Miracle-dz/UniFAR-FTUs huggingface dataset:
Serotonergic Drugs Inhibit Chikungunya Virus Infection at Different Stages of the Cell Entry Pathway

The rapid spread of mosquito-borne viral diseases in humans puts a huge economic burden on developing countries. For many of these infections, including those caused by chikungunya virus (CHIKV), there are no specific treatment possibilities to alleviate disease symptoms. Understanding the virus-host interactions that are involved in the viral replication cycle is imperative for the rational design of therapeutic strategies. In this study, we discovered an antiviral compound, elucidated its mechanism of action, and propose serotonergic drugs as potential host-directed antivirals for CHIKV. ABSTRACT Chikungunya virus (CHIKV) is an important reemerging human pathogen transmitted by mosquitoes. The virus causes an acute febrile illness, chikungunya fever, which is characterized by headache, rash, and debilitating (poly)arthralgia that can reside for months to years after infection. Currently, effective antiviral therapies and vaccines are lacking. Due to the high morbidity and economic burden in the countries affected by CHIKV, there is a strong need for new strategies to inhibit CHIKV replication. The serotonergic drug 5-nonyloxytryptamine (5-NT) was previously identified as a potential host-directed inhibitor for CHIKV infection. In this study, we determined the mechanism of action by which the serotonin receptor agonist 5-NT controls CHIKV infection. Using time-of-addition and entry bypass assays, we found that 5-NT predominantly inhibits CHIKV in the early phases of the replication cycle, at a step prior to RNA translation and genome replication. Intriguingly, however, no effect was seen during virus-cell binding, internalization, membrane fusion and genomic RNA (gRNA) release into the cell cytosol. In addition, we show that the serotonin receptor antagonist methiothepin mesylate (MM) also has antiviral properties toward CHIKV and specifically interferes with the cell entry process and/or membrane fusion. Taken together, pharmacological targeting of 5-HT receptors may represent a potent way to limit viral spread and disease severity. IMPORTANCE The rapid spread of mosquito-borne viral diseases in humans puts a huge economic burden on developing countries. For many of these infections, including those caused by chikungunya virus (CHIKV), there are no specific treatment possibilities to alleviate disease symptoms. Understanding the virus-host interactions that are involved in the viral replication cycle is imperative for the rational design of therapeutic strategies. In this study, we discovered an antiviral compound, elucidated its mechanism of action, and propose serotonergic drugs as potential host-directed antivirals for CHIKV.
Evaluation of Antimalarial Activity of Methanolic Root Extract of Myrica salicifolia A Rich (Myricaceae) Against Plasmodium berghei–Infected Mice

Background. The management and control of malaria has become gradually challenging due to the spread of drug-resistant parasites, lack of effective vaccine, and the resistance of vector to insecticides. Consequently, novel agents are urgently needed from different sources including from medicinal plants. In Ethiopia and Uganda, Myrica salicifolia root is traditionally claimed for the treatment of malaria. The aim of this study was to evaluate the in vivo antimalarial activity of root crude extract of M salicifolia. Methods. The parasite, Plasmodium berghei was used in this study since it is an appropriate parasite that is most commonly used because of its higher accessibility. A 4-day suppressive test was employed to evaluate the antimalarial effect of crude extract against early infection. The curative and prophylactic effect of the crude extract was further tested by Rane’s test and residual infection procedure. Parasitemia, survival time, packed cell volume, body weight, and rectal temperature of mice were used as evaluation parameters. Windows SPSS version 24 was used to analyze the data and analysis of variance followed by Tukey’s honestly significant difference to compare results between groups. Results. The root crude extract of M salicifolia significantly (P < .05-.0001) suppressed parasitemia. The crude extract exhibited a chemosuppression of 40.90. Conclusion. The development of new antimalarial agents and the finding supports the traditional claims and previous in vitro studies.
Hard and soft tissue analysis of alveolar ridge preservation in esthetic zone using deproteinized bovine bone mineral and a saddle connective tissue graft: A long-term prospective case series.

AIM Although alveolar ridge preservation (ARP) procedures appear to limit bone resorption after dental extraction, long-term outcomes remain limited. The objective of this prospective case series was to evaluate the long-term hard and soft tissue changes after ARP procedure in the aesthetic area, using deproteinized bovine bone mineral (DBBM) and saddle connective tissue graft. MATERIALS AND METHODS Fifteen patients were subjected to ARP and impressions and CT scans were taken at baseline and 3 months. After 5 to 7 years, a secondary long-term clinical and radiological analysis was carried out. Horizontal alveolar bone changes, soft tissue profiles and implant outcomes were assessed. RESULTS Although a limited hard and soft tissue remodeling occurred during the first 3 months after ARP, from 3 months to the long-term evaluation, the alveolar bone dimensions remained stable and the soft tissue profiles significantly increased, in the more cervical levels. The implant survival rate after 5 to 7 years yielded 100% and peri-implant bone levels and soft tissue health were good. CONCLUSION Within the limits of the study, the present data confirms the long-term effectiveness of ARP using DBBM and a saddle connective tissue graft offering stable hard and soft tissue conditions up to 5 to 7 years.
The content of reablement: Exploring occupational and physiotherapy interventions

Statement of context Occupational therapists and physiotherapists in a Swedish municipality answered a web-based survey about their reablement interventions. Critical reflection on practice There were overlapping areas as well as differences regarding the focus of occupational and physiotherapy interventions. Regarding the duration of interventions, occupational therapy was implemented over a short time span in contrast to physiotherapy, which had a longer duration. Both professions used valid and reliable instruments to a very limited extent. Implications for practice If other areas than self-care and mobility are to be addressed within reablement there is a need to critically reflect on the focus, content and duration of reablement interventions. Valid and reliable assessments can be utilised to a greater extent to guide goal-setting, the focus of interventions and to evaluate effects.
Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei

Objective Interference with the transmission of sensory signals along visual and auditory pathways has been implicated in the pathogenesis of hallucinations. The relay centres for vision (the lateral geniculate nucleus) and hearing (the medial geniculate nucleus) appear to be susceptible to the uptake of circulating mercury. We therefore investigated the distribution of mercury in cells of both these geniculate nuclei. Materials and methods Paraffin-embedded tissue sections containing the lateral geniculate nucleus were obtained from 50 adults (age range 20–104 years) who at autopsy had a variety of clinicopathological conditions, including neurological and psychiatric disorders. The medial geniculate nucleus was present in seven sections. Sections were stained for mercury using autometallography. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury. Results Ten people had mercury in cells of the lateral geniculate nucleus, and in the medial geniculate nucleus of three of these. Medical diagnoses in these individuals were: none (3), Parkinson disease (3), and one each of depression, bipolar disorder, multiple sclerosis, and mercury self-injection. Mercury was distributed in different groups of geniculate capillary endothelial cells, neurons, oligodendrocytes, and astrocytes. Mass spectrometry confirmed the presence of mercury. Conclusion Mercury is present in different combinations of cell types in the lateral and medial geniculate nuclei in a proportion of people from varied backgrounds. This raises the possibility that mercury-induced impairment of the function of the geniculate nuclei could play a part in the genesis of visual and auditory hallucinations. Although these findings do not provide a direct link between mercury in geniculate cells and hallucinations, they suggest that further investigations into the possibility of toxicant-induced hallucinations are warranted.
Factors associated with medication persistence among ischemic stroke patients: a systematic review

ABSTRACT Objective An investigation of the prevalence of medication persistence and associated factors in order to inform effective strategies for improving medication persistence. Methods A systematic review of the literature from 2010 to the present was performed, using the PRISMA protocol. Primary and empirical observational studies of adult ischemic stroke or transient ischemic attack patients were included. PubMed, CINAHL, Web of Science, Cochrane Library, and PsycInfo databases were searched using the key terms stroke, ischemic stroke, medication persistence, medication adherence, and patient compliance. Results Of four hundred twenty-eight journal articles retrieved, a final 18 articles were included. Short-term medication persistence was 46.2–96.7%, and long-term medication persistence was 41.7–93.0%. Identified hospital-related factors for medication persistence were stroke unit care, in-hospital medical complications, and early follow-up visit. Demographic factors for medication persistence were older age, and high/adequate financial status; disease-related factors were disease history, stroke subtype, and symptom severity. Age less than 75, female sex, comorbidity, antiplatelet medication switch, and polypharmacy were identified as factors of medication nonpersistence. Conclusions Stroke patients’ medication persistence decreases over time, and persistence on antiplatelets, anticoagulants, and statin was poor. Several factors were associated with medication persistence, and these factors should be considered in future secondary preventative strategies.
[The Catalan Society of Occupational Health(@SCSL) facing the big challenge of COVID-19].

Con la llegada a España del SARS-CoV-2, el incremento exponencial de enfermos de COVID-19 y sus lamentables consecuencias para un número importante de personas, la @SCSL ha tenido que adaptarse a esta nueva situación. El virus se ha propagado en muchos hogares, en numerosas empresas y en todos los centros sanitarios, sociosanitarios y residenciales del país, llegando incluso a situarnos al borde del colapso asistencial. Esta nueva variable, en forma de riesgo biológico, llegó provocando en la población trabajadora un desequilibrio de la siempre compleja relación bidireccional entre el trabajo y la salud…
Genome-wide identification and functional analysis of ARF transcription factors in Brassica juncea var. tumida

Auxin signalling is vital for plant growth and development, from embryogenesis to senescence. Recent studies have shown that auxin regulates biological processes by mediating gene expression through a family of functionally original DNA-binding auxin response factors, which exist in a large multi-gene family in plants. However, to date, no information has been available about characteristics of the ARF gene family in Brassica juncea var. tumida. In this study, 65 B. juncea genes that encode ARF proteins were identified in the B. juncea whole-genome, classified into three phylogenetical groups and found to be widely and randomly distributed in the A-and B-genome. Highly conserved proteins were also found within each ortholog based on gene structure and conserved motifs, as well as clustering level. Furthermore, promoter cis-element analysis of BjARFs demonstrated that these genes affect the levels of plant hormones, such as auxin, salicylic, gibberellin acid, MeJA, abscisic acid, and ethylene. Expression analysis showed that differentially expressed BjARF genes were detected during the seedling stage, tumor stem development and the flowering period of B. juncea. Interestingly, we found that BjARF2b_A, BjARF3b_A, BjARF6b_A, and BjARF17a_B were significantly expressed in tumor stem, and an exogenous auxin assay indicated that these genes were sensitive to auxin and IAA signaling. Moreover, eight of the nine BjARF10/16/17 genes and all of the BjARF6/8 genes were involved in post-transcriptional regulation, targeted by Bj-miR160 and Bj-miR167c, respectively. This analysis provides deeper insight of diversification for ARFs and will facilitate further dissection of ARF gene function in B. juncea.
Happiness as a strength in the promotion of adolescent and adult young health.

OBJECTIVES to assess the relation between sociodemographic characteristics of young people associated with the subjectivity of being happy; to evaluate the relationship between the subjectivity of being happy and the perception of health status; to evaluate the relationship between the subjectivity of being happy and the school and family environments and peer groups at school. METHODS this is an observational study, with an intentional sample of 1,069 young Portuguese people, with ages varying from 14 to 24, most of them women, attending secondary education. The self-filling questionnaire was used. RESULTS there are statistically significant associations between the subjectivity of being happy and schooling, perception of health status, family APGAR, school and family involvement, absence of problems or teasing by peers at school. CONCLUSIONS a positive and holistic care coupled with the potential of obtaining and consolidating healthy lifestyles for young people will enable health professionals to perceive them as agents of individual and social change.
Maize Plant Architecture Is Regulated by the Ethylene Biosynthetic Gene ZmACS71

Alteration of the C terminus of 1-aminocyclopropane-1-carboxylic acid (ACC) Synthase 7 (ZmACS7), an ethylene biosynthetic protein, enhances the stability of this enzyme, thus increasing ACC and ethylene production, which in turn alters plant architecture in maize. Plant height and leaf angle are two crucial determinants of plant architecture in maize (Zea mays) and are closely related to lodging resistance and canopy photosynthesis at high planting density. These two traits are primarily regulated by several phytohormones. However, the mechanism of ethylene in regulating plant architecture in maize, especially plant height and leaf angle, is unclear. Here, we characterized a maize mutant, Semidwarf3 (Sdw3), which exhibits shorter stature and larger leaf angle than the wild type. Histological analysis showed that inhibition of longitudinal cell elongation in the internode and promotion in the auricle were mainly responsible for reduced plant height and enlarged leaf angle in the Sdw3 mutant. Through positional cloning, we identified a transposon insertion in the candidate gene ZmACS7, encoding 1-aminocyclopropane-1-carboxylic acid (ACC) Synthase 7 in ethylene biosynthesis of maize. The transposon alters the C terminus of ZmACS7. Transgenic analysis confirmed that the mutant ZmACS7 gene confers the phenotypes of the Sdw3 mutant. Enzyme activity and protein degradation assays indicated that the altered C terminus of ZmACS7 in the Sdw3 mutant increases this protein’s stability but does not affect its catalytic activity. The ACC and ethylene contents are dramatically elevated in the Sdw3 mutant, leading to reduced plant height and increased leaf angle. In addition, we demonstrated that ZmACS7 plays crucial roles in root development, flowering time, and leaf number, indicating that ZmACS7 is an important gene with pleiotropic effects during maize growth and development.
Effectiveness of mindfulness-integrated cognitive behavior therapy on anxiety, depression and hope in multiple sclerosis patients: a randomized clinical trial.

INTRODUCTION Multiple sclerosis (MS) is a chronic medical condition that attracts particular attention because of the high risks associated with it. MS patients suffer from medical problems, depression, anxiety, and reduced hopefulness. These issues can increase the severity of the disease and treatment resistance and reduce patients' individual and social efficacy. Mindfulness-integrated cognitive behavior therapy (MICBT) is a new approach that is being applied in chronic diseases and can be used in combination with existing treatments. Therefore, the present study investigated the efficacy of MICBT in terms of anxiety, depression, and hope in MS patients. METHODS A sample of 20 patients with MS was randomly selected at Shafa Hospital in Kerman City, Iran. Patients were then assigned to one of two groups of 10 people using a random number table. The experimental group received MICBT. The control group also received the same therapy after study completion. The assessment tools used in this study included the Beck Depression Inventory-Second Edition (BDI-II), Beck Anxiety Inventory (BAI), and Miller Hope Scale (MHS). Measurements were conducted at three stages: pre-test, post-test, and follow-up. For data analysis, means and standard deviations were calculated and one-way analysis of covariance was conducted using SPSS 24. RESULTS Compared with controls, MICBT was effective for reducing depression (P < 0.001, F = 72.55), anxiety (P < 0.001, F = 100.75). Additionally, MICBT was effective in improving hope (P < 0.001, F = 45.36). Changes were maintained in the follow-up phase. CONCLUSION The MICBT affects depression, anxiety and hope of MS patients. Therefore, mental health professionals can benefit from the results obtained in the present study to reduce depression and anxiety and increase hope in this group of patients. CLINICAL TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT201601030258N4.
Changes in miRNA expressions in the injured small intestine of mice following high-dose radiation exposure

The small intestine is one of the most highly regenerative and radiosensitive tissues in mammals, including humans. Exposure to high doses of ionizing radiation causes serious intestinal damage. Recently, several investigations have been conducted using radioprotective agents to determine ways for reducing intestinal damage caused by radiation exposure. However, a thorough understanding of functional changes occurring in the small intestine of mice exposed to high-dose radiation is necessary for developing novel and more potent radioprotective agents. In this study, we examined changes in microRNA (miRNA/miR) expressions in the small intestine of mice at 72 h after X-ray exposure (10 Gy). We identified seven upregulated miRNAs and six downregulated miRNAs in the small intestine of mice following radiation exposure using miRNA microarray analysis. Particularly, miR-34a-5p was highly expressed, which was confirmed by reverse transcription-quantitative PCR. Forkhead box P1 (Foxp1) was predicted to be a target of the mRNA of miR-34a-5p using OmicsNet. Decreased Foxp1 expression in the small intestine following radiation exposure was confirmed, suggesting that Foxp1 expression recovery may induce the suppression of radiation-induced enteritis. Therefore, miR-34a-5p is a potential target molecule for developing novel radioprotective agents.
Application of weighted gene co-expression network analysis to explore the potential diagnostic biomarkers for colorectal cancer

Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Although mechanistic studies have been conducted on the pathogenesis of CRC, the molecular mechanism of CRC tumorigenesis remains unclear. In the present study, the weighted gene co-expression network analysis was performed for the Gene Expression Omnibus (GEO) dataset GSE87211, in order to analyze the key modules involved in the pathogenesis of CRC. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the key module genes to analyze the functional pathways involved. The hub genes were screened using the Cytoscape platform and verified by a second GEO dataset, GSE21510. Finally, 10 hub genes were identified in 2 key modules (the green and brown modules) as the genes most significantly associated with the tumorigenesis of CRC. The 5 hub genes from the green module included collagen type I α1 chain, collagen type XII α1 chain, collagen triple helix repeat containing 1, inhibin subunit βa (INHBA) and chromobox 2 (CBX2), while the 5 hub genes from the brown module included bestrophin 2 (BEST2), carbonic anhydrase 2, glucagon, solute carrier family 4 member 4 and gliomedin. The 2 key modules with the 10 hub genes identified may regulate the occurrence and development of CRC through the extracellular matrix pathway, PI3K-Akt and chemokine signaling pathways, thus providing a reference for understanding the complex mechanism of tumorigenesis in CRC. Of note, few studies have reported the pathogenesis of CRC with the 3 identified hub genes, INHBA, CBX2 and BEST2. Further investigation of the molecular mechanism of these genes in CRC is recommended.
On-Pump vs Off-Pump coronary artery bypass surgery in atrial fibrillation. Analysis from the polish national registry of cardiac surgery procedures (KROK)

Background No single randomized study has ever before addressed the safety of On-Pump coronary artery bypass grafting (CABG) vs Off-Pump CABG in the setting of atrial fibrillation (AF) and data from small observational samples remain inconclusive. Methods and findings Procedural data from KROK (Polish National Registry of Cardiac Surgery Procedures) were retrospectively collected. Of initial 188,972 patients undergoing CABG, 7,913 presented with baseline AF (76.0% men, mean age 69.1±8.2) and underwent CABG without concomitant valve surgery between 2006–2019 in 37 reference centers across Poland. Mean follow-up was 4.7±3.5 years (median 4.3 IQR 1.7–7.4). Cox proportional hazards models were used for computations. Of included patients, 3,681 underwent On-Pump- (46.52%) as compared to 4,232 (53.48%) who underwent Off-Pump CABG. Patients in the latter group less frequently were candidates for complete revascularization (P<0.001). In an unadjusted comparison, On-Pump surgery was associated with significantly worse survival at 30 days: HR: 1.28; 95%CIs: (1.07–1.53); P = 0.007. Along the 13-year study period, the trend shifted in favor of On-Pump CABG: HR: 0.92; 95%CIs: (0.83–0.99); P = 0.005. After rigorous propensity matching, 636 pairs were identified. The direction and magnitude of treatment effects was sustained with HRs of 3.58; (95%CIs: 1.34–9.61); p = 0.001 and 0.74; [95%CIs: 0.56–0.98]; p = 0.036) for 30-day and late mortality respectively. Conclusions Off-Pump CABG offered 30-day survival benefit to patients undergoing CABG surgery and presenting with underlying AF. On-Pump CABG was associated with significantly improved survival at long term.