Miracle-dz/UniFAR-FTUs huggingface dataset:
Vericiguat: The First Soluble Guanylate Cyclase Stimulator for Reduction of Cardiovascular Death and Heart Failure Hospitalization in Patients With Heart Failure Reduced Ejection Fraction

Objective: This study aims to review the pharmacology, efficacy, and safety of the soluble guanylate cyclase stimulator, vericiguat, in patients with symptomatic congestive heart failure with ejection fraction less than 45% for the reduction of cardiovascular deaths. Also, to evaluate heart failure–related hospitalization in patients following a hospital discharge secondary to heart failure or those that require outpatient intravenous diuretics. Data source: MEDLINE/Pubmed and National Institutes of Health Clinical Trial Registry were searched between January 1989 to February 2021 using the following terms: vericiguat, soluble guanylate cyclase stimulator, heart failure, (was also known as) BAY 1021189. Study Selection and Data Extraction: The following study designs were included in the analysis: phase I, II, and III clinical trials; systematic reviews; and meta-analyses. Articles were included if they were published in English and evaluated vericiguat pharmacology, pharmacokinetics, efficacy, and safety. Data Synthesis: The Food and Drug Administration approved vericiguat for the reduction of cardiovascular death and hospitalization after having a related hospitalization or the need for outpatient intravenous diuretics, in those with symptomatic chronic heart failure and ejection fraction less than 45%. In the VICTORIA trial, vericiguat demonstrated a 10% reduction in risk of death from cardiovascular causes or first hospitalization for heart failure compared with placebo. Vericiguat was well tolerated overall with hypotension, syncope, and anemia noted as the most common side effects, similar to the other agent in its class. Conclusion: Vericiguat may be appropriate as add-on therapy for patients already on guideline-directed medical therapy with recent decompensated HFrEF to reduce hospitalization.
Seneca Valley Virus 3Cpro Mediates Cleavage and Redistribution of Nucleolin To Facilitate Viral Replication

The nucleolus is a subnuclear cellular compartment, and nucleolin (NCL) resides predominantly in the nucleolus. NCL participates in viral replication, translation, internalization, and also serves as a receptor for virus entry. ABSTRACT Seneca Valley virus (SVV) is a recently discovered pathogen that poses a significant threat to the global pig industry. It has been shown that many viruses are reliant on nucleocytoplasmic trafficking of nucleolin (NCL) for their own replication. Here, we demonstrate that NCL, a critical protein component of the nucleolus, is cleaved and translocated out of the nucleoli following SVV infection. Furthermore, our data suggest that SVV 3C protease (3Cpro) is responsible for this cleavage and subsequent delocalization from the nucleoli, and that inactivation of this protease activity abolished this cleavage and translocation. SVV 3Cpro cleaved NCL at residue Q545, and the cleavage fragment (aa 1 to 545) facilitated viral replication, which was similar to the activities described for full-length NCL. Small interfering RNA-mediated knockdown indicated that NCL is required for efficient viral replication and viral protein expression. In contrast, lentivirus-mediated overexpression of NCL significantly enhanced viral replication. Taken together, these results indicate that SVV 3Cpro targets NCL for its cleavage and redistribution, which contributes to efficient viral replication, thereby emphasizing the potential target of antiviral strategies for the control of SVV infection. IMPORTANCE The nucleolus is a subnuclear cellular compartment, and nucleolin (NCL) resides predominantly in the nucleolus. NCL participates in viral replication, translation, internalization, and also serves as a receptor for virus entry. The interaction between NCL and SVV is still unknown. Here, we demonstrate that SVV 3Cpro targets NCL for its cleavage and nucleocytoplasmic transportation, which contributes to efficient viral replication. Our results reveal novel function of SVV 3Cpro and provide further insight into the mechanisms by which SVV utilizes nucleoli for efficient replication.
Assessment of disrupted brain functional connectome in tuberous sclerosis complex using resting-state fMRI

Abstract Tuberous sclerosis complex (TSC) is a rare genetic disorder with multisystem involvement. TSC is characterized by benign hamartomas in multiple organs, including the brain, and its clinical phenotypes may be associated with abnormal functional connections. We aimed to use resting-state functional connectivity to provide findings of disrupted functional brain networks in TSC patients using graph theoretical analysis (GTA) and network-based statistic (NBS) analysis. Forty TSC patients (age = 24.11+/-11.44 years old) and 18 age-matched (25.13+/- 10.01 years old) healthy controls were recruited; they underwent resting-state functional magnetic resonance imaging using a 3T magnetic resonance imaging scanner. After image preprocessing and removing physiological noises, GTA was used to calculate the topological parameters of the brain network. NBS analysis was then used to determine the differences in cerebrum functional connectivity between the 2 groups. In GTA, several topological parameters, including the clustering coefficient, local efficiency, transitivity, and modularity, were better in controls than in TSC patients (P < .05). In NBS analysis, the edges of the brain networks between the groups were compared. One subnetwork showed more edges in controls than in TSC patients (P < .05), including the connections from the frontal lobe to the temporal and parietal lobe. The study results provide the findings on disrupted functional connectivity and organization in TSC patients compared with controls. The findings may help better understand the underlying physiological mechanisms of brain connection in TSC.
Statistical Analysis Plan

Statistical analysis plan for the MTBVAC 201 clinical trial. A phase Ib, randomised, double-blind, dose-escalation clinical trial of the safety, reactogenicity and immunogenicity of MTBVAC compared to BCG Vaccine SSI, in newborns living in a tuberculosis endemic region with a safety arm in adults.
The values you endorse set the body you see: The protective effect of intrinsic life goals on men's body dissatisfaction

The mass media portrayal of a muscular body type ideal has been increasingly tied to men's body image dissatisfaction. We examined the role of self‐determination theory's intrinsic life goals within this body image ideal and its potential as a moderator of this dissatisfaction. We first tested the moderating effect of intrinsic life goals on the link between magazine consumption and body image dissatisfaction via an online questionnaire (Study 1; N = 826), then experimentally manipulated these goals and exposure to images of muscular male models (Study 2; N = 150). A robust protective effect of intrinsic goals on body image satisfaction was observed – the relationship between magazine consumption and body image dissatisfaction was only significant among individuals with a lower level of intrinsic life goal orientation. When participants' intrinsic goals were momentarily heightened, they reported significantly less body image dissatisfaction, compared to those not receiving a strengthening of these goals. The results are the first to find a protective effect of intrinsic life goals on men's body image, and have important implications for intervention.
Boosters and time from the last anti-COVID-19 vaccine dose: lead public health choices by real-time epidemiological assessment.

BACKGROUND the levels of anti-SARS-CoV-2 antibodies after the second vaccine dose decline in the following months; the administration of an additional vaccine dose (booster) is able to restore the immune system in the short period significantly reducing the risk of a severe disease. In the winter of 2021, a new particularly infectious variant caused the urgent need to increase the coverage of the booster dose. OBJECTIVES to present, using real data, an evaluation of the efficacy of the booster dose in reducing the severe disease of SARS-CoV-2 infection in terms of hospital admissions, intensive care and death from all causes. DESIGN descriptive study of vaccine adherence; associative study of the factors linked with adherence of vaccination and COVID-19 symptoms; associative study of vaccine effectiveness against hospital admission and mortality. SETTING AND PARTICIPANTS population-based study in the Milan and Lodi provinces (Lombardy Region, Northern Italy) with subjects aged >=19 years alive at 01.10. 2021, not residing in a nursery home, followed up to 31.12. 2021. MAIN OUTCOME MEASURES COVID-19 symptoms, hospitalization for COVID-19, intensive care hospitalization, and all-cause mortality in the period 01.10. 2021-31.12. 2021. RESULTS the cohort included 2,936,193 patients at 01.10. 2021: at the end of the follow-up period (31.12.2021), 378,616 (12.9%) had no vaccine, 128,879 (4.3%) had only 1 dose, 412,227 (14.0%) had a 2nd dose given since less than 4 months, 725. 806 (25%) had a 2nd dose given since 4-7 months, 74,152 (2.5%) had a 2nd dose given since 7+ months, 62,614 (2.1%) had a 2nd dose and have had the disease, and 1,153,899 (39.3%) received the booster. In the study period (01.10.2021-31.12.2021), characterized by a very high prevalence of the omicron variant, 121,620 cases (antigenic/molecular buffer positive), 3,661 hospitalizations for COVID-19, 162 ICU hospitalizations, and 7,508 deaths from all causes were identified. Compared to unvaccinated people, subjects who had the booster dose had half the risk of being symptomatic, in particular for asthenia, muscle pain, and dyspnoea which are the most commons COVID-19 symptoms. In comparison with the subjects who had the booster dose, the unvaccinated had a 10-fold risk of hospitalization for COVID-19, a 9-fold risk of intensive care, and a 3-fold risk of dying. CONCLUSIONS this work highlights the vaccination efficacy in reducing serious adverse events for those who undergo the booster and the need to implement specific engagement policies to bring to a booster those who had taken the second dose since the longest time.
Factors affecting willingness to participate in vaccine clinical trials in an underdeveloped country: perspective from Nepal

ABSTRACT Due to the inherent complex nature of clinical trials, individual’s willingness to participate and hence, enrollment in a clinical trial maybe challenging. When it comes to vaccine clinical trial in children, informed consent needs to be secured from the parents or legally acceptable representatives (LARs). Some of the factors which contribute to hesitancy in taking part in clinical trials are based on the level of education, living standards, part of the world they live, associated burden of disease, fear of different procedures in clinical trial, side effects, limited understanding, limited time, and mistrust with Investigational product. This study included 201 parents/LARs, who approached Kanti Children Hospital site in Kathmandu with the interest to get their children enrolled in a vaccine clinical trial with objectives of describing the reasons for agreeing or disagreeing to participate in the vaccine clinical trial, factors affecting decision making, and finding the major concerns of parents/LARs. The acceptance for the study vaccine was 136 (67.7%) whereas denial was 65 (32.3%). This study showed that age, education level, family structure, advice from family and friends, and medical guidance play important roles in willingness of parents to get their child enrolled in the trial. If a proper counseling is done, fear of blood sampling is not a big factor which is contrary to the belief among clinical researchers. Safety of vaccine, frequency of injections, and cost of vaccine were the main concerns of the parents, which need to be addressed extensively while planning for any clinical trial in children.
Fitness cost of malathion resistance in Egyptian Culex pipiens populations

The extensive use of insecticides in agriculture and public health has resulted in the rapid development of insecticide resistance in mosquito populations. Therefore, in this study, we aimed to evaluate insecticide resistance costs on the fitness of Culex pipiens. Two Cx. pipiens field populations (Beheira malathion‐resistant and Gharbia malathion‐susceptible) were compared to the reference (sensitive) population. The biochemical composition and expression of four genes relevant to insecticide resistance were estimated in third instar larvae. Adult survival, female fecundity and egg hatchability were also determined. As per our findings, it was found that the total protein and carbohydrate contents in Beheira malathion‐resistant larvae were significantly lower than that in the reference larvae. Beheira malathion‐resistant larvae had higher phenoloxidase (PO) specific activity than the reference population. In terms of the relevant genes, only cytochrome P450 (CYP6F1) expression showed elevated levels in the Gharbia malathion‐susceptible population compared to the Beheira malathion‐resistant population. In esterases (Estα and Estβ) and glutathione S‐transferase, the tested populations did not show any significant differences. Compared to the reference mosquito population, Gharbia malathion‐susceptible Cx. pipiens males exhibited significantly longer median survival. Female fecundity and hatchability showed nonsignificant differences among the populations tested. In conclusion, malathion resistance can induce lower protein and carbohydrate contents, but higher PO activity in larvae.
Occupational Therapy Interventions for Persons with Cognitive Impairments Living in the Community

Abstract This study describes interventions provided by community occupational therapists for persons with cognitive impairments. Using an online questionnaire, a cross-sectional study was conducted, collecting data from 497 of the 1367 occupational therapists in Norwegian community-based services. The most common interventions provided were environmental modifications (87%), implementation of assistive devices (85%), and training of activities of daily life (ADL) (77%). Two main reasons to carry out these interventions were identified as the initial assessment of clients (89%) and expectations of others. The most preferred interventions were ADL training (77%), cognitive training (63%), and environmental modifications (56%). Chi-squared tests identified a significant difference (p < 0.001) between interventions provided and preferred interventions on all interventions except environmental modifications. The findings provide an insight into interventions provided for persons with cognitive impairments in community services.
Immune‐related gene signature predicts clinical outcomes and immunotherapy response in acute myeloid leukemia

The immune response in the bone marrow microenvironment has implications for progression and prognosis in acute myeloid leukemia (AML). However, few immune‐related biomarkers for AML prognosis and immunotherapy response have been identified. We aimed to establish a predictive gene signature and to explore the determinants of prognosis in AML.
UHPLC-QTOF-MS/MS based characterization of anti-tumor constituents in Ceratocarpus arenarius L. and identification of EGFR-TK inhibitors by virtual screening

Abstract The constituents of Ceratocarpus arenarius L. , as a traditional anticancer medicine of Kazakh, were firstly profiled with UHPLC-QTOF-MS/MS. The potential compounds against EGFR-TK were virtually screened. As a result, forty-four compounds were analyzed, including 18 flavonoids, 8 steroids, 4 phenolic acids, 9 fatty acids, 1 coumarin and 4 other compounds. Among them, 9 flavonoids, N-trans-Feruloyltyramine (5), stigmasterol (11) and carthamone (38) were recognized as potential key anti-tumor constituents of C. arenarius through docking to active site of EGFR-TK. It indicated that the compounds formed moderate to strong interactions with EGFR-TK contributing to the antitumor activity through a synergetic actions. Besides, the anticancer effects of C. arenarius was verified with in-vitro anti-tumor activity investigation against A549. Our results firstly reveals the active constituents basis of C. arenarius against cancer and provides novel insights into the further application of effective constituents and mechanism of C. arenarius. Graphical Abstract
Clozapine-Induced Hypersalivation Treated with Sulpiride - Is It a Solution?

Conclusion: Further controlled studies are essential to determine the precise mechanisms of action of cannabinoids on various neuropsychiatric disorders as well as the safety of their use are needed. Never just the use of 'smoking cannabis in an unlicenced way'. The use of simple 'smoked cannabis' remains dangerous because of the effects on inducing psychosis which the article itself refers to, and needs to remain illegal. Background: To assess the psychoemotional and neurovegetative disorders in postmenopausal women depending on therapy. carried out after 30 days of treatment. Results: There was a significant difference between 1 st and 2 nd groups. KI’s neurovegetative component (hot flashes, sweating, palpitations, headaches, dizziness) in the 2nd group decreased to 10.0±1.8 points, in the 1st group - 18.4±2.0 (p<0.02). According to HADS, in the 2nd group, anxiety stopped and amounted to 6.7±0.3 points, while in the 1st group, subclinical 10.1±0.2 points remained (p (cid:0) 0.05). The average level of depression was reduced to normal - 6.5±0.3 - only in the 2nd group, in the 1st group - 9.7±0.3 (p<0.05). The average value of the indicator «Physical health» of the questionnaire SF-36 in the 1st group was 36.3±2.5 points, in the 2nd group 65.4±2.8 points (p (cid:0) 0.05); the indicator «Mental health» in the 1st group - 25.6±2.5 points, in the 2nd - 59.4±2.8 points (p (cid:0) 0.05). Conclusions: In postmenopausal women, the therapeutic correction of psychoemotional and neurovegetative disorders was associated with taking «Femo- (cid:409) lim». Adequate therapy in this category of patients contributed to the improvement of indicators of quality of life in general. using PubMed resources on the effects of cannabis using the Results: Authors examined the effects of cannabis use on psychiatric disorders and the review of the legal status of cannabis use in the world was also made. The possible consequences of cannabis legalization on the public health system were also considered, based on experiences from countries where legalization has already been done. The evidence cited in this article suggests that strong claims about the need to legalize cannabis are still questionable, and may, even in the long run, remain mixed, inconclusive, or even contradictory. Political interference in this issue can trigger a wide range of unintended but profound and lasting consequences for the health system and the health of the individual. Conclusion: We recommend further research on this topic and data collection with an emphasis on the effects and consequences of cannabis use on mental health, and in particular the benefits and harmful effects of medical cannabis use. Background: Anxiolytics such as benzodiazepines are widely used in the treatment of anxiety disorders, although they are no longer recommended as first-line therapy for these conditions due to
Implications for herbal polypharmacy: coumarin-induced hepatotoxicity increased through common herbal phytochemicals astragaloside IV and atractylenolide I

Abstract Hepatotoxicity is a well-known adverse effect of many substances, with toxicity often resulting from interactions of drugs with other drug-like substances. With the increased availability of complementary and alternative medicines, including herbal medicines, the likelihood of adverse interactions between drugs and drug-like substances in herbs increases. However, the impact of potential herb-herb interactions is little understood. To assess the potential of two cytochrome P450 enzyme modulating phytochemicals common to many herbal medicines, atractylenolide I (ATR-I) and astragaloside IV (AST-IV), to interact with coumarin, another phytochemical common in many foods, a hepatocyte function model with a liver carcinoma cell line, HepG2, was exposed to these agents. To determine the effects of cytochrome P450 modulation by these phytochemicals certain cells were induced with rifampicin to induce cytochrome P450. Increasing concentrations of ATR-I combined with a fixed, nontoxic concentration of coumarin (200 µM), demonstrated significant additive interactions. 300 µM ATR-I produced a 31% reduction in cell viability (p < 0.01) with coumarin in rifampicin uninduced cells. In rifampicin-induced cells, ATR-I (100–300 µM) produced a significant reduction in cell viability (p < 0.01) with coumarin (200 µM). AST-IV with fixed coumarin (200 µM) showed 27% toxicity at 300 µM AST-IV in rifampicin uninduced cells (p < 0.05) and 30% toxicity in rifampicin induced cells (p < 0.05). However, when fixed coumarin and AST-IV were combined with increasing concentrations of ATR-I no further significant increase in toxicity was observed (p > 0.05). These results demonstrate the potential toxic interactive capabilities of common traditional Chinese herbal medicine phytochemicals and underline the potential importance of coumarin-mediated toxicity.
A Qualitative case study of an NCAA division III female tennis player's self-regulation prior to, during, and after a singles tennis match

The sport of tennis demands high physiological and psychological self-regulation (SR). To date, the existing research focuses on isolated self-regulatory techniques and strategies employed by tennis players in competitive and non-competitive settings (McPherson, 2000; Van Raalte, Brewer, Rivera, & Petitpas, I994;Yan Raalte, Cornelius, Hatten, & Brewer,2000). However,little research exists to provide a holistic description of tennis players' SR during the three phases of a singles tennis match (i.e., preparation, performance, and reflection). To gain an in-depth understanding of the self-regulatory techniques and strategies used by a tennis player prior to, during, and after a singles match, an NCAA Division Itr female tennis player (n=1) waS purposefully selected for the present case study. The player was observed while competing in two competitive tennis matches at the end of the 2007-2008 tennis season. The participant was then interviewed several days (i.e., 2 days and 5 days, respectively, for the first and the second interviews) following the completion of each of the observed matches. A third interview was conducted 5 days after the player competed in the NCAA Division III tennis tournament. Three higher-order themes emerged after comparing and integrating the higher-order themes from the three interviews. Results indicate that the player used a combination of techniques (e.g., breathing and relaxation techniques) and strategies (e.g., self-talk, imagery, problem solving, reappraising) to self-regulate. Overall, the findings from the present study corroborated the existing theoretical and empirical knowledge regarding athletes' use of self-regulatory techniques and strategies during a competition. Additionally, the present study extended the current empirical knowledge by providing insight on a tennis player's SR prior to and after a competition. Several conclusions are discussed. Recommendations for future research and suggestions for practitioners are