Miracle-dz/UniFAR-FTUs huggingface dataset:
Bile Acid Profile and its Changes in Response to Cefoperazone Treatment in MR1 Deficient Mice

Mucosal associated invariant T-cells (MAIT cells) are activated following recognition of bacterial antigens (riboflavin intermediates) presented on major histocompatibility complex class I-related molecule (MR1). Our previous study showed that MR1−/− knock-out (KO) mice (lacking MAIT cells) harbor a unique microbiota that is resistant to antibiotic disruption and Clostridioides difficile colonization. While we have characterized the microbiota of this mouse strain, changes in global metabolic activity in these KO mice have not been assessed. Here, LC/MS-based untargeted metabolomics was applied to investigate the differences in the metabolome, specifically in the bile acid (BA) profile of wild-type (WT) and MR1−/− KO mice, as well as how antibiotics change these profiles. BA changes were evaluated in the intestinal content, cecum content, and stool samples from MR1−/− mice and WT mice treated with cefoperazone (Cef). Fecal pellets were collected daily and both intestinal and cecal contents were harvested at predetermined endpoints on day 0 (D0), day 1 (D1), day 3 (D3), and day 5 (D5). KO mice exhibited no changes in 6-hydroxymethyl-8-D-ribityllumazine (rRL-6-CH2OH; an MR1-restricted riboflavin derivative) in the stool samples at either time point vs. D0, while WT mice showed significant decreases in rRL-6-CH2OH in the stool samples on all treatment days vs. D0. Metabolomics analysis from cecal and stool samples showed that KO mice had more total BA intensity (KO/WT = ~1.7 and ~3.3 fold higher) than that from WT mice prior to Cef treatment, while the fold change difference (KO/WT = ~4.5 and ~4.4 fold) increased after five days of Cef treatment. Both KO and WT mice showed decreases in total BA intensity in response to Cef treatment, however, less dramatic decreases were present in KO vs. WT mice. Increases in taurocholic acid (TCA) intensity and decreases in deoxycholic acid (DCA) intensity in the stool samples from WT mice were associated with the depletion of certain gut bacteria, which was consistent with the previously reported microbiome data. Furthermore, the non-detected TCA and relatively higher DCA intensity in the KO mice might be related to Clostridioides difficile infection resistance, although this needs further investigation.
CORRELATION BETWEEN GLYCOSYLATED HEMOGLOBIN AND PLATELET ACTIVITY AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: To determine the correlation between glycosylated hemoglobinlevel and platelet activity among patients with type 2 diabestes mellitus(T2DM). Methodology: This study was conducted in the Department of Medicine,Khyber Teaching Hospital, Peshawar from January to June 2012. Through aComparative Cross Sectional Study Design, a total of 80 patients with T2DMwere selected from Medical Wards and OPDs and were grouped into thosewith glycated hemoglobin (HbA1c) levels < 7% (Group A, n=33) and thosewith HbA1c ≥ 7% (Group B, n=47 patients). Both the groups were comparedwith regards to MPV and HbA1c. Results: The mean age of patients was 47.41 ± 6.74 years. In group A there were 45.5% (15) males and 54.5% (18) females. In group B there were 48.9%(23) males and 51.1% (24) female patients. MPV was significantly higher in group B as compared to group A (9.21±0.76 fl vs. 8.29±0.46 fl; P < 0.001). Among the group B patients, a positive statistical Pearson’s correlation was seen between MPV and HbA1c levels (r = 0.589; p < 0.001). However, no statistical correlation was seen between MPV and the duration of DM and BMI. Conclusions: There is a significant association between poor glycemic controland increased platelet activity in patients with uncontrolled T2DM.
Designing Socially Assistive Robots for Alzheimer’s Disease and Related Dementia Patients and Their Caregivers: Where We Are and Where We Are Headed

Over the past few years there has been a large rise in the field of robotics. Robots are being in used in many industries, but there has not been a large surge of robots in the medical field, especially the robots for healthcare use. However, as the aging population keeps growing, current medical staff and healthcare providers are increasingly burdened by caring for the ever-growing number of senior patients, especially those with cognitive impairment of Alzheimer’s disease (AD) and Alzheimer’s disease-related dementia (ADRD) patients. As a result, we can expect to see a large increase in the field of medical robotics, especially in forms of socially assistive robots (SARs) for senior patients and healthcare providers. In fact, SARs can alleviate AD and ADRD patients and their caregivers’ unmet medical needs. Herein, we propose a design outline for such a SAR, based on a review of the current literature. We believe the next generation of SARs will enhance health and well-being, reduce illness and disability, and improve quality of life for AD and ADRD patients and their caregivers.
NIH Public Access

Chronic infectious diseases such as HIV, HBV, and HCV, among others, cause severe morbidity and mortality globally. Progressive decline in CD8 functionality, survival, and proliferative potential—a phenomenon referred to as CD8 exhaustion—is believed to be responsible for poor pathogen control in chronic infectious diseases. While the role of negative inhibitory receptors such as PD-1 in augmenting CD8 exhaustion has been extensively studied, the role of positive costimulatory receptors remains poorly understood. In this review, we discuss how one such costimulatory pathway, CD40–CD40L, regulates CD8 dysfunction and rescue. While the significance of this pathway has been extensively investigated in models of autoimmunity, acute infectious diseases, and tumor models, the role played by CD40–CD40L in regulating CD8 exhaustion in chronic infectious diseases is just beginning to be understood. Considering that monotherapy with blocking antibodies targeting inhibitory PD-1-PD-L1 pathway is only partially effective at ameliorating CD8 exhaustion and that humanized CD40 agonist antibodies are currently available, a better understanding of the role of the CD40–CD40L pathway in chronic infectious diseases will pave the way for the development of more robust immunotherapeutic and prophylactic vaccination strategies.
Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

SUMMARY Dysregulation of mechanosensitive Piezo2 channels is a hallmark of mechanical allodynia, yet the cellular mechanisms that sensitize mechanoreceptors are still poorly understood. Activation of Gi-coupled receptors sensitizes Piezo2 currents, but whether Gi-coupled receptors regulate the activity of Piezo2 channels is not known. Here, we found that activation of Gi-coupled receptors potentiates Piezo2 currents in dorsal root ganglion (DRG) neurons and in heterologous systems, but inhibits Piezo1 currents in heterologous systems. The potentiation, or inhibition of Piezo currents is abolished when blocking Gβγ with the c-terminal domain of the beta-adrenergic kinase (βARKct). Pharmacological inhibition of kinases downstream of Gβγ, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), also abolished the potentiation of Piezo2 currents. Hence, our studies illustrate an indirect mechanism of action of Gβγ to sensitize Piezo2 currents after activation of Gi-coupled receptors.
Hybrid TiO2–Polyaniline Photocatalysts and their Application in Building Gypsum Plasters

Hybrid materials of conjugated polymer and titanium(IV) oxide have attracted considerable attention concerning their potential benefits, including (i) efficient exploitation of visible light, (ii) a high adsorption capacity for organic contaminants, (iii) and effective charge carriers separation. The new class of the photocatalysts is promising for the removal of environmental pollutants in both aqueous and gaseous phases. For the first time, in this study, the polyaniline (PANI)–TiO2 hybrid composite was used for the degradation of phenol in water and toluene in the gas phase. Polyaniline–TiO2 was prepared by the in situ polymerization of aniline on the TiO2 surface. The obtained hybrid material was characterized by diffuse reflectance spectroscopy (DR/UV-Vis), X-ray diffraction (XRD), fast-Fourier transformation spectroscopy (FTIR), photoluminescence (PL) spectroscopy, microscopy analysis (SEM/TEM), and thermogravimetric analysis (TGA). An insight into the mechanism was shown based on the photodegradation analysis of charge carrier scavengers. Polyaniline is an efficient TiO2 photosensitizer for photodegradation in visible light (λ > 420 nm). The trapping experiments revealed that mainly h+ and ˙OH were the reactive oxygen species that were responsible for phenol degradation. Furthermore, the PANI–TiO2 hybrid nanocomposite was used in gypsum plaster to study the self-cleaning properties of the obtained building material. The effect of PANI–TiO2 content on the hydrophilic/hydrophobic properties and crystallographic structure of gypsum was studied. The obtained PANI–TiO2-modified gypsum plaster had improved photocatalytic activity in the reaction of toluene degradation under Vis light.
Beyond type 2 cytokines in asthma - new insights from old clinical trials

ABSTRACT Introduction: Human asthma is a heterogeneous disorder on molecular, pathological, and clinical levels. The paradigm of asthma as an allergic process driven by type 2 cytokines and mediators has led to targeted biologic therapies resulting in some clinical benefit in patient subsets. However, some patient subsets and clinical manifestations do not benefit from these interventions, thus redefining unmet needs. Clinical studies of type 2 directed therapies have identified new targets under investigation in clinical development; these include epithelial alarmins, non-type 2 cytokines, cytokine receptor signaling, mast cells and neuroinflammation. Areas covered: We consider lessons learned concerning asthma pathogenesis from observational studies and clinical trials of biologic agents that target type 2 mediators. We also provide a perspective on emerging therapeutic hypotheses to target processes independent of or orthogonal to type 2 inflammation in asthma. Expert opinion: Type 2 inflammation is continuous, not discrete, and is likely a modifier of underlying dysregulated airway physiology. Non-type 2 inflammatory mediators (e.g., IL17, IL6, IFNs), microbiome, alarmins (e.g., TSLP, IL33), mast cells and sensory neurons may represent orthogonal targets to type 2 mediators. There is a need to better match targets and outcome measures in biologically defined patient populations to appropriately test hypotheses in the clinic.
Assessment of Equity in Access to Percutaneous Coronary Intervention (PCI) Centres in Poland

The purpose of this study is to analyse the disparities in the distribution of percutaneous coronary intervention (PCI) centres in Poland and the impact of eventual inequities on access to the invasive treatment of acute myocardial infarctions (AMI). To examine the distribution of PCI centres against population size and geographic size in Poland, the Gini coefficient calculated based on the Lorenz Curve was engaged. In addition, the regression function was employed to estimate the impact of distribution of PCI centres on access to invasive procedures (coronarographies and primary percutaneous coronary intervention). Data were collected from the public statistical system and Polish National Health Fund database for the year 2018. The relation and the level of equity was measured based on the aggregated data at a district (voivodeship) level. The results of the Gini coefficient analysis show that the distribution of invasive cardiology units measured against population size is more equitable than when measured against geographic size. In addition, the regression analysis shows the moderate size of the positive correlation between number of PCI centres per 100,000 population and the number of all categories of the invasive treatment of AMI per 100,000 population, and the lack of similar correlation in case of the number of PCI centres expressed per 1000 km2, which could be evidence of an insufficiency of PCI centres in areas where the concentration of PCI centres per 100,000 population is lower. The main implication for policy makers that results from this research is the need for a correction of PCI centres distribution per 100,000 inhabitants to ensure better access to invasive procedures.
Attitude and readiness of Dentistry students in Kerman University of Medical Sciences concerning Tele-dentistry in 2017

Introduction: Tele-dentistry is the use of information and telecommunications technology for dental care, counseling, education and public awareness in the same way as remote medical. Tele-dentistry is a relatively new field that can change the dental care system. However, many dentists are unaware of the goals, benefits, and how to participate. Therefore, this study was conducted to determine the knowledge and attitude of dental students regarding telemedicine. Methods:The present study is descriptive-analytic. The study population consisted of all dental students in Kerman in year 2017 and sample of 230 students selected by proportional sampling. For data collection, a complete English translation of an English-language article in the Journal of Clinical and Diagnostic Research, whose validity was confirmed by three of the leading medical informatics specialists in English, was then used to analyze the data using the software SPSS 19. Results: The findings of this study showed that there is no significant difference between the students' age, sex and term of education with their knowledge of tele-dentistry (P>0.05). Knowledge and attitude of 72% of students in tele-dentistry is very low. 40% of them said tele-dentistry would be very beneficial and more than half of them would be willing to do tele-dentistry in the future. 81% of them agreed that tele-dentistry could be a good tool for health education and oral health, and effective in educating the health of a large number of people. 75% of them felt that distance dental care saves time, and 81% of students believed that tele-dentistry was not financially feasible. Conclusion: The results of this study showed that many respondents lacked adequate knowledge and knowledge about tele-dentistry. Hence, there is a huge need for awareness among dentists to further the future of dentistry in the future. Therefore, it is suggested that the related institutions take more serious measures for awareness and education about tele-dentistry for students.
Using the theory of self-affirmation and self-regulation strategies of mental contrasting and forming implementation intentions to reduce social anxiety symptoms

ABSTRACT Background and Objectives: Based on the results of past research on emotion regulation and positive behavioral change via self-affirmation, it was hypothesized that self-affirmation should help socially anxious individuals to reduce social anxiety symptoms. The effectiveness of a brief self-affirmation intervention framed in terms of implementation intentions (if–then plans with self-affirming cognitions) was compared against forming non-affirming implementation intentions (with distraction as a way of coping) and inactive control condition. Additionally, it was tested whether mental contrasting can augment the impact of the self-affirmation intervention. Design/Methods: Participants (N = 198, aged 18–45) were randomly assigned to one of three intervention conditions (self-affirming implementation intention, mental contrasting with self-affirming implementation intention, or non-affirming implementation intention) or an inactive control-group. Social anxiety symptoms were assessed at baseline and at one-week post-intervention. Results: The difference between the interventions and the control group was substantial. However, there were no differences in the reduction of overall social anxiety levels between the interventions. Each of the interventions produced a statistically significant reduction in social anxiety (Cohen's ds from −.40 to −.50). Conclusions: The results indicate no advantage for self-affirming over non-affirming implementation intentions in reducing social anxiety symptoms. Moreover, no superiority of mental contrasting was found.
Evaluating Activation and Absence of Negative Effect: Gamification and Escape Rooms for Learning

Innovation has allowed for and developed new ways of teaching and learning. Gamification is among the new training methodologies, which is a didactic approach based on the game structure with an attractive component for students. Within gamification, flipped learning and problem-based learning, escape rooms can be found as a technical aspect, which is focused on providing enigmas and tracks for the various educational content that students have assimilated through learning based on problem solving. The aim of this study is to identify how the use of gamification with the use of educational escape rooms affects activation and absence of a negative effect on students. 61 Master students of the Autonomous City of Ceuta participated in this case study. They were divided into three study groups (1 control group; 2 experimental groups) that followed different formative actions (control group—traditional; experimental groups—escape rooms). To achieve the objectives, a mixed research design based on quantitative and qualitative techniques was followed. The instrument used for data collection was the GAMEX (Gameful Experience Scale). The results reveal that the students who had taken a gamified formative action through escape rooms obtained better assessment results in the indicators concerning motivation, teamwork, commitment, activation, and absence of a negative effect on the learning process than those with the traditional methodology.
Evaluation of a Transdermal Drug Delivery System for Veterinary Patients

EVALUATION OF A TRANSDERMAL DRUG DELIVERY SYSTEM FOR VETERINARY PATIENTS Miyuki Kumagai Advisor: University of Guelph, 2014 Dr. Ronald Johnson Canine osteoarthritis (OA) is a progressive degenerative disease often leading to inflammation, pain and disuse of the affected joint. Meloxicam, commonly used to manage canine OA, is given as oral tablets or suspensions, or intravenous (IV) or subcutaneous (SC) injections. However, these routes are associated with decreased owner compliance and adverse drug reactions (ADRs) with chronic use. delivraTM uses the transdermal delivery route to transport meloxicam. Meloxicam compounded in delivraTM (TDM) was investigated to evaluate i) penetration of meloxicam into canine synovial fluid (SF) and plasma, ii) stability of TDM and iii) anti-inflammatory and analgesic properties of TDM. Results demonstrated that delivraTM was able to transport meloxicam to canine SF and plasma at comparable levels to oral Metacam® suspension and meloxicam was stable in delivraTM for up to 2 months. However, initial work with TDM did not demonstrate significant anti-inflammatory or analgesic effects in a rat model of
The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle

Hydrogen peroxide (H2O2) is an oxidizing agent that induces cellular damage at inappropriate concentrations and gives rise to an arrest during cell cycle progression, causing cell death. Recent evidence indicates that H2O2 also acts as a promoter for cell cycle progression by oxidizing specific thiol proteins. The intracellular concentration of H2O2 is regulated tightly, enabling its use as a cellular signaling molecule while minimizing its potential to cause cellular damage. Peroxiredoxins (Prxs) have peroxidase activity toward H2O2, organic hydroperoxides, and peroxynitrite for protecting cells from oxidative stress. They are suggested to work as signaling mediators, allowing the local accumulation of H2O2 by inactivating their peroxidase activity uniquely compared with other antioxidant proteins such as catalase and glutathione peroxidase. Given that Prxs are highly sensitive to oxidation by H2O2, they act as sensors and transducers of H2O2 signaling via transferring their oxidation state to effector proteins. The concentrations of intracellular H2O2 increase as the cell cycle progresses from G1 to mitosis. Here, we summarize the roles of Prxs with regard to the regulation of cell cycle-dependent kinase activity and anaphase-promoting complex/cyclosome in terms of changes in H2O2 levels. Protection of the cell from unwanted progression of the cell cycle is suggested to be a role of Prx. We discuss the possible roles of Prxs to control H2O2 levels.
Correlation between the measure for cluster proximity (MCP) and the percentage of consonants correct (PCC)

ABSTRACT A measure was recently proposed for the quantitative evaluation of consonant clusters in child developmental speech, the measure for cluster proximity (MCP). Its advantage over the widely used measure of the percentage of consonants correct (PCC) is that it differentiates the three main stages of cluster production: reduction, vowel epenthesis, and two-members, correct or not. The purpose of the present article is two-fold: a) to contrast MCP and PCC in two-member word-initial clusters produced within children with speech sound disorders (SSDs), tested before and after therapy, as well as in running speech within typically developing children, and b) to examine the correlation between the two measures across children in typical or atypical speech development. Data used are comprised of 34 sets with 18 word-initial cluster types, taken from the speech samples of 18 children. It is found that while there are generally large deviations between the two measures in individual clusters within and between children, the measures have a strong and statistically significant correlation when averaged over all clusters per child, or over all children per cluster class based on the manner of articulation. For the data at hand, a linear equation is obtained yielding MCP values from PCC values with a high coefficient of determination. The results suggest that PCC norms that are used to assess consonants can be used to predict MCP norms in order to assess consonant clusters in child developmental speech.
COVID‐19–Related School Closings and Risk of Weight Gain Among Children

The COVID-19 pandemic is causing substantial morbidity and mortality, straining health care systems, shutting down economies, and closing school districts. While it is a priority to mitigate its immediate impact, we want to call attention to the pandemic's longer-term effect on children's health: COVID-19, via these school closures, may exacerbate the epidemic of childhood obesity and increase disparities in obesity risk. In many areas of the U.S., the COVID-19 pandemic has closed schools and some of these school systems are not expected to re-open this school year. The experiences in Hong Kong, Taiwan and Singapore suggest that social distancing orders, if lifted after short periods, will have to be periodically re-instated to control COVID-19 flare ups. In short, we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.