Miracle-dz/UniFAR-FTUs huggingface dataset:
Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma

ABSTRACT Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear. This study was conducted to explore the effects of PD-L1-loaded exosomes on the tumor growth of OS. The exosomes were extracted from cells and tissues through ultracentrifugation. IFN-γ production was determined to evaluate the activity of Jurkat cells. The in vivo growth of OS cells was examined using a C3H xenograft model in mice, tumor volumes were monitored, and the proportion of CD3 + T cells in tumor tissues was detected. Results revealed that PD-L1 was significantly upregulated in the OS cell lines. MG63 and Saos-2 cells were the most abundant in PD-L1, so they were selected as investigation targets. PD-L1 was found to be also highly expressed in the exosomes isolated from MG63 and Saos-2 cells. The exosomes elicited significant inhibitory effects on IFN-γ secretion in Jurkat cells, which were abolished by the PD-L1 antibody or siRNAs. The in vivo growth of C3H cells was significantly facilitated by the overexpression of mPD-L1 or by the administration of mPD-L1-overloaded exosomes. The infiltration of CD3 + T cells was also decreased. The exosomes extracted from clinical PD-L1-positive OS tissues showed a promising inhibitory property against activated T cells. Therefore, PD-L1-loaded exosomes extracted from OS cells aggravated OS progression by suppressing T cell activities. Graphical abstract
Research on factors affecting the risk-taking behavior of personnel working in the forest products sector

Objectives. The fact that occupational accidents are a permanent problem in the forest products sector encouraged this research to be conducted on the factors affecting the risk-taking behavior (RTB) of employees in the sector. Understanding the RTB of employees in the sector would help managers to reduce occupational accidents and to develop effective safety interventions. Therefore, this study aimed to determine the effects of individual, organizational and workplace factors and sub-factors on the RTB of employees by using the structural equation model (SEM). Methods. A survey was conducted on 623 employees of the forest products sector in 64 enterprises in the provinces of Düzce, Bolu, Sakarya, Kocaeli and Yalova. Results. The results revealed that organizational and workplace factors had a significant effect on the RTB of the employees. However, no effect was found for individual factors, although the sub-factor of cognitive bias had a positive impact on RTB. In contrast, safety climate, safety training, use of personal protective equipment (PPE)-1 and working conditions negatively impacted the RTB of the employees. Conclusions. In terms of occupational health and safety, this study could serve to guide both sector managers and decision-makers on ways to improve the safety perception of their employees.
Applications and Mechanism of 3-Hydroxybutyrate (3HB) for Prevention of Colonic Inflammation and Carcinogenesis as a Food Supplement.

Inflammatory bowel disease and colorectal cancer are common diseases without effective prevention approach. 3-Hydroxybutyrate (3HB) reported to have multiple functions as an oral food supplement, is a small endogenous molecule of our ketone bodies. This study observes that 3HB cures mouse colitis and reduces their colorectal carcinogenesis. The mechanism was found to relate to 3HB cellular surface receptor GPR109a which can down-regulate NF-κB pathway, so as to decrease the percentage of M1 macrophages from 50% of dextran sulfate sodium salt (DSS) induced acute colitis mouse group to 42% DSS+3HB group mediating the inhibitory effect on the inflammation. The activation of GPR109a was also found to inhibit colonic carcinogenesis, depended on reduced myeloid derived suppressor cells (MDSCs) accumulation from 27% of DSS group to 19% of DSS+3HB group. The study concluded that 3HB significantly suppresses colonic inflammation and carcinogenesis, promising to benefit colon disease prevention in form of a food supplement. This article is protected by copyright. All rights reserved.
Are Regional Differences in Psychological Characteristics and Their Correlates Robust? Applying Spatial-Analysis Techniques to Examine Regional Variation in Personality

There is growing evidence that psychological characteristics are spatially clustered across geographic regions and that regionally aggregated psychological characteristics are related to important outcomes. However, much of the evidence comes from research that relied on methods that are theoretically ill-suited for working with spatial data. The validity and generalizability of this work are thus unclear. Here we address two main challenges of working with spatial data (i.e., modifiable areal unit problem and spatial dependencies) and evaluate data-analysis techniques designed to tackle those challenges. To illustrate these issues, we investigate the robustness of regional Big Five personality differences and their correlates within the United States (Study 1; N = 3,387,303) and Germany (Study 2; N = 110,029). First, we display regional personality differences using a spatial smoothing approach. Second, we account for the modifiable areal unit problem by examining the correlates of regional personality scores across multiple spatial levels. Third, we account for spatial dependencies using spatial regression models. Our results suggest that regional psychological differences are robust and can reliably be studied across countries and spatial levels. The results also show that ignoring the methodological challenges of spatial data can have serious consequences for research concerned with regional psychological differences.
Transfer of chemicals to a secondary container, from the introduction of new labelling regulation to COVID‐19 lockdown: A retrospective analysis of exposure calls to the Poison Control Centre of Rome, Italy, 2017–2020

The transfer of a chemical product from its original container to an unlabelled secondary container by consumers is a potential health hazard that may result in unintentional exposures and intoxications. The aim of this study was to describe the pattern of prevalence of exposures to transferred products in Italy from year 2017, when the new European labelling regulation for chemicals became fully operative, to 2020, year of the coronavirus 19 disease first outbreak. Calls to the Poison Control Centre (PCC) of Policlinico Umberto I Hospital ‐ Sapienza University of Rome were analysed retrospectively for characteristics, clinical presentation and circumstances related to the event. We registered 198 cases of interest. There was a reduction in cases from 2017 (4.9%) to 2019 (2.2%), followed by an increased prevalence in 2020 (4.2%) mainly due to the months “post‐lockdown. ” The transferred product was very frequently diluted, and an empty drinking bottle was usually used as secondary container. Exposures were mostly of minor severity, and no deaths occurred. The study highlights the importance of PCCs data in the evaluation of the hazard communication to users through labels and advises for public campaigns to promote safe behaviours during future lockdowns to prevent exposures at a later period.
Prediction modeling using routine clinical parameters to stratify survival in malignant pleural mesothelioma patients complicated with malignant pleural effusion

Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE.
Parts and Wholes in Scene Processing

Abstract During natural vision, our brains are constantly exposed to complex, but regularly structured, environments. Real-world scenes are defined by typical part–whole relationships, where the meaning of the whole scene emerges from configurations of localized information present in individual parts of the scene. Such typical part–whole relationships suggest that information from individual scene parts is not processed independently, but that there are mutual influences between the parts and the whole during scene analysis. Here, we review recent research that used a straightforward, but effective approach to study such mutual influences: By dissecting scenes into multiple arbitrary pieces, these studies provide new insights into how the processing of whole scenes is shaped by their constituent parts and, conversely, how the processing of individual parts is determined by their role within the whole scene. We highlight three facets of this research: First, we discuss studies demonstrating that the spatial configuration of multiple scene parts has a profound impact on the neural processing of the whole scene. Second, we review work showing that cortical responses to individual scene parts are shaped by the context in which these parts typically appear within the environment. Third, we discuss studies demonstrating that missing scene parts are interpolated from the surrounding scene context. Bridging these findings, we argue that efficient scene processing relies on an active use of the scene's part–whole structure, where the visual brain matches scene inputs with internal models of what the world should look like.
Light assisted synthesis of poly-para-phenylene on Ag(001)

A detailed study of poly-para-phenylene (PPP) obtained by light-assisted on-surface-synthesis (OSS) on Ag(100) was carried out by scanning tunneling microscopy and spectroscopy together with density functional theory calculations. The use of light in combination with heat allows to lower by 50 K annealing temperature the each stage of the Ullmann coupling. Debromination of the 4,4″ dibromo-p-terphenyl precursors was thus realized at 300 K, the formation of the first oligomers from the organometallic intermediate by silver bridging atom release at 423 K and PPP by complete elimination of the silver at 473 K. This approach to lower the reaction temperature permits to enhance the Ag(100) surface reactivity to become comparable to that of Cu(111). The underlying mechanism of light effect was proposed to occur via surface mediated excitation, with the creation of photoexcited electrons known as hot electrons correlated with surface plasmon excitation. This original pathway combining both light and heat provides an additional parameter to control OSS by separating the precursor activation stage from the diffusion.
AT1 receptor blocker inhibits HMGB1 expression in pressure overload-induced acute cardiac dysfunction by suppressing the MAPK/NF-κB signaling pathway

ABSTRACT Background High-mobility group box 1 (HMGB1) expression not only peaks during the early phase of pressure overload (PO), but also serves a role in the pathogenesis of PO-induced cardiac remodeling. Meanwhile, angiotensin II type 1 (AT1) receptor blockers reverse PO-induced cardiac remodeling and repress the secretion of inflammatory factors. However, whether AT1 receptor inhibitors decrease HMGB1 expression in the early stages of PO remains unknown. Materials and methods PO mouse models were established using transverse aortic constriction (TAC), in which losartan was administrated. Transthoracic echocardiography was performed 3 days after the operation, and serum and cardiac HMGB1 expression, as well as the expression levels of related proteins were measured. Results PO-induced acute cardiac dysfunction was observed 3 days after TAC, and was subsequently slightly, but not significantly relieved by losartan. The expression levels of HMGB1, tumor necrosis factor-α and interleukin-6 in both the serum and myocardium were upregulated in response to TAC, while they were significantly reduced by losartan. Moreover, the phosphorylation of extracellular signal-regulated kinases, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the myocardium were significantly increased under PO, and this was also prevented by losartan. Conclusion These data suggest that losartan may downregulate the expression of HMGB1 in acute cardiac dysfunction induced by PO by inhibiting the MAPKs/NF-κB signaling pathway, which indicates a novel beneficial role of AT1 receptor antagonists in ameliorating cardiac remodeling under PO.
Stroke Among Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry

Supplemental Digital Content is available in the text. Background and Purpose: Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry. Methods: In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death. Results: Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality. Conclusions: Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.
Computational and biophysical determination of pathogenicity of variants of unknown significance in cardiac thin filament

Point mutations within sarcomeric proteins have been associated with altered function and cardiomyopathy development. Difficulties remain, however, in establishing the pathogenic potential of individual mutations, often limiting the use of genotype in management of affected families. To directly address this challenge, we utilized our all-atom computational model of the human full cardiac thin filament (CTF) to predict how sequence substitutions in CTF proteins might affect structure and dynamics on an atomistic level. Utilizing molecular dynamics calculations, we simulated 21 well-defined genetic pathogenic cardiac troponin T and tropomyosin variants to establish a baseline of pathogenic changes induced in computational observables. Computational results were verified via differential scanning calorimetry on a subset of variants to develop an experimental correlation. Calculations were performed on 9 independent variants of unknown significance (VUS), and results were compared with pathogenic variants to identify high-resolution pathogenic signatures. Results for VUS were compared with the baseline set to determine induced structural and dynamic changes, and potential variant reclassifications were proposed. This unbiased, high-resolution computational methodology can provide unique structural and dynamic information that can be incorporated into existing analyses to facilitate classification both for de novo variants and those where established approaches have provided conflicting information.
Discriminant Validity of the Parent-Proxy Preschool HEAR-QL

Supplemental Digital Content is available in the text Objective: The parent-proxy Preschool HEAR-QL (Hearing Environments And Reflections on Quality of Life) is a quality of life (QOL) measure for 2 to 6-year-old children with hearing loss (HL). We compared Preschool HEAR-QL scores for children with HL and children with normal hearing (NH) to examine the measure's discriminant validity. Study Design: Cross-sectional study. Setting: Three tertiary care pediatric otolaryngology clinics. Patients: Two hundred forty-eight parents of children 2 to 6 years old with NH or HL participated. Interventions: None. Main Outcome Measure: The Preschool HEAR-QL has five domains: Behavior and Attention, Hearing Environments, New Social Situations, Social Interactions, and Communications. Scores range from 0 to 100; higher scores indicate higher QOL. Scores for children with NH and with HL were compared using analysis of variance (ANOVA) and area under the receiver operating characteristic (AUROC) curves. Results: Total HEAR-QL mean (SD) scores were higher for children with NH compared to children with HL (75.7 [10.5] vs. 67.5 [15.5], p < 0.001). Scores were not significantly different between children with unilateral and bilateral HL. Children 2 to 4 years old received lower Communications-domain scores than children 4 to 6 years old across all children (63.7 [25.4] vs. 74.1 [24.3], p = 0.01) and within the HL cohort (61.3 [25.1] vs. 72.6 [25.3]; p = 0.009). The Hearing Environments domain displayed excellent discrimination (AUROC = 0.858); other domains showed little to no discrimination. Conclusions: The Hearing Environments-domain of the Preschool HEAR-QL differentiated between children with and without HL. Children with NH had higher scores than children with HL on both Total HEAR-QL and Hearing Environment-domain scores.
Quantal analysis estimates docking site occupancy determining short‐term depression at hippocampal glutamatergic synapses

Before fusion, synaptic vesicles (SVs) pause at discrete release/docking sites. During repetitive stimulation, the probability of site occupancy changes following SV fusion and replenishment. The occupancy probability is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately because it usually blends with other synaptic parameters. Thus, the contribution of site occupancy to synaptic function, particularly to synaptic depression, remains elusive. Here, we directly estimated the occupancy probability at the hippocampal mossy fibre‐CA3 interneuron synapse showing synaptic depression, using statistics of counts of vesicular events detected by deconvolution. We found that this synapse had a particularly high occupancy (∼0.85) with a high release probability of a docked SV (∼0.8) under 3 mm external calcium conditions. Analyses of quantal amplitudes and SV counts indicated that quantal size reduction decreased the amplitudes of all responses in a train to a similar degree, whereas release/docking site number was unchanged during trains, suggesting that quantal size and release/docking site number had little influence on the extent of synaptic depression. Model simulations revealed that the initial occupancy with high release probability and slow replenishment determined the time course of synaptic depression. Consistently, decreasing external calcium concentration reduced both the occupancy and release probability, and the reductions in turn produced less depression. Based on these results, we suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus.
Extensor carpi ulnaris muscle shows unexpected slow-to-fast fiber-type switch in Duchenne muscular dystrophy dogs

ABSTRACT Aged dystrophin-null canines are excellent models for studying experimental therapies for Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. To establish the baseline, we studied the extensor carpi ulnaris (ECU) muscle in 15 terminal age (3-year-old) male affected dogs and 15 age/sex-matched normal dogs. Affected dogs showed histological and anatomical hallmarks of dystrophy, including muscle inflammation and fibrosis, myofiber size variation and centralized myonuclei, as well as a significant reduction of muscle weight, muscle-to-body weight ratio and muscle cross-sectional area. To rigorously characterize the contractile properties of the ECU muscle, we developed a novel in situ assay. Twitch and tetanic force, contraction and relaxation rate, and resistance to eccentric contraction-induced force loss were significantly decreased in affected dogs. Intriguingly, the time-to-peak tension and half-relaxation time were significantly shortened in affected dogs. Contractile kinetics predicted an unforeseen slow-to-fast myofiber-type switch, which we confirmed at the protein and transcript level. Our study establishes a foundation for studying long-term and late-stage therapeutic interventions in dystrophic canines. The unexpected myofiber-type switch highlights the complexity of muscle remodeling in dystrophic large mammals. This article has an associated First Person interview with the first author of the paper.
The Cardiovascular Side Effects of Electroconvulsive Therapy and Their Management

Abstract Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community because of misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Electroconvulsive therapy causes periprocedural hemodynamic variability because of the surges in parasympathetic and sympathetic nervous systems after the administration of the electrical charge. Patients experience an increase in cardiac workload, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest that cardiac complications occur most frequently in patients with underlying cardiovascular disease. We describe the cardiovascular complications that may result from ECT treatment and offer insight on how to mitigate these concerns if they occur. PubMed was queried using terms “electroconvulsive therapy” and “cardiovascular adverse effects. ” A table is provided with the common cardiovascular side effects of ECT and the most recent evidence-based treatment strategies to manage them. Generally, ECT is a safe procedure in which complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary team approach, the cardiovascular complications can be well managed and minimized. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide.