Miracle-dz/UniFAR-FTUs huggingface dataset:
Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine

Background Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. Material/Methods Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. Results Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1 kg for the first nociceptive phase (P<0.005). Conclusions In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.
High coping self-efficacy associated with lower odds of pre-frailty/frailty in older adults with chronic disease

Abstract Objectives Frailty affects an estimated 15% of community dwelling older adults. Few studies look at psychosocial variables like self-efficacy (confidence to perform well at a particular task or life domain) in relation to frailty. The purpose of this study was to evaluate associations between pre-frailty/frailty and self-efficacy. Methods This cross-sectional study enrolled community dwelling older adults 65 and older (N = 146) with at least one chronic condition. Scales included: 5-item FRAIL scale (including measures of Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight); coping self-efficacy used to measure confidence in one’s ability to problem solve, emotionally regulate and ask for support when problems in life occur; illness intrusiveness; patient health questionnaire to assess depressive symptoms; financial strain; life events count; social support; heart rate; tobacco use and body mass index. Logistic regression was used for model development. Results Roughly half (49.3%) of the participants were frail/pre-frail. High coping self-efficacy was associated with a 92% decreased odds of pre-frailty/frailty after adjustment for age, sex, race, co-morbidities, heart rate, a life events count, and body mass index. This relationship remained significant when illness intrusiveness and depression scores were added to the model (OR: 0.10; p-value = 0.014). Increases in age, co-morbidities, heart rate and body mass index were also significantly associated with higher adjusted odds of pre-frailty/frailty. Conclusions High coping self-efficacy was associated with greater odds of a robust state. Further consideration should be given to coping self-efficacy in frailty research and intervention development.
Psychological factors associated with protected sex among indirect female sex workers in Denpasar, Bali, Indonesia

ABSTRACT A cross-sectional study was conducted among indirect FSWs (a type of FSWs who provide sex services under the cover of entertainment or recreational enterprises) in Denpasar, Bali from August to October 2017 to investigate factors associated with protected sex with clients using the Health Belief Model (HBM) framework. The protected sex as a dependent variable was identified through self-reported consistency in using condoms with clients in the last month. Independent variables consisted of six HBM constructs and three main groups of modifying factors (personal, sex work, and interventional factors). Binary logistic regression was employed to identify the determinants. The prevalence of protected sex with clients in last month was 50.17% (95%CI = 41.50–80.83). Indirect FSWs were more likely to use condoms consistently if they completed senior high school or higher. Meanwhile, those working in a karaoke lounge, bar, or café were less likely to have protected sex than those in a massage parlour, spa, or beauty salon. Based on HBM, an increase of one-score of these following constructs increased likelihood of protected sex: perceived susceptibility, self-efficacy, and cues to action. Low protected sex among indirect FSWs indicates the need for public health interventions at individual, interpersonal, and institutional level.
The mechanosensitive Piezo1 channel is required for bone formation

Mechanical load of the skeleton system is essential for the development, growth, and maintenance of bone. However, the molecular mechanism by which mechanical stimuli are converted into osteogenesis and bone formation remains unclear. Here we report that Piezo1, a bona fide mechanotransducer that is critical for various biological processes, plays a critical role in bone formation. Knockout of Piezo1 in osteoblast lineage cells disrupts the osteogenesis of osteoblasts and severely impairs bone structure and strength. Bone loss that is induced by mechanical unloading is blunted in knockout mice. Intriguingly, simulated microgravity treatment reduced the function of osteoblasts by suppressing the expression of Piezo1. Furthermore, osteoporosis patients show reduced expression of Piezo1, which is closely correlated with osteoblast dysfunction. These data collectively suggest that Piezo1 functions as a key mechanotransducer for conferring mechanosensitivity to osteoblasts and determining mechanical-load-dependent bone formation, and represents a novel therapeutic target for treating osteoporosis or mechanical unloading-induced severe bone loss.
Comparison between Slow Freezing and Vitrification for Human Ovarian Tissue Cryopreservation and Xenotransplantation

Two methods for the cryopreservation of human ovarian tissue were compared using a xenotransplantation model to establish a safe and effective cryopreservation method. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital. The tissues were transplanted into 112 ovariectomized female severe combined immunodeficient mice 4 weeks after slow freezing or vitrification cryopreservation. Tissues were retrieved 4 weeks later. Primordial follicular counts decreased after cryopreservation and xenotransplantation, and were significantly higher in the slow freezing group than in the vitrification group (p < 0.001). Immunohistochemistry and TUNEL assay showed that the Ki-67 and CD31 markers of follicular proliferation and angiogenesis were higher in the slow freezing group (p < 0.001 and p = 0.006, respectively) and DNA damage was greater in the vitrification group (p < 0.001). Western blotting showed that vitrification increased cellular apoptosis. Anti-Müllerian hormone expression was low in transplanted samples subjected to both cryopreservation techniques. Electron microscopy revealed primordial follicle deformation in the vitrification group. Slow freezing for ovarian tissue cryopreservation is superior to vitrification in terms of follicle survival and growth after xenotransplantation. These results will be useful for fertility preservation in female cancer patients.
Comparator-based switched-capacitor circuits for scaled CMOS technologies

A comparator-based switched-capacitor (CBSC) design method for sampled-data systems utilizes topologies similar to traditional opamp-based methods but relies on the detection of the virtual ground using a comparator instead of forcing it with feedback. A prototype 10b CBSC 1.5b/stage pipelined ADC is implemented in a 0.18mum CMOS process. The converter operates at 8MHz and consumes 2.5mW
GF Japanese Resource Grammar

This thesis describes the implementation of the open-source Japanese resource grammar as a part of the GF Resource Grammar Library (RGL). GF (Grammatical Framework) is a grammar formalism for multilingual grammars and their applications intended at performing various natural language processing tasks. The RGL is a set of natural language grammars with a shared abstract syntax and different concrete parts implemented in GF. The Japanese resource grammar covers all the categories and rules of the GF abstract syntax, thus providing the full correlation with the resource grammars of other languages in the RGL. Due to some peculiarities of the Japanese language, the process of grammar development was complicated by a number of challenges that had not been observed before in the implementation of other GF grammars. One of the most important peculiarities is stylistic stratification in Japanese, which deeply affects its morphology and syntax. Moreover, a number of syntactic constructions predetermined in the abstract syntax are hardly possible in the natural Japanese language (e.g. some types of complex subordinate clauses). Being typologically distant from the European languages, Japanese brings up new issues in the discussion on the universal properties of languages and disputes the generality of some rules in the GF abstract syntax.
Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance

Antibiotics are a medical wonder, but an increasing frequency of resistance among most human pathogens is rendering them ineffective. If this trend continues, the consequences for public health and for the general community could be catastrophic. The current clinical pipeline, however, is very limited and is dominated by derivatives of established classes, the “me too” compounds. Here, we have exploited our recent identification of a bacterial toxin to transform it into antibiotics active on multidrug-resistant (MDR) gram-positive and -negative bacterial pathogens. We generated a new family of peptidomimetics—cyclic heptapseudopeptides—inspired from a natural bacterial peptide. Out of the 4 peptides studied, 2 are effective against methicillin-resistant Staphylococcus aureus (MRSA) in mild and severe sepsis mouse models without exhibiting toxicity on human erythrocytes and kidney cells, zebrafish embryos, and mice. These new compounds are safe at their active doses and above, without nephrotoxicity. Efficacy was also demonstrated against Pseudomonas aeruginosa and MRSA in a mouse skin infection model. Importantly, these compounds did not result in resistance after serial passages for 2 weeks and 4 or 6 days’ exposure in mice. Activity of heptapseudopeptides was explained by the ability of unnatural amino acids to strengthen dynamic association with bacterial lipid bilayers and to induce membrane permeability, leading to bacterial death. Based on structure determination, we showed that cationic domains surrounded by an extended hydrophobic core could improve bactericidal activity. Because 2 peptide analogs, Pep 16 and Pep19, are effective against both MRSA and P. aeruginosa in severe sepsis and skin infection models, respectively, we believe that these peptidomimetics are promising lead candidates for drug development. We have identified potential therapeutic agents that can provide alternative treatments against antimicrobial resistance. Because the compounds are potential leads for therapeutic development, the next step is to start phase I clinical trials.
D1.1: Representation of Risks in Online Communities

This report addresses risk representation, identification, assessment and forecasting in online communities. The goal is to set the corner stone for a framework that enables proactive management of risks and opportunities. The research results shown in this document cover risk evaluation techniques as well as risk management principles. This report is deliverable D1.1.
Modeling of motor bearing currents in PWM inverter drives

PWM inverters have recently been found to be a major cause of motor bearing failures in inverter-motor drive systems. Specifically, all inverters generate common mode voltages relative to the earth ground. The voltages provide coupling or bearing currents through motor parasitic capacitances to the rotor iron and then back from the bearings to the grounded stator case. In this paper, a model for bearing currents caused by PWM inverters is proposed. The model is based on transmission line theory which uses an equivalent lumped parameter /spl pi/-network to describe the parasitic coupling phenomenon. The model parameters are then identified by matching the calculated model outputs with those of experimental measurement. The validation of the method is demonstrated by the fact that the model can reproduce all the experimental results obtained on a test motor. An application of this method also gives a motor grounding current model. As the conducted EMI in drive systems is related to the grounding currents, the grounding current model can be used for the analysis of conducted EMI in motor-drive systems.
Exploring the link between diabetes and pancreatic cancer

ABSTRACT Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear. Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time–risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer. Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.
Detection of novel tick-borne pathogen, Alongshan virus, in Ixodes ricinus ticks, south-eastern Finland, 2019

The newly identified tick-borne Alongshan virus (ALSV), a segmented Jingmen virus group flavivirus, was recently associated with human disease in China. We report the detection of ALSV RNA in Ixodes ricinus ticks in south-eastern Finland. Screening of sera from patients suspected for tick-borne encephalitis for Jingmen tick virus-like virus RNA and antibodies revealed no human cases. The presence of ALSV in common European ticks warrants further investigations on its role as a human pathogen.
Cross‐Sectional Psychological and Demographic Associations of Zika Knowledge and Conspiracy Beliefs Before and After Local Zika Transmission

Perceptions of infectious diseases are important predictors of whether people engage in disease‐specific preventive behaviors. Having accurate beliefs about a given infectious disease has been found to be a necessary condition for engaging in appropriate preventive behaviors during an infectious disease outbreak, while endorsing conspiracy beliefs can inhibit preventive behaviors. Despite their seemingly opposing natures, knowledge and conspiracy beliefs may share some of the same psychological motivations, including a relationship with perceived risk and self‐efficacy (i.e., control). The 2015–2016 Zika epidemic provided an opportunity to explore this. The current research provides some exploratory tests of this topic derived from two studies with similar measures, but different primary outcomes: one study that included knowledge of Zika as a key outcome and one that included conspiracy beliefs about Zika as a key outcome. Both studies involved cross‐sectional data collections that occurred during the same two periods of the Zika outbreak: one data collection prior to the first cases of local Zika transmission in the United States (March–May 2016) and one just after the first cases of local transmission (July–August). Using ordinal logistic and linear regression analyses of data from two time points in both studies, the authors show an increase in relationship strength between greater perceived risk and self‐efficacy with both increased knowledge and increased conspiracy beliefs after local Zika transmission in the United States. Although these results highlight that similar psychological motivations may lead to Zika knowledge and conspiracy beliefs, there was a divergence in demographic association.
The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid

Abstract Hepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype–phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype–phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff—not naturally occurring in HAV infection—involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.
Mesenchymal Stem Cells Reduce Corneal Fibrosis and Inflammation via Extracellular Vesicle‐Mediated Delivery of miRNA

Mesenchymal stem cells from corneal stromal stem cells (CSSC) prevent fibrotic scarring and stimulate regeneration of transparent stromal tissue after corneal wounding in mice. These effects rely on the ability of CSSC to block neutrophil infiltration into the damaged cornea. The current study investigated the hypothesis that tissue regeneration by CSSC is mediated by secreted extracellular vesicles (EVs). CSSC produced EVs 130–150 nm in diameter with surface proteins that include CD63, CD81, and CD9. EVs from CSSC reduced visual scarring in murine corneal wounds as effectively as did live cells, but EVs from human embryonic kidney (HEK)293T cells had no regenerative properties. CSSC EV treatment of wounds decreased expression of fibrotic genes Col3a1 and Acta2, blocked neutrophil infiltration, and restored normal tissue morphology. CSSC EVs labeled with carboxyfluorescein succinimidyl ester dye, rapidly fused with corneal epithelial and stromal cells in culture, transferring microRNA (miRNA) to the target cells. Knockdown of mRNA for Alix, a component of the endosomal sorting complex required for transport, using siRNA, resulted in an 85% reduction of miRNA in the secreted EVs. The EVs with reduced miRNA were ineffective at blocking corneal scarring. Furthermore, CSSC with reduced Alix expression also lost their regenerative function, suggesting EVs as an obligate component in the delivery of miRNA. The results of these studies support an essential role for extracellular vesicles in the process by which CSSC cells block scarring and initiate regeneration of transparent corneal tissue after wounding. EVs appear to serve as a delivery vehicle for miRNA, which affects the regenerative action. Stem Cells Translational Medicine 2019;8:1192–1201
Evaluation of the referral management systems (RMS) used by GP practices in Northumberland: a qualitative study

Objective Exploring the views of stakeholders to the referral management systems (RMS) used by GP practices in Northumberland, UK to evaluate its perceived effectiveness. Design This was an in-depth qualitative semi-structured interview study. Participants and setting 32 participants (GPs, hospital consultants, referral support, hospital managers, Clinical Commissioning Group manager) in the North East of England, UK. Method Interviews using a grounded theory approach and thematic analysis. Results The main benefit of RMS mentioned by participants was that it allowed for unnecessary referrals to be vetted by consultants, and helps ensure patients are sent to the correct clinic. Generally, the consultants in our study felt that RMS did not significantly help them reject referrals. Some GPs experienced that RMS undermined GP autonomy and did not help when they had exhausted their abilities to manage a patient in primary care, and it was suggested that in some cases RMS may delay rather than prevent a referral. The main perceived disadvantage of RMS was the additional workload for GPs and consultants, and RMS was felt to be a barrier to commutation between GPs and consultants. Frustration with the system design and lack of knowledge of its cost-effectiveness were articulated. Conclusion Although RMS was reported to reduce some unnecessary referrals, the effect of referral delay and rejection is unknown. Although there were some positive attributes described, RMS was mostly received negatively by the stakeholders.
Oestrogen signalling drives ciliogenesis in human endometrial organoids.

The human endometrium is the inner lining of the uterus consisting of stromal and epithelial (secretory and ciliated) cells. It undergoes a hormonally regulated monthly cycle of growth, differentiation and desquamation. However, how these cyclic changes control the balance between secretory and ciliated cells remains unclear. Here, we established endometrial organoids to investigate the oestrogen-driven control of cell fate decisions in the human endometrial epithelium. We demonstrate that they preserve the structure, expression patterns, secretory properties and oestrogen responsiveness of their tissue of origin. Next, we show that the induction of ciliated cells is orchestrated by the coordinated action of oestrogen and NOTCH signalling. While oestrogen is the primary driver, inhibition of NOTCH signalling provides a permissive environment. However, inhibition of NOTCH alone is not sufficient to trigger ciliogenesis. Overall, we provide new insights into endometrial biology and propose endometrial organoids as a robust and powerful model to study ciliogenesis in vitro.