bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone secretagogue receptor constitutive activity impairs voltage‐gated calcium channel‐dependent inhibitory neurotransmission in hippocampal neurons
Authors: Martínez Damonte Valentina , Rodríguez Silvia Susana , Raingo Jesica 
Published: September 2018

Key points
Presynaptic CaV2 voltage‐gated calcium channels link action potentials arriving at the presynaptic terminal to neurotransmitter release. Hence, their regulation is essential to fine tune brain circuitry.
CaV2 channels are highly sensitive to G protein‐coupled receptor (GPCR) modulation. Our previous data indicated that growth hormone secretagogue receptor (GHSR) constitutive activity impairs CaV2 channels by decreasing their surface density.
We present compelling support for the impact of CaV2.2 channel inhibition by agonist‐independent GHSR activity exclusively on GABA release in hippocampal cultures. We found that this selectivity arises from a high reliance of GABA release on CaV2.2 rather than on CaV2.1 channels.
Our data provide new information on the effects of the ghrelin–GHSR system on synaptic transmission, suggesting a putative physiological role of the constitutive signalling of a GPCR that is expressed at high levels in brain areas with restricted access to its natural agonist.
AbstractGrowth hormone secretagogue receptor (GHSR) displays high constitutive activity, independent of its endogenous ligand, ghrelin. Unlike ghrelin‐induced GHSR activity, the physiological role of GHSR constitutive activity and the mechanisms that underlie GHSR neuronal modulation remain elusive. We previously demonstrated that GHSR constitutive activity modulates presynaptic CaV2 voltage‐gated calcium channels. Here we postulate that GHSR constitutive activity‐mediated modulation of CaV2 channels could be relevant in the hippocampus since this brain area has high GHSR expression but restricted access to ghrelin. We performed whole‐cell patch‐clamp in hippocampal primary cultures from E16‐ to E18‐day‐old C57BL6 wild‐type and GHSR‐deficient mice after manipulating GHSR expression with lentiviral transduction. We found that GHSR constitutive activity impairs CaV2.1 and CaV2.2 native calcium currents and that CaV2.2 basal impairment leads to a decrease in GABA but not glutamate release. We postulated that this selective effect is related to a higher CaV2.2 over CaV2.1 contribution to GABA release (∼40% for CaV2.2 in wild‐type vs. ∼20% in wild‐type GHSR‐overexpressing cultures). This effect of GHSR constitutive activity is conserved in hippocampal brain slices, where GHSR constitutive activity reduces local GABAergic transmission of the granule cell layer (intra‐granule cell inhibitory postsynaptic current (IPSC) size ∼−67 pA in wild‐type vs. ∼−100 pA in GHSR‐deficient mice), whereas the glutamatergic output from the dentate gyrus to CA3 remains unchanged. In summary, we found that GHSR constitutive activity impairs IPSCs both in hippocampal primary cultures and in brain slices through a CaV2‐dependent mechanism without affecting glutamatergic transmission.
The Impact of STRICTA and CONSORT on Reporting of Randomised Control Trials of Acupuncture: A Systematic Methodological Evaluation
Authors: Svenkerud Simen , MacPherson Hugh 
Published: September 2018

Background Clear and unambiguous reporting is essential for researchers and clinicians to be able to assess the quality of research. To enhance the quality of reporting, consensus-based reporting guidelines are commonly used. Objectives To update and extend previous research by evaluating the more recent impact of STRICTA (STandards for Reporting Interventions in Controlled Trials of Acupuncture) and CONSORT (CONsolidated Standards Of Reporting Trials) guidelines on the quality of reporting of acupuncture trials. Methods By random sampling, approximately 45 trials from each of five 2-year time periods between 1994 and 2015 were included in the study. Using scoring sheets based on the STRICTA and CONSORT checklist items (range 0 to 7 and 0 to 5, respectively), the distribution of items reported over time was investigated, with changes shown using scatterplots. The primary analysis used a before-and-after t-test to compare time periods. A meta-analysis investigated whether or not trials published in journals that endorsed STRICTA were associated with better reporting. Results The study included 207 trials. Improved reporting of items over time was observed, as represented by changes in the scatterplot slope and intercept. The mean STRICTA score increased from 4.27 in the 1994–1995 period to 5.53 in 2014–2015, an 18% improvement. The mean CONSORT score rose from 1.01 in the 1994–1995 period to 3.32 in 2014–2015, an increment of 46%. There was proportionately lower reporting for items related to practitioner background (STRICTA) and for randomisation implementation and allocation concealment (CONSORT). Trials published in journals that endorsed STRICTA had statistically significantly superior reporting of both STRICTA and CONSORT items overall. Conclusion This study has provided evidence of an improvement in reporting of STRICTA and CONSORT items over the time period from 1994 to 2015. Journals that endorse STRICTA have a better record in terms of reporting quality. Some evidence suggests that the publication of STRICTA has had a positive impact on reporting quality.
Bayesian approach to determining penetrance of pathogenic SDH variants
Authors: Benn Diana E , Zhu Ying , Andrews Katrina A , Wilding Mathilda , Duncan Emma L , Dwight Trisha , Tothill Richard W , Burgess John , Crook Ashley , Gill Anthony J , Hicks Rodney J , Kim Edward , Luxford Catherine , Marfan Helen , Richardson Anne Louise , Robinson Bruce , Schlosberg Arran , Susman Rachel , Tacon Lyndal , Trainer Alison , Tucker Katherine , Maher Eamonn R , Field Michael , Clifton-Bligh Roderick J 
Published: September 2018

BackgroundUntil recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C (SDHA–C) genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL).MethodsTwo cohorts were 575 unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA–C variants was calculated by comparing allelic frequencies in cases versus controls from ExAC (removing those variants contributed by The Cancer Genome Atlas).ResultsPathogenic SDHA–C variants were identified in 106 subjects (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC), 13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting for 21% of subjects with SDHA–C variants. Combining data from both cohorts, estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to 3.8%) for SDHA variants.ConclusionPathogenic variants in SDHB are more penetrant than those in SDHC and SDHA. Our findings have important implications for counselling and surveillance of subjects carrying these pathogenic variants.
TLR Stimulation during T-cell Activation Lowers PD-1 Expression on CD8+ T Cells
Authors: Zahm Christopher D. , Colluru Viswa T. , McIlwain Sean J. , Ong Irene M. , McNeel Douglas G. 
Published: September 2018

Abstract
Expression of T-cell checkpoint receptors can compromise antitumor immunity. Blockade of these receptors, notably PD-1 and LAG-3, which become expressed during T-cell activation with vaccination, can improve antitumor immunity. We evaluated whether T-cell checkpoint expression could be separated from T-cell activation in the context of innate immune stimulation with TLR agonists. We found that ligands for TLR1/2, TLR7, and TLR9 led to a decrease in expression of PD-1 on antigen-activated CD8+ T cells. These effects were mediated by IL12 released by professional antigen-presenting cells. In two separate tumor models, treatment with antitumor vaccines combined with TLR1/2 or TLR7 ligands induced antigen-specific CD8+ T cells with lower PD-1 expression and improved antitumor immunity. These findings highlight the role of innate immune activation during effector T-cell development and suggest that at least one mechanism by which specific TLR agonists can be strategically used as vaccine adjuvants is by modulating the expression of PD-1 during CD8+ T-cell activation. Cancer Immunol Res; 6(11); 1364–74. ©2018 AACR.
Inclusion Cysts after Fetal Spina Bifida Repair: A Third Hit?
Authors: Heye Pascal , Moehrlen Ueli , Mazzone Luca , Weil Robert , Altermatt Stefan , Wille David-Alexander , Scheer Ianina , Meuli Martin , Horst Maya 
Published: September 2018

<b><i>Introduction:</i></b> Fetal spina bifida repair (fSBR) has proven effective in the reversibility of hindbrain herniation, lower rate of shunt-dependent hydrocephalus, and independent ambulation. Besides distinct advantages, there are also concerns related to fSBR. One of these is the postnatal occurrence of inclusion cysts (IC). <b><i>Methods:</i></b> In a prospective study, 48 children who underwent fSBR were followed up. Postnatal assessment included clinical examination, cystometry, and spinal MRI. Indication for IC resection was the evidence of a spinal mass on MRI in the presence of deteriorating motor or bladder function, pain, or considerable growth of the IC. <b><i>Results:</i></b> Fourteen children (30%) developed IC, all within the first 2 years of life. Six children underwent IC resection; 4 children due to deteriorating function, 2 children due to doubling of the mass on MRI within 1 year. Following IC resection, 4/6 children (67%) demonstrated altered motor function and 6 children (100%) were diagnosed with neurogenic bladder dysfunction. <b><i>Conclusions:</i></b> Systematic follow-up of patients with a history of fSBR revealed a high incidence of IC. Whether these are of dysembryogenic or iatrogenic origin, remains unclear. Since both IC per se and IC resection may lead to loss of neurologic function, IC can be considered a “third hit”.
Changes in sexual activity of male patients with ankylosing spondylitis undergoing total hip arthroplasty
Authors: Fu Jun , Li Xiang , Liu Kan , Chen Jiying , Ni Ming , Yu Baozhan , Chai Wei , Hao Libo 
Published: September 2018

Introduction: Sexual activity is often an important component of life. To date, no studies have examined sexual activity before and after total hip arthroplasty (THA) in male patients with ankylosing spondylitis (AS). The purpose of the current study was to evaluate the effect of THA on sexual activity and to explore the most commonly reported and comfortable coital position for male AS patients with hip involvement. Methods: Data from 31 male AS patients who underwent THA for hip involvement were retrospectively reviewed. Information from the International Index of Erectile Function (IIEF), the Harris Hip Score (HHS) and other clinical parameters was collected and monitored over time. We compared the above-mentioned parameters before surgery and 2 years after surgery and analysed the correlation between changes on the IIEF and changes in clinical parameters. Results: The domain and total scores of the IIEF, except EF, were significantly higher after surgery than were those before surgery ( p < 0.05). There was a significant positive correlation between changes on the IIEF and improvement in flexion-extension range of motion (ROM), adduction-abduction ROM and HHS ( p < 0.05). Most patients (26/31, 83.9%) resumed sexual activity 5–12 weeks after surgery. The pre- and postoperative distributions of the most commonly reported and comfortable position were not significantly different (p > 0.05). Conclusions: Successful THA may improve sexual activity in male AS patients with hip involvement. Changes in hip ROM show the most significant correlation with improvement in sexual activity. Resumption of sexual activity occurs within 5–12 postoperative weeks.
Security and Radical Assessment in Open, Laparoscopic, Robotic Colorectal Cancer Surgery: A Comparative Study
Authors: Yang Shuai-Xi , Sun Zhen-Qiang , Zhou Quan-Bo , Xu Ji-Zhong , Chang Yuan , Xia Kun-Kun , Wang Gui-Xian , Li Zhen , Song Jun-Min , Zhang Zhi-Yong , Yuan Wei-Tang , Liu Jin-Bo 
Published: September 2018

Purpose: This retrospective study was designed to assess the safety and effectiveness of open, laparoscopic, robotic colorectal cancer surgery. Methods: Three hundred patients with colorectal cancer who underwent curative resection in the First Affiliated Hospital of Zhengzhou University between February 2014 and May 2016 were included. Patients were classified into open surgery group, laparoscopic surgery group, and robot-assisted group. Results: The blood loss in laparoscopic surgery group was less than that in open surgery group, and the blood loss in robot-assisted group less was than the open surgery group. The number of lymph node dissection in robot-assisted group was significantly larger than that in the open group ( P < .05). The distance between the lower edge of the tumor group and the distal margin in robotic group was longer than that of the laparoscopic surgery group and the open group ( P < .05). Three (2.8%) cases of urinary retention occurred in the open surgery group, 4 (3.92%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group, while 2 (1.87%) cases of sexual dysfunction occurred in the open surgery group, 2 (1.96%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group. The urinary retention and sexual dysfunction rate did not differ between the 3 groups ( P > .05), but the minimally invasive group showed a certain advantage over the open group. Conclusion: Compared to the traditional open surgery, minimally invasive surgery (especially in robot-assisted group) has advantages such as less intraoperative bleeding, rapid postoperative recovery, and radical cure; open group, laparoscopic surgery group, and robot-assisted group have a similar incidence of postoperative complications, but reduction in the incidence of anastomotic leakage and intestinal obstruction. Robot-assisted group has the potential advantage for pelvic autonomic nerve protection.
The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods
Authors: Kamel Hooman , Longstreth WT , Tirschwell David L , Kronmal Richard A , Broderick Joseph P , Palesch Yuko Y , Meinzer Caitlyn , Dillon Catherine , Ewing Irene , Spilker Judith A , Di Tullio Marco R , Hod Eldad A , Soliman Elsayed Z , Chaturvedi Seemant , Moy Claudia S , Janis Scott , Elkind Mitchell SV 
Published: September 2018

Rationale Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. Aims The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. Sample size estimate 1100 participants. Methods and design Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. Population studied Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m2 on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. Study outcomes The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. Discussion ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation.
Testing and monitoring direct oral anticoagulants
Authors: Connors Jean M. 
Published: September 2018

AbstractDirect oral anticoagulants (DOACs) have significantly improved the care of patients requiring anticoagulation. With similar or better efficacy and safety outcomes and easier use in the outpatient setting compared with the standard-of-care vitamin K antagonists and low molecular weight heparin, DOACs are now endorsed as first-line treatment of indications including prevention of stroke and systemic embolism in nonvalvular atrial fibrillation and treatment of venous thromboembolism. DOACs are easy-to-use oral agents that offer simple dosing and short half-lives, with no need to test levels because of the wide therapeutic window and limited drug-drug interactions. After almost a decade of DOAC use, the question of testing DOAC levels in certain clinical situations has become the focus of debate. Although guidance for using routine coagulation tests is available, these tests are inadequate for optimal care. DOAC-specific tests have been developed but have limited availability in Europe and less availability in the United States. None are licensed. DOAC testing may be useful in the setting of critical clinical situations such as life-threatening bleeding or need for emergent surgery, especially with the availability of DOAC reversal agents. Patients with characteristics that fall outside the normal range may benefit from the guidance that DOAC testing could offer. Obstacles to adopting DOAC testing have been raised, such as test reliability and staffing costs; however, these problems are rapidly being resolved. Further investigation of the role of DOAC testing is needed to explore its full potential and role in clinical practice.
Clinical application of high frequency jet ventilation in stereotactic liver ablations – a methodological study
Authors: Galmén Karolina , Freedman Jacob , Toporek Grzegorz , Goździk Waldemar , Harbut Piotr 
Published: September 2018

Background: Computer-assisted navigation during thermal ablation of liver tumours, may help to correct needle placement and improve ablation efficacy in percutaneous, laparoscopic and open interventions. The potential advantage of using high frequency jet-ventilation technique (HFJV) during the procedure is by minimising the amplitude of respiration-related upper-abdominal organs movements. The aim of this clinical methodological trial was to establish whether HFJV would give less ventilatory induced liver movements than conventional ventilation, during stereotactic navigated ablation of liver metastases under open surgery. Methods: Five consecutive patients scheduled for elective, open liver ablation under general propofol and remifentanil anaesthesia were included in the study protocol. During the stereotactic targeting of the tumours, HFJV was chosen for intraoperative lung ventilation. For tracking of liver movement, a rigid marker shield was placed on the liver surface and tracked with an optical position measurement system. A 4D position of the marker shield was measured for HFJV and conventional tidal volume lung ventilation (TV). At each time point the magnitude of liver displacement was calculated as an Euclidean distance between translational component of the marker shield's 3D position and previously estimated centroid of the translational motion. Results: The mean Euclidean liver displacement was 0.80 (0.10) mm for HFJV and 2,90 (1.03) mm for TV with maximum displacement going as far as 12 mm on standard ventilation (p=0.0001). Conclusion: HFJV is a valuable lung ventilation method for patients undergoing stereotactic surgical procedures in general anaesthesia when reduction of organ displacement is crucial.
Olecranon fractures in children and adolescents: Outcomes based on fracture fixation
Authors: Perkins C. A. , Busch M. T. , Christino M. A. , Axelrod J. , Devito D. P. , Fabregas J. A. , Flanagan J. C. , Murphy J. , Olszewski D. , Schmitz M. L. , Schrader T. , Willimon S. C. 
Published: September 2018

Purpose Open reduction and internal fixation with a tension band construct is the standard treatment for displaced transverse intra-articular olecranon fractures. The purpose of this study is to describe the outcomes of tension band fixation of olecranon fractures in children, specifically assessing the need for revision fixation and hardware removal. Methods Patients less than 18 years of age diagnosed with a displaced transverse intra-articular olecranon fracture and treated with tension band fixation between 2008 and 2017 were retrospectively enrolled. Operative treatment was with tension band wire (TBW) or tension band suture (TBS) constructs. Results A total of 46 patients, 36 male and ten female with a mean age of 12.3 years (6 to 17), were included. Surgical fixation was with TBW in 17 patients and TBS in 29 patients. Revision fixation due to failure and fracture displacement was required in 6% of the TBW group and 14% of the TBS group (p = 0.19). The patients who required revision fixation in the TBS group were older (14.7 years versus 11.6 years, p = 0.05) and heavier (70.5 kg versus 48.5 kg, p = 0.05) than those in the same group who did not require revision fixation. Conclusion Paediatric olecranon fractures treated with TBW or TBS fixation unite in the majority of patients with similar need for hardware removal due to prominence and/or pain between fixation techniques. In a select group of older patients weighing greater than 50 kg, TBS constructs demonstrate increased failure rates, requiring revision fixation, and should be avoided in this population group. Level of Evidence IV