bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Inflammatory Markers are Associated With Inadequate Post‐Induction Infliximab Trough in Pediatric Crohn's Disease
Authors: Constant Brad D. , Khushal Salina , Jiang Jiji , Bost James E. , Chaisson Ellen , Conklin Laurie S. 
Published: November 2020

ABSTRACTObjectives:In pediatric Crohn's disease, infliximab trough concentrations after standard weight‐based induction therapy are commonly below 7 μg/mL. Clinical treatment outcomes are associated with post‐induction infliximab trough concentration. Markers of inflammation are associated with low infliximab concentrations during maintenance dosing. We sought to determine if early markers of disease activity are associated with inadequate post‐induction infliximab trough concentrations in pediatric Crohn's disease.Methods:We performed a retrospective single‐center case‐control study of pediatric Crohn's disease patients to assess the association between baseline and week‐2 biomarkers (albumin, C‐reactive protein, and erythrocyte sedimentation rate) and inadequate post‐induction infliximab trough concentration (<7 μg/mL) in patients treated with standard 5 mg/kg dosing. Baseline and week‐2 biomarker values were coded as dichotomous variables at clinically useful thresholds. Univariable logistic regression was used to calculate odds ratios of developing an inadequate infliximab trough concentration for each threshold, as well as thresholds in combination.Results:Fifty‐five patients were evaluated. Early biomarker thresholds significantly associated with inadequate post‐induction infliximab trough concentrations included baseline C‐reactive protein >1 mg/dL (odds ratio [OR] 4.58; 95% confidence interval [CI] 1.24‐‐17.01), both baseline C‐reactive protein >0.5 mg/dL and albumin <3.5 g/dL (OR 8.31; 95% CI 1.99‐‐34.63), and week‐2 C‐reactive protein >0.5 mg/dL or albumin <3.5 mg/dL or erythrocyte sedimentation rate >25 mm/hour (OR 11.08; 95% CI 2.14‐‐57.22).Conclusions:Routine baseline and week‐2 markers of disease activity at clinically useful thresholds were associated with inadequate post‐induction infliximab trough concentration in pediatric Crohn's disease patients receiving standard weight‐based induction dosing.
Caregiver Decision‐making in Pediatric Intestinal Failure
Authors: Raghu Vikram Kalathur , Prathapan Krishnapriya M. , Hamm Megan E. , Rudolph Jeffrey A. , Norman Marie K. 
Published: November 2020

ABSTRACTBackground:Caregivers of children with intestinal failure (IF) face difficult decisions without a clear best alternative. Providers assist in decision‐making but often lack knowledge of caregiver perspectives. Using decision‐making around anemia treatment as a focal point, we explored how caregivers of children with IF prefer to make decisions. Our goal was to offer insight to guide providers as they assist in decision‐making.Methods:We conducted 12 half‐hour semistructured interviews with parents of children with IF. Interview questions addressed general decision‐making and specifics of iron supplementation, including key factors and stakeholders in decision‐making. Interviews were transcribed verbatim. Two investigators coded the transcripts and inductively derived themes.Results:Four themes were identified regarding decision‐making. They involved the search for reliable, accurate, and positive information; the role of caretakers on the medical team; the relationships between caretakers and the medical team; and effective communication. Themes around anemia treatment included: identification of anemia by bloodwork; proactive supplementation; individualized regimens; prioritizing safety and convenience.Conclusions:Understanding caregiver perspectives regarding anemia treatment in pediatric IF identifies opportunities for systematic quality improvement.
Clinical Hypnosis in Pediatric Crohn's Disease
Authors: Lee Amanda , Moulton Dedrick , Mckernan Lindsey , Russell Alexandra , Slaughter James C. , Acra Sari , Walker Lynn 
Published: November 2020

ABSTRACTObjective:The aim of this study was to implement clinical hypnosis (CH) as an adjunctive therapy for adolescents with Crohn's disease (CD) and to assess the impact of CH on quality of life (QoL), abdominal pain, psychosocial measures, and disease activity compared with standard care.Methods:Forty adolescents with CD were randomized to a hypnosis intervention (HI) or waitlist control (WC) group. The intervention consisted of 1 in‐person CH session, self‐hypnosis education, and recordings for home practice. Data was collected at baseline, after the 8‐week intervention, and at week 16. The primary outcome was patient‐ and parent‐reported QoL; secondary outcomes were patient‐reported abdominal pain, depression, anxiety, and sleep; school absences; and disease activity by Pediatric Crohn's Disease Activity Index. Paired and independent t‐tests were used to compare differences from baseline to postintervention within and between groups.Results:Forty patients (50% girls, mean 15.8 years) were enrolled from February to May 2019. Seventy‐eight percent had inactive disease, and 55% had abdominal pain. Post intervention, significant improvements were noted in HI parent‐reported QoL compared with WC in total score (P = 0.05), social functioning (P = 0.01), and school functioning (P = 0.04) but patient‐reported QoL was unchanged. Abdominal pain severity significantly improved in HI compared with WC (P = 0.03). School absences decreased in significantly more intervention than control patients (P = 0.01). Patients who practiced self‐hypnosis consistently showed a trend toward greater QoL improvement than those who did not (P = 0.1).Conclusions:CH is an acceptable and feasible adjunct in CD and may improve psychosocial QoL and abdominal pain. Further research is warranted.
Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era
Authors: Ruderman Stephanie A. , Crane Heidi M. , Nance Robin M. , Whitney Bridget M. , Harding Barbara N. , Mayer Kenneth H. , Moore Richard D. , Eron Joseph J. , Geng Elvin , Mathews William C , Rodriguez B , Willig Amanda L. , Burkholder Greer A. , Lindström Sara , Wood Brian R. , Collier Ann C. , Vannappagari Vani , Henegar Cassidy , Van Wyk Jean , Curtis Lloyd , Saag Michael S. , Kitahata Mari M. , Delaney Joseph A. C. 
Published: November 2020

Objectives:
Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.

Methods:
Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.

Results:
Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.

Conclusions:
There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.
Correlates of HIV Status Nondisclosure by Pregnant Women Living With HIV to Their Male Partners in Uganda: A Cross-Sectional Study
Authors: Bulterys Michelle A. , Sharma Monisha , Mugwanya Kenneth , Stein Gabrielle , Mujugira Andrew , Nakyanzi Agnes , Twohey-Jacobs Lorraine , Ware Norma C. , Heffron Renee , Celum Connie 
Published: November 2020

Background:
HIV status disclosure by pregnant women living with HIV (PWLHIV) to their male partners is associated with improved maternal and infant outcomes. Understanding relationship factors associated with nondisclosure of HIV status by PWLHIV to their partners can inform the design of interventions to facilitate disclosure.

Methods:
We conducted a cross-sectional study using enrollment data from 500 PWLHIV unaware of their male partners' HIV status and participating in a randomized clinical trial assessing secondary distribution of HIV self-testing kits in Kampala, Uganda. The primary outcome was women's HIV status nondisclosure to their partners. We conducted univariate and multivariate binomial regressions to assess the association between baseline sociodemographic, HIV history, and relationship characteristics with HIV status nondisclosure.

Results:
68.2% of the 500 PWLHIV had not disclosed their HIV status to their partner(s). Factors associated with higher likelihood of nondisclosure included relationship duration <1 year [adjusted prevalence ratio (aPR = 1.25); 95% confidence interval (CI): 1.02 to 1.54], being in a polygamous relationship (aPR = 1.21; 95% CI: 1.07 to 1.36), unmarried (aPR = 1.20; 95% CI: 1.07 to 1.35), uncertainty about whether their partner had ever tested for HIV (aPR = 1.55; 95% CI: 1.28 to 1.88), and a lack of social support from people aware of their status (aPR = 1.32; 95% CI: 1.18 to 1.49).

Conclusion:
Relationship factors, including shorter-term, unmarried, and polygamous relationships and uncertainty about partner's HIV testing history, were associated with higher likelihood of pregnant women's nondisclosure of HIV status to their partner. Interventions that facilitate couples' HIV testing and disclosure, provide counseling to reduce relationship dissolution in serodiscordant couples, and offer peer support for women may increase disclosure.

ClinicaltrialsRegistration:

Clinicaltrials.gov ID number: NCT03484533.
Sexual Behavior Among Men Who Have Sex With Men: The Need for More Targeted Outreach to Men Who Also Have Sex With Cisgender Women
Authors: Mayer Megan E. , White Edward , Montano Michalina A. , Lama Javier R. , Sanchez Hugo , Cabello Robinson , Sanchez Jorge , Pasalar Siavash , Duerr Ann 
Published: November 2020

Background:
In Peru, as in the Americas overall, men who have sex with men (MSM) are disproportionately affected by HIV. Most research focuses on practices between cisgender men, whereas many MSM report male and female partners, cisgender, transgender, or both.

Methods:
Data for these analyses were from a treatment-as-prevention study in Lima (the Sabes study). We compared demographics and behaviors of MSM who reported cisgender women partners in the past 3 months (MSMW) and MSM who reported both cisgender and transgender women partners (MSMW-T) to MSM who reported only male partners (MSMO). We calculated HIV incidence in each group during 2-year follow-up.

Results:
Compared with MSMO, MSMW and MSMW-T more often self-identify as heterosexual or bisexual and report insertive sex practices. MSMW reported condomless sex with cisgender women: vaginal (72%), anal sex (18%). One-third of MSMW reported condomless receptive anal sex with men in the past 3 months, with 24% of MSMW overall who reported both condomless receptive sex with men and condomless insertive vaginal or anal sex with cisgender women. Of these, 17% were HIV infected. HIV incidence did not differ significantly between groups.

Conclusion:
Most MSMW and MSMW-T report bisexual or heterosexual orientation and prefer insertive sex. MSMW and MSMW-T (47% and 29%, respectively) engage in receptive anal intercourse. In both groups, the majority who engaged in condomless receptive sex with men (76% MSMW, 85% MSMW-T) also engaged in condomless vaginal and/or anal sex with women, indicating need for intervention.
Simulation Innovation
Authors: Drake Hilary , Abbey Darin , Holmes Chelsea , Macdonald Anna , Mackinnon Laura , Slinn JoAnne , Baylis Jared 
Published: November 2020

Summary Statement
The coronavirus disease 19 (COVID-19) pandemic, caused by severe acute respiratory distress syndrome coronavirus 2, has spread globally and requires effective preparedness within healthcare institutions. The British Columbia Simulation Network COVID-19 Simulation Guide was created to disseminate information throughout the province of British Columbia, Canada, and to allow simulation educators, from novice to expert, to participate in COVID-19 simulations. As of July 15, 2020, the guide had been downloaded 465 times from the British Columbia Simulation Network website, with downloads in 41 countries around the world. The guide has been frequently updated and revised to reflect evolving guidelines as new knowledge about COVID-19 was established.
Use of an integrated pan-cancer oncology enrichment NGS assay to measure tumour mutational burden and detect clinically actionable variants
Authors: Pestinger Valerie , Smith Matthew , Sillo Toju , Findlay John M , Laes Jean-Francois , Martin Gerald , Middleton Gary , Taniere Phillipe , Beggs Andrew D 
Published: November 2020

AbstractIntroductionThe identification of tumour mutational burden (TMB) as a biomarker of response to PD-1 immunotherapy has necessitated the development of genomic assays to measure this. We carried out comprehensive molecular profiling of cancers using the Illumina TruSight Oncology panel (TSO500) and compared to whole genome sequencing.MethodsCancer samples derived from formalin fixed material were profiled on the TSO500 panel, sequenced on an Illumina NextSeq 500 instrument and processed through the TSO500 Docker Pipeline. Either FASTQ files (PierianDx) or VCF files (OncoKDM) were processed to understand clinical actionabilityResultsIn total, 108 samples (a mixture of colorectal, lung, oesophageal and control samples) were processed via the DNA panel. There was good correlation between TMB, SNV, indels and CNV as predicted by TSO500 and WGS (R2>0.9) and good reproducibility, with less than 5% variability between repeated controls. For the RNA panel, 13 samples were processed, with all known fusions observed via orthogonal techniques detected. For clinical actionability 72 Tier 1 variants and 297 Tier 2 variants were identified with clinical trials identified for all patients.ConclusionsThe TruSight Oncology 500 assay accurately measures TMB, MSI, single nucleotide variants, indels, copy number/structural variation and gene fusions when compared to whole genome sequencing and orthogonal technologies. Coupled with a clinical annotation pipeline this provides a powerful methodology for identification of clinically actionable variants.
Peeling Back the Layers: First Phylogenomic Insights into the Ledebouriinae (Scilloideae, Asparagaceae)
Authors: Howard Cody Coyotee , Crowl Andrew A. , Harvey Timothy S. , Cellinese Nico 
Published: November 2020

AbstractThe Ledebouriinae (Scilloideae, Asparagaceae) are a widespread group of bulbous geophytes found predominantly throughout seasonal climates in sub-Saharan Africa, with a handful of taxa in Madagascar, the Middle East, India, and Sri Lanka. Phylogenetic relationships within the group have been historically difficult to elucidate. Here, we provide the first phylogenomic perspective into the Ledebouriinae. Using the Angiosperms353 targeted enrichment probe set, we consistently recovered four major clades (i.e., twoLedebouriaclades,Drimiopsis, andResnova). The twoLedebouriaclades closely align with geography, either consisting almost entirely of sub-Saharan African taxa (LedebouriaClade A), or East African and non-African taxa (LedebouriaClade B). Our results suggest that the Ledebouriinae likely underwent a rapid radiation leading to rampant incomplete lineage sorting. We additionally find evidence for potential historical hybridization betweenDrimiopsisand a subclade withinLedebouriaClade A.
Disrupted visual cortical plasticity in early neurodegeneration
Authors: Papanikolaou Amalia , Rodrigues Fabio R. , Holeniewska Joanna , Phillips Keith , Saleem Aman B. , Solomon Samuel G. 
Published: November 2020

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.HighlightsVisual plasticity is disrupted at early stages of neurodegeneration in rTg4510 miceVisual plasticity is reduced in older animals, particularly during neurodegenerationInstinctive visual behaviours are reduced in neurodegenerationShort-term visual plasticity is reduced in neurodegeneration
Human-in-the-Loop Weight Compensation in Upper Limb Wearable Robots Towards Total Muscles’ Effort Minimization
Authors: Nasiri Rezvan , Aftabi Hamidreza , Ahmadabadi Majid Nili 
Published: November 2020

AbstractIn this paper: (1) We present a novel human-in-the-loop adaptation method for whole arm muscles’ effort minimization by means of weight compensation in the face of an object with an unknown mass. (2) This adaptation rule can also be used as a cognitive model for the identification of mass value using EMG sensors. (3) This adaptation rule utilizes the activation (myoelectric) signal of only four muscles in the upper limb to minimize the whole muscles’ effort. We analytically discuss the stability, optimality, and convergence of the proposed method. The effectiveness of this method for whole muscles’ effort reduction is studied by simulations (OpenSim software) on a generic and realistic model of the human arm, a model with 7-DOF and 50 Hill-type-muscles. The simulation results show the presented method’s performance and applicability for weight compensation and mass estimation in upper limb assistive robots. In addition, the simulations in OpenSim completely support that the suggested set of mono-articular muscles are sufficient for whole muscles’ effort reduction.
Immune modulating drug MP1032 with SARS-CoV-2 antiviral activity in vitro: A potential multi-target approach for prevention and early intervention treatment of COVID-19
Authors: Schumann Sara , Kaiser Astrid , Nicoletti Ferdinando , Mangano Katia , Fagone Paolo , van Wijk Eduard , Yan Yu , Schulz Petra , Ludescher Beate , Niedermaier Michael , von Wegerer Joerg , Rauch Pia , Setz Christian , Schubert Ulrich , Brysch Wolfgang 
Published: November 2020

AbstractAt least since March 2020, the multiorgan disease COVID-19 has a firm grip on the world. Although most of the cases are mild, patients from risk populations could develop a cytokine storm, which is characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper will introduce the small molecule MP1032, describe its mode of action, and give rationale why it is a promising option for prevention/treatment of SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-pthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting antioxidant activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, immune-regulatory and PARP-1 modulating properties, coupled with antiviral effects against SARS-CoV-2 were shown in various cell models. Efficacy has been preclinically elucidated in LPS-induced endotoxemia, a model with excessively activated immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-months daily administrations, no serious adverse drug reactions occurred highlighting the outstanding safety profile of MP1032.
Cognitive Practice Effects Delay Diagnosis; Implications for Clinical Trials
Authors: Sanderson-Cimino Mark , Elman Jeremy A. , Tu Xin M. , Gross Alden L. , Panizzon Matthew S. , Gustavson Daniel E. , Bondi Mark W. , Edmonds Emily C. , Eglit Graham M.L. , Eppig Joel S. , Franz Carol E. , Jak Amy J. , Lyons Michael J. , Thomas Kelsey R. , Williams McKenna E. , Kremen William S. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2020

AbstractObjectivePractice effects on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). This reduces opportunities for slowing Alzheimer’s disease progression and can hinder clinical trials. Using a novel method, we assessed the ability of practice-effect-adjusted diagnoses to detect MCI earlier, and tested the validity of these diagnoses based on AD biomarkers.MethodsOf 889 Alzheimer’s Disease Neuroimaging Initiative participants who were cognitively normal (CN) at baseline, 722 returned at 1-year-follow-up (mean age=74.9±6.8). Practice effects were calculated by comparing returnee scores at follow-up to demographically-matched individuals who had only taken the tests once, with an additional adjustment for attrition effects. Practice effects for each test were subtracted from follow-up scores. The lower scores put additional individuals below the impairment threshold for MCI. CSF amyloid-beta, phosphorylated tau, and total tau were measured at baseline and used for criterion validation.ResultsPractice-effect-adjusted scores increased MCI incidence by 26% (p<.001). Adjustment increased proportions of amyloid-positive MCI cases (+20%) and reduced proportions of amyloid-positive CNs (−6%) (ps<.007). With the increased MCI base rate, adjustment for practice effects would reduce the sample size needed for detecting significant drug treatment effects by an average of 21%, which we demonstrate would result in multi-million-dollar savings in a clinical trial.InterpretationAdjusting for practice effects on cognitive testing leads to earlier detection of MCI. When MCI is an outcome, this reduces recruitment needed for clinical trials, study duration, staff and participant burden, and can dramatically lower costs. Importantly, biomarker evidence also indicates improved diagnostic accuracy.