Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel RNA sequencing-based prognostic nomogram to predict survival for patients with cutaneous melanoma

Abstract Background: Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). Methods: We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. Results: A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. Conclusions: We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.
Rationale and design of a phase II trial of osimertinib as first-line treatment for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (SPIRAL-0 study).

Background Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has a potent inhibitory effect against both T790M resistance mutations and EGFR-TKI sensitizing in EGFR, with a relatively low affinity for wild-type EGFR. Osimertinib has been approved as a therapeutic agent for patients with T790M-mutation positive advanced non-small cell lung cancer. As a first-line treatment, osimertinib may significantly prolong progression-free survival (PFS) in comparison with the earlier generation first-line standard treatment. Osimertinib has been reported to provide survival benefits to EGFR mutation-positive patients. However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remains to be established. Methods In this single arm, prospective, open-label, multicenter, phase II trial, 40 subjects aged ≥75 years with EGFR mutation-positive advanced non-small-cell-lung cancer will be recruited. Patients will be treated with osimertinib 80 mg/day until disease progresses or until the patient meets a discontinuation criterion. The primary endpoint is 1-year PFS. Secondary endpoints are overall response rate, PFS, overall survival, and safety. Thirty-seven patients are required for the present study, as calculated based on normal approximation with a one-sided α level of 5% and 80% power, assuming that the expected 1-year PFS is 70% and the 1-year PFS threshold is 50%. Discussion We are conducting an intervention study to investigate the safety and efficacy of osimertinib as a first-line treatment agent for EGFR mutation-positive NSCLC in patients aged ≥75 years. Trial registration number jRCTs071180007.
An overview of siderophore biosynthesis among fluorescent Pseudomonads and new insights into their complex cellular organization.

Siderophores are iron-chelating molecules produced by bacteria to access iron, a key nutrient. These compounds have highly diverse chemical structures, with various chelating groups. They are released by bacteria into their environment to scavenge iron and bring it back into the cells. The biosynthesis of siderophores requires complex enzymatic processes and expression of the enzymes involved is very finely regulated by iron availability and diverse transcriptional regulators. Recent data have also highlighted the organization of the enzymes involved in siderophore biosynthesis into siderosomes, multi-enzymatic complexes involved in siderophore synthesis. An understanding of siderophore biosynthesis is of great importance, as these compounds have many potential biotechnological applications because of their metal-chelating properties and their key role in bacterial growth and virulence. This review focuses on the biosynthesis of siderophores produced by fluorescent Pseudomonads, bacteria capable of colonizing a large variety of ecological niches. They are characterized by the production of chromopeptide siderophores, called pyoverdines, which give the typical green color characteristic of fluorescent pseudomonad cultures. Secondary siderophores are also produced by these strains and can have highly diverse structures (such as pyochelins, pseudomonine, yersiniabactin, corrugatin, achromobactin, and quinolobactin). This article is protected by copyright. All rights reserved.
An Accelerated Finite-Time Convergent Neural Network for Visual Servoing of a Flexible Surgical Endoscope With Physical and RCM Constraints

This article designs and analyzes a recurrent neural network (RNN) for the visual servoing of a flexible surgical endoscope. The flexible surgical endoscope is based on a commercially available UR5 robot with a flexible endoscope attached as an end-effector. Most of the existing visual servo control frameworks of the robotic endoscopes or robot arms have not considered either the physical limits of the robot or the remote center of motion (RCM) constraints (i.e., the fulcrum effect). To tackle this issue, this article first conducts the kinematic modeling of the flexible robotic endoscope to achieve automation by visual servo control. The kinematic modeling results in a quadratic programming (QP) framework with physical limits and RCM constraints involved, making the UR5 robot applicable to surgical field. To solve the QP problem and accomplish the visual task, an RNN activated by a sign-bi-power activation function (AF) is proposed. The motivation of using the sign-bi-power AF is to enable the RNN to exhibit an accelerated finite-time convergence, which is more preferred in time-critical applications. Theoretically, the finite-time convergence of the RNN is rigorously proved using the Lyapunov theory. Compared with the previous AFs applied to the RNN, theoretical analysis shows that the RNN activated by the sign-bi-power AF delivers an accelerated convergence speed. Comparative validations are performed, showing that the proposed finite-time convergent neural network is effective to achieve visual servoing of the flexible endoscope with physical limits and RCM constraints handled simultaneously.
Neoadjuvant apatinib plus S-1 in locally advanced pulmonary adenocarcinoma

Abstract Rationale: About one-third of the lung tumors are staged as locally advanced at the time of initial diagnosis; however, the optimal induction treatment before curative resection has not been elucidated. To date, the evidence regarding the preoperative apatinib plus S-1 for locally advanced pulmonary adenocarcinoma is scarce. Patient concerns: A 29-year-old female was admitted because of persistent cough, sputum, and chest distress for 2 months. Diagnoses: Primary pulmonary adenocarcinoma (cT3N2M0, IIIB) with unknown driver gene mutation status. Interventions: The patient had received 4 months of neoadjuvant therapy using oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval), followed by anatomical lobectomy with curative intent. Adjuvant apatinib (425 mg daily for a month, and 250 mg daily for another month) plus S-1 at the same dosage were administered for 2 months. Thereafter, maintenance of low-dose S-1 monotherapy (40 mg, twice daily for 4 weeks with a 2-week drug-free interval) was continued for 6 months. Outcomes: The adverse events were tolerable and well-controlled. A postoperative recurrence-free survival for 2 years and a half up to now was indicated. Lessons: Preoperative apatinib plus S-1 showed efficacy in locally advanced pulmonary adenocarcinoma. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.
Rs10757274 gene polymorphisms in coronary artery disease

Abstract Background: It has been reported the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2BAS1) might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to investigate the association between rs10757274 polymorphism and the risk of CAD. Objectives: The present study aimed to investigate the relationship between rs10757274 polymorphism and the risk of CAD. Methods: All studies of the rs10757274 SNP with CAD that were published between 2007 and 2018 were retrieved from the PubMed database. Meta-analysis was performed with Stata 14.0 software. The effect size of the rs10757274 SNP with CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI). Results: Eleven studies including 52,209 subjects (cases: 7990, controls: 44,219) were included in the final data combination. Pooled overall analyses showed that rs10757274 (allele model: P < .001; dominant model: P < .001; recessive model: P < .001; Heterozygote codominant: P = .002; Homozygote codominant: P < .001) polymorphisms were significantly associated with the likelihood of CAD. Significant heterogeneity between individual studies appears in all 5 models. Further subgroup analyses revealed that rs10757274 polymorphisms were all significantly correlated with the likelihood of CAD and no heterogeneity were observed in West Asians. Conclusions: Our findings indicated that rs10757274 polymorphisms may serve as genetic biomarkers of CAD, especially in West Asians.
Unraveling the Impact of Gold(I)-Thiolate Motifs on the Aggregation-Induced Emission of Gold Nanoclusters.

Aggregation-induced emission (AIE) provides an efficient strategy to synthesize highly luminescent metal nanoclusters (NCs), however, rational control of emission energy and intensity of metal NCs is still challenging. This communication reveals the impact of surface Au(I)-thiolate motifs on the AIE properties of Au NCs, by employing a series of water-soluble glutathione (GSH)-coordinated Au complexes and NCs as a model (i.e., [Au10SR10], [Au15SR13], [Au18SR14], and [Au25SR18]-, where SR denotes thiolate ligand). Detailed spectroscopic investigations manifest that the emission wavelength of Au NCs is adjustable in a broad spectrum from visible to near-infrared II (NIR-II) regime by controlling the length of the Au(I)-SR motifs on NC surface. More interestingly, reducing the length of Au(I)-SR motifs also changes the origin of cluster luminescence from AIE-type phosphorescence to Au(0)-core-dictated fluorescence. This effect becomes more prominent when the degree of aggregation of Au NCs increases in solution. The findings revealed in this study not only provide fundamental insights into the emission origin of metal NCs, but also offer guiding principles in rational design of luminescent metal NCs.
Serotonin modulates optimized coding of natural stimuli through increased neural and behavioural responses via enhanced burst firing

The function of serotonergic fibres onto sensory areas remains poorly understood We show that serotonin application enhances sensory neural and behavioural responses to second order stimuli Enhanced neural responses most likely occurred because of increased burst firing Changes in neural sensitivity due to burst firing were the best predictor of changes in behavioural sensitivity Our results suggest that serotonin optimizes coding of stimuli encountered during aggression.
Germline variant burden in multidrug resistance transporters is a therapy‐specific predictor of survival in breast cancer patients

Multidrug resistance due to facilitated drug efflux mediated by ATP‐binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease‐specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug‐specific for subgroups treated with the MRP1 substrates cyclophosphamide (log‐rank p = 0.0011) and doxorubicin (log‐rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log‐rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine.
Chemical reactivity theory (CRT) study of small drug-like biologically active molecules

Abstract New biochemical screening and design based technology are used to identify the small molecules in targeting RNA. These approaches has develop potential drug like small molecule for RNA-targeted therapeutics. Chemical Reactivity Theory (CRT) is used to study these drug-like, biologically active small molecules that target RNA. Twenty two small molecules based on structure (1–6), information (7–9), fragment (10–19), small molecular microarrays (20), and use of phenotypic assays (21–22) are selected for the studies of several DFT-based global reactivity and local reactivity descriptors to provide complete explanation for the reactivity of these complexes by chemical reactivity method. Higher HOMO-LUMO gap indicated the structural stability for the studied complexes. The complexes reflect greater thermodynamic stability. Further the results predicted that high aromaticity and hardness are measures of high stability and low reactivity for the studied complexes. It was observed that a good, more reactive, nucleophile can be described by a lower value of μ, ω while a good electrophile can be described by a high value of μ, ω. TDDFT results predicted that few complexes can be used as fluorescent biomarkers as their emission wavelength lies in the visible region. Communicated by Ramaswamy H. Sarma
Methylenetetrahydrofolate reductase C677T (Ala>Val, rs1801133 C>T) polymorphism decreases the susceptibility of hepatocellular carcinoma: a meta-analysis involving 12,628 subjects

Abstract C677T (Ala>Val, rs1801133 C>T), a non-synonymous variant of methylenetetrahydrofolate reductase (MTHFR) gene, has been found to be associated with an impair enzyme activity of MTHFR. The relationship of MTHFR rs1801133 with hepatocellular carcinoma (HCC) has been extensively investigated. However, the findings were conflicting. Recently, more investigations have been conducted on the relationship of MTHFR rs1801133 with HCC. To obtain a more precise assessment on the effect of this non-synonymous variant to the development of HCC, a pooled-analysis was performed. This meta-analysis consisted of 19 independent case–control studies. By using the odds ratio (OR) combined with 95% confidence interval (CI), the relationship of MTHFR rs1801133 with HCC risk was determined. A total of 19 independent case–control studies were included. Finally, 6,102 HCC cases and 6,526 controls were recruited to examine the relationship of MTHFR rs1801133 with HCC risk. In recessive model (TT vs. CC/CT), the findings reached statistical significance (OR, 0.90; 95%CI, 0.82–0.98; P = 0.016). Subgroup analysis also found an association between MTHFR rs1801133 polymorphism and the decreased risk of HCC in hepatitis/virus related patients (recessive model: OR, 0.85; 95%CI, 0.72–0.99; P = 0.035, and allele model: OR, 0.90; 95%CI, 0.81–0.99; P = 0.028). Subgroup analyses indicated that extreme heterogeneity existed in Asian population, larger sample size investigation, hospital-based study and normal/healthy control subgroups. The shape of Begger’s seemed symmetrical. Egger’s linear regression test also confirmed these evaluations. Sensitivity analyses suggested that our findings were stable. In summary, our results highlight that MTHFR rs1801133 polymorphism decreases HCC susceptibility. The relationship warrants a further assessment.
FAM46B is a prokaryotic-like cytoplasmic poly(A) polymerase essential in human embryonic stem cells

Abstract Family with sequence similarity (FAM46) proteins are newly identified metazoan-specific poly(A) polymerases (PAPs). Although predicted as Gld-2-like eukaryotic non-canonical PAPs, the detailed architecture of FAM46 proteins is still unclear. Exact biological functions for most of FAM46 proteins also remain largely unknown. Here, we report the first crystal structure of a FAM46 protein, FAM46B. FAM46B is composed of a prominently larger N-terminal catalytic domain as compared to known eukaryotic PAPs, and a C-terminal helical domain. FAM46B resembles prokaryotic PAP/CCA-adding enzymes in overall folding as well as certain inter-domain connections, which distinguishes FAM46B from other eukaryotic non-canonical PAPs. Biochemical analysis reveals that FAM46B is an active PAP, and prefers adenosine-rich substrate RNAs. FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. FAM46B is localized to both cell nucleus and cytosol, and is indispensable for the viability of human embryonic stem cells. Knock-out of FAM46B is lethal. Knock-down of FAM46B induces apoptosis and restricts protein synthesis. The identification of the bacterial-like FAM46B, as a pluripotent stem cell-specific PAP involved in the maintenance of translational efficiency, provides important clues for further functional studies of this PAP in the early embryonic development of high eukaryotes.
Vitamin Substitution Beyond Childhood.

BACKGROUND Vitamins are vitally important, but they are not always adequately supplied with the diet. In this review, we present the advantages and disadvantages of vitamin supplementation and the indications for it in various life situations. METHODS This review is based on pertinent publications retrieved by a selective search of the literature. RESULTS The German National Nutrition Survey II (Nationale Verzehrsstudie II) showed that most people in Germany consume adequate amounts of vitamins in their diet, with the exception of vitamin D and folate. Supplements are often taken by adults who already consume a balanced diet. Depending on the vitamin, 3-13% of survey respondents took vitamin supplements; the ones most often taken were vitamins C and E. No convincing evidence has yet demonstrated a health benefit from vitamin supplemen- tation in addition to a balanced diet for the primary prevention of nutrition-associated diseases. Vitamin supplementation is indicated in certain specific life situations, e.g., pregnancy, but otherwise unnecessary, unless a deficiency has been diagnosed or the individual is at elevated risk. CONCLUSION Vitamin supplementation is recommended for certain population groups: folic acid for pregnant women, vitamin B12 for vegans and persons with resorption disorders, vitamin D for persons with insufficient endogenous synthesis. In all other ietary changes alone. In general, the of vitamin supplementation need to be considered, and its benefits weighed against its risks.
Colostrum supplementation with n-3 fatty acids and α-tocopherol alters plasma polyunsaturated fatty acid profile and decreases an indicator of oxidative stress in newborn calves

ABSTRACT Our objective was to characterize the effects of supplementing newborn calves with n-3 fatty acids (FA) and α-tocopherol on blood lipid profiles and oxidant status in early life. Sixteen calves received 0 or 60 mL of 1:1 fish and flaxseed oil with 200 mg of α-tocopherol in 2.8 L of colostrum within 6 h after birth. Colostrum was >22% on the Brix scale. Blood was sampled on d 1, 2, 4, 7, 14, and 21 after birth for assessment of plasma polyunsaturated FA, α-tocopherol, total serum protein, and oxidant status index, an indirect indicator of oxidative stress that examines the balance between the concentration of reactive oxygen and nitrogen species and antioxidant capacity in serum. Health was observed daily. Weight and hip height were recorded at birth, 3 wk, and 8 wk. Data were analyzed with a Mixed procedure of SAS 9.4 (SAS Institute Inc., Cary, NC). Treatment did not alter concentration of total protein in blood serum, prevalence of diarrhea or other signs of disease, or rate of growth. Feeding n-3 FA and α-tocopherol increased plasma concentrations of the n-3 FA, including α-linolenic, eicosapentaenoic, and docosahexaenoic acids, with a concomitant decrease in oxidant status index during the first week of life. Concentrations of α-tocopherol decreased with supplementation, but all calves maintained adequate concentrations. Oxidant status index of treated calves returned to the level of control calves by d 14. We conclude that a colostrum supplement of n-3 FA and α-tocopherol is safe to administer to newborn calves, reduces oxidant status in the first week of life, and may improve health and performance.
Real-Time Associations Between Glucose Levels and Fatigue in Type 2 Diabetes: Sex and Time Effects

Objective: Fatigue is a pervasive and serious complaint among aging adults with type 2 diabetes. Anecdotally, hyperglycemia was thought to cause fatigue, but prior cross-sectional analyses failed to find any relationship between glucose levels and fatigue. However, study methodology may have caused this relationship to be missed. Our aim was to use concurrent and continuous data across 5 days to examine real-time momentary relationships between glucose and fatigue levels by week, day, and time of day. Additionally, we explored how these relationships differed by sex. Method: Participants (N = 54, 51% male, 54% non-White) wore continuous glucose monitors and wrist actigraphy into which they inputted fatigue ratings 6–8 times daily during waking hours across 5 days. Generalized estimation equation models were used to explore the relationship between glucose and fatigue when averaged by week, day, and time of day. Differences by sex were also explored. Results: HbA1c and baseline and real-time fatigue were higher in women than in men. Baseline HbA1c and self-reported general fatigue were unrelated. Fatigue levels averaged by day and time of day were higher in women than in men (p < .05). Glucose and fatigue were significantly related at all levels of data (weekly, daily, and time of day) in women but not men. Conclusions: Our findings suggest that, when measured concurrently, glucose excursions may affect fatigue levels in women.