Miracle-dz/UniFAR-FTUs huggingface dataset:
Tryptophan: From Diet to Cardiovascular Diseases

Cardiovascular disease (CVD) is one of the major causes of mortality worldwide. Inflammation is the underlying common mechanism involved in CVD. It has been recently related to amino acid metabolism, which acts as a critical regulator of innate and adaptive immune responses. Among different metabolites that have emerged as important regulators of immune and inflammatory responses, tryptophan (Trp) metabolites have been shown to play a pivotal role in CVD. Here, we provide an overview of the fundamental aspects of Trp metabolism and the interplay between the dysregulation of the main actors involved in Trp metabolism such as indoleamine 2, 3-dioxygenase 1 (IDO) and CVD, including atherosclerosis and myocardial infarction. IDO has a prominent and complex role. Its activity, impacting on several biological pathways, complicates our understanding of its function, particularly in CVD, where it is still under debate. The discrepancy of the observed IDO effects could be potentially explained by its specific cell and tissue contribution, encouraging further investigations regarding the role of this enzyme. Thus, improving our understanding of the function of Trp as well as its derived metabolites will help to move one step closer towards tailored therapies aiming to treat CVD.
Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses

Obesity is a chronic condition involving low-grade inflammation and increased oxidative stress; thus, obese and overweight people have lower values of serum bilirubin. Essentially, bilirubin is a potent endogenous antioxidant molecule with anti-inflammatory, immunomodulatory, antithrombotic, and endocrine properties. This review paper presents the interplay between obesity-related pathological processes and bilirubin, with a focus on adipose tissue and adipokines. We discuss potential strategies to mildly increase serum bilirubin levels in obese patients as an adjunctive therapeutic approach.
Diagnostic Effect of Consultation Referral from Gastroenterologists to Generalists in Patients with Undiagnosed Chronic Abdominal Pain: A Retrospective Study

This study aimed to investigate consultation outcomes from gastroenterologists to generalist physicians for the diagnostic workup of undiagnosed chronic abdominal pain. This was a single-center, retrospective, descriptive study. Patients were included who were ≥15 years old and consulted from the Department of Gastroenterology to the Department of Diagnostic Medicine, to establish a diagnosis for chronic abdominal pain, at the Dokkyo University Hospital from 1 April 2016 to 31 August 2020. We retrospectively reviewed the patients’ medical charts and extracted data. A total of 12 cases were included. Eight patients (66.7%) were diagnosed with and treated for functional gastrointestinal disorders (FGID) at the Department of Gastroenterology; their lack of improvement under treatment for FGID was the reason for their referral to the Department of Diagnostic Medicine for further examination. After this consultation, new possible diagnoses were generated for eight patients (66.7%). Six of the eight patients (75.0%) were diagnosed with abdominal wall pain (anterior cutaneous nerve entrapment syndrome, n = 3; myofascial pain, n = 1; falciform pain, n = 1; and herpes zoster non-herpeticus; n = 1). Consultation referral from gastroenterologists to generalists could generate new possible diagnoses in approximately 70% of patients with undiagnosed chronic abdominal pain.
The Evolution and Prognostic Role of Tumour-Infiltrating Lymphocytes and Peripheral Blood-Based Biomarkers in Inflammatory Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Simple Summary Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer (BC) in which higher levels of stromal tumour-infiltrating lymphocytes (sTIL) before neo-adjuvant chemotherapy (NACT) are associated with a better outcome. The role of sTIL in patients with residual disease (RD) after NACT is not clearly established. In this study, we showed that a high number of sTIL after NACT was associated with a worse outcome. Furthermore, we also demonstrated that sTIL decreased more during NACT in IBC compared to subtype-matched non-IBC patients (nIBC) treated with NACT. We also looked at the effect of NACT on some peripheral immune markers. Unlike the sTIL, we could not demonstrate a prognostic effect of these markers after NACT and their change was not significantly different between IBC and nIBC, indicating that the effect of NACT on the peripheral immune response seems to be similar in IBC and nIBC. Abstract Introduction: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer (BC) in which the (prognostic) role of stromal tumour-infiltrating lymphocytes (sTIL) and the peripheral circulating immune cells in patients with residual disease (RD) after neo-adjuvant chemotherapy (NACT) is not clearly established. Methodology: To describe the evolution of sTIL and some peripheral inflammation markers (Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio and Lymphocyte-to-monocyte ratio) after NACT in IBC, we retrospectively collected clinicopathological variables for 125 stage III IBC patients. sTILs were scored by three different researchers on an H&E slide of the mastectomy specimen. A cohort of subtype-matched non-IBC breast cancer patients (nIBC) treated with NACT was included for comparison. Results: There was no significant difference in the pre- and posttreatment sTIL scores between IBC and nIBC and in both groups the number of sTIL was significantly lower after NACT. However, the IBC phenotype did correlate with a stronger decrease of sTIL after NACT (OR: 0.25, 95% CI: 0.073–0.76, p = 0.018). The change in the peripheral immune markers was not significantly different between IBC and nIBC. After NACT, 75 patients had residual disease. In this group, a high number of sTIL before NACT (HR: 0.23, 95% CI: 0.05–1.02, p = 0.05) was prognostic for a longer OS, while a low number of sTIL after NACT (HR: 0.33, 95% CI: 0.11–0.98, p = 0.046) and a low residual cancer cellularity (HR: 0.20, 95% CI: 0.08–0.52, p < 0.001) was associated with a longer DFS. Conclusions: IBC is associated with a significantly stronger decrease of sTIL after NACT compared to nIBC. Furthermore, a high number of sTIL after NACT was associated with a worse prognosis in IBC.
The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.
Validity, Reliability and Sensitivity to Change of Three Consumer-Grade Activity Trackers in Controlled and Free-Living Conditions among Older Adults

Wrist-worn consumer-grade activity trackers are popular devices, developed mainly for personal use. This study aimed to explore the validity, reliability and sensitivity to change of movement behaviors metrics from three activity trackers (Polar Vantage M, Garmin Vivoactive 4s and Garmin Vivosport) in controlled and free-living conditions when worn by older adults. Participants (n = 28; 74 ± 5 years) underwent a videotaped laboratory protocol while wearing all three trackers. On a separate occasion, participants (n = 17 for each of the trackers) wore one (randomly assigned) tracker and a research-grade activity monitor ActiGraph wGT3X-BT simultaneously for six consecutive days. Both Garmin trackers showed excellent performance for step counts, with a mean absolute percentage error (MAPE) below 20% and intraclass correlation coefficient (ICC2,1) above 0.90 (p < 0.05). The MAPE for sleep time was within 10% for all the trackers tested, while it was far beyond 20% for all other movement behaviors metrics. The results suggested that all three trackers could be used for measuring sleep time with a high level of accuracy, and both Garmin trackers could also be used for step counts. All other output metrics should be used with caution. The results provided in this study could be used to guide choice on activity trackers aiming for different purposes—individual use, longitudinal monitoring or in clinical trial setting.
Recent Progress on Improving the Quality of Bran-Enriched Extruded Snacks

The incorporation of milling by-products, in particular bran, into starch-based extruded snacks allows manufacturers to address two consumer demands at once, i.e., those for goods that are more sustainably produced and of higher nutritional value. However, the higher fiber content in bran than in refined cereal flours poses a limit to the amount that can be included without compromising the quality of extruded snacks, which crucially depends on expansion. Thus, several studies have focused on the effect of bran on the physicochemical characteristics of extruded snacks, leading to the need to review the recent findings in this area. Opportunities, challenges, and potential solutions of bran-enriched snacks are addressed, and several current knowledge gaps are highlighted. Specifically, the first part of the review presents the effects of extrusion cooking on bran’s compositional aspects, focusing on structural changes and product quality. After summarizing the main quality traits of extruded snacks (e.g., expansion rate, bulk density, and textural attributes), the effects of bran enrichment on the physical and sensory characteristics of the final product are discussed. Finally, bran pre-treatments as well as processing optimization are discussed as approaches to improve the quality of bran-enriched snacks.
Double Mutant Analysis with the Large Flower Mutant, ohbana1, to Explore the Regulatory Network Controlling the Flower and Seed Sizes in Arabidopsis thaliana

Two growth processes, cell proliferation and expansion, determine plant species-specific organ sizes. A large flower mutant in Arabidopsis thaliana, ohbana1 (ohb1), was isolated from a mutant library. In the ohb1 flowers, post-mitotic cell expansion and endoreduplication of nuclear DNA were promoted. The whole-genome resequencing and genetic analysis results showed that the loss of function in MEDIATOR16 (MED16), a mediator complex subunit, was responsible for the large flower phenotypes exhibited by ohb1. A phenotypic analysis of the mutant alleles in MED16 and the double mutants created by crossing ohb1 with representative large flower mutants revealed that MED16 and MED25 share part of the negative petal size regulatory pathways. Furthermore, the double mutant analyses suggested that there were genetically independent pathways leading to cell size restrictions in the floral organs which were not related to the MED complex. Several double mutants also formed larger and heavier seeds than the wild type and single mutant plants, which indicated that MED16 was involved in seed size regulation. This study has revealed part of the size-regulatory network in flowers and seeds through analysis of the ohb1 mutant, and that the size-regulation pathways are partially different between floral organs and seeds.
Mechanical Properties and In Vitro Evaluation of Thermoplastic Polyurethane and Polylactic Acid Blend for Fabrication of 3D Filaments for Tracheal Tissue Engineering

Surgical reconstruction of extensive tracheal lesions is challenging. It requires a mechanically stable, biocompatible, and nontoxic material that gradually degrades. One of the possible solutions for overcoming the limitations of tracheal transplantation is a three-dimensional (3D) printed tracheal scaffold made of polymers. Polymer blending is one of the methods used to produce material for a trachea scaffold with tailored characteristics. The purpose of this study is to evaluate the mechanical and in vitro properties of a thermoplastic polyurethane (TPU) and polylactic acid (PLA) blend as a potential material for 3D printed tracheal scaffolds. Both materials were melt-blended using a single screw extruder. The morphologies (as well as the mechanical and thermal characteristics) were determined via scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, tensile test, and Differential Scanning calorimetry (DSC). The samples were also evaluated for their water absorption, in vitro biodegradability, and biocompatibility. It is demonstrated that, despite being not miscible, TPU and PLA are biocompatible, and their promising properties are suitable for future applications in tracheal tissue engineering.
Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives

Simple Summary Metastatic colorectal cancer (mCRC) accounts for relevant cancer-related morbidity and mortality. Novel investigations have reshaped the molecular makeup of mCRC, emphasizing a high degree of heterogeneity that can be leveraged to establish a new concept of biomarker-guided therapy. In contrast to the old-fashioned, “one-size-fits-all” therapeutic approach, within a precision oncology approach, a deeper molecular selection is indeed felt to improve the efficacy of targeted systemic treatments. Here, we review available treatment options in patients with refractory mCRC, who have already received chemotherapy regimens containing fluoropyrimidines, oxaliplatin, irinotecan, antiangiogenic agents, and, when indicated, epidermal growth factor receptor inhibitors. In addition, we examine those molecular pathways now included among the most promising areas of clinical research that will eventually drive innovative and more individualized treatment strategies. Abstract Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and dynamic complexity of CRC. On the other, such discoveries are leading to newer biomarker-driven strategies that add to existing anti-epidermal growth factor receptor (EGFR) and anti-angiogenic approaches. In addition, the availability of a wide molecular profiling has relevant implications for patient prognosis and treatment benefits. Here, we will review the molecular underpinnings and clinical data supporting novel targeted treatments under development for refractory mCRC harboring BRAF mutations, KRAS G12C mutations, HER2 amplification, and less common molecular alterations, such as the re-arrangements of NTRK, ALK, and ROS1. Additionally, we will discuss novel strategies driving the rechallenge of EGFR antibodies and the incorporation of newer anti-angiogenic agents in the therapeutic armamentarium.
Epigenetic Response of Yarrowia lipolytica to Stress: Tracking Methylation Level and Search for Methylation Patterns via Whole-Genome Sequencing

DNA methylation is a common, but not universal, epigenetic modification that plays an important role in multiple cellular processes. While definitely settled for numerous plant, mammalian, and bacterial species, the genome methylation in different fungal species, including widely studied and industrially-relevant yeast species, Yarrowia lipolytica, is still a matter of debate. In this paper, we report a differential DNA methylation level in the genome of Y. lipolytica subjected to sequential subculturing and to heat stress conditions. To this end, we adopted repeated batch bioreactor cultivations of Y. lipolytica subjected to thermal stress in specific time intervals. To analyze the variation in DNA methylation between stressed and control cultures, we (a) quantified the global DNA methylation status using an immuno-assay, and (b) studied DNA methylation patterns through whole-genome sequencing. Primarily, we demonstrated that 5 mC modification can be detected using a commercial immuno-assay, and that the modifications are present in Y. lipolytica’s genome at ~0.5% 5 mC frequency. On the other hand, we did not observe any changes in the epigenetic response of Y. lipolytica to heat shock (HS) treatment. Interestingly, we identified a general phenomenon of decreased 5 mC level in Y. lipolytica’s genome in the stationary phase of growth, when compared to a late-exponential epigenome. While this study provides an insight into the subculturing stress response and adaptation to the stress at epigenetic level by Y. lipolytica, it also leaves an open question of inability to detect any genomic DNA methylation level (either in CpG context or context-less) through whole-genome sequencing. The results of ONT sequencing, suggesting that 5 mC modification is either rare or non-existent in Y. lipolytica genome, are contradicted with the results of the immunoassay.
Analysis of Shape Memory Behavior and Mechanical Properties of Shape Memory Polymer Composites Using Thermal Conductive Fillers

Shape memory polymers (SMPs) are attracting attention for their use in wearable displays and biomedical materials due to their good biocompatibility and excellent moldability. SMPs also have the advantage of being lightweight with excellent shape recovery due to their low density. However, they have not yet been applied to a wide range of engineering fields because of their inferior physical properties as compared to those of shape memory alloys (SMAs). In this study, we attempt to find optimized shape memory polymer composites. We also investigate the shape memory performance and physical properties according to the filler type and amount of hardener. The shape memory composite was manufactured by adding nanocarbon materials of graphite and non-carbon additives of Cu. The shape-recovery mechanism was compared, according to the type and content of the filler. The shape fixation and recovery properties were analyzed, and the physical properties of the shape recovery composite were obtained through mechanical strength, thermal conductivity and differential scanning calorimetry analysis.
Modeling of Self-Assembled Peptide Nanotubes and Determination of Their Chirality Sign Based on Dipole Moment Calculations

The chirality quantification is of great importance in structural biology, where the differences in proteins twisting can provide essentially different physiological effects. However, this aspect of the chirality is still poorly studied for helix-like supramolecular structures. In this work, a method for chirality quantification based on the calculation of scalar triple products of dipole moments is suggested. As a model structure, self-assembled nanotubes of diphenylalanine (FF) made of L- and D-enantiomers were considered. The dipole moments of FF molecules were calculated using semi-empirical quantum-chemical method PM3 and the Amber force field method. The obtained results do not depend on the used simulation and calculation method, and show that the D-FF nanotubes are twisted tighter than L-FF. Moreover, the type of chirality of the helix-like nanotube is opposite to that of the initial individual molecule that is in line with the chirality alternation rule general for different levels of hierarchical organization of molecular systems. The proposed method can be applied to study other helix-like supramolecular structures.
Methylglyoxal Adducts Levels in Blood Measured on Dried Spot by Portable Near-Infrared Spectroscopy

The altered glucose metabolism characterising cancer cells determines an increased amount of methylglyoxal in their secretome. Previous studies have demonstrated that the methylglyoxal, in turn, modifies the protonation state (PS) of soluble proteins contained in the secretomes of cultivated circulating tumour cells (CTCs). In this study, we describe a method to assess the content of methylglyoxal adducts (MAs) in the secretome by near-infrared (NIR) portable handheld spectroscopy and the extreme learning machine (ELM) algorithm. By measuring the vibration absorption functional groups containing hydrogen, such as C-H, O-H and N-H, NIR generates specific spectra. These spectra reflect alterations of the energy frequency of a sample bringing information about its MAs concentration levels. The algorithm deciphers the information encoded in the spectra and yields a quantitative estimate of the concentration of MAs in the sample. This procedure was used for the comparative analysis of different biological fluids extracted from patients suspected of having cancer (secretome, plasma, serum, interstitial fluid and whole blood) measured directly on the solute left on a surface upon a sample-drop cast and evaporation, without any sample pretreatment. Qualitative and quantitative regression models were built and tested to characterise the different levels of MAs by ELM. The final model we selected was able to automatically segregate tumour from non-tumour patients. The method is simple, rapid and repeatable; moreover, it can be integrated in portable electronic devices for point-of-care and remote testing of patients.
Comparison of Quantification Methods to Estimate Farm-Level Usage of Antimicrobials in Medicated Feed in Dairy Farms from Québec, Canada

Monitoring antimicrobial usage (AMU) in dairy cattle is becoming common in a growing number of countries, with the ultimate goal to improve practices, reduce the development of antimicrobial resistance, and protect human health. However, antimicrobials delivered as feed additives can be missed by some of the quantification methods usually implemented. Our objective was to compare three methods of quantification of in-feed AMU in Québec dairy herds. We recruited 101 dairy producers for one year in the Québec province. Quantities of antimicrobials were calculated by farm from: (1) feed mills invoices (reference method); (2) veterinary prescriptions; and (3) information collected during an in-person interview of each producer. We standardized AMU rates in kilograms per 100 cow-years and compared the reference method to both alternative methods using concordance correlation coefficients and Bland–Altman plots. Antimicrobial usage was well estimated by veterinary prescriptions (concordance correlation coefficient (CCC) = 0.66) or by the approximation using producer’s data (CCC = 0.73) when compared with actual deliveries by feed mills. Users of medically important antimicrobials for human medicine (less than 10% of the farms) were easily identified using veterinary prescriptions. Given that veterinary prescriptions were mostly electronic (90%), this method could be integrated as part of a monitoring system in Québec.