Miracle-dz/UniFAR-FTUs huggingface dataset:
The age-standardized incidence, mortality, and case fatality rates of COVID-19 in 79 countries: a cross-sectional comparison and their correlations with associated factors

OBJECTIVES During the coronavirus disease 2019 (COVID-19) pandemic, crude incidence and mortality rates have been widely reported; however, age-standardized rates are more suitable for comparisons. In this study, we estimated and compared the age-standardized incidence, mortality, and case fatality rates (CFRs) among countries and investigated the relationship between these rates and factors associated with healthcare resources: gross domestic product per capita, number of hospital beds per population, and number of doctors per population. METHODS The incidence, mortality, and CFRs of 79 countries were age-standardized using the World Health Organization standard population. The rates for persons 60 years or older were also calculated. The relationships among the rates were analysed using trend lines and coefficients of determination (R2). Pearson correlation coefficients between the rates and the healthcare resource-related factors were calculated. RESULTS The countries with the highest age-standardized incidence, mortality, and CFRs were Czechia (14,253 cases/100,000), Mexico (182 deaths/100,000), and Mexico (6.7%), respectively. The R2 between the incidence and mortality rates was 0.852 for all ages and 0.945 for those 60 years or older. The healthcare resources-related factors were associated positively with incidence rates and negatively with CFRs, with weaker correlations among the elderly. CONCLUSIONS Compared to age-standardized rates, crude rates showed greater variation among countries. Medical resources may be important in preventing COVID-19-related deaths; however, considering the small variation in fatality among the elderly, preventive measures such as vaccination are more important, especially for the elderly population, to minimize the mortality rates.
Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease

Abstract Background Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. Methods We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used. Results There were 436 patients enrolled (mean age, 17 years, range 2–26 years; 58% male; 71% Crohn’s disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (n = 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2. Conclusions The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.
Mixture proportional hazards cure model with latent variables

A mixture proportional hazards cure model with latent variables is proposed. The proposed model assesses the effects of the observed and latent risk factors on the hazards of uncured subjects and the cure rate through a proportional hazards model and a logistic model, respectively. Factor analysis is employed to measure the latent variables through correlated multiple indicators. Maximum likelihood estimation is performed through a Gaussian quadratic technique that approximates the integration over the latent variables. A piecewise constant function is used for the unspecified baseline hazard of uncured subjects. The proposed method can be conveniently implemented by using SAS Proc NLMIXED. Simulation studies are conducted to evaluate the performance of the proposed approach. An application to a study concerning the risk factors of chronic kidney disease for type 2 diabetic patients is provided.
Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension

Abstract Aims Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution. Methods and results We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility, and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and microvasculature. Conclusion This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.
Gaucher disease – therapeutic aspects in Romania

Gaucher disease is a rare autosomal recessive disease caused by the beta-glicosidase activity deficiency, which will lead to substrate accumulation mainly in the liver, spleen or bone marrow. The main symptoms are liver and spleen enlargement, anemia and low platelet count, bone crisis and fatigue. Several treatment options are available, as enzyme replacement therapy, substrate reduction therapy, or chaperones treatment whose effect is still studied. There are 77 adult patients treated at this time in Romania, 54 with intravenous enzyme replacement ant 23 with oral substrate reduction therapy. No severe adverse effects have been reported by now. All patients had improved disease related symptoms after the receiving of the treatment.
Philips IntelliSpace Cognition digital test battery: Equivalence and measurement invariance compared to traditional analog test versions

Abstract Objective: To collect evidence of validity for a selection of digital tests on the Philips IntelliSpace Cognition (ISC) platform. Method: A total of 200 healthy participants (age 50-80) completed both the ISC battery and an analog version of the battery during separate visits. The battery included the following screeners and cognitive tests: Mini-Mental State Examination (2nd edition), Clock Drawing Test, Trail-Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCFT), Letter Fluency, Star Cancellation Test, and Digit Span Test. The ISC tests were administered on an iPad Pro and were automatically scored using designated algorithms. The analog tests were administered in line with existing guidelines and scored by trained neuropsychologists. Criterion validity was established through relative agreement coefficients and raw score equivalence tests. In addition,measurement invariance analysis was used to compare the factor structures of both versions. Finally, we explored effects of demographics and experience with digital devices on performance. Results: We found fair to excellent relative agreement between test versions. Absolute equivalence was found for RAVLT, Letter Fluency, Star Cancellation Test, and Digit Span Test. Importantly, we demonstrated equal loadings of the digital and analog test versions on the same set of underlying cognitive domains. Demographic effects were mostly comparable between modalities, and people’s experience with digital devices was found to only influence performance on TMT B. Conclusions: This study provides several sources of evidence for the validity of the ISC test battery, offering an important step in validating ISC for clinical use. Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2021. 1974565.
Glial ER and GAP junction mediated Ca2+ waves are crucial to maintain normal brain excitability

Astrocytes play key roles in regulating multiple aspects of neuronal function from invertebrates to humans and display Ca2+ fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca2+ dynamics represent a key mechanism for how astrocytes modulate neuronal activity. An unresolved issue is the origin and contribution of specific glial Ca2+ signaling components at distinct astrocytic domains to neuronal physiology and brain function. The Drosophila model system offers a simple nervous system that is highly amenable to cell‐specific genetic manipulations to characterize the role of glial Ca2+ signaling. Here we identify a role for ER store‐operated Ca2+ entry (SOCE) pathway in perineurial glia (PG), a glial population that contributes to the Drosophila blood–brain barrier. We show that PG cells display diverse Ca2+ activity that varies based on their locale within the brain. Ca2+ signaling in PG cells does not require extracellular Ca2+ and is blocked by inhibition of SOCE, Ryanodine receptors, or gap junctions. Disruption of these components triggers stimuli‐induced seizure‐like episodes. These findings indicate that Ca2+ release from internal stores and its propagation between neighboring glial cells via gap junctions are essential for maintaining normal nervous system function.
Changes in Serum Cytokines Throughout Pregnancy in Women With Polycystic Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade inflammation and increased incidence of pregnancy complications, but its influence on the maternal immune system in pregnancy is unknown. Longitudinal serum cytokine profiling is a sensitive measure of the complex immunological dynamics of pregnancy. Objective This work aimed to determine the immunological dynamics of serum cytokines throughout pregnancy in women with PCOS and compare it to pregnancy in women without PCOS. Methods A post hoc analysis was conducted of longitudinal serum samples from 2 randomized, placebo-controlled multicenter studies of pregnant women with PCOS and 2 studies of pregnant women without PCOS. Pregnant women with PCOS (n = 358) and without PCOS (n = 258, controls) provided 1752 serum samples from 4 time points in pregnancy (weeks 10, 19, 32, and 36). Main outcome measures included maternal serum levels of 22 cytokines and C-reactive protein (CRP) at 4 time points in pregnancy. Results Women with PCOS showed marked immunological changes in serum cytokines throughout pregnancy. Compared to controls, women with PCOS showed higher levels of 17 cytokines and CRP at week 10 of pregnancy and a distinct cytokine development throughout pregnancy. The immunological dynamics in women with PCOS was significantly affected by maternal body mass index, smoking, and fetal sex. Conclusion Pregnancy in women with PCOS was associated with a strong early mobilization of inflammatory and other serum cytokines persisting throughout pregnancy, indicating a more activated immune status. These findings provide a novel basis for further study of PCOS and pregnancy complications.
Systematic review and meta-analysis of aortic valve-sparing surgery versus replacement surgery in ascending aortic aneurysms and dissection in patients with Marfan syndrome and other genetic connective tissue disorders

Background Aortic aneurysm and dissection are important causes of morbimortality in patients with Marfan syndrome (MFS) and other connective tissue diseases that affect the cardiovascular tissues. Timely intervention through different surgical techniques improves the prognosis. Both sparing and replacement-type interventions of the aortic valve are used, but selection depends on the condition of the patient at the time of diagnosis, the patient’s emergency condition, surgeon preference and hospital resources. Previous meta-analyses have suggested an advantage with the use of sparing-type interventions, but this finding must be updated and extended to patients with other connective tissue disorders. The objetive of this study is to evaluate the outcomes of valve-sparing root replacement versus aortic root replacement procedures in patients with MFS and similar connective tissue diseases that present with aortic aneurysm or dissection. Methods A systematic review of cohort studies that evaluated sparing-type (preserving, remodeling, reimplantation, Yacoub, David or Florida Sleeve) or replacement-type (repair, Bentall, Button-Bentall, composite valve graft or Cabrol) procedures in patients with Marfan, Loeys-Dietz, Beals-Hecht or Ehlers-Danlos syndromes was done. Studies were retrieved from the SCOPUS, MEDLINE, CINAHL, EMBASE and LILACS electronic databases up to January 2020 without language restrictions. Only studies that directly compared sparing- versus replacement-type procedures were included in the meta-analysis. Results A total of 33 studies (n=1,807 subjects) reported sparing-type surgical interventions and 26 studies (n=2,218 subjects) reported replacement-type surgical interventions. Pooled rates of endocarditis, thromboembolism and aneurysm were higher in replacement-type surgical intervention studies. Sixteen studies were included in the meta-analysis. Sparing-type interventions were associated with a reduced risk of endocarditis (RR =0.13, 95% CI: 0.03–0.61); however, replacement-type interventions favored freedom from valve reoperation (RR =2.39, 95% CI: 1.24–4.60). All studies were at low risk of bias. Conclusions The choice of the best surgical technique is dependent on the type of disease (MFS or other connective tissue diseases) as well as the accompanying aortic and cardiovascular damage, since these key factors are heterogeneous. Although the results of this meta-analysis tend to show some advantages for one type of surgical intervention over the other and viceversa, the surgeon can only make the best decision during the surgical act.
The Association of Delayed Care With Depression Among US Middle-Aged and Older Adults During the COVID-19 Pandemic: Cross-sectional Analysis

Background During the COVID-19 pandemic, the depression level among US adults has significantly increased. Age disparity in depression during the pandemic has been reported in recent studies. Delay or avoidance of medical care is one of the collateral damages associated with the COVID-19 pandemic, and it can lead to increased morbidity and mortality. Objective This study aimed to assess the prevalence of depression and delayed care among US middle-aged adults and older adults during the pandemic, as well as investigate the association of delayed care with depression among those 2 age groups. Methods This cross-sectional study used data from the 2020 Health and Retirement Study (HRS) COVID-19 Project (Early, Version 1.0). Univariate analyses, bivariate analyses, and binary logistic regression were applied. US adults older than 46 years were included. Depression was measured by the Composite International Diagnostic Interview-Short Form (CIDI-SF). Delayed care was measured by the following 4 items: delayed surgery, delayed seeing a doctor, delayed dental care, and other delayed care. Results A total of 3246 participants were identified. More than half of the participants were older than 65 years (n=1890, 58.2%), and 274 (8.8%) participants had depression during the pandemic. Delayed dental care was positively associated with depression among both middle-aged adults (OR 2.05, 95% CI 1.04-4.03; P=.04) and older adults (OR 3.08, 95% CI 1.07-8.87; P=.04). Delayed surgery was positively associated with depression among older adults (OR 3.69, 95% CI 1.06-12.90; P=.04). Self-reported pain was positively related to depression among both age groups. Middle-aged adults who reported higher education levels (some college or above) or worse self-reported health had a higher likelihood of having depression. While perceived more loneliness was positively associated with depression among older adults, financial difficulty was positively associated with depression among middle-aged adults. Conclusions This study found that depression was prevalent among middle-aged and older adults during the pandemic. The study highlighted the collateral damage of the COVID-19 pandemic by identifying the association of delayed surgery and dental care with depression during the pandemic. Although surgery and dental care cannot be delivered by telehealth, telehealth services can still be provided to address patients’ concerns on delayed surgery and dental care. Moreover, the implementation of telemental health services is needed to address mental health symptoms among US middle-aged and older adults during the pandemic. Future research that uses more comprehensive measurements for delayed care is needed to decipher the path through which delayed care is associated with depression.
Basic concepts of radiation emergency medicine

Nuclear and radiological accidents are not frequent but may lead to major consequences in the population. For the health systems, the need to handle a large number of victims will probably remain as an exception. However, a high number of affected victims can be expected in some terrorist scenarios. In addition, medical accidents in radiotherapy, fluoroscopy and diagnostic radiology have increased the number of patients with severe radiation injuries considerably, especially in developed countries. Given the increased use of ionising radiation for industrial and medical purposes and new technological applications emerging, the number of accidents may increase in the future. Consequently, the early identification and adequate management of these emergencies is a priority, as well as the need for medical preparedness, requiring knowledge about various emergency scenarios and planning appropriate responses to them before they occur. Unfortunately, medical professionals have a substantial knowledge gap in identifying and treating injured persons affected by ionising radiation. As managing radiation accidents is a very challenging process, exercises must be carried out to organise a well-trained multidisciplinary group of professionals to manage any radiation accident properly. Efforts on a continuously updated guidance system should be developed. In addition, new approaches to foster sustainable interdisciplinary and international cooperative networks on radiation injuries are necessary. Lessons learned from past nuclear and radiological emergencies have significantly contributed to strengthening scientific knowledge and increasing the available medical information on the effects of ionising radiation in the human body. In this context, radiation emergency medicine has emerged as a discipline that contributes to the diagnosis, treatment, medical follow-up and prognosis of persons affected by radiation injuries in a nuclear or a radiological emergency. In this paper, we review some relevant concepts related to the medical preparedness and multidisciplinary response required to attend to persons affected by these emergencies.
Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.

Objective Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental versus genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Methods Heritability of thyroid stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7,522,526 single nucleotide polymorphisms as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n= 1115) followed by meta-analysis to maximise power for discovery. Results Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Conclusion Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.
Preoperative Short Physical Performance Battery as a predictor of prolonged hospitalization after coronary artery bypass grafting in older patients

Objective The study aimed to evaluate the predictive value of the Short Physical Performance Battery (SPPB) and its three components for identifying the requirement for a prolonged hospitalization for coronary artery bypass grafting (CABG) in older patients. Methods This prospective, observational study included 425 older patients who consecutively underwent selective CABG surgery. All patients were assessed for the SPPB. We analysed the association of the postoperative length of hospital stay with the SPPB and three components. Receiver operating characteristic curve analysis was performed to determine the validity of the SPPB for predicting older patients with a prolonged hospitalization (>8 days). Results The SPPB and its three individual components were independent risk factors for a prolonged postoperative length of hospital stay. Only the SPPB summary score and the 4-m gait speed components showed good discriminative capabilities. An SPPB score cut-off of 9.5 provided the best accuracy for identifying a prolonged hospitalization. A poor physical performance (SPPB <10 score) was related to an increased risk of adverse cardiac and cerebrovascular events within 6 months after discharge. Conclusions This study provides evidence for clinical utility of the SPPB score for identifying older patients undergoing CABG who are at risk of prolonged hospitalization.