Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychological Inflexibility as a Predictor of Sexual Functioning Among Women with Vulvovaginal Pain: A Prospective Investigation

Abstract Objective Persistent vulvovaginal pain affects many women and often has adverse effects on sexual functioning. Psychological inflexibility related to pain is associated with distress and functional disability across different types of chronic pain conditions, but little is known about the role of psychological inflexibility in vulvovaginal pain. The present study examines psychological inflexibility related to pain as a predictor of sexual functioning over time among women with vulvovaginal pain. Methods Questionnaires including measures of psychological inflexibility, pain severity, and sexual functioning were administered to female university students at two points in time. One hundred thirty women with vulvovaginal pain responded to the questionnaire at baseline and at follow-up after 10 months. A multiple regression model was used to explore psychological inflexibility and pain severity as predictors of sexual functioning at follow-up. Results Higher levels of psychological inflexibility and more severe pain at baseline were associated with poorer sexual functioning 10 months later. In analysis adjusting for baseline levels of sexual functioning, psychological inflexibility was the only significant predictor of sexual functioning at follow-up. Conclusions The findings provide preliminary evidence that psychological inflexibility is associated with sexual adjustment over time among women with vulvovaginal pain and point to the relevance of further examinations of the psychological inflexibility model in the context of vulvovaginal pain.
Diet and Diabetes in Relation to Coronary Artery Disease

The prevalence rate of diabetes in Indians appears to be greater than that of Western populations . This may be due to rapid changes in diet and lifestyle of urbans resulting in central obesity. Beta-cells of pancreas and arterial endothelial cells are highly susceptible to damage due to free radicals and diet deficient in antioxidant vitamins A,E and C. Carotene may not be able to provide necessary protection resulting in a decrease in insulin action and development of diabetes mellitus. Insulin resistance becomes worst in presence of higher dietary fat intake leading to central obesity and associated disturbances. It seems that antioxidant deficiency and central obesity are two independent risk factors of non-insulin dependent diabetes which also predisposes to CVD. The prevalence rates of diabetes mellitus (8.6%) and of CAD (8.6%) in our study were comparable with industrialised countries. For each, quintile of waisthip ratio (WHR) above 0.88, dietary fat intake was higher and physical activity lower than that for lower WHR. Plasma insulin, blood glucose and triglycerides for each upper quintile of WHR were significantly higher than for lower quintiles. It is possible that populations with higher prevalence of diabetes and cardiovascular risk can be benefitted by increased intake of antioxidant rich foods such as fruits, vegetables and oils. It seems that any increase in fat intake beyond 21% energy per day, any increase in body mass index above 21 and WHR beyond 0.88 should be avoided to prevent diabetes and CVD. "Eating at least 600g/day of fruits, vegetables and legumes especially before major meals can decrease cardiovascular risk" is the major conclusion of our research.
Healthcare Platform and Big Data Analysis Based Personal Fitness Healthcare Service Model

Human beings are living longer these days thanks to developments in medical technology and health care services, and accordingly, the global population is rapidly aging. The increasing aging generation is causing unexpected social problems, one of the most critical of which is government health care costs. Personal gene analysis results and record-based personal health care ICT services should predict and prevent personal diseases while improving wellness. Technically, gene sequencing technology development not only reduces the time to decode genetic information but also decreases the cost. Various disease-related gene mutations have been found, and gene sequencing service is a new paradigm in personal health care. In socioeconomic terms, the proposed service model not only accurately diagnoses diseases to provide effective health care but also reduces government health care costs while promoting personal well-being. In this paper, we propose a PGAR (personal gene analysis record) and PHR (personal health care record)-based personal health care service. We implemented this big data analysis-based health care platform for more accurate disease prediction and prevention. When the personal smart health care ICT service is used, it significantly reduces personal health care costs in hospitals.
The GPR17 Receptor—A Promising Goal for Therapy and a Potential Marker of the Neurodegenerative Process in Multiple Sclerosis

One of the most important goals in the treatment of demyelinating diseases such as multiple sclerosis (MS) is, in addition to immunomodulation, reconstruction of the lost myelin sheath. The modulator of the central nervous system myelination is the metabotropic receptor coupled to the G-protein: GPR17. GPR17 receptors are considered to be sensors of local damage to the myelin sheath, and play a role in the reconstruction and repair of demyelinating plaques caused by ongoing inflammatory processes. GPR17 receptors are present on nerve cells and precursor oligodendrocyte cells. Under physiological conditions, they are responsible for the differentiation and subsequent maturation of oligodendrocytes, while under pathological conditions (during damage to nerve cells), their expression increases to become mediators in the demyelinating processes. Moreover, they are essential not only in both the processes of inducing damage and the death of neurons, but also in the local repair of the damaged myelin sheath. Therefore, GPR17 receptors may be recognized as the potential goal in creating innovative therapies for the treatment of the neurodegenerative process in MS, based on the acceleration of the remyelination processes. This review examines the role of GRP17 in pathomechanisms of MS development.
The Transient Receptor Potential Channel Vanilloid 1 (TRPV1) is Critical in Innate Airway Epithelial Responses to Protease Allergens.

The airway epithelium plays a critical role in innate responses to airborne allergens by secreting IL-1 family cytokines such as interleukin (IL)-1α and IL-33, as alarmins that subsequently orchestrate appropriate immune responses. Previous studies revealed that epithelial IL-33 secretion by allergens such as A. alternaria (ALT) or house dust mite (HDM) involves Ca2+-dependent signaling, via initial activation of ATP-stimulated type 2 purinoceptors (P2YR2) and subsequent activation of the NADPH oxidase DUOX1. We sought to identify proximal mechanisms by which epithelial cells sense these allergens, and here highlight the importance of protease-activated receptors (PAR2) and transient receptor potential (TRP) Ca2+ channels such as TRP Vanilloid 1 (TRPV1) in these responses. Combined studies of primary human nasal and mouse tracheal epithelial cells, as well as immortalized human bronchial epithelial cells (HBE1), indicated the importance of both PAR2 and TRPV1 in IL-33 secretion by both ALT and HDM, based on both pharmacological and genetic approaches. TRPV1 was also critically involved in allergen-induced ATP release, activation of DUOX1, and redox-dependent activation of EGFR. Moreover, genetic deletion of TRPV1 dramatically attenuated allergen-induced IL-33 secretion and subsequent type 2 responses in mice in vivo. TRPV1 not only contributed to ATP release and P2YR2 signaling, but was also critical in downstream innate responses to ATP, indicating potentiating effects of P2YR2 on TRPV1 activation. In aggregate, our studies illustrate a complex relationship between various receptor types, including PAR2 and P2YR2, in epithelial responses to asthma-relevant airborne allergens and highlight the central importance of TRPV1 in such responses.
Melatonin Promotes the Proliferation of Chicken Sertoli Cells by Activating the ERK/Inhibin Alpha Subunit Signaling Pathway

Melatonin influences physiological processes such as promoting proliferation and regulating cell development and function, and its effects on chicken Sertoli cells are unknown. Therefore, we investigated the effects of melatonin on cell proliferation and its underlying mechanisms in chicken Sertoli cells. Chicken Sertoli cells were exposed to varying melatonin concentrations (1, 10, 100, and 1000 nM), and the melatonin-induced effects on cell proliferation were measured by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), real-time qPCR, and western blotting. We found that 1000 nM melatonin significantly (p < 0.05) promoted cell proliferation in chicken Sertoli cells. Furthermore, melatonin significantly (p < 0.05) increased the expression of inhibin alpha subunit (INHA), and the silencing of INHA reversed the melatonin-induced effects on Sertoli cell proliferation. We also found that melatonin activates the extracellular-regulated protein kinase (ERK) signaling pathway. To explore the role of the ERK signaling pathway in melatonin-induced cell proliferation, PD98059 (an inhibitor of EKR1/2) was used to pre-treat chicken Sertoli cells. The melatonin-induced proliferation of chicken Sertoli cells was reversed by PD98059, with decreased cell viability, weakened cell proliferation, and down-regulated expression of the proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and INHA. In summary, our results indicate that melatonin promotes the proliferation of chicken Sertoli cells by activating the ERK/inhibin alpha subunit signaling pathway.
LOX-1: A potential driver of cardiovascular risk in SLE patients

Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients’ blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients.
Fast Prototyping Microfluidics: Integrating Droplet Digital Lamp for Absolute Quantification of Cancer Biomarkers

Microfluidic (MF) advancements have been leveraged toward the development of state-of-the-art platforms for molecular diagnostics, where isothermal amplification schemes allow for further simplification of DNA detection and quantification protocols. The MF integration with loop-mediated isothermal amplification (LAMP) is today the focus of a new generation of chip-based devices for molecular detection, aiming at fast and automated nucleic acid analysis. Here, we combined MF with droplet digital LAMP (ddLAMP) on an all-in-one device that allows for droplet generation, target amplification, and absolute quantification. This multilayer 3D chip was developed in less than 30 minutes by using a low-cost and extremely adaptable production process that exploits direct laser writing technology in “Shrinky-dinks” polystyrene sheets. ddLAMP and target quantification were performed directly on-chip, showing a high correlation between target concentration and positive droplet score. We validated this integrated chip via the amplification of targets ranging from five to 500,000 copies/reaction. Furthermore, on-chip amplification was performed in a 10 µL volume, attaining a limit of detection of five copies/µL under 60 min. This technology was applied to quantify a cancer biomarker, c-MYC, but it can be further extended to any other disease biomarker.
Application of an Inter-Species Extrapolation Method for the Prediction of Drug Interactions between Propolis and Duloxetine in Humans

Duloxetine (DLX) is a potent drug investigated for the treatment of depression and urinary incontinence. DLX is extensively metabolized in the liver by two P450 isozymes, CYP2D6 and CYP1A2. Propolis (PPL) is one of the popular functional foods known to have effects on activities of CYPs, including CYP1A2. Due to the high probability of using DLX and PPL simultaneously, the present study was designed to investigate the potent effect of PPL on pharmacokinetics (PKs) of DLX after co-administration in humans. A PK study was first conducted in 18 rats (n = 6/group), in which the plasma concentration of DLX and its major metabolite 4-hydroxy duloxetine (4-HD) with or without administration of PPL was recorded. Population PKs and potential effects of PPL were then analyzed using NONMEM software. Lastly, these results were extrapolated from rats to humans using the allometric scaling and the liver blood flow method. PPL (15,000 mg/day) exerts a statistically significant increase in DLX exposures at steady state, with a 20.2% and 24.6% increase in DLX Cmax,ss and the same 28.0% increase in DLX AUCss when DLX (40 or 60 mg) was administered once or twice daily, respectively. In conclusion, safety issues are required to be attended to when individuals simultaneously use DLX and PPL at high doses, and the possibility of interactions between DLX and PPL might be noted.
Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.
Plant Growth Promotion Abilities of Phylogenetically Diverse Mesorhizobium Strains: Effect in the Root Colonization and Development of Tomato Seedlings

Mesorhizobium contains species widely known as nitrogen-fixing bacteria with legumes, but their ability to promote the growth of non-legumes has been poorly studied. Here, we analyzed the production of indole acetic acid (IAA), siderophores and the solubilization of phosphate and potassium in a collection of 24 strains belonging to different Mesorhizobium species. All these strains produce IAA, 46% solubilized potassium, 33% solubilize phosphate and 17% produce siderophores. The highest production of IAA was found in the strains Mesorhizobium ciceri CCANP14 and Mesorhizobium tamadayense CCANP122, which were also able to solubilize potassium. Moreover, the strain CCANP14 showed the maximum phosphate solubilization index, and the strain CCANP122 was able to produce siderophores. These two strains were able to produce cellulases and cellulose and to originate biofilms in abiotic surfaces and tomato root surface. Tomato seedlings responded positively to the inoculation with these two strains, showing significantly higher plant growth traits than uninoculated seedlings. This is the first report about the potential of different Mesorhizobium species to promote the growth of a vegetable. Considering their use as safe for humans, animals and plants, they are an environmentally friendly alternative to chemical fertilizers for non-legume crops in the framework of sustainable agriculture.
“I’m not homeless, I’m houseless”: identifying as homeless and associations with service utilization among Los Angeles homeless young people

ABSTRACT Little is known about homeless young people’s identification of being homeless and how that identity may or may not be associated with service utilization. This study of 444 homeless young people attending Los Angeles area drop-in centers explores the associations of demographic characteristics, homelessness characteristics, negative lifetime experiences, mental health symptoms, technology use, and past month service utilization with identifying as homeless. Fifty-two percent of the sample identified as being homeless. Being Black, a current traveler, and history of injection drug use were all significantly associated with a decreased likelihood in identifying as homeless. However, having fair/poor health, accessing shelter services, and reporting one’s own substance use as a reason for homelessness were all significantly associated with identifying as homeless. There are important service implications for reaching young people who are in need of services but may not identify with the target population label of homeless.
An Overview on ERAP Roles in Infectious Diseases

Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8+ T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.
Effects of Diaphorina citri Population Density on Daily Timing of Vibrational Communication Calls: Potential Benefits in Finding Forage

Adult Diaphorina citri (ACP) use visual and chemical cues to locate young citrus flush shoots on which they forage and oviposit, and they use vibrational communication duetting calls as cues to help locate mates. For individual pairs, calling and mating usually peaks between 10:00 and 15:00. To explore whether call rates (calls/h) are affected by interactions with nearby conspecifics, rates were compared in small citrus trees on which either 5 or 25 ACP female and male pairs had been released at 17:00 for later recording from sunrise (06:00) to 22:00. Final ACP locations were noted 40 h after release. Call rates were similar in both treatments during normal mating hours. However, rates were significantly higher for low- than high-density treatments between 06:00 and 10:00, which suggests calling during this period may be affected by conspecific density. Both sexes aggregated on flush at both densities. We discuss the potential that ACP producing calls near sunrise, outside of normal mating hours, might benefit from gains in reproductive fitness in low-density contexts if they call not only to locate mates but also to locate preferred flush—in which case, co-opting of vibrations to disrupt both mating and foraging may be feasible.
Synergies between Surface Microstructuring and Molecular Nanopatterning for Controlling Cell Populations on Polymeric Biointerfaces

Polymeric biointerfaces are already being used extensively in a wide set of biomedical devices and systems. The possibility of controlling cell populations on biointerfaces may be essential for connecting biological systems to synthetic materials and for researching relevant interactions between life and matter. In this study, we present and analyze synergies between an innovative approach for surface microstructuring and a molecular nanopatterning procedure of recent development. The combined set of techniques used may be instrumental for the development of a new generation of functional polymeric biointerfaces. Eukaryotic cell cultures placed upon the biointerfaces developed, both before and after molecular patterning, help to validate the proposal and to discuss the synergies between the surface microstructuring and molecular nanopatterning techniques described in the study. Their potential role in the production of versatile polymeric biointerfaces for lab- and organ-on-a-chip biodevices and towards more complex and biomimetic co-culture systems and cell cultivation set-ups are also examined.
Analysis of regulatory T cells and CTLA-4 expression in pregnant women according to seropositivity to Toxoplasma gondii

Abstract Pregnancy is considered a period in which immunomodulation occurs, although it is important for the maintenance of the foetus, could contribute to infections as Toxoplasma gondii. Immune response cells such as regulatory T cells participate in this immunomodulation, and surface molecules such as CTLA-4 develop an immunosuppressive role, could contribute to the establishment of the parasite. This study aimed to evaluate the presence of regulatory T cells and the expression of CTLA-4 in parturient and non-pregnant seropositive and seronegative for anti-T. gondii antibodies. Sixty-two participants were evaluated, 14 parturient with negative serology, 23 parturient with positive serology, 16 non-pregnant women seronegative and 9 non-pregnant women seropositive. Immunophenotyping was performed for characterize TCD4+Foxp3+ cells, T CD4+CD25-Foxp3+, TCD4+CD25highFoxp3+, TCD4+CTLA-4+, TCD4+CD25-CTLA-4+ and TCD4+CD25highCTLA-4+. We observed a lower level of CD4+CD25highFoxp3+ cells from seropositive parturient compared with seropositive non-pregnant cells. Significative levels of CD4+CD25-Foxp3+ cells from seronegative pregnant were observed compared with seropositive pregnant cells. Furthermore, the higher level of CD4+CD25-CTLA-4+ cells populations was detected in seropositive pregnant cells compared with seropositive non-pregnant. Although a significant increase in CTLA-4 cells was observed in pregnant women positive for anti-T. gondii antibodies, this increase did not cause a risk of reactivation of the infection.