Miracle-dz/UniFAR-FTUs huggingface dataset:
Single nucleotide polymorphisms in treatment of polycystic ovary syndrome: a systematic review

Abstract As 15–20% of reproductive aged females are suffering from polycystic ovary syndrome (PCOS), a large number of pharmacological preparations are frequently available in the market for the treatment of PCOS; however, they seem to be ineffective and cause undesirable side effects. This has emphasized the need to optimize dosage regimens for individualized treatment. The objective of this systematic review is to review single nucleotide polymorphisms (SNPs) associated with drugs used for the treatment of PCOS to understand pharmacogenetics variability of patients to drug response there by helping clinicians in designing tailored treatments and possibly reducing adverse drug reactions. A comprehensive electronic literature search was conducted to highlight some clinically relevant SNPs that act to influence PCOS and associated co-morbidities. A total of 16 studies were included in this review. These genetic variations can be used as a potential target for pharmacotherapy and pharmacogenetic clinical trials for better diagnosis, management, and treatment planning.
Anti-Biofilm Effect of Selected Essential Oils and Main Components on Mono- and Polymicrobic Bacterial Cultures

Biofilms are surface-associated microbial communities resistant to sanitizers and antimicrobials. Various interactions that can contribute to increased resistance occur between the populations in biofilms. These relationships are the focus of a range of studies dealing with biofilm-associated infections and food spoilage. The present study investigated the effects of cinnamon (Cinnamomum zeylanicum), marjoram (Origanum majorana), and thyme (Thymus vulgaris) essential oils (EOs) and their main components, i.e., trans-cinnamaldehyde, terpinen-4-ol, and thymol, respectively, on single- and dual-species biofilms of Escherichia coli, Listeria monocytogenes, Pseudomonas putida, and Staphylococcus aureus. In dual-species biofilms, L. monocytogenes was paired with each of the other three bacteria. Minimum inhibitory concentration (MIC) values for the individual bacteria ranged between 0.25 and 20 mg/mL, and trans-cinnamaldehyde and cinnamon showed the highest growth inhibitory effect. Single-species biofilms of L. monocytogenes, P. putida, and S. aureus were inhibited by the tested EOs and their components at sub-lethal concentrations. Scanning electron microscopy images showed that the three-dimensional structure of mature biofilms embedded in the exopolysaccharide matrix disappeared or was limited to micro-colonies with a simplified structure. In most dual-species biofilms, to eliminate living cells from the matrix, concentrations exceeding the MIC determined for individual bacteria were required.
Nurr1, Pitx3, and α7 nAChRs mRNA Expression in Nigral Tissue of Rats with Pedunculopontine Neurotoxic Lesion

Background and Objectives: The knowledge that the cholinergic neurons from pedunculopontine nucleus (PPN) are vulnerable to the degeneration in early stages of the Parkinson disease progression has opened new perspectives to the development of experimental model focused in pontine lesions that could increase the risk of nigral degeneration. In this context it is known that PPN lesioned rats exhibit early changes in the gene expression of proteins responsible for dopaminergic homeostasis. At the same time, it is known that nicotinic cholinergic receptors (nAChRs) mediate the excitatory influence of pontine-nigral projection. However, the effect of PPN injury on the expression of transcription factors that modulate dopaminergic neurotransmission in the adult brain as well as the α7 nAChRs gene expression has not been studied. The main objective of the present work was the study of the effects of the unilateral neurotoxic lesion of PPN in nuclear receptor-related factor 1 (Nurr1), paired-like homeodomain transcription factor 3 (Pitx3), and α7 nAChRs mRNA expression in nigral tissue. Materials and Methods: The molecular biology studies were performed by means of RT-PCR. The following experimental groups were organized: Non-treated rats, N-methyl-D-aspartate (NMDA)-lesioned rats, and Sham operated rats. Experimental subjects were sacrificed 24 h, 48 h and seven days after PPN lesion. Results: Nurr1 mRNA expression, showed a significant increase both 24 h (p < 0.001) and 48 h (p < 0.01) after PPN injury. Pitx3 mRNA expression evidenced a significant increase 24 h (p < 0.001) followed by a significant decrease 48 h and seven days after PPN lesion (p < 0.01). Finally, the α7 nAChRs nigral mRNA expression remained significantly diminished 24 h, 48 h (p < 0.001), and 7 days (p < 0.01) after PPN neurotoxic injury. Conclusion: Taking together these modifications could represent early warning signals and could be the preamble to nigral neurodegeneration events.
Adherence to guidelines on documentation required for registration to London GP practice websites: a mixed-methods cross-sectional study.

BACKGROUND The most common obstacle to registration with a GP practice in the UK is difficulty presenting proof of address. NHS guidelines stipulate that inability to provide ID or proof of address is not reasonable grounds to refuse registration. Practices may ask patients to present ID/proof of address, but need a policy in case patients cannot. AIM To find out how many London GP practice websites ask for documentation without a policy for where this cannot be provided and compare how GP practice websites describe the registration process in patient-facing material. DESIGN AND SETTING Cross-sectional study of practices from 10 London boroughs (n = 100). METHOD A proforma was piloted and then implemented, recording whether practices 'demanded', 'requested', or 'mentioned' photo ID or proof of address and whether there was a plan for patients without documentation. Text relating to documentation from all 100 practices for registration was subjected to thematic analysis. RESULTS Out of 100 practices 75% asked for documentation. The majority of these were 'demanded'. A plan was included for people without documentation in 12% of practice websites. Five themes emerged from analysis of website content: reassuring people without documentation; diverse requirements between practices; conflating administration and treatment; withholding treatment; and immigration and ethnicity. CONCLUSION Many practice websites breached NHS Standard Operating Principles and possibly the Equalities Act 2010. All practices should create a clear policy for patients who do not have photo ID/proof of address (for example, including a named receptionist), and update their websites accordingly.
Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF‐α production in human macrophages and cross the blood‐brain barrier in mice

Among the main bacteria implicated in the pathology of periodontal disease, Aggregatibacter actinomycetemcomitans (Aa) is well known for causing loss of periodontal attachment and systemic disease. Recent studies have suggested that secreted extracellular RNAs (exRNAs) from several bacteria may be important in periodontitis, although their role is unclear. Emerging evidence indicates that exRNAs circulate in nanosized bilayered and membranous extracellular vesicles (EVs) known as outer membrane vesicles (OMVs) in gram‐negative bacteria. In this study, we analyzed the small RNA expression profiles in activated human macrophage‐like cells (U937) infected with OMVs from Aa and investigated whether these cells can harbor exRNAs of bacterial origin that have been loaded into the host RNA‐induced silencing complex, thus regulating host target transcripts. Our results provide evidence for the cytoplasmic delivery and activity of microbial EV‐derived small exRNAs in host gene regulation. The production of TNF‐α was promoted by exRNAs via the TLR‐8 and NF‐κB signaling pathways. Numerous studies have linked periodontal disease to neuroinflammatory diseases but without elucidating specific mechanisms for the connection. We show here that intracardiac injection of Aa OMVs in mice showed successful delivery to the brain after crossing the blood‐brain barrier, the exRNA cargos increasing expression of TNF‐α in the mouse brain. The current study indicates that host gene regulation by microRNAs originating from OMVs of the periodontal pathogen Aa is a novel mechanism for host gene regulation and that the transfer of OMV exRNAs to the brain may cause neuroinflammatory diseases like Alzheimer's. —Han, E. ‐C. , Choi, S. ‐Y. , Lee, Y. , Park, J.‐W. , Hong S. ‐H. , Lee, H. ‐J. Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF‐α production in human macrophages and cross the blood‐brain barrier in mice. FASEB J. 33, 13412–13422 (2019). www.fasebj. org
Three‐Dimensional Echocardiography for Transcatheter Aortic Valve Replacement Sizing: A Systematic Review and Meta‐Analysis

Background Transcatheter aortic valve replacement (TAVR) is the standard of care for many patients with severe symptomatic aortic stenosis and relies on accurate sizing of the aortic annulus. It has been suggested that 3‐dimensional transesophageal echocardiography (3D TEE) may be used instead of multidetector computed tomography (MDCT) for TAVR planning. This systematic review and meta‐analysis compared 3D TEE and MDCT for pre‐TAVR measurements. Methods and Results A systematic literature search was performed. The primary outcome was the correlation coefficient between 3D TEE– and MDCT‐measured annular area. Secondary outcomes were correlation coefficients for mean annular diameter, annular perimeter, and left ventricular outflow tract area; interobserver and intraobserver agreements; mean differences between 3D TEE and MDCT measurements; and pooled sensitivities, specificities, and receiver operating characteristic area under curve values of 3D TEE and MDCT for discriminating post‐TAVR paravalvular aortic regurgitation. A random effects model was used. Meta‐regression and leave‐one‐out analysis for the primary outcome were performed. Nineteen studies with a total of 1599 patients were included. Correlations between 3D TEE and MDCT annular area, annular perimeter, annular diameter, and left ventricular outflow tract area measurements were strong (0.86 [95% CI, 0.80–0.90]; 0.89 [CI, 0.82–0.93]; 0.80 [CI, 0.70–0.87]; and 0.78 [CI, 0.61–0.88], respectively). Mean differences between 3D TEE and MDCT between measurements were small and nonsignificant. Interobserver and intraobserver agreement and discriminatory abilities for paravalvular aortic regurgitation were good for both 3D TEE and MDCT. Conclusions For pre‐TAVR planning, 3D TEE is comparable to MDCT. In patients with renal dysfunction, 3D TEE may be potentially advantageous for TAVR measurements because of the lack of contrast exposure.
A Multifunctional Biosurfactant Extract Obtained from Corn Steep Water as Bactericide for Agrifood Industry

The increase of crop production along with stricter requirements on food security have augmented the demand of new and eco-friendly bactericides. Most of the bactericides used at the moment consist of persistent organic substances, representing a risk for environmental and human health. For instance, agriculture bactericides used for crop protection includes copper-based, dithiocarbamate and amide bactericides, which are not biodegradable, resulting in the necessity of further research about the production of new active principles that attack microorganisms without producing any harmful effect on human health or environment. The biosurfactant extract evaluated in this work as a bactericide, is obtained from corn steep water, a residual stream of corn wet milling industry, which is fermented spontaneously by probiotic lactic acid bacteria that possess the capacity to produce biosurfactants. In previous works, it has been demonstrated that this biosurfactant extract is able to promote the growth of Lactobacillus casei in drinkable yogurts, though its antimicrobial activity against pathogenic strains has not been evaluated at the moment. The results obtained in this work have proved that this biosurfactant extract is effective as bactericide against Pseudomonas aeruginosa and Escherichia coli, at concentrations of 1 mg/mL, opening the door to its use in agrifood formulations for reducing the use of chemical pesticides and preservatives.
Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy

Significance Glioblastoma (GB) is the most lethal brain malignancy without an effective treatment. In this study, we demonstrate that tumor-induced change in chaperone-mediated autophagy (CMA) in host perivascular cells is a targetable process to prevent GB progression. CMA regulates pericyte interaction with tumor cells and sustains the acquired immunosuppressive function of pericytes, which is required for tumor survival. Blockage of CMA results in changes in the protein levels involved in cell-to-cell interaction and affects the pericyte secretory phenotype, resulting in defective GB adhesion and diminished tumor survival. This work reveals a previously unknown capacity of GB to modulate host pericyte CMA to assist in its own progression. Our results highlight the possibility of targeting CMA to treat this aggressive disease. The contractile perivascular cells, pericytes (PC), are hijacked by glioblastoma (GB) to facilitate tumor progression. PC’s protumorigenic function requires direct interaction with tumor cells and contributes to the establishment of immunotolerance to tumor growth. Cancer cells up-regulate their own chaperone-mediated autophagy (CMA), a process that delivers selective cytosolic proteins to lysosomes for degradation, with pro-oncogenic effects. However, the possible impact that cancer cells may have on CMA of surrounding host cells has not been explored. We analyzed the contribution of CMA to the GB-induced changes in PC biology. We have found that CMA is markedly up-regulated in PC in response to the oxidative burst that follows PC–GB cell interaction. Genetic manipulations to block the GB-induced up-regulation of CMA in PC allows them to maintain their proinflammatory function and to support the induction of effective antitumor T cell responses required for GB clearance. GB-induced up-regulation of CMA activity in PC is essential for their effective interaction with GB cells that help tumor growth. We show that CMA inhibition in PC promotes GB cell death and the release of high immunogenic levels of granulocyte-macrophage colony stimulating factor (GM-CSF), through deregulation of the expression of cell-to-cell interaction proteins and protein secretion. A GB mouse model grafted in vivo with CMA-defective PC shows reduced GB proliferation and effective immune response compared to mice grafted with control PC. Our findings identify abnormal up-regulation of CMA as a mechanism by which GB cells elicit the immunosuppressive function of PC and stabilize GB–PC interactions necessary for tumor cell survival.
Influence of Nanosilica on Mechanical Properties, Sorptivity, and Microstructure of Lightweight Concrete

This study presents the results of an experimental investigation of the effects of nanosilica (NS) on the strength development, transport properties, thermal conductivity, air-void, and pore characteristics of lightweight aggregate concrete (LWAC), with an oven-dry density <1000 kg/m3. Four types of concrete mixtures, containing 0 wt. %, 1 wt. %, 2 wt. %, and 4 wt. % of NS were prepared. The development of flexural and compressive strengths was determined for up to 90 days of curing. In addition, transport properties and microstructural properties were determined, with the use of RapidAir, mercury intrusion porosimetry (MIP), and scanning electron microscopy (SEM) techniques. The experimental results showed that NS has remarkable effects on the mechanical and transport properties of LWACs, even in small dosages. A significant improvement in strength and a reduction of transport properties, in specimens with an increased NS content, was observed. However, the positive effects of NS were more pronounced when a higher amount was incorporated into the mixtures (>1 wt.%). NS contributed to compaction of the LWAC matrix and a modification of the air-void system, by increasing the amount of solid content and refining the fine pore structure, which translated to a noticeable improvement in mechanical and transport properties. On the other hand, NS decreased the consistency, while increasing the viscosity of the fresh mixture. An increment of superplasticizer (SP), along with a decrement of stabilizer (ST) dosages, are thus required.
Corrosion Behavior of SMA490BW Steel and Welded Joints for High-Speed Trains in Atmospheric Environments

Currently, high-speed trains work under various atmospheric environments, and the bogie as a key component suffers serious corrosion. To investigate the corrosion behavior of bogies in industrial atmospheric environments, the periodic immersion wet/dry cyclic corrosion test for SMA490BW steel and automatic metal active gas (MAG) welded joints used for bogies was conducted in the present work. Corrosion weight loss rate, structure, and composition of rust layers as well as electrochemistry parameters were investigated. The results showed that the corrosion weight loss rate decreased with increasing corrosion time; furthermore, the corrosion weight loss rate of the welded joints was lower than that of SMA490BW steel. The XRD results showed that the rust layers formed on SMA490BW steel and its welded joints were mainly composed of α-FeOOH, γ-FeOOH, Fe2O3, and Fe3O4. The observation of surface morphology indicated that the rust layers of the welded joints were much denser and had a much finer microstructure compared with those of SMA490BW steel. After corrosion for 150 h, the corrosion potential of the welded joints with rust layers was higher than that of SMA490BW steel. In short, the welded joints exhibited better corrosion resistance than SMA490BW steel because of the higher content of alloy elements, as shown in this work.
Predictors of Abstinence from Smoking: A Retrospective Study of Male College Students Enrolled in a Smoking Cessation Service

There were high smoking rates among young male college students in Korea. We aimed to investigate the prevalence of and factors affecting abstinence from smoking following smoking cessation service attendance in this population. Data were collected between 1 August 2015 and 20 August 2018. Participants were administered more than nine face-to-face and telephone counseling sessions by trained tobacco cessation specialists for six months. Follow-up assessments were conducted at 4, 6, and 12 weeks, and 6 months after the quit date. A total of 3978 male college student smokers were enrolled; their mean age was 23.17 (±3.45) years. Almost one-third of the participants (64.9%) reported that they had attempted to quit during the past year. The number of cigarettes smoked per day, CO ppm, and Fagerström Test of Nicotine Dependence score at the baseline were negatively associated with abstinence, while motivational variables—importance, confidence, and readiness—were positively associated with abstinence. Our results suggest that provision of visiting smoking cessation services can be an active intervention platform for college student smokers who need professional assistance or support. Active and accessible support should be provided to such people. Visiting a smoking cessation service may result in increased long-term abstinence rates in such students.
Ovarian Follicle Depletion Induced by Chemotherapy and the Investigational Stages of Potential Fertility-Protective Treatments—A Review

Ovarian follicle pool depletion, infertility, and premature menopause are all known sequelae of cancer treatment that negatively impact the quality of life of young cancer survivors. The mechanisms involved in this undesired iatrogenic ovarian damage have been intensively studied, but many of them remain unclear. Several chemotherapeutic drugs have been shown to induce direct and indirect DNA-damage and/or cellular stress, which are often followed by apoptosis and/or autophagy. Damage to the ovarian micro-vessel network induced by chemotherapeutic agents also seems to contribute to ovarian dysfunction. Another proposed mechanism behind ovarian follicle pool depletion is the overactivation of primordial follicles from the quiescent pool; however, current experimental data are inconsistent regarding these effects. There is great interest in characterizing the mechanisms involved in ovarian damage because this might lead to the identification of potentially protective substances as possible future therapeutics. Research in this field is still at an experimental stage, and further investigations are needed to develop effective and individualized treatments for clinical application. This review provides an overview of the current knowledge and the proposed hypothesis behind chemotherapy-induced ovarian damage, as well as current knowledge on possible co-treatments that might protect the ovary and the follicles from such damages.
The 40 kDa Linear Polyethylenimine Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection by Blocking Its Attachment to Permissive Cells

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in pigs worldwide. The causative agent is the PRRS virus (PRRSV). In this study, we explored polyethylenimine (PEI), a cationic polymer with different forms (linear or branched), to inhibit the replication of PRRSV. Our results demonstrate that the linear but not the 40 kDa branched PEI, or the 25 kDa linear PEI, were well tolerated in cultured cells and exhibited a broad-spectrum inhibition of heterogeneous PRRSV-2 isolates in both MARC-145 cells and primary porcine pulmonary alveolar macrophages (PAMs). Further analysis suggests that PEI could prevent the attachment of PRRSV virions to the susceptible cells. Notably, PEI had a minimal effect on PRRSV internalization in MARC-145 cells, whereas PEI promoted the internalization of PRRSV virions in PAMs, which suggests that these two types of cells might have different internalization processes of PRRSV virions. In conclusion, our data demonstrate that PEI could be used as a novel inhibitor against PRRSV.
Dietary Micronutrient Supplementation for 12 Days in Obese Male Mice Restores Sperm Oxidative Stress

Male obesity, which often co-presents with micronutrient deficiencies, is associated with sub-fertility. Here we investigate whether short-term dietary supplementation of micronutrients (zinc, selenium, lycopene, vitamins E and C, folic acid, and green tea extract) to obese mice for 12 days (designed to span the epididymal transit) could improve sperm quality and fetal outcomes. Five-week-old C57BL6 males were fed a control diet (CD, n = 24) or high fat diet (HFD, n = 24) for 10 weeks before allocation to the 12-day intervention of maintaining their original diets (CD, n = 12, HFD n = 12) or with micronutrient supplementation (CD + S, n = 12, HFD + S, n = 12). Measures of sperm quality (motility, morphology, capacitation, binding), sperm oxidative stress (DCFDA, MSR, and 8OHdG), early embryo development (2-cell cleavage, 8OHdG), and fetal outcomes were assessed. HFD + S males had reduced sperm intracellular reactive oxygen species (ROS) concentrations and 8OHdG lesions, which resulted in reduced 8OHdG lesions in the male pronucleus, increased 2-cell cleavage rates, and partial restoration of fetal weight similar to controls. Sub-fertility associated with male obesity may be restored with very short-term micronutrient supplementation that targets the timing of the transit of sperm through the epididymis, which is the developmental window where sperm are the most susceptible to oxidative damage.