Miracle-dz/UniFAR-FTUs huggingface dataset:
A Multisite Study Investigating Child and Parent Proxy Reported Quality of Life in Children With Cleft Lip and/or Palate

Objective This observational, multisite cohort study explored health-related quality of life (HRQoL) in children with cleft lip and/or palate (CL/P), including interrater agreement and ratings for this group relative to clinical cutoff scores and published means for healthy and chronically ill children. Methods Participants (338 children ages 8-10 years, 45.9% male and their parents, 82.0% female) across 6 sites completed the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL). Results Intraclass correlation revealed poor interrater agreement for most HRQoL domains. Although ratings were generally higher than those expected for children with a chronic illness, child ratings were below healthy means for school functioning, and parent proxy ratings were below healthy means for all domains except physical functioning. Lower ratings consistent with chronic illness means were found for self-reported emotional and psychosocial functioning in children with cleft lip and palate (CLP), as well as parent proxy-reported emotional, school, and psychosocial functioning for children with cleft palate (CP). Scores were most likely to be in the clinical range for children with CP for social, school, and total functioning. Conclusion Although parent proxy report provides important information about observed functioning, poor interrater agreement indicates that both child and parent proxy reported HRQoL should be included in outcomes assessment for CL/P. HRQoL ratings may be higher for children with CL/P compared to youth with other chronic illnesses, but psychosocial functioning may be negatively impacted when compared with healthy youth, particularly for emotional, social, and school functioning in children with CLP or CP.
On the prospect of achieving accurate joint estimation of selection with population history

Abstract As both natural selection and population history can affect genome-wide patterns of variation, disentangling the contributions of each has remained as a major challenge in population genetics. We here discuss historical and recent progress towards this goal—highlighting theoretical and computational challenges that remain to be addressed, as well as inherent difficulties in dealing with model complexity and model violations—and offer thoughts on potentially fruitful next steps.
Retraction: MicroRNA-153 Inhibits Osteosarcoma Cells Proliferation and Invasion by Targeting TGF-β2

Although the corresponding author initially replied to acknowledge receipt of our message, PLOS ONE did not receive responses to the queries regarding these concerns by the end of the original deadline and extension. The unresolved concerns call into question the validity and provenance of the reported results and the adherence of this article to the PLOS Authorship policy. Therefore, the PLOS ONE Editors retract this article [1]. All authors did not comment on the retraction decision, did not respond directly or could not be reached.
The β-TrCP-Mediated Pathway Cooperates with the Keap1-Mediated Pathway in Nrf2 Degradation In Vivo

Nrf2 activates cytoprotective gene expression, and Nrf2 activity is regulated through at least two protein degradation pathways: the Keap1-mediated and β-TrCP-mediated pathways. To address the relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2SA mutant that harbored two substitution mutations of serine residues interacting with β-TrCP. ABSTRACT Nrf2 activates cytoprotective gene expression, and Nrf2 activity is regulated through at least two protein degradation pathways: the Keap1-mediated and β-TrCP-mediated pathways. To address the relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2SA mutant that harbored two substitution mutations of serine residues interacting with β-TrCP. The homozygous (Nrf2SA/SA) mice grew normally, with Nrf2 levels comparable to those of wild-type (WT) mice under unstressed conditions. However, when Keap1 activity was suppressed, high levels of Nrf2 accumulated in Nrf2SA/SA macrophages compared with that in WT macrophages. We crossed Nrf2SA/SA mice with mice in which Keap1 was knocked down to two different levels. We found that the Nrf2SA/SA mutation induced higher Nrf2 activity when the Keap1 level was strongly reduced, and these mice showed severe growth retardation. However, activation and growth retardation were not evident when Keap1 was moderately suppressed. These increases in Nrf2 activity induced by the Nrf2SA mutation caused severe hyperplasia and hyperkeratosis in the esophageal epithelium but did not cause abnormalities in the other tissues/organs examined. These results indicate that the β-TrCP-mediated pathway cooperates with the Keap1-mediated pathway to regulate Nrf2 activity, which is apparent when the Keap1-mediated pathway is profoundly suppressed.
Trainee Perspectives on Race, Antiracism, and the Path toward Justice in Kidney Care.

Introduction In 1999, researchers introduced a Black race coefficient of 1.21 to the estimated glomerular filtration rate (eGFR) on the basis of the observation that participants who self-identified as Black had a 21% higher measured GFR after controlling for age, sex, and serum creatinine than those who did not self-identify as Black. Use of this coefficient mitigated underestimation bias among Black individuals and overestimation bias among non-Black individuals in the study population, but did not consider confounding from socioeconomic and structural factors, problematic views of race as biology, or potential implications of race-based differential treatment. The subsequent 2009 Chronic Kidney Disease Epidemiology Collaboration equation similarly derived a Black race coefficient of 1.16. In 2021, the recommendation by the joint National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Task Force to adopt calculations of eGFR without race sent waves through the medical community (1). Consensus recognition that race-adjusted eGFR causes harm marked a positive and long-needed step forward for nephrology and the greater medical community. Patients, transdisciplinary experts, and medical trainees contributed in key ways to this movement through grassroots organizing, outreach and education, scientific research and scholarly discourse, and policy and organized medicine. Yet, these perspectives are often excluded or erased from dominant narratives. In this article, writing as trainees ourselves, we recognize the foundational social science and activism upon which the movement to redress raceadjusted eGFR was built, explore motivations for trainee involvement, highlight trainee and patient contributions, and outline next steps to advance equity in kidney care and beyond.
Motivational Interviewing to Encourage Agricultural Producers’ Use of Hearing Protection Devices: A Mixed-Method Feasibility Study

Background: Workers in production agriculture are frequently exposed to high noise levels and face unique barriers to implementing hearing protection, leading to occupational hearing loss. Motivational interviewing is a promising approach to assist workers in preserving their hearing. Methods: This pilot study used a mixed-method approach to evaluate the feasibility of an innovative motivational interviewing intervention for agricultural producers from February to May 2021. Qualitative data included coaches’ and participants’ comments and were coded using a structural coding approach. Quantitative data included Likert-type-style responses given by participants in a post-intervention survey. Data types were then integrated. Results: Sixteen participants were recruited during the 4-month pilot. Participants’ satisfaction scores averaged above six on a 7-point scale for all satisfaction questions. Implementation factors included the intervention’s flexibility, services provided by the coaches beyond motivational interviewing, and difficulties with recruitment. Conclusions/Applications to Practice: This motivational interviewing intervention was highly acceptable to participants, but factors affecting implementation may challenge scalability.
The habenular volume and PDE7A allelic polymorphism in major depressive disorder: preliminary findings

Abstract Objectives The habenula is a brain structure implicated in depression, yet with unknown molecular mechanisms. Several phosphodiesterases (PDEs) have been associated with a risk of depression. Although the role of PDE7A in the brain is unknown, it has enriched expression in the medial habenula, suggesting that it may play a role in depression. Methods We analysed: (1) habenula volume assessed by 3-T magnetic resonance imaging (MRI) in 84 patients with major depressive disorder (MDD) and 41 healthy controls; (2) frequencies of 10 single nucleotide polymorphisms (SNPs) in PDE7A gene in 235 patients and 41 controls; and (3) both indices in 80 patients and 27 controls. The analyses considered gender, age, body mass index and season of the MRI examination. Results The analysis did not reveal habenula volumetric changes in MDD patients regardless of PDE7A SNPs. However, in the combined group, the carriers of one or more mutations among 10 SNPs in the PDE7A gene had a lower volume of the left habenula (driven mainly by rs972362 and rs138599850 mutations) and consequently had the reduced habenular laterality index in comparison with individuals without PDE7A mutations. Conclusions Our findings suggest the implication of the PDE7A gene into mechanisms determining the habenula structure.
Changes in Cognitive and Functional Status and in Quality of Life of Older Outpatients during the COVID-19 Pandemic

Background: Older adults denoted one of the populations that mostly suffered from the consequences of the COVID-19 pandemic. The cost of confinement was paid in terms of social isolation, distance from relatives and friends, lack of social support, and limited access to the healthcare system, which had a negative impact on health of older adults with comorbidities and frailty. Objectives: The purpose of the present study was to report the consequences of the COVID-19 pandemic on cognitive performances, functional status, and health-related quality of life among frail outpatients, compared to pre-pandemic status. Method: The current sample was part of a larger sample of frail and pre-frail outpatients, who were first evaluated at the clinic between April and May 2019 and who underwent a first follow-up evaluation between April and May 2020. Those outpatients who have undergone the first follow-up evaluation were contacted between April and May 2021 and were asked to voluntarily participate in a second telephone-based evaluation. Cognitive performances (through Mini Mental State Examination – MMSE), functional independency in basic and instrumental daily activities, physical and mental components of health-related quality of life (SF-12 PCS and SF-12 MCS, respectively) were evaluated and compared to previous evaluations. Results: Seventy one outpatients (mean age of 80.69 years) completed the present follow-up evaluation. Patients reported significantly lower cognitive performances (mean MMSE 19.37; p < 0.001), lower physical quality of life (mean score 31.69; p < 0.001), and lower mental quality of life (mean score 38.79; p < 0.001) compared to both pre-pandemic baseline and the first follow-up. Moreover, patients showed a significantly reduced independency in basic daily activities (mean score 3.8; p = 0.004), and a significantly reduced independency in managing telephone (p = 0.012) and medications (p = 0.035), compared to baseline. Conclusions: The COVID-19 pandemic has been a prolonged stressor over time, which has markedly affected health-related quality of life of outpatients, and it can be considered a stressor that might have contributed to the patients’ greater cognitive and functional vulnerability.
Mapping HIV prevalence in Nigeria using small area estimates to develop a targeted HIV intervention strategy

Objective Although geographically specific data can help target HIV prevention and treatment strategies, Nigeria relies on national- and state-level estimates for policymaking and intervention planning. We calculated sub-state estimates along the HIV continuum of care in Nigeria. Design Using data from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) (July–December 2018), we conducted a geospatial analysis estimating three key programmatic indicators: prevalence of HIV infection among adults (aged 15–64 years); antiretroviral therapy (ART) coverage among adults living with HIV; and viral load suppression (VLS) rate among adults living with HIV. Methods We used an ensemble modeling method called stacked generalization to analyze available covariates and a geostatistical model to incorporate the output from stacking as well as spatial autocorrelation in the modeled outcomes. Separate models were fitted for each indicator. Finally, we produced raster estimates of each indicator on an approximately 5×5-km grid and estimates at the sub-state/local government area (LGA) and state level. Results Estimates for all three indicators varied both within and between states. While state-level HIV prevalence ranged from 0.3% (95% uncertainty interval [UI]: 0.3%–0.5%]) to 4.3% (95% UI: 3.7%–4.9%), LGA prevalence ranged from 0.2% (95% UI: 0.1%–0.5%) to 8.5% (95% UI: 5.8%–12.2%). Although the range in ART coverage did not substantially differ at state level (25.6%–76.9%) and LGA level (21.9%–81.9%), the mean absolute difference in ART coverage between LGAs within states was 16.7 percentage points (range, 3.5–38.5 percentage points). States with large differences in ART coverage between LGAs also showed large differences in VLS—regardless of level of effective treatment coverage—indicating that state-level geographic targeting may be insufficient to address coverage gaps. Conclusion Geospatial analysis across the HIV continuum of care can effectively highlight sub-state variation and identify areas that require further attention in order to achieve epidemic control. By generating local estimates, governments, donors, and other implementing partners will be better positioned to conduct targeted interventions and prioritize resource distribution.
RELATIONS BETWEEN SYSTEMS OF MOTOR, COGNITIVE AND CONATIVE VARIABLES OF TOP-CLASS HANDBALL PLAYERS ODNOSI MED SISTEMI GIBALNIH, KOGNITIVNIH IN KONATIVNIH SPREMENLJIVK VRHUNSKIH ROKOMETAŠEV

A sample of 180 handball players of the first and second Serbian handball league were examined according to a system of 27 variables (12 motor, 3 cognitive and 12 conative variables). The aim was to determine the statistically significant relations between the systems of variables of motor abilities, cognitive variables and variables of conative characteristics. The data were processed by canonical correlation analysis. With the application of Bartlett’s Chi-square test (χ2 ) between the system of motor variables and the system of cognitive variables, three canonical correlations were obtained (Rc=.57, Rc=.45, Rc=.35) which are statistically significant on the level of p=. 00 that is p=. 01. Between the system of motor variables and the system of conative variables two canonical correlations were obtained (Rc = .62 and Rc = .59), which are statistically significant on the level of p=. 00. The results of the research showed that top-class handball players achieve better results concerning motor variables of the motion structure, tonus regulation, intensity and duration of excitation and synergy regulation if they have increased values concerning cognitive variables of efficiency of serial processing (IT – 1) as well as concerning conative variables of the efficiency of the system of regulation and control of the defence reaction (ALPHA), the efficiency of the system of regulation and control of offence reaction (SIGMA) and the efficiency of the system of coordination of regulative functions (DELTA).
Females Exhibit Relative Resistance to Depressive Effects of TNF on the Myocardium

Background— Tumor necrosis factor- α (TNF) plays a critical role in myocardial dysfunction following acute injury. It is unknown, however, if a gender-specific response to TNF infusion exists in isolated rat hearts. Elucidating such mechanisms is important to understanding the myocardial gender differences during acute injury. We hypothesize that females will exhibit a relative resistance to TNF-induced myocardial dysfunction compared to males and that mestrual cycle would influence the degree of female myocardial resistance to TNF-induced myocardial functional depression. Methods— Adult male, proestrus female, and metestrus/diestrus female hearts were subjected to 60 minutes of TNF infusion at 10,000 pg/ml·min via Langendorff. Myocardial contractile function (left ventricular developed pressure, and the positive/negative first derivative of pressure) was continuously recorded. Results— 10,000pg/ml min of TNF markedly depressed myocardial function in males compared with other doses of TNF. Myocardial function was significantly decreased in males compared to females following TNF infusion. Additionally, both the proestrus and metestrus/diestrus females exhibited equal resistance to TNF-induced myocardial dysfunction. Conclusion— Our study shows that females exhibit a significantly greater degree of resistance to TNF induced myocardial depression. Moreover, data from this study suggests that fluctuations in estrogen during the reproductive cycle may have little to no influence on TNF-induced myocardial depression.
Perceptions of delay when afflicted by an acute myocardial infarction during the first wave of the COVID-19 pandemic

Abstract Aims To describe the perceptions of delay in medical care-seeking, when afflicted by an acute myocardial infarction (AMI) during the first wave of the pandemic. Methods and results A qualitative descriptive study with an inductive approach. Fourteen semi-structured interviews were conducted, analysed by qualitative content analysis with a manifest approach. One category and six sub-categories emerged. The decision was reached when the health threat was perceived as critical, which made the earlier thoughts of the pandemic fade away. The risk of infection during medical visits caused fear of contracting the disease. This resulted in hesitation, neglect of symptoms, and avoidance of healthcare visits. Following recommendations from authorities and media about personal responsibility was motivated by fear, affecting the care-seeking. Conclusion It appears that the COVID-19 pandemic raised the threshold for deciding to seek medical care when presenting with an AMI. The pandemic led to increased patient delay due to several reasons among which fear of contracting the disease was prominent. The emotion of fear was related to the external threat to one's own health, due to COVID-19, and not fear of symptoms related to an AMI. The media reporting the healthcare system as overloaded increased insecurity and may have had an influence on delay.
A So-Far Overlooked Secondary Conformation State in the Binding Mode of SARS-CoV-2 Spike Protein to Human ACE2 and Its Conversion Rate Are Crucial for Estimating Infectivity Efficacy of the Underlying Virus Variant

The current SARS-CoV-2 pandemic is characterized by the high infectivity of SARS-CoV-2 and its derived variants of concern (VOCs). It has been widely assumed that the reason for its increased cell entry compared with SARS-CoV (2002) is due to alterations in the viral spike protein, where single amino acid residue substitutions can increase affinity for hACE2. ABSTRACT Since its outbreak in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread with high transmission efficiency across the world, putting health care as well as economic systems under pressure. During the course of the pandemic, the originally identified SARS-CoV-2 variant has been multiple times replaced by various mutant versions, which showed enhanced fitness due to increased infection and transmission rates. In order to find an explanation for why SARS-CoV-2 and its emerging mutated versions showed enhanced transmission efficiency compared with SARS-CoV (2002), an enhanced binding affinity of the spike protein to human angiotensin converting enzyme 2 (hACE2) has been proposed by crystal structure analysis and was identified in cell culture models. Kinetic analysis of the interaction of various spike protein constructs with hACE2 was considered to be best described by a Langmuir-based 1:1 stoichiometric interaction. However, we demonstrate in this report that the SARS-CoV-2 spike protein interaction with hACE2 is best described by a two-step interaction, which is defined by an initial binding event followed by a slower secondary rate transition that enhances the stability of the complex by a factor of ~190 (primary versus secondary state) with an overall equilibrium dissociation constant (KD) of 0.20 nM. In addition, we show that the secondary rate transition is not only present in SARS-CoV-2 wild type (“wt”; Wuhan strain) but also found in the B.1. 1.7 variant, where its transition rate is 5-fold increased. IMPORTANCE The current SARS-CoV-2 pandemic is characterized by the high infectivity of SARS-CoV-2 and its derived variants of concern (VOCs). It has been widely assumed that the reason for its increased cell entry compared with SARS-CoV (2002) is due to alterations in the viral spike protein, where single amino acid residue substitutions can increase affinity for hACE2. So far, the interaction of a single unit of the CoV-2 spike protein has been described using the 1:1 Langmuir interaction kinetic. However, we demonstrate here that there is a secondary state binding step that may be essential for novel VOCs in order to further increase their infectivity. These findings are important for quantitatively understanding the infection process of SARS-CoV-2 and characterization of emerging SARS-CoV-2 variants of spike proteins. Thus, they provide a tool for predicting the potential infectivity of the respective viral variants based on secondary rate transition and secondary complex stability.