Miracle-dz/UniFAR-FTUs huggingface dataset:
Trends in Corticosteroid Use During the Era of Biologic Therapy: A Population-Based Analysis

INTRODUCTION: Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. METHODS: We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. RESULTS: The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1–4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1–2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. DISCUSSION: Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.
Updated strategies in the management of acute variceal haemorrhage

Purpose of review This article reviews the most recent studies regarding the management of acute esophageal variceal haemorrhage. Recent findings New randomized control trials and meta-analyses confirmed the role of early transjugular intrahepatic portosystemic shunt (TIPS) in the management of acute variceal haemorrhage in Child-Pugh C (10–13) and B patients with active bleeding. A recent randomized controlled trial focused on the duration of vasoactive therapy showed no difference between 2 and 5 days of octreotide. A randomized trial showed decreased use of blood products for the correction of coagulopathy using a thromboelastography-guided approach (vs. conventional parameters) as well as decreased bleeding rates when compared with standard of care. A meta-analysis found that for rescue of variceal bleeding, self-expanding metallic stents were more efficacious and safer than balloon tamponade. In addition, studies showed that Child-Pugh C patients and those with hepatic vein pressure gradient more than 20 were at the highest risk of treatment failure, while model for end-stage liver disease was highly predictive of in-hospital mortality. Summary In patients with severe coagulopathy and uncontrolled bleeding, TEG-based transfusion strategies are recommended. Antibiotics should be used for all cirrhotic patients presenting with upper gastrointestinal bleeding, but should be tailored in accordance to local resistance patterns. Early TIPS for high-risk patients has been shown to have a significant survival benefit. Certain aspects of the management of variceal bleeding remain poorly studied such as the role of early TIPS in Child-B patients as well as strategies for rescue therapy in patients who are not TIPS candidates, and require further investigation.
Brain activity during meditation in first-time meditators

Abstract Aim of the study The electrophysiological correlates of meditation states in both short and long-term meditators have been increasingly documented; however, little is known about the brain activity associated with first-time meditation experiences. The goal of this study was to investigate the electrophysiological correlates of a single guided mindfulness meditation session in subjects with no previous meditation experience. Materials and methods We analyzed electroencephalogram (EEG) changes in signal power, hemispheric asymmetry, and information flow between EEG channels, in 16 healthy subjects who were new to meditation practice. Results Our results show that information flow decreases in the theta (4–8 Hz) and alpha ranges (8–13 Hz) during mindfulness meditation exercise as compared to control: a passive listening condition. These changes are accompanied by a general trend in the decrease of alpha power over the whole scalp. One possible interpretation of these results is that there is an increased level of alertness/vigilance associated with the meditation task rather than reaching the target state. Conclusions Our study expands on the existing body of knowledge concerning neural oscillations during breathing meditation practice by showing that in participants with no previous meditation training, EEG correlates are different from the electrophysiological signatures of mindfulness meditation found in studies of more advanced practitioners.
Antibacterial properties of capsaicin and its derivatives and their potential to fight antibiotic resistance – A literature survey

Antibiotic resistance is endangering public health globally and gives reason for constant fear of virtually intractable bacterial infections. Given a limitation of novel antibiotic classes brought to market in perspective, it is indispensable to explore novel, antibiotics-independent ways to fight bacterial infections. In consequence, the antibacterial properties of natural compounds have gained increasing attention in pharmacological sciences. We here performed a literature survey regarding the antibacterial effects of capsaicin and its derivatives constituting natural compounds of chili peppers. The studies included revealed that the compounds under investigation exerted i. ) both direct and indirect antibacterial properties in vitro depending on the applied concentrations and the bacterial strains under investigation; ii. ) synergistic antibacterial effects in combination with defined antibiotics; iii. ) resistance-modification via inhibition of bacterial efflux pumps; iv. ) attenuation of bacterial virulence factor expression; and v. ) dampening of pathogen-induced immunopathological responses. In conclusion, capsaicin and its derivatives comprise promising antimicrobial molecules which could complement or replace antibiotic treatment strategies to fight bacterial infections. However, a solid basis for subsequent clinical trials requires future investigations to explore the underlying molecular mechanisms and in particular pharmaceutical evaluations in animal infection models.
Factors associated with SARS‐CoV‐2 infection in patients attending an acute hospital ambulatory assessment unit

To describe the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in mild‐to‐moderate patients attending for assessment. This observational study was conducted in a Model 4 tertiary referral center in Ireland. All patients referred for SARS‐CoV‐2 assessment over a 4‐week period were included. Patient demographics, presenting symptoms, comorbidities, medications, and outcomes (including length of stay, discharge, and mortality) were collected. Two hundred and seventy‐nine patients were assessed. These patients were predominantly female (62%) with a median age of 50 years (SD 16.9). Nineteen (6.8%) patients had SARS‐CoV‐2 detected. Dysgeusia was associated with a 16‐fold increased prediction of SARS‐CoV‐2 positivity (p = .001; OR, 16.8; 95% CI, 3.82–73.84). Thirteen patients with SARS‐COV‐2 detected (68.4%) were admitted, in contrast with 38.1% (99/260) of patients with SARS‐CoV‐2 non‐detectable or not tested (p = .001). Female patients were more likely to be hospitalized (p = .01) as were current and ex‐smokers (p = .05). We describe olfactory disturbance and fever as the main presenting features in SARS‐CoV‐2 infection. These patients are more likely to be hospitalized with increased length of stay; however, they make up a minority of the patients assessed. “Non‐detectable” patients remain likely to require prolonged hospitalization. Knowledge of predictors of hospitalization in a “non‐detectable” cohort will aid future planning and discussion of patient assessment in a SARS‐CoV‐2 era.
Longitudinal Associations between Callous-unemotional (CU) Traits and School-based Affiliative Relationships among South Korean Children

ABSTRACT Objective Callous-unemotional traits (CU) traits are characterized by low empathy, guilt, and reduced sensitivity to others’ feelings, along with a reduced drive for social affiliation. However, little is known about the relationships between CU traits and social affiliation in the school context, or the influence of gender on these associations. This study tested reciprocal associations between CU traits and school-based affiliative relationships and explored gender as a potential moderator. Method The sample included South Korean children aged 10 to 12 years (N = 218, M = 11.03, SD = .65, 52% boys). Children reported on CU traits, antisocial behavior, teacher-student relationship quality, and peer affiliation. Three-wave longitudinal cross-lagged models tested reciprocal associations between CU traits and affiliation with both teachers and peers, with multi-group modeling employed to test the moderating effect of gender. Results Higher CU traits at time 1 predicted decreases in teacher affiliation at time 2 controlling for CU traits, teacher-child affiliation, and antisocial behavior at time 1, while lower teacher-child affiliation at time 2 predicted increases in CU traits at time 3 accounting for CU traits, teacher-child affiliation, and antisocial behavior at time 2. However, there were no reciprocal associations between CU traits and teacher affiliation nor significant associations between CU traits and peer affiliation. Gender did not moderate any pathways between CU traits and teacher or peer affiliation. Conclusions Findings indicate CU traits may reduce teacher-child affiliation, potentially escalating risk for further increases in CU traits. Thus, teacher-child affiliation may represent an important target for school-based intervention for children with elevated CU traits regardless of gender.
State Policy and Mental Health Outcomes under COVID-19.

CONTEXT The COVID-19 pandemic has caused enormous damage to physiological health and economic security, especially among racial and ethnic minorities. We examine downstream effects on mental health, how effects vary by race and ethnicity, and the role of existing state-level social policies in softening the pandemic's impact. METHODS We analyze an online, multi-wave Census Bureau survey fielded to nearly a million respondents between late April and July 2020. The survey includes questions measuring psychological distress as well as indirect measures of experience with the pandemic. We combine these data with state-level measures of COVID cases, lock-down orders, unemployment filings, and safety net policy. FINDINGS We find significant mental stress among all respondents and a sizeable gap between non-white and white respondents. Adjusting for pandemic experiences eliminates this gap. The effect of losing work due to the pandemic is slightly offset by state policies such as unemployment benefit size and Medicaid expansion. The magnitude of these offsetting effects is similar across racial/ethnic groups. CONCLUSIONS The racialized impacts of the pandemic are exacerbated by inequalities in state policy exemplifying structural racism. If the least generous states matched the policies of the most generous, inequalities caused by the pandemic would be diminished.
Ferroelectric hysteresis in simultaneously stretched and corona-poled PVDF films

SSCP (simultaneous stretching and corona poling) of PVDF (polyvinylidene fluoride) films has enhanced the ferroelectric properties. D-E hysteresis loops of these films were observed by using the Sawyer-Tower method in the field range 35 to 80 MV/m. The dependence of ferroelectric hysteresis on poling field has also been studied. The average value of remanent polarization /spl ap/82 mC/m/sup 2/ was observed for the SSCP (simultaneous stretching and corona poling) films, which is significantly higher than the value P/spl ap/62 mC/m/sup 2/ observed for the STCP (stretched and then corona poled) films. Coercive fields of E/sub c//spl ap/61 and 50 MV/m were obtained for the SSCP and the STCP films respectively. A comparison of the IR spectra of the SSCP and the STCP films in perpendicularly polarized light E/sub /spl perp// indicates that the dipolar orientation is better in the SSCP films.
Functional brain imaging in larval zebrafish for characterising the effects of seizurogenic compounds acting via a range of pharmacological mechanisms

Functional brain imaging using genetically encoded Ca2+ sensors in larval zebrafish is being developed for studying seizures and epilepsy as a more ethical alternative to rodent models. Despite this, few data have been generated on pharmacological mechanisms of action other than GABAA antagonism. Assessing larval responsiveness across multiple mechanisms is vital to test the translational power of this approach, as well as assessing its validity for detecting unwanted drug‐induced seizures and testing antiepileptic drug efficacy.
Removal of methylene blue from textile waste water using kaolin and zeolite-x synthesized from Ethiopian kaolin

The wastewater generated from textile factories is linked to one of the main water pollution problems; therefore, it is important to reduce the pollutants in industrial effluents before their discharge into environment. The present study was to investigate the appropriateness zeolite-x and kaolin as effective adsorbents for removal of methylene blue from the textile wastewater. Batch adsorption experiments were carried out to assess parameters that influence the adsorption process. The prepared zeolite-x and kaolin were characterized by Fourier Transform Infrared and X-ray diffraction techniques. The results of this study showed that the particle size is 40.77 nm and 0.45 nm kaolin and zeolite-x respectively. The performance of zeolite-x adsorbent is best at the optimum pH 4 with removal efficiency of 97.77% and kaolin adsorbent at pH 6 with removal efficiency of 86.86%. The optimum contact time was obtained at 60 and 80 minutes for zeolite–x and kaolin respectively. While optimum adsorbent dosage was obtained at 0.4 and 0.6 grams with removal efficiency of 97.12% and 87.75% for the zeolite-x and kaolin adsorption experiment respectively. The confirmed square sum errors values are 1.0×10−4 and 1.0×10−3 for zeolite-x and kaolin, respectively. The Adsorption isotherms results have well fitted to Freundlich isotherm than Langmuir isotherm. The adsorption kinetics results were best fitted the pseudo second order model. The result shows that the zeolite-x has high removal efficiency than kaolin at the same operating conditions. Application of this method can be economically, environmentally, and socially feasible to address wastewater problems. Further research has to be carried out on the removal capacity of this adsorbent for organic dyes not only from the textile industry but also from leather industries and soap industries.
A PSR-Framework-Based Health Assessment of Ulansuhai Lake in China

A Pressure-State-Response (PSR) framework was developed to realize a holistic health assessment of the Ulansuhai Lake in the Inner Mongolia. A total of 25 indicators including ecological character indicators, ecological function indicators and social environment indicators were organized to assess the lake ecosystem health. The Ulansuhai Lake was regionalized into three sub-regions (I, II, and III) in the consideration of ecological and environmental characters the lake. Results indicate the lake is in the state of Alert or Worse. The comprehensive health indices (CHI) of three sub-regions are 0.346, 0.385, and 0.445, respectively, reflecting obvious regional differences in ecosystem health of the lake. The current study may provide useful information for valid wetland restoration and management
Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

BACKGROUND Polygenic risk scores (PRS) have been demonstrated to identify women of European, Asian and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS We assembled genotype data for women of African ancestry, including 9,241 cases and 10,193 controls. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve (AUC). We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry, and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS For overall BC, the odds ratios per standard deviation of PRS313 was 1.27 (95%CI = 1.23 to 1.31), with an AUC of 0.571 (95%CI = 0.562 to 0.579). Compared to women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38 to 1.72). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared to that reported in European, Asian and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
Propionate catabolism by CD-associated adherent-invasive E. coli counteracts its anti-inflammatory effect

ABSTRACT Crohn’s disease (CD) is a chronic and disabling inflammatory disorder of the gut that is profoundly influenced by intestinal microbiota composition, host genetics and environmental factors. Several groups worldwide have described an imbalance of the gut microbiome composition, called dysbiosis, in CD patients, with an increase in Proteobacteria and Bacteroidetes and a decrease in Firmicutes. A high prevalence of adherent-invasive Escherichia coli (AIEC) pathobionts has been identified in the intestinal mucosa of CD patients. A significant loss in the bacteria that produce short-chain fatty acids (SCFAs) with anti-inflammatory properties, such as propionate, is also a consequence of dysbiosis in CD patients. Here, the AIEC reference strain LF82 was able to degrade propionate in the gut, which was sufficient to counteract the anti-inflammatory effect of propionate both in in vitro models and in mice with DSS-induced colitis. The consumption of propionate by AIEC pathobionts leads to an increase in TNF-α production by macrophages upon infection through the bacterial methyl-citrate pathway. To induce the protective effects of SCFAs on the inflamed gut, we used a G-protein-coupled receptor 43 agonist (GPR43 agonist) that is not metabolizable by intestinal bacteria. Interestingly, this agonist showed anti-inflammatory properties and decreased the severity of colitis in AIEC-infected mice, as assessed by an improvement in the disease activity index (DAI) and a decrease in AIEC pathobiont encroachment. Taken together, these results highlight the effectiveness of GPR43 agonist treatment in the control of gut inflammation and improved our understanding of the ability of AIEC to modulate propionate availability to create an infectious niche to its advantage.
Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity.

Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca 2+ distribution, inositol 1,4,5-trisphosphate receptor (IP 3R) abundance, and the activities of voltage-gated K + channels (K V) and Ca 2+-activated K + channels (BK Ca) were examined in rat cerebral vascular smooth muscle cells (VSMCs). Results An increase of cytoplasmic Ca 2+ and a decrease of mitochondrial/sarcoplasmic reticulum (SR) Ca 2+ were observed in HU rat cerebral VSMCs. The abundance of fusion proteins (mitofusin 1/2 [MFN1/2]) and fission proteins (dynamin-related protein 1 [DRP1] and fission-mitochondrial 1 [FIS1]) was significantly downregulated and upregulated, respectively in HU rat cerebral VSMCs. The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats, and IP 3R protein/mRNA levels were significantly upregulated. The current densities and open probabilities of K V and BK Ca decreased and increased, respectively. Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1. It also decreased IP 3R expression levels and restored the activities of the K V and BK Ca channels. MitoTEMPO restored the Ca 2+ distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries. Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Manifestations of domination: Assessments of social dominance in rodents

Social hierarchies are ubiquitous features of virtually all animal groups. The varying social ranks of members within these groups have profound effects on both physical and emotional health, with lower‐ranked individuals typically being the most adversely affected by their respective ranks. Thus, reliable measures of social dominance in preclinical rodent models are necessary to better understand the effects of an individual's social rank on other behaviors and physiological processes. In this review, we outline the primary methodologies used to assess social dominance in various rodent species: those that are based on analyses of agonistic behaviors, and those that are based on resource competition. In synthesizing this review, we conclude that assays based on resource competition may be better suited to characterize social dominance in a wider variety of rodent species and strains, and in both males and females. Lastly, albeit expectedly, we demonstrate that similarly to many other areas of preclinical research, studies incorporating female subjects are lacking in comparison to those using males. These findings emphasize the need for an increased number of studies assessing social dominance in females to form a more comprehensive understanding of this behavioral phenomenon.