Miracle-dz/UniFAR-FTUs huggingface dataset:
Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS

Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.
MoTBFs: An R Package for Learning Hybrid Bayesian Networks Using Mixtures of Truncated Basis Functions

This paper introduces MoTBFs , an R package for manipulating mixtures of truncated basis functions. This class of functions allows the representation of joint probability distributions involving discrete and continuous variables simultaneously, and includes mixtures of truncated exponentials and mixtures of polynomials as special cases. The package implements functions for learning the parameters of univariate, multivariate, and conditional distributions, and provides support for parameter learning in Bayesian networks with both discrete and continuous variables. Probabilistic inference using forward sampling is also implemented. Part of the functionality of the MoTBFs package relies on the bnlearn package, which includes functions for learning the structure of a Bayesian network from a data set. Leveraging this functionality, the MoTBFs package supports learning of MoTBF-based Bayesian networks over hybrid domains. We give a brief introduction to the methodological context and algorithms implemented in the package. An extensive illustrative example is used to describe the package, its functionality, and its usage.
No association between use of angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID‐19 in the COvid MEdicaTion (COMET) study

Since the outbreak of SARS‐CoV‐2, also known as COVID‐19, conflicting theories have circulated on the influence of angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID‐19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID‐19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID‐19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.
Effect of baking treatment and materials composition on the properties of bulky PMMA–silica hybrid sol–gel materials with low volume shrinkage

A series of bulky PMMA-silica hybrid sol- gel materials had been successfully prepared through the conventional HCl-catalyzed sol- gel approach with 2-hy- droxyethyl methyl methacrylate (HEMA) as coupling agent under pumping pretreatment (i.e., exhaustive vacuum evac- uation). In this work, the hydroxyl groups of HEMA mono- mers were first cohydrolyzed with various contents of tet- raethyl orthosilicate (TEOS) to afford chemical bonding for the forming silica networks by removal of solvent and by- product of sol- gel reactions through pumping pretreatment before gelation reactions. Subsequently, the resultant vis- cous solution was then copolymerized with methyl methac- rylate (MMA) monomers at specific feeding ratios by using benzoyl peroxide (BPO) as free-radical initiator. Eventually, transparent bulky organic-inorganic hybrid sol- gel materi- als loaded with different silica content were always achieved. The obtained bulky hybrid sol- gel materials were found to be transparent, crack-free, and of relatively low volume shrinkages even in high silica content. The as-pre- pared bulky hybrid sol- gel materials were then character- ized through silicon element mapping studies of energy- dispersive X-ray (EDX) and transmission electron micros- copy (TEM). Effect of heating process at 150°C for 5 h after polymerization and material composition on the thermal properties, mechanical strength, and optical clarity of a se- ries of bulky PMMA-silica hybrid sol- gel materials was investigated and compared by thermogravimetric analysis (TGA), thermomechanical analysis (TMA), hardness test, dynamic mechanical analysis (DMA), and UV-vis transmis- sion spectroscopy, respectively. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1151-1159, 2006
Atherogenic Index of Plasma in Obstructive Sleep Apnoea

Background: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity. Methods: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index. Results: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all p < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score (ρ = 0.19), the apnoea-hypopnoea index (ρ = 0.40) and oxygen desaturation index (ρ = 0.43, all p < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all p > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C. Conclusions: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C.
LncRNA H19-Derived miR-675-5p Accelerates the Invasion of Extravillous Trophoblast Cells by Inhibiting GATA2 and Subsequently Activating Matrix Metalloproteinases

The invasion of extravillous trophoblast (EVT) cells into the maternal decidua, which plays a crucial role in the establishment of a successful pregnancy, is highly orchestrated by a complex array of regulatory mechanisms. Non-coding RNAs (ncRNAs) that fine-tune gene expression at epigenetic, transcriptional, and post-transcriptional levels are involved in the regulatory mechanisms of EVT cell invasion. However, little is known about the characteristic features of EVT-associated ncRNAs. To elucidate the gene expression profiles of both coding and non-coding transcripts (i.e., mRNAs, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs)) expressed in EVT cells, we performed RNA sequencing analysis of EVT cells isolated from first-trimester placentae. RNA sequencing analysis demonstrated that the lncRNA H19 and its derived miRNA miR-675-5p were enriched in EVT cells. Although miR-675-5p acts as a placental/trophoblast growth suppressor, there is little information on the involvement of miR-675-5p in trophoblast cell invasion. Next, we evaluated a possible role of miR-675-5p in EVT cell invasion using the EVT cell lines HTR-8/SVneo and HChEpC1b; overexpression of miR-675-5p significantly promoted the invasion of both EVT cell lines. The transcription factor gene GATA2 was shown to be a target of miR-675-5p; moreover, small interfering RNA-mediated GATA2 knockdown significantly promoted cell invasion. Furthermore, we identified MMP13 and MMP14 as downstream effectors of miR-675-5p/GATA2-dependent EVT cell invasion. These findings suggest that miR-675-5p-mediated GATA2 inhibition accelerates EVT cell invasion by upregulating matrix metalloproteinases.
A cross-sectional analysis of risk factors for cardiovascular diseases in older females: association between body fat distribution and physical fitness

ABSTRACT This study aimed to determine whether body fat distribution and physical fitness would be associated with risk factors for cardiovascular diseases (CVDs) in post-menopausal females. Android fat distribution were more likely to have altered total cholesterol (TC), high-density lipoprotein (HDL-C), triglycerides (TG), glycemic levels (GL) body fat percentage (%BF), and body mass index (BMI), and those with inadequate physical fitness showed clear alterations in TC, HDL-C, and TG. Gynoid fat distribution group fared better regarding CVD risk. In conclusion, adequate physical fitness demonstrates a protective factor against CVDs, with the greatest benefit to those with gynoid fat distribution.
Superior semicircular canal dehiscence syndrome: Diagnostic criteria consensus document of the committee for the classification of vestibular disorders of the Bárány Society

This paper describes the diagnostic criteria for superior semicircular canal dehiscence syndrome (SCDS) as put forth by the classification committee of the Bárány Society. In addition to the presence of a dehiscence of the superior semicircular canal on high resolution imaging, patients diagnosed with SCDS must also have symptoms and physiological tests that are both consistent with the pathophysiology of a ‘third mobile window’ syndrome and not better accounted for by another vestibular disease or disorder. The diagnosis of SCDS therefore requires a combination of A) at least one symptom consistent with SCDS and attributable to ‘third mobile window’ pathophysiology including 1) hyperacusis to bone conducted sound, 2) sound-induced vertigo and/or oscillopsia time-locked to the stimulus, 3) pressure-induced vertigo and/or oscillopsia time-locked to the stimulus, or 4) pulsatile tinnitus; B) at least 1 physiologic test or sign indicating that a ‘third mobile window’ is transmitting pressure including 1) eye movements in the plane of the affected superior semicircular canal when sound or pressure is applied to the affected ear, 2) low-frequency negative bone conduction thresholds on pure tone audiometry, or 3) enhanced vestibular-evoked myogenic potential (VEMP) responses (low cervical VEMP thresholds or elevated ocular VEMP amplitudes); and C) high resolution computed tomography (CT) scan with multiplanar reconstruction in the plane of the superior semicircular canal consistent with a dehiscence. Thus, patients who meet at least one criterion in each of the three major diagnostic categories (symptoms, physiologic tests, and imaging) are considered to have SCDS.
Dysregulation of Protein Kinase C in Adult Depression and Suicide: Evidence From Postmortem Brain Studies

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study, we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region (Brodmann area 9) in 24 normal control subjects, 24 depressed suicide (DS) subjects, and 12 depressed nonsuicide (DNS) subjects. The levels of mRNA in the prefrontal cortex were determined by quantitative real-time reverse transcription PCR, and the protein expression was determined by western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ, and PKCε and decreased protein expression in either the membrane or the cytosol fraction of PKC isozymes PKCα, PKCβI, PKCβII, and PKCδ in DS and DNS subjects compared with normal control subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of the adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.
Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study

Limited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIV-positive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART−) and 171 individuals without HIV (HIV−) in Mthatha, Eastern Cape Province of South Africa. Flow-mediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART− and HIV− participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV− and HIV+ART− participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART.
Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop

Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration.
Crossover of Rate-Limiting Process in Plasma Gel Growth by Contact with Source of Gelator

Plasma is regarded as a solution of precursor polymers specifically transformed to gel-forming polymers by a reaction with initiators. We developed a theory for the gel growth dynamics of plasma induced by contact with a source of gelators that are yielded by the initiation. In developing the theory, we combined the Ginzburg–Landau type dynamics with the gelator diffusion dynamics expressed by the moving boundary picture. The theory predicts the crossover of the rate-limiting process in the time course of the thickness of the gel layer X from the energy-limited process expressed by X∼t to the diffusion-limited process expressed by X∼t, where t is the time elapsed from when the plasma comes into contact with the source of gelators. A demonstration experiment was performed by placing a tissue factor coating plate as the initiator in plasma. Log–log plot of X vs. t showed a crossover as predicted by the theory, and the parameters characterizing plasma were determined.
Comparison of murine behavioural and physiological responses after forced exercise by electrical shock versus manual prodding

What is the central question of this study? Forced treadmill exercise using electrical shock is the most common technique in rodent exercise studies. Here, we examined how the use of electrical shock during forced treadmill exercise affects behavioural and physiological responses in comparison to a novel non‐electrical shock technique. What is the main finding and its importance? In comparison to mice that underwent traditional treadmill running induced by electrical shock, mice that underwent forced running using a novel technique involving gentle prodding to induce running showed: (i) higher locomotor activity; (ii) less anxiety‐like behaviour; and (iii) altered exercise‐induced muscle pain immediately after exercise.
Interventions on health care providers to improve seasonal influenza vaccination rates among patients: a systematic review and meta-analysis of the evidence since 2000

Abstract Background Seasonal influenza vaccination (SIV) rates remain suboptimal in many populations, even in those with universal SIV. Objective To summarize the evidence on interventions on health care providers (physicians/nurses/pharmacists) to increase SIV rates. Methods We systematically searched/selected full-text English publications from January 2000 to July 2019 (PROSPERO-CRD42019147199). Our outcome was the difference in SIV rates between patients in intervention and non-intervention groups. We calculated pooled difference using an inverse variance, random-effects model. Results We included 39 studies from 8370 retrieved citations. Compared with no intervention, team-based training/education of physicians significantly increased SIV rates in adult patients: 20.1% [7.5–32.7%; I2 = 0%; two randomized controlled trials (RCTs)] and 13.4% [8.6–18.1%; I2 = 0%; two non-randomized intervention studies (NRS)]. A smaller increase was observed in paediatric patients: 7% (0.1–14%; I2 = 0%; two NRS), and in adult patients with team-based training/education of physicians and nurses together: 0.9% (0.2–1.5%; I2 = 30.6%; four NRS). One-off provision of guidelines/information to physicians, and to both physicians and nurses, increased SIV rates in adult patients: 23.8% (15.7–31.8%; I2 = 45.8%; three NRS) and paediatric patients: 24% (8.1–39.9%; I2 = 0%; two NRS), respectively. Use of reminders (prompts) by physicians and nurses slightly increased SIV rates in paediatric patients: 2.3% (0.5–4.2%; I2 = 0%; two RCTs). A larger increase was observed in adult patients: 18.5% (14.8–22.1%; I2 = 0%; two NRS). Evidence from both RCTs and NRS showed significant increases in SIV rates with varied combinations of interventions. Conclusions Limited evidence suggests various forms of physicians’ and nurses’ education and use of reminders may be effective for increasing SIV rates among patients.