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IoT devices are sorely underutilized in the medical field, especially within machine learning for medicine, yet they offer unrivaled benefits. IoT devices are low cost, energy efficient, small and intelligent devices [1].In this paper, we propose a distributed federated learning framework for IoT devices, more specifically for IoMT (In-ternet of Medical Things), using blockchain to allow for a decentralized scheme improving privacy and efficiency over a centralized system; this allows us to move from the cloud based architectures, that are prevalent, to the edge.The system is designed for three paradigms: 1) Training neural networks on IoT devices to allow for collaborative training of a shared model whilst decoupling the learning from the dataset [2] to ensure privacy [3]. Training is performed in an online manner simultaneously amongst all participants, allowing for training of actual data that may not have been present in a dataset collected in the traditional way and dynamically adapt the system whilst it is being trained. 2) Training of an IoMT system in a fully private manner such as to mitigate the issue with confidentiality of medical data and to build robust, and potentially bespoke [4], models where not much, if any, data exists. 3) Distribution of the actual network training, something federated learning itself does not do, to allow hospitals, for example, to utilize their spare computing resources to train network models.

In collaboration with the American Medical Women's Association, The Permanente Journal is pleased to present this special issue in celebration of Women in Medicine Month in September 2020. This designation was created by the American Medical Association to recognize the growing number of women in the profession. We aim to introduce the history, education, leadership, society beliefs and inequities faced, reflections on bias, and perspectives on work-life-balance. We hope you will allow the personal stories, commentaries, and research reports to inspire you to create workplaces and life moments with a view toward equity and inclusion., (Copyright © 2020 The Permanente Press. All rights reserved.)

Prior research has suggested that gender differences in physicians' salaries can be accounted for by the tendency of women to enter primary care fields and work fewer hours. However, in examining starting salaries by gender of physicians leaving residency programs in New York State during 1999-2008, we found a significant gender gap that cannot be explained by specialty choice, practice setting, work hours, or other characteristics. The unexplained trend toward diverging salaries appears to be a recent development that is growing over time. In 2008, male physicians newly trained in New York State made on average $16,819 more than newly trained female physicians, compared to a $3,600 difference in 1999.

Introduction: Healthcare system delays in the diagnosis of tuberculosis can increase the risk of its nosocomial transmission. We aimed to determine whether different physicians' specialties and experience influenced this diagnostic delay., Methods: We retrospectively reviewed the cases of 167 patients with smear-positive pulmonary tuberculosis who were hospitalized from September, 2004, to August, 2006, for 5 components of healthcare system delays according to the World Health Organization definitions and analyzed the impact of physicians' specialties and their experience (annual number of patients treated for tuberculosis) on these delays., Results: The median suspicion delay was significantly longer for patients in surgical departments than those in medical departments (4 days versus 1 day, P = 0.001) and for patients treated by nontuberculosis specialists than those treated by tuberculosis specialists (including pulmonologists, infectious diseases specialists and thoracic surgeons; 3 days versus 1 day, P < 0.001). Both were independent factors related to suspicion delay examined by multivariate analysis. The annual number of tuberculosis patients in each department had a significant negative correlation with suspicion delay (r = -0.303, P < 0.001)., Conclusions: Patients treated by surgeons and nontuberculosis specialists who were inexperienced in treating tuberculosis experienced a longer suspicion delay. Enhancing knowledge about tuberculosis among all physicians in the hospital, encouraging staff to consult tuberculosis specialists to confirm a diagnosis and implementing early alarm systems are crucial to improving the correct diagnosis of tuberculosis and to reducing delays in treatment.

From the experience of a U.S. Army Air Defense Artillery "battalion-plus" task force serving a 6-month rotation in the Kingdom of Saudi Arabia, we compiled the requirements for specialty consultations on deployed personnel in the predeployment screening phase, during deployment (including both inpatient hospitalizations and medical evacuations), and immediately upon return to home station. We required a wide variety of specialty expertise. In every phase of the operation, we consulted orthopedic surgery most often. Nonsurgical and surgical specialists were consulted in roughly equal numbers. Almost every field of adult medicine was represented in our sample. The distribution of consultations across specialties differs from what would be expected in combat but is similar to that seen in the few other studies of comparable populations. Excellent host nation support allowed us to use specialty expertise to an almost ideal extent. These data represent the most complete "snapshot" that has been taken of the requirements for specialty medical consultations in a military operation other than war (MOOTW). They demonstrate that under MOOTW conditions, even a healthy Army population requires the assistance of a full panel of medical specialties. They should serve as a benchmark for planners estimating the medical specialty needs that the Army must provide. Military medicine must provide access to essentially all medical specialties for personnel deployed under MOOTW conditions, whether through host nation support, telemedicine, or medical evacuation.

Medicine and law are more closely intertwined than ever before, particularly regarding issues of life-sustaining treatment for the elderly. The legal system's potential as a positive force in medical decision making has been limited by pervasive misperceptions by physicians of its processes and role. Identifying these myths and misperceptions is a first step toward a more effective partnership of medicine and law on behalf of the dying or demented patient.

We prospectively studied the communication between 27 referring practitioners and their consultants for 464 consecutive patient referrals from a general internal medicine group practice at a university medical center. The rates of referral among practitioners varied from 0 to 28.1 per 100 patients visits. Though referring physicians provided patient background information in 98% of the cases, they made explicit the purpose of the referral in only 76% of the cases. They contacted consultants directly in only 9% of the cases. In return, consultants communicated their findings to referring practitioners in only 55% of the consultations. Referring physicians who personally contacted consultants or who supplied them with more clinical information were more likely to learn the results of the consultation. While communication between the referring physicians and consultants in this setting is limited, it may be improved if referring physicians supply more clinical information to consultants and contact them directly.

Abstract Objectives Odontogenic keratocysts exhibit frequent recurrence, distinctive histopathological traits, a tendency towards aggressive clinical behavior, and a potential linkage to the nevoid basal cell carcinoma syndrome. The aim of this systematic review is to compile insights concerning the control of this condition and assess the effectiveness of various treatment approaches in reducing the likelihood of recurrence. Materials and methods The following systematic review adhered to the PRISMA guidelines. The systematic revision was registered on PROSPERO and structured around the questions related to the population, intervention, control, outcome and study design (PICOS). Results After conducting a search on the PubMed database, we initially identified 944 records. After using end-note software to remove duplicate entries, results totally with 462 distinct records. A thorough review of the titles and abstracts of these articles led to the selection of 50 papers for in-depth examination. Ultimately, following the application of our eligibility criteria, we incorporated 11 articles into our primary outcome analysis. Conclusion Among the studies examined, the most common location for these lesions was found to be in the area of the mandibular ramus and the posterior region of the mandible. In cases where the exact location wasn’t specified, the mandible emerged as the predominant site. When we considered the characteristics of these lesions in studies that mentioned locularity, most were described as unilocular in two studies, while in two other studies, the prevalence of multilocular lesions was observed. Risk factors associated with keratocyst recurrence include younger patient age, the presence of multilocular lesions, larger lesion size, and a longer anteroposterior dimension. Certain treatment methods have demonstrated a lack of relapses. These include the use of 5-fluorouracil, marsupialization, enucleation with peripheral ostectomy or resection, enucleation and curettage, as well as resection without creating continuity defects. However, it is important to note that further research is essential. Prospective studies and randomized trials are needed to collect more comprehensive evidence regarding the effectiveness of various treatment approaches and follow-up protocols for managing odontogenic keratocysts. Clinical relevance Odontogenic keratocysts still enter into differential diagnoses with other lesions that affect the jaw bones such as ameloblastama and other tumor forms, furthermore it is not free from recurrence, therefore the therapeutic approach to the lesion aimed at its elimination can influence both the possible recurrence and complications, knowledge of the surgical methods that offer the most predictable and clinically relevant result for the management of follow-up and recurrences.

Abstract Background Hunter–Schreger bands (HSB) are optical phenomena observed on tooth surfaces under polarized light, resulting from the intersection of enamel prisms. Anthropological studies demonstrate the prevalence of HSB in large mammals, contributing to enamel resistance. Historically, John Hunter and Schreger depicted HSB in dental literature. In dentistry, HSB play a role in non-carious cervical lesions (NCCL) and internal dental perikymata, suggesting their potential for personal identification. Personal identification, crucial in both daily and professional life, involves biometric characteristics, such as fingerprints or facial recognition. The need for non-invasive, rapid, and user-friendly methods has prompted the exploration of using HSB dental images for personal identification. The review aimed to consolidate studies employing HSB for personal identification. Methods The scoping review was carried out strictly following the PRISMA–ScR checklist; the search was carried out on tree databases (PubMed, Scopus, Science Direct,) and a register (Cochrane library). Results The research produced a number of bibliographic sources totaling 410. With the removal of duplicates, 334 were obtained; potentially eligible articles amounted to 14, of which only 4 fully complied with the criteria of eligibility. Conclusions From the data in the literature, we can assert that HSB could be used in personal identification, as they are characteristics that are difficult to change and easily detectable.

Abstract The heart coordinates its functional parameters for optimal beat-to-beat mechanical activity. Reliable detection and quantification of these parameters still represent a hot topic in cardiovascular research. Nowadays, computer vision allows the development of open-source algorithms to measure cellular kinematics. However, the analysis software can vary based on analyzed specimens. In this study, we compared different software performances in in-silico model, in-vitro mouse adult ventricular cardiomyocytes and cardioids. We acquired in-vitro high-resolution videos during suprathreshold stimulation at 0.5-1-2 Hz, adapting the protocol for the cardioids. Moreover, we exposed the samples to inotropic and depolarizing substances. We analyzed in-silico and in-vitro videos by (i) MUSCLEMOTION, the gold standard among open-source software; (ii) CONTRACTIONWAVE, a recently developed tracking software; and (iii) ViKiE, an in-house customized video kinematic evaluation software. We enriched the study with three machine-learning algorithms to test the robustness of the motion-tracking approaches. Our results revealed that all software produced comparable estimations of cardiac mechanical parameters. For instance, in cardioids, beat duration measurements at 0.5 Hz were 1053.58 ms (MUSCLEMOTION), 1043.59 ms (CONTRACTIONWAVE), and 937.11 ms (ViKiE). ViKiE exhibited higher sensitivity in exposed samples due to its localized kinematic analysis, while MUSCLEMOTION and CONTRACTIONWAVE offered temporal correlation, combining global assessment with time-efficient analysis. Finally, machine learning reveals greater accuracy when trained with MUSCLEMOTION dataset in comparison with the other software (accuracy > 83%). In conclusion, our findings provide valuable insights for the accurate selection and integration of software tools into the kinematic analysis pipeline, tailored to the experimental protocol.

Abstract Background The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. Methods We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. Results Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or “long COVID,” suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Conclusions Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q

Background Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still’s disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients.Methods Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters.Results K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients.Conclusions Four patient clusters in Still’s disease may be recognised by a multidimensional characterisation (‘Juvenile/Transitional’, ‘Uncomplicated’, ‘Hyperferritinemic’ and ‘Catastrophic’). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.

Objective Still’s disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still’s disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still’s disease.Methods Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still’s disease.Results A total of 411 patients suffering from Still’s disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still’s disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by an impairment of steroid synthesis due to an altered production of 21-hydroxylase enzyme. Corticoid hormones are involved in the development and functioning of many organs. The aim of the present study was to review the international literature to collect data regarding oral manifestations of CAH. A review of the literature describing oral features of patients affected by CAH was performed using electronic databases (PubMed and Scopus). The data about number of patients, form of CAH, and oral findings were extracted and analyzed. Seven studies were included in the final analysis. The principal findings reported regarded an advanced dental development observed in patients with CAH. One paper reported amelogenesis imperfecta and periodontal issues. The dentist could be the first specialist involved in the CAH syndrome diagnosis, identifying the characteristic features described above, especially for the classical simple virilizing and non-classical form.

Objectives To better define the spectrum of new-onset post-COVID-19 and post-COVID-19 vaccine inflammatory rheumatic diseases (IRD) from a large multicentric observational study.Methods Consecutive cases of IRD encountered during a 12-month period and satisfying one of the following inclusion criteria: (a) onset of the rheumatic manifestations within 4 weeks from SARS-CoV-2 infection or (b) onset of the rheumatic manifestations within 4 weeks from the administration of one of the COVID-19 vaccines ws recruited.Results The final analysis cohort comprised 267 patients, of which 122 (45.2%) in the post-COVID-19 and 145 (54.8%) in the postvaccine cohort. Distribution of IRD categories differed between the two cohorts: the post-COVID-19 cohort had a higher percentage of patients classified as having inflammatory joint diseases (IJD, 52.5% vs 37.2%, p=0.013) while the post-vaccine cohort had a higher prevalence of patients classified as polymyalgia rheumatica (PMR, 33.1% vs 21.3%, p=0.032). No differences were detected in the percentage of patients diagnosed with connective tissue diseases (CTD 19.7% vs 20.7%, p=0.837) or vasculitis (6.6% vs 9.0%, p=0.467). Despite the short follow-up period, IJD and PMR patients’ response to first-line therapy was favourable, with both groups achieving a drop in baseline disease activity scores of ~30% and ~70% respectively.Conclusion Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis.

Abstract The coordinated communication between the mitochondria and nucleus is essential for cellular activities. Nonetheless, the pathways involved in this crosstalk are scarcely understood. The protease Lonp1 was previously believed to be exclusively located in the mitochondria, with an important role in mitochondrial morphology, mtDNA maintenance, and cellular metabolism, in both normal and neoplastic cells. However, we recently detected Lonp1 in the nuclear, where as much as 22% of all cellular Lonp1 can be found. Nuclear localization is detectable under all conditions, but the amount is dependent on a response to heat shock (HS). Lonp1 in the nucleus interacts with heat shock factor 1 (HSF1) and modulates the HS response. These findings reveal a novel extramitochondrial function for Lonp1 in response to stress.

Abstract Background Sebaceous carcinoma is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. Sebaceous carcinoma in the oral cavity is extremely rare, with only 14 cases reported in literature. We reported the fourth case of sebaceous carcinoma involving the lip Case presentation A 71-year-old Caucasian male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extraoral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation, and salivary gland neoplasms. Operation was performed under local anesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascular stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein and epithelial membrane antigen, but negative for carcinoembryonic antigen. Based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered. Conclusion The histogenesis, differential diagnosis, and clinicopathological conditions of this disease according to literature are reviewed. Sebaceous carcinoma should be distinguished from other tumors full of vacuolated clear cells. A periodic acid-Schiff stain and immunohistochemical stain for Ki-67, P53, cytokeratin, S-100, epithelial membrane antigen, and androgen receptor can be useful for the diagnosis.

Abstract Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values

To fully appreciate genetics, one must understand the link between genotype (DNA sequence) and phenotype (observable characteristics). Advances in high-throughput genomic sequencing technologies and applications, so-called "-omics," have made genetic sequencing readily available across fields in biology from applications in non-traditional study organisms to precision medicine. Thus, understanding these tools is critical for any biologist, especially those early in their career. This comprehensive review discusses the chronological development of different sequencing methods, the bioinformatics steps to analyzing this data, and social and ethical issues raised by these techniques that must be discussed and evaluated, including anticipatory guides and discussion questions for active engagement in the classroom. Additionally, the Supporting Information includes a case study to apply technical and ethical concepts from the text.

The marine sponge Lendenfeldia sp., collected from the Southern waters of Taiwan, was subjected to chemical composition screening, resulting in the isolation of four new 24-homoscalarane compounds, namely lendenfeldaranes R–U (1–4). The structures and relative stereochemistry of the new metabolites 1–4 were assigned based on NMR studies. The absolute configurations of compounds 1–4 were determined by comparing the calculated and experimental values of specific optical rotation. The antioxidant and anti-inflammatory activities of the isolated compounds were assayed using superoxide anion generation and elastase release assays. These assays are used to determine neutrophilic inflammatory responses of respiratory burst and degranulation. Compounds 2 and 4 inhibited superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB) with IC50: 3.98–4.46 μM. Compounds 2 and 4 inhibited fMLP/CB-induced elastase release, with IC50 values ranging from 4.73 to 5.24 μM. These findings suggested that these new 24-homoscalarane compounds possess unique structures and potential anti-inflammatory activity.

Abstract Spinal metastases often occur in the advanced stages of breast, lung or prostate cancer, resulting in a significant impact on the patient’s quality of life. Current treatment modalities for spinal metastases include both systemic and localized treatments that aim to decrease pain, improve mobility and structural stability, and control tumour growth. With the development of non-toxic photosensitizer drugs, photodynamic therapy (PDT) has shown promise as a minimally invasive non-thermal alternative in oncology, including for spinal metastases. To apply PDT to spinal metastases, predictive algorithms that optimize tumour treatment and minimize the risk of spinal cord damage are needed to assess the feasibility of the treatment and encourage a broad acceptance of PDT in clinical trials. This work presents a framework for PDT modelling and planning, and simulates the feasibility of using a BPD-MA mediated PDT to treat bone metastases at two different wavelengths (690 nm and 565 nm). An open-source software for PDT planning, PDT-SPACE, is used to evaluate different configurations of light diffusers (cut-end and cylindrical) fibres with optimized power allocation in order to minimize the damage to spinal cord or maximize tumour destruction. The work is simulated on three CT images of metastatically involved vertebrae acquired from three patients with spinal metastases secondary to colorectal or lung cancer. Simulation results show that PDT at a 565 nm wavelength has the ability to treat 90% of the metastatic lesion with less than 17% damage to the spinal cord. However, the energy required, and hence treatment time, to achieve this outcome with the 565 nm is infeasible. The energy required and treatment time for the longer wavelength of 690 nm is feasible ( $${\sim }\,40$$ ∼ 40 min), but treatment aimed at 90% of the metastatic lesion would severely damage the proximal spinal cord. PDT-SPACE provides a simulation platform that can be used to optimize PDT delivery in the metastatic spine. While this work serves as a prospective methodology to analyze the feasibility of PDT for tumour ablation in the spine, preclinical studies in an animal model are ongoing to elucidate the spinal cord damage extent as a function of PDT dose, and the resulting short and long term functional impairments. These will be required before there can be any consideration of clinical trials.

COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

Abstract Background Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. Methods A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27–June 11, 2020). Clinical characteristics and the times from symptoms’ onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. Results Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39–2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29–2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13–1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55–0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25–0.63), yet both sexes had a high level of multimorbidity. The times from symptoms’ onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45–5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13–1.90). Conclusions Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

The aim of this study is to evaluate a 3D (Three Dimensional) Traditional Chinese Medicine (TCM) e-learning platform and determine the factors affecting students' intention to continue to use the platform in TCM courses. Students from two classes were invited to participate in the experiment. To compare the effectiveness of both learning methods, one class serves as the control group and used the traditional classroom lecture method while the other serves as the experimental group using the 3D e-learning platform. To determine the factors affecting TCM students' intention to continue to use the platform, we propose an evaluation model modified from the post-acceptance model of information systems. Data collected from the experimental group students are used to test the proposed research model via the PLS-SEM method. We find that TCM students using the 3D e-learning platform outperformed those who used the traditional classroom lecture method. Meanwhile, the integrated evaluation model is found to provide reasonable explanatory power regarding TCM students' intention to continue to use the e-learning platform.

BackgroundConversational agents or chatbots are computer programs that simulate conversations with users. Conversational agents are increasingly used for delivery of behavior change interventions in health care. Behavior change is complex and comprises the use of one or several components collectively known as behavioral change techniques (BCTs). ObjectiveThe objective of this scoping review is to identify the BCTs that are used in behavior change–focused interventions delivered via conversational agents in health care. MethodsThis scoping review will be performed in line with the Joanna Briggs Institute methodology and will be reported according to the PRISMA extension for scoping reviews guidelines. We will perform a comprehensive search of electronic databases and grey literature sources, and will check the reference lists of included studies for additional relevant studies. The screening and data extraction will be performed independently and in parallel by two review authors. Discrepancies will be resolved through consensus or discussion with a third review author. We will use a data extraction form congruent with the key themes and aims of this scoping review. BCTs employed in the included studies will be coded in line with BCT Taxonomy v1. We will analyze the data qualitatively and present it in diagrammatic or tabular form, alongside a narrative summary. ResultsTo date, we have designed the search strategy and performed the search on April 26, 2021. The first round of screening of retrieved articles is planned to begin soon. ConclusionsUsing appropriate BCTs in the design and delivery of health care interventions via conversational agents is essential to improve long-term outcomes. Our findings will serve to inform the development of future interventions in this area. International Registered Report Identifier (IRRID)PRR1-10.2196/30166

Introduction Chiari 1 malformation (CM1) is a structural abnormality of the hindbrain characterised by the descent of the cerebellar tonsils through the foramen magnum. The management of patients with CM1 remains contentious since there are currently no UK or international guidelines for clinicians. We therefore propose a collaborative, prospective, multicentre study on the investigation, management and outcome of CM1 in the UK: the UK Chiari 1 Study (UKC1S). Our primary objective is to determine the health-related quality of life (HRQoL) in patients with a new diagnosis of CM1 managed either conservatively or surgically at 12 months of follow-up. We also aim to: (A) determine HRQoL 12 months following surgery; (B) measure complications 12 months following surgery; (C) determine the natural history of patients with CM1 treated conservatively without surgery; (D) determine the radiological correlates of presenting symptoms, signs and outcomes; and (E) determine the scope and variation within UK practice in referral patterns, patient pathways, investigations and surgical decisions.Methods and analysis The UKC1S will be a prospective, multicentre and observational study that will follow the British Neurosurgical Trainee Research Collaborative model of collaborative research. Patients will be recruited after attending their first neurosurgical outpatient clinic appointment. Follow-up data will be collected from all patients at 12 months from baseline regardless of whether they are treated surgically or not. A further 12-month postoperative follow-up timepoint will be added for patients treated with decompressive surgery. The study is expected to last three years.Ethics and dissemination The UKC1S received a favourable ethical opinion from the East Midlands Leicester South Research Ethics Committee (REC reference: 20/EM/0053; IRAS 269739) and the Health Research Authority. The results of the study will be published in peer-reviewed medical journals, presented at scientific conferences, shared with collaborating sites and shared with participant patients if they so wish.

Zika virus (ZIKV) poses a serious public health threat due to its association with birth defects in developing fetuses and Guillain-Barré Syndrome in adults. We are developing a ZIKV vaccine based on virus-like particles (VLPs) generated in transiently transfected HEK293 cells. The genetic construct consists of the prM and envelope structural protein genes of ZIKV placed downstream from a heterologous signal sequence. To better understand the humoral responses and correlates of protection (CoP) induced by the VLP vaccine, we evaluated VLP immunogenicity with and without alum in immune-competent mice (C57Bl/6 x Balb/c) and observed efficient induction of neutralizing antibody as well as a dose-sparing effect of alum. To assess the efficacy of the immune sera, we performed passive transfer experiments in AG129 mice. Mice that received the immune sera prior to ZIKV infection demonstrated significantly reduced viral replication as measured by viral RNA levels in the blood and remained healthy, whereas control mice succumbed to infection. The results underscore the protective effect of the antibody responses elicited by this ZIKV VLP vaccine candidate. These studies will help define optimal vaccine formulations, contribute to translational efforts in developing a vaccine for clinical development, and assist in the definition of immunologic CoP.

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Bioethics on trial. Remarks and critical Observations After the definitive consecration of Bioethics, both at the academic and at the public level some scholars, from the early years of the new century, have begun to move criticism into various aspects of the discipline. In the present paper, after a brief medicineintroduction of historical character (§ 2), I will present some of these criticisms (§ 3) by highlighting strengths and weaknesses (§ 4). In the final paragraph (§5), I maintain that bioethics, despite some critical elements, can still be an important discipline both to understand the transformations of our society induced by biomedical developments and to provide homo technologicus with useful tools to guide his own moral conduct.

Abstract Background Langerhans cell histiocytosis is a sporadic disease caused by an uncontrolled pathogenic clonal proliferation of dendritic cells that have Langerhans cell characteristics. New treatment protocols provided by the HISTSOC-LCH-III (NCT00276757) trial show an improvement in the survival of children with langerhans cell histiocytosis. Case presentation We report a case of Langerhans cell histiocytosis, which presented as an osteolytic lesion of the left pre-maxillae enclosing the deciduous incisor and canine in a 7-month-old white Italian boy. He was treated with chemotherapy. He achieved complete remission after 7 months and after 24 months no signs of recurrence were observed. Conclusions As a result of this treatment, anesthetic sequelae and loss of teeth were avoided; in addition, we prevented a loss of the vertical dimension of occlusion.

Passive Ultrasonic Irrigation (PUI) represents one of the most used systems to improve the endodontic irrigants activity. PUI acts increasing the reaction rate of NaOCl, with an increase of dentinal debris and smear layer removal. There is a stronger shear stress and a vapor lock reduction. Aim of this systematic review was to figure out the effects of the PUI on the vapor lock removal, during irrigation. Literature research has been carried out by two reviewers, consulting online databases such as PubMed, EBSCO, and Google Scholar, using keywords like Vapor Lock, Vapour Lock, and Vapor Lock Endodontic. The articles list has been screened based on titles and abstracts, applying eligibility and inclusion criteria. The three articles were eligible for quantitative and statistical analysis, by using RevManager Software Version 5.3. Results show statistical heterogeneity (P=0.08; I2 index=61%) in the vapor lock elimination between the use of PUI and PPI, with an overall Odds Ratio=0.08, CI=95% [0.03;0.25]. PUI resulted to be a useful technique to improve NaOCl activity for vapor lock removal, despite PPI alone using a needle.

BACKGROUND:Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care. METHODS:Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ≥1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0. RESULTS:A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported. CONCLUSION:The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.