bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deuterium metabolic imaging and hyperpolarized13C-MRI of the normal human brain at clinical field strength reveals differential cerebral metabolism
Authors: Kaggie Joshua D , Khan Alixander S , Matys Tomasz , Schulte Rolf F , Locke Matthew J , Grimmer Ashley , Frary Amy , Graves Martin J , McLean Mary A , Gallagher Ferdia A 
Published: February 2022

AbstractDeuterium metabolic imaging (DMI) and hyperpolarized13C-pyruvate MRI (13C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications for cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans, and how they simultaneously probe both glycolytic and oxidative metabolism. DMI was undertaken 1-2 hours after oral administration of [6,6’-2H2]glucose, and13C-MRI was performed immediately following intravenous injection of hyperpolarized [1-13C]pyruvate in ten and nine normal volunteers within each arm. DMI provided maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine.13C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. There was clear spectral separation in the spectroscopic imaging data with both DMI and13C-HPMRI at 3 T. The ratio of13C-lactate/13C-bicarbonate (mean = 3.7 ± 1.2) acquired with13C-HPMRI was higher than the equivalent2H-lactate/2H-Glx ratio (mean = 0.18 ± 0.09) acquired with DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and glycolytic metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.
Evaluating Fomite Risk of Brown Paper Bags Storing Personal Protective Equipment Exposed to SARS-CoV-2: A Quasi-Experimental Study
Authors: Unger Kyirsty , Dietz Leslie , Horve Patrick , Van Den Wymelenberg Kevin , Lin Amber , Kinney Erin , Kea Bory 
Published: February 2022

AbstractIntroductionLiterature is lacking on the safety of storing contaminated PPE in paper bags for reuse, potentially increasing exposure to frontline healthcare workers (HCW) and patients.ObjectivesTo evaluate the effectiveness of paper bags as a barrier for fomite transmission of SARS-CoV-2 by storing limited reusable face masks, respirators, and face shields.MethodsThis quasi-experimental study evaluated the presence of SARS-CoV-2 on the interior and exterior surfaces of paper bags containing PPE that had aerosolized exposures in clinical and simulated settings. Between May and October 2020, 30 unique PPE items were collected from critical and intermediate care COVID-19 units at two urban hospitals. Exposed PPE, worn by either an infected patient or HCW during a SARS-CoV-2 aerosolizing event, were placed into an unused brown paper bag. Samples were tested at 30-minute and 12-hour intervals.ResultsA total of 177 swabs were processed from 30 PPE samples. We found a (12/177 total) 6.8% positivity rate among all samples across both collection sites. Highest positivity rates were associated with ventilator disconnection (1/6 samples, 16.7% positivity) and exposure to respiratory droplets from coughing (2/24 samples, 8.3% positivity), compared to exposure to high-flow nasal cannula (8/129 samples, 6.2% positivity) or tracheostomy surgery (1/18 samples, 5.6% positivity). Positivity rates differed between hospital units. Total positivity rates were similar between 30-minute (6.7%) and 12-hour (6.9%) sample testing time intervals. Control samples exposed to inactivated SARS-CoV-2 droplets had higher total viral counts than samples exposed to nebulized aerosols.ConclusionsData suggests paper bags are not a significant fomite risk for SARS-CoV-2 transmission. However, controls demonstrated a risk with droplet exposure. Data can inform guidelines for storing and re-using PPE in situations of limited supplies during future pandemics.
Clinical outcomes in hospitalized vaccine-breakthrough COVID-19 cases compared with contemporary unvaccinated hospitalized adults
Authors: Wolff Marcelo , Gilabert Margarita , Hernández Rodrigo 
Published: February 2022

SummaryThe inactivated SARS-CoV-2 vaccine (CoronaVac®) has been the principal vaccine used in Chile’s pre-booster immunization campaign. We compared major outcomes in 260 hospitalized vaccinated vs 507 unvaccinated adults with COVID-19 (mid-2021). The vaccinated group was much older, required less critical care, had lower hospital mortality (adjusted by age), and had shorter hospitalization than the unvaccinated. Benefits were most pronounced in those older than 59 yearsObjectiveTo compare major outcomes in fully vaccinated and unvaccinated adult persons hospitalized for COVID-19 in a general private hospital in Santiago, Chile during mid2021.
History of SARS-CoV-2 infection, anti-spike IgG antibody kinetics and neutralization capacities following the second and third dose of BNT162b2 vaccine in nursing home residents
Authors: Jeulin H. , Labat C. , Duarte K. , Toupance S. , Nadin G. , Craus D. , Georgiopoulos I. , Gantois I. , Goehringer F. , Benetos A. 
Published: February 2022

AbstractImportanceDuration of post-vaccination protection against COVID-19 in individuals is a critical issue, especially in nursing home (NH) residents, i.e. one of the most vulnerable populations.ObjectiveTo estimate the duration of the IgG(S) response to the mRNA BNT162b2 vaccine in NH residents with (COV-Yes) or without (COV-No) history of natural infection with SARS-CoV-2.Design, setting and participantsIgG(S) quantification was carried out at 3 different time periods following administration of the Pfizer BioNtech vaccine: three then seven months after the 2nd dose and one month after the 3rd dose. 574 COV-Yes and COV-No NH residents were included in 2 cohorts: Main (n=115, mean age 84 years) or Confirmatory (n=459, mean age 88 years).ExposureAll subjects received the BNT162b2 vaccine.Main outcomes and measurementsIgG(S) antibodies and seroneutralization capacity.ResultsNeutralization capacity was strongly correlated with IgG(S) levels (R2:76%) without any difference between COV-Yes and COV-No groups for the same levels of IgG(S). COV-Yes, compared to the COV-No subjects showed 5-fold and 15-fold higher IgG(S) titers 3 and 7 months after the 2nd dose, but less than 2-fold higher IgG(S) after the 3rd dose, due to a more pronounced effect of the 3rd dose in the COV-No group. These results were similar in both cohorts. After the 2nd dose, duration of assumed robust protection (IgG(S) >264 BAU/ml) was 2-fold higher in the COV-Yes vs. COV-No group: 12.60 (10.69-14.44) vs 5.76 (3.91-8.64) months, and this advantage was mainly due to the higher IgG(S) titers after the 2nd dose and secondary to a slower decay over time. After the 3rd dose, duration (months) of robust protection was estimated at 11.87 (9.88-14.87) (COV-Yes) and 8.95 (6.85-11.04) (COV-No).Conclusions and relevanceIn old subjects living in NH, history of SARS-CoV-2 infection provides a clear advantage in the magnitude and duration of high IgG(S) titers following the 2nd dose. Importantly, the 3rd dose induces a much more pronounced IgG(S) response than the 2nd dose in COV-No subjects, the effect of which should be able to ensure in these subjects a prolonged protection against severe forms of COVID-19.
Can you hear me now? Clinical applications of audio recordings
Authors: Kumar Anish , Jaquenoud Theo , Becker Jacqueline Helcer , Cho Dayeon , Mindt Monica Rivera , Federman Alex , Pandey Gaurav 
Published: February 2022

AbstractAudio and speech have several implicit characteristics that have the potential for the identification and quantification of clinical disorders. This PRISMA-guided review is designed to provide an overview of the landscape of automated clinical audio processing to build data-driven predictive models and infer phenotypes of a variety of neuropsychiatric, cardiac, respiratory and other disorders. We detail the important components of this processing workflow, specifically data acquisition and processing, algorithms used and their customization for clinical applications, commonly used tools and software, and benchmarking and evaluation methodologies. Finally, we discuss important open challenges for the field, and potential strategies for addressing them.
Trends in Racial and Ethnic Disparities in Barriers to Timely Medical Care Among US Adults, 1999 to 2018
Authors: Caraballo César , Ndumele Chima D. , Roy Brita , Lu Yuan , Riley Carley , Herrin Jeph , Krumholz Harlan M. 
Published: February 2022

ABSTRACTBackgroundRacial and ethnic disparities in delayed medical care due to reasons not related to cost of care remain understudied. We aimed to describe recent 20-year trends in such disparities.MethodsThe study used data from the National Health Interview Survey from 1999–2018 and included individuals ≥18 years of age. Respondents were categorized by their sex, income, and self-reported race and ethnicity. The main outcomes were trends in disparities in any of 5 specific barriers to timely medical care: inability to get through by phone, no appointment available soon enough, long waiting times, inconvenient doctor’s office/clinic hours, or lack of transportation.ResultsThe study included 590,603 adults (mean age 46.0 [SE, 0.07] years; 51.9% female). Of these, 4.7% were Asian, 11.8% Black, 13.8% Latino/Hispanic, and 69.7% White. In 1999, the proportion reporting any of the barriers to timely medical care was 7.3% among Asian, 6.9% among Black, 7.9% among Latino/Hispanic, and 7.0% among White individuals (P >0.05 for each difference with White individuals). From 1999 to 2018, this proportion increased across all 4 race/ethnicity groups (P<0.001 for each), slightly increasing the disparities between groups. In 2018, compared with White individuals, the proportion reporting any barrier was 2.1 and 3.1 percentage points higher among Black and Latino/Hispanic individuals (P=0.03 and P=0.001, respectively). The racial/ethnic disparities increased mostly among males and were attenuated when stratified by income level.ConclusionsFrom 1999 to 2018, barriers to timely medical care increased for all populations with increasing disparities between racial/ethnic groups.
Five years follow-up of patients with non-melanoma skin cancer treated with HeberFERON
Authors: Duncan-Roberts Y , Garcia-Vega Y , Collazo-Caballero S , Rodriguez-Garcia M , Zalazar-Sedano M , Rodríguez-Rojas JL , Tuero-Iglesias A , Valenzuela-Silva C , Raices-Cruz I , Castro-Basart N , Garcia-Iglesias E , Pereda-Lamela L , Hernández-Rodríguez R , Arteaga-Hernandez E , Muzio-Gonzalez V , Bello-Rivero I 
Published: February 2022

ABSTRACTIntroductionNon-melanoma skin cancer is the most common tumor. The combination of IFN-alpha 2b and IFN-gamma has been used as a new therapeutic opportunity to treat basal cell carcinomas and cutaneous squamous cell carcinomas. The aim of this report is to record prospectively the recurrence and new lesions rates in patients participating in phase II clinical trials.MethodsPhase II clinical trials (double-blind randomized one center study, InCarbacel-III, in patients with basal cell carcinoma; and open, non-randomized multicenter study, CECIN, in patients with cutaneous squamous cell carcinomas), with the use of the combination of IFN-alpha 2b and IFN-gamma were conducted to evaluate the efficacy, safety and the 5-year duration of clinical responses. Both studies were approved by institutional ethic committees and all the patients given their written informed consent. The investigational treatment was administered, peri- or intralesionally, three times per week, during 3 weeks. Clinical (RECIST 1.0) responses were evaluated three months after the end of treatment.ResultsThe combination of IFNs in InCarbacel-III study showed the best clinical response (complete response of 64.3%, overall response of 85.7%) with the highest doses (10.5 MIU); without patient’s recurrence at 5 years follow-up (3.5 MUI and 10.5 MUI groups). The frequency of new lesions decreased in the treated patients 8 times. In the CECIN study 14 patients achieved complete response and 4 partial responses (overall response rate 67%). Up to the 5-year follow-up none of the patients with complete response had recurrence or new lesion. In both studies the cosmetic results were excellent and the reported adverse events were mostly of mild intensity.ConclusionsThe use of the combination of IFN-alpha 2b and IFN-gamma showed efficacy in basal cell carcinoma and cutaneous squamous cell carcinoma promoting a long term response for at least 5 years and decreasing the rate of new lesions, safely and with excellent cosmetic effects.
Genetic immune response and antibody repertoire of heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort
Authors: Lee Hye Kyung , Go Jinyoung , Sung Heungsup , Kim Seong Who , Walter Mary , Knabl Ludwig , Furth Priscilla , Hennighausen Lothar , Huh Jin Won 
Published: February 2022

AbstractHeterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2 or ChAdOx1. Yet, the molecular transcriptome, the germline allelic variants of immunoglobulin loci and anti-Omicron antibody levels induced by the heterologous vaccination have not been formally investigated. Moreover, there is a paucity of COVID vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 51 office workers from the Republic of Korea after a heterologous ChAdOx1-BNT162b2 vaccination or a homologous ChAdOx1-ChAdOx1 vaccination. Anti-spike-specific IgG antibody levels in the heterologous group increased from 14,000 U/ml to 142,000 AU/ml within eight days after the BNT162b2 vaccination. In contrast, antibody levels in the homologous group increased two-fold after the second ChAdOx1 dose. Antibody titers against the Omicron spike protein as compared to the ancestral strain were reduced to a lesser extent in the heterologous group. RNA-seq conducted on immune cells demonstrated a stronger activation of interferon-induced genetic programs in the heterologous cohort. An increase of specific IGHV clonal transcripts encoding neutralizing antibodies was preferentially detected in the heterologous cohort. Enrichment of B cell and CD4+ T cell responses were observed following both heterologous and homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the ChAdOx1-BNT162b2 cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous ChAdOx1 vaccinations but equivalent to that seen in homologous BNT162b2 vaccination.
Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity
Authors: Grenier-Larouche Thomas , Kwee Lydia Coulter , Deleye Yann , Leon-Mimila Paola , Walejko Jacquelyn M. , McGarrah Robert W. , Marceau Simon , Trahan Sylvain , Racine Christine , Carpentier André C , Lusis Aldons J. , Ilkayeva Olga , Vohl Marie-Claude , Huertas-Vazquez Adriana , Tchernof André , Shah Svati H. , Newgard Christopher B , White Phillip J 
Published: February 2022

ABSTRACTHepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). We aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-ketoacids (BCKAs) and hepatic BCKDK expression are associated with the presence and severity of non-alcoholic fatty liver disease (NAFLD).Eighty metabolites (3 BCKA, 14 amino acids, 43 acylcarnitines, 20 ceramides) were quantified in plasma from 288 bariatric surgery patients with severe obesity (BMI > 35 kg/m2) with scored liver biopsy samples. Metabolite principal component analysis (PCA) factors, BCKA, branched-chain amino acids (BCAA), and the BCKA:BCAA ratio were tested for associations with steatosis grade and presence of non-alcoholic steatohepatitis (NASH). Of all analytes tested, only the valine-derived BCKA, α-ketoisovalerate, and the BCKA:BCAA ratio were associated with both steatosis grade and NASH. Gene expression analysis in liver samples from two independent bariatric surgery cohorts showed that hepatic BCKDK mRNA expression correlates with steatosis, ballooning, and levels of the lipogenic transcription factor SREBP1. Experiments in AML12 hepatocytes showed that SREBP1 inhibition lowers BCKDK mRNA expression. These findings demonstrate that higher plasma levels of BCKA and hepatic expression of BCKDK are features of human NAFLD/NASH and identify SREBP1 as a transcriptional regulator of BCKDK.
Deploying wearable sensors for pandemic mitigation
Authors: Duarte Nathan , Arora Rahul K. , Bennett Graham , Wang Meng , Snyder Michael P. , Cooperstock Jeremy R. , Wagner Caroline E. 
Published: February 2022

ABSTRACTWearable sensors can continuously and passively detect potential respiratory infections, before or absent symptoms. However, the population-level impact of deploying these devices during pandemics is unclear. We built a compartmental model of Canada’s second COVID-19 wave and simulated wearable sensor deployment scenarios, systematically varying detection algorithm accuracy, uptake, and adherence. With current detection algorithms and 4% uptake, we found that deploying wearable sensors could have averted 9% of second wave SARS-CoV-2 infections, though 29% of this reduction is attributed to incorrectly quarantining uninfected device users. Improving detection specificity and offering confirmatory rapid tests each minimized incorrect quarantines and associated costs. With a sufficiently low false positive rate, increasing uptake and adherence became effective strategies for scaling averted infections. We concluded that wearable sensor deployment can meaningfully contribute to pandemic mitigation; in the case of COVID-19, technology improvements or supporting measures are required to reduce social and economic costs to acceptable levels.
Both general- and central- obesity are causally associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study
Authors: De Silva Kushan , Demmer Ryan T. , Jönsson Daniel , Mousa Aya , Teede Helena , Forbes Andrew , Enticott Joanne 
Published: February 2022

ABSTRACTIntroductionObesity is observed in a majority of women with polycystic ovarian syndrome (PCOS). Using body mass index (BMI) as a proxy, previous Mendelian randomization studies revealed general obesity potentially causes PCOS. Central obesity frequently demonstrates a stronger association with PCOS, although evidence on its causality is sparse.ObjectivesTo investigate causal effects of both central- and general- obesity on the development of PCOS via two-sample Mendelian randomization (2SMR).MethodsSummary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables – weight and height), from the IEU Open GWAS Project. As the outcome data, we acquired summary data from a large-sample GWAS (96391 samples; 219 cases and 96172 controls) from the FinnGen cohort. Four 2SMR methods were applied: inverse variance weighted (IVW); MR Egger (MRE); weighted median (WME); weighted mode (WMO). Single SNP-, leave-one-out-, heterogeneity-, horizontal pleiotropy- and outlier- analyses were conducted. Genetic architectures underlying causal associations were explored.ResultsAll SNPs selected as instrumental variables demonstrated no weak instrument bias (F > 10). Three anthropometric exposures, namely, BMI (OR: 5.55 – 7.24, WC (OR: 6.79 – 24.56), and HC (OR: 6.78 – 24.56), significantly causally associated with PCOS as per IVW, WME, and WMO models. Single SNP- and leave-one-out- sensitivity analysis results were indicative of robust causal estimates. No significant heterogeneity, horizontal pleiotropy, and outliers were observed. We observed a considerable degree of overlap (7 SNPs; 17 genes) across significant causal findings as well as a number of SNPs and genes that were not shared between causal associations.ConclusionsThis study revealed that both and general- and central obesity potentially cause PCOS. Findings underscore the importance of addressing obesity and adiposity for the prevention and management of PCOS.
Choroid plexus volume predicts expansion of chronic lesions and brain atrophy
Authors: Klistorner Samuel , Barnett Michael H , Graham Stuart L , Wang Chenyu , Klistorner Alexander 
Published: February 2022

Background and ObjectivesThe expansion of long-standing multiple sclerosis (MS) lesions and an enlargement of choroid plexus are linked to chronic inflammation and microglial activation. In the current study, we investigated the association between plexus volume and subsequent lesion expansion in patients with relapsing remitting MS.MethodsPre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 49 patients with relapsing-remitting MS. Choroid plexus volume and lesion activity were analysed between baseline and 48 months.ResultsPlexus volume remained stable during follow-up period. There was a strong correlation between baseline plexus volume and subsequent rate of chronic lesion expansion (r=0.77, p<0.001), which was stronger in close proximity to CSF. Furthermore, baseline plexus volume was also associated with change of Mean Diffusivity (MD) inside expanding area (r=0.55, p<0.001). There was, however, no correlation between baseline plexus volume and volume of new lesions. A cut-off of 98 × 10−5 plexus/TIV ratio predicted future lesion expansion with a sensitivity of 85% and specificity of 76%. Plexus volume larger than a cut-off was associated with >8-fold increased risk of chronic lesion expansion. Furthermore, baseline plexus volume significantly correlated with change of MD in lesional core during the study period (r=0.67, p<0.001) and with central brain atrophy (r=0.57, p<0.001).ConclusionOur data demonstrate that baseline plexus volume predicts subsequent expansion of chronic periventricular MS lesions and associated tissue damage.