tbuckley/cabot-search huggingface dataset:
Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC
Authors: Timothy F Cloughesy, Joseph Landolfi, Michael A Vogelbaum, Derek Ostertag, James B Elder, Stephen Bloomfield, Bob Carter, Clark C Chen, Steven N Kalkanis, Santosh Kesari, Albert Lai, Ian Y Lee, Linda M Liau, Tom Mikkelsen, Phioanh Nghiemphu, David Piccioni, William Accomando, Oscar R Diago, Daniel J Hogan, Dawn Gammon, Noriyuki Kasahara, Thian Kheoh, Douglas J Jolly, Harry E Gruber, Asha Das, Tobias Walbert
Journal: Neuro-Oncology (2018)

Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of antitumor immunity. Recurrent high-grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months. In this setting, relapse is nearly universal and most responses are transient.In this Toca 511 ascending-dose phase I trial (NCT01470794), HGG patients who recurred after standard of care underwent surgical resection and received Toca 511 injected into the resection cavity wall, followed by orally administered cycles of Toca FC.Among 56 patients, durable complete responses were observed. A subgroup was identified based on Toca 511 dose and entry requirements for the follow-up phase III study. In this subgroup, which included both isocitrate dehydrogenase 1 (IDH1) mutant and wild-type tumors, the durable response rate is 21.7%. Median duration of follow-up for responders is 35.7+ months. As of August 25, 2017, all responders remain in response and are alive 33.9+ to 52.2+ months after Toca 511 administration, suggesting a positive association of durable response with overall survival.Multiyear durable responses have been observed in rHGG patients treated with Toca 511 + Toca FC in a phase I trial, and the treatment will be further evaluated in a randomized phase III trial. Among IDH1 mutant patients treated at first recurrence, there may be an enrichment of complete responders.
MUCOSAL INCISION DEEP BIOPSY IS USEFUL AND SAFE DIAGNOSTIC TECHNIQUE FOR SUBEPITHELIAL TUMORS
Authors: JS Moon, KH Ko, YM Woo, JY Kim, TY Park, SH Ryu, YS Kim, SY Seol
Journal: Endoscopy (2018)

Acquiring sufficient tissue is important for the definite diagnosis of subepithelial tumors (SETs). Better tissue sampling techniques are needed to improve pathological diagnosis. The aim of this study was to evaluate the usefulness and safety of mucosal incision deep biopsy.
Latent Growth and Dynamic Structural Equation Models
Authors: Kevin J. Grimm, Nilam Ram
Journal: Annual Review of Clinical Psychology (2018)

Latent growth models make up a class of methods to study within-person change—how it progresses, how it differs across individuals, what are its determinants, and what are its consequences. Latent growth methods have been applied in many domains to examine average and differential responses to interventions and treatments. In this review, we introduce the growth modeling approach to studying change by presenting different models of change and interpretations of their model parameters. We then apply these methods to examining sex differences in the development of binge drinking behavior through adolescence and into adulthood. Advances in growth modeling methods are then discussed and include inherently nonlinear growth models, derivative specification of growth models, and latent change score models to study stochastic change processes. We conclude with relevant design issues of longitudinal studies and considerations for the analysis of longitudinal data.
Abdominal Wound Closure: Choice of Suture
Authors: T E Bucknall
Journal: Journal of the Royal Society of Medicine (1981)

Experiments were designed to test suture materials for their use in potentially infected abdominal wound closure. The nearest to the ideal, at present available, is a monofilament nonabsorbable suture, the one tested being monofilament nylon. The suture retained adequate strength in the infected and noninfected state over a 70-day period. This is particularly important as infection has been shown to result in low wound strength in the early phases of healing. The monofilamentous nature of this suture represented an advantage when sutures were examined electronmicroscopically. Infected, braided sutures viewed for the first time by electronmicroscopy were shown to contain bacteria and polymorphonuclear cells, even after 70 days implantation. The normal absorption and encapsulation of these sutures was delayed by the presence of infection. Polyglycolic acid had marked strength when new but rapidly weakened after implantation. This together with slowed absorption in the infected state is a disturbing feature in terms of wound failure and sinus formation respectively.
Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarcinoma Invasion and Tumor Growth
Authors: Nicola Rath, June Munro, Marie Francene Cutiongco, Alicja Jagiełło, Nikolaj Gadegaard, Lynn McGarry, Mathieu Unbekandt, Evdokia Michalopoulou, Jurre J. Kamphorst, David Sumpton, Gillian Mackay, Claire Vennin, Marina Pajic, Paul Timpson, Michael F. Olson
Journal: Cancer Research (2018)

Abstract The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small-molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancreatic cancer progression and that conditional ROCK activation accelerates mortality in a genetically modified LSL-KrasG12D; LSL-p53R172H; Pdx1-Cre; (KPC) mouse pancreatic cancer model. In this study, we show that treatment of KPC mouse and human TKCC5 patient-derived pancreatic tumor cells with AT13148, as well as the ROCK-selective inhibitors Y27632 and H1152, act comparably in blocking ROCK substrate phosphorylation. AT13148, Y27632, and H1152 induced morphologic changes and reduced cellular contractile force generation, motility on pliable discontinuous substrates, and three-dimensional collagen matrix invasion. AT13148 treatment reduced subcutaneous tumor growth and blocked invasion of healthy pancreatic tissue by KPC tumor cells in vivo without affecting proliferation, suggesting a role for local tissue invasion as a contributor to primary tumor growth. These results suggest that AT13148 has antitumor properties that may be beneficial in combination therapies or in the adjuvant setting to reduce pancreatic cancer cell invasion and slow primary tumor growth. AT13148 might also have the additional benefit of enabling tumor resection by maintaining separation between tumor and healthy tissue boundaries. Significance: Preclinical evaluation of a small-molecule ROCK inhibitor reveals significant effects on PDAC invasion and tumor growth, further validating ROCK kinases as viable therapeutic targets in pancreatic cancer. Cancer Res; 78(12); 3321–36. ©2018 AACR.
Abstract 16937: Glycemic Response to a Single Food is Influenced by Plasma HgbA1c Concentrations
Authors: Nirupa R Matthan, Lynne M Ausman, Hocine Tighiouart, Elizabeth J Reverri, Alice H Lichtenstein
Journal: Circulation (2014)

The utility of glycemic index (GI) values for chronic disease risk management remains controversial. While absolute GI value determinations for individual foods have been shown to vary significantly in individuals with type 1 or type 2 diabetes, there is a dearth of data on the reliability of GI value determinations and potential sources of variability among healthy adults. Our objective was to determine the intra-individual (within an individual) and inter-individual (among individuals) variability in glycemic response to a single food challenge as well as biological factors that potentially mediate this response. GI value for white bread relative to glucose was determined in 63 volunteers free from chronic disease with fasting glucose values   5.7 (57 ± 11 vs. 66 ± 15, p=0.03). These data indicate substantial variability in individual responses to GI value determinations, suggesting that it is unlikely to be good approach to guide food choices in the clinical setting. Additionally, glycemic control, even in healthy individuals, significantly contributes to the variability in glycemic response among individuals.
Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D<sub>3</sub>, after a summer holiday in Northern Europe
Authors: J. Narbutt, P.A. Philipsen, A. Lesiak, T. Sandberg Liljendahl, D. Segerbäck, J. Heydenreich, D. Chlebna-Sokol, P. Olsen, G.I. Harrison, A. Pearson, K. Baczynska, M. Rogowski-Tylman, H.C. Wulf, A.R. Young
Journal: British Journal of Dermatology (2018)

Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children.To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV).Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy.The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol μmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday.Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.
Abstract 15445: New Oral Anticoagulants for Cancer-Associated Venous Thromboembolism: A Meta-Analysis
Authors: Satyanarayana Vaidya, Sonu Gupta, Santhosh R Devarapally
Journal: Circulation (2017)

Introduction: The efficacy and safety of newer oral anticoagulants (NOA) compared to warfarin (VKI) in preventing the recurrence of venous thromboembolism (VTE) is well documented. Hypothesis: Howe...
Five new medical schools: a decline in standards is inevitable
Authors: Philip F Harris
Journal: BMJ (2018)

I read with great concern that the government plans to create “five new medical schools to increase home grown doctors.”1 This is in response to increasing levels of morbidity in an ageing population and a rise in general practitioners taking early retirement. The government’s top priority should be to reform the NHS to relieve stressful working conditions and stop the brain drain of experienced …
Catalytic hairpin assembly gel assay for multiple and sensitive microRNA detection
Authors: Wenhao Dai, Jing Zhang, Xiangdan Meng, Jie He, Kai Zhang, Yu Cao, Dongdong Wang, Haifeng Dong, Xueji Zhang
Journal: Theranostics (2018)

As important modulators of gene expression, microRNAs (miRNAs) have been identified as promising biomarkers with powerful predictive value in diagnosis and prognosis for several diseases, especially for cancers.Here we report a facile, multiple and sensitive miRNA detection method that uses conventional gel electrophoresis and catalytic hairpin assembly (CHA) system without any complex nanomaterials or enzymatic amplification.Methods: In this study, three pairs of hairpin probes are rationally designed with thermodynamically and kinetically preferable feasibility for the CHA process.In the present of target miRNA, the stem of the corresponding hairpin detection probe (HDP) will be unfolded and expose the concealed domain.The corresponding hairpin assistant probe (HAP) then replaces the hybridized target miRNA to form specific HDP/HAP complexes and releases miRNA based on thermodynamically driven entropy gain process, and the released miRNA triggers the next recycle to produce tremendous corresponding HDP/HAP complexes. Results:The results showed that the CHA gel assay can detect miRNA at fM levels and shows good capability of discriminating miRNA family members and base-mismatched miRNAs.It is able to analyze miRNAs extracted from cell lysates, which are consistent with the results of conventional polymerase chain reaction (PCR) method.Depending on the length of the designed hairpin probes, the CHA gel assay consisting of different hairpin probes effectively discriminated and simultaneously detected multiple miRNAs in homogenous solution and miRNAs extracted from cell lysates. Conclusion:The work highlights the practical use of a conventional gel electrophoresis for sensitive interesting nucleic acid sequences detection.
Transjugular intrahepatic portosystemic shunt versus betablocker and/or endotherapy for prevention of variceal rebleeding in adults with EHPVO
Authors: H. Chen, J. Fan, S. Tang, C. He, Y. Lv, Q. Wang, H. Liu, J. Yuan, B. Luo, T. Yu, X. Yuan, Z. Yin, G. Han
Journal: Journal of Hepatology (2018)
Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control
Authors: Louise Lang Lehrskov, Mark Preben Lyngbaek, Line Soederlund, Grit Elster Legaard, Jan Adam Ehses, Sarah Elizabeth Heywood, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard
Journal: Cell Metabolism (2018)
The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation
Authors: Dapeng Wang, Huitian Diao, Adam J. Getzler, Walter Rogal, Megan A. Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W. Goldrath, Matthew E. Pipkin
Journal: Immunity (2018)
Taking a Closer Look at the Biomarker Test for Mild Traumatic Brain Injury
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Quality and Safety in Health Care, Part XXXIX
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

Models to predict patient risk in undergoing a percutaneous coronary intervention (PCI) have been put forward by authors studying data from the CathPCI Registry. CathPCI data can be used to improve processes and decrease the rate of complications. Outcome data from the CathPCI Registry can be used to assess not only institutional performance but also the performance of the physicians performing the PCI. CathPCI data can also be used to assess the complication rate from various types of vascular closure devices.
Government Actions to Curb the Opioid Epidemic
Authors: Mary van den Berg-Wolf
Journal: JAMA (2018)

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
Abstract 18506: Right Ventricular and Pulmonary Vascular Reserve in Heart Failure With Preserved Ejection Fraction: An Exercise Cardiac Magnetic Resonance Study
Authors: Thibault Petit, Guido Claessen, Andre La Gerche, Maarten Vanhaverbeke, Sander Trenson, Rik Willems, Johan Van Cleemput, Walter Droogné, Jan Bogaert, Piet Claus, Marion Delcroix, Hein Heidbuchel, Stefan Janssens
Journal: Circulation (2015)

Introduction: Right ventricular dysfunction (RVD) is a marker of adverse outcome in HFpEF patients. While RVD in HFpEF has been demonstrated using dobutamine stress and invasive hemodynamic studies, detailed assessment of RV and pulmonary vascular (PV) function using simultaneous exercise cardiac MRI and invasive hemodynamic measurements has never been performed. Methods In a prospective study, we performed CPET to determine maximal power output (Pmax) in patients with HFpEF (n=11, age 73±9 years) and in healthy controls (n=8, age 53±7 years). We also investigated asymptomatic subjects with echocardiographic evidence of LV concentric remodeling (LVCR) and impaired relaxation (n=4, age 63±7 years). All participants then performed a three-stage supine bicycle exercise test during real-time CMR imaging (at 25%, 50% and 66% of Pmax) with continuous recording of pulmonary arterial pressures using fluid-filled catheters. We determined the ratio of mPAP relative to cardiac output (mPAP/CO slope) as a measure of PV reserve and the change in RV end-systolic pressure volume ratio (dRVESPR) as a measure for RV contractile reserve. Results At rest, there was no difference in LV or RV ejection fraction (EF) between HFpEF patients and controls (p=NS). However, during exercise, HFpEF patients showed a decline in RVEF (-3.9±1.7%), contrasting with a marked increase in RVEF in the control group (+12.49±2.33%, p&lt;0.001 for interaction workload*group, figure 1A). HFpEF patients had a greater mPAP/CO slope (p&lt;0.001, figure 1B) and a significantly lower dRVESPVR (p&lt;0.001) than controls. Interestingly, asymptomatic subjects with LVCR showed an intermediate response to exercise (figure 1A-B). Conclusion In patients with HFpEF, RV functional reserve and pulmonary pressure-flow relationships are markedly impaired. These data suggest an important role for cardiac exercise MRI in phenotyping heart failure patients and guiding RV or pulmonary vasculature targeted therapy.
VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells
Authors: Fanyang Kong, Lei Li, Guokun Wang, Xuan Deng, Zhaoshen Li, Xiangyu Kong
Journal: Gut (2018)

We read with great interest the recent publication by Ferrer-Mayorga et al ,1 concerning Vitamin D receptor (VDR) signalling’s impacts on cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). In line with one previous publication regarding VDR in pancreatic cancer (PC),2 activation of VDR signalling in stromal fibroblasts predicts a favourable clinical outcome in CRC. Both reports set the concept in principle that VDR agonists can be explored as a therapy against tumor-associated stroma in PC and CRC. However, detailed mechanisms involved in VDR’s regulation of tumor-stroma crosstalk remained to be elucidated.

Recent publications identified exosomal miRNAs as critical mediators for cellular communication. In this study, we aimed to investigate whether exosomal miRNAs were implicated in VDR’s regulation against the protumoural activity of CAFs. Three immortalised CAF cell lines were generated from PC patients following the protocol reported previously.3 Exosomes released by CAFs were labelled with fluorescent dye 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI) and incubated with PC cell lines (PANC-1 and SW1990) for 24 hours. Analysis using fluorescence microscopy (figure 1A) and flow cytometry (figure …
Genomes of Distinctive Species Reveal Clues to Human Health and Disease
Authors: Tracy Hampton
Journal: JAMA (2018)

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