Ad5‐nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants

alexandrossfakianakis shared this article with you from Inoreader Ad5‐nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants via Journal of Medical Virology Abstract Background Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Methods Plasma was collected from InV pre-vaccinated Omicron infected patients (OIPs), unvaccinated OIPs between 0-22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. Results InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days post-infection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3- and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35112 and 28186 during 11-22 DPI, about 2.6- and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-, 5.6-, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. Conclusion InV and Ad5-nCoV booster could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative. This article is protected by copyright. All rights reserved. View on Web

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Somatic loss of the Y chromosome is associated with arsenic exposure among Bangladeshi men

alexandrossfakianakis shared this article with you from Inoreader Somatic loss of the Y chromosome is associated with arsenic exposure among Bangladeshi men via International Journal of Epidemiology - Advance Access Abstract Background Arsenic exposure increases the risk of several cancers in humans and contributes to genomic instability. Somatic loss of the Y chromosome (LoY) is a potential biomarker of genomic instability and cancer risk. Smoking is associated with LoY, but few other carcinogens have been investigated. We tested the cross-sectional association between arsenic exposure and LoY in leukocytes among genotyped Bangladeshi men (age 20–70 years) from the Health Effects of Arsenic Longitudinal Study. Methods We extracted the median of logR-ratios from probes on the Y chromosome (mLRR-chrY) from genotyping arrays (n = 1364) and estimated the percentage of cells with LoY (% LoY) from mLRR-chrY. We evaluated the association between arsenic exposure (measured in drinking water and urine) and LoY using multivariable linear and logistic regression models. T he association between LoY and incident arsenic-induced skin lesions was also examined. Results Ten percent of genotyped men had LoY in at least 5% of cells and % LoY increased with age. Among men randomly selected for genotyping (n = 778), higher arsenic in drinking water, arsenic consumed and urinary arsenic were associated with increased % LoY (P = 0.006, P = 0.06 and P = 0.13, respectively). LoY was associated with increased risk of incident skin lesions (P = 0.008). Conclusion Arsenic exposure was associated with increased LoY, providing additional evidence that arsenic contributes to genomic instability. LoY was associated with developing skin lesions, a risk factor for cancer, suggesting that LoY may be a biomarker of susceptibility in arsenic-exposed populations. The effect of arsenic on somatic events should be further explored in cancer-prone tissue types. View on Web

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Control of Pre‐phonatory Glottal Shape by Intrinsic Laryngeal Muscles

alexandrossfakianakis shared this article with you from Inoreader Control of Pre‐phonatory Glottal Shape by Intrinsic Laryngeal Muscles via The Laryngoscope Complex interactions between intrinsic laryngeal muscles and their effects on the vocal fold pre-phonatory posture were studied. The thyroarytenoid (TA) was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the lateral cricoarytenoid (LCA). The cricothyroid (CT) contributed minimally to vocal fold medial shape but elongated the glottis. Objectives Surgical manipulations to treat glottic insufficiency aim to restore the physiologic pre-phonatory glottal shape. However, the physiologic pre-phonatory glottal shape as a function of interactions between all intrinsic laryngeal muscles (ILMs) has not been described. Vocal fold posture and medial surface shape were investigated across concurrent activation and interactions of thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid/interarytenoid (LCA/IA) muscles. Study Design In vivo canine hemilarynx model. Methods The ILMs were stimulated across combinations of four graded levels each from low-to-high activation. A total of 64 distinct medial surface postures (4 TA × 4 CT × 4 LCA/IA levels) were captured using high-speed video. Using a custom 3D interpolation algorithm, the medial surface shape was reconstructed. Results Combined activation of ILMs yielded a range of unique pre-phonatory postures. Both LCA/IA and TA activation adducted the vocal fold but with greater contribution from TA. The transition from a convergent to a rectangular glottal shape was primarily mediated by TA muscle activation but LCA/IA and TA together resulted in a smooth rectangular glottis compared to TA alone, which caused rectangular glottis with inferomedial bulging. CT activation resulted in a lengthened but slightly abducted glottis. Conclusions TA was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the LCA/IA. CT contributed minimally to vocal fold medial shape but elongated the glottis. These findings further refine laryngeal posture goals in surgical correction of glottic insufficiency. Level of Evidence N/A, Basic science Laryngoscope, 2022 View on Web

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Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy

alexandrossfakianakis shared this article with you from Inoreader Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy via Pediatric Blood & Cancer Abstract Background The purpose of this study is to analyze renal function outcomes in abdominal neuroblastoma patients undergoing proton therapy (PT). Procedure From 2011 to 2019, two single-institution Institutional Review Board-approved protocols prospectively enrolled neuroblastoma patients for data collection. To assess renal function, serum creatinine (Cr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) before proton therapy (pre-PT) were compared with the values at last follow-up. Results A total of 30 children with abdominal neuroblastoma with median age 3.5 years (range, 0.9–9.1) at time of PT were included in this study. All patients underwent chemotherapy and resection of primary tumor prior to PT. Two patients required radical nephrectomy. Median follow-up after PT was 35 months. Mean dose to ipsilateral and contralateral kidney was 13.9 and 5.4 Gy, respectively. No patients developed hypertension or renal dysfunction during follow-up. There was no statistically significant change in serum BUN (p = .508), CrCl (p = .280), or eGFR (p = .246) between pre-PT and last follow-up. Conclusion At a median follow-up of almost 3 years, renal toxicity was uncommon after PT. Longer follow-up and larger patient cohort data are needed to further assess impact of PT on renal function in this population. View on Web

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Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant

alexandrossfakianakis shared this article with you from Inoreader Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant via Pediatric Blood & Cancer Abstract Pediatric and adolescent and young adult (AYA) patients who receive many blood product transfusions, such as individuals with sickle cell disease (SCD), severe aplastic anemia (SAA) or indolent hematologic malignancies, are at high risk for developing donor-specific antibodies (DSA). DSAs with mean fluorescence intensity (MFI) greater than 5000 have been associated with significant graft failure, but lower MFI values between 2000 and 5000 may result in poor graft function after hematopoietic cell transplant (HCT). Desensitization strategies have been developed to reduce the DSA burden in HCT recipients before graft infusion, but the experience with these strategies in the pediatric and AYA populations is not well described in the literature. Here, we describe our experience with successful desensitization by using a combination of treatment strategies in five pediatric and AYA patients, including a novel use of daratumumab in a young adult patient who had refractory DSAs and had s uffered serious side effects from conventional desensitization strategies. The presence of elevated DSAs in pediatric and AYA recipients of a human leukocyte antigen (HLA)-mismatched haploidentical HCT can be overcome by a multipronged treatment strategy. View on Web

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Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers

alexandrossfakianakis shared this article with you from Inoreader Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers via Fundamental & Clinical Pharmacology Abstract The susceptibility of cells to DNA damage and their DNA repair ability are crucial for cancer therapy. Homologous recombination is one of the major repairing mechanisms for DNA double-strand breaks. Approximately half of ovarian cancer (OvCa) cells harbor homologous recombination deficiency (HRD). Considering that HRD is a major hallmark of OvCas, scholars proposed HRD scoring to evaluate the HRD degree and guide the choice of therapeutic strategies for OvCas. In the last decade, synthetic lethal strategy by targeting poly (ADP-ribose) polymerase (PARP) in HR-deficient OvCas has attracted considerable attention in view of its favorable clinical effort. We therefore suggested that the uses of other DNA damage/repair-targeted drugs in HR-deficient OvCas might also offer better clinical outcome. Here, we reviewed the current small molecule compounds which targeted DNA damage/repair pathways, and discussed the HRD scoring system to guide their clinical uses. View on Web

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Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer

alexandrossfakianakis shared this article with you from Inoreader Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer via Head & Neck Abstract Background We aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC). Methods Retrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC. Results All 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post-RT (N = 141): 0.68 (0.35) and long-term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04). Conclusions Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC. Level of Evidence 3 View on Web

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

alexandrossfakianakis shared this article with you from Inoreader Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection via Brain Pathology The human frontal cortex of SAD, FAD, and APOEch is characterized by specific astrocyte phenotypes which define the integrity of Gliovascular unit. ApoE3ch mutation in an E280A carrier might be related to the promotion of astrocytic and gliovascular homeostatisis despite the massive load of Aβ. This study provides new insights into the potential relevance of the gliovascular unit in the development and protection of AD. Abstract In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch. View on Web

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