Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with type 2 diabetes mellitus in Chinese Korean ethnicity population

Abstract Presently, data on the type 2 diabetes mellitus (T2DM) in Chinese Korean ethnicity are very scarce. This study aimed to explore the relationship between the transcription factor 7-like 2 (TCF7L2) and T2DM in Chinese Korean ethnicity population. This case-control study involved 43 T2DM Chinese Korean ethnicity patients (T2DM group) and 43 healthy Chinese Korean ethnicity normoglycemic subjects as controls (Control group). All included participants aged from 40 to 75 years old. Clinical and biological data were collected to determine the phenotypic traits. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze the TCF7L2 by genotyping for rs7903146 (C/T). Spectrophotometer with Chronolab kits was used to conduct the biochemical analyses. TCF7L2 was associated with T2DM in the Chinese Korean ethnicity population (P < .01 for alleles, and P < .05 for genotypes). Significant differences were found 2 groups regarding the T allele (37.2% T2DM patients vs 15.1% healthy subjects, P < .01), and G allele (62.8% T2DM patients vs 84.9% healthy subjects, P < .01). The risk genotypes were GG (83.7% T2DM patients, vs 44.2% healthy control, P < .01), GT (4.7% T2DM patients, vs 20.9% healthy control, P = .04), and TT (11.6% T2DM patients, vs 34.9% healthy control, P = .01). The results of this study demonstrated that TCF7L2 is associated with T2DM in the Chinese Korean ethnicity population, which is an important risk factor for T2DM in this population.
Depression and anxiety in patients with different rare chronic diseases: A cross-sectional study

Objective Empirical evidence on depression and anxiety in patients with rare diseases is scarce but can help improve comprehensive treatment. The objectives of this study were to investigate the frequency of depression and anxiety in this heterogeneous population and to examine aspects associated with increased psychopathology. Methods N = 300 patients with 79 different rare diseases (female:80%, age:M = 44.3(12.8), range:16–74 years) participated in a cross-sectional online study. We determined the percentages of patients reporting elevated depression (PHQ-9) and anxiety (GAD-7) scores. We calculated two linear regressions with depression and anxiety as outcomes. Predictor variables were diagnosis-related aspects (diagnosis assigned to ICD-10 chapter, visibility of symptoms, time since diagnosis, comorbid diseases), perceived somatic-symptom-severity (PHQ-15), illness-perceptions (consequences, control, identity, concern, understanding and treatment control; B-IPQ-R), coping mechanisms (constructive attitudes, active engagement in life) and social support (heiQ). We controlled for gender, age and depression or anxiety depending on the outcome. Results 42% of the patients (95%CI [36.41%,47.59%]) reported depression scores indicating moderately or severely elevated symptom levels. Regarding anxiety, this applies to 23% (95%CI [18.54%,28.06%]). Variables significantly associated with depression were higher perceived somatic-symptom-severity (B = 0.41,p < .001), less control (B = .17,p < .05), lower levels of concern (B = -0.32,p < .01) and less constructive attitudes (B = -1.40,p < .001). No diagnosis-related variables were associated with depression. Variables significantly associated with anxiety were diseases of the circulatory system compared to congenital malformations (B = 1.88,p < .05), less consequences (B = -0.32,p < .05) and more concern (B = -0.32,p < .01). Conclusion The data reveal first insights into depression and anxiety in patients with different rare diseases. High percentages of patients showed clinically relevant symptom burden. No diagnosis-related differences were found in depression while anxiety seems to be particularly frequent in patients with rare diseases of the circulatory system. Besides perceived somatic symptom severity, cognitive appraisal seems to be linked to depression. Supporting patients in coping with their disease may help reduce psychopathology and therefore improve overall health.
Characterization of a Novel Third-Generation Anti-CD24-CAR against Ovarian Cancer

Novel therapeutic approaches against ovarian cancer (OC) are urgently needed because of its high rate of recurrence even after extensive surgery and multi-agent chemotherapy. We aimed to develop a novel anti-CD24 chimeric antigen receptor (CAR) as an immunotherapeutic approach against OC cells and cancer stem cells (CSC). CSC represents a subpopulation of the tumor characterized by enhanced chemoresistance as well as the increased capability of self-renewal and metastasis. We designed a codon-optimized third-generation CAR containing the highly active single chain variable fragment (scFv) “SWA11” against CD24. We equipped the human NK-cell line NK-92 with the anti-CD24 CAR and an anti-CD19 control CAR using lentiviral transduction. Engineered NK-92 cells showed high cytotoxic activity against CD24-positive OC cell lines (SKOV3, OVCAR3). This effect was restricted to CD24-expressing cells as shown after lentiviral transduction of CD24-negative cell lines (A2780, HEK-293T) with CD24 transmembrane proteins. Additionally, NK-92 cells equipped with our novel anti-CD24 CAR were highly effective against patient-derived primary ovarian cancer cells. The activation of NK cells was shown by specific IFNγ secretion upon antigen stimulation. To further reduce possible off-target effects in vivo, we applied a dual-CAR approach using an anti-CD24-CD28-41BB fusion protein linked via a 2A sequence to an anti-mesothelin-CD3ζ-CAR. The dual-CAR was simultaneously active against CD24 and mesothelin expressing cells. Our novel anti-CD24-CAR showed a highly cytotoxic effect against OC cell lines and primary OC cells and will be evaluated in future in vivo trials as a promising immunotherapeutic approach against OC.
A combined computational strategy of sequence and structural analysis predicts the existence of a functional eicosanoid pathway in Drosophila melanogaster

This study reports on a putative eicosanoid biosynthesis pathway in Drosophila melanogaster and challenges the currently held view that mechanistic routes to synthesize eicosanoid or eicosanoid-like biolipids do not exist in insects, since to date, putative fly homologs of most mammalian enzymes have not been identified. Here we use systematic and comprehensive bioinformatics approaches to identify most of the mammalian eicosanoid synthesis enzymes. Sensitive sequence analysis techniques identified candidate Drosophila enzymes that share low global sequence identities with their human counterparts. Twenty Drosophila candidates were selected based upon (a) sequence identity with human enzymes of the cyclooxygenase and lipoxygenase branches, (b) similar domain architecture and structural conservation of the catalytic domain, and (c) presence of potentially equivalent functional residues. Evaluation of full-length structural models for these 20 top-scoring Drosophila candidates revealed a surprising degree of conservation in their overall folds and potential analogs for functional residues in all 20 enzymes. Although we were unable to identify any suitable candidate for lipoxygenase enzymes, we report structural homology models of three fly cyclooxygenases. Our findings predict that the D. melanogaster genome likely codes for one or more pathways for eicosanoid or eicosanoid-like biolipid synthesis. Our study suggests that classical and/or novel eicosanoids mediators must regulate biological functions in insects–predictions that can be tested with the power of Drosophila genetics. Such experimental analysis of eicosanoid biology in a simple model organism will have high relevance to human development and health.
Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis

Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked mutants of human FUS in mice produces progressive motor phenotypes accompanied by characteristic ALS-like pathology. FUS levels are autoregulated by a mechanism in which human FUS downregulates endogenous FUS at mRNA and protein levels. Increasing wild-type human FUS expression achieved by saturating this autoregulatory mechanism produces a rapidly progressive phenotype and dose-dependent lethality. Transcriptome analysis reveals mis-regulation of genes that are largely not observed upon FUS reduction. Likely mechanisms for FUS neurotoxicity include autophagy inhibition and defective RNA metabolism. Thus, our results reveal that overriding FUS autoregulation will trigger gain-of-function toxicity via altered autophagy-lysosome pathway and RNA metabolism function, highlighting a role for protein and RNA dyshomeostasis in FUS-mediated toxicity.
Universality of local weak interactions and its application for interferometric alignment

Significance In this combined theoretical and experimental work, we describe and demonstrate a universal feature of local couplings of spatially preselected and postselected systems. All weak couplings, independently of their physical nature, are modified in the same universal manner, characterized by the weak value of local projection. We present a general analysis which neither relies on a specific form of the coupling nor is restricted to weak interactions. This allows us to define a consistent paradigm of the presence of a quantum particle, much more intricate than the concept of the presence of a classical particle. Furthermore, we discovered that Gaussian pointers remain reliable beyond the weak regime, which enabled a simple and efficient alignment method for interferometric setups. The modification of the effect of interactions of a particle as a function of its preselected and postselected states is analyzed theoretically and experimentally. The universality property of this modification in the case of local interactions of a spatially preselected and postselected particle has been found. It allowed us to define an operational approach for the characterization of the presence of a quantum particle in a particular place: the way it modifies the effect of local interactions. The experiment demonstrating this universality property provides an efficient interferometric alignment method, in which the position of the beam on a single detector throughout one phase scan yields all misalignment parameters.
Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism

Significance Genomically humanized animals overcoming species differences are invaluable for biomedical research. Although rats would be preferred over mice for several applications, generation of a humanized model is restricted to mice due to the difficulty of complex genetic manipulations in rats. In this study, we successfully generated humanized rats with megabase-sized gene clusters via combination of chromosome transfer using mouse artificial chromosome vector and genome editing technologies. In the humanized UGT2 and CYP3A transchromosomic rats described in this paper, the expression of the human genes, as well as the pharmacokinetics and metabolism of relevant probe substrates, accurately mimic the situation in humans. Thus, the advanced technologies can be used to generate fully humanized rats useful for biomedical research. Although “genomically” humanized animals are invaluable tools for generating human disease models as well as for biomedical research, their development has been mainly restricted to mice via established transgenic-based and embryonic stem cell-based technologies. Since rats are widely used for studying human disease and for drug efficacy and toxicity testing, humanized rat models would be preferred over mice for several applications. However, the development of sophisticated humanized rat models has been hampered by the difficulty of complex genetic manipulations in rats. Additionally, several genes and gene clusters, which are megabase range in size, were difficult to introduce into rats with conventional technologies. As a proof of concept, we herein report the generation of genomically humanized rats expressing key human drug-metabolizing enzymes in the absence of their orthologous rat counterparts via the combination of chromosome transfer using mouse artificial chromosome (MAC) and genome editing technologies. About 1.5 Mb and 700 kb of the entire UDP glucuronosyltransferase family 2 and cytochrome P450 family 3 subfamily A genomic regions, respectively, were successfully introduced via the MACs into rats. The transchromosomic rats were combined with rats carrying deletions of the endogenous orthologous genes, achieved by genome editing. In the “transchromosomic humanized” rat strains, the gene expression, pharmacokinetics, and metabolism observed in humans were well reproduced. Thus, the combination of chromosome transfer and genome editing technologies can be used to generate fully humanized rats for improved prediction of the pharmacokinetics and drug–drug interactions in humans, and for basic research, drug discovery, and development.
Perceived Body Appearance and Eating Habits: The Voice of Young and Adult Students Attending Higher Education

This study examined the relationship between social-environmental influences and body image perception. Specifically, the study explored the perceived body appearance among young and older students attending higher education, and their eating experiences, as related to four main social-environmental circles: family, friends, work colleagues, and media. The present study interviewed 30 students (14 men and 16 women) ages 20–40. The findings show that most of the participants were concerned about their appearance, reported on various eating habits rooted on family tradition. Findings revealed differences among gender and age groups regarding, especially regarding sport and dissatisfaction with their own perceived appearance. Although more women reported on healthy eating habits and doing sport, they reported higher dissatisfaction with their body appearance. It was found that in both groups, family habits and their parents’ remarks about bodies had an ongoing effect and significant influence on their body self-perceptions. Further health promotion should be directed in particular to individuals with a perceived negative body image, in order to enhance positive body self-perception, implementing heathy eating habits and engaging higher commitment to sport.
Cell Cycle Arrest in Different Cancer Cell Lines (Liver, Breast, and Colon) Induces Apoptosis under the Influence of the Chemical Content of Aeluropus lagopoides Leaf Extracts

Natural products, especially secondary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. Aeluropus lagopoides is one of the common halophyte plants that survive under stressed conditions, and has been used for healing wounds and as a painkiller. The bioactivity and the chemical composition of this plant have been poorly investigated. Consequently, the chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), and n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites were evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using a SulphoRhodamine-B (SRB) test. Their mechanisms of action were verified by observing the appearance of apoptotic bodies using the fluorescent microscope, while their antiproliferative impacts were evaluated using a flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate had the highest cytotoxicity and thus the greatest anticancer activity effect on HepG2 with IC50 (24.29 ± 0.85 and 11.22 ± 0.679 µg/mL, respectively). On the other hand, flow cytometer results showed that secondary metabolites could inhibit the cell cycle in the G0/G1 phase. To ascertain the chemical composition–function relationship, the extracts were analyzed using LC-MS/MS. Accordingly, A. lagopoides hexane and ethyl acetate extracts may contain agents with anticancer potential.
An Improved Method for Cell Type-Selective Glycomic Analysis of Tissue Sections Assisted by Fluorescence Laser Microdissection

Lectin microarray (LMA) is a highly sensitive technology used to obtain the global glycomic profiles of endogenous glycoproteins in biological samples including formalin-fixed paraffin-embedded tissue sections. Here, we describe an effective method for cell type-selective glycomic profiling of tissue fragments collected by laser microdissection (LMD) under fluorescent histochemical visualization. We optimized each step of histochemical staining and confirmed the reliability and validity of glycomic profiling. Using the optimized procedure, glycomic profiles were obtained with 0.5 mm2 of stained thymic sections (5-μm-thick) from 8-week-old C57BL/6J male mice. The glycomic profiles of Ulex europaeus agglutinin-I (UEA-I)-stained medullary regions showed higher UEA-I signals than those of the morphologically determined medulla regions, indicating the utility of this method for UEA-I(+) cell-selective analysis. To further evaluate this method, tissue fragments was serially collected from stained and unstained areas of medullary epithelial cell probes (UEA-I and anti-cytokeratin 5 antibody) and a cortex-staining probe (peanut agglutinin). The medullary regions assigned by the three probes showed significantly different glycomic profiles, highlighting the difference in subpopulation recognition among the three probes, which was consistent with previous reports. In conclusion, our fluorescence LMD-LMA method enabled cell type-selective tissue glycomic analysis of pathological specimens and animal models, especially for glyco-biomarker discovery.
Ripe and Raw Pu-Erh Tea: LC-MS Profiling, Antioxidant Capacity and Enzyme Inhibition Activities of Aqueous and Hydro-Alcoholic Extracts

Herein, we reported a detailed profiling of soluble components of two fermented varieties of Chinese green tea, namely raw and ripe pu-erh. The identification and quantification of the main components was carried out by means of mass spectrometry and UV spectroscopy, after chromatographic separation. The antioxidant capacity towards different radical species, the anti-microbial and the enzyme inhibition activities of the extracts were then correlated to their main constituents. Despite a superimposable qualitative composition, a similar caffeine content, and similar enzyme inhibition and antimicrobial activities, raw pu-erh tea extract had a better antioxidant capacity owing to its higher polyphenol content. However, the activity of raw pu-erh tea seems not to justify its higher production costs and ripe variety appears to be a valid and low-cost alternative for the preparation of products with antioxidant or antimicrobial properties.
Isolated third nerve palsy with pupillary involvement resulting from carotid-cavernous sinus fistula

Rationale: Isolated third nerve palsy with pupillary involvement caused by a posterior drainage carotid-cavernous sinus fistula (CCF) is relatively rare. Diagnosis of a posterior drainage CCF can often be delayed due to its unapparent congestive signs. Patient concerns: Here, we present the case of a young male patient with right-sided CCF, who presented with right-side headache and partial third nerve palsy with pupillary involvement. The diagnosis was confirmed using time-of-flight magnetic resonance angiography (TOF-MRA) and digital subtraction angiography (DSA). Diagnoses: A right-sided CCF was detected, which was primarily supplied by the dural branch of the right middle meningeal artery and venous drainage into the right inferior petrosal sinus. Interventions: The patient was treated with transarterial coil embolization. Outcomes: At 2 months, ride-side headache was significantly improved and ptosis and limited extraocular muscle movement were partially resolved. Lessons: CCF might not always present with ocular congestion. Although uncommon, white-eye and painful third nerve palsy with pupillary involvement may be caused by a posterior drainage CCF.
Assessment of cholestasis in drug-induced liver injury by different methods

Abstract Cholestasis in drug-induced liver injury (DILI) can be assessed by biochemical and pathologic methods, but the agreement between the 2 methods remains unclear. The aim of this study was to identify the accurate method for assessment of cholestasis in DILI. The DILI standard established and revised by the Council for International Organizations of Medical Sciences (CIOMS) (R values were calculated by liver function at different time points), cholestatic liver disease guideline (European Association for the Study of the Liver, EASL), and liver pathology were used to assess, compare, and analyze the cholestasis in 133 patients with DILI. The R values at different time points in CIOMS standard had no statistical difference for the assessment of cholestatic DILI (a = 0.05, &khgr;2 = 1.51, P = .679). There were statistical differences among the results of CIOMS, EASL, and pathology (a = 0.05, &khgr;2 = 99.97, P < .001). EASL standard had no statistical difference with pathology (a = 0.003, &khgr;2 = 8.00, P = .005). CIOMS and EASL standards based on biochemical parameters underestimated cholestatic DILI, as compared to liver pathology.
Hybrid Composite-Metal Stack Drilling with Different Minimum Quantity Lubrication Levels

Hybrid stack drilling is a very common operation used in the assembly of high-added-value components, which combines the use of composite materials and metallic alloys. This process entails the complexity of machining very dissimilar materials, simultaneously, on account of the interactions that are produced between them, during machining. This study analyzed the influence of Minimum Quantity Lubrication (MQL) on the performance of diamond-coated carbide tools when drilling Ti/carbon fiber reinforced plastics (CFRP)/Ti stacks. The main wear mechanism observed was diamond-coating detachment, followed by fragile breaks in the main cutting-edge. The tests done with the lower lubrication levels have shown an important adhesion of titanium (mainly on the secondary cutting-edge) and a higher friction between the tool and the workpiece, producing higher temperatures on the cutting region and a thermal softening effect on the workpiece. These phenomena affect the evolution of cutting power consumption with tool wear in the titanium layer. Regarding the quality of the test specimen, no significant differences were observed between the lubrication levels tested.
Design of a 1-bit MEMS Gyroscope using the Model Predictive Control Approach

In this paper, a bi-level Delta-Sigma modulator-based MEMS gyroscope design is presented based on a Model Predictive Control (MPC) approach. The MPC is popular because of its capability of handling hard constraints. In this work, we propose to combine the 1-bit nature of the bi-level Delta-Sigma modulator output with the MPC to develop a 1-bit processing-based MPC (OBMPC). This paper will focus on the affine relationship between the 1-bit feedback and the in-loop MPC controller, as this can potentially remove the multipliers from the controller. In doing so, the computational requirement of the MPC control is significantly alleviated, which makes the 1-bit MEMS Gyroscope feasible for implementation. In addition, a stable constrained MPC is designed, so that the input will not overload the quantizer while maintaining a higher Signal-to-Noise Ratio (SNR).