bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Global Research Agenda for Pediatric HIV
Authors: Penazzato Martina , Irvine Cadi , Vicari Marissa , Essajee Shaffiq M. , Sharma Aditi , Puthanakit Thanyawee , Abrams Elaine J. , Doherty Meg 
Published: July 2018

Background:
Despite progress, 2016 still saw 160,000 new infections and 120,000 AIDS-related deaths among children. Evidence gaps on how to best diagnose, treat, and deliver services to children living with HIV remain. A global research prioritization exercise was undertaken by WHO and CIPHER to focus research efforts in the context of diminishing resources.

Methods:
The Child Health and Nutrition Research Initiative methodology was adapted and used, as described by Irvine et al.
1
Outcomes were reviewed by an expert group and 5 priority themes identified for testing, antiretroviral treatment, and service delivery, accounting for existing policies, published literature and ongoing research.

Results:
A total of 749 questions were submitted by 269 individuals from 62 countries. For HIV testing, priority themes included strategies and interventions to improve access, uptake and linkage to care, including with novel diagnostic tools and entry points beyond antenatal care. For treatment, priorities included strategies to improve adherence, short- and long-term outcomes and management of coinfections, optimal drug formulations, and early ART. For service delivery, priorities included strategies or interventions to improve access, uptake and retention in care, including psychosocial and family support and approaches to HIV disclosure and reduction of stigma and discrimination.

Conclusions:
This is the largest Child Health and Nutrition Research Initiative exercise undertaken in HIV. The results provide guidance to focus future research in pediatric HIV for impact. Global commitment to support priority research, adequate investment, and strong leadership is urgently needed to improve the health and well-being of children living with and affected by HIV.
A Global Research Agenda for Adolescents Living With HIV
Authors: Armstrong Alice , Nagata Jason M. , Vicari Marissa , Irvine Cadi , Cluver Lucie , Sohn Annette H. , Ferguson Jane , Caswell Georgina , Njenga Lucy Wanjiku , Oliveras Carlo , Ross David , Puthanakit Thanyawee , Baggaley Rachel , Penazzato Martina 
Published: July 2018

Background:
Despite growing interest in undertaking research in adolescent HIV, the current pace of interventional research in particular remains very low compared with the needs of adolescents living with HIV (ALHIV). More robust evidence is needed to inform innovative and targeted interventions that bridge research gaps, inform policy, and improve outcomes for adolescents. A global research prioritization exercise was undertaken by WHO and CIPHER to focus efforts on priority research in the context of diminishing resources.

Methods:
The Child Health and Nutrition Research Initiative (CHNRI) methodology was adapted and used. Outcomes were reviewed by an expert group and 5 priority themes identified for testing, treatment, and service delivery, accounting for existing policies, published literature, and ongoing research.

Results:
A total of 986 research questions were submitted by 323 individuals from 67 countries. For HIV testing, priority themes included strategies and interventions to improve access, uptake, and linkage to care, and self-testing, particularly for key populations. For treatment, priorities included strategies to monitor and improve adherence, novel drug delivery systems, preventions and management of coinfections, optimal drug sequencing, and short- and long-term outcomes. For service delivery, priorities included service delivery models across the cascade, strategies to improve retention in care and sexual and reproductive health, support for pregnant ALHIV, and the provision of psychosocial support.

Conclusions:
This prioritized research agenda assists in focusing future research in ALHIV and will help to fill critical knowledge gaps. Key stakeholders, donors, program managers, and researchers should all support these priority questions and themes to collaboratively drive the adolescent HIV research agenda forward.
Using Observational Data to Inform HIV Policy Change for Children and Youth
Authors: Sohn Annette H. , Judd Ali , Mofenson Lynne , Vicari Marisa , Jerene Degu , Leroy Valeriane , Bekker Linda-Gail , Davies Mary-Ann 
Published: July 2018

Abstract:
Observational data characterizing the pediatric and adolescent HIV epidemics in real-world settings are critical to informing clinical guidelines, governmental HIV programs, and donor prioritization. Global expertise in curating and analyzing these data has been expanding, with increasingly robust collaborations and the identification of gaps in existing surveillance capacity. In this commentary, we describe existing sources of observational data for children and youth living with HIV, focusing on larger regional and global research cohorts, and targeted surveillance studies and programs. Observational data are valuable resources to cross-validate other research and to monitor the impact of changing HIV program policies. Observational studies were among the first to highlight the growing population of children surviving perinatal HIV and transitioning to adolescence and young adulthood, and have raised serious concerns about high rates of treatment failure, loss to follow-up, and death among older perinatally infected youth. The use of observational data to inform modeling of the current global epidemic, predict future patterns of the youth cascade, and facilitate antiretroviral forecasting are critical priorities and key end products of observational HIV research. Greater investments into data infrastructure are needed at the local level to improve data quality and at the global level to faciliate reliable interpretation of the evolving patterns of the pediatric and youth epidemics. Although this includes harmonized data forms, use of unique patient identifiers to allow for data linkages across routine data sets and electronic medical record systems, and competent data managers and analysts are essential to make optimal use of the data collected.
Nothing About Us Without RIGHTS—Meaningful Engagement of Children and Youth: From Research Prioritization to Clinical Trials, Implementation Science, and Policy
Authors: Oliveras Carlo , Cluver Lucie , Bernays Sarah , Armstrong Alice 
Published: July 2018

Abstract:
This article presents a new agenda for the meaningful engagement of youth in guiding research and policy. It has been codeveloped with youth, adolescents, and children who are living with and affected by HIV. We set out 6 basic requirements (we call them RIGHTS) that hold across clinical trials, observational studies, implementation science, service delivery, and policy development. These requirements are based on a literature review and in-depth consultations with children, adolescents, and youth, which have taken place over a decade in the HIV/AIDS epidemic. Youth engagement must be adequately Resourced with time, training, technical support, and funds. It must be Impactful, with youth informed of how their inputs have been directly used in research, policy, and programming. It must be Genuine, with youth understanding the intentions of the project and choosing to take part. It is essential that we ensure that participation is Harmless, and that it is responsive to the emotional and mental health needs of youth. Processes of participation should be Teen friendly, designed to be enjoyable and relevant to youth priorities. Finally, regarding Skills building, participation should allow for the competencies and skills developed to be recognized in youth education and career experience (without advertising the HIV aspect if this is inappropriate for young people). We propose that these 6 basic requirements be endorsed by all research organizations, and that they become a core component of research in the HIV response.
Experience With the Use of Rituximab for the Treatment of Rheumatoid Arthritis in a Tertiary Hospital in Spain
Authors: Cañamares Iciar , Merino Leticia , López Jorge , Llorente Irene , García-Vadillo Alberto , Ramirez Esther , López-Bote Juan Pedro , Benedí Juana , Muñoz-Calleja Cecilia , Álvaro-Gracia José M. , Castañeda Santos , González-Álvaro Isidoro 
Published: July 2018

Background/Objective
There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions.

Methods
Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration.

Results
A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7–13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration.

Conclusions
Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therapy.
Phenytoin Could Potentially Increase Hepatic Clearance of 99mTc-Sestamibi in Myocardial Perfusion Imaging
Authors: Kavanal Anwin Joseph , Singh Deepa , Sood Ashwani , Parmar Madan , Mittal Bhagwant Rai 
Published: July 2018

Abstract
Myocardial perfusion imaging (MPI) is one of the most commonly used nuclear medicine imaging modalities for coronary artery disease evaluation and risk stratification. The authors present incidental image findings in a patient who underwent MPI twice because of development of seizures just before the first SPECT-MPI acquisition. The projection images for first MPI done without medication (phenytoin) showed the retention of hepatic tracer activity. After a few days from restarting of phenytoin, the repeat MPI showed complete hepatic clearance of tracer. This case highlights the possible pharmacokinetic interaction between phenytoin intake and 99mTc-sestamibi, resulting in faster hepatic clearance of the radiotracer.
Utility of Timed Up and Go in Outpatient Cardiology Clinics
Authors: Albarrati Ali , Nazer Rakan 
Published: July 2018

Abstract

Purpose
The aim of the study was to examine if the Timed Up and Go (TUG) Test would be a feasible, reproducible, and valid measure in patients post-coronary artery bypass grafting (CABG).

Design
Cross-sectional study, controls and patients post-CABG, outpatient clinic.

Methods
Participants performed the TUG Test and the 6-Minute Walking Distance (6MWD) Test. Reliability was measured within observer on two occasions.

Findings
Patients and controls were similar in age. The patients had greater TUG mean (SD) of 14.4 seconds (4.9 seconds) and lower 6MWD of 358 m (76 m) compared with TUG of 8.2 seconds (2.7 seconds) and 6MWD of 487 m (56 m) in controls. In patients, intraclass correlation for the TUG was .98 (95% CI [.96, .98]) between the measurements. In patients, there was a high correlation between the TUG Test and the 6MWD Test, r = −.70, p < .001.

Conclusion
The TUG Test demonstrated to be a feasible, reproducible, and valid measure in patients post-CABG.

Clinical Relevance
The TUG Test could serve as a screening tool for physical performance in clinics.
Recurrent or De Novo Allograft Steatosis and Long-term Outcomes After Liver Transplantation
Authors: Narayanan Praveena , Mara Kristin , Izzy Manhal , Dierkhising Ross , Heimbach Julie , Allen Alina M. , Watt Kymberly D. 
Published: July 2018

Background
Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes.

Methods
A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes.

Results
Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001).

Conclusions
Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.
Deciphering the Contribution of γδ T Cells to Outcomes in Transplantation
Authors: McCallion Oliver , Hester Joanna , Issa Fadi 
Published: July 2018

Abstractγδ T cells are a subpopulation of lymphocytes expressing heterodimeric T-cell receptors composed of γ and δ chains. They are morphologically and functionally heterogeneous, innate yet also adaptive in behavior, and exhibit diverse activities spanning immunosurveillance, immunomodulation, and direct cytotoxicity. The specific responses of γδ T cells to allografts are yet to be fully elucidated with evidence of both detrimental and tolerogenic roles in different settings. Here we present an overview of γδ T-cell literature, consider ways in which their functional heterogeneity contributes to the outcomes after transplantation, and reflect on methods to harness their beneficial properties.
Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation
Authors: Magnusson Jesper , Westin Johan , Andersson Lars-Magnus , Lindh Magnus , Brittain-Long Robin , Nordén Rickard , Riise Gerdt C. 
Published: July 2018

Background
Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development.

Method
Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded.

Results
Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment.

Conclusions
This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.
Patient-Reported Outcome After Ostomy Surgery for Chronic Constipation
Authors: Iqbal Fareed , van der Ploeg Valerie , Adaba Franklin , Askari Alan , Murphy Jamie , Nicholls R. John , Vaizey Carolynne 
Published: July 2018

PURPOSE:
The purpose of this study was to describe experiences of and evaluate psychosocial and health-related quality of life of individuals undergoing ostomy surgery for severe, chronic constipation.

METHODS:
A search of the local ostomy archive and the electronic hospital episode statistics database was performed in a large tertiary referral center. Study outcomes were evaluated retrospectively using clinical notes and prospectively via administration of the City of Hope Ostomy Quality of Life questionnaire, Medical Outcomes Study Short Form-36, Hospital Anxiety and Depression tool, and a specially designed ostomy-specific questionnaire. Questionnaires were mailed and returned via post.

RESULTS:
Twenty-four patients, with a median age of 44 years (interquartile range [IQR] = 31-56), who underwent ileostomy (n = 20) and colostomy (n = 4) over a 13-year period participated in the study. The vast majority of respondents (91%; n = 22) were female. Ten (41%) underwent laparoscopic surgery, 13 (54%) underwent open procedures, and 1 was converted from laparoscopic to open surgery. The mean length of stay (5.5 days vs 5.4 days) and the rate of complication did not differ between the 2 approaches. Fourteen patients (13 females, median age = 47.5 years; IQR = 23-70 years) responded to the postal questionnaires (58.3%). Adverse effects on health-related quality of life in the physical and social well-being domains were reported, and a further 86% of respondents reported psychological morbidity related to their ostomy. However, more than 70% were satisfied (median follow-up = 17 months; IQR = 0.16-8 years) with their quality of life despite a 20% reoperation rate.

CONCLUSIONS:
An ostomy is a justified last-resort treatment option in selected individuals with severe, chronic constipation. Patients should be warned of the negative effects on health-related quality of life and the risk of complications. We advocate using an algorithm presented in this article.
Biological Approach for Managing Severe Gunshot Wounds
Authors: Muñoz Victoria , Martinez Carmen , Echevarria Begoña , Fernández Mª Isabel , Pino Ander , Anitua Eduardo 
Published: July 2018

BACKGROUND:
Autologous formulations rich in bioactive proteins promote cutaneous tissue regeneration. This case report describes our experiences with a platelet-based autologous formulation in the management of a hard-to-heal and severe gunshot wound.

CASE:
A healthy, 34-year-old man suffered an accidental gunshot wound of his right foot. After cleansing with saline and application of vacuum-assisted closure therapy for a period of 5 weeks, the resulting full-thickness wound had a surface area of 20 cm2 and did not show progress toward closure despite ongoing treatment. Plasma-rich growth factor (PRGF) therapy was used in order to promote tissue regeneration. The patient's own blood was drawn, centrifuged, and platelet-rich plasma was obtained. Intradermal injections of freshly activated platelet-rich plasma were administered into the wound edges, and a fibrin membrane was applied on the wound bed. Afterward, a novel topical ointment based on the patient's own growth factors was used as a daily therapy over the affected tissue.

RESULTS:
This full-thickness wound healed after 16 weeks of autologous growth factor therapy. The patient was able to walk without pain.

CONCLUSION:
Plasma-rich growth factor therapy successfully healed this full-thickness wound that did not respond to a period of 5 weeks with negative pressure wound therapy using a vacuum-assisted device. Healing occurred after 16 weeks of treatment, and he was able to resume walking without pain or functional deficits.
Gap junctions set the speed and nucleation rate of stage I retinal waves
Authors: Malte Kähne , Sten Rüdiger , Alexandre Kihara , Benjamin Lindner 
Published: July 2018

AbstractSpontaneous waves in the developing retina are essential in the formation of the retinotopic mapping in the visual system. From experiments in rabbits, it is known that the earliest type of retinal waves (stage I) is nucleated spontaneously, propagates at a speed of 451±91μm/sec and relies on gap junction coupling between ganglion cells. Because gap junctions (electrical synapses) have short integration times, it has been argued that they cannot set the low speed of stage I retinal waves. Here, we present a theoretical study of a two-dimensional neural network of the ganglion cell layer with gap junction coupling and intrinsic noise. We demonstrate that this model can explain observed nucleation rates as well as the comparatively slow propagation speed of the waves. From the interaction between two coupled neurons, we estimate the wave speed in the model network. Furthermore, using simulations of small networks of neurons (N≤260), we estimate the nucleation rate in form of an Arrhenius escape rate. These results allow for informed simulations of a realistically sized network, yielding values of the gap junction coupling and the intrinsic noise level that are in a physiologically plausible range.Author summaryRetinal waves are a prominent example of spontaneous activity that is observed in neuronal systems of many different species during development. Spatio-temporally correlated bursts travel across the retina at a few hundredμm/sec to facilitate the maturation of the underlying neuronal circuits. Even at the earliest stage, in which the network merely consists of ganglion cells coupled by electric synapses (gap junctions), it is unclear which mechanisms are responsible for wave nucleation and transmission speed. We propose a model of gap-junction coupled noisy neurons, in which waves emerge from rare stochastic fluctuations in single cells and the wave’s transmission speed is set by the latency of the burst onset in response to gap-junction currents between neighboring cells.