bluuebunny/crossref_metadata_2025 huggingface dataset:
821Surrounding greenness is associated with slower biological ageing based on epigenetics
Authors: Xu Rongbin , Li Shuai , Li Shanshan , Abramson Michael , Hopper John , Guo Yuming
Published: September 2021

Background

High surrounding greenness has many health benefits, but few studies have evaluated these from the perspective of epigenetics.

Methods

We derived Horvath’s DNA methylation age (DNAmAge), Hannum’s DNAmAge, PhenoAge, and GrimAge from DNA methylation data measured from peripheral blood samples of 479 Australian women in 130 families. The DNA methylation age acceleration (DNAmAgeAC) was calculated as the residuals after regressing DNAmAge on chronological age. Greenness was represented by the satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) within 300m, 500m, 1000m and 2000m surrounding participants’ home addresses. The greenness-DNAmAgeAC association was evaluated using a within-sibship design fitted by linear mixed effect models, adjusting for familial clustering and important covariates.

Results

Our analyses based on the whole sample suggested that the greenness-DNAmAgeAC association was only statistically significant for GrimAge acceleration. Each inter-quartile range (IQR) increase in NDVI within 1000m was associated with 0.59 (95% CI: 0.18, 1.01) year decrease in GrimAge acceleration. Greenness was also inversely associated with GrimAge’s three DNA methylation based components (cystatin-C, growth differentiation factor 15, and smoking pack-years). For participants at higher 50% area-level socioeconomic status (SES), each IQR increase in NDVI within 1000m was associated with 1.24 (95%CI: 0.39, 2.09) year and 0.79 (95%CI: 0.29, 1.30) year decrease in Hannum’s DNAmAgeAC and GrimAge acceleration, respectively.

Conclusions

Higher surrounding greenness was associated with slower biological aging measured by GrimAge acceleration and Hannun’s DNAmAgeAC in Australian women, particularly among those who lived in areas at higher SES.

Key messages

Epigenetics provides a potential mechanism for why surrounding greenness is an important health issue for community construction.
506Mathematical modelling of the transmission of Neisseria gonorrhoeae in men who have sex with men
Authors: Xu Xianglong , Chow Eric P.F , Shen Mingwang , Ong Jason J. , Hoebe Christian JPA , Williamson Deborah , Hocking Jane , Fairley Christopher K , Zhang Lei
Published: September 2021

Background

There is controversy about what sexual practices or secretions (e.g. saliva) transmit Neisseria gonorrhoeae in men who have sex with men (MSM). To date, no studies have modelled potential transmission when one sexual practice follows another in the same sexual encounter or the role of sexual secretions in transmission.

Methods

We developed eight compartmental models to examine three additional transmission routes: (1) oral sex followed by anal sex (or vice versa); (2) using saliva as a lubricant for penile-anal sex, and (3) oral sex followed by oral-anal sex (rimming) or vice versa. For comparison, we used a baseline model that did not include any of these three transmission routes. The seven other models added one of the additional transmission routes or combinations of the three of them to the baseline model.

Results

The baseline model could replicate infection at the single anatomical site but underestimated infection at more than one anatomical site (‘multi-site infection’). When we added the three transmission routes to the baseline model, oral sex followed by anal sex or vice versa could replicate the prevalence of multi-site infection. The other two transmission routes alone or together could not replicate multi-site infection without the inclusion of oral sex followed by anal sex.

Conclusions

Our model suggests sexual practices that involve oral followed by anal sex (or vice versa) may be important for explaining the high proportion of multi-site infection.

Key messages

For Neisseria gonorrhoeae transmission, additional transmission routes are necessary to replicate multi-site infection.
1197Identification of insulin signaling pathway-related circulating circRNAs as novel biomarkers of type 2 diabetes
Authors: Yan Yu-xiang , Lu Ya-Ke , Chu Xi , Sun Yue , Dong Jing
Published: September 2021

Background

The underlying molecular mechanism of type 2 diabetes (T2D) and insulin resistance is that abnormalities occur in the complex insulin signaling pathway. Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. This study screened and validated the insulin signaling pathway-related circulating circRNAs, which are associated with T2D.

Methods

Based on circRNA microarray, candidate circRNAs involved in the insulin PI3K/Akt signaling pathway were selected and validated by RT-qPCR. The association between circRNAs and T2D and their clinical significance were further assessed by logistic regression model, correlation analysis and ROC curve in a large cohort. The miRNA targets of validated circRNAs was verified by dual-luciferase reporter assay.

Results

A total of 370 upregulated circRNAs and 180 downregulated circRNAs were differentially expressed between new T2D cases and controls. hsa_circ_0063425, hsa_circ_0056891 and hsa_circ_0104123 were selected as candidate circRNAs for validation. Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, impaired fasting glucose (IFG) and insulin resistance. The two-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significantly positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels.

Conclusion

hsa_circ_0063425 and hsa_circ_0056891 are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.

Key messages

Insulin signaling pathway-related circulating circRNAs was identification as novel biomarkers of type 2 diabetes.

Keywords

circRNA; type 2 diabetes; insulin signaling; biomarker.
1438Dynamics of inter-farm transmission of highly pathogenic avian influenza integrating vehicle movements and phylogenetic information
Authors: Yoo Dae-sung , Chul Chun Byung
Published: September 2021

Background

Highly pathogenic avian influenza (HPAI), a zoonotic infectious disease, has been considered a severe threat to public health. The fundamental prevention and control strategy against HPAI includes minimizing the outbreaks of poultry holdings where the virus primarily spreads through animal trade and poultry production associated vehicle movement (PPVM). However, very few attempts have been made to elucidate the association between PPVM and HPAI transmission compared to studies on poultry trade. Therefore, our study aimed to elucidate the role of PPVM on HPAI transmission.

Methods

We performed network analysis using PPVM data based on a global positioning system (GPS), with phylogenetic information of the HPAI virus for reliable estimation. Moreover, the contribution of PPVM to HPAI infection was estimated by Bayesian inference.

Results

The network analysis revealed that the connection via PPVM between the same genetic group of infected premises (IPs) was more prevalent than that of different genotype IPs. Moreover, the similarity of farm poultry species and the overlapped integrators between inter-linked IPs was associated with potential transmission route formation. Additionally, the contribution of PPVM among phylogenetically clustered IPs was estimated to have 28.25% of HPAI infections in IPs on average.

Conclusions

HPAI control strategies including targeted movement restriction and standstill should be established against the HPAI transmission via PPVM.

Key messages

This is a solid and novel study depicting the need for combining epidemiological analysis with data regarding molecular epidemiology of pathogens.
962Adolescent Alcohol Use Trajectories: A Prospective Study of Risk Factors and Adulthood AUD Outcomes
Authors: Yuen Wing See , Chan Gary , Clare Philip , Bruno Raimondo , Boland Veronica , Aiken Alexandra , Kypri Kypros , Horwood John , McCambridge Jim , Degenhardt Louisa , Slade Tim , Wadolowski Monika , Hutchinson Delyse , Najman Jake , McBride Nyanda , Mattick Richard , Peacock Amy
Published: September 2021

Background

Adolescents often display heterogenous trajectories of alcohol use. Initiation and escalation of drinking may be an important predictor of later harms. Previous attempts to conceptualise these trajectories lacked adjustment for known confounders of adolescent drinking, which our study has aimed to address by modelling dynamic changes in drinking whilst adjusting for parent, child, and peer factors.

Methods

Survey data from a longitudinal cohort of Australian adolescents (n = 1813) were used to model latent class alcohol use trajectories over five annual follow-ups (Mage=13.9 and 17.8 years). Regression models determined whether child, parent, and peer factors at baseline (Mage =12.9 years) predicted trajectory membership and whether trajectories predicted self-reported symptoms of AUD in early adulthood (Mage =18.8 years).

Results

We identified a four-class solution: abstaining (n = 352); late-onset moderate drinking (n = 503); early-onset moderate drinking (n = 663); and early-onset heavy drinking (n = 295). Alcohol-specific household rules reduced risk of early-onset heavy drinking compared to late-onset moderate drinking (RRR: 0.31; 99.5% CI: 0.11, 0.83), whereas substance-using peers increased this risk (RRR: 3.43; 99.5% CI: 2.10, 5.62). Early-onset heavy drinking increased odds of meeting criteria for AUD in early adulthood (OR: 7.68; 99.5% CI: 2.41, 24.47).

Conclusions

Our study provides evidence that early initiation and heavy alcohol use throughout adolescence is associated with increased risk of alcohol-related harm compared to recommended maximum levels of consumption (late-onset, moderate drinking).

Key messages

Parenting factors and peer influences in early adolescence should be considered to reduce risk of early initiation and heavy drinking, which in turn reduces risk of later harm.
1472Spatial clusters and affecting factors on Alzheimer's disease death in South Korea
Authors: Yum Sujin , Hong Kwan , Kim Jeehyun , Gomez Raquel Elizabeth Gomez , Chun Byung Chul
Published: September 2021

Background

The prevalence of dementia is increasing worldwide; and dementia deaths are also increasing. In South Korea, deaths from Alzheimer's disease (AD) ranked 9th in the 2018 cause of death statistics, and the ranking has risen.

Methods

We collected 2009 to 2018 AD deaths and related data from Statistics Korea and Community Health Survey. SaTScan software was used for detecting and evaluating the clusters with high risk in AD deaths, and R version 4.0.3 was used for mapping and analysis of affecting factors.

Results

A total of 39,412 people died from AD during 10 years in Korea, 7.7 per 100,000 inhabitants. While 98.7% of deaths were above-65 age, the proportion of under 65 was also rising. The global Moran index of 10 years’ AD deaths was 0.2 (P < 0.01), and the clusters were detected primarily in southern rural region. According to the spatial regression analysis, AD deaths in 2018 were increased in area with lower dementia screening rate, long-term care workers, and higher home-care service usage rate in long-term care, inhabitants educated about dementia.

Conclusions

Some clusters of AD deaths were identified, and they were influenced by institutional factors. It is necessary that the local government considers characteristics of each region when implementing the dementia policies.

Key messages

AD deaths in South Korea were increasing from 2009 to 2018, and their clusters were observed in southern regions. AD deaths in 2018 were influenced by dementia-related policies.
71Advanced Environmental Epidemiology for Health and Climate Research
Authors: Zhang Ying
Published: September 2021

Focus and outcomes for participants

The symposium will focus on insights and applications of advanced environmental epidemiology methods in health and climate research. The symposium will help the participants

Rationale for the symposium, including for its inclusion in the Congress

Climate change is the greatest health challenge in the 21st century. The most recent Lancet Countdown report (Watts et al. 2019) and the MJA-Lancet Countdown Australian reports (Zhang et al. 2018; Beggs et al. 2019) on health and climate change research have once again highlighted the global vulnerability to health risks from climate change. Epidemiology plays an important role in informing policy to protect the public’s health from a changing climate. However, limited research has been conducted in the field, which may be due to the methodological challenges to conducting research in climate change epidemiology (Xun et al. 2010). However, there are opportunities for advancing epidemiological research in the context of climate change, as highlighted in the recent paper published in the American Journal of Epidemiology (Anderson et al. 2019). The proposed symposium aligns precisely with the conference theme on methodological innovations in epidemiology and the need for epidemiologists who are keen to address non-traditional epidemiological health risks to support decision-making under a changing climate. This symposium will be a timely event to build capacity needed to address more extreme weather events and disasters related to climate change in Australia and globally.

Presentation program (90 minutes)

The symposium will have 6 presentations, 15 minutes each including Q&A.

Names and short biography of presenters
861Mendelian randomization on habitual coffee intake and plasma lipid profile: evidence from UK Biobank
Authors: Zhou Ang , Hyppönen Elina
Published: September 2021

Background

Long-term heavy coffee consumption may adversely affect individuals’ cardiovascular disease (CVD) risk. As hyperlipidemia is a well-established contributor to CVD, we investigated the association between habitual coffee intake and plasma lipid profile.

Methods

We used data from up to 362,571 UK Biobank participants to examine associations between coffee intake and plasma lipid profiles, including LDL-C, HDL-C, total-C, triglycerides, ApoA1 and ApoB. Inverse variance weighted mendelian randomization (MR) was used to interrogate the causal nature of coffee-lipid associations, complemented by pleiotropy-robust methods, including MR-median, MR-Mode, MR-PRESSO and MR-Egger.

Results

We observed positive dose-dependent associations between self-reported coffee intake and plasma concentration of LDL-C, ApoB and total-C, with the highest lipid levels seen among participants drinking >6 cups/day (Plinear trend≤1.97E-57 for all). Genetic instrument for coffee intake was robustly associated with self-reported intake in the UK Biobank (F-statistic = 416). One cup increase in genetically instrumented intake was associated with 0.07 mmol/L (95%CI 0.03 to 0.12), 0.02 g/L (95%CI 0.01 to 0.03), and 0.09 mmol/L (95%CI 0.04 to 0.14) increase in LDL-C, ApoB, and total-C, respectively. Pleiotropy-robust methods provided largely consistent results albeit with greater imprecision when using MR-Egger.

Conclusions

Our phenotypic and genetic analysis consistently suggests that long-term heavy coffee consumption can lead to unfavourable lipid profile, which could potentially increase individuals’ risk for CVD. Individuals with elevated cholesterol may need to reduce their daily coffee intake.

Key messages

Our study provides evidence that long-term heavy coffee consumption can lead to unfavourable lipid profile.
Alternaria spp. Associated with Leaf Blight of Maize in Heilongjiang Province, China
Authors: Xu Xi , Zhang Li , Yang Xilang , Cao Hanshui , Li Jingjing , Cao Peng , Guo Lifeng , Wang Xiangjing , Zhao Junwei , Xiang Wensheng
Published: September 2021

Maize (Zea mays L.) is a major economic crop worldwide. Maize can be infected by Alternaria species causing leaf blight that can result in significant economic losses. In this study, 168 Alternaria isolates recovered from symptomatic maize leaves were identified based on morphological characteristics, pathogenicity, and multilocus sequence analyses of the genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the internal transcribed spacer of ribosomal DNA (rDNA ITS), the RNA polymerase II second largest subunit (RPB2), and histone3 (HIS3). Maize isolates grouped to four Alternaria species including Alternaria tenuissima, A. alternata, A. burnsii, and Alternaria sp. Notably, A. tenuissima (71.4%) was the most prevalent of the four isolated species, followed by A. alternata (21.5%), Alternaria sp. (4.1%), and A. burnsii (3.0%). Pathogenicity tests showed that all four Alternaria species could produce elliptic to nearly round, or strip, lesions on leaves of maize, gray-white to dry white in the lesion centers and reddish-brown at the edges. The average disease incidence (58.47%) and average disease index (63.55) of maize leaves inoculated with A. alternata were significantly higher than levels resulting from A. tenuissima (55.28% and 58.49), Alternaria sp. (55.34% and 58.75), and A. burnsii (56% and 55). Haplotype analyses indicated that there were 14 haplotypes of A. tenuissima and five haplotypes of A. alternata in Heilongjiang Province and suggested the occurrence of a population expansion. Results of the study showed that Alternaria species associated with maize leaf blight in Heilongjiang Province are more diverse than those that have been previously reported. This is the first report globally of A. tenuissima, A. burnsii, and an unclassified Alternaria species as causal agents of leaf blight on maize.
Validation of the Giannella Risk Score for the Prediction of Infection by Carbapenemase-producing Enterobacteriaceae in the Pediatric Population
Authors: Garazzino Silvia , Balletto Elisa , Licciardi Francesco , Denina Marco , Carraro Francesca , Contino Amalia , Palmero Candida , Ugolotti Elisabetta , Silvestro Erika , Castagnola Elio
Published: September 2021

Background:

Despite efforts made to prevent the spread of multi–drug-resistant bacteria, carbapenemase-producing Enterobacteriaceae (CPE) has become one of the most dangerous threat worldwide. However, data on the epidemiology of CPE and on the correlation between CPE colonization and infection are scanty. The objectives of this study were first to describe the epidemiologic characteristics of colonizations and invasive CPE infections in the pediatric population, and second, to apply the Giannella Risk Score (GRS) to the pediatric population for the assessment of the risk of invasive CPE infection in patients with already known colonization.

Methods:

Pediatric patients with evidence of colonization by CPE were retrospectively enrolled. For each colonized patient, the subsequent development of an infection by CPE was then assessed for a 90-day period after the first CPE isolation; GRSs were compared between patients who had developed any type of CPE infection and those without infection.

Results:

A total of 215 patients (113 males and 102 females) with at least 1 isolation of CPE during hospitalization were analyzed. Median age was 5.6 years [interquartile range (IQR), 1.89–12.2 years]. Overall, 28 CPE infections (13%) were documented: 23 blood stream infections and 5 complicated urinary tract infections. The 30-day mortality of invasive CPE infections was 34.8%. The GRS values in patients with any CPE infection were statistically higher than in noninfected patients: median GRS 9 (IQR, 4–12.5) versus 4 (IQR, 2–4), respectively; P < 0.0001. The analysis of the receiver operating characteristic curves identified a GRS cut-off value ≥8 as the best predictor of CPE infection. The likelihood ratio of the results was <2 and the informedness of the test had a value <0.50.

Conclusions:

Our study confirms that the spread of CPE is an impelling problem also in the pediatric population, with a high mortality rate of invasive infections. However, the application of the GRS appears to be poorly informative in the pediatric setting; it might sometimes help to identify patients at very low-risk of CPE infection, in whom it is reasonable to spare targeted antimicrobial treatments.
Pharmacological treatments of neuropathic pain: real-life comparisons using propensity score matching
Authors: Moisset Xavier , Pagé M. Gabrielle , Pereira Bruno , Choinière Manon
Published: September 2021

Studies comparing different drug treatments for chronic neuropathic pain (NP) are very limited. We, therefore, examined 4 recommended treatments, namely, antidepressants (duloxetine, venlafaxine, and tricyclic antidepressants), antiepileptics (gabapentine and pregabalin), weak opioids, and strong opioids, among patients with NP evaluated before first visit in a tertiary pain treatment centre and 6 months later. Patients with both a clinical diagnosis of NP and a DN4 score ≥3/7 were selected from patients enrolled in the Quebec Pain Registry. Each participant was assigned an inverse weighting of the probability of receiving any NP treatment, taking into account their age, sex, baseline pain intensity, pain duration, pain catastrophizing tendency, education level, employment, and comedications at 6-month follow-up (M6). Patients were considered as improved if they presented at least a 30% reduction on average pain intensity at M6 compared with baseline. A total of 944 patients completed both baseline and M6 evaluations. Overall, 23.0% of patients were significantly improved for pain intensity at M6. There was no significant difference in proportions patients taking or not antidepressants, gabapentinoids, or weak opioids. Among patients taking strong opioids (N = 288), 13.9% (N = 40/288) were improved vs 27.0% (177/656) of those who were not on opioids (P < 0.004). Inverse probability of treatment weighting confirmed that the proportion of patients who improved was significantly lower among those taking strong opioids compared with those who did not (P < 0.001). In conclusion, long-term use of strong opioids is a treatment suited for a limited proportion of patients with chronic NP.
Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial
Authors: Vela Jonathan , Dreyer Lene , Petersen Kristian Kjær , Arendt-Nielsen Lars , Duch Kirsten Skjærbæk , Kristensen Salome
Published: September 2021

Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval −9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.
Behavioral outcomes of complete Freund adjuvant–induced inflammatory pain in the rodent hind paw: a systematic review and meta-analysis
Authors: Burek Dominika J. , Massaly Nicolas , Yoon Hye Jean , Doering Michelle , Morón Jose A.
Published: September 2021

Many analgesics inadequately address the psychiatric comorbidities of chronic and persistent pain, but there is no standard preclinical model of pain-altered behavior to support the development of new therapies. To explore this conflicting and inconclusive literature, we conducted a focused systematic review and meta-analysis on the effect of complete Freund adjuvant–induced (CFA) rodent hind paw inflammation on multiple classical indicators of exploratory behavior, stress coping, and naturalistic behavior. Our primary objective was to define CFA's effect on assays including, but not limited to, the elevated plus maze and forced swim test. Our secondary objective was to discover how variables such as species and strain may influence outcomes in such assays. We searched Ovid MEDLINE, Embase, Scopus, and Web of Science in April and October 2020 for studies with adult rodents injected with CFA into the hind paw and subsequently tested for aspects of “anxiety-like” or “depressive-like” behaviors. Forty-four studies evaluated performance in the elevated plus or zero maze, open field test, light–dark box, place escape and avoidance paradigm, forced swim test, tail suspension test, sucrose preference test, wheel running, and burrowing assay. Complete Freund adjuvant modestly but significantly decreased exploratory behavior, significantly increased passive stress coping in the tail suspension test but not the forced swim test, and significantly decreased preference for sucrose and naturally rewarding activity. Subgroup analyses revealed significant differences between species and animal sourcing. Based on the evidence provided here, we conclude future studies should focus on CFA's effect on natural rewards and naturalistic behaviors.
Use of NOACs Versus Vitamin K Antagonist in Atrial Fibrillation Catheter Ablation: An Updated Meta-analysis With Subgroup Analysis
Authors: Bhogal Sukhdeep , Mawa Kajal , Bhandari Tarun , Ramu Vijay
Published: September 2021

Background:

Current guidelines give class I recommendations for uninterrupted use of dabigatran rivaroxaban as an alternative to vitamin K antagonist (VKA) in patients of atrial fibrillation (AF) who are undergoing catheter ablation. The recent randomized controlled trials have shown similar efficacy of novel oral anticoagulants when compared to VKA in these patients. We sought to perform a meta-analysis with a focus on subgroup analysis of novel oral anticoagulants.

Methods:

We searched PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through August 2020. Six RCTs studies (n = 2260) comparing the use of NOACs versus VKA in patients with AF undergoing catheter ablation were included. The odds ratio (OR) with 95% confidence interval was computed and P < 0.05 was considered as a level of significance. Major adverse cardiac events (MACE) were considered as a primary endpoint.

Results:

Our results showed a significant difference in MACE between NOACs and VKA [OR 0.57 (0.37–0.88); P = 0.01] and in major bleeding events [OR 0.55 (0.35–0.86); P = 0.009], which is mainly derived from the use of dabigatran. No significant difference in MACE or major bleeding events was found on the subgroup analysis of rivaroxaban and apixaban over VKA therapy.

Conclusion:

Uninterrupted use of NOACs is safe and effective alternative for the prevention of cerebral thromboembolism and reducing the risk of major bleeding in patients undergoing catheter ablation of AF. However, the individual subgroup analysis showed that only dabigatran is superior to VKA in terms of reducing MACE through a reduction in major bleeding. The rivaroxaban, apixaban and edoxaban are non-inferior to VKA therapy based on these results. Further studies are needed to generalize these recommendations in morbidly obese patients.
Prediction of Genetic Alterations in Oncogenic Signaling Pathways in Squamous Cell Carcinoma of the Head and Neck: Radiogenomic Analysis Based on Computed Tomography Images
Authors: Wu Linyong , Lin Peng , Zhao Yujia , Li Xin , Yang Hong , He Yun
Published: September 2021

Objective

This study investigated the role of radiomics in evaluating the alterations of oncogenic signaling pathways in head and neck cancer.

Methods

Radiomics features were extracted from 106 enhanced computed tomography images with head and neck squamous cell carcinoma. Support vector machine–recursive feature elimination was used for feature selection. Support vector machine algorithm was used to develop radiomics scores to predict genetic alterations in oncogenic signaling pathways. The performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve.

Results

The alterations of the Cell Cycle, HIPPO, NOTCH, PI3K, RTK RAS, and TP53 signaling pathways were predicted by radiomics scores. The AUC values of the training cohort were 0.94, 0.91, 0.94, 0.93, 0.87, and 0.93, respectively. The AUC values of the validation cohort were all greater than 0.7.

Conclusions

Radiogenomics is a new method for noninvasive acquisition of tumor molecular information at the genetic level.
Comparison of Radiation Dose and Image Quality Between Split-Filter Twin Beam Dual-Energy Images and Single-Energy Images in Single-Source Contrast-Enhanced Chest Computed Tomography
Authors: Zhou Li-Na , Zhao Shi-Jun , Wang Ruo-Bing , Wang Ya-Wen , Yang Shou-Xin , Wu Ning
Published: September 2021

Objective

To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT).

Methods

Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate.

Results

The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001).

Conclusions

The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.
Modified Maximal Levator Palpebrae Superioris Shortening in Correcting Congenital Severe Ptosis in Children
Authors: Liu Ninghua , He Aijuan , Wu Dan , Zhang Jing , Song Nan
Published: September 2021

Objective

This study aims to evaluate the clinical effect of modified maximal levator palpebrae superioris shortening method for severe congenital ptosis.

Methods

A retrospective case series was performed including 66 eyes from 62 patients who underwent modified maximal levator palpebrae superioris shortening surgery to treat severe congenital ptosis between February 2015 and November 2018. Preoperative and postoperative margin reflex distance 1 and levator muscle function were recorded. The surgical results were graded as good, satisfied, and poor for functional and cosmetic improvement of the eyelids, and the incidence of complications was also documented.

Results

The mean patient age at the time of surgery was 4.6 ± 1.8 years (2–9 years), and the mean follow-up time was 36.3 ± 14.1 (12–55 months). A mean significant improvement in margin reflex distance 1 and levator function after operation was noted (P < 0.01). The eyelid height and symmetry were satisfied in 59 patients, with success rate of 95.2%. For the patients in the levator function (≤2 mm) group, the success rate was 87.5%. Moreover, the levator function (≤2 mm) group had a higher rate of poor results than levator function (2–4 mm) group (12.5% vs 2.2%). Overcorrection (6.5%) and eyelid fold deformity (11.3%) were the most frequent postoperative complications.

Conclusion

Modified maximal levator palpebrae superioris shortening was effective and endurable in the treatment of severe congenital ptosis with poor levator function, including in patients whose levator function was less than 2 mm.
Disconnected Motor Intention and Spatial Attention in a Case of Probable Marchiafava-Bignami Disease
Authors: Kobayashi Shunsuke , Hirose Masaki , Akutsu Yukiko , Hirayama Kazumi , Ishida Yoshinori , Ugawa Yoshikazu
Published: September 2021

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism that typically causes demyelination and necrosis of the corpus callosum. Here, we report a man with probable MBD with callosal and right medial paracentral lesions who presented with abnormal reaching behavior and ideomotor apraxia of the left hand. He exhibited difficulty in reaching with the left hand when a target object was placed on his right-hand side, and he exhibited rightward bias when using his right hand in a line bisection task. These disturbances in reaching suggest disruption of the top–down control of motor intention and spatial attention at the corpus callosum.
Neuropsychological Profile of an Adolescent Female With Ectodermal Dysplasia With Hypohidrosis
Authors: Kaczorowski Jessica A. , Doty Nathan , Shrewsbury Amanda , Doyle Alysa E. , Tan Queenie K-G. , Braaten Ellen
Published: September 2021

The ectodermal dysplasias are a group of rare genetic disorders that are caused by abnormalities in cell and tissue development of the embryonic ectoderm. A paucity of research has systematically examined the cognitive, academic, and psychological phenotype of individuals with ectodermal dysplasia. We describe the neuropsychological profile of a female adolescent with ectodermal dysplasia with hypohidrosis. Using a battery of standardized tests, we assessed the adolescent’s intellectual functioning, language processing, visuospatial and visuomotor functioning, perceptual reasoning, sensory–motor functioning, memory, executive functioning, academic functioning, emotional and behavioral functioning, and adaptive functioning. Results from the testing indicated that the adolescent possessed relative verbal strengths, with scores generally falling in the low average to average range. However, she exhibited severe deficits in visuospatial functioning, visuomotor construction/organization, visuomotor integration, visual memory, executive functioning, reading, and math. She also presented with symptoms of anxiety and depression but had relatively strong adaptive skills. Based on the testing results from our evaluation, the adolescent met the criteria for specific learning disorders with impairment in reading and math, generalized anxiety disorder, and major depressive disorder. To our knowledge, this is the first case report to comprehensively characterize the full neuropsychological and academic profile of an adolescent female with ectodermal dysplasia with hypohidrosis. Recommendations from the evaluation are presented to inform clinical practice with, and future research of, this population.
Covid-19 Vaccine Effectiveness in Healthcare Personnel in six Israeli Hospitals (CoVEHPI)
Authors: Katz Mark A. , Harlev Efrat Bron , Chazan Bibiana , Chowers Michal , Greenberg David , Peretz Alon , Tshori Sagi , Levy Joseph , Yacobi Mili , Hirsch Avital , Amichay Doron , Weinberger Ronit , Dor Anat Ben , Taraday Elena Keren , Reznik Dana , Chayat Chen Barazani , Sagas Dana , Zvi Haim Ben , Berdinstein Rita , Rashid Gloria , Avni Yonat Shemer , Mandelboim Michal , Zuckerman Neta , Rainy Nir , Akriv Amichay , Dagan Noa , Kepten Eldad , Barda Noam , Balicer Ran D.
Published: September 2021

Background

Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate real-world VE in a closely monitored population.

Methods

We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test.

Findings

Of the 1,567 HCP enrolled between December 27, 2020 and February 15, 2021, 1,250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR- confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.

Interpretation

Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 during a period of predominant alpha variant circulation.

Funding

Clalit Health Services
Cardiovascular disease and all-cause mortality risk prediction from abdominal CT using deep learning
Authors: Elton Daniel C. , Chen Andy , Pickhardt Perry J. , Summers Ronald M.
Published: September 2021

Cardiovascular disease is the number one cause of mortality worldwide. Risk prediction can help incentivize lifestyle changes and inform targeted preventative treatment. In this work we explore utilizing a convolutional neural network (CNN) to predict cardiovascular disease risk from abdominal CT scans taken for routine CT colonography in otherwise healthy patients aged 50-65. We find that adding a variational autoencoder (VAE) to the CNN classifier improves its accuracy for five year survival prediction (AUC 0.787 vs. 0.768). In four-fold cross validation we obtain an average AUC of 0.787 for predicting five year survival and an AUC of 0.767 for predicting cardiovascular disease. For five year survival prediction our model is significantly better than the Framingham Risk Score (AUC 0.688) and of nearly equivalent performance to method demonstrated in Pickhardt et al. (AUC 0.789) which utilized a combination of five CT derived biomarkers.
Combined PD-L1 and TIM-3 blockade improves the expansion of fit human CD8+ antigen-specific T cells for adoptive immunotherapy
Authors: Lak Shirin , Janelle Valérie , Djedid Anissa , Boudreau Gabrielle , Brasey Ann , Lisi Véronique , Carli Cédric , Busque Lambert , Lavallée Vincent-Philippe , Delisle Jean-Sébastien
Published: September 2021

Background

The stimulation and expansion of antigen-specific T cells ex vivo enables the targeting of a multitude of cancer antigens. However, clinical scale T-cell expansion from rare precursors requires repeated stimulations ex vivo leading to T-cell terminal effector differentiation and exhaustion that adversely impact therapeutic potential. We leveraged immune checkpoint blockade relevant to antigen-specific CD8+ human T cells to improve the expansion and function of T cells targeting clinically relevant antigens.

Methods

A clinically-compliant protocol relying on peptide-pulsed monocyte-derived dendritic cells and cytokines was used to expand antigen-specific CD8+ targeting the oncogenic Epstein-Barr virus (EBV) and the tumor associated antigen (TAA) Wilms Tumor 1 (WT1) protein. The effects of antibody-mediated blockade of immune checkpoints applied to the cultures (T-cell expansion, phenotypes and function) were assessed at various time points. Genomic studies including single cell RNA (scRNA) sequencing and T-cell receptor sequencing were performed on EBV-specific T cells to inform about the impact of immune checkpoint blockade on the clonal distribution and gene expression of the expanded T cells.

Results

Several immune checkpoints were expressed early by ex vivo expanded antigen-specific CD8+ T cells, including PD-1 and TIM-3 with co-expression matching evidence of T-cell dysfunction as the cultures progressed. The introduction of anti-PD-L1 (expressed by the dendritic cells) and anti-TIM-3 antibodies in combination (but not individually) to the culture led to markedly improved antigen-specific T-cell expansion based on cell counts, fluorescent multimer staining and functional tests. This was not associated with evidence of T-cell dysfunction when compared to T cells expanded without immune checkpoint blockade. Genomics studies largely confirmed these results, showing that double blockade does not impart specific transcriptional programs or patterns on TCR repertoires. However, our data indicate that combined blockade may nonetheless alter gene expression in a minority of clonotypes and have donor-specific impacts.

Conclusions

The manufacturing of antigen-specific CD8+ T cells can be improved in terms of yield and functionality using blockade of TIM-3 and the PD-L1/PD-1 axis in combination. Overcoming the deleterious effects of multiple antigenic stimulations through PD-L1/TIM-3 blockade is a readily applicable approach for several adoptive-immunotherapy strategies.
Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels
Authors: Rottenstreich Amihai , Zarbiv Gila , Oiknine-Djian Esther , Vorontsov Olesya , Zigron Roy , Kleinstern Geffen , Wolf Dana G. , Porat Shay
Published: September 2021

Objective

We aimed to assess the impact of early versus late third trimester maternal SARS-CoV-2 vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies.

Methods

Maternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered during 27-36 weeks gestation. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)- specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples.

Results

The study cohort consisted of 171 parturients (median age, 31 years; median gestational age, 39.7 weeks): 83 (48.5%) immunized at early 3rdtrimester (1stdose at 27-31 weeks), and 88 (51.5%) immunized at late 3rdtrimester (1stdose at 32-36 weeks). All mother-infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late 3rdtrimester vaccination and were positively correlated with increasing time since vaccination (r=□0.26; P=0.001). The median placental transfer ratios of anti-S and anti-RBD specific IgG were increased following early versus late 3rdtrimester immunization (anti-S ratio:1.3 vs. 0.9, anti-RBD-specific ratio:2.3 vs. 0.7, P<0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late 3rdtrimester immunization (1.9 vs. 0.8, P<0.001), and was positively associated with longer duration from vaccination (r=□0.77; P<0.001).

Conclusions

Early- as compared to late third trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may optimize neonatal seroprotection.
Elastomeric Harnesses Decrease Aerosol Particles Leak and Improve the Fit of Surgical Masks
Authors: Ingabire Jeannette , McKenney Hannah , Sebesta Charles , Badhiwala Krishna , Avants Ben , Kemere Caleb , Kapur Sahil , Robinson Jacob T.
Published: September 2021

Importance

The outbreak of Coronavirus diseases 2019 (COVID-19) disease has increased demand for N95 respirators, surgical masks, and other facial coverings to stop the spread of SARS-CoV-2. Research shows that N95 respirators perform the best at filtering viral droplets and aerosols, however these masks are much more difficult to manufacture and expensive to distribute on a large scale, which led to shortages during the pandemic. Surgical masks, on the other hand, were more widely available and have been previously used to mitigate the spread of tuberculosis and influenza.

Objectives

To evaluate the filter filtration efficiency (FFE) of three elastomeric harness designs in hospital and research settings in order to improve facemask seal.

Design, setting and participants

A multi-institutional collaboration between engineers and health professionals, conducted between November 2020 and March 2021, was set up to design an elastomeric harness to improve the face seal of a surgical mask. Three elastomeric harness designs were created with harness designs 1 and 2 tested in a research laboratory setting and harness design 2.1 tested in a hospital setting. The initial harness design 1 was laser cut for testing and design 2 was developed to improve the detected particle leakage around the nose bridge area by introducing more material in that region. Design 2.1 is developed for hospital settings with less material around the nose bridge to reduce vision disruption. The designs were tested on mannequins and human volunteers using IR imaging and standard fit testing equipment.

Main Outcomes and Measures

Our elastomeric harness can improve the seal of a surgical mask allowing it to pass the fit test used to evaluate N95 respirators. 24/39 participants achieved a passing score of 100 or more while wearing the second harness design. IR imaging determined that the nasal sidewalls region of the mask is most prone to leakage when using our first elastomeric harness.

Conclusions and Relevance

Overall, these results confirm that elastomeric harnesses combined with surgical masks improve their ability to filter aerosolized particles, which is especially important when in close proximity to individuals who are infectious or while performing aerosol-generating medical procedures.