Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges in the prevention or treatment of RSV with emerging new agents in children from low- and middle-income countries

ABSTRACT Introduction Respiratory syncytial virus (RSV) causes approximately 120,000 deaths annually in children <5 years, with 99% of fatalities occurring in low- and middle-income countries (LMICs). Areas covered There are numerous RSV interventions in development, including long-acting monoclonal antibodies, vaccines (maternal and child) and treatments which are expected to become available soon. We reviewed the key challenges and issues that need to be addressed to maximize the impact of these interventions in LMICs. The epidemiology of RSV in LMICs was reviewed (PubMed search to 30 June 2020 inclusive) and the need for more and better-quality data, encompassing hospital admissions, community contacts, and longer-term respiratory morbidity, emphasized. The requirement for an agreed clinical definition of RSV lower respiratory tract infection was proposed. The pros and cons of the new RSV interventions are reviewed from the perspective of LMICs. Expert opinion We believe that a vaccine (or combination of vaccines, if practicable) is the only viable solution to the burden of RSV in LMICs. A coordinated program, analogous to that with polio, involving governments, non-governmental organizations, the World Health Organization, the manufacturers and the healthcare community is required to realize the full potential of vaccine(s) and end the devastation of RSV in LMICs.
Delaying surgery for patients with a previous SARS‐CoV‐2 infection

With at least 28 elective million operations delayed during the first three months of the COVID-19 pandemic, the number of patients who will require surgery after a previous SARS-CoV-2 infection is likely to increase rapidly1. Operating on patients with an active perioperative SARS-CoV-2 infection is now known to carry a very high pulmonary complication and mortality rate2. Urgent information is needed to guide whether postponing surgery in patients with a previous SARS-CoV-2 infection leads to a clinical benefit, and the optimal length of delay.
Surveillance of COVID-19 school outbreaks, Germany, March to August 2020

Mitigation of the coronavirus disease (COVID-19) pandemic in Germany included school closures in early March 2020. After reopening in April, preventive measures were taken in schools. We analysed national surveillance system data on COVID-19 school outbreaks during different time periods. After reopening, smaller outbreaks (average: 2.2/week) occurred despite low incidence in the general population. School closures might have a detrimental effect on children and should be applied only cautiously and in combination with other measures.
4-Acetylantroquinonol B Inhibits Osteoclastogenesis by Inhibiting the Autophagy Pathway in a Simulated Microgravity Model

Astronauts suffer from 1–2% bone loss per month during space missions. Targeting osteoclast differentiation has been regarded as a promising strategy to prevent osteoporosis in microgravity (μXg). 4-acetylantroquinonol B (4-AAQB), a ubiquinone from Antrodia cinnamomea, has shown anti-inflammatory and anti-hepatoma activities. However, the effect of 4-AAQB on μXg-induced osteoclastogenesis remains unclear. In this study, we aimed to explore the mechanistic impact of 4-AAQB on osteoclast formation under μXg conditions. The monocyte/macrophage-like cell line RAW264.7 was exposed to simulated μXg (Rotary Cell Culture System; Synthecon, Houston, TX, USA) for 24 h and then treated with 4-AAQB or alendronate (ALN) and osteoclast differentiation factor receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclastogenesis, bone resorption activity, and osteoclast differentiation-related signaling pathways were analyzed using tartrate-resistant acid phosphatase (TRAP) staining, actin ring fluorescent staining, bone resorption, and western blotting assays. Based on the results of TRAP staining, actin ring staining, and bone resorption assays, we found that 4-AAQB significantly inhibited μXg-induced osteoclast differentiation. The critical regulators of osteoclast differentiation, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, and dendritic cell-specific transmembrane protein (DC-STAMP), were consistently decreased. Meanwhile, osteoclast apoptosis and cell cycle arrest were also observed along with autophagy suppression. Interestingly, the autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) showed similar effects to 4-AAQB. In conclusion, we suggest that 4-AAQB may serve as a potential agent against μXg-induced osteoclast formation.
A Call for Leadership and Management Competency Development for Directors of Medical Services—Evidence from the Chinese Public Hospital System

Background: A competent medical leadership and management workforce is key to the effectiveness and efficiency of health service provision and to leading and managing the health system reform agenda in China. However, the traditional recruitment and promotion approach of relying on clinical performance and seniority provides limited incentive for competency development and improvement. Methods: A three-component survey including the use of a validated management competency assessment tool was conducted with Directors of Medical Services (n = 143) and Deputy Directors of Medical Services (n = 152) from three categories of hospital in Jinan, Shandong Province, China. Results: The survey identified the inadequacy of formal and informal management training received by hospital medical leaders before commencing their management positions and confirms that the low self-perceived competency level across two medical management level and three hospitals was beyond acceptable. The study also indicates that the informal and formal education provided to Chinese medical leaders have not been effective in developing the required management competencies. Conclusions: The study suggests two system level approaches (health and higher education systems) and one organization level approach to formulate overall medical leadership and management workforce development strategies to encourages continuous management competency development and self-improvement among clinical leaders in China.
Superfrogs in the city: 150 year impact of urbanization and agriculture on the European Common Frog

Despite growing pressure on biodiversity deriving from increasing anthropogenic disturbances, some species successfully persist in altered ecosystems. However, these species' characteristics and thresholds, as well as the environmental frame behind that process are usually unknown. We collected data on body size, fluctuating asymmetry (FA), as well as nitrogen stable isotopes (δ15N) from museum specimens of the European Common Frog, Rana temporaria, all originating from the Berlin–Brandenburg area, Germany, in order to test: (a) if specimens have changed over the last 150 years (1868–2018); and (b) if changes could be attributed to increasing urbanization and agricultural intensity. We detected that after the Second World War, frogs were larger than in pre‐war Berlin. In rural Brandenburg, we observed no such size change. FA analysis revealed a similar tendency with lower levels in Berlin after the war and higher levels in Brandenburg. Enrichment of δ15N decreased over time in both regions but was generally higher and less variable in sites with agricultural land use. Frogs thus seem to encounter favorable habitat conditions after pollution in postwar Berlin improved, but no such tendencies were observable in the predominantly agricultural landscape of Brandenburg. Urbanization, characterized by the proportion of built‐up area, was not the main associated factor for the observed trait changes. However, we detected a relationship with the amount of urban greenspace. Our study exemplifies that increasing urbanization must not necessarily worsen conditions for species living in urban habitats. The Berlin example demonstrates that public parks and other urban greenspaces have the potential to serve as suitable refuges for some species. These findings underline the urgency of establishing, maintaining, and connecting such habitats, and generally consider their importance for future urban planning.
Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next‐generation sequencing technique

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3‐internal tandem duplication (FLT3‐ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation. In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse‐free survival (RFS), DNMT3A, FLT3‐ITD, or RUNX1 mutation predicted a higher likelihood of remission‐induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3‐ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation‐related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next‐generation sequencing screening.
Response of soil physical-chemical properties to rocky desertification succession in South China Karst

Karst rocky desertification has been an important ecological issue hindering the economy and society development of South China Karst region,and the control of rocky desertification has been clearly listed in the national projects of economy and society development. But there are short of soil researches in karst rocky desertification ecosystem,and the succession of soil physical-chemical properties is still unclear in the process of rocky desertification,which hardly hinders the control of rocky desertification well work.Based on these problems, in this study, firstly, three typical rocky desertification regions, that is, Yachi, Hongfenghu,and Huajiang of Guizhou Province,representing three different typical karst landforms of plateau mountain, plateau basin,and plateau gorge,respectively,were selected as experiment areas,and 45 sample plots with area of 20 m × 20 m,respectively,were set up for the 5 typical degrees of rocky desertification,that is,no,potential,low,middle,and high,in these three experimental areas. Then,the soil physical-chemical properties were surveyed and analyzed by the methods of chemical determination and mathematical statistics. Results show that 1) there are obvious differences of soil physical-chemical properties between different degrees of rocky desertification, specifically, bulk density, capillary porosity,total porosity,field moisture capacity,capillary moisture capacity,pH,organic matter content,hydrolysis nitrogen content,available phosphorus content,and total potassium content. But,not as expected,the soil degeneration do not always raise with the increased degree of rocky desertification. In fact, with the increased degree of rocky desertification,the soil degenerate firstly and then improve; 2) Organic matter content,nitrogen content,capillary moisture capacity,bulk density,and porosity all are remarkable correlation with other factors of soil physical-chemical properties, and they are the key factors of soil physical-chemical properties,which have important functions in advancing the soil nutrient cycle and improving the soil physical-chemical properties; 3) Principal component analysis also show that organic matter content,nitrogen content,potassium content,bulk density,moisture capacity,and porosity are the key factors in evaluating the degrees of rocky desertification. Based on these results,the theory,that is,bare rocks have a collected action for soil nutrients in karst rocky desertification ecosystem,was raised,and the response and its mechanism of soil physicalchemical properties to rocky desertification succession was presented. Results have important values in the protection of karst forest ecosystem and the control of rocky desertification.
Polo-like kinase 1 as a prognostic and therapeutic target in high-grade brain tumors

ii PREFACE . iii TABLE OF CONTENTS . vi LIST OF TABLES . x LIST OF FIGURES . xi LIST OF ABBREVIATIONS . xiv ACKNOWLEDGEMENTS . xviii DEDICATION . xix CHAPTER 1: INTRODUCTION . 1 1.1 High-grade brain tumors . 1 1.1.1 Challenges . 1 1.1.1.1 Detection . 2 1.1.1.2 Blood-brain barrier . 2 1.1.1.3 Radiation . 3 1.1.2 Glioblastoma (GBM) . 3 1.1.2.1 GBM clinical attributes . 4 1.1.2.2 Current treatment and temozolomide (TMZ) resistance . 5 1.1.2.3 Molecular pathology and classification of GBM . 10 1.1.2.4 Mouse models and cell of origin . 15 1.1.3 Medulloblastoma (MB) . 17 1.1.3.1 MB clinical attributes . 17 1.1.3.2 Current treatment protocols . 18 1.1.3.3 Hijacking cerebellar development . 22 1.1.3.4 Molecular classification of MB . 27 1.1.3.5 Mouse models and cell of origin . 33
Regulatory Scope and Its Mental and Social Supports

Adaptive functioning requires the ability to both immerse oneself in the here and now as well as to move beyond current experience. We leverage and expand construal-level theory to understand how individuals and groups regulate thoughts, feelings, and behavior to address both proximal and distal ends. To connect to distant versus proximal events in a way that meaningfully informs and guides responses in the immediate here and now, people must expand versus contract their regulatory scope. We propose that humans have evolved a number of mental and social tools that enable the modulation of regulatory scope and address the epistemic, emotive, and executive demands of regulation. Critically, across these tools, it is possible to distinguish a hierarchy that varies in abstractness. Whereas low-level tools enable contractive scope, high-level tools enable expansion. We review empirical results that support these assertions and highlight the novel insights that a regulatory-scope framework provides for understanding diverse phenomena.
A systematic review of animal models and sex as a variable in itch research

Introduction: Pruritus (or itch) research has gained momentum in the last decades and use of animal models to study itch behavior are a vital part of the research. Recent studies have found that many fields using animal models, including neuroscience, are predisposed toward using male animals in preclinical research. To address sex bias in animal research, the National Institutes of Health (NIH) began requiring researchers to include sex as a variable beginning in June 2015. Here, we test whether researchers studying itch are biased toward using males in preclinical research. Methods: The NIH’s PubMed database was searched for primary research articles written between August 2007 and December 2018 using the words “Itch” and “Pruritus. ” The following information was extracted from articles fitting our inclusion criteria: type of itch (acute or chronic), the animal model and the sex of the animals used, and whether researchers considered sex as a variable. z-Tests, binomial tests, and the Cochran-Armitage test for trend were used to explore relationships between animal models and the usage of both sexes. Results: We found 5.3%±1.2% of papers in a given year used 1 of our 4 animal models. Mice were the most frequently used animal model, followed by rats, nonhuman primates, and dogs. Overall, researchers used male animals regardless of the animal model used. In preclinical research conducted on both male and female animals, sex was not considered a variable in a majority of these studies. Finally, since 2015, there has not been a change in the usage of male or female mice. Briefly, the incidence of papers utilizing both sexes has not changed. Discussion: We have found that itch researchers have a bias towards males in animal research. This bias has not changed since the NIH’s mandate to include sex as a variable in preclinical research.
Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study

Isatuximab, an anti‐CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open‐label, single‐arm, multicenter, phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent cycles. Cohort 1 (n = 3) received 10 mg/kg QW/Q2W; cohort 2 (n = 5) received 20 mg/kg QW/Q2W. No dose‐limiting toxicities occurred; the recommended dose for the single‐arm phase 2 study (n = 28) was 20 mg/kg QW/Q2W. The overall safety profile was consistent with the current knowledge of isatuximab. The most common adverse events were infusion reactions (42.9%; 12/28); all were grade 1/2 and generally occurred during the first infusion. The overall response rate with 20 mg/kg QW/Q2W isatuximab was 36.4% (12/33); patients with high‐risk cytogenetic abnormalities had comparable results. In phase 2, the median progression‐free survival was 4.7 (95% confidence interval, 3.75 to not reached) months. Median overall survival was not reached. Isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM including high‐risk cytogenetic patients. This trial is registered at ClinicalTrials.gov as NCT02812706.
MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Purpose: Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis. Methods: Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared. Results: Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis. Conclusion: The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.
Long term follow-up of Trypanosoma cruzi infection and Chagas disease manifestations in mice treated with benznidazole or posaconazole

Chagas' Disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for up to 41% of the heart failures in endemic areas in South America and is an emerging infection in regions of North America, Europe, and Asia. Treatment is suboptimal due to two factors. First, the lack of an adequate biomarker to predict disease severity and response to therapy; and second, up to 120-days treatment course coupled with a significant incidence of adverse effects from the drug currently used. Because the disease can manifest itself clinically a few years to decades after infection, controversy remains concerning the suitability of current drug treatment (benznidazole), and the efficacy of alternative drugs (e.g. posaconazole). We therefore followed the clinical course, and PCR detection of parasite burden, in a mouse model of infection for a full year following treatment with benznidazole or posaconazole. Efficacy of the two drugs depended on whether the treatment was performed during the acute model or the chronic model of infection. Posaconazole was clearly superior in treatment of acute disease whereas only benznidazole had efficacy in the chronic model. These results have important implications for the design and analysis of human clinical trials, and the use of specific drugs in specific clinical settings.
Early childhood general anesthesia exposure associated with later developmental delay: A national population-based cohort study

Exposure to general anesthesia has been reported to induce neurotoxicity, impair learning, memory, attention, motor functions, as well as affect behavior in adult rodents and nonhuman primates. Though many have speculated similar effects in humans, previous literature has shown conflicting findings. To investigate the differences in risk of developmental delay among young children exposed to general anesthesia compared to matched unexposed individuals, a population-based cohort study was conducted with a longitudinal dataset spanning 2000 to 2013 from the Taiwan National Health Insurance Research Database (NHIRD). Procedure codes were used to identify children who received anesthesia. For each exposed child, two unexposed children matched by gender and age were enrolled into the comparison cohort. Neurocognitive outcome was measured by the presence of ICD-9-CM codes related to developmental delay (DD). Cox regression models were used to obtain hazard ratios of developing DD after varying levels of anesthesia exposure. After excluding 4,802 individuals who met the exclusion criteria, a total of 11,457 children who received general anesthesia before two years of age was compared to 22,914 children (matched by gender and age) unexposed to anesthesia. Increased risk of DD was observed in the exposure group with a hazard ratio (HR) of 1.320 (95% CI 1.143–1.522, P < 0.001). Subgroup analysis demonstrated further elevated risks of DD with multiple anesthesia exposures (1 anesthesia event: HR 1.145, 95% CI 1.010–1.246, P = 0.04; 2 anesthesia events: HR 1.476, 95% CI 1.155–1.887, P = 0.005; ≥3 anesthesia events: HR 2.222, 95% CI 1.810–2.621, P < 0.001) and longer total anesthesia durations (Total anesthesia <2 hours: HR 1.124, 95% CI 1.003–1.499, P = 0.047; Total anesthesia 2–4 hours: HR 1.450, 95% CI 1.157–1.800, P = 0.004; Total anesthesia > 4 hours: HR 1.598, 95% CI 1.343–1.982, P < 0.001) compared with children unexposed to anesthesia. These results suggest that children exposed to general anesthesia before two years of age have an increased risk of DD. This risk is further elevated with increased frequency of anesthesia, and longer total anesthesia duration. The findings of this study should prompt clinical practitioners to proceed with caution when assessing young patients and planning managements involving procedures requiring general anesthesia.