Miracle-dz/UniFAR-FTUs huggingface dataset:
Attachment anxiety and the curvilinear effects of expressive suppression on individuals' and partners' outcomes.

Suppressing the expression of negative emotions tends to undermine individuals' and their partners' wellbeing. However, sometimes expressive suppression may be relatively innocuous given that individuals commonly withhold negative emotions in order to maintain close relationships, and this may be especially the case when expressive suppression is enacted by people who exhibit amplified expressions of negative emotions, such as those high in attachment anxiety. The current research examined when and for whom expressive suppression may be more or less costly by testing whether the curvilinear effect of individuals' expressive suppression on individuals' and partners' outcomes is moderated by individuals' attachment anxiety. Our results across 3 dyadic studies revealed a linear effect of expressive suppression when predicting individuals' outcomes: greater expressive suppression had costs for individuals (lower relationship satisfaction, reported responsiveness and discussion success, and greater discussion threat). Furthermore, in 4 of the 5 models, a moderated curvilinear effect of expressive suppression emerged when predicting partners' outcomes. For individuals low in attachment anxiety, low levels of expressive suppression did not incur costs for their partners' relationship satisfaction, perceptions of individuals' responsiveness, discussion success, and discussion threat. Once expressive suppression surpassed moderate levels, however, greater expressive suppression had a detrimental effect on partners' outcomes. In contrast, for individuals high in attachment anxiety, the negative effect of moderate-to-high levels of expressive suppression on partners' outcomes was attenuated. These novel results demonstrate how considering curvilinear methods can uncover when and for whom expressive suppression may be more or less costly in intimate relationships. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Emergence of pstS-Null Vancomycin-Resistant Enterococcus faecium Clone ST1478, Canada, 2013–2018

Rates of vancomycin-resistant enterococci bloodstream infections have remained relatively low in Canada. We recently observed an increase of 113% in these infections rates, which coincided with emergence of Enterococcus faecium pstS-null sequence type 1478. The proportion of this sequence type increased from 2.7% to 38.7% for all tested isolates from 2013–2018.
Lysine Demethylase KDM6A in Differentiation, Development, and Cancer

Lysine demethylase 6A (KDM6A), also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases, which also includes UTY and KDM6B (JMJD3). The KDM6A protein contains six tetratricopeptide repeat (TPR) domains and an enzymatic Jumonji C (JmjC) domain that catalyzes the removal of di- and trimethylation on H3K27. KDM6A physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (KMT2D). Since its identification as an H3K27 demethylase in 2007, studies have reported KDM6A’s critical roles in cell differentiation, development, and cancer. ABSTRACT Lysine demethylase 6A (KDM6A), also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases, which also includes UTY and KDM6B (JMJD3). The KDM6A protein contains six tetratricopeptide repeat (TPR) domains and an enzymatic Jumonji C (JmjC) domain that catalyzes the removal of di- and trimethylation on H3K27. KDM6A physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (KMT2D). Since its identification as an H3K27 demethylase in 2007, studies have reported KDM6A’s critical roles in cell differentiation, development, and cancer. KDM6A is important for differentiation of embryonic stem cells and development of various tissues. Mutations of KDM6A cause Kabuki syndrome. KDM6A is frequently mutated in cancers and functions as a tumor suppressor. KDM6A is redundant with UTY and functions largely independently of its demethylase activity. It regulates gene expression, likely through the associated transcription factors and MLL3/4 on enhancers. However, KDM6A enzymatic activity is required in certain cellular contexts. Functional redundancy between H3K27 demethylase activities of KDM6A and KDM6B in vivo has yet to be determined. Further understanding of KDM6A functions and working mechanisms will provide more insights into enhancer regulation and may help generate novel therapeutic approaches to treat KDM6A-related diseases.
Preventative therapeutic approaches for hypertrophic cardiomyopathy

Sarcomeric gene mutations are associated with the development of hypertrophic cardiomyopathy (HCM). Current drug therapeutics for HCM patients are effective in relieving symptoms, but do not prevent or reverse disease progression. Moreover, due to heterogeneity in the clinical manifestations of the disease, patients experience variable outcomes in response to therapeutics. Mechanistically, alterations in calcium handling, sarcomeric disorganization, energy metabolism and contractility participate in HCM disease progression. While some similarities exist, each mutation appears to lead to mutation‐specific pathophysiology. Furthermore, these alterations may precede or proceed development of the pathology. This review assesses the efficacy of HCM therapeutics from studies performed in animal models of HCM and human clinical trials. Evidence suggests that a preventative rather than corrective therapeutic approach may be more efficacious in the treatment of HCM. In addition, a clear understanding of mutation‐specific mechanisms may assist in informing the most effective therapeutic mode of action.
Longitudinal neuroanatomical and behavioral analyses show phenotypic drift and variability in the Ts65Dn mouse model of Down syndrome

ABSTRACT Mouse models of Down syndrome (DS) have been invaluable tools for advancing knowledge of the underlying mechanisms of intellectual disability in people with DS. The Ts(1716)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with DS, including neuroanatomical changes and impaired learning and memory. In this study, we use rigorous metrics to evaluate multiple cohorts of Ts65Dn ranging from 2014 to the present, including a stock of animals recovered from embryos frozen within ten generations after the colony was first created in 2010. Through quantification of prenatal and postnatal brain development and several behavioral tasks, our results provide a comprehensive comparison of Ts65Dn across time and show a significant amount of variability both across cohorts as well as within cohorts. The inconsistent phenotypes in Ts65Dn mice highlight specific cautions and caveats for use of this model. We outline important steps for ensuring responsible use of Ts65Dn in future research. This article has an associated First Person interview with the first author of the paper. Summary: Comparative analyses of temporal cohorts of the Ts65Dn mouse model of Down syndrome reveal phenotypic variability affecting neurodevelopment and learning and memory behaviors, calling into question the validity of this model.
Rapid Growth of the colloidal crystal films from the concentrated aqueous ethanol suspension.

Developing a rapid fabrication of colloidal crystal film is one of the technical issues to apply to wide and various application fields. We have been investigating a drying process of colloidal ethanol (EtOH) aqueous suspension formed by electrophoretic deposition. Here the detailed formation mechanism of the colloidal crystal films with the closest packing structure was investigated by optical microscope and spectroscopy. The growth mechanism from the colloidal suspension to the colloidal crystal film was found to consist of 4 stages. In the 1st stage, concentrated colloidal suspension changed to order structure, i.e., non-closely packed colloidal crystal by Alder phase transition. After this crystallization, we observed Bragg's diffraction peak and structural color. In the 2nd stage, the diffraction peak shifts toward the shorter wavelength direction (blue shift), due to the reduction of the interparticle distance of the non-closely packed colloidal crystal. Finally, this peak shift continued to until the closely packed colloidal crystal film was formed. In the 3rd stage, the diffraction peak kept almost a similar wavelength due to the liquid film of EtOH aqueous covering on the colloidal crystal film. In the 4th stage, the colloidal crystal film changed from wet to dry condition. The structural color changes from green to blue by the evaporation of the solvent from the interspace of the colloidal crystal film. This color change is explained by the change of the refractive index of the interparticle medium from solvent to air. One of the key findings in our process is a rapid crystal growth using concentrated colloid EtOH aqueous suspension. Drying the concentrated suspension formed a closely packed colloidal crystal film within 55 seconds. This process has the potential for high-speed deposition of the colloidal crystalline thin films.
Preoperative quantitative sensory testing and robot-assisted laparoscopic hysterectomy for endometrial cancer: can chronic postoperative pain be predicted?

Abstract Objectives Chronic postoperative pain is prevalent after robot-assisted laparoscopic hysterectomy for endometrial cancer. Preoperative Quantitative Sensory Testing (QST) has been utilized to identify patients at risk of developing chronic postoperative pain after a range of surgical procedures. The aim of this prospective, observational study was to (1) determine the prevalence of chronic postoperative pain, (2) assess selected preoperative risk factors for chronic postoperative pain, and (3) evaluate if preoperative QST profiling could predict the development of chronic postoperative pain following robot-assisted laparoscopic hysterectomy for endometrial cancer. Methods One-hundred and sixty consecutive patients were included and handheld pressure algometry, cuff pressure algometry, temporal summation of pain, conditioned pain modulation, and heat pain thresholds were assessed prior to surgery. Patients were asked to fill out a questionnaire concerning pain in the pre- and post-operative time period six months after surgery. Chronic postoperative pain was defined as persistent, moderate to severe pain (mean visual analogue scale (VAS)≥3) on a daily basis six months after surgery. Results The prevalence of chronic postoperative pain after robot-assisted laparoscopic hysterectomy for endometrial cancer was of 13.6% (95% CI 8.4–20.4%). Patients that would develop chronic postoperative pain had a lower BMI (p=0.032), a higher prevalence of preoperative pelvic pain (p<0.001), preoperative heat pain hyperalgesia (p=0.043) and a higher level of acute postoperative pain (p<0.001) when compared to patients that would not develop chronic postoperative pain. A logistic regression model demonstrated that the presence of preoperative pelvic pain was a significant, independent predictive risk factor for development of chronic postoperative pain (OR=6.62, 95% CI 2.26–19.44), whereas none of the QST parameters could predict postoperative pain. Conclusions Preoperative QST assessment could not predict the development of chronic postoperative pain despite preoperative heat pain hyperalgesia in patients that would develop chronic postoperative pain.
Transportation Risk Behaviors Among High School Students — Youth Risk Behavior Survey, United States, 2019

Motor-vehicle crashes are a leading cause of death and nonfatal injury among U.S. adolescents, resulting in approximately 2,500 deaths and 300,000 nonfatal injuries each year. Risk for motor-vehicle crashes and resulting injuries and deaths varies, depending on such behaviors as seat belt use or impaired or distracted driving. Improved understanding of adolescents’ transportation risk behaviors can guide prevention efforts. Therefore, data from the 2019 Youth Risk Behavior Survey were analyzed to determine prevalence of transportation risk behaviors, including not always wearing a seat belt, riding with a driver who had been drinking alcohol (riding with a drinking driver), driving after drinking alcohol, and texting or e-mailing while driving. Differences by student characteristics (age, sex, race/ethnicity, academic grades in school, and sexual identity) were calculated. Multivariable analyses controlling for student characteristics examined associations between risk behaviors. Approximately 43.1% of U.S. high school students did not always wear a seat belt and 16.7% rode with a drinking driver during the 30 days before the survey. Approximately 59.9% of students had driven a car during the 30 days before the survey. Among students who drove, 5.4% had driven after drinking alcohol and 39.0% had texted or e-mailed while driving. Prevalence of not always wearing a seat belt was higher among students who were younger, black, or had lower grades. Riding with a drinking driver was higher among Hispanic students or students with lower grades. Driving after drinking alcohol was higher among students who were older, male, Hispanic, or had lower grades. Texting while driving was higher among older students or white students. Few differences existed by sexual identity. Multivariable analyses revealed that students engaging in one transportation risk behavior were more likely to engage in other transportation risk behaviors. Traffic safety and public health professionals can use these findings to reduce transportation risk behaviors by selecting, implementing, and contextualizing the most appropriate and effective strategies for specific populations and for the environment.
A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting vif/CBFβ interaction

HIV remains a health challenge worldwide, partly because of the continued development of resistance to drugs. Therefore, it is urgent to find new HIV inhibitors and targets. Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 family members (APOBEC3) are important host restriction factors that inhibit HIV-1 replication by their cytidine deaminase activity. HIV-1 viral infectivity factor (Vif) promotes proteasomal degradation of APOBEC3 proteins by recruiting the E3 ubiquitin ligase complex, in which core-binding factor β (CBFβ) is a necessary molecular chaperone. Interrupting the interaction between Vif and CBFβ can release APOBEC3 proteins to inhibit HIV-1 replication and may be useful for developing new drug targets for HIV-1. In this study, we identified a potent small molecule inhibitor CBFβ/Vif-3 (CV-3) of HIV-1 replication by employing structure-based virtual screening using the crystal structure of Vif and CBFβ (PDB: 4N9F) and validated CV-3's antiviral activity. We found that CV-3 specifically inhibited HIV-1 replication (IC50 = 8.16 µm; 50% cytotoxic concentration >100 µm) in nonpermissive lymphocytes. Furthermore, CV-3 treatment rescued APOBEC3 family members (human APOBEC3G (hA3G), hA3C, and hA3F) in the presence of Vif and enabled hA3G packaging into HIV-1 virions, which resulted in Gly-to-Ala hypermutations in viral genomes. Finally, we used FRET to demonstrate that CV-3 inhibited the interaction between Vif and CBFβ by simultaneously forming hydrogen bonds with residues Gln-67, Ile-102, and Arg-131 of CBFβ. These findings demonstrate that CV-3 can effectively inhibit HIV-1 by blocking the interaction between Vif and CBFβ and that this interaction can serve as a new target for developing HIV-1 inhibitors.
Comparing two dry needling interventions for plantar heel pain: a randomised controlled trial

Objectives To compare the effectiveness of dry needling (DN) versus percutaneous needle electrolysis (PNE) for improving the level of pain, function and quality of life (QoL) of patients suffering from plantar heel pain (PHP) provoked by myofascial trigger points. Design A prospective, parallel-group, randomised controlled trial with blinded outcome assessment. Setting A single treatment facility in the State of Kuwait. Participants 118 participants were screened for eligibility. Of these, 102 participants were enrolled (30 men (49.5±8.9 years) and 72 women (48.1±8.8 years)) and 68 of them completed the trial. Interventions Two parallel groups, one study arm received DN and a stretching protocol whereas the other arm received percutaneous needling electrolysis with a stretching protocol. Primary and secondary outcome measures The primary outcome measure was the Foot Pain domain of the Foot Health Status Questionnaire, with 13 questions related to foot health-related domains. Secondary outcome measures included the 0–10 numerical rating scale pain visual analogue scale (VAS) scores, performed before and after each treatment session. In addition, QoL was measured using the EuroQoL-5 dimensions. All measurements were taken at baseline, at 4, 8, 12, 26 and 52 weeks. Results Foot Pain domain improved at all time points for DN group (p<0.001; 29.7 (17.8 to 41.5)) and percutaneous needling electrolysis group (p<0.001; 32.7 (18.3 to 47.0)), without significant differences between groups. Pain VAS scores decreased at all time points for both DN (p<0.001; −2.6 (−4.0 to −1.2)) and percutaneous needling electrolysis group (p<0.001; −3.0 (−4.5 to −1.6)). QoL improved at 4 weeks for both DN (p<0.01; 0.15 (0.5 to 0.25)) and percutaneous needling electrolysis group (p<0.01; 0.09 (0.01 to 0.17)) and at 8 and 52 weeks for the PNE group (p<0.01; 0.10 (0.02 to 0.18)), with significant differences between groups for the QoL at 52 weeks (p<0.05; 0.10 (0.01 to 0.18)). There were two small haematomas in the PNE group and one in the DN group. No serious adverse events were reported. Conclusions Both PNE and DN were effective for PHP management, reducing mean and maximum pain since the first treatment session, with long lasting effects (52 weeks) and significant differences between groups in the case of QoL at 52 weeks in favour of the PNE group. Trial registration number NCT03236779.
Lower estimated bone strength and impaired bone microarchitecture in children with type 1 diabetes

Introduction Patients with type 1 diabetes has an increased risk of fracture. We wished to evaluate estimated bone strength in children and adolescents with type 1 diabetes and assess peripheral bone geometry, volumetric bone mineral density (vBMD) and microarchitecture. Research design and methods In a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) was performed of the radius and tibia in 84 children with type 1 diabetes and 55 healthy sibling controls. Estimated bone strength was assessed using a microfinite element analysis solver. Multivariate regression analyses were performed adjusting for age, sex, height and body mass index. Results The median age was 13.0 years in the diabetes group vs 11.5 years in healthy sibling controls. The median (range) diabetes duration was 4.2 (0.4−15.9) years; median (range) latest year Hb1Ac was 7.8 (5.9−11.8) % (61.8 (41−106) mmol/mol). In adjusted analyses, patients with type 1 diabetes had reduced estimated bone strength in both radius, β −390.6 (−621.2 to −159.9) N, p=0.001, and tibia, β −891.9 (−1321 to −462.9) N, p<0.001. In the radius and tibia, children with type 1 diabetes had reduced cortical area, trabecular vBMD, trabecular number and trabecular bone volume fraction and increased trabecular inhomogeneity, adjusted p<0.05 for all. Latest year HbA1c was negatively correlated with bone microarchitecture (radius and tibia), trabecular vBMD and estimated bone strength (tibia). Conclusion Children with type 1 diabetes had reduced estimated bone strength. This reduced bone strength could partly be explained by reduced trabecular bone mineral density, adverse microarchitecture and reduced cortical area. We also found increasing latest year HbA1c to be associated with several adverse changes in bone parameters. HR-pQCT holds potential to identify early adverse bone changes and to explain the increased fracture risk in young patients with type 1 diabetes.
Functions of the BamBCDE Lipoproteins Revealed by Bypass Mutations in BamA

The folding and insertion of β-barrel outer membrane proteins (OMPs) are conserved processes in mitochondria, chloroplasts, and Gram-negative bacteria. In Gram-negative bacteria, OMPs are assembled into the outer membrane (OM) by the heteropentomeric β-barrel assembly machine (BAM complex). In this study, we probe the function of the individual BAM proteins and how they coordinate assembly of a diverse family of OMPs. Furthermore, we identify a gain-of-function bamA mutant capable of assembling OMPs independently of all four other BAM proteins. This work advances our understanding of OMP assembly and sheds light on how this process is distinct in Gram-negative bacteria. ABSTRACT The heteropentomeric β-barrel assembly machine (BAM complex) is responsible for folding and inserting a diverse array of β-barrel outer membrane proteins (OMPs) into the outer membrane (OM) of Gram-negative bacteria. The BAM complex contains two essential proteins, the β-barrel OMP BamA and a lipoprotein BamD, whereas the auxiliary lipoproteins BamBCE are individually nonessential. Here, we identify and characterize three bamA mutations, the E-to-K change at position 470 (bamAE470K), the A-to-P change at position 496 (bamAA496P), and the A-to-S change at position 499 (bamAA499S), that suppress the otherwise lethal ΔbamD, ΔbamB ΔbamC ΔbamE, and ΔbamC ΔbamD ΔbamE mutations. The viability of cells lacking different combinations of BAM complex lipoproteins provides the opportunity to examine the role of the individual proteins in OMP assembly. Results show that, in wild-type cells, BamBCE share a redundant function; at least one of these lipoproteins must be present to allow BamD to coordinate productively with BamA. Besides BamA regulation, BamD shares an additional essential function that is redundant with a second function of BamB. Remarkably, bamAE470K suppresses both, allowing the construction of a BAM complex composed solely of BamAE470K that is able to assemble OMPs in the absence of BamBCDE. This work demonstrates that the BAM complex lipoproteins do not participate in the catalytic folding of OMP substrates but rather function to increase the efficiency of the assembly process by coordinating and regulating the assembly of diverse OMP substrates. IMPORTANCE The folding and insertion of β-barrel outer membrane proteins (OMPs) are conserved processes in mitochondria, chloroplasts, and Gram-negative bacteria. In Gram-negative bacteria, OMPs are assembled into the outer membrane (OM) by the heteropentomeric β-barrel assembly machine (BAM complex). In this study, we probe the function of the individual BAM proteins and how they coordinate assembly of a diverse family of OMPs. Furthermore, we identify a gain-of-function bamA mutant capable of assembling OMPs independently of all four other BAM proteins. This work advances our understanding of OMP assembly and sheds light on how this process is distinct in Gram-negative bacteria.