Miracle-dz/UniFAR-FTUs huggingface dataset:
Most Orthopaedic Studies Using the National Inpatient Sample Fail to Adhere to Recommended Research Practices: A Systematic Review.

BACKGROUND The National Inpatient Sample (NIS) database is accessible, inexpensive, and increasingly used in orthopaedic research, but it has complex design features that require nuanced methodological considerations for appropriate use and interpretation. A recent study showed poor adherence to recommended research practices for the NIS across a broad spectrum of medical and surgical fields, but the degree and patterns of nonadherence among orthopaedic publications remain unclear. QUESTIONS/PURPOSES In this study, we sought: (1) to quantify nonadherence to recommended research practices provided by the Agency for Healthcare Research and Quality (AHRQ) for using the NIS data in orthopaedic studies from 2016-2017; and, (2) to identify the most common nonadherence practices. METHODS We evaluated all 136 manuscripts published across the 74 orthopaedic journals listed on Scimago Journal & Country Rank that used the NIS from January 2016 through December 2017. Of those studies, 2% (3 of 136) were excluded because NIS was not used for analysis. The studies were evaluated for adherence to seven recommended research practices by the AHRQ: (1) identifying observations as hospitalization events rather than unique patients; (2) not performing state-level analyses; (3) limiting hospital-level analyses to data from year 1988-2011; (4) not performing physician-level analyses; (5) avoiding the use of nonspecific secondary diagnosis codes to infer in-hospital events; (6) using survey-specific analysis methods that account for clustering, stratification, and weighting; and (7) accounting for data changes in trend analyses spanning major transition periods in the data set (1997-1998 and 2011-2012). RESULTS Overall, 93% (124 of 133) of the studies did not adhere to one or more practices. For each of the research practices assessed, 80% (106 of 133) of the studies did not account for the clustering and stratification in survey design; 56% (75 of 133) implied records were unique patients rather than hospitalization events; 41% (54 of 133) inappropriately used secondary diagnosis codes to infer in-hospital events. CONCLUSIONS Nearly all manuscripts published in orthopaedic journals using the NIS database in 2016 and 2017 failed to adhere to recommended research practices. Future research quantifying variations in study results on the basis of adherence to recommended research practices would be of value. CLINICAL RELEVANCE With the ubiquitous presence of large-database studies in orthopaedic journals, our work points to the importance of rigorous methodological appraisal when evaluating results, and encourages journals to require the use of the methodology checklists upon submission of such studies. More research is needed to determine whether deviations from recommended research practices actually lead to biased conclusions that affect patient care and policy-related decisions.
The social context of nearest neighbors shapes educational attainment regardless of class origin

Significance Much neighborhood research has focused on contemporary and segregated cities in the United States, but less on small and more homogenous cities. Additionally, neighborhood conditions are often estimated using administrative borders, which bias results. We adopt a long-term perspective on the importance of childhood neighbors, using more realistic methods of neighborhood conditions. We estimate individual neighborhoods at the address level, using geocoded longitudinal microdata (1939 to 2015) for a medium-sized Swedish town. We show that even when growing up in an economically relatively equal population, when higher education expanded greatly, the social class of the nearest childhood neighbors was important for educational achievements, regardless of social class and schools. Associations are strongest for boys, but with similar patterns across genders. We study the association between sociospatial neighborhood conditions throughout childhood and educational attainment in adulthood. Using unique longitudinal microdata for a medium-sized Swedish town, we geocode its population at the address level, 1939 to 1967, and link individuals to national registers, 1968 to 2015. Thus, we adopt a long-term perspective on the importance of nearby neighbors during a period when higher education expanded. Applying a method for estimating individual neighborhoods at the address level, we analyze the association between the geographically weighted social class of the nearest 6 to 100 childhood neighbors (ages 2 to 17), and the likelihood of obtaining a university degree by age 40, controlling for both family social class and school districts. We show that even when growing up in a town with relatively low economic inequality, the social class of the nearest same-age neighbors in childhood was associated with educational attainment, and that the associations were similar regardless of class origin. Growing up in low-class neighborhoods lowered educational attainment; growing up in high-class neighborhoods increased attainment. Social class and neighborhoods reinforced each other, implying that high-class children clustered with each other had much higher odds of obtaining a university degree than low-class children from low-class neighborhoods. Thus, even if all groups benefited from the great expansion of free higher education in Sweden (1960s to 1970s), the large inequalities between the classes and neighborhoods remained unchanged throughout the period. These findings show the importance of an advantageous background, both regarding the immediate family and the networks of nearby people of the same age.
Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection

We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol−1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.
Community acquired pneumonia: a cost-of-illness analysis in Greece.

INTRODUCTION Community acquired pneumonia (CAP) is an acute respiratory infection with high clinical and economic burden, especially when hospitalisation is required. The present study aimed to assess the mean direct cost per CAP outpatient and inpatient care in Greece, in the absence of previous estimates. METHODS A retrospective analysis of patients at a tertiary hospital, treated between October 2015 and March 2016, was conducted. Resource use data for inpatients and outpatients were collected (diagnostic tests, medication, physician visits and length of hospitalisation, where applicable). Cost calculations followed a third party payer perspective. Additionally, two regression models were employed to identify the determinants of hospitalisation and the main drivers of inpatient and outpatient cost. RESULTS Overall, 149 inpatients and 100 outpatients were included in the analysis. Mean hospitalisation duration was 11.35 days (standard deviation (SD)=9.71 days). Mean direct cost per patient was €110.64 (SD=€58.23) and €7406.56 (SD=€12,124.93) for outpatient and inpatient cases respectively. (At the time period for the study, €1.00 was approximately A$1.50.) The main inpatient cost driver was hospitalisation (94.97%), followed by medication (3.30%) and diagnostic tests (0.87%). For outpatients, key cost drivers, in order of magnitude, were prescribed medication (38.84%), diagnostic tests (33.51%) and physician visits (17.54%). The regression analyses showed that the probability of hospitalisation increases with age and number of symptoms, whereas average cost is mainly influenced by gender, duration and number of symptoms, and the presence of comorbidities. CONCLUSION The results indicate that, in Greece, CAP is accompanied by a significant economic burden, mainly attributable to hospitalisation. Interventions toward reducing the influence of contributors to the incidence and probability of hospitalisation are essential from a clinical and policy perspective. Also, the association of symptoms - in terms of number and duration - and age with hospitalisation probability and costs highlights that special attention should be given to the high risk groups of the population, such as the elderly and the rural residents, both in terms of preventive and therapeutic services.
Real‐life effectiveness and short‐term (16‐week) tolerance of guselkumab for psoriasis: a Belgian retrospective multicentre study

We read with great interest the multicenter and retrospective study of Fougerosse et al1 that investigated real-life effectiveness and tolerance of guselkumab at week 16 in the treatment of cutaneous psoriasis. In the same manner, we conducted the first multicenter study in Belgium aiming to investigate real-life effectiveness and tolerance of guselkumab at week 16 in the treatment of cutaneous psoriasis. Guselkumab is the first selective interleukin (IL)-23 p19 inhibitor (Tremfya®, Janssen Biotech, Inc., Horsham, PA, USA) marketed and reimbursed in Belgium.
Strategies for testing intervention matching schemes in cancer.

Personalized Medicine, or the tailoring of health interventions to an individual's nuanced and often unique genetic, biochemical, physiological, behavioral and/or exposure profile, is seen by many as a biological necessity given the great heterogeneity of pathogenic processes underlying most diseases. However, testing, and ultimately proving the benefit of, strategies or algorithms connecting the mechanisms of action of specific interventions to patient pathophysiological profiles (referred to here as 'intervention matching schemes' (IMS)) is complex for many reasons. We argue that IMS are likely to be pervasive, if not ubiquitous, in future health care, but raise important questions about their broad deployment and the contexts within which their utility can be proven. For example, one could question the need to, the efficiency associated with, and the reliability of, strategies for comparing competing or perhaps complementary IMS. We briefly summarize some of the more salient issues surrounding the vetting of IMS in cancer contexts and argue that IMS are at the foundation of many modern clinical trials and intervention strategies, as in basket, umbrella and adaptive trials. In addition, IMS are at the heart of proposed 'rapid learning systems' in hospitals, and implicit in cell replacement strategies such as cytotoxic T-cell therapies targeting patient-specific neo-antigen profiles. We also consider the need for sensitivity to issues surrounding the deployment of IMS and comment on directions for future research.
Socioeconomic Deprivation Does Not Impact Liver Transplantation Outcome for HCC: A Survival Analysis From a National Database.

BACKGROUNDS AND AIMS To investigate the value of European Deprivation Index (EDI) and Hepatocellular carcinoma (HCC) characteristics and their relationships with outcome after liver transplantation. METHODS Patients undergoing liver transplantation (LT) for HCC were included from a national database (from "Agence de la Biomédecine" between 2006 and 2016. Characteristics of the patients were blindly extracted from the Database. Thus, EDI was calculated in 5 quintiles and prognosis factors of survival were determined according to a Cox model. RESULTS Among the 3865 included patients, 33.9% were in the 5 quintile (quintile 1, N= 562 (14.5%); quintile 2, N=647 (16.7%); quintile 3, N= 654 (16.9%); quintile 4, N= 688 (17.8%)). Patients in each quintile were comparable regarding HCC history, especially median size of HCC, number of nodules of HCC and AFP score. In the univariate analysis of the crude survival, having more than 2 nodules of HCC before LT and time on waiting-list were associated with a higher risk of death (p<0.0001 and p=0.03 respectively). EDI, size of HCC, MELD score, CHILD score were not statistically significant in the crude and net survival. In both survival, time on waiting-list and number of HCC ≥ 2 were independent factor of mortality after LT for HCC (p=0.009 and 0.001 respectively and p=0.03 and 0.02 respectively). CONCLUSION EDI does not impact overall survival after LT for HCC. Number of HCC and time on waiting-list are independent prognostic factors of survival after LT for HCC.
Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage in vitro

ABSTRACT Satellite cells (SC) are muscle stem cells that can regenerate adult muscles upon injury. Most SC originate from PAX7+ myogenic precursors set aside during development. Although myogenesis has been studied in mouse and chicken embryos, little is known about human muscle development. Here, we report the generation of human induced pluripotent stem cell (iPSC) reporter lines in which fluorescent proteins have been introduced into the PAX7 and MYOG loci. We use single cell RNA sequencing to analyze the developmental trajectory of the iPSC-derived PAX7+ myogenic precursors. We show that the PAX7+ cells generated in culture can produce myofibers and self-renew in vitro and in vivo. Together, we demonstrate that cells exhibiting characteristics of human fetal satellite cells can be produced in vitro from iPSC, opening interesting avenues for muscular dystrophy cell therapy. This work provides significant insights into the development of the human myogenic lineage. Highlighted Article: Characterization of human skeletal muscle development in vitro using scRNA-seq of a FACS-sorted PAX7-YFP iPSC reporter line shows the developmental stages of the PAX7+ precursors and their myogenic potential.
Challenges faced by residential aged care staff in decision-making for residents with dementia

Care staff in residential aged care facilities (nursing homes) in Australia are obligated, under the Australian National Framework for Action on Dementia 2015–2019, to support residents to exercise choice and make decisions. Research indicates, however, that care staff are often given little guidance regarding which residents’ decisions should be supported or how to make decisions on their behalf. This lack of guidance can result in a denial of residents’ rights and inconsistent treatment by staff, placing residents’ wellbeing at risk. Through providing an analysis of the responses of staff at RACFs in Victoria and Queensland to two case scenarios, this study seeks to provide some understanding of the difficulties staff face in supporting residents’ self-determination and their own need for greater organisational support.
Screening‐Level Estimates of Environmental Release Rates, Predicted Exposures, and Toxic Pressures of Currently Used Chemicals

We describe a procedure to quantify emissions of chemicals for environmental protection, assessment, and management purposes. The procedure uses production and use volumes from registration dossiers and combines these with Specific Environmental Release Category data. The procedure was applied in a case study. Emission estimations were made for chemicals registered under the European Union chemicals regulations for industrial chemicals (Registration, Evaluation, Authorisation and Restriction of Chemicals [REACH]) and for the active ingredients of medicines and crop protection products. Emissions themselves cannot be validated. Instead, emission estimates were followed by multimedia fate modeling and mixture toxic pressure modeling to arrive at predicted environmental concentrations (PECs) and toxic pressures for a typical European water body at steady state, which were compared with other such data. The results show that screening‐level assessments could be performed, and yielded estimates of emissions, PECs, and mixture toxic pressures of chemicals used in Europe. Steady‐state PECs agreed fairly well with measured concentrations. The mixture toxic pressure at steady state suggests the presence of effects in aquatic species assemblages, whereby few compounds dominate the predicted impact. The study shows that our screening‐level emission estimation procedure is sufficiently accurate and precise to serve as a basis for assessment of chemical pollution in aquatic ecosystems at the scale of river catchments. Given a recognized societal need to develop methods for realistic, cumulative exposures, the emission assessment procedure can assist in the prioritization of chemicals in safety policies (such as the European Union REACH regulation), where “possibility to be used safely” needs to be demonstrated, and environmental quality policies (such as the European Union Water Framework Directive), where “good environmental quality” needs to be reached. Environ Toxicol Chem 2020;39:1839–1851. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
The effect of the reconstruction algorithm for the pulmonary nodule detection under the metal artifact caused by a pacemaker

Abstract The aim was to compare the effects of metal artifacts from a pacemaker on pulmonary nodule detection among computed tomography (CT) images reconstructed using filtered back projection (FBP), single-energy metal artifact reduction (SEMAR), and forward-projected model-based iterative reconstruction solution (FIRST). Nine simulated nodules were placed inside a chest phantom with a pacemaker. CT images reconstructed using FBP, SEMAR, and FIRST were acquired at low and standard dose, and were evaluated by 2 independent radiologists. FIRST demonstrated the most significantly improved metal artifact and nodule detection on low dose CT (P < .0032), except at 10 mA and 5-mm thickness. At standard-dose CT, SEMAR showed the most significant metal artifact reduction (P < .00001). In terms of nodule detection, no significant differences were observed between FIRST and SEMAR (P = .161). With a pacemaker present, FIRST showed the best nodule detection ability at low-dose CT and SEMAR is comparable to FIRST at standard dose CT.
Impact of Cardiovascular Disease on Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19).

BACKGROUND To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047). CONCLUSIONS CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19.
Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17 Adjuvanticity

Key Points TNF is required for mycobacteria-induced upregulation of MINCLE and DECTIN-2. Inhibition of TNF in vivo abrogates Th17 responses by a MINCLE-dependent adjuvant. Visual Abstract TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette–Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.
Redistribution of inhibitory force feedback between a long toe flexor and the major ankle extensor muscles following spinal cord injury

Inhibitory pathways from Golgi tendon organs project widely between muscles crossing different joints and axes of rotation. Evidence suggests that the strength and distribution of this intermuscular inhibition is dependent on motor task and corresponding signals from the brainstem. The purpose of the present study was to investigate whether this sensory network is altered after spinal cord hemisection as a potential explanation for motor deficits observed after spinal cord injury (SCI). Force feedback was assessed between the long toe flexor and ankle plantarflexor (flexor hallucis longus), and the three major ankle extensors, (combined gastrocnemius, soleus, and plantaris muscles) in the hind limbs of unanesthetized, decerebrate, female cats. Data were collected from animals with intact spinal cords (control) and lateral spinal hemisections (LSHs) including chronic LSH (4–20 weeks), subchronic LSH (2 weeks), and acute LSH. Muscles were stretched individually and in pairwise combinations to measure intermuscular feedback between the toe flexor and each of the ankle extensors. In control animals, three patterns were observed (balanced inhibition between toe flexor and ankle extensors, stronger inhibition from toe flexor to ankle extensor, and vice versa). Following spinal hemisection, only strong inhibition from toe flexors onto ankle extensors was observed independent of survival time. The results suggest immediate and permanent reorganization of force feedback in the injured spinal cord. The altered strength and distribution of force feedback after SCI may be an important future target for rehabilitation.