Validation of a Novel Fluorescent Lateral Flow Assay for Rapid Qualitative and Quantitative Assessment of Total Anti-SARS-CoV-2 S-RBD Binding Antibody Units (BAU) from Plasma or Fingerstick Whole-Blood of COVID-19 Vaccinees

Background: Limited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). Aim: This study aimed to evaluate the performance of the fluorescence LFA FinecareTM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113) against the following reference methods: (i) the FDA-approved GenScript surrogate virus-neutralizing assay (sVNT); and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®. Methods: Plasma from 488 vaccinees was tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM. Results and conclusions: FinecareTM showed 100% specificity, as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlation r = 0.9, p < 0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r = 0.5, p < 0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralizing antibody (nAb) post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r = 0.6, p < 0.0001) and moderate correlation with VITROS® (r = 0.5, p < 0.0001) and CL-900i® (r = 0.4, p < 0.0001), suggesting that FinecareTM can be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.This work was made possible by grant number UREP28-173-3-057 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors

Light Sterile Neutrinos and Short Baseline Neutrino Oscillation Anomalies

We study two possible explanations for short baseline neutrino oscillation anomalies, such as the LSND and MiniBooNE anti-neutrino data, and for the reactor anomaly. The first scenario is the mini-seesaw mechanism with two eV-scale sterile neutrinos. We present both analytic formulas and numerical results showing that this scenario could account for the short baseline and reactor anomalies and is consistent with the observed masses and mixings of the three active neutrinos. We also show that this scenario could arise naturally from an effective theory containing a TeV-scale VEV, which could be related to other TeV-scale physics. The minimal version of the mini-seesaw relates the active-sterile mixings to five real parameters and favors an inverted hierarchy. It has the interesting property that the effective Majorana mass for neutrinoless double beta decay vanishes, while the effective masses relevant to tritium beta decay and to cosmology are respectively around 0.2 and 2.4 eV. The second scenario contains only one eV-scale sterile neutrino but with an effective non-unitary mixing matrix between the light sterile and active neutrinos. We find that though this may explain the anomalies, if the non-unitarity originates from a heavy sterile neutrino with a large (fine-tuned) mixing angle, this scenario is highly constrained by cosmological and laboratory observations.Comment: 25 pages, 6 figure

Dynamics of Anti-S IgG Antibodies Titers after the Second Dose of COVID-19 Vaccines in the Manual and Craft Worker Population of Qatar

There is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibody titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. A total of 300 male participants who received any of the following vaccines BNT162b2/Comirnaty, mRNA-1273, ChAdOx1-S/Covishield, COVID-19 Vaccine Janssen/Johnson, or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan–Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibody titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. Participants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13,720.9 AU/mL (IQR 6426.5 to 30,185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/mL; IQR, 3757.9 to 16,577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7–5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2–4.5 months) and 7.63 months (IQR, 6.3–8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. This evidence on anti-S IgG antibody titers should be considered for informing decisions on the durability of the neutralizing activity and thus protection against infection after the full course of primary vaccination in individuals receiving different type (mRNA verus non-mRNA) vaccines and those with natural infection.The World Health Organization (WHO) - grant number [2021/1183356-0]

Prospective Long-term Health-related Quality of Life Outcomes After Surgery, Radiotherapy, or Active Surveillance for Localized Prostate Cancer

Background: Localized prostate cancer (PCa) treatment is associated with reduced health-related quality of life (HRQoL). Current literature is limited by short-term follow-up. Objective: To prospectively evaluate the 5-yr HRQoL outcomes in men undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), or active surveillance (AS). Design, setting, and participants: We prospectively evaluated HRQoL in patients with low-risk/favorable intermediate-risk PCa enrolled in the Center for Prostate Disease Research multicenter database between 2007 and 2017. Intervention: Of 1012 patients included in the study, 252 (24.9%) underwent AS, 557 (55.0%) RP, and 203 (20.0%) EBRT. Patients complete the Expanded Prostate Cancer Index Composite and the 36-item Medical Outcomes Study Short Form at baseline and thereafter each year up to 5 yr after treatment. Outcome measurements and statistical analysis: Temporal changes in HRQoL were compared between treatments and were modeled using linear regression models adjusted for baseline HRQoL, demographic, and clinical characteristics. Results and limitations: RP showed the least irritative symptoms and worse incontinence in comparison with AS (p < 0.001 for both subdomains) or EBRT (p < 0.001 for both subdomains) at all time points. RP sexual domain score was worse than the scores of AS (mean difference 22.3 points, 95% confidence interval [CI] 10.5–27.8, p < 0.001) and EBRT (mean difference 16.9 points, 95% CI 12.5–20.3, p < 0.001) during years 1–3 and not different from that of EBRT (mean difference 2.9 points, 95% CI –4.8 to 8.3, p = 0.3) at years 4 and 5. Bowel function and bother were worse for EBRT than for AS (p < 0.001 for both subdomains) and RP (p < 0.001 for both subdomains) at all time points. During the 3–5-yr period, AS demonstrated the worst decline in all mental health domains (p < 0.001 in comparison with both EBRT and RP). Conclusions: RP results in worse long-term urinary function and incontinence, but in less irritative and obstructive symptoms than EBRT and AS. Sexual domain scores were least affected by AS, while RP shows similar scores to EBRT at long term. Long-term HRQoL changes are critical for advising patients. Patient summary: We evaluated long-term health-related quality of life (HRQoL) in a large US population treated for localized prostate cancer. HRQoL outcomes varied according to treatment modality and time. These changes should inform patients about their expected outcomes following treatment

The effect of race on treatment patterns and subsequent health-related quality of life outcomes in men undergoing treatment for localized prostate cancer.

INTRODUCTION: Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT). METHODS: Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey. RESULTS: In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p \u3c 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT. CONCLUSION: AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men

Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India

<div><p>Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with <i>HNF1A</i> Ser3Cys, two <i>PDX1</i> Glu224Lys, His94Gln, two <i>NEUROD1</i> Glu59Gln, Phe318Ser, one <i>INS</i> Gly44Arg, one <i>GCK</i>, <i>one ABCC8</i> Arg620Cys and one <i>BLK</i> Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding</p></div

Detailed diagrammatic algorithm of the study with flow chart of NGS screening of the subject.

<p>Detailed diagrammatic algorithm of the study with flow chart of NGS screening of the subject.</p