Miracle-dz/UniFAR-FTUs huggingface dataset:
Dental students’ attitudes and hesitancy toward COVID‐19 vaccine

Abstract Background Dentists are a group of providers who have been identified by CDC at high risk of exposure to COVID‐19 through their contact with patients. This would apply to dental students as well. Thus, it is important to achieve high COVID‐19 vaccination rates in this group. Further, as healthcare providers, they are entrusted with providing health recommendations and advocating for their patients, community, and profession, including vaccinations. Methods Using ualtricsXM an online platform, in 2020, a survey was administered anonymously to dental students at three dental schools to assess the attitudes of dental students to the novel COVID‐19 vaccine. Factors and reasons associated with vaccine hesitancy and acceptance toward the COVID‐19 vaccine and likelihood of recommending and giving the vaccination to patients were assessed. Results Nearly, all participants had positive attitudes toward vaccines in general, agreed they would likely be exposed to COVID‐19, and personally knew someone who had COVID‐19; however, only 56% are willing to take a COVID‐19 vaccine as soon as an FDA‐approved vaccine was available. Of those unwilling to take the vaccine, 63% reported they would take it if mandated by the health systems/dental school; however, 16.3% of the overall respondents would not take the COVID‐19 vaccine even if mandated. Several factors are associated with vaccine acceptance and the likelihood of recommending the vaccination, such as trusting public health experts, concerns about side effects, and agreeing with vaccine mandates. Conclusion Our results highlight the need for an educational curriculum about the safety and effectiveness to promote the uptake of COVID‐19 vaccine.
Risk factors for mortality in patients undergoing peritoneal dialysis: a systematic review and meta-analysis

Abstract Aim Inconsistent investigations of the risk factors for all-cause mortality in patients undergoing peritoneal dialysis (PD) were reported. The present meta-analysis aimed to assess the impact of some clinical characteristics on the risk of mortality in PD patients. Methods PubMed and Embase were systematically searched for studies evaluating the risk factors for all-cause mortality in PD patients. Hazard ratio (HR) and 95% confidence interval (CI) were derived using a random-effect or fixed-effect model considering the heterogeneity across studies. Result A total of 26 studies were included in this meta-analysis in accordance with the inclusion and exclusion criteria. Age, primary cardiovascular diseases, diabetes mellitus, and high level of alkaline phosphatase showed significant positive associations with elevated risk of all-cause and cardiovascular mortality in PD patients, while hemoglobin acted as a benefit factor. Furthermore, early onset of peritonitis, high peritoneal transport status, elevated body mass index and high-sensitivity C-reactive protein could also considerably increase the risk of all-cause mortality. The absolute serum level of magnesium, potassium, and uric acid required to improve survival in PD patients should be verified further. Conclusions Multiple factors could affect the risk of mortality in PD patients.
A Live-Attenuated Zika Virus Vaccine with High Production Capacity Confers Effective Protection in Neonatal Mice

Zika virus (ZIKV), a mosquito-borne flavivirus that has caused global outbreaks since 2013, is associated with severe neurological disorders, such as Guillian-Barré syndrome in adults and microcephaly in infants. The ZIKV epidemic has gradually subsided, but a safe and effective vaccine is still desirable to prevent its potential recurrence, especially in countries of endemicity with competent mosquito vectors. ABSTRACT Zika virus (ZIKV) infection during pregnancy has been linked to congenital abnormalities, such as microcephaly in infants. An efficacious vaccine is desirable for preventing the potential recurrence of ZIKV epidemic. Here, we report the generation of an attenuated ZIKV (rGZ02a) that has sharply decreased virulence in mice but grows to high titers in Vero cells, a widely approved cell line for manufacturing human vaccines. Compared to the wild-type ZIKV (GZ02) and a plasmid-launched rGZ02p, rGZ02a has 3 unique amino acid alterations in the envelope (E, S304F), nonstructural protein 1 (NS1, R103K), and NS5 (W637R). rGZ02a is more sensitive to type I interferon than GZ02 and rGZ02p, and causes no severe neurological disorders in either wild-type neonatal C57BL/6 mice or type I interferon receptor knockout (Ifnar1−/−) C57BL/6 mice. Immunization with rGZ02a elicits robust inhibitory antibody responses with a certain long-term durability. Neonates born to the immunized dams are effectively protected against ZIKV-caused neurological disorders and brain damage. rGZ02a as a booster vaccine greatly improves the protective immunity primed by Ad2-prME, an adenovirus-vectored vaccine expressing ZIKV prM and E proteins. Our results illustrate that rGZ02a-induced maternal immunity can be transferred to the neonates and confer effective protection. Hence, rGZ02a may be developed as an alternative live-attenuated vaccine and warrants further evaluation. IMPORTANCE Zika virus (ZIKV), a mosquito-borne flavivirus that has caused global outbreaks since 2013, is associated with severe neurological disorders, such as Guillian-Barré syndrome in adults and microcephaly in infants. The ZIKV epidemic has gradually subsided, but a safe and effective vaccine is still desirable to prevent its potential recurrence, especially in countries of endemicity with competent mosquito vectors. Here, we describe a novel live-attenuated ZIKV, rGZ02a, that carries 3 unique amino acid alterations compared to the wild-type GZ02 and a plasmid-launched rGZ02p. The growth capacity of rGZ02a is comparable to GZ02 in Vero cells, but the pathogenicity is significantly attenuated in two mice models. Immunization with rGZ02a elicits robust inhibitory antibody responses in the dams and effectively protects their offspring against ZIKV disease. Importantly, in a heterologous prime-boost regimen, rGZ02a effectively boosts the protective immunity primed by an adenovirus-vectored vaccine. Thus, rGZ02a is a promising candidate for a live-attenuated ZIKV vaccine.
The impact of age on antiretroviral drug pharmacokinetics in the treatment of adults living with HIV

ABSTRACT Introduction People living with HIV (PLWH) are aging and will receive life-long treatment: despite substantial improvement in drug efficacy and tolerability, side effects still occur and they can blunt antiretroviral treatment effectiveness. Since age may affect drug exposure and may be associated with side-effects we aimed at reviewing available data on the effect of age on antiretrovirals’ pharmacokinetics in adult patients. Areas covered We searched public databases and major conference proceedings for data on age and pharmacokinetics/pharmacodynamics in PLWH. We limited our review to currently used drugs and focused on population pharmacokinetics and physiologically-based pharmacokinetic modeling studies. Expert opinion Available evidence of a potential detrimental effect in elderly PLWH is limited by study design and small sample sizes. Careful consideration of undoubtful benefits and potential harms is advised when prescribing ARVs to geriatric patients and the knowledge of pharmacokinetics changes need to be included in the process. With the ‘greying’ of the pandemic we need studies with a specific focus on geriatric patients living with HIV that will consider specific phenotypes and associated changes (including sarcopenia).
A perfusable vascularized full-thickness skin model for potential topical and systemic applications

Vascularization of reconstructed tissues is one of the remaining hurdles to be considered to improve both the functionality and viability of skin grafts and the relevance of in vitro applications. Our study, therefore, sought to develop a perfusable vascularized full-thickness skin equivalent that comprises a more complex blood vasculature compared to existing models. We combined molding, auto-assembly and microfluidics techniques in order to create a vascularized skin equivalent representing (a) a differentiated epidermis with a physiological organization and correctly expressing K14, K10, Involucrin, TGM1 and Filaggrin, (b) three perfusable vascular channels with angiogenic sprouts stained with VE-Caderin and Collagen IV, (c) an adjacent microvascular network created via vasculogenesis and connected to the sprouting macrovessels. Histological analysis and immunostaining of CD31, Collagen IV, Perlecan and Laminin proved the integrity of vascular constructs. In order to validate the vascularized skin potential of topical and systemic applications, caffeine and minoxidil, two compounds with different chemical properties, were topically applied to measure skin permeability and benzo[a]pyrene pollutant was systemically applied to evaluate systemic delivery. Our results demonstrated that perfusion of skin reconstructs and the presence of a complex vascular plexus resulted in a more predictive and reliable model to assess respectively topical and systemic applications. This model is therefore aimed at furthering drug discovery and improving clinical translation in dermatology.
Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

Patients with unbalanced X‐autosome translocations are rare and usually present a skewed X‐chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X‐autosome translocations, confirmed by G‐banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late‐replication on the autosomal regions of the derivative chromosomes. All patients showed phenotypical overlap with patients presenting deletions of the autosomal late‐replicating regions, suggesting that the inactivation of autosomal segments may be responsible for their phenotype. Our data highlight the importance of the XCI spread into autosomal regions for establishing the clinical picture in patients carrying unbalanced X‐autosome translocations, and the incorporation of EdU as a novel and precise tool to evaluate the inactivation status in such patients.
Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica

Lipid transfer proteins (LTPs) are the key contributor of organelle-specific lipid distribution and cellular lipid homeostasis. Here, we report a novel implication of LTPs in phagocytosis, trogocytosis, pinocytosis, biosynthetic secretion, recycling of pinosomes, and motility of the parasitic protist E. histolytica, the etiological agent of human amoebiasis. We show that two StAR-related lipid transfer (START) domain-containing LTPs (named as EhLTP1 and 3) are involved in these biological pathways in an LTP-specific manner. Our findings provide novel implications of LTPs, which are relevant to the elucidation of pathophysiology of the diseases caused by parasitic protists.
Parameter variations in personalized electrophysiological models of human heart ventricles

The objectives of this study were to evaluate the accuracy of personalized numerical simulations of the electrical activity in human ventricles by comparing simulated electrocardiograms (ECGs) with real patients’ ECGs and analyzing the sensitivity of the model output to variations in the model parameters. We used standard 12-lead ECGs and up to 224 unipolar body-surface ECGs to record three patients with cardiac resynchronization therapy devices and three patients with focal ventricular tachycardia. Patient-tailored geometrical models of the ventricles, atria, large vessels, liver, and spine were created using computed tomography data. Ten cases of focal ventricular activation were simulated using the bidomain model and the TNNP 2006 cellular model. The population-based values of electrical conductivities and other model parameters were used for accuracy analysis, and their variations were used for sensitivity analysis. The mean correlation coefficient between the simulated and real ECGs varied significantly (from r = 0.29 to r = 0.86) among the simulated cases. A strong mean correlation (r > 0.7) was found in eight of the ten model cases. The accuracy of the ECG simulation varied widely in the same patient depending on the localization of the excitation origin. The sensitivity analysis revealed that variations in the anisotropy ratio, blood conductivity, and cellular apicobasal heterogeneity had the strongest influence on transmembrane potential, while variation in lung conductivity had the greatest influence on body-surface ECGs. Futhermore, the anisotropy ratio predominantly affected the latest activation time and repolarization time dispersion, while the cellular apicobasal heterogeneity mainly affected the dispersion of action potential duration, and variation in lung conductivity mainly led to changes in the amplitudes of ECGs and cardiac electrograms. We also found that the effects of certain parameter variations had specific regional patterns on the cardiac and body surfaces. These observations are useful for further developing personalized cardiac models.
IMPACT OF HEARTBURN AND REGURGITATION ON INDIVIDUALS' WELL-BEING IN THE GENERAL POPULATION: A BRAZILIAN NATIONAL SURVEY.

BACKGROUND Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.
Correlation analysis of periodontal tissue dimensions in the esthetic zone using a non-invasive digital method

Purpose Direct intraoral scanning and superimposing methods have recently been applied to measure the dimensions of periodontal tissues. The aim of this study was to analyze various correlations between labial gingival thickness and underlying alveolar bone thickness, as well as clinical parameters among 3 tooth types (central incisors, lateral incisors, and canines) using a digital method. Methods In 20 periodontally healthy subjects, cone-beam computed tomography images and intraoral scanned files were obtained. Measurements of labial alveolar bone and gingival thickness at the central incisors, lateral incisors, and canines were performed at points 0–5 mm from the alveolar crest on the superimposed images. Clinical parameters including the crown width/crown length ratio, keratinized gingival width, gingival scallop, and transparency of the periodontal probe through the gingival sulcus were examined. Results Gingival thickness at the alveolar crest level was positively correlated with the thickness of the alveolar bone plate (P<0.05). The central incisors revealed a strong correlation between labial alveolar bone thickness at 1 and 2 mm, respectively, inferior to the alveolar crest and the thickness of the gingiva at the alveolar crest line (G0), whereas G0 and labial bone thickness at every level were positively correlated in the lateral incisors and canines. No significant correlations were found between clinical parameters and hard or soft tissue thickness. Conclusions Gingival thickness at the alveolar crest level revealed a positive correlation with labial alveolar bone thickness, although this correlation at identical depth levels was not significant. Gingival thickness, at or under the alveolar crest level, was not associated with the clinical parameters of the gingival features, such as the crown form, gingival scallop, or keratinized gingival width.
Commentary: Herpes simplex virus stromal keratitis preferred practice patterns among ophthalmologists vis-à-vis the Herpetic Eye Diseases Study

Dear Editor, In this issue of the Indian Journal of Ophthalmology (IJO), an interesting article[1] discusses the practice patterns of Indian ophthalmologists in managing herpetic stromal keratitis compared with the findings of Herpetic Eye Disease Study (HEDS). HEDS[2‐4] was a landmark that gave ophthalmologists the guidelines in the management of herpes simplex virus (HSV) keratitis. It was a multicentric study primarily from the United States. However, topical acyclovir not being available in the United States, the role of topical trifluridine and oral acyclovir were studied along with the role of topical and systemic corticosteroids in the treatment of herpes simplex stromal keratitis and iridocyclitis.
Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain: Regional patterns and uncertainties

The regional variability in tundra and boreal carbon dioxide (CO2) fluxes can be high, complicating efforts to quantify sink‐source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990–2015 from 148 terrestrial high‐latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO2 fluxes and test the accuracy and uncertainty of different statistical models. CO2 fluxes were upscaled at relatively high spatial resolution (1 km2) across the high‐latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE‐focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO2 sink strength was larger in the boreal biome (observed and predicted average annual NEE −46 and −29 g C m−2 yr−1, respectively) compared to tundra (average annual NEE +10 and −2 g C m−2 yr−1). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO2 budget, estimated using the annual NEE ensemble prediction, suggests the high‐latitude region was on average an annual CO2 sink during 1990–2015, although uncertainty remains high.
May human epididymis 4 protein play a role in the etiopathogenesis of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome?

Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is an extremely advanced form of preeclampsia. Currently, there is no parameter or marker to predict this syndrome; however, it is emphasized that vascular endothelial damage and abnormal immune responses can be the possible etiologies of HELLP syndrome. It is known that human epididymis protein 4 (HE4) is a protease inhibitor and previous studies have shown that HE4 protein levels are increased in many malignancies and inflammatory conditions. Considering that metalloproteinases may also play a role in endothelial damage, which is thought to be involved in the etiopathogenesis of HELLP syndrome, we thought that HE4 protein, which is a protease inhibitor, may be associated with vascular damage. We aimed to investigate the relationship between HELLP syndrome and HE4 protein and to identify a biomarker that can be utilized in the diagnosis of HELLP syndrome.