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Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathway regulates cell morphology, polarity, and cytoskeletal remodeling. We observed the activation of ROCK1/myosin light chain (MLC2) signaling pathway in buffalopox virus (BPXV) infected Vero cells. ROCK1 depletion by siRNA and specific small molecule chemical inhibitors (Thiazovivin and Y27632) resulted in a reduced BPXV replication, as evidenced by reductions in viral mRNA/protein synthesis, genome copy numbers and progeny virus particles. Further, we demonstrated that ROCK1 inhibition promotes deadenylation of viral mRNA (mRNA decay), mediated via inhibiting interaction with PABP [(poly(A)-binding protein] and enhancing the expression of CCR4-NOT (a multi-protein complex that plays an important role in deadenylation of mRNA). In addition, ROCK1/MLC2 mediated cell contraction, and perinuclear accumulation of p-MLC2 was shown to positively correlate with viral mRNA/protein synthesis. Finally, it was demonstrated that the long-term sequential passage (P = 50) of BPXV in the presence of Thiazovivin does not select for any drug-resistant virus variants. In conclusion, ROCK1/MLC2 cell signaling pathway facilitates BPXV replication by preventing viral mRNA decay and that the inhibitors targeting this pathway may have novel therapeutic effects against buffalopox., (© 2022. The Author(s).)

Background: Heartworms, Dirofilaria immitis, are known to be widespread in dogs and cats in the USA, but there have been no country-wide prevalence studies performed to date. There have also been no large-scale studies to determine whether the closely related species, Dirofilaria repens, occurs in the USA., Methods: To provide this large-scale data, we examined whole blood samples (n = 2334) submitted from around the USA to the Molecular Diagnostic Laboratory at Auburn University between 2016 and 2022. Quantitative PCRs for D. immitis (targeting 16S rRNA) and D. repens (targeting cytochrome c oxidase subunit 1 gene) were performed to determine the presence of Dirofilaria DNA. DNA sequencing was performed to confirm the results., Results: Dirofilaria immitis DNA was found in 6.3% (68/1080) of the dogs from 17/39 states, and 0.3% (4/1254) of the cats from 4/42 states. None of the dogs or cats were positive for D. repens. The average 16S rRNA copy number of D. immitis in the dogs was 1,809,604 in 200 µl whole blood, while only a single copy was found in each of the four D. immitis-positive cats. The prevalence of D. immitis in dogs of different ages, sexes, and breeds did not differ significantly, but the prevalence in Southern states (7.5%, 60/803) was significantly higher than in the Western (1.7%, 1/58), Midwest (3.3%, 4/120), and Northeastern states (3.1%, 3/98) (P < 0.05). Dogs positive for D. immitis were identified in each study year (2016: 4.2%, 2/48; 2017: 9.8%, 4/41; 2018: 5.1%, 8/156; 2019: 4.9%, 15/306; 2020: 9.8%, 26/265; 2021: 4.9%, 13/264). Interestingly, dogs infected with Hepatozoon spp. (11.8%, 37/313) were significantly more likely to also be positive for D. immitis than dogs without evidence of Hepatozoon infection (3.9%, 30/760) (P < 0.0001)., Conclusions: To our knowledge, this is the first nationwide molecular survey of Dirofilaria spp. in dogs and cats in the USA, and the largest molecular survey of canine and feline dirofilariosis worldwide. Further studies are warranted to combine PCR with standard heartworm diagnostics to better understand the prevalence of Dirofilaria spp. and aid in determining the risks posed to dogs and cats in the USA., (© 2022. The Author(s).)

Background: There has been growing interest in studying postprandial glucose responses using continuous glucose monitoring (CGM) in nondiabetic individuals. Accurate measurement of glucose responses to meals can facilitate applications such as precision nutrition and early detection of diabetes., Objectives: We aimed to quantify the discordance between simultaneous postprandial glucose measurements made using plasma and CGM., Methods: We studied 10 nondiabetic older adults who randomly consumed 9 predefined meals of varying macronutrient compositions. Glucose was measured for 8 h after the meal by the CGM, blood samples for plasma collection were taken regularly, and plasma glucose was quantified using gold-standard laboratory measurement and a fingerstick blood glucose meter. The primary outcome measured was the mean absolute relative difference (MARD) of CGM and fingerstick measurements relative to the gold standard. Secondary outcomes were Bland-Altman statistics, Clarke Error Grid, and time in range metrics. Additional subgroup analyses were performed by stratifying the postprandial glucose measurements based on the macronutrient composition of the meals., Results: When compared against the gold-standard postprandial glucose measurements, the fingerstick meter was more accurate (MARD: 8.0%; 95% CI: 7.6%, 8.6%) than the CGM (MARD: 13.7%; 95% CI: 13.1%, 14.3%; P < 0.0001). After the meals, Bland-Altman analysis demonstrated that the CGM underestimated the 8-h gold-standard glucose rise by 12.8 mg/dL on average (P < 0.0001), whereas the fingerstick meter did so by 5.5 mg/dL on average (P < 0.0001). The CGM underestimated the time spent in the 70-180 mg/dL range (P = 0.002) and overestimated the time spent <70 mg/dL (P < 0.0001) compared with the other 2 methods., Conclusions: We discovered discordance between gold standard, fingerstick, and CGM in measuring plasma glucose concentrations after a meal. Consequently, emerging applications of CGM in healthy individuals, such as precision nutrition and diabetes onset prediction, may need to account for these discordances.This trial was registered at clinicaltrials.gov as NCT04928872., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Fatigued skin, defined as dehydrated skin with lack of visual facial firmness and dull appearance, can be attributed to intrinsic and extrinsic factors of aging. An anti-aging daily serum (AADS) containing a unique sunflower sprout extract (SSE) was formulated to target fatigued and photodamaged skin., Aims: Utilizing both preclinical and clinical testing models, the efficacy of the AADS was investigated to improve fatigued and photodamaged skin., Patients/method: Preclinical studies included in vitro analysis of adenosine triphosphate (ATP) production in fatigued dermal fibroblasts, inhibition of ultraviolet radiation A (UVA) induced advanced glycation end products (AGEs) in keratinocytes, and ex vivo gene expression after incubation with the SSE. An institutional review board (IRB)-approved short-term, 7-day, clinical case study was conducted on 28 female subjects, Fitzpatrick skin type I-IV, aged 30-60 years with moderate overall photodamage and skin fatigue. This was a double-blinded, randomized, controlled, single-center case study testing the AADS alone and in combination with an anti-aging facial moisturizer (AAFM)., Results: The SSE boosted intracellular ATP production in fatigued fibroblasts and reduced the formation of AGEs in keratinocytes. The SSE increased expression of genes related to epidermal keratinization and downregulated genes related to inflammation. Statistically significant improvement was found after 7 days of twice-daily use of the AADS alone and in combination with the AAFM. Products were well tolerated and perceived by subjects., Conclusion: Preclinical results combined with the clinical results strongly suggest that the AADS containing the SSE was tolerable and effective in targeting fatigued and photodamaged skin., (© 2022 Wiley Periodicals LLC.)

Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In this study, we have demonstrated that inhibition of p38 mitogen-activated protein kinase (a cellular protein) suppresses buffalopox virus (BPXV) protein synthesis by targeting p38-MNK1-eIF4E signaling pathway. In order to provide insights into the evolution of drug resistance, we selected resistant mutants by long-term sequential passages (P; n = 60) in the presence of p38 inhibitor (SB239063). The P60-SB239063 virus exhibited significant resistance to SB239063 as compared to the P60-Control virus. To provide mechanistic insights on the acquisition of resistance by BPXV-P60-SB239063, we generated p38-α and p38-ϒ (isoforms of p38) knockout Vero cells by CRISPR/Cas9-mediated genome editing. It was demonstrated that unlike the wild type (WT) virus which is dependent on p38-α isoform, the resistant virus (BPXV-P60-SB239063) switches over to use p38-ϒ so as to efficiently replicate in the target cells. This is a rare evidence wherein a virus was shown to bypass the dependency on a critical cellular factor under selective pressure of a drug., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Mycotoxins are secondary metabolites produced by fungi that infect a wide range of foods worldwide. Nivalenol (NIV), a type B trichothecene produced by numerous Fusarium species, has the ability to infect a variety of foods both in the field and during post-harvest handling and management. NIV is frequently found in cereal and cereal-based goods, and its strong cytotoxicity poses major concerns for both human and animal health. To address these issues, this review briefly overviews the sources, occurrence, chemistry and biosynthesis of NIV. Additionally, a brief overview of several sophisticated detection and management techniques is included, along with the implications of processing and environmental factors on the formation of NIV. This review's main goal is to offer trustworthy and current information on NIV as a mycotoxin concern in foods, with potential mitigation measures to assure food safety and security.

Objectives: We aimed at the identification of the association of comorbidities with the COVID-19 severity and hospitalization., Methods: It is a retrospective cross-sectional study to investigate the variation in age, sex, dwelling, comorbidities, and medication with the COVID-19 severity and hospitalization by enrolling 1025 recovered individuals while comparing their time of recovery with or without comorbidities., Results: COVID-19 patients mostly suffered from fever. The predominant underlying medical conditions in them were hypertension (HTN) followed by diabetes mellitus (DM). Patients with cardiovascular disease (CVD) (54.3%) and hepatic disorders (HD) (43.6%) experienced higher severity. The risk of symptomatic cases was higher in aged (odds ratio, OR = 1.04, 95% CI = 1.02-1.06) and comorbid (OR = 1.87, 95% CI = 1.34-2.60) patients. T-test confirmed the differences between the comorbid and non-comorbid patients' recovery duration. The presence of multiple comorbidities increased the time of recovery (15-27 days) and hospitalization (20-40%). Increased symptomatic cases were found for patients having DM+HTN whereas CVD+Asthma patients were found with higher percentage of severity. Besides, DM+CKD (chronic kidney disease) was associated with higher hospitalization rate. Higher odds of severity were found for DM+CVD (OR = 4.42, 95% CI = 1.81-10.78) patients. Hospitalization risk was also increased for them (OR = 5.14, 95% CI = 2.02-13.07). Moreover, if they had HTN along with DM+CVD, they were found with even higher odds (OR = 6.82, 95% CI = 2.37-19.58) for hospitalization., Conclusion: Our study indicates that people who are aged, females, living in urban area and have comorbid conditions are at a higher risk for developing COVID-19 severity. Clinicians and health management authorities should prioritize these high-risk groups to reduce mortality attributed to the disease., (Copyright: © International Journal of Health Sciences.)

Vacuolar ATPases (V-ATPases) are large multisubunit proton pumps conserved among all eukaryotic cells that are involved in diverse functions including acidification of membrane-bound intracellular compartments. The ATP6AP1 gene encodes an accessory subunit of the vacuolar (V)-ATPase protein pump. Pathogenic variants in ATP6AP1 have been described in association with a congenital disorder of glycosylation (CDG), which are highly variable, but often characterized by immunodeficiency, hepatopathy, and neurologic manifestations. Although the most striking and common clinical feature is hepatopathy, the phenotypic and genotypic spectrum of ATP6AP1-CDG continues to expand. Here, we report identical twins who presented with acute liver failure and jaundice. Prenatal features included cystic hygroma, atrial septal defect, and ventriculomegaly. Postnatal features included pectus carinatum, connective tissue abnormalities, and hypospadias. Whole-exome sequencing (WES) revealed a novel de novo in-frame deletion in the ATP6AP1 gene (c.230&#95;232delACT;p.Tyr77del). Although both twins have the commonly reported clinical feature of hepatopathy seen in other individuals with ATP6AP1-CDG -related disorder, they do not have neurological sequelae. This report expands the phenotypic spectrum of ATP6AP1-CDG- related disorder with both probands exhibiting unique prenatal and postnatal features, including fetal ventriculomegaly, umbilical hernia, pectus carinatum, micropenis, and hypospadias. Furthermore, this case affirms that neurological features described in the initial case series on ATP6AP1-CDG do not appear to be central, whereas the prenatal and connective tissue manifestations may be more common than previously thought. This emphasizes the importance of long-term clinical follow-up and variant interpretation using current updated recommendations., (© 2022 Barua et al.; Published by Cold Spring Harbor Laboratory Press.)

(1) Introduction: Adult-onset pilocytic astrocytoma (APA) accounts for only 1.5% of all brain tumors, and studies regarding APA are limited. This review is focused on the history, clinical course, cytogenetics, neuroimaging features, management, and outcome of APAs. (2) Methods: Using a systematic search protocol in Google Scholar, PubMed, and Science Direct databases, the authors extracted cases of APA predilecting the temporal lobe from inception to December 2020. Articles lacking necessary data were excluded from this study. Data were analyzed using IBM SPSS 23 statistical package software. (3) Results: A total of 32 patients, 14 (43.8%) males and 18 (56.2%) females, with a male/female ratio of 0.77/1, were grouped. The mean age of the patients was 34.22 ± 15.17 years, ranging from 19 to 75. The tumors were predominantly located in the left side. We have also discussed the clinical presentation, and headache was the most common complaint, followed by visual disturbance. Preoperative neuroimaging features demonstrated cystic lesions in 16 patients, with mural nodule in 5 patients; intracerebral hemorrhage was present in 1 patient, and solid enhancing mass was observed in 3 patients. Only our reported case presented as a solid calcified mass. Most of the patients (78.1%) underwent a gross total resection (GTR), only 5 (21.9%) underwent subtotal resection (STR). The outcome and prognosis history were excellent, and no recurrence was observed. (4) Conclusion: Most of the APAs of the temporal lobe follow benign clinical courses, but some patients exhibit aggressive clinical behavior. There was no history of recurrence after treatment at up to 27 years of follow-up.

Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders., (© 2022. The Author(s).)

Avian influenza viruses (AIV) increase commercial and backyard poultry mortality and morbidity, reduces egg production, and elevates public health risk. Household ducks propagate and transmit HPAI and LPAI viruses between domesticated and wild birds in Southeast Asian countries, including Bangladesh. This study was conducted to identify epidemiological factors associated with AIV infection among household ducks at Chattogram, Bangladesh. We randomly selected and collected blood and oropharyngeal swab samples from 281 households ducks. We evaluated the serum for AIV antibody using cELISA and tested for H5 and H9 subtypes using the HI test. We tested the swabs with real-time reverse transcriptase PCR (rRT-PCR) for M gene, and H5, H9 subtypes. In the duck populations, the household level AIV sero-prevalence was 57.7% (95% CI: 51.6-63.3) and RNA prevalence was 2.4% (95% CI: 1.0-5.0). H5 and H9 subtype sero-prevalence was 31.5% (95% CI: 22.2-42.0) and 23.9% (95% CI: 15.6-33.9). H5 and H9 subtype RNA prevalence were 0% (95% CI: 0.0-1.3) and 2.4% (95% CI: 1.0-5.0). We determined household-level OR (Odds Ratios) for the "combined (mixed materials-mud and concrete or metallic)" category was 2.2 (95% CI: 1.1-4.2) compared with "wooden/bamboo" category (p = 0.02); 2.8 (95% CI: 1.2-6.6) in households with duck plague vaccine coverage compared with no coverage (p = 0.01); and 2.4 (95% CI: 0.6-9.7) in households that threw dead birds in bushes and the roadside compared with households that buried or threw dead birds in garbage pits (p = 0.21). M gene phylogenetic analysis compared M gene sequences to previously reported Bangladeshi H9N2 isolates. The evidence presented here shows AIV circulation in the Chattogram, Bangladesh study areas. AIV reduction can be achieved through farmer education of proper farm management practices., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Adaptive modulation received significant attention for underwater acoustic (UA) communication systems with the aim of increasing the system efficiency. It is challenging to attain a high data rate in UA communication, as UA channels vary fast, along with the environmental factors. For a time-varying UA channel, a self-adaptive system is an attractive option, which can choose the best method according to the channel condition to guarantee the continuous connectivity and high performance constantly. A real-time orthogonal frequency-division multiplexing (OFDM)-based adaptive UA communication system is presented in this paper, employing the National Instruments (NI) LabVIEW software and NI CompactDAQ device. In this paper, the received SNR is considered as a performance metric to select the transmission parameters, which are sent back to the transmitter for data transmission. In this research, a UA OFDM communication system is developed, employing adaptive modulation schemes for a nonstationary UA environment which allows to select subcarriers, modulation size, and allocate power adaptively to enhance the reliability of communication, guarantee continuous connectivity, and boost data rate. The recent UA communication experiments carried out in the Canning River, Western Australia, verify the performance of the proposed adaptive UA OFDM system, and the experimental results confirm the superiority of the proposed adaptive scheme.

This two-dimensional study makes significant incursions into the health-environment literature by interrogating whether non-renewable energy moderates the impact of environmental degradation on mortality rates. It further aligns with the 2030 United Nations Sustainable Development Goals and 11, which aim to ensure healthy lives and promote well-being for all at all ages and make cities and human settlements inclusive, safe, resilient and sustainable. It contributes to the health-environment literature by investigating the intrinsic relationships among mortality rates, carbon emissions (environmental degradation), and non-renewable energy consumption. The study uses an unbalanced sample of 42 Asia and Pacific countries to determine (1) whether carbon emissions exaggerate the incidence of mortality rates and (2) if the interaction of non-renewable energy with carbon emissions enhances or alters the impact of carbon emissions on mortality rates. Consistent findings from the panel spatial correlation consistent least-squares dummy variables (PSCC-LSDV) and two-step system generalized method of moments (GMM) techniques reveal that (i) carbon emissions exacerbate mortality rates; (ii) non-renewable energy consumption exhibit mortality-reducing properties; (iii) non-renewable energy attenuates the impact of carbon emissions on mortality rates, (iv) persistency in mortalities occurs; and (v) the health-environment-energy dynamics differ across income groups. The paper's conjecture is expected to channel a new line of discourse on how non-renewable energy influences the environment and health outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - a novel coronavirus has rapid spread, and caused community infection around the globe. During the absence of a vaccine, people focused more on an immunity-boosting diet and needed clear knowledge about immunity-boosting foods. However, after the vaccination drive, the importance of food as a natural source of immunomodulation cannot be neglected. So, the purpose of this review was to describe the role of vital nutrient in boosting immune system of body apart from other factors like adequate sleep, exercise, and low stress levels. Macrophages, neutrophils, natural killer cells, dendritic cells, B-cells, and T-cells are the important components having important role in maintaining immunity of the human body. The first four-act as the initial mediators of innate host defense, and the latter two produce antibodies for pathogen destruction. The review investigated vital nutrients like vitamin-C, A, E and D, iron, zinc, folic acid, probiotics, and prebiotics affecting these immune components in some extent. Fruits, vegetables, spices, herbs, seeds, nuts, cereals, millets, and superfoods like chlorella and spirulina are good sources of these nutrients. However, fortified foods, functional foods, encapsulated foods with bioactive compounds and plant-based foods have shown immense potential in boosting immunity against viral infections like COVID-19. Some clinical trials and retrospective cohort studies have shown reduction in the severity of COVID-19 patients with relation to plant-based diet, vitamin D and C doses, probiotic, and zinc salts application., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Overlapping microdeletions of chromosome 3q26-3q28 have been reported in eight individuals. The common phenotype observed in these individuals include intrauterine growth restriction, short stature, microcephaly, feeding difficulties, facial dysmorphisms, limb abnormalities and developmental delay. The most striking clinical features shared among all reported cases is prenatal and postnatal growth restriction and neurodevelopmental abnormalities., Case Presentation: We identified two additional individuals with overlapping deletions and shared clinical features by high-resolution SNP oligonucleotide microarray, and refined the smallest region of overlap (SRO) to a 1.2 Mb genomic location in chromosome 3q27.1 by reviewing and comparing all published cases. We evaluated the SRO using ACMG/ClinGen current recommendations for classifying copy number variants (CNVs), and discussed the contribution of the genes deleted in the SRO to the abnormal phenotype observed in these individuals., Conclusions: This study provides further evidence supporting the existence of a novel 3q27.1 microdeletion syndrome and suggests that haploinsufficiency of potential candidate genes, DVL3, AP2M1, and PARL in the SRO in 3q27.1 is responsible for the phenotype., (© 2022. The Author(s).)

Citrinin (CIT) is a mycotoxin produced by different species of Aspergillus , Penicillium , and Monascus . CIT can contaminate a wide range of foods and feeds at any time during the pre-harvest, harvest, and post-harvest stages. CIT can be usually found in beans, fruits, fruit and vegetable juices, herbs and spices, and dairy products, as well as red mold rice. CIT exerts nephrotoxic and genotoxic effects in both humans and animals, thereby raising concerns regarding the consumption of CIT-contaminated food and feed. Hence, to minimize the risk of CIT contamination in food and feed, understanding the incidence of CIT occurrence, its sources, and biosynthetic pathways could assist in the effective implementation of detection and mitigation measures. Therefore, this review aims to shed light on sources of CIT, its prevalence in food and feed, biosynthetic pathways, and genes involved, with a major focus on detection and management strategies to ensure the safety and security of food and feed.

Since the first COVID-19 lockdown in India was declared, all scientific conferences and related activities have been conducted in online formats (1). The ACS(I) [Association of Cutaneous Surgeons (India)] conducted its Annual National Conference called ACSICON-2021 for over 1150 delegates in mid-2021 in a hybrid mode. ACS(I) was one of the first organizations to embrace the hybrid conferencing strategy in the post-COVID-19 era in India. However, while meeting feedback and testimonials are typically gathered, there is very little public data documenting conference attendees' viewpoints. The goal of this research study was to look at the viewpoints of medical conference attendees (such as physicians and medical professionals) on hybrid conferencing as a future trend, the danger of infectivity and transmissibility of COVID-19 during and after the event, the effectiveness of stringent safety protocols and vaccination in preventing the disease and thereby assess the feasibility of hybrid conference as the most convenient mode of learning interaction in the current COVID-19 era and also Post COVID-19 era., Materials and Methods: The physical attendees were surveyed post-ACSICON 2021 conference online, using a mixed-methods technique. Attendees were given a 16-point questionnaire using Google Forms that covered subjects including the COVID-19 preventive procedure, immunization status, infection rates during and after the conference, and overall satisfaction with the hybrid conference. A total of 231 people were sent the survey questionnaire., Results: Only 0.4% ( n = 1) of the participants reported being infected by COVID-19 virus after the conference. 86% ( n = 198) of the respondents also felt that all the necessary precautions were taken during the ACSICON 2021conference. Most of the respondents (82%, n = 189) rated the hybrid conference interaction to be more satisfying than an online conference. An overwhelming majority of the respondents (92%, n = 209) found hybrid conferences to be a safer option than regular conference., Conclusion: The COVID-19 pandemic's scope has forced a paradigm change in medical practice and research (1). ACSICON 2021 is an example of how, with careful organization, strict implementation of meticulous preventive procedures, and strict adherence to the COVID-19 protocol, medical conferences may be held without danger of infection and its transmission. Given the pace with which vaccinations are being administered, a new reality in which technology and live networking intersect via hybrid conferences will result in a more engaging and adaptable medical conference experience. In the long run, this can bring about a significant shift in the conduct of scientific meetings to best suit delegates' needs and conveniences., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Cutaneous and Aesthetic Surgery.)

We report the in vitro antiviral activity of DZNep (3-Deazaneplanocin A; an inhibitor of S-adenosylmethionine-dependent methyltransferase) against SARS-CoV-2, besides demonstrating its protective efficacy against lethal infection of infectious bronchitis virus (IBV, a member of the Coronaviridae family). DZNep treatment resulted in reduced synthesis of SARS-CoV-2 RNA and proteins without affecting other steps of viral life cycle. We demonstrated that deposition of N6-methyl adenosine (m6A) in SARS-CoV-2 RNA in the infected cells recruits heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA binding protein which serves as a m6A reader. DZNep inhibited the recruitment of hnRNPA1 at m6A-modified SARS-CoV-2 RNA which eventually suppressed the synthesis of the viral genome. In addition, m6A-marked RNA and hnRNPA1 interaction was also shown to regulate early translation to replication switch of SARS-CoV-2 genome. Furthermore, abrogation of methylation by DZNep also resulted in defective synthesis of the 5' cap of viral RNA, thereby resulting in its failure to interact with eIF4E (a cap-binding protein), eventually leading to a decreased synthesis of viral proteins. Most importantly, DZNep-resistant mutants could not be observed upon long-term sequential passage of SARS-CoV-2 in cell culture. In summary, we report the novel role of methylation in the life cycle of SARS-CoV-2 and propose that targeting the methylome using DZNep could be of significant therapeutic value against SARS-CoV-2 infection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is minimal experience in continuous glucose monitoring (CGM) among underserved racial/ethnic minority populations with or at risk of type 2 diabetes (T2D), and therefore a lack of CGM-driven insight for these individuals. We analyzed breakfast-related CGM profiles of free-living, predominantly Hispanic/Latino individuals at-risk of T2D, with pre-T2D, or with non-insulin treated T2D., Methods: Starting February 2019, 119 participants in Santa Barbara, CA, USA, (93 female, 87% Hispanic/Latino [predominantly Mexican-American], age 54·4 [±12·1] years), stratified by HbA 1c levels into (i) at-risk of T2D, (ii) with pre-T2D, and (iii) with non-insulin treated T2D, wore blinded CGMs for two weeks. We compared valid CGM profiles from 106 of these participants representing glucose response to breakfast using four parameters., Findings: A "northeast drift" was observed in breakfast glucose responses comparing at-risk to pre-T2D to T2D participants. T2D participants had a significantly higher pre-breakfast glucose level, glucose rise, glucose incremental area under the curve (all p  < 0·0001), and time to glucose peak ( p  < 0·05) compared to pre-T2D and at-risk participants. After adjusting for demographic and clinical covariates, pre-breakfast glucose and time to peak ( p  < 0·0001) were significantly associated with HbA 1c . The model predicted HbA 1c within (0·55 ± 0·67)% of true laboratory HbA 1c values., Interpretation: For predominantly Hispanic/Latino adults, the average two-week breakfast glucose response shows a progression of dysglycemia from at-risk of T2D to pre-T2D to T2D. CGM-based breakfast metrics have the potential to predict HbA 1c levels and monitor diabetes progression., Funding: US Department of Agriculture (Grant #2018-33800-28404), a seed grant from the industry board fees of the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (Award #1648451), and the Elsevier foundation., Competing Interests: DK reports non-financial support from Abbott Diabetes Care, during the conduct of the study; grants from Lilly, personal fees from Sanofi, personal fees from NovoNordisk, personal fees from Glooko, outside the submitted work. NG, CC, AL, and WB report non-financial support from Abbott Diabetes Care, grants from US Dept of Agriculture, during the conduct of the study; grants from Lilly, outside the submitted work. SB and AS declare no competing interest(s)., (© 2021 The Author(s).)

This report presents a research study plan on human subjects - the influence of stress and alcohol in simulated traffic situations under an H2020 project named SIMUSAFE. This research study focuses on road-users', i.e., car drivers, motorcyclists, bicyclists and pedestrians, behaviour in relation to retrospective studies, where interaction between the users are considered. Here, the study includes sample size, inclusion/exclusion criteria, detailed study plan, protocols, potential test scenarios and all related ethical issues. The study plan has been included in a national ethics application and received approval for implementation., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Ahmed MU et al.)

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is caused by de novo loss-of-function variants in the SON gene (MIM #617140). This multisystemic disorder is characterized by intellectual disability, seizures, abnormal brain imaging, variable dysmorphic features, and various congenital anomalies. The wide application and increasing accessibility of whole exome sequencing (WES) has helped to identify new cases of ZTTK syndrome over the last few years. To date, there have been approximately 45 cases reported in the literature. Here, we describe 15 additional individuals with variants in the SON gene, including those with missense variants bringing the total number of known cases to 60. We have reviewed the clinical and molecular data of these new cases and all previously reported cases to further delineate the most common as well as emerging clinical findings related to this syndrome. Furthermore, we aim to delineate any genotype-phenotype correlations specifically for a recurring pathogenic four base pair deletion (c.5753&#95;5756del) along with discussing the impact of missense variants seen in the SON gene., (© 2021 Wiley Periodicals LLC.)

To provide more complete data on SARS-CoV-2 infections in dogs and cats in the U.S., we conducted a serosurvey on convenience serum samples from dogs ( n =1336) and cats ( n =956) collected from 48 states of the USA in 2020. An ELISA targeting the antibody against nucleocapsid identified eleven positive and two doubtful samples in cats, and five positive and five doubtful samples in dogs. A surrogate neutralization assay detecting antibodies blocking the attachment of the spike protein to ACE2 was positive with three of the ELISA positive and doubtful samples, and one of 463 randomly selected ELISA negative samples. These four positive samples were confirmed by SARS-CoV-2 virus neutralization testing. All were from cats, in New York, Florida, and New Jersey ( n =2). The serosurvey results, one of the largest yet completed on dogs and cats globally, support the OIE and CDC positions that currently there is no evidence that pets play a role in the spread of SARS CoV-2 in humans.

Due to the advancement of science and technology, modern cars are highly technical, more activity occurs inside the car and driving is faster; however, statistics show that the number of road fatalities have increased in recent years because of drivers' unsafe behaviors. Therefore, to make the traffic environment safe it is important to keep the driver alert and awake both in human and autonomous driving cars. A driver's cognitive load is considered a good indication of alertness, but determining cognitive load is challenging and the acceptance of wire sensor solutions are not preferred in real-world driving scenarios. The recent development of a non-contact approach through image processing and decreasing hardware prices enables new solutions and there are several interesting features related to the driver's eyes that are currently explored in research. This paper presents a vision-based method to extract useful parameters from a driver's eye movement signals and manual feature extraction based on domain knowledge, as well as automatic feature extraction using deep learning architectures. Five machine learning models and three deep learning architectures are developed to classify a driver's cognitive load. The results show that the highest classification accuracy achieved is 92% by the support vector machine model with linear kernel function and 91% by the convolutional neural networks model. This non-contact technology can be a potential contributor in advanced driver assistive systems.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved to generate several antigenic variants. These variants have raised concerns whether pre-existing immunity to vaccination or prior infection would be able to protect against the newly emerging SARS-CoV-2 variants or not. We isolated SARS-CoV-2 from the coronavirus disease 2019 (COVID-19)-confirmed patients in the beginning of the first (April/May 2020) and second (April/May 2021) waves of COVID-19 in India (Hisar, Haryana). Upon complete nucleotide sequencing, the viruses were found to be genetically related with wild-type (WT) and Delta variants of SARS-CoV-2, respectively. The Delta variant of SARS-CoV-2 produced a rapid cytopathic effect (24-36 h as compared to 48-72 h in WT) and had bigger plaque size but a shorter life cycle (~6 h as compared to the ~8 h in WT). Furthermore, the Delta variant achieved peak viral titers within 24 h as compared to the 48 h in WT. These evidence suggested that the Delta variant replicates significantly faster than the WT SARS-CoV-2. The virus neutralization experiments indicated that antibodies elicited by vaccination are more efficacious in neutralizing the WT virus but significantly less potent against the Delta variant. Our findings have implications in devising suitable vaccination, diagnostic and therapeutic strategies, besides providing insights into understanding virus replication and transmission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khandelwal, Chander, Kumar, Nagori, Verma, Mittal, T, Kamboj, Verma, Khatreja, Pal, Gulati, Tripathi, Barua and Kumar.)

Background: Pathogenic variants in KDM5C are a cause of X-linked intellectual disability in males. Other features in males include short stature, dysmorphic features, seizures and spasticity. In some instances, female relatives were noted to have learning difficulties and mild intellectual disabilities, but full phenotypic descriptions were often incomplete. Recently, detailed phenotypic features of five affected females with de novo variants were described. (Clin Genet 98:43-55, 2020) Four individuals had a protein truncating variant and 1 individual had a missense variant. All five individuals had developmental delay/intellectual disability and three neurological features., Case Presentation: Here we report a three-year-old female with global developmental delay, hypotonia and ataxia. Through whole exome sequencing, a de novo c.1516A > G (p.Met506Val) variant in KDM5C was identified. This missense variant is in the jumonji-C domain of this multi domain protein where other missense variants have been previously reported in KDM5C related disorder. The KDM5C gene is highly intolerant to functional variation which suggests its pathogenicity. The probands motor delays and language impairment is consistent with other reported female patients with de novo variants in KDM5C. However, other features reported in females (distinctive facial features, skeletal abnormalities, short stature and endocrine features) were absent. To the best of our knowledge, our proband is the first female patient reported with a diagnosis of ataxia., Conclusions: This case report provides evidence for an emerging and phenotypic variability that adds to the literature of the role of KDM5C in females with neurodevelopmental disorders as well as movement disorders., (© 2021. The Author(s).)

Reverse transcription fluorescence resonance energy transfer-polymerase chain reaction (FRET-PCRs) were designed against the two most common mutations in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (A23403G in the spike protein; C14408T in the RNA-dependent RNA polymerase). Based on high-resolution melting curve analysis, the reverse transcription (RT) FRET-PCRs identified the mutations in american type culture collection control viruses, and feline and human clinical samples. All major makes of PCR machines can perform melting curve analysis and thus further specifically designed FRET-PCRs could enable active surveillance for mutations and variants in countries where genome sequencing is not readily available., (© 2021 Wiley Periodicals LLC.)

Mitogen-activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal-related kinases (ERK)-1/2, p38 proteins, Jun amino-terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity., (© 2021 John Wiley & Sons Ltd.)

Lassa haemorrhagic fever is listed in WHO's Blueprint priority list of diseases and pathogens prioritized for research and development, affecting several hundreds of thousands of people each year. Lassa fever is spread via infected Natal multimammate mice and also through human-to-human contacts and it is a particular threat to pregnant women. Despite its importance, relatively few mathematical models have been established for modelling Lassa fever transmission up to now. We establish and study a new compartmental model for Lassa fever transmission including asymptomatic carriers, quarantine and periodic coefficients to model annual weather changes. We determine parameter values providing the best fit to data from Nigerian states Edo and Ondo from 2018-20. We perform uncertainty analysis and PRCC analysis to assess the importance of different parameters and numerical simulations to estimate the possible effects of control measures in eradicating the disease. The results suggest that the most important parameter which might be subject of control measures is death rate of mice, while mouse-to-human and human-to-human transmission rates also significantly influence the number of infected. However, decreasing the latter two parameters seems insufficient to eradicate the disease, while a parallel application of decreasing transmission rates and increasing mouse death rate might be able to stop the epidemic., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Alzheimer's disease (AD) is characterized by memory loss and cognitive decline. Additionally, abnormal extracellular amyloid plaques accumulation and nerve damage caused by intracellular neurofibrillary tangles, and tau protein are characteristic of AD. Furthermore, AD is associated with oxidative stress, impaired mitochondrial structure and function, denormalization, and inflammatory responses. Recently, besides the amyloid β hypothesis, another hypothesis linking AD to systemic diseases has been put forth by multiple studies as a probable cause for AD. Particularly, type 2 diabetes mellitus (T2DM) and its features, including hyperinsulinemia, and chronic hyperglycemia with an inflammatory response, have been shown to be closely related to AD through insulin resistance. The brain cannot synthesize or store glucose, but it does require glucose, and the use of glucose in the brain is higher than that in any other organ in the mammalian body. One of the therapeutic drugs for T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitor, suppresses the degradation of incretins, glucagon-like peptides and glucose-dependent insulinotropic peptide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, recently used in T2DM treatment, have a unique mechanism of action via inhibition of renal glucose reabsorption, and which is different from the mechanisms of previously used medications. This manuscript reviews the pathophysiological relationship between the two diseases, AD and T2DM, and the pharmacological effects of therapeutic T2DM drugs, especially DPP-4 inhibitors, and SGLT2 inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sim, Barua, Kim, Lee and Lee.)

Purpose: Dysphagia is reported following lung transplantation. Characteristics and trajectory for dysphagia are poorly understood. This retrospective study explored dysphagia and medicine regimes in patients following lung transplant., Method: Medical records and endoscopic recordings of 101 patients (M:50yrs, range 20-67yrs, SD 13yrs) were reviewed. Standardised endoscopic swallowing measures were reported. Discharge reports were analysed for medicines known to cause dysphagia., Result: All patients received bilateral sequential single-lung transplant. Prevalence of referral to speech pathology was 65% with 37 requiring more than one instrumental assessment. Twenty-nine patients were referred to otorhinolaryngology with suspected laryngeal abnormalities. Seventy-five percent of patients ( n  = 49/65) who received an instrumental assessment aspirated; of whom 63% aspirated silently (31/49). Diet on first day transferred from Intensive Care Unit (ICU) was significantly associated with intubation duration, ICU and hospital length of stay, tracheostomy and vocal fold paralysis ( p  < 0.001). In contrast, pre-operative reflux was significantly associated with diet on discharge ( p  < 0.05). Only three patients remained enterally fed on discharge. Polypharmacy (concurrent use of 5+ medicines) was prevalent., Conclusion: Endoscopic, radiographic and/or manometric assessment of dysphagia in patients prior to, and following, lung transplant may allow for early management and prevention of secondary complications. Teams must consider pre-surgical reflux, length of stay in ICU and current medicine regimes when managing patients.

Agmatine, an endogenous derivative of arginine, has been found to be effective in treating idiopathic pain, convulsion, stress-mediated behavior, and attenuate the withdrawal symptoms of drugs like morphine. In the early stages of ischemic brain injury in animals, exogenous agmatine treatment was found to be neuroprotective. Agmatine is also considered as a putative neurotransmitter and is still an experimental drug. Chemically, agmatine is called agmatine 1-(4-aminobutyl guanidine). Crystallographic study data show that positively-charged guanidine can bind to the protein containing Gly and Asp residues, and the amino group can interact with the complimentary sites of Glu and Ser. In this study, we blocked the amino end of the agmatine by conjugating it with FITC, but the guanidine end was unchanged. We compared the neuroprotective function of the agmatine and agmatine-FITC by treating them in neurons after excitotoxic stimulation. We found that even the amino end blocked neuronal viability in the excitotoxic condition, by NMDA treatment for 1 h, was increased by agmatine-FITC, which was similar to that of agmatine. We also found that the agmatine-FITC treatment reduced the expression of nitric oxide production in NMDA-treated cells. This study suggests that even if the amino end of agmatine is blocked, it can perform its neuroprotective function.

The persistent dwindling of the biocapacity has caused the ecological footprint (EF) to keep increasing in the top ten tourist destinations over the last three decades. Moreso, economic growth, natural resource rent, and urbanization substantially increased for the same period. Tourism contributes to economic prosperity. However, growth in tourism promotes an increase in energy consumption, natural resource exploration, transportation, and consequential ecological distortions. It is important to understand the predictors of EF to suggest suitable policies for environmental sustainability. Hence, this study examines the predictors of EF by considering factors that could influence EF. More precisely, the study analyzes the linkage among economic growth, natural resource rent, urbanization, energy intensity, and tourism using some of the most advanced and reliable econometric techniques, such as Westerlund's (J Appl Econ 23(2):193-233, 2008) cointegration technique, and the continuously updated full modified (CUP-FM) and continuously updated bias-corrected (CUP-BC), long-run estimators. The outcomes of the analysis indicate that EF has a negative association with urbanization and natural resources, which implies that an abundance of natural resources and increasing urban population can help to reduce environmental degradation. Likewise, energy intensity helps in decreasing EF, while economic growth adds to EF. Tourist arrival and tourist receipt also add to EF and, therefore, negatively affect environmental quality. Finally, policy directions are discussed to reduce environmental degradation without reducing economic growth., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The diabetes epidemic is expanding rapidly in India, with 69.2 million people living with diabetes in 2015. This study assessed the spatial pattern and determinants of diagnosed diabetes prevalence in the districts of six states and one union territory (UT) in southern India - a region that has a high prevalence of diabetes. Using cross-sectional population-based survey data from the 2012-13 District Level Household and Facility Survey-4, the prevalence and magnitude of diagnosed diabetes at district level for the population aged 18 years and above were computed. Moran's I was calculated to explore the spatial clustering of diagnosed diabetes prevalence. Ordinary Least Square (OLS) and Spatial Lag (SL) regression models were carried out to investigate the spatial determinants of diagnosed diabetes prevalence. The prevalence of diagnosed diabetes was found to be substantially higher than that of self-reported diabetes in southern India (7.64% vs 2.38%). Diagnosed diabetes prevalence in the study area varied from 10.52% in Goa to 4.89% in Telangana. The Moran's I values signified positive moderate autocorrelation. Southern India had 14.15 million individuals with diagnosed diabetes in 2012-13. Bangalore had the highest number of persons with diagnosed diabetes, and Palakkad had the smallest number. In the OLS and SL models, the proportion of people with secondary education and above, wealthy and Christian populations were found to be significant determinants of diagnosed diabetes prevalence. In addition, in the OLS model, the proportion of Scheduled Tribe population showed a negative relationship with diagnosed diabetes prevalence. In order to prevent or postpone the onset age for diabetes, there is a need to raise awareness about diabetes in India.

Agmatine, the primary decarboxylation product of L-arginine, generated from arginine decarboxylase. Since the discovery of agmatine in the mammalian brain in the 1990s, an increasing number of agmatine-mediated effects have been discovered, demonstrating the benefits of agmatine on ischemic strokes, traumatic brain injury and numerous psychological disorders such as depression, anxiety, and stress. Agmatine also has cellular protective effects and contributes to cell proliferation and differentiation in the central nervous system (CNS). Neural progenitor cells are an important component in the recovery and repair of many neurological disorders due to their ability to differentiate into functional adult neurons. Recent data has revealed that agmatine can regulate and increase proliferation and the fate of progenitor cells in the adult hippocampus. This review aims to summarise and discuss the role of agmatine in the CNS; specifically, the effects and relationship between agmatine and neural progenitor cells and how these ideas can be applied to potential therapeutic application.

Purpose: Head and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18 FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury., Methods: Data for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18 FDG-PET-CT scans, and physician-reported xerostomia assessment at 3-6 months post-RT (Xero 3-6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18 FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0-5 Gy, 5-10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT., Results: 432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3-6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10-50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC = 0.78 (95%CI: 0.66-0.85; p < 0.0001)., Conclusion: We sought to quantify pre- and post-RT 18 FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The COVID-19 pandemic is producing significant economic and social cost globally. As a cure or a treatment is yet unavailable, social distancing is considered the key way to prevent it. Mobility restrictions and confinement measures implemented across the world are considered to help reduce air pollution. However, empirical examination of the link between public mobility changes and air pollution during the COVID-19 period remains unavailable. This paper examines the short and long run impacts of mobility changes on carbon monoxide (CO) emissions by employing three dynamic estimators on a panel of 35 countries covering daily data from 15 February to April 17, 2020 - a period when most countries went into strict lockdowns. Findings show a consistent evidence at the all-countries level and across regions that long-run indoor mobility increases reduce CO emissions, while outdoor mobility increases across places such as transit stations, workplaces, grocery & pharmacies, retail & recreation, and parks drive up emissions. Among the regions studied, Europe excluding the EU and the UK (-8.4%), followed by East Asia and the Pacific (-4.3%), sees a larger emissions reduction from increased indoor mobility. While short-run effects are limited in general, emissions in US-Canada respond to indoor and outdoor mobility changes in both the short (1.1%) and long run (-1.4%). Findings overall indicate that reducing unnecessary outdoor mobility could help in maintaining air quality in the post-pandemic world., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor. Interestingly, emetine exhibited protective efficacy against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment led to a decrease in viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 mRNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation of protein translation). Further, molecular docking and molecular dynamics simulation studies suggested that emetine may bind to the cap-binding pocket of eIF4E, in a similar conformation as m7-GTP binds. Additionally, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathway for its effective replication in the target cells. Collectively our results suggest that further detailed evaluation of emetine as a potential treatment for COVID-19 may be warranted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Continuous glucose monitoring (CGM) has demonstrable benefits for people living with diabetes, but the supporting evidence is almost exclusively from White individuals with type 1 diabetes. Here, we have quantified CGM profiles in Hispanic/Latino adults with or at-risk of non-insulin treated type 2 diabetes (T2D)., Methods: 100 participants (79 female, 86% Hispanic/Latino [predominantly Mexican], age 54·6 [±12·0] years) stratified into (i) at risk of T2D, (ii) with pre-diabetes (pre-T2D), and (iii) with non-insulin treated T2D, wore blinded CGMs for 2 weeks. Beyond standardized CGM measures (average glucose, glucose variability, time in 70-140 mg/dL and 70-180 mg/dL ranges), we also examined additional CGM measures based on the time of day., Findings: Standardized CGM measures were significantly different for participants with T2D compared to at-risk and pre-T2D participants ( p <0·0001). In addition, pre-T2D participants spent more time between 140 and 180 mg/dL during the day than at-risk participants ( p <0·01). T2D participants spent more time between 140 and 180 mg/dL both during the day and overnight compared to at-risk and pre-T2D participants (both p <0·0001). Time in 70-140 mg/dL range during the day was significantly correlated with HbA 1c ( r =-0·72, p <0·0001), after adjusting for age, sex, BMI, and waist circumference ( p <0·0001)., Interpretation: Standardized CGM measures show a progression of dysglycemia from at-risk of T2D, to pre-T2D, and to T2D. Stratifying CGM readings by time of day and the range 140-180 mg/dL provides additional metrics to differentiate between the groups., Funding: US Department of Agriculture (Grant #2018-33800-28404) and NSF PATHS-UP ERC (Award #1648451)., Competing Interests: DK reports non-financial support from Abbott Diabetes Care, during the conduct of the study; grants from Lilly, personal fees from Sanofi, personal fees from NovoNordisk, personal fees from Glooko, outside the submitted work. NG, CC, AL, and WB report non-financial support from Abbott Diabetes Care, grants from US Dept of Agriculture, during the conduct of the study; grants from Lilly, outside the submitted work. SB and AS declare no competing interest(s)., (© 2021 The Authors.)

Pancreatic ductal adenocarcinoma (PDAC) is therapeutically recalcitrant and metastatic. Partial epithelial to mesenchymal transition (EMT) is associated with metastasis; however, a causal connection needs further unraveling. Here, we use single-cell RNA sequencing and genetic mouse models to identify the functional roles of partial EMT and epithelial stabilization in PDAC growth and metastasis. A global EMT expression signature identifies ∼50 cancer cell clusters spanning the epithelial-mesenchymal continuum in both human and murine PDACs. The combined genetic suppression of Snail and Twist results in PDAC epithelial stabilization and increased liver metastasis. Genetic deletion of Zeb1 in PDAC cells also leads to liver metastasis associated with cancer cell epithelial stabilization. We demonstrate that epithelial stabilization leads to the enhanced collective migration of cancer cells and modulation of the immune microenvironment, which likely contribute to efficient liver colonization. Our study provides insights into the diverse mechanisms of metastasis in pancreatic cancer and potential therapeutic targets., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 [95% confidence interval (C.I.): 0.61-0.90], significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barua, Elhalawani, Volpe, Al Feghali, Yang, Ng, Elgohari, Granberry, Mackin, Gunn, Hutcheson, Chambers, Court, Mohamed, Fuller, Lai and Rao.)

Chemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody-drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. The surface of PTXNRs was functionalized at 2' OH nucleophilic site using carbonyldiimidazole and conjugated to TTZ through the lysine residue interaction forming PTXNR-TTZ conjugates (ADNs). The size, shape, and surface charge of ADNs were characterized using scanning electron microscopy (SEM), SEM, and zeta potential, respectively. Using fluorophore labeling and response surface analysis, the percentage conjugation efficiency was found > 95% with a PTX to TTZ mass ratio of 4 (molar ratio ≈ 682). In vitro therapeutic efficiency of PTXNR-TTZ was evaluated in two HER2 positive breast cancer cell lines: BT-474 and SK-BR-3, and a HER2 negative MDA-MB-231 breast cancer cell using MTT assay. PTXNR-TTZ inhibited > 80% of BT-474 and SK-BR-3 cells at a higher efficiency than individual PTX and TTZ treatments alone after 72 h. A combination index analysis indicated a synergistic combination of PTXNR-TTZ compared with the doses of single-drug treatment. Relatively lower cytotoxicity was observed in MCF-10A human breast epithelial cell control. The molecular mechanisms of PTXNR-TTZ were investigated using cell cycle and Western blot analyses. The cell cycle analysis showed PTXNR-TTZ arrested > 80% of BT-474 breast cancer cells in the G2/M phase, while > 70% of untreated cells were found in the G0/G1 phase indicating that G2/M arrest induced apoptosis. A similar percentage of G2/M arrested cells was found to induce caspase-dependent apoptosis in PTXNR-TTZ treated BT-474 cells as revealed using Western blot analysis. PTXNR-TTZ treated BT-474 cells showed ~ 1.3, 1.4, and 1.6-fold higher expressions of cleaved caspase-9, cytochrome C, and cleaved caspase-3, respectively than untreated cells, indicating up-regulation of caspase-dependent activation of apoptotic pathways. The PTXNR-TTZ ADN represents a novel nanoparticle design that holds promise for targeted and efficient anti-cancer therapy by selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest.

Aerosol affects Earth's climate and the health of its inhabitants. A major contributor to aerosol formation is the oxidation of volatile organic compounds. Monoterpenes are an important class of volatile organic compounds, and recent research demonstrate that they can be converted to low-volatility aerosol precursors on sub-second timescales following a single oxidant attack. The α-pinene + O 3 system is particularly efficient in this regard. However, the actual mechanism behind this conversion is not understood. The key challenge is the steric strain created by the cyclobutyl ring in the oxidation products. This strain hinders subsequent unimolecular hydrogen-shift reactions essential for lowering volatility. Using quantum chemical calculations and targeted experiments, we show that the excess energy from the initial ozonolysis reaction can lead to novel oxidation intermediates without steric strain, allowing the rapid formation of products with up to 8 oxygen atoms. This is likely a key route for atmospheric organic aerosol formation.

Monogalactosyldiacylglycerol (MGDG) is the most abundant type of glycoglycerolipid found in the plant cell membrane and mostly in the chloroplast thylakoid membrane. The amphiphilic nature of MGDG is attractive in pharmaceutical fields for interaction with other biological molecules and hence exerting therapeutic anti-cancer, anti-viral, and anti-inflammatory activities. In this study, we investigated the therapeutic efficacy of cyanobacteria derived MGDG to inhibit breast cancer cell growth. MGDG was extracted from a cyanobacteria Synechocystis sp. PCC 6803 followed by a subsequent fractionation by column chromatographic technique. The purity and molecular structure of MGDG were analyzed by nuclear magnetic resonance (NMR) spectroscopy analysis. The presence of MGDG in the extracted fraction was further confirmed and quantified by high-performance liquid chromatography (HPLC). The anti-proliferation activity of the extracted MGDG molecule was tested against BT-474 and MDA-MB-231 breast cancer cell lines. The in vitro study showed that MGDG extracted from Synechocystis sp. PCC 6803 induced apoptosis in (70 ± 8) % of BT-474 (p < 0.001) and (58 ± 5) % of MDA-MB-231 cells (p < 0.001) using ~ 60 and 200 ng/ml of concentrations, respectively. The half-maximal inhibitory concentration, IC 50 of MGDG extracted from Synechocystis sp. PCC 6803 were (27.2 ± 7.6) and (150 ± 70) ng/ml in BT-474 and MDA-MB-231 cell lines, respectively. Quantification of caspase-3/7 activity using flow cytometry showed (3.0 ± 0.4) and (2.1 ± 0.04)-fold (p < 0.001) higher protein expressions in the MGDG treated BT-474 and MDA-MB-231 cells, respectively than untreated controls conferring to the caspase-dependent apoptosis. The MGDG did not show any significant cytotoxic side effects in human dermal fibroblasts cells. A commercially available MGDG control did not induce any apoptotic cell death in cancer cells substantiating the potential of the MGDG extracted from Synechocystis sp. PCC 6803 for the treatment of breast cancer cells through the apoptosis-mediated pathway.

Lumpy skin disease (LSD) has devastating economic impact. During the last decade, LSD had spread to climatically new and previously disease-free countries, which also includes its recent emergence in the Indian subcontinent (2019). This study deals with the LSD outbreak(s) from cattle in Ranchi (India). Virus was isolated from the scabs (skin lesions) in the primary goat kidney cells. Phylogenetic analysis based on nucleotide sequencing of LSD virus (LSDV) ORF011, ORF012 and ORF036 suggested that the isolated virus (LSDV/Bos taurus-tc/India/2019/Ranchi) is closely related to Kenyan LSDV strains. Further, we adapted the isolated virus in Vero cells. Infection of the isolated LSDV to Vero cells did not produce cytopathic effect (CPE) until the 4th blind passage, but upon adaptation, it produced high viral titres in the cultured cells. The kinetics of viral DNA synthesis and one-step growth curve analysis suggested that Vero cell-adapted LSDV initiates synthesizing its genome at ~24 hours post-infection (hpi) with a peak level at ~96 hpi whereas evidence of progeny virus particles was observed at 36-48 hours (h) with a peak titre at ~120 h. To the best of our knowledge, this study describes the first successful isolation of LSDV in India, besides providing insights into the life cycle Vero cell-adapted LSDV., Competing Interests: The authors have declared that no competing interests exist

The COVID-19 pandemic is damaging economies across the world, including financial markets and institutions in all possible dimensions. For banks in particular, the pandemic generates multifaceted crises, mostly through increases in default rates. This is likely to be worse in developing economies with poor financial market architecture. This paper utilizes Bangladesh as a case study of an emerging economy and examines the possible impacts of the pandemic on the country's banking sector. Bangladesh's banking sector already has a high level of non-performing loans (NPLs) and the pandemic is likely to worsen the situation. Using a state-designed stress testing model, the paper estimates the impacts of the COVID-19 pandemic on three particular dimensions-firm value, capital adequacy, and interest income-under different NPL shock scenarios. Findings suggest that all banks are likely to see a fall in risk-weighted asset values, capital adequacy ratios, and interest income at the individual bank and sectoral levels. However, estimates show that larger banks are relatively more vulnerable. The decline in all three dimensions will increase disproportionately if NPL shocks become larger. Findings further show that a 10% NPL shock could force capital adequacy of all banks to go below the minimum BASEL-III requirement, while a shock of 13% or more could turn it to zero or negative at the sectoral level. Findings call for immediate and innovative policy measures to prevent a large-scale and contagious banking crisis in Bangladesh. The paper offers lessons for other developing and emerging economies similar to Bangladesh., Competing Interests: Conflict of interestThey have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Springer Nature Switzerland AG 2020.)

Background: In 2017 hundreds of thousands of 'Rohingya' fled to camps for Forcefully Displaced Myanmar Nationals (FDMN) in Cox's Bazar, Bangladesh., Objective: To describe the FDMNs presenting for care at public health facilities in Bangladesh so as to understand the health problems faced by the FDMNs and the burden on these public health facilities., Methods: This study combined a retrospective review of existing hospital and clinic data with prospective surveillance in government health care centres., Findings: The retrospective data showed a 26% increase in the number of consultations at the Kutupalong community clinic, the primary health facility closest to the camps, from 19,567 in 2015 to 26,309 in 2019. There was a corresponding 11% increase in admissions to health facilities in the area, from 80,991 in 2017 to 91,424 in 2019. Prospective surveillance of 9,421 FDMNs seeking health care from July 2018 to December 2019 showed that 29% had an infectious disease, 20% nutritional problems, 12% pregnancy-related conditions and 7% trauma or injury., Conclusions: Great uncertainty remains regarding the return of FDMN to their home country of Myanmar. The current on-going protests following the military coup adds further insecurity to the status of the Rohingya. The presence of a large migrant population relative to a smaller host community burdens the limited facilities and resources of the public health sector. Continued support by the international public health community and civil society organizations is needed.

Chlamydia suis is an important, highly prevalent, and diverse obligate intracellular pathogen infecting pigs. In order to investigate the prevalence and diversity of C. suis in the U.S., 276 whole blood samples from feral swine were collected as well as 109 fecal swabs and 60 whole blood samples from domestic pigs. C. suis -specific peptide ELISA identified anti- C. suis antibodies in 13.0% of the blood of feral swine (26/276) and 80.0% of the domestic pigs (48/60). FRET-qPCR and DNA sequencing found C. suis DNA in 99.1% of the fecal swabs (108/109) and 21.7% of the whole blood (13/60) of the domestic pigs, but not in any of the assayed blood samples (0/267) in feral swine. Phylogenetic comparison of partial C. suis ompA gene sequences and C. suis -specific multilocus sequencing typing (MLST) revealed significant genetic diversity of the C. suis identified in this study. Highly genetically diverse C. suis strains are prevalent in domestic pigs in the USA. As crowding strongly enhances the frequency and intensity of highly prevalent Chlamydia infections in animals, less population density in feral swine than in domestic pigs may explain the significantly lower C. suis prevalence in feral swine. A future study is warranted to obtain C. suis DNA from feral swine to perform genetic diversity of C. suis between commercial and feral pigs.

The proliferation of misinformation on social media platforms is faster than the spread of Corona Virus Diseases (COVID-19) and it can generate hefty deleterious consequences on health amid a disaster like COVID-19. Drawing upon research on the stimulus-response theory (hypodermic needle theory) and the resilience theory, this study tested a conceptual framework considering general misinformation belief, conspiracy belief, and religious misinformation belief as the stimulus; and credibility evaluations as resilience strategy; and their effects on COVID-19 individual responses. Using a self-administered online survey during the COVID-19 pandemic, the study obtained 483 useable responses and after test, finds that all-inclusive, the propagation of misinformation on social media undermines the COVID-19 individual responses. Particularly, credibility evaluation of misinformation strongly predicts the COVID-19 individual responses with positive influences and religious misinformation beliefs as well as conspiracy beliefs and general misinformation beliefs come next and influence negatively. The findings and general recommendations will help the public, in general, to be cautious about misinformation, and the respective authority of a country, in particular, for initiating proper safety measures about disastrous misinformation to protect the public health from being exploited., Competing Interests: None., (© 2020 The Authors.)