bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Metric for Quantification of Iodine Contrast Enhancement (Q-ICE) in Computed Tomography
Authors: Szczykutowicz Timothy P. , Viggiano Ben , Rose Sean , Pickhardt Perry J. , Lubner Meghan G. 
Published: September 2021

Background
Poor contrast enhancement is related to issues with examination execution, contrast prescription, computed tomography (CT) protocols, and patient conditions. Currently, our community has no metric to monitor true enhancement on routine single-phase examinations because this requires knowledge of both pre- and postcontrast CT number.

Purpose
We propose an automatable solution to quantifying contrast enhancement without requiring a dedicated noncontrast series.

Methods
The difference in CT number between a target region in an enhanced and unenhanced image defines the metric “quantification of iodine contrast enhancement” (Q-ICE). Quantification of iodine contrast enhancement uses the noncontrast bolus tracking baseline image from routine abdominal examinations, which mitigates the need for a dedicated noncontrast series. We applied this method retrospectively to 312 patient livers from 2 sites between 2017 and 2020. Each site used a weight-based contrast injection protocol for weights 60 to 113 kg and a constant volume less than 60 kg and greater than 113 kg. Hypothesis testing was performed to compare Q-ICE between sites and detect Q-ICE dependence on weight and kilovoltage (kV).

Results
Mean Q-ICE differed between sites (P = 0.004) by 4.96 Hounsfield unit with 95% confidence interval (1.63–8.28), albeit this difference was roughly 2 times smaller than the SD in Q-ICE across patients at a single site. For patients between 60 and 113 kg, we did not observe evidence of Q-ICE varying with patient weight (P = 0.920 and 0.064 for 120 and 140 kV, respectively). The Q-ICE did vary with patient weight for patients less than 60 kg (P = 0.003) and greater than 113 kg (P = 0.04). We observed a roughly 10 Hounsfield unit reduction in Q-ICE liver for patients scanned with 140 versus 120 kV. We observed several underenhancing examinations with an arterial phase appearance motivating our CT protocol optimization team to consider increasing the delay for slowly enhancing patients.

Conclusions
A quality metric for quantifying CT contrast enhancement was developed and suggested tangible opportunities for quality improvement and potential financial savings.
Monosodium Urate Crystal Deposition in Coronary Artery Plaque by 128-Slice Dual-Energy Computed Tomography: An Ex Vivo Phantom and In Vivo Study
Authors: Feuchtner Gudrun M. , Plank Fabian , Beyer Christoph , Schwabl Christoph , Held Julia , Bellmann-Weiler Rosa , Weiss Guenther , Gruber Johann , Widmann Gerlig , Klauser Andrea S. 
Published: September 2021

Objective
Monosodium uric acid (MSU) crystals may accumulate in the coronary plaque. The objective was to assess whether dual-energy computed tomography (DECT) allows for detection of MSU in coronary plaque.

Methods
Patients were examined with 128-slice DECT applying a cardiac electrocardiogram-gated and peripheral extremity protocol. Patients were divided into 3 groups: gout (tophi >1 cm in peripheral joints), hyperuricemia (>6.5 mg/dL serum uric acid), and controls. The groups were matched for cardiovascular risk factors. Monosodium uric acid–positive (+) and calcified plaque were distinguished, and the coronary artery calcium score was calculated. Ex vivo phantom: MSU solutions were diluted in different NaCL solutions (5%/10%/15%/20%/25%). Coronary artery models with 2 different plaque types (MSU+ and calcified) were created.

Results
A total of 96 patients were included (37 with gout, 33 with hyperuricemia, and 26 controls). Monosodium uric acid–positive plaques were found more often in patients with gout as compared with controls (91.9% vs 0.38%; P < 0.0001), and the number of plaques was higher (P < 0.0001). Of 102 MSU+ plaques, 26.7% were only MSU+ and 74.2% were mixed MSU+/calcified. Monosodium uric acid–positive plaque had mean 232.3 Hounsfield units (range, 213–264). Coronary artery calcium score was higher in patients with gout as compared with controls (659.1 vs 112.4 Agatston score; P < 0.001). Patients with gout had more MSU+ plaques as compared with patients with hyperuricemia (91.6% vs 2.9%; P < 0.0001), and coronary artery calcium score was higher (659.1 vs 254 Agatston score; P < 0.001), but there was no difference between patients with hyperuricemia and controls. Ex vivo phantom study: MSU crystals were detected by DECT in solutions with a concentration of 15% or greater MSU and could be distinguished from calcified.

Conclusions
Coronary MSU+ plaques can be detected by DECT in patients with gout.
Genetic and Demographic Predictors of Latent Reading Ability in Two Cohorts
Authors: Lancaster Hope Sparks , Dinu Valentin , Li Jing , Gruen Jeffrey R ,   The GRaD Consortium
Published: August 2021

AbstractReading ability is a complex skill requiring multiple proficiencies (e.g., phonological awareness, decoding, and comprehension). Reading ability has genetic and environmental components that create the potential for significant gene-gene and gene-environment interactions, but the evidence for these interactions is limited. We used data from the Avon Longitudinal Study of Parents and Children and the Genes, Reading and Dyslexia Study to assess the contributions of genetic and demographic features to a continuous latent reading ability score. We then used this score as the phenotype on which to predicate genome-wide single nucleotide polymorph screening, followed by feature selection using an elastic net analysis. Results from the elastic net models showed that genetic and demographic features predicted reading ability for both cohorts. Five single nucleotide polymorphisms were associated with latent reading in the Avon Longitudinal Study of Parents and Children, as well as in the Genes, Reading and Dyslexia cohorts. For both cohorts, larger vocabularies were positively associated with latent reading ability. Genes within the neuron migration pathway were overrepresented in the Avon Longitudinal Study of Parents and Children cohort. We provide support that genes involved in early brain development have an impact on latent reading ability performance. Our findings also indicate high generalizability of genetic findings between cohorts, using our approach.
Prolonged SARS-CoV-2 infection in patients with lymphoid malignancies
Authors: Lee Christina Y. , Shah Monika K. , Hoyos David , Solovyov Alexander , Douglas Melanie , Taur Ying , Maslak Peter G. , Babady N. Esther , Greenbaum Benjamin , Kamboj Mini , Vardhana Santosha A. 
Published: August 2021

ABSTRACTCoronavirus disease 2019 (COVID-19) infection results in high mortality rates in patients with hematologic malignancies. Persistent and/or recurrent COVID-19 has not yet been demonstrated in this population. We identified patients with B-cell lymphomas as having a particularly high risk for persistent SARS-CoV-2 positivity. Subsequent analysis of patients with lymphoid malignancies and COVID-19 identified discrete risk factors for severity of primary infection as compared to disease chronicity. Active therapy and diminished T-cell counts were key drivers of acute mortality in lymphoma patients with COVID-19 infection. Conversely, B-cell depleting therapy was the primary driver of re-hospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population.Statement of SignificanceWe establish persistent symptomatic COVID-19 infection as a novel clinical syndrome in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.
Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomized controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)
Authors: Khare Satyajeet P. , Madhok Ayush , Patta Indumathi , Sukla Krishna K. , Wagh Vipul V. , Kunte Pooja S. , Raut Deepa , Bhat Dattatray , Kumaran Kalyanaraman , Fall Caroline , Tatu Utpal , Chandak Giriraj R. , Yajnik Chittaranjan S. , Galande Sanjeev 
Published: August 2021

AbstractIn The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomized controlled trial ‘Pune Rural Intervention in Young Adolescents (PRIYA)’. The interventions included: 1) vitamin B12+multi-micronutrients the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) and proteins (B12+MMN), 2) vitamin B12 (B12 alone), and 3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-Adenosyl Methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.
Thalamic deep brain stimulation modulates circadian and infradian cycles of seizure risk in epilepsy
Authors: Gregg Nicholas M. , Sladky Vladimir , Nejedly Petr , Mivalt Filip , Kim Inyong , Balzekas Irena , Sturges Beverly K. , Crowe Chelsea , Patterson Edward E. , Van Gompel Jamie J. , Lundstrom Brian N. , Leyde Kent , Denison Timothy J. , Brinkmann Benjamin H. , Kremen Vaclav , Worrell Gregory A. 
Published: August 2021

AbstractChronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (infradian) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months. All subjects had circadian and infradian cycles in the rate of interictal epileptiform spikes (IES). There was seizure phase locking to circadian and infradian IES cycles in five and seven out of eight subjects, respectively. Thalamic DBS modified circadian (all 3 subjects) and infradian (analysis limited to the human participant) IES cycles. DBS modified seizure clustering and circadian phase locking in the human subject. Multiscale cycles in brain excitability and seizure risk are features of human and canine epilepsy and are modifiable by thalamic DBS.
Associations between residential exposure to volatile organic compounds (VOCs) and liver injury markers
Authors: Wahlang Banrida , Gripshover Tyler C. , Gao Hong , Krivokhizhina Tatiana , Keith Rachel J. , Sithu Israel D. , Rai Shesh N. , Bhatnagar Aruni , McClain Craig J. , Srivastava Sanjay , Cave Mathew C. 
Published: August 2021

ABSTRACTOccupational exposures to volatile organic compounds (VOCs) have been associated with numerous health complications including steatohepatitis and liver cancer. However, the potential impact of environmental/residential VOC exposures on liver health and function is largely unknown. To address this knowledge gap, the objective of this cross-sectional study is to investigate associations between VOCs and liver injury biomarkers in community residents. Subjects were recruited from six Louisville neighborhoods, and informed consent was obtained. Exposure biomarkers included 16 creatinine-adjusted urinary metabolites corresponding to 12 parent VOCs. Serological disease biomarkers measured included cytokertain-18 (K18 M65 and M30), liver enzymes and direct bilirubin. Associations between exposure and disease biomarkers were assessed using generalized linear models. Smoking status was confirmed through urinary cotinine levels. The population comprised of approximately 60% females and 40% males; White persons accounted 78% of the population; with more nonsmokers (n=413) than smokers (n=250). When compared to nonsmokers, Males (45%) and Black persons (26%) were more likely to be smokers. In the overall population, metabolites of acrolein, acrylonitrile, acrylamide, 1,3-butadiene, crotonaldehyde, styrene and xylene were positively associated with alkaline phosphatase (ALP). These associations persisted in smokers, with the exception of crotonaldehyde, and addition of N,N dimethylformamide and propylene oxide metabolites. Although no positive associations were observed for K18 M30, the benzene metabolite was positively associated with bilirubin, irrespective of smoking status. Taken together, the results demonstrated that selected VOCs were positively associated with liver injury biomarkers. These findings will enable better risk assessment and identification of populations vulnerable to liver disease.
Predicting brain amyloid-β PET phenotypes with graph convolutional networks based on functional MRI and multi-level functional connectivity
Authors: Li Chaolin , Liu Mianxin , Xia Jing , Mei Lang , Yang Qing , Shi Feng , Zhang Han , Shen Dinggang 
Published: August 2021

AbstractThe detection of amyloid-β (Aβ) deposition in the brain provides crucial evidence in the clinical diagnosis of Alzheimer’s disease (AD). However, the efficiency of the current PET-based brain Aβ examination suffers from both coarse, visual inspection-based bi-class stratification and high scanning cost and risks. In this work, we explored the feasibility of using non-invasive functional magnetic resonance imaging (fMRI) to predict Aβ-PET phenotypes in the AD continuum with graph learning on brain networks. First, three whole-brain Aβ-PET phenotypes were identified through clustering and their association with clinical phenotypes were investigated. Second, both conventional and high-order functional connectivity (FC) networks were constructed using resting-state fMRI and the network topological architectures were learned with graph convolutional networks (GCNs) to predict such Aβ-PET phenotypes. The experiment of Aβ-PET phenotype prediction on 258 samples from the AD continuum showed that our algorithm achieved a high fMRI-to-PET prediction accuracy (78.8%). The results demonstrated the existence of distinguishable brain Aβ deposition phenotypes in the AD continuum and the feasibility of using artificial intelligence and non-invasive brain imaging technique to approximate PET-based evaluations. It can be a promising technique for high-throughput screening of AD with less costs and restrictions.
Population impact of SARS-CoV-2 variants with enhanced transmissibility and/or partial immune escape
Authors: Bushman Mary , Kahn Rebecca , Taylor Bradford P. , Lipsitch Marc , Hanage William P. 
Published: August 2021

SummarySARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic – especially that of immune escape – remains a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. We show that variants with enhanced transmissibility easily rise to high frequency, whereas partial immune escape, on its own, often fails to do so. However, when these phenotypes are combined, enhanced transmissibility can carry the variant to high frequency, at which point partial immune escape may limit the ability of vaccination to control the epidemic. Our findings suggest that moderate immune escape poses a low risk unless combined with a substantial increase in transmissibility.
Child and caregiver mental health during 12 months of the COVID-19 pandemic in Australia: findings from national repeated cross-sectional surveys
Authors: Price Anna M. H. , Measey Mary-Anne , Hoq Monsurul , Rhodes Anthea , Goldfeld Sharon 
Published: August 2021

ABSTRACTBackgroundThere are calls for research into the mental health consequences of living through the COVID-19 pandemic. Australia’s initial, effective suppression of COVID-19 offers insights into these indirect impacts in the relative absence of the disease. We aimed to describe the mental health experiences of Australian caregivers and children over 12 months, reporting differences related to demographic, socioeconomic and lockdown characteristics.MethodsData were from Australia’s only nationally representative, repeated cross-sectional survey of caregivers with children (0-17 years). N=2020 caregivers participated in June 2020, N=1434 in September 2020, and N=2508 in July 2021. Caregivers reported their mental health (poor versus not, Kessler-6), and perceived impacts of the pandemic on theirs and their children’s mental health (negative versus none/positive). Data were weighted to approximate population distributions of caregiver age, gender, sole-caregiving, number and ages of children, state/territory and neighbourhood-level disadvantage.ResultsPerceived impacts on mental health were more frequently negative for female (versus male) caregivers and older (versus younger) children. Poor caregiver mental health (K6) was more common for families experiencing socioeconomic adversity (especially financial), while perceived impacts were more frequently negative for more socially advantaged groups. Caregivers who experienced the least total lockdown reported similar K6 over time. Otherwise, poor mental health and perceived negative impacts increased over time with increasing total length of lockdown.ConclusionDespite Australia’s low infection rates, the negative mental health experiences of the COVID-19 pandemic are real and concerning. Addressing poor mental health must be central to ongoing pandemic recovery efforts for families and children.What is known about this topic?-The global evidence shows that, for general adult populations, psychological distress peaked in the first months of the COVID-19 pandemic before appearing to improve.-Less is known about mental health over time of living through the pandemic, especially for caregivers and children. There are urgent calls for research.-Due to low infection rates, Australia’s experience can provide insight into the mental health impacts of lockdown with minimal compounding harms of the virus.What this study adds-From June 2020 to July 2021, Australia’s lockdowns were detrimental for caregiver and child mental health.-Negative mental health experiences differed by caregiver gender, child age and family socioeconomic characteristics.-Pandemic response and recovery planning must consider both family mental health and socioeconomic security.
Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease
Authors: Sandholm Niina , Cole Joanne B , Nair Viji , Sheng Xin , Liu Hongbo , Ahlqvist Emma , van Zuydam Natalie , Dahlström Emma H , Fermin Damian , Smyth Laura J , Salem Rany M , Forsblom Carol , Valo Erkka , Harjutsalo Valma , Brennan Eoin P , McKay Gareth , Andrews Darrell , Doyle Ross , Looker Helen C , Nelson Robert G , Palmer Colin , McKnight Amy Jayne , Godson Catherine , Maxwell Alexander P , Groop Leif , McCarthy Mark I , Kretzler Matthias , Susztak Katalin , Hirschhorn Joel N , Florez Jose C , Groop Per-Henrik ,   for the GENIE Consortium
Published: August 2021

AbstractBackgroundDiabetes is the leading cause of kidney disease, and heritability studies demonstrate a substantial, yet poorly understood, contribution of genetics to kidney complications in people with diabetes.MethodsWe performed genome-wide association study (GWAS) meta-analyses using ten different phenotypic definitions of diabetic kidney disease (DKD), including nearly 27,000 individuals with diabetes, and integrated the results with various kidney omics datasets.ResultsThe meta-analysis identified a novel low frequency intronic variant (rs72831309) in the TENM2 gene encoding teneurin transmembrane protein 2 associated with a lower risk of the combined chronic kidney disease (CKD; eGFR<60 ml/min/1.73 m2) and DKD (microalbuminuria or worse) phenotype (“CKD-DKD”, odds ratio 2.08, p=9.8×10−9). Gene-level analysis identified ten genes associated with DKD (COL20A1, DCLK1, EIF4E, PTPRN-RESP18, GPR158, INIP-SNX30, LSM14A, and MFF, p<2.7×10−6). Integration of GWAS data with human glomerular and tubular expression data in a transcriptome-wide association study demonstrated higher tubular AKIRIN2 gene expression in DKD versus non-DKD controls (p=1.1×10−6). The lead SNPs within the DCLK1, AKIRIN2, SNX30 and three other gene regions significantly alterated the methylation at this region in kidneys (p<2.2×10−11). Expression of target genes in kidney tubules or glomeruli correlated with relevant pathological phenotypes. For example, tubular TENM2 expression positively correlated with eGFR (p=2.3×10−9) and negatively with tubulointerstitial fibrosis (p=4.7×10−9), tubular DCLK1 expression positively correlated with fibrosis (p=1.6×10−12), and SNX30 level positively correlated with eGFR (p=7.6×10−13) and negatively with fibrosis (p<2×10−16).ConclusionsGWAS meta-analysis and integration with renal omics data points to novel genes contributing to pathogenesis of DKD.