Category: Statistics

Sci Rep. 2021 Apr 28;11(1):9154. doi: 10.1038/s41598-021-88733-3.

ABSTRACT

We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.56 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.

PMID:33911167 | DOI:10.1038/s41598-021-88733-3

Transl Psychiatry. 2021 Apr 29;11(1):252. doi: 10.1038/s41398-021-01367-x.

ABSTRACT

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

PMID:33911068 | DOI:10.1038/s41398-021-01367-x

Nat Commun. 2021 Apr 28;12(1):1935. doi: 10.1038/s41467-020-20536-y.

ABSTRACT

Haplotype-resolved genome assemblies are important for understanding how combinations of variants impact phenotypes. To date, these assemblies have been best created with complex protocols, such as cultured cells that contain a single-haplotype (haploid) genome, single cells where haplotypes are separated, or co-sequencing of parental genomes in a trio-based approach. These approaches are impractical in most situations. To address this issue, we present FALCON-Phase, a phasing tool that uses ultra-long-range Hi-C chromatin interaction data to extend phase blocks of partially-phased diploid assembles to chromosome or scaffold scale. FALCON-Phase uses the inherent phasing information in Hi-C reads, skipping variant calling, and reduces the computational complexity of phasing. Our method is validated on three benchmark datasets generated as part of the Vertebrate Genomes Project (VGP), including human, cow, and zebra finch, for which high-quality, fully haplotype-resolved assemblies are available using the trio-based approach. FALCON-Phase is accurate without having parental data and performance is better in samples with higher heterozygosity. For cow and zebra finch the accuracy is 97% compared to 80-91% for human. FALCON-Phase is applicable to any draft assembly that contains long primary contigs and phased associate contigs.

PMID:33911078 | DOI:10.1038/s41467-020-20536-y

J Korean Assoc Oral Maxillofac Surg. 2021 Apr 30;47(2):91-98. doi: 10.5125/jkaoms.2021.47.2.91.

ABSTRACT

OBJECTIVES: Hyaluronoglucosaminidase (hyaluronidase) increases the local intercellular permeability of the peripheral lymphatic channel and capillaries, which may help reduce edema. In the present study, the effects of hyaluronidase on postoperative edema and pain reduction were evaluated.

MATERIALS AND METHODS: The study included 38 patients who underwent guided bone regeneration (GBR) surgery before implantation. Patients were randomly assigned to either the control group (n=20) or the test group (n=18). Hyaluronidase was injected into the GBR site of subjects in the test group. Postoperative edema was evaluated by measuring the distance between specific facial landmarks immediately after surgery (T1) and 2-4 days after surgery (T2). The degree of pain at T2 and at 10-14 days after surgery (T3) was assessed.

RESULTS: In the test group, the degree of swelling was lower than in the control group, however, only two measurements, from the tragus to the mouth corner and from the outer canthus to the mouth corner, showed statistically significant differences (P=0.012 and P=0.001, respectively). The anti-edema effect of hyaluronidase was more effective in the maxilla than in the mandible. In the maxilla, the percentage of facial swelling was significant for three measurements. However, in the mandible, the percentage of facial swelling was significant for only one measurement. Low levels of pain that were similar at T2 and T3 were reported in both groups.

CONCLUSION: The results indicate the degree of swelling was lower in the test group and hyaluronidase appeared to be more effective in the maxilla. The degree of pain reduction was similar between groups. Further in vivo and randomized controlled trials with larger sample sizes are warranted.

PMID:33911041 | DOI:10.5125/jkaoms.2021.47.2.91

Occup Environ Med. 2021 Apr 28:oemed-2020-107253. doi: 10.1136/oemed-2020-107253. Online ahead of print.

ABSTRACT

OBJECTIVES: There has been no research on sedentary behaviour in the occupational domain that occupies a large portion of the daily life.

METHODS: We conducted a meta-analysis to investigate the association between sedentary work and colorectal cancer. We searched PubMed, Embase and Cochrane databases up to 12 August 2020 for peer-reviewed journal articles that assessed the association between sedentary work and colon or rectal cancer. Pooled estimates of ORs were obtained using random effects models. Statistical tests for publication bias, heterogeneity and sensitivity analysis were applied.

RESULTS: Of the 5 381 studies initially identified, 23 studies with 64 reports were eligible for inclusion. Sedentary work significantly increased the risk of colon cancer (pooled OR=1.21, 95% CI 1.11 to 1.31, p value ≤0.0001) and rectal cancer (pooled OR=1.08, 95% CI 1.00 to 1.16, p value=0.0395). The adjustment for leisure time physical activity attenuated the association and made the risk estimates non-significant for sedentary behaviour, but the association was independent of sex, control of body mass index and assessment of sedentary behaviour.

CONCLUSIONS: We found evidence of association between sedentary work and the risk of colon or rectal cancer. Limiting excessive sedentary work could be an important means of preventing colon and rectal cancer.

PMID:33910983 | DOI:10.1136/oemed-2020-107253

mSphere. 2021 Apr 28;6(2):e00203-21. doi: 10.1128/mSphere.00203-21.

ABSTRACT

Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention.IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

PMID:33910993 | DOI:10.1128/mSphere.00203-21

Neurology. 2021 Apr 28:10.1212/WNL.0000000000012125. doi: 10.1212/WNL.0000000000012125. Online ahead of print.

ABSTRACT

OBJECTIVE: To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.

METHODS: To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms “quantitative” and “optical coherence tomography” from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts, and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.

RESULTS: One hundred sixteen authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point-checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans; we suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants’ consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.

CONCLUSIONS: The modified Delphi method resulted in an expert-led guideline (evidence class III, GRADE criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, fundoscopic imaging, post-acquisition data selection, post-acquisition analysis, nomenclature and abbreviations, and statistical approach. It will still be essential to update these recommendations to new research and practices regularly.

PMID:33910937 | DOI:10.1212/WNL.0000000000012125

BMJ Open. 2021 Apr 28;11(4):e043565. doi: 10.1136/bmjopen-2020-043565.

ABSTRACT

OBJECTIVE: Tuberculosis is a major public health problem and is the second leading cause of death worldwide. BCG vaccination is a life-saving and important part of standard tuberculosis control measures, particularly in Ethiopia where tuberculosis is endemic. The End Tuberculosis Strategy targets of 2020 have not been achieved. Exploring spatial variations in BCG vaccination among children is vital to designing and monitoring effective intervention programmes. Therefore, this study aimed to explore the spatial variation in BCG vaccination among children in Ethiopia.

DESIGN: Cross-sectional study design.

SETTING: Ethiopia.

PARTICIPANTS: Children aged 0-35 months.

PRIMARY OUTCOME: BCG vaccination coverage.

METHODS: Data from the 2016 Ethiopian Demographic and Health Survey were used and a total of 4453 children aged 0-35 months were included. Spatial autocorrelation analysis, cluster and outlier analysis, hotspot analysis, spatial interpolation, and spatial scan statistics were carried out to identify geographical risk areas for BCG vaccine utilisation. ArcGIS V.10.6 and SaTScan V.9.6 statistical software were employed to explore spatial pattern and significant hotspot areas for BCG vaccination among children.

RESULTS: BCG vaccination was spatially clustered in Ethiopia at the regional level (Global Moran’s I=0.516, p<0.001). A total of 51 most likely clusters of low BCG vaccination were identified in the Somali and Afar regions (log-likelihood ratio=136.58, p<0.001). Significant secondary clusters were also identified in North West Gambela, South Amhara, South West Addis Ababa, North East Southern Nations, Nationalities, and People’s Region, and South West Oromia.

CONCLUSION: A low probability of receiving BCG vaccination was found among children in the Somali and Afar regions. Therefore, these areas should be given attention when designing effective immunisation strategies to improve BCG vaccination among children in order to reduce the burden of tuberculosis in Ethiopia.

PMID:33910946 | DOI:10.1136/bmjopen-2020-043565

J Virol. 2021 Apr 28:JVI.00330-21. doi: 10.1128/JVI.00330-21. Online ahead of print.

ABSTRACT

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. We recently showed that 8/16 rhesus macaques (RMs) vaccinated with a rDNA/rRRV-SIVnfl regimen were significantly protected against intrarectal (IR) challenge with SIVmac239. Here we investigated the longevity of this vaccine-mediated protection. Despite receiving no additional booster immunizations, the protected rDNA/rRRV-SIVnfl vaccinees maintained detectable cellular and humoral anti-SIV immune responses for more than 1.5 years after the rRRV boost. To assess if these responses were still protective, the rDNA/rRRV-SIVnfl vaccinees were subjected to a second round of marginal-dose IR SIVmac239 challenges, with eight SIV-naïve RMs serving as concurrent controls. After three SIV exposures, 8/8 control animals became infected, compared to 3/8 vaccinees. This difference in SIV acquisition was statistically significant (P = 0.0035). The three vaccinated monkeys that became infected exhibited significantly lower viral loads than those in unvaccinated controls. Collectively, these data illustrate the ability of rDNA/rRRV-SIVnfl vaccination to provide long-term immunity against stringent mucosal challenges with SIVmac239. Future work is needed to identify the critical components of this vaccine-mediated protection and the extent to which it can tolerate sequence mismatches in the challenge virus.IMPORTANCEWe report on the long-term follow-up of a group of rhesus macaques (RMs) that received an AIDS vaccine regimen and were subsequently protected against rectal acquisition of simian immunodeficiency virus (SIV) infection. The vaccination regimen employed included a live recombinant herpesvirus vector that establishes persistent infection in RMs. Consistent with the recurrent SIV antigen expression afforded by this herpesvirus vector, vaccinees maintained detectable SIV-specific immune responses for more than 1.5 years after the last vaccination. Importantly, these vaccinated RMs were significantly protected against a second round of rectal SIV exposures performed one year after the first SIV challenge phase. These results are relevant for HIV vaccine development because they show the potential of herpesvirus-based vectors to maintain functional antiretroviral immunity without the need for repeated boosting.

PMID:33910957 | DOI:10.1128/JVI.00330-21

Br J Ophthalmol. 2021 Apr 28:bjophthalmol-2020-318696. doi: 10.1136/bjophthalmol-2020-318696. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The COVID-19 has facilitated a paradigm shift in the sphere of ophthalmic telemedicine: its utility is no longer limited to providing care to remote regions, rather it is expeditiously being adopted as the new standard of care. The aim of our paper is to explore the current attitudes of oculoplastic surgeons towards telemedicine and its utility in the present landscape and its prospects in the future.

METHODS: A 39-item questionnaire was distributed to consultant oculoplastic surgeons practising across the UK and anonymised responses were collected and analysed.

RESULTS: The COVID-19 pandemic has allowed rapid implementation of telemedicine services in oculoplastic departments across the UK with 86.6% of the respondents incorporating telemedicine into the routine clinical practice. Clinicians reported a statistically significant increase in utility of telemedicine, confidence in using telemedicine and quality of infrastructure available to employ telemedicine following the COVID-19 outbreak. The greatest utility of telemedicine is in triaging, postoperative assessment and eyelid lesion assessment. Main barriers to implementation of telemedicine included difficulties in conducting clinical examinations, lack of administrative support and poor access to digital technologies for patients. Overall, most clinicians were satisfied with the impact of telemedicine services and almost all experts foresee themselves continuing to use telemedicine in the future.

CONCLUSIONS: Telemedicine has become an integral part of the oculoplastic service delivery since the COVID-19 pandemic its use is likely to continue. Further development of digital infrastructure and improvement of clinical examination capabilities are required to enable its wider adoption.

PMID:33910884 | DOI:10.1136/bjophthalmol-2020-318696