bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cross Sectional Study To Assess The Attitude Regarding Online Lecture Among Nursing College Students After Impact of Covid-19 At Selected College of Nursing, Nadiad
Authors: Nagar Kailash
Published: July 2021

Background

In December 2019, a pathogenic human corona virus SARS- CoV-2, corona virus disease 2019 (COVID-19), was recognized and has caused serious illness and numerous deaths. The epidemics of COVID-19 have been recorded over 200 countries, territories, and areas with 2 878 196 confirmed cased and 198 668 death cases.

Aims

The current study is to assess the attitude of nursing college students regarding online classes.

Objective

1. To determine the perceptions of students towards e-learning during the lock down. 2. To assess nursing students attitude towards the online lectures

Methodology

Setting and Design

Descriptive cross sectional survey research design was used and not probability sampling methods was used to drawn samples through online Google form. The sample collected from nursing college students and study setting was Dinsha Patel College of nursing, Nadiad, Gujarat. There were total 20 attitude question with five point rating scale were used. Total sample were 136 nursing college students. Data has been collected online through Google form.

Statistical Analysis used

Descriptive statistics applied where, data was analyzed by using SPSS software, and Frequency, percentage, tables etc were used to represent the statistical data.

Results

Out of 136, 64(47.05%) were belong age 17-18 years, 115(84.56%) were female, 68(50%) were GNM students, 51(37.50%) B.Sc. nursing Students, 83(61.02%) were third year, 75(55.24%) were live urban, 61(44.86%) were rural area, 56(41.17%) were travel 21-30km, 40(29.41%) more than 30km, 65(47.79%) have above 15000 monthly family income 132(97.05%) were used mobile for online lecture 79(58.08%) were have average network.

Attitude regarding Online Classes where 7 (5.14%) had Inadequate Attitude 86(63.25%) had Moderate Attitude, 43(31.61%) Had adequate Attitude.

Conclusions

Regarding the online lecture 63.25% nursing college students has moderate attitude and 31.61% had adequate attitude it means now days students are line online classes than physical mode due to various reasons such as, time consuming, reduce traveling, risk of accidents and corona, more time can spend with family etc
Serum asymmetric dimethyl arginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis
Authors: Ikenaka Kensuke , Maeda Yasuhiro , Hotta Yuji , Nagano Seiichi , Kakuda Keita , Tatebe Harutsugu , Atsuta Naoki , Ito Daisuke , Aguirre Cesar , Kimura Yasuyoshi , Baba Kousuke , Katsuno Masahisa , Tokuda Takahiko , Kimura Kazunori , Sobue Gen , Mochizuki Hideki
Published: July 2021

Objective

To investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.

Methods

Serum ADMA levels of patients with sporadic ALS (n = 68) and disease control patients (n = 54) were measured using liquid chromatography-tandem mass spectrometry. Serum samples were obtained at the time of patient registration for diagnosis. Correlations of ADMA level and other markers (nitric oxide [NO] and neurofilament light chain [NFL] levels) were analyzed. Changes in the ALS Functional Rating Scale–Revised (ALSFRS-R) score from the onset of disease (ALSFRS-R preslope) was used to assess disease progression. Survival was evaluated using the Cox proportional hazards model and Kaplan–Meier analysis.

Results

The concentration of ADMA in CSF was substantially higher in patients with ALS than in disease controls. Serum ADMA level correlated with CSF ADMA level (r = 0.591, p < 0.0001), and was independently associated with the ALSFRS-R preslope (r = 0.505. p < 0.0001). Patients with higher serum ADMA levels had less favorable prognoses. CSF ADMA level significantly correlated with CSF NfL level (r = 0.456, p = 0.0002) but not with NO level (r = 0.194, p = 0.219).

Conclusion

ADMA level is an independent biomarker of ALS disease progression and prognosis, and reflects the degree of motor neuron degeneration. The increased ADMA level in ALS patients was not associated with the inhibition of NO production.
Epidemiological dynamics of SARS-CoV-2 VOC Gamma in Rio de Janeiro, Brazil
Authors: Rebello Moreira Filipe Romero , D’arc Mirela , Mariani Diana , Herlinger Alice Laschuk , Schiffler Francine Bittencourt , Rossi Átila Duque , de Carvalho Leitão Isabela , dos Santos Miranda Thamiris , Calvano Cosentino Matheus Augusto , de Paula Tôrres Marcelo Calado , dos Santos Cunha da Costa Raíssa Mirella , Alves Gonçalves Cássia Cristina , Faffe Débora Souza , Galliez Rafael Mello , da Costa Ferreira Junior Orlando , Aguiar Renato Santana , dos Santos André Felipe Andrade , Voloch Carolina Moreira , Pinto Castiñeiras Terezinha Marta Pereira , Tanuri Amilcar
Published: July 2021

The emergence and widespread circulation of SARS-CoV-2 variants of concern (VOC) or interest (VOI) imposes an enhanced threat to global public health. In Brazil, one of the countries most severely impacted throughout the pandemic, a complex dynamics involving variants co-circulation and turnover events has been recorded with the emergence and spread of VOC Gamma in Manaus in late 2020. In this context, we present a genomic epidemiology investigation based on samples collected between December 2020 and May 2021 in the second major Brazilian metropolis, Rio de Janeiro. By sequencing 244 novel genomes through all epidemiological weeks in this period, we were able to document the introduction and rapid dissemination of VOC Gamma in the city, driving the rise of the third local epidemic wave. Molecular clock analysis indicates this variant has circulated locally since the first weeks of 2021 and only seven weeks were necessary for it to achieve a frequency above 70%, consistent with rates of growth observed in Manaus and other states. Moreover, a Bayesian phylogeographic reconstruction indicates VOC Gamma spread throughout Brazil between December 2020 and January 2021, and that it was introduced in Rio de Janeiro through at least 13 events coming from nearly all regions of the country. Comparative analysis of RT-qPCR cycle threshold (Ct) values provides further evidence that VOC Gamma induces higher viral loads (N1 target; mean reduction of Ct: 2.7, 95% CI = ±0.7). This analysis corroborates the previously proposed mechanistic basis for this variant enhanced transmissibility and distinguished epidemiological behavior. Our results document the evolution of VOC Gamma and provide independent assessment of scenarios previously studied in Manaus, therefore contributing to the better understanding of the epidemiological dynamics currently being surveyed in other Brazilian regions.
Estimation of Oral Disease Burden from Claims and Self-Reported Data
Authors: Okunseri Christopher , Frantsve-Hawley Julie , Thakkar-Samtani Madhuli , Okunev Ilya , Tranby Eric P.
Published: July 2021

Objective

To examine the use of Medicaid, commercial claims, and self-reported survey data to estimate the prevalence of oral disease burden.

Methods

We analyzed 2018 Medicaid claims from IBM Watson Medicaid Marketscan database, commercial claims from the IBM Dental Database, and Medical Expenditure Panel Survey (MEPS) data. The estimate of oral disease burden was based on standard metrics using periodontal and caries-related treatment procedure codes. Examples are restorations: D2000-D2999, root Canals: D3230 – D3334, periodontics: D4000 – D4999, prosthodontics: D5000 – D6999 and extractions: D7000 - D7251. A direct comparison between the data sets was also done. Enrollees from the different databases were broken down by gender, race/ethnicity, and into age groups.

Results

Medicaid and commercial enrollees were 11.6 million and 10.5 million. The weighted proportion from MEPS for Medicaid and commercial plans ranged from 80-208 million people. Prevalence of caries-related treatments was estimated for IBM Watson and MEPS for total enrollees for Medicaid (13% vs. 12%); and commercial claims (25% vs. 17%), respectively. Prevalence of periodontal related treatments was estimated for IBM Watson and MEPS total enrollees for Medicaid (0.7% vs. 0.5%) and commercial claims (7% vs. 1.6%), respectively. Prevalence of dental diseases was higher in patients with at least one visit for Medicaid, commercial plans, and MEPS. Prevalence based on specific procedures were higher in commercial plans than in Medicaid.

Conclusions

Claims data has the potential to serve as a proxy measure for the estimate of dental disease burden in a population. In addition, in rare events, claims data provides a better estimate of disease burden because it is based on a larger dataset.
Depressive disorders are associated with increased peripheral blood cell deformability: A cross-sectional case-control study (Mood-Morph)
Authors: Walther Andreas , Mackens-Kiani Anne , Eder Julian , Herbig Maik , Herold Christoph , Kirschbaum Clemens , Guck Jochen , Wittwer Lucas Daniel , Beesdo-Baum Katja , Kräter Martin
Published: July 2021

Background

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders.

Method

We performed a cross-sectional case-control study using image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high-risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified.

Results

We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with an increased cell deformability in monocytes and neutrophils, while in current persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in current major depressive disorder, while for lifetime major depressive disorder no differences could be identified.

Conclusions

This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive for persistent immune response.
Informing University Covid-19 Decisions Using Simple Compartmental Models
Authors: Hurt Benjamin , Adiga Aniruddha , Marathe Madhav , Barrett Christopher L.
Published: July 2021

Tracking the COVID-19 pandemic has been a major challenge for policy makers. Although, several efforts are ongoing for accurate forecasting of cases, deaths, and hospitalization at various resolutions, few have been attempted for college campuses despite their potential to become COVID-19 hot-spots. In this paper, we present a real-time effort towards weekly forecasting of campus-level cases during the fall semester for four universities in Virginia, United States. We discuss the challenges related to data curation. A causal model is employed for forecasting with one free time-varying parameter, calibrated against case data. The model is then run forward in time to obtain multiple forecasts. We retrospectively evaluate the performance and, while forecast quality suffers during the campus reopening phase, the model makes reasonable forecasts as the fall semester progresses. We provide sensitivity analysis for the several model parameters. In addition, the forecasts are provided weekly to various state and local agencies.
Object and Instance Detection Within Image Scenes
Authors: Adenisimi Daniel
Published: July 2021

This paper compares state-of-the-art methods in object and instance detection, and examines why YOLO (You Only Look Once) outperforms top detection methods. Different Pascal VOC dataset is used as the benchmark to explore mean average precision(mAP). YOLO is twice as accurate to prior works on real-time detection. The outcome of of merging YOLO with Fast R-CNN is an increased mean average precision (mAP) which results in performance boost. Hence, YOLO is an enhanced model of top detection methods.
A cGAMP-containing hydrogel for prolonged SARS-CoV-2 RBD subunit vaccine exposure induces a broad and potent humoral response
Authors: Böhnert Volker , Gale Emily C. , Lahey Lauren J. , Yan Jerry , Powell Abigail E. , Ou Ben S. , Carozza Jacqueline A. , Li Lingyin , Appel Eric A.
Published: July 2021

The receptor binding domain (RBD) of the SARS-CoV-2 virus spike protein has emerged as a promising target for generation of neutralizing antibodies. Although the RBD subunit is more stable than its encoding mRNA, RBD-based subunit vaccines have been hampered by RBD’s poor immunogenicity. We hypothesize that this limitation can be overcome by sustained co-administration with a more potent and optimized adjuvant than standard adjuvants. The endogenous innate immune second messenger, cGAMP, holds promise as potent activator of the anti-viral STING pathway. Unfortunately, delivery of cGAMP as a therapeutic exhibits poor performance due to poor pharmacokinetics and pharmacodynamics from rapid excretion and degradation by its hydrolase ENPP1. To overcome these limitations, we sought to create an artificial immunological niche enabling slow release of cGAMP and RBD to mimic natural infections in which immune activating molecules are co-localized with antigen. Specifically, we co-encapsulated cGAMP and RBD in an injectable polymer-nanoparticle (PNP) hydrogel. This cGAMP-adjuvanted hydrogel vaccine elicited more potent, durable, and broad antibody responses with improved neutralization as compared to dose-matched bolus controls and hydrogel-based vaccines lacking cGAMP. The cGAMP-adjuvanted hydrogel platform developed is suitable for delivery of other antigens and may provide enhanced immunity against a broad range of pathogens.
Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection
Authors: Li Lei , Honda-Okubo Yoshikazu , Huang Ying , Jang Hyesun , Carlock Michael A. , Baldwin Jeremy , Piplani Sakshi , Bebin-Blackwell Anne G. , Forgacs David , Sakamoto Kaori , Stella Alberto , Turville Stuart , Chataway Tim , Colella Alex , Triccas Jamie , Ross Ted M , Petrovsky Nikolai
Published: July 2021

The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19™). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. The Advax-SM adjuvanted vaccine induced high titers of binding antibody against spike protein that were able to neutralise the original wildtype virus on which the vaccine was based as well as the variant B.1.1.7 lineage virus. The Covax-19 vaccine also induced potent spike-specific CD4+ and CD8+ memory T-cells with a dominant Th1 phenotype, and this was shown to be associated with cytotoxic T lymphocyte killing of spike labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus 2 weeks after the second immunisation. Notably, ferrets that received two 25 or 50μg doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting the possibility that Covax-19 vaccine may in addition to protection against lung infection also have the potential to block virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.
Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy
Authors: Moor Matthias B. , Suter-Riniker Franziska , Horn Michael P. , Aeberli Daniel , Amsler Jennifer , Möller Burkhard , Njue Linet M. , Medri Cesare , Angelillo-Scherrer Anne , Borradori Luca , Radonjic-Hoesli Susanne , Jafari Morteza Seyed , Chan Andrew , Hoepner Robert , Bacher Vera Ulrike , Mani Laila-Yasmin , Iype Joseena Mariam , Hirzel Cédric , Maurer Britta , Sidler Daniel
Published: July 2021

Background

B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation.

Methods

Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by interferon-γ release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29).

Results

Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-γ release was detected in 20% of patients and 75% of healthy controls (p<0.001). Only 11% of patients, but 75%of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/µl), and CD4+ lymphocyte count (>653/µl) predicted humoral vaccine response (area under the curve [AUC]: 67% [CI 56-78], 67% [CI 55-80] and 66% [CI 54-79], (positive predictive value [PPV]: 0.78, 0.7 and 0.71).

Conclusion

This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital,ClinicalTrials.govnumber,NCT04877496)
Ultrasound Guided Brachial Plexus Block in Upper Extremity Surgeries: Experiences from a Tertiary Care Hospital of Bangladesh
Authors: Ali Mohammad , Johora Fatema , Mahboob Sabiha , Nilufar Sonia , Shirin Mst. Arifa
Published: July 2021

Brachial plexus block has been gained popularity after its introduction because of provision of quality anesthesia and optimal postoperative analgesia in upper arm surgeries, and introduction of ultrasound guidance in recent years further enhances the practice because of efficacy and safety of procedure. This retrospective observational study evaluated the outcome and safety of ultrasound-guided brachial plexus block (supraclavicular and interscalene approach) in a tertiary care hospital of Bangladesh over 3-years period (January 2017 to December 2019) through analyzing preoperative anesthesia evaluation form, anesthesia documents and postoperative records. 113 patients were covered during the study period, of which 59 (52.2%) were males and 54 (47.8%) were females. Mean age of the patients were 38.94 ± 20.37 years. Majority of the patients (63.7%) were in ASA grading I. Operative time for surgeries were 115.30 ± 35.19 minutes. duration of sensory and motor block were 618 ± 55 minutes and 450 ± 74 minutes respectively. And first dose of postoperative analgesic was given after 705 ± 94 minutes of surgery. Tachycardia and hypertension were observed in 4.4% patients, where failure of motor blockade and puncture of subclavian vein were recoreded 1.8% and 0.9% respectively. Current study found that with ultrasound guidance in skilled hands, brachial plexus blockade through combination of supraclavicular and interscalene approaches can provide quality anesthesia and analgesia with minimal complications.
Surgical Treatments for Lumbar Spine Diseases: A Systematic Review and Meta-Analysis
Authors: Wasinpongwanich Kanthika , Nopsopon Tanawin , Pongpirul Krit
Published: July 2021

Purpose

Surgical treatment is mandatory in some patients with lumbar spine diseases. To obtain spine fusion, many operative techniques were developed with different fusion rates and clinical results. This study aimed to collect randomized controlled trial (RCT) data to compare fusion rate, clinical outcomes, complications among Transforaminal Lumbar Interbody Fusion (TLIF), and other techniques for lumbar spine diseases.

Methods

A systematic literature search of PubMed, Embase, Scopus, Web of Science, and CENTRAL databases was searched for studies up to 13 February 2020. The meta-analysis was done using a random-effects model. Pooled risk ratio (RR) or mean difference (MD) with a 95% confidence interval of fusion rate, clinical outcomes, and complication in TLIF and other techniques for lumbar diseases.

Results

The literature search identified 3,682 potential studies, 15 RCTs (915 patients) were met our inclusion criteria and were included in the meta-analysis. Compared to other techniques, TLIF had slightly lower fusion rate (RR=0.84 [95% CI 0.72, 0.97], p=0.02, I2=0.0%) at 1-year follow-up while there was no difference on fusion rate at 2-year follow up (RR=1.06 [95% CI 0.96, 1.18], p=0.27, I2=69.0%). The estimated risk ratio of total adverse events (RR=0.90 [95% CI 0.59, 1.38], p=0.63, I2=0.0%) and revision rate (RR=0.78 [95%CI 0.34, 1.79], p=0.56, I2=39.0%) showed no difference. TLIF had approximately half an hour more operative time than other techniques (MD=31.88 [95% CI 5.33, 58.44], p=0.02, I2=92.0%). There was no significant difference between TLIF and other techniques in terms of the blood loss, and clinical outcomes.

Conclusions

Besides fusion rate at 1-year follow-up and operative time, our study demonstrated similar outcomes of TLIF with other techniques for lumbar diseases in regard to fusion rate, clinical outcomes, and complications.
Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes among schoolchildren exposed to scarlet fever: a longitudinal multi-cohort molecular epidemiology contact tracing study
Authors: Cordery Rebecca , Purba Amrit K. , Begum Lipi , Mills Ewurabena , Mosavie Mia , Vieira Ana , Jauneikaite Elita , Leung Rhoda CY , Siggins Matthew K. , Ready Derren , Hoffman Peter , Lamagni Theresa , Sriskandan Shiranee
Published: July 2021

Background

Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014-2018. We aimed to assess the impact of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments.

Methods

We undertook a prospective, contact tracing study in schools with 2 consecutive scarlet fever cases that were reported to local Health Protection teams in London between March 1st and May 31st in 2018 and 2019. We cultured throat swabs from cases, household contacts, and classroom contacts at four time points. We also cultured hand swabs and cough plates from all cases, and from classroom contacts in 2019. Surface swabs from toys and other fomites in classrooms were cultured in 2018, and settle plates from classrooms were collected in 2019. Any sample with S. pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain.

Findings

Six classes, comprising 12 scarlet fever cases, 17 household contacts, and 278 classroom contacts were recruited from March 1st to May 31st in 2018 and the same period in 2019. Prevalence of the outbreak S. pyogenes strain in throat swabs from asymptomatic classroom contacts was high, increasing from 9.6% (11/115) in week 1, to 26.9% (34/126) in week 2, to 24.1% (26/108) in week 3, then 14.3% (5/35) in week 4. Colonisation with non-outbreak and non-genotyped S. pyogenes strains was 1.7% (2/115); 3.9% (5/126); 5.6% (6/108); and 0/35 in the same weeks. Genome sequencing showed clonality of isolates within each of six classes, confirming recent transmission accounted for high carriage. When transmissibility was tested, children who were asymptomatic carriers of emm4 and emm3.93 had positive cough plates on 1/14 (7.1%) and 7/21 (33.3%) occasions respectively. Only 1/60 surface swabs taken in 3 classrooms yielded the outbreak S. pyogenes strain. In contrast, 2/12 and 6/12 settle plates placed in elevated locations yielded the outbreak S. pyogenes strain in the two classrooms tested.

Interpretation

S. pyogenes transmission in schools is intense and may occur prior to, or inspite of reported treatment of cases, underlining a need for rapid case management. Despite guideline adherence, heavy shedding of S. pyogenes by small numbers of classroom contacts may perpetuate outbreaks, and airborne transmission has a plausible role in spread. The findings highlight the need for research to improve understanding and assess effectiveness of interventions to reduce S. pyogenes airborne transmission.
Transmission dynamics of COVID-19 in Ghana and the impact of public health interventions
Authors: Ofori Sylvia K. , Schwind Jessica S. , Sullivan Kelly L. , Cowling Benjamin J. , Chowell Gerardo , Fung Isaac Chun-Hai
Published: July 2021

The study characterized COVID-19 transmission in Ghana in 2020-21 by estimating the time-varying reproduction number (Rt) and exploring its association with various public health interventions at the national and regional levels. Ghana experienced four pandemic waves with epidemic peaks in July 2020, and January, August and December, 2021. The epidemic peak was the highest nationwide in December 2021 with Rt ≥2. Throughout 2020-21, per-capita cumulative case count by region increased with population size. Mobility data suggested negative correlation between Rt and staying home in the first 90 days of the pandemic. The relaxation of movement restrictions and religious gatherings were not associated with increased Rt in the regions with lower case burdens. Rt decreased from above 1 when schools reopened in January 2021 to below 1 after vaccination rollout in March 2021. Findings indicated most public health interventions were associated with Rt reduction at the national and regional levels.
Sulfation of O-glycans on mucin-type proteins from serous ovarian epithelial tumors
Authors: Thomsson Kristina A. , Vitiazeva Varvara , Mateoiu Constantina , Jin Chunsheng , Liu Jining , Holgersson Jan , Weijdegard Birgitta , Sundfeldt Karin , Karlsson Niclas G.
Published: July 2021

Despite that sulfated O-linked glycans are abundant on ovarian cancer (OC) glycoproteins, their regulation during cancer development and involvement in cancer pathogenesis remain unexplored. We characterized O-glycans carrying sulfation on galactose residues and compared their expression to defined sulfotransferases regulated during OC development. Desialylated sulfated oligosaccharides were released from acidic glycoproteins in the cyst fluid from one patient with a benign serous cyst and one patient with serous OC. Oligosaccharides characterized by LC-MSn were identified as core 1 and core 2 O-glycans up to the size of decamers, and with 1-4 sulfates linked to GlcNAc residues and to C-3 and/or C-6 of Gal. To study the specificity of the potential ovarian sulfotransferases involved, Gal3ST2 (Gal-3S)-, Gal3ST4 (Gal-3S)-, and CHST1 (Gal-6S)-encoding expression plasmids were transfected individually into CHO cells also expressing the P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b (PSGL-1/mIg G2b) fusion protein and the human core 2 transferase (GCNT1). Characterization of the PSGL-1/mIg G2b O-glycans showed that Gal3ST2 preferentially sulfated Gal on the C-6 branch of core 2 structures and Gal3ST4 preferred Gal on the C-3 branch independently if core-1 or-2. CHST1 sulfated Gal residues on both the C-3 (core 1/2) and C-6 branches of core 2 structures. Using serous ovarian tissue micro array, Gal3ST2 was found to be decreased in tissue classified as malignant compared to tissues classified as benign or borderline, with the lowest expression in poorly differentiated malignant tissue. Neither Gal3ST4 nor CHST1 were differentially expressed in benign, borderline or malignant tissue, and there was no correlation between expression level and differentiation stage. The data displays a complex sulfation pattern of O-glycans on OC glycoproteins and that aggressiveness of the cancer is associated with a decreased expression of the Gal3ST2 transferase.
Assessment of COVID-19 risk and prevention effectiveness among spectators of mass gathering events
Authors: Yasutaka Tetsuo , Murakami Michio , Iwasaki Yuichi , Naito Wataru , Onishi Masaki , Fujita Tsukasa , Imoto Seiya
Published: July 2021

There is a need to evaluate and minimise the risk of novel coronavirus infections at mass gathering events, such as sports. In particular, to consider how to hold mass gathering events, it is important to clarify how the local infection prevalence, the number of spectators, the capacity proportion, and the implementation of preventions affect the infection risk. In this study, we used an environmental exposure model to analyse the relationship between infection risk and infection prevalence, the number of spectators, and the capacity proportion at mass gathering events in football and baseball games. In addition to assessing risk reduction through the implementation of various preventive measures, we assessed how face-mask-wearing proportion affects infection risk. Furthermore, the model was applied to estimate the number of infectors who entered the stadium and the number of newly infected individuals, and to compare them with actual reported cases. The model analysis revealed an 86%–95% reduction in the infection risk due to the implementation of face-mask wearing and hand washing. Among the individual measures, face-mask wearing was particularly effective, and the infection risk increased as the face-mask-wearing proportion decreased. A linear relationship was observed between infection risk at mass gathering events and the infection prevalence. Furthermore, the number of newly infected individuals was also dependent on the number of spectators and the capacity proportion independent of the infection prevalence, confirming the importance of considering spectator capacity in infection risk management. These results highlight that it is beneficial for organisers to ensure prevention compliance and to mitigate or limit the number of spectators according to the prevalence of local infection. Both the estimated and reported numbers of newly infected individuals after the events were small, below 10 per 3–4 million spectators, despite a small gap between these numbers.
Epigenome-wide DNA methylation profiling of healthy COVID-19 recoverees reveals a unique signature in circulating immune cells
Authors: Huoman Johanna , Sayyab Shumaila , Apostolou Eirini , Karlsson Lovisa , Porcile Lucas , Rizwan Muhammad , Sharma Sumit , Das Jyotirmoy , Rosén Anders , Lerm Maria
Published: July 2021

Background

Epigenetic alterations upon microbial challenge have been described as both a defence strategy and a result of pathogenic manipulation. While most COVID-19 studies focus on inflammatory and immune-mediated responses, little is known about epigenetic modifications in response to SARS-CoV-2 infection.

Methods

Epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation and module identification analyses.

Results

Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo, comprising 66 genes of which six (TP53, INS, HSPA4, SP1, ESR1 and FAS) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome.

Conclusions

Altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. As in vitro SARS-CoV-2 infection corroborated in vivo exposure results, this indicates DNA methylation is involved in immune cell responses to challenge with this virus. Future studies should determine whether this reflects host-induced protective antiviral defence or targeted viral hijacking to evade host defence.
Transient beta modulates decision thresholds during human action-stopping
Authors: Muralidharan Vignesh , Aron Adam R , Schmidt Robert
Published: July 2021

Action-stopping in humans involves bursts of beta oscillations in prefrontal-basal ganglia regions. To determine the functional role of these beta bursts we took advantage of the Race Model framework describing action-stopping. We incorporated beta bursts in three race model variants, each implementing a different functional contribution of beta to action-stopping. In these variants, we hypothesized that a transient increase in beta could 1) modulate decision thresholds, 2) change stop accumulation rates, or 3) promote the interaction between the Stop and the Go process. We then tested the model predictions using EEG recordings in humans performing a Stop-signal task. We found that the model variant in which beta increased decision thresholds for a brief period of time best explained the empirical data. The model parameters fitted to the empirical data indicated that beta bursts involve a stronger decision threshold modulation for the Go process than for the Stop process. This suggests that prefrontal beta influences stopping by temporarily holding the response from execution. Our study further suggests that human action-stopping could be multi-staged with the beta acting as a pause, increasing the response threshold for the Stop process to modulate behavior successfully. Our novel approach of introducing transient oscillations into the race model and testing against human neurophysiological data allowed us to discover potential mechanisms of prefrontal beta, possibly generalizing its role in situations requiring executive control over actions.
Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms
Authors: Pividori Milton , Lu Sumei , Li Binglan , Su Chun , Johnson Matthew E. , Wei Wei-Qi , Feng Qiping , Namjou Bahram , Kiryluk Krzysztof , Kullo Iftikhar , Luo Yuan , Sullivan Blair D. , Voight Benjamin F. , Skarke Carsten , Ritchie Marylyn D. , Grant Struan F.A. , Greene Casey S.
Published: July 2021

Genes act in concert with each other in specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. In this regard, the role of individual genes in disease-relevant mechanisms can be hypothesized with transcriptome-wide association studies (TWAS), which have represented a significant step forward in testing the mediating role of gene expression in GWAS associations. However, modern models of the architecture of complex traits predict that gene-gene interactions play a crucial role in disease origin and progression. Here we introduce PhenoPLIER, a computational approach that maps gene-trait associations and pharmacological perturbation data into a common latent representation for a joint analysis. This representation is based on modules of genes with similar expression patterns across the same conditions. We observed that diseases were significantly associated with gene modules expressed in relevant cell types, and our approach was accurate in predicting known drug-disease pairs and inferring mechanisms of action. Furthermore, using a CRISPR screen to analyze lipid regulation, we found that functionally important players lacked TWAS associations but were prioritized in trait-associated modules by PhenoPLIER. By incorporating groups of co-expressed genes, PhenoPLIER can contextualize genetic associations and reveal potential targets missed by single-gene strategies.
A new platform for high-throughput therapy testing on iPSC-derived, immature airway from Cystic Fibrosis Patients
Authors: Jiang Jia Xin , Wellhauser Leigh , Laselva Onofrio , Utkina Irina , Bozoky Zoltan , Gunawardena Tarini , Ngan Zoe , Xia Sunny , Eckford Paul D.W. , Ratjen Felix , Moraes Theo J. , Parkinson John , Wong Amy P. , Bear Christine
Published: July 2021

Induced pluripotent, stem cell (iPSC)-derived models of airway tissue have successfully modeled the primary defect in regulated chloride conductance caused by the major Cystic Fibrosis causing mutation, F508del. However, it remains unclear if iPSC-derived airway cultures can be used in high-throughput therapy development for F508del and rarer mutations. There is an urgent need for airway tissue models that reflect the variability of patient-specific responses and are scalable for therapy development. In the current work, we describe a robust, high-throughput fluorescence assay of mutant CFTR function in iPSCs differentiated to immature airway epithelium. This assay measures reproducible functional responses to modulators targeting either the major CF mutant F508del or the nonsense mutant: W1282X-CFTR. We show that the ranking of patient-specific responses to interventions in this stem-cell based model recapitulates the ranking observed in primary nasal epithelial cultures obtained from the same individuals. In summary, these proof-of-concept studies show that this novel platform has the potential to support therapy development and precision medicine for Cystic Fibrosis patients.
Lightsheet Optical Tweezer (LOT) for Optical Manipulation of Microscopic Particles and Live Cells
Authors: Mondal Partha Pratim , Singh Ankur , Joshi Prakash , Basumatary Jigmi , Baro Neptune
Published: July 2021

A light sheet based optical tweezer (LOT) is developed to trap microscopic dielectric particles and live HeLa cells. The technique requires the generation of a tightly focussed diffraction-limited light sheet which is realized by a combination of cylindrical lens and high NA objective lens. The field pattern generated at the geometrical focus is a tightly focussed line (alongx-axis) perpendicular to the beam propagation direction (z-axis). Spherical beads undergoing Brownian motion in the solution are trapped by the gradient potential, and the time (to reach trap-center under the influence of gradient potential) is estimated from the fast CMOS camera (operating at 230frames/sec). High-speed imaging of beads at varying laser power shows a steady increase in the stiffness of LOT with a maximum of 0.00118pN/nmat 52.5mW. This is an order less than traditional optical point-traps. The trapped beads displayed free movement along the light-sheet axis (x-axis), exhibiting a single degree of freedom. Subsequently, LOT is used to optically trap and pattern dielectric beads and HeLa cells in a line. We could successfully pattern 8 dielectric beads and 3 HeLa cells in a straight line. We anticipate that LOT can be used to study the 1D-physics of microscopic particles and help understand the patterned growth of live cells.
Relaxation time asymmetry in stator dynamics of the bacterial flagellar motor
Authors: Perez-Carrasco Ruben , Franco-Oñate María-José , Walter Jean-Charles , Dorignac Jérôme , Geniet Fred , Palmeri John , Parmeggiani Andrea , Walliser Nils-Ole , Nord Ashley L
Published: July 2021

The bacterial flagellar motor (BFM) is the membrane-embedded rotary molecular motor which turns the flagellum that provides thrust to many bacterial species. This large multimeric complex, composed of a few dozen constituent proteins, has emerged as a hallmark of dynamic subunit exchange. The stator units are inner-membrane ion channels which dynamically bind and unbind to the peptidoglycan at the rotor periphery, consuming the ion motive force (IMF) and applying torque to the rotor when bound. The dynamic exchange is known to be a function of the viscous load on the flagellum, allowing the bacterium to dynamically adapt to its local viscous environment, but the molecular mechanisms of exchange and mechanosensitivity remain to be revealed. Here, by actively perturbing the steady-state stator stoichiometry of individual motors, we reveal a stoichiometry-dependent asymmetry in stator remodeling kinetics. We interrogate the potential effect of next-neighbor interactions and local stator unit depletion and find that neither can explain the observed asymmetry. We then simulate and fit two mechanistically diverse models which recapitulate the asymmetry, finding stator assembly dynamics to be particularly well described by a two-state catch-bond mechanism.
Bioactivity, chemical profiling, and 16S rRNA-based phylogeny of haloalkaliphilic Nocardiopsis sp. GhM-HA-6 isolated from the Gulf of Khambhat
Authors: Trivedi Nisha D. , Thumar Jignasha T.
Published: July 2021

Objectives

Actinomycetes are well known sources of antibiotics, however; recently the focus of antimicrobial research has been turning towards actinomycetes of extreme environments. Therefore, present work would highlight the isolation, identification and characterization of antimicrobial metabolites produced by marine haloalkaliphilic actinomycetes.

Methods

Saline soil sample was collected from Ghogha coast (Gulf of Khambhat), Bhavnagar, Western India. Isolation was carried out using selective media while identification was done based on morphological, cultural and molecular characterization. The antimicrobial potential was checked by spot inoculation method. Optimization was carried out by the one variable at a time (OVAT) method. The antimicrobial compounds were extracted using ethyl acetate and characterized by GC-MS.

Results

The haloalkaliphilic actinomycetes Nocardiopsis sp. GhM-HA-6 was isolated from saline soil of Ghogha coast using starch agar with 10% w/v NaCl and pH 9 and was identified as Nocardiopsis sp. based on morphology, cultural characteristics and 16S rRNA phylogenetic analysis (NCBI Genbank Accession number: KF384492). The organism showed antimicrobial activity against five Gram positive and three Gram negative bacteria while the isolate didn’t show any antifungal activity. Results of optimization showed that the highest production of antimicrobial compounds was obtained using starch broth with 0.5% w/v starch, 1% w/v yeast extract, 10% w/v NaCl and pH 9. GC-MS analysis of ethyl acetate extract of the isolate showed presence of total 18 compounds including various antimicrobial compounds like 2, 4-bis (1, 1-dimethylethyl)-Phenol, various types of alkanes and their derivatives.

Conclusion

Haloalkaliphilic actinomycete Nocardiopsis sp. GhM-HA-6, from a rarely explored marine habitat, can be a source of antimicrobial compounds with the novel biotechnological applications.
Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome
Authors: Wang Jing , Fröhlich Henning , Torres Felipe Bodaleo , Silva Rangel Leal , Agarwal Amit , Rappold Gudrun A.
Published: July 2021

There is increasing evidence that mitochondrial homeostasis - influenced by both genetic and environmental factors - is crucial in neurodevelopment. FOXP1 syndrome is a neurodevelopmental disorder that manifests motor dysfunction, intellectual disability, autism and language impairment. In this study, we used aFoxp1+/−mouse model to address whether cognitive and motor deficits in FOXP1 syndrome are associated with mitochondrial dysfunction and oxidative stress. Here we show that genes with a role in mitochondrial biogenesis and dynamics (e.g.Foxo1,Pgc-1α,Tfam,Opa1, andDrp1)were dysregulated in the striatum ofFoxp1+/−mice at different postnatal stages. Furthermore, in the striatum ofFoxp1+/−animals, mitochondrial membrane potential was disrupted, and reactive oxygen species, lipid peroxidation and cytochrome c release were significantly elevated. These features can explain the reduced neurite branching, learning and memory, endurance, and motor coordination that we observed in these animals. Taken together, we provide strong evidence of mitochondrial dysfunction inFoxp1+/−mice, suggesting that insufficient energy supply and excessive oxidative stress underlies the cognitive and motor impairment in FOXP1 deficiency.
U2 snRNA structure is influenced by SF3A and SF3B proteins but not by SF3B inhibitors
Authors: Urabe Veronica K. , Stevers Meredith , Ghosh Arun K. , Jurica Melissa S.
Published: July 2021

U2 snRNP is an essential component of the spliceosome. It is responsible for branch point recognition in the spliceosome A-complex via base-pairing of U2 snRNA with an intron to form the branch helix. Small molecule inhibitors target the SF3B component of the U2 snRNP and interfere with A-complex formation during spliceosome assembly. We previously found that the first SF3B inhibited-complex is less stable than A-complex and hypothesized that SF3B inhibitors interfere with U2 snRNA secondary structure changes required to form the branch helix. Using RNA chemical modifiers, we probed U2 snRNA structure in A-complex and SF3B inhibited splicing complexes. The reactivity pattern for U2 snRNA in the SF3B inhibited-complex is indistinguishable from that of A-complex, suggesting that they have the same secondary structure conformation, including the branch helix. This observation suggests SF3B inhibited-complex instability does not stem from an alternate RNA conformation and instead points to the inhibitors interfering with protein component interactions that normally stabilize U2 snRNP’s association with an intron. In addition, we probed U2 snRNA in the free U2 snRNP in the presence of SF3B inhibitor and again saw no differences. However, increased protection of nucleotides upstream of Stem I in the absence of SF3A and SF3B proteins suggests a change of secondary structure at the very 5′ end of U2 snRNA. Chemical probing of synthetic U2 snRNA in the absence of proteins results in similar protections and predicts a previously uncharacterized extension of Stem I. Because this stem must be disrupted for SF3A and SF3B proteins to stably join the snRNP, the structure has the potential to influence snRNP assembly and recycling after spliceosome disassembly.