Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycyrrhizin Use for Multi-Drug Resistant Pseudomonas aeruginosa: In Vitro and In Vivo Studies

Purpose Our purpose was to test glycyrrhizin (GLY) effects and ciprofloxacin interactions on multidrug resistant (MDR) isolates of Pseudomonas aeruginosa in vitro and in vivo in a mouse model of keratitis. Methods A Hardy-disk tested antibiotic sensitivity of isolates MDR9 (nonocular) and B1045 (ocular). GLY MIC (both isolates) and ciprofloxacin was determined spectrophotometrically. A live/dead assay using confocal microscopy and plate count, tested GLY effects on bacterial permeabilization/viability. Proteomics profiled bacterial efflux pumps (MDR9 vs. PAO1); RT-PCR comparatively tested GLY effects on their mRNA expression levels. The activity of efflux pumps was tested using ethidium bromide (EB); and scanning electron microscopy (SEM) visualized the effects of GLY treatment of bacteria. A combination of GLY and ciprofloxacin was tested in C57BL/6 mice (begun 18 hours after infection) and disease scored, photographed and MPO and plate counts done. Results MDR9 was resistant to 6/12 and B1045 to 7/12 antibiotics (both to ciprofloxacin). MIC GLY for MDR9 was 40 mg/mL and 15 mg/mL for B1045. Ciprofloxacin MIC (32 μg/mL) was reduced 2-fold to 16 μg/mL when ciprofloxacin and GLY were combined. GLY altered bacterial membrane permeability and reduced viability. Proteomics revealed increased efflux pumps in MDR9 versus PAO1; GLY reduced their mRNA expression levels and EB suggested decreased activity. In C57BL/6 mice, treatment with GLY and ciprofloxacin versus ciprofloxacin, significantly reduced clinical scores, plate count, and MPO. Conclusions GLY decreases MDR by: altering bacterial parameters, including viability and efflux pump activity. In vivo, it increases the effectiveness of ciprofloxacin, reducing ocular disease, plate count, and MPO activity.
Interspecific, ontogenetic, and sexual variation in ozopore morphology among cosmetid harvestmen (Arachnida, Opiliones, Laniatores)

The ozopores of cosmetid harvestmen rest upon lateral projections of the carapace, have simple or highly reduced channels, and are partially obscured by enlarged dorsal processes associated with coxae I and II. Rather than use scent gland secretions to form a chemical shield on the dorsum, the cosmetid harvestman exhibits a unique defensive behavior known as “leg dabbing” in which the distal tip of tarsus I or II is dipped into fluid that accumulate at the base of coxa II and the droplet on the tarsus is pointed toward the predator. Relatively little is known about interspecific variation in ozopore morphology among cosmetid harvestmen. In this study, we used scanning electron microscopy to examine the ozopores of males and females of nine species as well as those of antepenultimate nymphs for two species. Among adults, we found differences between species in the shapes of the ozopores (round or subtriangular), the morphology of the dorsal and lateral channels (if present), and the relative size, shape and armature of the dorsal posterior process (dpp) of coxa I and the dorsal anterior process (dap) of coxa II. Our observations suggest that the morphology of dpp I and dap II could be sources for systematic characters in future phylogenetic studies of the Cosmetidae. We observed ontogenetic differences but relatively little intersexual variation in the morphology of the ozopore. The ozopores of nymphs are generally more oval than those of adults and the opening of the ozopore of the nymph is less obstructed, if at all, by the dorsal coxal processes of legs I–II. These morphological differences suggest that nymphs may use scent gland secretions in a manner different from that of adults.
Robotic vs laparoscopic hemihepatectomy: A comparative study from a single center

Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH.
Persistent increase in ventral hippocampal long‐term potentiation by juvenile stress: A role for astrocytic glutamine synthetase

A traumatic childhood is among the most important risk factors for developing stress‐related psychopathologies such as posttraumatic stress disorder or depression later in life. However, despite the proven role of astrocytes in regulating transmitter release and synaptic plasticity, the contribution of astrocytic transmitter metabolism to such stress‐induced psychopathologies is currently not understood. In rodents, childhood adversity can be modeled by juvenile stress exposure, resulting in increased anxiety, and impaired coping with stress in adulthood. We describe that such juvenile stress in rats, regardless of additional stress in adulthood, leads to reduced synaptic efficacy in the ventral CA1 (vCA1) Schaffer collaterals, but increased long‐term potentiation (LTP) of synaptic transmission after high‐frequency stimulation. We tested whether the glutamate–glutamine‐cycle guides the lasting changes on plasticity observed after juvenile stress by blocking the astrocytic glutamate‐degrading enzyme, glutamine synthetase (GS). Indeed, the pharmacological inhibition of GS by methionine sulfoximine in slices from naïve rats mimics the effect of juvenile stress on vCA1‐LTP, while supplying glutamine is sufficient to normalize the LTP. Assessing steady‐state mRNA levels in the vCA1 stratum radiatum reveals distinct shifts in the expression of GS, astrocytic glutamate, and glutamine transporters after stress in juvenility, adulthood, or combined juvenile/adult stress. While GS mRNA expression levels are lastingly reduced after juvenile stress, GS protein levels are maintained stable. Together our results suggest a critical role for astrocytes and the glutamate–glutamine cycle in mediating long‐term effects of juvenile stress on plasticity in the vCA1, a region associated with anxiety and emotional memory processing.
Frontline Science: Abnormalities in the gut mucosa of non‐obese diabetic mice precede the onset of type 1 diabetes

Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non‐obese diabetic (NOD) mice during disease progression compared to non‐obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria‐bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre‐diabetic NOD mice, and cross‐fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.
The miR-122 inhibition alleviates lipid accumulation and inflammation in NAFLD cell model

Abstract Background Accumulating evidence showed that the expression of miR-122 was abnormal in NAFLD patients; however, the role of miR-122 on lipid accumulation and inflammation in NAFLD is not clear. Methods RT-qPCR was applied to detect the expression levels of miR-122 and pro-inflammatory cytokines following transfected with miR-122 inhibitor or treated with oleic acid (OA). Detection of lipid accumulation was performed by triglyceride content test and oil red o staining assay. Western blotting was applied to detect the protein levels of TLR7, TLR4, MyD88 and NF-κBp65. Results We found that the OA promoted lipid accumulation and pro-inflammatory cytokines secretion and activated TLR4/MyD88/NF-κBp65 signalling pathway, which were restored following transfected with miR-122 inhibitor. Conclusions These results suggested that miR-122 inhibition alleviates lipid accumulation and inflammation in L02 cell induced by OA may through inhibiting TLR4/MyD88/NF-κBp65 signalling pathway. The protective mechanism of miR-122 inhibition in NAFLD must be explored in future studies.
β-Peltoboykinolic Acid from Astilbe rubra Attenuates TGF-β1-Induced Epithelial-to-Mesenchymal Transitions in Lung Alveolar Epithelial Cells

Epithelial-to-mesenchymal transition (EMT) is increasingly recognized as contributing to the pathogenesis of idiopathic pulmonary fibrosis. Therefore, novel plant-based natural, active compounds have been sought for the treatment of fibrotic EMT. The aim of the present study was to investigate the inhibitory effects of Astilbe rubra on TGF-β1-induced EMT in lung alveolar epithelial cells (A549). A. rubra was subjected to extraction using 70% ethanol (ARE), and ethanol extracts of the aerial part and that of the rhizome were further partitioned using various solvents. Protein expression and cell motility were investigated to evaluate the inhibitory effects of ARE on EMT. EMT occurred in A549 cells treated with TGF-β1, but was prevented by co-treatment with ARE. The dichloromethane fractions showed the strongest inhibitory effect on TGF-β1-induced EMT. β-Peltoboykinolic acid was isolated from the dichloromethane fractions of A. rubra by activity-oriented isolation. β-Peltoboykinolic acid not only attenuated TGF-β1-induced EMT, but also the overproduction of extracellular matrix components including type I collagen and fibronectin. The Smad pathway activated by TGF-β1 was inhibited by co-treatment with β-peltoboykinolic acid. Taken together, these results indicate that β-peltoboykinolic acid from A. rubra and dichloromethane fractions shows potential as an antifibrotic agent in A549 cells treated with TGF-β1.
Ternary Trends in Nursing Home Information Technology and Quality Measures in the United States

Nursing home information technology (NH IT) adoption trends are not measured regularly. Evidence indicates digital footprints are growing, but gaps about NH IT adoption and quality impacts remain. We hypothesize as NH IT adoption grows, quality improves. This research assessed ternary (2014-2017) trends in IT and quality measures using a primary survey of U.S. NHs. Survey measures included nine dimensions/domains and total IT sophistication. Administrators completed 815 Year 1 surveys. Each year mean total IT sophistication scores in nine dimensions/domains consistently increased. Eighteen significant correlations (r > .13, absolute value) between IT sophistication and quality measures existed. Regression shows that for every 10 units increase in administrative activity extent of IT use, a decrease of 1.3% occurs in the percentage of low-risk long-stay residents with bowel or bladder incontinence. Increases in NH IT sophistication positively impact quality. Estimating ongoing trends in NH IT sophistication provides new information that should be consistently available.
Diet Quality and Diet Diversity in Eight Latin American Countries: Results from the Latin American Study of Nutrition and Health (ELANS)

This study aimed to assess diet quality score (DQS), considering healthy and unhealthy foods and nutrients, and diet diversity score (DDS) as indicators of risk of noncommunicable diseases in eight Latin American countries, and to verify the possible differences considering country, sex, age, socioeconomic, and nutritional status. A multicenter household population-based cross-sectional survey was conducted with 9218 individuals (age range 15–65 years). Sociodemographic and anthropometric data were collected. Dietary intake was measured using two non-consecutive 24-h recalls and diet quality and diversity were assessed. In the whole sample, scores were observed from 63.0% ± 9.3% to total DQS, 65.0% ± 13.6% to healthy dietary items and 60.2% ± 13.6% to unhealthy items, and 5.6 ± 1.1 out of 9 points to DDS. Women presented lower DDS compared to men (5.5 ± 1.1 vs. 5.6 ± 1.1, p < 0.001). Healthy DQS was higher as the socio-economic level increased, and unhealthy DQS was the opposite (p < 0.05). Total DQS was significantly lower only at the low socio-economic level (p < 0.05). Chile and Venezuela showed the lowest healthy (62.2 ± 15.2 and 61.9 ± 11.7, p < 0.05) and total DQS (61.4 ± 10.3, 61.2 ± 8.7, p < 0.05). No effects were observed when considering the age and anthropometric measurements. Promoting consumption of a diverse and high-quality diet is an essential challenge to accomplish.
Cognitive Control along the Language Spectrum: From the Typical Bilingual Child to Language Impairment

Abstract Cognitive control refers to the ability to perform goal-directed behaviors in the presence of other compelling actions or in the face of habitual practices. Cognitive control functions play a critical role in children's language processing and literacy development. In recent years, many clinicians have expanded their assessment and treatment to target specific cognitive skills. Our goal is to provide a review of recent findings on cognitive control functions in children with different language status (i.e., monolingual and bilingual children with and without language impairment). While children with language impairment show performance deficits in specific cognitive functions (e.g., working memory updating and interference control), typically developing bilingual children often outperform their monolingual peers in cognitive control tasks. However, the relationship between bilingualism and cognitive control has been controversial. Several factors that influence these variations are discussed. Given the findings on the joint impact of bilingualism and language impairment on cognitive control functions, we identify conditions in which bilingualism attenuates the negative effects of the language deficit and conditions in which language impairment has a stronger effect than bilingualism. Critical issues of bilingual assessment, suggestions, and future directions are discussed.
Identifying Risk of Depressive Symptoms in Adults With Physical Disabilities Receiving Rehabilitation Services: Propensity Score Approaches

Objective To compare the risk of depressive symptoms in adults with physical disabilities between rehabilitation-receivers and non-receivers. Methods A total of 3,568 adults with physical disabilities were retrieved from the 2014 Korean National Survey on People with Disabilities database. Four covariate adjustment methods (a multivariable regression model, inverse probability of treatment weighting [IPTW] adjusted for normalized weight, IPTW with stabilized weight, and greedy algorithm with 1:1 propensity score matching) were used to estimate the odds of having depressive symptoms. The dependent variable was depressive symptoms and the independent variable was the use of rehabilitation services. Baseline covariates were 19 demographic variables and 10 chronic condition variables. Results The four covariate adjustment methods revealed that adults with physical disabilities receiving rehabilitation services had a higher risk of depressive symptoms than those who did not receive these services (adjusted odds ratio, 1.191–1.294). Conclusion Our findings suggest that adults with physical disabilities receiving rehabilitation services have higher risk of developing depressive symptoms. Therefore, rehabilitation professionals need to pay attention to depressive symptoms and establish therapeutic strategies that can reduce such risk in rehabilitation settings.
Dynamic Training of Hand Gesture Recognition System

We developed an augmented reality tool for vision-based hand gesture recognition in a camera-projector system. Our recognition method uses modified Fourier descriptors for the classification of static hand gestures. Hand segmentation is based on a background subtraction method, which is improved to handle background changes. Most of the recognition methods are trained and tested by the same service-person, and training phase occurs only preceding the interaction. However, there are numerous situations when several untrained users would like to use gestures for the interaction. In our new practical approach the correction of faulty detected gestures is done during the recognition itself. Our main result is the quick on-line adaptation to the gestures of a new user to achieve user-independent gesture recognition.
Healthcare resource utilization and costs in patients with HIV-1 who switched first-line antiretroviral therapy

Abstract Objectives: This study compared healthcare utilization and costs associated with switching the first-line protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) based antiretroviral (ARV) regimen due to reasons other than virologic failure among patients with HIV-1. Methods: This was a retrospective analysis of commercial and Medicare Advantage with Part D enrollees in two US administrative claims databases. The study population comprised adults with HIV-1 infection initiating antiretroviral therapy (ART) on PI- or NNRTI-containing regimens from 1 January 2006 to 31 December 2015. Patients with a subsequent change in anchor agent were assigned to the switch cohort; the non-switch cohort was constructed using propensity score matching of three non-switching patients for each patient in the switch cohort. Patient characteristics and per patient per month healthcare resource utilization and costs were compared between the cohorts during the pre-switch, switch (15 days before and after switching) and post-switch periods. Costs during the switch period were also estimated with a multivariable-adjusted model. Results: The matched study population consisted of 1204 patients who switched their first-line PI- or NNRTI-based regimen and 3612 patients who did not. Compared with the non-switch cohort, patients who switched had higher healthcare resource utilization during the pre-switch, switch and post-switch periods. Mean unadjusted non-ART costs in the switch cohort were nearly double ($2944 versus $1530, p < .001), more than double ($2562 versus $1215, p < .001) and 1.5 times higher ($1473 versus $968, p < .001) than costs in the non-switch cohort in the pre-switch, switch and post-switch periods, respectively. Conclusions: Patients with HIV-1 who initiated PI- or NNRTI-based regimens and switched ARTs for reasons other than virologic failure used more healthcare resources and incurred greater costs relative to patients in the non-switch cohort. This study highlights the importance of initiating patients on appropriate first-line ART to avoid the need to switch due to reasons other than virologic failure.
Deletion of the Cardiomyocyte Glucocorticoid Receptor Leads to Sexually Dimorphic Changes in Cardiac Gene Expression and Progression to Heart Failure

Background The contribution of glucocorticoids to sexual dimorphism in the heart is essentially unknown. Therefore, we sought to determine the sexually dimorphic actions of glucocorticoid signaling in cardiac function and gene expression. To accomplish this goal, we conducted studies on mice lacking glucocorticoid receptors (GR) in cardiomyocytes (cardioGRKO mouse model). Methods and Results Deletion of cardiomyocyte GR leads to an increase in mortality because of the development of spontaneous cardiac pathology in both male and female mice; however, females are more resistant to GR signaling inactivation in the heart. Male cardioGRKO mice had a median survival age of 6 months. In contrast, females had a median survival age of 10 months. Transthoracic echocardiography data showed phenotypic differences between male and female cardioGRKO hearts. By 3 months of age, male cardioGRKO mice exhibited left ventricular systolic dysfunction. Conversely, no significant functional deficits were observed in female cardioGRKO mice at the same time point. Functional sensitivity of male hearts to the loss of cardiomyocyte GR was reversed following gonadectomy. RNA‐Seq analysis showed that deleting GR in the male hearts leads to a more profound dysregulation in the expression of genes implicated in heart rate regulation (calcium handling). In agreement with these gene expression data, cardiomyocytes isolated from male cardioGRKO hearts displayed altered intracellular calcium responses. In contrast, female GR‐deficient cardiomyocytes presented a response comparable with controls. Conclusions These data suggest that GR regulates calcium responses in a sex‐biased manner, leading to sexually distinct responses to stress in male and female mice hearts, which may contribute to sex differences in heart disease, including the development of ventricular arrhythmias that contribute to heart failure and sudden death.
The Interplay between Colon Cancer Cells and Tumour-Associated Stromal Cells Impacts the Biological Clock and Enhances Malignant Phenotypes

Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.