Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of within- and between-person assessments of alcohol expectancies and valuations on use and consequences moderated by sex.

BACKGROUND Alcohol expectancies (AE; beliefs about the likelihood of outcomes) and valuations (beliefs about the desirability of outcomes) may help explain alcohol use by young adults. However, it remains unclear how variability in AE and valuations over time are related to alcohol-related outcomes, and whether these associations are moderated by sex. The current study addressed these gaps in knowledge by examining within-person variability among positive and negative AEs, valuations, and alcohol-related outcomes over a 12-month period. METHODS Data were collected from 433 college students (Mage = 20.06; 59.81% women) who completed surveys at 4 timepoints: at baseline and 3-month, 6-month, and 12-month follow-up. RESULTS We found substantial within-person variability in both AE and valuations (intraclass correlation coefficients ranged from 50% to 66%), and differences in variability by sex, with women showing more variability than men. Multilevel models revealed that weekly drinking was significantly higher at timepoints in which participants held relatively greater AE for sociability, sexuality, and risk/aggression, but lower when participants expected greater effects on self-perception. Weekly drinking was also higher when participants reported more favorable valuation of risk/aggression. Participants experienced significantly more negative consequences at timepoints in which they held relatively greater AE for sexuality and self-perception. No AEs were associated with a reduced likelihood of negative consequences. Participants experienced more negative consequences at timepoints in which they reported more favorable valuation of self-perception No valuations were associated with fewer consequences. Several between- and within-person associations were moderated by sex. CONCLUSIONS These findings suggest that AE and valuations are dynamic, that young adults' beliefs about the effects of alcohol varied over time, and that both negative and positive AE and valuations may be important correlates of alcohol use and consequences. These findings have implications for interventions designed to challenge expectancies and valuations with the goal of reducing alcohol use and associated consequences.
Evaluating livestock farmers knowledge, beliefs, and management of arboviral diseases in Kenya: A multivariate fractional probit approach

Globally, arthropod-borne virus (arbovirus) infections continue to pose substantial threats to public health and economic development, especially in developing countries. In Kenya, although arboviral diseases (ADs) are largely endemic, little is known about the factors influencing livestock farmers’ knowledge, beliefs, and management (KBM) of the three major ADs: Rift Valley fever (RVF), dengue fever and chikungunya fever. This study evaluates the drivers of livestock farmers’ KBM of ADs from a sample of 629 respondents selected using a three-stage sampling procedure in Kenya’s three hotspot counties of Baringo, Kwale, and Kilifi. A multivariate fractional probit model was used to assess the factors influencing the intensity of KBM. Only a quarter of the farmers had any knowledge of ADs while over four-fifths of them could not manage any of the three diseases. Access to information (experience and awareness), income, education, religion, and distance to a health facility considerably influenced the intensity of farmers’ KBM of ADs in Kenya. Thus, initiatives geared towards improving access to information through massive awareness campaigns are necessary to mitigate behavioral barriers in ADs management among rural communities in Kenya.
N-acetyl cysteine ameliorates aortic fibrosis by promoting M2 macrophage polarization in aging mice

ABSTRACT Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear. Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice. Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined. Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis. Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.
Identification of novel potential inhibitors of varicella-zoster virus thymidine kinase from ethnopharmacologic relevant plants through an in-silico approach

Abstract Although Varicella or chickenpox infection which is caused by the varicella-zoster virus (VZV) has significantly been managed through vaccination, it remains an infection that poses threats to the nearest future due to therapeutic drawbacks. The focus of this research was geared towards in silico screening for the identification of novel compounds in plants of ethnopharmacological relevance in the treatment of chicken pox in West Africa. The work evaluated 65 compounds reported to be present in Achillea millefolium, Psidium guajava and Vitex doniana sweet to identify potential inhibitors of thymidine kinase, the primary drug target of varicella zoster virus. Out of the 65 compounds docked, 42 of these compounds were observed to possess binding energies lower than −7.0 kcal/mol, however only 20 were observed to form hydrogen bond interactions with the protein. These interactions were elucidated using LigPlot+ and MM-PBSA analysis with residue Ala134 predicted as critical for binding. Pharmacological profiling predicted three potential lead compounds comprising myricetin, apigenin- 4' -glucoside and Abyssinone V to possess good pharmacodynamics properties and negligibly toxic. The molecules were predicted as antivirals including anti-herpes and involved in mechanisms comprising inhibition of polymerase, ATPase and membrane integrity, which were corroborated previously in other viruses. These drug-like compounds are plausible biotherapeutic moieties for further biochemical and cell-based assaying to discover their potential for use against chickenpox. Communicated by Ramaswamy H. Sarma
Effectiveness and safety of bevacizumab in extensive-disease small cell lung cancer: a systemic review and meta-analysis

Background Small cell lung cancer (SCLC) is highly invasive and poorly prognostic. The effects of chemotherapy with bevacizumab are promising on other tumors but unclear in extensive-disease SCLC (ED-SCLC). A systemic review and meta-analysis were performed to investigate the efficacy and toxicity in ED-SCLC patients. Methods A review of current studies was performed on electronic databases and other sources to identify publications of ED-SCLC patients who received bevacizumab. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and complications. Results Nine relevant articles with six single-arm and three two-arm studies were identified. Four hundred seventy-six patients were included, of which 368 and 108 were untreated and relapse patients. Most patients were performance status 0–1 (71.6%) and male (58.1%). The comparisons showed CT/bevacizumab slightly prolonged OS (HR =0.84) but significantly improved PFS (HR =0.74). The ORRs of untreated and relapse patients were 71% and 19%, though no significant difference was observed than CT/placebo. The most grade 3–4 complication and bevacizumab-associated complications were neutropenia and hypertension, whose rates were 33% and 6%. Patients who received CT/bevacizumab had a higher hypertension rate than CT/placebo (6% vs. 2%). No different complication rate was observed between high and lose dose groups. Discussion The present study suggests that bevacizumab in the combination of standard chemotherapy provides better PFS than chemotherapy alone. Although the combined regimen is well-tolerated, no superiority in OS or response rate is observed.
Effects of Manual Therapies and Resistance Exercise on Postexercise Hypotension in Women With Normal Blood Pressure

Abstract Monteiro, ER, Pescatello, LS, Winchester, JB, Corrêa Neto, VG, Brown, AF, Budde, H, Marchetti, PH, Silva, JG, Vianna, JM, and Novaes, JdS. Effects of manual therapies and resistance exercise on postexercise hypotension in women with normal blood pressure. J Strength Cond Res 36(4): 948–954, 2022—The purpose of this investigation was to examine the acute effects of resistance exercise (RE) and different manual therapies (static stretching and manual massage [MM]) performed separately or combined on blood pressure (BP) responses during recovery in women with normal BP. Sixteen recreationally strength-trained women (age: 25.1 ± 2.9 years; height: 158.9 ± 4.1 cm; body mass: 59.5 ± 4.9 kg; body mass index: 23.5 ± 1.9 kg·m−2; baseline systolic BP median: 128 mm Hg; and baseline diastolic BP median: 78 mm Hg) were recruited. All subjects performed 6 experiments in a randomized order: (a) rest control (CON), (b) RE only (RE), (c) static-stretching exercise only (SS), (d) MM only, (e) RE immediately followed by SS (RE + SS), and (f) RE immediately followed by MM (RE + MM). RE consisted of 3 sets of bilateral bench press, back squat, front pull-down, and leg press exercises at 80% of 10RM. Static stretching and MM were applied unilaterally in 2 sets of 120 seconds to each of the quadriceps, hamstring, and calf regions. Systolic (SBP) and diastolic BP were measured before (rest) and every 10 minutes for 60 minutes following (Post 10–60) each intervention. There were significant intragroup differences for RE in Post-50 (p = 0.038; d = −2.24; ∆ = −4.0 mm Hg). Similarly, SBP intragroup differences were found for the SS protocol in Post-50 (p = 0.021; d = −2.67; ∆ = −5.0 mm Hg) and Post-60 (p = 0.008; d = −2.88; ∆ = −5.0 mm Hg). Still, SBP intragroup differences were found for the MM protocol in Post-50 (p = 0.011; d = −2.61; ∆ = −4.0 mm Hg) and Post-60 (p = 0.011; d = −2.74; ∆ = −4.0 mm Hg). Finally, a single SBP intragroup difference was found for the RE + SS protocol in Post-60 (p = 0.024; d = −3.12; ∆ = −5.0 mm Hg). Practitioners should be aware that SS and MM have the potential to influence BP responses in addition to RE or by themselves and therefore should be taken into consideration for persons who are hypertensive or hypotensive.
Reviewing Evidence on the Relations Between Oral Reading Fluency and Reading Comprehension for Adolescents

In this article, I systematically review evidence on the relations between oral reading fluency (ORF) and reading comprehension (RC) for adolescents with limited reading proficiency (ALRP) in Grades 6 to12. I organized findings from 23 studies into five themes: (a) unclear role of ORF in the simple view of reading model for ALRP, (b) ALRP have distinct reader profiles, (c) ORF consists of more than automaticity, (d) the role of ORF varies, and (e) oral reading automaticity has tenuous predictive value for ALRP. Results suggest that knowledge of an adolescent’s ORF, as commonly defined and assessed, provides helpful information about an adolescent’s reader profile but is not sufficient to evaluate instructional needs or measure progress. I conclude the article with a discussion on implications for researchers, assessment developers, practitioners, and school administrators.
Heterogeneity Analysis of Chest CT Predict Individual Prognosis of COVID-19 Patients.

BACKGROUND Ground-glass opacity (GGO) and consolidation opacity (CLO) are the common CT lung opacities, and their heterogeneity may have potential for prognosis ofcoronavirus disease-19 (COVID-19) patients. OBJECTIVE This study aimed to estimate clinical outcomes in individual COVID-19 patients using histogram heterogeneity analysis based on CT opacities. METHODS 71 COVID-19 cases' medical records were retrospectively reviewed from a designated hospital in Wuhan, China, from January 24th to February 28th at the early stage of the pandemic. Two characteristic lung abnormity opacities, GGO and CLO, were drawn on CT images to identify the heterogeneity using quantitative histogram analysis. The parameters (mean, mode, kurtosis, and skewness) were derived from histograms to evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. RESULTS A total of 57 COVID-19 cases were eligible for the study cohort after excluding 14 cases. The highest lung abnormalities were GGO mixed with CLO in both the survival populations (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as follows: GGO_skewness: specificity=66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity=76.92%, and AUC=0.746. Nomogram based on histogram parameters can predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively. CONCLUSION Histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.
Tacrine Induces Endoplasmic Reticulum–Stressed Apoptosis via Disrupting the Proper Assembly of Oligomeric Acetylcholinesterase in Cultured Neuronal Cells

Acetylcholinesterase inhibitors (AChEIs), the most developed treatment strategies for Alzheimer’s disease (AD), will be used in clinic for, at least, the next decades. Their side effects are in highly variable from drug to drug with mechanisms remaining to be fully established. The withdrawal of tacrine (Cognex) in the market makes it as an interesting case study. Here, we found tacrine could disrupt the proper trafficking of proline-rich membrane anchor-linked tetrameric acetylcholinesterase (AChE) in the endoplasmic reticulum (ER). The exposure of tacrine in cells expressing AChE, e.g., neurons, caused an accumulation of the misfolded AChE in the ER. This misfolded enzyme was not able to transport to the Golgi/plasma membrane, which subsequently induced ER stress and its downstream signaling cascade of unfolded protein response. Once the stress was overwhelming, the cooperation of ER with mitochondria increased the loss of mitochondrial membrane potential. Eventually, the tacrine-exposed cells lost homeostasis and underwent apoptosis. The ER stress and apoptosis, induced by tacrine, were proportional to the amount of AChE. Other AChEIs (rivastigmine, bis(3)-cognitin, daurisoline, and dauricine) could cause the same problem as tacrine by inducing ER stress in neuronal cells. The results provide guidance for the drug design and discovery of AChEIs for AD treatment. SIGNIFICANCE STATEMENT Acetylcholinesterase inhibitors (AChEIs) are the most developed treatment strategies for Alzheimer’s disease (AD) and will be used in clinic for at least the next decades. This study reports that tacrine and other AChEIs disrupt the proper trafficking of acetylcholinesterase in the endoplasmic reticulum. Eventually, the apoptosis of neurons and other cells are induced. The results provide guidance for drug design and discovery of AChEIs for AD treatment.
The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders

Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon‐like peptide 1 (GLP‐1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP‐1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti‐addiction treatment. Studies in rodents and non‐human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP‐1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered.
Effects of YAP1 and SFRP2 overexpression on the biological behavior of colorectal cancer cells and their molecular mechanisms.

Background Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. Methods We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. Results The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. Conclusions Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC.
Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.

AIMS In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. METHODS AND RESULTS Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13-17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). CONCLUSION On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
A community‐based trial of a psychosocial eHealth intervention for parents of children with cancer

The Electronic Surviving Cancer Competently Intervention Program (eSCCIP), a psychosocial eHealth intervention for parents and caregivers of children with cancer (parents), was delivered in a community‐based psychosocial oncology center. Primary endpoints were intervention acceptability, feasibility, and accessibility, with a secondary exploratory focus on psychosocial outcomes.
Evaluation of urinary acetaminophen metabolites and its association with the genetic polymorphisms of the metabolising enzymes, and serum acetaminophen concentrations in preterm neonates with patent ductus arteriosus

Abstract Acetaminophen is gaining importance as a first-line drug for treating patent ductus arteriosus (PDA) in neonates. Predominant metabolites of acetaminophen in preterm neonates vary from that of adults; and the drug is predominantly metabolised by conjugation and partly by Cytochrome P450 (CYP) enzymes. We carried out the present study to identify the principal urine metabolites of acetaminophen (glucuronide/sulphate) in preterm neonates with hemodynamically significant PDA receiving intravenous acetaminophen, and to evaluate the prevalence of single nucleotide polymorphisms (SNPs) in the key CYP enzymes (CYP1A2*3, CYP1A2*4, CYP1A2*1C, CYP1A2*1K, CYP1A2*6, CYP2D6*10, CYP2E1*2, CYP2E1*5B, CYP3A4*1B, CYP3A4*2, CYP3A4*3, CYP3A5*3, CYP3A5*7, and CYP3A5*11) and their effect on urinary metabolites and serum acetaminophen concentrations. Nineteen (32.8%) neonates had heterozygous CYP1A2*1C, two (3.3%) with heterozygous CYP1A2*1K, 15 (27.8%) and two (3.7%) had heterozygous and homozygous CYP2D6*10, two (3.7%) had heterozygous CYP2E1*5B, seven (12.3%) and three (5.3%) had heterozygous and homozygous CYP3A4*1B, and three (5.5%) had CYP3A5*7 amongst the study population. Acetaminophen sulphate predominated over glucuronide metabolite at all time points. Postnatal days of life was significantly associated with an increase in the urine acetaminophen metabolites with decreased serum acetaminophen concentrations. A significant prevalence of SNPs in the key CYP enzymes related to acetaminophen metabolism was observed in our neonatal population. Population pharmacokinetic-pharmacodynamic modelling incorporating genetic and metabolite data is urgently needed for implementation of precision medicine in this vulnerable population.