Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of Cstb duplication on APP/amyloid-β pathology and cathepsin B activity in a mouse model

People with Down syndrome (DS), caused by trisomy of chromosome 21 have a greatly increased risk of developing Alzheimer’s disease (AD). This is in part because of triplication of a chromosome 21 gene, APP. This gene encodes amyloid precursor protein, which is cleaved to form amyloid-β that accumulates in the brains of people who have AD. Recent experimental results demonstrate that a gene or genes on chromosome 21, other than APP, when triplicated significantly accelerate amyloid-β pathology in a transgenic mouse model of amyloid-β deposition. Multiple lines of evidence indicate that cysteine cathepsin activity influences APP cleavage and amyloid-β accumulation. Located on human chromosome 21 (Hsa21) is an endogenous inhibitor of cathepsin proteases, CYSTATIN B (CSTB) which is proposed to regulate cysteine cathepsin activity in vivo. Here we determined if three copies of the mouse gene Cstb is sufficient to modulate amyloid-β accumulation and cathepsin activity in a transgenic APP mouse model. Duplication of Cstb resulted in an increase in transcriptional and translational levels of Cstb in the mouse cortex but had no effect on the deposition of insoluble amyloid-β plaques or the levels of soluble or insoluble amyloid-β42, amyloid-β40, or amyloid-β38 in 6-month old mice. In addition, the increased CSTB did not alter the activity of cathepsin B enzyme in the cortex of 3-month or 6-month old mice. These results indicate that the single-gene duplication of Cstb is insufficient to elicit a disease-modifying phenotype in the dupCstb x tgAPP mice, underscoring the complexity of the genetic basis of AD-DS and the importance of multiple gene interactions in disease.
CHARMM-GUI LBS Finder & Refiner for Ligand Binding Site Prediction and Refinement

A protein performs its task by binding a variety of ligands in its local region that is also known as the ligand-binding-site (LBS). Therefore, accurate prediction, characterization, and refinement of LBS can facilitate protein functional annotations and structure-based drug design. In this work, we present CHARMM-GUI LBS Finder & Refiner (https://www.charmm-gui.org/input/lbsfinder) that predicts potential LBS, offers interactive features for local LBS structure analysis, and prepares various molecular dynamics (MD) systems and inputs by setting up distance restraint potentials for LBS structure refinement. LBS Finder & Refiner supports 5 different commonly used simulation programs, such as NAMD, AMBER, GROMACS, GENESIS, and OpenMM, for LBS structure refinement together with hydrogen mass repartitioning. The capability of LBS Finder & Refiner is illustrated through LBS structure predictions and refinements of 48 modeled and 20 apo benchmark target proteins. Overall, successful LBS structure predictions and refinements are seen in our benchmark tests. We hope that LBS Finder & Refiner is useful to predict, characterize, and refine potential LBS on any given protein of interest.
Ending the HIV epidemic using National HIV Behavioral Surveillance (NHBS): Recommendations based on DC model

Introduction Social network strategies have been used by health departments to identify undiagnosed cases of HIV. Heterosexual cycle (HET4) of National HIV Behavioral Surveillance (NHBS) is a social network strategy implemented in jurisdictions. The main objectives of this research are to 1) evaluate the utility of the NHBS HET cycle data for network analysis; 2) to apply statistical analysis in support of previous HIV research, as well as to develop new research results focused on demographic variables and prevention/intervention with respect to heterosexual HIV risk; and 3) to employ NHBS data to inform policy with respect to the EHE plan. Method We used data from the 2016 NHBS HET4 (DC). A total of 747 surveys were collected. We used the free social-network analysis package, GEPHI, for all network visualization using adjacency matrix representation. We additionally conducted logistic regression analysis to examine the association of selected variables with HIV status in three models representing 1) demographic and economic effects, 2) behavioral effects, and 3) prevention-intervention effects. Results The results showed 3% were tested positive. Seed 1 initiated the largest networks with 426 nodes (15 positives); seed 4 with 273 nodes (6 positives). Seed 3 had 35 nodes (2 positives). All 23 HIV diagnoses were recruited from 4 zip-codes across DC. The risk of testing positive was higher among people high-school dropouts (Relative Risk (RR) (25.645); 95 CI% 5.699, 115.987), unemployed ((4.267); 1.295, 14.064), returning citizens ((14.319); 4.593, 44.645). We also found in the final model higher association of pre-exposure prophylaxis (PrEP) awareness among those tested negative ((4.783); 1.042, 21.944) and HIV intervention in the past 12 months with those tested positive ((17.887); 2.350,136.135). Conclusion The network visualization was used to address the primary aim of the analysis-evaluate the success of the implementation of the NHBS as a social network strategy to find new diagnoses. NHBS remains one of the strongest behavioral supplements for DC’s HIV planning activities. As part of the evaluation process our analysis helps to understand the impact of demographic, behavioral, and prevention efforts on peoples’ HIV status. We strongly recommend other jurisdictions use network visualizations to evaluate the efficacy in reaching hidden populations.
Argumentation Analysis of Risk Assessments: The Case of Perfluorooctanoic Acid

Risk assessment of chemicals can be based on toxicology and/or epidemiology. The choice of toxicological or epidemiological data can result in different health‐based guidance values (HBGVs). Communicating the underlying argumentation is important to explain these differences to the public and policymakers. In this article, we explore the argumentation used to justify the use of toxicological or epidemiological data in the derivation of HBGVs in four different risk assessments for the chemical Perfluorooctanoic acid (PFOA). The pragma‐dialectical argumentation theory (PDAT) is hereby applied. The argumentations to select relevant health endpoints or certain studies to infer causality appeared mainly based on “symptomatic relations,” that is, study results are used as characteristic of what was claimed to be a causal relation without delving into the actual causal argumentation that preceded it. Starting points that are at the basis of the chain of arguments remained implicit. Argumentation to use epidemiological and/or toxicological data was only briefly mentioned and the underlying argumentative foundation that led to the conclusion was seldom found or not addressed at all. The decision to include/exclude information was made based on the availability of data, or the motives for the choice remained largely unclear. We conclude that more depth in argumentation and a subordinative chain of arguments is needed to better disclose the underlying reasoning leading to a certain health‐based guidance value (HBGV). More explicit identification and discussion of starting points could be a valuable addition to general risk assessment frameworks for maximum use of toxicological and epidemiological data and shared conclusions of the assessment.
Longitudinal analysis of client appointment adherence under Universal Test and Treat strategy: A stepped‐wedge trial

Universal Test and Treat (UTT) strategies are being adopted across sub‐Saharan Africa based on clinical benefits to morbidity and mortality and to attain targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS). Universal Test and Treat is expected to change the client population at clinics, due to more asymptomatic HIV clients initiating antiretroviral therapy (ART). We assessed the impact of UTT on client appointment adherence at 14 government‐managed health facilities in Eswatini's public sector health system.
Mediating effect of fear and externality of happiness in the association between psychological maltreatment and psychological well-being

ABSTRACT This study aims to explore whether psychological maltreatment predicts young adults’ psychological well-being through fear of happiness and externality of happiness. The current study included 490 young adults from a public university in an urban city in Turkey. Participants were 36% male, and they ranged in age from 18 to 39 years (M= 21.77, SD = 2.40). Findings from the study revealed that psychological maltreatment had a significant predictive effect on psychological well-being, fear of happiness, and externality of happiness. Further, fear of happiness and externality of happiness mediated the impact of psychological maltreatment on psychological well-being. These findings indicate that fear and externality of happiness are important sources that can help to explain the association between childhood psychological maltreatment and psychological well-being among young adults. Therefore, there is a need to design a more comprehensive prevention and intervention approach for improving people’s psychological well-being in the context of psychological maltreatment.
Combination of preoperative red cell distribution width and neutrophil to lymphocyte ratio as a prognostic marker for gastric cancer patients.

Background The neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width (RDW) play an important role in the prognosis of several cancers, but their prognostic value in patients with stage II-III gastric cancer (GC) is unclear. We aimed to evaluate the prognostic value of the RDW-NLR (R-NLR) score based on RDW and NLR in stage II-III GC patients after radical surgery. Methods Preoperative RDW and NLR clinicopathological data were retrospectively reviewed and analyzed from stage II-III GC patients who underwent radical gastrectomy. The optimal cut-off values for pre-RDW-variation coefficient (pre-RDW-cv) and pre-NLR were defined as 14.10% and 2.015, respectively. The R-NLR score was defined as 2 (both elevated RDW and NLR), 1 (one of these was elevated), or 0 (neither were elevated). Prognostic factors were identified by univariate and multivariate analyses. Results A total of 151 patients were included in this study, and 65 (43.05%), 54 (35.76%), and 32 (21.19%) patients had an R-NLR score of 0, 1 and 2, respectively. The preoperative R-NLR score was significantly correlated with tumor size and gender (all P<0.05). The 5-year overall survival (OS) in the R-NLR 0, 1, and 2 groups was 52.30%, 44.40%, and 31.20%, respectively (P=0.031), while the 5-year DFS was 47.70%, 13.30%, and 18.80%, respectively (P<0.001). Further, while the 5-year disease-free survival (DFS) rate was significantly improved in low RDW-cv and NLR patients compared with those with high RDW-cv and NLR (all P<0.05), but not OS (all P>0.05). Multivariate analysis demonstrated that the R-NLR score was independently correlated with OS [hazard ratio (HR), 1.527; P=0.007] and DFS (HR, 1.939; P=0.001). Conclusions We validated the preoperative R-NLR score to be a promising predictor for stage II-III GC patients who have undergone radical gastrectomy.
Visualization of Collagen–Mineral Arrangement using Atom Probe Tomography

Bone is a complex, hierarchical structure comprised of two distinct phases: the organic, collagen– rich phase and the inorganic mineral–rich phase. This collagen–mineral arrangement has implications for bone function, aging, and disease. However, strategies to extract a single mineralized collagen fibril to investigate the interplay between components with sufficient resolution have been mostly confined to in vitro systems that only approximate the biological environment or transmission electron microscopy studies with lower spatial and chemical resolution. Therefore, there is extensive debate over the location of mineral with respect to collagen in in vivo mineralized tissues as visualization and quantification of the mineral in a living system is difficult or impossible. Herein, we have developed an approach to artificially extract a single mineralized collagen fibril from bone to analyze its composition and structure atom-by-atom with 3D resolution and sub-nanometer accuracy using atom probe tomography. This enables, for the first time, a method to probe fibril-level mineralization and collagen–mineral arrangement from an in vivo system with both the spatial and chemical precision required to comment on collagen– mineral arrangement. Using atom probe tomography, 4D (spatial + chemical) reconstructed volumes of leporine bone were generated with accuracy from correlative scanning electron microscopy. Distinct, winding collagen fibrils were identified with mineralized deposits both encapsulating and incorporated into the collagenous structures. This work demonstrates a novel fibril-level detection method that can be used to probe structural and chemical changes of bone and contribute new insights to the debate on collagen–mineral arrangement in mineralized tissues such as bones, and teeth.
Sensory-Motor and Affective-Fatigue Factors are Associated with Symbol Digit Performance in Multiple Sclerosis

Abstract Objectives: The oral Symbol Digit Modalities Test (SDMT) has become the standard for the brief screening of cognitive impairment in persons with multiple sclerosis (PwMS). It has been shown to be sensitive to sensory-motor factors involving rudimentary oral motor speed and visual acuity, as well as multiple sclerosis (MS) affective-fatigue factors including depression, fatigue, and anxiety. The present study was designed to provide a greater understanding of these noncognitive factors that might contribute to the oral SDMT by examining all these variables in the same sample. Methods: We examined 50 PwMS and 49 healthy controls (HCs). All participants were administered the oral SDMT, two sensory-motor tasks (visual acuity and oral motor speed), and three affective-fatigue measures (depression, fatigue, and anxiety). Results: Partially consistent with hypotheses, we found that sensory-motor skills, but not affective-fatigue factors, accounted for some of the group differences between the MS and HC groups on the oral SDMT, reducing the MS/HC group variance predicted from 10% to 4%. Also, PwMS with below average sensory-motor abilities had oral SDMT scores that were lower than PwMS with intact sensory-motor skills (p < .05). Finally, 71% of PwMS in the below-average sensory-motor group were impaired on the oral SDMT compared with 14% of the intact group (p = .006). Conclusions: When the oral SDMT is used as the sole screening tool for cognitive impairment in MS, clinicians should know that limitations in visual acuity and rudimentary oral motor speed should be considered as possibly being associated with performance on it in MS.
Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

Abstract Flueggea suffruticosa is a traditional Chinese medicine that has been commonly used for the treatment of inflammatory ailments, including rheumatism and lumbago. Suffrutines A and suffrutines B are a pair of novel E,E and Z,E isomeric indolizidine alkaloids isolated from the roots of F. suffruticosa. However, their anti-inflammatory activity has not been reported thus far. The aim of this study was to investigate the inhibitory effect of inflammatory mediators and possible mechanisms of suffrutines A and B in lipopolysaccharide-induced RAW264.7 cells. Results showed that suffrutines A and B could remarkably inhibit the production of nitric oxide, prostaglandin E2, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in lipopolysaccharide-induced RAW264.7 cells. Further evaluation demonstrated that compared with suffrutines A, suffrutines B could more significantly inhibit the phosphorylation of IKKα/β, the degradation of IκBα, and the nuclear translocation of the p65 and p52 subunits in the canonical and non-canonical nuclear factor-κB pathways. Therefore, suffrutines B exhibited more potent inhibitory activity on inflammatory mediators than suffrutines A.
Asymptomatic morphometric vertebral fractures and its associated factors: A cross-sectional study among adults in a selected urban area in Selangor, Malaysia

Objective This study aimed to determine the prevalence of vertebral fractures (VF) in a selected urban population in Malaysia and to explore possible variables associated with VF in the study population. Methods A cross-sectional study involving community-living, healthy subjects aged between 45–90 years from the state of Selangor, Malaysia, were invited to attend a bone health check-up. Subjects with diseases known to affect bone metabolism or were on treatment for osteoporosis (OP) were excluded. Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry (DXA). Lateral and antero-posterior view lumbar spine x-rays were performed and VF was determined by the semi-quantitative Genant method. Results A total of 386 subjects were studied. Asymptomatic morphometric VF were found in 44 (11.4%) subjects. T12 was the most common vertebrae to be fractured. The prevalence of VF was significantly higher in menopausal women (12.4%) compared to non-menopausal women, in those above the age of 60 (18.5%), in those of Chinese ethnicity (16.5%), in those with a low body fat percentage (17.1%) and among those with OP (27.0%). The mean (standard deviation) 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in those with VF compared to those without VF, 67.64 (23.50) and 57.47 (21.71) nmol/L, respectively. However, after multiple regression analysis, age over 60 years and OP on DXA BMD measurement were the only significant associated factors for VF. Conclusion Overall, 11.4% of a selected Malaysian urban population had asymptomatic morphometric VF. Age over 60 years and OP on DXA BMD measurement, but not 25(OH)D levels, were associated with VF.
Effects of Electrical Automatic Massage on Cognition and Sleep Quality in Alzheimer's Disease Spectrum Patients: A Randomized Controlled Trial

Purpose Muscle relaxation following electrical automatic massage (EAM) has been found to reduce fatigue, depression, stress, anxiety, and pain in individuals with various conditions. However, the effects of EAM have not been extensively explored in patients with Alzheimer's disease (AD). Materials and Methods Here, we conducted a randomized controlled study to evaluate the effects of EAM on the cognitive and non-cognitive functions of patients with AD spectrum disorders. Results We found that EAM attenuated changes in attention-associated cognitive scores and subjective sleep quality relative to those in controls. Conclusion While further studies in a clinical setting are needed to support our findings, these encouraging results suggest that EAM may be an alternative therapy for the management of associated symptoms in AD (ClinicalTrials.gov ID: NCT03507192, 24/04/2018).
Personalized 0D‐1D multiscale hemodynamic modeling and wave dynamics analysis of cerebral circulation for an elderly patient with dementia

Senile dementia is associated with pronounced alterations in cerebral circulation. A fundamental understanding of intracranial hemodynamics and wave dynamics is essential for assessing dementia risk. Recent findings suggest that higher carotid artery wave intensity (WI) can predict future cognitive impairments in the elderly. However, wave power (WP) is more advantageous for assessing the risk of cognitive impairment and dementia because of its conservative form, which allows quantification of detailed WP distribution among the entire cerebrovascular network. Unfortunately, intracranial hemodynamics and wave dynamics in elderly patients with dementia remain poorly understood due to ethical issues and technical challenges. In this paper, we proposed a novel and easily achievable personalized methodology for the 0D‐1D model of cerebral circulation using widely available clinical data on transcranial Doppler ultrasonography velocity, cerebral artery anatomy from magnetic resonance imaging, and brachial artery pressure. Using the proposed model, we simulated the cerebral blood flows and compared the wave dynamics between a healthy elderly subject and one living with dementia. Moreover, we performed a variance‐based global sensitivity analysis to quantify the model‐predicted WI and WP sensitivity to the uncertainties of model inputs. This provided more precise information for model personalization and further insights into the wave dynamics of cerebral circulation. In conclusion, the proposed personalized model framework provides a practical approach for patient‐specific modeling and WI/WP analysis of cerebral circulation through noninvasive clinical data. The wave dynamics features of higher WI and lower WP in cerebral arteries may be an invaluable biomarker for assessing dementia risk.
Knot-Tying versus Knotless Suture Anchors for Arthroscopic Bankart Repair: A Comparative Study

Purpose This study aimed to compare the results of using knotless and knot-tying suture anchors in arthroscopic Bankart repair. Materials and Methods The patients who underwent arthroscopic Bankart repair between 2011 and 2017 using knot-tying and knotless suture anchors were retrospectively reviewed. We collected demographic data, clinical scores (pain visual analogue scale), functional visual analogue scale, American Shoulder and Elbow Society scores, and Rowe score), and range of motion (ROM). Re-dislocation and subjective anterior apprehension test rates between the two techniques were also analyzed. Results Of the 154 patients who underwent arthroscopic Bankart repair, 115 patients (knot-tying group: n=61 and knotless group: n=54) were included in this study. Of the 115 patients, 102 were male and 13 were female. The mean patient age was 27 years (range: 17–60), and the mean follow-up period was 43 months (range: 24–99). There were no significant differences in the final clinical scores and ROM between the two groups. Re-dislocation was observed in 6 (9.8%) and 4 (7.3%) patients in the knot-tying and knotless groups, respectively. Apprehension was observed in 11 (18.0%) and 12 (22.2%) patients in the knot-tying and knotless groups, respectively. There were no significant differences between the two groups in regards to re-dislocation and anterior apprehension. Conclusion Re-dislocation rates and clinical scores were similar with the use of knotless and knot-tying suture anchors in arthroscopic Bankart repair after a minimal 2 year follow-up.
Testing the reliability of CT scan-based dental wear magnitude scoring.

OBJECTIVES Digital models are now frequently used in biological anthropology (bioanthropology) research. Despite several studies validating this type of research, none has examined if the assessment of dental wear magnitude based on Computerized Tomography (CT) scans is reliable. Thus, this study aims to fill this gap and assess if dental wear magnitude scoring based on CT scans provides results consistent with scoring based on direct observation of the physical specimens. MATERIALS AND METHODS Dental wear magnitude from 412 teeth of 35 mandibles originating from the Portuguese Muge and Sado Mesolithic shell-middens was scored. The mandibles were also CT scanned and visualized using 3D Slicer. CT scan-based scoring of dental wear magnitude was then undertaken. Two scoring rounds were undertaken for each observation method (totaling four scoring rounds) and an intra-observer error test was performed. The averaged results of the two observation methods were compared via boxplots with paired cases. RESULTS Intra-observer error was negligible and non-significant. Scoring results are comparable between the two observation methods. Notwithstanding, some differences were found, in which CT scan assessment generally overestimates dental wear when compared to direct observation. DISCUSSION Our results generally validate the use of CT scans in studies of dental wear magnitude. Notwithstanding several caveats relating to CT scanning and visualization limitations should be considered to avoid over or under-estimation of dental wear.