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https://www.readbyqxmd.com/read/28812537/leveraging-network-analytics-to-infer-patient-syndrome-and-identify-causal-genes-in-rare-disease-cases
#1
Andreas Krämer, Sohela Shah, Robert Anthony Rebres, Susan Tang, Daniel Rene Richards
BACKGROUND: Next-generation sequencing is widely used to identify disease-causing variants in patients with rare genetic disorders. Identifying those variants from whole-genome or exome data can be both scientifically challenging and time consuming. A significant amount of time is spent on variant annotation, and interpretation. Fully or partly automated solutions are therefore needed to streamline and scale this process. RESULTS: We describe Phenotype Driven Ranking (PDR), an algorithm integrated into Ingenuity Variant Analysis, that uses observed patient phenotypes to prioritize diseases and genes in order to expedite causal-variant discovery...
August 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28811148/metagenomes-from-deep-baltic-sea-sediments-reveal-how-past-and-present-environmental-conditions-determine-microbial-community-composition
#2
Ian P G Marshall, Søren M Karst, Per H Nielsen, Bo Barker Jørgensen
Microbial communities that lived near the sediment surface in the past become slowly buried and are the source of deep subsurface communities thousands of years later. We used metagenomes to analyse how the composition of buried microbial communities may change to conform to altered environmental conditions at depth. Sediment samples were collected from down to 85m below sea floor during the Integrated Ocean Drilling Program Expedition 347, "Baltic Sea Paleoenvironment". The sediments vary in age, organic carbon content, porewater salinity, and other parameters that reflect the changing Baltic environment from the last ice age and throughout the Holocene...
August 12, 2017: Marine Genomics
https://www.readbyqxmd.com/read/28810955/embedded-mental-health-promotion-of-psychological-hygiene-within-a-submarine-squadron
#3
James Rapley, John Chin, Brian McCue, Mathew Rariden
INTRODUCTION: Psychological fitness is an important component to operational unit readiness and success. Embedding behavioral health providers can reduce unplanned personnel losses (UPL) as a result of psychological stress. The U.S. Submarine Forces implemented the Submarine Squadron 6 (CSS-6) Embedded Mental Health Pilot (EMHP) Program to address this type of UPL, which is classified as a Code 2 loss. The aim of the study is to evaluate the effectiveness of the EMHP Program at reducing UPL by improving psychological readiness through expedited access to care...
July 2017: Military Medicine
https://www.readbyqxmd.com/read/28809393/ythdc2-is-an-n-6-methyladenosine-binding-protein-that-regulates-mammalian-spermatogenesis
#4
Phillip J Hsu, Yunfei Zhu, Honghui Ma, Yueshuai Guo, Xiaodan Shi, Yuanyuan Liu, Meijie Qi, Zhike Lu, Hailing Shi, Jianying Wang, Yiwei Cheng, Guanzheng Luo, Qing Dai, Mingxi Liu, Xuejiang Guo, Jiahao Sha, Bin Shen, Chuan He
N(6)-methyladenosine (m(6)A) is the most common internal modification in eukaryotic mRNA. It is dynamically installed and removed, and acts as a new layer of mRNA metabolism, regulating biological processes including stem cell pluripotency, cell differentiation, and energy homeostasis. m(6)A is recognized by selective binding proteins; YTHDF1 and YTHDF3 work in concert to affect the translation of m(6)A-containing mRNAs, YTHDF2 expedites mRNA decay, and YTHDC1 affects the nuclear processing of its targets. The biological function of YTHDC2, the final member of the YTH protein family, remains unknown...
August 15, 2017: Cell Research
https://www.readbyqxmd.com/read/28808969/methods-of-assessing-sting-activation-and-trafficking
#5
Vladislav Pokatayev, Nan Yan
The signaling adapter protein STING is crucial for the host immune response to cytosolic DNA and cyclic dinucleotides. Under basal conditions, STING resides on the endoplasmic reticulum (ER ) , but upon activation, it traffics through secretory pathway to cytoplasmic vesicles, where STING activates downstream immune signaling. Classical STING activation and trafficking are triggered by binding of cyclic dinucleotide ligands. STING signaling can also be activated by gain-of-function mutations that lead to constitutive trafficking of STING...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807405/initiation-of-a-multidisciplinary-rapid-response-team-to-massive-and-submassive-pulmonary-embolism
#6
Brett J Carroll, Heather Pemberton, Kenneth A Bauer, Louis M Chu, Jeffrey L Weinstein, Barbara L Levarge, Duane S Pinto
Pulmonary embolism (PE) can result in rapid clinical decompensation in many patients. With increasing patient complexity and advanced treatment options for PE, multidisciplinary, rapid response teams can optimize risk stratification and expedite management strategies. The Massive And Submassive Clot On-call Team (MASCOT) was created at our institution, which comprised specialists from cardiology, pulmonology, hematology, interventional radiology, and cardiac surgery. MASCOT offers rapid consultation 24 hours a day with a web-based conference call to review patient data and discuss management of patients with high-risk PE...
July 26, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28804642/e-learning-for-medical-imaging-specialists-introducing-blended-learning-in-a-nuclear-medicine-specialist-course
#7
Torjan Haslerud, Andreas Julius Tulipan, Robert M Gray, Martin Biermann
BACKGROUND: While e-learning has become an important tool in teaching medical students, the training of specialists in medical imaging is still dominated by lecture-based courses. PURPOSE: To assess the potential of e-learning in specialist education in medical imaging. MATERIAL AND METHODS: An existing lecture-based five-day course in Clinical Nuclear Medicine (NM) was enhanced by e-learning resources and activities, including practical exercises...
July 2017: Acta Radiologica Open
https://www.readbyqxmd.com/read/28801417/optic-nerve-sheath-diameter-sonography-for-the-diagnosis-of-increased-intracranial-pressure-a-systematic-review-and-meta-analysis-protocol
#8
Alex Koziarz, Niv Sne, Fraser Kegel, Waleed Alhazzani, Siddharth Nath, Jetan H Badhiwala, Timothy Rice, Paul Engels, Faidi Samir, Andrew Healey, Kamyar Kahnamoui, Laura Banfield, Sunjay Sharma, Kesava Reddy, Gregory W J Hawryluk, Andrew W Kirkpatrick, Saleh A Almenawer
INTRODUCTION: Increased intracranial pressure (ICP) is a significant neurological issue that may lead to permanent neurological sequelae. When evaluating patients with traumatic brain injury, it is crucial to identify those with high ICP in order to expedite ICP lowering measures and maintain adequate cerebral perfusion. Several measures are used to recognise patients with increased ICP including CT scan, MRI, ICP monitor, and lumbar puncture (LP). However, these tests can be invasive, associated with radiation exposure, contraindicated, or not readily available...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28800466/monitoring-and-modulating-ion-traffic-in-hybrid-lipid-polymer-vesicles
#9
Walter F Paxton, Patrick T McAninch, Komandoor E Achyuthan, Sun Hae Ra Shin, Haley L Monteith
Controlling the traffic of molecules and ions across membranes is a critical feature in a number of biologically relevant processes and highly desirable for the development of technologies based on membrane materials. In this paper, ion transport behavior of hybrid lipid/polymer membranes was studied in the absence and presence of ion transfer agents. A pH-sensitive fluorophore was used to investigate ion (H(+)/OH(-)) permeability across hybrid lipid/polymer membranes as a function of the fraction of amphiphilic block copolymer...
August 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28796587/metastasis-free-survival-is-a-strong-surrogate-of-overall-survival-in-localized-prostate-cancer
#10
Wanling Xie, Meredith M Regan, Marc Buyse, Susan Halabi, Philip W Kantoff, Oliver Sartor, Howard Soule, Noel W Clarke, Laurence Collette, James J Dignam, Karim Fizazi, Wendy R Paruleker, Howard M Sandler, Matthew R Sydes, Bertrand Tombal, Scott G Williams, Christopher J Sweeney
Purpose Adjuvant therapy for intermediate-risk and high-risk localized prostate cancer decreases the number of deaths from this disease. Surrogates for overall survival (OS) could expedite the evaluation of new adjuvant therapies. Methods By June 2013, 102 completed or ongoing randomized trials were identified and individual patient data were collected from 28 trials with 28,905 patients. Disease-free survival (DFS) and metastasis-free survival (MFS) were determined for 21,140 patients from 24 trials and 12,712 patients from 19 trials, respectively...
August 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28796496/discovery-of-clinical-candidate-n-1s-1-3-fluoro-4-trifluoromethoxy-phenyl-2-methoxyethyl-7-methoxy-2-oxo-2-3-dihydropyrido-2-3-b-pyrazine-4-1h-carboxamide-tak-915-a-highly-potent-selective-and-brain-penetrating-phosphodiesterase-2a-inhibitor-for-the-treatment
#11
Satoshi Mikami, Shinji Nakamura, Tomoko Ashizawa, Izumi Nomura, Masanori Kawasaki, Shigekazu Sasaki, Hideyuki Oki, Hironori Kokubo, Isaac D Hoffman, Hua Zou, Noriko Uchiyama, Kosuke Nakashima, Naomi Kamiguchi, Haruka Imada, Noriko Suzuki, Hiroki Iwashita, Takahiko Taniguchi
Phosphodiesterase (PDE) 2A inhibitors have emerged as a novel mechanism with potential therapeutic option to ameliorate cognitive dysfunction in schizophrenia or Alzheimer's disease through upregulation of cyclic nucleotides in the brain, and thereby achieve potentiation of cyclic nucleotide signaling pathways. This article details the expedited optimization of our recently disclosed pyrazolo[1,5-a]pyrimidine lead compound 4b, leading to the discovery of clinical candidate 36 (TAK-915), which demonstrates an appropriate combination of potency, PDE selectivity, and favorable pharmacokinetic (PK) properties, including brain penetration...
August 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28795146/refining-the-policy-for-timing-of-kidney-transplant-waitlist-qualification
#12
Benjamin J Lee, Charles E McCulloch, Barbara A Grimes, Sindhu Chandran, Isabel Elaine Allen, Cynthia Delgado, Chi-Yuan Hsu
BACKGROUND: Earlier qualification for the kidney transplant waitlist expedites transplant and is therefore associated with improved outcomes. U.S. Organ Procurement and Transplantation Network policies state that "measured or calculated creatinine clearance or glomerular filtration rate less than or equal to 20 mL/min" triggers waitlist time accrual. The choice of qualification method is somewhat arbitrary, and the policy implies that decline in renal function is monotonic. METHODS: (1) We used survival analysis to quantify temporal differences in waitlist qualification by applying 3 kidney-function-estimating equations (Cockcroft-Gault, Modification of Diet in Renal Disease study, Chronic Kidney Disease Epidemiology Collaboration) to serial creatinine measurements from 3 patient cohorts: 1 of waitlisted patients at a major U...
August 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28794936/light-emitting-agents-for-noninvasive-assessment-of-kidney-function
#13
REVIEW
Jiaguo Huang, Norbert Gretz
The noninvasive assessment of kidney function and diagnosis of kidney disease have long been challenges. Traditional methods are not routinely available, because the existing protocols are cumbersome, time consuming, and invasive. In the past few years, significant progress in the area of diagnosing kidney function and disease on the basis of light-emitting agents has been made. Herein, we briefly review light-emitting agents, including organic fluorescent agents and inorganic renal clearable luminescent nanoparticles for the noninvasive and real-time monitoring of kidney function and disease...
August 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28794232/resolvin-d1-improves-the-resolution-of-inflammation-via-activating-nf-%C3%AE%C2%BAb-p50-p50-mediated-cyclooxygenase-2-expression-in-acute-respiratory-distress-syndrome
#14
Ye Gao, Huawei Zhang, Lingchun Luo, Jing Lin, Dan Li, Sisi Zheng, Hua Huang, Songfan Yan, Jingxiang Yang, Yu Hao, Hui Li, Fang Gao Smith, Shengwei Jin
Acute respiratory distress syndrome (ARDS) is a severe illness characterized by uncontrolled inflammation. The resolution of inflammation is a tightly regulated event controlled by endogenous mediators, such as resolvin D1 (RvD1). Cyclooxygenase-2 (COX-2) has been reported to promote inflammation, along with PGE2, in the initiation of inflammation, as well as in prompting resolution, with PGD2 acting in the later phase of inflammation. Our previous work demonstrated that RvD1 enhanced COX-2 and PGD2 expression to resolve inflammation...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28794012/surgeon-major-thomas-heazle-parke-1857-1893-irish-doctor-soldier-and-explorer
#15
EDITORIAL
Andrew Parke
Surgeon Major Thomas Heazle Parke (1857-1893) was a doctor from Drumsna, County Roscommon, who after completing his education at the Royal College of Surgeons in Ireland joined the British army as a medical officer. After several years of serving in Ireland and Egypt, he volunteered to be medical officer of the Emin Pasha Relief Expedition of 1887-1889. This was to become Henry Morton Stanley's largest, longest and most controversial African expedition. The epic journey saw Stanley, his eight European officers and 800 African porters take almost 3 years to cross the African continent from West to East via the Congo River, Southern Sudan and Uganda...
August 8, 2017: Journal of the Royal Army Medical Corps
https://www.readbyqxmd.com/read/28793388/morphological-molecular-and-toxin-analysis-of-field-populations-of-alexandrium-genus-from-the-argentina-sea
#16
Elena Fabro, Gastón O Almandoz, Martha Ferrario, Uwe John, Urban Tillmann, Kerstin Toebe, Bernd Krock, Allan Cembella
In the Argentine Sea, blooms of toxigenic dinoflagellates of the Alexandrium tamarense species complex have led to fish and bird mortalities and human deaths as a consequence of paralytic shellfish poisoning (PSP). Yet little is known about the occurrence of other toxigenic species of the genus Alexandrium, or of their toxin composition beyond coastal waters. The distribution of Alexandrium species and related toxins in the Argentine Sea was determined by sampling surface waters on an oceanographic expedition during austral spring from ~39 to 48º S...
August 9, 2017: Journal of Phycology
https://www.readbyqxmd.com/read/28793374/pain-assessment-by-emergency-nurses-at-triage-in-the-emergency-department-a-qualitative-study
#17
Marilène Vuille, Maryline Foerster, Eliane Foucault, Olivier Hugli
AIM: To investigate the assessment of pain intensity in the specific context of triage. BACKGROUND: Acute pain affects most patients admitted in emergency departments (ED) but pain relief in this setting remains insufficient. Evaluation of pain and its treatment at the time of patient triage expedites the administration of analgesia, but may be awkward at this time-pressured moment. The assessment of pain intensity by a validated pain scale is a critical initial step, and a patient's self-reporting is widely considered as the key to effective pain management...
August 9, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28792544/triple-dissociation-of-duration-perception-regulating-mechanisms-top-down-attention-is-inherent
#18
Yong-Jun Lin, Shinsuke Shimojo
The brain constantly adjusts perceived duration based on the recent event history. One such lab phenomenon is subjective time expansion induced in an oddball paradigm ("oddball chronostasis"), where the duration of a distinct item (oddball) appears subjectively longer when embedded in a series of other repeated items (standards). Three hypotheses have been separately proposed but it remains unresolved which or all of them are true: 1) attention prolongs oddball duration, 2) repetition suppression reduces standards duration, and 3) accumulative temporal preparation (anticipation) expedites the perceived item onset so as to lengthen its duration...
2017: PloS One
https://www.readbyqxmd.com/read/28792293/the-opioid-epidemic-challenges-of-sustained-remission
#19
Nitin Chopra, Lauren H Marasa
Opioid use disorder is a growing epidemic, with an alarming number of associated deaths. In 2014, in the United States, 18,893 lethal overdoses were related to prescription opioids and 10,574 due to heroin. Despite the growing number of treatment options for substance use disorders, which are chronic, relapsing-remitting conditions, relapse rates remain as high as 91%. In the United States, 7.5 million children reside with at least one patient who abuses drugs or alcohol. Mothers are twice as likely to lose custody of their children...
March 2017: International Journal of Psychiatry in Medicine
https://www.readbyqxmd.com/read/28791010/uses-of-next-generation-sequencing-technologies-for-the-diagnosis-of-primary-immunodeficiencies
#20
REVIEW
Michael Seleman, Rodrigo Hoyos-Bachiloglu, Raif S Geha, Janet Chou
Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission, and with variable penetrance...
2017: Frontiers in Immunology
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