Miracle-dz/UniFAR-FTUs huggingface dataset:
Papain Ameliorates Lipid Accumulation and Inflammation in High-Fat Diet-Induced Obesity Mice and 3T3-L1 Adipocytes via AMPK Activation

Papain is a proteolytic enzyme present in the leaves, fruits, roots, and latex of the Carica papaya (papaya) plant. Although it exhibits a wide range of activities, there are no reports on the anti-obesity effects of papain. This study examined the anti-obesity effect and obesity-involved anti-inflammatory mechanism of papain in in vivo and in vitro models using high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Oral administration of papain reduced HFD-induced weight of the body, liver, and adipose tissues of mice. Papain also reduced hepatic lipid accumulation and adipocyte size. Moreover, serum total cholesterol and triglyceride levels were markedly reduced in papain-treated mice. In addition, papain inhibited the differentiation of preadipocytes and oil accumulation in 3T3-L1 preadipocytes and rat primary preadipocytes. Mechanistically, papain significantly downregulated the protein levels of key adipogenesis regulators and reversed the expression of pro-inflammatory cytokines and adipokines in HFD-induced obese mice and 3T3-L1 preadipocytes. Papain also markedly enhanced activation of the AMP-activated protein kinase pathway in both models. Collectively, these results suggest that papain exerts anti-obesity effects in HFD-induced mice and 3T3-L1 preadipocytes by regulating levels of adipogenic factors involved in lipid metabolism and inflammation; thus, it could be useful in the prevention and treatment of obesity.
Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation

Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses.
Species-Specific Humoral Immune Responses in Sheep and Goats upon Small Ruminant Lentivirus Infections Inversely Correlate with Protection against Virus Replication and Pathological Lesions

Maedi-Visna-like genotype A strains and Caprine arthritis encephaltis-like genotype B strains are small ruminant lentiviruses (SRLV) which, for incompletely understood reasons, appear to be more virulent in sheep and goats, respectively. A 9-month in vivo infection experiment using Belgian genotype A and B SRLV strains showed that almost all homologous (genotype A in sheep; genotype B in goats) and heterologous (genotype A in goats; genotype B in sheep) intratracheal inoculations resulted in productive infection. No differences in viremia and time to seroconversion were observed between homologous and heterologous infections. Higher viral loads and more severe lesions in the mammary gland and lung were however detected at 9 months post homologous compared to heterologous infection which coincided with strongly increased IFN-γ mRNA expression levels upon homologous infection. Pepscan analysis revealed a strong antibody response against immune-dominant regions of the capsid and surface proteins upon homologous infection, which was absent after heterologous infection. These results inversely correlated with protection against virus replication in target organs and observed histopathological lesions, and thus require an in-depth evaluation of a potential role of antibody dependent enhancement in SRLV infection. Finally, no horizontal intra- and cross-species SRLV transmission to contact animals was detected.
Alliance with the School Personnel Is Crucial for the Management of Food Allergy and Anaphylaxis in School Children

Background: School nurses play an important role in coping with food allergy (FA) in schoolchildren, but in schools with no school nurse, the school personnel should be prepared to manage health emergencies. This study aimed to evaluate allergy management competences in primary schools in Cyprus. Methods: The study was conducted September 2016 to May 2017 in 11/13 primary schools, selected by stratified random sampling. Information was collected from a principal/designated teacher using a questionnaire from the EuroPrevall Project, adapted for Cypriot teachers. Results: An average of six children with FA per school was reported in the preceding three years. Protocols for the management of chronic diseases, including allergies, were in place in 8/11 schools. Regarding recognition of FA, 8/11 respondents knew some of the signs and symptoms. In an allergic emergency, 9/11 would call the child’s parent/caregiver first and 2/11 emergency medical support. Epinephrine auto-injector (EIA) was reported by 2/11 respondents to be available in the school, but only one reported training in its use. Conclusions: The preparedness of primary schools in Cyprus did not meet safety standards regarding the preparedness of school personnel to cope with an allergic reaction in children with FA, including the use of EIA.
Liquid Biopsy from Bile-Circulating Tumor DNA in Patients with Biliary Tract Cancer

Simple Summary Utilization of cell free DNA for diagnosing and monitoring patients with biliary tract cancers is emerging and promising. The strength of the present study is in its description of a novel approach using bile rather than blood or tissue samples, which is particularly relevant in biliary tract cancers. This paper largely serves as a proof of concept that ctDNA from bile is potentially feasible. Abstract Although liquid biopsy of blood is useful for cancer diagnosis and prediction of prognosis, diagnostic and prognostic value of ctDNA in bile fluid for BTCs are not clear yet. To determine whether liquid biopsy for circulating tumor DNA (ctDNA) can replace tissue biopsy when assessing somatic mutations in biliary tract cancers (BTCs). Bile samples were obtained from 42 patients with BTC. Matched formalin-fixed paraffin-embedded (FFPE) samples were obtained from 20 of these patients and matched plasma samples from 16 of them. Droplet digital PCR (ddPCR) was used for detection KRAS somatic mutation. KRAS mutations were identified in the bile ctDNA of 20 of 42 (48%) patients. Patients with mutant KRAS showed significantly worse survival than those with wild-type KRAS (2-year survival rates: 0% vs. 55.5%, respectively; p = 0.018). There was 80.0% mutational concordance between the paired bile ctDNA and FFPE samples, and 42.9% between the plasma and FFPE samples. On transcriptomic sequencing of one set of paired bile and FFPE samples, expression level of KRAS-associated signaling oncogenes in the bile and tissue samples showed a strong positive correlation (r = 0.991, p < 0.001). Liquid biopsy of bile reliably detect mutational variants within the bile ctDNA of BTC patients. These results suggest that bile is an effective biopsy fluid for ctDNA analysis.
Understanding the Origin of Metal Gate Work Function Shift and Its Impact on Erase Performance in 3D NAND Flash Memories

We studied the metal gate work function of different metal electrode and high-k dielectric combinations by monitoring the flat band voltage shift with dielectric thicknesses using capacitance–voltage measurements. We investigated the impact of different thermal treatments on the work function and linked any shift in the work function, leading to an effective work function, to the dipole formation at the metal/high-k and/or high-k/SiO2 interface. We corroborated the findings with the erase performance of metal/high-k/ONO/Si (MHONOS) capacitors that are identical to the gate stack in three-dimensional (3D) NAND flash. We demonstrate that though the work function extraction is convoluted by the dipole formation, the erase performance is not significantly affected by it.
Analysis of the Microbial Intestinal Tract in Broiler Chickens during the Rearing Period

Simple Summary In chickens, as for humans and other animals, the intestinal microbiota plays a pivotal role in growth promotion and healthiness. This study analyzed gut microbiota composition and predicted functions in healthy chickens fed a standard diet without antibiotics. The microbiota changes significantly according to the four intestine segments (duodenum, jejunum, ileum, and caecum) and, to a lower extent, to age. Abstract Gut microbiota contributes to animal health. However, identifying which microorganisms or associated functions are involved remains, still, difficult to assess. In the present study, the microbiota of healthy broiler chickens, under controlled diet and farm conditions, was investigated by 16S rRNA gene sequencing in four intestine segments and at four ages. In detail, 210 Ross-308 male chickens were raised according to the EU guidelines and fed on a commercial diet. The duodenum, jejunum, ileum, and caecum microbiota were analyzed at 11, 24, 35, and 46 days of life. Although the microbial composition was revealed as homogeneous 11 days after chicks hatched, it was found to be similar in the proximal intestine segments and different in ileum and caecum, where almost the same genera and species were detected with different relative abundances. Although changes during the later growth stage were revealed, each genus remained relatively unchanged. Lactobacillus mostly colonized the upper tract of the intestine, whereas the Escherichia/Shigella genus the ileum. Clostridium and Bacteroides genera were predominant in the caecum, where the highest richness of bacterial taxa was observed. We also analyze and discuss the predicted role of the microbiota for each intestine segment and its potential involvement in nutrient digestion and absorption.
Multi-Omic Approaches to Breast Cancer Metabolic Phenotyping: Applications in Diagnosis, Prognosis, and the Development of Novel Treatments

Simple Summary Breast cancer (BC) is a heterogeneous tumor type and has become the leading cause of cancer worldwide, with 685,000 deaths forecast in 2020. The clinical management of BC patients remains challenging, and there exists an urgent need for improved diagnostic, prognostic, and therapeutic strategies. Multi-omics platforms represent a promising tool for discovering novel biomarkers and identifying new therapeutic targets. In addition, the ongoing development of multi-omics approaches may foster the identification of more robust and accurate algorithms for data analysis. This review aims to summarize the results of recent multi-omics-based studies focused on the characterization of the metabolic phenotype of BC. Abstract Breast cancer (BC) is characterized by high disease heterogeneity and represents the most frequently diagnosed cancer among women worldwide. Complex and subtype-specific gene expression alterations participate in disease development and progression, with BC cells known to rewire their cellular metabolism to survive, proliferate, and invade. Hence, as an emerging cancer hallmark, metabolic reprogramming holds great promise for cancer diagnosis, prognosis, and treatment. Multi-omics approaches (the combined analysis of various types of omics data) offer opportunities to advance our understanding of the molecular changes underlying metabolic rewiring in complex diseases such as BC. Recent studies focusing on the combined analysis of genomics, epigenomics, transcriptomics, proteomics, and/or metabolomics in different BC subtypes have provided novel insights into the specificities of metabolic rewiring and the vulnerabilities that may guide therapeutic development and improve patient outcomes. This review summarizes the findings of multi-omics studies focused on the characterization of the specific metabolic phenotypes of BC and discusses how they may improve clinical BC diagnosis, subtyping, and treatment.
Potency of Urea-Treated Halloysite Nanotubes for the Simultaneous Boosting of Mechanical Properties and Crystallization of Epoxidized Natural Rubber Composites

Halloysite nanotubes (HNTs) are naturally occurring tubular clay made of aluminosilicate sheets rolled several times. HNT has been used to reinforce many rubbers. However, the narrow diameter of this configuration causes HNT to have poor interfacial contact with the rubber matrix. Therefore, increasing the distance between layers could improve interfacial contact with the matrix. In this work, Epoxidized Natural Rubber (ENR)/HNT was the focus. The HNT layer distance was successfully increased by a urea-mechanochemical process. Attachment of urea onto HNT was verified by FTIR, where new peaks appeared around 3505 cm−1 and 3396 cm−1, corresponding to urea’s functionalities. The intercalation of urea to the distance gallery of HNT was revealed by XRD. It was also found that the use of urea-treated HNT improved the modulus, tensile strength, and tear strength of the composites. This was clearly responsible for interactions between ENR and urea-treated HNT. It was further verified by observing the Payne effect. The value of the Payne effect was found to be reduced at 62.38% after using urea for treatment. As for the strain-induced crystallization (SIC) of the composites, the stress–strain curves correlated well with the results from synchrotron wide-angle X-ray scattering.
Impairment of the Hypothalamus–Pituitary–Thyroid Axis Caused by Naturally Occurring GATA2 Mutations In Vitro

The transcription factor GATA2 regulates gene expression in several cells and tissues, including hematopoietic tissues and the central nervous system. Recent studies revealed that loss-of-function mutations in GATA2 are associated with hematological disorders. Our earlier in vitro studies showed that GATA2 plays an essential role in the hypothalamus–pituitary–thyroid axis (HPT axis) by regulating the genes encoding prepro-thyrotropin-releasing hormone (preproTRH) and thyroid-stimulating hormone β (TSHβ). However, the effect of GATA2 mutants on the transcriptional activity of their promoters remains unelucidated. In this study, we created five human GATA2 mutations (R308P, T354M, R396Q, R398W, and S447R) that were reported to be associated with hematological disorders and analyzed their functional properties, including transactivation potential and DNA-binding capacity toward the preproTRH and the TSHβ promoters. Three mutations (T354M, R396Q, and R398W) within the C-terminal zinc-finger domain reduced the basal GATA2 transcriptional activity on both the preproTRH and the TSHβ promoters with a significant loss of DNA binding affinity. Interestingly, only the R398W mutation reduced the GATA2 protein expression. Subsequent analysis demonstrated that the R398W mutation possibly facilitated the GATA2 degradation process. R308P and S447R mutants exhibited decreased transcriptional activity under protein kinase C compared to the wild-type protein. In conclusion, we demonstrated that naturally occurring GATA2 mutations impair the HPT axis through differential functional mechanisms in vitro.
Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections

Accurate preoperative diagnosis of periprosthetic joint infections (PJIs) can be very challenging, especially in patients with chronic PJI caused by low-virulence microorganisms. Serum parameters, such as serum C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR), are—among other diagnostic test methods—widely used to distinguish septic from aseptic failure after total hip or knee arthroplasty and are recommended by the AAOS in the preoperative setting. However, they are systemic parameters, and therefore, unspecific. Nevertheless, they may be the first and occasionally the only preoperative indication, especially when clinical symptoms are lacking. They are easy to obtain, cheap, and are available worldwide. In the last decade, different novel serum biomarkers (percentage of neutrophils, neutrophils to lymphocytes ratio, platelet count to mean platelet volume ratio, fibrinogen, D-Dimer, Il-6, PCT) were investigated to find a more specific and accurate serum parameter in the diagnosis of PJI. This article reviews the diagnostic value of established (serum CRP, ESR, WBC) and ‘novel’ serum inflammatory biomarkers (fibrinogen, D-dimer, interleukin-6 (IL-6), procalcitonin, percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), platelet count to mean platelet volume ratio (PC/mPV)) for the preoperative diagnosis of periprosthetic joint infections.
Factors Affecting the Initiation of a Shared Decision Making Program in Obstetric Practices

As healthcare systems progress toward initiatives that increase patient engagement, stakeholder hopes are that shared decision making (SDM) will become routine practice. Yet, there is limited empirical evidence to guide such SDM program implementations, particularly in obstetric practices. The first stage of any project implementation is the “initiation stage”, in which project leaders define a project’s purpose and stakeholders and structures are put in place to support the new initiative. Our study’s objective was to identify factors affecting the initiation stage of an SDM program implementation project for TOLAC, trial of labor after Cesarean. We conducted a multiple-case study of an SDM program implementation in three obstetric settings in Washington State. The research design and analysis were guided by implementation science frameworks and project management literature. Data sources included interviews with key informants from the State, SDM tool vendors, and three project sites, as well as implementation documents. The study results provide insight into how the identified project implementation factors provide an essential foundation for informing project planning, execution, and reflection/evaluation. In this study, the State’s decision aid certification program pressured the project sites to shape the project purpose and engage stakeholders that would meet immediate project requirements (specifically, state requirements). The study reveals that external demands may not be in perfect alignment with the internal necessities required for an SDM program’s long-term viability and sustainability. Findings may be used by implementers and researchers to model and strategize the early stages of SDM program implementation projects, particularly in the obstetric setting.
Investigating the Short-Term Effects of Cold Stress on Metabolite Responses and Metabolic Pathways in Inner-Mongolia Sanhe Cattle

Simple Summary Cold stress is a major environmental stressor affecting cattle performance in temperate regions, which causes impaired welfare and economic losses to cattle producers. The identification of biological mechanisms associated with cold stress response is paramount for developing effective mitigation strategies, such as genomic selection. In this study, we assessed the short-term effects of hyper-cold stress on metabolite responses and metabolic pathways in the serum of Inner-Mongolia Sanhe cattle. Moreover, 19 differential metabolites were found, mainly involved in amino acid metabolism. A further integration of metabolome results and gene expression highlighted the regulation of metabolic changes and related pathways in severe cold exposure, such as “aminoacyl-tRNA biosynthesis” and “valine, leucine, and isoleucine degradation”. In summary, we presented new insights on the short-term effects of severe cold stress as well as metabolites and metabolic pathways associated with cold stress response in Inner-Mongolia Sanhe cattle. Abstract Inner-Mongolia Sanhe cattle are well-adapted to low-temperature conditions, but the metabolic mechanisms underlying their climatic resilience are still unknown. Based on the 1H Nuclear Magnetic Resonance platform, 41 metabolites were identified and quantified in the serum of 10 heifers under thermal neutrality (5 °C), and subsequent exposure to hyper-cold temperature (−32 °C) for 3 h. Subsequently, 28 metabolites were pre-filtrated, and they provided better performance in multivariate analysis than that of using 41 metabolites. This indicated the need for pre-filtering of the metabolome data in a paired experimental design. In response to the cold exposure challenge, 19 metabolites associated with cold stress response were identified, mainly enriched in “aminoacyl-tRNA biosynthesis” and “valine, leucine, and isoleucine degradation”. A further integration of metabolome and gene expression highlighted the functional roles of the DLD (dihydrolipoamide dehydrogenase), WARS (tryptophanyl-tRNA synthetase), and RARS (arginyl-tRNA synthetase) genes in metabolic pathways of valine and leucine. Furthermore, the essential regulations of SLC30A6 (solute carrier family 30 (zinc transporter), member 6) in metabolic transportation for propionate, acetate, valine, and leucine under severe cold exposure were observed. Our findings presented a comprehensive characterization of the serum metabolome of Inner-Mongolia Sanhe cattle, and contributed to a better understanding of the crucial roles of regulations in metabolites and metabolic pathways during cold stress events in cattle.