tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: the LIR!C Trial
Authors: E Joline de Groof, Toer W Stevens, Emma J Eshuis, Tjibbe J Gardenbroek, Judith E Bosmans, JM van Dongen, Bregje Mol, Christianne J Buskens, Pieter C F Stokkers, Ailsa Hart, Geert R D’Haens, Willem A Bemelman, Cyriel Y Ponsioen
Journal: Gut (2019)

Evaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn's disease failing conventional therapy.A multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn's disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.In total, 143 patients were randomised. Mean Crohn's disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €-8931; 95% CI €-12 087 to €-5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €-5729, 95% CI €-10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.Laparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.Dutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).
Acute kidney injury is associated with microvascular myocardial damage following myocardial infarction
Authors: Sebastian Johannes Reinstadler, Andreas Kronbichler, Martin Reindl, Hans-Josef Feistritzer, Veronika Innerhofer, Agnes Mayr, Gert Klug, Martin Tiefenthaler, Gert Mayer, Bernhard Metzler
Journal: Kidney International (2017)
Phase I/IB trial of eribulin and everolimus in patients with triple-negative metastatic breast cancer.
Authors: Thehang H. Luu, Suzette Blanchard, John Hosei Yim
Journal: Journal of Clinical Oncology (2014)

TPS2637 Background: Eribulin mesylate is a synthetic analog of halichondrin B via tubulin-based anti-mitotic mechanism, leads to G2/M cell cycle arrest, disruption of mitotic spindles, apoptotic cell death and inhibits the phosphorylation of AKT in TNBC cells. Everolimus inhibits mTOR pathway. With mTOR inhibition, pAKT is enhanced, seen at 24 hours with everolimus alone in TNBC cell lines Ser473 and SKBR3. Combination of eribulin and everolimus suppressed both pAKT and pS6K1 at 24 hours. Based on our preclinical findings, we hypothesize that everolimus and eribulin will have a synergistic effect with inproved clinical activity in metastatic TNBC. Objectives: phase I/IB trial of everolimus plus eribulin in metastatic TNBC. Phase I determines the safety & tolerability and the recommended Phase II dose (RP2D), while the Phase IB will evaluate event free survival rate at RP2D. Methods: Eligibility: Metastatic TNBC who progressed on anthracyclines/taxanes, and previous chemotherapy for metastatic disease (up to 3 prior lines). Dose schedule: eribulin 1.4 mg/m2 on days 1,8 every 21 days. Everolimus will be started at 5mg oral daily day 1 to 21 and escalated to maximum of 10mg. Study Design: Phase I use toxicity equivalence range design with dose-limiting toxicities is 0.20-0.35, levels of ≥0.51 will be too toxic. Patients enter in cohorts of three. Phase I will end when 12 patients at a single dose level with toxicity level <0.51. Phase IB will use Simon’s Optimal two-stage design which will enroll up to 15 patients to evaluate event-free survival (EFS) rate at RP2D. Based on the EMBRACE trial, the 4-month EFS is 45% for eribulin and we target a 4-month EFS rate of ≥70% (25% improvement) for the combination. The secondary endpoints include response rate using RECIST, overall survival, toxicity, and pharmacokinetics since both drugs are substrates for the membrane transporter P-glycoprotein. Further secondary objective is proteomic analysis of PI3K pathway. Blood and skin punch biopsy from normal skin will be performed. Analysis performed by Luminex and mass spectrometry, and western blotting for pAKT (Ser473), and AKT, p4E-BP1 (ser65/Thr70) and 4E-BP1, pS6K1 (Thr389) and S6K1, and pS6 (Ser235/236) and S6. Clinical trial information: na.
Short DNA Hairpins Compromise Recombinant Adeno-Associated Virus Genome Homogeneity
Authors: Jun Xie, Qin Mao, Phillip W.L. Tai, Ran He, Jianzhong Ai, Qin Su, Ye Zhu, Hong Ma, Jia Li, Shoufang Gong, Dan Wang, Zhen Gao, Mengxin Li, Li Zhong, Heather Zhou, Guangping Gao
Journal: Molecular Therapy (2017)

Short hairpin (sh)RNAs delivered by recombinant adeno-associated viruses (rAAVs) are valuable tools to study gene function in vivo and a promising gene therapy platform. Our data show that incorporation of shRNA transgenes into rAAV constructs reduces vector yield and produces a population of truncated and defective genomes. We demonstrate that sequences with hairpins or hairpin-like structures drive the generation of truncated AAV genomes through a polymerase redirection mechanism during viral genome replication. Our findings reveal the importance of genomic secondary structure when optimizing viral vector designs. We also discovered that shDNAs could be adapted to act as surrogate mutant inverted terminal repeats (mTRs), sequences that were previously thought to be required for functional self-complementary AAV vectors. The use of shDNAs as artificial mTRs opens the door to engineering a new generation of AAV vectors with improved potency, genetic stability, and safety for both preclinical studies and human gene therapy. Short hairpin (sh)RNAs delivered by recombinant adeno-associated viruses (rAAVs) are valuable tools to study gene function in vivo and a promising gene therapy platform. Our data show that incorporation of shRNA transgenes into rAAV constructs reduces vector yield and produces a population of truncated and defective genomes. We demonstrate that sequences with hairpins or hairpin-like structures drive the generation of truncated AAV genomes through a polymerase redirection mechanism during viral genome replication. Our findings reveal the importance of genomic secondary structure when optimizing viral vector designs. We also discovered that shDNAs could be adapted to act as surrogate mutant inverted terminal repeats (mTRs), sequences that were previously thought to be required for functional self-complementary AAV vectors. The use of shDNAs as artificial mTRs opens the door to engineering a new generation of AAV vectors with improved potency, genetic stability, and safety for both preclinical studies and human gene therapy.
TCTAP A-125 A Newly Designed Guiding Sheath Provides a Novel Option for a Crossover Approach in Endovascular Therapy
Authors: Noriyuki Wakana, Kan Zen, Kazuaki Yakabe, Daisuke Kambayashi, Taku Kato, Yoshinori Tsubakimoto, Takuo Nakagami, Shinichiro Yamaguchi, Kenji Yanishi, Naohiko Nakanishi, Takeshi Nakamura, Satoaki Matoba
Journal: Journal of the American College of Cardiology (2017)
Real-time fMRI-based self-regulation of brain activation across different visual feedback presentations
Authors: Florian Krause, Caroline Benjamins, Michael Lührs, Judith Eck, Quentin Noirhomme, Mona Rosenke, Sascha Brunheim, Bettina Sorger, Rainer Goebel
Journal: Brain-Computer Interfaces (2017)

The current study is a first exploration of real-time self-regulation of functional magnetic resonance imaging (fMRI) activation based on several different visual neurofeedback presentations. Six healthy participants were engaged in self-regulation of regional fMRI activation in the posterior parietal cortex (PPC), by performing a mental calculation task. In different MR sessions, feedback was presented in the form of either a thermometer display (in vertical orientation), a circle display (increasing or decreasing in physical size), or a numbers display (Arabic digits). While self-regulation levels did differ between individuals, all six participants were able to significantly up-regulate their PPC activation with all three neurofeedback presentations. In addition to a successful general up-regulation, five out of six participants were furthermore capable of gradual self-regulation to multiple intensity levels. Taken together, the current study is a proof-of-concept demonstration of the feasibility of using multiple visual feedback presentations during gradual self-regulation of regional fMRI activation. Implications for future neurofeedback research and applications are discussed.
Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA)
Authors: Sivabaskari Pasupathy, Rosanna Tavella, John F. Beltrame
Journal: Circulation (2017)

Article, see p 1481 M yocardial infarction with nonobstructive coronary arteries (MINOCA) is clinically defined by the presence of the universal acute myocardial infarction (AMI) criteria, absence of obstructive coronary artery disease (≥50% stenosis), and no overt cause for the clinical presentation at the time of angiography (eg, classic features for takotsubo cardiomyopathy). 1 With the more frequent contemporary use of coronary angiography in AMI, clinicians have been regularly confronted with this puzzling problem and seeking guidance in its management.An article by Lindahl et al 2 in this issue of Circulation represents a major step forward in MINOCA and thereby warrants taking stock of the past, present, and future management strategies of this intriguing condition. Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA)The Past, Present, and Future Management
Protective effects of <i>Helicobacter pylori</i> for IBD are related to the <i>cagA-</i>positive strain
Authors: A R Lord, L A Simms, K Hanigan, R Sullivan, P Hobson, G L Radford-Smith
Journal: Gut (2017)

We read with interest the article by Castano-Rodriguez et al ,1 describing the role of Helicobacter pylori and Campylobacter spp in inflammatory bowel disease (IBD). While H. pylori infection has been shown to be protective against IBD, there is some ambiguity about the biological underpinnings of this effect. There is a spectrum of H pylori exposure across Caucasian populations with lower rates identified in Australian and USA studies.2 Importantly, Australia and other ‘new world’ regions such as the USA currently have some of the highest published incidence and prevalence rates for IBD.3–5

Multiple strains of H. pylori are observed, most notably, those with an active cytotoxin-associated gene A ( cagA ) and those without. The prevalence of the cagA gene in H. pylori is reported to be between 60% and 100% in western and eastern populations, respectively,6 potentially confounding any analysis on the …
Ego Strength and Physiological Responsivity
Journal: JAMA (1963)

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
Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival
Authors: Laura Behar, David Chadwick, Angela Dunne, Christopher I. Jones, Claire Proctor, Chakravarthi Rajkumar, Paula Sharratt, Philip Stanley, Angela Whiley, Mark Wilks, Martin J. Llewelyn
Journal: Journal of Infection (2017)
TRAINING VOLUME AND CONCUSSION RISK IN MALE YOUTH ICE HOCKEY PLAYERS: A PRIMARY PREVENTION PERSPECTIVE
Authors: Tracy Blake, Kerry MacDonald, Luz Palacios-Derflingher, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background There is a growing body of evidence illustrating the contribution of training load to musculoskeletal injury risk. There is a gap in the literature, however, regarding the impact of training on concussion risk. Objective To evaluate the association between sport-specific participation volume and concussion risk in male youth ice hockey players. Design Cohort study. Setting Community ice rinks and sport medicine clinics (2011–15 hockey seasons). Patients (or Participants) Male Pee Wee (11–12 years old), Bantam (13–14 years old) and Midget (15–17 years old) ice hockey players were eligible. Players were excluded if they reported unhealed injuries at study entry, had missing/systematically incomplete hockey participation exposure data, or if they sustained a concussion but participation volume could not be estimated from the day of injury. Interventions (or Assessment of Risk Factors) Cumulative hockey participation volume (CPHV) was estimated based on participation exposure data reported by team designate. The association between concussion risk and total 7-day and 28-day CHPV was evaluated using multivariable logistic regression [OR (95%CI)]. Models were adjusted for concussion history and cluster by player (α&lt;0.05). ORs with 95%CI that did not cross one were considered significant. Main Outcome Measurements Medically diagnosed concussion. Results Participants who met the inclusion criteria (n=1235/1990) sustained 34 medically diagnosed concussions. Increased concussion risk was associated with hourly increases in 7-day CHPV [OR=1.16 (95%CI: 1.08–1.25), p&lt;0.05] and 28-day CHPV [OR=1.04 (95%CI: 1.01–1.06), p&lt;0.05]. There was no evidence of effect modification or confounding by concussion history. Conclusions Increased hockey participation volume was associated with increased concussion risk in male youth ice hockey players. This is the first study to explore the association between training volume and concussion risk. Future research utilizing objective volume measurements and training response tools will be critical to the development of primary concussion prevention strategies that optimize the role of training load.
In-situ solvothermal processing of polycaprolactone/hydroxyapatite nanocomposites with enhanced mechanical and biological performance for bone tissue engineering
Authors: Saeed Moeini, Mohammad Reza Mohammadi, Abdolreza Simchi
Journal: Bioactive Materials (2017)

The interest in biodegradable polymer-matrix nanocomposites with bone regeneration potential has been increasing in recent years. In the present work, a solvothermal process is introduced to prepare hydroxyapatite (HA) nanorod-reinforced polycaprolactone in-situ. A non-aqueous polymer solution containing calcium and phosphorous precursors is prepared and processed in a closed autoclave at different temperatures in the range of 60-150 °C. Hydroxyapatite nanorods with varying aspect ratios are formed depending on the processing temperature. X-ray diffraction analysis and field-emission scanning electron microscopy indicate that the HA nanorods are semi-crystalline. Energy-dispersive X-ray spectroscopy and Fourier transform infrared spectrometry determine that the ratio of calcium to phosphorous increases as the processing temperature increases. To evaluate the effect of in-situ processing on the mechanical properties of the nanocomposites, highly porous scaffolds (>90%) containing HA nanorods are prepared by employing freeze drying and salt leaching techniques. It is shown that the elastic modulus and strength of the nanocomposites prepared by the in-situ method is superior (∼15%) to those of the ex-situ samples (blended HA nanorods with the polymer solution). The enhanced bone regeneration potential of the nanocomposites is shown via an in vitro bioactivity assay in a saturated simulated body fluid. An improved cell viability and proliferation is also shown by employing (3-(4,5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) (MTT) assay in human osteosarcoma cell lines. The prepared scaffolds with in vitro regeneration capacity could be potentially useful for orthopaedic applications and maxillofacial surgery.
Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo
Authors: Lena Allweiss, Tassilo Volz, Katja Giersch, Janine Kah, Giuseppina Raffa, Joerg Petersen, Ansgar W Lohse, Concetta Beninati, Teresa Pollicino, Stephan Urban, Marc Lütgehetmann, Maura Dandri
Journal: Gut (2017)

Objective The stability of the covalently closed circular DNA (cccDNA) in nuclei of non-dividing hepatocytes represents a key determinant of HBV persistence. Contrarily, studies with animal hepadnaviruses indicated that hepatocyte turnover can reduce cccDNA loads but knowledge on the proliferative capacity of HBV-infected primary human hepatocytes (PHHs) in vivo and the fate of cccDNA in dividing PHHs is still lacking. This study aimed to determine the impact of human hepatocyte division on cccDNA stability in vivo. Methods PHH proliferation was triggered by serially transplanting hepatocytes from HBV-infected humanised mice into naïve recipients. Cell proliferation and virological changes were assessed by quantitative PCR, immunofluorescence and RNA in situ hybridisation. Viral integrations were analysed by gel separation and deep sequencing. Results PHH proliferation strongly reduced all infection markers, including cccDNA (median 2.4 log/PHH). Remarkably, cell division appeared to cause cccDNA dilution among daughter cells and intrahepatic cccDNA loss. Nevertheless, HBV survived in sporadic non-proliferating human hepatocytes, so that virological markers rebounded as hepatocyte expansion relented. This was due to reinfection of quiescent PHHs since treatment with the entry inhibitor myrcludex-B or nucleoside analogues blocked viral spread and intrahepatic cccDNA accumulation. Viral integrations were detected both in donors and recipient mice but did not appear to contribute to antigen production. Conclusions We demonstrate that human hepatocyte division even without involvement of cytolytic mechanisms triggers substantial cccDNA loss. This process may be fundamental to resolve self-limiting acute infection and should be considered in future therapeutic interventions along with entry inhibition strategies.
Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017
Authors: Lasse S Vestergaard, Jens Nielsen, Tyra G Krause, Laura Espenhain, Katrien Tersago, Natalia Bustos Sierra, Gleb Denissov, Kaire Innos, Mikko J Virtanen, Anne Fouillet, Theodore Lytras, Anna Paldy, Janos Bobvos, Lisa Domegan, Joan O’Donnell, Matteo Scortichini, Annamaria de Martino, Kathleen England, Neville Calleja, Liselotte van Asten, Anne C Teirlinck, Ragnhild Tønnessen, Richard A White, Susana P Silva, Ana P Rodrigues, Amparo Larrauri, Inmaculada Leon, Ahmed Farah, Christoph Junker, Mary Sinnathamby, Richard G Pebody, Arlene Reynolds, Jennifer Bishop, Diane Gross, Cornelia Adlhoch, Pasi Penttinen, Kåre Mølbak
Journal: Eurosurveillance (2017)

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.
Development of a novel frailty index to predict mortality in patients with end‐stage liver disease
Authors: Jennifer C. Lai, Kenneth E. Covinsky, Jennifer L. Dodge, W. John Boscardin, Dorry L. Segev, John P. Roberts, Sandy Feng
Journal: Hepatology (2017)

Cirrhosis is characterized by muscle wasting, malnutrition, and functional decline that confer excess mortality not well quantified by the Model for End‐Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty index to capture these extrahepatic complications of cirrhosis and enhance mortality prediction in patients with cirrhosis. Consecutive outpatients listed for liver transplantation at a single transplant center without MELD exceptions were assessed with candidate frailty measures. Best subset selection analyses with Cox regression identified subsets of frailty measures that predicted waitlist mortality (=death or delisting because of sickness). We selected the frailty index by balancing statistical accuracy with clinical utility. The net reclassification index (NRI) evaluated the %patients correctly reclassified by adding the frailty index to MELDNa. Included were 536 patients with cirrhosis with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final frailty index consisted of: grip strength, chair stands, and balance. The ability of MELDNa and the frailty index to correctly rank patients according to their 3‐month waitlist mortality risk (i.e., concordance‐statistic) was 0.80 and 0.76, respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings ( P = 0.005) and 3% of nondeaths/delistings ( P = 0.17) with a total NRI of 19% ( P &lt; 0.001). Compared to those with robust frailty index scores (&lt;20th percentile), cirrhotics with poor frailty index scores (&gt;80th percentile) were more impaired by gait speed, difficulty with Instrumental Activities of Daily Living, exhaustion, and low physical activity ( P &lt; 0.001 for each). Conclusion : Our frailty index for patients with cirrhosis, comprised of three performance‐based metrics, has construct validity for the concept of frailty and improves risk prediction of waitlist mortality over MELDNa alone. (H epatology 2017;66:564–574).