tbuckley/cabot-search huggingface dataset:
Polypill: Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core–Shell, Multilayer, and Gradient Concentration Profiles (Adv. Healthcare Mater. 16/2018)
Authors: Alexander P. Haring, Yuxin Tong, Justin Halper, Blake N. Johnson
Journal: Advanced Healthcare Materials (2018)

In article 1800213, Blake N. Johnson and co-workers demonstrate how extrusion-based 3D printing enables the programming of delayed, pulsed, and continuous temporal release profiles in multi-component oral tablets, also known as polypills, via the use of core-shell, multilayer, and gradient spatial distributions of actives, respectively. Mass transfer processes are considered for design, quality, and performance of additively-manufactured pharmaceutical systems.
Hancock tells GPs: don’t stockpile drugs or overprescribe as Brexit approaches
Authors: Ingrid Torjesen
Journal: BMJ (2018)

The health and social care secretary for England has warned GPs and hospitals not to stockpile drugs or write longer prescriptions for patients in the weeks leading up to Brexit.

In a letter to GPs, NHS organisations, community pharmacies, and other service providers,1 Matt Hancock said that local stockpiling is unnecessary because the government has developed plans to ensure continuity of supply if the UK leaves the EU on 29 March 2019 with no deal agreed.

Drug companies will be asked to ensure that they have an additional six weeks’ supply of medicines in the UK on top of their own normal stock levels, “in case imports from the EU through certain routes are affected.” Separate arrangements will be made for the air transport of medicines with short shelf lives, such as medical radioisotopes. Hancock has written to makers of pharmaceuticals, medical devices, and clinical consumables to set out further …
Lorcaserin — Elixir or Liability?
Authors: Julie R. Ingelfinger, Clifford J. Rosen
Journal: New England Journal of Medicine (2018)

More than 1.9 billion adults worldwide (39%) are overweight; of these adults, more than 650 million (13%) are obese, according to the World Health Organization. In the United States alone, recent studies suggest that more than 40% of adults are obese.1 A nonpharmacologic approach consisting of exercise, diet, and behavior modification remains the cornerstone of treatment.2 However, many affected patients cannot lose or maintain their weight loss with that approach. Hence, medical and surgical options (e.g., bariatric surgery) have been developed to reduce and maintain weight loss. Among the patients who are considering their options, the long-term safety of any . . .
Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma
Authors: Yannis Metaxas, Gareth Rivalland, Laetitia A. Mauti, Dirk Klingbiel, Steven Kao, Sabine Schmid, Anna K. Nowak, Oliver Gautschi, Tammo Bartnick, Brett G. Hughes, Hasna Bouchaab, Sacha I. Rothschild, Nick Pavlakis, Sibylle Wolleb, Ulf Petrausch, Kenneth O'Byrne, Patrizia Froesch, Melanie Löffler-Baumann, Susanne Pratsch-Peter, Prudence Russell, Walter Mingrone, Spasenija Savic, Bibhusal Thapa, Martin Früh, Miklos Pless, Roger von Moos, Thomas John
Journal: Journal of Thoracic Oncology (2018)
Skin Self-examination for Skin Cancer Prevention
Authors: Ryan M. Svoboda, Robert J. Friedman, Darrell S. Rigel
Journal: JAMA (2018)

To the Editor The US Preventive Services Task Force (USPSTF) Recommendation Statement on skin cancer prevention1 suggested a lack of evidence to support skin self-examination as an effective secondary prevention practice. We have concerns about possible oversights in the USPSTF analysis.
Social connectedness and engagement in preventive health services: an analysis of data from a prospective cohort study
Authors: Mai Stafford, Christian von Wagner, Sarah Perman, Jayne Taylor, Diana Kuh, Jessica Sheringham
Journal: The Lancet Public Health (2018)

<h2>Summary</h2><h3>Background</h3> Evidence of the possible health benefits of social connectedness is increasing. We aimed to examine poor social connectedness as a possible barrier to participation in preventive health services among older people (aged 53–69 years). <h3>Methods</h3> We analysed data from a prospective cohort study of 5362 socially stratified births from the Medical Research Council National Survey of Health and Development enrolled in England, Scotland, and Wales in March 1946. At ages 68–69 years, participants reported participation in blood pressure and cholesterol measurement, eyesight and dental check-ups, influenza immunisation, and bowel and breast cancer screening. Our primary outcome measure summed participation across all these tests and services at ages 68–69 years. We tested associations between structural and functional social connectedness from ages 53 years to 69 years and total count of participation in these preventive services in Poisson models controlling for sex, education, occupational class, employment, chronic illnesses, and general practitioner consultations for health problems. <h3>Findings</h3> 940 (44%) of 2132 participants attended all preventive services within the recommended timeframes. At ages 68–69 years, being unmarried or not cohabiting (incident rate ratio [IRR] 1·33, 95% CI 1·20–1·47) and small personal social networks (IRR 1·51, 1·32–1·71) were independently associated with non-participation in more services, with associations consistent across most services. High social relationship quality at ages 68–69 years (IRR 0·91, 95% CI 0·87–0·95) and increasing social relationship quality from ages 53 years to 69 years (IRR 0·93, 0·89–0·97) were associated with low risk of non-participation. <h3>Interpretation</h3> Individuals with poor social connectedness appear to be at greater risk of not engaging in the full range of preventive services than individuals with good social connectedness. Improvement of access to social contacts and networks in older ages is already recommended for the maintenance of good mental health. This study suggests that social connectedness could also improve participation in a wide range of preventive health services, and hence could improve use of the health-care system and population health. <h3>Funding</h3> UK Medical Research Council.
Abstract 16157: A TBX5 Driven Gene Regulatory Network Prevents Atrial Fibrillation
Authors: Rangarajan D Nadadur, Michael Broman, Bastiaan Boukens, Stefan Mazurek, Jeffrey Steimle, Jenna Bekeny, Igor Efimov, Christopher Weber, Vincent Christoffels, Elizabeth McNally, Ivan Moskowitz
Journal: Circulation (2015)

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The genetics of AF are complex, but recent GWAS have revealed a number of AF risk loci, including TBX5 . TBX5 plays a critical role in heart development, and continues to be expressed in the adult atria. We assessed the role of Tbx5 in the adult heart by removing Tbx5 from the mouse at 6 weeks-of-age. Adult Tbx5 mutant mice developed spontaneous sustained atrial fibrillation, characterized by surface electrocardiogram (ECG), intracardiac ECGs, and ex vivo whole heart optical mapping. Tbx5 mutant isolated cardiomycytes showed prolonged action potentials, disrupted calcium handling, and abnormal automaticity. Tbx5 mutant atrial gene expression analysis revealed down-regulation of numerous conduction system effectors genes including Scn5a, Ryr2, Gja1, Atp2a2 , Dsp , and numerous potassium channels. We also observed Tbx5 dependence of the transcription factor gene Pitx2 , the number one locus associated with AF by GWAS. We identified an enhancer upstream of PITX2 that interacts with the PITX2 promoter by 4C and whose activity is TBX5 dependent and modulated by common SNP rs1906595, which alters a canonical TBX5 binding site. We also identified cis-regulatory elements at Scn5a, Ryr2, Gja1, Atp2a2 , and Dsp , locus co-regulated by Tbx5 and Pitx2. We describe a TBX5-driven atrial molecular network including Pitx2 that determines atrial conduction properties.
Abstract 13551: Invasive Hemodynamic Assessment of Cardiac Output State After MitraClip Therapy
Authors: Frantisek Bednar, Viktor Kocka, Tomas Budesinsky, Hana Linkova, Petr Tousek
Journal: Circulation (2015)

Introduction: MitraClip therapy has become a therapeutic alternative for high surgical risk patients with symptomatic mitral regurgitation (MR). There are limited data about early and no data about later hemodynamic consequences after MR correction and about the impact of elimination of regurgitant flow on cardiac output state . Methods: We studied invasive hemodynamic parameters before operation (conscious non-sedated patients, T1), immediately after MitraClip implantation (still under general anaesthesia, T2) and on day 1 (late) after procedure (conscious, extubated patients, T3) using right heart cathetrization. Results: Of 25 MitraClip patients (72% male; mean age 70y) with functional MR, in 20 were performed invasive measurements in all time points. MitraClip implantation resulted in an increase in cardiac index (CI) from 1.8±0.5 (T1) to 2.4±0.5(T2) and to 3.2±0.5 L/min/m2 (T3), in a decrease in systemic vascular resistance index (SVRI) from 3759±847 (T1) to 2508±551 (T2) and to 1679±360 dyn.s.cm-5/m2 (T3), in a decreese in pulmonary capillary wedge pressure (PCWP) from 17±5 (T1) to 13±5(T2) and to 10±4mmHg(T3), in a decrease in pulmonary vascular resistance index (PVRI) from 598±362 (T1) to 532±260 (T2) and to 363±184 dyn.s.cm-5/m2 (T3), (all p&lt;0.05). Conclusion: MR reduction after successful MitraClip implantation significantly increases CI immediately (27%) and late (75%) and leads to concomitant decrease in SVRI, PVRI and PCWP immediately (33%, 11% and 25%) and late (55%, 39% and 41%) after procedure. No patients showed worsening of cardiac output state immediately (T2) and late (T3) after MR correction.
Abstract 16351: Arrhythmic Events in Brugada Syndrome: A Nation-Wide Israeli Survey of the Clinical Characteristics, Treatment and Long-Term Follow-Up (ISRABRU-VF)
Authors: Eran Leshem, Michael Rahkovich, Anna Mazo, Mahmoud Suleiman, Miri Blich, Avishag Laish-Farkash, Yuval Konstantino, Rami Fogelman, Boris Strasberg, Michael Geist, Israel Chetboun, Moshe Swissa, Michael Ilan, Yoav Michowitz, Raphael Rosso, Michael Glikson, Bernard Belhassen
Journal: Circulation (2016)

Background: Since the first report on Brugada syndrome (BrS), only sparse information has been reported on the detailed characteristics and management of the small subset of patients who had an arr...
Echovirus 30 detection in an outbreak of acute myalgia and rhabdomyolysis, Brazil 2016–2017
Authors: I.P. Sousa, F.M. Burlandy, S.T.S. Lima, A.C.B. Maximo, M.A.A. Figueiredo, Z. Maia, E.E. da Silva
Journal: Clinical Microbiology and Infection (2018)
Diagnosis of axillar lymph node status and sentinel node biopy (SNB) by indocyanin green (ICG) fluorescence imaging in early breast cancer patients.
Authors: Kazufumi Hisamatsu
Journal: Journal of Clinical Oncology (2012)

e11503 Background: In breast cancer patients, diagnosis of Axillar lymph node (Ax LN) status is practical use in deciding treatment strategy. But, diagnostic methods are different by different institution. The purpose of this study was to review diagnostic methods of Ax LN status. Methods: From December 2006, 483 cases were underwent breast cancer operation and within 356 (74%) clinical node negative primary breast cancer cases underwent Sentinel Node biopsy (SNB) by indocyanine green (ICG) fluorescence imaging. Dye was injected sub dermal in the areola. After one minute massage, subcutaneous lymphatic channel draining from the areola to the axilla was observed by Image processing and measuring system (PDE C9830, Hamamatsu Photonics Co). Skin incision was done at the point which fluorescence imaging disappeared (ASCO2011, Electronic Publication only). From September 2010, Aspiration Biopsy Cytology (ABC) of Ax LN (LN-ABC), Ultrasonography (US) and CT were done as routine workup in breast cancer patients. Node positive cases were received pre-operative chemotherapy or Ax LN dissection and node negative cases were underwent SNB by ICG fluorescence imaging during operation. Results: From December 2006, SNB were done 356 clinical node negative primary breast cancer cases. SN was detected 342 cases, detective rate was 96 %. This rate was as good as SNB done by radioactive colloid (Phytate radiolabelled by Tc98) with dye (detective rate was 95%, ASCO2011). The lymph node metastasis was detected 48 cases (14%). From Sep 2010 to Oct 2011, LN-ABC was done 49 cases of the 142 primary breast cancer patients. Fourteen cases were LN-ABC positive and 35cases were LN-ABC negative. Positive SNB were detected 3 of the 35 cases (2 cases had micro metastasis and one case had macro metastasis). Within three SNB positive cases, pre-operative US and CT had no positive finding. Positive LN-ABC cases (14 cases) were received pre-operative therapy or Ax LN dissection. Conclusions: These results suggest that LN-ABC was useful procedure detecting positive Ax LN and SNB by ICG fluorescence imaging was useful and easy tool in operative breast cancer patients.
Abstract 12367: Increased Risk of Mortality With Vasopressor Use in Traumatic Hemorrhage Shock: A Nationwide Cohort Study in Japan
Authors: Makoto Aoki, Toshikazu Abe, Shuichi Hagiwara, Kiyohiro Oshima
Journal: Circulation (2017)

Introduction: Traumatic hemorrhagic shock requires resuscitation with excessive fluids that may also increase patient mortality. Vasopressors have been temporarily used to decrease the amount of fl...
Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study
Authors: Ryan Malcolm Hum, David Deambrosis, Su Han Lum, Emma Davies, Denise Bonney, Malcolm Guiver, Andrew Turner, Robert Francis Wynn, Prashant Hiwarkar
Journal: The Lancet Haematology (2018)
Short-Term Mitochondrial Permeability Transition Pore Opening Modulates Histone Lysine Methylation at the Early Phase of Somatic Cell Reprogramming
Authors: Zhongfu Ying, Ge Xiang, Lingjun Zheng, Haite Tang, Lifan Duan, Xiaobing Lin, Qiuge Zhao, Keshi Chen, Yi Wu, Guangsuo Xing, Yiwang Lv, Linpeng Li, Liang Yang, Feixiang Bao, Qi Long, Yanshuang Zhou, Xueying He, Yaofeng Wang, Minghui Gao, Duanqing Pei, Wai-Yee Chan, Xingguo Liu
Journal: Cell Metabolism (2018)
GATA2 zinc finger 1 mutations are associated with distinct clinico-biological features and outcomes different from GATA2 zinc finger 2 mutations in adult acute myeloid leukemia
Authors: Feng-Ming Tien, Hsin-An Hou, Cheng-Hong Tsai, Jih-Luh Tang, Yu-Chiao Chiu, Chien-Yuan Chen, Yuan-Yeh Kuo, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Chien-Ting Lin, Shang-Ju Wu, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Yi Huang, Ming Yao, Wen-Chien Chou, Hwei-Fang Tien
Journal: Blood Cancer Journal (2018)

Abstract Mutations of the GATA binding protein 2 ( GATA2 ) gene in myeloid malignancies usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in different locations of GATA2 may have distinct impact on clinico-biological features and outcomes in AML patients, but little is known in this aspect. In this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and identified 44 GATA2 mutations in 43 (6.2%) patients, including 31 in ZF1, 10 in ZF2, and three outside the two domains. Different from GATA2 ZF2 mutations, ZF1 mutations were closely associated with French-American-British (FAB) M1 subtype, CEBPA double mutations ( CEBPA double-mut ), but inversely correlated with FAB M4 subtype, NPM1 mutations, and FLT3 -ITD. ZF1-mutated AML patients had a significantly longer overall survival (OS) than GATA2- wild patients and ZF2-mutated patients in total cohort as well as in those with intermediate-risk cytogenetics and normal karyotype. ZF1 mutations also predicted better disease-free survival and a trend of better OS in CEBPA double-mut patients. Sequential analysis showed GATA2 mutations could be acquired at relapse. In conclusion, GATA2 ZF1 mutations are associated with distinct clinico-biological features and predict better prognosis, different from ZF2 mutations, in AML patients.
Beyond market behavior: Evolved cognition and folk political economic beliefs
Authors: Talbot M. Andrews, Andrew W. Delton
Journal: Behavioral and Brain Sciences (2018)

Abstract Boyer &amp; Petersen (B&amp;P) lay out a compelling theory for folk-economic beliefs, focusing on beliefs about markets. However, societies also allocate resources through mechanisms involving power and group decision-making (e.g., voting), through the political economy. We encourage future work to keep folk political economic beliefs in mind, and sketch an example involving pollution and climate change mitigation policy.
Abstract 13578: 12-Lead Electrocardiograms Can Be Reconstructed Using the 3 Electrodes of a Subcutaneous Implantable Cardioverter Defibrillator
Authors: Peter L Cronbach, David G Wilson, Saul E Greenhut, Berthold Stegemann, Daniele Panfilo, John M Morgan
Journal: Circulation (2015)

Background: Data from reduced lead ECG configurations can be transformed to reconstruct a 12-lead ECG. The sensing electrodes of a subcutaneous ICD (S-ICD) could provide a suitable basis for such a system. Reconstruction of a 12-lead ECG from conventional S-ICD vectors has not previously been demonstrated. Hypothesis: A 12-lead ECG signal can be accurately derived from S-ICD electrode vectors. Methods: Participants with ICDs (N=61) underwent 3 minute ECGs with electrodes in the standard S-ICD and 12-lead positions. Participants were randomised to either a training (N=31) or validation (N=30) group. Two participants and one further lead were subsequently excluded from the validation group due to technical faults. The transformation was a linear combination of the 2 independent S-ICD vectors to each of the 8 independent leads of the 12-lead ECG, with coefficients selected that minimized the root mean square error (RMSE) between recorded and derived ECGs when applied to the training group. The transformation was then applied to the validation group and agreement between the recorded and derived lead pairs was measured by Pearson correlation coefficient (r) and normalised RMSE (NRMSE). Results: In total, 335 lead pairs were compared (figure1). Distribution of r and NRMSE were skewed. Mean r = 0.731 (SE 0.021), Median r = 0.903 (SE 0.015). NRMSE Mean = 0.227 (SE 0.011) Median = 0.167 (SE 0.008). 252/335 (75.2%) of all pairs had an r &gt; 0.7 (indicating very strong positive correlation). Figure 1: Example 12-lead ECG, recorded (blue line) and derived (red line). Participant randomly selected from top 20% by mean Pearson correlation coefficient. Conclusions: We have demonstrated reconstruction of a 12-lead ECG from S-ICD vectors. The agreement between derived and measured signals was generally excellent and comparable with other widely accepted reduced lead systems. If perfected, the ability to generate 12-lead data from an S-ICD could help clinicians to localise and treat arrhythmias.
Development, Function, and Clinical Significance of Plasmacytoid Dendritic Cells in Chronic Myeloid Leukemia
Authors: Sabrina Inselmann, Ying Wang, Susanne Saussele, Lea Fritz, Christin Schütz, Magdalena Huber, Simone Liebler, Thomas Ernst, Dali Cai, Sarah Botschek, Cornelia Brendel, Raffaele A. Calogero, Dinko Pavlinic, Vladimir Benes, Edison T. Liu, Andreas Neubauer, Andreas Hochhaus, Andreas Burchert
Journal: Cancer Research (2018)

Plasmacytoid dendritic cells (pDC) are the main producers of a key T-cell-stimulatory cytokine, IFNα, and critical regulators of antiviral immunity. Chronic myeloid leukemia (CML) is caused by BCR-ABL, which is an oncogenic tyrosine kinase that can be effectively inhibited with ABL-selective tyrosine kinase inhibitors (TKI). BCR-ABL-induced suppression of the transcription factor interferon regulatory factor 8 was previously proposed to block pDC development and compromise immune surveillance in CML. Here, we demonstrate that pDCs in newly diagnosed CML (CML-pDC) develop quantitatively normal and are frequently positive for the costimulatory antigen CD86. They originate from low-level BCR-ABL-expressing precursors. CML-pDCs also retain their competence to maturate and to secrete IFN. RNA sequencing reveals a strong inflammatory gene expression signature in CML-pDCs. Patients with high CML-pDC counts at diagnosis achieve inferior rates of deep molecular remission (MR) under nilotinib, unless nilotinib therapy is combined with IFN, which strongly suppresses circulating pDC counts. Although most pDCs are BCR-ABL-negative in MR, a substantial proportion of BCR-ABL+ CML-pDCs persists under TKI treatment. This could be of relevance, because CML-pDCs elicit CD8+ T cells, which protect wild-type mice from CML. Together, pDCs are identified as novel functional DC population in CML, regulating antileukemic immunity and treatment outcome in CML.Significance: CML-pDC originates from low-level BCR-ABL expressing stem cells into a functional immunogenic DC-population regulating antileukemic immunity and treatment outcome in CML. Cancer Res; 78(21); 6223-34. ©2018 AACR.
Effects of Leptin on the Skeleton
Authors: Ian R Reid, Paul A Baldock, Jillian Cornish
Journal: Endocrine Reviews (2018)

Abstract Leptin originates in adipocytes, including those in bone marrow, and circulates in concentrations 20 to 90 times higher than those in the cerebrospinal fluid. It has direct anabolic effects on osteoblasts and chondrocytes, but it also influences bone indirectly, via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g., pituitary). Leptin’s role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced length and bone mineral content of long bones but increased vertebral trabecular bone. A consistent bone phenotype in human leptin deficiency has not been established. Systemic leptin administration in animals and humans usually exerts a positive effect on bone mass, and leptin administration into the cerebral ventricles usually normalizes the bone phenotype in leptin-deficient mice. Reflecting the role of the sympathetic nervous system in mediating the central catabolic effects of leptin on the skeleton, β-adrenergic agonists and antagonists have major effects on bone in mice, but this is not consistently seen in humans. The balance of the central and peripheral effects of leptin on bone remains an area of substantial controversy and might vary between species and according to other factors such as body weight, baseline circulating leptin levels, and the presence of specific pathologies. In humans, leptin is likely to contribute to the positive relationship observed between adiposity and bone density, which allows the skeleton to respond appropriately to changes in soft tissue mass.