tbuckley/cabot-search huggingface dataset:
HuBC1-IL12: A very potent immunocytokine which targets the oncofetal fibronectin in the extracellular matrix of tumor vasculature
Authors: Kin-Ming Lo, Yan Lan, Scott Lauder, Jinyang Zhang, Beatrice Brunkhorst, Rakesh Verma, Nigel Courtenay-Luck, Stephen D. Gillies
Journal: Cancer Research (2004)

4686  IL-12 is a heterodimeric cytokine with potent anti-tumor activity, but its use in the clinic has been hampered by its severe systemic toxicity. Here we describe a fusion protein, huBC1-IL12, which specifically targets IL-12 to the tumor vasculature and therefore has therapeutic potential. HuBC1 is a humanized antibody that targets a cryptic sequence of the human ED-B-containing fibronectin isoform, B-FN, which is present in the subendothelial extracellular matrix (ECM) of most aggressive tumors. B-FN is one of the best tumor markers because it is oncofetal and angiogenesis-associated, and is undetectable in most normal adult tissues. The original murine BC1 antibody has been used successfully for immunoscintigraphy to image brain tumor mass in glioblastoma patients. In huBC1-IL12, each of the immunoglobulin heavy chains is genetically fused to the N-terminus of the IL-12 p35 subunit, which in turn is disulfide-bonded to the p40 subunit, resulting in a hexameric molecule of MW of ∼300 kilodaltons. Because of the interstitial pressure of a solid tumor, the ECM of the tumor neovasculature should be more accessible than the tumor cells themselves to an intravenously administered drug, making B-FN an ideal target for immunotherapy with a complex molecule such as huBC1-IL12. Since human IL12 has no biological activity in mice, we first produced huBC1-muIL12 as a surrogate molecule for animal tumor models. Despite the poor PK profile of this molecule in mice, one cycle of treatment with huBC1-muIL12 showed very potent anti-tumor activity in several xenogeneic models, such as PC3mm2, A431, and HT29 subcutaneous tumor models and PC3mm2 lung metastasis model, in SCID mice which lack T and B cells. A fusion protein that contains human IL12 (huBC1-huIL12), which is therefore a suitable molecule for investigation as a therapeutic, has also been produced. This protein has been shown to have a longer serum half-life than huBC1-muIL12 in mice, and retains both antigen binding and IL-12 activity in in vitro assays.
3'-deoxy-3'-[18F]fluorothymidine position emission tomography for target delineation in resected malignant gliomas before radiotherapy.
Authors: Fen Zhao, Minghuan Li, Zheng Fu, Jinming Yu
Journal: Journal of Clinical Oncology (2013)

e13052 Background: To analyze the FLT PET image feature of malignant gliomas and evaluate the usefulness in the visualization of residual tumor volume compared with MRI. Methods: Patients with postoperative residual malignant gliomas were enrolled on this prospective trial. MRI and PET were performed in the same week, 1 to 4 weeks after surgical resection.,we compared the SUVmax of tumor and the T/N ratio between the grade III and IV gliomas and the residual tumor volume and the geometric position defined by FLT uptake and the abnormalities signals on MRI were compared using FLT PET/MRI fusion images. Results: 19 patients were analyzed. The SUVmax were 0.86±28 for grade 3 gliomas , and 2.68±2.22 or 2.05±0.44(with or without one gliosarcoma whose SUVmax was as high as 9.6) for grade IV gliomas (P &lt;0.001). The mean (±SD) value of T/N ratio in grade IV gliomas were 15.43±10.47 or 12.48±2.20(including or not of the gliosarcoma ) and 4.84±1.77 in gade III gliomas(P &lt;0.001). The mean Vol-T1, Vol-T2 and Vol-PET was 13.08cm3,33.46cm3 , and 15.04cm3 , respectively. The Vol-PET were not significant larger than the Vol-T1( P&gt;0.05). The areas between the increased FLT PET activity and abnormality in MRI were imperfectly correlated .In 13 (68.4%) and 11 patients(57.90%) , the FLT uptake regions exceeded the area of contrast enhancement and the area of hyperintensity areas on the MRI. In 5 (26.3%) and 4(21.05%) of 19 patients, FLT uptake extended 25 mm from the margin of Gd enhancement and hyperintensity areas. And the FLT uptake was measured up to 43mm and 39mm outside of the Gd enhancement and hyperintensity areas on MRI. Conclusions: FLT PET was found to be useful in assessment of grade in malignant gliomas. FLT PET can provide complement information to the MRI for defining the remaining tumor volume accurately in patients with malignant gliomas postoperative residual .
Additional resource needs for viral hepatitis elimination through universal health coverage: projections in 67 low-income and middle-income countries, 2016–30
Authors: David Tordrup, Yvan Hutin, Karin Stenberg, Jeremy A Lauer, David W Hutton, Mehlika Toy, Nick Scott, Marc Bulterys, Andrew Ball, Gottfried Hirnschall
Journal: The Lancet Global Health (2019)

BackgroundThe World Health Assembly calls for elimination of viral hepatitis as a public health threat by 2030 (ie, −90% incidence and −65% mortality). However, WHO's 2017 cost projections to achieve health-related Sustainable Development Goals did not include the resources needed for hepatitis testing and treatment. We aimed to estimate the incremental commodity cost of adding scaled up interventions for testing and treatment of hepatitis to WHO's investment scenarios.MethodsWe added modelled costs for implementing WHO recommended hepatitis testing and treatment to the 2017 WHO cost projections. We quantified additional requirements for diagnostic tests, medicines, health workers' time, and programme support across 67 low-income and middle-income countries, from 2016–30. A progress scenario scaled up interventions and a more ambitious scenario was modelled to reach elimination by 2030. We used 2018 best available prices of diagnostics and generic medicines. We estimated total costs and the additional investment needed over the projection of the 2016 baseline cost.FindingsThe 67 countries considered included 230 million people living with hepatitis B virus (HBV) and 52 million people living with hepatitis C virus (HCV; 90% and 73% of the world's total, respectively). Under the progress scenario, 3250 million people (2400 million for HBV and 850 million for HCV) would be tested and 58·2 million people (24·1 million for HBV and 34·1 million for HCV) would be treated (total additional cost US$ 27·1 billion). Under the ambitious scenario, 11 631 million people (5502 million for HBV and 6129 million for HCV) would be tested and 93·8 million people (32·2 million for HBV and 61·6 million for HCV) would be treated (total additional cost $58·7 billion), averting 4·5 million premature deaths and leading to a gain of 51·5 million healthy life-years by 2030. However, if affordable HCV medicines remained inaccessible in 13 countries where medicine patents are protected, the additional cost of the ambitious scenario would increase to $118 billion. Hepatitis elimination would account for a 1·5% increase to the WHO ambitious health-care strengthening scenario costs, avert an additional 4·6% premature deaths, and add an additional 9·6% healthy life-years from 2016–30.InterpretationAccess to affordable medicines in all countries will be key to reach hepatitis elimination. This study suggests that elimination is feasible in the context of universal health coverage. It points to commodities as key determinants for the overall price tag and to options for cost reduction strategies.FundingWHO, United States Centers for Disease Control and Prevention, Unitaid.
Impact of Prolonged Spaceflight on Orthostatic Tolerance During Ambulation and Blood Pressure Profiles in Astronauts
Authors: Qi Fu, Shigeki Shibata, Jeffrey L. Hastings, Steven H. Platts, Douglas M. Hamilton, Michael W. Bungo, Michael B. Stenger, Christine Ribeiro, Beverley Adams-Huet, Benjamin D. Levine
Journal: Circulation (2019)

Background: Astronauts returning to earth usually demonstrate reduced orthostatic tolerance when assessed on a tilt table or quiet standing, but no studies have evaluated postflight orthostatic tolerance during activities of daily living, when it is most clinically relevant. Ambulatory blood pressure (BP) variability also is associated with orthostatic intolerance in certain patient populations and can capture clinically significant orthostatic hypotension during activities of daily living, especially when measured on a beat-to-beat basis. We evaluated the impact of prolonged spaceflight on orthostatic tolerance and BP profiles in astronauts. Methods: Ambulatory beat-to-beat BP was recorded using a portable device for multiple 24-hour time periods before, during, and after 6 months of spaceflight in 12 astronauts (4 women; age 48±5 [mean±SD] years). BP variability in the time domain was calculated as the SD. Systolic BP distribution during activities of daily living was characterized by skewness and kurtosis. Results: In contrast with results from previous studies that used tilt tables or stand tests, no astronaut experienced orthostatic intolerance/hypotension during activities of daily living before or after spaceflight. Also, 24-hour systolic BP decreased in space (120±10 mm Hg before spaceflight versus 106±9 mm Hg during spaceflight; P &lt;0.01), but it returned to normal upon landing (122±13 mm Hg). Diastolic BP was unchanged during and after spaceflight. Systolic and diastolic BP variability remained the same before, during, and after spaceflight (both P &gt;0.05). The skewness of systolic BP increased in space (0.74±0.51 versus 1.43±1.00; P =0.001), indicating that signal fluctuations became asymmetrical; however, it returned to preflight levels after landing (0.51±0.42). The kurtosis increased in space (5.01±7.67 versus 11.10±11.79; P =0.010), suggesting that fluctuations concentrated around the mean with a narrow distribution; however, it also returned to preflight levels (2.21±2.56) after return to earth. Conclusions: Given current countermeasures including in-flight exercise training and volume resuscitation on return, no astronauts experienced orthostatic hypotension or intolerance during routine (for landing day) activities in the initial 24 hours after landing following 6 months in space. Prolonged exposure to spaceflight had little impact on systolic BP variability and its distribution, although the latter showed a transient change in space (accompanied by mild relative hypotension), all of which returned to preflight values after return to earth.
Demographics, management and outcome of females and males with acute respiratory distress syndrome in the LUNG SAFE prospective cohort study
Authors: Bairbre A. McNicholas, Fabiana Madotto, Tài Pham, Emanuele Rezoagli, Claire H. Masterson, Shahd Horie, Giacomo Bellani, Laurent Brochard, John G. Laffey
Journal: European Respiratory Journal (2019)

Rationale We wished to determine the influence of sex on the management and outcomes in acute respiratory distress syndrome (ARDS) patients in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods We assessed the effect of sex on mortality, intensive care unit and hospital length of stay, and duration of invasive mechanical ventilation (IMV) in patients with ARDS who underwent IMV, adjusting for plausible clinical and geographic confounders. Findings Of 2377 patients with ARDS, 905 (38%) were female and 1472 (62%) were male. There were no sex differences in clinician recognition of ARDS or critical illness severity profile. Females received higher tidal volumes (8.2±2.1 versus 7.2±1.6 mL·kg −1 ; p&lt;0.0001) and higher plateau and driving pressures compared with males. Lower tidal volume ventilation was received by 50% of females compared with 74% of males (p&lt;0.0001). In shorter patients (height ≤1.69 m), females were significantly less likely to receive lower tidal volumes. Surviving females had a shorter duration of IMV and reduced length of stay compared with males. Overall hospital mortality was similar in females (40.2%) versus males (40.2%). However, female sex was associated with higher mortality in patients with severe confirmed ARDS (OR for sex (male versus female) 0.35, 95% CI 0.14–0.83). Conclusions Shorter females with ARDS are less likely to receive lower tidal volume ventilation, while females with severe confirmed ARDS have a higher mortality risk. These data highlight the need for better ventilatory management in females to improve their outcomes from ARDS.
Cortical Neurogenesis Requires Bcl6-Mediated Transcriptional Repression of Multiple Self-Renewal-Promoting Extrinsic Pathways
Authors: Jerome Bonnefont, Luca Tiberi, Jelle van den Ameele, Delphine Potier, Zachary B. Gaber, Xionghui Lin, Angéline Bilheu, Adèle Herpoel, Fausto D. Velez Bravo, François Guillemot, Stein Aerts, Pierre Vanderhaeghen
Journal: Neuron (2019)

During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional and epigenetic analyses with in vivo functional studies to demonstrate that Bcl6, a transcriptional repressor previously reported to promote cortical neurogenesis, acts as a driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 represses its targets through Sirt1 recruitment followed by histone deacetylation. Our data identify a molecular logic by which a single cell-intrinsic factor represses multiple extrinsic pathways that favor self-renewal, thereby ensuring robustness of neuronal fate transition.
“Autistic people”? Who do you mean?
Authors: Yonata Levy
Journal: Behavioral and Brain Sciences (2019)

Abstract Jaswal &amp; Akhtar (J&amp;A) offer evidence against lack of social motivation in “autistic people,” providing no further phenotypic details as to the autism spectrum disorder (ASD) subgroups that they refer to. I will argue that given the extensive behavioral and neurobiological heterogeneity among people who receive the diagnosis, reference to “autistic people” is misleading. As a consequence, J&amp;A's claims are difficult to interpret.
Rapamycin Increases Collateral Circulation in Rodent Brain after Focal Ischemia as detected by Multiple Modality Dynamic Imaging
Authors: Jixian Wang, Xiaojie Lin, Zhihao Mu, Fanxia Shen, Linyuan Zhang, Qing Xie, Yaohui Tang, Yongting Wang, Zhijun Zhang, Guo-Yuan Yang
Journal: Theranostics (2019)

Rationale: Brain collaterals contribute to improving ischemic stroke outcomes.However, dynamic and timely investigations of collateral blood flow and collateral restoration in whole brains of living animals have rarely been reported.Methods: Using multiple modalities of imaging, including synchrotron radiation angiography, laser speckle imaging, and micro-CT imaging, we dynamically explored collateral circulation throughout the whole brain in the rodent middle cerebral artery occlusion model. Results:We demonstrated that compared to control animals, 4 neocollaterals gradually formed between the intra-and extra-arteries in the skull base of model animals after occlusion (p<0.05).Two main collaterals were critical to the supply of blood from the posterior to the middle cerebral artery territory in the deep brain (p<0.05).Abundant small vessel and capillary anastomoses were detected on the surface of the cortex between the posterior and middle cerebral artery and between the anterior and middle cerebral artery (p<0.05).Collateral perfusion occurred immediately (≈15 min) and was maintained for up to 14 days after occlusion.Further study revealed that administration of rapamycin at 15 min after MCAO dilated the existing collateral vessels and promoted collateral perfusion.Principal conclusions: Our results provide evidence of collateral functional perfusion in the skull base, deep brain, and surface of the cortex.Rapamycin was capable of enlarging the diameter of collaterals, potentially extending the time window for ischemic stroke therapy.
Abstract 14529: Increased Inpatient Mortality in Atrial Flutter and Fibrillation Admissions During October to April: A Nationwide Analysis
Authors: Shawn Lee, Alejandro Lemor, Farid Gholitabar, Carlos A Gongora, Abel Casso Dominguez, Paul T Kroner, Carolina Hurtado, Daniel Castaneda, Davendra Mehta
Journal: Circulation (2016)

Background: Patients admitted with diagnoses of atrial flutter and/or fibrillation (AF) are associated with significant inpatient mortality. We evaluated seasonal variation of admission in patients...
Effect of thoracic radiotherapy in extensive-disease small cell lung cancer on progression-free and overall survival: A retrospective review.
Authors: James Matthew Wilson, Anna Grundy, Kate Best, Paula M Mulvenna, Rhona McMenemin
Journal: Journal of Clinical Oncology (2012)

e17519 Background: Extensive-disease small cell lung cancer (ED-SCLC) carries a poor prognosis. The current standard practice of 4-6 cycles of a platinum based chemotherapy (PC) leads to a median survival of only 9-11 months. The role of thoracic radiotherapy (TRT) in ED-SCLC remains controversial. We report patient outcomes with ED-SCLC with respect to whether they received TRT or not. Methods: The practice of two oncologists from 2005-2009 was retrospectively reviewed. Patient age, performance status (PS) at presentation and site of progression were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated with respect to the patient receiving 4-6 cycles of PC or not and then again in this subgroup with respect to whether or not they had TRT at any time after chemotherapy. Survival data was compared using the log-rank test. Results: 141 patients age 42-86 years old (mean 67.4 years) were identified. 58% were PS 0-2. 56 patients (40%) completed 4-6 cycles of PC with a median PFS of 8.4 months compared to 2.4 months in those that did not (p&lt;0.001), median OS was 8.9 and 3.1 months (p&lt;0.001). Of the 45 who had the site of progression recorded - 49% progressed within the thorax. Of 87 patents who received any chemotherapy, 43 received TRT and 44 did not with median PFS of 7.8 and 5.4 months respectively (p= 0.003) and median OS of 8.9 and 5.9 months (p=0.002). In the 56 patients who received 4-6 cycles of PC, median PFS was 9.2 with and 7.7 months without TRT (p=0.02). Median OS was 10.2 months with and 7.7 without TRT (p=0.02). Conclusions: Patients who received TRT at some point in their treatment demonstrated improved median PFS and OS. The role of TRT in ED-SCLC warrants further evaluation. The results of the REST trial are eagerly anticipated.
Collaborative Care for Adults With Obesity and Depression
Authors: Calum D. Moulton, Thahesh Tharmaraja, Christopher W. P. Hopkins
Journal: JAMA (2019)

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
TP53 abnormalities and chromosomal aneuploidy in acute panmyelosis with myelofibrosis
Authors: Milena Pantic, Dietmar Pfeifer, Silke Kapp-Schwoerer, Gabriele Ihorst, Heiko Becker, Robert Zeiser, Justus Duyster, Annette Schmitt-Graeff
Journal: Leukemia (2019)
Economic analysis of TORCH: Erlotinib versus cisplatin and gemcitabine as first-line therapy for advanced non-small cell lung cancer (NSCLC).
Authors: Carmen Chung, Wanrudee Isaranuwatchai, Massimo Di Maio, Haiyan Jiang, Anthea Lau, Jeffrey S. Hoch, Ronald Feld, Ming Sound Tsao, Cesare Gridelli, Fortunato Ciardiello, Charles Andrew Butts, Ciro Gallo, Francesco Perrone, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2013)

e19031 Background: The TORCH (“Tarceva or Chemotherapy”) randomized phase III trial demonstrated that first-line erlotinib compared to cisplatin/gemcitabine in unselected advanced NSCLC patients yielded inferior survival, but no major differences in global quality of life. We determined the incremental costs and utility between arms, including in the EGFR mutation positive subgroup. Methods: Direct medical resource utilization data and EQ5D scores were collected prospectively during the trial. Costs for medications, outpatient visits, investigations and toxicity management including hospitalization were determined, and presented in 2012 Canadian dollars (CAD). The outcome of the analysis was the incremental cost per life year and quality-adjusted life-years (QALYs) gained. Results: The incremental mean cost per patient in the chemotherapy arm was $4,163CAD, largely related to drug and outpatient visit costs, while higher costs from hospitalization and adverse events were seen in the erlotinib arm. Mean overall and quality-adjusted survival times were longer in the chemotherapy arm. In the subset of patients with EGFR mutations (n=39), mean survival was not significantly different between arms (1.35 years for chemotherapy versus 1.29 years for erlotinib, p-value=0.86), but quality-adjusted survival favoured erlotinib treatment (i.e. mean QALYs were 1.04 for chemotherapy, and 1.40 for erlotinib). The incremental cost-effectiveness ratio for initial erlotinib in the EGFR mutation positive subgroup was $30,301 CAD per QALY. Conclusions: Initial chemotherapy in unselected advanced NSCLC yields better survival at minimal increased cost compared to erlotinib. In the EGFR mutation positive subgroup, first-line erlotinib is cost effective compared to first-line platinum doublet therapy, supporting routine EGFR genotyping to select first-line therapy in advanced NSCLC.
Abstract 13654: Doctor and Nurse Risk Assessment Accuracy in Patients Suspected of Acute Coronary Syndrome in the Emergency Room
Authors: Carolyn M Astley, Allyson Chapple, Anthony Chuang, Robyn Clark, Matthew Horsfall, Andrew Blyth, Derek P Chew
Journal: Circulation (2017)

Introduction: Patients with undifferentiated chest pain constitute a large proportion of emergency room (ER) presentations, creating a significant resource burden. Currently timely and accurate ris...
Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV
Authors: Willem D.F. Venter, Michelle Moorhouse, Simiso Sokhela, Lee Fairlie, Nkuli Mashabane, Masebole Masenya, Celicia Serenata, Godspower Akpomiemie, Ambar Qavi, Nomathemba Chandiwana, Shane Norris, Matthew Chersich, Polly Clayden, Elaine Abrams, Natasha Arulappan, Alinda Vos, Kaitlyn McCann, Bryony Simmons, Andrew Hill
Journal: New England Journal of Medicine (2019)

Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries.