bluuebunny/crossref_metadata_2025_split huggingface dataset:
The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data
Authors: Bretscher Michael T. , Dahal Prabin , Griffin Jamie , Stepniewska Kasia , Bassat Quique , Baudin Elisabeth , D’Alessandro Umberto , Djimde Abdoulaye A. , Dorsey Grant , Espié Emmanuelle , Fofana Bakary , González Raquel , Juma Elizabeth , Karema Corine , Lasry Estrella , Lell Bertrand , Lima Nines , Menéndez Clara , Mombo-Ngoma Ghyslain , Moreira Clarissa , Nikiema Frederic , Ouédraogo Jean B. , Staedke Sarah G. , Tinto Halidou , Valea Innocent , Yeka Adoke , Ghani Azra C. , Guerin Philippe J. , Okell Lucy C. 
Published: February 2020

Abstract
Background
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.

Methods
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.

Results
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7–15.7) for AL and 15.2 days (95% CI 12.8–18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7–18.6 days for AL and 10.2–18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.

Conclusion
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety
Authors: Leonard Charles E. , Brensinger Colleen M. , Dawwas Ghadeer K. , Deo Rajat , Bilker Warren B. , Soprano Samantha E. , Dhopeshwarkar Neil , Flory James H. , Bloomgarden Zachary T. , Gagne Joshua J. , Aquilante Christina L. , Kimmel Stephen E. , Hennessy Sean 
Published: February 2020

Abstract
Background
The low cost of thiazolidinediones makes them a potentially valuable therapeutic option for the > 300 million economically disadvantaged persons worldwide with type 2 diabetes mellitus. Differential selectivity of thiazolidinediones for peroxisome proliferator-activated receptors in the myocardium may lead to disparate arrhythmogenic effects. We examined real-world effects of thiazolidinediones on outpatient-originating sudden cardiac arrest (SCA) and ventricular arrhythmia (VA).

Methods
We conducted population-based high-dimensional propensity score-matched cohort studies in five Medicaid programs (California, Florida, New York, Ohio, Pennsylvania | 1999–2012) and a commercial health insurance plan (Optum Clinformatics | 2000–2016). We defined exposure based on incident rosiglitazone or pioglitazone dispensings; the latter served as an active comparator. We controlled for confounding by matching exposure groups on propensity score, informed by baseline covariates identified via a data adaptive approach. We ascertained SCA/VA outcomes precipitating hospital presentation using a validated, diagnosis-based algorithm. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression that accounted for clustering within matched pairs. We prespecified Medicaid and Optum findings as primary and secondary, respectively; the latter served as a conceptual replication dataset.

Results
The adjusted HR for SCA/VA among rosiglitazone (vs. pioglitazone) users was 0.91 (0.75–1.10) in Medicaid and 0.88 (0.61–1.28) in Optum. Among Medicaid but not Optum enrollees, we found treatment effect heterogeneity by sex (adjusted HRs = 0.71 [0.54–0.93] and 1.16 [0.89–1.52] in men and women respectively, interaction term p-value = 0.01).

Conclusions
Rosiglitazone and pioglitazone appear to be associated with similar risks of SCA/VA.
Molecular implications of MUC5AC-CD44 axis in colorectal cancer progression and chemoresistance
Authors: Pothuraju Ramesh , Rachagani Satyanarayana , Krishn Shiv Ram , Chaudhary Sanjib , Nimmakayala Rama Krishna , Siddiqui Jawed A. , Ganguly Koelina , Lakshmanan Imayavaramban , Cox Jesse L. , Mallya Kavita , Kaur Sukhwinder , Batra Surinder K. 
Published: February 2020

AbstractBackgroundDifferential expression of mucins has been associated with several cancers including colorectal cancer (CRC). In normal physiological conditions, secretory mucin MUC5AC is not expressed in the colonic mucosa, whereas its aberrant expression is observed during development of colon cancer and its precursor lesions. To date, the molecular mechanism of MUC5AC in CRC progression and drug resistance remains obscure.MethodsMUC5AC expression was determined in colon tissue microarray by immunohistochemistry. A RNA interference and CRISPR/Cas9-mediated system was used to knockdown/knockout the MUC5AC in CRC cell lines to delineate its role in CRC tumorigenesis using in vitro functional assays and in vivo (sub-cutaneous and colon orthotopic) mouse models. Finally, CRC cell lines and xenograft models were used to identify the mechanism of action of MUC5AC.ResultsOverexpression of MUC5AC is observed in CRC patient tissues and cell lines. MUC5AC expression resulted in enhanced cell invasion and migration, and decreased apoptosis of CRC cells. MUC5AC interacted with CD44 physically, which was accompanied by the activation of Src signaling. Further, the presence of MUC5AC resulted in enhanced tumorigenesis and appearance of metastatic lesions in orthotopic mouse model. Additionally, up-regulation of MUC5AC resulted in resistance to 5-fluorouracil (5-FU) and oxaliplatin, and its knockout increased sensitivity to these drugs. Finally, we observed that up-regulation of MUC5AC conferred resistance to 5-FU through down-regulation of p53 and its target genep21and up-regulation of β-catenin and its target genesCD44andLgr5.ConclusionOur findings suggest that differential expression of secretory mucin MUC5AC results in enhanced tumorigenesis and also confers chemoresistance via CD44/β-catenin/p53/p21 signaling.
The safety of spinal manipulative therapy in children under 10 years: a rapid review
Authors: Corso Melissa , Cancelliere Carol , Mior Silvano , Taylor-Vaisey Anne , Côté Pierre 
Published: February 2020

AbstractIntroductionThe safety of spinal manipulative therapy (SMT) in children is controversial. We were mandated by the College of Chiropractors of British Columbia to review the evidence on this issue.ObjectivesWe conducted a rapid review of the safety of SMT in children (< 10 years). We aimed to: 1) describe adverse events; 2) report the incidence of adverse events; and 3) determine whether SMT increases the risk of adverse events compared to other interventions.Evidence reviewWe searched MEDLINE, CINAHL, and Index to Chiropractic Literature from January 1, 1990 to August 1, 2019. We used rapid review methodology recommended by the World Health Organization. Eligible studies (case reports/series, cohort studies and randomized controlled trials) were critically appraised. Studies of high and acceptable methodological quality were included. The lead author extracted data. Data extraction was independently validated by a second reviewer. We conducted a qualitative synthesis of the evidence.FindingsMost adverse events are mild (e.g., increased crying, soreness). One case report describes a severe adverse event (rib fracture in a 21-day-old) and another an indirect harm in a 4-month-old. The incidence of mild adverse events ranges from 0.3% (95% CI: 0.06, 1.82) to 22.22% (95% CI: 6.32, 54.74). Whether SMT increases the risk of adverse events in children is unknown.ConclusionThe risk of moderate and severe adverse events is unknown in children treated with SMT. It is unclear whether SMT increases the risk of adverse events in children < 10 years.
Identification of small RNAs involved in nitrogen fixation in Anabaena sp. PCC 7120 based on RNA-seq under steady state conditions
Authors: He Ping , Cai Xiaodan , Chen Kangming , Fu Xuelin 
Published: February 2020

Abstract
Purpose
Anabaena sp. PCC7120 is a genetically tractable model organism for nitrogen fixation and photosynthesis research. The importance of small regulatory RNAs (sRNAs) as mediators of a number of cellular processes in bacteria has begun to be recognized. Bacterial sRNA binds to target genes through base pairing, and play a regulatory role. Many studies have shown that bacterial sRNA can regulate cell stress response, carbon and nitrogen fixation, and so on. However, little is known about sRNAs in Anabaena sp. PCC 7120 regarded to nitrogen fixation under later steady state.

Methods
To provide a comprehensive study of sRNAs in this model organism, the sRNA (< 200 nt) extracted from Anabaena sp. PCC 7120 under nitrogen step-down treatment of 12 days, together with the sRNA from the control, was analyzed using deep RNA sequencing. Possible target genes regulated by all identified putative sRNAs were predicted by IntaRNA and further analyzed for functional categorizations for biological pathways.

Result
Totally, 14,132 transcripts were produced from the de novo assembly. Among them, transcripts that are located either in the intergenic region or antisense strand were kept, which resulted in 1219 sRNA candidates, for further analysis. RPKM-based differential expression analysis showed that 418 sRNAs were significantly differentially expressed between the samples from control (nitrogen addition, N+) and nitrogen depletion, (N−). Among them, 303 sRNAs were significantly upregulated, whereas 115 sRNAs were significantly downregulated. RT-PCR of 18 randomly chosen sRNAs showed a similar pattern as RNA-seq result, which confirmed the reliability of the RNA-seq data. In addition, the possible target genes regulated by unique sRNAs of Anabaena sp. PCC 7120 under nitrogen addition (N+) condition or that under nitrogen depletion (N−) condition were analyzed for functional categorization and biological pathways, which provided the evidences that sRNAs were indeed involved in many different metabolic pathways.

Conclusion
The information from the present study provides a valuable reference for understanding the sRNA-mediated regulation of the nitrogen fixation in Anabaena PCC 7120 under steady state conditions.
Decreased expression of LRA4, a key gene involved in rhamnose metabolism, caused up-regulated expression of the genes in this pathway and autophagy in Pichia pastoris
Authors: Jiao Jian , Wang Shuai , Tian Hui , Xu Xinxin , Zhang Yuhong , Liu Bo , Zhang Wei 
Published: February 2020

AbstractIn a previous study, we developed Pichia pastoris GS115m, an engineered strain with decreased expression of one key gene, LRA4, in rhamnose metabolism. P. pastoris GS115m/LacB was subsequently constructed via introducing a β-galactosidase gene, LacB, under the control of rhamnose-inducible PLRA3 into P. pastoris GS115m. P. pastoris GS115m/LacB greatly improved recombinant protein production relative to the parental strain (P. pastoris GS115/LacB). In the present study, transcriptomes of P. pastoris GS115m/LacB and P. pastoris GS115/LacB grown in YPR medium were analyzed. P. pastoris GS115m/LacB was found to suffer from the mild carbon source starvation. To attenuate the starvation stress, P. pastoris GS115m/LacB attempted to enhance rhamnose metabolism by elevating the transcription levels of rhamnose-utilization genes LRA1-3 and RhaR. The transcription level of LacB under the control of PLRA3 thereby increased, resulting in the improved production of recombinant protein in P. pastoris GS115m/LacB. It was also revealed that P. pastoris GS115m/LacB cells coped with carbon starvation mostly via autophagy.
Adherence to recommended practices for perioperative anesthesia care for older adults among US anesthesiologists: results from the ASA Committee on Geriatric Anesthesia-Perioperative Brain Health Initiative ASA member survey
Authors:   on behalf of the ASA Committee on Geriatric Anesthesia and the ASA Perioperative Brain Health Initiative, Deiner Stacie , Fleisher Lee A. , Leung Jacqueline M. , Peden Carol , Miller Thomas , Neuman Mark D. 
Published: February 2020

Abstract
Background
While specific practices for perioperative care of older adults have been recommended, little is known regarding adherence by US physician anesthesiologists to such practices. To address this gap in knowledge, the ASA Committee on Geriatric Anesthesia and the ASA Perioperative Brain Health Initiative undertook a survey of ASA members to characterize current practices related to perioperative care of older adults.

Methods
We administered a web-based questionnaire with items assessing the proportion of practice focused on delivery of care to older adults, adherence to recommended practices for older surgical patients, resource needs to improve care, and practice characteristics.

Results
Responses were collected between May 24, 2018, and June 29, 2018. A total of 25,587 ASA members were invited to participate, and 1737 answered at least one item (6.8%). 96.4% of respondents reported that they had cared for a patient aged 65 or older within the last year. 47.1% of respondents (95% confidence interval, 44.6%, 49.7%) reported using multimodal analgesia among patients aged 65 and older at least 90% of the time, and 25.5% (95% CI, 23.3%, 27.7%) provided preoperative information regarding postoperative cognitive changes at least 90% of the time. Over 80% of respondents reported that preoperative screening for frailty or dementia, postoperative screening for delirium, and preoperative geriatric consultation occurred in fewer than 10% of cases. Development of practice guidelines for geriatric anesthesia care and expansion of web-based resources were most frequently prioritized by respondents as initiatives to improve care in this domain.

Discussion
Most survey respondents reported providing anesthesia care to older adults, but adherence to recommended practices varied across the six items assessed. Reported rates of screening for common geriatric syndromes, such as frailty, delirium, and dementia, were low among survey respondents. Respondents identified multiple opportunities for ASA initiatives to support efforts to improve care for older surgical patients.
Estimation of technical efficiency of black cumin (Nigella sativa L.) farming in northwest Ethiopia: a stochastic frontier approach
Authors: Dessie Abebe Birara , Abate Tadie Mirie , Adane Betelhem Tsedalu , Tesfa Tiru , Getu Shegaw 
Published: February 2020

AbstractEthiopia is one of the east African countries which produce and exports various spices to other countries. Black cumin (Nigella sativa L.) is an important stiff annual flowering plant which mainly grows by producers for its seeds. An increasing demand of black cumin seed and oil in local, national and international market for medicinal, consumption and commercial purpose makes the best alternative crop for small holder farmers in Ethiopia. In spite of its importance, not much has been done to improve its production and productivity in Ethiopia. Therefore, this research was designed to examining efficiency variations and factors influencing technical inefficiency levels of producers on black cumin production in northwest Ethiopia. Primary data were collected using a semi-structured questionnaire administered on 188 black cumin producers selected using systematic random sampling technique. Moreover, various data analysis methods such as descriptive statistics and stochastic frontier model were used for analyzing the data. The empirical result obtained by applying maximum likelihood estimate of stochastic frontier model revealed that seed (p < 0.01) labor (p < 0.05), chemical (p < 0.01) and land (p < 0.05) were significant input variables in determining black cumin production. The mean technical efficiency level of black cumin producer was generally low, about 53.1%. The mean value of actual yield, potential yield and yield gap was 3.131, 5.832 and 2.701 quintals, respectively. Moreover, the result of stochastic frontier model together with the inefficiency parameters revealed that market price of black cumin (p < 0.01) and access of extension service (p < 0.1) were significant variables and positively influenced the efficiency levels of black cumin producers. Whereas age of producers (p < 0.05) and distance to farm plot (p < 0.01) negatively influenced the technical efficiency levels of black cumin producers. Therefore, the study recommends that adoption of latest agricultural technologies; development of institutions, agricultural extension services and infrastructure are advisable to improve the efficiency and commercial value of black cumin production.
Structural modeling of dissatisfaction, complaint behavior, and revisiting intentions in hairdressing services
Authors: Lee Hye Won , Kim Mi Young 
Published: February 2020

AbstractThis study aims to present a comprehensive model that effectively explains dissatisfaction, complaint behavior, and revisiting intentions of hair service consumers through an empirical analysis. In order to empirically verify the conceptual model, a questionnaire was developed based on previous studies and responses that were collected through an online survey agency. Subjects were Korean female consumers in their 20s to 50s who experienced dissatisfaction with hair services in the salons they visited during the past year. The conceptual model suggested in the theoretical research was analyzed empirically through the structural equation modeling (SEM) test and finally suggested after ordering, eliminating unnecessary paths. According to the results, dissatisfaction with the hair service significantly affects the complaint behavior and the revisiting intentions while the complaint behavior has a mediating effect between dissatisfaction and the revisiting intentions. Analysis showed that dissatisfaction with human response services and private complaint behaviors are the factors that most negatively influence revisiting intentions. It was confirmed that businesses should focus on the management of the customer service delivered by the employees and on word of mouth. Public complaint behavior was proven to increase revisiting intentions of consumers, needing more attention. This study aims to provide plausible reasons and objective materials to the establishment of a solid theoretical base for the research on dissatisfaction, complaint behavior, and revisiting intentions of hair service consumers. It is expected that the results of this study will help create differentiated marketing strategies for unsatisfied and complaining consumers.
Music Use for Sedation in Critically ill Children (MUSiCC trial): study protocol for a pilot randomized controlled trial
Authors:   the Canadian Critical Care Trials Group, Garcia Guerra Gonzalo , Joffe Ari , Sheppard Cathy , Hewson Krista , Dinu Irina A. , de Caen Allan , Jou Hsing , Hartling Lisa , Vohra Sunita 
Published: February 2020

Abstract
Background
Stress induced by pain and anxiety is common in pediatric intensive care unit (PICU) patients. Sedation/analgesia in PICU is usually achieved through various analgesics and sedatives. Excessive use of these drugs can put patients at risk for hemodynamic/respiratory instability, prolonged ventilation, withdrawal, delirium, and critical illness polyneuromyopathy.
The use of non-pharmacologic interventions has been recommended by sedation guidelines. However, non-pharmacological measures in PICU, including music and noise reduction, have been inadequately studied.

Methods
The Music Use for Sedation in Critically ill Children (MUSiCC trial) pilot study is an investigator-initiated, three-arm, randomized controlled trial (RCT) on the use of music for sedation in PICU. The main goal of the study is to demonstrate feasibility of a music trial in PICU and to obtain the necessary information to plan a larger trial. The study compares music versus noise cancelation versus control in sedated and mechanically ventilated children admitted to PICU. In the music group, children receive the music (modified classical music) three times a day for 30 min at a time. Music is delivered with noise cancelation headphones. The noise cancelation group receives the same intervention but with a no music (sham playlist). The control group receives usual care with no specific intervention. Children remain in the study until extubation or a maximum of 7 days. The primary outcomes of the study are feasibility and sedation/analgesia requirements. Secondary outcomes include change in vital signs before and during the intervention, ICU delirium, and adverse effects related to the intervention. The estimated sample size is 20 subjects per group for a total of 60 children.

Discussion
Despite being recommended by current guidelines, evidence to support the use of music in PICU is lacking. Music has the potential to reduce sedation requirements and their negative side effects. This pilot RCT will demonstrate feasibility and provide the necessary information to plan a larger trial focusing on the effectiveness of the intervention.

Trial registration
The study was registered at ClinicalTrials.gov (NCT03497559) on April 13, 2018.