Miracle-dz/UniFAR-FTUs huggingface dataset:
Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell-dominant allergic airway inflammation through delivery of miR-146a-5p

ABSTRACT Group 2 innate lymphoid cells (ILC2s) are recently reported to play a more critical role in allergic diseases. We previously identified that mesenchymal stromal cells (MSCs) elicited therapeutic effects on allergic airway inflammation. Small extracellular vesicles (sEV) derived from MSCs possess striking advantages including low immunogenicity and high biosafety, and is extremely promising cell-free therapeutic agents. However, the effects of MSC-sEV on ILC2s are still unclear. Additionally, scalable isolation protocols are required for the mass production of homogenous MSC-sEV especially in clinical application. We previously reported that induced pluripotent stem cells-derived MSCs were the ideal cellular source for the large preparation of MSC-sEV. Here we developed a standardized scalable protocol of anion-exchange chromatography for isolation of MSC-sEV, and investigated the effects of MSC-sEV on ILC2 function from patients with allergic rhinitis and in a mouse ILC2-dominant asthma model. The characterization of MSC-sEV was successfully demonstrated in terms of size, morphology and specific markers. Using flow cytometry and human Cytokine Antibody Array, MSC-sEV but not fibroblasts-sEV (Fb-sEV) were found to significantly inhibit the function of human ILC2s. Similarly, systemic administration of MSC-sEV but not Fb-sEV exhibited an inhibition of ILC2 levels, inflammatory cell infiltration and mucus production in the lung, a reduction in levels of T helper 2 cytokines, and alleviation of airway hyperresponsiveness in a mouse model of asthma. Using RNA sequencing, miR-146a-5p was selected as the candidate to mediate the above effects of MSC-sEV. We next revealed the uptake of ILC2s to MSC-sEV, and that transfer of miR-146a-5p in MSC-sEV to ILC2s in part contributed to the effects of MSC-sEV on ILC2s in vitro and in a mouse model. In conclusion, we demonstrated that MSC-sEV were able to prevent ILC2-dominant allergic airway inflammation at least partially through miR-146a-5p, suggesting that MSC-sEV could be a novel cell-free strategy for the treatment of allergic diseases.
Tensions in Maternal Care for Children, Youth, and Adults With Autism Spectrum Disorder

This study explored the experiences of mothers caring for an individual with autism spectrum disorder (ASD) ranging from 5 to 25 years of age, and examined pervasive tensions in caregiving. Guided by ethnographic methods, a retrospective cross-sectional study was conducted. Interviews with 85 mothers were analyzed inductively. Prevalent tensions in maternal caregiving were identified: (a) difficulties obtaining, yet resistance to, an ASD diagnosis; (b) identified giftedness of the child versus notions of deficit imposed by others; (c) disability-related behaviors erroneously interpreted as ‘poor parenting’; (d) contradictory considerations in diagnosis disclosure; (e) the invisibility yet pervasiveness of ASD; (f) extensive need for, yet the lack of, accessible services; (g) ASD-related care demands versus other pressing responsibilities; (h) arguments for inclusive versus exclusive services; and (i) aims of nurturing independence versus managing safety risk. Tensions were heightened by insufficient supports relative to need. Implications and recommendations for practice and policy are offered.
Antioxidant Effect of Virgin Coconut Oil on Urea and Creatinine Levels on Maximum Physical Activity

BACKGROUND: Maximal physical activity can produce an imbalance between reactive oxygen species (ROS) and antioxidants which are possibly related to fatigue and tissue injury. One of the natural sources that contain antioxidants is virgin coconut oil (VCO). AIM: This study aimed to determine the protective effects antioxidant of virgin coconut oil (VCO) treatment on urea and creatine level on maximum physical activity METHODS: This study used 24 healthy male rats. The rats were divided into four groups, randomly consisted of six rats in each group. The control group (P0) was given 2 mL water, the treatment groups (VCO-1, VCO-2, and VCO-4) were given VCO 1 mL/200 gBW, 2 mL/200 gBW and 4 ml/200 gBW, respectively, per day using gavage spuit. After 28 days, the rats were forced to perform maximal activity by putting the rats in water with no exit. Blood samples were collected immediately after the maximum physical activity. The urea, creatinine, malondialdehyde and glutation peroxidase level was then measured. RESULTS: This study used 24 healthy male rats. The rats were divided into four groups randomly consisted of six rats in each group. The control group (P0) was given 2 mL water, the treatment groups (VCO-1, VCO-2, and VCO-4) were given VCO 1 mL/200 gBW, 2 mL/200 gBW and 4 ml/200 gBW, respectively, per day using gavage spuit. After 28 days, the rats were forced to perform the maximal activity by putting the rats in water with no exit. Blood samples were collected immediately after the maximum physical activity. The urea, creatinine, malondialdehyde and glutathione peroxidase level was then measured. CONCLUSION: The results of this study indicate that virgin coconut oil is effective in the prevention of oxidative stress following maximum physical activity.
Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells

Although baicalin, a flavonoid derived from Scutellaria baicalensis Georgi, has been reported to have anti-tumor activity in various cancers, the molecular mechanism remains imperfect. Here, we show that baicalin inhibits cell growth, migration and invasion and induces cell apoptosis by inhibiting cell cycle, viability, the epithelial-mesenchymal transition (EMT) and cellular stemness in colorectal cancer (CRC) cells. In detail, baicalin treatment in CRC cells induces cell cycle arrest in G1 phase and promotes p53-independent cell apoptosis, inhibits both endogenous and exogenous TGFβ1-induced EMT of colorectal cancer cells by inhibiting TGFβ/Smad pathway. Cell sphere-formation experiments show that baicalin has a strong inhibitory efficacy on the stemness of CRC cells by decreasing the marker proteins of cancer stem cell (CSC) and inhibits the formation of CSC-like cell spheres in CRC cells. In vivo experiments also identify that baicalin has an anti-tumor effect by down-regulating the levels of marker proteins of cell cycle, EMT and stemness in the orthotopic transplantation tumors of CRC cells in BALB/c nude mice. Collectively, our in vitro and in vivo results indicate that multiple inhibition of cell cycle, EMT and stemness is the real molecular mechanism of baicalin in effectively inducing cell growth inhibition and apoptosis in CRC cells.
Heat knockdown resistance and chill‐coma recovery as correlated responses to selection on mating success at high temperature in Drosophila buzzatii

Abstract Reproduction and related traits such as mating success are strongly affected by thermal stress. We tested direct and correlated responses to artificial selection in replicated lines of Drosophila buzzatii that were selected for mating success at high temperature. Knockdown resistance at high temperature (KRHT) and chill‐coma recovery (CCR) were tested as correlated selection responses. Virgin flies were allowed to mate for four hours at 33°C in three replicated lines (S lines) to obtain the selected flies and then returned at 25°C to lay eggs. Other three replicated lines were maintained at 25°C without any selection as control (C lines). After 15 selection generations, KRHT and CCR were measured. Both traits were assessed in flies that did not receive any hardening pretreatments as well as in flies that were either heat or cold hardened. Thermotolerance traits showed significant correlated responses with higher KRHT in S than in C lines, both with a heat‐hardening pretreatment and without a heat‐hardening pretreatment. CCR time was longer in S than in C lines both with a cold‐hardening pretreatment and without a cold‐hardening pretreatment. Hardening treatments improved both KRHT and CCR in all cases excepting KRHT in C lines. Overall, KRHT and CCR showed an antagonistic pattern of correlated responses to our selection regime, suggesting either pleiotropy or tightly linked trait‐specific genes partially affecting KRHT and CCR.
Maternal predator‐exposure affects offspring size at birth but not telomere length in a live‐bearing fish

Abstract The perception of predation risk could affect prey phenotype both within and between generations (via parental effects). The response to predation risk could involve modifications in physiology, morphology, and behavior and can ultimately affect long‐term fitness. Among the possible modifications mediated by the exposure to predation risk, telomere length could be a proxy for investigating the response to predation risk both within and between generations, as telomeres can be significantly affected by environmental stress. Maternal exposure to the perception of predation risk can affect a variety of offspring traits but the effect on offspring telomere length has never been experimentally tested. Using a live‐bearing fish, the guppy (Poecilia reticulata), we tested if the perceived risk of predation could affect the telomere length of adult females directly and that of their offspring with a balanced experimental setup that allowed us to control for both maternal and paternal contribution. We exposed female guppies to the perception of predation risk during gestation using a combination of both visual and chemical cues and we then measured female telomere length after the exposure period. Maternal effects mediated by the exposure to predation risk were measured on offspring telomere length and body size at birth. Contrary to our predictions, we did not find a significant effect of predation‐exposure neither on female nor on offspring telomere length, but females exposed to predation risk produced smaller offspring at birth. We discuss the possible explanations for our findings and advocate for further research on telomere dynamics in ectotherms.
Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Variation in key transcription factors and glycogenes modifies IgG glycosylation and has an influence on inflammatory diseases. Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.
Stigmatization and discrimination as predictors of self-esteem of people living with HIV and AIDS in Nigeria

Background Self-esteem is a major psychological health issue. People living with HIV and AIDS have been found to be victims of discrimination and stigmatization which affect their self-esteem. Objectives The study investigated the influence of stigma and discrimination on self-esteem of people living with HIV and AIDS (PLHIV). Methods The design was a cross-sectional study carried out in four teaching hospitals in south-eastern Nigeria between 13th July 2016 – 11th May 2017. Four hundred and eighty-four (174 males and 310 females) PLHIV participated in the study. Quantitative study supplemented by qualitative in-depth interviews were used to collect data regarding discrimination, stigma and self-esteem of PLHIV whilst a structured questionnaire was used to elicit information about the socio-demographic variables. Results Stigmatization and discrimination were found to have significant influence on self-esteem of PLHIV. The results indicate that stigmatization and discrimination, together with income, work status, AIDS diagnosis status, and medication use status significantly influence self-esteem of PLHIV. These results imply that stigmatization and discrimination influences on self-esteem among PLHIV. Conclusion Conclusively, intervention programmes should evolve enlightenment through television, movies, and educational programs that incorporate the ill effects of discrimination and stigma so as to boost self-esteem of PLHIV.
Preoperative evaluation of residual tumor in patients with endometrial carcinoma by using 18F-FDG PET/CT

Purpose: To evaluate the value of 18F-FDG positron emission tomography (PET)/computed tomography (CT) for determining the presence of residual tumors after curettage in patients with endometrial cancer. Methods: Preoperative 18F-FDG PET/CT was performed in 90 women with endometrial cancer. PET/CT parameters and clinical characteristics were compared between patients with and without residual tumors. The clinical characteristics of patients with residual tumors that showed low 18F-FDG uptake were also analyzed. Results: Among the 90 patients, 86 had residual tumors. ROC analysis identified a lesion SUVmax value of 5.0 as the optimal cut-off value for predicting whether or not patients had a residual tumor. With the SUVmax cut-off of 5, the sensitivity, specificity, positive predictive value, and negative predictive values for residual tumor prediction were 87.2%, 100%, 100%, and 26.7%, respectively. Univariate analysis showed significant associations between the high PET group (SUVmax > 5) and low PET group (SUVmax ≤ 5), and histologic type (P = 0.043) and tumor size (P < 0.001) in patients with residual tumors. In patients with low-grade and clear cell carcinomas and a tumor size < 1.35 cm, the probability of being in the low-PET group was 47.6%. In such patients, major parts of the residual tumors showed low 18F-FDG uptake, similar to that in patients with no residual tumors. Conclusion: SUVmax was the lone predictive value for the presence of residual tumors after curettage in patients with endometrial cancer. Lesion SUVmax greater than 5 suggested a high possibility of residual tumors. In patients with low-grade and clear cell carcinomas with tumor size < 1.35 cm, residual tumors may present low 18F-FDG uptake, mimicking the metabolic phenotypes of patients without residual tumors.
Two distinct phenotypes of plaque erosion assessed by multimodality intracoronary imaging: a case series

Abstract Background Pathological studies have reported that patients with acute coronary syndrome (ACS) may have different plaque morphologies at culprit lesions, and one of the underlying mechanisms for ACS is plaque erosion. However, the morphological features of plaque erosion obtained by multiple intracoronary imaging modalities have not been fully elucidated. Case summary We experienced two cases with ACS of culprit lesions exhibiting optical coherence tomography (OCT)-defined plaque erosion. Additional examinations using near-infrared spectroscopy (NIRS)–intravascular ultrasound and coronary angioscopy suggested the presence of two distinct phenotypes of plaque erosion. These two types of erosion differ in the extent of NIRS-derived lipid core burden and coronary angioscopy-derived luminal surface colour. Discussion OCT-defined plaque erosion may not be the unique entity but have at least two distinct plaque morphologies, and NIRS and/or coronary angioscopy may provide incremental ability of discriminating these plaque phenotypes classified as plaque erosion by OCT.
Effect of Saurauia vulcani Korth. Leaves on Superoxide Dismutase, HbA1c Levels and Insulin Expression in Hyperglycemic Rats

AIM: This study aimed to investigate Saurauia vulcani Korth. leaves. the activity of ethanol extract in hypoglycemic, superoxide dismutase (SOD), glycosylated haemoglobin (HbA1c) and detection of insulin expression by immunochemistry METHODS: Saurauia vulcani Korth. Leaves powder was extracted by maceration method with ethanol 96%. The extract was administrated orally in doses of 100 mg/kg BW for 27 days. Diabetes was induced in rats by administered of Nicotinamide (NA) 230 mg/kg BW and streptozotocin (STZ) 65 mg/kg BW. Level of blood glucose, SOD, HbA1c were measured, and histopathology pancreas was observed to determine insulin expression with immunochemistry RESULTS: Ethanol extract of Saurauia vulcani Korth. Leaves (EESL) shown a significantly (*p < 0.05) reduced in blood glucose levels at 104.25 ± 2.562 mg/dL and HbA1c level at 32.53 ± 0.188 ng/mL, but increased SOD level at 60.64 ± 0.740 pg/mL and histopathology study shown secretion insulin as seen number of expressions of insulin / slice 31.00 ± 0.315. CONCLUSION: The result of this study showed EESL possess the hypoglycemic activity and increase the level of SOD but decrease the level of HbA1c in diabetic rat condition. The mechanism of the activity is suggested by stimulating the insulin secretion of pancreas β-cells which were damaged.
Life Expectancy of Insured People With and Without Hepatitis C Virus Infection, 2007–2017

Abstract Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.
Evaluating the safety and tolerability of inpatient sacubitril/valsartan initiation in a community hospital

ABSTRACT Background Sacubitril/valsartan has been incorporated into guidelines based on the results of the PARADIGM-HF trial, which demonstrated reduced mortality in stable patients with heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan is recommended in addition to other HF therapies in place of an angiotensin-converting-enzyme inhibitor or angiotensin-receptor-blocker. Objectives To evaluate the safety and tolerability of sacubitril/valsartan initiation in a community hospital. Design/methods This single-center, retrospective review evaluated patients that received ≥24 hours of sacubitril/valsartan therapy August 2015-March 2018. The primary outcome included the incidence of hypotensive events during hospitalization. Secondary outcomes included: incidence of inpatient acute kidney injury (AKI) and hyperkalemia, rates of inpatient discontinuation, and change in ejection fraction (EF) ≥30 days after initiation. Results Of the 59 patients included, 21 (35.6%) experienced a hypotensive event. A total of 6 patients (10.2%) discontinued therapy while inpatient, which was more likely in patients that developed AKI (n = 3; p = 0.005) or those who experienced a hypotensive event (n = 5; p = 0.018). There was a significant difference in mean EF from baseline to ≥ 30 days post-initiation (24.8% vs. 33.2%; p = 0.018). Conclusion Careful patient selection and monitoring for hypotension, AKI, and hyperkalemia can help increase successful outcomes and improve patient safety.
Formulation and Antibacterial Activity of Plectranthus amboinicus (Lour.) Spreng Leaves Ethanolic Extract as Herbal Mouthwash Against Halitosis Caused Bacteria

BACKGROUND: Halitosis is one of the unpleasant conditions which could alter the self-confidence and cause serious illness. One of the treatments to overcome halitosis is by using mouthwash. Plectranthus amboinicus (Lour.) Spreng is one of the plants that is known to have antibacterial activity which can be used to overcome halitosis caused bacteria. AIM: To formulate the Plectranthus amboinicus (Lour.) Spreng leaves ethanolic extract as herbal mouthwash and to evaluate the antibacterial activity against Streptococcus mutans and Staphylococcus aureus bacteria. METHODS: The methods of the study included the characterization and screening of Plectranthus amboinicus (Lour.) Spreng leaves dried powder; the extraction process by maceration using 96% ethanol; the antibacterial activity test of Plectranthus amboinicus (Lour.) Spreng leaves ethanolic extract and the formulation and evaluation of mouthwash dosage form with various concentrations of Plectranthus amboinicus (Lour.) Spreng leaves ethanolic extract. RESULTS: The characterization results showed that the Plectranthus amboinicus (Lour.) Spreng leaves powder contained 7.92% of water, 29.26% of water-soluble substance, 13.32% of ethanol soluble substance, 0.82% of total ash and 0.66% of acid insoluble ash. The screening examination gave glycoside, saponin, flavonoid, tannin and steroid/triterpenoid positive results. The antibacterial activity test of the Plectranthus amboinicus (Lour.) Spreng mouthwash showed that the dosage form with 2% of Plectranthus amboinicus (Lour.) Spreng extract successfully inhibited the growth of bacteria with 12.00 and 11.25 mm of inhibition diameter for both Staphylococcus aureus and Streptococcus mutans, respectively. CONCLUSION: The Plectranthus amboinicus (Lour.) Spreng leaves ethanolic extract can be formulated in mouthwash dosage form and has antibacterial activity against Staphylococcus aureus and Streptococcus mutans bacteria.
Enhanced CRISPR-Cas9 correction of Duchenne muscular dystrophy in mice by a self-complementary AAV delivery system

Self-complementary AAV-packaged CRISPR-Cas9 genome editing components rescue Duchenne muscular dystrophy. Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disease caused by mutations in the dystrophin gene (DMD). Previously, we applied CRISPR-Cas9–mediated “single-cut” genome editing to correct diverse genetic mutations in animal models of DMD. However, high doses of adeno-associated virus (AAV) are required for efficient in vivo genome editing, posing challenges for clinical application. In this study, we packaged Cas9 nuclease in single-stranded AAV (ssAAV) and CRISPR single guide RNAs in self-complementary AAV (scAAV) and delivered this dual AAV system into a mouse model of DMD. The dose of scAAV required for efficient genome editing were at least 20-fold lower than with ssAAV. Mice receiving systemic treatment showed restoration of dystrophin expression and improved muscle contractility. These findings show that the efficiency of CRISPR-Cas9–mediated genome editing can be substantially improved by using the scAAV system. This represents an important advancement toward therapeutic translation of genome editing for DMD.
Die Chorea Huntington im Kindesalter

By the case report of a 7 years old girl problems and difficulties in diagnosing early manifested Chorea Huntington are discussed. Dementia, rigor and akinesis are the presenting signs; choreatic movements are usually not present. Seizures occur frequently. Family history gives important informations; the autosomal dominant gene mostly is transmitted by the father. Although knowledges of biochemical changes in movement disorders are increasing, there are presently only a few possibilities to ameliorate signs and symptoms of chorea by pharmacological measures.