Miracle-dz/UniFAR-FTUs huggingface dataset:
Second Primary Tumors in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience

Background and Objectives: In this study, we investigated the frequency and type of second primary malignant tumors (SPMTs) accompanying gastrointestinal stromal tumors (GISTs), patient and tumor characteristics, and follow-up and survival data. Materials and Methods: We included 20 patients with SPMTs from a total of 103 patients with GISTs in a single center in Turkey. At the time of GIST diagnosis, patient age, sex, presentation symptoms, localization, pathological features of the tumor, stage, recurrence risk scoring for localized disease, treatments received, time of SPMT association, follow-up times, and survival analysis were recorded for each patient. Localization, histopathology, and stage of SPMT accompanying GISTs were also recorded accordingly. Results: SPMT was detected in 19.4% of patients with GISTs. Of the patients, 50% were men and 50% were women. The mean age at the time of diagnosis of GIST was 63.8 ± 10.81 years (range: 39–77 years). Of the GISTs, 60% were localized in the stomach, 25% in the small intestine, and 70% were at low risk. Of the SPMTs, 60% were in the gastrointestinal system. SPMTs were diagnosed as synchronous with GISTs in 50% of the patients. The mean follow-up period of the patients from the diagnosis of GIST was 45.6 (0.43–129.6) months. When the data were finalized, 5% died due to GIST, 35% died due to SPMT, and 15% died due to non-disease-related causes. Conclusions: SPMT was detected in 19.4% of patients with GISTs. GISTs were frequently located in the stomach, and most of them were at low risk. The most common SPMTs were gastrointestinal system tumors, and their coexistence was found to be synchronous. Most patients died due to SPMT during follow-up.
Synthesis of Fe3O4 Nanoparticles Using Controlled Ammonia Vapor Diffusion under Ultrasonic Irradiation

Fe3O4 nanoparticles were synthesized for the first time via an ammonia vapor diffusion process under ultrasonic irradiation. The possible ultrasound mechanism and the process of ammonia diffusion and reaction has been deduced. Influences of experiment parameters such as reaction time, temperature on the morphology, and size of products were also investigated in detail. Morphology and magnetic properties of products were carefully studied by Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), Scanning electron microscopes (SEM), and vibrating sample magnetometer (VSM). The synthesized Fe3O4 nanoparticles possess superparamagnetic properties at room temperature, and the saturation magnetization is 70.5 emu/g.
Capillary Electrophoresis Mass Spectrometry-Based Metabolomics of Plasma Samples from Healthy Subjects in a Cross-Sectional Japanese Population Study

For large-scale metabolomics, such as in cohort studies, normalization protocols using quality control (QC) samples have been established when using data from gas chromatography and liquid chromatography coupled to mass spectrometry. However, normalization protocols have not been established for capillary electrophoresis–mass spectrometry metabolomics. In this study, we performed metabolome analysis of 314 human plasma samples using capillary electrophoresis–mass spectrometry. QC samples were analyzed every 10 samples. The results of principal component analysis for the metabolome data from only the QC samples showed variations caused by capillary replacement in the first principal component score and linear variation with continuous measurement in the second principal component score. Correlation analysis between diagnostic blood tests and plasma metabolites normalized by the QC samples was performed for samples from 188 healthy subjects who participated in a Japanese population study. Five highly correlated pairs were identified, including two previously unidentified pairs in normal healthy subjects of blood urea nitrogen and guanidinosuccinic acid, and gamma-glutamyl transferase and cysteine glutathione disulfide. These results confirmed the validity of normalization protocols in capillary electrophoresis–mass spectrometry using large-scale metabolomics and comprehensive analysis.
Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.
Toward Resource Recovery from Wastewater: Extraction of Phosphorus from Digested Sludge Using a Hybrid Forward Osmosis–Membrane Distillation Process

We demonstrate the simultaneous extraction of phosphorus and clean water from digested sludge centrate using a forward osmosis (FO)–membrane distillation (MD) hybrid process. In this FO–MD hybrid process, FO concentrates orthophosphate and ammonium for subsequent phosphorus recovery in the form of struvite (MgNH4PO4·6H2O), while MD is used to recover the draw solution and extract clean water from the digested sludge centrate. A decline in water flux was observed during the FO process, but fouling was largely reversible after a brief, simple membrane flushing using deionized water. The FO process also provides an effective pretreatment capacity to the subsequent MD process, which exhibited stable water flux. The use of MgCl2 as the draw solute for the FO process is another novel aspect of the system. The reverse salt flux of magnesium to the concentrated digested sludge across the FO membrane and the diffusion of protons away from the digested sludge create favorable conditions for the formation of struvit.
Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function

To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study, we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5−/− zebrafish had smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post-fertilization, loss of rod and cone opsins were observed in zebrafish exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function and loss of visual photoreceptor pigments. Abnormal levels of RPE65 together with a reduced c-wave amplitude indicate a dysfunctional RPE. The retinal phenotype in Exoc5−/− mice was present at 20 weeks, but was more pronounced at 27 weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. Together, these data suggest that exocyst-mediated signaling in the RPE is required for RPE structure and function, indirectly leading to photoreceptor degeneration.
Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.
PPARgamma: A Potential Intrinsic and Extrinsic Molecular Target for Breast Cancer Therapy

Over the last decades, the breast tumor microenvironment (TME) has been increasingly recognized as a key player in tumor development and progression and as a promising prognostic and therapeutic target for breast cancer patients. The breast TME, representing a complex network of cellular signaling—deriving from different stromal cell types as well as extracellular matrix components, extracellular vesicles, and soluble growth factors—establishes a crosstalk with cancer cells sustaining tumor progression. A significant emphasis derives from the tumor surrounding inflammation responsible for the failure of the immune system to effectively restrain breast cancer growth. Thus, effective therapeutic strategies require a deeper understanding of the interplay between tumor and stroma, aimed at targeting both the intrinsic neoplastic cells and the extrinsic surrounding stroma. In this scenario, peroxisome proliferator-activated receptor (PPAR) γ, primarily known as a metabolic regulator, emerged as a potential target for breast cancer treatment since it functions in breast cancer cells and several components of the breast TME. In particular, the activation of PPARγ by natural and synthetic ligands inhibits breast cancer cell growth, motility, and invasiveness. Moreover, activated PPARγ may educate altered stromal cells, counteracting the pro-inflammatory milieu that drive breast cancer progression. Interestingly, using Kaplan–Meier survival curves, PPARγ also emerges as a prognostically favorable factor in breast cancer patients. In this perspective, we briefly discuss the mechanisms by which PPARγ is implicated in tumor biology as well as in the complex regulatory networks within the breast TME. This may help to profile approaches that provide a simultaneous inhibition of epithelial cells and TME components, offering a more efficient way to treat breast cancer.
Identification and Validation of Reference Genes for Gene Expression Analysis in Schima superba

Real-time quantitative PCR (RT-qPCR) is a reliable and high-throughput technique for gene expression studies, but its accuracy depends on the expression stability of reference genes. Schima superba is a fast-growing timber species with strong resistance. However, thus far, reliable reference gene identifications have not been reported in S. superba. In this study, 19 candidate reference genes were selected and evaluated for their expression stability in different tissues of S. superba. Three software programs (geNorm, NormFinder, and BestKeeper) were used to evaluate the reference gene transcript stabilities, and comprehensive stability ranking was generated by the geometric mean method. Our results show that SsuACT was the most stable reference gene and that SsuACT + SsuRIB was the best reference gene combination for different tissues. Finally, the stable and less stable reference genes were verified using SsuSND1 expression in different tissues. To our knowledge, this is the first report to verify appropriate reference genes for normalizing gene expression in S. superba for different tissues, which will facilitate the future elucidation of gene regulations in this species and useful references for relative species.
Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism.
Contradictory Effect of Coronary Collateral Circulation on Regional Myocardial Perfusion That Assessed by Quantitative Myocardial Perfusion Scintigraphy

Background Previous studies showed conflicting results about the contribution of coronary collateral circulation (CCC) to myocardial perfusion and function. The aim of this study was to investigate these contradictory problems by gated myocardial perfusion scintigraphy (gated MPS) for the first time. Methods The current cohort was retrospectively selected among patients who underwent gated MPS and coronary angiography within 2 months. Two different groups including 96 patients were assessed by gated MPS to detect the understanding of the miscellaneous effect of CCC on myocardial perfusion. Group 1 consisted of those who had collateral arteries that were not-well-developed (Rentrop grade 0 - 1) (n = 58), while group 2 consisted of those who had collateral arteries that were well-developed (Rentrop grade 2 - 3) (n = 38). Results There was no statistically significant difference between groups 1 and 2 in terms of perfusion and functional parameters obtained from gated MPS. Furthermore, no statistically significant difference was found in the phase analysis parameters which is a novel technique to evaluate left ventricular synchronization. On the other hand the left ventricular mass index values were high and quite close to the statistically significant value (P = 0.059) in group 2. Conclusions The current results that obtained by using the gated MPS technique for the first time in the evaluation of CCC showed that the well-developed collateral circulation has a positive effect on myocardial perfusion and function, but this effect was not statistically significant. Results need to be supported by large scale of patients’ size.
Green Extraction Techniques for Obtaining Bioactive Compounds from Mandarin Peel (Citrus unshiu var. Kuno): Phytochemical Analysis and Process Optimization

In this study, an efficient utilization and valorization of mandarin peel (Citrus unshiu Marc. var. Kuno) was investigated using innovative and green extraction techniques. The first step of this study included the extraction and analysis of the volatile compounds by performing a supercritical CO2 (SC-CO2) extraction under different operating pressure conditions (100 and 300 bar). The analysis of volatile compounds of the obtained extracts was conducted by gas chromatography-mass spectrometry (GC-MS), and limonene was found to be the dominant volatile component (13.16% at 100 bar; 30.65% at 300 bar). After SC-CO2 treatment, the exhausted citrus peel waste enriched with bioactive compounds was subjected to subcritical water extraction (SWE) in a wide temperature range (130–220 °C) using different solvent-solid ratio (10–30 mL/g) in time periods from 5 to 15 min, in order to obtain bioflavonoids. Identification and quantification of present bioflavonoids was conducted by high-performance liquid chromatography with a with a diode array detector (HPLC), and hesperidin (0.16–15.07 mg/g) was determined as the most abundant flavanon in mandarin peel with other polyphenolic compounds that were possible by-products of thermal degradation. At higher temperatures, the presence of 5-hydroxymethylfurfural (5-HMF) and chlorogenic acid were detected. Antiradical activity and total phenolic content in the extracts were determined using spectrophotometric methods, while the process optimization was performed by response surface methodology (RSM).
FIRST EXAMPLE OF LONG DISTANCE STEREOCONTROLLED SYNTHESIS IN 1-AZA-3,7- DIOXABICYCLO[3.3.0.]OCTANE SERIES

The diastereoselective synthesis of (lÄ*J'5*,2S*,2'Ä*>55*,5'Ä*,8Ä*,8'5*)-bis-l,4-{l-aza-5-methyl-8-(4-nitrophenyl)-3,7dioxabicyclo[3.3. 0]octane-2-yl}benzene is described as the first example of a long distance stereocontrolled synthesis of this type of structure. The thermodynamic control of the reaction together with complete NMR evidence to support the stereochemistry of this compound are discussed. INTRODUCTION The l-aza-3,7-dioxabicyclo[3.3. 0]octane heterocyclic saturated system A (Scheme 1) as an easily available analogue of the core alkaloid pyrolizidine Β is known since de pioneering works of Senkus (1,2), Pierce (3, 4) and Bergmann (5). 4 ^ 6 4 6 3 0 5 1 θ 7 3< 1,1 2 φ 8 2 φ 8
Simultaneous Determination of Multi-active Components in Calculus Bovis for Quality Control by High Performance Liquid Chromatography-Evaporative Light Scattering Detection

To establish a high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD) method for the rapid simultaneous determination of seven components in Calculus Bovis,furthermore,to provide an effective approach for quality control of this Chinese medicine material,the components were separated and analyzed on a Ultimate AQ-C18 column.A mixture of acetonitrile-water(0.2%formic acid) was selected as the mobile phase with the flow rate of 1 mL/min using gradient elution program.An Alltech 2000ES evaporative light scattering detector(ELSD) was connected to this HPLC equipment with the drift tube temperature of 100℃and nitrogen gas flow-rate of 1.9 L/min.Under the selected chromatographic condition,cholesterol,bile acids and its sodium salts had ideal resolutions and good peak shapes.The experimental results showed that the logarithm of peak area of each standard component was linearly correlated to the logarithm of injected mass within an acceptable range(r0.9972) with the recoveries of 98.8%-112.7% and the limits of detection of 0.001-0.007 g/L.The established HPLC-ELSD method is simple,quick and could be used for the simultaneous determination of multicomponent contents in Calculus Bovis,further to reflect the differences of internal quality and provide more references for the quality control of this rare medical material.
Endoscopic Evaluation of Biliary Strictures: Current and Emerging Techniques

The diagnosis of biliary strictures in clinical practice can be challenging. Discriminating between benign and malignant biliary strictures is important to prevent the morbidity and mortality associated with incorrect diagnoses. Missing a malignant biliary stricture may delay surgery, resulting in poor prognostic outcomes. Conversely, it has been demonstrated that approximately 20% of patients who undergo surgery for suspected biliary malignancies have a benign etiology on histopathology. Traditional tissue sampling using endoscopic retrograde cholangiography does not always produce a definitive diagnosis, with a considerable proportion of cases remaining as indeterminate biliary strictures. Recent advances in endoscopic techniques have the potential to improve the diagnostic and prognostic accuracy of biliary strictures.
End User Evaluation of the FAIR4Health Data Curation Tool

The aim of this study is to build an evaluation framework for the user-centric testing of the Data Curation Tool. The tool was developed in the scope of the FAIR4Health project to make health data FAIR by transforming them from legacy formats into a Common Data Model based on HL7 FHIR. The end user evaluation framework was built by following a methodology inspired from the Delphi method. We applied a series of questionnaires to a group of experts not only in different roles and skills, but also from various parts of Europe. Overall, 26 questions were formulated for 16 participants. The results showed that the users are satisfied with the capabilities and performance of the tool. The feedbacks were considered as recommendations for technical improvement and fed back into the software development cycle of the Data Curation Tool.
The Association between Well-being Behaviors and Resilience in Health Care Workers

Engaging in well-being behaviors may promote resilience, which can protect against burnout. This descriptive, correlational analysis utilized baseline data from health care workers enrolled in the Web-based Implementation of the Science for Enhancing Resilience longitudinal study (N = 2,383). The study aimed to describe the association of (a) types of well-being behaviors (regular exercise, yoga, meditation, spent time with a close friend, vacation) and (b) total number of well-being behaviors with resilience (emotional thriving and emotional recovery), covarying for sociodemographic and professional characteristics. General linear model findings indicated that each well-being behavior was significantly associated with greater emotional thriving, while only exercise and spending time with friends were significantly related to greater emotional recovery. Emotional thriving and emotional recovery were also significantly higher among health care workers reporting more well-being behaviors. Engaging in well-being behaviors may be one part of the solution toward increasing resilience in health care workers that warrants further investigation.