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https://www.readbyqxmd.com/read/29785566/delineating-a-new-feature-of-constitutional-mismatch-repair-deficiency-cmmrd-syndrome-breast-cancer
#1
Lisa Bush, Melyssa Aronson, Uri Tabori, Brittany B Campbell, Raymond B Bedgood, Kory Jasperson
Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive hereditary cancer condition, characterized by an exceptionally high risk of cancer, a propensity for childhood malignancies, and cutaneous features reminiscent of neurofibromatosis type 1 (NF1). We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelic MSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27...
May 21, 2018: Familial Cancer
https://www.readbyqxmd.com/read/29781950/report-of-the-key-opinion-leaders-meeting-on-stem-cell-derived-beta-cells
#2
Jon Odorico, James Markmann, Douglas Melton, Julia Greenstein, Albert Hwa, Cristina Nostro, Alireza Rezania, Jose Oberholzer, Daniel Pipeleers, Luhan Yang, Chad Cowan, Danwei Huangfu, Dieter Egli, Uri Ben-David, Ludovic Vallier, Shane T Grey, Qizhi Tang, Bart Roep, Camilo Ricordi, Ali Naji, Giuseppe Orlando, Daniel G Anderson, Mark Poznansky, Barbara Ludwig, Alice Tomei, Dale L Greiner, Melanie Graham, Melissa Carpenter, Giovanni Migliaccio, Kevin D'Amour, Bernhard Hering, Lorenzo Piemonti, Thierry Berney, Mike Rickels, Thomas Kay, Ann Adams
Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells...
April 30, 2018: Transplantation
https://www.readbyqxmd.com/read/29779158/diffusion-weighted-magnetic-resonance-enterography-for-prediction-of-response-to-tumor-necrosis-factor-inhibitors-in-stricturing-crohn-s-disease
#3
Marianne M Amitai, Eyal Klang, Asaf Levartovsky, Noa Rozendorn, Shelly Soffer, Gadeer Ali Taha, Bella Ungar, Tomer Greener, Shomron Ben-Horin, Rami Eliakim, Uri Kopylov
BACKGROUND AND AIMS: Distinguishing between fibrotic and inflammatory strictures in Crohn's disease (CD) is still challenging. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however, the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify imaging features, including DWI, which can predict response to anti-inflammatory treatment in patients with stricturing CD...
May 19, 2018: Abdominal Radiology
https://www.readbyqxmd.com/read/29777125/development-of-an-algorithm-to-identify-patients-with-physician-documented-insomnia
#4
Uri Kartoun, Rahul Aggarwal, Andrew L Beam, Jennifer K Pai, Arnaub K Chatterjee, Timothy P Fitzgerald, Isaac S Kohane, Stanley Y Shaw
We developed an insomnia classification algorithm by interrogating an electronic medical records (EMR) database of 314,292 patients. The patients received care at Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH), or both, between 1992 and 2010. Our algorithm combined structured variables (such as International Classification of Diseases 9th Revision [ICD-9] codes, prescriptions, laboratory observations) and unstructured variables (such as text mentions of sleep and psychiatric disorders in clinical narrative notes)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775092/a-prospective-multi-centre-us-clinical-trial-to-determine-accuracy-of-febridx-point-of-care-testing-for-acute-upper-respiratory-infections-with-and-without-a-confirmed-fever
#5
Nathan I Shapiro, Wesley H Self, Jeffrey Rosen, Stephan C Sharp, Michael R Filbin, Peter C Hou, Amisha D Parekh, Michael C Kurz, Robert Sambursky
BACKGROUND: FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting. METHODS: A prospective, multicentre, observational cohort study of acute upper respiratory tract infections (URIs), with and without a confirmed fever at the time of enrolment, was performed to evaluate the diagnostic accuracy of FebriDx to identify clinically significant bacterial infection with host response and acute pathogenic viral infection...
May 18, 2018: Annals of Medicine
https://www.readbyqxmd.com/read/29774332/tuning-the-molecular-weight-of-polymeric-amphiphiles-as-a-tool-to-access-micelles-with-a-wide-range-of-enzymatic-degradation-rates
#6
Gadi Slor, Nitsan Papo, Uri Hananel, Roey J Amir
Enyzme-responsive polymeric assemblies hold great potential for biomedical applications due to the over-expression of disease-associated enzymes, which can be utilized to activate such systems only in afflicted tissues. Herein we demonstrate that the overall molecular weight of polymeric amphiphiles, which have the same hydrophilic/hydrophobic ratio, can be tuned to create polymeric micelles with an extreme range of degradation rates. This approach expands the available set of molecular parameters that can be adjusted to tune the degradation rate of polymeric assemblies, paving new possibilities for rational design of polymeric systems with controlled degradation rates...
May 18, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#7
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29771035/-analysis-of-clinical-characteristics-of-141-patients-with-postviral-olfactory-dysfunction
#8
J Tian, Y X Wei, L Li, Z F Sun, B Q Wang
Objective: The aim of this study is to investigate the clinical features of the patients with postviral olfactory dysfunction (PVOD). Method: Clinical information of 141 consecutive outpatients with PVOD were collected and analyzed based on a questionnaire, including age, gender, months of onset, and symptoms. Sniffin'Sticks Test was used as a psychophysical olfactory test to evaluate olfactory function. Result: Retrospective analysis of 141 patients with PVOD, the male to female ratio of patients was 1.0:2...
May 20, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29765537/stat3-activated-cd36-facilitates-fatty-acid-uptake-in-chronic-lymphocytic-leukemia-cells
#9
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29763813/age-and-gymnastic-experience-effects-on-sensory-reweighting-processes-during-quiet-stand
#10
Albert Busquets, Silvia Aranda-Garcia, Blai Ferrer-Uris, Michel Marina, Rosa Angulo-Barroso
BACKGROUND: The relative contribution of sensory inputs to control balance while standing is dynamically adjusted. These sensory reweighting processes could be impacted by age and sport expertise capabilities, especially when the sport emphasizes equilibrium like artistic gymnastics. RESEARCH QUESTION: The aim of this study was to explore the sensory reweighting processes to adjust standing posture in children and adults with different gymnastic expertise (gymnasts, G, and non-gymnast, NG)...
May 8, 2018: Gait & Posture
https://www.readbyqxmd.com/read/29762113/cervicothoracic-pedicle-morphometry-using-an-osteological-collection-to-characterize-trends-in-pedicle-size
#11
Mhamad Faour, Charles C Yu, Navkirat Bajwa, Jason O Toy, Uri M Ahn, Nicholas U Ahn
Pedicle screws are a common treatment option for spinal instability. Despite their popularity, pedicle screws carry the risk of transpedicular violation with subsequent neural and vascular damage. This study measured the pedicle dimensions of 500 dry specimens in an osteological collection. The data provide the orthopedic spine surgeon with an accurate measure of pedicle morphometry in light of previously limited and contradictory results. The study demonstrates that pedicle height at the cervicothoracic junction tends to increase with body height, particularly for females...
2018: Journal of Surgical Orthopaedic Advances
https://www.readbyqxmd.com/read/29762112/lumbar-discography-is-associated-with-poor-return-to-work-status-following-lumbar-fusion-surgery-in-a-workers-compensation-setting
#12
Joshua T Anderson, Jeffrey A O'Donnell, Arnold R Haas, Rick Percy, Stephen T Woods, Uri M Ahn, Nicholas U Ahn
Lumbar discography (LD) is used to guide surgical decision making in patients with degenerative disc disease (DDD). Its safety and diagnostic accuracy are under contention. This study evaluates LD's efficacy within the workers' compensation (WC) population. Multivariate logistic regression analysis was used to determine the impact that undergoing LD before lumbar fusion for DDD had on return to work (RTW) rates among 1407 WC subjects. Discography was negatively associated with RTW status (p = .042; OR 0.76); 22...
2018: Journal of Surgical Orthopaedic Advances
https://www.readbyqxmd.com/read/29743242/cyclin-dependent-kinase-7-cdk7-mediated-phosphorylation-of-the-cdk9-activation-loop-promotes-p-tefb-assembly-with-tat-and-proviral-hiv-reactivation
#13
Uri Mbonye, Benlian Wang, Giridharan Gokulrangan, Wuxian Shi, Sichun Yang, Jonathan Karn
The HIV trans-activator Tat recruits the host transcription elongation factor P-TEFb to stimulate proviral transcription. Phosphorylation of Thr186 on the activation loop (T-loop) of cyclin-dependent kinase 9 (CDK9) is essential for its kinase activity and assembly of CDK9 and cyclin T1 (CycT1) to form functional P-TEFb. Phosphorylation of a second highly conserved T-loop site, Ser175, alters the competitive binding of Tat and the host recruitment factor bromodomain containing 4 (BRD4) to P-TEFb. Here, we investigated the intracellular mechanisms that regulate these key phosphorylation events required for HIV transcription...
May 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29742882/pediatric-high-grade-gliomas-in-the-context-of-cancer-predisposition-syndromes
#14
REVIEW
Orli Michaeli, Uri Tabori
Germline mutations in cancer causing genes result in high risk of developing cancer throughout life. These cancer predisposition syndromes (CPS) are especially prevalent in childhood brain tumors and impact both the patient's and other family members' survival. Knowledge of specific CPS may alter the management of the cancer, offer novel targeted therapies which may improve survival for these patients, and enables early detection of other malignancies. This review focuses on the role of CPS in pediatric high grade gliomas (PHGG), the deadliest group of childhood brain tumors...
May 2018: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/29741984/myc-protein-expression-is-an-important-prognostic-factor-in-acute-myeloid-leukemia
#15
Maro Ohanian, Uri Rozovski, Rashmi Kanagal-Shamanna, Lynne V Abruzzo, Sanam Loghavi, Tapan Kadia, Andrew Futreal, Kapil Bhalla, Zhuang Zuo, Yang O Huh, Sean M Post, Peter Ruvolo, Guillermo Garcia-Manero, Michael Andreeff, Steven Kornblau, Gautam Borthakur, Peter Hu, L Jeffrey Medeiros, Koichi Takahashi, Marisa J Hornbaker, Jianhua Zhang, Graciela M Nogueras-González, Xuelin Huang, Srdan Verstovsek, Zeev Estrov, Sherry Pierce, Farhad Ravandi, Hagop M Kantarjian, Carlos E Bueso-Ramos, Jorge E Cortes
As new drugs targeting MYC show clinical activity in acute myeloid leukemia (AML), understanding MYC expression in AML is of critical importance. We assessed MYC protein expression by immunohistochemistry in bone marrow of patients with untreated AML (n = 265). Overall, 90% of patients demonstrated MYC overexpression and MYC immunopositivity ≤6% was associated with superior complete remission (CR) duration of 23 months versus 12 months for MYC immunopositivity >6% (p = .028). Among 241 patients at higher risk for relapse, including those ≥55 years of age and patients with intermediate- and high-risk AML, MYC immunopositivity ≤6% conferred significantly superior median overall survival (OS) (24 versus 13 months; p = ...
May 9, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29741482/mortality-risk-after-transcatheter-aortic-valve-implantation-analysis-of-the-predictive-accuracy-of-the-transcatheter-valve-therapy-registry-risk-assessment-model
#16
Pablo Codner, Waqas Malick, Remi Kouz, Amisha Patel, Cheng-Han Chen, Juan Terre, Uri Landes, Torsten Peter Vahl, Isaac George, Tamim Nazif, Ajay J Kirtane, Omar K Khalique, Rebecca T Hahn, Martin B Leon, Susheel Kodali
AIMS: Risk assessment tools currently used to predict mortality in transcatheter aortic valve implantation (TAVI) were designed for patients undergoing cardiac surgery. We aim to assess the accuracy of the TAVI dedicated American College of Cardiology / Transcatheter Valve Therapies (ACC/TVT) risk score in predicting mortality outcomes. METHODS AND RESULTS: Consecutive patients (n=1038) undergoing TAVI at a single institution from 2014 to 2016 were included. The ACC/TVT registry mortality risk score, the Society of Thoracic Surgeons - Patient Reported Outcomes (STS-PROM) score and the EuroSCORE II were calculated for all patients...
May 8, 2018: EuroIntervention
https://www.readbyqxmd.com/read/29721203/patient-derived-xenografts-pdx-predict-an-effective-heparanase-based-therapy-for-lung-cancer
#17
Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29717169/ung-1-and-apn-1-are-the-major-enzymes-to-efficiently-repair-5-hydroxymethyluracil-dna-lesions-in-c-elegans
#18
Arturo Papaluca, J Richard Wagner, H Uri Saragovi, Dindial Ramotar
In Caenorhabditis elegans, two DNA glycosylases, UNG-1 and NTH-1, and two AP endonucleases, APN-1 and EXO-3, have been characterized from the base-excision repair (BER) pathway that repairs oxidatively modified DNA bases. UNG-1 removes uracil, while NTH-1 can remove 5-hydroxymethyluracil (5-hmU), an oxidation product of thymine, as well as other lesions. Both APN-1 and EXO-3 can incise AP sites and remove 3'-blocking lesions at DNA single strand breaks, and only APN-1 possesses 3'- to 5'-exonulease and nucleotide incision repair activities...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29703020/flumazenil-reduces-respiratory-complications-during-anesthesia-emergence-in-children-with-preoperative-upper-respiratory-tract-infections
#19
Ruiqiang Sun, Guolin Wang, Xuesong Gao, Shuzhen Wang
Despite its benignity, upper respiratory infections (URIs) 1 increase the risk of postoperative respiratory complications during the perioperative and postoperative periods. Flumazenil could improve the symptoms of respiratory obstruction.To evaluate the effect of flumazenil on the occurrence of respiratory complications during anesthesia emergence of children with preoperative URI.This was a prospective study of 164 consecutive pediatric patients who underwent strabismus surgery under general anesthesia at the Tianjin Eye Hospital between August 2016 and April 2017...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29702294/worldwide-practice-patterns-in-lynch-syndrome-diagnosis-and-management-based-on-data-from-the-international-mismatch-repair-consortium
#20
Jennifer Y Pan, Robert W Haile, Allyson Templeton, Finlay Macrae, FeiFei Qin, Vandana Sundaram, Uri Ladabaum
BACKGROUND AND AIMS: Families with a history of Lynch syndrome often do not adhere to guidelines for genetic testing and screening. We investigated practice patterns related to Lynch syndrome worldwide, to ascertain potential targets for research and public policy efforts METHODS: We collected data from the International Mismatch Repair Consortium [IMRC], which comprises major research and clinical groups engaged in the care of families with Lynch syndrome worldwide. IMRC institutions were invited to complete a questionnaire to characterize diagnoses of Lynch syndrome and management practice patterns...
April 24, 2018: Clinical Gastroenterology and Hepatology
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