In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT‐qPCR assays for SARS‐CoV‐2 detection using whole genome sequencing

alexandrossfakianakis shared this article with you from Inoreader In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT‐qPCR assays for SARS‐CoV‐2 detection using whole genome sequencing via Journal of Medical Virology ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world, presenting a new threat to global public human health. Due to the large number of mutations accumulated by SARS-CoV-2 Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for diagnosing coronavirus disease 2019 (COVID-19). Thus, we aimed to assess the impact of the currently endemic Omicron sublineages BA.4 and BA.5 on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease 2019 (COVID-19) diagnosis via in silico analysis. We employed whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and Omicron VoC viral genome. Methods In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for specifically detecting SARS-CoV-2 Omicron BA.4 and BA.5 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. Mismatches between amplicon regions of SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and clustering analysis of corresponding amplicon sequences was carried out. Results From the 1164 representative SARS-CoV-2 Omicron VoC BA.4 sublineage genomes analyzed, a substitution in the first five nucleotides (C to T) of the amplicon's 3' end were observed in all samples resulting in 0% sensitivity for assays HKUnivRdRp/Hel (mismatch in reverse primer) and CoremCharite N (mismatch in both forward and reverse primers). Due to a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC), the sensitivity of ChinaCDC N assay was at 0.69%. The 10 nucleotide mismatches in the reverse primer resulted in 0.09% sensitivity for Omicron sublineage BA.4 for Thai N assay. Of the 1926 BA.5 sublineage genomes, HKUnivRdRp/Hel assay also had 0% sensitivity. A sensitivity of 3.06% was observed for ChinaCDC N assay because of a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC). Similarly, due to the 10 nucleotide mismatches in the reverse primer, Thai N assay's sensitivity was low at 0.21% for sublineage BA.5. Further, 8 assays for BA.4 sublineage retained high sensitivity (more than 97%) and 9 assays for BA.5 sublineage retained more than 99% sensitivity. Conclusion We observed four assays (HKUnivRdRp/Hel, ChinaCDC N, Thai N, CoremCharite N) that could potentially result in false negative results for SARS-CoV-2 Omicron VoCs BA.4 and BA.5 sublineages. Interestingl y, CoremCharite N had 0% sensitivity for Omicron Voc BA.4 but 99.53% sensitivity for BA.5. In addition, 66.67% of the assays for BA.4 sublineage and 75% of the assays for BA.5 sublineage retained high sensitivity. Further, amplicon clustering and additional substitutions analysis along with sensitivity analysis could be used for modification and development of RT-qPCR assays for detecting SARS-CoV-2 Omicron VoC sublineages. This article is protected by copyright. All rights reserved. View on Web

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Using the serratus anterior free flap for dynamic facial reanimation: Systematic review

alexandrossfakianakis shared this article with you from Inoreader Using the serratus anterior free flap for dynamic facial reanimation: Systematic review via Head & Neck Abstract It was the purpose of this study to evaluate the role of the serratus anterior free flap (SAFF) with its long thoracic nerve (LTN) as composite flap for dynamic facial reanimation. A total of 10 studies, published between 2004 and 2021, met inclusion criteria. Clinical data of 48 patients were used for the systematic review and analysis. One to three slips were used, mainly as one-stage procedures (n = 39; 81.3%), to create different force vectors. Single or double innervated muscle transfers were utilized in 32 (66.7%) and 16 (33.3%) cases with additionally harvested skin paddles in 4 (8.3%) patients. The LTN was mostly anastomosed to the ipsilateral masseteric nerve (45.8%; n = 22) or to remaining facial nerve branches (37.5%; n = 18), while cross-facial-nerve-grafting was rarely used (16.7%; n = 8). The SAFF as composite flap with different force vectors proved to be a good candidate for immediate dynamic facia l reanimation after any midface defects. View on Web

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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis

alexandrossfakianakis shared this article with you from Inoreader Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis in Denmark: A Bayesian Hierarchical Analysis via Epidemiology - Featured Articles - Featured Articles Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis. View on Web

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Gestational Hypertensive Disorders and Maternal Breast Cancer Risk

alexandrossfakianakis shared this article with you from Inoreader Gestational Hypertensive Disorders and Maternal Breast Cancer Risk in a Nationwide Cohort of 40,720 Parous Women via Epidemiology - Featured Articles - Featured Articles Background: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35–74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer. View on Web

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Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function

alexandrossfakianakis shared this article with you from Inoreader Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractThe synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48  h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that th... View on Web

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Volumetric change of bony cavity and shrinkage speed after marsupialization for odontogenic keratocyst and unicystic ameloblastoma

alexandrossfakianakis shared this article with you from Inoreader Volumetric change of bony cavity and shrinkage speed after marsupialization for odontogenic keratocyst and unicystic ameloblastoma via International Journal of Oral and Maxillofacial Surgery via MedWorm.com The aim of this study was to evaluate the efficacy of marsupialization treatment for odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) based on the three-dimensional volumetric change over time, and to determine the difference between OKC and UA in terms of the absolute volume reduction (AVR) and absolute shrinkage speed (ASS), and whether they are correlated with the preoperative volume, time after marsupialization (time between marsupialization and second treatment), and patient age. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B

alexandrossfakianakis shared this article with you from Inoreader Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B via Journal of Medical Virology Abstract Objectives We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB). Methods The serum levels of hub genes were examined by qRT-PCR in three cohorts of CHB patients. Results For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842 and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801 and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression. Conclusion The novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients. This article is protected by copyright. All rights reserved. View on Web

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