bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a gluteal activation warm-up on explosive exercise performance
Authors: Parr Matt , Price Phil DB , Cleather Daniel J 
Published: June 2017

ObjectivesTo evaluate the effect of a gluteal activation warm-up on the performance of an explosive exercise (the high hang pull (HHP)).MethodsSeventeen professional rugby union players performed one set of three HHPs (with 80% of their one repetition maximum load) following both a control and activation warm-up. Peak electrical activity of the gluteus maximus and medius was quantified using electromyography (EMG). In addition, the kinematics and kinetics of nine players was also recorded using force plate and motion capture technology. These data were analysed using a previously described musculoskeletal model of the right lower limb in order to provide estimates of the muscular force expressed during the movement.ResultsThe mean peak EMG activity of the gluteus maximus was significantly lower following the activation warm-up as compared with the control (p<0.05, effect size d=0.30). There were no significant differences in the mean peak estimated forces in gluteus maximus and medius, the quadriceps or hamstrings (p=0.053), although there was a trend towards increased force in gluteus maximus and hamstrings following the activation warm-up. There were no differences between the ground reaction forces following the two warm-ups.ConclusionThis study suggests that a gluteal activation warm-up may facilitate recruitment of the gluteal musculature by potentiating the glutes in such a way that a smaller neural drive evokes the same or greater force production during movement. This could in turn potentially improve movement quality.
Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System
Authors: Serebruany Victor , Cherepanov Vasily , Fortmann Seth , Kim Moo Hyun 
Published: June 2017

ObjectiveThe comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.MethodsWe selected CDR from the FAERS database linked to four NOACs and warfarin. The primary endpoints were differences in proportional reporting ratios (PRRs), and Chi-Square (χ2)for dabigatran, rivaroxaban, apixaban and edoxaban when compared with warfarin.ResultsThe FAERS database contains significantly less death reports associated with all NOACs combined (14 917 out of 128 267 reports (11.63%); PRR=1.089; χ2=70.0; p=6.05e−17) than for warfarin (19 493 out of 153 911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or (9.79%); PRR=1.293; χ2=359.4; p=3.72e−80), apixaban (1693 out of 17 789 reports (9.52%); PRR=1.331; χ2=145.8; p=1.43e−33) and edoxaban (53 out of 755 reports (7.02%); PRR=1.804; χ2=21.18; p=4.18e−06) were favourable as compared with warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out of 46 250 reports (15.11%); PRR=0.838; χ2=185.2; p=3.61e−42) were higher than for warfarin.ConclusionOverall, based on these CDR, NOACs appear to be associated with a mortality benefit over warfarin. Among NOACs, we observed remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban) but unfavourable signal for the direct thrombin inhibitor (dabigatran). However, these data are clearly not sufficient to change the prescription patterns.
Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells
Authors: Feeley Kyle P. , Adams Clare M. , Mitra Ramkrishna , Eischen Christine M. 
Published: June 2017

Abstract
p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T-cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell-cycle arrest, prolonging survival of mice with these tumors. p53−/− fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to premalignant cells. Mdm2 deletion in p53−/− cells upregulated p53 transcriptional target genes that induce apoptosis and cell-cycle arrest. Mdm2 deletion also increased levels of p73, a p53 family member. RNAi-mediated attenuation of p73 rescued the transcriptional and biological effects of Mdm2 loss, indicating that p73 mediates the consequences of Mdm2 deletion. In addition, Mdm2 deletion differed from blocking Mdm2 interaction with p53 family members, as Nutlin-3 induced G1 arrest but did not activate apoptosis in p53−/− sarcoma cells. Our results indicate that, in contrast to current dogma, Mdm2 expression is required for cell survival even in the absence of p53. Moreover, our results suggest that p73 compensates for loss of p53 and that targeting Mdm2 in p53-deficient cancers has therapeutic potential. Cancer Res; 77(14); 3823–33. ©2017 AACR.
Pigs, Unlike Mice, Have Two Distinct Colonic Stem Cell Populations Similar to Humans That Respond to High-Calorie Diet prior to Insulin Resistance
Authors: Charepalli Venkata , Reddivari Lavanya , Radhakrishnan Sridhar , Eriksson Elisabeth , Xiao Xia , Kim Sung Woo , Shen Frank , Vijay-Kumar Matam , Li Qunhua , Bhat Vadiraja B. , Knight Rob , Vanamala Jairam K.P. 
Published: June 2017

Abstract
Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HCD (23% fat) for 13 weeks. HCD- and SD-consuming pigs had similar total calorie intake, serum iron, insulin, and glucose levels. However, HCD elevated both colonic proliferative zone (KI-67) and stem cell zone (ASCL-2 and BMI-1). Proliferative zone correlated with elevated innate colonic inflammatory markers TLR-4, NF-κB, IL6, and lipocalin-2 (r ≥ 0.62, P = 0.02). Elevated gut bacterial phyla proteobacteria and firmicutes in HCD-consuming pigs correlated with proliferative and stem cell zone. Colonic proteome data revealed the upregulation of proteins involved in cell migration and proliferation and correlated with proliferative and stem cell zone expansion. Our study suggests that pig colon, unlike mice, has two distinct stem cells (ASCL-2 and BMI-1) similar to humans, and HCD increases expansion of colonic proliferative and stem cell zone. Thus, pig model can aid in the development of preventive strategies against gut bacterial dysbiosis and inflammation-promoted diseases, such as colon cancer. Cancer Prev Res; 10(8); 442–50. ©2017 AACR.
Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAFV600E Melanoma Lines with Vemurafenib
Authors: Frazao Alexandra , Colombo Marina , Fourmentraux-Neves Emmanuelle , Messaoudene Meriem , Rusakiewicz Sylvie , Zitvogel Laurence , Vivier Eric , Vély Frédéric , Faure Florence , Dréno Brigitte , Benlalam Houssem , Bouquet Fanny , Savina Ariel , Pasmant Eric , Toubert Antoine , Avril Marie-Françoise , Caignard Anne 
Published: June 2017

Abstract
Over 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and overactivation of the MAPK pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient, and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK-cell receptors. We have investigated the effect of vemurafenib on the immunogenicity of seven BRAF-mutated melanoma cells to NK cells and on their growth and sensitivity to NK-cell–mediated lysis. We showed that vemurafenib treatment modulated expression of ligands for two activating NK receptors, increasing expression of B7-H6, a ligand for NKp30, and decreasing expression of MICA and ULBP2, ligands for NKG2D. Vemurafenib also increased expression of HLA class I and HLA-E molecules, likely leading to higher engagement of inhibitory receptors (KIRs and NKG2A, respectively), and decreased lysis of vemurafenib-treated melanoma cell lines by cytokine-activated NK cells. Finally, we showed that whereas batimastat (a broad-spectrum matrix metalloprotease inhibitor) increased cell surface ULBP2 by reducing its shedding, vemurafenib lowered soluble ULBP2, indicating that BRAF signal inhibition diminished expression of both cell-surface and soluble forms of NKG2D ligands. Vemurafenib, inhibiting BRAF signaling, shifted the balance of activatory and inhibitory NK ligands on melanoma cells and displayed immunoregulatory effects on NK-cell functional activities. Cancer Immunol Res; 5(7); 582–93. ©2017 AACR.
Electrocardiographic Preexcitation and Risk of Cardiovascular Morbidity and Mortality
Authors: Skov Morten W. , Rasmussen Peter V. , Ghouse Jonas , Hansen Steen M. , Graff Claus , Olesen Morten S. , Pietersen Adrian , Torp-Pedersen Christian , Haunsø Stig , Køber Lars , Svendsen Jesper H. , Holst Anders G. , Nielsen Jonas B. 
Published: June 2017

Background—
The majority of available data on the clinical course of patients with ventricular preexcitation in the ECG originates from tertiary centers. We aimed to investigate long-term outcomes in individuals from a primary care population with electrocardiographic preexcitation.

Methods and Results—

Digital ECGs from 328 638 primary care patients were collected during 2001 to 2011. We identified 310 individuals with preexcitation (age range, 8–85 years). Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. The median follow-up time was 7.4 years (quartiles, 4.6–10.3 years). Compared with the remainder of the population, patients with preexcitation had higher adjusted hazards of atrial fibrillation (hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.07–4.70) and heart failure (HR, 2.11; 95% CI, 1.27–3.50). Subgroup analysis on accessory pathway location revealed a higher adjusted hazard of heart failure for a right anteroseptal accessory pathway (HR, 5.88; 95% CI, 2.63–13.1). There was no evidence of a higher hazard of death among individuals with preexcitation when looking across all age groups (HR, 1.07; 95% CI, 0.68–1.68). However, a statistically significant (
P
=0.01) interaction analysis (<65 versus ≥65 years) indicated a higher hazard of death for patients with preexcitation ≥65 years (HR, 1.85; 95% CI, 1.07–3.18).

Conclusions—
In this large ECG study, individuals with preexcitation had higher hazards of atrial fibrillation and heart failure. The higher hazard of heart failure seemed to be driven by a right anteroseptal accessory pathway. Among elderly people, we found a statistically significant association between preexcitation and a higher hazard of death.
Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial
Authors: Dean Olivia M , Kanchanatawan Buranee , Ashton Melanie , Mohebbi Mohammadreza , Ng Chee Hong , Maes Michael , Berk Lesley , Sughondhabirom Atapol , Tangwongchai Sookjaroen , Singh Ajeet B , McKenzie Helen , Smith Deidre J , Malhi Gin S , Dowling Nathan , Berk Michael 
Published: June 2017

Objective: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. Methods: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery–Asberg Depression Rating Scale (primary outcome), Clinical Global Impression–Improvement and Clinical Global Impression–Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. Results: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery–Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression–Improvement score – effect size (95% confidence interval) = −0.62 [−1.8, −0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score – effect size (confidence interval) = −0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score – 0.79 [−4.5, −1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [−1.7, −0.4], p = 0.017. Conclusion: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.
Modular minimal invasive extracorporeal circuits: another step toward universal applicability?
Authors: El-Essawi Aschraf , Morjan Mohammed , Breitenbach Ingo , Bechri Ahmed , Brouwer Rene , Harringer Wolfgang 
Published: June 2017

Introduction: Safety concerns have been one of the main reasons opposing a wider acceptance of minimal invasive extracorporeal circuits (MiECC). Following an extensive experience and a multitude of modifications, we have set out to employ a modular MiECC as a universal extracorporeal circuit. Methods: A total of 129 cardiac surgical procedures were performed by a single surgeon in 2013. Excluding procedures done under circulatory arrest or with the potential need of such, the MiECC was utilized in almost 90% of surgeries. Of sixty-two (simple procedures) patients who underwent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or CABG + AVR, 82% were non-elective, 10% had a left ventricular ejection fraction (EF) <30% and most had an impaired renal function. Thirty-eight patients had more complex surgeries (complex procedures), 37% of which were urgent, 15% had an EF <30% and the majority had renal dysfunction. Results: The 30-day mortality was 5% in simple procedures and 2.5% in complex procedures. The incidence of postoperative atrial fibrillation was 13% and 16%, respectively. Optimum outcome was defined as a freedom from all complications and blood transfusions and was achieved in 52% and 42%, respectively. Conclusions: This report shows that modular MiECC can be employed with a high safety margin in cardiac surgery. Furthermore, it emphasizes the impact that minimal invasive philosophy could have in improving patient care.
Early pulmonary compliance increase during cardiac surgery predicted post-operative lung dysfunction
Authors: Sacuto Yann , Sacuto Thierry 
Published: June 2017

Introduction: Lung dysfunction following cardiac surgery is currently viewed as the consequence of atelectasis and lung injury. While the mechanism of atelectasis has been largely detailed, the pathogenesis of lung injury after cardiopulmonary bypass is still unclear. Based upon clinical and experimental studies, we hypothesized that lungs could be injured through a mechanical phenomenon. Methods: We recorded pulmonary compliance at six key moments of a heart operation in 62 adult patients undergoing elective cardiac surgery. We focused on the period lasting from anesthetic induction to aorta unclamping. We calculated the variation of static and dynamic pulmonary compliance caused by thorax opening; ΔCstat1 and ΔCdyn1 and that caused by cardiopulmonary bypass, ΔCstat2 and ΔCdyn2. Blood gases were performed under standardized ventilation after anesthetic induction and after surgical closure. The PaO2/FiO2 ratio was calculated. ∆PaO2/FiO2 was the criterion for lung dysfunction. We compared ΔCstat1 and ΔCdyn1 with both ∆PaO2/FiO2 and, respectively, ΔCstat2 and ΔCdyn2. Results: Static and dynamic compliance increased with the opening of the thorax and decreased with the start of cardiopulmonary bypass. The PaO2/FiO2 ratio diminished after surgery. ΔCstat1 and ΔCdyn1 were negatively correlated with both ∆PaO2/FiO2 (r=-0.42; p<0.001 and r=-0.44; p<0.001) and, respectively, with ΔCstat2 and ΔCdyn2 (r=-0.59; p<0.001 and r=-0.53; p<0.001). Conclusions: Increased pulmonary compliance induced by the opening of the thorax is correlated with worsened intrapulmonary shunt after cardiopulmonary bypass. A mechanical phenomenon could be partly responsible for post-operative hypoxemia.
Complications after hand surgery in patients with a raised International Normalized Ratio
Authors: Zimmerman R. M. , Paryavi E. , Zimmerman N. B. , Means K. R. 
Published: June 2017

A multicentre database was used to compare complications in 231 patients with an elevated International Normalized Ratio with 1626 control patients with a normal International Normalized Ratio. Patients with International Normalized Ratios measured within 48 hours of hand surgery were identified. Logistic regression models were used to assess the association between anticoagulation and reoperation rates, emergency department visits and hospital readmissions for the first 30 days after operation. The group with a raised International Normalized Ratio had a significantly higher Charlson Comorbidity Score. An elevated International Normalized Ratio was associated with an odds ratio for a post-operative emergency department visit of 3.3 and an odds ratio of 4.7 for readmission. There was no statistically significant difference in early reoperations between the two groups. Level of evidence: III
The disulfide isomerase ERp72 supports arterial thrombosis in mice
Authors: Zhou Junsong , Wu Yi , Chen Fengwu , Wang Lu , Rauova Lubica , Hayes Vincent M. , Poncz Mortimer , Li Hong , Liu Tong , Liu Junling , Essex David W. 
Published: June 2017

Key PointsIntravascular ERp72 supports platelet accumulation and fibrin generation through the a and a′ active sites. ERp72 functions separately from protein disulfide isomerase and ERp57 in supporting platelet aggregation.
Blocking the Cycle: Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic, Hormone Receptor–Positive Breast Cancer
Authors: Wander Seth A. , Mayer Erica L. , Burstein Harold J. 
Published: June 2017

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old postmenopausal woman was diagnosed with breast cancer 6 years ago when she presented with a stage II (T2N1), right-sided, invasive ductal carcinoma considered grade 2 of 3 on core biopsy, with a positive fine-needle aspiration of a palpable, ipsilateral axillary lymph node. Immunohistochemical analysis was positive for estrogen and progesterone receptor expression and negative for human epidermal growth factor receptor 2 (HER2) overexpression. She received neoadjuvant dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy, followed by breast-conserving surgery and axillary lymph node dissection, which revealed residual disease in three of 11 nodes. She received adjuvant radiation therapy and initiated letrozole, with excellent compliance during the interval 6-year period. While receiving adjuvant letrozole therapy, she reported 3 months of worsening back pain. Skeletal scintigraphy and cross-sectional imaging confirmed widespread osseous metastatic disease and right supraclavicular lymph node enlargement ( Fig 1 ). Core biopsy of the involved lymph node confirmed estrogen receptor (ER)–positive (90%), progesterone receptor–negative, HER2-negative recurrent metastatic breast cancer. The patient reported mild pain that was adequately controlled with over-the-counter anti-inflammatory medications. She has remained active with an excellent performance status.
Caspase-9 has a nonapoptotic function in Xenopus embryonic primitive blood formation
Authors: Tran Hong Thi , Fransen Mathias , Dimitrakopoulou Dionysia , Van Imschoot Griet , Willemarck Nicolas , Vleminckx Kris 
Published: June 2017

ABSTRACT
Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of normal embryonic and fetal development. However, it has become clear that specific caspases also have functions independent of cell death. In order to identify novel apoptotic and nonapoptotic developmental caspase functions, we designed and transgenically integrated novel fluorescent caspase reporter constructs in developing Xenopus embryos and tadpoles. This model organism has an external development, allowing direct and continuous monitoring. These studies uncovered a nonapoptotic role for the initiator caspase-9 in primitive blood formation. Functional experiments further corroborated that caspase-9, but possibly not the executioners caspase-3 and caspase-7, are required for primitive erythropoiesis in the early embryo. These data reveal a novel nonapoptotic function for the initiator caspase-9 and, for the first time, implicate nonapoptotic caspase activity in primitive blood formation.