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https://www.readbyqxmd.com/read/29161432/modeling-mutant-wild-type-interactions-to-ascertain-pathogenicity-of-prokr2-missense-variants-in-patients-with-isolated-gnrh-deficiency
#1
Kimberly H Cox, Luciana M B Oliveira, Lacey Plummer, Braden Corbin, Thomas Gardella, Ravikumar Balasubramanian, William F Crowley
A major challenge in human genetics is the validation of pathogenicity of heterozygous missense variants. This problem is well-illustrated by PROKR2 variants associated with Isolated GnRH Deficiency (IGD). Homozygous, loss of function variants in PROKR2 were initially implicated in autosomal recessive IGD; however, most IGD-associated PROKR2 variants are heterozygous. Moreover, while IGD patient cohorts are enriched for PROKR2 missense variants similar rare variants are also found in normal individuals. To elucidate the pathogenic mechanisms distinguishing IGD-associated PROKR2 variants from rare variants in controls, we assessed 59 variants using three approaches: (i) in silico prediction, (ii) traditional in vitro functional assays across 3 signaling pathways with mutant-alone transfections, and (iii) modified in vitro assays with mutant and wild-type expression constructs co-transfected to model in vivo heterozygosity...
November 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29161301/detection-and-quantification-of-dengue-virus-using-a-novel-biosensor-system-based-on-dengue-ns3-protease-activity
#2
Ming-Shu Hsieh, Mei-Yu Chen, Chun-Hsiang Hsieh, Chien-Hsiung Pan, Guann-Yi Yu, Hsin-Wei Chen
BACKGROUND: The traditional methods, plaque assays and immuno-focus assays, used to titrate infectious dengue virus (DENV) particles are time consuming and labor intensive. Here, we developed a DENV protease activity detection system (DENPADS) to visualize DENV infection in cells based on dengue protease activity. METHODOLOGY/PRINCIPAL FINDINGS: Dengue NS3 protease cleaves NS4B-NS5. BHK-21 cells stably expressing the sensor module comprising DENV-2 NS4 and the 10 amino-terminal amino acids of NS5 (N10NS5) fused with the SV40 nuclear localization signal (NLS) and Cre recombinase (Cre), were generated...
2017: PloS One
https://www.readbyqxmd.com/read/29161277/women-s-opinion-on-the-justification-of-physical-spousal-violence-a-quantitative-approach-to-model-the-most-vulnerable-households-in-bangladesh
#3
Raaj Kishore Biswas, Nusma Rahman, Enamul Kabir, Farabi Raihan
Bangladesh is a culturally conservative nation with limited freedom for women. A number of studies have evaluated intimate partner violence (IPV) and spousal physical violence in Bangladesh; however, the views of women have been rarely discussed in a quantitative manner. Three nationwide surveys in Bangladesh (2007, 2011, and 2014) were analyzed in this study to characterize the most vulnerable households, where women themselves accepted spousal physical violence as a general norm. 31.3%, 31.9% and 28.7% women in the surveys found justification for physical violence in household in 2007, 2011 and 2014 respectively...
2017: PloS One
https://www.readbyqxmd.com/read/29161257/regulation-of-camp-and-gsk3-signaling-pathways-contributes-to-the-neuronal-conversion-of-glioma
#4
Jinsoo Oh, Yongbo Kim, Lihua Che, Jeong Beom Kim, Gyeong Eon Chang, Eunji Cheong, Seok-Gu Kang, Yoon Ha
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator)...
2017: PloS One
https://www.readbyqxmd.com/read/29161213/laparoscopic-management-of-penetrating-thoracoabdominal-trauma
#5
Megan C Prunty, Siddharth Kudav, Jacob A Quick
BACKGROUND: Traumatic thoracoabdominal injuries can involve multiple organs and multiple cavities, which increases the complexity of surgical management. Traditionally, these injuries required laparotomy and thoracotomy. However, minimally invasive intervention may be reasonable for stable patients. MATERIALS AND METHODS: We present a case of a thoracoabdominal gunshot wound resulting in multiorgan, multicavity injury to the lung, diaphragm, and liver. We performed hepatorrhaphy and diaphragm repair, and addressed a retained hemothorax through a transabdominal laparoscopic approach...
November 21, 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/29160615/defining-the-field-of-sequence-controlled-polymers
#6
REVIEW
Jean-François Lutz
Over the last ten years, the development of synthetic polymers containing controlled monomer sequences has become a prominent topic in fundamental and applied polymer science. This emerging area is particularly broad and combines classical polymer chemistry tools with techniques imported from other domains such as biology, biochemistry, organic synthesis, engineering, and bioanalytics. Consequently, it also generates new structures, terminologies, and applications that are not within the traditional scope of polymer science...
November 21, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29160155/design-and-manufacturing-ofpatient-specific-orthodonticappliances-by-computer-aided-engineering-techniques
#7
Sandro Barone, Paolo Neri, Alessandro Paoli, Armando Viviano Razionale
Orthodontic treatments are usually performed using fixed brackets or removable oral appliances, which are traditionally made from alginate impressions and wax registrations. Among removable devices, eruption guidance appliances are used for early orthodontic treatments in order to intercept and prevent malocclusion problems. Commercially available eruption guidance appliances, however, are symmetric devices produced using a few standard sizes. For this reason, they are not able to meet all the specific patient's needs since the actual dental anatomies present various geometries and asymmetric conditions...
November 1, 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/29160086/anatomic-and-radiologic-study-of-renal-avascular-plane-brodel-s-line-and-its-potential-relevance-on-percutaneous-and-surgical-approaches-to-the-kidney
#8
Veronica Macchi, Edgardo Picardi, Antonino Inferrera, Andrea Porzionato, Alessandro Crestani, Giacomo Novara, Raffaele De Caro, Vincenzo Ficarra
OBJECTIVE: The aim of the present anatomic and radiologic study was to evaluate the location, extension and characteristics of the Brödel's plane and eventually define its different patterns. MATERIAL AND METHODS: We evaluated 15 human normal kidneys sampled from un-embalmed cadavers without clinical history or anatomical evidence of renal diseases. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins...
November 21, 2017: Journal of Endourology
https://www.readbyqxmd.com/read/29160024/a-conceptual-framework-for-understanding-the-perspectives-on-the-causes-of-the-science-practice-gap-in-ecology-and-conservation
#9
Diana Bertuol-Garcia, Carla Morsello, Charbel N El-Hani, Renata Pardini
Applying scientific knowledge to confront societal challenges is a difficult task, an issue known as the science-practice gap. In Ecology and Conservation, scientific evidence has been seldom used directly to support decision-making, despite calls for an increasing role of ecological science in developing solutions for a sustainable future. To date, multiple causes of the science-practice gap and diverse approaches to link science and practice in Ecology and Conservation have been proposed. To foster a transparent debate and broaden our understanding of the difficulties of using scientific knowledge, we reviewed the perceived causes of the science-practice gap, aiming to: (i) identify the perspectives of ecologists and conservation scientists on this problem, (ii) evaluate the predominance of these perspectives over time and across journals, and (iii) assess them in light of disciplines studying the role of science in decision-making...
November 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29159332/a-biomaterial-screening-approach-reveals-microenvironmental-mechanisms-of-drug-resistance
#10
Alyssa D Schwartz, Lauren E Barney, Lauren E Jansen, Thuy V Nguyen, Christopher L Hall, Aaron S Meyer, Shelly R Peyton
Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment...
November 21, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29159232/application-of-bi-clustering-of-gene-expression-data-and-gene-set-enrichment-analysis-methods-to-identify-potentially-disease-causing-nanomaterials
#11
Andrew Williams, Sabina Halappanavar
This article contains data related to the research article 'Application of bi-clustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials' (Williams and Halappanavar, 2015) [1]. The presence of diverse types of nanomaterials (NMs) in commerce has grown significantly in the past decade and as a result, human exposure to these materials in the environment is inevitable. The traditional toxicity testing approaches that are reliant on animals are both time- and cost- intensive; employing which, it is not possible to complete the challenging task of safety assessment of NMs currently on the market in a timely manner...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29159019/introducing-sit-stand-desks-increases-classroom-standing-time-among-university-students
#12
Matthew Jerome, Kathleen F Janz, Barbara Baquero, Lucas J Carr
Excessive sedentary behavior has been associated with many negative health outcomes. While an understudied health topic, there is evidence that university students are excessively sedentary. Sit-stand desks have been shown to reduce sedentary time among pre-university students (ages 5-18 years) and sedentary workers but have not been tested in university classrooms. This study tested the effects of introducing sit-stand desks into a university classroom on student's classroom sitting and standing behaviors...
December 2017: Preventive Medicine Reports
https://www.readbyqxmd.com/read/29158425/improving-metabolic-health-through-precision-dietetics-in-mice
#13
William T Barrington, Phillip Wulfridge, Ann E Wells, Carolina Mantilla Rojas, Selene Y F Howe, Amie Perry, Kunjie Hua, Michael A Pellizzon, Kasper D Hansen, Brynn H Voy, Brian J Bennett, Daniel Pomp, Andrew P Feinberg, David W Threadgill
The incidence of diet-induced metabolic disease has soared the last half-century despite national efforts to improve health through universal dietary recommendations. Studies comparing dietary patterns of populations with health outcomes have historically provided the basis for healthy diet recommendations. However, evidence that population-level diet responses are reliable indicators of responses across individuals is lacking.  This study investigated how genetic differences influence health responses to several popular diets in mice, which are similar to humans in genetic composition and propensity to develop metabolic disease, but enable precise genetic and environmental control...
November 20, 2017: Genetics
https://www.readbyqxmd.com/read/29158372/enhancing-next-generation-sequencing-guided-cancer-care-through-cognitive-computing
#14
Nirali M Patel, Vanessa V Michelini, Jeff M Snell, Saianand Balu, Alan P Hoyle, Joel S Parker, Michele C Hayward, David A Eberhard, Ashley H Salazar, Patrick McNeillie, Jia Xu, Claudia S Huettner, Takahiko Koyama, Filippo Utro, Kahn Rhrissorrakrai, Raquel Norel, Erhan Bilal, Ajay Royyuru, Laxmi Parida, H Shelton Earp, Juneko E Grilley-Olson, D Neil Hayes, Stephen J Harvey, Norman E Sharpless, William Y Kim
BACKGROUND: Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human "molecular tumor boards" (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB...
November 20, 2017: Oncologist
https://www.readbyqxmd.com/read/29158287/development-of-a-premium-quality-plasma-derived-ivig-iqymune%C3%A2-utilizing-the-principles-of-quality-by-design-a-worked-through-case-study
#15
Philippe Paolantonacci, Philippe Appourchaux, Béatrice Claudel, Monique Ollivier, Richard Dennett, Laurent Siret
Polyvalent human normal immunoglobulins for intravenous use (IVIG), indicated for rare and often severe diseases, are complex plasma-derived protein preparations. A Quality by Design (QbD) approach has been used to develop the LFB new generation IVIG, targeting a high level of purity to generate an enhanced safety profile while maintaining a high level of efficacy. A modular approach of QbD was implemented consisting of five consecutive steps to cover all the stages from the product design to the final product control strategy...
November 20, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/29157743/next-generation-microbiological-risk-assessment-meta-omics-the-next-need-for-integration
#16
Luca Cocolin, Marios Mataragas, Francois Bourdichon, Agapi Doulgeraki, Marie-France Pilet, Balamurugan Jagadeesan, Kalliopi Rantsiou, Trevor Phister
The development of a multi-omics approach has provided a new approach to the investigation of microbial communities allowing an integration of data, which can be used to better understand the behaviour of and interactions between community members. Metagenomics, metatranscriptomics, metaproteomics and metabolomics have the potential of producing a large amount of data in a very short time, however an important challenge is how to exploit and interpret these data to assist risk managers in food safety and quality decisions...
November 13, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29157573/thirteen-years-and-counting-outcomes-of-a-concurrent-asn-bsn-enrollment-program
#17
REVIEW
Stephen Heglund, Jessica Simmons, Diane Wink, Jean D'Meza Leuner
In their 2011 report, The Future of Nursing, the Institute of Medicine called for 80% of the nursing workforce to be comprised of baccalaureate prepared Registered Nurses by the year 2020. One suggested approach to achieve this goal is the creation of programs that allow students to progress through associate and baccalaureate nursing preparation simultaneously. This paper describes the University of Central Florida's 13-year experience after implementing a Concurrent Enrollment Program. Development and structure of the program, advisement and curriculum details, facilitators and barriers are described...
November 2017: Journal of Professional Nursing: Official Journal of the American Association of Colleges of Nursing
https://www.readbyqxmd.com/read/29157474/private-and-institutionalised-patients-use-of-homeopathy-in-the-early-nineteenth-century
#18
Silvia Waisse
Medicine underwent a major crisis in the 18th century and several approaches, including homeopathy, were formulated to fill the void left by the fall of traditional Galenic medicine. While most of the literature deals with the reasons doctors had to shift to homeopathy, the patients' views became the focus of increasing scholarly attention along the past 20 years. In this article I present and discuss the current knowledge about the socio-demographic characteristics and medical complaints of patients who sought homeopathic care in the early 19th century in both private and institutional settings...
November 2017: Homeopathy: the Journal of the Faculty of Homeopathy
https://www.readbyqxmd.com/read/29157446/dynamic-visualization-of-multi-level-molecular-data-the-director-package-in-r
#19
Katherine Icay, Chengyu Liu, Sampsa Hautaniemi
BACKGROUND AND OBJECTIVE: High-throughput measurement technologies have triggered a rise in large-scale cancer studies containing multiple levels of molecular data. While there are a number of efficient methods to analyze individual data types, there are far less that enhance data interpretation after analysis. We present the R package Director, a dynamic visualization approach to linking and interrogating multiple levels of molecular data after analysis for clinically meaningful, actionable insights...
January 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29157139/authors-response-to-letter-to-the-editor-bar-velocities-capable-of-optimising-the-muscle-power-in-strength-power-exercises-by-loturco-pereira-abad-tabares-moraes-kobal-kitamura-nakamura-2017
#20
Irineu Loturco
Our study in the Journal of Sports Sciences was originally designed to test whether the bar-velocity is a precise indicator of the power training intensity (i.e., optimum loads) in different exercises commonly included in athletes' training programs. Furthermore, we presented secondary findings, related to the actual results obtained in our assessments. As a cross-sectional study with clear objectives, we focused on discussing issues and applications pertaining to neuromuscular training interventions, such as: (1) describing the advantages of using bar-velocities to control the power training intensity, (2) defining a range of loads capable of maximizing the power production in certain ballistic and traditional exercises, and (3) revealing the differences between these exercises and the respective implications for training...
November 20, 2017: Journal of Sports Sciences
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