The biological father of an 11-year-old girl infects his daughter, who returns to her biological mother's family before the father's diagnosis. The daughter endures a 1-day, mild illness. However, despite close physical contact prior to and during the girl's illness, her mother, stepfather and 1-year-old half-brother were not infected.

Mammals have experienced a massive decline in their populations and geographic ranges worldwide. The sloth bear, Melursus ursinus (Shaw, 1791), is one of many species facing conservation threats. Despite being endangered in Nepal, decades of inattention to the situation have hindered their conservation and management. We assessed the distribution and patterns of habitat use by sloth bears in Chitwan National Park (CNP), Nepal. We conducted sign surveys from March to June, 2020, in 4 × 4 km grids (n = 45). We collected detection/non-detection data along a 4-km trail that was divided into 20 continuous segments of 200 m each. We obtained environmental, ecological, and anthropogenic covariates to understand determinants of sloth bear habitat occupancy. The data were analyzed using the single-species single-season occupancy method, with a spatially correlated detection. Using repeated observations, these models accounted for the imperfect detectability of the species to provide robust estimates of habitat occupancy. The model-averaged occupancy estimate for the sloth bear was 69% and the detection probability was 0.25. The probability of habitat occupancy by sloth bears increased with the presence of termites and fruits and in rugged, dry, open, undisturbed habitats. Our results indicate that the sloth bear is elusive, functionally unique, and widespread in CNP. Future conservation interventions and action plans aimed at sloth bear management must adequately consider their habitat requirements.

Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. Both hydroxychloroquine and azithromycin continue to be administered in US clinical trials examining their potential role in prevention of infection, treatment of mild infection in ambulatory patients, and in combination with other medical regimens in treatment of patients with severe disease. These drugs also continue to be clinically utilized in hospitalized patients around the globe, often without continuous telemetry due to lack of resources. Concern regarding use of hydroxychloroquine without adequate rhythm monitoring in clinical trials has been recently expressed.1 A review of clinicaltrials.gov at the time of submission of this correspondence reveals actively recruiting trials of combined hydroxychloroquine/azithromycin with or without additional COVID-19 therapies, for both ambulatory and hospitalized patients within and outside the US. The potential for hydroxychloroquine and azithromycin to cause QT prolongation is counterbalanced by very low risk of pro-arrhythmia in the general population, and emerging evidence of relatively low risk of Torsades de Pointes (TdP) in COVID-19 patients.2,3,4,5 Thus delineation of the determinants of significant QTc prolongation and pro-arrhythmic risk for hydroxychloroquine/azithromycin is very important, especially given mounting evidence of inefficacy in COVID-19 treatment.

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

Title: Notch4, uncovering an immunomodulator in allergic asthmaAuthors: Beatriz Moyaa, Manali Mukherjeeb and Parameswaran Nairba. Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spainb. Division of Respirology, Department of Medicine, McMaster University, Hamilton & Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, CanadaCorrespondence to : Beatriz Moya. Allergy Department. Hospital Universitario 12 de Octubre, Madrid, SpainEmail:[email protected] : Dr. Mukherjee is supported by investigator award from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation. She has received honorarium from AZ, GSK and her university has received grants from Methapharm Speciality Pharmaceuticals. Dr. Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. He has received honoraria from AZ, Sanofi, Teva, Merck, Novartis and Equillium and his university has received research grants from AZ, Teva, Sanofi, Novartis, BI and Methapharm. The authors recognize Dr. Anna Globinska for graphical abstract design and Dr. Rodrigo Jiménez-Saiz for critical review of the manuscript.Keywords: Allergic asthma; Airway inflammation; Th2 cell; Th17 cell; Treg cell; Notch4 receptorAbbreviations: Th, T helper; UFPs, pollutant ultrafine particles; AMs, alveolar macrophages; Treg cells, regulatory T cells; ILC2s, type 2 innate lymphoid cells; GDF15, cytokine growth and differentiation factor 15; IL, interleukin; IL-6R, interleukin-6 receptor; IL-4R, interleukin-4 receptorWord count: 918/1000

Background: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). Methods: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles Network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc – 2010-2015) and medical costs. Results: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8,627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza-associated) was 31,490 (95% CI: 24,542-39,012), with an average cost of \euro141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥ 65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. Conclusions: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.

Objectives: To assess the feasibility of using Image1 S™ endoscopic enhancement system for discrimination of the vascular patterns in laryngeal lesions. Design: Forty patients presenting with benign, dysplastic and malign laryngeal lesions were examined with Image1 S system. The vascular patterns were classified by a group of the authors/ according to the ELS guideline, as perpendicular or longitudinal, in all lesions. Endoscopic images of the vascular patterns are evaluated through an online survey by a group of otolaryngologists with different levels of clinical expertise. The qualitative evaluation of the vascular patterns in two groups were compared to investigate the consistency. The relationship between the vascular patterns and the pathological results was statistically analyzed. Results: Eleven patient presented with benign, 13 patients with dysplastic and 16 patients with malignant pathology. The vascular patterns were longitudinal in 9 lesions, perpendicular in 28 lesions and undetectable in 3 lesions. The relevance between the vascularization pattern and the pathological diagnosis was found to be significant (χ2= 20.30, p < 0,001). The qualitative evaluation of the vascular patterns by the two groups of observers was significantly close to each other (=0.63). The survey also showed that spectral modes producing high contrast images were preferred by 81,9% of the participants over white light images. Conclusion: This study demonstrated the usefulness and feasibility of Image1 S endoscopic enhancement system to predict the diagnosis from vascular changes in laryngeal lesions.

AIM Ropeginterferon alfa-2b is a new site-specific conjugated 40 kDa branched polyethylene-glycol recombinant interferon (IFN). The aim of the study was to determine its safety, pharmacokinetics (PK) and pharmacodynamic (PD). METHODS Ropeginterferon alfa-2b was evaluated first in human in 48 healthy male volunteers after a single dose subcutaneous injection by either 24, 48, 90, 180, 225, 270mcg of the product or 180mcg of marketed pegylated (peg)-IFN alfa-2a. Within each dosing group, 6 subjects received ropeginterferon alfa-2b and 2 subjects received peg-IFN alfa-2a. RESULTS Dose-related increases in ropeginterferon alfa-2b PK parameters (Cmax, AUC, and AUC0-t) were observed over the dose range 24 to 270mcg. The geometric mean values for these PK parameters of ropeginterferon alfa-2b were higher than that of peg-IFN alfa-2a at the 180mcg dose level of 176%, 166%, and 182%, respectively. Mean PD parameters (Emax, Tmax, and AUC0-t) for ropeginterferon alfa-2b increased with dose for both biomarkers neopterin and 2’, 5’-OAS. Ropeginterferon alfa-2b has similar PD profiles as peg-IFN alfa-2a. The treatment related adverse events are similar between the two study drugs, but the overall incidence was numerically lower for ropeginterferon alfa-2b (83%) than peg-IFN alfa-2a (100%) at the 180mcg dose level. CONCLUSIONS Single subcutaneous dose of Ropeginterferon alfa-2b of up to 270mcg is safe and well tolerated. It displays dose related increase in PK and PD parameters, potentially less frequent injection, and better safety profiles. Ropeginterferon alfa-2b is being developed for diseases in which previous peg-IFN use has been limited by side effects.

Aims: This study aims to analyze the novel Coronavirus disease (COVID-19) related testicular pain in hospitalized patients due to COVID-19 and to review as an etiological factor for epididymitis, orchitis or both. Methods: A total of 91 patients were included in the study. A questionnaire was formed for the questioning of testicular pain or epididymo-orchitis in patients with COVID-19. Demophrahics and past medical history was also recorded. Patients’ neutrophil and lymphocyte counts, neutrophil-lymphocyte ratios (NLR), C-reactive protein (CRP) levels and D-dimer values were recorded. Patients with COVID-19 were divided into two groups according to absence or presence of testicular pain or epididymo-orchitis as group 1 and group 2. All results were compared for both groups. Results: The median age of patients was similar in both groups. Testicular pain was occured in 10.98% of the patients. Clinical presentation of epididymo-orchitis was diagnosed in only one patient. No statistically significant difference was reported in terms of patients’ age, levels of CRP and D-Dimer or NLR and results of questionnaire form queries between the two groups (p>0.05). Conclusion: Testicular pain was observed more frequently in hospitalized COVID-19 cases. While no inflammation marker which is related to predict of testicular pain or epididymo-orchitis was found in patients with COVID-19.

1. Fire and frost represent two major hurdles for the persistence of trees in open grassy biomes and have both been proposed as drivers of grassland-forest boundaries in Africa. 2. We assess the response of young tree seedlings, which represent a vulnerable stage in tree recruitment, to traumatic fire and frost disturbances. 3. In a greenhouse experiment, we investigated how seedling traits predicted survival and resprouting ability in response to fire vs frost; we characterised survival strategies of seedlings in response to the two disturbances, and we documented how the architecture of surviving seedlings is affected by fire vs frost injury. 4. Survival rates were similar under both treatments. However, different species displayed different levels of sensitivity to fire and frost. Seedling survival was higher for older seedlings and seedlings with more basal leaves. Survivors of a fire event lost more biomass than the survivors of a frost event. However, the architecture of recovered fire and frost treated seedlings were mostly similar. Seedlings that recovered from fire and frost treatments were often shorter than those that had not been exposed to any disturbance, with multiple thin branches, which may increase vulnerability to the next frost or fire event. 5. Synthesis. Fire caused more severe aboveground damage compared to frost, suggesting that trees in these open grassland systems may be subjected to a seedling release bottleneck maintained by fire. However, the woody species composition will almost certainly be influenced by phenomena that affect the timing and frequency of seedling exposure to damage, as mortality was found to be dependent on seedling age. Therefore, changes in fire regime and climate (esp. changes that bring about less frost and reduced fire intensity and frequency) are likely to result in changes in the composition and the structure of the woody components of these systems.

Purpose: To investigate the effect of mirabegron 50 mg/daily for JJ stent-related symptoms after ureteroscopic stone surgery. Methods: Medical records of 145 patients who were given a single daily oral dose of 50 mg of mirabegron for relieving stent-related symptoms were retrospectively analyzed. Demographic and clinical data and stone parameters were recorded. All participants completed the Turkish version of the Ureter Symptom Score Questionnaire (USSQ-T) on the postoperative seventh day, and again after at least three weeks, before JJ stent removal. The severity of stent-related symptoms was statistically compared before and after the mirabegron treatment. Results: The mean urinary symptoms score decreased significantly from 30.87 ± 9.43 to 22.61 ± 6.78 (p < 0.0001), mean body pain score decreased significantly from 21.82 ± 11.22 to 14.03 ± 7.52 (p < 0.0001), mean work performance score decreased from 10.50 ± 8.61 to 7.02 ± 6.51 (p < 0.0001), and mean general health score decreased significantly from 15.43 ± 6.50 to 11.12 ± 3.70 (p < 0.0001). The mean sexual matters score significantly decreased from 3.88 ± 3.40 to 2.48 ± 2.03 (p < 0.0001), the additional problem score decreased from 9.31 ± 4.61 to 6.51 ± 2.83 (p < 0.0001), and the overall quality of life (QoL) score decreased from 5.18 ± 1.94 to 4.23 ± 1.71 after mirabegron use (p < 0.0001). Conclusion: Daily use of 50g of mirabegron significantly improved stent-related symptoms, sexual matters, and quality of life.

The identification of the mechanisms underlying co-occurrence patterns of species is a way to identify which processes (niche, neutral or both) structure metacommunities. In this paper, our goals are to identify patterns of co-occurrence in neotropical stream fish and determine which processes structure the metacommunity and the gradients that underlie this structure. Our results pointed out that the metacommunity formed by the total pool of species is structured by a nested pattern (Hyperdispersed Species Loss) of co-occurrence and the mass effect mechanism. On the other hand, a set of core species displays a Clementisian pattern and is structured by the species sorting mechanism. Both, hyperdispersed species loss and the Clementisian patterns point to a discrete set of communities in the metacommunity. These communities could be isolated by physicochemical conditions, or physical barriers, like dams or waterfalls.

The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe 4 adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.

Synthetic biology is the engineering approach to edit or write the genome aiming to design the biological devices (promoters, transcription factors, TFBS, terminators etc.) of an organism to achieve the improved properties, while, metabolic engineering aiming to engineer the microbes to produce metabolites on industrial scale through recombinant DNA technologies. Recently, both synthetic biology and metabolic engineering fields are growing quickly and are used to produce metabolites of interest. The main theme of Synthetic Biology – Metabolic Engineering book is to review the tools and techniques used in synthetic biology and metabolic engineering to design and engineer the microbes to produce value-added metabolites and its application in industrial biotechnology. The book is written by the world-renowned metabolic engineers and synthetic biologists in series of Advances in Biochemical Engineering/Biotechnology and primarily elaborates the synergy between metabolic engineering and synthetic biology.

A bone regeneration scaffold is typically designed as a platform to effectively heal a bone defect while preventing soft tissue infiltration. Despite the wide variety of scaffold materials currently available, such as collagen, critical problems in achieving bone regeneration remain, including a rapid absorption period and low tensile strength as well as high costs. Inspired by extracellular matrix protein and topographical cues, we developed a polycaprolactone-based scaffold for bone regeneration using a soluble eggshell membrane protein (SEP) coating and a nanotopography structure for enhancing the physical properties and bioactivity. The scaffold exhibited adequate flexibility and mechanical strength as a biomedical platform for bone regeneration. The highly aligned nanostructures and SEP coating were found to regulate and enhance cell morphology, adhesion, proliferation, and differentiation in vitro. In a calvarial bone defect mouse model, the scaffolds coated with SEP applied to the defect site promoted bone regeneration along the direction of the nanotopography in vivo. These findings demonstrate that bone-inspired nanostructures and SEP coatings have high potential to be applicable in the design and manipulation of scaffolds for bone regeneration.

Background LIVE (Less Invasive Ventricular Enhancement) with Revivent TC™ is an innovative therapy for symptomatic ischemic Heart Failure (HF). It is designed to reconstruct a negatively remodeled left ventricle (LV) after an anterior myocardial infarction (MI) by plication of the scar tissue. Its indications are specific and, as with any other structural heart intervention, the success of the procedure starts with appropriate patient selection. We aim to present the indications of the technique, crucial aspects in patient selection and individual case planning approach. Methods and Results After clinical evaluation, transthoracic echocardiography is the first imaging modality to be performed in a potential candidate for the therapy. However, definitive indication and detailed case planning rely on late gadolinium-enhanced cardiac magnetic resonance imaging or multiphasic contrast-enhanced cardiac computed tomography. These imaging modalities also assist with relative or absolute contra-indications for the procedure. Individual assessment is done to tailor the procedure to the specifics of the LV anatomy and location of the myocardial scar. Conclusion LIVE procedure is a unique intervention to treat symptomatic heart failure and ischemic cardiomyopathy after anterior MI. It is a highly customizable intervention that allows a patient-tailored approach, based on multimodality imaging assessment and planification.

Benthic macrofauna is regularly used in monitoring programmes, however the vast majority of benthic eukaryotic biodiversity lies mostly in microscopic organisms, such as meiofauna (invertebrates < 1 mm) and protists, that rapidly responds to environmental change. These communities have traditionally been hard to sample and handle in the laboratory, but DNA sequencing has made such work less time consuming. Compared to DNA sequencing that captures both alive and dead organisms, environmental RNA (eRNA) can be used to better target alive communities. Here, we assessed the biodiversity of three known bioindicator microeukaryote groups (nematodes, foraminifera, and ciliates) in sediment samples collected at seven coastal sites along an organic carbon (OC) gradient. We aimed to investigate if eRNA shotgun sequencing can be used to simultaneously detect differences in 1) biodiversity of multiple microeukaryotic communities, and 2) functional feeding traits of nematodes. Results showed that biodiversity was lower for nematodes and foraminifera in high OC (6.2–6.9 %), when compared to low OC sediments (1.2–2.8 %). The beta diversity for all three groups were different along the OC gradient, as well as the classified feeding type of nematode genera (with more non-selective deposit feeders in high OC sediment). High relative abundant genera included nematode Sabatieria and foraminifera Elphidium in high OC, and Cryptocaryon-like ciliates in low OC sediments. Considering that future sequencing technologies are likely to decrease in cost, the use of eRNA shotgun sequencing to assess biodiversity of living benthic microeukaryotes could be a powerful tool in recurring monitoring programmes.

Aims: It is evident that COVID-19 pandemic have affected the medical practice and training of residents. In this study, we evaluated the Physical Examination (PE) habits of residents working in a university hospital and how their PE practices did change during the pandemic. Methods: This single-center, non-interventional, cross-sectional descriptive study was conducted in a university hospital using an online survey questionnaire from 5 to 20 October 2020. Results: 308 residents participated in the study of whom 172 of them (55.8%) were female and the median age was 27 (IQR:3). Among all, 263 participants (85.4%) declared that they have worked in the areas where suspected/confirmed COVID-19 patients were being served. A total of 262 (85%) residents stated that PE habits have changed generally during the pandemic. There was a significant difference between those residents who have worked in the COVID-19 areas (n=230,87.5%) and those who have not (n=32, 71.1%) (p=0.004). PE habits of Internal Medicine Residents were more changed than others (p<0.001). The main reason for the change in PE habits in general (77.9%) and during the examination of suspected/confirmed COVID-19 patients (89.7%) were ‘’self-protection”. Reliance on laboratory and radiologic investigations during practice and not having a thought that less PE will disrupt the diagnosis and course of COVID-19 were also independent risk factors for performing less PE in suspected/confirmed COVID-19 patients. Discussion: This study clearly demonstrated that the COVID-19 pandemic has had a serious impact on the PE habits of the residents while examing patients in general and with COVID-19.