bluuebunny/crossref_metadata_2025_split huggingface dataset:
EpiSmart Crosslinking for Keratoconus: A Phase 2 Study
Authors: Epstein Randy J. , Belin Michael W. , Gravemann Deborah , Littner Roxanne , Rubinfeld Roy S. 
Published: September 2022

Purpose:
The aim of this study was to assess changes in visual acuity after epithelium-on (“epi-on”) corneal crosslinking after a diagnosis of keratoconus.

Methods:
Subjects with corneal ectatic diseases were enrolled in a prospective, randomized, controlled, open-label, multicenter trial. Subjects were randomized to 1 of 3 treatment groups and treated with an epi-on crosslinking system including riboflavin/sodium iodide and pulsed UVA exposure (EpiSmart, CXL Ophthalmics, Encinitas, CA). The UVA treatment groups were 2.4 J/cm2 over 20 minutes, 3.6 J/cm2 over 20 minutes, and 3.6 J/cm2 over 30 minutes. The primary end point was logarithm of the minimum angle of resolution corrected distance visual acuity (CDVA). Secondary end points were logarithm of the minimum angle of resolution uncorrected distance visual acuity (UCVA), maximum corneal curvature (Kmax), and minimum corneal thickness. Data were assessed 6 and 12 months post-operatively, using t-tests for differences from baseline.

Results:
Two thousand two hundred twenty-eight subjects were treated with epi-on crosslinking. One thousand nine hundred twenty-two subjects had a diagnosis of keratoconus; other treated eyes had postsurgical and other ectasias. At 6 and 12 months, the subjects with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax; minimum corneal thickness was unchanged. One hundred ninety-five subjects (8.7%) reported at least 1 adverse event (AE). A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in >1% of subjects. There were no serious AEs related to the treatment.

Conclusions:
EpiSmart epi-on crosslinking resulted in mean improvements in CDVA, UCVA, and Kmax at both 6 and 12 months and an excellent safety and efficacy profile in subjects with keratoconus, with few significant side effects. Differences between UVA treatment groups were not significant.
A programmatic taxonomy to define, differentiate, and classify nurse practitioner postgraduate training
Authors: Rettie Candice S. , Huynh DoQuyen 
Published: September 2022

ABSTRACT
Postgraduate residencies and fellowships have become a growing foundational element in the early career path for new nurse practitioners (NPs) and for NPs changing areas of specialization. The proposed programmatic taxonomy provides a straightforward method to recognize and classify NP postgraduate training programs with differing missions, structures, and outcome objectives. Models of postgraduate training for NPs are identified, defined, and differentiated. Each model can serve as an essential and specific purpose for the sponsoring organization. The programmatic models for NP postgraduate training programs are residency, fellowship, and “additional programs.” Differences between residency and fellowship are described. The taxonomy then compares and contrasts the three models on five overarching programmatic characteristics, namely, mission, goals, environment, evaluation, and duration. The potential impact of adopting the NP postgraduate training taxonomy on the NP profession, the public, funding, accreditation, and the early career development of NPs is explored. Recommendations for next steps are suggested.
Qualitative plasma viral load determination as a tool for screening of viral reservoir size in PWH
Authors: Laeremans Thessa , D’haese Sigrid , Aernout Jonathan , Barbé Kurt , Pannus Pieter , Rutsaert Sofie , Vancutsem Ellen , Vanham Guido , Necsoi Coca , Spiegelaere Ward De , Couttenye Marie , Herssens Natacha , Scheerder Marie-Angélique De , Wit Stéphane De , Vandekerckhove Linos , Florence Eric , Aerts Joeri L. , Allard Sabine D. 
Published: September 2022

Objective(s):
Suppression of viral replication in patients on antiretroviral therapy (ART) is determined by plasma viral load (pVL) measurement. Whenever pVL reaches values below the limit of quantification, the qualitative parameter ’target detected’ or ’target not detected’ is available but often not reported to the clinician. We investigated whether qualitative pVL measurements can be used to estimate the viral reservoir size.

Design:
The study recruited 114 people with HIV (PWH) who are stable on ART between 2016 and 2018. The percentage of pVL measurements qualitatively reported as ’target detected’ (PTD) within a 2-year period was calculated.

Methods:
t-DNA and US-RNA were used to estimate viral reservoir size and were quantified on peripheral blood mononuclear cells (PBMCs) using droplet digital PCR.

Results:
A median of 6.5 pVL measurements over a 2-year period was evaluated for each participant to calculate PTD. A positive correlation was found between t-DNA and PTD (r = 0.24; P = 0.011) but not between US-RNA and PTD (r = 0.1; P = 0.3). A significantly lower PTD was observed in PWH with a small viral reservoir, as estimated by t-DNA less than 66 copies/106 PBMCs and US-RNA less than 10 copies/106 PBMCs, compared with PWH with a larger viral reservoir (P = 0.001). We also show that t-DNA is detectable whenever PTD is higher than 56% and that ART regimen does not affect PTD.

Conclusion:
Our study shows that PTD provides an efficient parameter to preselect participants with a small viral reservoir based on already available pVL data for future HIV cure trials.
Cancer in patients with and without HIV infection in the national cancer registry of Rwanda
Authors: Hagenimana Marc , Kodan Asha E. , George Nivya , Businge Lydia , Francois Uwikindi , Nsanzimana Sabin , Riedel David J. 
Published: September 2022

Objective:
As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time.

Design:
Retrospective cohort study.

Methods:
Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV–). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis.

Results:
Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV– individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV (P < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs (P < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time.

Conclusions:
The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.
Amplitude of Somatosensory Evoked Potentials (SEPs) Recorded in Short-Latency SEP Condition Is 80% of That in Giant SEP Condition
Authors: Demura Ai , Demura Yutaka , Sato Kazuaki , Kinoshita Masako 
Published: September 2022

Purpose:
Giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex (C-reflex) are useful to detect cortical motor hyperexcitability in patients with myoclonic epilepsy. The recording conditions of giant SEPs are different from those of short-latency SEPs (SSEPs). We investigated the waveform characteristics obtained for each condition.

Methods:
Forty-eight upper limbs of 24 adult normal subjects (12 men, age 35.5 ± 9.7 years [mean ± SD]) were investigated. Somatosensory evoked potentials of each subject were recorded in both conditions on the same day. The main differences in recording conditions were reference electrodes (SSEP: Fz vs. giant SEP: the earlobe electrode ipsilateral to the stimulated limb), stimulus rate (5 vs. 1 Hz), and bandpass filter (20 Hz–3 kHz vs. 1 Hz–1 kHz). Somatosensory evoked potentials were elicited by unilateral percutaneous electrical stimulation of the median nerve at the wrist with intensity of 110% of the movement threshold and recoded at C3'/C4'.

Results:
The amplitudes of N20 onset–N20 and N20–P25 were significantly larger in giant SEP condition than in SSEP condition (p < 0.001). The mean + 3SD of N20–P25 amplitude was 10.0 μV in giant SEP condition and 7.8 μV in SSEP condition. The N20–P25 amplitude was significantly correlated between giant SEP condition and SSEP condition (R = 0.64, p < 0.001). C-reflex was not elicited.

Conclusions:
The amplitude of SEPs in SSEP condition is equivalent to 80% of that in giant SEP condition. The information is useful for detecting cortical hyperexcitability in various neurological disorders including myoclonic epilepsy.
Effectiveness of Digital Delivery of Diabetes-Related Lifestyle Interventions in Decreasing A1c: A Systematic Review
Authors: Rapoport Hannah 
Published: September 2022

AbstractBackgroundDigital delivery of lifestyle interventions offers a potentially effective, affordable, and convenient option for patients to prevent and monitor type 2 diabetes (T2D) (Khan et al., 2019). Hemoglobin A1c (A1c) is a measure used to monitor T2D progression. Standard of care- based approaches to encourage lifestyle modification have been shown to decrease A1c, yet high healthcare costs and travel-related barriers limit the accessibility of these strategies. Rising T2D rates globally underscore the immediate need to identify the most comparably effective options that decrease A1c and address disease prevention and management.ObjectivesThis systematic review examines the effectiveness of digital delivery of lifestyle interventions in decreasing A1c among adults globally both overall and compared to standard ofcare and monitoring only based approaches.MethodsBased on application of the Navigation Guide systematic review methodology, 10 studies conducted in eight countries met the inclusion criteria and were evaluated for bias, quality, and strength of evidence. Conclusions were drawn from evaluating quantitative results.ResultsA systematic review of the literature demonstrated sufficient evidence of an association between digital delivery of lifestyle interventions and decreased A1c trends. Research did not show significant differences in A1c changes among the intervention groups when compared to the standard of care and monitoring only based control groups.ConclusionsThese results indicate that while the digital delivery of lifestyle interventions is effective in lowering A1c levels in T2D patients, these interventions do not outperform standard of care and monitoring only based approaches to prevent and manage T2D.
Clinical testing panels for ALS: global distribution, consistency, and challenges
Authors: Dilliott Allison A. , Al Nasser Ahmad , Elnageeb Marwa , Fifita Jennifer , Henden Lyndal , Keseler Ingrid M. , Lenz Steven , Marriott Heather , McCann Emily , Mesaros Maysen , Opie-Martin Sarah , Owens Emma , Palus Brooke , Ross Justyne , Wang Zhanjun , White Hannah , Al-Chalabi Ammar , Andersen Peter M. , Benatar Michael , Blair Ian , Cooper-Knock Johnathan , Drury Luke , Harrington Elizabeth , Heckmann Jeannine , Landers John , Moreno Cristiane , Nel Melissa , Rampersaud Evadnie , Roggenbuck Jennifer , Rouleau Guy , Traynor Bryan , van Blitterswijk Marka , van Rheenen Wouter , Veldink Jan , Weishaupt Jochen , Harms Matthew B. , Farhan Sali M.K. 
Published: September 2022

AbstractObjectiveIn 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.MethodsWe reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests.Results14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes.ConclusionsThe variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
Plasma multi-omics analysis reveals very long chain ceramides as validated biomarkers of Friedreich’s ataxia
Authors: Wang Dezhen , Cotticelli M. Grazia , Himes Blanca E. , Lynch David R. , Mesaros Clementina 
Published: September 2022

AbstractFriedreich’s Ataxia (FRDA) is an autosomal neurodegenerative disease caused by the deficiency of the protein frataxin. Frataxin is a critical enzyme in the assembly of iron-sulfur clusters that are cofactors for several metabolic enzymes. To identify metabolic features that could be used as potential biomarkers for FRDA in plasma, we performed a multi-omics analysis using a discovery-validation cohort design. We combined metabolomics, lipidomics and proteomics from several liquid chromatography-high resolution mass spectrometry platforms. The analyses revealed that FRDA patients compared to healthy controls and unaffected carriers had dysregulated sphingolipids metabolism, phospholipid metabolism, citric acid cycle, amino acid metabolism, and apolipoprotein metabolism. Using an ROC, the decreased very long chain ceramides can distinguished FRDA patients from healthy controls with AUC from 0.75 to 0.85. Using induced pluripotent stem cell differentiated cardiomyocytes (iPSC-CMs), we demonstrated that frataxin deficiency preferentially affected ceramide synthase (CerS2), enriching long chain ceramides, and depleting very long chain ceramides. The ceramide metabolism was differentially regulated in two of the affected tissues in FRDA: heart and muscles. A machine-learning model improved the prediction of FRDA using the combination of three plasma metabolites (AUC > 0.9). In conclusion, decreased very long chain ceramides are reliable plasma biomarkers for FRDA patients.One Sentence SummaryNew plasma lipids biomarkers of Friedreich’s Ataxia (FRDA) were validated using a discovery-validation design with two independent cohorts.
Effects of more natural housing conditions on the muscular and skeletal characteristics of female C57BL/6J mice
Authors: Mieske Paul , Scheinpflug Julia , Yorgan Timur Alexander , Brylka Laura , Palme Rupert , Hobbiesiefken Ute , Preikschat Juliane , Diederich Kai , Lewejohann Lars 
Published: September 2022

AbstractBackgroundEnrichment of home cages in laboratory experiments offers clear advantages, but has been criticized in some respects. First, there is a lack of definition, which makes methodological uniformity difficult. Second, there is concern that the enrichment of home cages may increase the variance of results in experiments. Here, the influence of more natural housing conditions on physiological parameters of female C57BL/6J mice was investigated from an animal welfare point of view. For this purpose, the animals were kept in three different housing conditions: conventional cage housing, enriched housing and the semi-naturalistic environment. The focus was on musculoskeletal changes after long-term environmental enrichment.ResultsThe housing conditions had a long-term effect on the body weight of the test animals. The more complex and natural the home cage, the heavier the animals. This was associated with increased adipose deposits in the animals. There were no significant changes in muscle and bone characteristics except for single clues (femur diameter, bone resorption marker CTX-1). Additionally, the animals in the semi naturalistic environment (SNE) were found to have the fewest bone anomalies. Housing in the SNE appears to have the least effect on stress hormone concentrations. The lowest oxygen uptake was observed in enriched cage housing.ConclusionsDespite increasing values, observed body weights were in the normal and strain-typical range. Overall, musculoskeletal parameters were slightly improved and age-related effects appear to have been attenuated. The variances in the results were not increased by more natural housing. This confirms the suitability of the applied housing conditions to ensure and increase animal welfare in laboratory experiments.
Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome
Authors: Mohler Kyle , Moen Jack , Rogulina Svetlana , Rinehart Jesse 
Published: September 2022

AbstractInteractions between proteins from intracellular pathogens and host proteins in an infected cell are often mediated by post-translational modifications encoded in the host proteome. Identifying protein modifications, such as phosphorylation, that dictate these interactions remains a defining challenge in unraveling the molecular mechanisms of pathogenesis. We have developed a platform in engineered bacteria that displays over 110,000 phosphorylated human proteins coupled to a fluorescent reporter system capable of identifying the host-pathogen interactome of phosphoproteins (H-PIP). This resource broadly enables cell-type independent interrogation and discovery of proteins from intracellular pathogens capable of binding phosphorylated human proteins. As an example of the H-PIP platform, we generated a unique, high-resolution SARS-CoV-2 interaction network which expanded our knowledge of viral protein function and identified understudied areas of host pathology.
POPULATION PHARMACOKINETICS OF BENZNIDAZOLE IN NEONATES, INFANTS AND CHILDREN USING A NEW PEDIATRIC FORMULATION
Authors: Altcheh Jaime , Moscatelli Guillermo , Caruso Martin , Moroni Samanta , Bisio Margarita , Miranda Maria Rosa , Monla Celia , Vaina Maria , Valdez Maria , Moran Lucrecia , Ramirez Teresa , Patiño Oscar Ledesma , Riarte Adelina , Gonzalez Nicolas , Fernandes Jayme , Alves Fabiana , Ribeiro Isabela , Garcia-Bournissen Facundo 
Published: September 2022

AbstractBackgroundThere is a major need for information on pharmacokinetics (PK) of benznidazole in children with Chagas disease (CD). We present herein the results of a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BZN (100 mg and the 12.5 mg dispersible tablet, developed in a collaboration of DNDi and LAFEPE).Methods81 children 0-12 years of age were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination or at least two positive conventional serologies. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times: at Day 0, at 2 – 5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12 – 24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment.ResultsForty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95 – 11.8; range 1.79 – 19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25 – 3.77; range 0.14 – 7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7 – 8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance).ConclusionWe observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs.
Populational analysis of the immunoglobulin G response to different COVID-19 vaccines in Brazil
Authors: Paula Nigella M. , Conzentino Marcelo S. , Gonçalves Ana C.A. , da Silva Renata , Weissheimer Karin V. , Kluge Carlos H.S. , Marins Paulo H.S.A. , Camargo Haxley S.C. , Farias Lucas R.P. , Sant’Ana Thamyres P. , Vargas Letícia R. , Aldrighi Juliane D. , Lima Ênio S. , Jacotenski Guiomar T. , Pedrosa Fabio O. , Gonçalves Alan G. , Joucoski Emerson , Huergo Luciano F. 
Published: September 2022

ABSTRACTVaccination is a strategy that confers protection against symptomatic infections and/or development of severe COVID-19. In Brazil, COVID-19 vaccination began in January 2021 and has been performed using vaccines from different manufactures including CoronaVac (Sinovac), ChAdOx1 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech). One of the main protective mechanisms triggered by vaccination involves the production of IgG antibodies reactive to the Spike antigen of SARS-CoV-2, the levels of which correlates with vaccine efficacy. Although phase III clinical studies confirmed the efficacy of the vaccines used in Brazil, there are just few studies comparing vaccine immunogenicity in a real-world scenario. This study aimed to depict the IgG response to natural infections and to vaccination using different types of vaccines at population scale in Matinhos, a city located in south of Brazil. Nucleocapsid seroconversion rates indicated that more than a quarter of the cohort has been subjected to natural infections by SARS-CoV-2 by the first trimester of 2022. Spike seroconversion rates achieved >95% by February 2022 and maintained stable as far as June 2022 confirming the effectiveness of the vaccination program. Immunogenicity concerning IgG reactive to Spike was higher using the BNT162b2 vaccine, followed by ChAdOx1 and CoronaVac. Natural infections boosted IgG levels reactive to Spike in those individuals that completed primary vaccination with ChAdOx1 and CoronaVac but not with BNT162b2. The levels of IgG reactive to Spike increased with the number of vaccine doses administered. The application of BNT162b2 as booster dose resulted in high levels of IgG reactive to Spike which were similar despite the type of the vaccine used during primary vaccination.