tbuckley/cabot-search huggingface dataset:
Survival of melanoma patients with brain metastases treated with ipilimumab combined with stereotactic radiosurgery.
Authors: Karim Tazi, Cody Chiuzan, Keisuke Shirai
Journal: Journal of Clinical Oncology (2013)

e20019 Background: Historically, melanoma with brain metastases has a poor prognosis and is a major contributor to patient morbidity and mortality. Recently, the use of ipilimumab has improved overall survival in stage IV melanoma; however, the outcome of patients with brain metastases remains unclear. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). Methods: All patients with metastatic melanoma treated with ipilimumab from April 2010 to March 2012 were identified and stratified by presence (A) or absence (B) of brain metastases. All patients with brain metastases received SRS. Performance status, dates of stage IV diagnosis, brain SRS and cycle 1 of ipilimumab administration were recorded. We used the Disease Specific Graded Prognostic Assessment (DS-GPA) to estimate the predicted survival. Overall survival was defined as time (months) from the date of the stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and compared using a two-tailed log-rank test. Results: Twelve of 30 patients treated with ipilimumab had brain metastases. Median age was 66 years. Median DS-GPA score was 3 (estimated mean survival of 8.7 months). Four patients (33%) in group A and 6 patients (33%) in group B died as of last follow-up. Median number of SRS treatment was 1 (1 to 4), and median total treated lesions were 3 (1-14). Median survivals from date of Stage IV for A and B were 29.1 and 32.9 months, respectively (p=0.67). The estimated 2 year survival rates from date of cycle 1 ipilimumab administration for A and B were 58% (95% CI: 32-100%) and 55% (95% CI: 32-93%), respectively. Ten out of 12 patients in group A maintained an ECOG PS of 0-1 as of last follow-up. Conclusions: Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases. Ipilimumab and SRS do not seem to adversely impact quality of life.
Anti-Myeloma Activity of Combined Inhibition of the Proteasome with Carfilzomib (CFZ) and XPO1/CRM1-Dependent Nuclear Export By Selinexor (KPT-330) Via a Novel Mechanism of Intracellular Activation of Caspase 10-Dependent Apoptosis
Authors: Shaun Rosebeck, Mattina Alonge, Jagoda Jasielec, Dilara McCauley, Sharon Shacham, Michael Kauffman, Andrzej Jakubowiak
Journal: Blood (2014)
Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo
Authors: Sumati Bhatia, Daniel Lauster, Markus Bardua, Kai Ludwig, Stefano Angioletti-Uberti, Nicole Popp, Ute Hoffmann, Florian Paulus, Matthias Budt, Marlena Stadtmüller, Thorsten Wolff, Alf Hamann, Christoph Böttcher, Andreas Herrmann, Rainer Haag
Journal: Biomaterials (2017)
Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis and Suppresses Medulloblastoma Formation
Authors: Katherine Tech, Andrey P. Tikunov, Hamza Farooq, A. Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C. Green, Hedi Liu, Yisu Li, Andrew J. Mungall, Richard A. Moore, Yussanne Ma, Steven J.M. Jones, Marco A. Marra, Matthew G. Vander Heiden, Michael D. Taylor, Jeffrey M. Macdonald, Timothy R. Gershon
Journal: Cancer Research (2017)

Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation, and tumorigenesis. We observed a dichotomous pattern of PKM expression, in which postmitotic neurons throughout the brain expressed the constitutively active PKM1 isoform, while neural progenitors and medulloblastomas exclusively expressed the less active PKM2. Isoform-specific Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed reduced lactate production and increased SHH-driven proliferation. 13C-flux analysis showed that Pkm2 deletion reduced the flow of glucose carbons into lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2 deletion accelerated tumor formation in medulloblastoma-prone ND2:SmoA1 mice, indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect. These findings show that distal and proximal disruptions of glycolysis have opposite effects on proliferation, and that efforts to block the oncogenic effect of aerobic glycolysis must target reactions upstream of PKM. Cancer Res; 77(12); 3217-30. ©2017 AACR.
Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes
Authors: Wayne A. Ray, Katherine T. Murray, Sarah Meredith, Sukumar Suguna Narasimhulu, Kathi Hall, C. Michael Stein
Journal: New England Journal of Medicine (2004)

Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A.We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time-concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication.The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors.The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided.
Using foresight to prioritise the present
Authors: Adam Bulley, Gillian Pepper, Thomas Suddendorf
Journal: Behavioral and Brain Sciences (2017)

Abstract Planning for the future may encourage apparently “impulsive” behaviour when the future is anticipated to be bleak. Thus, a seeming failure of self-control in reactive violence could be caused not by a disinclination to plan ahead, but by virtue of this ability. Furthermore, we point to empirical and theoretical shortcomings in the authors' case, such as a failure to distinguish proximate and ultimate explanations.
Abstract 123: SUMO1 Modification Regulates SR Calcium ATPase Pump, SERCA2a in Heart Failure
Authors: Changwon Kho, Ahyoung Lee, Dongtak Jeong, Jae Gyun Oh, Antoine Chaanine, Woo Jin Park, Roger Hajjar
Journal: Circulation Research (2012)

Background: The cardiac calcium ATPase, SERCA2a, is a critical pump responsible for Ca2+ re-uptake during excitation-contraction coupling. Impaired Ca2+ uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. However, the underlying mechanisms of SERCA2a’s dysfunction remain incompletely understood. Methods and Results: In this study, we show that SERCA2a is modified by SUMO1 at lysine sites 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. SUMO1 and SERCA2a SUMOylation levels were both decreased in mouse and pig models of heart failure and failing human left ventricles. To determine whether reduced SUMO1 levels are responsible for reduced SERCA2a protein levels and reduced cardiac function, we used an adenovirus associated virus-mediated gene delivery approach to up-regulate SUMO1 in trans aortic constriction-induced mouse model of heart failure. We found that increasing SUMO1 levels led to a restoration of SERCA2a levels, improved hemodynamic performance, and reduced mouse mortality. By contrast, down-regulation of SUMO1 using small hairpin RNA accelerated cardiac functional deterioration and was accompanied by decreased SERCA2a function. Conclusion: In this study, we study a new mechanism for modulation of SERCA2a activity and beneficial effects of SUMO1 in the setting of heart failure. It suggests that changes in post-translational modifications of SERCA2a could negatively affect cardiac function in heart failure. Our data may provide a new platform for the design of therapeutic strategies for heart failure.
Hyperhomocysteinemia in relation to total and cardiovascular death after coronary bypass grafting.
Authors: D Girelli, N Martinelli, O Olivieri, E Trabetti, G Pizzolo, S Friso, C Bozzini, I Tenuti, G Faccini, Lotto, Pf Pignatti, A Mazzucco, R Corrocher
Journal: Blood (2005)
Safety of Endoscopic Sphincterotomy in Patients with Periampullary Diverticulum
Authors: A Zaheer, M Kirca, S Jamal, S McKiernan, N Keeling, N Mahmud
Journal: Endoscopy (2006)

Background: Periampullary duodenal diverticula (PAD) are generally an incidental finding in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). There is uncertainty about the increased risk of complications especially with endoscopic sphincterotomy (ES).
Identification of a Human Clonogenic Progenitor with Strict Monocyte Differentiation Potential: A Counterpart of Mouse cMoPs
Authors: Shunsuke Kawamura, Nobuyuki Onai, Fuyuki Miya, Taku Sato, Tatsuhiko Tsunoda, Kazutaka Kurabayashi, Satoshi Yotsumoto, Shoko Kuroda, Katsuto Takenaka, Koichi Akashi, Toshiaki Ohteki
Journal: Immunity (2017)
Abstract 337: Reversal of Pathological Responses to Pressure Overload by Inhibition of Phospholipase Cbeta1b
Authors: David R Grubb, Helen Kiriazis, Xiao-jun Du, Julie McMullen, Elizabeth Woodcock
Journal: Circulation Research (2015)

The immediate downstream effector of Galpahq is the early signaling enzyme phospholipase Cbeta1b (PLCbeta1b), which is selectively elevated in failing human myocardium. When delivered to the adult mouse heart, expression of PLCbeta1b causes rapid contractile dysfunction. PLCbeta1b targets to the sarcolemma for activation through an interaction with Shank3/Homer1C/TrpC4α using a specific C-terminal sequence of 32aa. The targeting/activity of PLCbeta1b can be inhibited by expression of a sarcolemmal targeted mini-gene composed of this 32aa sequence (lyn-FLAG-PLCbeta1b-CT, b-CT). rAAV6-b-CT, or blank virus, was delivered IV (1011vg/mouse) and trans-aortic-constriction (TAC) or sham-operation was performed 8 weeks later. TAC induced maximal hypertrophy by 8 weeks after TAC, followed by contractile dysfunction and lung congestion from 16 weeks. Expression of rAAV6-b-CT prior to TAC reduced the hypertrophic response and prevented the contractile dysfunction and lung congestion. Expressing a modified b-CT peptide that does not inhibit PLCbeta1b signaling had no effect on hypertrophy, contractility or lung congestion following TAC. We conclude that PLCbeta1b can be effectively targeted by preventing its binding to the sarcolemma and that this inhibition ameliorates pathological responses following acute pressure overload. The binding of PLCbeta1b to its sarcolemmal scaffold provides the basis for the development of a new class of inotropic agent.
Delaying ACL reconstruction and treating with exercise therapy alone may alter prognostic factors for 5-year outcome: an exploratory analysis of the KANON trial
Authors: Stephanie R Filbay, Ewa M Roos, Richard B Frobell, Frank Roemer, Jonas Ranstam, L Stefan Lohmander
Journal: British Journal of Sports Medicine (2017)

Aim Identify injury-related, patient-reported and treatment-related prognostic factors for 5-year outcomes in acutely ACL-ruptured individuals managed with early reconstruction plus exercise therapy, exercise therapy plus delayed reconstruction or exercise therapy alone. Methods Exploratory analysis of the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) trial ( ISRCTN84752559 ). Relationships between prognostic factors (baseline cartilage, meniscus and osteochondral damage, baseline extension deficit, baseline patient-reported outcomes, number of rehabilitation visits, graft/contralateral ACL rupture, non-ACL surgery and ACL treatment strategy) and 5-year Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms, sport/recreation and quality of life (QOL) scores were explored using multivariable linear regression. Estimates were adjusted for sex, age, body mass index, preinjury activity level, education and smoking. Results For all participants (n=118), graft/contralateral ACL rupture, non-ACL surgery and worse baseline 36-item Short-Form Mental Component Scores were associated with worse outcomes. Treatment with exercise therapy alone was a prognostic factor for less knee symptoms compared with early reconstruction plus exercise therapy (regression coefficient 10.1, 95% CI 2.3 to 17.9). Baseline meniscus lesion was associated with worse sport/recreation function (−14.4, 95% CI −27.6 to –1.3) and osteochondral lesions were associated with worse QOL (−12.3, 95% CI −24.3 to –0.4) following early reconstruction plus exercise therapy. In the same group, undergoing additional non-ACL surgery and worse baseline KOOS scores were prognostic for worse outcome on all KOOS subscales. Following delayed reconstruction, baseline meniscus damage was a prognostic factor for less pain (14.3, 95% CI 0.7 to 27.9). Following exercise therapy alone, undergoing non-ACL surgery was prognostic for worse pain. Conclusions Treatment-dependent differences in prognostic factors for 5-year outcomes may support individualised treatment after acute ACL rupture in young active individuals. Trial registration number Current Controlled Trials ISRCTN84752559 .
Occurrence of Acute Cerebellar Syndrome After Topical Application of Fluorouracil
Authors: Jo-David Fine, Anna Dewan, Jami L. Miller
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Early MMF Discontinuation Is an Effective and Safe Measure to Decrease CMV Reactivation in Patients Submitted to Unmanipulated Haploidentical Transplant with Post-Cy Immunosuppression
Authors: Mariana Nassif Kerbauy, Lucila Nassif Kerbauy, Iracema Esteves, Jairo Jose Nascimento Sobrinho, Jose Mauro Kutner, Morgani Rodrigues, Fabio Pires de Souza Santos, Guilherme Fleury Perini, Luis Fernando Aranha Camargo, Jacyr Pasternak, Juliana Folloni Fernandes, Luiz Fernando Alves Lima Mantovani, Angela Mandelli Venancio, Gabriele Zamperlini Netto, Cinthya Corrêa da Silva, Fabio Rodrigues Kerbauy, Andreza Alice Feitosa Ribeiro, Nelson Hamerschlak
Journal: Blood (2016)
Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging
Authors: Mandy L. Ballinger, Ana Best, Phuong L. Mai, Payal P. Khincha, Jennifer T. Loud, June A. Peters, Maria Isabel Achatz, Rubens Chojniak, Alexandre Balieiro da Costa, Karina Miranda Santiago, Judy Garber, Allison F. O’Neill, Rosalind A. Eeles, D. Gareth Evans, Eveline Bleiker, Gabe S. Sonke, Marielle Ruijs, Claudette Loo, Joshua Schiffman, Anne Naumer, Wendy Kohlmann, Louise C. Strong, Jasmina Bojadzieva, David Malkin, Surya P. Rednam, Elena M. Stoffel, Erika Koeppe, Jeffrey N. Weitzel, Thomas P. Slavin, Bita Nehoray, Mark Robson, Michael Walsh, Lorenzo Manelli, Anita Villani, David M. Thomas, Sharon A. Savage
Journal: JAMA Oncology (2017)

<h3>Importance</h3> Guidelines for clinical management in Li-Fraumeni syndrome, a multiple-organ cancer predisposition condition, are limited. Whole-body magnetic resonance imaging (WBMRI) may play a role in surveillance of this high-risk population. <h3>Objective</h3> To assess the clinical utility of WBMRI in germline<i>TP53</i>mutation carriers at baseline. <h3>Data Sources</h3> Clinical and research surveillance cohorts were identified through the Li-Fraumeni Exploration Research Consortium. <h3>Study Selection</h3> Cohorts that incorporated WBMRI for individuals with germline<i>TP53</i>mutations from January 1, 2004, through October 1, 2016, were included. <h3>Data Extraction and Synthesis</h3> Data were extracted by investigators from each cohort independently and synthesized by 2 investigators. Random-effects meta-analysis methods were used to estimate proportions. <h3>Main Outcomes and Measures</h3> The proportions of participants at baseline in whom a lesion was detected that required follow-up and in whom a new primary malignant neoplasm was detected. <h3>Results</h3> A total of 578 participants (376 female [65.1%] and 202 male [34.9%]; mean [SD] age, 33.2 [17.1] years) from 13 cohorts in 6 countries were included in the analysis. Two hundred twenty-five lesions requiring clinical follow-up were detected by WBMRI in 173 participants. Sixty-one lesions were diagnosed in 54 individuals as benign or malignant neoplasms. Overall, 42 cancers were identified in 39 individuals, with 35 new localized cancers treated with curative intent. The overall estimated detection rate for new, localized primary cancers was 7% (95% CI, 5%-9%). <h3>Conclusions and Relevance</h3> These data suggest clinical utility of baseline WBMRI in<i>TP53</i>germline mutation carriers and may form an integral part of baseline clinical risk management in this high-risk population.
The role of adolescence in geographic variation in violent aggression
Authors: Abigail A Marsh
Journal: Behavioral and Brain Sciences (2017)

In explaining variation in violent aggression across populations, the age structures of those populations must be considered. Adolescents between the ages of 15 and 25 are disproportionately responsible for violent aggression in every society, and increases in violence tend to follow population "youth bulges." Large numbers of adolescents in equatorial regions may account for observed relationships between geography and violence.
CAR T Cells Administered in Combination with Lymphodepletion and PD-1 Inhibition to Patients with Neuroblastoma
Authors: Andras Heczey, Chrystal U. Louis, Barbara Savoldo, Olga Dakhova, April Durett, Bambi Grilley, Hao Liu, Mengfeng F. Wu, Zhuyong Mei, Adrian Gee, Birju Mehta, Huimin Zhang, Nadia Mahmood, Haruko Tashiro, Helen E. Heslop, Gianpietro Dotti, Cliona M. Rooney, Malcolm K. Brenner
Journal: Molecular Therapy (2017)

Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor. Eleven patients were treated with CARTs. The infusions were safe, and no dose-limiting toxicities occurred. CARTs were detectable in cohort 1, but the lymphodepletion induced by Cy/Flu increased circulating levels of the homeostatic cytokine interleukin (IL)-15 (p = 0.003) and increased CART expansion by up to 3 logs (p = 0.03). PD-1 inhibition did not further enhance expansion or persistence. Antitumor responses at 6 weeks were modest. We observed a striking expansion of CD45/CD33/CD11b/CD163+ myeloid cells (change from baseline, p = 0.0126) in all patients, which may have contributed to the modest early antitumor responses; the effect of these cells merits further study. Thus, CARTs are safe, and Cy/Flu can further increase their expansion. Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor. Eleven patients were treated with CARTs. The infusions were safe, and no dose-limiting toxicities occurred. CARTs were detectable in cohort 1, but the lymphodepletion induced by Cy/Flu increased circulating levels of the homeostatic cytokine interleukin (IL)-15 (p = 0.003) and increased CART expansion by up to 3 logs (p = 0.03). PD-1 inhibition did not further enhance expansion or persistence. Antitumor responses at 6 weeks were modest. We observed a striking expansion of CD45/CD33/CD11b/CD163+ myeloid cells (change from baseline, p = 0.0126) in all patients, which may have contributed to the modest early antitumor responses; the effect of these cells merits further study. Thus, CARTs are safe, and Cy/Flu can further increase their expansion.