Miracle-dz/UniFAR-FTUs huggingface dataset:
An Updated Systematic Review and Meta-analysis of Duloxetine for Knee Osteoarthritis Pain

Objective: We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain. Methods: A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient’s Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072). Results: Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=−0.74; 95% confidence interval [CI], −0.92 to −0.57; P<0.00001; I 2=13%; 5 trials; 1695 patients); patient general activity (MD=−0.76; 95% CI, −0.96 to −0.56; P<0.00001; I 2=0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=−4.22; 95% CI, −5.14 to −3.30; P<0.00001; I 2=26%; 5 trials; 1986 patients); Patient’s Global Impression of Improvement (MD=−0.48; 95% CI, −0.58 to −0.37; P<0.00001; I 2=29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=−0.34; 95% CI, −0.44 to −0.24; P<0.00001; I 2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=−1.68; 95% CI, −3.45 to 0.08; P=0.06; I 2=100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P=0.84; I 2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs. Conclusion: Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.
Bio-based multilayer films: A review of the principal methods of production and challenges

Abstract The development of biodegradable packaging materials has been drawing attention worldwide to minimize the environmental impact of traditional petroleum-based plastics. Nevertheless, it is challenging to obtain bio-based materials with suitable properties for packaging applications. Films produced from a single biopolymer often lack some important properties. An alternative to overcome this limitation is the multilayer assembly. Under this technology, two or more materials with specific and complementary properties are combined into a single-layered structure, thus improving the performance of bio-polymer plastics. This review presents the main aspects of bio-based multilayer film production technologies, discussing their advantages and disadvantages, which have to be considered to produce the most suitable film for each specific application. Most of the studies reported that such films resulted in increased mechanical performance and decreased water, oxygen, and dioxide carbon permeability. This approach allows the addition of compounds leading to antioxidant or antibacterial activity. Finally, a discussion about the future challenges is also presented. Graphical Abstract
ATP2B1 genotypes rs2070759 and rs2681472 polymorphisms and risk of hypertension in Saudi population

Abstract This study examined an association of ATP2B1 gene polymorphism and hypertension in the Saudi population. The 246 hypertensive cases and 300 healthy human controls were genotyped. The results showed that genotypes rs.207075 (CA + AA) [p = 0.05; OR: 95% CI, 1.5:(1.0 to 2.4) and p = 0.001, OR: 95% CI, 2.4: (1.5 to 4.0) and rs2681472 (CT + TT) [p = 0.05; OR: 95% CI, 1.5 (1.0 to 2.4) and p = 0.006 OR: 95% CI, 2.0 (1.2 to 3.1) respectively] associated with the risk of hypertension. Cases carrying the recessive models: [(CA + AA)/(CT + TT)] and [(AA)/(TT)] genotypes confer a strong susceptibility risk of hypertension [p = 0.002; OR: (95%CI) 1.8 (1.2 to 2.6) and p = 0.001; OR: (95%CI) 2.6 (1.5 to 4.7) respectively]. However, cases with body-mass-index (BMI)<25, carrying homozygous mutant genotypes [AA, rs2070759, p = 0.007; OR: (95%CI) 2.75(1.37 to 5.5) and (TT, rs2681472, p = 0.05; OR: (95%CI) 1.96 (1.03 to 3.72)] as well as A allele of rs2070759 [p = 0.006; OR: (95%CI) 1.62 (1.16 to 2.25)] and T allele of rs2681472, p = 0.04, 1.43(1.03 to 1.98)] showed a significant association with high risk of hypertension. In short, a significant association between ATP2B1 gene polymorphism and risk of hypertension was noticed. In addition, individuals carrying recessive genotypes have greater risk in developing hypertension than those carrying dominant genotypes. Moreover, cases with high-risk BMI associated with ATP2B1 variants may play a critical role in developing hypertension. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021. 1973034 .
Adverse Maternal Environment and Postweaning Western Diet Alter Hepatic CD36 Expression and Methylation Concurrently with Nonalcoholic Fatty Liver Disease in Mouse Offspring

ABSTRACT Background The role of an adverse maternal environment (AME) in conjunction with a postweaning Western diet (WD) in the development of nonalcoholic fatty liver disease (NAFLD) in adult offspring has not been explored. Likewise, the molecular mechanisms associated with AME-induced NAFLD have not been studied. The fatty acid translocase or cluster of differentiation 36 (CD36) has been implicated to play a causal role in the pathogenesis of WD-induced steatosis. However, it is unknown if CD36 plays a role in AME-induced NAFLD. Objective This study was designed to evaluate the isolated and additive impact of AME and postweaning WD on the expression and DNA methylation of hepatic Cd36 in association with the development of NAFLD in a novel mouse model. Methods AME constituted maternal WD and maternal stress, whereas the control (Con) group had neither. Female C57BL/6J mice were fed a WD [40% fat energy, 29.1% sucrose energy, and 0.15% cholesterol (wt/wt)] 5 wk prior to pregnancy and throughout lactation. Non invasive variable stressors (random frequent cage changing, limited bedding, novel object, etc.) were applied to WD dams during the last third of pregnancy to produce an AME. Con dams consumed the control diet (CD) (10% fat energy, no sucrose or cholesterol) and were not exposed to stress. Male offspring were weaned onto either CD or WD, creating 4 experimental groups: Con-CD, Con-WD, AME-CD, and AME-WD, and evaluated for metabolic and molecular parameters at 120 d of age. Results AME and postweaning WD independently and additively increased the development of hepatic steatosis in adult male offspring. AME and WD independently and additively upregulated hepatic CD36 protein and mRNA expression and hypomethylated promoters 2 and 3 of the Cd36 gene. Conclusions Using a mouse AME model together with postweaning WD, this study demonstrates a role for CD36 in AME-induced NAFLD in offspring and reveals 2 regions of environmentally induced epigenetic heterogeneity within Cd36.
What does complete revascularization mean in 2021? – Definitions, implications, and biases

Purpose of review Coronary revascularization is known to be an excellent treatment for coronary artery disease. However, whether incomplete myocardial revascularization compromises long-term outcomes, as compared to complete revascularization (CR), remains contentious. Herein, we review the concept of and evidence on CR/incomplete revascularization (ICR) and discuss future perspectives. Recent findings When possible, achieving CR in coronary artery bypass grafting is desirable; nonetheless, ICR is also a reasonable option to balance the therapeutic benefits against the risks. Summary Although angiography-based assessment currently remains the standard of care, fractional flow reserve guidance may reduce the number of lesions requiring revascularization, which may be helpful for an appropriate surgical revascularization strategy. In particular, utilizing this approach may refine hybrid revascularization procedures, especially among high-risk patients.
RNA binding protein serine/arginine splicing factor 1 promotes the proliferation, migration and invasion of hepatocellular carcinoma by interacting with RecQ protein-like 4 mRNA

ABSTRACT Abnormally high expression of RecQ protein-like 4 (RECQL4) has been observed in many cancers, including hepatocellular carcinoma (HCC). We aimed to explore the effects of RECQL4 on HCC progression and the possible mechanisms. RECQL4 expression in HCC tissues and its correlation with the prognosis of HCC patients were analyzed using GEPIA2 and UALCAN databases. After detecting RECQL4 levels in several human HC cell lines, RECQL4 was silenced by siRNA transfection. Cell viability, migration and invasion were tested with CCK-8, wound healing and transwell assays. The levels of epithelial–mesenchymal transition (EMT) proteins were evaluated by western blotting. The ENCORI database was adopted for the analysis of the correlation between RECQL4 and serine/arginine splicing factor 1 (SRSF1) in HCC tissues. RNA immunoprecipitation and actinomycin D addition assay were employed to evaluate the combination of these two genes. SRSF1 was overexpressed to assess the biological function of HCC cells with RECQL4 silencing. Results suggested that RECQL4 was overexpressed in HCC tissues and cell lines, which was related to poor prognosis of HCC patients. RECQL4 loss-of-function repressed the proliferation, migration, invasion and EMT of HCC cells. RECQL4 was positively correlated with SRSF1 in HCC tissues. Moreover, SRSF1 was confirmed as an RNA binding protein of RECQL4. Further experiments found that SRSF1 knockdown reduced the stability of RECQL4 mRNA. Rescue assays indicated that SRSF1 overexpression crippled the braking effects of RECQL4 knockdown on the progression of HCC cells. Collectively, SRSF1 can bind to RECQL4 mRNA and enhance its stability, thereby promoting the progression of HCC.
In vitro Antimalarial activity against P. falciparum (CQS-10 and CQR-K1 strain) and β-Haematin inhibition of novel synthesized Quinoline-Triazole analogues

Chloroquine (CQ) analogues are the most important scaffolds used as an anti-malarial drug, and helping human world to control and eradicate malaria for decades. Biologically, it is expected that CQ is selectively deposited in the food vacuole of the parasite, and exerting its antimalarial effect by preventing the polymerization of the toxic heme. Researchers are involved in synthesizing a number of CQ analogues to overcome its drug-resistance properties but still the toxicity has been a major problem with many of them. Nevertheless, the question of whether this problem can be overcome remains of great interest. Our vision is thus to continue with this approach, we have synthesized more hydrophilic derivatives which are likely to be less toxic 4-aminosubstituted-7-chloroquinolines analogous. Our previous experience says that the production of this class of compounds is not a problem, but purification of these quinoline analogues are very challenging. After synthesizing a series of more hydrophilic derivatives which were biologically potent, we have synthesized a series of Chloro- and Cyano- substituted quinoline-triazole conjugates and other lipophilic antimalarial scafolds in competitive yield. These quinoline-triazole analogues were showing good to moderate In vitro antimalarial activity against P. falciparum (CQS-10 & CQR-K1 strain) and also showing β-haematin inhibition activity. For synthesizing quinoline-triazole conjugates, we have synthesized amine-triazole counterpart first and then coupled with the 4,7-Dichloro or 4-Chloro-7-Cyano-quinoline. These compounds are well characterized by NMR, mass, IR and other analytical tools. These compounds will be submitted for testing against CYP3A4, an enzyme important in drug metabolism inhibition which is often related to adverse drug effects and for hERG liability. In vitro antimalarial activity will be measured in chloroquine sensitive and resistant P. falciparum and drug metabolism tested in mice. At the same time association with Fe(III)PPIX and β-haematin inhibition and then that you will be testing various biological properties in the future. References: J. Egan, R. Hunter, C. H. Kaschula, H. M. Marques, A. Misplon, J. C. Walden, J. Med. Chem. 2000, 43, 283 H. Kaschula, T. J. Egan, R. Hunter, N. Basilico, S. Parapini, D. Tarameli, E. Pasini, D. Monti, J. Med. Chem. 2002, 45, 3531. J. Egan, K. R. Koch, P. L. Swan, C. Clarkson, D. A. V. Schalkwyk, P. J. Smith, J. Med. Chem. 2004, 47, 2926. Zhishiri, M. C. Joshi, R. Hunter, K. Chibale, P. J. Smith, R. L. Summers, R. E. Martin, T. J. Egan, J. Med. Chem. 2011, 54(19), 6956-6968. C. Joshi, K. J. Wicht, D. Taylor, R. Hunter, P. J. Smith, T. J. Egan, Eur. J. Med. Chem. 2013, 69, 338-347
Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques

Supplemental Digital Content is available in the text Objective: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women. Design: Two macaque models of increasing vaginal STI severity were used for efficacy assessment. Methods: The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis. Six animals were CAB-LA treated and five were controls. The second study (n = 9) included a triple STI model with repeated exposures to C. trachomatis, T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time. Results: All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P < 0.001) or one challenge (log-rank P = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers, and seroconversion. Conclusion: In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.
Efficacy of propolis fluoride and nano silver fluoride for inhibition of streptococcus mutans and enterococcus faecalis biofilm formation

Objective: The objective of this study is to investigate the potency of propolis fluoride (PPF) and nano silver fluoride (NSF) as fluoride-based varnishes for inhibiting Streptococcus mutans and Enterococcus faecalis biofilm formation. In this study, both varnishes were compared to silver diamine fluoride (SDF) varnish, the gold standard for anticariogenic agents. Methods: The suspensions of S. mutans and E. faecalis were cultured and then plated into 96 - well plates and combined with SDF (38%), NSF (3.16, 3.66, and 4.16%), or PPF (3, 6, and 10%). E. faecalis was incubated in an anaerobic environment for 24 h, and the same protocol was used for S. mutans . The amount of biofilm inhibition was evaluated by optical density measurements at 570 nm using a microplate reader. Data were analyzed using one-way ANOVA. Results: The minimum inhibitory concentration (MIC) of PPF for S. mutans was 3%, and minimum bactericidal concentration (MBC) was 10%. The MIC of PPF for E. faecalis was at 6%, but no MBC was established . The MIC of NSF for S. mutans was 3.16%, and the MBC was 4.16%. The MIC of NSF for E. faecalis was 3.16%, while the MBC was 4.16%. Biofilm formation was inhibited dose-dependently by both NSF and PPF. Conclusion: NSF and PPF fluoride-based varnishes show clear antibacterial effects that are comparable to those obtained with SDF fluoride-based varnish.
The role of minimally invasive plate osteosynthesis (MIPO) technique for treating 3- and 4-part proximal humerus fractures in the elderly. A case study

Background and aim of the work: Proximal humeral fractures incidence in the elderly population is increasing. Treatment management is complicated by fracture complexity and patients’ comorbidities. The aim of our prospective study is the outcome evaluation of the role of minimally invasive plate osteosynthesis (MIPO) for elderly patients with a 3- or 4-parts proximal humeral fractures having an intact medial wall. Methods: N=45 patients were selected using inclusion criteria (>75yo, unilateral 3- or 4-parts proximal humeral fracture and with a surgical indication). We analyzed n=42 fractures treated with MIPO (3 patients had been reversed to ORIF and arthroplasty intraoperatively): n=20 4-parts fractures and n=22 were 3-parts. Of the 42 operated patients 17 identified as male and 25 as female (mean age 84yo). A trans-deltoid approach has been used with minimal surgical exposure and tissue damage to preserve the local tissue for early shoulder mobilization. Results: At follow-up, the DASH recorded mean value was 72, while the Constant mean score was 68. Complications have been recorded in 23,8% of patients with 4-parts fractures having the highest complication frequency. Mean shoulder joint ROM was recorded: anterior elevation 75°, lateral elevation 80°, abduction 90°, intra-rotation 50°, extra-rotation 25°. The following factors were identified influencing the outcome: >8mm calcar fragment, head valgus impaction and periosteal medial hinge preservation. Conclusions: The increase in population longevity matches the increase in complex humeral fracture frequency. We strongly for management consensus for proximal humerus fracture, in a similar way as for neck femoral fractures. MIPO is excellent in reducing soft tissue damage and complications for elderly patients with limited functional demand. (www.actabiomedica.it)
Do cognitive reserve and executive functions matter to perform the reading the mind in the eyes test in late lifespan?

Abstract Theory of Mind (ToM) is the capacity to understand the feelings and emotional states (i.e., affective ToM) or intentions, goals, and beliefs (i.e., cognitive ToM) of others. Previous evidence on the effect of executive functions and educational attainment on affective ToM is controversial. This study was conducted to investigate: (1) the nature of the associations between affective ToM and some indexes of cognitive reserve (i.e., years of education, vocabulary) in late adulthood when age was controlled; (2) whether cognitive reserve (e.g., years of education, leisure activities, vocabulary) and age predicted affective ToM in late adulthood; (3) the associations between affective ToM and some executive functions measures in late adulthood, controlling for the effect of age; (4) whether executive functioning predicted affective ToM performance; (5) whether some executive functions (i.e., cognitive flexibility and inhibition) mediated between vocabulary score (i.e., used as an index of cognitive reserve) and affective ToM score. Fifty-six 75–93-year-old community-dwellers completed a battery of tasks to assess some executive functions and affective ToM skills (i.e., through the Reading the Mind in the Eyes Test). It was found that vocabulary, age, and participation in outdoor socio-recreational leisure activities predicted 31% of the variance in the Reading the Mind in the Eyes condition. Moreover, significant relationships were found between ToM and some executive functions, that is, cognitive flexibility and inhibition predicted 34% of the ToM score. Finally, cognitive flexibility and inhibition mediate between cognitive reserve (i.e., assessed in terms of vocabulary) and Reading the Mind in the Eyes test score.
Features of intracranial interictal epileptiform discharges associated with memory encoding

Interictal epileptiform discharges (IEDs) were shown to be associated with cognitive impairment in persons with epilepsy. Previous studies indicated that IED rate, location, timing, and spatial relation to the seizure onset zone could predict an IED's impact on memory encoding and retrieval if they occurred in lateral temporal, mesial temporal, or parietal regions. In this study, we explore the influence that other IED properties (e.g., amplitude, duration, white matter classification) have on memory performance. We were specifically interested in investigating the influence that lateral temporal IEDs have on memory encoding.
COVID-19 in Pregnancy

Objective: To define the symptomatology of SARS-CoV-2 infection in pregnancy and associations between occupation, sociodemographic factors, and comorbidities with the severity of COVID-19 disease in pregnancy in all trimesters, regardless of hospitalization. Methods: We studied a retrospective cohort of a public health surveillance sample of persons with COVID-19 infection diagnosed during pregnancy. Data was collected March 2020 to August 2020 regarding symptoms, disease severity, comorbidities, obstetric history, and occupation. Results: One hundred sixty-three individuals were identified. Constitutional (64%) and lower respiratory symptoms (61%) were most common. Seventeen individuals (13.6%) were hospitalized, and one person (0.7%) died due to COVID-19. Risk factors for severe disease were age and an occupation that had high intensity exposure to people. Conclusions: Occupational exposure is a risk factor for severe COVID-19 disease in pregnancy, justifying policy measures to ensure protection of this vulnerable population.
A Summary of Phenotypes Observed in the In Vivo Rodent Alpha-Synuclein Preformed Fibril Model

The use of wildtype recombinant alpha-synuclein preformed fibrils (aSyn PFFs) to induce endogenous alpha-synuclein to form pathological phosphorylation and trigger neurodegeneration is a popular model for studying Parkinson’s disease (PD) biology and testing therapeutic strategies. The strengths of this model lie in its ability to recapitulate the phosphorylation/aggregation of aSyn and nigrostriatal degeneration seen in PD, as well as its suitability for studying the progressive nature of PD and the spread of aSyn pathology. Although the model is commonly used and has been adopted by many labs, variability in observed phenotypes exists. Here we provide summaries of the study design and reported phenotypes from published reports characterizing the aSyn PFF in vivo model in rodents following injection into the brain, gut, muscle, vein, peritoneum, and eye. These summaries are designed to facilitate an introduction to the use of aSyn PFFs to generate a rodent model of PD—highlighting phenotypes observed in papers that set out to thoroughly characterize the model. This information will hopefully improve the understanding of this model and clarify when the aSyn PFF model may be an appropriate choice for one’s research.