Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Effects of SGLT2 Inhibitor Ipragliflozin and Metformin on NASH in Type 2 Diabetic Mice

ABSTRACT Background and aim: Sodium-glucose cotransporter (SGLT) 2 is responsible for most of the glucose reabsorption in the kidneys and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In recent years, nonalcoholic steatohepatitis (NASH), the pathogenesis of which is strongly associated with insulin resistance, obesity, and type 2 diabetes, has become a considerable healthcare burden worldwide. However, there is currently no established pharmacotherapy for NASH. Here, we investigated the therapeutic effects of the SGLT2 selective inhibitor ipragliflozin alone and in combination with metformin on NASH in high fat and cholesterol diet-fed KK/Ay type 2 diabetic mice. Results: This diabetic model had hyperglycemia, insulin resistance, and obesity, and also exhibited steatosis, inflammation, and fibrosis in the liver, pathological features resembling those in human NASH. Four-week repeated administration of ipragliflozin significantly improved not only hyperglycemia, insulin resistance, and obesity but also hyperlipidemia and NASH-associated symptoms including hepatic steatosis and fibrosis. In addition, ipragliflozin attenuated inflammation and oxidative stress in the liver. Repeated administration of metformin also significantly improved symptoms of type 2 diabetes with NASH to a comparable degree to that by ipragliflozin. In addition, combination treatment with ipragliflozin and metformin additively improved these symptoms. Conclusions: These results demonstrate that the SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also NASH in type 2 diabetic mice, suggesting that treatment with ipragliflozin alone and in combination with metformin may be effective for treating type 2 diabetes with NASH.
An internal deletion of ADAR rescued by MAVS deficiency leads to a minute phenotype

Abstract The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as ‘self’. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR. We analyze AdarΔ7-9 mice that show a unique growth defect phenotype when rescued by Mavs. We show that AdarΔ7-9 can form a truncated, unstable, editing deficient protein that is mislocalized. Histological and hematologic analysis of these mice indicate multiple tissue- and hematopoietic defects. Gene expression profiling shows dysregulation of Rps3a1 and Rps3a3 in rescued AdarΔ7-9. Consistently, a distortion in 40S and 60S ribosome ratios is observed in liver cells. This dysregulation is also seen in AdarΔ2-13; Mavs−/− but not in AdarE861A/E861A; Ifih1−/− mice, suggesting editing-independent functions of ADAR in regulating expression levels of Rps3a1 and Rps3a3. In conclusion, our study demonstrates the importance of ADAR in post-natal development which cannot be compensated by ADARB1.
Comparison of immunofluorescence and chemiluminescence assays for measuring ACTH in equine plasma.

BACKGROUND The chemiluminescence (CL) and immunofluorescence (IF) assays yield different results for basal adrenocorticotropin hormone concentrations [ACTH] in pony plasma. It is unclear whether this difference also occurs in basal samples from horses or samples from ponies following thyrotropin-releasing hormone (TRH) stimulation. OBJECTIVES To compare the results of [ACTH] analysis by CL and IF methods in basal samples from horses and pony samples following TRH stimulation. STUDY DESIGN Method comparison. METHODS Plasma [ACTH] was measured concurrently using CL and IF methods in 12 ponies (basal and post TRH stimulation) in November and basal samples from horses (n = 45; November and May). RESULTS CL and IF methods yielded different results (P<0.01). The median difference (CL - IF) (95%CI) for ponies was 5.9 (0.1-7.5)pg/ml at baseline and 227.9 (61-1001)pg/ml post TRH; and horses 1.9 (1.1-5.4)pg/ml in November and 9.4 (8.2-11.5)pg/ml in May, at baseline. Correlation was good in ponies at baseline (R=0.80, p=0.003) but not post TRH, and good in horses in November and May (R=0.68 and 0.71, p<0.001). Bland-Altman analysis demonstrated moderate bias and wide 95% limits of agreement (95%LOA) in ponies at baseline (bias 5.5pg/ml; 95%LOA -9.9-20.9pg/ml) and horses in May (bias 10.6pg/ml; 95%LOA -9-30.3pg/ml) and very large bias and wide 95%LOA in ponies post TRH (bias 477pg/ml; 95%LOA -633-1587pg/ml). Using CL cut-offs of >29pg/ml and >110pg/ml, agreement was moderate (ƙ=0.67) and very good (ƙ=0.82) for binary classification of PPID in ponies at baseline and post TRH; and good (ƙ=0.73) for horses in November, but poor (ƙ=0.40) in May. MAIN LIMITATIONS Limited numbers of horses with [ACTH] above threshold values. CONCLUSIONS The assays yielded different absolute values, particularly in post TRH samples from ponies, suggesting TRH stimulates secretion of cross-reacting peptides other than ACTH. Agreement for binary classification for PPID was moderate to good, except in basal samples from horses in May.
Long non-coding RNA FTX alleviates hypoxia/reoxygenation-induced cardiomyocyte injury via miR-410-3p/Fmr1 axis.

OBJECTIVE Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the roles and underlying mechanisms of five prime to Xist (FTX) in myocardial I/R injury using cardiomyocyte hypoxia/reoxygenation (H/R) model. MATERIALS AND METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the expression of FTX, microRNA-410-3p (miR-410-3p) and fragile X mental retardation 1 (Fmr1) mRNA. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to evaluate cell proliferation and apoptosis, respectively. Western blot assay was conducted to examine the protein levels of apoptosis-associated factors and Fmr1. Specific kits were used to detect the levels of oxidative stress-associated factors. Dual-luciferase reporter assay was performed to verify the association between miR-410-3p and FTX or Fmr1. RESULTS FTX was reduced in myocardial I/R injury patients' serum and H/R-stimulated H9c2 cells. FTX overexpression relieved cell damage caused by H/R treatment through inducing cell proliferation and repressing cell apoptosis and oxidative stress in H9c2 cells. FTX was a sponge for miR-410-3p and the impact of FTX overexpression on H/R-induced cell injury was abolished by miR-410-3p elevation in H9c2 cells. Fmr1 was identified as a target of miR-410-3p and Fmr1 knockdown reversed the effect on H/R-induced cell damage mediated by miR-410-3p inhibition in H9c2 cells. Moreover, FTX positively regulated Fmr1 expression through sponging miR-410-3p in H9c2 cells. CONCLUSIONS FTX regulated H/R-induced cardiomyocyte damage by upregulating Fmr1 via sponging miR-410-3p.
The most abundant maternal lncRNA Sirena1 acts post-transcriptionally and impacts mitochondrial distribution

Abstract Tens of thousands of rapidly evolving long non-coding RNA (lncRNA) genes have been identified, but functions were assigned to relatively few of them. The lncRNA contribution to the mouse oocyte physiology remains unknown. We report the evolutionary history and functional analysis of Sirena1, the most expressed lncRNA and the 10th most abundant poly(A) transcript in mouse oocytes. Sirena1 appeared in the common ancestor of mouse and rat and became engaged in two different post-transcriptional regulations. First, antisense oriented Elob pseudogene insertion into Sirena1 exon 1 is a source of small RNAs targeting Elob mRNA via RNA interference. Second, Sirena1 evolved functional cytoplasmic polyadenylation elements, an unexpected feature borrowed from translation control of specific maternal mRNAs. Sirena1 knock-out does not affect fertility, but causes minor dysregulation of the maternal transcriptome. This includes increased levels of Elob and mitochondrial mRNAs. Mitochondria in Sirena1−/− oocytes disperse from the perinuclear compartment, but do not change in number or ultrastructure. Taken together, Sirena1 contributes to RNA interference and mitochondrial aggregation in mouse oocytes. Sirena1 exemplifies how lncRNAs stochastically engage or even repurpose molecular mechanisms during evolution. Simultaneously, Sirena1 expression levels and unique functional features contrast with the lack of functional importance assessed under laboratory conditions.
Comparison of an Online-Only Parkinson’s Disease Research Cohort to Cohorts Assessed In Person

Background: Online tools for data collection could be of value in patient-oriented research. The Fox Insight (FI) study collects data online from individuals with self-reported Parkinson’s disease (PD). Comparing the FI cohort to other cohorts assessed through more traditional (in-person) observational research studies would inform the representativeness and utility of FI data. Objective: To compare self-reported demographic characteristics, symptoms, medical history, and PD medication use of the FI PD cohort to other recent observational research study cohorts assessed with in-person visits. Methods: The FI PD cohort (n = 12,654) was compared to 3 other cohorts, selected based on data accessibility and breadth of assessments: Parkinson’s Progression Markers Initiative (PPMI; PD n = 422), Parkinson’s Disease Biomarker Program (PDBP; n = 700), and PD participants in the LRRK2 consortium without LRRK2 mutations (n = 508). Demographics, motor and non-motor assessments, and medications were compared across cohorts. Where available, identical items on surveys and assessments were compared; otherwise, expert opinion was used to determine comparable definitions for a given variable. Results: The proportion of females was significantly higher in FI (45.56%) compared to PPMI (34.36%) and PDBP (35.71%). The FI cohort had greater educational attainment as compared to all other cohorts. Overall, prevalence of difficulties with motor experiences of daily living and non-motor symptoms in the FI cohort was similar to other cohorts, with only a few significant differences that were generally small in magnitude. Missing data were rare for the FI cohort, except on a few variables. Discussion: Patterns of responses to patient-reported assessments obtained online on the PD cohort of the FI study were similar to PD cohorts assessed in-person.
Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy

To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI‐based immunosuppression. Seventy‐six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post‐HTx. Biopsy‐proven ACR within year 1 post‐HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post‐HTx. Median age was 53 years (45–61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ∆MIT (maximal intimal thickness)BL‐3Y was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ∆MITBL‐3Y (r = −0.025, P = 0.83). The number of 1R was not a significant predictor of ∆MITBL‐3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.
Demography and Natural Selection Have Shaped Genetic Variation in the Widely Distributed Conifer Norway Spruce (Picea abies)

Abstract Under the neutral theory, species with larger effective population size are expected to harbor higher genetic diversity. However, across a wide variety of organisms, the range of genetic diversity is orders of magnitude more narrow than the range of effective population size. This observation has become known as Lewontin’s paradox and although aspects of this phenomenon have been extensively studied, the underlying causes for the paradox remain unclear. Norway spruce (Picea abies) is a widely distributed conifer species across the northern hemisphere, and it consequently plays a major role in European forestry. Here, we use whole-genome resequencing data from 35 individuals to perform population genomic analyses in P. abies in an effort to understand what drives genome-wide patterns of variation in this species. Despite having a very wide geographic distribution and an corresponding enormous current population size, our analyses find that genetic diversity of P. abies is low across a number of populations (π = 0.0049 in Central-Europe, π = 0.0063 in Sweden-Norway, π = 0.0063 in Finland). To assess the reasons for the low levels of genetic diversity, we infer the demographic history of the species and find that it is characterized by several reoccurring bottlenecks with concomitant decreases in effective population size can, at least partly, provide an explanation for low polymorphism we observe in P. abies. Further analyses suggest that recurrent natural selection, both purifying and positive selection, can also contribute to the loss of genetic diversity in Norway spruce by reducing genetic diversity at linked sites. Finally, the overall low mutation rates seen in conifers can also help explain the low genetic diversity maintained in Norway spruce.
Executive impairments in Obsessive Compulsive Disorder: A systematic review with emotional and non-emotional paradigms.

Precedent: Impairments in executive functioning may be associated with compulsive symptoms in Obsessive Compulsive Disorder (OCD). The aim of this study was to conduct a systematic review of cognitive flexibility, inhibitory control and working memory in OCD patients, using emotional and non-emotional paradigms. METHOD we reviewed research published in PubMed, Web of Science, PsychInfo, Scopus, Scielo, and ProQuest Psychology databases, from January 2008 to April 2019. The review followed a two-stage process. In the first stage, we selected only studies using neutral stimuli paradigms, while in the second we selected executive-emotional paradigms. RESULTS The first stage of the review provided 16 final results, while the second stage, with emotional stimuli, provided 3 results. CONCLUSIONS There is some initial evidence for the existence of executive impairments in OCD, as expressed in the performance and/or processing of working memory inhibitory control and cognitive flexibility. There is also initial evidence that these latter two could be modulated by the presentation or mental representation of negative valence stimuli or images, as well as the presence of aversive contingencies.
Naturally-acquired protection against upper respiratory symptoms involving group A Streptococcus in a longitudinal cohort study.

BACKGROUND Pharyngitis due to group A Streptococcus (GAS) represents a major cause of outpatient visits and antibiotic use in the United States. A leading vaccine candidate targets 30 of the >200 emm types of GAS. We aimed to assess natural protection conferred by GAS against respiratory symptoms. METHODS In a 5-year study among school-aged children in Pittsburgh, Pennsylvania, pharyngeal cultures were obtained from children at 2-week intervals, and active surveillance was conducted for respiratory illnesses. We assessed protection via the relative odds of previous detection of homologous strains (defined by field-inversion gel electrophoresis banding pattern), emm types, and emm clusters at visits where GAS was detected with symptoms, versus visits where GAS was detected without symptoms. We used a cluster bootstrap of children to adjust estimates for repeated sampling. RESULTS At visits where previously-detected GAS emm types were identified, we estimated 81.8% (95%CI: 67.1-91.7%) protection against typical pharyngitis symptoms among children re-acquiring the same strain, and 94.5% (83.5-98.6%) protection among children acquiring a distinct strain. We estimated 77.1% (33.7-96.3%) protection against typical symptoms among children acquiring partially-heterologous emm types belonging to a previously-detected emm cluster. Protection was evident after both symptomatic and asymptomatic detections of GAS. We did not identify strong evidence of protection against atypical respiratory symptoms. CONCLUSIONS Within a 5-year longitudinal study, previous detection of GAS emm types was associated with protection against typical symptoms when homologous strains were subsequently detected. Naturally-acquired protection against partially-heterologous types suggests emm type-based vaccines may have broader strain coverage than what has been previously assumed.
Partial river flow recovery with forest age is rare in the decades following establishment

Forest regeneration and expansion are occurring in many countries, with 80 million ha established from 2000 to 2012 under the Bonn accord and 17.5 million ha established from 1990 to 2005 according to the Food and Agriculture Organisation. Multiple reviews have linked increasing forest cover with reduced river flow and potentially detrimental effects downstream. Previous reviews have investigated trends in river flow response over time, but the influence of forest age remains uncertain. Partial river flow recovery (towards non‐forested conditions) has been reported in decades following forest establishment, but the role of climate in driving these trends has not been explored. Here, we evaluate river flow trends in 43 studies following forest establishment, which provide sufficient information to distinguish the effects of ageing forests from variable climate. Our meta‐analysis supports previous findings showing that forestation reduces annual river flow (by 23% after 5 years and 38% after 25 years) with greater reductions in catchments with higher mean annual precipitation, larger increases in forest cover, and which were idle, rather than agricultural land, prior to forestation. The impact of forests on river flow is sensitive to annual precipitation and potential evapotranspiration, but responses are highly variable. Forests affect river flow less when annual precipitation is low, and sensitivity to precipitation decreases as catchment aridity increases. The majority of catchments demonstrated persistent river flow declines after forest establishment. However, nine catchments showed partial flow recovery after an initial decrease, with peak flow reductions at an average age of 15 and across a range of tree species. The mean rate of recovery was 34 mm/year over 5 years. Partial flow recovery with forest age cannot be commonly expected, however, and forestation programmes should take into account that changes to annual river flow are likely to persist for up to five decades.
Understanding the Interrelationship between Education, Income, and Obesity among Adults in Saudi Arabia

Objective: To examine the association of sociodemographic variables with the odds of being obese among adults in Saudi Arabia, and to examine whether or not the association between the educational level and the odds of being obese among adults in Saudi Arabia is modified by the income level. Methods: A total of 3,925 participants were recruited for this cross-sectional study. Sociodemographic and anthropometric data were collected using standardized procedures. Unadjusted and adjusted logistic regression models were examined, with a dichotomous obesity status variable as the outcome. Furthermore, an interaction term for income level with educational level was tested and appeared significant. Thus, additional regression models were run in order to examine the association between educational level and obesity status separately among the low- and higher-income groups. Results: Compared to participants with a college degree or higher, illiterate participants and those with an elementary education had higher odds of obesity (OR: 2.76, 95% CI: 1.81–4.22, and OR: 2.68, 95% CI: 1.89–3.82, respectively). However, participants with a low income had lower odds than participants who had a higher income (OR: 0.84, 95% CI: 0.70–0.99). Examining the association between educational level and obesity while stratifying by income revealed that a negative association between education and obesity exists among both income groups. However, the magnitude of the ORs was higher among participants with higher income, suggesting a stronger association between education and obesity among wealthier individuals. Conclusion: Individuals in the highest income bracket with lower levels of education may have greater odds of obesity. Targeting them in intervention programs is warranted.
Clinical effects of Triperygium glucosides on diabetic nephropathy

Objective To investigate the clinical effect and safety of Triperygium glucosides(TG) on patients with diabitic nephropathy(DN). Methods 65 cases with DN were selected at Shuyang Xiehe Hospital,inpatients and outpatients, from August 2006 to September 2009.65 cases were randomly divided into TG group and control group.The control group was received routine therapy for DN.The TG 20mg,3 times daily were given to each ease for three months in TG group besides routine therapy,three months later,the TG 10mg,3 times daily were given to them,the clinical effect was observed after a period of six months.Results Six months later,there was a significant difference in the 24 hours urinary protein content bewteen two groups(P0.05),but there was no significant difference in the creatinine clearance rate and alanine transaminase and white blood cell.Conclusion The curative effect of TG on DN is better than routine.