Miracle-dz/UniFAR-FTUs huggingface dataset:
Zofenopril: Blood pressure control and cardio-protection

Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardio-protective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes.
Efficacy of the Systane iLux Thermal Pulsation System for the Treatment of Meibomian Gland Dysfunction After 1 Week and 1 Month: A Prospective Study

Objectives: To assess 1-week and 1-month efficacy of Systane iLux thermal pulsation treatment for meibomian gland dysfunction (MGD). Methods: This prospective, nonrandomized, open-label, multicenter study enrolled 30 adult patients (60 eyes) who had a Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score greater than 6 and total meibomian gland secretion (MGS) score equal to or less than 12 in each eye. All participants received thermal pulsation treatment bilaterally. Primary efficacy measures included MGS score (sum of grades for 15 glands graded on a scale of 0–3; 0 [no secretion], 1 [inspissated], 2 [cloudy], and 3 [clear liquid]) and tear breakup time (TBUT). Secondary efficacy measures were SPEED and Ocular Surface Disease Index (OSDI) scores. Results: The mean age of patients was 52.9±11.9 years. After 1 week, the mean MGS score improved significantly from 4.1±3.1 to 15.8±7.1 (right eye, OD) and 3.7±3.1 to 16.7±7.6 (left eye, OS); mean TBUT improved significantly from 4.9±4.1 to 8.4±3.6 (OD) and 5.2±4.2 to 8.9±3.9 (OS); and mean SPEED and OSDI scores improved significantly from 16.1±5.3 to 7.2±6.1 and 45.2±21.3 to 19.0±16.8, respectively (all P<0.001). After 1 month, the mean MGS score improved to 18.3±8.2 (OD) and 18.6±7.3 (OS); mean TBUT improved to 9.7±3.8 (OD) and 9.6±3.5 (OS); and mean SPEED and OSDI scores improved to 7.0±5.6 and 16.7±14.5, respectively (all P<0.001). No adverse events were reported. Conclusions: Systane iLux thermal pulsation treatment for MGD resulted in a statistically significant increase in meibomian gland secretion, improvement in tear film stability, and reduction in dry eye symptoms as early as both 1 week and 1 month.
Doppler ultrasound screening in patients with newly diagnosed heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a disease that presents with concurrent thrombocytopenia and thrombophilia in the setting of heparin product usage. It is caused by heparin-induced antiplatelet factor 4 (PF4) antibodies that bind PF4 (classically in the presence of heparin), forming large PF4-antibody com-plexes. Platelet and monocyte Fc receptors bind to the antibody Fc domains in these complexes, leading to platelet activation with release of procoagulant microparticles and expression of tissue factor by activated monocytes. The result is a consumptive coagulopathy with both thrombocytopenia and thrombophilia. 1 Acute HIT is associated with a high rate of arterial and venous thromboembolism in the ﬁ rst month after diagnosis. 2-4 Heparin discontinuation alone is insuf ﬁ cient to abrogate clotting risk, 5 and so the American Society of Hematology (ASH) 2018 guidelines recommend “ discontinuation of heparin and initiation of non-heparin anticoagulant ” 6 (p3375) for patients with newly diagnosed HIT. For patients without thrombosis at the time of diagnosis (isolated HIT), the ASH guidelines recommend continuation of nonheparin anticoagulation at therapeutic intensity, at least until platelet recovery, but for no longer than 3 months. In addition, the guidelines suggest “ bilateral lower-extremity compression ultrasound to screen for asymptomatic proximal deep vein thrombosis (DVT) ” 6 (p3364) in patients with acute isolated HIT (ie, no known thrombosis), as this may change the duration of anticoagulation. However, whereas the recommendation to stop heparin and start an alternative anticoagulant
Leveraging Human Plasma‐Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Cytochrome P450 3A4 by Modafinil

Preparations of plasma‐derived small extracellular vesicles (sEVs) were deployed as liquid biopsy to study cytochrome P450 (CYP) 3A4 (CYP3A4) induction following modafinil 400 mg once daily × 14 days (young healthy volunteers, N = 10 subjects). Induction was confirmed using the 4β‐hydroxycholesterol‐to‐cholesterol (4βHC/C) ratio, a plasma CYP3A4/5 biomarker, with a mean 2.1‐fold increase (Day 15 vs. Day 1; 90% confidence interval (CI) = 1.8–2.3; P value = 0.0004). Proteomic analysis revealed the induction (mean Day 15 vs. Day 1 fold‐increase (90% CI)) of both liver (1.3 (1.1–1.5), P value = 0.014) and nonliver (1.9 (1.6–2.2), P value = 0.04) sEV CYP3A4 protein expression. In CYP3A5 nonexpresser subjects, the baseline (pre‐dose) 4βHC/C plasma ratio was more highly correlated with liver sEVs (r = 0.937, P value = 0.001) than nonliver sEVs (r = 0.619, P value = 0.101) CYP3A4 protein expression. When CYP3A5 expressers (CYP3A5*1/*3) were included, the correlation with liver sEVs (r = 0.761, P value = 0.011) and nonliver sEVs (r = 0.391, P value = 0.264) CYP3A4 protein was weaker. Although modafinil‐induced changes in plasma 4βHC/C ratio did not correlate with sEVs CYP3A4 protein expression, the individual subject sEVs proteomic data were used successfully to predict victim drug (midazolam, triazolam, dextromethorphan, 17α‐ethinylestradiol, and abemaciclib) area under the plasma concentration‐time curve (AUC) ratios (AUCRs) following modafinil. Based on the AUCR values, modafinil was classified as a weak to moderate CYP3A4 inducer (vs. rifampicin). For the first time, it was possible to deploy plasma‐derived sEVs to study CYP3A4 induction beyond rifampicin, a more potent CYP3A4 inducer.
Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia in Subarachnoid Hemorrhage in Response to Hypoxic Postconditioning

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O2 for 2 hours) initiated 3 hours after SAH provides strong protection against cerebral vasospasm, microvessel thrombi, and neurological deficits. By pharmacologic and genetic inhibition of SIRT1 (sirtuin 1) using EX527 and global Sirt1 −/− mice, respectively, we demonstrated that this multifaceted DCI protection is SIRT1 mediated. Moreover, genetic overexpression of SIRT1 using Sirt1‐Tg mice, mimicked the DCI protection afforded by hypoxic postconditioning. Finally, we found that post‐SAH administration of resveratrol attenuated cerebral vasospasm, microvessel thrombi, and neurological deficits, and did so in a SIRT1‐dependent fashion. Conclusions The present study indicates that hypoxic postconditioning provides powerful DCI protection when initiated at clinically relevant time points, and that pharmacologic augmentation of SIRT1 activity after SAH can mimic this beneficial effect. We conclude that conditioning‐based therapies administered after SAH hold translational promise for patients with SAH and warrant further investigation.
Similarities and Differences in Substance Use Patterns Among Lesbian, Gay, Bisexual, and Heterosexual Mexican Adult Smokers.

Purpose: This study aimed to characterize the patterns of smoking, e-cigarette use, other substance use (alcohol and marijuana), and depression by sexual orientation in a sample of Mexican adult smokers. Methods: Data came from a 2018-2020 (six waves) online survey of adult smokers, recruited from a commercial research panel (92.5% heterosexual, n = 4786; 3.1% lesbian/gay, n = 160; and 4.4% bisexual, n = 229). After stratifying the data by sex, logistic, multinomial, and linear logistic regression models were estimated (depending on the outcome), including as independent variables sexual orientation (i.e., gay/lesbian, bisexual, heterosexual = Reference), age, education, household income, and wave. Results: Being a gay male was independently associated with greater smoking dependence (β = 0.20; 95% confidence interval [CI]: 0.02 to 0.39), greater likelihood of preference for flavored capsule cigarettes (adjusted odds ratio [AOR] = 2.10, 95% CI: 1.33 to 3.28), and depression diagnosis (AOR = 2.85, 95% CI: 1.64 to 4.95). Bisexual males had higher e-cigarette dependence (β = 0.37; 95% CI: 0.05 to 0.68, among dual users only) and were more likely to have been diagnosed with depression (AOR = 2.34, 95% CI: 1.30 to 4.18). Lesbian females were more likely to prefer menthol cigarettes (AOR = 3.32, 95% CI: 1.60 to 6.86), to have used marijuana more than once (AOR = 3.23, 95% CI: 1.83 to 5.72), and to have depressive symptoms (AOR = 1.85, 95% CI: 1.04 to 3.29). Bisexual females had a greater likelihood of depressive symptoms (AOR = 1.71, 95% CI: 1.14 to 2.56) and depression diagnosis (AOR = 2.22, 95% CI: 1.43 to 3.42). Conclusion: Lesbian, gay, and bisexual adult smokers in Mexico appear more likely than heterosexual adult smokers to report having depression. Substance use and depression among sexual minority populations need to be addressed further.
Speech production in Mandarin-speaking children with cochlear implants: a systematic review

Abstract Objective This study aimed to systematically review and critically appraise the literature describing the phonetic characteristics and accuracy of the consonants, vowels and tones produced by Mandarin-speaking children with cochlear implants (CIs). Design The protocol in this review was designed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EBSCOhost, PubMed, Scopus, PsycINFO, ProQuest Central databases were searched for relevant articles which met the inclusion criteria. Study sample A total of 18 journal papers were included in this review. Results The results revealed that Mandarin-speaking children with CIs perform consistently more poorly in their production of consonants, in particular on fricatives, have a smaller and less well-defined vowel space, and exhibit greater difficulties in tone realisation, notably T2 and T3, when compared to their normal-hearing (NH) peers. The results from acoustic and accuracy analyses are negatively correlated with CI implantation age, but largely positively correlated with hearing age. Conclusions Findings of this review highlight the factors that influence consonant, vowel and tone production in Mandarin-speaking children with CIs, thereby providing critical information for clinicians and researchers working with this population.
Evaluation of Fungcoal as a bioprocess technology for self-cladding of waste coal dumps

Low-grade coal, a poor source of energy, has long been regarded as waste material by the coal mining industry. Biological degradation of this coal material by ligninolytic fungal strains presents a viable strategy towards eliminating this unusable fossil fuel. To this end, a novel and patented bioprocess termed Fungcoal was developed. Fungcoal is a biological process utilised in the in situ treatment of waste coal and is based on the mutualistic relationship between the fungus Neosartorya fischeri and the graminaceous species Cynodon dactylon. The process facilitates the rapid conversion of waste coal into soil-like material that stimulates establishment of vegetation for eventual coal dump rehabilitation. While a number of in vitro studies have identified various fungal strains as efficient coal degraders, the mechanisms involved in the Fungcoal-stimulated degradation process have not been fully elucidated. Furthermore, implementation of Fungcoal at both pilot and commercial scale has not been achieved. Thus the objective of this work was to investigate Fungcoal as a bioprocess via examining the role of coal degrading fungi (CDF) and grasses as biocatalysts in coal biodegradation and for the self-cladding of waste coal dumps. Initially, waste coal degradation by N. fischeri, strain ECCN 84, was investigated, specifically focusing on the mechanisms underpinning the process. In vitro studies showed the addition of waste coal induced active fungal colonisation resulting in increased fungal biomass. Increased extracellular laccase (LAC) activity, occuring concomitantly with an increase in hyphal peroxisome proliferation, was also observed in the coal supplied fungal cultures. Analysis of the colonised waste coal revealed a time dependent reduction in the percentage weight of elemental carbon coupled with an increase in elemental oxygen. The results supported metabolism and degradation of waste coal by N. fischeri strain ECCN 84 and involvement of fungal extracellular laccase. The contribution of C. dactylon, a C4 grass species to in situ biodegradation of waste coal in the presence of coal degrading and mycorrhizal fungi (MF) was also investigated. Enhanced degradation of the waste coal into a humic soil-like material was observed within the rhizosphere. Analysis of the resultant substrate revealed an increased concentration of highly oxidised humic-like substances (HS). Fungi remained viable in the rhizosphere up to 47 weeks post-inoculation and cultivation of C. dactylon, indicating the resultant humic substance-rich rhizosphere provided an environment conducive for microbial proliferation and activity. Furthermore, humic substance enrichment of waste coal substrates supported germination and seedling emergence of several agronomic species including Zea mays (corn), Phaseolus vulgaris (bean), Pisum sativum (pea), and Spinacia oleracea (spinach). Use of various cladding materials to support coal biodegradation, by fungus-grass mutualism and rehabilitation of waste dumps was evaluated at commercial scale. While…
Comparison of the Effect of Ultrasound-Guided Injection of Botulinum Toxin Type A and Corticosteroid in the Treatment of Chronic Plantar Fasciitis

Supplemental digital content is available in the text. Objective The aim of the study was to compare the efficacy of ultrasound-guided injection of botulinum toxin type A with corticosteroid in patients with chronic plantar fasciitis (PF). Design This randomized controlled trial was conducted on 35 patients with chronic plantar fasciitis. Participants were randomly allocated into two groups: one group received methylprednisolone in to the plantar fascia (n = 18) and the other group received botulinum toxin type A injection into the flexor digitorum brevis and quadratus plantae (n = 17). All injections were performed under ultrasound guidance. Patients were evaluated using the Visual Analog Scale, Foot and Ankle Ability Measures, and plantar fascia thickness before the intervention, 3 wks, 12 wks, and 6 mos after the treatment. Results In both groups, patients’ pain and function improved significantly up to 3 wks after injection. In the botulinum toxin type A group, morning Visual Analog Scale improved significantly at 12 wks after intervention and the improvement was sustained for another 3 mos. In the botulinum toxin type A group, Foot and Ankle Ability Measures–sports subscale improved in all evaluated points, whereas in the corticosteroid group, the improvement was significant only when comparing follow-ups values to baseline. Conclusions Both ultrasound-guided botulinum toxin type A and corticosteroid injection were effective in the treatment of plantar fasciitis. Our study showed that the effects of botulinum toxin type A injection last longer than those of steroid injection.
Effectiveness of Physical Activity Interventions among Rural Cancer Survivors: A Systematic Review and Meta-Analysis

This review estimated the effectiveness of behavior change interventions to increase physical activity (PA) among rural adult cancer survivors. PubMed Medline, CINAHL, and PsychINFO were systematically searched through July 2020. Two independent investigators screened citations to identify studies to increase PA in adults residing in rural areas who had received any cancer diagnosis. Meta-analyses were conducted to assess proportion of participants achieving PA goal, paired mean difference (MD) in aerobic PA and strength training, and retention from baseline to post-intervention. Seven studies met inclusion criteria encompassing a total of 722 participants (591 in intervention and 131 controls). Overall quality of evidence was low to medium. The pooled proportion of participants achieving PA goals (150–225 min/wk) was 39% [95% confidence interval (CI), 18%–62%]. The mean time spent engaging in aerobic PA increased from baseline to post-intervention (range, 6–52 weeks) by 97.7 min/wk (95% CI, 75.0–120.4), and the MD in time spent on strength training was 12.2 min/wk (95% CI, −8.3–32.8). The pooled retention rate was 82% (95% CI, 69%–92%) at 6 to 78 weeks. Because of the modest intervention effects, low quality of evidence, and small number of studies, further rigorously designed behavior change interventions, including randomized controlled trials with long-term follow up, are needed to confirm efficacy for increasing PA in rural cancer survivors and to test innovative implementation strategies to enhance reach and effectiveness.
The relationship between plasma proadrenomedullin level and severity of the disease in patients with isolated rheumatic mitral stenosis.

OBJECTIVE In this study, we aimed to determine the plasma proadrenomedullin (ProADM) levels in patients with rheumatic mitral stenosis (MS), to evaluate the relationship between ProADM levels and the echocardiographic parameters that represent the severity of stenosis and symptoms, and to compare the ProADM and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, which is a well-known marker for rheumatic MS. METHODS Our study included 53 consecutive patients with isolated rheumatic MS and 45 volunteers with similar age and gender features. Patients with MS were divided into two groups based on the presence of an indication for intervention. Detailed echocardiographic examinations were performed on all participants, and blood samples were collected to detect the NT-proBNP and ProADM levels. RESULTS NT-proBNP and ProADM levels were significantly higher in the rheumatic MS group compared with the control group. In rheumatic MS groups, patients with an indication for intervention had higher levels of NT-proBNP and ProADM compared with patients without an indication for intervention. Moreover, NT-proBNP and ProADM levels were found to be significantly correlated with echocardiographic parameters, which revealed the severity of stenosis in various degrees. Both parameters increased as the New York Heart Association (NYHA) class increased, and this increase had a statistical significance. Additionally, the cut-off values of both parameters (NT-proBNP: 119.9 pg/mL, ProADM: 6.15 nmol/L) could detect patients with an indication for intervention with high sensitivity and specificity rates. NT-proBNP was found to be slightly more effective in this regard. CONCLUSION The increased NT-proBNP and ProADM levels in patients with isolated rheumatic MS can help clinicians in distinguishing patients with an indication for intervention by providing additional information to echocardiography.
Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer’s cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer’s/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.