bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology
Authors: Ambartsumyan Lusine , Khlevner Julie , Nurko Samuel , Rosen Rachel , Kaul Ajay , Pandolfino John E. , Ratcliffe Elyanne , Yacob Desale , Li B.U.K. , Punati Jaya , Sood Manu , Rao Satish S.C. , Levitt Marc A. , Cocjin Jose T. , Rodriguez Leonel , Flores Alejandro , Rosen John M. , Belkind‐Gerson Jaime , Saps Miguel , Garza Jose M. , Fortunato John E. , Schroedl Rose L. , Keefer Laurie A. , Friedlander Joel , Heuckeroth Robert O. , Rao Meenakshi , El‐Chammas Khalil , Vaz Karla , Chumpitazi Bruno P. , Sanghavi Rina , Matta Sravan K.R. , Danialifar Tanaz , Di Lorenzo Carlo , Darbari Anil 
Published: April 2020

ABSTRACTObjectives:Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology – AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies.Methods:The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought‐provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment‐based approach.Conclusions:The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.
Protocol to Measure Hair Cortisol in Low Mass Samples From Very Preterm Infants
Authors: Nist Marliese Dion , Sullenbarger Brent A. , Harrison Tondi M. , Pickler Rita H. 
Published: April 2020

Background
Hair cortisol is a measure of chronic or repeated hypothalamic–pituitary–adrenal axis activation in response to physical or psychological stressors. Hair cortisol has been successfully used as a measure of chronic stress in adults and children; however, its use as a valid measure in preterm infants has been limited by challenges in measuring cortisol in the low mass samples collectable from these infants.

Objectives
The purpose of this report is to present a novel protocol for the measurement of hair cortisol in very low mass hair samples.

Methods
Small changes were made to previously published protocols. After washing and pulverizing the hair samples, a double methanol cortisol extraction was performed. Samples were spiked with a known quantity of cortisol and analyzed in duplicate using an enzyme-linked immunosorbent assay.

Results
Hair cortisol was detectable in samples weighing between 0.4 and 10.9 mg. The mean cortisol level was 23.74 pg/mg hair (SD = 26.38).

Discussion
With small changes to previously published laboratory protocols, cortisol is quantifiable in low mass hair samples from preterm infants. This technical advance is an important step toward quantifying the stress experiences of hospitalized preterm infants.
Risk factors for loss to follow-up from antiretroviral therapy programmes in low-income and middle-income countries
Authors: Frijters Elise M. , Hermans Lucas E. , Wensing Annemarie M.J. , Devillé Walter L.J.M. , Tempelman Hugo A. , De Wit John B.F. 
Published: April 2020

Introduction:
Loss to follow-up (LTFU) rates from antiretroviral treatment (ART) programmes in low- and middle-income countries (LMIC) are high, leading to poor treatment outcomes and onward transmission of HIV. Knowledge of risk factors is required to address LTFU. In this systematic review, risk factors for LTFU are identified and meta-analyses performed.

Methods:
PubMed, Embase, Psycinfo and Cochrane were searched for studies that report on potential risk factors for LTFU in adults who initiated ART in LMICs. Meta-analysis was performed for risk factors evaluated by at least five studies. Pooled effect estimates and their 95% confidence intervals (95% CI) were calculated using random effect models with inverse variance weights. Risk of bias was assessed and sensitivity analyses performed.

Results:
Eighty studies were included describing a total of 1 605 320 patients of which 87.4% from sub-Saharan Africa. The following determinants were significantly associated with an increased risk of LTFU in meta-analysis: male sex, older age, being single, unemployment, lower educational status, advanced WHO stage, low weight, worse functional status, poor adherence, nondisclosure, not receiving cotrimoxazole prophylactic therapy when indicated, receiving care at secondary level and more recent year of initiation. No association was seen for CD4+ cell count, tuberculosis at baseline, regimen, and geographical setting.

Conclusion:
There are several sociodemographic, clinical, patient behaviour, treatment-related and system level risk factors for LTFU from ART programs. Knowledge of risk factors should be used to better target retention interventions and develop tools to identify high-risk patients.
HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life
Authors: Ajibola Gbolahan , Moyo Sikhulile , Mohammed Terrence , Moseki Seretlogelwa , Jack Disaro , Sakoi Maureen , Batlang Oganne , Maswabi Kenneth , Bennett Kara , Hughes Michael D. , Lockman Shahin , Makhema Joseph M. , Lichterfeld Mathias , Kuritzkes Daniel R. , Shapiro Roger L. 
Published: April 2020

Background:
Risk for nondiagnostic and false-positive HIV testing has not been quantified for neonates.

Methods:
From April 2015 to July 2018, we screened HIV-exposed infants in Botswana less than 96 h from birth by qualitative DNA PCR. Repeat blood draws for DNA and RNA PCR testing occurred for initial positive and indeterminate results to establish final diagnosis. We compared screening DNA PCR cycle threshold values with final HIV status of the child.

Results:
Of 10 622 HIV-exposed infants, 10 549 (99.3%) had no HIV DNA detected (negative), 42 (0.4%) had HIV DNA detected (positive), and 31 (0.3%) tested indeterminate at first HIV screen. Repeat testing identified 2 (5.0%) of 40 positive screens (2 declined additional testing) as false positives and confirmed 2 (6.5%) of 31 indeterminate screens as infected. Median cycle threshold value at screening was 28.1 (IQR 19.8--34.8) for children with final positive status, and 35.5 (IQR 32.8--41.4) for indeterminates who were ultimately negative. Six (15%) of 40 infants with final positive status had cycle threshold value greater than 33 at first screen, whereas 3 (9.7%) of 31 indeterminates with final negative status had cycle threshold value 33 or less at first screen. This threshold resulted in a negative predictive value of 82% and a positive predictive value of 92% for a single screen.

Conclusion:
Although a DNA PCR cycle threshold value of 33 was predictive of the final HIV status in newborns, overlap occurred for true positives, false positives, and initial indeterminates. Testing additional samples should be standard practice for positive and indeterminate HIV DNA PCR tests in the first week of life.
Expanding community engagement in HIV clinical trials: a pilot study using crowdsourcing
Authors: Day Suzanne , Mathews Allison , Blumberg Meredith , Vu Thi , Mason Hailey , Rennie Stuart , Kuruc JoAnne D. , Gay Cynthia L. , Margolis David M. , Tucker Joseph D. 
Published: April 2020

Objective:
To assess the potential for crowdsourcing to complement and extend community advisory board (CAB) feedback on HIV clinical trials. Crowdsourcing involves community members attempting to solve a problem and then sharing solutions.

Methods:
CAB and crowdsourced approaches were implemented in the context of a phase 1 HIV antibody trial to collect feedback on informed consent, participation experiences, and fairness. CAB engagement was conducted through group discussions with members of an HIV CAB. Crowdsourcing involved open events intended to engage the local community, including interactive video modules, animated vignettes, and a creative idea contest. Open coding and analysis of emergent themes were conducted to compare CAB and crowdsourced feedback.

Results:
The crowdsourcing activities engaged 61 people across three events; nine people engaged in CAB feedback. Compared with CAB participants, crowdsourcing participants had lower levels of education and income, and higher levels of disability and unemployment. Overlap in CAB and crowdsourced feedback included recommendations for enhancing communication and additional support for trial participants. Crowdsourcing provided more detailed feedback on the impact of positive experiences and socio-economic factors on trial participation. CAB feedback included greater emphasis on institutional regulations and tailoring trial procedures. Crowdsourced feedback emphasized alternative methods for learning about trials and concerns with potential risks of trial participation.

Conclusion:
Conducting crowdsourcing in addition to CAB engagement can yield a broader range of stakeholder feedback to inform the design and conduct of HIV clinical trials.

Video abstract:

http://links.lww.com/QAD/B707
Generation of HIV-1-infected patients’ gene-edited induced pluripotent stem cells using feeder-free culture conditions
Authors: Ye Lin , Wang Jiaming , Teque Fernando , Xie Fei , Tan Yuting , Kan Yuet Wei , Levy Jay A. 
Published: April 2020

Objectives:
The discovery of induced pluripotent stem cells (iPSC) has brought promise to regenerative medicine as it breaks the ethical barrier of using embryonic stem cells. Such cell culture-derived patient-specific autologous stem cells are needed for transplantation. Here we report deriving HIV-1-infected patients’ iPSC lines under transgene-free methods and under feeder-free and xeno-free culture conditions to meet the requirement for clinical application.

Methods and results:
We have reprogrammed patients’ peripheral blood mononuclear cells with EBNA1/OriP episomal vectors, or a defective and persistent Sendai virus vector (SeVdp) to ensure a nonintegrating iPSC generation. Both single picked and pooled iPSC lines demonstrated high pluripotency and were able to differentiate into various lineage cells in vivo. The established cell lines could be modified by genetic editing using the TALENs or CRISPR/Cas 9 technology to have a bi-allelic CCR5Δ32 mutations seamlessly. All generated iPSC lines and modified cell lines had no evidence of HIV integration and maintained normal karyotype after expansion.

Conclusions:
This study provides a reproducible simple procedure for generating therapeutic grade iPSCs from HIV-infected patients and for engineering these cells to possess a naturally occurring genotype for resistance to HIV-1 infection when differentiated into immune cells.
Characteristics and outcomes of extracorporeal life support in pediatric trauma patients
Authors: Behr Christopher A. , Strotmeyer Stephen J. , Swol Justyna , Gaines Barbara A. 
Published: April 2020

BACKGROUND
Extracorporeal life support utilizing extracorporeal membrane oxygenation (ECMO) techniques has been used in the pediatric population for numerous indications, but its use in trauma has been understudied. We sought to examine the indications, characteristics, and outcomes of children placed on ECMO for trauma and hypothesized that outcomes would be equivalent to those of patients placed on ECMO for other indications.

METHODS
We performed a retrospective review of all pediatric trauma patients in the Extracorporeal Life Support Organization registry from 1989 to 2018. Patient characteristics, indications for ECMO, pre- and post-ECMO ventilator settings and blood chemistry, complications, and survival rates were examined. Categories were stratified by mode: venovenous (VV), veno-arterial (VA), or conversion. Data were analyzed using SPSS software, with significance considered at p value less than 0.05.

RESULTS
We identified 573 patients with a median age of 4.82 years. The majority of patients (62.3%) were male and on VA support (54.5%). Drowning (38.7%) was the most common mechanism, followed by burns (21.1%) and thoracic trauma (17.8%). Complication rates were high (81.9%), with the most frequent types being cardiovascular, mechanical, and hemorrhagic. Incidences of complications (overall and by type) were similar to those reported in other Extracorporeal Life Support Organization cohorts. Overall survival was 55.3% and was significantly higher (p = 0.00) for patients on VV (74.3%) compared with those on VA (41.7%), even when controlling for mechanism.

CONCLUSION
Survival and complication rates of pediatric trauma patients on ECMO are comparable to those reported for other indications. Trauma should not be considered a contraindication for ECMO.

LEVEL OF EVIDENCE
Therapeutic, level V.
Passage through exceptional point: case study
Authors: Znojil Miloslav 
Published: April 2020

The description of unitary evolution using non-Hermitian but ‘hermitizable’ Hamiltonians
H
is feasible via an
ad hoc
metric
Θ
=
Θ
(
H
) and a (non-unique) amendment 〈
ψ
1
|
ψ
2
〉 → 〈
ψ
1
|
Θ
|
ψ
2
〉 of the inner product in Hilbert space. Via a proper fine-tuning of
Θ
(
H
) this opens the possibility of reaching the boundaries of stability (i.e. exceptional points) in many quantum systems sampled here by the fairly realistic Bose–Hubbard (BH) and discrete anharmonic oscillator (AO) models. In such a setting, it is conjectured that the EP singularity can play the role of a quantum phase-transition interface between different dynamical regimes. Three alternative ‘AO ↔ BH’ implementations of such an EP-mediated dynamical transmutation scenario are proposed and shown, at an arbitrary finite Hilbert-space dimension
N
, exact and non-numerical.
Cytoplasmic flows caused by actomyosin contraction drive interkinetic nuclear migration
Authors: Badugu Amarendra , Käch Andres 
Published: April 2020

AbstractInterkinetic nuclear migration (IKNM) is the process by which the nucleus migrates between apical and medial surfaces of pseudostratified epithelia. Previous studies have proposed force generating mechanisms, acting primarily on the nucleus. Having observed in drosophila wing discs that cytoplasmic components (lipid droplets and mitochondria) migrate alongside the nucleus, we used live imaging and particle tracking to demonstrate that the cytoplasm flows are responsible for the nucleus migration. We identify that nuclear migration in mitotic cells is preceded by a fast basal-to-apical flow of cytoplasm occurring over short time scales. We further show that, for the migration of basally located nuclei to an apical position, a slower flow of cytoplasm is responsible over a longer time scale. Our findings indicate that these flows are driven by acto-myosin contractile forces. These flows increase the hydrostatic pressure under the nucleus to exert a lifting force, much like a piston in a hydraulic cylinder.
A systematic review to assess seizure risk with chloroquine therapy in persons with epilepsy
Authors: Pati Sandipan 
Published: April 2020

ABSTRACTBackgroundThe goal of this systematic review is to assess the published literature for seizure risk with chloroquine therapy in persons with and without epilepsy. With the COVID-19 pandemic, there is a desperate need for therapy against the SARS CoV-2 virus. Chloroquine is one proposed medication that has received substantial public attention. However, drug labeling in the package insertion states that persons with epilepsy have the risk of chloroquine provoking seizures, and this has increased questions and anxiety in the epilepsy community.MethodsPubMed (1970 to March 27, 2020) and the Embase (1970 to March 27, 2020) were searched with the terms chloroquine and seizure or epilepsy. Selected studies were reviewed, and the adverse drug reaction was classified.ResultsOnly nine out of 27 studies were deemed eligible for systematic analysis. Out of the nine studies, only one was a prospective study (N=109), two were case series (N=6), and the remaining 6 were case reports. The dose of chloroquine ranged between 100-500 mg/day, except in one patient, the seizure was after taking 1000 mg. The strength of causality for the drug causing seizures in healthy and persons with epilepsy was mostly possible or unlikely, and none were certain. The only clinical trial that evaluated seizure risk with chloroquine failed to find any significant relation.ConclusionAlthough the drug insertion label states an increased risk of seizure, the systematic review highlights that such a statement is not supported by any class I studies but by anecdotal case reports. The only randomized clinical study revealed that seizures were not associated with an increased blood level of chloroquine or its metabolite. The present systematic review should provide reassurance to busy clinicians and persons with epilepsy that chloroquine, if prescribed to treat COVID-19, lacks any substantial evidence to suggest that the medication increases the risk of seizure.
The first month of the COVID-19 outbreak in 46 sub-Saharan African countries. A comparative analysis of growth rates
Authors: Prince Martin J. , Alem Atalay , Chibanda Dixon , Fairall Lara , Fekadu Abebaw , Hanlon Charlotte , Lund Crick , Leather Andy , Petersen Inge , Verhey Ruth , Wurie Haja 
Published: April 2020

ABSTRACTBackgroundThe COVID-19 outbreak in sub-Saharan African countries started after those in Asia, Europe and North America, on 28th February 2020. The susceptibility to infection of populations in that region has been debated. Outbreaks on the scale of those seen elsewhere would pose substantial challenges. There are reasons for concern that transmission may be high and difficult to control, rapidly exceeding capacity to meet the needs for hospitalization and critical care.MethodsWe obtained data on daily new confirmed cases for all 46 countries from the World Health Organization, and used these to model and visualize growth trajectories using an AutoRegressive Integrated Moving Average (ARIMA) model. We then estimated doubling times from growth rates estimated from Poisson regression models, and by back counting from the most recent observation. We also calculated the time from 1st to 50th case, and the time from 5th to 100th case. These indicators were compared with the same summary indicators of growth at the same stage of the outbreak in highly affected European countries.ResultsKenya was the only country with clear evidence of exponential growth. Nineteen countries had either reported no cases, were in the first few days of the outbreak, or had reported fewer than 10 cases over a period of two or more weeks. For the remaining 27 countries we identified four growth patterns: slow linear growth, more rapid linear growth, variable growth patterns over the course of the outbreak, and early signs of possible exponential growth. For those in the last three groups, doubling times ranged from 3 to 4 days, times from 1st to 50th case from 12 to 29 days, and from 5th to 100th case from eight to 15 days. These early indicators are comparable to those in European countries that have gone on to have substantial outbreaks, and time to 50th case was shorter suggesting lesser effectiveness of contact-tracing and quarantine in the early phase.ConclusionThe 46 sub-Saharan African countries, home to over one billion people, are at a tipping point with clear potential for the outbreak to follow a similar course as in HIC in the global north. Radical population-level physical distancing measures may be required, but their impact on poor, disadvantaged and vulnerable people and communities need mitigating. Health systems in the region need urgent technical and material support, with testing, personal protection, and hospital/ critical care.
Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences
Authors: Olusola Babatunde A. , Olaleye David O. , Odaibo Georgina N. 
Published: April 2020

AbstractIn 2018, an estimated 38 million people lived with HIV-1 infection resulting in 770,000 deaths. More than 50% of this infection and its associated deaths occurred in Sub-Saharan Africa. There is the need to develop an HIV-1 vaccine if the epidemic would be effectively controlled. Cytotoxic T Lymphocytes (CTL) epitopes within the Major Hydrophobic Region (MHR) have been shown to be highly immunogenic and immuno-dominant. These conserved epitopes have recently been the focus of vaccines studies. Despite the West African epicenter having one of the highest numbers of diverse circulating HIV-1 strains, very few longitudinal studies have checked the frequencies of CTL immune escape variants on epitopes within and without the MHR for HIV-1 strains circulating in the region.In this study we describe non-synonymous substitutions within and without the MHR of HIV-1 GAG genes isolated from 10 infected Nigerians at the early stages of HIV-1 infection. Furthermore, we analyzed these substitutions longitudinally in five infected individuals from the early stages of infection up until when antibodies become detectable. We identified 3 non synonymous substitutions within the MHR of HIV-1 GAG genes isolated from the early HIV infected individuals. Fourteen and nineteen mutations outside the MHR were observed before and after detection of antibodies respectively while 4 mutations were found within the MHR. These substitutions include previously mapped CTL epitope immune escape mutants. CTL immune pressure likely leave different footprints on HIV-1 GAG epitopes within and outside the MHR. This information is crucial for future vaccine designs for use in the West African region.