health
https://www.readbyqxmd.com/read/28846879/insufficient-sleep-is-associated-with-impaired-nitric-oxide-mediated-endothelium-dependent-vasodilation
#13
Anthony R Bain, Brian R Weil, Kyle J Diehl, Jared J Greiner, Brian L Stauffer, Christopher A DeSouza
BACKGROUND AND AIMS: Habitual short nightly sleep duration is associated with increased atherosclerotic cardiovascular disease risk and morbidity. Vascular endothelial dysfunction represents an important mechanism that may underlie this heightened cardiovascular risk. Impaired endothelium-dependent vasodilation, particularly NO-mediated vasodilation, contributes to the development and progression of atherosclerotic vascular disease and acute vascular events. We tested the hypothesis that chronic insufficient sleep is associated with impaired NO-mediated endothelium-dependent vasodilation in middle-aged adults...
August 18, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28827282/a-novel-image-based-high-throughput-screening-assay-discovers-therapeutic-candidates-for-adult-polyglucosan-body-disease
#14
Leonardo J Solmesky, Netaly Khazanov, Hanoch Senderowitz, Peixiang Wang, Berge A Minassian, Igor M Ferreira, Wyatt W Yue, Alexander Lossos, Miguel Weil, Or Kakhlon
Glycogen storage disorders (GSDs) are caused by excessive accumulation of glycogen. Some GSDs [adult polyglucosan (PG) body disease (APBD), and Tarui and Lafora diseases] are caused by intracellular accumulation of insoluble inclusions, called PG bodies (PBs), which are chiefly composed of malconstructed glycogen. We developed an APBD patient skin fibroblast cell-based assay for PB identification, where the bodies are identified as amylase-resistant periodic acid-Schiff's-stained structures, and quantified...
September 28, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28826214/improved-intraoperative-detection-of-ovarian-cancer-by-folate-receptor-alpha-targeted-dual-modality-imaging
#15
Marlène C H Hekman, Otto C Boerman, Desirée L Bos, Leon F A G Massuger, Susan Weil, Luigi Grasso, Katherine A Rybinski, Egbert Oosterwijk, Peter F A Mulders, Mark Rijpkema
Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgG1 antibody that specifically recognizes the folate receptor alpha (FRα). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FRα-targeted dual-modality imaging using (111)In-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model...
October 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28817942/-the-current-status-of-diagnostic-tools-for-leptospirosis
#16
Mitsumasa Saito, Yasuhiko Nikaido, Masahiro Matsumoto, Midori Ogawa, Sharon Y A M Villanueva
Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira spp. The severity of leptospirosis vary from mild, flu-like disease to a more severe form, Weil's disease causing jaundice, hemorrhage, renal failure, and even death. Every year, 300,000‒500,000 cases of severe leptospirosis are reported around the world, with the case fatality rate being 10‒30%. The usual diagnostic tools for leptospirosis are 1) direct observation of leptospires in blood and urine under dark-field microscope, 2) isolation of leptospires from blood, cerebrospinal fluid (CSF), or urine samples by culture, 3) microscopic agglutination test (MAT) to detect anti-Leptospira antibodies in serum, and 4) PCR to detect Leptospira DNA...
August 15, 2017: JARMAM: Journal of the Association for Rapid Method and Automation in Microbiology
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#17
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28808688/adaptive-mistranslation-accelerates-the-evolution-of-fluconazole-resistance-and-induces-major-genomic-and-gene-expression-alterations-in-candida-albicans
#18
Tobias Weil, Rodrigo Santamaría, Wanseon Lee, Johan Rung, Noemi Tocci, Darren Abbey, Ana R Bezerra, Laura Carreto, Gabriela R Moura, Mónica Bayés, Ivo G Gut, Attila Csikasz-Nagy, Duccio Cavalieri, Judith Berman, Manuel A S Santos
Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole...
July 2017: MSphere
https://www.readbyqxmd.com/read/28758712/spatiotemporally-controlled-release-of-rho-inhibiting-c3-toxin-from-a-protein-dna-hybrid-hydrogel-for-targeted-inhibition-of-osteoclast-formation-and-activity
#19
Jasmina Gačanin, Anna Kovtun, Stephan Fischer, Victoria Schwager, Johanna Quambusch, Seah Ling Kuan, Weina Liu, Felix Boldt, Chuang Li, Zhongqiang Yang, Dongsheng Liu, Yuzhou Wu, Tanja Weil, Holger Barth, Anita Ignatius
In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks...
July 31, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28730418/total-and-free-cortisol-levels-during-1-%C3%AE-g-25-%C3%AE-g-and-250-%C3%AE-g-cosyntropin-stimulation-tests-compared-to-insulin-tolerance-test-results-of-a-randomized-prospective-pilot-study
#20
Seenia Peechakara, James Bena, Nigel J Clarke, Michael J McPhaul, Richard E Reitz, Robert J Weil, Pablo Recinos, Laurence Kennedy, Amir H Hamrahian
PURPOSE: The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. METHOD: The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12)...
July 20, 2017: Endocrine
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