tbuckley/cabot-search huggingface dataset:
Abstract 16918: A Transient Increase in Left Ventricular Load Leads to Cardiac Troponin I Release in the Absence of Myocardial Ischemia
Authors: Brian R Weil, Rebeccah F Young, Vijay Iyer, Gen Suzuki, John M Canty
Journal: Circulation (2015)

Introduction: Although elevated serum cardiac troponin I (cTnI) concentrations are widely used as a biomarker for the detection of myocardial infarction, increased serum cTnI levels have been observed in the absence of ischemia in fluid overload states such as renal failure and advanced heart failure. Hypothesis: Transient left ventricular (LV) stretch induced by a reversible elevation in preload without ischemia leads to significant transcardiac cTnI release. Methods: Propofol-sedated swine (n=12) received intravenous phenylephrine (PE; 300 μg/min) for one hour to transiently raise LV end-diastolic pressure (EDP) to ∼30 mmHg. Hemodynamics were monitored throughout the experiment and myocardial perfusion was measured at baseline and during PE with fluorescent microspheres to exclude subendocardial ischemia. Serial blood sampling from the aorta and coronary sinus was performed to assess transcardiac cTnI release before, during, and after PE infusion. Results: PE induced a significant rise in mean arterial pressure (MAP; from 99 ± 5 to 172 ± 5 mmHg, P&lt;0.05) and LVEDP (from 16 ± 2 to 30 ± 3 mmHg, p&lt;0.05) that normalized 15 minutes after the infusion was stopped (MAP: 94 ± 7 mmHg, LVEDP: 17 ± 2 mmHg). Subendocardial blood flow was unaffected by PE infusion (0.9 ± 0.1 mL/min/g vs. 0.8 ± 0.1 mL/min/g at baseline). Serial blood sampling revealed significant transcardiac cTnI release 60-minutes after cessation of PE (Table). The next day, circulating cTnI levels remained elevated but there was no longer a significant gradient between the aorta and coronary sinus. Conclusions: These results demonstrate that a transient increase in LV preload produces measurable transcardiac cTnI release that results in sustained elevations in circulating cTnI. This response occurs without a change in subendocardial blood flow, indicating that elevations in hemodynamic load may provoke cardiomyocyte damage independently of ischemia-induced cell necrosis in the normal heart.
In silico and preclinical drug screening identifies dasatinib as a targeted therapy for T-ALL
Authors: S Laukkanen, T Grönroos, P Pölönen, H Kuusanmäki, J Mehtonen, J Cloos, G Ossenkoppele, B Gjertsen, B Øystein, C Heckman, M Heinäniemi, M Kontro, O Lohi
Journal: Blood Cancer Journal (2017)

In silico  and preclinical drug screening identifies dasatinib as a targeted therapy for T-ALL
設計されたヒドロゲルの系統的最適化は脳卒中脳の移植後のヒト神経幹細胞の生存と分化の選択的制御を可能にする【Powered by NICT】
Authors: Moshayedi Pouria, R Nih Lina, L Llorente Irene, R Berg Andrew, Cinkornpumin Jessica, E Lowry William, Segura Tatiana, Carmichael S. Thomas
Journal: Biomaterials (2016)
PhaseI/II study of paclitaxel, carboplatin and UFT in chemo-naive patients with advanced non-small lung cancer (NSCLC)
Authors: Y. Ono, M. Hino, R. Narato, Y. Tanaka, R. Kamizuru, K. Kitamura, T. Uehara, S. Kudoh
Journal: Journal of Clinical Oncology (2004)

7256 Background: Combination therapy with paclitaxel (PTX) and carboplatin (CBDCA) is the standard regimen for advanced NSCLC. Although the survival of patients with advanced NSCLC is prolonged using this combination, the survival benefit is inadequate. UFT, a combination anticancer drug for oral was consisting of tegafur and uracil at a molar ratio of 1:4, is used especially widely in Japan. It has been reported that a 400mg/m2 dose of UFT corresponds to a continuous infusion of 5FU at 200–300 mg/m2. Sequential exposure to PTX followed by 5-FU has been reported to give additive effects in vitro. Furthermore, the clinical effectiveness of cisplatin and UFT combination chemotherapy was reported in patients with advanced NSCLC. Besides, carboplatin is a platinumbased agent similar to cisplatin. For these reasons, we conducted a phase I/II study of triple treatment with these 3 drugs for advanced NSCLC. Methods: 21 chemo-naive patients with advanced NSCLC were entered into this phase I dose-escalation study. Patients were treated with various doses of systemic PTX followed by CBDCA on Day 1. Oral UFT (400mg/m2) was given on Days 1–5 and 8–12. Treatment cycles were repeated every 21 days. At least 3 patients were enrolled for each dose level. Once the phase II dose was established, total 23 patients received therapy at this dose level to further examine the regimen's efficacy and tolerability. Results: Main signs toxiciting were neutropenia and paresthesia, but they were tolerable and reversible. The MTD was not reached at the highest dose level after the first cycle. Since previous studies recommended PTX 225mg/m2 and CBDCA AUC 6 for a two-drug therapy, the recommended doses for the phase II study of our regimen were determined to be PTX 225mg/m2 on Day 1, CBDCA AUC 6 on day 1, and UFT 400mg/m2 on Days 1–5 and 8–12. In this phase II study, the response rate was 34.7% (PR 8 SD10 PD5), 95%CI 16.4–57.3.Conclusions: Promising activity and acceptable toxicity supports the development of this combination as a feasible chemotherapeutic option for patients with advanced NSCLC. No significant financial relationships to disclose.
A Review in Detection and Monitoring Gait Disorders Using In-Shoe Plantar Measurement Systems
Authors: Julian Andres Ramirez-Bautista, Jorge Adalberto Huerta-Ruelas, Silvia Liliana Chaparro-Cardenas, Antonio Hernandez-Zavala
Journal: IEEE Reviews in Biomedical Engineering (2017)

Gait is an important part of our life, as it affects many daily activities. Special footwear is fundamental to obtain an ergonomic gait and to extract data for analysis. The plantar foot pressure can be employed to detect many kinds of disorders, suggest improvements in treatments, rehabilitation tasks, patient monitoring, development of orthopedic devices, and other applications. In recent years, attention to this topic has grown and is reflected in many works issued in both commercial and academic groups, and has focused on the development of devices for foot plantar pressure measurement with applications in medicine, sports, and research. First works on this subject appeared around 1963 and have continuously evolved with emerging technologies. This paper reviews the reported developments in the field of footwear-embedded sensors for gait measurement, monitoring, diagnosis, and analysis in rehabilitation. Future work is proposed to improve the field of measurement of the footprint with electronic devices.
Moving Upstream — Anti-TSLP in Persistent Uncontrolled Asthma
Authors: Elisabeth H. Bel
Journal: New England Journal of Medicine (2017)

At least 15% of patients with asthma have a poor response to standard therapy with inhaled glucocorticoids and long-acting bronchodilators.1 Even after nonadherence to treatment and inadequate inhalation technique are addressed, a substantial percentage of patients continue to have frequent exacerbations and hospitalizations.2 Over the past three decades, research has led to an improved understanding of the complex biologic mechanisms of airway inflammation. This, in turn, has led to the development of several monoclonal antibody–based, targeted add-on treatments for asthma that are approved by the Food and Drug Administration or are in phase 3 of development. These include monoclonal antibodies . . .
Three years of experience with a novel “virtual” pneumonia follow-up clinic
Authors: Christopher R. Wilcox, Jamie V. Krishnan, Claire Duffus, Ben G. Marshall
Journal: European Respiratory Journal (2017)

Community-acquired pneumonia (CAP) remains the leading cause of adult mortality from infectious disease in the developed world, and carries a huge economic burden [1]. The annual expenditure attributable to CAP is estimated at 10 billion euros and 10 billion dollars for hospitals in Europe and the USA, respectively [2]. Furthermore, older people are disproportionally affected by CAP, and the projected increases in the elderly population over the coming years will put increasing strain on health services [2]. A virtual pneumonia follow-up service provides significant efficiency savings and retains high quality patient care <http://ow.ly/AUov30dRIXe>
Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Children with Severe Hemophilia a
Authors: Guy Young, Raina Liesner, K John Pasi, Beatrice Nolan, Stefan Lethagen, Lynda M Cristiano, Elisa Tsao, Bent Winding, Johnny Mahlangu
Journal: Blood (2016)
Disparities in breast cancer presentation and treatment of older women, by insurance status.
Authors: Carling Ursem, Gretchen Genevieve Kimmick, Roger T. Anderson, Wenke Hwang, Fabian Camacho
Journal: Journal of Clinical Oncology (2013)

e17516 Background: Disparities are known to exist in breast cancer outcomes by age and socioeconomic status (SES), but there is little data regarding these disparities in the elderly. We studied older women in North Carolina (NC) using insurance status as an indicator of SES. Methods: From the 1999-2002 NC Central Cancer Registry, we identified women age ≥65 years presenting with nonmetastatic breast cancer, having surgery within 60 days of diagnosis, no neoadjuvant therapy, and insured by Medicare only (M) or dual Medicaid/Medicare (dMM). Chi-square tests followed by Tukey Style Multiple Comparison of Proportions were used to compare baseline characteristics and treatment received. Multivariate analyses including age, race, Charlson comorbidity, tumor size, lymph node status (LN), ER/PR status, HER2 status, and relevant treatment components, were used to determine predictors of use of chemotherapy. Results: The study population, n=3088 with mean age 75 (SD 6.69) years, included 560 dMM and 2528 M insured women. In dMM, tumors were larger (23.5 mm vs 18.5 mm, p&lt;0.001), more likely poorly differentiated (p=0.04), and node positive (p=0.004). dMM were significantly less likely to have breast conserving surgery (vs mastectomy, p&lt;0.001), radiation therapy after surgery (&lt;0.001), adjuvant chemotherapy (0.007), and adjuvant endocrine therapy (&lt;0.001). Significant predictors of receipt of adjuvant chemotherapy were: for dMM, white race (OR 0.22, 95% CI 0.06-0.78), positive LN (vs negative LN; 6.00, 1.44-25.02); for M, age 65-69 (vs 75+; 7.43, 3.64-15.18), age 70-74 (vs 75+; 4.93, 95% CI 2.38-10.22), larger tumor size (1.73, 1.09-2.74), positive LN (9.25, 4.80-17.83), and ER/PR negative (4.98, 2.29-10.85). Conclusions: Breast cancers in low SES, older patients are higher grade, larger, and more advanced, yet they less often receive adjuvant chemotherapy. Future work should focus on interventions to increase receipt of standard of care treatment among this population.
血管平滑筋細胞の表現型応答を制御するElovl6による脂肪酸組成の撹乱:AMPK‐KLF4依存性シグナリングの新たな細胞内役割
Authors: Koide Taiki, Sunaga Hiroaki, Matsui Hiroki, Iso Tatsuya, Koitabashi Norimichi, Matsuzaka Takashi, Shimano Hitoshi, Yokoyama Tomoyuki, Kurabayashi Masahiko
Journal: Circulation (2016)
Buparlisib/BKM120 PI3 Kinase Therapy in B Cell and T Cell Non-Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL): Identification of Resistance Pathways and Biomarker Discovery
Authors: Afshin Beheshti, Michael E Coyle, Ravi Dashnamoorthy, Andrew M Evens
Journal: Blood (2016)
Survival and Cardiovascular Outcomes of Patients With Secondary Mitral Regurgitation
Authors: Anna Sannino, Robert L. Smith, Gabriele G. Schiattarella, Bruno Trimarco, Giovanni Esposito, Paul A. Grayburn
Journal: JAMA Cardiology (2017)

The outcomes of patients with left ventricular (LV) dysfunction and secondary mitral regurgitation (SMR) are still controversial.To clarify the role of SMR in the outcomes of patients with ischemic or idiopathic cardiomyopathies.MEDLINE, ISI Web of Science, and Scopus databases were searched for studies published up to March 2017.Studies reporting data on outcomes in patients with SMR were included. Duplicate publication data, studies lacking data on SMR grade and its correlation with outcomes, mixed data on SMR and primary mitral regurgitation, studies not clearly reporting the outcome of interest, and studies with fewer than 100 patients were excluded. Of the initial 3820 articles identified, 1.4% were finally included.The study met PRISMA requirements. Two of us independently screened articles for fulfillment of inclusion criteria.The primary outcome, set after data collection, was the incidence of all-cause mortality in patients with and without SMR. Secondary outcomes included hospitalization for heart failure (HF), cardiac mortality, and a composite end point of death, HF hospitalization, and cardiac transplant.Fifty-three studies and 45 900 patients were included in the meta-analysis. The mean (SD) length of follow-up was 40.8 (22.2) months. In 26 of 36 studies reporting LV function by SMR grade, increasing SMR severity was associated with worse LV function. When SMR was categorized as present or absent, all-cause mortality was significantly higher in the patients with SMR (17 studies, 26 359 patients; risk ratio [RR],1.79; 95% CI, 1.47-2.18; P < .001, I2 = 85%); when SMR was qualitatively graded, the incidence of all-cause mortality was significantly increased in patients having any degree of SMR compared with patients not having SMR (21 studies, 21 081 patients; RR, 1.96; 95% CI, 1.67-2.31; P < .001, I2 = 74%). Finally, when SMR was quantitatively graded, it remained associated with an increased all-cause mortality rate (9 studies, 3649 patients; RR, 1.97; 95% CI, 1.71-2.27; P < .001, I2 = 0%). Moreover, SMR was associated with an increased risk of hospitalization for HF (16 studies, 10 171 patients; RR, 2.26; 95% CI, 1.92-2.67; P < .001, I2 = 41%), cardiac mortality (12 studies, 11 896 patients; RR, 2.62; 95% CI, 1.87-3.69; P < .001, I2 = 74%), and death, HF, and transplant (11 studies, 8256 patients; RR, 1.63; 95% CI, 1.33-1.99; P < .001, I2 = 78%).To our knowledge, this study is the first meta-analysis to date to demonstrate that SMR, even when mild, correlates with adverse outcomes in patients with ischemic or idiopathic cardiomyopathies. Because SMR is an intrinsic consequence of LV dysfunction, causality between SMR and mortality should not be implied.
Government needs coherent policy to tackle rising clinical negligence costs, says financial watchdog
Authors: Ingrid Torjesen
Journal: BMJ (2017)

A coherent, cross government strategy is needed to tackle the rising cost of clinical negligence claims, and the Department of Health should work with the Ministry of Justice to develop this by September 2018, the National Audit Office (NAO) has said.1

Many of the factors contributing to rising clinical negligence costs have been identified by the Department of Health and NHS Resolution (formerly the NHS Litigation Authority), said the NAO’s report—but the factors likely to be most effective fall within the remit of more than one government department or are largely outside the health system’s control. They include developments in the legal market, the increasing level of damages awarded for high value claims, and changes in the discount rate used by …
The Complement-Fixing Capacity of the Rabbit-Papilloma-Virus Protein&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: W. Ray Bryan, Dorothy W. Beard, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1940)

Journal Article The Complement-Fixing Capacity of the Rabbit-Papilloma-Virus Protein Get access W. Ray Bryan, W. Ray Bryan research fellow Department of Surgery, Duke University School of MedicineNational Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy W. Beard, Dorothy W. Beard research assistant in experimental surgery Department of Surgery, Duke University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Beard J. W. Beard assistant professor of surgery, in charge of Experimental Surgery Department of Surgery, Duke University School of Medicine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 2, October 1940, Pages 197–203, https://doi.org/10.1093/jnci/1.2.197 Published: 01 October 1940
in vitroおよびin vivoにおけるシリカナノ粒子により誘発された血液脳関門機能障害:酸化ストレスとRho kinase/JNKシグナル伝達経路の関与【Powered by NICT】
Authors: Liu Xin, Sui Baiyan, Sun Jiao
Journal: Biomaterials (2017)
LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis
Authors: Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C. Wood, Derek Oldridge, Choong Yong Ung, Janine H. van Ree, Amish Khan, Brittany M. Salazar, Edroaldo Lummertz da Rocha, Mark W. Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S. John Weroha, Antonio R. Perez-Atayde, Donna S. Neuberg, Alexander Meves, Mark A. McNiven, Jan M. van Deursen, Hu Li, John M. Maris, A. Thomas Look
Journal: Cancer Cell (2017)
All watched over by machines of loving grace: an optimistic view of big data
Authors: Brian McKinstry
Journal: BMJ (2017)

Heath presents a dystopian view of big data and telehealth surveillance.1 Access to more information might increase false positives, but these will be reduced as artificial intelligence (AI) continues to learn from individual experiences to provide more precisely tailored alerts.2 The soulless vision presented by Heath is not our experience with …
Definition and recommendations for advance care planning: an international consensus supported by the European Association for Palliative Care
Authors: Judith A C Rietjens, Rebecca L Sudore, Michael Connolly, Johannes J van Delden, Margaret A Drickamer, Mirjam Droger, Agnes van der Heide, Daren K Heyland, Dirk Houttekier, Daisy J A Janssen, Luciano Orsi, Sheila Payne, Jane Seymour, Ralf J Jox, Ida J Korfage
Journal: The Lancet Oncology (2017)
NHS plans to spend £100m on recruiting overseas GPs
Authors: Anne Gulland
Journal: BMJ (2017)

The NHS is set to spend £100m (€109m; $129m) on agency fees over the next three years in a bid to recruit 2000-3000 GPs from overseas.

Last week NHS England announced its latest international recruitment drive,1 aiming to employ 600 GPs from overseas in 2017-18 and “at least” 2000 doctors by 2020-21—compared with an …
Safety and Feasibility of Antiretroviral Preexposure Prophylaxis for Adolescent Men Who Have Sex With Men Aged 15 to 17 Years in the United States
Authors: Sybil G. Hosek, Raphael J. Landovitz, Bill Kapogiannis, George K. Siberry, Bret Rudy, Brandy Rutledge, Nancy Liu, D. Robert Harris, Kathleen Mulligan, Gregory Zimet, Kenneth H. Mayer, Peter Anderson, Jennifer J. Kiser, Michelle Lally, Jennifer Brothers, Kelly Bojan, Jim Rooney, Craig M. Wilson
Journal: JAMA Pediatrics (2017)

Adolescents represent a key population for implementing preexposure prophylaxis (PrEP) interventions worldwide, yet tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP is only licensed for adults. To examine the safety of and adherence to PrEP along with changes in sexual risk behavior among adolescent men who have sex with men (MSM). Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) was a PrEP demonstration project that evaluated the safety, tolerability, and acceptability of TDF/FTC and patterns of use, rates of adherence, and patterns of sexual risk behavior among healthy young MSM aged 15 to 17 years. Participants were recruited from adolescent medicine clinics and their community partners in 6 US cities, had negative test results for human immunodeficiency virus (HIV) but were at high risk for acquiring an infection, and were willing to participate in a behavioral intervention and accept TDF/FTC as PrEP. All participants completed an individualized evidence-based behavioral intervention and were provided with daily TDF/FTC as PrEP for 48 weeks. The main objectives were to: (1) provide additional safety data regarding TDF/FTC use among young MSM who had negative test results for HIV; (2) examine the acceptability, patterns of use, rates of adherence, and measured levels of tenofovir diphosphate in dried blood spots; and (3) examine patterns of risk behavior when young MSM were provided with a behavioral intervention in conjunction with open-label TDF/FTC. Among 2864 individuals screened (from August 2013 to September 2014), 260 were eligible and 78 were enrolled (mean [SD] age, 16.5 [0.73] years), of whom 2 (3%) were Asian/Pacific Islander, 23 (29%) were black/African American, 11 (14%) were white, 16 (21%) were white Hispanic, and 26 (33%) were other/mixed race/ethnicity. Over 48 weeks of PrEP use, 23 sexually transmitted infections were diagnosed in 12 participants. The HIV seroconversion rate was 6.4 (95% CI: 1.3-18.7) per 100 person-years. Tenofovir diphosphate levels consistent with a high degree of anti-HIV protection (>700 fmol/punch) were found in 42 (54%), 37 (47%), 38 (49%), 22 (28%), 13 (17%), and 17 (22%) participants at weeks 4, 8, 12, 24, 36, and 48, respectively. Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 enrolled a diverse sample of adolescent MSM at risk for HIV who consented to study participation. Approximately half achieved protective drug levels during the monthly visits, but adherence decreased with quarterly visits. Youth may need additional contact with clinical staff members to maintain high adherence. clinicaltrials.gov Identifier: NCT01769456.
The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis
Authors: Daniel Freeman, Bryony Sheaves, Guy M Goodwin, Ly-Mee Yu, Alecia Nickless, Paul J Harrison, Richard Emsley, Annemarie I Luik, Russell G Foster, Vanashree Wadekar, Christopher Hinds, Andrew Gumley, Ray Jones, Stafford Lightman, Steve Jones, Richard Bentall, Peter Kinderman, Georgina Rowse, Traolach Brugha, Mark Blagrove, Alice M Gregory, Leanne Fleming, Elaine Walklet, Cris Glazebrook, E Bethan Davies, Chris Hollis, Gillian Haddock, Bev John, Mark Coulson, David Fowler, Katherine Pugh, John Cape, Peter Moseley, Gary Brown, Claire Hughes, Marc Obonsawin, Sian Coker, Edward Watkins, Matthias Schwannauer, Kenneth MacMahon, A Niroshan Siriwardena, Colin A Espie
Journal: The Lancet Psychiatry (2017)

BackgroundSleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations.MethodsWe did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251.FindingsBetween March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (−2·22, −2·98 to −1·45, Cohen's d=0·19; p<0·0001), and hallucinations (−1·58, −1·98 to −1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported.InterpretationTo our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision.FundingWellcome Trust.