bluuebunny/crossref_metadata_2025_split huggingface dataset:
FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
Authors: Rothrock John F. , Adams Aubrey Manack , Lipton Richard B. , Silberstein Stephen D. , Jo Esther , Zhao Xiang , Blumenfeld Andrew M. ,   on behalf of the FORWARD Study investigative group
Published: September 2019

ObjectiveTo compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention.BackgroundThe efficacy* of onabotulinumtoxinA and topiramate has been established in placebo‐controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real‐world conditions, representing a blend of efficacy and tolerability).MethodsIn this multicenter, randomized, parallel‐group, post‐authorization, open‐label prospective study (FORWARD; ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate “immediate release” 50‐100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29‐32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs).ResultsWe enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA.In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7‐9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA.ConclusionsWhile using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment.
Association of rs2651899 Polymorphism in the Positive Regulatory Domain 16 and Common Migraine Subtypes: A Meta‐Analysis
Authors: Lee Hsun‐Hua , Chen Chih‐Chung , Ong Jiann‐Ruey , Lin Yuan‐Feng , Lee Fei‐Peng , Hu Chaur‐Jong , Wang Yuan‐Hung 
Published: September 2019

BackgroundMigraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome‐wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta‐analysis to examine this issue.MethodsWe performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO).ResultsSix studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta‐analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively.ConclusionOur major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).
‘The Future is Probably Now’: Understanding of illness, uncertainty and end‐of‐life discussions in older adults with heart failure and family caregivers
Authors: Im Jennifer , Mak Susanna , Upshur Ross , Steinberg Leah , Kuluski Kerry 
Published: September 2019

AbstractBackgroundEarlier end‐of‐life communication is critical for people with heart failure given the uncertainty and high‐risk of mortality in illness. Despite this, end‐of‐life communication is uncommon in heart failure. Left unaddressed, lack of end‐of‐life discussions can lead to discordant care at the end of life.ObjectiveThis study explores patients' and caregivers’ understanding of illness, experiences of uncertainty, and perceptions of end‐of‐life discussions in advanced illness.DesignInterpretive descriptive qualitative study of older adults with heart failure and family caregivers. Fourteen semi‐structured interviews were conducted with 19 participants in Ontario, Canada. Interviews were transcribed verbatim and content analysis was used to analyse the data.Main resultsUnderstanding of illness was shaped by participants’ illness‐related experiences (e.g. symptoms, hospitalizations and self‐care routines) and the ability to adapt to challenges of illness. Participants were knowledgeable of heart failure management, and yet, were limited in their understanding of the consequences of illness. Participants adapted to the challenges of illness which appeared to influence their perception of overall health. Uncertainty reflected participants’ inability to connect manifestations of heart failure as part of the progression of illness towards the end of life. Most participants had not engaged in prior end‐of‐life discussions.ConclusionDetailed knowledge of heart failure management does not necessarily translate to an understanding of the consequences of illness. The ability to adapt to illness‐related challenges may delay older adults and family caregivers from engaging in end‐of‐life discussions. Future research is needed to examine the impact of addressing the consequences of illness in facilitating earlier end‐of‐life communication.
Hemostasis critical values among Iranian clinical laboratories “National Survey of 157 Clinical Laboratories”
Authors: Dorgalaleh Akbar , Shiravand Yavar , Dabbagh Ali , Tabibian Shadi , Hosseini Maryam Sadat , Mansouri Tourghabeh Hassan , Rashidpanah Jamal , Narouei Fateme , Shams Mahmood , Gholami Mohammad Saeed , Saneei Moghaddam Esmaei , Shahreki Hojat 
Published: September 2019

AbstractBackgroundImmediate reporting of critical values or test results significantly outside the normal range has a growing role in the management of patients, especially in life‐threatening conditions. Due to the lack of international consensus, diverse approaches are used for determination of thresholds, reporting, documentation, and follow‐up. In this study, we assessed how Iranian laboratories manage critical values for hemostasis.MethodsWe designed a standard questionnaire to assess different aspects of hemostasis critical values, including the number of coagulation tests with a defined critical value, critical values reporting, documentation, and follow‐up policies. All results were self‐reported and correctness of the data was not assessed by the authors.ResultsA total of 166 (66.4%) out of 250 laboratories completed the questionnaire; most (52.4%) were private. About 97% of responding laboratories had a critical values policy. These were defined for 64.3% (n: 27) of all coagulation tests (n: 42) performed in Iranian laboratories. Activated partial thromboplastin time (APTT), prothrombin time/international normalized ratio (PT/INR), platelet count, factor XI, and factor XIII assays had defined critical values among all laboratories performing these tests. Almost all laboratories reported critical values within 1 hour, after confirmation of the result on the same sample (70% of the laboratories) or a new one (13.4% of the laboratories). State and private laboratories had the same critical value reporting policy for in and outpatients, with laboratory technicians reporting critical results to nurses, for the most part.ConclusionAlthough critical value policy is widely used among Iranian laboratories, there is no consensus policy for the reporting of hemostasis critical values, or documentation, threshold determination, and follow‐up processes. It is impossible to determine whether non‐responding laboratories had any critical values reporting policy. Results thus are biased toward laboratories that did.
Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord
Authors: Lin Wenping , Chen Wenkai , Liu Weifeng , Xu Zhengquan , Zhang Liqun 
Published: September 2019

SummaryThe neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti‐inflammatory cells that restrain post‐SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up‐regulated in infiltrating Treg cells. Using lentivirus‐mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin‐10, and transforming growth factor‐β in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide‐stimulated spinal cord CD11b+ myeloid cells. Knock‐down of SIRT4 enhanced the anti‐inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down‐regulated 5′ AMP‐activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin‐10 in SIRT4‐overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post‐SCI neuroinflammation is regulated.
The impact of grape processing and carbonic maceration on the microbiota of early stages of winemaking
Authors: Guzzon R. , Malacarne M. , Larcher R. , Franciosi E. , Toffanin A. 
Published: September 2019

Abstract

Aims
The work investigates the impact of grapes processing at the beginning of winemaking on the composition of microbiota during the oenological fermentations and on the composition of obtained wines.

Methods and Results
The experiments were conducted in a biodynamic winery to exclude interference due to microbial starters. Three winemaking protocols, with different pre-fermentative management of grapes, were followed by plate count and next generation sequencing on 16S for bacteria and internal transcribed spacer sequencing (ITS) for yeast. Chemical and sensory characterization of wine was performed. The grape processing influenced the evolution of microbiota (especially lactic and acetic acid bacteria) and the fermentation rate. The highest biodiversity was observed in the experiment carried out with whole grapes and carbonic maceration, with the presence of bacterial groups not usually found in winemaking (Bacteroidales, Clostridiales, Oscillospira). The different microbiotas influenced the organic acid profile of wines, the content of biogenic ammines and the perception of organoleptic descriptors linked to the vine cultivar (Syrah).

Conclusions
Carbonic maceration impacts on the evolution of the microbiota and the wine features. The absence of addition of starters and sulphur dioxide would seem to be correlated with the high microbial biodiversity.

Significance and Impact of the Study
Carbonic maceration is a traditional winemaking practice, today there are difficulties in its managing because the anaerobiosis stimulates spoilage micro-organisms. The work elucidates the reasons of these difficulties and identified some microbial groups rarely associated with winemaking. The ratio of ethanol accumulation along with physical management of grapes and the supply of oxygen during the early stages of winemaking are powerful instruments of oenological variability, able to offer new possibilities to winemakers in order to defining the quality of red wines.
Exosomes derived from pro‐inflammatory bone marrow‐derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization
Authors: Xu Ruqin , Zhang Fangcheng , Chai Renjie , Zhou Wenyi , Hu Ming , Liu Bin , Chen Xuke , Liu Mingke , Xu Qiong , Liu Ningning , Liu Shiming 
Published: September 2019

AbstractExosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre‐conditioning bone marrow‐derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). This study aimed to investigate whether LPS‐primed BMSC‐derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI. Here, we found that exosomes derived from BMSCs, in both Exo and L‐Exo groups, increased M2 macrophage polarization and decreased M1 macrophage polarization under LPS stimulation, which strongly depressed LPS‐dependent NF‐κB signalling pathway and partly activated the AKT1/AKT2 signalling pathway. Compared with Exo, L‐Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post‐infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre‐conditioning BMSC‐derived exosomes may develop into a promising cell‐free treatment strategy for clinical treatment of MI.
Do bulk‐fill resins decrease the restorative time in posterior teeth? A systematic review and meta‐analysis of in vitro studies
Authors: Bellinaso Mariana D. , Soares Fabio Z. M. , Rocha Rachel de Olivera 
Published: September 2019

AbstractThe aim of the present study was to compare the restorative time for filling cavities in posterior teeth using bulk‐fill and conventional resin composites through a systematic review and meta‐analysis. A search for clinical trials and laboratory studies was performed in PubMed/MEDLINE, Scopus, the Latin American and Caribbean Health Sciences Literature database, the Brazilian Library in Dentistry, Cochrane Library, Clinical Trials, and ReBEC (Registro Brasileiro de Ensaios Clínicos) databases without publication year or language restriction. Two reviewers identified eligible studies according to the inclusion criteria: bulk‐fill compared to conventional resin in class I or II, and the restorative time as an outcome. A meta‐analysis of the restorative time mean difference between composites was performed (inverse variance method, random effects model; Z‐test, P ≤ .05). From the 662 eligible studies, 133 were selected for full‐text analysis; three were included in the systematic review and in the meta‐analysis. Overall, the restorative time was lower when bulk‐fill was used (P = .0007, Z = 3.37), as the subgroup full‐body bulk‐fill (P < .00001, Z = 21.00). There was no difference in restorative time between flowable bulk‐fill and conventional resins (P = .08, Z = 1.76). Moderate‐to‐substantial heterogeneity was detected. Full‐body bulk‐fill composites decrease the restorative time in posterior teeth compared to conventional resins. Full‐body bulk‐fill resins require a shorter restorative time to perform restorations in posterior teeth than conventional resins, but the same is not valid for flowable bulk‐fill resin composites.
Effect of porous tantalum on the biological response of human peripheral mononuclear cells exposed to Porphyromonas gingivalis
Authors: Temponi Eduardo Frois , Souza Paulo Eduardo Alencar , Souto Giovanna Ribeiro , Magalhães Luísa Mourão Dias , Dutra Walderez Ornelas , Gollob Kenneth John , Silva Tarcília Aparecida , Soares Rodrigo Villamarim 
Published: September 2019

AbstractAimTo evaluate biological behavior of human peripheral mononuclear cells (PBMC) in contact with porous tantalum (PT) and Porphyromonas gingivalis (Pg).MethodsPg was incubated for 8 hours. The groups formed were: PBMC (control), PBMC + PT, PBMC + Pg and PBMC + PT + Pg. Cell viability was evaluated using MTT assay. The morphology and adhesion of PBMC to PT was evaluated using scanning electron microscopy. Expression of interleukin (IL)‐10, transforming growth factor (TGF)‐β, matrix metallopeptidase (MMP)‐9 and receptor activator of nuclear factor‐κΒ ligand (RANKL) was determined by enzyme‐linked immunosorbent assay.ResultsMTT assay revealed that PT did not interfere in the mitochondrial activity of PBMC (P > .05). Scanning electron microscopy showed the adherence of PBMC to PT. IL‐10 levels in PBMC + PT were similar to PBMC and lower than PBMC + Pg. TGF‐β levels in PBMC + PT were higher than PBMC and PBMC + Pg. MMP‐9 levels in PBMC + PT were similar to PBMC and lower than PBMC + Pg and PBMC + PT + Pg. RANKL levels in PBMC + PT were lower than in PBMC.ConclusionPT did not affect PBMC viability, allowed cell adhesion, reduced expression of RANKL and enhanced TGF‐β in comparison with the control group.
The evasion of fiscal and labor regulations: Firm behavior and optimal tax policy
Authors: Cuff Katherine , Mongrain Steeve , Roberts Joanne 
Published: September 2019

AbstractFirms face many fiscal and labor regulations, but they may evade these legal requirements in several different ways. We develop a model that captures these two types of evasion decisions and unlike existing literature assume firms can evade labor regulations independently from income tax responsibilities. We characterize firms’ entry and evasion behavior and find that the design of the tax system can generate both positive and negative correlations between evasion decisions consistent with what is observed empirically. We then characterize optimal government policies given the firms’ decisions. We obtain intuitive optimal tax rules that highlight the trade‐offs the government faces when firms have multiple margins on which to evade.
Effect of dietary digestible lysine level on growth performance, blood metabolites and meat quality of broilers 23–38 days of age
Authors: Zarghi Heydar , Golian Abolghasem , Nikbakhtzade Mahdie 
Published: September 2019

AbstractThis study was done to evaluate the effects of different dietary digestible lysine (dig Lys) levels on growth performance, blood metabolites, carcass and breast yield, and breast meat quality of broilers 23–38 days of age. Three hundred 23‐day‐old Cobb‐500 male broiler chickens were allocated to a completely randomized design with five treatments (finisher diet containing 0.88%, 0.94%, 1.00%, 1.06% and 1.12% dig Lys) and six replicates of 10 birds each. Feed intake (FI) was not affected by different dietary dig Lys levels. Weight gain (WG) linearly increased and feed conversion ratio (FCR) linearly decreased with an increasing dietary dig Lys levels. With increasing dietary dig Lys levels, carcass and breast yield and breast meat hue angle (h*) linearly increased, but abdominal fat decreased quadratically, whereas breast meat lightness (L*) and ether extract composition linearly decreased. Dietary dig Lys levels did not show any significant effect on serum metabolites, breast meat cooking loss and water holding capacity. Based on the linear broken‐line regression models, the weight gain, feed conversion ratio and breast yield were optimized when dietary dig Lys levels were 0.95%, 1.01% and 1.02% respectively. It is concluded that Lys requirements vary according to what productive parameter is taken for optimization. A minimum of 1.02% dig Lys concentration in the finisher diet is suggested to optimize breast yield, feed efficiency and performance in broiler chickens.
Predicting early risk of chronic kidney disease in cats using routine clinical laboratory tests and machine learning
Authors: Bradley Richard , Tagkopoulos Ilias , Kim Minseung , Kokkinos Yiannis , Panagiotakos Theodoros , Kennedy James , De Meyer Geert , Watson Phillip , Elliott Jonathan 
Published: September 2019

AbstractBackgroundAdvanced machine learning methods combined with large sets of health screening data provide opportunities for diagnostic value in human and veterinary medicine.Hypothesis/ObjectivesTo derive a model to predict the risk of cats developing chronic kidney disease (CKD) using data from electronic health records (EHRs) collected during routine veterinary practice.AnimalsA total of 106 251 cats that attended Banfield Pet Hospitals between January 1, 1995, and December 31, 2017.MethodsLongitudinal EHRs from Banfield Pet Hospitals were extracted and randomly split into 2 parts. The first 67% of the data were used to build a prediction model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate the model performance.ResultsThe final model was a recurrent neural network (RNN) with 4 features (creatinine, blood urea nitrogen, urine specific gravity, and age). When predicting CKD near the point of diagnosis, the model displayed a sensitivity of 90.7% and a specificity of 98.9%. Model sensitivity decreased when predicting the risk of CKD with a longer horizon, having 63.0% sensitivity 1 year before diagnosis and 44.2% 2 years before diagnosis, but with specificity remaining around 99%.Conclusions and clinical importanceThe use of models based on machine learning can support veterinary decision making by improving early identification of CKD.