Miracle-dz/UniFAR-FTUs huggingface dataset:
Auditory salience using natural scenes: An online study

Salience is the quality of a sensory signal that attracts involuntary attention in humans. While it primarily reflects conspicuous physical attributes of a scene, our understanding of processes underlying what makes a certain object or event salient remains limited. In the vision literature, experimental results, theoretical accounts, and large amounts of eye-tracking data using rich stimuli have shed light on some of the underpinnings of visual salience in the brain. In contrast, studies of auditory salience have lagged behind due to limitations in both experimental designs and stimulus datasets used to probe the question of salience in complex everyday soundscapes. In this work, we deploy an online platform to study salience using a dichotic listening paradigm with natural auditory stimuli. The study validates crowd-sourcing as a reliable platform to collect behavioral responses to auditory salience by comparing experimental outcomes to findings acquired in a controlled laboratory setting. A model-based analysis demonstrates the benefits of extending behavioral measures of salience to broader selection of auditory scenes and larger pools of subjects. Overall, this effort extends our current knowledge of auditory salience in everyday soundscapes and highlights the limitations of low-level acoustic attributes in capturing the richness of natural soundscapes.
Making Employee Influencers: Exploring Personal Branding on Linkedin and if it Leads to Pro-Social Organizational Behaviors or Employee Advocacy

Within social media networks, a new form of influencers is emerging in the form of the employee influencer. The development of online advocacy tools such as LinkedIn Elevate now allows companies to directly leverage these employee influencer efforts. However, it is not understood if employee influencers will display similar personal branding characteristics as mainstream influencers. The study analyzes 363 profiles of employees at a British pharmaceutical company using multinomial logistic regression to explore the predictability of employee advocacy and pro-social organizational behavior based on personal branding. Our findings show personal branding is likely to predict advocacy. We also found that personal branding can predict pro-social behavior towards other individuals. Certain elements of personal branding on LinkedIn can help organizations to determine which employees might emerge as employee influencers. This research contributes to our understanding of personal branding on online platforms, employee advocacy and how we can determine potential ‘employee influencers’.
Association between hepatic oxygenation on near-infrared spectroscopy and clinical factors in patients undergoing hemodialysis

The hepato-splanchnic circulation directly influences oxygenation of the abdominal organs and plays an important role in compensating for the blood volume reduction that occurs in the central circulation during hemodialysis (HD) with ultrafiltration. However, the hepato-splanchnic circulation and oxygenation cannot be easily evaluated in the clinical setting of HD therapy. We included 185 HD patients and 15 healthy volunteers as the control group in this study. Before HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting the hepato-splanchnic circulation and oxygenation, was monitored using an INVOS 5100c oxygen saturation monitor. Hepatic rSO2 was significantly lower in patients undergoing HD than in healthy controls (56.4 ± 14.9% vs. 76.2 ± 9.6%, p < 0.001). Multivariable regression analysis showed that hepatic rSO2 was independently associated with body mass index (BMI; standardized coefficient: 0.294), hemoglobin (Hb) level (standardized coefficient: 0.294), a history of cardiovascular disease (standardized coefficient: -0.157), mean blood pressure (BP; standardized coefficient: 0.154), and serum albumin concentration (standardized coefficient: 0.150) in Model 1 via a simple linear regression analysis. In Model 2 using the colloid osmotic pressure (COP) in place of serum albumin concentration, the COP (standardized coefficient: 0.134) was also identified as affecting hepatic rSO2. Basal hepatic oxygenation before HD might be affected by BMI, Hb levels, a history of cardiovascular disease, mean BP, serum albumin concentration, and the COP. Further prospective studies are needed to clarify whether changes in these parameters, including during HD, affect the hepato-splanchnic circulation and oxygenation in HD patients.
Substantial acetylcholine reduction in multiple brain regions of Mecp2-deficient female rats and associated behavioral abnormalities

Rett syndrome (RTT) is a neurodevelopmental disorder with X-linked dominant inheritance caused mainly by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The effects of various Mecp2 mutations have been extensively assessed in mouse models, but none adequately mimic the symptoms and pathological changes of RTT. In this study, we assessed the effects of Mecp2 gene deletion on female rats (Mecp2+/−) and found severe impairments in social behavior [at 8 weeks (w), 12 w, and 23 w of age], motor function [at 16 w and 26 w], and spatial cognition [at 29 w] as well as lower plasma insulin-like growth factor (but not brain-derived neurotrophic factor) and markedly reduced acetylcholine (30%–50%) in multiple brain regions compared to female Mecp2+/+ rats [at 29 w]. Alternatively, changes in brain monoamine levels were relatively small, in contrast to reports on mouse Mecp2 mutants. Female Mecp2-deficient rats express phenotypes resembling RTT and so may provide a robust model for future research on RTT pathobiology and treatment.
Pathways from maternal depressive symptoms to children’s academic performance in adolescence: A 13‐year prospective‐longitudinal study

Abstract The pathways through which exposure to maternal depressive symptoms in early childhood are linked to academic performance during adolescence are poorly understood. This study tested pathways from maternal depressive symptoms (age 2–5) to adolescent academic performance (age 15) through cumulative parenting risk (age 7) and subsequent child functioning (age 10), using multi‐informant data from a prospective longitudinal community study spanning 13 years (N = 389, 47% male, 68% White). Structural equation models testing indirect effects revealed small associations between maternal depressive symptoms and increased cumulative parenting risk and poorer child functioning, and, via these pathways, with poorer academic performance. Thus, childhood exposure to maternal depressive symptoms may be associated with pathways of risk that could limit children's educational opportunities.
In situ design of advanced titanium alloy with concentration modulations by additive manufacturing

Description Fine-scale strengthening swirls Creatively combining different alloys using additive manufacturing methods has the potential to produce materials with interesting properties. Zhang et al. use laser powder bed fusion to combine small amounts of 316L stainless steel into Ti64 titanium alloy. This process creates an alloy with a distinctive microstructure that retains high strength while substantially improving ductility. The design strategy should be useful for improving mechanical properties in other alloy system as well. —BG Fine-scale concentration modulation created by combining 316L stainless steel with Ti64 titanium alloy improves mechanical properties. Additive manufacturing is a revolutionary technology that offers a different pathway for material processing and design. However, innovations in either new materials or new processing technologies can seldom be successful without a synergistic combination. We demonstrate an in situ design approach to make alloys spatially modulated in concentration by using laser-powder bed fusion. We show that the partial homogenization of two dissimilar alloy melts—Ti-6Al-4V and a small amount of 316L stainless steel—allows us to produce micrometer-scale concentration modulations of the elements that are contained in 316L in the Ti-6Al-4V matrix. The corresponding phase stability modulation creates a fine scale–modulated β + α′ dual-phase microstructure that exhibits a progressive transformation-induced plasticity effect, which leads to a high tensile strength of ~1.3 gigapascals with a uniform elongation of ~9% and an excellent work-hardening capacity of >300 megapascals. This approach creates a pathway for concentration-modulated heterogeneous alloy design for structural and functional applications.
Developmental changes within the extended face processing network: A cross‐sectional functional magnetic resonance imaging study

In the field of face processing, the so‐called “core network” has been intensively researched. Its neural activity can be reliably detected in children and adults using functional magnetic resonance imaging (fMRI). However, the core network's counterpart, the so‐called “extended network,” has been less researched. In the present study, we compared children's and adults’ brain activity in the extended system, in particular in the amygdala, the insula, and the inferior frontal gyrus (IFG). Using fMRI, we compared the brain activation pattern between children aged 7–9 years and adults during an emotional face processing task. On the one hand, children showed increased activity in the extended face processing system in relation to adults, particularly in the left amygdala, the right insula, and the left IFG. On the other hand, lateralization indices revealed a “leftward bias” in children's IFG compared to adults. These results suggest that brain activity associated with face processing is characterized by a developmental decrease in activity. They further show that the development is associated with a rightward migration of face‐related IFG activation, possibly due to the competition for neural space between several developing brain functions (“developmental competition hypothesis”).
Estimation of regional polygenicity from GWAS provides insights into the genetic architecture of complex traits

The number of variants that have a non-zero effect on a trait (i.e. polygenicity) is a fundamental parameter in the study of the genetic architecture of a complex trait. Although many previous studies have investigated polygenicity at a genome-wide scale, a detailed understanding of how polygenicity varies across genomic regions is currently lacking. In this work, we propose an accurate and scalable statistical framework to estimate regional polygenicity for a complex trait. We show that our approach yields approximately unbiased estimates of regional polygenicity in simulations across a wide-range of various genetic architectures. We then partition the polygenicity of anthropometric and blood pressure traits across 6-Mb genomic regions (N = 290K, UK Biobank) and observe that all analyzed traits are highly polygenic: over one-third of regions harbor at least one causal variant for each of the traits analyzed. Additionally, we observe wide variation in regional polygenicity: on average across all traits, 48.9% of regions contain at least 5 causal SNPs, 5.44% of regions contain at least 50 causal SNPs. Finally, we find that heritability is proportional to polygenicity at the regional level, which is consistent with the hypothesis that heritability enrichments are largely driven by the variation in the number of causal SNPs.
A Higher Initial Tensioning Force of an ACL Graft Results in a Higher Graft Force After Screw Fixation Irrespective of the Screw Diameter: A Biomechanical Study

Background: The intra-articular graft force (IAGF) in anterior cruciate ligament reconstruction decreases quickly over the first hours after surgery. Nevertheless, little is known about whether the initial extra-articular tensioning force (EATF) and screw diameter affect the graft force after fixation. Purpose: To investigate the effects of different EATFs on the IAGF of a soft tissue graft fixated via a bioabsorbable interference screw over 100 minutes after fixation and to evaluate the effects of different screw diameters within 1 mm of the tunnel width during this process. Study Design: Controlled laboratory study. Methods: In this biomechanical study, a porcine quadruple-strand soft tissue graft was inserted into the tibial anterior cruciate ligament tunnel. On the extra-articular side, 3 loads were applied during retrograde insertion of the bioabsorbable interference screw (6, 7, and 8 mm): 20 N, 80 N, and maximum manual EATF (Nmax). Nine study groups consisting of 10 tibiae each were created to test the effects of different EATFs and screw sizes. The IAGF was measured up to 100 minutes after the EATF was released. Results: An EATF ≥80 N resulted in a larger IAGF for all screw sizes at 100 minutes. There were no significant associations between the IAGF at 100 minutes and different screw diameters. Inserting the tibial screw significantly increased the IAGF in all groups, with the exception of Nmax applied in groups with 7- or 8-mm screws. When compared with the end of screw insertion, after the release of the EATF, the IAGF dropped by 55% to 77 % at 100 minutes. Conclusion: An initial EATF ≥80 N is associated with a significantly larger IAGF at 100 minutes in this cadaveric simulation. The IAGF in soft tissue grafts decreased substantially after the retrograde placement of an interference screw. A recommendation regarding screw diameter with respect to the IAGF cannot be given. Clinical Relevance: To obtain a higher residual graft force after bioabsorbable interference screw fixation, an initial EATF ≥80 N should be applied according to this model. The significant decrease in graft force after the release of the EATF indicates that the reconstructed knee cannot be mechanically stabilized after the surgery.
Treatment Trials in Pre-COPD and Young COPD: Time to Move Forward.

Chronic Obstructive Pulmonary Disease is the end-result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts we propose therapeutic trials in two major groups of subjects: those "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized clinical trials (RCTs). We highlight the need of RCTs focused on young COPD or Pre-COPD patients to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCTs design including potential outcomes such as lung function, patient reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in (1) young adults with COPD and (2) those with pre-COPD at any age.
A New Tool for Safety Evaluation and a Combination of Measures for Efficacy Assessment of Cotransplanting Human Allogenic Neuronal Stem Cells and Mesenchymal Stem Cells for the Treatment of Parkinson Disease: Protocol for an Interventional Study

Background Parkinson disease (PD) is a neurodegenerative disorder associated with a broad spectrum of motor and nonmotor symptoms. Any proposed cure needs to address the many aspects of the disease. Stem cell therapy may have potential in this regard as indicated in recent preclinical and clinical studies. Objective This protocol aims to examine the safety and therapeutic benefit of human Wharton jelly-derived mesenchymal stem cells (WJ-MScs) and their derivatives, neuronal stem cells (NSCs) in PD. Methods This clinical trial is a double-arm, single-blinded, phase I-II interventional study. Participants have been allocated to 1 of 2 groups: one receiving allogeneic WJ-MSCs alone, the other receiving NSCs and WJ-MScs. Participants are being followed-up and assessed over a period of 6 months. To assess safety, an incidence of treatment-emergent adverse events (TEAEs) tool tailored for PD is being used immediately and up to 6 months after treatment. For efficacy assessment, a number of factors are being used, including the gold standard severity test and the Unified Parkinson Disease Rating Scale. In addition, the following standardized assessments for different common symptoms in PD are being included: motor (both subjectively and objectively assessed with wearable sensors), sensory, quality of life and psychological well-being, cognition, and sleep quality. Furthermore, immune-modulatory cytokines and neuronal damage versus regeneration markers in PD, including the neuronal protein linked to PD, α-synuclein, are being monitored. Results Ten patients have been enrolled in this study and thus participant recruitment has been completed. The study status is active and beyond the recruiting stage. Study chart implementation, data collection, and analysis are ongoing. Conclusions The combination of NSCs and MSCs in PD may be useful for harnessing the best of the immunomodulation and neural repair characteristics of these cell types. The tailored comprehensive and scaled TEAEs and the variety of evaluation tools used enables a comprehensive assessment of this cellular therapy treatment protocol. A consideration of this expanded tool set is important in the design of future clinical studies for PD. Trial Registration ClinicalTrials.gov NCT03684122; https://clinicaltrials.gov/ct2/show/NCT03684122 International Registered Report Identifier (IRRID) DERR1-10.2196/29695
Automatic Mobile Health Arrhythmia Monitoring for the Detection of Atrial Fibrillation: Prospective Feasibility, Accuracy, and User Experience Study

Background Atrial fibrillation (AF) is the most common tachyarrhythmia and associated with a risk of stroke. The detection and diagnosis of AF represent a major clinical challenge due to AF’s asymptomatic and intermittent nature. Novel consumer-grade mobile health (mHealth) products with automatic arrhythmia detection could be an option for long-term electrocardiogram (ECG)-based rhythm monitoring and AF detection. Objective We evaluated the feasibility and accuracy of a wearable automated mHealth arrhythmia monitoring system, including a consumer-grade, single-lead heart rate belt ECG device (heart belt), a mobile phone application, and a cloud service with an artificial intelligence (AI) arrhythmia detection algorithm for AF detection. The specific aim of this proof-of-concept study was to test the feasibility of the entire sequence of operations from ECG recording to AI arrhythmia analysis and ultimately to final AF detection. Methods Patients (n=159) with an AF (n=73) or sinus rhythm (n=86) were recruited from the emergency department. A single-lead heart belt ECG was recorded for 24 hours. Simultaneously registered 3-lead ECGs (Holter) served as the gold standard for the final rhythm diagnostics and as a reference device in a user experience survey with patients over 65 years of age (high-risk group). Results The heart belt provided a high-quality ECG recording for visual interpretation resulting in 100% accuracy, sensitivity, and specificity of AF detection. The accuracy of AF detection with the automatic AI arrhythmia detection from the heart belt ECG recording was also high (97.5%), and the sensitivity and specificity were 100% and 95.4%, respectively. The correlation between the automatic estimated AF burden and the true AF burden from Holter recording was >0.99 with a mean burden error of 0.05 (SD 0.26) hours. The heart belt demonstrated good user experience and did not significantly interfere with the patient’s daily activities. The patients preferred the heart belt over Holter ECG for rhythm monitoring (85/110, 77% heart belt vs 77/109, 71% Holter, P=.049). Conclusions A consumer-grade, single-lead ECG heart belt provided good-quality ECG for rhythm diagnosis. The mHealth arrhythmia monitoring system, consisting of heart-belt ECG, a mobile phone application, and an automated AF detection achieved AF detection with high accuracy, sensitivity, and specificity. In addition, the mHealth arrhythmia monitoring system showed good user experience. Trial Registration ClinicalTrials.gov NCT03507335; https://clinicaltrials.gov/ct2/show/NCT03507335
Factors Associated With Low-Value Cancer Screenings in the Veterans Health Administration

Key Points Question What rates and factors are associated with low-value screenings (outside clinical guidelines) for common cancers in the Veterans Health Administration? Findings In this cohort study of 5 993 010 veterans, less than 3% of cancer screening recipients received a low-value test for breast, cervical, or colorectal cancer, but 39% of men screened for prostate cancer received a low-value test. No single factor (patient, clinician, clinical, or organizational characteristic) was associated with low-value screening receipt across these 4 cancer types. Meaning Findings suggest that low-value prostate cancer screenings are common in the Veterans Health Administration, although factors associated with low-value screenings differ by cancer type.
Virtual screening and structure-based 3D pharmacophore approach to identify small-molecule inhibitors of SARS-CoV-2 Mpro

Abstract The outbreak caused by a coronavirus 2 has required quick and potential treatment strategies. The main protease enzyme Mpro plays an important role in the viral replication which renders it an important target for discovering SARS-CoV-2 inhibitors. In this study, 3D pharmacophore structure-based virtual screening and molecular docking were conducted using MOE and Bristol University Docking Engine (BUDE). Around 400,000 molecules of ZINC15 database were docked against the crystal structure of main protease, followed by 3D pharmacophore filtration. Six top-ranked hits (ZINC58717986, ZINC60399606, ZINC58662884, ZINC45988635, ZINC54706757 and ZINC17320595) were identified based on their strong spatial affinity and forming H-bonds with key residues H41, E166, Q189 and T190 of the binding pocket of Mpro SARS-CoV-2. The 6 hits subjected to molecular dynamics simulations for 100 ns followed by binding free energy calculations using MM-PBSA technique. Interestingly, three hits showed free binding energy (ΔGbinding) lower than tert-butyl N-[1-[(2S)-1-[[(2S)-4-(benzylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]amino]-3-cyclopropyl-1-oxopropan-2-yl]-2-oxopyridin-3-yl]carbamate (α-ketoamide 13 b) (ΔGbinding) −76.67 ± 0.5 kJ/mol which suggested their potential against SARS-CoV-2. The best binding free energy candidates, ZINC58717986 (ΔGbinding) −98.41 ± 0.7 kJ/mol. The second-best hit candidate, ZINC54706757 (ΔGbinding) −83.4 ± 0.6 kJ/mol and the third one ZINC17320595 (ΔGbinding) −78.85 ± 0.5 kJ/mol. Per residue decomposition free energy indicates H41, S46, H164, E166, D187, Q189 and Q192 are hot spot residues while residues M49, M165, L167 and P168 contribute to the hydrophobic interactions. The pharmacokinetic study suggests that the selected 6 hits possess drug-like properties. The 3D pharmacophore virtual screening, molecular dynamics and MM-PBSA approaches facilitated identification 3 promising hits with low free binding energy as SARS-CoV-2 inhibitors. Communicated by Ramaswamy H. Sarma Graphical Abstract