tbuckley/cabot-search huggingface dataset:
Effect of a Behavioral Intervention Strategy for Adoption and Maintenance of a Physically Active Lifestyle: The Italian Diabetes and Exercise Study 2 (IDES_2)
Authors: Stefano Balducci, Valeria D’Errico, Jonida Haxhi, Massimo Sacchetti, Giorgio Orlando, Patrizia Cardelli, Martina Vitale, Lucilla Bollanti, Francesco Conti, Silvano Zanuso, Antonio Nicolucci, Giuseppe Pugliese
Journal: Diabetes Care (2017)

OBJECTIVE Adherence to physical activity (PA) recommendations is hampered by the lack of effective strategies to promote behavior change. The Italian Diabetes and Exercise Study 2 (IDES_2) is a randomized controlled trial evaluating a novel behavioral intervention strategy for increasing PA and decreasing sedentary time (SED-time) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS The study randomized 300 physically inactive and sedentary patients with type 2 diabetes 1:1 to receive theoretical and practical counseling once yearly for 3 years (intervention group [INT]) or standard care (control group [CON]). Here, we report the 4-month effects on objectively (accelerometer) measured daily light-intensity PA (LPA), moderate-to-vigorous–intensity PA (MVPA), and SED-time, and cardiovascular risk factors. RESULTS LPA and MVPA both increased, and SED-time decreased in both groups, although changes were significantly more marked in INT participants (approximately twofold for LPA and SED-time and approximately sixfold for MVPA). A significant reduction in HbA1c was observed only in INT subjects. An increase in LPA &amp;gt;0.92 h · day−1 and in MVPA &amp;gt;7.33 min · day−1 and a decrease in SED-time &amp;gt;1.05 h · day−1 were associated with an average decrease in HbA1c of ∼1% and also with significant improvements in fasting glucose, body weight, waist circumference, and hs-CRP. Changes in PA and SED-time were independent predictors of improvements in HbA1c. CONCLUSIONS This behavioral intervention is effective in the short term for increasing LPA and MVPA and reducing SED-time. Significant improvements in cardiometabolic risk profiles were observed in subjects experiencing the most pronounced changes in PA and SED-time, even if below the recommended level.
Contemporary evolutionary psychology and the evolution of intelligence
Authors: David M G Lewis, Laith Al-Shawaf, Mike Anderson
Journal: Behavioral and Brain Sciences (2017)

Abstract Burkart et al.'s impressive synthesis will serve as a valuable resource for intelligence research. Despite its strengths, the target article falls short of offering compelling explanations for the evolution of intelligence. Here, we outline its shortcomings, illustrate how these can lead to misguided conclusions about the evolution of intelligence, and suggest ways to address the article's key questions.
Differential Impact on Survival of Electrocardiographic Q-Wave Versus Enzymatic Myocardial Infarction After Percutaneous Intervention
Authors: Gregg W. Stone, Roxana Mehran, George Dangas, Alexandra J. Lansky, Ran Kornowski, Martin B. Leon
Journal: Circulation (2001)

Background — The relative prognostic importance of ECG myocardial infarction (MI) after intervention compared with varying degrees of enzymatic elevation has not been characterized, and the device-specific implications of periprocedural MI are also unknown. Methods and Results — Serial creatine phosphokinase (CPK)-MB levels were determined after elective percutaneous intervention of 12 098 lesions in 7147 consecutive patients at a tertiary referral center. Procedural, in-hospital, and follow-up data were collected by independent research nurses, and clinical and ECG events were adjudicated by a separate committee. Stents were implanted in 50.6% of lesions, atheroablation was performed in 54.8%, and PTCA alone was performed in 9.8%. The peak periprocedural CPK-MB level was &gt;3× the upper limit of normal (ULN) in 17.9% of patients, and Q-wave MI developed in 0.6%. By multivariate analysis, the periprocedural development of new Q waves was the most powerful independent determinant of death (2-year mortality rate, 38.3%; hazard ratio, 9.9; P &lt;0.0001). Non–Q-wave MI with CPK-MB &gt;8× ULN was also a strong predictor of death (2-year mortality rate, 16.3%; hazard ratio, 2.2; P &lt;0.0001); survival was unaffected by lesser degrees of CPK-MB elevation. Though CPK-MB elevation was more common after atheroablation and stenting than PTCA, the rates of Q-wave MI and survival were device-independent. Conclusions — Myonecrosis after percutaneous intervention is common in a high-risk referral population dominated by atheroablation and stent use. Large periprocedural infarctions (signified by new Q waves and CPK-MB &gt;8×ULN) are powerful determinants of death, whereas lesser degrees of CPK-MB release and specific device use do not adversely affect survival.
抗感染生物学的利用性のデリミターとしての細菌細胞エンベロープ ― グラム陰性細菌内膜のin vitro透過モデル
Authors: Graef Florian, Vukosavljevic Branko, Michel Jean-Philippe, Wirth Marius, Ries Oliver, De Rossi Chiara, Windbergs Maike, Rosilio Veronique, Ducho Christian, Gordon Sarah, Lehr Claus-Michael
Journal: Journal of Controlled Release (2016)
Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury
Authors: Di Wu, Michelle C. Klaw, Theresa Connors, Nikolai Kholodilov, Robert E. Burke, Marie-Pascale Côté, Veronica J. Tom
Journal: Molecular Therapy (2017)
Leveraging Behavioral Economics to Improve Heart Failure Care and Outcomes
Authors: Leslie L. Chang, Adam D. DeVore, Bradi B. Granger, Zubin J. Eapen, Dan Ariely, Adrian F. Hernandez
Journal: Circulation (2017)

Behavioral challenges are often present in human illness, so behavioral economics is increasingly being applied in healthcare settings to better understand why patients choose healthy or unhealthy behaviors. The application of behavioral economics to healthcare settings parallels recent shifts in policy and reimbursement structures that hold providers accountable for outcomes that are dependent on patient behaviors. Numerous studies have examined the application of behavioral economics principles to policy making and health behaviors, but there are limited data on applying these concepts to the management of chronic conditions, such as heart failure (HF). Given its increasing prevalence and high associated cost of care, HF is a paradigm case for studying novel approaches to improve health care; therefore, if we can better understand why patients with HF make the choices they do, then we may be more poised to help them manage their medications, influence daily behaviors, and encourage healthy decision making. In this article, we will give a brief explanation of the core behavioral economics concepts that apply to patients with HF. We will also examine how to craft these concepts into tools such as financial incentives and social networks that may improve the management of patients with HF. We believe that behavioral economics can help us understand barriers to change, encourage positive behaviors, and offer additional approaches to improving the outcomes of patients with HF.
In situ depot comprising phase-change materials that can sustainably release a gasotransmitter H2S to treat diabetic wounds
Authors: Wei-Chih Lin, Chieh-Cheng Huang, Shu-Jyuan Lin, Meng-Ju Li, Yen Chang, Yu-Jung Lin, Wei-Lin Wan, Po-Chien Shih, Hsing-Wen Sung
Journal: Biomaterials (2017)
A phase II study of GDC-0032 (taselisib) for previously treated PI3K positive patients with stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400B.
Authors: James Lloyd Wade, Corey J. Langer, Mary Redman, Charu Aggarwal, Jeffrey D Bradley, Jeffrey Crawford, Jieling Miao, Katie Griffin, Roy S. Herbst, Karen Kelly, David R. Gandara, Vassiliki Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2017)

9054 Background: Lung-MAP (S1400) is a National Clinical Trials Network “umbrella” trial for previously-treated SqNSCLC. Sub-study S1400B included patients (pts) with tumors harboring PI3K mutations.Taselisib (GDC-0032), a potent, small molecule inhibitor of Class 1 PI3K with beta isoform sparing selectivity, has been shown to be a potent inhibitor in preclinical models of PIK3CA-mutant tumors. Methods: Eligibility stipulated progressive SqNSCLC after primary platinum-based therapy and presence of a PIK3CA mutation as determined by Foundation Medicine (FMI+) NGS. . The primary analysis population was a subgroup of the total PIK3CA mutation group (GNE+) with alterations limited to substitutions: E542K, E545A, E545G, E545K, E545Q, H1047L, H1047R, H1047Y. Primary endpoint was response rate (RR) in GNE+ pts. The initial protocol randomized PIK3 mt (+) pts to taselisib 4 mg po daily or docetaxel, but was amended to single arm phase II trial of taselisib with interim analysis based on first 20 eligible GNE+ pts evaluable for response, stipulating closure for futility if &lt; 2 responses were observed. Results: 26 eligible pts, 7% of those registered to S1400, received taselisib; of these , 21 (81%) were GNE+. Of the 20 eligible, response-evaluable GNE+ pts, one pt with PIK3CA E545K gene alteration responded (5% RR, 95% Confidence Interval [CI] 1%, 24%). 13 pts had stable disease. Median PFS was 2.5 mos (95% CI, 1.7-4.0 mos) and 2.7 mos (95% CI, 1.8-3.4 mos) among GNE+ and FMI+ pts, respectively. 26 FMI+ pts were evaluable for toxicity: two grade 5 events (cardiac arrest, respiratory failure), neither clearly attributable to treatment, were recorded, along with one instance each of grade 4 AEs (dyspnea, thrombocytopenia, pneumonitis). Grade 3 AEs included 5 pts each with hyperglycemia or diarrhea, and 3 with lymphopenia. Overall survival data is premature. Conclusions: Study S1400B failed to meet its primary endpoint and was closed December 2016 at interim analysis for futility. Toxicities were manageable. The trial is unique in cataloguing the diversity of mutations in the PI3K pathways in SqNSCLC Clinical trial information: NCT02785913.
Abstract 208: Parkin Contributes to the Development of Cardiac Hypertrophy in Response to Cardiac Pressure Overload
Authors: Sarah E Shires, Dieter A Kubli, Eileen R Gonzalez, Nicole H Purcell, Åsa B Gustafsson
Journal: Circulation Research (2015)

Parkin is an E3 ubiquitin ligase known to mediate mitochondrial clearance by marking damaged mitochondria for autophagy. Our lab has previously shown that Parkin is important for stress adaptation following myocardial infarction, and that loss of Parkin leads to accumulation of dysfunctional mitochondria. However, whether Parkin plays a role in cardiac adaptation to pressure overload is currently unknown. Here we investigated the functional importance of Parkin in cardiac hypertrophy and development of heart failure in response to hemodynamic stress. Wild type (WT), Parkin knock out (Parkin -/- ), and cardiac-specific Parkin transgenic (Parkin-TG) mice were subjected to trans-aortic constriction (TAC). Cardiac anatomy and function was evaluated by histology and echocardiography. Inflammation and hypertrophy gene expression profiles were assessed using qPCR and immunohistochemistry. We discovered that after 2 weeks of TAC, cardiac hypertrophy markers were not increased in hearts from Parkin -/- mice, and there was no increase in the heart weight to body weight ratio (HW/BW). However, after 8 weeks of TAC, Parkin -/- mice showed similar cardiac hypertrophy and loss of function as WT hearts. Parkin deficient hearts also displayed increased interstitial and perivascular fibrosis compared to WT hearts after 8 weeks of TAC. This suggests that there is a delay in activating the hypertrophy program in the absence of Parkin, and that lack of Parkin leads to excessive fibrosis. In contrast, Parkin-TG mice showed a rapid development of hypertrophy and progression to heart failure compared to WT mice. Interestingly, we observed no differences in either mitochondrial content or LC3 levels after two weeks of TAC in Parkin-TG hearts, suggesting that the rapid development of hypertrophy and early progression to heart failure was not due to excessive mitophagy. These data suggest that Parkin plays an important role in the activation of the cardiac hypertrophy program and that this function may be independent of its role in regulating mitophagy. Thus, this study provides novel insight into the functional importance of Parkin in the heart. Additional studies are needed to determine the mechanism of how Parkin regulates cardiac hypertrophy.
Adult sepsis – A nationwide study of trends and outcomes in a population of 23 million people
Authors: Chien-Chang Lee, Chia-Hung Yo, Meng-tse Gabriel Lee, Kuang-Chau Tsai, Shih-Hao Lee, Yueh-Sheng Chen, Wan-Chien Lee, Tzu-Chun Hsu, Sie-Hue Lee, Shy-Shin Chang
Journal: Journal of Infection (2017)
Didactic training vs. computer-based self-learning in the prediction of diminutive colon polyp histology by trainees: a randomized controlled study
Authors: Taimur Khan, Birtukan Cinnor, Neil Gupta, Lindsay Hosford, Ajay Bansal, Mojtaba Olyaee, Sachin Wani, Amit Rastogi
Journal: Endoscopy (2017)

Abstract Background and study aim Experts can accurately predict diminutive polyp histology, but the ideal method to train nonexperts is not known. The aim of the study was to compare accuracy in diminutive polyp histology characterization using narrow-band imaging (NBI) between participants undergoing classroom didactic training vs. computer-based self-learning. Participants and methods Trainees at two institutions were randomized to classroom didactic training or computer-based self-learning. In didactic training, experienced endoscopists reviewed a presentation on NBI patterns for adenomatous and hyperplastic polyps and 40 NBI videos, along with interactive discussion. The self-learning group reviewed the same presentation of 40 teaching videos independently, without interactive discussion. A total of 40 testing videos of diminutive polyps under NBI were then evaluated by both groups. Performance characteristics were calculated by comparing predicted and actual histology. Fisher’s exact test was used and P &lt; 0.05 was considered significant. Results A total of 17 trainees participated (8 didactic training and 9 self-learning). A larger proportion of polyps were diagnosed with high confidence in the classroom group (66.5 % vs. 50.8 %; P &lt; 0.01), although sensitivity (86.9 % vs. 95.0 %) and accuracy (85.7 % vs. 93.9 %) of high-confidence predictions were higher in the self-learning group. However, there was no difference in overall accuracy of histology characterization (83.4 % vs. 87.2 %; P = 0.19). Similar results were noted when comparing sensitivity and specificity between the groups. Conclusion The self-learning group showed results on a par with or, for high-confidence predictions, even slightly superior to classroom didactic training for predicting diminutive polyp histology. This approach can help in widespread training and clinical implementation of real-time polyp histology characterization.
Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1
Authors: Mei Xue, Wei Chen, An Xiang, Ruiqi Wang, He Chen, Jingjing Pan, Huan Pang, Hongli An, Xiang Wang, Huilian Hou, Xu Li
Journal: Molecular Cancer (2017)

To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells. We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed. We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls. Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.
Drug related deaths in Scotland double in 10 years
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The number of drug related deaths in Scotland has more than doubled in 10 years and is now two and a half times the UK average.

Statistics from the National Records of Scotland show that there were 867 drug related deaths in Scotland in 2016.1 This was a 23% rise from 706 deaths in 2015 and a 106% increase from the 421 recorded in 2006.

Recent figures showed that the number of deaths from drug poisoning reached record levels in England and Wales last year.2

Scotland’s drug death rate in 2016 of 160 deaths …
Chemotherapy-Associated Peripheral Neuropathy in Patients With Early-Stage Breast Cancer: A Systematic Review
Authors: Donna R. Rivera, Patricia A. Ganz, Meghan S. Weyrich, Hanna Bandos, Joy Melnikow
Journal: JNCI Journal of the National Cancer Institute (2017)

Breast cancer is the most common cancer among women worldwide, and survival rates are increasing. Chemotherapy-associated peripheral neuropathy (PN) is clinically important because of effects on quality of life (QOL) and potential effects on dose limitations. This adverse drug reaction is associated with certain classes of chemotherapy and commonly presents as peripheral sensory neuropathy whose natural course is largely unknown. The literature was reviewed to determine the frequency and characteristics of PN associated with adjuvant chemotherapy in early-stage breast cancer (ESBC) to explore the potential impact on long-term (one or more years after diagnosis) health outcomes and QOL. MEDLINE, PubMed, Embase, and the Cochrane Library were searched for relevant English-language randomized controlled trials, systematic reviews, meta-analyses, and case-control and cohort studies published between January 1990 and July 1996. Included studies were limited to current adjuvant regimens (eg, anthracyclines, taxanes, cyclophosphamide, platinum compounds). Two investigators independently reviewed abstracts, full-text articles, and extracted data from fair- and good-quality studies. Discrepancies in quality assessment and data extraction were resolved by consensus. We identified 364 articles; 60 were eligible for full-text review. Only five reports of four studies provided data beyond one year post-treatment initiation. Studies used different measures to assess PN. Neuropathic symptoms persisted in 11.0% to more than 80% of participants at one to three years following treatment. There is a paucity of data describing persistent PN in ESBC patients. Consistent use of validated measures and well-conducted randomized clinical trials or observational studies are needed to evaluate the incidence, persistence, and QOL associated with the long-term effects of PN.
Ring Sideroblasts and SF3B1 Mutations in Myelodysplastic Syndromes (MDS): Are They Two Faces of the Same Coin? a Study on Behalf of the MDS Clinical Research Consortium (MDS CRC)
Authors: Rami S. Komrokji, John Barnard, David P Steensma, Amy E. DeZern, Gail J. Roboz, Najla Alali, Jaime Fensterl, Guillermo Garcia-Manero, Mikkael A. Sekeres
Journal: Blood (2016)
The potential for targeted rewriting of epigenetic marks in COPD as a new therapeutic approach
Authors: Dan-Dan Wu, Juan Song, Sabine Bartel, Susanne Krauss-Etschmann, Marianne G. Rots, Machteld N. Hylkema
Journal: Pharmacology & Therapeutics (2017)

Chronic obstructive pulmonary disease (COPD) is an age and smoking related progressive, pulmonary disorder presenting with poorly reversible airflow limitation as a result of chronic bronchitis and emphysema. The prevalence, disease burden for the individual, and mortality of COPD continues to increase, whereas no effective treatment strategies are available. For many years now, a combination of bronchodilators and anti-inflammatory corticosteroids has been most widely used for therapeutic management of patients with persistent COPD. However, this approach has had disappointing results as a large number of COPD patients are corticosteroid resistant. In patients with COPD, there is emerging evidence showing aberrant expression of epigenetic marks such as DNA methylation, histone modifications and microRNAs in blood, sputum and lung tissue. Therefore, novel therapeutic approaches may exist using epigenetic therapy. This review aims to describe and summarize current knowledge of aberrant expression of epigenetic marks in COPD. In addition, tools available for restoration of epigenetic marks are described, as well as delivery mechanisms of epigenetic editors to cells. Targeting epigenetic marks might be a very promising tool for treatment and lung regeneration in COPD in the future.
酸化還元性ヘテロナノ結晶は活性化可能なT_1とT_2二重モード磁気共鳴イメージングのための機能磁気緩和スイッチ【Powered by NICT】
Authors: Kim Myeong-Hoon, Son Hye-Young, Kim Ga-Yun, Park Kwangyeol, Huh Yong-Min, Haam Seungjoo
Journal: Biomaterials (2016)
Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification
Authors: Christella E Widjaja, Jocelyn G Olvera, Patrick J Metz, Anthony T Phan, Jeffrey N Savas, Gerjan de Bruin, Yves Leestemaker, Celia R Berkers, Annemieke de Jong, Bogdan I Florea, Kathleen Fisch, Justine Lopez, Stephanie H Kim, Daniel A Garcia, Stephen Searles, Jack D Bui, Aaron N Chang, John R Yates, Ananda W Goldrath, Hermen S Overkleeft, Huib Ovaa, John T Chang
Journal: Journal of Clinical Investigation (2017)

During an immune response, CD8+ T lymphocytes can undergo asymmetric division, giving rise to daughter cells that exhibit distinct tendencies to adopt terminal effector and memory cell fates. Here we show that “pre-effector” and “pre-memory” cells resulting from the first CD8+ T cell division in vivo exhibited low and high rates of endogenous proteasome activity, respectively. Pharmacologic reduction of proteasome activity in CD8+ T cells early during differentiation resulted in acquisition of terminal effector cell characteristics, whereas enhancement of proteasome activity conferred attributes of memory lymphocytes. Transcriptomic and proteomic analyses revealed that modulating proteasome activity in CD8+ T cells affected cellular metabolism. These metabolic changes were mediated, in part, through differential expression of Myc, a transcription factor that controls glycolysis and metabolic reprogramming. Taken together, these results demonstrate that proteasome activity is an important regulator of CD8+ T cell fate and raise the possibility that increasing proteasome activity may be a useful therapeutic strategy to enhance the generation of memory lymphocytes.