Miracle-dz/UniFAR-FTUs huggingface dataset:
Strong phenotypic trait correlations between mating partners do not result from assortative mating in wild great tits (Parus major)

There is considerable debate about the occurrence of assortative mating between phenotypic traits measured within natural populations. Meta‐analyses have implied that assortative mating occurs generally in natural populations, but recent work indicates these conclusions largely result from biased data. Specifically, estimates of phenotypic correlations between mating partners do not solely result from nonrandom associations between individual‐level traits of partners but also from other biological processes (joint phenotypic plasticity, indirect genetic effects), methodological practices (observer bias) and other unexplained residual correlations (e.g. correlated measurement error). This paper puts this critique to test. First, we estimated the overall phenotypic correlation between phenotypic traits of mating partners for a wild population of great tits. Second, we estimated various key variance components to reveal the extent to which phenotypic correlations between partners resulted from assortative mating, reversible plasticity, social partner effects and methodological practices. We performed our analyses for a range of phenotypic traits (body mass, breathing rate, exploration behaviour, wing and tarsus length) to derive general conclusions not hinging on the specifics of the traits involved. Our analyses support the conclusion that patterns of assortative mating exist at first glance but occur because of the biasing effects of correlated residuals likely caused by a combination of phenotypic responses to unknown environmental factors or measurement error—not because of intrinsic patterns of assortative mating.
Asymmetry in scales enhances learning of new musical structures

Significance This study examines a fundamental aspect of human cognition: how listeners learn musical systems. It provides evidence that certain types of symmetry featured in musical scales help listeners process melodic and tonal information more easily. We propose that this cognitive benefit is the reason for the prevalence of unevenly spaced notes in scales across musical cultures. From a broader perspective, this work provides a cognitive perspective on the trade-off between cross-cultural diversity and fundamental similarity in a universal human activity, music. Despite the remarkable variability music displays across cultures, certain recurrent musical features motivate the hypothesis that fundamental cognitive principles constrain the way music is produced. One such feature concerns the structure of musical scales. The vast majority of musical cultures use scales that are not uniformly symmetric—that is, scales that contain notes spread unevenly across the octave. Here we present evidence that the structure of musical scales has a substantial impact on how listeners learn new musical systems. Three experiments were conducted to test the hypothesis that nonuniformity facilitates the processing of melodies. Novel melodic stimuli were composed based on artificial grammars using scales with different levels of symmetry. Experiment 1 tested the acquisition of tonal hierarchies and melodic regularities on three different 12-tone equal-tempered scales using a finite-state grammar. Experiments 2 and 3 used more flexible Markov-chain grammars and were designed to generalize the effect to 14-tone and 16-tone equal-tempered scales. The results showed that performance was significantly enhanced by scale structures that specified the tonal space by providing unique intervallic relations between notes. These results suggest that the learning of novel musical systems is modulated by the symmetry of scales, which in turn may explain the prevalence of nonuniform scales across musical cultures.
Changes to the genetic counseling workforce as a result of the COVID‐19 pandemic

The COVID‐19 pandemic has affected all aspects of our lives. The full impact of the pandemic is still unfolding and will take years to fully understand. This longitudinal study followed a sample of 189 genetic counselors from June to November of 2020, starting with an online retrospective baseline survey of pre‐COVID‐19 functioning and continuing with a monthly online survey (average retention = 89.2%) to assess changes in self‐reported stress, employment status, billing practices, self‐efficacy, and their use of telehealth. Participants were recruited from specific states representing geographic diversity with publicly available databases of contact information as well as social media. The sample was largely reflective of the professional demographics reported in the 2020 Professional Status Survey (PSS). Comparisons were made between the PSS, baseline assessment of pre‐COVID‐19 status, June, and November data. Genetic counselor workload did not significantly change in terms of hours worked from baseline to November, though patients served per week dropped initially before returning to pre‐COVID‐19 levels. Genetic counselors were increasingly working remotely and supervising students less frequently in November compared to pre‐COVID‐19 baseline. Approximately 50% of the sample were unable to bill for services throughout the study period, with billing practices not changing during this time. Approximately 40% experienced a negative employment change in June, which dropped to ~10% in November. Personal and family stress levels were elevated during the study period, while financial stress increased from baseline to June it returned to pre‐COVID‐19 levels by November. Self‐efficacy for common genetic counseling skills decreased from baseline to June but returned to baseline levels by November. The results suggest the workforce faced transitions but has rebounded in most areas studied. The pandemic highlighted pre‐existing billing issues, and the current billing structures were not able to shift in the face of practice transitions. The long‐term implications of the pandemic remain to be seen, but the results indicate returns toward baseline data in most areas with the exceptions of supervision, personal and family stress, and billing.
The Store-and-Forward Telemedicine Service User-satisfaction Questionnaire: Development and validation of a questionnaire to monitor and assess health care providers' experiences

Introduction With wider adoption of store-and-forward telemedicine accelerating, particularly post-coronavirus disease 2019, it is essential to understand health care providers’ (HCPs) satisfaction with digital solutions offered by telemedicine organizations to (continuously) guarantee service quality. We developed the Store-and-Forward Telemedicine Service User-satisfaction Questionnaire to monitor and assess HCPs’ experiences with contracted telemedicine organizations. Methods Questionnaire construction (phase 1) consisted of exploratory literature search on validated telemedicine satisfaction questionnaires, a telemedicine domain and human factors expert focus group, stakeholder focus group (customer service employee and telemedicine account managers), and two pre-testing rounds among 18 HCPs. The pilot questionnaire (phase 2) was sent to 2179 HCPs for validity and reliability assessment. Results Phase 1: Two validated questionnaires (73 items overall) were used as input for Store-and-Forward Telemedicine Service User-satisfaction Questionnaire. Revisions resulted in 61 items. Phase 2: the pilot 61-item Store-and-Forward Telemedicine Service User-satisfaction Questionnaire instrument was completed by 181 of 2179 invited HCPs. Forty-one mandatory items of the pilot Store-and-Forward Telemedicine Service User-satisfaction Questionnaire rated on a 5-point Likert scale were included in psychometric analyses and resulted in six reliable scales: training, communication, organization policy and strategy, interaction platform, usage platform, and working conditions. Discussion The Store-and-Forward Telemedicine Service User-satisfaction Questionnaire is a reliable and valid questionnaire for measuring HCPs’ satisfaction with store-and-forward telemedicine services as part of a continuous quality improvement cycle. Reimbursement questions were excluded due to low response. As adoption of telemedicine may be impeded by financial compensation issues, this requires consideration in future telemedicine questionnaires. Store-and-Forward Telemedicine Service User-satisfaction Questionnaire including video consultation items is needed to monitor also synchronous services as these expanded in the coronavirus disease 2019 pandemic.
The RNA regulatory programs that govern lymphocyte development and function

Lymphocytes require of constant and dynamic changes in their transcriptome for timely activation and production of effector molecules to combat external pathogens. Synthesis and translation of messenger (m)RNAs into these effector proteins is controlled both quantitatively and qualitatively by RNA binding proteins (RBPs). RBP‐dependent regulation of RNA editing, subcellular location, stability, and translation shapes immune cell development and immunity. Extensive evidences have now been gathered from few model RBPs, HuR, PTBP1, ZFP36, and Roquin. However, recently developed methodologies for global characterization of protein:RNA interactions suggest the existence of complex RNA regulatory networks in which RBPs co‐ordinately regulate the fate of sets of RNAs controlling cellular pathways and functions. In turn, RNA can also act as scaffolding of functionally related proteins modulating their activation and function. Here we review current knowledge about how RBP‐dependent regulation of RNA shapes our immune system and discuss about the existence of a hidden immune cell epitranscriptome.
Inhibition of IRAK1/4 enhances the antitumor effect of lenvatinib in anaplastic thyroid cancer cells

Anaplastic thyroid cancer (ATC) is an extremely aggressive tumor associated with poor prognosis due to a lack of efficient therapies. In Japan, lenvatinib is the only drug approved for patients with ATC; however, its efficacy is limited. Therefore, novel therapeutic strategies are urgently required for patients with ATC. The present study aimed to identify compounds that enhance the antiproliferative effects of lenvatinib in ATC cells using a compound library. IRAK1/4 Inhibitor I was identified as a candidate compound. Combined treatment with lenvatinib and IRAK1/4 Inhibitor I showed synergistic antiproliferative effects via the induction of cell cycle arrest at G2/M phase in the ATC cell lines 8305C, HTC/C3, ACT‐1, and 8505C. Furthermore, IRAK1/4 Inhibitor I enhanced the inhibition of ERK phosphorylation by lenvatinib in 8305C, HTC/C3, and 8505C cells. In an HTC/C3 xenograft mouse model, tumor volume was lower in the combined IRAK1/4 Inhibitor I and lenvatinib group compared with that in the vehicle control, IRAK1/4 Inhibitor I, and lenvatinib groups. IRAK1/4 Inhibitor I was identified as a promising compound that enhances the antiproliferative and antitumor effects of lenvatinib in ATC.
Prediction of Solubilities and Partition Coefficients in Polymers Using COSMO-RS

Recent results concerning the prediction of thermodynamic properties of solutes in polymers are presented. In particular, the computation of vapor–liquid and gas–liquid equilibria (i.e., liquid and gas solubilities) in different polymers and partition coefficients between the polymer and a solvent phase are addressed. Calculations have been carried out using COSMO-RS theory which combines quantum-chemical calculations with efficient statistical thermodynamics for intermolecular interactions. Predictions for vapor–liquid equilibria and for partition coefficients have been improved by incorporation of polymer-specific entropic contributions due to free volume effects. It is demonstrated that a high predictive accuracy is obtained if the polymer is sufficiently characterized by its composition, density, and crystallinity. The approach is currently limited to gaseous and liquid solutes and to linear, i.e. non-cross-linked polymers without any significant swelling.
Successful Application of a Galanin-Coated Scaffold for Periodontal Regeneration

The nervous system exerts finely tuned control over all aspects of the life of an organism, including pain, sensation, growth, and development. Recent developments in tissue regeneration research have increasingly turned to small molecule peptides to tailor and augment the biological response following tissue loss or injury. In the present study, we have introduced the small molecule peptide galanin (GAL) as a novel scaffold-coating agent for the healing and regeneration of craniofacial tissues. Using immunohistochemistry, we detected GAL and GAL receptors in healthy periodontal tissues and in the proximity of blood vessels, while exposure to our periodontal disease regimen resulted in a downregulation of GAL. In a 3-dimensional bioreactor culture, GAL coating of collagen scaffolds promoted cell proliferation and matrix synthesis. Following subcutaneous implantation, GAL-coated scaffolds were associated with mineralized bone-like tissue deposits, which reacted positively for alizarin red and von Kossa, and demonstrated increased expression and protein levels of RUNX2, OCN, OSX, and iBSP. In contrast, the GAL receptor antagonist galantide blocked the effect of GAL on Runx2 expression and inhibited mineralization in our subcutaneous implantation model. Moreover, GAL coating promoted periodontal regeneration and a rescue of the periodontal defect generated in our periodontitis model mice. Together, these data demonstrate the efficacy of the neuropeptide GAL as a coating material for tissue regeneration. They are also suggestive of a novel role for neurogenic signaling pathways in craniofacial and periodontal regeneration.
The minimal important change for the QuickDASH in patients with thumb carpometacarpal arthritis

Evaluating the effect of treatment through change in patient-reported outcomes requires an understanding of the minimal important change. The aim of this study was to report the minimal important change for the Quick Disability of the Arm, Shoulder and Hand questionnaire (QuickDASH) in patients receiving surgical treatment for thumb carpometacarpal joint osteoarthritis. Three hundred and fifteen patients were seen before and 6 months following surgery. Two methods were used to calculate the minimal important change: a distribution-based method calculating the standard error of measurement and an anchor-based method based on the receiver operating characteristic curve. The minimal important change for QuickDASH was estimated to be 18.2 points using the anchor-based method. The area under the receiver operating curve was 0.82, indicating a satisfactory accuracy. The minimal important change was estimated to be 10.3 points using the distribution-based method. These values may be useful in future research on thumb carpometacarpal joint osteoarthritis. Level of evidence: III
Size-Dependent Exciton–Phonon Coupling in CdSe Nanocrystals through Resonance Raman Excitation Profile Analysis

Resonance Raman excitation profiles, including absolute Raman cross sections, have been measured for the optical phonons of organic ligand capped spherical CdSe nanocrystals with average diameters ranging from 2.6 to 5.2 nm. The absorption spectra, fundamental excitation profiles, overtone to fundamental intensity ratios, and depolarization ratio dispersion profiles are simulated using a model for the exciton–phonon coupling strengths in the various excitonic transitions that contribute to the resonance enhancement. The resonance Raman cross sections increase strongly with nanocrystal size as expected from the increased transition dipole moments (oscillator strengths) in the larger particles. However, the exciton–phonon coupling strengths, particularly for the lowest energy excitonic transition (1Se–1S3/2), are relatively independent of nanocrystal size over this range, perhaps decreasing slightly with increasing size. This result is consistent with calculations of exciton–phonon coupling using an atomist.
Predictors of plasma leakage among dengue patients in Thailand: A plasma-leak score analysis

Delayed plasma leakage recognition could lead to improper fluid administration resulting in dengue shock syndrome, subsequently, multi-organ failure, and death. This prospective observational study was conducted in Bangkok, Thailand, between March 2018 and February 2020 to determine predictors of plasma leakage and develop a plasma leakage predictive score among dengue patients aged ≥15 years. Of 667 confirmed dengue patients, 318 (47.7%) developed plasma leakage, and 349 (52.3%) had no plasma leakage. Multivariate analysis showed three independent factors associated with plasma leakage, including body mass index ≥25.0 kg/m2 (odds ratio [OR] = 1.784; 95% confidence interval [CI] = 1.040–3.057; P = 0.035), platelet count <100,000/mm3 on fever days 3 to 4 (OR = 2.151; 95% CI = 1.269–3.647; P = 0.004), and aspartate aminotransferase or alanine aminotransferase ≥100 U/l on fever days 3 to 4 (OR = 2.189; 95% CI = 1.231–3.891; P = 0.008). Because these three parameters had evidence of equality, each independent factor was weighted to give a score of 1 with a total plasma-leak score of 3. Higher scores were associated with increased plasma leakage occurrence, with ORs of 2.017 (95% CI = 1.052–3.869; P = 0.035) for score 1, 6.158 (95% CI = 2.914–13.015; P <0.001) for score 2, and 6.300 (95% CI = 2.419–16.407; P <0.001) for score 3. The area under the receiver operating characteristics curves for predicting plasma leakage was good (0.677 [95% CI = 0.616–0.739]). Patients with a plasma-leak score ≥1 had high sensitivity (88.8%), and those with a plasma-leak score of 3 had high specificity (93.4%) for plasma leakage occurrence. This simple and easily accessible clinical score might help physicians provide early and timely appropriate clinical dengue management in endemic areas.
“Sharing Success with Someone”: Building therapeutic alliance in physiotherapist-delivered physical activity coaching for healthy aging

ABSTRACT Introduction Therapeutic alliance, a goal-orientated partnership between clients and practitioners, can enhance program engagement and adherence, and improve treatment outcomes and satisfaction. Objectives To develop an empirical model that describes how therapeutic alliances can be operationalized in clinical and research settings and use this in our evaluation of the Coaching for Healthy Ageing (CHAnGE) trial. Methods Secondary analysis of interviews with participants in the CHAnGE trial (n = 32) and a focus group with the physiotherapists who delivered health coaching in that trial (n = 3). Analysis was inductive (thematic) and deductive (using a therapeutic alliance model derived from a literature review and informed by earlier analyses). Results Data from participants and physiotherapists indicated that health coaching in CHAnGE built effective therapeutic alliances (i.e. it facilitated collaborative decision-making and trusting person-centered relationships) which were underpinned by professional skills and structural supports. Components of the intervention that strengthened therapeutic alliance were health coaching training, home visits, the coaching format, and provision of free activity monitors. Conclusion This study identifies key concepts and practical ‘building blocks’ of therapeutic alliance, showing how these were operationalized within an intervention. This may help those in clinical and research settings to recognize the importance and characteristics of therapeutic alliance and put it into practice.
Human‐induced pluripotent stem cell‐derived cardiomyocytes: Cardiovascular properties and metabolism and pharmacokinetics of deuterated mexiletine analogs

Prolongation of the cardiac action potential (AP) and early after depolarizations (EADs) are electrical anomalies of cardiomyocytes that can lead to lethal arrhythmias and are potential liabilities for existing drugs and drug candidates in development. For example, long QT syndrome‐3 (LQTS3) is caused by mutations in the Nav1.5 sodium channel that debilitate channel inactivation and cause arrhythmias. We tested the hypothesis that a useful drug (i.e., mexiletine) with potential liabilities (i.e., potassium channel inhibition and adverse reactions) could be re‐engineered by dynamic medicinal chemistry to afford a new drug candidate with greater efficacy and less toxicity. Human cardiomyocytes were generated from LQTS3 patient‐derived induced pluripotent stem cells (hIPSCs) and normal hIPSCs to determine beneficial (on‐target) and detrimental effects (off‐target) of mexiletine and synthetic analogs, respectively. The approach combined “drug discovery” and "hit to lead” refinement and showed that iterations of medicinal chemistry and physiological testing afforded optimized compound 22. Compared to mexiletine, compound 22 showed a 1.85‐fold greater AUC and no detectable CNS toxicity at 100 mg/kg. In vitro hepatic metabolism studies showed that 22 was metabolized via cytochrome P‐450, as previously shown, and by the flavin‐containing monooxygenase (FMO). Deuterated‐22 showed decreased metabolism and showed acceptable cardiovascular and physicochemical properties.
Perceived Onset Time of Medical Conditions: The Interplay Between Subjective Fear and Risk in Four Lifestyle Domains

Engaging in unhealthy behaviors (e.g., smoking, drinking) and not engaging in healthy ones (e.g., exercising, consuming fruit and vegetables) are both relatively prevalent among individuals despite the available information about their risks for health. People’s perception of an event’s time course can be used to gauge their risk perception for that event thus casting light on any possible misperception and suggesting directions for health-promoting interventions. This study investigates people’s perception of the time of onset of 5 noncommunicable diseases (e.g., “having high blood pressure”) associated with 4 health-related behaviors: Smoking, drinking, exercising, and eating fruit and vegetable. Participants from Italy (N = 214) and the UK (N = 151) gave onset time estimates of how long they thought it would take for 5 noncommunicable diseases to occur in the life of an 18-year-old person who starts or stops adopting those health-related behaviors. Results showed that participants who rated the noncommunicable diseases as more likely to themselves perceived the onset time of these diseases as more temporally proximal. Participants who were more afraid of developing the noncommunicable diseases estimated their onset time as delayed.