bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children with Hemiparesis Arm and Movement Project (CHAMP): protocol for a multisite comparative efficacy trial of paediatric constraint-induced movement therapy (CIMT) testing effects of dosage and type of constraint for children with hemiparetic cerebral palsy
Authors: Ramey Sharon Landesman , DeLuca Stephanie , Stevenson Richard D , Case-Smith Jane , Darragh Amy , Conaway Mark 
Published: January 2019

IntroductionThe Children with Hemiparesis Arm and Movement Project (CHAMP) addresses two pressing issues concerning paediatric constraint-induced movement therapy (CIMT): effects of two dosages and two types of constraint on functional outcomes. Systematic reviews conclude that CIMT is one of the most efficacious treatments, but wide variations in treatment protocols, outcome measures and patient characteristics have prevented conclusions about potential effects of dosage levels and constraint methods.Methods and analysisCHAMP is a multisite comparative efficacy randomised controlled trial of 135 children (2–8 years) with hemiparetic cerebral palsy. The 2×2 factorial design tests two dosage levels—60 hours (3.0 hours/day, 5 days/week × 4 weeks) and 30 hours (2.5 hours/day, 3 days/week × 4 weeks) and two constraint conditions—full-arm, full-time cast and part-time splint, plus usual and customary (UCT) controls, yielding five groups: (1) 60 hours CIMT+full-time cast, (2) 60 hours CIMT+part-time splint, (3) 30 hours CIMT+full-time cast, (4) 30 hours CIMT+part-time splint and (5) UCT. Trained therapists deliver the standardised ACQUIREc protocol for CIMT. Blinded assessments at baseline, end of treatment, and 6 and 12 months post treatment include the Assisting Hand Assessment, and subscales from the Peabody Developmental Motor Scales-2 and modified Quality of Upper Extremity Skills Test. Parents complete the Pediatric Motor Activity Log and Pediatric Evaluation of Disability Inventory. A new Fidelity of Implementation Rehabilitation Measure monitors treatment delivery. Data analyses involve repeated-measures multivariate analysis of co-variance controlling for selected baseline variables.Ethics and disseminationEthics boards at site universities approved the study protocol. To promote equipoise, parents of UCT controls are offered ACQUIREc after 6 months. A Data Safety and Monitoring Committee reviews results regularly, including measures of child and family stress. We will disseminate CHAMP results via peer-reviewed publications and presentations to professional and advocacy organisations.Trial registration numberNCT01895660; Pre-results.
Chinese herbal medicine for postpartum constipation: a protocol of systematic review and meta-analysis
Authors: Zhai Jingbo , Li Yan , Lin Jingyi , Dong Shuo , Si Jinhua , Zhang Junhua 
Published: January 2019

IntroductionConstipation is one of the most common gastrointestinal symptoms in postpartum mothers. The choice of treatments for postpartum constipation remains a challenging clinical problem. Chinese herbal medicine has become increasingly popular as an alternative therapy for constipation. This systematic review aims to evaluate the efficacy and safety of Chinese herbal medicine for postpartum constipation.Methods and analysisWe will search PubMed (1946 to present), EMBASE (1974 to present), Cochrane Central Register of Controlled Trials (all years), Web of Science (1900 to present), Chinese Biomedical Literatures Database (1978 to present), China National Knowledge Infrastructure (1979 to present) and WANFANG data (1998 to present) to identify any eligible study. No restriction will be put on the language, publication date or status of the study. The primary outcome will be the spontaneous bowel movement. Secondary outcomes will be stool consistency, quality of life, transit time, relief of constipation symptoms and adverse events. We will perform the meta-analysis when more than one trial examines the same intervention and outcomes with comparable methods in similar populations. If the heterogeneity is not significant statistically (p>0.10 or I2<50%), the fixed-effect model will be built to estimate the overall intervention effects. Otherwise, the random-effect model will be used to provide more conservative results.Ethics and disseminationNo ethical issues are foreseen because no primary data will be collected. The results will be published in a peer-reviewed scientific journal.PROSPERO registration numberCRD42018093741
Can online self-reports assist in real-time identification of influenza vaccination uptake? A cross-sectional study of influenza vaccine-related tweets in the USA, 2013–2017
Authors: Huang Xiaolei , Smith Michael C , Jamison Amelia M , Broniatowski David A , Dredze Mark , Quinn Sandra Crouse , Cai Justin , Paul Michael J 
Published: January 2019

IntroductionThe Centers for Disease Control and Prevention (CDC) spend significant time and resources to track influenza vaccination coverage each influenza season using national surveys. Emerging data from social media provide an alternative solution to surveillance at both national and local levels of influenza vaccination coverage in near real time.ObjectivesThis study aimed to characterise and analyse the vaccinated population from temporal, demographical and geographical perspectives using automatic classification of vaccination-related Twitter data.MethodsIn this cross-sectional study, we continuously collected tweets containing both influenza-related terms and vaccine-related terms covering four consecutive influenza seasons from 2013 to 2017. We created a machine learning classifier to identify relevant tweets, then evaluated the approach by comparing to data from the CDC’s FluVaxView. We limited our analysis to tweets geolocated within the USA.ResultsWe assessed 1 124 839 tweets. We found strong correlations of 0.799 between monthly Twitter estimates and CDC, with correlations as high as 0.950 in individual influenza seasons. We also found that our approach obtained geographical correlations of 0.387 at the US state level and 0.467 at the regional level. Finally, we found a higher level of influenza vaccine tweets among female users than male users, also consistent with the results of CDC surveys on vaccine uptake.ConclusionSignificant correlations between Twitter data and CDC data show the potential of using social media for vaccination surveillance. Temporal variability is captured better than geographical and demographical variability. We discuss potential paths forward for leveraging this approach.
Assessment of healthcare costs of amputation and prosthesis for upper and lower extremities in a Qatari healthcare institution: a retrospective cohort study
Authors: Al-Thani Hassan , Sathian Brijesh , El-Menyar Ayman 
Published: January 2019

ObjectivesTo evaluate the healthcare cost of amputation and prosthesis for management of upper and lower extremities in a single institute.DesignRetrospective cohort study conducted between 2000 and 2014.ParticipantsAll patients who underwent upper (UEA) and lower extremities amputation (LEA) were identified retrospectively from the operating theatre database. Collected data included patient demographics, comorbidities, interventions, costs of amputations including hospitalisation expenses, length of hospital stay and mortality.Outcome measuresIncidence, costs of amputation and hospitalisation according to the level of the amputation and cost per bed days, length of hospital stay and mortality.ResultsA total of 871 patients underwent 1102 (major 357 and minor 745) UEA and LEA. The mean age of patients was 59.4±18.3, and 77.2% were males. Amputations were most frequent among elderly (51.1%). Two-third of patients (75.86%, 95% CI 72.91% to 78.59%) had diabetes mellitus. Females, Qatari nationals and non-diabetics were more likely to have higher mean amputation and hospital stay cost. The estimated total cost for major and minor amputations were US$3 797 930 and US$2 344 439, respectively. The cumulative direct healthcare cost comprised total cost of all amputations, bed days cost and prosthesis cost and was estimated to be US$52 126 496 and per patient direct healthcare procedure cost was found to be US$59 847. The total direct related therapeutic cost was estimated to be US$26 096 046 with per patient cost of US$29 961. Overall per patient cost for amputation was US$89 808.ConclusionsThe economic burden associated with UEA and LEA-related hospitalisations is considerable. Diabetes mellitus, advanced age and sociodemographic factors influence the incidence of amputation and its associated healthcare cost. The findings will help to showcase the economic burden of amputation for better management strategies to reduce healthcare costs. Furthermore, larger prospective studies focused on cost-effectiveness of primary prevention strategies to minimise diabetic complication are warranted.
Prevalence and correlates of advance care directives among older Australians accessing health and residential aged care services: multicentre audit study
Authors: Detering Karen M , Buck Kimberly , Ruseckaite Rasa , Kelly Helana , Sellars Marcus , Sinclair Craig , Clayton Josephine M , Nolte Linda 
Published: January 2019

ObjectivesIt is important that the outcomes of advance care planning (ACP) conversations are documented and available at the point of care. Advance care directives (ACDs) are a subset of ACP documentation and refer to structured documents that are completed and signed by competent adults. Other ACP documentation includes informal documentation by the person or on behalf of the person by someone else (eg, clinician, family). The primary objectives were to describe the prevalence and correlates of ACDs among Australians aged 65 and over accessing health and residential aged care services. The secondary aim was to describe the prevalence of other ACP documentation.Design and settingA prospective multicentre health record audit in general practices (n=13), hospitals (n=12) and residential aged care facilities (RACFs; n=26).Participants503 people attending general practice, 574 people admitted to hospitals and 1208 people in RACFs.Primary and secondary outcome measuresPrevalence of one or more ACDs; prevalence of other ACP documentation.Results29.8% of people had at least one ACD on file. The majority were non-statutory documents (20.9%). ACD prevalence was significantly higher in RACFs (47.7%) than hospitals (15.7%) and general practices (3.2%) (p<0.001), and varied across jurisdictions. Multivariate logistic regression showed that the odds of having an ACD were positively associated with greater functional impairment and being in an RACF or hospital compared with general practice. 21.6% of people had other ACP documentation.ConclusionsIn this study, 30% of people had ACDs accessible and a further 20% had other ACP documentation, suggesting that approximately half of participants had some form of ACP. Correlates of ACD completion were greater impairment and being in an RACF or hospital. Greater efforts to promote and standardise ACDs across jurisdictions may help to assist older people to navigate and complete ACDs and to receive care consistent with their preferences.Trial registration numberACTRN12617000743369.
Fixed-dose combination antihypertensives and risk of medication errors
Authors: Moriarty Frank , Bennett Kathleen , Fahey Tom 
Published: January 2019

ObjectiveWhile fixed-dose combinations (FDC) can improve adherence, they may add complexity to the prescribing/dispensing process, potentially increasing risk of medication errors. This study aimed to determine if prescriptions for antihypertensive FDCs increase the risk of therapeutic duplication and drug–drug interactions (DDI).MethodsThis retrospective observational study used administrative pharmacy claims data from the Irish Primary Care Reimbursement Service. Prescriptions dispensed to adults in 2015 were included if they contained an antihypertensive FDC, or the same drugs prescribed separately. The outcomes were therapeutic duplication and potentially serious DDI involving FDC drugs. Relative risk (RR) of these outcomes, adjusted for prescription and patient factors, was determined using generalised linear models with Poisson distributions and propensity score matching.ResultsThis study included 307 833 FDC prescriptions (67.0%) and 151 632 separate component prescriptions. Half of patients prescribed FDCs were female with a mean age of 67.1 (SD 12.5) years and, compared with separate component prescriptions, FDCs were less often coprescribed with other cardiovascular medications. Therapeutic duplication occurred in 0.8% of prescriptions, most often involving calcium channel blockers, and 10.6% contained a DDI (most often amlodipine and simvastatin). The RR of therapeutic duplication on FDC prescriptions compared with separate component prescriptions was 1.46 (95% CI 1.17 to 1.83) and the adjusted RR was 2.06 (95% CI 1.64 to 2.60). For DDIs, there was no significant difference between FDC and separate component prescriptions after confounder adjustment.ConclusionsThis study found FDCs were associated with increased risk of duplication. When considering prescribing FDCs, this safety consideration should be weighed against potential benefits.
On the nonperturbative graviton propagator
Authors: Khatsymovsky V. M. 
Published: January 2019

To reduce general relativity to the canonical Hamiltonian formalism and construct the path (functional) integral in a simpler and, especially in the discrete case, less singular way, one extends the configuration superspace, as in the connection representation. Then we perform functional integration over connection. The module of the result of this integration arises in the leading order of the expansion over a scale of the discrete lapse-shift functions and has maxima at finite (Planck scale) areas/lengths and rapidly decreases at large areas/lengths, as we have mainly considered previously; the phase arises in the leading order (Regge action) of the stationary phase expansion. Now we consider the possibility of confining ourselves to these leading terms in a certain region of the parameters of the theory; consider background edge lengths as an optimal starting point for the perturbative expansion of the theory; estimate the background length scale and consider the form of the graviton propagator. In parallel with the general simplicial structure, we consider the simplest periodic simplicial structure with a part of the variables frozen (“hypercubic”), for which also the propagator in the leading approximation over metric variations can be written in a closed form.
Application of periodic density functional theory calculations for exploring copper(II) coordination effects on the mesophase behavior of p-n-alkoxybenzoic acids
Authors: Wang Li-Fen , You Cheng-Xian 
Published: January 2019

Copper(II) benzoates ([Formula: see text]OBA-Cu) with various terminal alkoxy carbon numbers, [Formula: see text]–12, were prepared from [Formula: see text]-[Formula: see text]-alkoxy benzoic acids (nOBAs). Fourier transform infrared (IR) experiments suggested that dimerization through copper(II) chelating bidentate coordination created [Formula: see text]OBA-Cu with a linear rod-like structure, similar to the hydrogen-bonded structure of its parent [Formula: see text]OBA. However, the coordination structure of [Formula: see text]OBA-Cu changed during heating. Periodic density functional theory calculations provided valuable insight into the possible arrangement of the parent and copper(II)-coordinated [Formula: see text]OBAs. The formation of binuclear complexes between two adjacent [Formula: see text]OBA-Cu dimers forced [Formula: see text]OBA-Cu to arrange itself in a layer and exhibit smectic A mesophase. Accordingly, four types of IR stretching absorption of benzoyl carbonyl were observed in binuclear [Formula: see text]OBA-Cu complexes, replacing the original symmetric and asymmetric vibrations of benzoyl carboxylate in chelating bidentate coordination. The lateral association by [Formula: see text]–[Formula: see text] interactions between adjacent parent [Formula: see text]OBA dimers preferred a progressive smectic C arrangement. The origin of the odd–even effect was understood from the consideration of the molecular structure.
Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition
Authors: Rajendran Praveen , Johnson Gavin , Li Li , Chen Ying-Shiuan , Dashwood Mohaiza , Nguyen Nhung , Ulusan Ahmet , Ertem Furkan , Zhang Mutian , Li Jia , Sun Deqiang , Huang Yun , Wang Shan , Leung Hon-Chiu , Lieberman David , Beaver Laura , Ho Emily , Bedford Mark , Chang Kyle , Vilar Eduardo , Dashwood Roderick 
Published: January 2019

AbstractThere continues to be interest in targeting epigenetic “readers, writers, and erasers” for the treatment of cancer and other pathologies. However, a mechanistic understanding is frequently lacking for the synergy observed when combining deacetylase and bromodomain inhibitors. Here we identify cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane. N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl “reader” proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. Treatment with the BET inhibitor JQ1 synergized with sulforaphane in colon cancer cells and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with sulforaphane+JQ1 in combination implicated a BET/BRD9 acetyl switch and a shift in the pool of acetyl “reader” proteins in favor of BRD9-regulated target genes.Significance:These results highlight the competition that exists among the “readers” of acetylated histone and nonhistone proteins and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments.
Colorectal Carcinomas Containing Hypermethylated MLH1 Promoter and Wild-Type BRAF/KRAS Are Enriched for Targetable Kinase Fusions
Authors: Cocco Emiliano , Benhamida Jamal , Middha Sumit , Zehir Ahmet , Mullaney Kerry , Shia Jinru , Yaeger Rona , Zhang Liying , Wong Donna , Villafania Liliana , Nafa Khedoudja , Scaltriti Maurizio , Drilon Alexander , Saltz Leonard , Schram Alison M. , Stadler Zsofia K. , Hyman David M. , Benayed Ryma , Ladanyi Marc , Hechtman Jaclyn F. 
Published: January 2019

Abstract

Kinase fusions are rare and poorly characterized in colorectal carcinoma, yet they present unique opportunities for targeted therapy. In this study, we characterized kinase fusions from patients with advanced colorectal carcinoma who had MSK-IMPACT testing of their tumors between January 2014 and June 2018. Patients were analyzed for the presence of fusions, microsatellite instability (MSI), and RAS/BRAF mutations. Mismatch repair (MMR), IHC, and promoter hypermethylation status of MLH1 (MLH1ph) in microsatellite instability-high (MSI-H) colorectal carcinoma with fusions were investigated. Fusion transcripts were confirmed using a targeted RNA-seq panel assay. Of 2,314 colorectal carcinomas with MSK-IMPACT testing, 21 harbored kinase fusions. Overall 57% (12/21) of colorectal carcinoma fusions were MSI-H/MMR-D. Loss of MLH1 and MLH1ph was confirmed in all 12 and all 10 cases with available material, respectively. Fusions were present in 5% of MSI-H/MMR-D colorectal carcinoma compared with 0.4% of MSS/MMR-P colorectal carcinoma (P &lt; 0.001) and 15% of MSI-H/MMR-D colorectal carcinoma with wild-type RAS/BRAF. Of 24 total MLH1-deficient colorectal carcinomas with MLH1ph and wild-type RAS/BRAF, 10 (42%) harbored kinase fusions. Kinase fusions in MSI-H colorectal carcinoma were associated with sporadic MLH1ph rather than with Lynch syndrome, and these patients may be eligible for kinase inhibitors, particularly following resistance or toxicity in response to immunotherapy. These findings identify a molecular subset of colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.

Significance: A high frequency of targetable kinase fusions in BRAF/RAS wild-type, MSI-H colorectal carcinoma offers a rationale for routine screening to identify patients with colorectal carcinoma with kinase fusions that may be responsive to kinase inhibitors.
See related commentary by Valeri, p. 1041
Particulate Matter and Traffic-Related Exposures in Relation to Breast Cancer Survival
Authors: DuPré Natalie C. , Hart Jaime E. , Holmes Michelle D. , Poole Elizabeth M. , James Peter , Kraft Peter , Laden Francine , Tamimi Rulla M. 
Published: January 2019

AbstractBackground:Although particulate matter (PM) has not been consistently associated with breast cancer risk, two studies have reported harmful associations for breast cancer survival. We examined PM exposures and breast cancer survival in two U.S.-based prospective cohort studies.Methods:The Nurses' Health Study (NHS) and NHSII are cohorts with detailed data on medical history, lifestyle factors, and causes of death. Women with Stage I–III breast cancer (n = 8,936) were followed through June 2014. Residential PM was estimated using spatio-temporal models. We performed Cox regression to estimate hazard ratios (HR) of breast cancer–specific mortality and all-cause mortality for 10 μg/m3 increases in post-diagnosis PM.Results:There were 1,211 breast cancer–specific deaths. Overall, PM was not associated with breast cancer–specific mortality [PM2.5: HR, 1.09; 95% confidence interval (CI), 0.87–1.36; PM2.5-10: HR, 1.03; 95% CI, 0.85–1.24; PM10: HR, 1.05; 95% CI, 0.89–1.24], but was associated with modest increases in all-cause mortality (PM2.5: HR, 1.12; 95% CI, 0.96–1.30; PM2.5-10: HR, 1.12; 95% CI, 1.00–1.24; PM10: HR, 1.09; 95% CI, 1.01–1.18). However, among participants with Stage I disease, PM2.5 was associated with higher breast cancer–specific mortality (HR, 1.64; 95% CI, 1.11–2.43).Conclusions:PM was not associated with breast cancer–specific death overall; however, higher PM was associated with all-cause mortality. Higher PM2.5 was associated with higher breast cancer–specific mortality among patients with Stage I breast cancer even after adjustment.Impact:Studies on ambient PM and breast cancer survival demonstrate that PM2.5 may have broader health effects than previously recognized and warrants further research on breast tumor progression.