tbuckley/cabot-search huggingface dataset:
A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).
Authors: A. Oliver Sartor, David Laidley, Frederic Pouliot, Stephan Probst, Robert Sabbagh, Giuseppe Esposito, Fred Saad, Nancy Stambler, Evan Y. Yu
Journal: Journal of Clinical Oncology (2021)

TPS187 Background: PSMA is a transmembrane glycoprotein overexpressed in prostate cancer (PC) and further upregulated in castrate resistant disease. 1095 is a novel PSMA-targeted small molecule radioligand therapeutic that binds to the extracellular domain of PSMA selectively with high affinity, internalized, and delivers a targeted lethal radiation dose to PC cells. 18 F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown robust diagnostic performance for detecting recurrent and metastatic PC. In the ARROW study, pts must demonstrate 18 F-DCFPyL avidity prior to 1095 treatment. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at multiple sites in the US and Canada. Eligible male pts must have metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18 F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional doses administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Due to the COVID-19 pandemic, enrollment was halted in April 2020 but is reopening in October 2020. Clinical trial information: NCT03939689.
607 NEUTRALIZING HOST RESPONSES IN HEPATITIS C VIRUS INFECTION TARGET VIRAL ENTRY AT POST-BINDING STEPS AND MEMBRANE FUSION
Authors: A. Haberstroh, E.K. Schnober, P. Carolla, M.B. Zeisel, H. Barth, B. Gissler, H.E. Blum, F.L. Cosset, G. Koutsoudakis, R. Bartenschlager, E. Depla, A. Owsianka, A.H. Patel, C. Schuster, F. Stoll-Keller, M. Doffoël, M. Dreux, T.F. Baumert
Journal: Journal of Hepatology (2008)
Incorrect Units
Journal: JAMA (1990)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase II Study of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN).
Authors: Andrea M Gross, Andrea Baldwin, Eva Dombi, Pamela Wolters, Patricia Whitcomb, Marielle Holmblad, Staci Martin, Michael J. Fisher, AeRang Kim, Brian D. Weiss, Scott M. Paul, Wade Clapp, Kathleen Farrell, Michaele Smith, Joseph Fontana, Alessandra Brofferio, Seth M. Steinberg, Laurence A Doyle, Brigitte C. Widemann
Journal: Journal of Clinical Oncology (2016)

TPS10586 Background: PN, which develop in 25-40% of individuals with NF1, are typically diagnosed and exhibit the fastest growth in young children. They can be associated with substantial morbidity including disfigurement, pain and loss of function. There are no effective medical treatments for PN. Selumetinib, an oral MEK1/2 inhibitor, may mediate anti-tumor effects in PN by inhibition of Ras signaling. A recently completed phase I study of selumetinib in children with NF1 and inoperable PN showed promising results with confirmed partial responses ( ≥ 20% decrease in PN volume by volumetric MRI analysis) in > 50% of patients, which were associated with clinical improvement in some patients. Methods: The objectives of this study are to determine the confirmed partial and complete response rate to selumetinib in patients with PN related morbidity (stratum 1, primary endpoint) and without significant PN related morbidity (stratum 2, secondary endpoint), and to prospectively evaluate its effect on PN related pain, quality of life (QOL), appearance, and PN related functional impairment (stratum 1). Additionally, the pharmacokinetics and pharmacodynamics (ERK phosphorylation in peripheral blood mononuclear cells, cytokines) of selumetinib will be evaluated. Patients 2-18 years old with NF1 and inoperable PN are eligible and will be assigned to stratum 1 or 2 depending on the presence of PN related morbidity (disfigurement, pain, functional impairment: motor, airway, bowel/bladder, vision, other) at enrollment. Selumetinib is administered at the recommended pediatric dose of 25 mg/m2/dose PO BID on a continuous dosing schedule for 28-day cycles. Changes in PN size will be assessed after every 4 cycles using MRI with centralized volumetric analysis. Prospective, standardized evaluations of pain, QOL, photography of visible PN, and PN related function will be performed at baseline and then after every 4 cycles. Medication adherence will be assessed throughout. Fifty patients will be enrolled on stratum 1 (target response rate 36%, null response rate 15%). This CTEP sponsored multi-site phase II study (NCT02407405) has enrolled 21 patients to date. Clinical trial information: NCT02407405.
Long-term ambient concentrations of total suspended particulates and oxidants as related to incidence of chronic disease in California Seventh-Day Adventists.
Authors: D E Abbey, P K Mills, F F Petersen, W L Beeson
Journal: Environmental Health Perspectives (1991)

Cancer incidence and mortality in a cohort of 6000 nonsmoking California Seventh-Day Adventists were monitored for a 6-year period, and relationships with long-term cumulative ambient air pollution were observed. Total suspended particulates (TSP) and ozone were measured in terms of numbers of hours in excess of several threshold levels corresponding to national standards as well as mean concentration. For all malignant neoplasms among females, risk increased with increasing exceedance frequencies of all thresholds of TSP except the lowest one, and those increased risks were highly statistically significant. For respiratory cancers, increased risk was associated with only one threshold of ozone, and this result was of borderline significance. Respiratory disease symptoms were assessed in 1977 and again in 1987 using the National Heart, Lung and Blood Institute respiratory symptoms questionnaire on a subcohort of 3914 individuals. Multivariate analyses which adjusted for past and passive smoking and occupational exposures indicated statistically significantly (p less than 0.05) elevated relative risks ranging up to 1.7 for incidence of asthma, definite symptoms of airway obstructive disease, and chronic bronchitis with TSP in excess of all thresholds except the lowest one but not for any thresholds of ozone. A trend association (p = 0.056) was noted between the threshold of 10 pphm ozone and incidence of asthma. These results are presented within the context of standards setting for these constituents of air pollution.
HDAC8 Mediates Homologous Recombination and Cytoskeleton Integrity in Myeloma with Potential Impact on Cell Growth and Survival
Authors: Maria Gkotzamanidou, Masood Shammas, Jesus Martin Sanchez, Lai Ding, Stephane Minvielle, Florence Magrangeas, Herve Avet-Loiseau, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2014)
Immunoaugmentative Therapy
Authors: Robert G. Houston
Journal: JAMA (1988)

<h3>7b the Editor.—</h3> As a medical writer, I am puzzled by the attack on immunoaugmentative therapy (IAT) in the June 17 issue of<i>JAMA</i>,<sup>1</sup>for 11 (41%) of the 27 experts in the survey disagree that its effectiveness is unacceptable.<sup>1</sup>The article cites three articles by Burton and coworkers reporting antitumor properties of IAT proteins in animals, contradicting the Food and Drug Administration's editorial comment<sup>2</sup>that there are "no data on efficacy." A later such study<sup>3</sup>in mice reported that "small tumors disappeared in two hours." If the Food and Drug Administration rebuffed a two-year effort for an Investigational New Drug classification, should it not share the blame for the lack of clinical trials? The article terms IAT "unequivocally dangerous" based on alleged contamination of serum tested before mid-1985, notably in regard to human immunodeficiency virus (HIV). It admits, however, that Western blot tests, essential for
THE FUTURE GREAT UNIVERSITY.
Journal: JAMA (1893)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Suicide Attempts and Physical Fighting Among High School Students—United States, 2001
Journal: JAMA (2004)

Violence is a major cause of morbidity and mortality, particularly among youths. In the United States, homicide and suicide are the second and third leading causes of death, respectively, for persons aged 13-19 years. Although suicide commonly is associated with anxiety, depression, and social withdrawal, research suggests a link between violent behaviors directed at oneself (i.e., suicidal behaviors) and violent behaviors directed at others among adolescents. Certain students who engage in extreme forms of violence, such as school shootings, exhibit suicidal ideation or behavior before or during the attack. However, suicidal behavior also might be associated with involvement in less extreme forms of violent behaviors, such as physical fighting, which might be a risk factor for more severe forms of violence. To characterize any potential association between suicide attempts and fighting, CDC analyzed self-reported 2001 data from a nationally representative sample of high school students in the United States. The results of that analysis indicated that students who reported attempting suicide during the preceding 12 months were nearly four times more likely also to have reported fighting than those who reported not attempting suicide. Prevention programs that seek to reduce both suicidal and violent behaviors are needed. Because prevalence of this association was determined to be highest in the 9th grade, these efforts might be most effective if implemented before students reach high school.
Aspirin and perioperative blood loss
Authors: E. L. Michelson
Journal: JAMA (1981)

<h3>In Reply.—</h3> Dr Michelson writes that "I cannot agree with the statement... that an average additional blood loss of 400 mL 'is not of great clinical importance.' " Our overall figures of blood loss include eight different groups of patients. That is to say, we compared patients with primary operations who then had normotensive or hypotensive anesthesia and broke those groups down into patients who received 1.2 or 3.6 g of aspirin a day. There was a second major group composed of patients undergoing revision total-hip arthroplasty. They received either normotensive or hypotensive anesthesia, and each of those groups was subdivided into patients receiving 1.2 vs 3.6 g of aspirin a day. The results in all of these subsets were then compared with those of control subjects who had the corresponding characteristics, ie, primary or secondary total-hip replacement and normotensive or hypotensive anesthesia. If Dr Michelson refers to Table 3, he
JCAR015 in ALL: A Root-Cause Investigation
Journal: Cancer Discovery (2017)

After conducting an internal probe of the five deaths that halted JCAR015's development for acute lymphoblastic leukemia, Juno Therapeutics has concluded that multiple factors were at play. A surge in inflammatory cytokine levels from rapid, early T-cell proliferation may have provoked the blood-brain barrier disruption seen in these patients, inducing fatal cerebral edema.
OP28 * THE ROLE OF GENDER IN CNS TUMOUR INCIDENCE AND SURVIVAL
Authors: R. K. Mathew, S. Alli, J. Hayes, R. Parslow, P. D. Chumas
Journal: Neuro-Oncology (2014)

INTRODUCTION: Evidence exists, in germ cell tumours (GCT) and medulloblastoma subcategories, that gender significantly influences incidence and outcome - perhaps through susceptibility to tumour genesis, and sensitivity to treatment. The role of gender in other CNS tumours is unclear. METHOD: Age-adjusted incidence (2000-2007) and overall survival (OS, 1998-2007) rates were collected from the Surveillance Epidemiology and End Result (SEER) registry (covering 28% of US patients) for common CNS tumours in age epochs ranging 0-80 years. Patients with histologically confirmed, ICD-03 coded, first tumours, were included. Mortality was defined as any cause of death within 1- or 5-years of diagnosis. Results were statistically analysed by Incidence Rate Ratio (IRR), Kaplan-Meier and Log Rank (Cox Proportional Regression Hazard) Testing (p < 0.05). RESULTS: Significantly higher incidence was observed in males with grade II astrocytomas (IRR 1.19), high grade gliomas (IRR 1.18-1.26), oligodendrogliomas (IRR 1.12), lymphoma (IRR 1.18), embryonal (IRR 1.17-1.21), and GCTs (IRR 1.51) (all p < 0.05). No significant difference in incidence was seen between gender in pilocytics, ependymomas and meningiomas. 1- and 5-year OS was better in; older females with meningiomas, oligodendrogliomas and ependymomas; younger males with anaplastic astrocytomas. 5-year OS was better in; females aged <5 years with ependymomas, females aged 10-24 years with medulloblastomas; females aged 20-39 with grade II astrocytomas. CONCLUSION: Gender is a significant factor in predisposing to certain CNS tumours and treatment response - possibly through epigenetic and hormonal differences. Further investigation is needed.
Cabozantinib in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort.
Authors: Fabian Finkelmeier, Bernhard Scheiner, Catherine Leyh, Jan Best, Thorben Wilhelm Fründt, Carolin Czauderna, Alica Beutel, Dominik Bettinger, Johannes Weiß, Tobias Meischl, Fabian Kuetting, Dirk Thomas Waldschmidt, Michael Schultheiß, Thomas Jens Ettrich, Arndt Weinmann, Henning Wege, Marino Venerito, Christian Lange, Matthias Pinter, Oliver Waidmann
Journal: Journal of Clinical Oncology (2020)

e16668 Background: The multikinase inhibitor cabozantinib has been approved by the European Medicines Agency in November 2018 for hepatocellular carcinoma (HCC) prior treated with sorafenib. We report, to our knowledge, for the first time safety and efficacy data of an international, multicenter, real-world cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 10 centers in Austria and Germany. Patients´ characteristics, side effects, duration of treatment and survival data were analyzed until January 17, 2020. Results: 74 patients were identified of whom 65 patients were male (88%) and 9 were female (12%). The median age at the start of cabozantinib treatment was 66 years. The most common underlying liver diseases included hepatitis C in 15 (20%), hepatitis B in 6 (8%), alcohol in 17 (23%) and NAFLD/NASH in 20 (27%) patients, respectively. 64 patients (86%) had BCLC stage C and 43 patients (58%) were Child Pugh A. Cabozantinib was used as systemic second- and third-line treatment in 37 (50%), and 25 (34%) patients, respectively. In the remaining patients cabozantinib was used in further lines. The median starting dose was 40 mg (20-60 mg). In 26 patients (35%) a dose reduction due to side effects was performed. Following best responses under cabozantinib were documented: partial response in 4 (5%), stable disease in 22 (30%), and progressive disease in 24 (32%) patients, respectively. 24 patients (32%) had not yet been evaluable. The median duration of cabozantinib treatment was 4.4 months. 35 patients (47%) had died at day of data analysis. The median overall survival from start of cabozantinib treatment was 7.7 months. Most common adverse events were fatigue and diarrhea. Conclusions: Cabozantinib treatment was effective, safe and feasible in patients with advanced HCC. Patients in the real life setting had more advanced liver disease – only 58% of patients were Child A. Duration of treatment was similar to the phase 3 trial (CELESTIAL). However, overall survival was shorter, probably due to more advanced liver disease.
Evaluation of Levodopa for Parkinsonism. Levodopa (Dopar, Larodopa)
Journal: JAMA (1971)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Editorial Board
Authors: Gail Shapiro, Lanny Rosenwasser, Wash Denver, D Metcalfe, Immediate Past, William Busse, Robert Rich, James Kemp, Atlanta Ga, San Diego, Robert Bush, Louis Mendelson, West Hartford, Thomas Casale, Lawrence Schwartz, William Henderson, Seattle Wash, William Shearer, Robert Lemanske, Gillian Shepherd, New York, Gailen Marshall, Donald Leung, Colo Deputy, Harold Nelson, Stanley Szefler, Colo Associate, James Crapo, Erwin Gelfand, Gary Larsen, Bruce Bochner, Philip Norman, Kay Whalen
Journal: Journal of Allergy and Clinical Immunology (2001)
Abstract 147: The Valosin-Containing Protein Regulates Mitochondrial Respiration and Membrane Permeability via Inducible Nitric Oxide Synthase in the Mouse Heart
Authors: Shaunrick A Stoll, Ning Zhou, Hongyu Qiu
Journal: Circulation Research (2017)

Introduction: Mitochondrial dysfunction plays a critical role in mediating cell death during ischemia/reperfusion (IR). We previously found that overexpressing valosin-containing protein (VCP), an ATPase associate-binding protein, in a transgenic (TG) mouse heart increases the expression of inducible nitric oxide synthase (iNOS) and reduces infarct size during IR. We tested the hypothesis that VCP mediates cardiac protection by increasing mitochondrial respiration and inhibiting the opening of the mitochondrial permeability transition pore (mPTP) via iNOS. Methods and Results: Cardiac mitochondria were isolated from the heart tissues of adult VCP TG and their litter-matched WT mice (N=6/group). VCP TG mice increased the expression of VCP by 3.1 folds and iNOS by 4.5 folds in the mitochondrial fraction vs WT ( p &lt;0.01). Mitochondrial respiration was determined by oxygen consumption rate (OCR) in an airtight chamber with a Clark-type electrode. Compared to WT, mitochondria from VCP TG showed a significant increase in OCR during ADP-dependent State 3 under Complex I stimulation while no significant change was seen in oligomycin induced-State 4, increasing the efficiency of mitochondrial respiration, as measured by the respiratory control ratio (State 3/State 4). VCP TG mice also displayed a significant increase in their maximum respiration capacity versus WT, measured after the addition of the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone. However, there was no difference between VCP TG and WT on Complex II-dependent respiration rate, suggesting VCP’s predominance on Complex I-stimulated respiration. mPTP opening was induced by Ca 2+ overload in isolated mitochondria and was measured by a swelling assay. Compared to WT mice, VCP TG showed significantly less mitochondrial swelling under the Ca 2+ overload ( p &lt;0.05). To test whether protection by VCP is mediated by iNOS, a bigenic VCP TG /iNOS knock out mouse was generated. Deletion of iNOS from the VCP TG abolishes the effects of VCP on mitochondrial respiration and mPTP opening. Conclusion: VCP prevents the opening of the mPTP and increases mitochondrial respiratory efficiency in an iNOS dependent manner, which may represent a novel mechanism of cardiac protection.