Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Peppermint Oil in a Randomized Double-blind Trial of Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in the Netherlands, from August 2016 through March 2018; 189 patients were included in the intent to treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care); 178 completed the study. Patients were randomly assigned to groups given 182 mg small intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared to baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS Abdominal pain response did not differ significantly between peppermint oil and placebo groups: 29/62 patients in the small intestinal-release peppermint oil group had a response (46.8%, P=.170 vs placebo), 26/63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P=.385 vs placebo), and 22/64 patients in the placebo group had a response (34.4%). We did not find differences among groups in overall relief (9.7%, P=.317 and 1.6%, P=.351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P=.016), discomfort (P=.020), and IBS severity (P=.020). Adverse events, although mild, were more common in both peppermint oil groups (P<.005). CONCLUSIONS In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using FDA/EMA recommended endpoints. The small intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic release peppermint oil for treatment of IBS. Clinicaltrials.gov no: NCT02716285.
The Functional Role of Thalamocortical Coupling in the Human Motor Network

The amplitude of high broadband activity in human cortical field potentials indicates local processing and has repeatedly been shown to reflect motor control in the primary motor cortex. In a group of male and female subjects affected by essential tremor and undergoing deep brain stimulation surgery, ventral intermediate nucleus low-frequency oscillations (<30 Hz) entrain the corticomotor high broadband activity (>40 Hz) during rest, relinquishing that role during movement execution. This finding suggests that there is significant cross-rhythm communication between thalamocortical regions, and motor behavior corresponds to changes in thalamocortical phase-amplitude coupling profiles. Herein, we demonstrate that thalamocortical coupling is a crucial mechanism for gating motor behavior. SIGNIFICANCE STATEMENT We demonstrate, for the first time, how thalamocortical coupling is mediating movement execution in humans. We show how the low-frequency oscillation from the ventral intermediate nucleus, known as the motor nucleus of the thalamus, entrains the excitability of the primary motor cortex, as reflected by the phase-amplitude coupling between the two regions. We show that thalamocortical phase-amplitude coupling is a manifestation of a gating mechanism for movement execution mediated by the thalamus. These findings highlight the importance of incorporating cross-frequency relationship in models of motor behavior; and given the spatial specificity of this mechanism, this work could be used to improve functional targeting during surgical implantations in subcortical regions.
A deep learning framework to generate realistic population and mobility data

Census and Household Travel Survey datasets are regularly collected from households and individuals and provide information on their daily travel behavior with demographic and economic characteristics. These datasets have important applications ranging from travel demand estimation to agent-based modeling. However, they often represent a limited sample of the population due to privacy concerns or are given aggregated. Synthetic data augmentation is a promising avenue in addressing these challenges. In this paper, we propose a framework to generate a synthetic population that includes both socioeconomic features (e.g., age, sex, industry) and trip chains (i.e., activity locations). Our model is tested and compared with other recently proposed models on multiple assessment metrics.
Health Policies in Romania to Reduce the Mortality Caused by Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the main cause of death in Romania. The objective of the paper is to explain the number of deaths caused by the diseases of circulatory system in relation to health expenditures per capita, the number of public hospitals with cardiology sections and the number of cardiologists. The analysis in the paper is based on panel data models and Bayesian linear models. A panel data approach for Romanian macro-regions in the period from 1995–2016 was used to show that an increase in the number of cardiologists would reduce the number of deaths caused by the diseases of circulatory system. The Bayesian approach to national data indicated that the increase in expenditures per capita would alleviate the incidence of deaths caused by CVD. The public health policies in relation to patients with CVD should focus on the future on higher expenditures per person, but the number of public hospitals and doctors treating these diseases should also continue to grow. Future healthcare policies should be also focused on reducing the number of specialists migrating to wealthier countries.
Two Years of Viral Metagenomics in a Tertiary Diagnostics Unit: Evaluation of the First 105 Cases

Metagenomic next-generation sequencing (mNGS) can capture the full spectrum of viral pathogens in a specimen and has the potential to become an all-in-one solution for virus diagnostics. To date, clinical application is still in an early phase and limitations remain. Here, we evaluated the impact of viral mNGS for cases analyzed over two years in a tertiary diagnostics unit. High throughput mNGS was performed upon request by the treating clinician in cases where the etiology of infection remained unknown or the initial differential diagnosis was very broad. The results were compared to conventional routine testing regarding outcome and workload. In total, 163 specimens from 105 patients were sequenced. The main sample types were cerebrospinal fluid (34%), blood (33%) and throat swabs (10%). In the majority of the cases, viral encephalitis/meningitis or respiratory infection was suspected. In parallel, conventional virus diagnostic tests were performed (mean 18.5 individually probed targets/patients). mNGS detected viruses in 34 cases (32%). While often confirmatory, in multiple cases, the identified viruses were not included in the selected routine diagnostic tests. Two years of mNGS in a tertiary diagnostics unit demonstrated the advantages of a single, untargeted approach for comprehensive, rapid and efficient virus diagnostics, confirming the utility of mNGS in complementing current routine tests.
Risk Assessment of kINPen Plasma Treatment of Four Human Pancreatic Cancer Cell Lines with Respect to Metastasis

Cold physical plasma has limited tumor growth in many preclinical models and is, therefore, suggested as a putative therapeutic option against cancer. Yet, studies investigating the cells’ metastatic behavior following plasma treatment are scarce, although being of prime importance to evaluate the safety of this technology. Therefore, we investigated four human pancreatic cancer cell lines for their metastatic behavior in vitro and in chicken embryos (in ovo). Pancreatic cancer was chosen as it is particularly metastatic to the peritoneum and systemically, which is most predictive for outcome. In vitro, treatment with the kINPen plasma jet reduced pancreatic cancer cell activity and viability, along with unchanged or decreased motility. Additionally, the expression of adhesion markers relevant for metastasis was down-regulated, except for increased CD49d. Analysis of 3D tumor spheroid outgrowth showed a lack of plasma-spurred metastatic behavior. Finally, analysis of tumor tissue grown on chicken embryos validated the absence of an increase of metabolically active cells physically or chemically detached with plasma treatment. We conclude that plasma treatment is a safe and promising therapeutic option and that it does not promote metastatic behavior in pancreatic cancer cells in vitro and in ovo.
Semantic annotations in OGC standards

Copyright © 2009 Open Geospatial Consortium, Inc. To obtain additional rights of use, visit http://www.opengeospatial. org/legal/. Warning This document is not an OGC Standard. This document is an OGC Discussion Paper and is therefore not an official position of the OGC membership. It is distributed for review and comment. It is subject to change without notice and may not be referred to as an OGC Standard. Further, an OGC Discussion Paper should not be referenced as required or mandatory technology in procurements.
The Clinical Link between Human Intestinal Microbiota and Systemic Cancer Therapy

Clinical interest in the human intestinal microbiota has increased considerably. However, an overview of clinical studies investigating the link between the human intestinal microbiota and systemic cancer therapy is lacking. This systematic review summarizes all clinical studies describing the association between baseline intestinal microbiota and systemic cancer therapy outcome as well as therapy-related changes in intestinal microbiota composition. A systematic literature search was performed and provided 23 articles. There were strong indications for a close association between the intestinal microbiota and outcome of immunotherapy. Furthermore, the development of chemotherapy-induced infectious complications seemed to be associated with the baseline microbiota profile. Both chemotherapy and immunotherapy induced drastic changes in gut microbiota composition with possible consequences for treatment efficacy. Evidence in the field of hormonal therapy was very limited. Large heterogeneity concerning study design, study population, and methods used for analysis limited comparability and generalization of results. For the future, longitudinal studies investigating the predictive ability of baseline intestinal microbiota concerning treatment outcome and complications as well as the potential use of microbiota-modulating strategies in cancer patients are required. More knowledge in this field is likely to be of clinical benefit since modulation of the microbiota might support cancer therapy in the future.
Relationship between unintentional overfilling and the long-term outcome of primary root canal treatments and non-surgical retreatment: a retrospective radiographic assessment.

AIM To determine retrospectively the long-term radiographic outcome of root canal treatments and root canal retreatments with unintentional overfilling. METHODOLOGY A total of 220 root canal treatments (143 primary/ 77 retreatments) with postoperative unintentional overfilling and performed by two endodontists during their 45 years of private practice were included in the study. Lateral condensation techniques and nine different sealers were used. Overfilling was confirmed with a post-operative periapical radiograph and patients were scheduled regularly for recall visits. Average recall time was 4.86 years (maximum= 30 years). Two calibrated observers evaluated the radiographs and determined the long-term outcome using the PAI score pooled in a 3-category scale. The persistence or resorption of the extruded material was registered. The Kappa coefficient (K) was calculated and a logistic regression was used for further analysis. Odds ratios and their 95% CI were estimated. RESULTS The level of inter-observer agreement was 66.1%. Primary root canal treatments had a significantly (p=0.015) greater rate of success (91.6%) than retreatments (81.8%). Tooth location (p=0.019) was the only other factor that significantly affected the outcome. The type of extruded material, and its resorption or persistence did not relate to outcome. Persistence of extruded material was significantly affected by tooth location and recall time after treatment. CONCLUSION The outcome of root canal treatment with unintentional overfilling was not associated with the type of extruded material or its resorption or persistence. The persistence of extruded material did not relate to a favorable or unfavorable outcome. This article is protected by copyright. All rights reserved.
Transactions between Maternal and Child Depressive Symptoms Emerge Early in Life

ABSTRACT Maternal depression is a robust risk factor for children’s internalizing symptoms; however, the intergenerational transmission of mood disorders is likely more complex than unidirectional parent-directed effects. Theoretical models support transactional associations between maternal and child symptomatology over time but have not been well examined, especially in younger high-risk samples. The present investigation examined predictive transactional relations between maternal depression and children’s internalizing in toddlerhood and early childhood using a cross-lagged panel model. Participants were 162 low-income, largely racial/ethnic minority mothers and their offspring (32% African American, 16% White, 52% Other/Multiethnic; 53% female) who were assessed when children were 18 months and 4 years old. There were significant cross-sectional relations between maternal depressive and child internalizing symptoms when children were 18 months but not 4 years of age. Cross-lagged associations were evident such that maternal depression symptoms at 18 months were positively associated with internalizing symptoms among children at 4 years, adjusting for prior maternal symptom levels and the cross-sectional correlations between maternal–child symptoms at 18 months. Within the same model, children’s internalizing symptoms at 18 months were also positively associated with maternal depressive symptoms at 4 years, adjusting for prior child symptom levels and cross-sectional correlations. This study is among the first to demonstrate that transactional relations between maternal and child mood symptoms occur as early as toddlerhood/early childhood. Findings highlight the potential utility of inclusive, family-focused interventions that support both parents and children in the treatment of early emotional problems.
Tutte Polynomial Activities.

Unlike Whitney's definition of the corank-nullity generating function $T(G;x+1,y+1)$, Tutte's definition of his now eponymous polynomial $T(G;x,y)$ requires a total order on the edges of which the polynomial is a posteriori independent. Tutte presented his definition in terms of internal and external activities of maximal spanning forests. Although Tutte's original definition may appear somewhat ad hoc upon first inspection, subsequent work by various researchers has demonstrated that activity is a deep combinatorial concept. In this survey, we provide an introduction to activities for graphs and matroids. Our primary goal is to survey several notions of activity for graphs which admit expansions of the Tutte polynomial. Additionally, we describe some fundamental structural theorems, and outline connections to the topological notion of shellability as well as several topics in algebraic combinatorics.
From dolastatin 13 to cyanopeptolins, micropeptins, and lyngbyastatins: the chemical biology of Ahp-cyclodepsipeptides.

Covering: 1989 up to 2019Ahp-cyclodepsipeptides (also known as Ahp-containing cyclodepsipeptides, cyanopeptolins, micropeptins, microginines, and lyngbyastatins, and by many other names) are a family of non-ribosomal peptide synthesis (NRPS)-derived natural products with potent serine protease inhibitory properties. Here, we review their isolation and structural elucidation from natural sources as well as studies of their biosynthesis, molecular mode of action, and use in drug discovery efforts. Accordingly, this summary aims to provide a comprehensive overview of the current state-of-the-art Ahp-cyclodepsipeptide research.
Effect of Tillage and Mulching on Soil Fertility and Grain Yield of Sorghum

Received: 22 July, 2014 Accepted: 18 September, 2014 Published:20 October, 2014 A field trail was carried out to evaluate the effect of different tillage and mulching practices on grain yield of sorghum and soil fertility. The experiment was comprised of three tillage practices i.e.T1= zero tillage (ZT) (direct seed sowing with manual drill), T2= reduced tillage (RT) (one cultivation followed by planking) and T3= conventional tillage(CT) (three cultivation followed by planking) in main plots and three mulching practices i.e.no mulch application (control) (M1), poultry manure mulch (M2) and wheat straw mulch (M3) at the rates of 0,10 and 7.5 tones ha respectively in sub-plots. Tillage affected all physiochemical soil properties except soil pH and organic matter. Mulch had a significant on soil ph, EC, organic matter, bulk density and soil NPK. Among all mulching practices poultry manure mulch was found superior in improving soil fertility and grain yield.Tillage affected grain yield and maximum grain yield was recorded in conventional tillage (2.75 t ha) followed by minimum tillage (2.62 t ha) and zero tillage (2.11 t ha). Mulch also affected grain yield, maximum was recorded in poultry manure (2.50 t ha) and minimum where no mulch (2.48 t ha) was applied. It can be concluded that reduced tillage operations and poultry manure mulching is suitable for improving soil properties and grain yield of sorghum. © 2014 PSCI Publisher All rights reserved.
Comprehensive Profiling of the Rheumatoid Arthritis Antibody Repertoire

Autoantibodies against citrullinated proteins are found in 64–89% of rheumatoid arthritis (RA) patients, with 88–99% specificity. This study was undertaken to create an unbiased, comprehensive profile of serum antibodies against the human proteome, including the citrullinome and the homocitrullinome, in RA patients, using a high‐density peptide array.
Effect of length of apical root resection on the biomechanical response of a maxillary central incisor in various occlusal relationships.

AIM To investigate the stress distribution and tooth displacement of a maxillary central incisor with various apical root resection lengths and occlusal relationships using finite element analysis. METHODOLOGY A maxillary central incisor was scanned by MicroCT. First, the finite element (FE) intact incisor model with dentine, enamel, pulp and root surrounded by alveolar bone and periodontal ligament was designed based on the MicroCT image data. Then, six FE models with varying lengths of apical root resection were established to simulate the clinical treatment and reveal the clinically applicable limit of apical root resection during endodontic microsurgery. For each model under different loading conditions, the maximum Von-Mises stress (σ max) at the root apex, root cervix, alveolar bone and periodontal ligament and the maximum tooth displacement (△R max) were calculated and compared. RESULTS In normal occlusions, more than 6 mm of root resection resulted in a marked increase in the △R max values (> 10%) and σ max values of alveolar bone (> 50%); the stress levels at the root apex increased dramatically when the apical root was resected more than 7mm. With increased overjet, apical root resection did not change the stress level markedly until it reached 8mm, but the △R max increased markedly (>10%) if the root was resected more than 5mm. With deep overbites, the σ max increased significantly (>50%) when the root was resected more than 4mm while the △R max decreased. With increased overjet and deep overbite, more than 6mm of resection resulted in a substantial σ max increase (>50%) of alveolar bone and the △R max increased markedly (>10%) when the root was resected 8mm. Additionally, the σ max and the △R max values were greater with increased overjet and lower with deep overbites. CONCLUSIONS Using finite element analysis, apical root resection of more than 6 mm resulted in a marked increase of stress distribution and tooth displacement in normal and increased overjet with deep overbite occlusal relationships. In increased overjets or deep overbites, more than 5 mm or 4 mm, respectively, stress distribution and tooth displacement increased markedly. This article is protected by copyright. All rights reserved.
Melatonin Inhibits Apoptosis and Oxidative Stress of Mouse Leydig Cells via a SIRT1-Dependent Mechanism

The purpose of the present study is to examine the effects of melatonin on apoptosis and oxidative stress in mouse Leydig cells and to elucidate the mechanisms responsible for these effects. Our results indicated that 10 ng/mL of melatonin significantly promoted cell viability, the ratio of EdU-positive (5-Ethynyl-2′-deoxyuridine) cells, and increased the mRNA expression of proliferating cell nuclear antigen (PCNA), cyclin D1(CCND1), and cell division control protein 42 (CDC42) (p < 0.05). We also observed that melatonin inhibited apoptosis of mouse Leydig cells, accompanied with increased B-cell lymphoma-2 (BCL-2) and decreased BCL2 associated X (BAX) mRNA and protein expression. Moreover, addition of melatonin significantly decreased the reactive oxygen species (ROS) production and malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, while it increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels (p < 0.05). In addition, we also found that melatonin increased the expression of SIRT1 (Silent information regulator 1) (p < 0.05). To explore the role of SIRT1 signaling in melatonin-induced cells, mouse Leydig cells were pretreated with EX527, an inhibitor of SIRT1. The protective effects of melatonin on mouse Leydig cells were reversed by EX527, as shown by decreased cell proliferation and increased cell apoptosis and oxidative stress. In summary, our results demonstrated that melatonin inhibited apoptosis and oxidative stress of mouse Leydig cells through a SIRT1-dependent mechanism.