Miracle-dz/UniFAR-FTUs huggingface dataset:
Grape Seed Proanthocyanidins Target the Enteroendocrine System in Cafeteria-Diet-Fed Rats.

SCOPE The effects on the enteroendocrine system of three different grape seed proanthocyanidin extract (GSPE) treatments are analyzed in rats on a cafeteria diet for 17 weeks. METHODS AND RESULTS GSPE is administered in a corrective manner (15 last days of the cafeteria diet) at two doses, 100 and 500 mg GSPE per kg bw. A third, longer treatment in which GSPE (500 mg kg-1 bw) is administered daily every other week during the 17 weeks of the cafeteria diet is also tested. Most GSPE treatments lead to ghrelin accumulation in the stomach, limited CCK secretion in the duodenum, and increased GLP-1 and PYY mRNA in colon. GSPE also increases cecal hypertrophy and reduces butyrate content. When the treatment is administered daily every other week during 17 weeks, there is also an increase in colon size. These effects are accompanied by a reduced food intake at the end of the experiment when GSPE is administered at 500 mg GSPE kg-1 during the last 15 days, but not on the other treatments, despite an observed reduction in body weight in the longer treatment. CONCLUSION GSPE modulates the enteroendocrine system in models in which it also reduces food intake or body weight.
NAPC: A Neural Algorithm for Automated Passenger Counting in Public Transport on a Privacy-Friendly Dataset

Real-time load information in public transport is of high importance for both passengers and service providers. Neural algorithms have shown a high performance on various object counting tasks and play a continually growing methodological role in developing automated passenger counting systems. However, the publication of public-space video footage is often contradicted by legal and ethical considerations to protect the passengers’ privacy. This work proposes an end-to-end Long Short-Term Memory network with a problem-adapted cost function that learned to count boarding and alighting passengers on a publicly available, comprehensive dataset of approx.13,000 manually annotated low-resolution 3D LiDAR video recordings (depth information only) from the doorways of a regional train. These depth recordings do not allow the identification of single individuals. For each door opening phase, the trained models predict the correct passenger count (ranging from 0 to 67) in approx.96% of boarding and alighting, respectively. Repeated training with different training and validation sets confirms the independence of this result from a specific test set.
DPDRC, a Novel Machine Learning Method about the Decision Process for Dimensionality Reduction before Clustering

This paper examines the critical decision process of reducing the dimensionality of a dataset before applying a clustering algorithm. It is always a challenge to choose between extracting or selecting features. It is not obvious to evaluate the importance of the features since the most popular methods to do it are usually intended for a supervised learning technique process. This paper proposes a novel method called “Decision Process for Dimensionality Reduction before Clustering” (DPDRC). It chooses the best dimensionality reduction method (selection or extraction) according to the data scientist’s parameters and the profile of the data, aiming to apply a clustering process at the end. It uses a Feature Ranking Process Based on Silhouette Decomposition (FRSD) algorithm, a Principal Component Analysis (PCA) algorithm, and a K-means algorithm along with its metric, the Silhouette Index (SI). This paper presents five scenarios based on different parameters. This research also aims to discuss the impacts, advantages, and disadvantages of each choice that can be made in this unsupervised learning process.
Blood Cell In Vitro Cytokine Production in Response to Lipopolysaccharide Stimulation in a Healthy Population: Effects of Age, Sex, and Smoking

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18–55 years was conducted. Whole blood samples were stimulated for 24 h with LPS and concentrations of IL-6, IL-10, and TNF-α were determined in the culture media. Among parameters considered, statistical regression analysis indicated that smoking (change in R2 = 0.064, p < 0.001) and sex (change in R2 = 0.070, p < 0.001) were the main predictors for IL-10 production, with higher values for women and non-smokers. Age was also found to be a significant predictor (change in R2 = 0.021, p < 0.001), with higher values for younger ages. Age (change in R2 = 0.089, p = 0.013) and smoking (change in R2 = 0.037, p = 0.002) were found to be negative predictors for IL-6 production. Regarding TNF-α-stimulated production, age (change in R2 = 0.029, p = 0.009) and smoking (change in R2 = 0.022, p = 0.022) were found to be negative predictors. Furthermore, sex (change in R2 = 0.016, p = 0.045) was found to be a significant predictor, with lower values for women. In conclusion, sex, age, and smoking were found to be independent determinants of stimulated cytokine production. While female sex is associated with higher IL-10 and lower TNF-α production, aging and smoking are associated with lower IL-6, IL-10, and TNF-α production.
Therapeutic Potency of Gallium verum Extract on Ethanol-Induced Gastric Ulcer in Rats

Gallium verum, lady's bedstraw is an herbaceous annual plant belonging to the genus Rubiaceae; it possessed antioxidant, cytotoxic for cancer cells, antimicrobial, protective and endocrine effects. This work aimed to investigate the curative effects of G. verum extract on gastric ulcers following absolute ethanol administration in the healthy rat. Eighteen rats were randomly divided into three main groups; rats were fastened for 24 hours before ethanol administration. All groups except control administered ethanol (5 ml/kg body weight; orally). The rats were administrated distilled water (Ulcer group) or G. verum extract (100mg/kg) one hour later. G. verum extract caused a significant decrease in ulcer index, gastric juice volume, malondialdehyde, and nitric oxide, while gastric juice pH, glutathione, glutathione-S-transferase, and catalase increased significantly. The histological lesion score showed a significant enhancement in group G. verum compared to the ulcer group that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB p65 and TNF-α showed a significant decrease in G. verum group. G. verum extract is a promising treatment modality against gastric injury through its powerful antioxidant, acid neutralizing, healing promotion, and ant-inflammation effects.
Region-Specific Effects of Trigeminal Capsaicin Stimulation.

AIMS To investigate the region-specific effects of painful trigeminal capsaicin stimulation in healthy participants. METHODS Twenty healthy participants (10 men and 10 women) participated in four sessions in which they received application of 0.05 mL Vaseline (placebo) or capsaicin cream (0.1%) to a different area innervated by the three branches of the trigeminal nerve: the supraorbital area (V1), the nasal mucosa (V1/V2), and the maxillary (V2) and mandibular (V3) oral mucosa. The participants rated their perceived sensations on a 0-50-100 numeric rating scale (NRS). Thermal (5°C, 23°C, and 50°C) and mechanical (32 mN and 256 mN) sensitivities were assessed. The Schirmer tearing test was used to monitor the lacrimation level as a local measure of autonomic activity, and the Task Force Monitor was used to record systemic autonomic activity. Data were analyzed using repeated measures analysis of variance. RESULTS Capsaicin application evoked significantly higher overall NRS scores (P < .001) and induced significantly higher ratings to the heat stimuli (P < .009) in all sessions compared to control. For lacrimation level, capsaicin stimulation resulted in a significant increase compared to control (P < .0002) only in the nasal mucosa session. CONCLUSION Topical application of capsaicin cream to the different branches of the trigeminal nerve caused higher NRS scores along with an altered somatosensory sensitivity. Furthermore, in the nasal mucosa session, a robust local and generalized parasympathetic activation appeared following capsaicin application.
The yeast mitochondrial pyruvate carrier is a hetero‐dimer in its functional state

The mitochondrial pyruvate carrier (MPC) is critical for cellular homeostasis, as it is required in central metabolism for transporting pyruvate from the cytosol into the mitochondrial matrix. MPC has been implicated in many diseases and is being investigated as a drug target. A few years ago, small membrane proteins, called MPC1 and MPC2 in mammals and Mpc1, Mpc2 and Mpc3 in yeast, were proposed to form large protein complexes responsible for this function. However, the MPC complexes have never been isolated and their composition, oligomeric state and functional properties have not been defined. Here, we identify the functional unit of MPC from Saccharomyces cerevisiae. In contrast to earlier hypotheses, we demonstrate that MPC is a hetero‐dimer, not a multimeric complex. When not engaged in hetero‐dimers, the yeast Mpc proteins can also form homo‐dimers that are, however, inactive. We show that the earlier described substrate transport properties and inhibitor profiles are embodied by the hetero‐dimer. This work provides a foundation for elucidating the structure of the functional complex and the mechanism of substrate transport and inhibition.
Gestational Age, Birth Weight, and Outcomes Six Years After the Norwood Procedure

Controlling for the overlapping and competing risks of lower gestational age and birth weight demonstrates they have independent effects on different outcomes in HLHS. BACKGROUND: Preterm delivery and low birth weight (LBW) are generally associated with worse outcomes in hypoplastic left heart syndrome (HLHS), but an individual preterm or small neonate may do well. We sought to explore the interactions between gestational age, birth weight, and birth weight for gestational age with intermediate outcomes in HLHS. METHODS: We analyzed survival, growth, neurodevelopment, length of stay, and complications to age 6 years in subjects with HLHS from the Single Ventricle Reconstruction trial. Univariate and multivariable survival and regression analyses examined the effects and interactions of LBW (<2500 g), weight for gestational age, and gestational age category. RESULTS: Early-term delivery (n = 234) was more common than term (n = 219) delivery. Small for gestational age (SGA) was present in 41% of subjects, but only 14% had LBW. Preterm, compared with term, delivery was associated with an increased risk of death or transplant at age 6 years (all: hazard ratio = 2.58, confidence interval = 1.43–4.67; Norwood survivors: hazard ratio = 1.96, confidence interval = 1.10–3.49) independent of LBW and weight for gestational age. Preterm delivery, early-term delivery, LBW, and SGA were each associated with lower weight at 6 years. Neurodevelopmental outcomes were worst in the LBW cohort. CONCLUSIONS: Preterm delivery in HLHS was associated with worse survival, even beyond Norwood hospitalization. LBW, SGA, and early-term delivery were associated with worse growth but not survival. LBW was associated with worse neurodevelopment, despite similar length of stay and complications. These data suggest that preterm birth and LBW (although often concomitant) are not equivalent, impacting clinical outcomes through mechanisms independent of perioperative course complexity.
International collaborative actions and transparency to understand, diagnose, and develop therapies for rare diseases

Rare diseases, which affect over 350 million people worldwide and frequently go undiagnosed or misdiagnosed for years, suffer from sparse and dispersed medical knowledge leading to even rarer approved and effective therapeutic options for patients. A vast, unmet need for research and investment to advance diagnostic capabilities and therapeutic development must be confronted, despite the myriad of challenges faced. Several fundamental shifts are changing the landscape of rare diseases research and development, particularly with the application and extension of results to common diseases and the advancement of personalized medicine initiatives. Collaborative strategies that pool resources and knowledge are vital, including team science, research networks, novel funding models, shared knowledge platforms, and innovative regulatory frameworks. Importantly, patients are also increasingly involved as research partners and funders, pushing for open science and transparency, and breaking down data silos and geographical borders, often enabled by online platforms accessible from across the globe. The International Rare Diseases Research Consortium (IRDiRC), established in 2011, has been working diligently to unify stakeholders (e.g., funding bodies, companies, umbrella patient advocacy groups, researchers, and experts) to seek and drive solutions that aim to accelerate diagnosis and therapeutic development for rare diseases worldwide. Further and future advances will depend on continued collaborations and cooperation among stakeholders, working hand in hand with patients, and exponentially improving research and development efficiency. Critically, engagement with stakeholders from underrepresented populations and less‐developed countries must be prioritized, to enable all people living with a rare disease to receive an accurate diagnosis, care, and therapy.
Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Gene therapy is a rapidly emerging remedial route for many serious incurable diseases, such as central nervous system (CNS) diseases. Currently, nucleic acid medicines, including DNAs encoding therapeutic or destructive proteins, small interfering RNAs or microRNAs, have been successfully delivered to the CNS with gene delivery vectors using various routes of administration and have subsequently exhibited remarkable therapeutic efficiency. Among these vectors, non‐viral vectors are favorable for delivering genes into the CNS as a result of their many special characteristics, such as low toxicity and pre‐existing immunogenicity, high gene loading efficiency and easy surface modification. In this review, we highlight the main types of therapeutic genes that have been applied in the therapy of CNS diseases and then outline non‐viral gene delivery vectors.
A non‐death function of the mitochondrial apoptosis apparatus in immunity

Apoptosis is a frequent form of programmed cell death, but the apoptotic signaling pathway can also be engaged at a low level, in the absence of cell death. We here report that such sub‐lethal engagement of mitochondrial apoptosis signaling causes the secretion of cytokines from human epithelial cells in a process controlled by the Bcl‐2 family of proteins. We further show that sub‐lethal signaling of the mitochondrial apoptosis pathway is initiated by infections with all tested viral, bacterial, and protozoan pathogens and causes damage to the genomic DNA. Epithelial cells infected with these pathogens secreted cytokines, and this cytokine secretion upon microbial infection was substantially reduced if mitochondrial sub‐lethal apoptosis signaling was blocked. In the absence of mitochondrial pro‐apoptotic signaling, the ability of epithelial cells to restrict intracellular bacterial growth was impaired. Triggering of the mitochondrial apoptosis apparatus thus not only causes apoptosis but also has an independent role in immune defense.
Regulation of death receptor signaling by the autophagy protein TP53INP2

TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death‐receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor‐induced apoptosis. TP53INP2 binds caspase‐8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase‐8 by TRAF6. We have defined a TRAF6‐interacting motif (TIM) and a ubiquitin‐interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase‐8 to TRAF6 for further polyubiquitination of caspase‐8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase‐8, and subsequently reduce levels of death receptor‐induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL‐induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase‐8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway.
Visualizing Risky Behaviors Induces a Stronger Neural Response in Brain Areas Responsible for Mental Imagery and Emotions Than Visualizing Neutral Behaviors

In the present study, we used a neuroimaging technique (fMRI) to test the prediction that visualizing risky behaviors induces a stronger neural response in brain areas responsible for emotions and mental imagery than visualizing neutral behaviors. We identified several brain regions that were activated when participants produced mental images of risky versus neutral behaviors and these regions overlap with brain areas engaged in visual mental imagery, speech imagery and movement imagery. We also found that producing mental images of risky behaviors, in contrast to neutral behaviors, increased neural activation in the insula – a region engaged in emotional processing. This finding is in line with previous results demonstrating that the insula is recruited by tasks involving induction of emotional recall/imagery. Finally, we observed an increased BOLD signal in the cingulate gyrus (mid-cingulate area), which is associated with reward-based decision making and monitoring of decision outcomes. In summary, we demonstrated that mental images of risky behaviors, compared to risk-free behaviors, increased neural activation in brain areas engaged in mental imagery processes, emotional processing and decision making. These findings imply that the evaluation of everyday risky situations may originate in visualizing the potential consequences of risk taking and may be driven by emotional responses that result from mental imagery.
The Incredible Years® Teacher Classroom Management programme and its impact on teachers' professional self-efficacy, work-related stress, and general well-being: Results from the STARS randomized controlled trial.

BACKGROUND Teaching is a stressful occupation with poor retention. The Incredible Years® Teacher Classroom Management (TCM) programme is a training programme that research has demonstrated may be an effective intervention for improving children's mental health, but little research has explored any impacts there may be on the teachers' own professional confidence and mental health. AIMS In this paper, we evaluate whether TCM may lead to changes in teachers' well-being, namely a reduction in burnout and an improvement in self-efficacy and mental health. SAMPLE Eighty schools across the South West of England were recruited between September 2012 and September 2014. Headteachers were asked to nominate one class teacher to take part. METHODS Eighty teachers were randomized to either attend a TCM course (intervention) or not (control). TCM was delivered to groups of up to 12 teachers in six whole-day workshops that were evenly spread between October and April. At baseline and 9-month follow-up, we measured teachers' mental health using the Everyday Feelings Questionnaire (EFQ), burnout using the Maslach Burnout Inventory-General Survey (MBI-GS), and self-efficacy using the Teachers' Sense of Efficacy Scale-Short (TSES-Short). RESULTS Using linear regression models, there was little evidence of differences at follow-up between the intervention and control teachers on the outcomes (the smallest p-value was .09). CONCLUSIONS Our findings did not replicate previous research that TCM improved teachers' sense of efficacy. However, there were limitations with this study including low sample size.
High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified. Transcriptomic analysis revealed significantly higher expression of a number of genes related to proliferation, (CDKN2A, MELK, CDK1, MKI67, CCNB2, BUB1, FOXM1, CDKN3), but significantly lower expression of genes related to a favorable immune response (NCAM1, ARG1, CD160, IL18, CX3CL1). Compared to the RNA sequencing results, good correlation was achieved with relative quantitative PCR analysis for NCAM1 and CDKN2A. Quantification of NCAM1 positive cells with immunohistochemistry showed epithelial reduction of NCAM1 in CIN3/AIS lesions. In conclusion, NCAM1 and CDKN2A are two promising candidates to distinguish whether women are at high risk of developing cervical cancer and in need of frequent follow-up.
Systematic Review and Appraisal of the Cross‐Cultural Validity of Functional Status Assessment Measures in Rheumatoid Arthritis

We conducted a systematic review and appraisal of the cross‐cultural adaptation and cross‐cultural validity of the Health Assessment Questionnaire (HAQ) and its derivatives, and of the more recent Patient‐Reported Outcomes Measurement Information System (PROMIS) functional status assessment measures (FSAMs) in rheumatoid arthritis.