bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload–Induced Cardiac Dysfunction
Authors: Wang Ying , Sano Soichi , Oshima Kosei , Sano Miho , Watanabe Yosuke , Katanasaka Yasufumi , Yura Yoshimitsu , Jung Changhee , Anzai Atsushi , Swirski Filip K. , Gokce Noyan , Walsh Kenneth 
Published: June 2019

Background:
Although the complex roles of macrophages in myocardial injury are widely appreciated, the function of neutrophils in nonischemic cardiac pathology has received relatively little attention.

Methods:
To examine the regulation and function of neutrophils in pressure overload–induced cardiac hypertrophy, mice underwent treatment with Ly6G antibody to deplete neutrophils and then were subjected to transverse aortic constriction.

Results:
Neutrophil depletion diminished transverse aortic constriction–induced hypertrophy and inflammation and preserved cardiac function. Myeloid deficiency of Wnt5a, a noncanonical Wnt, suppressed neutrophil infiltration to the hearts of transverse aortic constriction–treated mice and produced a phenotype that was similar to the neutropenic conditions. Conversely, mice overexpressing Wnt5a in myeloid cells displayed greater hypertrophic growth, inflammation, and cardiac dysfunction. Neutrophil depletion reversed the Wnt5a overexpression–induced cardiac pathology and eliminated differences in cardiac parameters between wild-type and myeloid-specific Wnt5a transgenic mice.

Conclusions:
These findings reveal that Wnt5a-regulated neutrophil infiltration has a critical role in pressure overload–induced heart failure.
Tractor Rollover Protection: Is the Incorrect Use of Foldable Rollover Protective Structures Due to Human or to Technical Issues?
Authors: Micheletti Cremasco Margherita , Caffaro Federica , Giustetto Ambra , Vigoroso Lucia , Paletto Giuseppe , Cavallo Eugenio 
Published: June 2019

Objective: To identify the critical behaviors that may hinder the correct use of foldable rollover protective structures (FROPS) on tractors and to explore the influence of user factors and FROPS technical characteristics. Background: FROPS are effective in preventing fatal injuries in rollover accidents if they are in the upright position. However, many farmers leave FROPS folded down. Method: Twenty farmers and sixteen models of tractors were involved in the study. Operators were observed while raising the FROPS, and the observed behaviors were correlated with user factors and FROPS technical features. Results: In the initial rotation of the FROPS, higher lowered roll-bar to ground distance and FROPS pivot-pin to ground distance required more awkward and unbalanced postures ( p = .02 and p = .01, respectively). When rotating the FROPS in upright position, smaller stature of the participants and higher FROPS pivot-pin to ground distance were significantly correlated with using the tractor’s rear 3-point lower links as a supporting surface ( p = .01 and p = .02, respectively). Conclusion: FROPS might be revised considering users’ comfort in use and anthropometric variability, to improve reachability, avoid risky behaviors, and enhance FROPS operation. Application: Technical solutions to enhance FROPS accessibility may be developed, particularly by providing safe surfaces to support operators and highlighting the grasping points. Further best practices and information on correct gestures to handle the FROPS should be included in the tractor manual.
miR-33-5p knockdown attenuates abdominal aortic aneurysm progression via promoting target adenosine triphosphate-binding cassette transporter A1 expression and activating the PI3K/Akt signaling pathway
Authors: Zhao Lingfeng , Huang Jian , Zhu Yancui , Han Shengbin , Qing Kaixiong , Wang Jin , Feng Yaoyu 
Published: June 2019

Purpose: The aim of this study was to investigate the role of miR-33-5p in abdominal aortic aneurysm progression, which regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux and lipid accumulation in THP-1 macrophage-derived foam cells through the PI3K/Akt pathway. Methods: Quantitative reverse transcription polymerase chain reaction was used to evaluate the expression level of miR-33-5p and ABCA1 mRNA in abdominal aortic aneurysm patient and normal person tissues. The relationship between miR-33-5p and ABCA1 was examined by dual luciferase report assay. High-performance liquid chromatography was used to evaluate the levels of cholesterol contents. Cholesterol efflux detection was performed by liquid scintillator. The expression of inflammatory cytokines was detected by quantitative reverse transcription polymerase chain reaction. Western blot was applied to determine the expression levels of ABCA1, PI3K (p-PI3K), and Akt (p-Akt). Results: The quantitative reverse transcription polymerase chain reaction analysis results revealed miR-33-5p overexpression in abdominal aortic aneurysm tissues, but the expression level of ABCA1 was lower in abdominal aortic aneurysm tissues than non-abdominal aortic aneurysm tissues. Subsequently, the dual luciferase report gene assay confirmed that ABCA1 was a target of miR-33-5p, and miR-33-5p-negative regulated ABCA1 expression. Moreover, the expression levels of p-PI3K, p-Akt, and ABCA1 were decreased in THP-1 cell transferred with ABCA1 siRNA, but knockdown of miR-33-5p had an opposite effect. Furthermore, knockdown of miR-33-5p decreased the expression of MMP-2, MMP-9, TNF-α, total cellular cholesterol, and promoted cholesterol efflux in THP-1-derived foam cells. Importantly, LY294002 (PI3K inhibitor) or si-ABCA1 completely inhibited the stimulatory effects of miR-33-5p inhibitor. Conclusion: This study has found that knockdown of miR-33-5p induced ABCA1 expression and promoted inflammatory cytokines and cholesterol efflux likely via activating the PI3K/Akt signaling pathway.
Evaluation of Meniscal Regeneration in a Mini Pig Model Treated With a Novel Polyglycolic Acid Meniscal Scaffold
Authors: Otsuki Shuhei , Nakagawa Kosuke , Murakami Tomohiko , Sezaki Shunsuke , Sato Hideki , Suzuki Masakazu , Okuno Nobuhiro , Wakama Hitoshi , Kaihatsu Kunihiro , Neo Masashi 
Published: June 2019

Background:Meniscal injury is a severe impediment to movement and results in accelerated deterioration of the knee joint.Purpose:To evaluate the effect of a novel meniscal scaffold prepared from polyglycolic acid coated with polylactic acid/caprolactone on the treatment of meniscal injury in a mini pig model.Study Design:Controlled laboratory study.Methods:The model was established with a 10-mm resection at the anterior medial meniscus on both knee joints. A scaffold was implanted in the right knee joint. The meniscal scaffold was inserted and sutured next to the native meniscus. The histological analysis was performed to determine meniscal regeneration with safranin O staining, cell proliferation with PCNA, inflammation with TNF, and collagen structure and production with picrosirius red and immunofluorescence. Cartilage degeneration was evaluated with Safranin O. Meniscal regeneration and joint fluid were evaluated with magnetic resonance imaging.Results:Although compressive stress and elastic modulus were significantly lower in the scaffold than in the native porcine menisci, ultimate tensile stress was similar. Implanted scaffolds were covered with tissue beginning at 4 weeks, with increased migration of proliferating cells to the implant area at 4 and 8 weeks. Scaffolds were absorbed with freshly produced collagen at 24 weeks. Cartilage degeneration was significantly lower in the meniscus-implanted group than in the meniscectomy group. Magnetic resonance imaging results did not show severe accumulation of joint fluids, suggesting negligible inflammation. Density of the implanted menisci was comparable with that of the native menisci.Conclusion:Meniscal scaffold prepared from polyglycolic acid has therapeutic potential for meniscal regeneration.Clinical Relevance:This meniscal scaffold can improve biological knee reconstruction and prevent the increase of total knee arthroplasty.
Increased Glenoid Retroversion Is Associated With Increased Rotator Cuff Strength in the Shoulder
Authors: Cameron Kenneth L. , Tennent David J. , Sturdivant Rodney X. , Posner Matthew A. , Peck Karen Y. , Campbell Scot E. , Westrick Richard B. , Owens Brett D. 
Published: June 2019

Background:The rotator cuff muscles are critical secondary stabilizers in the shoulder. Increased glenoid retroversion and rotator cuff strength have been associated with the risk of posterior shoulder instability; however, the effect of increased glenoid retroversion on rotator cuff strength remains unclear.Purpose/Hypothesis:The purpose was to examine the association between glenoid version and rotator cuff strength in the shoulder in a young and healthy population with no history of shoulder instability. The hypothesis was that increased glenoid retroversion would be associated with increases in rotator cuff muscle strength.Study Design:Cross-sectional study; Level of evidence, 3.Methods:A prospective cohort study was conducted over a 4-year period within a high-risk population to identify the risk factors for shoulder instability. Analyzed participants included 574 freshmen entering a United States service academy. Baseline data collected upon entry into the study included magnetic resonance imaging measurements of glenoid version. Rotator cuff strength was also assessed at baseline using a handheld dynamometer. Internal and external rotation strength were assessed with the glenohumeral joint positioned in neutral and in 45° of abduction. The current study represents an analysis of the baseline data from this cohort.Results:The mean age, height, and weight of participants was 18.77 ± 0.97 years, 176.81 ± 8.48 cm, and 73.80 ± 12.45 kg, respectively. The mean glenoid version at baseline was 7.79°± 4.85° of retroversion. Univariate linear regression analyses demonstrated that increased glenoid retroversion was associated with increased internal and external rotation strength of the rotator cuff in neutral and 45° of abduction ( P < .001). Similar results were observed in multivariable models controlling for important confounding variables.Conclusion:The results of this study demonstrate that as glenoid retroversion increases, internal and external rotation strength of the rotator cuff also increase in a young and healthy athletic population. These compensatory changes may contribute to increased glenohumeral dynamic stability in the presence of worse static stability with increasing retroversion.
Recombinant Human Platelet–Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/β-TCP)-Collagen Matrix as an Alternative to Autograft
Authors: Daniels Timothy R. , Anderson John , Swords Michael P. , Maislin Greg , Donahue Rafe , Pinsker Ellie , Quiton Jovelyn D. 
Published: June 2019

Background: Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet–derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (β-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/β-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. Methods: Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/β-TCP-collagen ( n = 69) or autograft ( n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/β-TCP-collagen–treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. Results: In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/β-TCP-collagen to autograft. Safety-related outcomes were equivalent. Conclusion: PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/β-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. Level of Evidence: Level I, prospective randomized study.
CINCA Syndrome With New NLRP3 Mutation and Unreported Complication of Thyroid Carcinoma
Authors: Salehzadeh Farhad , Barak Manuchehr , Hosseiniasl Saied , Shahbazfar Ehsan 
Published: June 2019

Background: Chronic infantile neurologic cutaneous and articular syndrome (CINCA) is the most severe phenotype of cryopyrin-associated periodic syndromes (CAPS) and is caused by a missense mutation in NLRP3 gene. Case presentation: We are reporting a 15-year-old male patient with complaints of chronic arthritis and mental involvement. Further investigations showed a heterozygous c.785G>A missense mutation in Exon 3 of NLRP3 gene and coexisting medullary thyroid carcinoma 2 years later. Conclusions: This case showed a recently identified gene variant of NLRP3 in a CINCA patient, as a heterozygous c.785G>A missense mutation in Exon 3 of NLRP3 gene and coexisted medullary thyroid carcinoma as an unreported complication of CINCA.
Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: Pooled analysis of clinical trials
Authors: Comi Giancarlo , Miller Aaron E , Benamor Myriam , Truffinet Philippe , Poole Elizabeth M , Freedman Mark S 
Published: June 2019

Background: In Phase 3 studies, teriflunomide reduced relapse rates and disability progression compared with placebo; however, decreases in lymphocyte counts were also observed. Objective: To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates among patients in pooled analyses of Phase 3 core and extension studies. Methods: Four randomized trials (TEMSO, TOWER, TENERE, and TOPIC) compared teriflunomide 7 mg or 14 mg treatment with either placebo and/or subcutaneous interferon (IFN) β-1a 44 µg in patients with relapsing forms of multiple sclerosis (MS) (or first clinical episode suggestive of MS in TOPIC). Results: In 1895, patients ever exposed to teriflunomide, mean (standard deviation) absolute lymphocyte counts declined from Week 0 (1.89 (0.59)) to Week 24 (1.67 (0.52)) and then remained stable thereafter. In the core plus extension studies (up to 10.7 years), 7.3% and 2.2% experienced Grade 1 and Grade 2 lymphopenia, respectively. Infections were reported in 56.9% of patients without lymphopenia, 60.9% with Grade 1 lymphopenia, and 54.8% with Grade 2 lymphopenia. Serious infections occurred in 3.7%, 4.3%, and 7.1%, respectively. Conclusion: Long-term risk of lymphopenia and infections in patients who continue to receive teriflunomide is low, demonstrating a limited impact on adaptive and innate immunity.
An expansion study of genotype-driven weekly irinotecan and capecitabine in combination with neoadjuvant radiotherapy for locally advanced rectal cancer with UGT1A1 *1*1 genotype
Authors: Guan Yun , Shen Yunzhu , Xu Ye , Li Chao , Wang Jingwen , Gu Weilie , Lian Peng , Huang Dan , Cai Sanjun , Zhang Zhen , Zhu Ji 
Published: June 2019

Background: In our previous dose-escalation study, we uncovered the maximum tolerated dose (MTD) of weekly irinotecan was escalated to 80 mg/m2 and 65 mg/m2 for UDP glucuronosyltransferase family 1 member A1 (UGT1A1) *1*1 and *1*28 rectal cancer patients in neoadjuvant chemoradiotherapy (nCRT). This is an expansion study for *1*1 patients. Methods: Patients with clinical stage T3–4, N0–2 rectal cancer eligible for preoperative chemoradiotherapy were screened for the UGT1A1*28 genotype. A total of 52 patients with the *1*1 genotype were enrolled. Whole-pelvic intensity-modulated radiation therapy was given in 50 Gy/25 fractions. Concurrently, irinotecan of 80 mg/m2 and capecitabine of 625 mg/m2 twice daily from Monday to Friday were administered weekly. Primary endpoint was toxicities; secondary endpoints included pathological complete response (pCR), tumour-regression grading, treatment compliance, overall survival, local recurrence and disease-free survival. Results: All patients completed capecitabine-based radiotherapy as scheduled, and 42 (81%) patients completed more than three cycles of weekly irinotecan. Overall, grade 3/4 toxicities were observed in 20 cases, including 11 leucopenia, 10 neutropenia and 12 diarrhoea. Forty-three patients (83%) underwent a radical surgery, and 12 were evaluated as pCR. Another four patients accepted a watch-and-wait strategy because of clinical complete response (CCR). Conclusions: Our data demonstrated manageable toxicities and an encouraging CCR rate for UGT1A1 *1*1 genotype in an enhanced neoadjuvant therapy. A phase III trial is ongoing to evaluate the value of irinotecan in neoadjuvant therapy (CinClare) [ClinicalTrials.gov identifier: NCT02605265].
Age of First Exposure to American Football and Behavioral, Cognitive, Psychological, and Physical Outcomes in High School and Collegiate Football Players
Authors: Brett Benjamin L. , Huber Daniel L. , Wild Alexa , Nelson Lindsay D. , McCrea Michael A. 
Published: June 2019

Background: Although some studies have observed a relationship between age of first exposure (AFE) to American football and long-term outcomes, recent findings in collegiate athletes did not observe a relationship between AFE and more intermediate outcomes at early adulthood. This, however, requires independent replication. Hypothesis: There will be no association between AFE to football and behavioral, cognitive, emotional/psychological, and physical functioning in high school and collegiate athletes. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Active high school and collegiate football players (N = 1802) underwent a comprehensive preseason evaluation on several clinical outcome measures. Demographic and health variables that significantly differed across AFE groups were identified as potential covariates. General linear models (GLMs) with AFE as the independent variable were performed for each clinical outcome variable. Similar GLMs that included identified covariates, with AFE as the predictor, were subsequently performed for each clinical outcome variable. Results: After controlling for covariates of age, concussion history, race, and a diagnosis of ADHD, earlier AFE (<12 vs ≥12 years) did not significantly predict poorer performance on any clinical outcome measures (all P > 0.05). A single statistically significant association between AFE group and somatization score was recorded, with AFE <12 years exhibiting lower levels of somatization. Conclusion: In a large cohort of active high school and collegiate football student-athletes, AFE before the age of 12 years was not associated with worse behavioral, cognitive, psychological, and physical (oculomotor functioning and postural stability) outcomes. Clinical Relevance The current findings suggest that timing of onset of football exposure does not result in poorer functioning in adolescence and young adults and may contribute to resilience through decreased levels of physically related psychological distress.
Injury in Brazilian Jiu-Jitsu Training
Authors: Petrisor Brad A. , Del Fabbro Gina , Madden Kim , Khan Moin , Joslin Jeff , Bhandari Mohit 
Published: June 2019

Background: Brazilian jiu-jitsu (BJJ) is a grappling-based martial art that can lead to injuries both in training and in competition. There is a paucity of data regarding injuries sustained while training in BJJ, in both competitive and noncompetitive jiu-jitsu athletes. Hypothesis: We hypothesize that most BJJ practitioners sustain injuries to various body locations while in training and in competition. Our primary objective was to describe injuries sustained while training for BJJ, both in practice and in competition. Our secondary objectives were to classify injury type and to explore participant and injury characteristics associated with wanting to quit jiu-jitsu after injury. Study Design: Descriptive epidemiology study. Methods: We conducted a survey of all BJJ participants at a single club in Hamilton, Ontario, Canada. We developed a questionnaire including questions on demographics, injuries in competition and/or training, treatment received, and whether the participant considered discontinuing BJJ after injury. Results: A total of 70 BJJ athletes participated in this study (response rate, 85%). Ninety-one percent of participants were injured in training and 60% of competitive athletes were injured in competitions. Significantly more injuries were sustained overall for each body region in training in comparison with competition ( P < 0.001). Two-thirds of injured participants required medical attention, with 15% requiring surgery. Participants requiring surgical treatment were 6.5 times more likely to consider quitting compared with those requiring other treatments, including no treatment (odds ratio [OR], 6.50; 95% CI, 1.53-27.60). Participants required to take more than 4 months off training were 5.5 times more likely to consider quitting compared with those who took less time off (OR, 5.48; 95% CI, 2.25-13.38). Conclusion: The prevalence of injury is very high among BJJ practitioners, with 9 of 10 practitioners sustaining at least 1 injury, commonly during training. Injuries were primarily sprains and strains to fingers, the upper extremity, and neck. Potential participants in BJJ should be informed regarding significant risk of injury and instructed regarding appropriate precautions and safety protocols. Clinical Relevance: Clinicians should be aware of the substantial risk of injury among BJJ practitioners and the epidemiology of the injuries as outlined in this article.
Day-case laparoscopic nephrectomy: Feasibility and safety
Authors: Ragavan Narasimhan , Dholakia Kunal , Baskaran Jegadish , Ramesh Malarvizhi 
Published: June 2019

Purpose: The method of surgery and its recovery play an important part in a success of any surgery. Implementing a minimal invasive approach with enhanced recovery protocol permits Nephrectomy to be performed as a day-case (DC) procedure. Here we report our initial experience with laparoscopic nephrectomy (LN) as DC surgery with an aim to assess its feasibility and safety. Patients and methods: In this retrospective observational study, nine patients underwent DC LN performed by a single surgeon (NR). LN was performed in the standard way followed by enhanced recovery pathway of care for DC. We collected data regarding demographic information, medical co-morbidities, preoperative outcomes, complications and readmission rates. The data was analysed and evaluated. Results: There were four (44.4%) women and five (55.5%) men with a median age of 35 years (range 17–52 years). Eight (88.9%) patients had benign diseases associated with non-functioning kidneys and one (11.1%) patient had a renal tumour. All patients (100%) were successfully discharged the same day with no major complication (Clavien Dindo Grade > I). Readmission rates were 0%. Conclusion: In our small series, DC LN is feasible and safe with a belief that the results are easily reproducible. Increasing experience in laparoscopic surgery with implementation of enhanced recovery protocol may help to increase the success rate of LN as DC.