bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEO6860, modality-selective TRPV1 antagonist: a randomized, controlled, proof-of-concept trial in patients with osteoarthritis knee pain
Authors: Arsenault Pierre , Chiche Dan , Brown William , Miller Jeffrey , Treister Roi , Leff Richard , Walker Philippe , Katz Nathaniel 
Published: October 2018

Abstract

Introduction:
NEO6860 is a TRPV1 antagonist when activated by capsaicin but not by heat or pH, developed to relieve pain without the adverse events reported with non–modality-selective TRPV1 antagonists.

Objective:
The primary Objective of this study was to evaluate the analgesic efficacy and safety of NEO6860 after 1 day oral dosing in patients with Kellgren-Lawrence stage I, II or III osteoarthritis of the knee.

Method:
This randomized, double-blinded, 3-period crossover, phase II study compared 1 day (2 doses) of NEO6860 (500 mg twice a day), placebo, and naproxen in 54 patients with osteoarthritis knee pain. Primary endpoint was reduction in pain intensity (PI) on Numerical Rating Scale after exercise, using the staircase test, 8 hours after dose.

Results:
Level of PI, compared with baseline, was numerically lower during NEO6860 and naproxen periods vs placebo at 3 and 24 hours, but not at 8 hours after first dose. A statistically significant effect for naproxen and a trend for NEO6860 were observed at 3 and 24 hours. Least square means' (95% confidence interval) change in PI at 24 hours was −0.67 (−1.09 to −0.26), −0.97 (−1.39 to −0.55), −0.29 (−0.71 to 0.13) for NEO6860, naproxen, and placebo, respectively. NEO6860 exposure was ∼1.6 times higher compared with previous phase I. In this study, NEO6860 safety profile was less favorable than naproxen or placebo. Possibly NEO6860-related adverse events included: feel hot, headache, nausea, dizziness, fatigue, hypoaesthesia, and increased blood pressure.

Conclusion:
In this exploratory study, NEO6860 did not statistically significantly outperform placebo but showed an analgesic trend, without impacting body temperature and heat pain perception. Further studies are warranted to explore the potential of NEO6860 in other pain indications. We intent to optimize the dose and evaluate analgesic synergism with other mechanism.
Low-Level Laser Treatment Is Ineffective for Capsular Contracture: Results of the LaTCon Randomized Controlled Trial
Authors: Azimi Farhad , Flitcroft Kathy , Mathieu Erin , Karantonis Rebecca , Snook Kylie , Spillane Andrew J. 
Published: October 2018

Background:
Breast reconstruction with implants can be complicated by symptomatic capsular contracture, especially after radiotherapy. A phase I, nonrandomized clinical trial demonstrated improvement in capsular contracture and avoidance of revision surgery with low-level laser therapy. This phase II, double-blind, randomized controlled trial assessed the efficacy of low-level laser for treating capsular contracture in women with breast reconstruction following mastectomy for breast cancer.

Methods:
Participants had completed their definitive implant-based reconstruction a minimum of 6 months previously and were randomized to weekly treatments over 6 weeks with either an active or inactive low-level laser handpiece (Riancorp LTU-904). Pain, tightness, arm movement, and appearance were assessed by patient questionnaires. Breast symmetry, shape, naturalness, softness, and grade of contracture were assessed by clinician reports. Participants were assessed at 1 and 6 months after completion of the treatments.

Results:
A total of 42 patients (intervention arm, n = 20; placebo, n = 22) were assessed in the trial. Thirty-two had postmastectomy radiotherapy. There was no significant difference in the change in any patient-reported outcomes or clinician-reported outcomes of breast symmetry, shape, or naturalness for the two groups. There was a significantly greater improvement in clinician-reported breast softness (p < 0.05) and degree of contracture (p < 0.05) in the placebo group at both 1- and 6-month follow-up.

Conclusion:
Low-level laser is not an effective therapy for breast implant capsular contracture in reconstruction patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, I.
Arthroscopic Ganglionectomy in the Pediatric Population
Authors: Ben-Amotz Oded , Pezeshk Ronnie A. , Sammer Douglas M. , Cheng Jonathan 
Published: October 2018

Background:
Arthroscopic dorsal wrist ganglionectomy is an established alternative to open excision in the adult population. The purpose of this study was to retrospectively compare outcomes of arthroscopic and open dorsal wrist ganglionectomy in the pediatric population.

Methods:
All patients who underwent arthroscopic or open dorsal wrist ganglionectomy at a single pediatric institution between 2011 and 2014 were retrospectively evaluated by chart review and telephone interview. The primary outcome variable was whether or not the cyst had recurred. Other outcome measures included the incidence of complications, and patient-rated outcome measures such as satisfaction, pain, function, and aesthetics.

Results:
There were eight cases of arthroscopic and 19 cases of open ganglionectomy, with a mean age of 14 years. At an average follow-up of 2 years, the recurrence rate was one of eight for the arthroscopic group and two of 19 for the open group. No patients in the arthroscopic group reported functional limitations, compared with three patients in the open group. On a 10-point scar appearance scale, with 1 being not satisfied at all and 10 being highly satisfied, the median score in the arthroscopic group was 9.5, compared with 8 in the open group. No patients in the arthroscopic group had residual pain at the surgical site, compared with nine patients in the open group, a finding that was statistically significant. All patients in the arthroscopic group reported that they would undergo surgery again, whereas two patients in the open group would not undergo surgery again.

Conclusion:
Arthroscopic dorsal wrist ganglionectomy compares favorably with open ganglionectomy in the pediatric population.
Vascularized Composite Allotransplantation: Alternatives and Catch-22s
Authors: Diaz-Siso J. Rodrigo , Borab Zachary M. , Plana Natalie M. , Parent Brendan , Stranix John T. , Rodriguez Eduardo D. 
Published: October 2018

Summary:
Technical success has been achieved in several forms of vascularized composite allotransplantation, including hand, face, penis, and lower extremity. However, the risks of lifelong immunosuppression have limited these procedures to a select group of patients for whom nontransplant alternatives have resulted in unsatisfactory outcomes. Recent reports of facial allograft failure, and subsequent reconstruction using autologous tissues, have reinforced the idea that a surgical contingency plan must be in place in case this devastating complication occurs. Interestingly, backup plans in the setting of vascularized composite allotransplantation consist of the nontransplant alternatives that were deemed suboptimal in the first place. Moreover, these options may have been exhausted before transplantation, and may therefore be limited in the case of allograft loss or reamputation. In this article, the authors describe the surgical and nonsurgical alternatives to hand, face, penis, and lower extremity transplantation. In addition, the authors explore the ethical implications of approaching vascularized composite allotransplantation as a “last resort” or as a “high-risk, improved-outcome” procedure, focusing on whether nontransplant options eventually preclude vascularized composite allotransplantation, or whether vascularized composite allotransplantation limits future nontransplant reconstruction.
Alar Cinching with Subcutaneous Flaps: A Procedure to Achieve Narrowing of the Nasal Base while Controlling the Alar Axis and Sidewall Curvature
Authors: Hirohi Toshitsugu , Ng Donald , Nagai Koji , Yoshimura Kotaro 
Published: October 2018

Background:Insufficient narrowing of alar width, alar distortion, and noticeable scarring are commonly encountered after alar base reduction. The authors aimed to demonstrate an alar cinching with subcutaneous flaps procedure to reduce the alar width while controlling the alar axis and sidewall curvature.Methods:A retrospective chart review of 560 patients who underwent alar base reduction between 2000 and 2015 was performed. The clinical outcomes of alar cinching with subcutaneous flaps were compared to those of vestibular floor excision with cinching suture. Mean change in alar width was compared to assess narrowing efficacy between the two groups. In addition, mean changes in interalar distance for the upper, middle, and lower parts of the alae were compared to evaluate the alteration of alar axes.Results:Seventy-three patients who underwent alar base narrowing alone (alar cinching with subcutaneous flaps,n= 42; vestibular floor excision with cinching suture,n= 31) were identified. Alar cinching with subcutaneous flaps was significantly more effective than vestibular floor excision with cinching suture in reducing alar width. In patients with vertical alar axes, alar cinching with subcutaneous flaps achieved more uniform narrowing of the entire alae, resulting in prevention of alar distortion. The incidence of complications after alar cinching with subcutaneous flaps was 5.7 percent.Conclusions:Alar cinching with subcutaneous flaps achieved sufficient narrowing of the nasal base in the long-term follow-up in patients with any type of alar axis and enabled the reduction of sidewall curvature while eliminating the need for wedge resection.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.
A 26-Year Experience with Microsurgical Reconstruction of Hemifacial Atrophy and Linear Scleroderma
Authors: Chen Jenny T. , Schmid Daniel B. , Israel Jacqueline S. , Siebert John W. 
Published: October 2018

Background:
Parry Romberg disease (hemifacial atrophy) and linear scleroderma (coup de sabre) are progressive, usually unilateral facial atrophies of unknown cause. The gold standard treatment for these patients has been microsurgical reconstruction following the “burning out” of the facial atrophy and stable contour for 2 years.

Methods:
The authors report their experience treating patients with hemifacial atrophy and linear scleroderma with free tissue transfers between 1989 and 2016. A modified parascapular flap based on the circumflex scapular artery was most commonly used.

Results:
A total of 177 patients were included. The most common complication was hematoma, occurring in 12 patients (7 percent). Follow-up ranged from 1 to 26 years. All patients subjectively experienced improved facial symmetry and aesthetics. No disease process has recurred to date, even in cases of severe, progressive disease.

Conclusions:
In the authors’ experience, patients treated early in their disease course have immediate and sustained correction of their deformity, with slowing or in most cases cessation of the disease process following free tissue transfer. The authors now advocate for immediate reconstruction for active disease, especially in young children.

CLINICAL QUESTIONS/LEVEL OF EVIDENCE:
Therapeutic, IV.
Inflammation Relates to Poorer Complex Motor Performance Among Adults Living With HIV on Suppressive Antiretroviral Therapy
Authors: Montoya Jessica L. , Campbell Laura M. , Paolillo Emily W. , Ellis Ronald J. , Letendre Scott L. , Jeste Dilip V. , Moore David J. 
Published: October 2018

Background:
Inflammatory processes have been suggested to underlie early neurologic abnormalities among persons living with HIV (HIV-positive), such as deficits in complex motor function, that are purported to remit with effective antiretroviral therapy (ART). We hypothesized that HIV will have negative direct and indirect effects through inflammation on complex motor performance.

Methods:
The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, aged 36–65 years, with balanced recruiting in each age decade (36–45, 46–55, and 56–65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-α) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test.

Results:
The HIV-positive group had worse complex motor performance (P = 0.001; Hedges g = −0.49) and a higher average inflammation burden composite score (P < 0.001; Hedges g = 0.78) than the HIV-negative group. Path analyses indicated that the indirect effect of HIV disease on complex motor performance through inflammation burden was statistically significant, accounting for 15.1% of the effect of HIV on complex motor performance.

Conclusions:
Although neurologic findings (eg, deficits in motor speed/dexterity) commonly associated with HIV infection typically remit with ART, our analysis indicates that inflammation plays an important role in worse complex motor skills among HIV-positive adults. Future studies of strategies for managing chronic inflammation in HIV should consider using an inflammation burden composite and examining its effect on complex motor performance.
Vaginal Jade Eggs: Ancient Chinese Practice or Modern Marketing Myth?
Authors: Gunter Jennifer , Parcak Sarah 
Published: October 2018

Objective
To identify evidence that vaginal jade eggs were recommended or used in sexual health practices or for pelvic muscle exercises in ancient Chinese culture.

Materials and Methods
A search of the online databases of 4 major Chinese art and archeology collections in the United States.

Results
More than 5000 jade objects were viewable in online databases. No vaginal jade eggs were identified.

Conclusions
No evidence was found to support the claim that vaginal jade eggs were used for any indication in ancient Chinese culture.
Genetic distance between complex repeats
Authors: Ferretti Luca , Ruiz-Herrera Aurora , Ledda Alice 
Published: October 2018

AbstractComplex nucleotide or aminoacid repeats with long units play an important role in proteins. The evolutionary analysis of these variants is challenging due to genetic diversity within repeat units as well as variability in the arrangement of different units along the repeat sequence. Here we present a new approach for the computation of genetic distances between complex repeats. This method takes into account evolutionary processes including point mutations, insertions and deletions of repeat units, as well as duplication of single units. We provide an algorithm for the computation of these distances along with the corresponding global pairwise alignment of repeats. As an example, we apply our approach to the evolution of repeat units in the highly polymorphic zinc-finger repeat domain of the PRDM9 protein across wild populations of house mice. This approach opens the way for new insights into the evolutionary history of polymorphic repeats.
One and Two Year Visual Outcomes from the Moorfields AMD Database - an Open Science Resource for the Study of Neovascular Age-related Macular Degeneration
Authors: Fasler Katrin , Moraes Gabriella , Wagner Siegfried K. , Kortuem Karsten U. , Chopra Reena , Faes Livia , Preston Gabriella , Pontikos Nikolas , Fu Dun Jack , Patel Praveen J. , Tufail Adnan , Lee Aaron Y. , Balaskas Konstantinos , Keane Pearse A. 
Published: October 2018

ABSTRACTObjectivesTo analyse treatment outcomes and share clinical data from a large, single-center, well-curated database (8174 eyes / 6664 patients with 120,756 single entries) of patients with neovascular age related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (VEGF). By making our depersonalised raw data openly available, we aim to stimulate further research in AMD, as well as setting a precedent for future work in this area.SettingRetrospective, comparative, non-randomised electronic medical record (EMR) database cohort study of the UK Moorfields AMD database with data extracted between 2008 and 2018.Participants3357 eyes/patients (61% female). Extraction criteria were ≥ 1 ranibizumab or aflibercept injection, entry of “AMD” in the diagnosis field of the EMR, and a minimum of one year of follow-up. Exclusion criteria were unknown date of first injection and treatment outside of routine clinical care at Moorfields before the first recorded injection in the database.Main outcome measuresPrimary outcome measure was change in VA at one and two years from baseline as measured in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Secondary outcomes were the number of injections and predictive factors for VA gain.ResultsMean VA gain at one-year and two years were +5.5±0.5 and +4.9±0.68 letters respectively. Fifty-four percent of eyes gained ≥5 letters at two years, 63% had stable VA (±≤14 letters), forty-four percent of eyes maintained good VA (≥70 letters). Patients received a mean of 7.7±0.06 injections during year one and 13.0±0.2 injections over two years.Younger age, lower baseline VA, and more injections were associated with higher VA gain at two years.ConclusionThis study benchmarks high quality EMR study results of real life AMD treatment and promotes open science in clinical AMD research by making the underlying data publicly available.Strengths and limitations of this study-Large sample size, retrospective, single centre, electronic medical record database study-High quality real life data-Open science approach with sharing of depersonalised raw data
Long Range Order and Short Range Disorder in Saccharomyces cerevisiae Biofilm
Authors: Piras Vincent , Chiow Adam , Selvarajoo Kumar 
Published: October 2018

Abstract:Biofilm, a colony forming cooperative response of microorganisms under environmental stress, is a major concern for food safety, water safety and drug resistance. Most current works focus on controlling biofilm growth by targeting single genes. Here, we investigated transcriptome-wide expressions of the biofilm yeast Saccharomyces cerevisiae in wildtype, and 6 previously identified biofilm regulating overexpression strains (DIG1, SAN1, TOS8, ROF1, SFL1, HEK2). When tested across various statistical distributions, all transcriptome-wide data fitted well with lognormal distribution above TPM value of 5. Using this threshold as a low expression filter, Pearson auto-and cross-correlation reveal a strong transcriptome-wide invariance among all genotypes, which is also reflected by the random selection of 50 gene expressions. Focusing on the 50 highly expressed genes, however, they differ significantly between the genotypes. Principal components analysis (PCA) shows global similarity between DIG1, SAN1, ROF1, SFL1 and HEK2. Thus, although single overexpression strains may show significant favourable local and acute expression changes (short range disorder), the almost unperturbed global and collective structure between the genotypes indicate gradual adaptive response converging to original stable biofilm states (long range order). Hierarchical clustering and Gene Ontology show 11 groups of local (e.g. mitochondria processes, amine & nucleotide metabolic processes) and 6 groups of global (e.g. transcription, translation & cell cycle) processes for all genotypes. These data indicate that there is a strong global regulatory structure that keeps the overall biofilm stable in all investigated strains.
CropSurveyor: a scalable open-source experiment management system for distributed plant phenotyping and IoT-based crop management
Authors: Reynolds Daniel , Ball Joshua , Bauer Alan , Griffiths Simon , Zhou Ji 
Published: October 2018

AbstractBackground:High-quality plant phenotyping and climate data lay the foundation of phenotypic analysis as well as genotype-by-environment interactions, which is important biological evidence not only to understand the dynamics between crop performance, genotypes, and environmental factors, but also for agronomists and farmers to monitor crops in fluctuating agricultural conditions. With the rise of Internet of Things technologies in recent years, many IoT-based remote sensing devices have been applied to phenotyping and crop monitoring that generate big plant-environment datasets every day; however, it is still technically challenging to calibrate, annotate, and aggregate big data effectively, especially when they were generated in multiple locations, and often at different scales.Findings:CropSurveyor is a PHP and SQL based server platform, which provides automated data collation, storage, device and experiment management through IoT-based sensors and distributed plant phenotyping workstations. It provides a two-component solution for monitoring biological experiments and networked devices, with interfaces specifically designed for distributed IoT devices and centralised data servers. Data transfer is performed automatically though an HTTP accessible RESTful API installed on both device-side and server-side of the CropSurveyor system, which synchronise daily representative crop growth images for quick and visual-based crop assessment, as well as detailed microclimate readings for GxE studies. CropSurveyor also supports the comparison of historical and ongoing crop performance whilst different experiments are being conducted.Conclusions:As an open-source experiment and data management system, CropSurveyor can be used to maintain and collate important crop performance and microclimate datasets captured by IoT sensors and distributed phenotyping installations. It provides near real-time environmental and crop growth monitoring in addition to historical and current data comparison through a single cloud-ready server system. Accessible both locally in the field through smart devices and remotely in an office using a PC, CropSurveyor has been used in wheat field experiments for prebreeding since 2016 and has the potential to enable scalable crop management and IoT-style agricultural practices in the near future.
Perfect Counterfactuals for Epidemic Simulations
Authors: Kaminsky Joshua , Keegan Lindsay T. , E. Metcalf C. Jessica , Lessler Justin 
Published: October 2018

AbstractSimulation studies are often used to predict the expected impact of control measures in infectious disease outbreaks. Typically, two independent sets of simulations are conducted, one with the intervetnion, and one without, and epidemic sizes (or some related metric) are compared to estimate the effect of the intervention. Since it is possible that controlled epidemics are larger than uncontrolled ones if there is substantial stochastic variation between epidemics, uncertainty intervals from this approach can include a negative effect even for an effective intervention. To more precisely estimate the number of cases an intervention will prevent within a single epidemic, here we develop a ‘single world’ approach to matching simulations of controlled epidemics to their exact uncontrolled counterfac-tual. Our method borrows concepts from percolation approaches prune out possible epidemic histories and create potential epidemic graph that can be ‘realized’ to create perfectly matched controlled and uncontrolled epidemics. We present an implementation of this method for a common class of compartmental models, and its application in a simple SIR model. Results illustrate how, at the cost of some computation time, this method substantially narrows confidence intervals and avoids non-sensical inferences.