tbuckley/cabot-search huggingface dataset:
Treatment of Spasticity in Multiple Sclerosis With Dantrolene
Authors: M. L. Horne
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The letter by Tolosa et al (233:1046, 1975) indicates misinterpretation of the Dykes review article (231:862-864, 1975). The statement in the Dykes article that appears to have precipitated the confusion should be clarified. It is true, as Dykes said, that "50% of children and 65% to 75% of adults benefited from the effects of the drug." These percentages referred, however, to patients with spasticity caused by other central nervous system diseases. The percentages were not intended to imply a population composed entirely of multiple sclerosis patients. Improvement of spasticity with dantrolene sodium in multiple sclerosis has been reliably reported to range from 30% to 40%.<sup>1</sup>The results reported by Tolosa et al are in the same "ball park." The complexity of the mechanism of this disease is well known. Attainment of such results in 30% of patients with spasticity previously refractory to alternative modalities would indicate
Streamlined analysis of duplex sequencing data with Du Novo
Authors: Nicholas Stoler, Barbara Arbeithuber, Wilfried Guiblet, Kateryna D. Makova, Anton Nekrutenko
Journal: Genome biology (2016)

Duplex sequencing was originally developed to detect rare nucleotide polymorphisms normally obscured by the noise of high-throughput sequencing. Here we describe a new, streamlined, reference-free approach for the analysis of duplex sequencing data. We show the approach performs well on simulated data and precisely reproduces previously published results and apply it to a newly produced dataset, enabling us to type low-frequency variants in human mitochondrial DNA. Finally, we provide all necessary tools as stand-alone components as well as integrate them into the Galaxy platform. All analyses performed in this manuscript can be repeated exactly as described at http://usegalaxy.org/duplex .
Introduction of the 13-valent pneumococcal conjugate vaccine in an isolated pneumococcal vaccine-naïve indigenous population
Authors: Lilly M. Verhagen, Ismar A. Rivera-Olivero, Meyke Hermsen, María Carolina Sisco, Mailis Maes, Berenice del Nogal, Debby Bogaert, Guy A.M. Berbers, Peter W.M. Hermans, Marien I. de Jonge, Jacobus H. de Waard
Journal: European Respiratory Journal (2016)

The introduction of pneumococcal conjugate vaccines (PCVs) has the greatest impact in populations that are most affected by pneumococcal carriage and disease, such as indigenous children [1]. Although ∼10% of the South American population consists of indigenous people living in remote settings, to our knowledge PCVs have not been evaluated in native South American children. The Warao people are an Amerindian population residing in wooden houses along the Orinoco River delta in Venezuela. Almost one-third of Warao children die during childhood and respiratory tract infections are a major cause of death [2]. This study is the first to evaluate the impact of 13-valent (PCV13) vaccination on nasopharyngeal colonisation rates and antibody response in PCV-naïve indigenous South American children. PCV13 catch-up regimens for children aged ≥ 24 months may need to include more than one vaccine dose <http://ow.ly/lstI3023i2R> The authors thank the participating families and the field workers involved in the recruitment and sampling of children, in particular the medical students of the Escuela de Medicina José Maria Vargas of the Universidad Central de Venezuela and Thor Küchler, Marcella Overeem and Stèphan Kraai (Laboratorio de Tuberculosis, Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela and Laboratory of Paediatric Infectious Diseases, Dept of Paediatrics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, the Netherlands). Furthermore, we thank Jochem Burghouts (Laboratorio de Tuberculosis, Instituto de Biomedicina, Universidad Central de Venezuela and Laboratory of Paediatric Infectious Diseases, Dept of Paediatrics, Radboud Institute for Molecular Life Sciences) for facilitation of study logistics. At the RIVM (National Institute for Health and Environment, Bilthoven, the Netherlands), we thank Irina Tcherniaeva for technical support. We are grateful to the personnel of the Laboratorio de Tuberculosis, Instituto de Biomedicina (Universidad Central de Venezuela, Caracas, Venezuela), and we acknowledge Rogier Donders (Dept of Health Evidence, Radboud University Medical Centre) for statistics support.
Cost effectiveness and tolerability of dose dense versus weekly paclitaxel chemotherapy in patients with early breast cancer: A real-world comparison.
Authors: Wanyi Kee, Raimundas Galiauskas, Brian Richard Bird, Kate Murphy, James Cook, Niamh Hughes, Maria Boyce, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2016)

e18264 Background: Paclitaxel (PAC) regimens used in early breast cancer include 3-weekly, 2-weekly dose-dense (dd) and weekly regimens. Both dd x4 and weekly x12 regimens are superior to the 3-weekly x4 regimen, particularly in ER-negative disease. We set out to compare whether either regimen is superior to the other in terms of cost-effectiveness and tolerability. Methods: We conducted a retrospective case-control study in patients receiving adjuvant PAC for early breast cancer between 2010 and 2015. Patients who received weekly x12 PAC were matched to patients receiving dd x4 PAC by age and year of diagnosis. Data on costs were collected including costs of dayward visits, chemotherapy administration, hospitalization and pegfilgrastim (if used). Data on tolerability included dose delays, hospitalizations and early cessation of planned PAC therapy (with or without alternative chemotherapy). T-test was used to analyze continuous data and chi-squared test was used to analyze categorical data. Results: 38 patients were included in the analysis. Dayward costs were higher for weekly chemotherapy (mean cost €12,259 vs €6371, P < 0.0001), while pegfilgrastim costs were lower as expected in this group (mean cost €108 vs €4003, P < 0.0001). Total costs incurred during the treatment course were not significantly different (mean cost €13,322 vs €11,576, P = 0.23). There were no significant differences in the rate of hospitalization (3 vs 4) and dose delays (4 vs 3). The weekly group were more likely to stop or change treatment without completing the planned number of PAC cycles (0 vs 6 patients, P = 0.008). Conclusions: Weekly and dd PAC regimens are associated with similar overall treatment costs in this real-world setting. Patients receiving weekly chemotherapy are more likely to discontinue therapy early and/or switch to a different drug/regimen. In the absence of evidence for superior efficacy of one regimen over another, we favor the dose dense regimen.
P0871 : Real life experience with interferon/ribavirin-free antiviral treatment in renal transplant recipients and endstage renal disease-patients on dialysis infected with hepatitis C virus
Authors: S. Beinhardt, K. Kozbial, A. Schmidt, C. Freissmuth, M. Mandorfer, R. Strassl, R. al Zoairy, R. Stauber, M. Strasser, G. Sunder-Plassmann, M. Trauner, M. Peck-Radosavljevic, W. Vogel, H. Hofer, P. Ferenci
Journal: Journal of Hepatology (2015)
Lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel for intracellular drug delivery to C6 glioma cells with P-gp inhibition and its tumor targeting
Authors: Bo Tang, Guihua Fang, Ying Gao, Yi Liu, Jinwen Liu, Meijuan Zou, Lihong Wang, Gang Cheng
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Successful chemotherapy with paclitaxel (PTX) is impeded by multidrug resistance (MDR) in tumor cells. In this study, lipid-albumin nanoassemblies co-loaded with borneol and paclitaxel (BOR/PTX LANs) were prepared to circumvent MDR in C6 glioma cells. The physiochemical properties including particle size, encapsulation efficiency and morphology were evaluated in vitro. Quantitative and qualitative investigations of cellular uptake were carried out in C6 glioma cells. The cytotoxicity of the BOR/PTX LANs was determined by MTT assay. After that, the tumor targeting was also evaluated in C6 glioma bearing mice by in vivo imaging analysis. BOR/PTX LANs have a higher entrapment efficiency (90.4 ± 1.2%), small particle size (107.5 ± 3.2 nm), narrow distribution (P.I. = 0.171 ± 0.02). The cellular uptake of PTX was significantly increased by BOR/PTX LANs compared with paclitaxel loaded lipid-albumin nanoassemblies (PTX LANs) in quantitative research. The result was further confirmed by confocal laser scanning microscopy qualitatively. The cellular uptake was energy-, time- and concentration-dependent, and clathrin- and endosome/lysosome-associated pathways were involved. The BOR/PTX LANs displayed a higher cytotoxicity agaist C6 glioma cells in comparion with PTX LANs and Taxol. Moreover, the encapsulation of BOR in LANs obviously increased the accumulation of the drug in tumor tissues, demonstrating the tumor targeted ability of BOR/PTX LANs. These results indicated that BOR/PTX LANs could overcome MDR by combination of drug delivery systems and P-gp inhibition, and shown the potential for treatment of gliomas.
Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass
Authors: G. Craig Wood, Peter N. Benotti, Clare J. Lee, Tooraj Mirshahi, Christopher D. Still, Glenn S. Gerhard, Michelle R. Lent
Journal: JAMA Surgery (2016)

Weight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood.To evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB).From June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery. The setting was a large rural integrated health system. Of 1033 eligible RYGB patients who consented to participate in longitudinal research and completed surgery before October 2007, a total of 726 (70.3%) had a weight entered in the electronic medical record 7 or more years after surgery and were included in the analyses after exclusions for pregnancy and mortality. Date of the long-term weight measurement was recorded between August 2010 and January 2016.The primary outcome was percentage weight loss (%WL) at 7 to 12 years after surgery. Preoperative clinical factors (>200) extracted from the electronic medical record included medications, comorbidities, laboratory test results, and demographics, among others.Among the 726 study participants, 83.1% (n = 603) were female and 97.4% (n = 707) were of white race, with a mean (SD) preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) of 47.5 (7.4). From the time of surgery to long-term follow-up (median, 9.3 postoperative years), the mean (SD) %WL was 22.5% (13.1%). Preoperative insulin use, history of smoking, and use of 12 or more medications before surgery were associated with greater long-term postoperative %WL (6.8%, 2.8%, and 3.1%, respectively). Preoperative hyperlipidemia, older age, and higher body mass index were associated with poorer long-term postoperative %WL (-2.8%, -8.8%, and -4.1%, respectively).Few preoperative clinical factors associated with long-term weight loss after RYGB were identified. Preoperative insulin use was strongly associated with better long-term %WL, while preoperative hyperlipidemia, higher body mass index, and older age were associated with poorer %WL. Our findings provide additional insight into preoperative identification of RYGB patients at higher risk for long-term suboptimal outcomes.
Peripheral Blood CD34+ Cell Patterns in Myelodysplastic Syndromes Stratified According to International Prognostic Scoring System (IPSS).
Authors: Clara Cesana, Ornella Rodeschini, Alfredo Molteni, Luca Santoleri, Mario Mella, Elisabetta Rovere, Antonio Monguzzi, Enrica Morra
Journal: Blood (2005)
Acetalated Dextran Microparticulate Vaccine Formulated via Coaxial Electrospray Preserves Toxin Neutralization and Enhances Murine Survival Following Inhalational <i>Bacillus Anthracis</i> Exposure
Authors: Matthew D. Gallovic, Kevin L. Schully, Matthew G. Bell, Margaret A. Elberson, John R. Palmer, Christian A. Darko, Eric M. Bachelder, Barbara E. Wyslouzil, Andrea M. Keane‐Myers, Kristy M. Ainslie
Journal: Advanced Healthcare Materials (2016)

Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress. rPA and the adjuvant resiquimod are encapsulated either in separate or the same acetalated dextran MPs. Using a murine model, the electrospray formulations lead to higher IgG2a subtype titers as well as comparable total IgG antibody titers and toxin neutralization relative to the FDA-approved vaccine (BioThrax). BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain, whereas 50% of the mice vaccinated with separately encapsulated electrospray MPs survive. Overall, this study demonstrates the potential use of electrospray for encapsulating protein antigens in polymeric MPs.
Latent Trajectories of Common Mental Health Disorder Risk Across 3 Decades of Adulthood in a Population-Based Cohort
Authors: Diana Paksarian, Lihong Cui, Jules Angst, Vladeta Ajdacic-Gross, Wulf Rössler, Kathleen R. Merikangas
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Epidemiologic evidence indicates that most of the general population will experience a mental health disorder at some point in their lives. However, few prospective population-based studies have estimated trajectories of risk for mental disorders from young through middle adulthood to estimate the proportion of individuals who experience persistent mental disorder across this age period. <h3>Objectives</h3> To describe the proportion of the population who experience persistent mental disorder across adulthood and to estimate latent trajectories of disorder risk across this age period. <h3>Design, Setting, and Participants</h3> A population-based, prospective cohort study was conducted between 1979 and 2008 in the canton of Zurich, Switzerland. A stratified random sample of 591 Swiss citizens was enrolled in 1978 at ages 19 years (men) and 20 years (women); 7 interviews were performed during a 29-year period. Men were sampled from military enrollment records and women from electoral records. From those initially enrolled, participants with high levels of psychiatric symptoms were oversampled for follow-up. Data analysis was performed from July 28, 2015, to June 8, 2016. <h3>Main Outcomes and Measures</h3> Latent trajectories, estimated using growth mixture modeling, of past-year mood/anxiety disorder (ie, major depressive episode, phobias, panic, generalized anxiety disorder, and obsessive-compulsive disorder), substance use disorder (ie, drug abuse or dependence and alcohol abuse or dependence), and any mental disorder (ie, any of the above) assessed during in-person semistructured interviews at each wave. Diagnoses were based on<i>DSM-III</i>,<i>DSM-III-R</i>, and<i>DSM-IV</i>criteria. <h3>Results</h3> Of the 591 participants at baseline, 299 (50.6%) were female. Persistent mental health disorder across multiple study waves was rare. Among 252 individuals (42.6%) who participated in all 7 study waves, only 1.2% met criteria for disorder every time. Growth mixture modeling identified 3 classes of risk for any disorder across adulthood: low (estimated prevalence, 40.0%; 95% CI, −8.7% to 88.9%), increasing-decreasing (estimated prevalence, 15.3%; 95% CI, 1.0% to 29.6%), and increasing (estimated prevalence, 44.7%; 95% CI, −0.9% to 90.1%). Although no classes were characterized by persistently high disorder risk, for those in the increasing-decreasing class, risk was high from the late 20s to early 40s. Sex-specific models indicated 4 trajectory classes for women but only 3 for men. <h3>Conclusions and Relevance</h3> Persistently high mental health disorder risk across 3 decades of adulthood was rare in this population-based sample. Identifying early determinants of sex-specific risk trajectories would benefit prevention efforts.
Histone H3K27 Trimethylation Modulates 5-Fluorouracil Resistance by Inhibiting PU.1 Binding to the DPYD Promoter
Authors: Rentian Wu, Qian Nie, Erin E. Tapper, Calvin R. Jerde, Garrett S. Dunlap, Shikshya Shrestha, Tarig A. Elraiyah, Steven M. Offer, Robert B. Diasio
Journal: Cancer Research (2016)

Abstract The antimetabolite 5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs. Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU response and toxicity. Although DPYD variants may affect 5-FU metabolism, they do not completely explain the reported variability in DPD function or the resultant differences in treatment response. Here, we report that H3K27 trimethylation (H3K27me3) at the DPYD promoter regulated by Ezh2 and UTX suppresses DPYD expression by inhibiting transcription factor PU.1 binding, leading to increased resistance to 5-FU. Enrichment of H3K27me3 at the DPYD promoter was negatively correlated with both DPYD expression and DPD enzyme activity in peripheral blood specimens from healthy volunteers. Lastly, tumor expression data suggest that DPYD repression by Ezh2 predicts poor survival in 5-FU–treated cancers. Collectively, the findings of the present article suggest that a previously uncharacterized mechanism regulates DPD expression and may contribute to tumor resistance to 5-FU. Cancer Res; 76(21); 6362–73. ©2016 AACR.
Evaluation of pseudoprogression rates and tumor progression patterns in a phase III trial of bevacizumab plus radiotherapy/temozolomide for newly diagnosed glioblastoma
Authors: Wolfgang Wick, Olivier L Chinot, Martin Bendszus, Warren Mason, Roger Henriksson, Frank Saran, Ryo Nishikawa, Cedric Revil, Yannick Kerloeguen, Timothy Cloughesy
Journal: Neuro-Oncology (2016)

Background.Evaluation of glioblastoma disease status may be complicated by treatment-induced changes and discordance between enhancing and nonenhancing MRI.Exploratory analyses are presented (prospectively assessed pseudoprogression and therapy-related tumor pattern changes) from the AVAglio trial (bevacizumab or placebo plus radiotherapy/temozolomide for newly diagnosed glioblastoma).Methods.MRI was done every 8 weeks (beginning 4 wk after chemoradiotherapy) using prespecified and standardized T1 and T2 protocols.Progressive disease (PD) at 10 weeks was reconfirmed at 18 weeks to distinguish pseudoprogression.Progression-free survival (PFS), excluding cases of confirmed pseudoprogression, was assessed (post-hoc/exploratory).Tumor progression patterns were determined at each disease assessment/PD (prespecified/exploratory).Results.Of patients with PD in the bevacizumab and placebo arms, 143/354 (40.4%) and 155/387 (40.1%), respectively, had PD due to contrast-enhancing lesions, and 51/354 (14.4%) and 53/387 (13.7%) had PD due to nonenhancing lesions.Of all patients in the bevacizumab arm (n ¼ 458), 2.2% had confirmed pseudoprogression versus 9.3% in the placebo arm (n ¼ 463).Baseline characteristics did not differ between patients with/without pseudoprogression (including for MGMT status).Excluding confirmed pseudoprogression, PFS (hazard ratio: 0.65, 95% CI: 0.56 -0.75; P , .0001,bevacizumab vs placebo) was comparable to the intentto-treat population.At PD, most patients had the same tumor focus (local/multifocal, .84%)and infiltrative profile (.88%) as at baseline; no shift to a diffuse or multifocal phenotype was observed.Conclusions.Pseudoprogression complicated progression assessment in a small but relevant number of patients but had negligible impact on PFS.Bevacizumab did not appear to adversely impact tumor progression patterns.
Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016
Authors: Luisa Barzon, Monia Pacenti, Elisa Franchin, Enrico Lavezzo, Marta Trevisan, Dino Sgarabotto, Giorgio Palù
Journal: Eurosurveillance (2016)

We describe the dynamics of Zika virus (ZIKV) infection in a man in his early 40s who developed fever and rash after returning from Haiti to Italy, in January 2016. Follow-up laboratory testing demonstrated detectable ZIKV RNA in plasma up to day 9 after symptom onset and in urine and saliva up to days 15 and 47, respectively. Notably, persistent shedding of ZIKV RNA was demonstrated in semen, still detectable at 181 days after onset.
Hispanics/Latinos With Type 2 Diabetes Have Functional and Symptomatic Pulmonary Impairment Mirroring Kidney Microangiopathy: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Oana L. Klein, Larissa Aviles-Santa, Jianwen Cai, Harold R. Collard, Alka M. Kanaya, Robert C. Kaplan, Gregory L. Kinney, Eliana Mendes, Lewis Smith, Gregory Talavera, Donghong Wu, Martha Daviglus
Journal: Diabetes Care (2016)

OBJECTIVE Type 2 diabetes mellitus (DM) has been associated with lung dysfunction, but this association has not been explored in Hispanics/Latinos. The relation between diabetic nephropathy and lung function and symptoms has not been explored. RESEARCH DESIGN AND METHODS The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large, multicenter, observational study, recruited 16,415 participants aged 18–74 years (14,455 with complete data on variables of interest), between 2008 and 2011 from four U.S. communities through a two-stage area household probability design. Baseline measurements were used for analyses. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and dyspnea score were compared between individuals with and without DM, overall, and stratified by albuminuria. The analyses were performed separately for those with and without preexisting lung disease (chronic bronchitis, emphysema, asthma). Linear regression with sampling weights was used for all analyses. RESULTS Among Hispanics/Latinos without lung disease, those with DM had lower mean FEV1 and FVC values and a higher mean dyspnea score than those without DM (mean [95% CI] FEV1 3.00 [2.96–3.04] vs. 3.10 [3.09–3.11] L, P &amp;lt; 0.01; FVC 3.62 [3.59–3.66] vs. 3.81 [3.79–3.83] L, P &amp;lt; 0.001; dyspnea score 0.60 [0.49–0.71] vs. 0.41 [0.34–0.49], P &amp;lt; 0.001). Hispanics/Latinos with DM and macroalbuminuria showed 10% lower FVC (P &amp;lt; 0.001), 6% lower FEV1 (P &amp;lt; 0.001), and 2.5-fold higher dyspnea score (P = 0.04) than those without DM and with normoalbuminuria. Similar findings but with higher impairment in FVC were found in Hispanics/Latinos with lung disease. CONCLUSIONS Hispanics/Latinos with DM have functional and symptomatic pulmonary impairment that mirror kidney microangiopathy. The progression of pulmonary impairment in adults with DM needs to be investigated further.
Inferring expressed genes by whole-genome sequencing of plasma DNA
Authors: Peter Ulz, Gerhard G Thallinger, Martina Auer, Ricarda Graf, Karl Kashofer, Stephan W Jahn, Luca Abete, Gunda Pristauz, Edgar Petru, Jochen B Geigl, Ellen Heitzer, Michael R Speicher
Journal: Nature Genetics (2016)