tbuckley/cabot-search huggingface dataset:
P15.05 High-dose methotrexate based immuno-chemotherapy with maintenance chemotherapy with High-dose methotrexate and deferred radiotherapy for elderly primary CNS lymphoma patients
Authors: K. Mishima, Y. Miyake
Journal: Neuro-Oncology (2017)

Introduction: High-dose methotrexate (HD-MTX)-based chemotherapy with whole brain irradiation (WBRT) improves the prognosis of PCNSL. However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. Therefore, developing novel treatment for the elderly patients is crucial. To assess the efficacy and toxicity of induction immunochemotherapy with rituximab (RIT) and HD-MTX, maintenance chemotherapy with HD-MTX and deferred WBRT in the treatment of elderly PCNSL patients, we conducted a retrospective analysis. Materials and Methods: Newly diagnosed elderly PCNSL patients (median age: 74 years) received biweekly RIT/ HD-MTX (375 mg/m2/dose; 3.5g/m2/dose) for 6 cycles followed by monthly RIT/MTX for 2 cycles (induction) and then were treated differently according to radiological response. With CR patents, HD-MTX was continued with every 3 months (maintenance) for 2 years. For PD patients, immunochemotherapy was interrupted and WBRT initiated immediately. Patients with PR and SD were treated with alternative chemotherapy with temozolomide and/or stereotactic radiotherapy or WBRT. Results: Twenty-eight patients were treated with the RIT/HD-MTX regimen. In 26 patients suitable for radiographic evaluation, 61.5% (16/26) had a CR, 23.1% (6/26) had a PR, 3.8 % (1/26) had a SD and 11.5% (3/26) had a PD. The median PFS was 24.6 months and median OS was 28.2 months for the entire cohort. Grade III-IV toxicities were observed in 8 of 28 patients and included neutropenia in 17.9%, thrombocytopenia in 3.6%, pneumonia in 10.7%, elevation of aminotransferases in 3.6%, and hyponatremia in 3.6%. Patients achieving a CR after induction immunochemotherapy (n=16) had a significantly longer OS (65.8 months) and PFS (52.4 months) than patients with less than CR (n=10) (OS: 13.9 months; PFS: 9.3 months) (P<.0001). Conclusions: The RIT/HD-MTX regimen and maintenance chemotherapy with HD-MTX seems to play a favorable role in elderly PCNSL patients with mild toxicity.
Poly (ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
Authors: Jie Zhang, Lucio Tentori, Pedro Lacal, Carlo Leonetti, Alessia Muzi, Annalisa Dorio, Marco Scarsella, Federica Ruffini, Weizheng Xu, Zhao-Qi Wang, Grazia Graziani
Journal: Cancer Research (2007)

4623  Poly(ADP-ribose) polymerase (PARP)-1 has recently been shown to promote tumor progression through its transcriptional regulatory activity. Since angiogenesis is an essential requirement for tumor growth, we investigated whether PARP inhibition might affect endothelial cell functions and vessel formation.  To this end, the effect of PARP inhibitors on endothelial cell proliferation, migration, tube formation and on in vivo angiogenesis, using a matrigel plug assay, was assessed. For the in vitro studies we used an immortalized human endothelial cell line (HUV-ST), which displays all major endothelial phenotypes and forms tubule-like networks in response to stimuli by growth factors.  The results indicated that the PARP inhibitor GPI 15427 (IC50 on endothelial PARP: 237 + 27 nM), at concentrations devoid of cytotoxic effects (0.5-1 uM), abrogated migration in response to vascular endothelail growth factor (VEGF) or placenta growth factor (PlGF) and hampered the ability of HUV-ST cells to form tubule-like networks. Moreover, the PARP inhibitor impaired in vivo angiogenesis as measured by the matrigel plug assay. The anti-angiogenic effect of the PARP inhibitor was confirmed in mice with PARP-1 gene deletion (PARP-1 KO), which displayed a defect of in vivo angiogenesis induced by growth factors.  These results from studies using either PARP inhibitors of PARP-1 KO mice provide evidence for targeting PARP for anti-angiogenesis. The discovery adds novel therapeutic implications to the use of PARP inhibitors for cancer treatment.
IFITM3 Is a Central Regulator of Lipid Raft Signaling and Essential for CD19 Surface Expression and PI3K Signaling in Human B Cell Malignancies
Authors: Jae-Woong Lee, Huimin Geng, Kadriye Nehir Cosgun, Lai N Chan, Zhengshan Chen, Eugene Park, Lars Klemm, Charles C. Bailey, Markus Müschen
Journal: Blood (2016)
EPIDEMIOLOGY OF SPORTS INJURIES AMONG MIDDLE SCHOOL STUDENTS
Authors: Shane Caswell, Matthew Prebble, Kaitlyn Romm, Jatin Ambegaonkar, Amanda Caswell, Nelson Cortes
Journal: British Journal of Sports Medicine (2017)

Background Participation in youth sports is increasing. Yet, limited research on the incidence and severity of injuries within middle school sports(MSS) exists. Objective Describe the epidemiology of injuries in MSS within a large metropolitan school system located in the US. Design Prospective descriptive epidemiology. Setting Injury data collected in 9-MSS programs during 2015–2016. Patients (or Participants) Boy(n=1194) and girl(n=1008) athletes(age=11–14 years) participating in 12 school sponsored sports. Interventions (or Assessment of Risk Factors) Each of the 9 schools was assigned an athletic trainer(AT) who attended all practices and games during the fall, winter, and spring sports seasons of 2015–2016. Main Outcome Measurements ATs collected injury and athlete-exposure(AE) data. Injury frequencies and rates with 95% confidence intervals(95%CI) for practices and games were described by sport for all injuries (no-time-loss and time-loss). Injury proportions were described by body region. Results 1643 injuries(182.6±64.8 injuries/school) were reported. Highest rates of injury were: Girls' basketball (39.4/1000AE 95% CI: 34.7–44.1), American football (30.7/1000AE 95% CI: 27.3–34.1), wrestling (28.7/1000AE 95% CI: 24.4–32.9), and girls' soccer (26.3/1000AE 95% CI: 22.1–30.6). Lowest rates of injury were: Girls' volleyball (9.1/1000AE 95% CI: 6.7–11.6), boys' baseball (10.2/1000AE 95% CI: 6.8–13.5), cheerleading (10.6/1000AE 95% CI: 8.5–12.8), and boys' soccer (14.7/1000AE 95% CI: 11.8–17.7). Most injuries occurred during practice (n=889, 54%) compared with games (n=390, 24%). The top three injured body regions injured were: lower extremity (n=744, 45%), upper extremity (n=409, 25%), and head (n=297, 18%). The highest rates of concussion were: football (2.9/1000AE 95% CI: 1.9–4.0), girls' soccer (2.2/1000AE 95% CI: 0.9–3.4), and cheerleading (1.1/1000AE 95% CI: 0.4–1.8). Most concussions occurred during practice (47.3%) compared with games (34.5%). Conclusions Consistent with previous research a greater proportion of MMS injuries occurred during practices than games. However, our finding that girls' basketball had the highest injury rate differs from prior research. Overall, our rates were higher than those previously reported, yet more precise given our sample size and detailed documentation AE. Our findings highlight the need for medical care at MMS practices and games.
Abstract 210: Titin Phosphorylation by Protein Kinase G as a Novel Mechanism of Diastolic Adaptation to Acute Hemodynamic Overload
Authors: João Almeida-Coelho, André M Leite-Moreira, João S Neves, Manuel Neiva-Sousa, Ricardo Castro-Ferreira, Nazha Hamdani, Wolfgang A Linke, Inês Falcão-Pires, André P Lourenço, Adelino F Leite-Moreira
Journal: Circulation Research (2015)

Titin is the main determinant of myocardial passive tension and its distensibility is increased via phosphorylation by protein kinase G (PKG), activated by nitric oxide (NO) and natriuretic peptides (NP) upon acute overload. We hypothesized whether myocardial stretch led to decreased stiffness, optimizing diastolic filling along with the usual increase in contractility. Intact rat Langendorff hearts, strips dissected from the LV or right atrium of cardiac surgery patients and rabbit papillary muscles were acutely stretched for 15min. Passive tension (PT) was measured in skinned cardiomyocytes extracted from the LV of control and stretched rat hearts for sarcomere lengths (SL) 1.8-2.3μm before and after incubation with PKG. Rabbit muscles were incubated with a PKG inhibitor or, simultaneously, a NO synthase inhibitor, a NO scavenger, a NP receptor A antagonist. All-total titin phosphorylation was stained with Pro-Q Diamond and indexed to total-protein signals using SYPRO Ruby. Values are given as mean±SEM and statistical significance was set to p&lt;0.05. After acute stretch there was a progressive decrease in passive tension/diastolic pressure over 15min: 27±8% and 27±6% in human atrium and ventricular muscles, respectively, and 43±2% in rabbit papillary muscles and isolated hearts. This decrease in myocardial stiffness was significantly blunted by PKG inhibition (40%) and NO/NP pathway inhibition (29%). PT of cardiomyocytes was significantly lower (≈60%) in the previously stretched group for all SL. A similar effect, only significant in the control group, was observed after incubation with PKG. Titin phosphorylation increased markedly 15 minutes after acute myocardial stretch in human (atrial: 11±1% vs 41±8%; LV: 27±8% vs 71±21%) and rabbit (13±2% vs 23±3%) myocardium. The progressive decrease in myocardial stiffness after acute hemodynamic overload is preserved at the myofilamental level and seems to depend on PKG activity, representing a potential therapeutic target in patients with pathologically rigid myocardium. Moreover, blocking PKG activation seems to attenuate this adaptive diastolic response. Therefore, titin phosphorylation by this kinase is probably involved in this new myocardial response to stretch in both animals and humans.
Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial
Authors: Petra Innerhofer, Dietmar Fries, Markus Mittermayr, Nicole Innerhofer, Daniel von Langen, Tobias Hell, Gottfried Gruber, Stefan Schmid, Barbara Friesenecker, Ingo H Lorenz, Mathias Ströhle, Verena Rastner, Susanne Trübsbach, Helmut Raab, Benedikt Treml, Dieter Wally, Benjamin Treichl, Agnes Mayr, Christof Kranewitter, Elgar Oswald
Journal: The Lancet Haematology (2017)
Challenges to Translation and the Hippocratic Oath by Premature Termination of Spinal Cord Stem Cell–Based Trials
Authors: Armin Curt, Allan D. Levi, Jan M. Schwab
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
P16.15 An intracranial chondrosarcoma mimicking a skull base meningioma
Authors: S. Lee, J. Baek
Journal: Neuro-Oncology (2017)

Introduction: A chondrosarcoma is very rare and accounts for 0.15% of all intracranial tumors. Due to its rarity, the diagnoses of another more common types of pathologic entities are often made, before the operation. Materials and Methods: A 41-year-old female patient presented to the hospital with aggravating headache. A brain CT and MRI scan revealed a 5*4*4 cm sized brain tumor in the right frontal lobe. Results: During operation, the frozen section suggested a sarcoma. Due to its hypervascularity and copious tumoral bleeding during operation, piecemeal removal was not feasible. Thus, the tumor was removed in a large piece with a dissection along the tumor margin. The histopathologic examination of the tumor displayed a chondroid differentiation, and accordingly, a chondrosarcoma was finally diagnosed. During the follow-up investigation for two years after the resection of the tumor, the patient had been in a good general state of health and no tumor recurrence had occurred. Conclusions: Even its rarity and radiological resembleance with other skull base tumors like a meningioma, a chondrosarcoma should be included in the differential diagnosis
Abstract 12920: Transforming Growth Factor-Beta-Dependent Pathway Induces the Cardiac Fibrosis and Remodeling in Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene-Disrupted Mice
Authors: Umadevi Subramanian, Venkateswara Gogulamudi, Isaac Kessler, David Chen, Kailash N Pandey
Journal: Circulation (2016)

Introduction: Targeted-ablation of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene ( Npr1 ) in mice exhibits hypertension and provokes congestive heart failure; however, the underlying mechanisms are not well understood. Hypothesis: To determine whether transforming growth factor-beta 1 (TGF)-β1 receptor antagonist, GW788388 inhibits the development of cardiac fibrosis and remodeling in GC-A/NPRA gene-disrupted mice. Methods: The adult male (16-20 weeks) Npr1 null mutant ( Npr1 -/- , 0-copy), heterozygous ( Npr1 +/- , 1-copy), and wild-type ( Npr1 +/+ , 2-copy) mice were orally administered with TGF-β1 receptor antagonist, GW788388 (2 mg/kg/day) for 28 days. The expression of cardiac fibrotic markers was analyzed using real-time PCR and Western blot. Heart weight-to-body weight (HW/BW) ratios were determined and heart functions were measured by echocardiographic analysis. Results: The Npr1 -/- mice showed markedly increased cardiac fibrosis and HW/BW ratio with increased expression of collagen-1α (3.5-fold), monocyte chemoattractant protein (4-fold), connective tissue growth factor (CTGF, 5-fold), α-smooth muscle actin (α-SMA, 4-fold), TGF-βRI (4-fold), TGF-βRII (3.5-fold) and SMAD proteins (SMAD-2, 5-fold; SMAD-3, 3-fold) compared with Npr1 +/+ mice. The expression of phosphorylated extracellular-regulated kinase (pERK1/2) was also up-regulated in Npr1 -/- mice. The treatment of Npr1 -/- mice with GW788388 significantly prevented the development of cardiac fibrosis and down-regulated the expression of fibrotic markers and SMAD proteins compared to vehicle-treated mice. In contrast, the expression of pERK1/2 proteins was unaffected in GW7885388-treated mice excluding the involvement of non-genomic pathway. The left ventricular dimensions (systole and diastole) and fractional shortening were significantly improved in the drug-treated Npr1 -/- mice. Conclusions: The results suggest that the cardiac fibrosis, remodeling, and dysfunction in Npr1 -/- mice are regulated through TGF-β-mediated SMAD-dependent canonical pathway. The findings will be important for the development of new molecular therapeutic targets for the treatment of cardiac fibrosis, remodeling, and dysfunction in human patients.
Time for an End to Juice in the Special Supplemental Nutrition Program for Women, Infants, and Children
Authors: Heather A. Ferris, Elvira Isganaitis, Florence Brown
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Association of MHC-II, PD-L1, and FoxP3 with Disease Status and Outcomes in Patients with Hodgkin Lymphoma
Authors: Santosha A. Vardhana, Neval Ozkaya, Eri Matsuki, Janine D. Pichardo, Alison J. Moskowitz, David J Straus, Amanda R Copeland, Ai Ni, Achim A Jungbluth, Craig H Moskowitz, Ahmet Dogan, Anas Younes
Journal: Blood (2016)
DYNAMIC TAPING AND HIGH FRONTAL PLANE KNEE PROJECTION ANGLE IN FEMALE VOLLEYBALL ATHLETES
Authors: Natalia Bittencourt, Marcela Leite, Alysson Zuin, Marina Pereira, Gabriela Gonçalves, Silvanio Signoretti
Journal: British Journal of Sports Medicine (2017)

Background Two-dimensional frontal plane knee projection angle (FPKPA) has been used to assess dynamic knee alignment during single leg squat in athletes with patellofemoral pain and to screen athletes who are at risk for anterior cruciate ligament (ACL) injury. The Dynamic Taping (DT) could be used in motor control training to decrease load of lower limbs muscles and improve movement pattern. Objective Compare FPKPA before and after the application of dynamic taping in female volleyball athletes. Design Cross-sectional study. Setting The FPKPA was used to measure knee medial motion. The ICC was 0.90 and the standard error of measurement (SEM) was 1.65°. All these measurements were performed at Minas Tenis Clube. Patients (or Participants) 18 female volleyball players participated in this study; the mean for age was 19.44±4.48 years; body mass, 72.28±8.20 kg; and height 182.67±7.63 cm. Interventions (or Assessment of Risk Factors) A spiral DT(double-layer /Powerband) technique was placed with the hip in 40° abduction, 20° extension and full available external rotation, aiming to resist hip adduction, flexion and internal rotation. The tape was applied by the same professional stretching until resistance begins such that increasing resistance would be created with any movement towards adduction, internal rotation and flexion thereby creating a deceleration force. Main Outcome Measurements The FPKPA was recorded during single leg squat until 80° knee flexion before and after the Dynamic Taping (R) application. Results 10 of 18 athletes had high FPKPA (&gt;8 o ) and the T-test revealed statistical difference pre and post DT (p&lt;0,0001). Pre DT Mean of FPKPA was 10.5 o and Post DT mean was 5.4 o . Conclusions This study has shown the DT application decreased FPKPA during single leg squat in female volleyball athletes. This approach could be an important tool to enhance movement quality and prevent knee injuries.
Delays in GP rescue package are “unacceptable,” says BMA
Authors: Gareth Iacobucci
Journal: BMJ (2017)

A much vaunted financial rescue package for GPs in England has failed to provide sufficient support to practices in its first 12 months, the BMA has said.

In a progress report on the first year of NHS England’s General Practice Forward View , the BMA said that delivery of the plan had been “confusing and inadequate” since its launch in April 2016.

The blueprint was widely welcomed by GP leaders last year after pledging an extra £2.4bn (€2.8bn; $3.1bn) for general practice by 2020-21 to redress years of underinvestment.1

But the BMA said that …
Abstract 19056: Discovery of Potent and Selective Neprilysin Inhibitors Exhibiting Sustained Pharmacodynamic Activity and Non-renal Elimination in Rats
Authors: David L Bourdet, Alex McNamara, Craig Hill, Kevin DeMent, Melissa Fleury, Cecile Yu, Laxminarayan G Hegde, William Martin, Sharath Hegde, Uwe Klein, Adam D Hughes
Journal: Circulation (2015)

Introduction: Neprilysin (NEP) inhibitors in combination with angiotensin-II receptor antagonists (ARNIs) have demonstrated benefits in patients with hypertension and chronic heart failure (CHF). A significant population of patients with cardiorenal diseases (e.g., CHF, chronic kidney disease and diabetic nephropathy) exhibit moderate to severe levels of renal impairment. Sacubitril (NEP inhibitor component of LCZ696) is extensively cleared by the kidney and systemic exposures are increased in patients with renal dysfunction thus potentially limiting its therapeutic utility. We aimed to identify potent and selective NEP inhibitors that exhibit non-renal excretion in order to discover agents that may provide optimal therapy in patients with renal dysfunction. Methods: In vitro enzyme activity assays at human NEP were used to assess inhibitory potencies and half-lives of the enzyme-inhibitor complexes. In vivo potentiation of ANP-induced plasma cGMP was evaluated after PO dosing in Sprague Dawley rats. Blood pressure was monitored in conscious Dahl Salt-Sensitive (Dahl/SS) hypertensive rats surgically implanted with telemetry transmitters. Urinary and biliary excretion was evaluated in bile-duct cannulated rats. Results: Selective NEP inhibitors (THRX-213068, THRX-134025, and THRX-124283) were identified with increased potency relative to LBQ657 (active moiety of sacubitril) at NEP (pKi 9.4, 9.3, 9.3 versus 8.2) and displayed longer enzyme residence time (T1/2 = 25, 145, and 190 versus 3 min). All three NEP inhibitors potentiated cGMP to a greater extent than LBQ657 in rat plasma after PO dosing (10 mg/kg). Sustained lowering of mean arterial pressure also was observed in Dahl/SS rats after PO dosing (24 hr average change -17 to -45 mm Hg). Negligible renal excretion was observed for all NEP inhibitors in rats after IV or PO dosing [&lt; 5% of dose relative to 40% (IV) for LBQ657]. Conclusions: Novel, potent, and selective NEP inhibitors were identified that exhibit sustained potentiation of cGMP and BP-lowering in rodent models. Negligible levels of renal excretion were observed in rats suggesting the possibility of providing consistent dosing in patients with cardiorenal diseases across various levels of renal dysfunction.