Miracle-dz/UniFAR-FTUs huggingface dataset:
Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Thus, since the molecular mechanisms underlying tolerance to amphetamine are still unknown, an animal model to identify the neurochemical mechanisms associated with drug tolerance is greatly needed. Here we took advantage of a unique behavior caused by amphetamine in Caenorhabditis elegans to investigate whether this simple, but powerful, genetic model develops tolerance following repeated exposure to amphetamine. We found that at least 3 treatments with 0.5 mM amphetamine were necessary to see a reduction in the amphetamine-induced behavior and, thus, to promote tolerance. Moreover, we found that, after intervals of 60/90 minutes between treatments, animals were more likely to exhibit tolerance than animals that underwent 10-minute intervals between treatments. Taken together, our results show that C. elegans is a suitable system to study tolerance to drugs of abuse such as amphetamines.
Development of a graph convolutional neural network model for efficient prediction of protein-ligand binding affinities

Prediction of protein-ligand interactions is a critical step during the initial phase of drug discovery. We propose a novel deep-learning-based prediction model based on a graph convolutional neural network, named GraphBAR, for protein-ligand binding affinity. Graph convolutional neural networks reduce the computational time and resources that are normally required by the traditional convolutional neural network models. In this technique, the structure of a protein-ligand complex is represented as a graph of multiple adjacency matrices whose entries are affected by distances, and a feature matrix that describes the molecular properties of the atoms. We evaluated the predictive power of GraphBAR for protein-ligand binding affinities by using PDBbind datasets and proved the efficiency of the graph convolution. Given the computational efficiency of graph convolutional neural networks, we also performed data augmentation to improve the model performance. We found that data augmentation with docking simulation data could improve the prediction accuracy although the improvement seems not to be significant. The high prediction performance and speed of GraphBAR suggest that such networks can serve as valuable tools in drug discovery.
Bioinformatic pipelines combining denoising and clustering tools allow for more comprehensive prokaryotic and eukaryotic metabarcoding

Environmental DNA metabarcoding is a powerful tool for studying biodiversity. However, bioinformatic approaches need to adjust to the diversity of taxonomic compartments targeted as well as to each barcode gene specificities. We built and tested a pipeline based on read correction with DADA2 allowing analysing metabarcoding data from prokaryotic (16S) and eukaryotic (18S, COI) life compartments. We implemented the option to cluster amplicon sequence variants (ASVs) into operational taxonomic units (OTUs) with swarm, a network‐based clustering algorithm, and the option to curate ASVs/OTUs using LULU. Finally, taxonomic assignment was implemented via the Ribosomal Database Project Bayesian classifier (RDP) and BLAST. We validated this pipeline with ribosomal and mitochondrial markers using metazoan mock communities and 42 deep‐sea sediment samples. The results show that ASVs and OTUs describe different levels of biotic diversity, the choice of which depends on the research questions. They underline the advantages and complementarity of clustering and LULU‐curation for producing metazoan biodiversity inventories at a level approaching the one obtained using morphological criteria. While clustering removes intraspecific variation, LULU effectively removes spurious clusters, originating from errors or intragenomic variability. Swarm clustering affected alpha and beta diversity differently depending on genetic marker. Specifically, d‐values > 1 appeared to be less appropriate with 18S for metazoans. Similarly, increasing LULU’s minimum ratio level proved essential to avoid losing species in sample‐poor data sets. Comparing BLAST and RDP underlined that accurate assignments of deep‐sea species can be obtained with RDP, but highlighted the need for a concerted effort to build comprehensive, ecosystem‐specific databases.
Bleomycin sclerotherapy following doxycycline lavage in the treatment of ranulas: A retrospective analysis and review of the literature

Objective A ranula is a mucus-filled salivary pseudocyst that forms in the floor of the mouth, commonly arising from the sublingual or submandibular salivary glands following obstruction or trauma. Complete excision of the injured gland and removal of the cyst content is the first-choice therapy, but has the potential for complications related to injury to nearby structures. As such, minimally invasive approaches such as percutaneous sclerotherapy have been investigated. We aim to contribute to the literature by assessing the efficacy and safety of our technique through our experience with 18 patients over the last decade. Methods This retrospective study evaluated 18 patients with intraoral and plunging ranulas treated by percutaneous bleomycin ablation. The primary endpoint was the treatment result. Secondary endpoints included bleomycin dosage and complications. Results The study evaluated 12 males and six females with a median age of 23.5 years (range 13–39 years). At a final follow-up of at least 2 months (6.5±5.5 months), four patients demonstrated complete response (22%) and 14 patients demonstrated residual presence, recurrence, or regrowth of the lesion (78%). There were no statistically significant associations between outcomes and history of prior treatment, number of treatments, and size or type of ranula. No complications were noted. Conclusions Our findings indicate that bleomycin, while safe for use in various head and neck malformations, is of limited utility in ranula therapy when the offending gland is not addressed primarily.
Toxicity and Degradation Study of Clofibric Acid by Treatment with Ozone in Water

ABSTRACT This article presents the results of the degradation of clofibric acid by ozonation. Furthermore, results of the toxic effect of clofibric acid and its intermediate compound, 4-chlorophene generated during the oxidation process, to alga Selenastrum capricornium, are also discussed. The degradation and mineralization of the compound are studied according to the optimized operating conditions. These variables include pH, conductivity, hydraulic retention time and the use of a mixing maze. All the trials are conducted in a purpose-built pilot-scale reactor. Working under the optimal operating conditions (pH = 9, HRT = 12.5 min and ozone dose = 14 ± 2 gN/m3), a degradation value of 98% was obtained, although mineralization of the compound did not occur. Results show that clofibric acid and its intermediate are toxic during the first 10 min of treatment for concentrations equal to or greater than 1 mg/L. Under optimal conditions toxicity is not observed for any concentrations.
Experiences of midlife and older African American men living with type 2 diabetes

ABSTRACT Objective Type 2 Diabetes Mellitus (T2DM) is a complicated disease that disproportionately affects African American men. Understanding the experiences of African American men living with T2DM is important for developing effective, culturally sensitive interventions. The purpose of this study was to describe how African American men view their T2DM and describe their perspectives on living with and self-managing T2DM. Design In-depth semi-structured qualitative interviews were conducted with 22 African American men aged 40–85 years diagnosed with T2DM. Interviews were transcribed and analyzed using NVivo 10 with thematic analysis. Results Disbelief, shock, and denial were commonly experienced reactions at initial diagnosis. Many participants defined diabetes using words such as ‘sugar’ or ‘glucose’ and reported an awareness of health complications caused by diabetes, such as amputations and diabetic comas. Participants expressed various perspectives and attitudes towards having diabetes, including avoidance/apathy, fatalism, guilt and shame, fear and concern, and self-mastery. The majority of men described efforts to self-manage diabetes via glucose monitoring, changing dietary habits, and exercise. Many participants expressed concern over the financial burden associated with managing diabetes and reported that high costs can hinder a patient’s ability to maintain active self-monitoring and deter patients from attending needed doctor’s visits. Many participants expressed confidence in their healthcare providers, although a few expressed feelings of distrust and being uninformed. Participants tended to most appreciate physicians who spent time discussing their condition and who made an effort to engage in open patient-provider communication. Conclusion Living with diabetes can be emotionally, physically, and mentally challenging. Efforts to improve adoption and maintenance of self-management behaviors may benefit from sensitivity to the patient’s attitude and perspectives towards diabetes self-management, assistance overcoming the financial burden of managing diabetes, and open patient-provider communication.
MicroRNA‐17‐5p restrains the dysfunction of Ang‐II induced podocytes by suppressing secreted modular calcium‐binding protein 2 via NF‐κB and TGFβ signaling

Glomerulonephritis, also known as nephritis syndrome (nephritis for short), is a common kidney disease. Previous research has proved that microRNAs (miRNAs) frequently regulate various diseases including nephritis. Nonetheless, the biological function and molecular mechanism of miR‐17‐5p are unclear in nephritis. In the current study, RT‐qPCR analysis showed that miR‐17‐5p was downregulated in Ang II‐induced podocytes. Also, according to the results from RT‐qPCR analysis, CCK‐8 assay, flow cytometric analysis, western blot analysis, and ELISA miR‐17‐5p elevation alleviated Ang II‐induced podocyte injury. Besides, luciferase reporter assay, western blot and RT‐qPCR analyses revealed that SMOC2 was targeted by miR‐17‐5p in Ang II‐induced podocytes. Additionally, rescue assays demonstrated that overexpressed SMOC2 counteracted the influence of overexpressed miR‐17‐5p on cell injury of Ang II‐induced podocytes. Moreover, our data suggested that miR‐17‐5p‐SMOC2 axis regulated TGFβ and NF‐κB signaling activation in Ang II‐induced podocytes. SMOC2 regulated cell viability, apoptosis and extracellular matrix (ECM) deposition in Ang II‐induced podocytes via TGFβ signaling, and SMOC2 regulated inflammation in Ang II‐induced podocytes through NF‐κB signaling. Overall, our study demonstrated that miRNA‐17‐5p restrained the dysfunction of Ang‐II induced podocytes by suppressing SMOC2 via the NF‐κB and TGFβ signaling.
Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: a Pilot Randomized Controlled Trial.

INTRODUCTION Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving and withdrawal symptoms, with post-cessation body weight as secondary outcome. METHODS Eighty-four prediabetic and/or overweight smokers were randomized (1:1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. RESULTS Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (RR = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP=97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. CONCLUSIONS Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. IMPLICATIONS Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.
Changes in medication use among long‐stay residents with dementia in Michigan during the pandemic

Persons with Alzheimer's disease and related dementias (ADRD) are particularly susceptible to consequences from the coronavirus (COVID) pandemic including social isolation, disruption of daily routine, and less direct care due to reductions in nursing home (NH) workforce. Neuropsychiatric symptoms (NPS), such as agitation, depression, and anxiety, which occur in >90% of persons with ADRD have likely been exacerbated by this pandemic. Staffing shortages and implementation of nonpharmacological strategies to treat NPS was challenging prior to COVID—such challenges have likely intensified following the start of the pandemic. Given reductions in staffing and increased behavioral symptoms among residents with ADRD, this may result in greater reliance on psychotropics such as antipsychotics to manage NPS. This analysis evaluated changes in central nervous system (CNS)-active medication prescribing among all longstay NH residents with ADRD within the state of Michigan following the start of the COVID pandemic.
Estimation and change of edentulism among the Korean population: Korea National Health and Nutrition Examination Survey 2007-2018

OBJECTIVES To estimate the prevalence of edentulism according to the socio-demographic variables of Korean adults between 2007 and 2018 and to analyze the trends. METHODS This study was conducted using raw data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2018. Edentulism was defined as the absence of upper and lower teeth or the retained root of the missing teeth. To obtain the prevalence of edentulism, complex sample frequency analysis and regression analysis were performed according to the socio-demographic variables to represent the national population. The Korean population structure in 2005 was exploited as a standard population to calculate age-standardized edentulism. RESULTS The prevalence of edentulism in 2016-2018 was 9.7% in the Korean elderly, and the change of age-standardized edentulism steadily declined over time from 2007, 12.8%. In particular, it decreased by approximately 20% in the period between 2016 and 2018 compared to that in 2007 for those in their 80s. The trend of the prevalence according to gender decreased significantly in women. According to the level of education, the greatest decrease was seen in the group with the lowest education, although the prevalence itself was higher than that seen in those who were more educated. CONCLUSIONS The prevalence of edentulism among the older Korean population has decreased over time. However, the concern is on those with lower education and men as these groups are still at higher risk for edentulism.
Impact of the Microstructure of CAD/CAM Blocks on the Bonding Strength and the Bonded Interface.

PURPOSE To investigate the relationship between the microstructure of CAD/CAM blocks and the quality of adhesion as function of the surface treatment and resin cement type. MATERIALS AND METHODS Two nano-ceramic composite resin CAD/CAM blocks, Lava Ultimate (LU) and Cerasmart (CS), and two Leucite-reinforced glass ceramic CAD/CAM IPS blocks, Empress® CAD (EM) and InitialTM LRF (IR), received either Hydrofluoric acid (HF) or sandblasting (SB) surface treatments. The blocks were then luted using two dual-cure resin cements, LinkForce (LF) and Multilink Automix (ML) with their corresponding silanes, resulting in 16 study groups. The luted blocks were then thermal-cycling (TC) for 5000 cycles and subjected to a microtensile bond strength (μTBS) test. Scanning electron microscopy (SEM) micrographs of the treated surfaces were analyzed using Image J software and XRD analyses were performed for the two ceramic blocks. The data obtained were submitted to Games-Howell post-hoc nonparametric test to compare combinations of groups or treatments and a linear mixed-effects model for the factors surface treatment, block type, and resin cement, together with their first-degree interactions (α = 0.05). RESULTS The lowest mean μTBS values were obtained with LU-HF, whereas the highest mean μTBS values were obtained with CS regardless of resin cement type and surface treatment method. IR-HF mean μTBS were significantly higher than IR-SB, EM-SB, and EM-HF. Analysis using Image J software demonstrated significant differences in the density and pore size after HF surface treatment. CONCLUSIONS The specific microstructure of each block material within the same family group impacted the micromechanical retention and the bonded interface strength. This article is protected by copyright. All rights reserved.
Expedited Partner Therapy in Female Adolescents: A Study of Acceptance and the Impact on Reinfection Rates

After introduction of expedited partner therapy to a female adolescent population, acceptance was low, and there were no significant differences in reinfection rates of Chlamydia trachomatis and Trichomonas vaginalis. Background Given the high risk of sexually transmitted infections (STIs) in adolescents and young adults (AYAs), this study evaluated expedited partner therapy (EPT) acceptance and STI reinfection rates in female AYA before and after availability of EPT. Methods The pre-EPT cohort was a 3-year (November 2012 to November 2015) retrospective chart review of female AYA positive for Chlamydia trachomatis (CT) and/or Trichomonas vaginalis (TV) before introduction of EPT. An EPT protocol for CT and TV infections was implemented after legalization in Ohio in 2016. The post-EPT cohort was a prospective review of patients positive for CT and TV for 2 years (5/2016–5/2018) after EPT introduction. We evaluated EPT acceptance and compared reinfection rates (positive test 1–6 months after initial infection) in the pre-EPT versus post-EPT cohorts and by EPT acceptance. Results Among patients offered EPT, 28% (67/237) with CT and 25% (24/97) with TV accepted EPT. There were no significant differences in the reinfection rates for CT or TV in the pre-EPT versus post-EPT cohorts (CT: 24% (57/240) vs 20% (38/192), P = 0.42; TV: 23% (22/97) versus 14% (12/87), P = 0.11). Although lower, reinfections rates were not significantly different among patients who accepted versus did not accept EPT (CT, 13% (6/48) vs 21% (23/110), P = 0.50 and TV, 6% (1/18) vs 18% (9/49), P = 0.69). Conclusions Despite the implementation of an EPT protocol, STI reinfection rates among female AYA remained high, and many declined EPT. Further research is needed to identify barriers to the provision and acceptance of EPT and ways to address these factors.
Measuring depression in adolescence: Evaluation of a hierarchical factor model of the Children’s Depression Inventory and measurement invariance across boys and girls

Background One of the most widely used instruments to measure depression in childhood and adolescence is Kovacs’s Children’s Depression Inventory (CDI). Even though this particular measure sparked massive interest among researchers, there is no clear consensus about its factorial structure. It has been suggested that inconsistencies in findings can be partly ascribed to the cultural context. The aim of this study was a) to examine and verify the factor structure of CDI in the Czech population and b) to assess gender-related psychometric differences using the mean and covariance structure (MACS) approach and differential item functioning (DIF) analysis. Methods The research sample consisted of 1,515 adolescents (ages 12 to 16 years, 53.7% female) from a non-clinical general population. Based on exploratory factor analysis (EFA) on a random subsample (N = 500), we proposed a model that was subsequently tested on the rest of the sample (N = 1,015) using confirmatory factor analysis (CFA). Following the MACS procedure, we assessed measurement invariance in boys and girls. The between-group comparison was further supplemented by a DIF analysis. Results The proposed hierarchical four-factor model (General Symptoms, Negative Self-Concept, Inefficiency, and Social Anhedonia) with a second-order factor of depression fitted the data reasonably well (χ2 = 1281.355; df = 320; RMSEA = 0.054, CFI = 0.925). Regarding gender differences, we found no substantial signs of measurement invariance using the MACS approach. Boys and girls differed in first-order latent means (girls scored higher on General Symptoms with a standardized mean difference of 0.52 and on Negative Self-Concept with a standardized mean difference of 0.31). DIF analysis identified three items with differential functioning. However, the levels of differential functioning were only marginal (in two items) or marginal/moderate and the presence of DIF does not substantially influence scoring of CDI. Conclusion In the general adolescent population in the Czech Republic, the CDI can be considered a reliable instrument for screening purposes in clinical settings and for use in research practice. Instead of the originally proposed five-factor model, we recommend using the newly established four-factor structure. The measure seems to show only marginal psychometric differences with respect to gender, and overall measurement invariance in boys and girls seems to be a tenable assumption.
Job Characteristics, Emotional Exhaustion, and Work–Family Conflict in Nurses

The purpose of this study is to identify whether emotional exhaustion, a component of burnout, mediates the relationship between job demands, job resources, and work–family conflict (WFC). A cross-sectional design was used with survey data. A total of 1,202 nurses in eastern Canada participated in this study. Data were collected via an online survey and analyzed using mediation analysis. The results indicated that job demands and emotional exhaustion predicted WFC. Moreover, emotional exhaustion partially mediated the relationship between job demands, supervisor support, and WFC. This model also showed that younger nurses had increased WFC. Our study indicates that there are several direct and indirect pathways leading to WFC. Moreover, workplace resources can reduce emotional exhaustion, which, in turn, may help maintain work–family balance in nurses. These findings contribute to the existing knowledge on the precursors and consequences of burnout symptoms.