The dissolved organic carbon(DOC) content of rivers is the most active part of the carbon cycle migration in the basin under consideration, and it is the basis for a comprehensive understanding of the regional carbon cycle. In this study, we periodically took samples from four monitoring stations in the Xiying River Basin of the Qilian Mountains in the northern Qinghai-Tibet Plateau. We calculated the fluxes of organic carbon in the rivers within the study area and will discuss the influencing factors of Dissolved Organic Carbon concentration in these rivers in this paper. Our results showed that: (1) The DOC concentration and output flux in the inland river runoff area are basically the same as those in the Heihe River Basin, but far lower than those in the low-latitude monsoon climate zone and most of the basins in the Eurasian Arctic region. This is mainly due to the small river runoff and low DOC concentration in the area. (2) The Dissolved Organic Carbon concentration and transport flux of the rivers show significant seasonal changes, with the Dissolved Organic Carbon content in summer and autumn being higher than in winter and spring. (3) The larger runoff causes higher concentrations of dissolved organic carbon in rivers. Runoff is the primary means of carbon migration in the Inland River Basin. There are significant carbon migrations from the upstream to the middle and downstream sections of the Inland River Basin.

Objective To analyze the incidence, predictors, and cost of 30-day left atrial appendage closure readmissions utilizing the Nationwide Readmissions Database (NRD) and to develop a scoring system to predict readmission risk. Background Determining incidence and predictors of 30-day readmission post-left atrial appendage closure can direct resources towards high-risk patients. Methods International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify patients. We excluded patients who were discharged or died in December 2016. Influential factors were identified by univariate analysis and clinical suspicion. Continuous variables were compared using the Student’s T-test and categorical variables were compared using chi-square or Fisher’s exact test. A logistic regression model and scoring system were developed and validated. Results 2975 patients were identified and 243 (8.2%) readmitted within 30 days. Non-routine disposition (p<0.0001), chronic pulmonary disease (p=0.0003), renal disease (p<0.0001), and anemia (p=0.009) were significant predictors of readmission. Readmitted patients had longer lengths of stay (2.8 days ± 4.8) and higher charges ($139,869.3 ± 94,574.3). Average length of stay and cost for rehospitalizations were 4.8 days ±4.9 and $62,577± 85,850. Top causes of readmission included atrial fibrillation, atrial flutter, congestive heart failure, sepsis and gastrointestinal bleeding. Mortality during rehospitalization was 1.2%. Our scoring system had a C-statistic of 0.679 (derivation) and 0.633 (validation). Conclusion Readmitted patients have longer and more expensive initial hospital admissions, and chronic cardiac, pulmonary, and renal issues. A simple scoring system may identify patients at risk for readmission

It has been reported that the prevalence of cases whose leads were located in the right ventricular lateral wall (RVLW), even though we intended to implant the leads in the right ventricular septum (RVS), is not uncommon. Among the cases whose leads were assumed to be implanted in the RVS, we experienced three cases whose leads were confirmed to be located in the RVLW by postoperative CT. We investigated the intra-operative fluoroscopic index common to these three leads. In the left anterior oblique view (LAO), the transverse movement of the lead-tip seemed to be exceptionally large in all cases. To assess this index, we compared to the consecutive twenty leads confirmed to be located in the RVS. The transverse movement of the lead-tip in the RVLW was clearly greater than that in the RVS (12.8±1.7 mm vs. 4.2±0.9 mm). This difference was large enough to be judged visually. Large transverse movement of the lead-tip in LAO may be a new visual fluoroscopic index that predicts anchoring to the RVLW.

Interfaces between biomaterials and living system are critical in regulating their interactions. Poor biocontact properties always limited the performance of biomaterials in biological environment. Surface engineering aims to control the interface interaction to further enhance the desired behavior of biomaterials. Upon implantation of biomaterials into the biological environment, a series of host responses are initiated. Non-specific protein adsorption on biomaterials is the essential stage of all biological reactions that associated with implants failure, device-related infections and blood-coagulation. In this review, we first focused on surface modification techniques to eliminate protein adsorption by emphasizing PEGylation of both macroscopic surface and nanoparticle system. Next, recent developments in surface engineering of biomaterials to optimize interactions between biomaterials and specific host tissue and organs are discussed. Optimizing the biocontact property of blood-contact devices can improve their hemocompatibility and maintain vascular homeostasis. Surface modifications of orthopedic and dental implants confer improved osteointegration and tribology performance. Controlling the surface chemistry and topography, and immobilizing biomolecules can aid the expansion and direct the differentiation of stem cells.

The current industrial production of polymer building blocks such as ε-caprolactone (ε-CL) and 6-hydroxyhexanoic acid (6HA) is a multi-step process associated with critical environmental issues such as the generation of toxic waste and high energy consumption. Consequently, there is a demand for more eco-efficient and sustainable production routes. This study deals with the generation of a platform organism that converts cyclohexane to such polymer building blocks without the formation of byproducts and under environmentally benign conditions. Based on kinetic and thermodynamic analyses of the individual enzymatic steps, we rationally engineered a 4-step enzymatic cascade in Pseudomonas taiwanensis VLB120 via stepwise biocatalyst improvement on the genetic level. We found that the intermediate product cyclohexanol severely inhibits the cascade and optimized the cascade by enhancing the expression level of downstream enzymes. The integration of a lactonase enabled exclusive 6HA formation without side products. The resulting biocatalyst showed a high activity of 44.8 ± 0.2 U gCDW-1 and fully converted 5 mM cyclohexane to 6HA within 3 h. This platform organism can now serve as a basis for the development of greener production processes for polycaprolactone and related polymers.

Oncocytic adenolipoma is a rare tumor composed of adipose tissue and oncocytic epithelial cells in different proportions presenting in the salivary gland. Until now, less than 20 such cases are reported. We report another such rare case presented as huge neck mass.

Outcomes in superior transeptal and left atrial approach: does the number of valves matter?Running Head: Approaches to the Mitral valve

Background: Little is known about whether coinfection of other respiratory tract viruses contributes to severity of COVID-19 pneumonia. Methods: We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia (64 cases co-infected with influenza A/B vs 64 negative influenza cases via pair-matching on age, sex, and days from onset of symptom). Results: Among 64 co-infected patients, 54 patients (84.4%) had co-infected with influenza A, and 10 (15.6%) with influenza B. The percentages for the severity of pneumonia on admission of the two groups, i.e., with influenza infection and without, were similar (P=0.945). The median duration (days) of viral shedding time from admission was longer for patients with influenza infection (17.0 day) than those without influenza infection (12.0 day) (P<0.001). However, the progression of lung CT in four weeks after onset of symptom were similar in both groups. The multivariable Cox proportional hazards model showed that the HR of pneumonia resolution on CT scans was 0.869 (P=0.612) for patients with influenza (95% CI 0.505, 1.495) compared with patients without influenza, while the HR of resolution in lung involvement was 1.878 (P=0.020) for patients with lopinavir/ritonavir, compared with patients without lopinavir/ritonavir (95% CI 1.103, 3.196). Patients who were treated with lopinavir/ritonavir presented with faster pneumonia resolution in two weeks after symptom onset both in the whole cohort (32.4% vs 13.8%, P=0.036) and in influenza co-infected group (37% vs 1%, P=0.001). Conclusions: Lopinavir/ritonavir eliminated the difference of lung involvement between influenza co-infected and non-infected groups, indicating lopinavir/ritonavir is associated with pneumonia resolution in COVID-19.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an exaggerated inflammatory reaction secondary to a host’s inadequate immune response causing a self-perpetuating loop of altered regulation. Signs and symptoms of HLH are compatible with other common diseases and are nonspecific. Underdiagnosis makes it difficult to estimate the real incidence of HLH, especially in developing countries. Materials and Methods: Retrospective, descriptive study of hospitalized pediatric patients admitted to a high-complexity institution in Cali, Colombia between 2012 and 2019 with HLH diagnosis. Medical history review to complete a virtual database. A secondary descriptive analysis was carried out. The study was approved by the Institutional Ethics Committee. Results: Twenty-one patients were included. 52.4% of the population was male with a median age of 9.3 years [IQR (3.0-13.7years)]. More than half of patients (66.6%) had viral isolation at diagnosis, the most frequent being Epstein-Barr Virus (EBV) (52.3%) and dengue (14.3%). Three patients had gene mutations (LYST, XIAP, and UNC13D). Ninety-five percent of the patients were treated with the HLH 2004 protocol, half of them received incomplete protocol with IgIV at high doses and/or systemic steroids, while the other half received the complete protocol including etoposide and cyclosporine. More than three-fourths (76.2%) required admission to an ICU with a median stay of 14 days [IQR (11-37 days)] and a median hospital stay of 30 days [IQR (18-93 days)]. 14.3% (n = 3) of patients died. Conclusions: HLH is an underdiagnosed pathology that requires greater sensitization in developing countries in order to make early diagnoses and obtain better outcomes.

Abstract Background: Considering the lack of definitive drug or vaccine, the non-pharmaceutical interventions need to be implemented to control the current coronavirus disease (COVID-19) outbreak, notably in countries with limited resources like Bangladesh. So, the study targeted the university students of Bangladesh as the representatives of the millennials to determine their level of awareness regarding COVID-19. Methods: A cross-sectional study was designed to determine the knowledge, attitude and practices with a co-produced perception section regarding COVID-19 among university students in Bangladesh. The survey was conducted from 16 to 23rd March, 2020. Descriptive and inferential analyses were performed with statistical significance defined as p < 0.05. Result: Among 1393 students participated in the study, about one-third of them had a positive attitude towards COVID-19 issues, although only 6.9% had good knowledge. While the majority of the participants followed sneezing/ coughing etiquette, frequent hand washing/sanitizing, limited body contact and public transport, etc., both good knowledge and positive attitude were significantly associated with respondents’ good practices. But despite the satisfactory hand hygiene behaviors, awareness is required about the type of sanitizers and the importance of washing hands for 20seconds. Promoting health educative activities through Facebook might be considered to improve the knowledge level, especially to raise awareness about rare symptoms and asymptomatic transmission. However, bazaars might be the potential point of the outbreak that needs to be controlled. Conclusion: The study supports the concerning lack of knowledge among the students along with suggesting the issues to be addressed for successful containment of COVID-19.

Diffuse alveolar hemorrhage is a serious disorder where bleeding occurs throughout the alveoli that originates from the pulmonary microvasculature. Pulmonary capillaritis is a common cause of DAH but overall is extremely rare albeit potentially deadly in the pediatric population. PC is typically associated with systemic autoimmune disorders and treatment revolves around control of the cause. Isolated pulmonary capillaritis occurs without an underlying association and is extremely uncommon, particularly in children. Because of this, treatment guidelines do not exist but the urgency of treatment remains due to serious sequelae that may occur, including sudden death. Here, an interesting case is presented involving a toddler with diffuse alveolar hemorrhage due to ANCA-negative isolated pulmonary capillaritis with a strong family history of autoimmune disease. After multiple relapses she is currently in remission following a several year treatment regimen that included rituximab, pulse steroids, IVIG, azathioprine and oral corticosteroids. We would like to acknowledge to Dr. Timothy Vece for his assistance in the final treatment protocol for this patient.

The purpose of this research was to investigate which genetic mutations are responsible for Uveal Melanoma (UM), a rare subtype of melanoma but the most frequent primary cancer of the eye. Genome data of UM patients was obtained from U.S. National Institute of Health’s (NIH) National Library of Medicine. Data was obtained from samples that were surgically collected from eye enucleations or resected from liver metastases. The DNA sequence from the cancerous cells was compared to a reference DNA sequence (from normal tissue pairs) to identify any nucleotide base pair mismatches. Gene functions of mutated genes were studied to investigate possible causal links to cancer, such as anomalies in genes that coded for proteins with a known role in tumor repression. A total of 130 genetic mutations were discovered (seven recurrent and 123 non-recurrent), with most mutations occurring in chromosomes 3 and 23. Recurrent mutations varied from 8.7% to 17.39% occurrence in the UM patient sample. The recurring genetic mutations were observed as missense mutations in the following genes: ALG1L2, DMD, IL1RAPL2, KIAA0825, LOC440040, NXF2, and PHYHD1. The research revealed UM is a heterogenous disease with homozygous mutations and is a recessive disorder.

Arterial blood gas analysis (ABG) is the gold standard test for carbon dioxide measurement. End-tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) are non-invasive alternative methods. Objective: to examine the use of PetCO2 and PtcCO2 as PaCO2surrogates in awake children. Methods: Prospective observational study. Consecutive awake children in stable condition referred to the Sleep Unit of Hospital de Pediatría Prof. Dr. J. P. Garrahan with suspected or confirmed SRRD requiring ABG were included. PetCO2 and PtcCO2 were recorded simultaneously during arterial puncture. PetCO2 and PtCO2 values were compared with PaCO2. Correlation coefficient and Bland-Altman analysis were applied. Sample size was calculated considering a mean difference ≤ 3 mmHg as clinically acceptable. Results: 68 sample sets were obtained from 67 patients. Median age was 9.11 years (0.23-18.76). During 94.1% of the procedures patients breathed spontaneously, 30% needed multiple punctures and 92% resulted in pain. Median (IQR) PaCO2 (mmHg) was 36.3 (31.45; 40.90), PetCO2 33.0 (29;39) and PtcCO2 38.8 (32.95;43.32). Correlation and agreement for PaCO2/PetCO2 and PaCO2/PtcCO2was: r= 0.6 and0.9, and media of bias=2.83(-9.97;15.64) and-1.88 (-9.01;5.24), respectively. Hypercapnia(PaCO2>45.0 mmHg) was present in 8/68 (11.8%) samples. Sensitivity, specificity, positive predictive value and negative predictive value to detect hypercapnia with PetCO2 was 38 %,98%,75% and 92%, respectively, and with PtcCO2, 100%, 90%, 57% and 100%, respectively. Conclusion: PtcCO2 showed better agreement with PaCO2 than PetCO2,.but because of the wide dispersion of values, neither method can replace the gold standard. Transcutaneous CO2might be a good screening tool to detect hypercapnia in awake children.

Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen (called double-conditioning regimen) comprising two cycles of total 800 mg/m2 of thiotepa and total 280 mg/m2 of melphalan is widely used. To re-evaluate the safety and the efficacy of this regimen for high-risk neuroblastoma, the medical records of 41 patients with high-risk neuroblastoma who underwent the double-conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were reviewed. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point. The median follow-up duration for living patients was 9.2 years (range = 5.5–14.0 years). The 5-year event-free survival (EFS) and overall survival (OS) rates from treatment initiation were 41.5% ± 7.7% and 56.1% ± 7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.9% ± 10.2%, which was significantly superior compared to MYCN-non-amplified high-risk neuroblastoma patients (16.7% ± 8.8%; P < 0.001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12–0.66). Of the 41 patients, 3 died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1). The double-conditioning regimen with thiotepa and melphalan is effective for high-risk neuroblastoma, especially in patients with MYCN amplification. However, the double-conditioning regimen is toxic and warrants special attention in clinical practice.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the global pandemic and caused hundreds of thousands of people died in the world, which is in urgent need to develop new drug therapy and pathogen progressive information. Although abundant anti-viral drugs has been directly practiced in some patients, there are no specific drug treatment due to the new SARS-CoV-2 virus, which cause great disaster and panic all over the world. Remdesivir has been recently a strong candidate for the treatment of COVID-19. Recently, due to the support of antiviral experiments in vitro and a case report by compassionate use of the drug, remdesivir has been a promising candidate treatment for the treatment of COVID-19. As a broad-spectrum anti-viral compound targeting the viral RNA dependent RNA polymerase, remdesivir has been shown to suppress the coronavirus, such as SARS-CoV and MERS-CoV. However, is remdesivir really a magic bullet for COVID-19, also a coronavirus? In this article, we first overview the general information about SARS-CoV-2 and its potential suppressing drug remdesivir. Then, we carefully discussed the limitation with the remdesivir antiviral study, including the case report by compassionate use of remdesivir. Finally, from the pharmaceutical perspective we explored the anti-virus capability of remdesivir against different viruses to see whether it’s a magic bullet for COVID-19. Therefore, this paper provides crucial evidence and objective theoretical basis on remdesivir to cure COVID-19 infections.

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

Background: CHEK2 variants are associated with intermediate breast cancer risk among other cancers. We aimed to comprehensively describe CHEK2 variants in a Spanish hereditary cancer (HC) cohort and adjust American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. Methods: First, three CHEK2 frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the whole CHEK2 coding region was analyzed by next-generation sequencing in 1,848 prospective patients with HC suspicion. We refined ACMGAMP criteria and applied different combinatorial rules to classify CHEK2 variants and define risk alleles. Results: We identified 10 CHEK2 null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; 2 can also be considered “established risk-alleles” and one as “likely risk-allele”. The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary non-polyposis colorectal cancer patients). Conclusions: Here we provide ACMG adjustment guidelines to classify CHEK2 variants. We hope that this work would be useful for variant classification of other genes with low effect variants

With reference to 1986,1995,2004,2011 and 2016 TM images of the Shengjin Lake National Nature Reserve in Anhui province, this paper used ERDAS and ARCGIS software to collect the different land use information on the experimental, buffer and core areas for more than 30 years. By combining the social and economic data and selecting the index which is about the ecological risk of land use to built the system of land utilization evaluation index on ecological risk . On this basis, the AHP and expert commonly were used to determine the weight of index and establish the assessment model on ecological risk of the land use by using the method of fuzzy mathematics. With reference to the ecological risk index which was calculated, and adopting the interpolation and three regression methods to built a forecasting model .Finally, the computer simulation was used to establish the early warning for ecological risk of the land use.

Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. Our paper aimed to delineate the disease genotype by presenting another patient, in whom novel, inframe variant within the MOCS2 gene was identified. Its clinical significance was supported by the medical history and analysis of the possible mutation consequences on a molecular level with the use of the available crystal structure of the human molybdopterin synthase complex. Moreover, potential pathomechanism resulting from molecular defect was presented, giving original insight into current knowledge on this rare disease, including treatment options.

Hibernation has been selected for increasing survival in harsh climatic environments. Seasonal variability in temperature may push the body temperatures of hibernating animals across boundaries of alternative states between euthermic temperature and torpor temperature, typical of either hibernation or summer dormancy. Nowadays, wearable electronics present a promising avenue to assess the occurrence of criticality in physiological systems, such as body temperature fluctuating between attractors of activity and hibernation. For this purpose, we deployed temperature loggers on two hibernating edible dormice for an entire year and under severe Mediterranean climate conditions. Highly stochastic body temperatures with sudden switches over time allowed us to assess the reliability of statistical leading indicators to anticipate tipping points when approaching a critical transition. Hibernation dynamics showed flickering, a phenomenon occurring when a system rapidly moves back and forth between two alternative attractors preceding the upcoming major shift. Flickering of body temperature increased when the system approached bifurcations, which were also anticipated by several metric- and model-based indicators. Gradual changes in air temperature drove long transient behavior (since flickering began long before bifurcations) and hysteresis. For hibernating animals, hysteresis may increase resilience when ending hibernation earlier than the optimal time, which may occur in regions where temperatures are sharply rising, especially during winter. Temporal changes in early indicators of critical transitions in hibernation dynamics may help to understand the effects of climate on evolutionary life histories and the plasticity of hibernating organisms to cope with shortened hibernation due to global warming.

In this brief report we describe an extraordinary case of a pediatric patient with a history of medulloblastoma who developed an intracranial mass-like lesion during growth hormone treatment. To our knowledge this is the first case report of a mass-like lesion as a consequence of parenchymal fluid leakage adjacent to an intraventricular catheter due to increased intracranial pressure during growth hormone therapy which has been proven by biopsy.

Genetic changes in juvenile myelomonocytic leukemia (JMML) determine distinct subtypes, treatments and outcomes. JMML with germline CBL mutation and somatic NRAS mutation possibly achieves spontaneous remission, but hematopoietic stem cell transplantation is indicated for other subtypes of JMML. We hereby report a child with JMML harboring a germline CBL mutation (c.1111T>C) and an NF1 variant (c.3352A>G) concurrently. After evaluation, we considered the NF1 variant not the major contributor. After one year of observation, this case had no signs of disease progression. This case highlights the importance of combining available evidence and clinical findings in caring patients with unusual genomic variations.

There is controversy over whether the use of montelukast increases neuropsychiatric events (NEs) in patients with asthma and allergic rhinitis. Our objective was to evaluate whether montelukast caused an increase in neuropsychiatric adverse reactions compared with placebo. We conducted a systematic review and meta-analysis to explore the relationship. The main result of the study was the incidence of NEs. Fifteen RCTs were screened and included for meta-analysis to merge statistics. The main results showed no significant increase in NEs compared with the placebo group. Similar results were seen in the occurrence of NEs in patients grouped by age and headache that the most common neuropsychiatric adverse event. Overall, montelukast did not significantly increase NEs in patients with AR and/or asthma compared with placebo.

Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John’s Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, BCG Atlas. Statistical models were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations, experimental studies and public health policies.