tbuckley/cabot-search huggingface dataset:
Human gastric cancer modelling using organoids
Authors: Therese Seidlitz, Sebastian R Merker, Alexander Rothe, Falk Zakrzewski, Cläre von Neubeck, Konrad Grützmann, Ulrich Sommer, Christine Schweitzer, Sebastian Schölch, Heike Uhlemann, Anne-Marlene Gaebler, Kristin Werner, Mechthild Krause, Gustavo B Baretton, Thilo Welsch, Bon-Kyoung Koo, Daniela E Aust, Barbara Klink, Jürgen Weitz, Daniel E Stange
Journal: Gut (2018)

Objective Gastric cancer is the second leading cause of cancer-related deaths and the fifth most common malignancy worldwide. In this study, human and mouse gastric cancer organoids were generated to model the disease and perform drug testing to delineate treatment strategies. Design Human gastric cancer organoid cultures were established, samples classified according to their molecular profile and their response to conventional chemotherapeutics tested. Targeted treatment was performed according to specific druggable mutations. Mouse gastric cancer organoid cultures were generated carrying molecular subtype-specific alterations. Results Twenty human gastric cancer organoid cultures were established and four selected for a comprehensive in-depth analysis. Organoids demonstrated divergent growth characteristics and morphologies. Immunohistochemistry showed similar characteristics to the corresponding primary tissue. A divergent response to 5-fluoruracil, oxaliplatin, irinotecan, epirubicin and docetaxel treatment was observed. Whole genome sequencing revealed a mutational spectrum that corresponded to the previously identified microsatellite instable, genomic stable and chromosomal instable subtypes of gastric cancer. The mutational landscape allowed targeted therapy with trastuzumab for ERBB2 alterations and palbociclib for CDKN2A loss. Mouse cancer organoids carrying Kras and Tp53 or Apc and Cdh1 mutations were characterised and serve as model system to study the signalling of induced pathways. Conclusion We generated human and mouse gastric cancer organoids modelling typical characteristics and altered pathways of human gastric cancer. Successful interference with activated pathways demonstrates their potential usefulness as living biomarkers for therapy response testing.
Medical Oncologists’ Beliefs, Practices, and Knowledge Regarding Marijuana Used Therapeutically: A Nationally Representative Survey Study
Authors: Ilana M. Braun, Alexi Wright, John Peteet, Fremonta L. Meyer, David P. Yuppa, Dragana Bolcic-Jankovic, Jessica LeBlanc, Yuchiao Chang, Liyang Yu, Manan M. Nayak, James A. Tulsky, Joji Suzuki, Lida Nabati, Eric G. Campbell
Journal: Journal of Clinical Oncology (2018)

Background Although almost every state medical marijuana (MM) law identifies cancer as a qualifying condition, little research supports MM's use in oncology. We hypothesized that the discrepancy between these laws and the scientific evidence base poses clinical challenges for oncologists. Oncologists' beliefs, knowledge, and practices regarding MM were examined in this study. Methods In November 2016, we mailed a survey on MM to a nationally-representative, random sample of 400 medical oncologists. Main outcome measures included whether oncologists reported discussing MM with patients, recommended MM clinically in the past year, or felt sufficiently informed to make such recommendations. The survey also queried oncologists' views on MM's comparative effectiveness for several conditions (including its use as an adjunct to standard pain management strategies) and its risks compared with prescription opioids. Bivariate and multivariate analyses were performed using standard statistical techniques. Results The overall response rate was 63%. Whereas only 30% of oncologists felt sufficiently informed to make recommendations regarding MM, 80% conducted discussions about MM with patients, and 46% recommended MM clinically. Sixty-seven percent viewed it as a helpful adjunct to standard pain management strategies, and 65% thought MM is equally or more effective than standard treatments for anorexia and cachexia. Conclusion Our findings identify a concerning discrepancy between oncologists' self-reported knowledge base and their beliefs and practices regarding MM. Although 70% of oncologists do not feel equipped to make clinical recommendations regarding MM, the vast majority conduct discussions with patients about MM and nearly one-half do, in fact, recommend it clinically. A majority believes MM is useful for certain indications. These findings are clinically important and suggest critical gaps in research, medical education, and policy regarding MM.
Evolution of Left Ventricular Assist Device Therapy for Advanced Heart Failure
Authors: Leslie W. Miller, Joseph G. Rogers
Journal: JAMA Cardiology (2018)

The mortality rate for the most advanced forms of heart failure with medical therapy alone remains unacceptably high at 30% to 80% at 1 year. In the past decade, left ventricular assist devices have assumed an increasingly prominent role in the management of these patients. This review included all English-language articles published over the past 15 years on left ventricular assist devices. Search topics focused on advanced heart failure and ventricular assist devices, including volume of implantations, patient selection, complications, cost, and recovery of function. The search also included all published clinical trials or reports of cohort studies as well as registry data.There has been significant progress in nearly all aspects of left ventricular assist device therapy, from patient selection to device design and postoperative management. Percutaneous devices have been developed to facilitate rapid deployment and provide short-term hemodynamic support. The devices have transitioned from pulsatile to continuous flow design and are now smaller, with enhanced durability more suited for long-term support. The mean survival following left ventricular assist device implantation is nearly 5 years. However, some complications, including bleeding, infection, pump thrombosis, and stroke, limit the potential of the therapy. There are many innovations now under investigation that promise to further improve outcomes and enhance patient satisfaction.Advanced or end-stage heart failure remains a major health care problem in terms of both patient morbidity and mortality as well as cost. Physicians and health care professionals need to become aware of the significant progress in the field of mechanical support of circulation with the use of ventricular assist devices.
Measuring what matters to patients: the development of the NASH-CHECK, a new patient-reported outcome instrument for nonalcoholic steatohepatitis
Authors: L. Doward, M.M. Balp, J. Twiss, C. Slota, D. Cryer, A. Langford, R. Collen, N. Agashivala, C. Brass, Q. Anstee, A. Sanyal
Journal: Journal of Hepatology (2018)
Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism
Authors: Graeme I. Lancaster, Katherine G. Langley, Nils Anton Berglund, Helene L. Kammoun, Saskia Reibe, Emma Estevez, Jacquelyn Weir, Natalie A. Mellett, Gerard Pernes, James R.W. Conway, Man K.S. Lee, Paul Timpson, Andrew J. Murphy, Seth L. Masters, Steve Gerondakis, Nenad Bartonicek, Dominik C. Kaczorowski, Marcel E. Dinger, Peter J. Meikle, Peter J. Bond, Mark A. Febbraio
Journal: Cell Metabolism (2018)
A state of the art review on optimal practices to prevent, recognize, and manage complications associated with intravascular devices in the critically ill
Authors: Jean-François Timsit, Mark Rupp, Emilio Bouza, Vineet Chopra, Tarja Kärpänen, Kevin Laupland, Thiago Lisboa, Leonard Mermel, Olivier Mimoz, Jean-Jacques Parienti, Garyphalia Poulakou, Bertrand Souweine, Walter Zingg
Journal: Intensive Care Medicine (2018)
A Comparison of the Updated Diamond-Forrester, CAD Consortium, and CONFIRM History-Based Risk Scores for Predicting Obstructive Coronary Artery Disease in Patients With Stable Chest Pain
Authors: Lohendran Baskaran, Ibrahim Danad, Heidi Gransar, Bríain Ó Hartaigh, Joshua Schulman-Marcus, Fay Y. Lin, Jessica M. Peña, Amanda Hunter, David E. Newby, Philip D. Adamson, James K. Min
Journal: JACC. Cardiovascular imaging (2018)
Accuracy, Safety, and Reliability of Novel Phase I Trial Designs
Authors: Heng Zhou, Ying Yuan, Lei Nie
Journal: Clinical Cancer Research (2018)

A number of novel model-based and model-assisted designs have been proposed to find the MTD in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation with overdose control (EWOC), and Bayesian logistic regression model (BLRM), and three model-assisted designs, including the modified toxicity probability interval (mTPI), Bayesian optimal interval (BOIN), and keyboard (equivalently mTPI-2) designs. We conduct numerical studies to assess their accuracy, safety, and reliability and the practical implications of various empirical rules used in some designs, such as skipping a dose and imposing overdose control. Our results show that the CRM outperforms EWOC and BLRM with higher accuracy of identifying the MTD. For the CRM, skipping a dose is not recommended, as it substantially increases the chance of overdosing patients while providing limited gain for identifying the MTD. EWOC and BLRM appear excessively conservative. They are safe but have relatively poor accuracy of finding the MTD. The BOIN and keyboard (equivalently mTPI-2) designs have similar operating characteristics, outperforming the mTPI, but the BOIN is more intuitive and transparent. The BOIN yields competitive performance comparable with the CRM but is simpler to implement and free of the issue of irrational dose assignment caused by model misspecification, thereby providing an attractive approach for designing phase I trials. Clin Cancer Res; 24(18); 4357-64. ©2018 AACR.
Hyping health effects: a news analysis of the ‘new smoking’ and the role of sitting
Authors: Josephine Y Chau, Gillian Reyes-Marcelino, Alexander CR Burnett, Adrian E Bauman, Becky Freeman
Journal: British Journal of Sports Medicine (2018)

Media reports of the ‘new smoking’ have proliferated with little consideration of the disease burden of emergent risk factors. We consider the example of prolonged sitting in particular. The ‘new smoking’ analogy is a powerful heuristic device that draws on the well-known dangers of tobacco smoking. Such attention-grabbing ‘factoids’ are rapidly disseminated and perpetuated,1 and can be difficult to dispel later.

We quantified which health risks have been called the ‘new smoking’ and consider the epidemiological evidence for and the implications of these comparisons. We searched the Factiva database for news stories containing the phrases ‘is the new smoking’ or ‘as bad as smoking’ in 2012–2016. News stories containing these phrases were independently coded for the health risk being compared with smoking, along with article characteristics (eg, headline, name of publication, date of publication).

We identified 614 unique news stories that contained the target phrases. The top 10 mentioned health risks and behaviours compared with smoking are presented in table 1. The most dominant topics were sitting and obesity, with 55% and 12% of stories, respectively. The total number of ‘new smoking’ or ‘as …
Elderly Israeli Holocaust survivors during the Persian Gulf War: a study of psychological distress
Authors: Z Solomon, E Prager
Journal: American Journal of Psychiatry (1992)

The aim of the current study was to systematically assess the psychological effects of the Persian Gulf War on a nonclinical group of elderly Israeli civilians with and without a Holocaust background.Sixty-one elderly Holocaust survivors and 131 elderly civilians without a Holocaust background completed questionnaires in their homes. Measures included sense of safety, symptoms of psychological distress, and levels of state and trait anxiety.Findings indicate that Holocaust survivors perceived higher levels of danger and reported more symptoms of acute distress than comparison subjects. In addition, they displayed higher levels of both state and trait anxiety.Findings do not support the notion that prior experience with extreme stress has an inoculating effect that leads to greater resilience in dealing with other forms of stress. On the contrary, Holocaust experience was found to render the elderly more vulnerable rather than less. These findings of greater vulnerability among Holocaust survivors are of particular significance since they stem from a nonclinical group.
Abstract 18229: Vacuolar Protein Sorting-Associated Protein 4A (VPS4A), a Target of miR-16, in Fibroblasts
Authors: Neeta Adhikari, Weihua Guan, Brain Capaldo, Marjorie Carlson, Sundaram Ramakrishnan, Dinesha Walek, Manu Gupta, Aaron Mackey, Paul J Barton, Jennifer L Hall
Journal: Circulation (2013)

. Members of the miR-16 family are up-regulated during ischemia and heart failure. The goal of these studies was to identify novel miR-16 mediated signaling pathways that may play a role in cardiovascular disease. We used bioinformatics to identify single nucleotide polymorphisms (SNPs) in binding sites of miR-16 using dbSNP and the exome sequencing project. Target genes with a SNP in a miR-16 binding site included cingulin 1 ( CGNL1 ), zinc finger protein with CRAB and SCAN domains 1 ( ZKSCAN1 ), uncoupling protein2 ( UCP2 ), vacuolar protein sorting- associated protein 4A ( VPS4A ), and a disintegrin and metalloproteinase with a thrombospondin motif 1 ( ADAMTS-1 ). The role of VPS4A in the heart is not known. VPS4A mRNA expression was greater in primary rat cardiac fibroblasts (0.41±0.02) compared to primary rat cardiac myocytes (0.21± 0.03) (n=3-4, p=0.003). Up-regulation of VPS4A in HEK 293T cells decreased cell number by 30% and 41% at 48h and 72h, respectively, compared to cells transfected with a control scrambled mimic (n=6, p&lt;0.01). Thus VPS4A was further studied for its direct interaction with miR-16. Overexpression of a miR-16 mimic decreased VPS4A protein expression by 38% and 52 % at 48h and 60h, respectively, compared to cells transfected with a control scrambled mimic (n=3, p&lt;0.01). Conversely, inhibiting endogenous miR-16 with a miR-16 inhibitor mimic increased VPS4A protein 1.5 fold (n=3, p&lt;0.01). miR-16 decreased luciferase activity of a VPS4A -3’UTR promoter construct; however the presence of rs16958754 in the miR-16 binding site inhibited the interaction (n=10, p&lt;0.01). In sum, we identified VPS4A as a novel downstream target of miR-16 in fibroblasts. This data supports a working model in which upregulation of miR-16 with heart failure decreases VPS4A , and promotes fibroblast proliferation. Work is underway to determine if the SNP rs16958754 may be protective under certain conditions in which limiting fibroblast proliferation may be beneficial.
Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial
Authors: E. Fokas, R. Fietkau, A. Hartmann, W. Hohenberger, R. Grützmann, M. Ghadimi, T. Liersch, P. Ströbel, G.G. Grabenbauer, U. Graeven, R -D Hofheinz, C -H Köhne, C. Wittekind, R. Sauer, M. Kaufmann, T. Hothorn, C. Rödel
Journal: Annals of Oncology (2018)

BackgroundSurrogate end points in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase III trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase III trial.Patients and methodsCox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1–4) were used to assess individual-level surrogacy of NAR for DFS.ResultsAfter a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS [75.9% (95% confidence interval [CI] 72.30% to 79.50%) versus 71.3% (95% CI 67.60% to 74.90%); P = 0.034; PC 1) and resulted in a shift toward lower NAR groups (P = 0.034, PC 2) compared with fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI 88.2% to 95.2%), 81.8% (95% CI 78.4% to 85.1%), and 58.1% (95% CI 52.4% to 63.9%) for low, intermediate, and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS [low versus high NAR: hazard ratio (HR) 4.670; 95% CI 3.106–7.020; P < 0.001; low versus intermediate NAR: HR 1.971; 95% CI 1.303–2.98; P = 0.001] in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC 4.ConclusionOur study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase III trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase III trial data sets should aim to confirm trial-level surrogacy.
Making the Case for Importance of Health Literacy in the Surgical Population
Authors: Jesse P. Wright, Kelvin Moses, Kamran Idrees
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Pathological characteristics and early post-hepatic-resection outcome of patients with hepatocellular carcinoma occurred after hepatitis C treatment with new direct-acting antivirals: a multicenter cohort study
Authors: A. Vitale, F.P. Russo, C. Sposito, A. Cucchetti, G.B.L. Sandri, S. Gruttadauria, S. DI Sandro, D. Ghinolfi, D. Nicolini, F. Trevisani
Journal: Journal of Hepatology (2018)
Usefulness of newly proposed albumin-bilirubin grade and its modification -Japan nationwide survey
Authors: A. Hiraoka, K. Michitaka, T. Kumada, N. Izumi, M. Kadoya, N. Kokudo, S. Kubo, Y. Matsuyama, O. Nakashima, M. Sakamoto, T. Takayama, T. Kokudo, K. Kashiwabara, M. Kudo
Journal: Journal of Hepatology (2018)
Particularities of hepatocellular carcinoma on chronic hepatitis C in the era of all-oral antiviral treatment
Authors: E.L. Iliescu, S. Ioanitescu, R. Dumitru, L. Toma, M.B. Ureche, A. Mercan-Stanciu, C. Iancu, M. Dodot
Journal: Journal of Hepatology (2018)
Abstract 19201: Clinical Impact of Cardiac Regenerative Therapy With Autologous Skeletal Stem Cell Sheet Implantation on Treating Severe Heart Failure
Authors: Keitaro Domae, Shigeru Miyagawa, Koichi Toda, Teruya Nakamura, Yasushi Yoshikawa, Satsuki Fukushima, Shunsuke Saito, Daisuke Yoshioka, Atsuhiro Saito, Tomomi Shimamoto, Toru Kuratani, Takayoshi Ueno, Yoshiki Sawa
Journal: Circulation (2015)

Background: Transplantation of autologous somatic tissue-derived cells into the heart has been shown to yield functional recovery of the failing heart via “paracrine effects” that enhance the native regenerative process. We have introduced skeletal stem cell (SSC) sheet methods for treating severe heart failure (HF), in which scaffold-free cell-sheets are attached on the epicardial surface to maximize the paracrine effects. We herein report feasibility, safety and efficacy of SSC sheet transplantation for treating advanced HF. Methods: This study enrolled 27 patients (mean age, 51±15 years, DCM in 15 patients and ICM in 12 patients) with chronic advanced HF despite optimum treatments. Scaffold-free cell-sheets containing SSC (average: 3.5±1.9х108 cells) was transplanted over the left ventricular (LV) free wall via the left thoracotomy. Average follow-up was 2.5 (0.6-5.1) years. Results: All patients discharged from the hospital without procedure-related complications. Re-In-hospital treatment for congestive HF was required in 8 patients, who we defined as non-responder (Group N: n=8), while the other patients who were free from in-hospital cardiac treatments were defined as responder (Group R: n=19). The Group R exhibited decreased NYHA functional class (2.8±0.6 to 1.6±1.1 p&lt;0.05) and increased 6-minute walk test (444±110 to 499±114m p&lt;0.05) at 6 months, while these values maintained until the latest follow-up. Echocardiographically, LV systolic and diastolic diameters significantly decreased and ejection fraction significantly increased. In addition, both LV end-systolic and diastolic wall stress, assessed by cardiac CT scanning, significantly decreased (systolic: 377±76 to 317±88, diastolic: 116±98 to 51±32 kdynes/cm2, p&lt;0.05 respectively) in the Group R. Multivariate analysis showed that preoperative duration of HF was a single independent risk factor for Group N with its hazard ratio 1.8 (p&lt;0.05). Three-year freedom from cardiac death was 92%, while that from recurrence of HF was 70%. Conclusions: SSC sheet transplantation was feasible and safe in advanced HF patients. Functional recovery, including reduced LV wall stress, was gained in the selected patients, who received this treatment in early stage of advanced HF.
The wrong or “right” effects of HCVon cardiac function in patients with low-mild liver fibrosis: A case-control study
Authors: A. Dalbeni, S. Romano, E. Imbalzano, A. Tagetti, G. Torin, A. Mantovani, G. Cavallon, V. Paon, C. Fava, L.I. Prat, F. Capra
Journal: Journal of Hepatology (2018)
Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association
Authors: Clifford J. Eskey, Philip M. Meyers, Thanh N. Nguyen, Sameer A. Ansari, Mahesh Jayaraman, Cameron G. McDougall, J. Kevin DeMarco, William A. Gray, David C. Hess, Randall T. Higashida, Dilip K. Pandey, Constantino Peña, Hermann C. Schumacher
Journal: Circulation (2018)

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.