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ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVaxTM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVaxTM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.

Background: Cervical cancer is a public health problem in India due to weak national screening policy compounded by lack of resources including scarcity of trained personnel to carry out community-based screening program. Para medical professionals (PMPs) are closely related to women in local communities. Hence, training PMPs by incorporating novel technology and reduced time duration to achieve adequate competence in screening is an area underutilized and needs to be explored. Materials and methods: A pilot cross sectional analytical study was conducted at a tertiary referral cancer center using a shorter version of educational intervention of 2 weeks duration (EI2W) involving PMPs. Pre- and post-training assessment of knowledge, attitude, and practice (KAP) was done using questionnaires consisting of 5 domains viz. awareness of cervical cancer, awareness of cervical pre-cancer, practical screening methodology (practice oriented), data management and aspects of human papilloma virus (HPV). Wilcoxon signed-rank test was used for comparison and the degree of change was measured using analysis of covariance (ANCOVA). A p value of

Background and Objectives: Dental caries is an infectious transmissible disease resulting from tooth-adherent specific bacteria, primarily Mutans streptococci. Fluoride varnish is an effective antimicrobial agent against Streptococcus mutans (S. mutans). The aim of the study was to evaluate the levels of S. mutans in children following application of a fluoride varnish containing CPP-ACP in mother–child pairs. Materials and Methods: Sixty children aged 18–36 months, at high caries risk along with their mothers formed the study group. Baseline levels of S. mutans in saliva of mothers and dental plaque of children was microbiologically assessed for S. mutans using the culture method. They were divided into three groups, consisting of 20 mother–child pairs. Group 1: Application of varnish to mother and saline as a placebo to child; Group 2: Applying varnish to child and saline as a placebo to mother; Group 3: Applying varnish to both mother and child. S. mutans levels in dental plaque of children were assessed at 3, 6, 9, and 12 months. Data obtained were subjected to statistical analysis using one way analysis of variance, paired t-test and multiple Post hoc tukey. The level of Significance was considered at 5% Results: In all the groups, there was a significant reduction of S. mutans levels in dental plaque of children at 3, 6, 9, and 12 months. The highest reduction in S. mutans was in Group 3 (95.33%) followed by (95.12%) in Group 2 and 40.6% in Group 1 (P < 0.05). Conclusion: Application of fluoride varnish containing CPP-ACP to the children gave equivocally significant reduction in S. mutans levels of dental plaque in children, as compared to applying in both mother and child.

Immunogens mimicking the native-like structure of surface-exposed viral antigens are considered promising vaccine candidates. Influenza viruses are important zoonotic respiratory viruses with high pandemic potential. Recombinant soluble hemagglutinin (HA) glycoprotein-based protein subunit vaccines against Influenza have been shown to induce protective efficacy when administered intramuscularly. Here, we have expressed a recombinant soluble trimeric HA protein in Expi 293F cells and purified the protein derived from the Inf A/Guangdong-Maonan/ SWL1536/2019 virus which was found to be highly virulent in the mouse. The trimeric HA protein was found to be in the oligomeric state, highly stable, and the efficacy study in the BALB/c mouse challenge model through intradermal immunization with the prime-boost regimen conferred complete protection against a high lethal dose of homologous and mouse-adapted InfA/PR8 virus challenge. Furthermore, the immunogen induced high hemagglutinin inhibition (HI) titers and showed cross-protection against other Inf A and Inf B subtypes. The results are promising and warrant trimeric HA as a suitable vaccine candidate.

AbstractThe aim of this research paper is to investigate the adoption of digital branding among specialty eatery start-ups in a post-pandemic environment. The study analyses the relevance of digital branding’s advantages and drawbacks, and examines the intention of specialty eateries to adopt digital branding. Additionally, the research investigates the mediating influence of digital support and awareness on the adoption of digital branding. A detailed Google-form-based survey was conducted on 231 small cafés and restaurants in Maharashtra’s major cities that opened after COVID-19 (Mumbai, Pune, Nagpur, and Thane) to collect primary data. The data was analysed using the AMOS (Analysis of Moment Structures) program. The study concludes that digital branding plays a crucial role as an independent branding strategy and enhances the performance of specialty eatery start-ups in the post-pandemic era. Furthermore, the study highlights the significant mediating effect of digital support and awareness on the adoption intention of digital branding. This research is the first of its kind to examine the intention of startups in the specialty eatery industry to use digital branding to reach their intended audience. The study utilizes a quantitative approach, contributing to the respective research area that has been predominantly qualitative in previous studies regarding digital branding adoption. The findings of this research provide valuable insights for specialty eatery start-ups and other related businesses to enhance their digital branding strategies.

Abstract Background Multiple primary melanoma (MPM) is known to be associated with familial melanoma. However, the association between MPM and other personal and familial cancers is not well documented. The objective of this study was to evaluate the association between MPM and personal history of other cancers or cancer history among first‐degree relatives (FDRs). Methods We performed a retrospective case–control study including cases with gender‐matched MPM and single primary melanoma (SPM) at a 1:2 ratio from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank. The associations between MPM and other cancers were evaluated using univariable and multivariable logistic regression models. Results In total, 378 patients (44.2% men; median age 52 years) were enrolled, including 252 with SPM and 126 with MPM. In comparison to patients with SPM, patients with MPM were more likely to have squamous cell carcinoma (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.001–3.79, p = 0.047) and prostate cancer (OR 2.72, 95% CI 1.07–7.01, p = 0.034). FDRs of patients with MPM had higher prevalence of melanoma (OR 2.37, 95% CI 1.31–4.28, p = 0.004) and prostate cancer (OR 2.92, 95% CI 1.47–6.14, p = 0.002) but not other cancers. In multivariable analysis, the association remained significant between MPM and squamous cell carcinoma (OR 2.18, 95% CI 1.08–4.39, p = 0.028), prostate cancer (OR 2.85, 95% CI 1.09–7.54, p = 0.032), FDR history of melanoma (OR 2.37, 95% CI 1.31–4.29, p = 0.004), and FDR history of prostate cancer (OR 3.26, 95% CI 1.59–6.83, p = 0.001). Conclusions Patients with MPM have a higher prevalence of personal and FDR histories of nonmelanoma skin cancers and prostate cancer.

Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.

Abstract Background Type 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction. Methods The microRNA (miRNA) content of circulating extracellular vesicles (EVs) was assessed in T2D models to identify biomarkers of coronary microvascular dysfunction/rarefaction. The potential source of circulating EV-encapsulated miRNAs was determined, and the mechanisms of induction and the function of candidate miRNAs were assessed in endothelial cells (ECs). Results We found an increase in miR-30d-5p and miR-30e-5p in circulating EVs that coincided with indices of coronary microvascular EC dysfunction (i.e., markers of oxidative stress, DNA damage/senescence) and rarefaction, and preceded echocardiographic evidence of diastolic dysfunction. These miRNAs may serve as biomarkers of coronary microvascular dysfunction as they are upregulated in ECs of the left ventricle of the heart, but not other organs, in db/db mice. Furthermore, the miR-30 family is secreted in EVs from senescent ECs in culture, and ECs with senescent-like characteristics are present in the db/db heart. Assessment of miR-30 target pathways revealed a network of genes involved in fatty acid biosynthesis and metabolism. Over-expression of miR-30e in cultured ECs increased fatty acid β-oxidation and the production of reactive oxygen species and lipid peroxidation, while inhibiting the miR-30 family decreased fatty acid β-oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to down-regulate the expression of eNOS, a key regulator of microvascular and cardiomyocyte function. Finally, knock-down of the miR-30 family in db/db mice decreased markers of oxidative stress and DNA damage/senescence in the microvascular endothelium. Conclusions MiR-30d/e represent early biomarkers and potential therapeutic targets that are indicative of the development of diastolic dysfunction and may reflect altered EC fatty acid metabolism and microvascular dysfunction in the diabetic heart.

Aims: The three main types of anastomotic configurations following colorectal resection are Side-to-Side Anastomosis (S-S), End-to-Side Anastomosis (E-S) and End-to-End Anastomosis (E-E). This study aims to present results from a local cohort supplemented by a systematic review with meta-analysis of existing literature to compare the post-operative outcomes between E-S and S-S. Methods: A cohort study of patients who underwent right colectomy with E-S or S-S anastomosis, was conducted at the National University Hospital Singapore. Electronic databases Embase and Medline were systematically searched from inception to 21 August 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Studies were included if they compared post-operative outcomes between E-S and S-S. Results: In the cohort study, 40 underwent E-S and 154 underwent S-S. Both post-operative ileus (12.5% vs. 29.2%, P = 0.041) and length of hospital stay (9.35 days vs. 14.04 days, P = 0.024) favoured E-S, but anastomotic bleed favoured S-S (15.0% vs. 3.2%, P = 0.004). Five studies were included in the meta-analysis with 860 E-S and 1126 S-S patients. Similarly, post-operative ileus (odds ratio [OR] =0.302; 95% confidence interval [CI]: 0.122–0.747; P = 0.010) and length of hospital stay (mean differences = ‒1.54 days; CI: ‒3.00 to ‒0.076 days; P = 0.039) favoured E-S. Additional sensitivity analysis including only stapled anastomosis showed a lower rate of anastomotic leak in E-S patients (OR = 0.185; 95% CI: 0.054–0.627; P = 0.007). Conclusions: This is the first systematic review to show that the E-S technique produces superior post-operative outcomes after right colectomy compared to S-S. However, the choice of anastomosis was largely surgeon dependent, but surgeon factors were not reported.

Introduction: Genital mycoplasmas namely Mycoplasma Hominis and Ureaplasma Urealyticum are sexually transmitted disease pathogens which are associated with genital infections, infertility, obstetric and neonatal complications. The pathogenesis, prevalence, epidemiology and antibiotic resistance of genital mycoplasmas in Indian women have been studied very minimally. Aim: To determine the prevalence and antibiotic susceptibility pattern of M.hominis and U.urealyticum among females presenting with genital tract infections Materials and Methods: The hospital-based descriptive cross-sectional study was carried out among 120 females of reproductive age group (15-49 years) attending Outpatient Department of Obstetrics and Gynaecology of a tertiary care centre in central Kerala, India, from January 2018 to December 2018. Endocervical/vaginal/urethral samples were collected depending on the clinical presentation. Detection, quantitation and antibiotic sensitivity pattern of M.hominis and U.urealyticum were performed using Mycoplasma IST 2 Kit. Data was analysed using Statistical Package for the Social Sciences (SPSS) version 11.5 and statistical association was analysed using Chi-square test. Results: The prevalence of genital mycoplasmas was 25.83%. U.urealyticum infection was present in 20 (20.8%) and M.hominis infection was present in 12 (10%) of the patients. Age group of 26-35 years was commonly affected. All isolates showed high susceptibility rates to doxycycline, josamycin and pristinamycin. Intermediate to high resistance was noted to commonly prescribed macrolides and quinolones. Conclusion: Genital mycoplasmas are prevalent in one-fourth of the study population with U.urealyticum infections being more common than M.hominis infections. The increased resistance rates to quinolones and macrolides warrants the need for routine screening and antibiotic susceptibility testing of these pathogens.

The growth of the “Internet” and the subsequent use of smartphones has led to heavy social media usage in recent years. Social media campaigns have been successful in influencing purchase intention. Ethnocentrism also affects the purchase intention (PI) of domestic products. ETH is an evolving field, particularly for the purchase intention of domestic products. Considering the same, we examined the impact of social media campaigns (SMC) and ethnocentrism (ETH) on the purchase intention of domestic products. The mediating role of ethnocentrism and the moderating role of country-of-origin image (COOI) are examined further. The proposed hypotheses were examined using structural equation modeling. Data was collected from 431 avid social media users in a region that saw massive protests through social media campaigns. The results exhibit the positive impact of social media campaigns and ethnocentrism positively over the purchase intention of domestic products. In addition, ethnocentrism was found to be a mediator between social media campaigns and the purchase intention of domestic products. Moreover, the country of origin image strengthens the positive relationship between social media campaigns and the purchase intention of domestic products. However, COOI dampened the positive relationship between social media campaigns and ethnocentrism. This study provides fresh insights and implications for theory and practice.

Introduction: The aim of this study was to compare the effect of pentetic acid (diethylenetriaminepentaacetic acid) with ethylenediaminetetraacetic acid (EDTA), as final chelating agents on the pushout bond strength of AH Plus sealer. Materials and Methods: Single-rooted mandibular premolars (n = 80) were collected. The canals were instrumented and were randomly divided into four groups (n = 20) according to the final irrigation protocol followed, where Group I: distilled water, Group II: 3% NaOCl and distilled water final rinse; Group III: 3% NaOCl and 17% EDTA as final irrigant, and Group IV: 3% NaOCl and 5% pentetic acid as final irrigant. Canals were then dried and filled with AH Plus sealer. Roots were sectioned transversely at 4 mm from apex, with 1 mm thickness, and tested for pushout bond strength. Results were analyzed using analysis of variance and post hoc Tukey's test. Results: Pushout bond strength of AH Plus was found to be best with 5% pentetic acid final rinse (0.841 ± 0.15 MPa), followed by 17% EDTA (0.83 ± 0.27 MPa), 3% NaOCl (0.68 ± 0.16 MPa), and distilled water (0.52 ± 0.04). However, there was no statistical difference between 5% pentetic acid and 17% EDTA when used as a final rinse (P < 0.05). The failure modes in Groups III and IV were mixed, whereas Groups I and II showed adhesive failure. Conclusion: Within the limits of the study, 5% pentetic acid was as effective as 17% EDTA and hence can be considered as a potential chelating agent in endodontic therapy.

PurposePrecision oncology, such as next generation sequencing (NGS) molecular analysis and bioinformatics are used to guide targeted therapies. The laboratory turnaround time (TAT) is a key performance indicator of laboratory performance. This study aims to formally apply statistical process control (SPC) methods such as CUSUM and EWMA to a precision medicine programme to analyze the learning curves of NGS and bioinformatics processes.Patients and MethodsTrends in NGS and bioinformatics TAT were analyzed using simple regression models with TAT as the dependent variable and chronologically-ordered case number as the independent variable. The M-estimator “robust” regression and negative binomial regression were chosen to serve as sensitivity analyses to each other. Next, two popular statistical process control (SPC) approaches which are CUSUM and EWMA were utilized and the CUSUM log-likelihood ratio (LLR) charts were also generated. All statistical analyses were done in Stata version 16.0 (StataCorp), and nominal P < 0.05 was considered to be statistically significant.ResultsA total of 365 patients underwent successful molecular profiling. Both the robust linear model and negative binomial model showed statistically significant reductions in TAT with accumulating experience. The EWMA and CUSUM charts of overall TAT largely corresponded except that the EWMA chart consistently decreased while the CUSUM analyses indicated improvement only after a nadir at the 82nd case. CUSUM analysis found that the bioinformatics team took a lower number of cases (54 cases) to overcome the learning curve compared to the NGS team (85 cases).ConclusionAs NGS and bioinformatics lead precision oncology into the forefront of cancer management, characterizing the TAT of NGS and bioinformatics processes improves the timeliness of data output by potentially spotlighting problems early for rectification, thereby improving care delivery.

ObjectiveThis study was conducted to better understand the pervasive gender barriers obstructing the progression of women in surgery by synthesising the perspectives of both female surgical trainees and surgeons.MethodsFive electronic databases, including Medline, Embase, PsycINFO, CINAHL and Web of Science Core Collection, were searched for relevant articles. Following a full-text review by three authors, qualitative data was synthesized thematically according to the Thomas and Harden methodology and quality assessment was conducted by two authors reaching a consensus.ResultsFourteen articles were included, with unfavorable work environments, male-dominated culture and societal pressures being major themes. Females in surgery lacked support, faced harassment, and had unequal opportunities, which were often exacerbated by sex-blindness by their male counterparts. Mothers were especially affected, struggling to achieve a work-life balance while facing strong criticism. However, with increasing recognition of the unique professional traits of female surgeons, there is progress towards gender quality which requires continued and sustained efforts.ConclusionThis systematic review sheds light on the numerous gender barriers that continue to stand in the way of female surgeons despite progress towards gender equality over the years. As the global agenda towards equality progresses, this review serves as a call-to-action to increase collective effort towards gender inclusivity which will significantly improve future health outcomes.

INTRODUCTION:Diabetes self-management education is a key aspect in the long-term management of type 2 diabetes. The patient and healthcare professional (HCP) perspective on the use of technology-assisted DSME has yet to be studied. Hence, the objective of this study was to better understand the factors that facilitate or hinder the adoptions of such education by adults with type 2 diabetes and their HCPs. METHODS:We systematically searched five databases (Medline, Embase, CINAHL, Web of Science Core Collection, and PsycINFO) until August 2019. The search included qualitative and mixed-method studies that reported the views of patients and HCPs regarding features, uses, and implementations of technology-assisted DSME. Data were synthesized through an inductive thematic analysis. RESULTS:A total of 13 articles were included, involving 242 patients, ranging from 18 to 81 years and included web-based, mobile application, digital versatile disc (DVD), virtual reality or telehealth interventions. Patients and HCPs had mixed views towards features of the technology-assisted interventions, with patients' personal qualities and HCPs' concerns affecting uses of the interventions. Patients generally preferred technologies that were easy to access, use, and apply and that had reliable information. Patients' ambitions motivated them, and personal attributes such as poor competence with technology, poor literacy, and language barriers acted as barriers. Patients especially liked the peer support that they received but did not like it when there was no regulation of advice on these platforms. HCPs believed that while the interventions were useful to patients, they faced difficulties with integration into their clinical workflows. CONCLUSION:This review explored the features of technology-assisted diabetes self-management education interventions that enhanced positive patient engagements and the negative aspects of both the platforms and the target groups. Technical support and training will be effective in managing these concerns and ensuring meaningful use of these platforms.

A 59-year-old male presented with episodic headaches and blurring vision, and papilledema (PE) on examination. He had been advised continuous positive airway pressure (CPAP) treatment for moderate obstructive sleep apnea (OSA) and an apneic–hypopneic index of 21 but had not commenced the treatment. Magnetic resonance imaging of the brain was normal, but a contrast examination was not done. Magnetic resonance venography performed to assess the PE, revealed cerebral venous thrombosis (CVT) affecting the superior sagittal, transverse, and sigmoid sinuses. Oral anticoagulants and CPAP resulted in a speedy reversal of both PE and CVT. CVT may complicate OSA and require identification and treatment. Contrast studies are crucial in the evaluation.

Catalytic conversion of CO2 into value‐added chemicals is necessary to mitigate the increasing global warming and energy‐related issues. The selective production of C2 or C2+ products by photoreduction of CO2 is a challenging task due to the sluggish kinetics of C─C coupling. Herein, the potential of a silver nanoparticle (Ag NP) incorporated metal‐organic framework (MOF), NU‐1000 is introduced, to harvest light and ease the uphill electron transfer. The growth of silver nanoparticles on thiol‐functionalized NU‐1000 is studied using the atomic pair distribution function (PDF) analysis. The C2 product formed using Ag@NU‐1000‐SH without any sacrificial agents is acetic acid, which is confirmed by 1H‐NMR and HRMS data. The catalyst displays a high acetate output of 293.58 µmolg−1h−1 with a selectivity of 79.4%. The XPS and DFT calculations evidence that the presence of the charge‐polarised states in the as‐synthesized catalyst act as asymmetric centers that favor the C─C coupling reaction. The combined experimental (in situ DRIFT spectroscopic studies) and theoretical calculations reveal that the C─C coupling takes place via the coupling of COOH*intermediates. [ABSTRACT FROM AUTHOR]

An 85-year-old man presented with an acute asymptomatic lateral neck mass in the context of deep tissue neck massages during the past year. He was referred to vascular surgery after an ultrasound examination of the neck revealed a thrombus in the external jugular vein. His past medical history and comorbidities were noncontributory. A multidisciplinary team of vascular surgeons and hematologists did not recommend any anticoagulation, given that the patient did not have any risk factors for thrombosis as well as normal D-dimer levels. The patient was maintained on his previous dose of aspirin (81 mg daily).