Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer

ABSTRACT Non-small cell lung cancer (NSCLC) is one of the main causes of death in the world. To improve the diagnostic level and find new biological targets，GSE datasets were selected from GEO databaseto analyze the differential expression genes and construct ceRNA network. Cell apoptosis detection showed that both the early and late apoptosis rates were increased after inhibition of COX10-AS1. Glycolysis cell-based assay also found that the content of L-lactate decreased significantly after using miR-142-5p mimics but increased after using si-COX10-AS1. Dual-luciferase reporter analysis showed that the luciferase activity of PAICS-WT reporter vector was inhibited by miR-142-5p mimics, but there was no significant change in PAICS-MUT reporter vector after transfection of miR-142-5p mimics. And overexpression of miR-142-5p reduced the level of PAICS, but inhibition of miR-142-5p expression increased the expression of PAICS. After using COX10-AS1, the expression of PAICS inhibited by miR-142-5p was restored. Through bioinformatics analysis, we constructed the COX10-AS1/miR-142-5p/PAICS axis, which is a ceRNA regulatory network. We confirmed that COX10-AS1 down-expression can restore the inhibitory effect of miR-142-5p on PAICS, promote the apoptosis of NSCLC cells, and inhibit the proliferation of NSCLC cells. This process may be mediated by the activation of glycolysis pathway. The glycolysis-related gene PAICS may be a new and significant target for the regulation of the development of NSCLC.
Strength and physical activity in osteoarthritis: The mediating role of kinesiophobia

The aim of this study was to investigate the association between muscle strength and physical activity level in people with knee osteoarthritis (OA), and determine whether this association is mediated by pain‐related fear of movement (kinesiophobia) and self‐reported pain. Cross‐sectional data from 37 subjects (age 58.8 ± 8.6 years, 25F/12M, BMI 33.5 ± 6.4 kg/m2) with OA of the knee were used. Isometric knee extensor and flexor muscle strength were measured using an isokinetic dynamometer. Physical activity, kinesiophobia, and pain were assessed by self‐report using the University of California, Los Angeles activity rating scale, Tampa Scale for Kinesiophobia, and The Knee Injury and Osteoarthritis Outcome Score pain subscale, respectively. The associations between strength measures, physical activity, kinesiophobia, and pain scores, were modeled by performing a parallel multiple mediation analysis and the significance of mediational effects (kinesiophobia and pain) were tested using a bootstrap approach. Lower knee flexion and extension strength were associated with lower physical activity scores and these relationships were mediated by higher kinesiophobia scores (more fear) but not pain scores. Knee extension strength was directly associated with physical activity scores after controlling for kinesiophobia and pain scores. These results suggest that muscle strength can influence physical activity directly and indirectly through fear of movement. Assessing these measures together in this population may help clinicians identify patients that are more likely to avoid physical activities due to not only muscle weakness but also fear of movement.
What do people believe caused their mental illness?

Anosognosia is a neurological term suggesting a brain lesion, even though localisation is not always clear. Decision making capacity is broader than anosognosia as people can be aware that they are ill, therefore demonstrating they do not have anosognosia, but can still lack an understanding of treatment options or an ability to weigh up the advantages and disadvantages of such options, which points towards a lack of decision making capacity. Furthermore, decision making capacity, when used in a legal context, is generally considered to be a binary option; someone either has or doesn’t have decision-making capacity. Anosognosia and insight tend to have various gradations instead.
A secondary structure-based position-specific scoring matrix applied to the improvement in protein secondary structure prediction

Protein secondary structure prediction (SSP) has a variety of applications; however, there has been relatively limited improvement in accuracy for years. With a vision of moving forward all related fields, we aimed to make a fundamental advance in SSP. There have been many admirable efforts made to improve the machine learning algorithm for SSP. This work thus took a step back by manipulating the input features. A secondary structure element-based position-specific scoring matrix (SSE-PSSM) is proposed, based on which a new set of machine learning features can be established. The feasibility of this new PSSM was evaluated by rigid independent tests with training and testing datasets sharing <25% sequence identities. In all experiments, the proposed PSSM outperformed the traditional amino acid PSSM. This new PSSM can be easily combined with the amino acid PSSM, and the improvement in accuracy was remarkable. Preliminary tests made by combining the SSE-PSSM and well-known SSP methods showed 2.0% and 5.2% average improvements in three- and eight-state SSP accuracies, respectively. If this PSSM can be integrated into state-of-the-art SSP methods, the overall accuracy of SSP may break the current restriction and eventually bring benefit to all research and applications where secondary structure prediction plays a vital role during development. To facilitate the application and integration of the SSE-PSSM with modern SSP methods, we have established a web server and standalone programs for generating SSE-PSSM available at http://10.life. nctu.edu. tw/SSE-PSSM.
Physical chemistry of the interface between attached micro-organisms and their support

The thermodynamic approach of adhesion and DLVO theory are complementary to predict initial bacterial adhesion; the interplay between short- and long-range forces, respectively, may be due to surface roughness. Due to the influence of electrical double layer interactions, adhesion can be promoted by treatments leading to modification of the cell or support surface properties. Adhesion is influenced by cell-cell interactions, by the cpresence of polymer molecules on the surface and by the composition of the medium. X-ray photoelectron spectroscopy can be applied to determine the elemental composition of the surface of microorganisms; some information on the chemical functions can also be obtained. The surface composition is related to physico-chemical properties which play a determining role in adhesion and flocculation, in particular the hydrophobicity and the zeta potential.
Effectiveness of brentuximab vedotin monotherapy in relapsed or refractory Hodgkin lymphoma: a systematic review and meta-analysis

Abstract This systematic review and meta-analysis aimed to determine the effectiveness of brentuximab vedotin (BV) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) in the clinical practice setting using most recent results. A total of 32 observational studies reporting on treatment patterns, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events were found. After four cycles, a random-effect model yielded pooled ORR and CR rates of 62.6% (95% confidence interval (CI): 56.0–68.9; I 2 = 9.7%) and 32.9% (95% CI, 20.8–46.3, I 2 = 64.8%), respectively. Regarding survival, 1-year, 2-year, and 5-year PFS ranged from 52.1% to 63.2%, 45.2% to 56.2%, and 31.9% to 33.0%, respectively. OS rates were 68.2–82.7%, 58.0–81.9%, and 58.0–62.0%, respectively. Most common adverse events were hematological toxicities (neutropenia: 13.3–23%, anemia: 8.8–39.0%, and thrombocytopenia: 4–4.6%), and grade ≥3 peripheral neuropathy (3.3–7.3%). This study supports the effectiveness and safety of BV in R/R cHL patients in the real-world setting.
Alkoxy cyanoacrylate-based nanoparticles with stealth and brain-targeting properties

Abstract Nanoparticles (NPs) with ‘stealth’ properties have been designed to decrease the phagocytosis of such particles by mononuclear phagocytes and to protect them from enzymatic degradation, thus improving circulation time and bioavailability after intravenous administration. Brain-targeting modifications endow NPs with the capacity to cross the blood–brain barrier, facilitating chemotherapy for brain diseases such as glioma. In this study, newly designed alkoxy cyanoacrylate (CA)-based NPs with stealth and brain-targeting properties were synthesised and evaluated. The monomers for NP core polymerisation were chemically modified to hydrophilic short alkoxy structure for stealth purposes and coated with polysorbate-80 for brain targeting. Two monomers (2-methoxyethyl CA and 2-(2-methoxyethyl)ethyl CA) were used to create NP2 and NP3, respectively. Both NPs were successfully loaded with anti-sense oligonucleotide (ASON) of transforming growth factor beta 2. Compared to traditional n-butyl CA-based ASON–NP1, ASON–NP3 was found to decrease phagocytosis by mononuclear macrophages (RAW264.7) and to increase cellular uptake by cancer cells. ASON–NP3 showed definite brain targeting and anti-cancer effects. This work provides a potential new strategy for preparing stealth NPs core, providing a new NP vehicle for clinical drug delivery that may be targeted to the brain and circulates in the blood for an extended period of time.
Design of Novel Phosphopantetheine Adenylyltransferase Inhibitors: a Potential New Approach to Tackle Mycobacterium tuberculosis.

BACKGROUND Tuberculosis (TB) has been a challenging disease worldwide, especially for the neglected poor populations. Presently, there are approximately 2 billion people infected with TB worldwide and 10 million people in the world fell ill with active TB, leading to 1.5 million deaths. INTRODUCTION The classic treatment is extensive and the drug and multi drug resistance of Mycobacterium tuberculosis has been a threat to the efficacy of the drugs currently used. Therefore, the rational design of new anti TB candidates is urgently needed. METHODS With the aim of contributing to face this challenge, 78 compounds have been proposed based on SBDD (Structure Based Drug Design) strategies applied to target the M. tuberculosis phosphopantetheine adenylyltransferase (MtPPAT) enzyme. Ligand Based Drug Design (LBDD) strategies were also used for establishing structure activity relationships (SAR) and for optimizing the structures. MtPPAT is important for the biosynthesis of coenzyme A (CoA) and it has been studied recently toward the discovery of new inhibitors. RESULTS After docking simulations and enthalpy calculations, the interaction of selected compounds with MtPPAT was found to be energetically favorable. The most promising compounds were then synthesized and submitted to anti M. tuberculosis and MtPPAT inhibition assays. CONCLUSION One of the compounds synthesized (MCP163), showed the highest activity in both of these assays.
A Cre-Dependent CRISPR/dCas9 System for Gene Expression Regulation in Neurons

Abstract Site-specific genetic and epigenetic targeting of distinct cell populations is a central goal in molecular neuroscience and is crucial to understand the gene regulatory mechanisms that underlie complex phenotypes and behaviors. While recent technological advances have enabled unprecedented control over gene expression, many of these approaches are focused on selected model organisms and/or require labor-intensive customization for different applications. The simplicity and modularity of clustered regularly interspaced short palindromic repeats (CRISPR)-based systems have transformed genome editing and expanded the gene regulatory toolbox. However, there are few available tools for cell-selective CRISPR regulation in neurons. We designed, validated, and optimized CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) systems for Cre recombinase-dependent gene regulation. Unexpectedly, CRISPRa systems based on a traditional double-floxed inverted open reading frame (DIO) strategy exhibited leaky target gene induction even without Cre. Therefore, we developed an intron-containing Cre-dependent CRISPRa system (SVI-DIO-dCas9-VPR) that alleviated leaky gene induction and outperformed the traditional DIO system at endogenous genes in HEK293T cells and rat primary neuron cultures. Using gene-specific CRISPR sgRNAs, we demonstrate that SVI-DIO-dCas9-VPR can activate numerous rat or human genes (GRM2, Tent5b, Fos, Sstr2, and Gadd45b) in a Cre-specific manner. To illustrate the versatility of this tool, we created a parallel CRISPRi construct that successfully inhibited expression from a luciferase reporter in HEK293T cells only in the presence of Cre. These results provide a robust framework for Cre-dependent CRISPR-dCas9 approaches across different model systems, and enable cell-specific targeting when combined with common Cre driver lines or Cre delivery via viral vectors.
Factors associated with the risk of diabetic foot in patients with diabetes mellitus in Primary Care.

OBJECTIVE To analyze factors associated with diabetic foot risk in patients with diabetes mellitus assisted in Primary Care. METHOD Observational, analytic, and transversal study took place in Teresina, Piauí, with diabetic patients who are assisted in Primary Care. Data collection took place through interviews, foot clinical exams, and medical record analysis. We used the Mann-Whitney, Pearson's Chi-square and multiple logistic regression statistics tests to analyze the data. The association power among categorical variables was measured by Odds Ratio . RESULTS 322 patients participated. Marital status with a partner presented a protection factor (p = 0.007). Risk factors for the development of the diabetic foot are: arterial hypertension (p = 0.045), obesity (p = 0.011), smoking (p = 0.027), not being submitted to follow ups (p = 0.046), inadequate control of capillary blood glucose (p < 0.001), indisposition to the care of the foot (p=0.014), and foot self-exam less frequently (p = 0.040). CONCLUSION Sociodemographic, clinical, and self-care aspects interfere in diabetic foot development, highlighting the necessity of effective follow up tracking and educational interventions for patients with diabetes mellitus in Primary Care.
Shifts in amino acid preferences as proteins evolve: A synthesis of experimental and theoretical work

Amino acid preferences vary across sites and time. While variation across sites is widely accepted, the extent and frequency of temporal shifts are contentious. Our understanding of the drivers of amino acid preference change is incomplete: To what extent are temporal shifts driven by adaptive versus nonadaptive evolutionary processes? We review phenomena that cause preferences to vary (e.g., evolutionary Stokes shift, contingency, and entrenchment) and clarify how they differ. To determine the extent and prevalence of shifted preferences, we review experimental and theoretical studies. Analyses of natural sequence alignments often detect decreases in homoplasy (convergence and reversions) rates, and variation in replacement rates with time—signals that are consistent with temporally changing preferences. While approaches inferring shifts in preferences from patterns in natural alignments are valuable, they are indirect since multiple mechanisms (both adaptive and nonadaptive) could lead to the observed signal. Alternatively, site‐directed mutagenesis experiments allow for a more direct assessment of shifted preferences. They corroborate evidence from multiple sequence alignments, revealing that the preference for an amino acid at a site varies depending on the background sequence. However, shifts in preferences are usually minor in magnitude and sites with significantly shifted preferences are low in frequency. The small yet consistent perturbations in preferences could, nevertheless, jeopardize the accuracy of inference procedures, which assume constant preferences. We conclude by discussing if and how such shifts in preferences might influence widely used time‐homogenous inference procedures and potential ways to mitigate such effects.
Dealing with elite sport competition demands: an exploration of the dynamic relationships between stress appraisal, coping, emotion, and performance during fencing matches

ABSTRACT The present research aimed to provide a more holistic analysis of stressful experiences in sport by examining how stress appraisal, coping and emotion are dynamically inter-related constructs and the extent to which their dynamic relationship is associated with objective performance. Based on process-oriented methods, two studies were conducted with elite athletes in order to investigate the dynamic relationship between these constructs and performance in highly demanding sport situations (Study 1: simulated competitive fencing matches during a training session; Study 2: real-life competitive fencing matches during an international competition). The results of the random coefficient regression models emphasise the dynamic nature of the relationship between stress appraisal, coping behaviour, emotion and objective performance over the course of fencing matches. They allowed identification of additional mediating effects of coping and emotion within dynamic relationships between stress appraisal and performance. These studies contribute to a deeper understanding of psychological adaptation in performance environments. The implications of the findings are discussed in relation to the design of effective coping interventions to support the learning of performance-related coping skills and the attainment of performance goals among individuals in highly demanding environments.
Use of a Portable Point-of-Care Instrumentation to Measure Human Milk Sodium and Potassium Concentrations.

Objective: Human milk (HM) sodium (Na) and potassium (K) concentrations, as well as the Na and K ratio (Na:K), are associated with stages of lactation and breast health. Portable point-of-care instruments to measure HM biomarkers related to secretory activation or tight junction disturbances would supply clinicians immediate information for individualized lactation care. This study compared HM concentrations of Na and K and Na:K measured by a biochemist with inductively coupled plasma optical emission spectrometry (ICP-OES) and measured by a clinician with ion-selective electrode probes (ISEPs). Design: HM samples (n = 92) were participant collected and donated on day 10 postpartum through a convenience sample of breastfeeding women in West Michigan. Na and K concentrations were determined using ICP-OES and ISEPs. Bland-Altman plots, paired sample t-test, and logistic regressions were completed using R 3.4. 4 and R Studio 1.2. 1335 with package Lattice. Results: Na concentrations were not significantly different with ICP-OES (13.0 ± 14.8 mM) and ISEPs (12.6 ± 13.7 mM, p = 0.06), whereas K concentrations (ICP-OES 16.1 ± 1.9 mM, ISEPs 14.4 ± 2.4 mM, p < 0.001) and Na:K (ICP-OES 0.81 ± 0.92, ISEPs 1.01 ± 1.62, p = 0.011) were significantly different. Between both methods, the Na, K, and Na: K linear relationships were statistically significant. Conclusion: With additional longitudinal and clinical usefulness research clinicians could use ISEPs to collect and interpret relevant lactation data to support individualized lactation interventions.
Analysis of the Microbial Community Structure in Coastal Sediment of an Ascidian Farm in South Korea through 16S rRNA Gene Amplicon Sequencing

Aquaculture places contamination pressure on the coastal environment. We investigated the microbial community structure changes in sediment in an ascidian Styela clava farm. Data profiling of the 16S rRNA gene amplicon sequence shows that the microbial diversity of sediment in the Styela clava farm is dominated by Proteobacteria phyla (relative abundance, 95.34 to 97.85%). ABSTRACT Aquaculture places contamination pressure on the coastal environment. We investigated the microbial community structure changes in sediment in an ascidian Styela clava farm. Data profiling of the 16S rRNA gene amplicon sequence shows that the microbial diversity of sediment in the Styela clava farm is dominated by Proteobacteria (relative abundance, 95.34 to 97.85%).
Predictors of Unmet Dental Health Needs in US Adults in 2018: A Cross-Sectional Analysis

Objective: To identify predictors of unmet dental needs for adults 18 y of age or older in the United States. Method: Using the Aday and Andersen framework and data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS), we ran logistic regression to estimate predictors for adults of not having a dental visit within 5 y and having lost any teeth using a national sample of 155,060 survey respondents. Results: Results showed that predisposing factors (age, race/ethnicity, gender, and educational attainment) and enabling factors (income and health insurance status) are important predictors for losing teeth due to decay or gum disease. Men, the elderly, and less educated and low-income residents were less likely to have seen a dentist within the past 5 y and more likely to have lost their permanent teeth. Compared to non-Hispanic White adults, Hispanics adults were more likely to have had a dental visit within the past 5 y. Unmet dental needs varied across states. People living in states with extensive Medicaid dental care benefit coverage were less likely to lose their teeth and more likely to have had a dental visit within the past 5 y. Conclusion: Efforts to improve oral health should address unmet dental needs of men and adults with low socioeconomic status. Studying the variation between state oral health care programs could further our understanding of how public policy can improve population oral health. Knowledge Transfer Statement: Men, non-Hispanic Blacks, mixed and other race minorities, and low socioeconomic status adults are most at risk of unmet dental needs. States can address these needs by expanding Medicaid coverage for adults.
Count Me Out: Perceptions of Black Patients Who are on Dialysis but Who are Not on a Transplant Waitlist

ABSTRACT End-stage renal disease (ESRD) is characterized by racial inequity; Blacks are 3 times more likely to develop ESRD than Whites. Transplant is the preferred treatment option since transplanted patients experience better clinical outcomes. Racial inequities persist at each of the steps required for transplantation. Despite the vast literature describing these racial inequities, it does not include dialysis patients’ awareness and understanding of treatment options, specifically for transplant. To address this gap, we purposely sampled Blacks in Detroit who were receiving dialysis and who were not active on any transplant waitlist to investigate their understanding and perceptions of transplants. We used uncertainty management theory (UMT) to better understand perceived barriers to getting and remaining on a transplant waitlist. We aimed to address a critical gap in the literature to inform approaches addressing this enduring inequity. For this qualitative study, we conducted individual, semi-structured interviews with 24 Black ESRD patients, aged 34–73 years: 9 male and 15 female. Participants shared their experiences of being on dialysis, perceptions, and understanding of transplants. We describe two key findings: 1) uncertainty for these patients is prevalent and multi-layered and 2) social support can both dissuade an individual from pursuing transplant (i.e., reluctance to ask family members to be donors) and it can result in decreasing uncertainty (e.g., participants wanting to pursue transplant to be with family). We highlight the specific need to improve patient education regarding treatment options and enhancing how relevant health information can be communicated.