Miracle-dz/UniFAR-FTUs huggingface dataset:
Seroprevalence and Virologic Surveillance of Enterovirus 71 and Coxsackievirus A6, United Kingdom, 2006–2017

Enterovirus A71 (EV-A71) and coxsackievirus A6 (CVA6) cause hand, foot and mouth disease (HFMD) and are occasionally linked to severe neurologic complications and large outbreaks worldwide. We estimated EV-A71 and CVA6 seroprevalence using cross-sectional age-stratified samples collected in 2006, 2011, and 2017. Seroprevalences of EV-A71 and CVA6 increased from 32% and 54% at 6–11 months to >75% by 10 years of age. Antibody titers declined after 20 years, which could indicate infrequent re-exposure in older populations. Age profiles for acquiring infections and mean titers were comparable in the 3 testing years, despite the marked increase in incidence of CVA6-related HFMD from 2010. The uncoupling of changes in disease severity from the infection kinetics of CVA6 as we inferred from the seroprevalence data, rather than incidence of infection over the 11-year study period, provides further evidence for a change in its pathogenicity.
Impact of Reticulated Platelets on Platelet Reactivity in Neonates

Neonatal megakaryopoiesis and platelet turnover form a developmentally unique pattern by generating a pool of newly released reticulated platelets from the bone marrow into the circulation. Reticulated platelets are more reactive and hyperaggregable compared to mature platelets, due to their high residual mRNA content, large size, increased expression of platelet surface receptors, and degranulation. The proportion of reticulated platelets in neonates is higher compared to that in adults. Due to the emergence of an uninhibited platelet subpopulation, the newly formed reticulated platelet pool is inherently hyporesponsive to antiplatelets. An elevated population of reticulated platelets is often associated with increased platelet reactivity and is inversely related to high on-treatment platelet reactivity, which can contribute to ischemia. Measurements of the reticulated platelet subpopulation could be a useful indicator of increased tendency for platelet aggregation. Future research is anticipated to define the distinct functional properties of newly formed reticulated or immature platelets in neonates, as well as determine the impact of enhanced platelet turnover and high residual platelet reactivity on the response to antiplatelet agents.
Effect of the dwell time deviation constraint on brachytherapy treatment planning for cervical cancer

Objective This study aimed to quantify the effect of the dwell time deviation constraint (DTDC) on brachytherapy treatment for cervical cancer. Methods A retrospective study was carried out on 20 patients with radical cervical cancer. The DTDC values changed from 0.0 to 1.0 by a step size of 0.2. We adjusted the optimization objectives to ensure that all plans were optimized to a high-risk clinical target volume (HRCTV) D90 (the dose to 90% of the HRCTV) = 6 Gy, while keeping the dose to the organs at risk as low as possible. The dose–volume histogram parameters and the dwell time data were compared between plans with different DTDC values. Results The HRCTV volume covered by 150% of the prescription dose gradually increased with increasing DTDC values. As the DTDC value increased from 0.0 to 1.0, the effective dwell point proportion increased from 61.78% to 90.30%. The mean dwell time initially decreased with an increase in the DTDC value, reached the minimum value at DTDC = 0.8, then slightly increased at DTDC = 1.0. Conclusions When using inverse planning simulated annealing optimization for radical cervical cancer cases, the recommended DTDC value is approximately 0.6 if the organ dose needs to be limited.
Domains and Methods Used to Assess Home Telemonitoring Scalability: Systematic Review

Background The COVID-19 pandemic catalyzed the adoption of home telemonitoring to cope with social distancing challenges. Recent research on home telemonitoring demonstrated benefits concerning the capacity, patient empowerment, and treatment commitment of health care systems. Moreover, for some diseases, it revealed significant improvement in clinical outcomes. Nevertheless, when policy makers and practitioners decide whether to scale-up a technology-based health intervention from a research study to mainstream care delivery, it is essential to assess other relevant domains, such as its feasibility to be expanded under real-world conditions. Therefore, scalability assessment is critical, and it encompasses multiple domains to ensure population-wide access to the benefits of the growing technological potential for home telemonitoring services in health care. Objective This systematic review aims to identify the domains and methods used in peer-reviewed research studies that assess the scalability of home telemonitoring–based interventions under real-world conditions. Methods The authors followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and used multiple databases (PubMed, Scopus, Web of Science, and EconLit). An integrative synthesis of the eligible studies was conducted to better explore each intervention and summarize relevant information concerning the target audience, intervention duration and setting, and type of technology. Each study design was classified based on the strength of its evidence. Lastly, the authors conducted narrative and thematic analyses to identify the domains, and qualitative and quantitative methods used to support scalability assessment. Results This review evaluated 13 articles focusing on the potential of scaling up a home telemonitoring intervention. Most of the studies considered the following domains relevant for scalability assessment: problem (13), intervention (12), effectiveness (13), and costs and benefits (10). Although cost-effectiveness was the most common evaluation method, the authors identified seven additional cost analysis methods to evaluate the costs. Other domains were less considered, such as the sociopolitical context (2), workforce (4), and technological infrastructure (3). Researchers used different methodological approaches to assess the effectiveness, costs and benefits, fidelity, and acceptability. Conclusions This systematic review suggests that when assessing scalability, researchers select the domains specifically related to the intervention while ignoring others related to the contextual, technological, and environmental factors, which are also relevant. Additionally, studies report using different methods to evaluate the same domain, which makes comparison difficult. Future work should address research on the minimum required domains to assess the scalability of remote telemonitoring services and suggest methods that allow comparison among studies to provide better support to decision makers during large-scale implementation.
Population genomics of transposable element activation in the highly repressive genome of an agricultural pathogen

The activity of transposable elements (TEs) can be an important driver of genetic diversity with TE-mediated mutations having a wide range of fitness consequences. To avoid deleterious effects of TE activity, some fungi have evolved highly sophisticated genomic defences to reduce TE proliferation across the genome. Repeat-induced point mutation (RIP) is a fungal-specific TE defence mechanism efficiently targeting duplicated sequences. The rapid accumulation of RIPs is expected to deactivate TEs over the course of a few generations. The evolutionary dynamics of TEs at the population level in a species with highly repressive genome defences is poorly understood. Here, we analyse 366 whole-genome sequences of Parastagonospora nodorum, a fungal pathogen of wheat with efficient RIP. A global population genomics analysis revealed high levels of genetic diversity and signs of frequent sexual recombination. Contrary to expectations for a species with RIP, we identified recent TE activity in multiple populations. The TE composition and copy numbers showed little divergence among global populations regardless of the demographic history. Miniature inverted-repeat transposable elements (MITEs) and terminal repeat retrotransposons in miniature (TRIMs) were largely underlying recent intra-species TE expansions. We inferred RIP footprints in individual TE families and found that recently active, high-copy TEs have possibly evaded genomic defences. We find no evidence that recent positive selection acted on TE-mediated mutations rather that purifying selection maintained new TE insertions at low insertion frequencies in populations. Our findings highlight the complex evolutionary equilibria established by the joint action of TE activity, selection and genomic repression.
A Review of Oxidative Stress Products and Related Genes in Early Alzheimer’s Disease

Oxidative stress is associated with the progression of Alzheimer’s disease (AD). Reactive oxygen species can modify lipids, DNA, RNA, and proteins in the brain. The products of their peroxidation and oxidation are readily detectable at incipient stages of disease. Based on these oxidation products, various biomarker-based strategies have been developed to identify oxidative stress levels in AD. Known oxidative stress-related biomarkers include lipid peroxidation products F2-isoprostanes, as well as malondialdehyde and 4-hydroxynonenal which both conjugate to specific amino acids to modify proteins, and DNA or RNA oxidation products 8-hydroxy-2’-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG), respectively. The inducible enzyme heme oxygenase type 1 (HO-1) is found to be upregulated in response to oxidative stress-related events in the AD brain. While these global biomarkers for oxidative stress are associated with early-stage AD, they generally poorly differentiate from other neurodegenerative disorders that also coincide with oxidative stress. Redox proteomics approaches provided specificity of oxidative stress-associated biomarkers to AD pathology by the identification of oxidatively damaged pathology-specific proteins. In this review, we discuss the potential combined diagnostic value of these reported biomarkers in the context of AD and discuss eight oxidative stress-related mRNA biomarkers in AD that we newly identified using a transcriptomics approach. We review these genes in the context of their reported involvement in oxidative stress regulation and specificity for AD. Further research is warranted to establish the protein levels and their functionalities as well as the molecular mechanisms by which these potential biomarkers are involved in regulation of oxidative stress levels and their potential for determination of oxidative stress and disease status of AD patients.
Electromagnetic navigation bronchoscopy localization of lung nodules for thoracoscopic resection

Background Thoracoscopic localization of small peripheral pulmonary nodules is a concern. Failure can lead to larger parenchymal resection or conversion to thoracotomy. This study evaluates our experience in preoperative electromagnetic navigation bronchoscopy-guided localization of small peripheral lung lesions. Methods From January 2017 to March 2020 clinical, radiographic, surgical, and pathological data of patients who underwent electromagnetic navigation bronchoscopy (ENB)-guided methylene blue pleural marking of highly suspected pulmonary lesions before a full thoracoscopic resection were evaluated. Localization was performed for solid or mixed subpleural nodules measuring <10 mm, solid nodules measuring <20 mm located at more than 1 cm from the pleura and any pure ground glass opacity. Successful localization was defined as successful identification and thoracoscopic resection of target lesions. Results Forty-eight patients were included: 30 solid nodules (63%), 12 pure GGO (25%) and 6 mixed (13%). The median largest diameter at CT-scan was 11 mm (IQR, 9–14 mm) while the median distance from the pleural surface was 12 mm (IQR, 6–16 mm). The median ENB length was 25 min (19–33 min). Localization procedure was successful in 45 cases (94%). No procedural-related complications were reported. Conclusions ENB is a safe and accurate preoperative procedure to localize small lung peripheral lesions. The high successful rate, the absence of related complications, the possibility of performing the procedure in the same operating room with a single general anesthesia, make ENB-guided dye marking an advantageous tool for thoracoscopic pulmonary resection.
Beliefs about social norms and racial inequalities predict variation in the early development of racial bias.

Racism remains a pervasive force around the world with widespread and well documented harmful consequences for members of marginalized racial groups. The psychological biases that maintain structural and interpersonal racism begin to emerge in early childhood, but with considerable individual variation - some children develop more racial bias than others. The present study (N = 116; 4-year-old children) provides novel insights into the developmental mechanisms underlying the emergence of racial bias by longitudinally documenting how two psychological processes-normative beliefs about interracial friendships and explanatory beliefs about racial inequalities-developmentally predict the emergence of pro-White/anti-Black racial bias during early childhood. In a 6-month, 3-wave, longitudinal study, we found that 4-year-old children's beliefs that their parents and peers do not value interracial friendships predicted increased racial bias in and across time and that children's endorsement of essentialist over extrinsic explanations for racial inequalities predicted the developmental trajectory of racial bias over time. These findings suggest that children's foundational beliefs about the social world developmentally predict the emergence of racial bias in early childhood and speak to the importance of early and persistent intervention efforts targeting children's normative beliefs about interracial friendships and explanatory beliefs about racial inequalities. This article is protected by copyright. All rights reserved.
Pneumothorax in otherwise healthy non-intubated patients suffering from COVID-19 pneumonia: a systematic review

Background Cases of spontaneous pneumothorax have been described in patients suffering from coronavirus disease 2019 (COVID-19) pneumonia. The aim of this study is to systematically review all the cases of spontaneous pneumothorax that occurred in healthy patients with no underlying lung disease and who did not receive invasive mechanical ventilation. Methods A PubMed research was conducted. The following data were collected: age, sex, side of the pneumothorax, smoking habit, time form onset of symptoms to the diagnosis of pneumothorax, the development of new bullous lesions on computed tomography and the type of treatment. In order to analyze the most homogeneous population possible, intubated patients were deliberately excluded. In total, 44 cases of spontaneous pneumothorax in otherwise healthy patients were taken into account. Since the available data were extracted from small observational studies, no particular bias risk assessment was performed. Descriptive statistics were used to synthesize results. Results There were 37 male (84.1%) and 6 female (13.6%) patients. The majority of patients (66%) were treated only by chest tube thoracostomy, which most of the times resulted in a complete resolution of the pneumothorax. Simple surveillance was applied in 10 cases. Three patients underwent minimally invasive surgery. In 14 cases (31.8%) air-filled lesions were detected on imaging. Eleven patients received corticosteroids during their hospital stay. In the majority of cases (86.3%) the pneumothorax was resolved. Discussion Even if the level of evidence, derived from case reports and small case series is low, the existence of a true secondary spontaneous pneumothorax due to SARS-CoV-2 should be recognized. Imaging techniques should be repeated throughout the clinical course of the patients in order to detect newly developed pulmonary complications. Surgical treatment is feasible and patients whose general condition permits, should be offered surgery according to the existing guidelines regarding spontaneous pneumothorax. National registries and databases are necessary in order to better understand the pathogenesis and complications of this novel entity.
Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation

Background Because the liver is central to the physiology of the body, primary hepatocytes are widely used in liver pathology and physiological research, such as liver drug screening, bioartificial liver support system, and cell therapy for liver diseases. However, the source of primary hepatocytes is limited. We describe a novel non-transgenic protocol that facilitates the rapid generation of hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), providing a new source of functional hepatocytes. Methods In this study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 3 MSCs were induced into hepatocyte-like cells using small-molecule compounds combined with cell factors in vitro. Functional hit 1 (FH1), a promising small molecule compound was achieved to replace HGF in the hepatocyte maturation stage to induce the hepatocyte-like cells differentiation. Results We rapidly induced hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and the cells were morphologically similarly to both hepatocytes derived from the hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They expressed mature hepatocyte special genes and achieved functions such as glycogen storage, albumin expression, urea secretion, cytochrome P450 activity, Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. Conclusions We successfully established a small-molecule protocol without using HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and cost-effective platform for in vitro studies of liver disease.
Diagnosis and Management of Osteoporosis in Advanced Kidney Disease: A Review.

Osteoporosis and fractures are common in persons with advanced chronic kidney disease (CKD) and on chronic dialysis. While the diagnosis of osteoporosis in this population can be difficult, imaging, especially with dual-energy X-Ray absorptiometry (DXA), is helpful in identifying persons with CKD at the highest risk of fracture. Although blood biomarkers including parathyroid hormone and bone-specific alkaline phosphatase concentrations can aid in assessing bone turnover state, bone biopsy remains the gold standard in determining bone turnover in persons with advanced kidney disease and osteoporosis. With the increasing armamentarium of osteoporosis drugs, it now may be possible to prevent many fractures t advanced CKD. Unfortunately, data on these drugs are limited in persons with advanced CKD. Clinicians, aided by advances in imaging, biomarkers and bone biopsy can now use these novel agents to target bone turnover abnormalities such as adynamic bone disease and high bone turnover disease. This review will discuss the most recent literature surrounding the diagnosis, management and monitoring of osteoporosis and fractures in persons with advanced CKD or on chronic dialysis.
Classifications in Brief: The International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine Classification of Meniscal Tears

The medial and lateral menisci are fibrocartilaginous, semilunar structures that play a critical role in load transmission, shock absorption, joint congruity, distribution of contact stresses, proprioception, articular cartilage lubrication and nutrition, and secondary stabilization [9, 16, 20, 22]. The smaller lateral meniscus is less likely to tear than the medial meniscus because of its greater mobility, which is the result of fewer capsular attachments and decreased bony conformity in the lateral compartment [15]. Meniscal deficiency is associated with a proportionate increase in contact stresses and predictable progression of secondary osteoarthritis [8, 10, 11, 24]. Familiarity with the biomechanical consequences of observation, abrasion, trephination, partial meniscectomy, meniscal repair, or meniscal transplantation is important when tailoring treatment to the individual patient and meniscal tear. In 1991, Cooper et al. [5] proposed a circumferential zone classification system for meniscal tears in which Zone 0 is the meniscosynovial junction, Zone 1 is the outer third, Zone 2 is the middle third, and Zone 3 is the inner third. This was the first standardized classification scheme to become broadly adopted. The rationale for this classification system is the microvasculature of the meniscus, in which the outer portion is more vascular and the inner portion is avascular. The capillaries traverse a width no deeper than 10% to 25% of the lateral meniscus and 10% to 30% of the medial meniscus [2, 3]. Unfortunately, observed agreement for grading of rimwidth was low (46% to 54%) in two studies [1, 5]. This classification system also incorporates a radial location scheme, subdividing each of the medial and lateral menisci into thirds labeled with a letter from A to F [5]. Dunn et al. [7] demonstrated higher observed agreement for a radial location scheme subdividing the meniscus into anterior and posterior halves, albeit with lower descriptive utility. In 2015, LaPrade et al. [14] further proposed a classification system of meniscal root tears consisting of five subtypes, which comprise (1) partial root tear, (2) complete radial root tear, (3) complete root tear with bucket-handle extension, (4) oblique root tear, and (5) root avulsion fracture. There is considerable heterogeneity and nonstandard terminology in the reporting of meniscal tears across disciplines and practices [6, 12, 17, 18]. In 2011, the International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) committee devised and validated an arthroscopic classification system of meniscal tears to standardize arthroscopic tear characterization, documentation, and outcome reporting.