Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrient Properties and Nuclear Magnetic Resonance-Based Metabonomic Analysis of Macrofungi

Many delicious and nutritional macrofungi are widely distributed and used in East Asian regions, considered as edible and medicinal foods. In this study, 11 species of dried and fresh, edible and medicinal macrofungi, Ganoderma amboinense, Agaricus subrufescens, Dictyophora indusiata, Pleurotus sajor-caju, Pleurotus ostreatus, Pleurotus geesteranu, Hericium erinaceus, Stropharia rugosoannulata, Pleurotus sapidus, Antrodia camphorata, and Lentinus edodes (Berk.) Sing, were investigated to determine the content of their nutritional components, including proteins, fat, carbohydrates, trace minerals, coarse cellulose, vitamins, and amino acids. The amino acid patterns and similarity of macrofungi were distinguished through principal component analysis and hierarchical cluster analyses, respectively. A total of 103 metabolic small molecules of macrofungi were identified by nuclear magnetic resonance spectroscopy and were aggregated by heatmap. Moreover, the macrofungi were classified by principal component analysis based on these metabolites. The results show that carbohydrates and proteins are two main components, as well as the nutritional ingredients, that differ among various species and varied between fresh and dried macrofungi. The amino acid patterns in L. edodes and A. subrufescens were different compared with that of the other tested mushrooms.
Fatty acid-binding proteins: functional understanding and diagnostic implications.

PURPOSE OF REVIEW Fatty acid-binding proteins (FABPs) are a family of small, abundant proteins with highly tissue-specific expression patterns whose different functions remain incompletely understood. The purpose of this review is to summarize recent findings regarding FABP functions and mechanisms of action, including their potential utilization as serum markers of tissue-specific metabolic diseases. RECENT FINDINGS FABPs are important not only in their tissues of origin but also appear to influence the metabolism and function of tissues distal to their sites of expression. This may be secondary to metabolic changes in their primary tissues, and/or a result of FABP secretion from these tissues leading to effects on distal sites. Their levels in the circulation are increasingly explored as potential biomarkers for tissue-specific disease prognosis and progression. SUMMARY The nine fatty acid-binding members of the FABP family have unique tissue-specific functions and important secondary effects on tissues in which they are not expressed. For many of the FABPs, circulating levels may be indicative of disease processes related to their primary tissues, and may influence physiological function in distal tissues.
Clinical analysis of pre-existing diabetes mellitus and dipeptidyl peptidase-4 inhibitors in patients with remitting seronegative symmetrical synovitis and pitting edema syndrome

Abstract Objectives: To analyze the association among remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, diabetes mellitus (DM), and antidiabetic drugs. Methods: We retrospectively analyzed the clinical and serologic manifestations of patients who had RS3PE syndrome with and without pre-existing DM. Then we performed a subanalysis in which patients with pre-existing DM were classified into two groups according to whether they were or were not taking a dipeptidyl peptidase 4 inhibitor (DPP4i), an antidiabetic drug that was suggested to have an association with the pathogenesis of RS3PE syndrome. Results: Pre-existing DM was found in 13 (35.1%) of 37 patients with RS3PE syndrome. No significant differences in age, gender, physical manifestations, and laboratory findings were observed between the patients with DM and those without DM. DPP4i had been administered to 6 of 13 patients with RS3PE and pre-existing DM. We observed no significant differences in manifestations of RS3PE syndrome before treatment; however, one relapse occurred in a patient with poorly controlled DM who had been continuing DPP4i therapy. Conclusion: This study revealed no evidence suggesting an association among RS3PE syndrome, DM, and antidiabetic drugs. DPP4i would be safe for use by most of patients with RS3PE syndrome. However, elderly patients and patients with poorly controlled DM might require careful observation.
Tracking Photodynamic- and Chemotherapy-Induced Redox-State Perturbations in 3D Culture Models of Pancreatic Cancer: A Tool for Identifying Therapy-Induced Metabolic Changes

The metabolic plasticity of cancer cells is considered a highly advantageous phenotype that is crucial for disease progression and acquisition of treatment resistance. A better understanding of cancer metabolism and its adaptability after treatments is vital to develop more effective therapies. To screen novel therapies and combination regimens, three-dimensional (3D) culture models of cancers are attractive platforms as they recapitulate key features of cancer. By applying non-perturbative intensity-based redox imaging combined with high-throughput image analysis, we demonstrated metabolic heterogeneity in various 3D culture models of pancreatic cancer. Photodynamic therapy and oxaliplatin chemotherapy, two cancer treatments with relevance to pancreatic cancer, induced perturbations in redox state in 3D microtumor cultures of pancreatic cancer. In an orthotopic mouse model of pancreatic cancer, a similar disruption in redox homeostasis was observed on ex vivo slices following photodynamic therapy in vivo. Taken together, redox imaging on cancer tissues combined with high-throughput analysis can elucidate dynamic spatiotemporal changes in metabolism following treatment, which will benefit the design of new metabolism-targeted therapeutic approaches.
Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis.

INTRODUCTION Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non-clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials. MATERIALS AND METHODS We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta-analysis of proportions for ORR and disease control rate (DCR). RESULTS Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%-37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%-23.7%) who achieved a complete remission. At a median follow-up of 24.5 monoths (95% CI, 17.7-32.6), median PFS was 4.9 monoths (95% CI, 3.53-10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment-related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD-1/PD-L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%-26.4%) and 53.4% (95% CI, 44.2%-62.5%). CONCLUSION Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted. IMPLICATIONS FOR PRACTICE This article reports on the clinical activity and safety of immune checkpoint inhibitors in non-clear cell kidney cancer. The retrospective data with the meta-analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.
Association between hearing loss and hereditary ATTR amyloidosis

Abstract Background: Hereditary transthyretin (TTR) related amyloidosis (ATTRv) is a life-threatening condition, which can potentially affect all organs. The objective was to identify the hearing status of patients with cardiac ATTRv and describe their audiological pattern. Methods: Nineteen patients with confirmed diagnosis of ATTRv cardiac amyloidosis (CA) underwent otoscopy and audiological tests, including pure tone and speech audiometry. Results: 74% were male, with a mean age of 72 ± 1.8 years. The main mutations were Val122Ile (n = 7) and Val30Met (n = 6). Objective hearing loss was detected in 17 patients (89%), whereas only 37% complained of hearing loss. ATTRv patients presented a different audiometric profile compared to patients of the same age with presbycusis: a higher prevalence and worse hearing thresholds compared to age-related expectations (ISO). Hearing loss affected all frequencies with, unexpectedly, mixed or conductive hearing loss (35%). According to the type of mutation, there was an increased rate of sensorineural or mixed/conductive hearing loss. Conclusions: the present study indicates that hearing loss is more prevalent and worse in patients with ATTRv amyloidosis than in the general population, while mostly clinically under-estimated. It suggests that ATTRv deposits could infiltrate the various anatomical structures of the inner and mild ear.
Biotechnology and Bioengineering

Funding information Air Force Office of Scientific Research, Grant/ Award Number: FA9550‐18‐1‐0012; National Science Foundation‐Division of Chemical, Bioengineering, Environmental, and Transport Systems, Grant/Award Number: 1403860 Abstract The use of X‐ray radiation in radiotherapy is a common treatment for many cancers. Despite several scientific advances, determination of radiation delivered to the patient remains a challenge due to the inherent limitations of existing dosimeters including fabrication and operation. Here, we describe a colorimetric nanosensor that exhibits unique changes in color as a function of therapeutically relevant radiation dose (3–15Gy). The nanosensor is formulated using a gold salt and maltose‐binding protein as a templating agent, which upon exposure to ionizing radiation is converted to gold nanoparticles. The formation of gold nanoparticles from colorless precursor salts renders a change in color that can be observed visually. The dose‐dependent multicolored response was quantified through a simple ultraviolet–visible spectrophotometer and the peak shift associated with the different colored dispersions was used as a quantitative indicator of therapeutically relevant radiation doses. The ease of fabrication, visual color changes upon exposure to ionizing radiation, and quantitative read‐out demonstrates the potential of protein‐facilitated biomineralization approaches to promote the development of next‐generation detectors for ionizing radiation.
Alcohol, tobacco and cannabis use are associated with job loss at follow-up: Findings from the CONSTANCES cohort

Background Substance use is more prevalent among unemployed subjects compared to employed ones. However, quantifying the risk subsequent of job loss at short-term according to substance use remains underexplored as well as examining if this association persist across various sociodemographic and occupational positions previously linked to job loss. We examined this issue prospectively for alcohol, tobacco, cannabis use and their combination, among a large population-based sample of men and women, while taking into account age, gender, overall health status and depressive symptoms. Methods From the French population-based CONSTANCES cohort, 18,879 working participants were included between 2012 and 2016. At baseline, alcohol use disorder risk according to the Alcohol Use Disorders Identification Test (mild, dangerous, problematic or dependence), tobacco (non-smoker, former smoker, 1–9, 10–19, >19 cigarettes/day) and cannabis use (never, not in past year, less than once a month, once a month or more) were assessed. Employment status at one-year (working versus not working) was the dependent variable. Logistic regressions provided Odds Ratios(OR(95%CI)) of job loss at one-year, adjusting for age, gender, self-reported health and depressive state (measured with the Center of Epidemiologic Studies Depression scale). Stratified analyses were performed for education, occupational grade, household income, job stress (measured with the Effort-Reward Imbalance), type of job contract, type of work time and history of unemployment. In sensitivity analyses, employment status over a three-year follow-up was used as dependent variable. Results Alcohol, tobacco and cannabis use were associated with job loss, from the second to the highest category: 1.46(95%CI:1.23–1.73) to 1.92(95%CI:1.34–2.75), 1.26(95%CI:1.09–1.46) to 1.78(95%CI:1.26–2.54) and 1.45(95%CI:1.27–1.66) to 2.68(95%CI:2.10–3.42), respectively, and with dose-dependent relationships (all p for trend <0.001). When introduced simultaneously, associations remained significant for the three substances without any between-substance interactions. Associations remained significant across almost all stratifications and over a three-year follow-up as well as after adjustment for all the sociodemographic and occupational factors. Conclusions Alcohol, tobacco and cannabis use were independently associated with job loss at short-term, with dose-dependent relationships. This knowledge will help refining information and prevention strategies. Importantly, even moderate levels of alcohol, tobacco or cannabis use are associated with job loss at short-term and all sociodemographic and occupational positions are potentially concerned.
Tyrosinase Inhibition Antioxidant Effect and Cytotoxicity Studies of the Extracts of Cudrania tricuspidata Fruit Standardized in Chlorogenic Acid

In the present study, various extracts of C. tricuspidata fruit were prepared with varying ethanol contents and evaluated for their biomarker and biological properties. The 80% ethanolic extract showed the best tyrosinase inhibitory activity, while the 100% ethanolic extract showed the best total phenolics and flavonoids contents. The HPLC method was applied to analyze the chlorogenic acid in C. tricuspidata fruit extracts. The results suggest that the observed antioxidant and tyrosinase inhibitory activity of C. tricuspidata fruit extract could partially be attributed to the presence of marker compounds in the extract. In this study, we present an analytical method for standardization and optimization of C. tricuspidata fruit preparations. Further investigations are warranted to confirm the in vivo pharmacological activity of C. tricuspidata fruit extract and its active constituents and assess the safe use of the plant for the potential development of the extract as a skin depigmentation agent.
Polysubstance Use among Patients Enrolling in Methadone Maintenance Treatment Program in a Vietnam Province with Drug-Driven HIV Epidemic

Methadone maintenance treatment (MMT) has been scaled up significantly in recent years. This study aimed to investigate the pattern of polysubstance use in 395 MMT patients and its contextualized associated factors. A cross-sectional study was performed in three outpatient MMT clinics in Nam Dinh Province. Multivariate Poisson regression was used to identify factors associated with polysubstance use status. The mean MMT duration and the current MMT dose was 3.3 years and 69.2 mg, respectively. Among participants, 24.8% reported daily alcohol use, 68.6% smoked regularly, and 6% used illicit drugs. Peer pressure and MMT suboptimal adherence were found to associate with continual usage of drugs (47.8%). Participants who lived with a spouse/partner, were self-employed, and smoked were more likely to drink alcohol. Those who drink were also more likely to smoke, and vice versa. Recommendations for policymakers include community-based education and promotional programs aiming to decrease substance usage in the community as well as encouraging and supporting the private health sector in establishing private MMT services and clinics. Further longitudinal studies on polysubstance usage among MMT patients should also be conducted.
Hybrid Coronary Artery Revascularization: A Review and Current Evidence

Objective The role of hybrid coronary revascularization (HCR), which utilizes the combination of minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery and percutaneous coronary intervention (PCI) of non-left anterior descending vessels to treat multivessel coronary artery disease, is expanding. We set out to provide a review of this technology. Methods We conducted a retrospective analysis of all minimally invasive hybrid operations performed at our institution from September 2004 to December 2018. An effective analysis comparing patients undergoing HCR vs off-pump or on-pump surgical coronary artery revascularization was undertaken using an adjusted analysis with inverse-probability weighting based on the propensity score. Outcomes that were assessed include death, myocardial infarction, stroke, atrial fibrillation, renal failure, requirement of blood transfusion, conversion to open procedure (in the hybrid group), length of stay in intensive care unit, and total length of stay in hospital. Intention-to-treat analysis was performed. An up-to-date literature review of HCR complements this study. Results Since 2004 a total of 191 consecutive patients (61.4±11.1 years; 142 males and 49 females) underwent HCR (robotic-assisted coronary artery bypass graft of the left internal thoracic artery to the left anterior descending coronary artery (LAD) and PCI of a non-LAD vessel) in a single- or double-stage fashion. Successful HCR occurred in 183 of the 191 patients (8 patients required intraoperative conversion to conventional coronary bypass). From our comparative analysis and literature review we found no significant difference between HCR and coronary artery bypass grafting groups with respect to in-hospital and 1-year follow-up. Conclusions Current evidences suggest that HCR is a feasible, safe, and effective coronary artery revascularization strategy in selected patients with multivessel coronary artery disease.
Assessing pathological changes within the nucleus ambiguus of horses with recurrent laryngeal neuropathy: An extreme, length‐dependent axonopathy

Equine recurrent laryngeal neuropathy (RLN) is a naturally occurring model of length‐dependent axonopathy characterized by asymmetrical degeneration of recurrent laryngeal nerve axons (RLn). Distal RLn degeneration is marked, but it is unclear whether degeneration extends to include cell bodies (consistent with a neuronopathy).
Association between plasma diacetylspermine and tumor spermine synthase with outcome in triple negative breast cancer.

BACKGROUND MYC is an oncogenic driver of development and progression in triple-negative breast cancer (TNBC). Ornithine decarboxylase, the rate-limiting enzyme in polyamine metabolism, is a transcriptional target of MYC. We therefore hypothesized that a plasma polyamine signature may be predictive of TNBC development and progression. METHODS Using liquid chromatography mass spectrometry, polyamine levels were determined in plasma samples from newly diagnosed patients with TNBC (n = 87) and cancer-free controls (n = 115). Findings were validated in plasma samples from an independent prospective cohort of 54 TNBC, 55 ER-/PR-/HER2+, and 73 ER+ cases, and 30 cancer-free controls. Gene expression data and clinical data for 921 and 2359 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA) repository and the Oncomine database, respectively. Relationships between plasma diacetylspermine (DAS) and tumor spermine synthase (SMS) mRNA expression with metastasis free survival and overall survival were determined using Cox proportional hazard models; Fisher's exact tests were used to assess risk of distant metastasis in relation to tumor SMS mRNA expression. RESULTS An increase in plasma DAS, a catabolic product of spermine mediated through SMS, was observed in the TNBC subtype of breast cancer. Plasma levels of DAS in TNBC associated with increased risk of metastasis (plasma DAS value ≥ 1.16 HR= 3.06, 95% CI = 1.15-8.13, 2-sided P = .03). SMS mRNA expression in TNBC tumor tissue was also found to be predictive of poor overall survival (top 25th percentile HR = 2.06, 95% CI = 1.04-4.08, 1-sided P= .04) and increased risk of distant metastasis in TNBC (comparison of lowest SMS quartile (reference) to highest SMS quartile Relative Risk= 1.90, 95% CI = 0.97-4.06, 1-sided Fisher's exact test P=. 03). CONCLUSION Metabolomic profiling identified plasma DAS as a predictive marker for TNBC progression and metastasis.
Lifetime Risk of Lower‐Extremity Peripheral Artery Disease Defined by Ankle‐Brachial Index in the United States

Background There are no available lifetime risk estimates of lower‐extremity peripheral artery disease (PAD). Methods and Results Using data from 6 US community‐based cohorts and the vital statistics, we estimated the prevalence and incidence of PAD, defined as an ankle‐brachial index < 0.90, at each year of age from birth to 80 years for white, black, and Hispanic men and women. Then, we used Markov Monte Carlo simulations in a simulated cohort of 100 000 individuals to estimate lifetime risk of PAD. On the basis of odds ratios of PAD for traditional atherosclerotic risk factors (eg, diabetes mellitus and smoking), we developed a calculator providing residual lifetime risk of PAD. In an 80‐year horizon, lifetime risks of PAD were 30.0% in black men and 27.6% in black women, but ≈19% in white men and women and ≈22% in Hispanic men and women. From another perspective, 9% of blacks were estimated to develop PAD by 60 years of age, while the same proportion was seen at ≈70 years for whites and Hispanics. The residual lifetime risk within the same race/ethnicity varied by 3.5‐ to 5‐fold according to risk factors (eg, residual lifetime risk in 45‐year‐old black men was 19.9% when current smoking, diabetes mellitus, and history of cardiovascular disease were absent versus 70.4% when all were present). Conclusions In the United States, ≈30% of blacks are estimated to develop PAD during their lifetime, whereas the corresponding estimate is ≈20% for whites and Hispanics. The residual lifetime risk within the same race/ethnicity substantially varies according to traditional risk factors.
Improvements of two criteria for multiaxial fatigue limit evaluation

The paper describes revisions of two different criteria intended for fatigue limit evaluation under multiaxial loading. The first revision concerns full derivation of material parameters to the criterion published recently by Ninic and by Papuga in different variants. The criterion is also tuned for the best possible output for load cases including mean loads. The second revision is a correction of the material parameters derivation of Papuga PI criterion. Both criteria are tested on a large data set of 407 experiments retrieved from FatLim database.