Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of algorithmic dementia ascertainment for racial/ethnic disparities research in the U.S. Health and Retirement Study.

BACKGROUND Disparities research in dementia is limited by lack of large, diverse, and representative samples with systematic dementia ascertainment. Algorithmic diagnosis of dementia offers a cost-effective alternate approach. Prior work in the nationally-representative Health and Retirement Study (HRS) has demonstrated that existing algorithms are ill-suited for racial/ethnic disparities work given differences in sensitivity and specificity by race/ethnicity. METHODS We implemented traditional and machine learning methods to identify an improved algorithm that (a) had ≤5 percentage point difference in sensitivity and specificity across racial/ethnic groups, (b) achieved ≥80% overall accuracy across racial/ethnic groups, and (c) achieved ≥75% sensitivity and ≥90% specificity overall. Final recommendations were based on robustness, accuracy of estimated race/ethnicity-specific prevalence and prevalence ratios compared to those using in-person diagnoses, and ease of use. RESULTS We identified six algorithms that met our pre-specified criteria. Our three recommended algorithms achieved ≤3 percentage point difference in sensitivity and ≤5 percentage point difference in specificity across racial/ethnic groups, as well as 77%-83% sensitivity, 92-94% specificity, and 90-92% accuracy overall in analyses designed to emulate out-of-sample performance. Pairwise prevalence ratios between non-Hispanic whites, non-Hispanic blacks, and Hispanics estimated by application of these algorithms are within 1% to 10% of prevalence ratios estimated based on in-person diagnoses. CONCLUSIONS We believe these algorithms will be of immense value to dementia researchers interested in racial/ethnic disparities. Our process can be replicated to allow minimally biasing algorithmic classification of dementia for other purposes.
Establishing Preferred Product Characterization for the Evaluation of RNA Vaccine Antigens

The preferred product characteristics (for chemistry, control, and manufacture), in addition to safety and efficacy, are quintessential requirements for any successful therapeutic. Messenger RNA vaccines constitute a relatively new alternative to traditional vaccine development platforms, and thus there is less clarity regarding the criteria needed to ensure regulatory compliance and acceptance. Generally, to identify the ideal product characteristics, a series of assays needs to be developed, qualified and ultimately validated to determine the integrity, purity, stability, and reproducibility of a vaccine target. Here, using the available literature, we provide a summary of the array of biophysical and biochemical assays currently used in the field to characterize mRNA vaccine antigen candidates. Moreover, we review various in vitro functional cell-based assays that have been employed to facilitate the early assessment of the biological activity of these molecules, including the predictive immune response triggered in the host cell. Messenger RNA vaccines can be produced rapidly and at large scale, and thus will particularly benefit from well-defined and well-characterized assays ultimately to be used for in-process, release and stability-indications, which will allow equally rapid screening of immunogenicity, efficacy, and safety without the need to conduct often lengthy and costly in vivo experiments.
Benefits of High Resolution PM2.5 Prediction using Satellite MAIAC AOD and Land Use Regression for Exposure Assessment: California Examples.

This study estimated annual average ambient fine particulate matter (PM2.5) concentrations at 1 km resolution using satellite Multi-Angle Implementation of Atmospheric Correction (MAIAC) aerosol optical depth (AOD), land use parameters, and meteorology in California for the year 2016 [cross-validation R2= 0.73 (site-based) and 0.81 (observation-based)]. Using these high-resolution PM2.5 estimates, regionally varying urban enhancements of PM2.5 concentrations, 1.43-2.77 µg/m3 (23.9-36.2%), were identified in the densely populated air basins of San Francisco Bay Area, San Joaquin Valley, and South Coast. On the other hand, within-urban PM2.5 variability was found to be 31.4-35.6% of between-urban variability across California. However, this pattern was not consistent from region to region, even showing higher within-urban variability (e.g., San Francisco Bay Area). In addition, satellite-based PM2.5 concentrations were statistically significantly associated with demographic factors (i.e., % people of color, % poverty, and % low education) with the strongest positive association with % people of color (1.05 and 2.72 µg/m3 increases per interquartile range (IQR) and range increases, respectively). The fine-scale PM2.5 estimates enabled the assessment of long-term PM2.5 exposures for all populations particularly benefitting rural populations and socially vulnerable populations widely distributed in each urban area. This study provided evidence of regionally varying exposure misclassification that would arise without accounting for rural and within-urban exposure variabilities.
Impaired interactions among white‐matter functional networks in antipsychotic‐naive first‐episode schizophrenia

Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white‐matter fibers in the brain. However, few studies have focused on white‐matter functional changes in schizophrenia. Considering that converging evidence suggests that white‐matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white‐matter network‐level interactions in antipsychotic‐naive first‐episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white‐matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network‐level interactions among these 11 white‐matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network‐based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white‐matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white‐matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white‐matter functional abnormalities.
Endometrial Gastric (Gastrointestinal)-type Mucinous Lesions

Supplemental Digital Content is available in the text. With the recent elucidation of gastric-type lesions in the female genital tract (especially in the cervix), occasional cases of endometrial adenocarcinoma displaying gastric (gastrointestinal) differentiation have been reported, but they are currently not recognized as a distinct pathologic entity. We report 9 cases of endometrial mucinous lesions which exhibit gastric (gastrointestinal)-type features by morphology and immunohistochemistry, including 4 adenocarcinomas and 5 benign mucinous lesions, in patients aged 32 to 85. The adenocarcinomas showed gastric-type morphology in all 4 cases and goblet cells in 1, with a component of benign gastric-type mucinous glands in 1 case. Immunohistochemically, the adenocarcinomas were positive for CK7 (4/4), CEA (4/4), MUC6 (3/3), PAX8 (3/4), CK20 (2/4), CDX2 (2/4), and estrogen receptor (1/4). They were negative for Napsin A (0/3), with mutation-type p53 staining in 2/4 cases, block-type p16 positivity in 1/4, and scattered chromogranin-positive cells in 1/2. Targeted next-generation sequencing revealed nonsense mutation in RB1 gene for the case with block-positive p16. Follow-up was available in all adenocarcinoma cases and indicated aggressive behavior; 2 patients were dead of disease at follow-up of 7 months to 3 years, 1 was alive with progression at 9 months, and 1 was alive without disease at 7 months. The benign mucinous lesions (including the benign component in 1 adenocarcinoma) exhibited gastric-type morphologic features in 5/6 cases, goblet cells in 5/6, and Paneth-like neuroendocrine cells in 1/6. These benign mucinous lesions were associated with an endometrial polyp in 5/6 cases. Cytologic atypia was present in 2/6 cases and a lobular architecture resembling cervical lobular endocervical glandular hyperplasia in 4/6. Immunohistochemically, the benign mucinous lesions were positive for CK7 (5/5), CDX2 (5/6), estrogen receptor (4/5), MUC6 (4/5), CK20 (3/5), PAX8 (3/5), and CEA (2/4), with scattered chromogranin-positive cells in 4/4 cases; in all cases tested Napsin A was negative, p53 was wild-type and p16 was negative. We propose the term “endometrial gastric (gastrointestinal)-type adenocarcinoma” for this distinctive group of rare aggressive endometrial carcinomas. We believe that benign or atypical gastric (gastrointestinal)-type mucinous lesions are putative precursors for these adenocarcinomas, comparable to recognized premalignant gastric-type lesions in the cervix and the vagina. Future recognition and reporting of these gastric-type endometrial mucinous lesions will help delineate their pathogenesis and clinical significance.
Antifibrotic efficacy of nintedanib in a cellular model of systemic sclerosis-associated interstitial lung disease.

OBJECTIVES Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%. Recently, nintedanib has been reported to exert anti-fibrotic activity on systemic sclerosis (scleroderma, SSc) skin fibroblasts and to diminish skin and lung fibrosis in mouse models. The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD). METHODS Study was performed using lung fibroblasts (LF) isolated from five patients with SSc-ILD and from three control subjects. RESULTS Nintedanib inhibited LF proliferation and migration in a concentration- and time-dependent manner. The proliferation rate of LF stimulated with PDGF in the presence of nintedanib was reduced 1.9-fold within 24 h as compared to cells stimulated with PDGF alone. Migration of SSc-ILD LF incubated with 100 nM nintedanib was reduced from 62.8±12.5% to 39.1±9.0% in the presence of PDGF and from 38.2±7.9% to 26.6±7.2% in serum-free medium. Nintedanib attenuated PDGF-induced Ca2+ efflux, reduced α-SMA promoter activity and α-SMA protein expression. Furthermore, nintedanib blocked PDGF-induced differentiation of normal LF to myofibroblasts, reduced production of collagen and fibronectin, and decreased contractility of SSc-ILD LF in both floating and fixed collagen gels. CONCLUSIONS Our data demonstrate significant antifibrotic efficacy of nintedanib in SSc-ILD LF suggesting that nintedanib has the potential not only to prevent but also to reverse the increased activity of LF consequently attenuating excessive lung fibrosis observed in SSc-ILD.
Experimental Models to Define the Genetic Predisposition to Liver Cancer

Hepatocellular carcinoma (HCC) is a frequent human cancer and the most frequent liver tumor. The study of genetic mechanisms of the inherited predisposition to HCC, implicating gene–gene and gene–environment interaction, led to the discovery of multiple gene loci regulating the growth and multiplicity of liver preneoplastic and neoplastic lesions, thus uncovering the action of multiple genes and epistatic interactions in the regulation of the individual susceptibility to HCC. The comparative evaluation of the molecular pathways involved in HCC development in mouse and rat strains differently predisposed to HCC indicates that the genes responsible for HCC susceptibility control the amplification and/or overexpression of c-Myc, the expression of cell cycle regulatory genes, and the activity of Ras/Erk, AKT/mTOR, and of the pro-apoptotic Rassf1A/Nore1A and Dab2IP/Ask1 pathways, the methionine cycle, and DNA repair pathways in mice and rats. Comparative functional genetic studies, in rats and mice differently susceptible to HCC, showed that preneoplastic and neoplastic lesions of resistant mouse and rat strains cluster with human HCC with better prognosis, while the lesions of susceptible mouse and rats cluster with HCC with poorer prognosis, confirming the validity of the studies on the influence of the genetic predisposition to hepatocarinogenesis on HCC prognosis in mouse and rat models. Recently, the hydrodynamic gene transfection in mice provided new opportunities for the recognition of genes implicated in the molecular mechanisms involved in HCC pathogenesis and prognosis. This method appears to be highly promising to further study the genetic background of the predisposition to this cancer.
Binocular Light-Field: Imaging Theory and Occlusion-Robust Depth Perception Application

Binocular stereo vision (SV) has been widely used to reconstruct the depth information, but it is quite vulnerable to scenes with strong occlusions. As an emerging computational photography technology, light-field (LF) imaging brings about a novel solution to passive depth perception by recording multiple angular views in a single exposure. In this paper, we explore binocular SV and LF imaging to form the binocular-LF imaging system. An imaging theory is derived by modeling the imaging process and analyzing disparity properties based on the geometrical optics theory. Then an accurate occlusion-robust depth estimation algorithm is proposed by exploiting multi-baseline stereo matching cues and defocus cues. The occlusions caused by binocular SV and LF imaging are detected and handled to eliminate the matching ambiguities and outliers. Finally, we develop a binocular-LF database and capture real-world scenes by our binocular-LF system to test the accuracy and robustness. The experimental results demonstrate that the proposed algorithm definitely recovers high quality depth maps with smooth surfaces and precise geometric shapes, which tackles the drawbacks of binocular SV and LF imaging simultaneously.
Less Pain and Reduced Risk of Early Postoperative Ileus After Clipless Versus Conventional Laparoscopic Appendectomy

Laparoscopic appendectomy (LA) is perceived as a procedure requiring a short hospital stay; however, some patients require prolonged hospitalization because of postoperative ileus and pain; therefore, we introduced clipless LA, using only an ultrasonic energy device only for coagulation. A total of 1013 patients (clipless LA; n=290 and conventional LA; n=723) who underwent LA at our hospital between January 2015 and February 2018 were analyzed. The mean operative time was shorter (P<0.001), and postoperative pain score at 24 hours was lower (P<0.001) for clipless than for conventional LA. There were no significant differences in postoperative complications, except with regard to early postoperative ileus (clipless LA; 18.1% vs. conventional LA; 31.6%, P=0.025), and the operative method had significantly influenced early postoperative ileus (relative risk, 0.505; 95% confidence interval, 0.257-0.994; P=0.048). Clipless LA is comparable to conventional LA with regard to operative safety but results in significantly less pain and postoperative ileus.
The Changing Nature of Palliative Care: Implications for Allied Health Professionals’ Educational and Training Needs

CareSearch is an Australian Government Department of Health funded repository of evidence-based palliative care information and resources. The CareSearch Allied Health Hub was developed in 2013 to support all allied health professionals working with palliative care clients in all clinical settings. This cross-sectional online survey sought to elicit allied health professionals palliative care experiences and subsequent considerations for educational and clinical practice needs. The survey was disseminated nationally via a range of organisations. Data was collected about palliative care knowledge, experience working with palliative care clients and professional development needs. Data were evaluated by profession, experience and practice setting. In total, 217 respondents answered one or more survey questions (94%). Respondents (65%) reported seeing >15 palliative care clients per month with 84% seen in hospital and community settings. Undergraduate education underprepared or partially prepared allied health professionals to work with these clients (96%) and 67% identified the need for further education. Access to postgraduate professional development was limited by available backfill and funding. Study findings support the importance of free, accessible, relevant educational and professional development resources to support clinical practice. This is particularly relevant for allied health professionals who have limited opportunities to attend formal professional development sessions.
rs34567942 a Novel Susceptibility Single Nucleotide Polymorphism for Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients.

imputation of SNPs, multi-allelic markers, amino acids, and classical HLA alleles using validated SNP2HLA pipelines were performed. Preliminary results in a subset of samples with HLA serology data showed that accuracy is very high for HLA-A, -B, -DRB1, and DQB1 (> 95%), and high for HLA-C (90%) in Europeans. Manhattan plots were generated using the R package qqman SNPs were queried against dbSNP and the ensembl variation database (http:// The results were combined with annotation results obtained snpEff
Association of hypertriglyceridemic waist-to-height ratio and its dynamic status with incident hypertension: the Rural Chinese Cohort Study.

OBJECTIVE We aimed to evaluate whether hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status was associated with hypertension (HTN). METHODS We examined data for 10 312 nonhypertensive participants aged at least 18 years from the Rural Chinese Cohort Study at the baseline examination who were followed until 2014 with a median follow-up of 6 years. HWHtR was defined by combined triglyceride level and waist-to-height ratio (WHtR). Multiple logistic regression models were used to examine the probability of incident HTN according to HWHtR and its transformation, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS A total of 127 men and 225 women with high triglyceride level and high WHtR (HTHWH) had incident HTN during follow-up. After adjusting for potential confounders, the probability of HTN was increased with HTHWH for men [OR 1.49 (95% CI 1.01-2.20)] but this association was not significant for women [1.21 (0.88-1.66)]. The results of the sensitivity analyses were robust for men and women. The ORs were generally consistent on subgroup analysis by age,BMI, SBP and DBP for men. As compared with persistent normal triglyceride level and normal WHtR (NTNWH), the transformation from baseline NTNWH to follow-up HTHWH was associated with increased probability of HTN for men [OR 4.16 (95% CI 2.21-7.84)]. However, for women, the association of changed HWHtR from baseline to follow-up with probability of HTN was not significant for almost all transformation groups. CONCLUSION HWHtR and its dynamic status was associated with incident HTN for rural Chinese men. From this cohort study, HWHtR may be an indicator for interventions aiming to reduce HTN among these men.
A Rabbit Model of Osteochondral Regeneration Using Three-Dimensional Printed Polycaprolactone-Hydroxyapatite Scaffolds Coated with Umbilical Cord Blood Mesenchymal Stem Cells and Chondrocytes

Background This study aimed to investigate a rabbit model of osteochondral regeneration using three-dimensional (3-D) printed polycaprolactone-hydroxyapatite (PCL-HA) scaffolds coated with umbilical cord blood mesenchymal stem cells (UCB-MSCs) and chondrocytes. Material/Methods Nine female New Zealand white rabbits were included in the study. The 3-D PCL-HA scaffolds were prepared using fused deposition modeling 3-D printing technology. Seeding cells were prepared by co-culture of rabbit UCB-MSCs and chondrocytes with a ratio of 3: 1. A total of 4×106 cells were seeded on 3-D PCL-HA scaffolds and implanted into rabbits with femoral trochlear defects. After 8 weeks of in vivo implantation, 12 specimens were sampled and examined using histology and scanning electron microscopy (SEM). The International Cartilage Repair Society (ICRS) macroscopic scores and histological results were recorded and compared with those of the unseeded PCL-HA scaffolds. Results Mean ICRS scores for the UCB-MSCs and chondrocyte-seeded PCL-HA scaffolds (group A) were significantly higher than the normal unseeded control (NC) PCL-HA scaffold group (group B) (P<0.05). Histology with safranin-O and fast-green staining showed that the UCB chondrocyte-seeded PCL-HA scaffolds significantly promoted bone and cartilage regeneration. Conclusions In a rabbit model of osteochondral regeneration using 3-D printed PCL-HA scaffolds, the UCB chondrocyte-seeded PCL-HA scaffold promoted articular cartilage repair when compared with the control or non-seeded PCL-HA scaffolds.
Developing pathways to clarify pathogenicity of unclassified variants in Osteogenesis Imperfecta genetic analysis

With increased access to genetic testing, variants of uncertain significance (VUS) where pathogenicity is uncertain are being increasingly identified. More than 85% Osteogenesis Imperfecta (OI) patients have pathogenic variants in COL1A1/A2. However, when a VUS is identified, there are no pathways in place for determining significance.
Early Alterations of Subchondral Bone in the Rat Anterior Cruciate Ligament Transection Model of Osteoarthritis

Objective Advances in research have shown that the subchondral bone plays an important role in the propagation of cartilage loss and progression of osteoarthritis (OA), but whether the subchondral bone changes precede or lead to articular cartilage loss remains debatable. In order to elucidate the subchondral bone and cartilage changes that occur in early OA, an experiment using anterior cruciate ligament transection (ACLT) induced posttraumatic OA model of the rat knee was conducted. Design Forty-two Sprague Dawley rats were divided into 2 groups: the ACLT group and the nonoperated control group. Surgery was conducted on the ACLT group, and subsequently rats from both groups were sacrificed at 1, 2, and 3 weeks postsurgery. Subchondral bone was evaluated using a high-resolution peripheral quantitative computed tomography scanner, while cartilage was histologically evaluated and scored. Results A significant reduction in the subchondral trabecular bone thickness and spacing was found as early as 1 week postsurgery in ACLT rats compared with the nonoperated control. This was subsequently followed by a reduction in bone mineral density and bone fractional volume at week 2, and finally a decrease in the trabecular number at week 3. These changes occurred together with cartilage degeneration as reflected by an increasing Mankin score over all 3 weeks. Conclusions Significant changes in subchondral bone occur very early in OA concurrent with surface articular cartilage degenerative change suggest that factors affecting bone remodeling and resorption together with cartilage matrix degradation occur very early in the disease.