Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Osteoporotic Fractures in Elderly Individuals: A Derivation and Internal Validation Study Using Healthcare Administrative Data

In Canada and other countries, osteoporosis is monitored as part of chronic disease population surveillance programs. Although fractures are the principal manifestation of osteoporosis, very few algorithms are available to identify individuals at high risk of osteoporotic fractures in current surveillance systems. The objective of this study was to derive and validate predictive models to accurately identify individuals at high risk of osteoporotic fracture using information available in healthcare administrative data. More than 270,000 men and women aged ≥66 years were randomly selected from the Quebec Integrated Chronic Disease Surveillance System. Selected individuals were followed between fiscal years 2006–2007 and 2015–2016. Models were constructed for prediction of hip/femur and major osteoporotic fractures for follow‐up periods of 5 and 10 years. A total of 62 potential predictors measurable in healthcare administrative databases were identified. Predictor selection was performed using a manual backward algorithm. The predictive performance of the final models was assessed using measures of discrimination, calibration, and overall performance. Between 20 and 25 predictors were retained in the final prediction models (eg, age, sex, social deprivation index, most of the major and minor risk factors for osteoporosis, diabetes, Parkinson's disease, cognitive impairment, anemia, anxio‐depressive disorders). Discrimination of the final models was higher for the prediction of hip/femur fracture than major osteoporotic fracture and higher for prediction for a 5‐year than a 10‐year period (hip/femur fracture for 5 years: c‐index = 0.77; major osteoporotic fracture for 5 years: c‐index = 0.71; hip/femur fracture for 10 years: c‐index = 0.73; major osteoporotic fracture for 10 years: c‐index = 0.68). The predicted probabilities globally agreed with the observed probabilities. In conclusion, the derived models had adequate predictive performance in internal validation. As a final step, these models should be validated in an external cohort and used to develop indicators for surveillance of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway

Abstract Scutellarin plays an anti-tumor role in A549 lung cancer cells, but the underlying mechanism is unclear. In this study, scutellarin was used to treat A549 cells for 12, 24, and 48 h, followed by the addition of Tempo, a selective scavenger of mitochondrial reactive oxygen species (ROS) and SB431542, a transforming growth factor (TGF)-β1 receptor inhibitor. A dihydroethidium fluorescence probe was used to measure the intracellular ROS level, Cell Counting Kit-8 (CCK-8) was used to detect cell viability, and flow cytometry was performed to examine apoptosis. Western blots were used to detect the total protein level of TGF-β1, p-smad2, and cleaved caspase-3 in A549 cells. The results showed that scutellarin significantly inhibited cell viability and increased apoptosis. Scutellarin also promoted intracellular ROS production, TGF-β1/smad2 signaling pathway activation, and cleaved caspase-3 expression, which was partly reversed by Tempo. Moreover, scutellarin-induced intracellular ROS production and cleaved caspase-3 expression were inhibited by blocking the TGF-β1/smad2 pathway with SB431542. In conclusion, scutellarin promoted apoptosis and intracellular ROS accumulation, which could be abrogated by Tempo and SB431542 treatment in A549 cells. Our study indicated that scutellarin induced A549 cell apoptosis via the TGF-β1/smad2/ROS/caspase-3 pathway.
Helmholtz-Zentrum Dresden-Rossendorf (HZDR) New insight in the uranium valence state determination in UyNd1-yO2-x

The charge compensation mechanisms in UyNd1−yO2±x and its consequence on the overall O stoichiometry (or O/M ratio where M=Nd+U) have been studied through the uranium valence state mixture evolution as a function of Nd content up to y=0.62 by means of high energy resolution fluorescence detection X-ray absorption spectroscopy (HERFD-XAS) at the U M4-edge. Our results clearly demonstrate the formation of U5+ at low Nd content (y < 0.15). Upon increasing the Nd content, oxygen vacancies and the formation of U6+ appear as competing mechanisms for intermediate Nd concentrations, leading to the co-existence of U4+/U5+/U6+ mixed valence and an overall hypostoichiometry (O/M < 2.00). Finally, the formation of U6+ associated with strongly distorted U local environment ∗Corresponding author Email addresses: rene.bes@aalto.fi (R. Bès) Preprint submitted to Journal of nuclear materials October 11, 2017 is observed for high Nd concentrations (y=0.62), leading to an overall hyperstoichiometry (O/M < 2.00).
Civic stage fright: Motivation and news satire engagement

This article explores news satire engagement and civic motivation, an area of concern in satire scholarship. Focused on what audiences ‘do’ with media, the ways in which young adults who regularly engage in news satire construct political efficacy is studied. Using a qualitative contextualising audience study, including in-depth interviews and focus groups with 31 young adults, a thematic analysis of transcript data identifies three discursive themes relating to civic anxieties; development and invitation, performance and knowledge, and conflict and ‘packaged deals’. These emphasise news satire as cultural form as well as shifting civic ideals and development processes: exposing how news satire’s ‘kynicism’ (non-nihilist criticism) connects to civic performance anxiety. The identified anxieties are understood as related to fears of exclusion, embarrassment and misrepresentation. The metaphor of civic stage fright is developed to further understand these, underscoring the role of emotion and social interaction in civic performance.
Quantifying the Changes of Mechanical and Electrical Properties of Paralyzed Muscle in Survivors With Cervical Spinal Cord Injury

Background: Survivors with spinal cord injury (SCI) have neuromuscular deficits such as muscle atrophy that lead to functional impairments. This study utilized myotonometry and electrical impedance myography (EIM) to quantitatively evaluate the changes in muscle mechanical properties and compositions after SCI. Methods: This study adopted a cross-sectional design. Eighteen SCI patients and 18 healthy individuals were recruited. The outcome measures were: (1) The myotonometer measured muscle mechanical parameters of oscillation frequency (freq), dynamic stiffness, logarithmic decrement (decr), mechanical stress relaxation time, and indication of creep. (2) The electrical impedance myography measured parameters of resistance (R), reactance (X), and phase angle (θ). (3) muscle strength (maxForce); (4) clinical scales of Manual Muscle Testing (MMT) and modified Ashworth scale (MAS). All outcome measures were compared between the bicep brachii muscle of the weaker side of the SCI group and the non-dominate side of the healthy group. Correlation analysis was performed at quantitative data and clinical scales. Results: Freq, stiffness, and maxForce of the SCI group were significantly lower (p < 0.01) than those of the healthy control. The relaxation time and creep were significantly higher in the SCI group than in the control group. Significant differences of R and Xc were observed between the two groups. Significant correlation was observed between freq, stiffness, and months past injury, and between Xc, creep, and relaxation time. Conclusions: Reduced muscle tone and stiffness might relate to muscle atrophy, and higher relax time and creep may be caused by poor contractile ability. The changes in EIM parameters could indirectly reflect the muscle cell size, and fatty and connective tissue alterations. These findings support the feasibility of myotonometer and EIM to quantify muscle mechanical and intrinsic properties in patients with SCI. The results could facilitate the understanding of neuromuscular changes that are related to functional impairments.
SARS-CoV-2, Trait Anxiety, and the Microbiome

During the COVID-19 pandemic, research on the relationships between the virus and its human host has become fundamental to understand this pathology and its effects. Attaining this profound understanding is critical for the effective containment and treatment of infections caused by the virus. In this review, we present some possible mechanisms by which psychopathological symptoms emerge following viral infections of the central nervous system (CNS). These proposed mechanisms are based on microbial communication and the induced priming of microglial antibody activation within the CNS through Toll-like receptor signaling. In this process, chronic microglial activation causes increased glutamate release in virally-altered, high-density neuronal structures, thereby modulating cognitive networks and information integration processes. This modulation, in turn, we suggest, affects the accuracy of sensory integration and connectivity of major control networks, such as the default mode network. The chronic activation of immunological responses and neurochemical shifts toward an elevated glutamate/gamma-aminobutyric acid ratio lead to negative reinforcement learning and suboptimal organismic functioning, for example, maintaining the body in an anxious state, which can later become internalized as trait anxiety. Therefore, we hypothesize that the homeostatic relationship between host, microbiome, and virome, would be decisive in determining the efficiency of subsequent immunological responses, disease susceptibility, and long-term psychopathological effects of diseases that impact the CNS, such as the COVID-19.
Factors Affecting e-Government Adoption by Dairy Farmers: A Case Study in the North-West of Spain

With the objective of assessing the farmers’ situation regarding the use of the ICT and their relations with the electronic government, a case study consisting in the realization of 34 face-to-face surveys was conducted between February and March 2020 in dairy farms in the region of Galicia (Spain). The sample was selected according to one of the most important online journals in the farming sector at a national level. From the census, we chose those farms considered most representative taking into account the main criteria: the level of PAC (Common Agrarian Politics) subsidies and milk production (litres/cow and year). The results show that the majority of the farmers used the internet, but on many an occasion, they were discontented in relation to the poor connection quality in their farms. In regard to the use of the electronic government for procedures related to their farms, many of them were able to perform them through the government website; however, there were procedures which the users defined as “complex” and which had to be outsourced to authorised entities. The results also show that the farmers do want to employ the e-government, mainly because of the time and cost saving; however, the current web pages do not meet the users’ expectations. Finally, this situation, applied to a region placed among the 10 most productive regions of milk, is comparable to what happens in other regions.
Cheap and Commonplace: Making the Case for BCG and γδ T Cells in COVID-19

Antigen-specific vaccines developed for the COVID-19 pandemic demonstrate a remarkable achievement and are currently being used in high income countries with much success. However, new SARS-CoV-2 variants are threatening this success via mutations that lessen the efficacy of antigen-specific antibodies. One simple approach to assisting with this issue is focusing on strategies that build on the non-specific protection afforded by the innate immune response. The BCG vaccine has been shown to provide broad protection beyond tuberculosis disease, including against respiratory viruses, and ongoing studies are investigating its efficacy as a tool against SARS-CoV-2. Gamma delta (γδ) T cells, particularly the Vδ2 subtype, undergo rapid expansion after BCG vaccination due to MHC-independent mechanisms. Consequently, γδ T cells can produce diverse defenses against virally infected cells, including direct cytotoxicity, death receptor ligands, and pro-inflammatory cytokines. They can also assist in stimulating the adaptive immune system. BCG is affordable, commonplace and non-specific, and therefore could be a useful tool to initiate innate protection against new SARS-CoV-2 variants. However, considerations must also be made to BCG vaccine supply and the prioritization of countries where it is most needed to combat tuberculosis first and foremost.
Biological Functions of Let-7e-5p in Promoting the Differentiation of MC3T3-E1 Cells

MicroRNAs let-7c and let-7f, two members of the let-7 family, were involved in regulating osteoblast differentiation and have an important role in bone formation. Let-7e-5p, which also belonged to the let-7 family, presented in the differentiation of adipose-derived stem cells and mouse embryonic stem cells. However, the role of let-7e-5p in osteoblast differentiation was unclear. Thus, this study aimed to elucidate the function of let-7e-5p in osteoblast differentiation and its mechanism. Firstly, we found that the let-7e-5p mimic promoted osteoblast differentiation but not the proliferation of MC3T3-E1 cells by positively regulating the expression levels of osteogenic-associated genes (RUNX2, OCN, OPN, and OSX), the activity of ALP, and formation of mineralized nodules. Moreover, we ascertained that the let-7e-5p mimic downregulated the post-transcriptional expression of SOCS1 by specifically binding to the 3′ untranslated region of SOCS1 mRNA. Also, let-7e-5p-induced SOCS1 downregulation increased the protein levels of p-STAT5 and IGF-1, which were both modulated by SOCS1 molecules. Furthermore, let-7e-5p abrogated the inhibition of osteogenic differentiation mediated by SOCS1 overexpression. Therefore, these results suggested that let-7e-5p regulated the differentiation of MC3T3-E1 cells through the JAK2/STAT5 pathway to upregulate IGF-1 gene expression by inhibiting SOCS1. These findings may provide a new insight into the regulatory role of let-7e-5p in osteogenic differentiation and imply the existence of a novel mechanism underlying let-7e-5p-mediated osteogenic differentiation.
Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition. Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status. Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26. Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.
Validation of the Surrogate Threshold Effect for Change in Bone Mineral Density as a Surrogate Endpoint for Fracture Outcomes: The FNIH‐ASBMR SABRE Project

The surrogate threshold effect (STE) is defined as the minimum treatment effect on a surrogate that is reliably predictive of a treatment effect on the clinical outcome. It provides a framework for implementing a clinical trial with a surrogate endpoint. The aim of this study was to update our previous analysis by validating the STE for change in total hip (TH) BMD as a surrogate for fracture risk reduction; the novelty of this study was this validation. To do so, we used individual patient data from 61,415 participants in 16 RCTs that evaluated bisphosphonates (nine trials), selective estrogen receptor modulators (four trials), denosumab (one trial), odanacatib (one trial), and teriparatide (one trial) to estimate trial‐specific treatment effects on TH BMD and all, vertebral, hip, and nonvertebral fractures. We then conducted a random effects meta‐regression of the log relative fracture risk reduction against 24‐month change in TH BMD, and computed the STE as the intersection of the upper 95% prediction limit of this regression with the line of no fracture reduction. We validated the STE by checking whether the number of fractures in each trial provided 80% power and determining what proportion of trials with BMD changes ≥ STE reported significant reductions in fracture risk. We applied this analysis to (i) the trials on which we estimated the STE; and (ii) trials on which we did not estimate the STE. We found that the STEs for all, vertebral, hip, and nonvertebral fractures were 1.83%, 1.42%, 3.18%, and 2.13%, respectively. Among trials used to estimate STE, 27 of 28 were adequately powered, showed BMD effects exceeding the STE, and showed significant reductions in fracture risk. Among the validation set of 11 trials, 10 met these criteria. Thus STE differs by fracture type and has been validated in trials not used to develop the approach. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Effects of short‐term soil tillage practice on activity and community structure of ammonia‐oxidizing bacteria and archaea under the double‐cropping rice field

The potential nitrification activity (PNA), population size and community composition of ammonia‐oxidizing bacteria (AOB) and ammonia‐oxidizing archaea (AOA) in paddy soil from a short‐term (5 years) tillage field experiment conducted at tillering stage of late rice were investigated using the shaken slurry method and quantitative real‐time polymerase chain reaction.
Host-pathogen interactions of clinical S. aureus isolates to induce infective endocarditis

ABSTRACT To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 Staphylococcus aureus (S. aureus) isolates, collected from patients with S. aureus endocarditis and from healthy individuals were investigated both in vitro and in vivo. S. aureus isolates were tested in vitro for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of S. aureus to induce vegetations on the aortic valves in vivo. In an animal model of IE valvular conspicuity was assessed by in vivo magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All S. aureus isolates tested in vivo caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured in vitro virulence profiles and cytotoxicity. Results from in vitro assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in S. aureus infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.
Anticoagulant effect of low concentration plasma trisodium citrate in continuous veno-venous hemofiltration.

BACKGROUND Effective anticoagulation is a prerequisite of continuous renal replacement therapy (CRRT). During CRRT, prolonged anticoagulant therapy should be administered to prevent extracorporeal clotting. The purpose of our study was to evaluate whether a low concentration of plasma trisodium citrate (TCA) was effective as an anticoagulation treatment for continuous veno-venous hemofiltration (CVVH). We also retrospectively analyzed the complications of regional citrate anticoagulation (RCA) in our hospital. METHODS We conducted this single-center retrospective study at a tertiary academic hospital. The study period was from July 1, 2019 to January 1, 2021. CVVH using the RCA protocol during the study period was performed. The RCA protocol and complications were included and analyzed. The concentrations of citrate in the blood and plasma were calculated. RESULTS In the current study, we used low-dose TCA as an anticoagulant in 288 CVVH runs for 78 patients. The median whole blood and plasma citrate concentrations were 2.13 mmol/L and 2.84 mmol/L, respectively. Although only a low concentration of citrate was used, RCA achieved expected anticoagulation and ensured the life span of the hemofilter during CVVH therapy. Although hypocalcemia was common during RCA, serious consequences could be prevented by timely adjustment of the protocol. Citrate intoxication was rare in patients without relative contraindications for citric acid. We did not find RCA-associated hypernatremia. CONCLUSIONS We recommend the use of a low concentration of TCA (2.5-3.0 mmol/L in plasma) in extracorporeal solution in the RCA protocol. Although RCA may cause some complications, serious complications can be prevented. Mild hypocalcemia and transient metabolic alkalosis can be corrected in a timely manner. We do not believe hypernatremia is a complication of RCA if the RCA protocol is appropriately applied.