Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.

Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.

COVID-19 in Pediatrics: Characteristics of Hospitalized Children in New Jersey.

OBJECTIVES: Understanding the risk factors, predictors, and clinical presentation of coronavirus disease 2019 (COVID-19) in pediatric patients with severe disease. METHODS: We conducted a retrospective chart review of pediatric patients admitted between March 1, 2020, and May 31, 2020, to a large health network in New Jersey with positive test results for severe acute respiratory syndrome coronavirus 2 on reverse transcriptase polymerase chain reaction, rapid testing, or serum immunoglobulin G testing; we included demographic characteristics, clinical features, and outcomes. RESULTS: A total of 81 patients ≤21 years old were admitted with positive test results for severe acute respiratory syndrome coronavirus 2 on reverse transcriptase polymerase chain reaction and/or serum immunoglobulin testing. Sixty-seven patients (82.7%) were admitted for management of acute COVID-19 infection, whereas 14 (17.3%) were admitted for management of multisystem inflammatory syndrome in children (MIS-C). Of the 81 hospitalized patients, 28 (34.6%) required intensive care. A majority of patients (42 [51.9%]) admitted for both acute COVID-19 infection and MIS-C were Hispanic. Underlying chronic health conditions were not present in most patients. Obesity (mean BMI of 41.1) was noted in the patients with MIS-C requiring ICU care, although not statistically significant. Absolute lymphopenia and elevated levels of inflammatory markers were statistically significant in the patients with MIS-C treated in the ICU. CONCLUSIONS: This study adds to the growing literature of potential risk factors for severe disease in pediatric patients due to COVID-19 infection and MIS-C. Patients of Hispanic ethnicity represented the majority of patients with both acute COVID-19 infection and MIS-C, despite only representing 10% to 20% of the population our hospitals serve. Infants and patients with chronic health conditions were not at increased risk for severe disease. Absolute lymphopenia and elevated levels of inflammatory markers were associated with more severe disease.

The periodontal senior case clinical challenge: Students' opinions of a formative virtual assessment during the COVID-19 emergency.

INTRODUCTION: Due to COVID-19, innovative, virtual educational methods are being developed to provide students with learning experiences comparable to established clinical practices. Our objective was to produce the Periodontal Senior Case Clinical Challenge (PSCCC) that would provide fourth-year students an alternative for senior case presentations and would be a formative assessment for which student opinions would be provided and analysed. The PSCCC would utilise an online, case-based, written, clinical assessment and follow-up, structured discussion to challenge students to demonstrate ability to apply didactic periodontal knowledge to patient-based experiences. We hypothesised the PSCCC would provide effective learning and a formative assessment. MATERIAL AND METHODS: Relevant didactic resources were distributed to 48 students for independent review. The PSCCC was delivered in two sections, (1) a case-based assessment via a virtual classroom with written student responses, and (2) oral discussions conducted via virtual meetings that were moderated and assessed by ten periodontists, with the collaboration of nine residents. A voluntary six-statement survey was used to evaluate the students' opinions of the PSCCC. The scores for 75% (36/48) of students who participated were evaluated for statistical and clinical importance. RESULTS: The value of our PSCCC was supported by 91.7% (33/36) of the analyses (p < .0008). DISCUSSION: The PSCCC was a successful alternative pathway to assess students' clinical and didactic integrated knowledge in periodontics. It provided a unified vision of treatment of the selected case, building on all aspects of the students' periodontal education whilst allowing interaction in a simultaneous, three-tiered educational approach, involving dental students, periodontal residents and faculty. CONCLUSION: In support of our hypothesis, for each of the 6 statements, ≥94.44% (34/36) of the scores given by the students were considered exceptionally strong clinical support for our pedagogical strategy that combines educational resources and can be successfully implemented in other programmes.

Temporal focusing multiphoton microscopy with optimized parallel multiline scanning for fast biotissue imaging.

SIGNIFICANCE: Line scanning-based temporal focusing multiphoton microscopy (TFMPM) has superior axial excitation confinement (AEC) compared to conventional widefield TFMPM, but the frame rate is limited due to the limitation of the single line-to-line scanning mechanism. The development of the multiline scanning-based TFMPM requires only eight multiline patterns for full-field uniform multiphoton excitation and it still maintains superior AEC. AIM: The optimized parallel multiline scanning TFMPM is developed, and the performance is verified with theoretical simulation. The system provides a sharp AEC equivalent to the line scanning-based TFMPM, but fewer scans are required. APPROACH: A digital micromirror device is integrated in the TFMPM system and generates the multiline pattern for excitation. Based on the result of single-line pattern with sharp AEC, we can further model the multiline pattern to find the best structure that has the highest duty cycle together with the best AEC performance. RESULTS: The AEC is experimentally improved to 1.7 µm from the 3.5 µm of conventional TFMPM. The adopted multiline pattern is akin to a pulse-width-modulation pattern with a spatial period of four times the diffraction-limited line width. In other words, ideally only four π / 2 spatial phase-shift scans are required to form a full two-dimensional image with superior AEC instead of image-size-dependent line-to-line scanning. CONCLUSIONS: We have demonstrated the developed parallel multiline scanning-based TFMPM has the multiline pattern for sharp AEC and the least scans required for full-field uniform excitation. In the experimental results, the temporal focusing-based multiphoton images of disordered biotissue of mouse skin with improved axial resolution due to the near-theoretical limit AEC are shown to clearly reduce background scattering.

SARS-CoV-2 nucleocapsid protein intranasal inoculation induces local and systemic T cell responses in mice.

SARS-CoV-2 nucleocapsid (N) protein has been proposed as a good vaccine target. N-specific T cells were observed in SARS-CoV-2 N immunized mice and COVID-19 convalescents. It is of importance to identify the T cell responses triggered by SARS-CoV-2 N protein. Intradermal immunization with SARS-CoV N protein was demonstrated to elicit non-protective T cell responses which may be avoided by intranasal vaccination. Therefore, we conducted intranasal vaccination of BALB/c mice with recombinant adenovirus type-5 expressing SARS-CoV-2 N protein. Such procedure induced CD8 T cell responses in the lung. Meanwhile CD4 T cell responses were observed in the spleen, which was associated with robust antibody production. Our study further supports the notion that SARS-CoV-2 N protein can work as a target for vaccine development.

Review of in vivo optical molecular imaging and sensing from x-ray excitation.

SIGNIFICANCE: Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources. AIM: A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo. APPROACH: The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution. RESULTS: While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins. CONCLUSIONS: Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.

Comparative transcriptomic and metabolomic analyses of carotenoid biosynthesis reveal the basis of white petal color in Brassica napus.

MAIN CONCLUSION: The molecular mechanism underlying white petal color in Brassica napus was revealed by transcriptomic and metabolomic analyses. Rapeseed (Brassica napus L.) is one of the most important oilseed crops worldwide, but the mechanisms underlying flower color in this crop are known less. Here, we performed metabolomic and transcriptomic analyses of the yellow-flowered rapeseed cultivar 'Zhongshuang 11' (ZS11) and the white-flowered inbred line 'White Petal' (WP). The total carotenoid contents were 1.778-fold and 1.969-fold higher in ZS11 vs. WP petals at stages S2 and S4, respectively. Our findings suggest that white petal color in WP flowers is primarily due to decreased lutein and zeaxanthin contents. Transcriptome analysis revealed 10,116 differentially expressed genes with a fourfold or greater change in expression (P-value less than 0.001) in WP vs. ZS11 petals, including 1,209 genes that were differentially expressed at four different stages and 20 genes in the carotenoid metabolism pathway. BnNCED4b, encoding a protein involved in carotenoid degradation, was expressed at abnormally high levels in WP petals, suggesting it might play a key role in white petal formation. The results of qRT-PCR were consistent with the transcriptome data. The results of this study provide important insights into the molecular mechanisms of the carotenoid metabolic pathway in rapeseed petals, and the candidate genes identified in this study provide a resource for the creation of new B. napus germplasms with different petal colors.

The ß-Cell Genomic Landscape in T1D: Implications for Disease Pathogenesis.

PURPOSE OF REVIEW: Type 1 diabetes (T1D) develops as a consequence of a combination of genetic predisposition and environmental factors. Combined, these events trigger an autoimmune disease that results in progressive loss of pancreatic ß cells, leading to insulin deficiency. This article reviews the current knowledge on the genetics of T1D with a specific focus on genetic variation in pancreatic islet regulatory networks and its implication to T1D risk and disease development. RECENT FINDINGS: Accumulating evidence suggest an active role of ß cells in T1D pathogenesis. Based on such observation several studies aimed in mapping T1D risk variants acting at the ß cell level. Such studies unravel T1D risk loci shared with type 2 diabetes (T2D) and T1D risk variants potentially interfering with ß-cell responses to external stimuli. The characterization of regulatory genomics maps of disease-relevant states and cell types can be used to elucidate the mechanistic role of ß cells in the pathogenesis of T1D.

Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy in Children: A Retrospective Single-Center Study.

BACKGROUND Although influenza primarily affects the respiratory system, it can cause severe neurological complications, especially in younger children, but knowledge about the early indicators of acute necrotizing encephalopathy (ANE) is limited. The main purpose of this article is to summarize the clinical characteristics, diagnosis, and treatment of neurological complications of influenza in children, and to identify factors associated with ANE. MATERIAL AND METHODS This was a retrospective study of children with confirmed influenza with neurological complications treated between 01/2014 and 12/2019 at Guangzhou Women and Children's Medical Center. A receiver operating characteristics curve analysis was performed to determine the prognostic value of selected variables. RESULTS Sixty-three children with IAE (n=33) and ANE (n=30) were included. Compared with the IAE group, the ANE group showed higher proportions of fever and acute disturbance of consciousness, higher alanine aminotransferase, higher aspartate aminotransferase, higher creatinine kinase, higher procalcitonin, higher cerebrospinal fluid (CSF) protein, and lower CSF white blood cells (all P<0.05). The areas under the curve (AUCs) for procalcitonin and CSF proteins, used to differentiate IAE and ANE, were 0.790 and 0.736, respectively. The sensitivity and specificity of PCT >4.25 ng/ml to predict ANE were 73.3% and 100.0%, respectively. The sensitivity and specificity of CSF protein >0.48 g/L to predict ANE were 76.7% and 69.7%, respectively. Thirteen (43.3%) children with ANE and none with IAE died (P<0.0001). CONCLUSIONS High levels of CSF protein and serum procalcitonin might be used as early indicators for ANE. All children admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications.

Novel tumour-infiltrating lymphocyte-related risk stratification based by flow cytometry for patients with de novo angioimmunoblastic T cell lymphoma.

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

Poultry disease occurrences and their impacts in Ethiopia.

Poultry production contributes significantly to the livelihoods of Ethiopian farmers and to the national economy although it is hampered by different factors, including poultry diseases. There is scarcity of published evidences on the occurrence and impacts of poultry diseases although such evidences are important for policy makers in designing appropriate interventions. A total of 595 households were interviewed and 11 FGDs were conducted to collect data on the occurrence of diseases and the number of dead chickens in the last 12 months. Hence, respiratory diseases, sudden death, and eye-face-head diseases were mentioned in all of the FGDs as the most frequently occurring disease in the districts. Of households interviewed, 86.1% reported poultry disease occurrence in the last 12 months, and gastrointestinal, eye-face-head, and neurological diseases were identified to be the top three ranked diseases of chickens in the districts. Flocks with access to diagnostic services (Adj. OR = 4.16; P = 0.004) and/or access to animal health providers (Adj. OR = 10.50; P = 0.001) were more likely to report disease occurrence. In the studied population, the diseases resulted in deaths of 2219 chickens valued at 352,219.5 Birr (11,740.65 USD) and a mean crude mortality of 31.87%. Female-lead households (mean difference = 5.95%; P = 0.018) and multiple age units present on the farm (mean difference = 20.92%; P = < 0.000) had higher chicken mortality. Similarly, higher mortality was reported in flocks without access to diagnosis (mean difference = 9.97%; P = < 0.000) and vaccination (mean difference = 12.34%; P = < 0.000) services. The high occurrence of disease and mortalities might be explained by a lack of an organized poultry health service delivery system in the country. Therefore, a carefully designed health service delivery system addressing needs of poultry producers, supported by relevant policy and corresponding strategies, is recommended to address the indicated challenges. Moreover, private health providers with well-defined roles need to be engaged to successfully and sustainably solve the poultry disease problems.

Hybrid reconstruction of distal nasal defects.

We present hybrid reconstruction of distal lateral "through-and-through" nasal defects (skin, cartilage, and mucosa) due to resection of tumor and/or infection. Retrospective descriptive study. The study was performed in multicenter clinics between July 2011 and September 2016. 13 patients with full thickness distal nasal defects secondary to tumor and/or infection were included. Defects included dorsal and/or caudal septum, upper lateral cartilage, or inner/outer nasal valve. Caudal-based turn-in flaps were planned and used to repair inner lining of nasal cavity. Conchal and septal cartilages were used as cartilage grafts. Skin defects were reconstructed with lateral nasal artery perforator flaps. All flaps healed uneventfully, without flap loss. Nasal passage collapse, adhesion, or difficulty in breathing were not seen. No hematoma, infection, and deformity at cartilage graft donor areas was observed. During nasal reconstruction, it is mandatory to consider 3D complex and functional structure of nose. The repair of skin defects may not be enough for functional restoration. We believe that single step reconstruction of full thickness nasal defects through hybrid reconstruction may lead to anticipated successful results.

Carotid intima-media thickness and serum proinflammatory cytokine levels in rosacea patients without cardiovascular risk factors.

There is a growing body of evidence linking rosacea to various systemic disorders, even though data regarding the association between rosacea and cardiovascular diseases are presently controversial. We sought to investigate the potential association of rosacea with subclinical atherosclerosis and serum proinflammatory/proatherogenic markers. This study included 44 patients with rosacea and 44 age-matched and sex-matched healthy control subjects. Patients with traditional cardiovascular risk factors or a history of cardiovascular events were excluded. Demographic, clinical, and laboratory data, including serum interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were assessed. Carotid intima-media thickness (CIMT) and carotid plaques were measured by carotid ultrasonography. Serum IL-1ß (P < .001), IL-6 (P < .001), TNF-α (P < .001), and hs-CRP (P < .001) levels were significantly higher in the patient group compared with the control group. Mean CIMT values did not differ significantly between the patient group and control group (P > .05). Patients with moderate to severe rosacea had a significantly greater CIMT than those with mild rosacea (P = .047). Rosacea patients with eye involvement had a significantly greater CIMT than those without eye involvement (P = .008). There was no significant correlation between CIMT values and inflammation parameters. As conclusion, in the absence of other traditional cardiovascular risk factors, rosacea does not seem to affect mean CIMT value. However, specific subgroups such as patients with moderate to severe disease or with eye involvement are associated with increased subclinical atherosclerosis and may require additional attention for cardiovascular disease prevention.

Communicating Scientific Uncertainty in an Age of COVID-19: An Investigation into the Use of Preprints by Digital Media Outlets.

In this article, we investigate the surge in use of COVID-19-related preprints by media outlets. Journalists are a main source of reliable public health information during crises and, until recently, journalists have been reluctant to cover preprints because of the associated scientific uncertainty. Yet, uploads of COVID-19 preprints and their uptake by online media have outstripped that of preprints about any other topic. Using an innovative approach combining altmetrics methods with content analysis, we identified a diversity of outlets covering COVID-19-related preprints during the early months of the pandemic, including specialist medical news outlets, traditional news media outlets, and aggregators. We found a ubiquity of hyperlinks as citations and a multiplicity of framing devices for highlighting the scientific uncertainty associated with COVID-19 preprints. These devices were rarely used consistently (e.g., mentioning that the study was a preprint, unreviewed, preliminary, and/or in need of verification). About half of the stories we analyzed contained framing devices emphasizing uncertainty. Outlets in our sample were much less likely to identify the research they mentioned as preprint research, compared to identifying it as simply "research." This work has significant implications for public health communication within the changing media landscape. While current best practices in public health risk communication promote identifying and promoting trustworthy sources of information, the uptake of preprint research by online media presents new challenges. At the same time, it provides new opportunities for fostering greater awareness of the scientific uncertainty associated with health research findings.

Spherical mesoporous silica designed for the removal of methylene blue from water under strong acidic conditions.

This work proposes a novel technology for environmental remediation based on mesoporous silica spheres, which were successfully synthesized by the solvothermal method using the cetyltrimethylammonium bromide as a structuring agent. The adsorbent was designed to remove cationic dyes at strong acidic conditions. The surface was modified by a careful thermal treatment aiming at the condensation of silanol to siloxane groups. The adsorbent was characterized by XRD, SEM, FTIR, N2 adsorption/desorption and the equilibrium technique to determine the pHpzc. The kinetic of the adsorption followed a pseudo-second-order model and the process was ruled by physical forces. The isotherms were fitted to Freundlich and Temkin models, indicating that the physisorption occurred with multilayer formation, with the interaction adsorbate-adsorbate being relevant to the whole process. The adsorption capacity was approximately 60 mg g-1 and the adsorbents performance in the fast-contact system showed removal of 65%wt. of a 93 mg L-1 methylene blue (MB) solution in a single application.

Effects of undernutrition on mortality and morbidity among adults living with HIV in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Undernutrition is one of the most common problems among people living with HIV, contributing to premature death and the development of comorbidities within this population. In Sub-Saharan Africa (SSA), the impacts of these often inter-related conditions appear in a series of fragmented and inconclusive studies. Thus, this review examines the pooled effects of undernutrition on mortality and morbidities among adults living with HIV in SSA. METHODS: A systematic literature search was conducted from PubMed, EMBASE, CINAHL, and Scopus databases. All observational studies reporting the effects of undernutrition on mortality and morbidity among adults living with HIV in SSA were included. Heterogeneity between the included studies was assessed using the Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's and Begg's tests at a 5% significance level. Finally, a random-effects meta-analysis model was employed to estimate the overall adjusted hazard ratio. RESULTS: Of 4309 identified studies, 53 articles met the inclusion criteria and were included in this review. Of these, 40 studies were available for the meta-analysis. A meta-analysis of 23 cohort studies indicated that undernutrition significantly (AHR: 2.1, 95% CI: 1.8, 2.4) increased the risk of mortality among adults living with HIV, while severely undernourished adults living with HIV were at higher risk of death (AHR: 2.3, 95% CI: 1.9, 2.8) as compared to mildly undernourished adults living with HIV. Furthermore, the pooled estimates of ten cohort studies revealed that undernutrition significantly increased the risk of developing tuberculosis (AHR: 2.1, 95% CI: 1.6, 2.7) among adults living with HIV. CONCLUSION: This review found that undernutrition has significant effects on mortality and morbidity among adults living with HIV. As the degree of undernutrition became more severe, mortality rate also increased. Therefore, findings from this review may be used to update the nutritional guidelines used for the management of PLHIV by different stakeholders, especially in limited-resource settings.