bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral administration of α-ketoglutarate enhances nitric oxide synthesis by endothelial cells and whole-body insulin sensitivity in diet-induced obese rats
Authors: Tekwe Carmen D , Yao Kang , Lei Jian , Li Xilong , Gupta Anand , Luan Yuanyuan , Meininger Cynthia J , Bazer Fuller W , Wu Guoyao 
Published: July 2019

Obesity is a risk factor for many chronic diseases, including hypertension, type-2 diabetes, and cancer. Interestingly, concentrations of branched-chain amino acids (BCAAs) in plasma are commonly associated with endothelial dysfunction in humans and animals with obesity. Because L-leucine inhibits nitric oxide synthesis by endothelial cells (EC), we hypothesized that dietary supplementation with AKG (a substrate for BCAA transaminase) may stimulate BCAA catabolism in the small intestine and extra-intestinal tissues, thereby reducing the circulating concentrations of BCAAs and increasing nitric oxide synthesis by endothelial cells. Beginning at four weeks of age, male Sprague-Dawley rats were fed a low-fat or a high-fat diet for 15 weeks. At 19 weeks of age, lean or obese rats continued to be fed for 12 weeks their respective diets and received drinking water containing 0 or 1% AKG ( n =  8/group). At 31 weeks of age, the rats were euthanized to obtain tissues. Food intake did not differ ( P >  0.05) between rats supplemented with or without AKG. Oral administration of AKG (250 mg/kg BW per day) reduced ( P <  0.05) concentrations of BCAAs, glucose, ammonia, and triacylglycerols in plasma, adiposity, and glutamine:fructose-6-phosphate transaminase activity in endothelial cells, and enhanced ( P <  0.05) concentrations of the reduced form of glutathione in tissues, nitric oxide synthesis by endothelial cells, and whole-body insulin sensitivity (indicated by oral glucose tolerance test) in both low-fat and high-fat rats. AKG administration reduced ( P <  0.05) white adipose tissue weights of rats in the low-fat and high-fat groups. These novel results indicate that AKG can reduce adiposity and increase nitric oxide production by endothelial cells in diet-induced obese rats. Impact statement Obesity is associated with elevated concentrations of branched-chain amino acids, including L-leucine. L-Leucine inhibits the synthesis of nitric oxide from L-arginine by endothelial cells, contributing to impairments in angiogenesis, blood flow, and vascular dysfunction, as well as insulin resistance. Reduction in the circulating levels of branched-chain amino acids through dietary supplementation with α-ketoglutarate to promote their transamination in the small intestine and other tissues can restore nitric oxide synthesis in the vasculature and reduce the weights of white adipose tissues, thereby improving metabolic profiles and whole-body insulin sensitivity (indicated by oral glucose tolerance test) in diet-induced obese rats. Our findings provide a simple and effective nutritional means to alleviate metabolic syndrome in obese subjects. This is highly significant to combat the current obesity epidemic and associated health problems in humans worldwide.
Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome
Authors: Zhang Liping , Yan Xiaoyu , Nandy Partha , Willmann Stefan , Fox Keith A. A. , Berkowitz Scott D. , Sharma Amarnath , Hermanowski-Vosatka Anne , Schmidt Stephan , Weitz Jeffrey I. , Garmann Dirk , Peters Gary 
Published: July 2019

Background: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. Methods: A post hoc exposure–response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. Results: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06–1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38–0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44–0.87 (no versus yes)]. Conclusions: The shallow slopes of the exposure–response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.
Distal biceps tendon repair via new knotless endobutton fixation: A biomechanical study
Authors: Rutka Victor , Weppe Florent , Duprey Sonia , Gras Laure-Lise 
Published: July 2019

Background Distal biceps tendon repair using endobutton fixation has shown the best biomechanical results in terms of pullout strength. Here, we compared Sethi’s enhanced tension adjustable endobutton technique known as the “tension slide technique” to a new knotless endobutton fixation technique without a post-fixation screw. Our new approach is as effective as the tension slide technique in terms of pullout strength and gapping after early mobilization. Methods A biomechanical cadaveric study with 16 paired arms was performed. With the radius held in place, the distal biceps tendon was loaded at 100 N for 500 cycles and the load was then increased until failure. Gapping after loading cycles and maximum load to failure were recorded and compared. Results Median bone-tendon gapping was 5.77 mm (interquartile range (IQR) 4.84–9.11) for tension slide technique and 4.72 mm (IQR 1.77–6.16) for the knotless fixation (p = 0.047). Median load to failure was 257.87 N (IQR 222.07–325.35) in the tension slide technique group and 407.78 N (IQR 358.54–485.20) in the knotless group (p = 0.047). Discussion The knotless endobutton provides better pullout strength and elongation results compared to the tension slide technique without the use of an interference screw, allowing early mobilization in order to faster return to daily living activities. Level of evidence: Basic science study.
Inter- and intra-rater reliability and clinical utility of the Brachial Plexus Outcome Measure: A pilot study
Authors: Brown Hazel , Bassett Paul , Quick Tom J 
Published: July 2019

Introduction Birth-related plexus injuries cause paralysis of the upper limb. The majority of patients spontaneously recover, but many suffer with long-term limitations in function. The Brachial Plexus Outcome Measure was developed to assess upper limb function in children with birth-related plexus injuries. This pilot study assessed the inter- and intrarater reliability in novice users. Information was also gained with regards to the perceived clinical utility of the tool. Methods Eleven therapists, experienced in the treatment of birth-related plexus injuries but naïve in the use of the Brachial Plexus Outcome Measure, were recruited as raters. Eight video-recorded assessments were independently scored. Four raters were randomly selected to repeat two of the analyses. The perceived clinical utility of the Brachial Plexus Outcome Measure was investigated via a questionnaire. Results Across the domains of the Brachial Plexus Outcome Measure, the majority of items scored ‘Fair’ for inter-rater reliability with kappa scores ranging from 0.13–0.46. Intra-rater agreement was better with the majority of items scoring 0.44–0.86 upon weighted kappa analysis. Participant scores for clinical utility were mixed. However, 7 of the 11 raters agreed that the Brachial Plexus Outcome Measure is useful as a pre- and post-intervention tool. Conclusions When compared to the inter-rater reliability of similar functional outcome measures, these results are less favourable. Future research and suggestions to improve the implementation, reliability and clinical utility of the Brachial Plexus Outcome Measure have been identified. These include better standardisation of equipment and improved instructional guidance. In addition, within the clinical setting, it is recommended that the same clinician assesses the same child over the course of their treatment.
Time course of attentional bias to painful facial expressions and the moderating role of attentional control: an eye-tracking study
Authors: Mazidi Mahdi , Dehghani Mohsen , Sharpe Louise , Dolatshahi Behrooz , Ranjbar Seyran , Khatibi Ali 
Published: July 2019

Introduction: This study investigated the time course of attention to pain and examined the moderating effect of attentional control in the relationship between pain catastrophizing and attentional bias in chronic pain patients. Methods: A total of 28 patients with chronic pain and 29 pain-free individuals observed pictures of pain, happy and neutral facial expressions while their gaze behaviour was recorded. Pain intensity and duration, anxiety, depression, stress, attentional control and pain catastrophizing were assessed by questionnaires. Results: In all subjects, the pattern of attention for pain faces was characterized by initial vigilance, followed by avoidance. No significant difference was found between the two groups in terms of orientation towards the stimuli, the duration of first fixation, the average duration of fixation or number of fixations on the pain stimuli. Attentional control moderated the relationship between catastrophizing and overall dwell time for happy faces in pain patients, indicating that those with high attentional control and high catastrophizing focused more on happy faces, whereas the reverse was true for those with low attentional control. Conclusion: This study supported the vigilance–avoidance pattern of attention to painful facial expressions and a moderation effect of attentional control in the association between pain catastrophizing and attentional bias to happy faces among pain patients.
Antimicrobial susceptibility patterns of organisms causing secondary abdominal infections in patients with perforated abdominal viscus
Authors: Kumar-M Praveen , Shafiq Nusrat , Kumar Pradeep , Gupta Ashish , Malhotra Samir , M. Naveen , Gautam Vikas , Ray Pallab , Gupta Rajesh , Gupta Vikas , Deen Yadav Thakur , Verma G. R. , Singh Rajinder , Singh Gurpreet 
Published: July 2019

Background: Secondary peritonitis, following intestinal perforation, constitutes a significant proportion of cases admitted as a surgical emergency and has a mortality rate of 6–21% worldwide. As a part of an antimicrobial stewardship program, we noted considerable variation among the choice of empirical regimens among such cases. Hence, we conducted a prospective study to generate the evidence for a rational empiric regimen for patients with secondary peritonitis following intestinal perforation. Methods: The study included a complete follow up of 77 cases of secondary peritonitis admitted during a 12 month period. The intraoperative fluid (peritoneal) sample of the patient was sent for culture and sensitivity pattern analysis. Results: The sites of perforation as seen in decreasing order were lower gastrointestinal (GI) (50.6%), upper GI (36.4%), and unclassified (13%). The most common organism found in the intraoperative fluid was Escherichia coli (47.9%) followed by Klebsiella pneumoniae (12.5%). amikacin, cefoperazone-sulbactam, piperacillin-tazobactam and imipenem were sensitive in 22 (out of 23 tested), 5 (out of 9), 13 (out of 13) and 22 (out of 22) isolates of E. coli and 3 (out of 6), 1 (out of 3), 4 (out of 6), 4 (out of 6) isolates of K. pneumoniae, respectively. The most common empirical antibiotic was cefoperazone-sulbactam (38.7%) followed by piperacillin-tazobactam (29.3%). Conclusion: Based on our prospective study, piperacillin-tazobactam or imipenem should be used empirically in patients presenting with complicated intra-abdominal infections secondary to perforated viscus, especially if they have sepsis or septic shock.
Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta‐analysis
Authors: Myneedu Kanchana , Deoker Abhizith , Schmulson Max J , Bashashati Mohammad 
Published: July 2019

BackgroundModulating gut microbiota is a potential treatment for irritable bowel syndrome (IBS). This meta‐analysis explored whether fecal microbiota transplantation (FMT) is successful in treating IBS.MethodsA systematic review was performed to find trials on FMT in IBS. Ratios and relative ratios (RR) of improvement for single‐arm trials (SATs) and randomized controlled trials (RCTs) were calculated, respectively. Changes in IBS Severity Scoring System (IBS‐SSS) and IBS Quality of Life (IBS‐QOL) instrument compared to baseline in FMT versus placebo groups were pooled.ResultsIn SATs, 59.5% (95% confidence interval (CI) 49.1–69.3) of IBS patients showed significant improvement. In RCTs, there were no differences between FMT and control in improvement (RR=0.93 (95% CI 0.50–1.75)) or changes in the IBS‐SSS and IBS‐QOL.ConclusionsFMT was not effective in IBS. Variations in FMT methods and patient factors may contribute to the heterogeneous results of the trials.
No Difference Between Posterolateral Corner Repair and Reconstruction With Concurrent ACL Surgery: Results From a Prospective Multicenter Cohort
Authors: Westermann Robert W. , Marx Robert G. , Spindler Kurt P. , Huston Laura J. ,   MOON Knee Group, Amendola Annunziato , Andrish Jack T. , Brophy Robert H. , Dunn Warren R. , Flanigan David C. , Jones Morgan H. , Kaeding Christopher C. , Matava Matthew J. , McCarty Eric C. , Parker Richard D. , Reinke Emily K. , Vidal Armando F. , Wolcott Michelle L. , Wolf Brian R. 
Published: July 2019

Background: Injuries to the posterolateral corner (PLC) may occur concurrently with anterior cruciate ligament (ACL) injury. Purpose/Hypothesis: This study evaluated the outcomes of patients who underwent operative management of PLC injuries concurrently with ACL reconstruction in a prospective multicenter cohort. We hypothesized that there would be no differences in outcomes between patients who were treated with PLC repair and PLC reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing ACL reconstruction were enrolled into a prospective longitudinal multicenter cohort between 2002 and 2008. Those with complete 6-year follow-up data (patient-reported outcomes and subsequent surgery information) were identified. Excluded from the study were patients with posterior cruciate ligament injuries. Patients who underwent PLC repair were compared with those who underwent PLC reconstruction with regard to interval from injury to surgery, need for revision surgery, and long-term outcomes at 6 years. Results: During the identified time frame, 3026 identified patients underwent primary ACL reconstruction; 34 (1.1%) also underwent concurrent PLC surgery (15 repairs, 19 reconstructions [18 allografts, 1 autograft]). With the numbers available, we did not detect significant differences between groups regarding the rate of meniscal or chondral injuries. Median time to PLC reconstruction was 121 days as compared with 19 days for concurrent ACL reconstruction and PLC repair ( P = .01). There were no between-group differences in Marx activity scores prior to surgery ( P = .4). At 6-year follow-up, there were no between-group differences in Knee injury and Osteoarthritis Outcome Score ( P = .36-.83) or International Knee Documentation Committee score ( P = .84); however, patients treated with PLC reconstructions had lower Marx activity scores (4.1 vs 9.4; P = .02). There was 1 ACL revision in the PLC reconstruction group, and 1 of the PLC repairs was revised to a reconstruction during the follow-up period. Conclusion: Good outcomes were achieved at 6-year follow-up with both repair and reconstruction of PLC injuries treated concurrently with ACL reconstruction. The PLC reconstruction group had lower activity levels 6 years after surgery. The present data suggest that, for appropriately selected patients undergoing acute surgical treatment of combined ACL and PLC injuries, PCL repair can achieve good long-term outcomes.
Novel associations between sex hormones and diabetic vascular complications in men and postmenopausal women: a cross-sectional study
Authors: Wang Chiyu , Zhang Wen , Wang Yuying , Wan Heng , Chen Yi , Xia Fangzhen , Zhang Kun , Wang Ningjian , Lu Yingli 
Published: July 2019

Abstract
Background
Associations between sex hormones and vascular remodeling have been extensively studied, but the results vary widely among different races and sex. We aimed to investigate whether total testosterone (TT), estrogen (E2), and dehydroepiandrosterone (DHEA) associate with macrovascular complications and diabetic kidney disease (DKD) among community-dwelling patients with diabetes.

Methods
A total of 4720 participants with type 2 diabetes were recruited from Shanghai, China. Common carotid artery (CCA) plaques and diameter were assessed by ultrasound. Cardiovascular disease (CVD) was defined by prior diagnosis of coronary heart disease, myocardial infarction or stroke. DKD was defined according to the ADA Guidelines.

Results
(1) In men, TT was negatively associated with CCA diameter (regression coefficient (β) − 0.044, 95% CI − 0.087, 0). E2 levels were positively associated with CVD and CCA plaque prevalence (OR 1.151, 95% CI 1.038, 1.277 and OR 1.13, 95% CI 1.017, 1.255, respectively). DHEA was negatively associated with CVD (OR 0.809, 95% CI 0.734, 0.893). In postmenopausal women, TT levels were negatively associated with CCA diameter (β − 0.046, 95% CI − 0.083, − 0.010) and positively associated with CVD (OR 1.154, 95% CI 1.038, 1.284). (2) In both men and postmenopausal women, TT levels were negatively associated with the albumin/creatinine ratio and DKD (β − 0.098, 95% CI − 0.154, − 0.043 and OR 0.887, 95% CI 0.790, 0.997 vs. β − 0.084, 95% CI − 0.137, − 0.031 and OR 0.822, 95% CI 0.731, 0.924, respectively) and DHEA levels were positively associated with DKD (OR 1.167, 95% CI 1.038, 1.313 vs. OR 1.251, 95% CI 1.104, 1.418, respectively).

Conclusions
Our study indicates that macrovascular complications were associated with low TT, DHEA and high E2 in men and with high TT in postmenopausal women. DKD was associated with low TT and high DHEA levels in both genders. Sex hormone replacement therapy requires careful and comprehensive consideration.
Trial registration ChiCTR1800017573, http://www.chictr.org.cn. Registered 04 August 2018
Neonatal Eating Assessment Tool - Mixed Breastfeeding and Bottle-Feeding (NeoEAT - Mixed Feeding): factor analysis and psychometric properties
Authors: Pados Britt Frisk , Thoyre Suzanne M. , Galer Kara 
Published: July 2019

Abstract
Background
Early identification of feeding difficulty in infancy is critical to supporting breastfeeding and ensuring optimal nutrition for brain development. The Neonatal Eating Assessment Tool (NeoEAT) is a parent-report assessment that currently has two versions: NeoEAT – Breastfeeding and NeoEAT – Bottle-feeding for use in breast and bottle-fed infants, respectively. There are currently no valid and reliable parent-report measures to assess feeding through a combination of both breast and bottle delivery. The purpose of this study was to conduct a factor analysis and test the psychometric properties of a new measure, the NeoEAT – Mixed Breastfeeding and Bottle-Feeding (NeoEAT – Mixed Feeding), including internal consistency reliability, test-retest reliability, construct validity and known-groups validity.

Methods
Parents of infants younger than 7 months who had fed by both bottle and breast in the previous 7 days were invited to participate. Internal consistency reliability was tested using Cronbach’s α. Test-retest reliability was tested between scores on the NeoEAT – Mixed Feeding completed 2 weeks apart. Construct validity was tested using correlations between the NeoEAT – Mixed-Feeding, the Infant Gastroesophageal Reflux Questionnaire - Revised (I-GERQ-R), and the Infant Gastrointestinal Symptoms Questionnaire (IGSQ). Known-groups validation was tested between healthy infants and infants with feeding problems.

Results
A total of 608 parents participated. Exploratory factor analysis revealed a 68-item scale with 5 sub-scales. Internal consistency reliability (Cronbach’s α = .88) and test-retest reliability (r = 0.91; p < .001) were both acceptable. Construct validity was demonstrated through correlations with the I-GERQ-R (r = 0.57; p < .001) and IGSQ (r = 0.5; p < .001). Infants with feeding problems scored significantly higher on the NeoEAT – Mixed Feeding, indicating more problematic feeding symptoms, than infants without feeding problems (p < .001), supporting known-groups validity.

Conclusions
The NeoEAT – Mixed Feeding is a 68-item parent-reported measure of breast- and bottle-feeding behavior for infants less than 7 months old that now has evidence of validity and reliability for use in clinical practice and research. The NeoEAT – Mixed Feeding can be used to identify infants with problematic feeding, guide referral decisions, and evaluate response to interventions.
Validation of a Cyclic Algorithm to Proxy Number of Lines of Systemic Cancer Therapy Using Administrative Data
Authors: Weymann Deirdre , Costa Sarah , Regier Dean A. 
Published: July 2019

PURPOSE Researchers are automating the process for identifying the number of lines of systemic cancer therapy received by patients. To date, algorithm development has involved manual modifications to predefined classification rules. In this study, we propose a supervised learning algorithm for determining the best-performing proxy for number of lines of therapy and validate this approach in four patient groups. MATERIALS AND METHODS We retrospectively analyzed BC Cancer pharmacy records from patients’ cancer diagnosis until end of follow-up (cohort-specific, 2014/2015). We created and validated a cyclic algorithm in patients with advanced cancers of varying histologies, diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. To assess internal and external validity, we used a split-sample approach for all analyses and considered lines of therapy identified through manual review as our criterion standard. We measured agreement using correlation coefficients, mean squared error, nonparametric hypothesis testing, and quantile-quantile plots. RESULTS Cohorts comprised 91 patients with advanced cancers, 121 with chronic lymphocytic leukemia, 440 with follicular lymphoma, and 679 with diffuse large B-cell lymphoma. Number of lines of therapy received and patients’ treatment period length varied substantially across cohorts. Despite these differences, our algorithm successfully identified a best-performing proxy for number of lines of therapy for each cohort, which was moderate to highly correlated with (within-sample: 0.73 ≤ Pearson correlation ≤ 0.84; out-of-sample: 0.52 ≤ Pearson correlation ≤ 0.76) and whose distribution did not significantly differ from the criterion standard within or out of sample ( P > .10). CONCLUSION Supervised learning is an ideal tool for generating a best-performing proxy that recognizes prescription drug patterns and approximates number of lines of therapy. Our cyclic approach can be used in jurisdictions with access to administrative pharmacy data.