Miracle-dz/UniFAR-FTUs huggingface dataset:
Disparities in Subjective Cognitive Impairment by Sexual Orientation and Gender in a National Population Based Study of U.S. Adults, 2013–2018

Objectives: This is the first national population-based study to examine cognitive impairment disparities among sexual minority mid-life and older adults. Methods: Using the National Health Interview Survey (2013–2018), we compared weighted prevalence of subjective cognitive impairment by sexual orientation and gender, among those aged 45 plus, applying logistic regressions adjusting for age, income, education, race/ethnicity, and survey years. Results: Sexual minorities (24.5%) were more likely to have subjective cognitive impairment than heterosexuals (19.1%). Sexual minority women had higher odds of greater severity, frequency, and extent of subjective cognitive impairment. Sexual minorities were also more likely to report activity limitations resulting from cognitive impairment and were no more likely to attribute limitations to dementia or senility. Discussion: Cognitive health disparities are of particular concern in this historically and socially marginalized population. The investigation of explanatory factors is needed, and targeted interventions and policies are warranted to address cognitive challenges faced by sexual minorities.
Complete denture replacement: a 20-year retrospective study of adults receiving publicly funded dental care.

PURPOSE There is little evidence as to what is the appropriate replacement interval for complete dentures. The aim of this study was to determine the longevity of complete dentures in a population of publicly insured adults across a 20 year observation period. METHODS The records of 187,227 Australian adults who accessed complete denture treatment through public clinics between 2000-2019 were assessed. Time to denture replacement was modelled using a Weibull regression and a competing risk regression to adjust for the competing risk of mortality. RESULTS Over a 20-year period, 27.7% of dentures were replaced, with a mean longevity of 6.06 (SD: 3.93) years. Pairs of complete dentures had greater mean longevity than single dentures (p<0.001). Approximately 4.6% of dentures provided were replaced within 2 years; 18.4% were replaced between 2 and 10 years and 4.6% of replacements occurred after 10 years.Over 70% of adults who received a complete denture did not replace it during the observation period. Dentures provided by denturists had higher levels of replacement than those made by dentists. Participants over 80 years of age had lower rates of denture replacement. Low socio-economic status and living outside a major city were associated with reduced rates of replacement for dentures under 10 years of age. CONCLUSION Complete dentures were commonly replaced after 6 years of service. Pairs of dentures lasted longer than single dentures.
Perceived learning environment and academic motivation: An explanatory mixed methods study in a Molecular Biology and Genetics program

Lack of motivation of students is a major concern for the instructors and administration in universities, and it is in their interest to address these issues in the most effective and efficient way. The purpose of this explanatory sequential mixed‐method study is to examine the predictive power of the learning environment on student academic motivation and to learn students' opinions on this issue. One hundred twenty students enrolled at the Molecular Biology and Genetics program completed the Academic Motivation and Learning Environment Perception scales, Quantitative findings indicated that only the activities dimension of the learning environment has a predictive power on academic motivation. Focus group interviews conducted with 16 students validated the quantitative findings. Students particularly drew attention to activities that foster active participation in the learning process, emphasizing the vitality of being engaged and of having real‐life experiences in their learning environment.
How do attitudes toward Covid-19 vaccine impact intentions to vaccinate in an emerging economy? The moderating effect of risk perception and Covid-19 anxiety

Abstract This article aims to investigate the factors influencing the relationship between attitudes toward Covid-19 vaccines and intention to vaccinate, specifically, risk perception and Covid-19 anxiety. The study’s results clearly demonstrate that only when the risk perception is minimal does vaccination intention improve with improved vaccine attitudes. The findings of this study provide valuable insights for policymakers, non-government organizations, marketers, and practitioners about the possible challenges in the execution of a Covid-19 vaccination program in an emerging economy. There is a need for tailored communication, community engagement and strictly following the standard operating procedure (SOP) inside the vaccination centers.
Supporting Self-Directed Learning: Development of a Faculty Evaluation Scale

Abstract Construct: We sought to assess medical education faculty members’ ability to support students in the development of self-regulated learning skills. Background: It is broadly agreed that medical students should become self-directed lifelong learners to succeed as physicians. To that end, many instruments have been developed that measure student attributes of self-directed learning (SDL). By contrast, no such analogous valid instrument is available to assess faculty familiarity in pedagogical strategies to promote SDL among students. Approach: An item bank with 45 items was created and its content-related validity evaluated by a panel of twenty experts. The items were selected and validated in the framework of Item Response Theory (IRT). The unidimensionality of all items within four constructs was assessed by using modified parallel analysis and 2 parameter IRT model calibration. The final version of the Recognition of Learning-Oriented Teaching Strategies (RoLOTS) instrument was validated by using the IRT marginal reliability as well as 2PL model calibrations. Different Item Functioning (DIF) in student-educators and gender was examined. Findings: The final version of RoLOTS included 20 items, with five in each of four subdomains: building content knowledge; the emotional and motivational aspects of learning; leveraging the social nature of the learning process; and metacognitive processes that promote student regulation of the learning process. Construct validity and reliability of each of the four domains were well supported by the results. Significant DIF was not detected in student-educator and gender. Conclusions: The RoLOTS successfully evaluated whether a faculty member is familiar with pedagogical tools to promote medical students’ self-directed learning, which can be used as a first step in needs-based professional development. Further research is needed to provide more validity and reliability evidence among groups with diverse SDL experience.
Probabilistic target definition and planning in patients with prostate cancer

Intro. Current radiation therapy (RT) planning guidelines handle uncertainties in RT using geometric margins. This approach is simple to use but oversimplifies complex underlying processes and is cumbersome for non-homogeneous dose prescriptions. In this work, we characterize the performance of a novel probabilistic target definition and planning (PTP) approach, which uses voxel-level tumor likelihood information in treatment plan optimization. Methods. We expanded a treatment planning system with probabilistic therapy planning functionality that utilizes non-binary target maps (TM) as voxel-level input to dose plan optimization. Different dose plans were calculated and compared for twelve prostate cancer patients with multiparametric magnetic resonance imaging derived TMs. Dose plans were created using both classical and PTP approaches for uniform and integrated dose boost prescriptions. Dose performance between the different approaches was compared using dose benchmarks on target and organ-at-risk (OAR) volumes. Results. Over all dose metrics, PTP was shown to be comparable to classical planning. For plans of uniform dose prescription, the PTP approach created plans within 1 Gy of the classical planning approach across all dose metrics, with no significant differences (p > 0.2). For plans with the integrated dose boost, PTP plans exhibited higher dose heterogeneity, but still showed target doses comparable to the classical approach, without increasing doses to OAR. Conclusion. In this work we introduce direct incorporation of probabilistic target definition into treatment planning. This treatment planning approach can produce both uniform dose plans and plans with integrated dose boosts that are comparable to ones created using classical dose planning. PTP is a flexible way to optimize external beam radiotherapy, as it is not limited by the use of margins. PTP can produce dose plans equivalent to classical planning, while also allows for greater versatility in dose prescription and direct incorporation of patient target definition uncertainty into treatment planning.
Comparing Continuous and Binary Group-based Trajectory Modeling Using Statin Medication Adherence Data

Supplemental Digital Content is available in the text. Background: Of 58 medication adherence group-based trajectory modeling (GBTM) published studies, 74% used binary and 26% used continuous GBTM. Few studies provided a rationale for this choice. No medication adherence studies have compared continuous and binary GBTM. Objective: The objective of this study was to assess whether continuous versus binary GBTM: (1) impacts adherence trajectory shapes; and (2) results in the differential classification of patients into adherence groups. Methods: Patients were prevalent statin users with myocardial infarction hospitalization, 66+ years old, and continuously enrolled in fee-for-service Medicare. Statin medication adherence was measured 6 months prehospitalization using administrative claims. Final GBTM specifications beyond default settings were selected using a previously defined standardized procedure and applied separately to continuous and binary (proportion of days covered ≥0.80) medication adherence measures. Assignment to adherence groups was compared between continuous and binary models using percent agreement of patient classification and the κ coefficient. Results: Among 113,296 prevalent statin users, 4 adherence groups were identified in both models. Three groups were consistent: persistently adherent, progressively nonadherent, and persistently nonadherent. The fourth continuous group was moderately adherent (progressively adherent in the binary model). When comparing patient assignment into adherence groups between continuous and binary trajectory models, only 78.4% of patients were categorized into comparable groups (κ=0.641; 95% confidence interval: 0.638–0.645). The agreement was highest in the persistently adherent group (∼94%). Conclusions: Continuous and binary trajectory models are conceptually different measures of medication adherence. The choice between these approaches should be guided by study objectives and the role of medication adherence within the study—exposure, outcome, or confounder.
Association Between Systemic Inflammation and Individual Symptoms of Depression: A Pooled Analysis of 15 Population-Based Cohort Studies.

OBJECTIVE Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to the differing symptom-specific effects of inflammation. Accordingly, the authors explored the associations between systemic inflammation and an array of individual symptoms of depression across multiple studies. METHODS This random-effects pooled analysis included 15 population-based cohorts and 56,351 individuals age 18 years and older. Serum or plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at baseline. Using validated self-report measures, 24 depressive symptoms were ascertained in 15 cross-sectional studies, and, in seven cohorts, were also assessed at follow-up (mean follow-up period, 3.2 years). RESULTS The prevalence of depressive symptoms ranged from 1.1% (suicidal ideation) to 21.5% (sleep problems). In cross-sectional analyses, higher concentrations of CRP were robustly associated with an increased risk of experiencing four physical symptoms (changes in appetite, felt everything was an effort, loss of energy, sleep problems) and one cognitive symptom (little interest in doing things). These associations remained after adjustment for sociodemographic variables, behavioral factors, and chronic conditions; in sex- and age-stratified analyses; in longitudinal analyses; when using IL-6 as the inflammatory marker of interest; in depressed individuals; and after excluding chronically ill individuals. For four exclusively emotional symptoms (bothered by things, hopelessness about the future, felt fearful, life had been a failure), the overall evidence was strongly against an association with inflammation. CONCLUSIONS These findings suggest symptom-specific rather than generalized effects of systemic inflammation on depression. Future trials exploring anti-inflammatory treatment regimens for depression may benefit from targeting individuals presenting with symptom profiles characterized by distinct inflammation-related physical and cognitive symptoms.
Native plants facilitate vegetation succession on amended and unamended mine tailings

Abstract Facilitating the establishment of native pioneer plant species on mine tailings with inherent metal and/or acid tolerance is important to speed up natural succession at minimal cost, especially in remote areas where phytoremediation can be labor intensive. We investigated vegetation community dynamics after ∼48 years of succession along two legacy Ni–Cu mine tailings and waste rock deposits in the Sudbury Basin, Ontario, Canada with and without various site amendments (i.e. liming and fertilization) and planting. Metal/acid tolerant pioneer plants (Betula papyrifera, Populus tremuloides, Pohlia nutans) appeared to facilitate the establishment of less tolerant species. Conifers and nitrogen-fixers less tolerant to site conditions were planted at the fully amended (limed, fertilized, planted) mine tailings site in the 1970s, but conifers were not propagating at the site or facilitating understory succession. The planted nitrogen-fixing leguminous species Lotus corniculatus was, however, associated with increased diversity. These findings have implications for long-term reclamation strategies in acidic mine waste deposits utilizing native species, as primary colonizing tree species are only recently emerging as candidates for phytoremediation. Novelty statement The potential for native species to act as facilitators for vegetation colonization has rarely been investigated on tailings, despite wide use in remediation of less toxic sites. This study provides a retrospective of over 40 years of plant growth following initial treatment of toxic tailings. We observed that regardless of tailings geochemical conditions, acid/metal tolerant pioneer plants were facilitating ecological succession on acidic Ni-Cu mine tailings sites.
Targeting Fc Receptor-Mediated Effects and the “Don't Eat Me” Signal with an Oncolytic Virus Expressing an Anti-CD47 Antibody to Treat Metastatic Ovarian Cancer

Purpose: mAbs blocking immune checkpoints have emerged as important cancer therapeutics, as exemplified by systemic administration of the IgG1 anti-CD47 mAb that blocks the “don't eat me” pathway. However, this strategy is associated with severe toxicity. Experimental Design: To improve therapeutic efficacy while reducing toxicities for ovarian cancer, we engineered an oncolytic herpesvirus (oHSV) to express a full-length, soluble anti-CD47 mAb with a human IgG1 scaffold (OV-αCD47-G1) or IgG4 scaffold (OV-αCD47-G4). Results: Both IgG1 and IgG4 anti-CD47 mAbs secreted by oHSV-infected tumor cells blocked the CD47–SIRPα signal pathway, enhancing macrophage phagocytosis against ovarian tumor cells. OV-αCD47-G1, but not OV-αCD47-G4, activated human NK-cell cytotoxicity and macrophage phagocytosis by binding to the Fc receptors of these cells. In vivo, these multifaceted functions of OV-αCD47-G1 improved mouse survival in xenograft and immunocompetent mouse models of ovarian cancer when compared with OV-αCD47-G4 and a parental oHSV. The murine counterpart of OV-αCD47-G1, OV-αmCD47-G2b, also enhanced mouse NK-cell cytotoxicity and macrophage phagocytosis and prolonged survival of mice bearing ovarian tumors compared with OV-αmCD47-G3. OV-αmCD47-G2b was also superior to αmCD47-G2b and showed a significantly better effect when combined with an antibody against PD-L1 that was upregulated by oHSV infection. Conclusions: Our data demonstrate that an oHSV encoding a full-length human IgG1 anti-CD47 mAb, when used as a single agent or combined with another agent, is a promising approach for improving ovarian cancer treatment via enhancing innate immunity, as well as performing its known oncolytic function and modulation of immune cells.
Intracerebral transplantation of autologous adipose‐derived stem cells for chronic ischemic stroke: A phase I study

Current therapy does not provide significant benefits for patients with chronic stroke. Pre‐clinical studies suggested that autologous adipose‐derived stem cells have benefits for the treatment of chronic stroke. This Phase I open‐label study was conducted to demonstrate the safety and efficacy of autologous adipose‐derived stem cells (GXNPC1) in chronic stroke. Three patients with chronic stroke were treated with stereotactic implantation of autologous adipose‐derived stem cells (1 × 108 cells). The primary endpoints of safety evaluation included adverse events, over a 6 months post‐implantation period. The secondary endpoints included improvements in neurological functions. Evolutional change of brain parenchyma was also followed with magnetic resonance imaging (MRI). All three participants improved significantly at 6 months follow‐up. The extent of improvement from pre‐treatment was: National Institutes of Health Stroke Scale improved 5‐15 points, Barthel Index: 25–50 points, Berg balance scale 0–21 points and Fugl‐Meyer modified sensation 3–28 points. All three patients had signal change along the implantation tract on MRI one month after surgery. There is no related safety issue through 6 months observation. Clinical measures of neurological symptoms of these patients with chronic stroke improved at 6 months without adverse effects after implantation of autologous adipose‐derived stem cells (GXNPC1), which might be correlated with post‐implantation changes on brain MRI.
Feasibility of administering the WAIS-IV using a home-based telehealth videoconferencing model

Abstract Objective: Use of telehealth to deliver neuropsychological services has proven to be a feasible approach, however, there is limited research which has examined the reliability of home-based assessment models using a comprehensive intelligence test. The aim of this study was to examine the reliability and feasibility of a home-based videoconferencing administration of the Wechsler Adult Intelligence Scales-4th Edition (WAIS-IV). Method: Thirty healthy participants (aged 18–40 years) completed the WAIS-IV both in-person and via home-based videoconferencing utilizing a randomized counter-balanced methodology to attempt to control for an order effect. Paper record forms for Coding/Symbol Search and Blocks were sent and returned via tamper proof courier packs. Participants completed an online survey of their experiences of TNP following completion of their assessments. Group mean comparisons, intra class correlation coefficients (ICCs) and Bland-Altman measures of bias were calculated. Results: Findings from both modalities were highly concordant across all WAIS-IV subtests and indices, with all ICCs rated as “excellent,” (≥0.9). There were no significant mean group differences and no evidence of proportional bias. The majority of participants were very satisfied with the use of videoconferencing as an application for cognitive assessment and high levels of participant compliance were observed. Conclusions: In this non-clinical cohort home-based videoconference administration of the WAIS-IV was feasible, reliable and acceptable. TNP may offer an alternative for those consumers where there are challenges in accessing a face-to-face service delivery model, thereby improving equity, and enabling continuation of service delivery. Future research is needed with a larger and more ethnically diverse clinical population.
NCATS Inxight Drugs: a comprehensive and curated portal for translational research

The United States has a complex regulatory scheme for marketing drugs. Understanding drug regulatory status is a daunting task that requires integrating data from many sources from the United States Food and Drug Administration (FDA), US government publications, and other processes related to drug development. At NCATS, we created Inxight Drugs (https://drugs.ncats.io), a web resource that attempts to address this challenge in a systematic manner. NCATS Inxight Drugs incorporates and unifies a wealth of data, including those supplied by the FDA and from independent public sources. The database offers a substantial amount of manually curated literature data unavailable from other sources. Currently, the database contains 125 036 product ingredients, including 2566 US approved drugs, 6242 marketed drugs, and 9684 investigational drugs. All substances are rigorously defined according to the ISO 11238 standard to comply with existing regulatory standards for unique drug substance identification. A special emphasis was placed on capturing manually curated and referenced data on treatment modalities and semantic relationships between substances. A supplementary resource 'Novel FDA Drug Approvals' features regulatory details of newly approved FDA drugs. The database is regularly updated using NCATS Stitcher data integration tool that automates data aggregation and supports full data access through a RESTful API.
Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER+/HER2− Breast Cancer

Purpose: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER+/HER2− breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers. Experimental Design: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1. Results: Higher baselines ER and PgR were significantly associated with a greater chance of complete cell-cycle arrest (CCCA: Ki67 <2.7%) at 14 weeks and higher baseline Ki67, c-PARP, and CCNE1 with a lower chance. The interaction with treatment was significant only for c-PARP. CCND1 levels were decreased c.20% by letrozole at 2 and 14 weeks but showed a tendency to increase with palbociclib. CCNE1 levels fell 82% (median) in tumors showing CCCA but were unchanged in those with no CCCA. Only 2/9 tumors showed CCCA 3–9 days after stopping palbociclib. ESR1 mutations were found in 2/4 tumors for which surgery took place ≥6 months after starting treatment. Conclusions: High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3–9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the “off” week of its schedule.