Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery

Introduction Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery. Methods Pancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F β-cells exposed to lipotoxic conditions. Results Sleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with diet-induced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F β-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F β-cells, but only guanylin upregulated Wnt4, a factor that controls β-cell proliferation and function. Discussion Together, sleeve gastrectomy reduced pancreatic steatosis and improved β-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.
Emotion recognition accuracy only weakly predicts empathic accuracy in a standard paradigm and in real life interactions

The relationship between decoding ability (Emotion recognition accuracy, ERA) for negative and positive emotion expressions from only video, only audio and audio-video stimuli and the skill to understand peoples’ unspoken thoughts and feelings (Empathic accuracy, EA) was tested. Participants (N = 101) from three groups (helping professionals with and without therapy training as well as non-helping professionals) saw or heard recordings of narrations of a negative event by four different persons. Based on either audio-video or audio-only recordings, the participants indicated for given time points what they thought the narrator was feeling and thinking while speaking about the event. A Bayesian regression model regressing group and ERA scores on EA scores was showing weak support only for the EA scores for ratings of unspoken feelings from audio only recordings. In a subsample, the quality of self-experienced social interactions in everyday life was assessed with a diary. The analysis of ERA and EA scores in relation to diary scores did not indicate much correspondence. The results are discussed in terms of relations between skills in decoding emotions using different test paradigms and contextual factors.
Systematic review of 31P-magnetic resonance spectroscopy studies of brain high energy phosphates and membrane phospholipids in aging and Alzheimer's disease

Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aβ) plaques. In vivo probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used 18F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in vivo in the human brain. 31Phosphorus-magnetic resonance spectroscopy (31P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the 31P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of 31P-MRS measures as biomarkers for the early detection of AD.
Gender differences in perceived legitimacy and status perception in leadership role

The present study examined the difference between women and men in perceiving leadership roles. Two experiments, one conducted online and the other in a lab, investigated the subjective experiences of Japanese men and women when they are assigned with different roles (e.g., leader vs. subordinate). Both studies revealed that women perceived their role as less legitimate when they were assigned leader role (vs. subordinate role). In contrast, men did not differ in their perceived legitimacy according to the assigned roles. This discrepancy in legitimacy perception in response to different roles between men and women accounted for a significant variance in women’s lower sense of status when they were a leader (vs. subordinate), but not among men. Our study results illustrate the psychological barrier operating for women in organizations that are embedded in a cultural context in which women leaders are highly underrepresented.
Blood immune cells as potential biomarkers predicting relapse-free survival of stage III/IV resected melanoma patients treated with peptide-based vaccination and interferon-alpha

Introduction Despite the recent approval of several therapies in the adjuvant setting of melanoma, tumor relapse still occurs in a significant number of completely resected stage III-IV patients. In this context, the use of cancer vaccines is still relevant and may increase the response to immune checkpoint inhibitors. We previously demonstrated safety, immunogenicity and preliminary evidence of clinical efficacy in stage III/IV resected melanoma patients subjected to a combination therapy based on peptide vaccination together with intermittent low-dose interferon-α2b, with or without dacarbazine preconditioning (https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26). In this setting, we then focused on pre-treatment patient immune status to highlight possible factors associated with clinical outcome. Methods Multiparametric flow cytometry was used to identify baseline immune profiles in patients’ peripheral blood mononuclear cells and correlation with the patient clinical outcome. Receiver operating characteristic curve, Kaplan-Meier survival and principal component analyses were used to evaluate the predictive power of the identified markers. Results We identified 12 different circulating T and NK cell subsets with significant (p ≤ 0.05) differential baseline levels in patients who later relapsed with respect to patients who remained free of disease. All 12 parameters showed a good prognostic accuracy (AUC>0.7, p ≤ 0.05) and 11 of them significantly predicted the relapse-free survival. Remarkably, 3 classifiers also predicted the overall survival. Focusing on immune cell subsets that can be analyzed through simple surface staining, three subsets were identified, namely regulatory T cells, CD56dimCD16- NK cells and central memory γδ T cells. Each subset showed an AUC>0.8 and principal component analysis significantly grouped relapsing and non-relapsing patients (p=0.034). These three subsets were used to calculate a combination score that was able to perfectly distinguish relapsing and non-relapsing patients (AUC=1; p=0). Noticeably, patients with a combined score ≥2 demonstrated a strong advantage in both relapse-free (p=0.002) and overall (p=0.011) survival as compared to patients with a score <2. Discussion Predictive markers may be used to guide patient selection for personalized therapies and/or improve follow-up strategies. This study provides preliminary evidence on the identification of peripheral blood immune biomarkers potentially capable of predicting the clinical response to combined vaccine-based adjuvant therapies in melanoma.
A detailed dosimetric comparative study of IMRT and VMAT in normal brain tissues for nasopharyngeal carcinoma patients treated with radiotherapy

Background Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). However, it can cause implicit RT-induced injury by irradiating normal brain tissue. To date, there have been no detailed reports on the radiated exact location in the brain, the corresponding radiation dose, and their relationship. Methods We analyzed 803 Chinese NPC patients treated with RT and used a CT brain template in a Montreal Neurological Institute (MNI) space to compare the group differences in RT dose distribution for different RT technologies (IMRT or VMAT). Results Brain regions that received high doses (>50 Gy) of radiation were mainly located in parts of the temporal and limbic lobes, where radioactive damage often occurs. Brain regions that accepted higher doses with IMRT were mainly located near the anterior region of the nasopharyngeal tumor, while brain regions that accepted higher doses with VMAT were mainly located near the posterior region of the tumor. No significant difference was detected between IMRT and VMAT for T1 stage patients. For T2 stage patients, differences were widely distributed, with VMAT showing a significant dose advantage in protecting the normal brain tissue. For T3 stage patients, VMAT showed an advantage in the superior temporal gyrus and limbic lobe, while IMRT showed an advantage in the posterior cerebellum. For T4 stage patients, VMAT showed a disadvantage in protecting the normal brain tissue. These results indicate that IMRT and VMAT have their own advantages in sparing different organs at risk (OARs) in the brain for different T stages of NPC patients treated with RT. Conclusion Our approach for analyzing dosimetric characteristics in a standard MNI space for Chinese NPC patients provides greater convenience in toxicity and dosimetry analysis with superior localization accuracy. Using this method, we found interesting differences from previous reports: VMAT showed a disadvantage in protecting the normal brain tissue for T4 stage NPC patients.
An miRNA-mRNA integrative analysis in human placentas and mice: role of the Smad2/miR-155-5p axis in the development of fetal growth restriction

Introduction: Functional disorder of the placenta is the principal cause of fetal growth restriction (FGR), usually cured with suitable clinical treatment and good nursing. However, some FGR mothers still give birth to small for gestational age (SGA) babies after treatment. The ineffectiveness of treatment in such a group of patients confused physicians of obstetrics and gynecology. Methods: In this study, we performed a microRNA-messenger RNA integrative analysis of gene expression profiles obtained from Gene Expression Omnibus. Differentially expressed genes were screened and checked using quantitative polymerase chain reaction. Target genes of significantly changed microRNA were screened and enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Function of the obtained microRNA-messenger RNA was evaluated using HTR-8/SVneo trophoblast cells, human umbilical vein endothelial cells, and heterozygote male mice. Result: MiR-155-5p was upregulated (p = 0.001, fold-change = 2.275) in fetal-side placentals. Among the hub genes identified as key targets for miR-155-5p in fetal reprogramming, Smad2 was downregulated (p = 0.002, fold change = 0.426) and negatively correlated with miR-155-5p expression levels (r = −0.471, p < 1.0 E – 04) in fetal-side placental tissues. The miR-155-5p mimic blocks Smad2 expression and suppresses villous trophoblast cell and endothelial cell function (proliferation, migration, and invasion), indicating a close relationship with placental development. Luciferase assays further confirmed the targeting of miR-155-5p to Smad2. Furthermore, Smad2+/− heterozygote male mice were born small with low body weight (p = 0.0281) and fat composition (p = 0.013) in the fourth week post-natal. Discussion: We provide the first evidence of the role of the Smad2/miR-155-5p axis in the placental pathologies of FGR. Our findings elucidate the pathogenesis of FGR and provide new therapeutic targets.
Multiplex PCR-based next generation sequencing as a novel, targeted and accurate molecular approach for periprosthetic joint infection diagnosis

Objectives Periprosthetic joint infection (PJI) diagnosis remains challenging, and the identification of the causative microorganism is, by far, the most important aspect. Here, we use multiple PCR-based targeted next-generation sequencing (tNGS) to detect pathogens in PJI. To explore 1. the ability of targeted next-generation sequencing (tNGS) to detect pathogens in PJI; 2. the consistency of tNGS, metagenomic NGS (mNGS), and culture results; and 3. the ability of tNGS to detect drug resistance genes in PJI. Methods PJI was diagnosed according to the Musculoskeletal Infection Society (MSIS) criteria. The microorganisms were detected by culture, mNGS and tNGS to compare the diagnostic effectiveness of the three methods for PJI and to compare their consistency in detecting microorganisms. Drug resistance genes were detected using tNGS. The costs and turnaround times of mNGS and tNGS were compared. Results Forty-three patients with PJI, 21 patients without PJI and 10 negative control cases were included. The culture, tNGS, and mNGS sensitivities for PJI diagnosis were 74.41%, 88.37%, and 93.02%, respectively, with no significant differences. The specificities were 90.48%, 95.24%, and 95.24%, respectively, with no significant differences. tNGS detected drug resistance genes in 37.5% of culture-positive PJIs. tNGS was superior to mNGS for turnaround time (14.5 h vs. 28 h) and cost ($150 vs. $260). Conclusions tNGS can effectively identify PJI pathogens and may provide drug resistance information, while tNGS is superior to mNGS regarding cost and turnaround time. A multidisciplinary, multi-technology based algorithm to diagnose PJI is appropriate. Highlights 298 microorganisms and 86 drug resistance genes were included in the tNGS panel. Diagnostic efficacy of tNGS is not inferior to that of commonly used indicators. tNGS is superior to mNGS in cost and turnaround time.
Study protocol: BRInging the Diabetes prevention program to GEriatric Populations

In the Diabetes Prevention Program (DPP) randomized, controlled clinical trial, participants who were ≥ 60 years of age in the intensive lifestyle (diet and physical activity) intervention had a 71% reduction in incident diabetes over the 3-year trial. However, few of the 26.4 million American adults age ≥65 years with prediabetes are participating in the National DPP. The BRInging the Diabetes prevention program to GEriatric Populations (BRIDGE) randomized trial compares an in-person DPP program Tailored for Older AdulTs (DPP-TOAT) to a DPP-TOAT delivered via group virtual sessions (V-DPP-TOAT) in a randomized, controlled trial design (N = 230). Eligible patients are recruited through electronic health records (EHRs) and randomized to the DPP-TOAT or V-DPP-TOAT arm. The primary effectiveness outcome is 6-month weight loss and the primary implementation outcome is intervention session attendance with a non-inferiority design. Findings will inform best practices in the delivery of an evidence-based intervention.
CEP55 as a promising biomarker and therapeutic target on gallbladder cancer

Introduction Gallbladder cancer (GBC) is a highly malignant biliary tumor with a poor prognosis. As existing therapies for advanced metastatic GBC are rarely effective, there is an urgent need to identify more effective targets for treatment. Methods Hub genes of GBC were identified by bioinformatics analysis and their expression in GBC was analyzed by tissue validation. The biological role of CEP55 in GBC cell and the underlying mechanism of the anticancer effect of CEP55 knockdown were evaluated via CCK8, colony formation assay, EDU staining, flow cytometry, western blot, immunofluorescence, and an alkaline comet assay. Results We screened out five hub genes of GBC, namely PLK1, CEP55, FANCI, NEK2 and PTTG1. CEP55 is not only overexpressed in the GBC but also correlated with advanced TNM stage, differentiation grade and poorer survival. After CEP55 knockdown, the proliferation of GBC cells was inhibited with cell cycle arrest in G2/M phase and DNA damage. There was a marked increase in the apoptosis of GBC cells in the siCEP55 group. Besides, in vivo, CEP55 inhibition attenuated the growth and promoted apoptosis of GBC cells. Mechanically, the tumor suppressor effect of CEP55 knockdown is associated with dysregulation of the AKT and ERK signaling networks. Discussion These data not only demonstrate that CEP55 is identified as a potential independent predictor crucial to the diagnosis and prognosis of gallbladder cancer but also reveal the possibility for CEP55 to be used as a promising target in the treatment of GBC.
Molecular and evolutionary basis of O-antigenic polysaccharide driven phage sensitivity in environmental pseudomonads

Pseudomonas protegens CHA0, a bacterial strain able to suppress plant pathogens as well as efficiently kill lepidopteran pest insects, has been studied as biocontrol agent to prevent ensuing agricultural damage. However, the success of this method is dependent on the efficient plant colonization by the bacterial inoculant while it faces competition from the resident microbiota as well as predators such as bacteriophages. One of these naturally occurring phages, ΦGP100, was found to drastically reduce the abundance of CHA0 once inoculated into plant microcosms, resulting in the loss of plant protection against a phytopathogen. Here, we investigated the molecular determinants implicated in the interaction between CHA0 and the phage ΦGP100 using a high-density transposon-sequencing approach. We show that lipopolysaccharide cell surface decorations, specifically the longer OBC3-type O-antigenic polysaccharide (O-PS, O-antigen) of the two dominant O-PS of CHA0 is essential for the attachment and infection of ΦGP100. Moreover, when exploring the distribution of the OBC3 cluster in bacterial genomes, we identified several parts of this gene cluster that are conserved in phylogenetically distant bacteria. Through heterologous complementation, we integrated an OBC3-type gene copy from a phylogenetically distant bacterium and were able to restore the phage sensitivity of a CHA0 mutant which lacked the ability to form long O-PS. Finally, we evidence that the OBC3 gene cluster of CHA0 displays a high genomic plasticity and likely underwent several horizontal acquisitions and genomic rearrangements. Collectively, this study underlines the complexity of phage-bacteria interaction and the multifunctional aspect of bacterial cell surface decorations. Importance The application of plant-beneficial microorganisms to protect crop plants is a promising alternative to the usage of chemicals. However, biocontrol research often faces difficulties to implement this approach due to the inconsistency of the bacterial inoculant to establish itself within the root microbiome. Beneficial bacterial inoculants can be decimated by the presence of their natural predators, notably bacteriophages (also-called phages). Thus, it is important to gain knowledge regarding the mechanisms behind phage-bacteria interaction to overcome this challenge. Here, we evidence that the major long O-antigenic polysaccharide (O-PS, O-antigen) of the widely used model plant-beneficial bacterium Pseudomonas protegens CHA0 is the receptor of its natural predator, phage ΦGP100. We examined the distribution of the gene cluster directing the synthesis of this O-PS and identified signatures of horizontal gene acquisitions. Altogether, our study highlights the importance of bacterial cell surface structure variation in the complex interplay between phages and their Pseudomonas hosts.
Investigation on the effect of MR elastomer based adaptive vibration absorbers on the radiated sound from circular elastic plates

This study aims to investigate the effect of using magnetorheological elastomer (MRE)-based adaptive tuned vibration absorbers (ATVA) on the sound transmission in an elastic plate. Sound transmission loss (STL) of an elastic circular thin plate is analytically studied. The plate is excited by a plane acoustic wave as an incident sound and the displacement of the plate is calculated using corresponding mode shapes of the system for clamped boundary condition. Rayleigh integral approach is used to express the transmitted sound pressure in terms of the plate’s displacement modal amplitude. In order to increase sound transmission loss of the plate, the MRE-based ATVA is considered. The basic idea is to be able to change the stiffness of the ATVA by varying magnetic field in order to reduce the transmitted acoustic energy of the host structure in a wide frequency range. Here, a MRE-based ATVA under the shear mode consisting of an oscillator mass, magnetic conductor, coils and MRE is investigated. In order to predict the viscoelastic characteristics of the field-dependent MRE based on the applied magnetic field, the double pole model is used. Finally, MRE-based ATVAs are integrated with the plate to absorb the plate energy with the aim of decreasing the transmitted sound power. Results show that plate with integrated MRE-based ATVAs suppresses the axisymmetric vibration of the plate and thus considerably improves the STL. Parametric studies on the influence of the position of MRE-based ATVAs and the effects of applied current on their performance are also presented.
Algorithm for Attribute Reduction in Ordered Information Systems Based on Relative Differential Quantity of Advantage Classes

The notions of a differential quantity between advantage classes and a differential quantity between relatively advantage classes are defined in ordered information systems,and a new index for measuring significance of the attributes of an ordered information system is also presented.Then,a heuristic reduction algorithm for ordered information systems is proposed.The proposed algorithm is of less time complexity since it adopts the strategy of removing unimportant attributes from the search space.Compared with the existing reduction algorithms developed for the ordered information systems,the presented algorithm has certain advantages in decreasing the number of searching attributes.Finally,a real example and some experimental results are used to demonstrate the feasibility and effectiveness of the proposed algorithm.