Miracle-dz/UniFAR-FTUs huggingface dataset:
Off-Label Use of Antineoplastic Drugs to Treat Malignancies: Evidence From China Based on a Nationwide Medical Insurance Data Analysis

Purpose: Cancer is a leading cause of morbidity and mortality worldwide. Off-label (OL) use of antineoplastic drugs to treat malignancies is prevalent. In this study, we quantified and characterized OL use of antineoplastic drugs to treat malignancies in China. Methods: This was a retrospective study using nationwide data collected from 2008 to 2010. Use of antineoplastic drugs was considered OL if they were used for indications not reflected in the package insert published by the National Medical Products Administration at the time of prescription. Descriptive analysis and Spearman rank correlation were used to evaluate the frequency and pattern of OL drug use. Results: In total, 51,382 patients with malignancies, 24 categories of antineoplastic drugs, and 77 types of malignancies treated with OL drugs were included in this study. Twenty commonly used antineoplastic drugs (ICD encoded as L01) were used OL in 10–61% of cases, and four commonly used endocrine therapy antineoplastic drugs (ICD encoded as L02) were used OL in 10–19% of cases. There was a significant negative correlation between the disease constituent ratio and the average OL use rate of antineoplastic drugs for various malignancies. In contrast, there was a significant positive correlation between the average OL use rate of antineoplastic drugs and the number of malignancies treated with OL drugs. Conclusion: This study provided information regarding OL use of antineoplastic drugs for treatment of malignancies, and showed that OL use was prevalent. In addition, uncommon malignancies were more likely to be treated with OL antineoplastic drugs. Furthermore, more commonly used antineoplastic drugs were more likely to be used OL.
Fiber Derived Microbial Metabolites Prevent Acute Kidney Injury Through G-Protein Coupled Receptors and HDAC Inhibition

Short-chain fatty acids (SCFA) derived from gut microbial fermentation of fiber have been shown to exert anti-inflammatory and immune-modulatory properties in acute kidney injury (AKI). However the direct mechanistic link between SCFAs, diet and the gut microbiome is yet to be established. Using the murine model of folic-acid nephropathy (FAN), we examined the effect of dietary fiber on development of AKI (day 2) and subsequent chronic kidney disease (CKD) (day 28). FAN was induced in wild-type and knockout mice lacking G protein–coupled receptors GPR41, GPR43, or GPR109A. Mice were randomized to high-fiber or normal-chow diets, or SCFAs in drinking water. We used 16S rRNA sequencing to assess the gut microbiome and 1H-NMR spectroscopy for metabolic profiles. Mice fed high-fiber were partially protected against development of AKI and subsequent CKD, exhibiting better kidney function throughout, less tubular injury at day 2 and less interstitial fibrosis and chronic inflammation at day 28 vs controls. Fiber modified the gut microbiome and alleviated dysbiosis induced by AKI, promoting expansion of SCFA-producing bacteria Bifidobacterium and Prevotella, which increased fecal and serum SCFA concentrations. SCFA treatment achieved similar protection, but not in the absence of GPR41 or GPR109A. Histone deacetylase activity (HDAC) was inhibited in kidneys of high-fiber fed mice. We conclude that dietary manipulation of the gut microbiome protects against AKI and subsequent CKD, mediated by HDAC inhibition and activation of GPR41 and GPR109A by SCFAs. This study highlights the potential of the gut microbiome as a modifiable target in the prevention of AKI.
Surface Topography, Bacterial Carrying Capacity, and the Prospect of Microbiome Manipulation in the Sea Anemone Coral Model Aiptasia

Aiptasia is an emerging model organism to study cnidarian symbioses due to its taxonomic relatedness to other anthozoans such as stony corals and similarities of its microalgal and bacterial partners, complementing the existing Hydra (Hydrozoa) and Nematostella (Anthozoa) model systems. Despite the availability of studies characterizing the microbiomes of several natural Aiptasia populations and laboratory strains, knowledge on basic information, such as surface topography, bacterial carrying capacity, or the prospect of microbiome manipulation is lacking. Here we address these knowledge gaps. Our results show that the surface topographies of the model hydrozoan Hydra and anthozoans differ substantially, whereas the ultrastructural surface architecture of Aiptasia and stony corals is highly similar. Further, we determined a bacterial carrying capacity of ∼104 and ∼105 bacteria (i.e., colony forming units, CFUs) per polyp for aposymbiotic and symbiotic Aiptasia anemones, respectively, suggesting that the symbiotic status changes bacterial association/density. Microbiome transplants from Acropora humilis and Porites sp. to gnotobiotic Aiptasia showed that only a few foreign bacterial taxa were effective colonizers. Our results shed light on the putative difficulties of transplanting microbiomes between cnidarians in a manner that consistently changes microbial host association at large. At the same time, our study provides an avenue to identify bacterial taxa that exhibit broad ability to colonize different hosts as a starting point for cross-species microbiome manipulation. Our work is relevant in the context of microbial therapy (probiotics) and microbiome manipulation in corals and answers to the need of having cnidarian model systems to test the function of bacteria and their effect on holobiont biology. Taken together, we provide important foundation data to extend Aiptasia as a coral model for bacterial functional studies.
Gut Structure and Microbial Communities in Sirex noctilio (Hymenoptera: Siricidae) and Their Predicted Contribution to Larval Nutrition

The European woodwasp, Sirex noctilio Fabricius, is a major invasive quarantine pest that attacks and kills pine trees outside of its native range. Insect gut structure and gut microbiota play crucial roles in various life activities. Despite a few reports in nutrition and survival, an extensive study on the S. noctilio larval gut microbiome is lacking. We studied the gut structure using a stereo microscope and used high throughput sequencing of the bacterial 16S rRNA genes and fungal internal transcribed spacer 2 (ITS2) regions to investigate gut microbiota in different developmental stages of S. noctilio, including larvae, adults, and larval frass. We used PICRUSt2 to predict the functional profiles. The larval gut was thin and thread-like from the oral cavity to the anus, carrying few xylem particles in the crop. Pseudomonas, Ralstonia, and Burkholderia s.l were the dominant bacteria in the guts of larvae, adults, and frass, respectively. Even though Pseudomonas was the most abundant among all bacteria, Zoogloea, Ruminobacter, and Nitrosospira, which might be involved in degrading organic matter and fixing nitrogen occurred exclusively in the larval gut indicating their possible role in the growth and development of larvae in pine tree xylem. Fungal communities did not change significantly across different developmental stages or the frass. Amylostereum was dominant in the woodwasp’s larval gut. Functional prediction of bacterial and fungal communities revealed that they may encod enzymes involved in degrading lignocellulose and fixing nitrogen. Ours is the first study that compares gut microbial communities present in S. noctilio larvae, adults, and frass. This study could provide an understanding of larval nutrient acquisition in nutrient-deficient host xylem to some extent. Our study may unlock novel strategies for the development of pest management approaches based on interfering with the gut microbiota and restricting their role in larval survival and development.
Visual Perception and Visuomotor Reaction Speed Are Independent of the Individual Alpha Frequency

While the resting-state individual alpha frequency (IAF) is related to the cognitive performance and temporal resolution of visual perception, it remains unclear how it affects the neural correlates of visual perception and reaction processes. This study aimed to unravel the relation between IAF, visual perception, and visuomotor reaction time. One hundred forty-eight (148) participants (28 non-athletes, 39 table tennis players, and 81 badminton players) investigated in three previous studies were considered. During a visuomotor reaction task, the visuomotor reaction time (VMRT) and EMG onset were determined. In addition, a 64-channel EEG system identified the N2, N2-r, and BA6 negativity potentials representing the visual and motor processes related to visuomotor reactions. Resting-state individual alpha frequency (IAF) in visual and motor regions was compared based on sport experience (athletes vs. non-athletes), discipline (badminton vs. table tennis), and reaction performance (fast vs. medium vs. slow reaction time). Further, the differences in the IAF were determined in relation to the speed of neural visual (high vs. medium vs. low N2/N2-r latency) and motor (high vs. medium vs. low BA6 negativity latency). Group comparisons did not reveal any difference in the IAF between athletes and non-athletes (p = 0.352, ηp2 = 0.02) or badminton and table tennis players (p = 0.221, ηp2 = 0.02). Similarly, classification based on the behavioral or neural performance indicators did not reveal any effects on the IAF (p ≥ 0.158, ηp2 ≤ 0.027). IAF was not correlated to any of the behavioral or neural parameters (r ≤ 0.10, p ≥ 0.221). In contrast to behavioral results on cognitive performance and visual temporal resolution, the resting state IAF seemed unrelated to the visual perception and visuomotor reaction speed in simple reaction tasks. Considering the previous results on the correlations between the IAF, cognitive abilities, and temporal sampling of visual information, the results suggest that a higher IAF may facilitate the amount and frequency but not the speed of information transfer.
Integrated Design of Working Fluid Mixtures and Absorption Refrigeration Cycles

This work presents a CAMD (computer-aided molecular design) approach for the design of working fluid mixtures used in ABR (absorption refrigeration) cycles. Compared to previous works, the proposed approach introduces two major improvements. It employs for the first time an ABR process model in the course of CAMD, hence enabling the evaluation of the generated mixtures considering process performance indicators. It enables for the first time the simultaneous generation and evaluation of molecular structures for both refrigerants and absorbents. The employed model and CAMD optimization problem formulation incorporates major ABR operational driving forces pertaining to efficient refrigeration, sufficient solubility of mixture components and ease of separation in the generator. The approach employs a multicriteria assessment methodology both during CAMD and for the evaluation of selected mixtures using a more rigorous ABR model at a second stage. The work identifies novel mixtures, with Acetaldehyde/2-Methoxyethyl acetate and Acetaldehyde/Methanediol exhibiting the highest performance. The latter exhibits 3% higher COP (coefficient of performance) and cooling output than the reference mixture NH3/H2O, whereas it operates at 87 and 89% lower high and low cycle pressures. The novel mixtures are also compared with novel mixtures previously identified through a heuristic approach by the authors. The latter mixtures indicate overall higher ABR performance but similar or worse performance in safety, health and environmental impact indices. Further performance improvements may be achieved by including into CAMD additional chemical groups to be able to simulate the complex absorbent structures available in published works.
Dunning-Kruger Effect: Intuitive Errors Predict Overconfidence on the Cognitive Reflection Test

The Cognitive Reflection Test (CRT) is a measure of analytical reasoning that cues an intuitive but incorrect response that must be rejected for successful performance to be attained. The CRT yields two types of errors: Intuitive errors, which are attributed to Type 1 processes; and non-intuitive errors, which result from poor numeracy skills or deficient reasoning. Past research shows that participants who commit the highest numbers of errors on the CRT overestimate their performance the most, whereas those with the lowest error-rates tend to slightly underestimate. This is an example of the Dunning-Kruger Effect (DKE). The present study examined how intuitive vs. non-intuitive errors contribute to overestimation in the CRT at different levels of performance. Female undergraduate students completed a seven-item CRT test and subsequently estimated their raw score. They also filled out the Faith in Intuition (FI) questionnaire, which is a dispositional measure of intuitive thinking. Data was separated into quartiles based on level of performance on the CRT. The results demonstrated the DKE. Additionally, intuitive and non-intuitive errors predicted miscalibration among low, but not high performers. However, intuitive errors were a stronger predictor of miscalibration. Finally, FI was positively correlated with CRT self-estimates and miscalibration, indicating that participants who perceived themselves to be more intuitive were worse at estimating their score. These results taken together suggest that participants who perform poorly in the CRT and also those who score higher in intuitive thinking disposition are more susceptible to the influences of heuristic-based cues, such as answer fluency, when judging their performance.
Development and Validation of a Prognostic Gene Signature in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC), one of the most common urologic cancer types, has a relatively good prognosis. However, clinical diagnoses are mostly done during the medium or late stages, when mortality and recurrence rates are quite high. Therefore, it is important to perform real-time information tracking and dynamic prognosis analysis for these patients. We downloaded the RNA-seq data and corresponding clinical information of ccRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 3,238 differentially expressed genes were identified between normal and ccRCC tissues. Through a series of Weighted Gene Co-expression Network, overall survival, immunohistochemical and the least absolute shrinkage selection operator (LASSO) analyses, seven prognosis-associated genes (AURKB, FOXM1, PTTG1, TOP2A, TACC3, CCNA2, and MELK) were screened. Their risk score signature was then constructed. Survival analysis showed that high-risk scores exhibited significantly worse overall survival outcomes than low-risk patients. Accuracy of this prognostic signature was confirmed by the receiver operating characteristic curve and was further validated using another cohort. Gene set enrichment analysis showed that some cancer-associated phenotypes were significantly prevalent in the high-risk group. Overall, these findings prove that this risk model can potentially improve individualized diagnostic and therapeutic strategies.
Roughness Effects of Crack Surfaces on the Elastic Moduli of Cracked Rocks

Crack surfaces are usually rough on various scales, and are sensitive to loading stresses and hence significantly affecting the mechanical properties of cracked rocks. We design a number of dry- and fluid-saturated numerical cracked samples to investigate the roughness influence of crack surfaces on the elastic stiffness. The fracture surface roughness is characterized by non-uniform fracture radii. We calculate the elastic moduli of cracked samples by finite-element simulation. Comparisons with the theoretical predictions by Gassmann and C&S (Ciz and Shapiro) (Ciz and Shapiro, Geophysics, 2007, 72(6), A75–A79) substitution equations demonstrate that the rough crack surfaces for both dry- and fluid-saturated samples can induce a stress concentration around the crack that reduces the elastic moduli and decreases the stiffness of rocks. For the fluid/solid-saturated cracks under the normal (shear) loading stresses, because the stress-concentration can induce shear (normal) strains around fracture, shear (bulk) modulus of the filling material will have contributions to the effective bulk (shear) modulus of rocks. The extra contribution, however, makes the Gassmann equation and C&S equation invalid.
Low Diffusive Methane Emissions From the Main Channel of a Large Amazonian Run-of-the-River Reservoir Attributed to High Methane Oxidation

The global development of hydropower dams has rapidly expanded over the last several decades and has spread to historically non-impounded systems such as the Amazon River’s main low land tributaries in Brazil. Despite the recognized significance of reservoirs to the global methane (CH4) emission, the processes controlling this emission remain poorly understood, especially in Tropical reservoirs. Here we evaluate CH4 dynamics in the main channel and downstream of the Santo Antônio hydroelectric reservoir, a large tropical run-of-the-river (ROR) reservoir in Amazonia. This study is intended to give a snapshot of the CH4 dynamics during the falling water season at the initial stage after the start of operations. Our results show substantial and higher CH4 production in reservoirs’ littoral sediment than in the naturally flooded areas downstream of the dam. Despite the large production in the reservoir or naturally flooded areas, high CH4 oxidation in the main channel keep the concentration and fluxes of CH4 in the main channel low. Similar CH4 concentrations in the reservoir and downstream close to the dam suggest negligible degassing at the dam, but stable isotopic evidence indicates the presence of a less oxidized pool of CH4 after the dam. ROR reservoirs are designed to disturb the natural river flow dynamics less than traditional reservoirs. If enough mixing and oxygenation remain throughout the reservoir’s water column, naturally high CH4 oxidation rates can also remain and limit the diffusive CH4 emissions from the main channel. Nevertheless, it is important to highlight that our results focused on emissions in the deep and oxygenated main channel. High emissions, mainly through ebullition, may occur in the vast and shallow areas represented by bays and tributaries. However, detailed assessments are still required to understand the impacts of this reservoir on the annual emissions of CH4.
Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes

Mounting evidence suggested that the gut microbiota has a significant role in the metabolism and disease status of the host. In particular, Type 2 Diabetes (T2D), which has a complex etiology that includes obesity and chronic low-grade inflammation, is modulated by the gut microbiota and microbial metabolites. Current literature supports that unbalanced gut microbial composition (dysbiosis) is a risk factor for T2D. In this review, we critically summarize the recent findings regarding the role of gut microbiota in T2D. Beyond these associative studies, we focus on the causal relationship between microbiota and T2D established using fecal microbiota transplantation (FMT) or probiotic supplementation, and the potential underlying mechanisms such as byproducts of microbial metabolism. These microbial metabolites are small molecules that establish communication between microbiota and host cells. We critically summarize the associations between T2D and microbial metabolites such as short-chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Additionally, we comment on how host genetic architecture and the epigenome influence the microbial composition and thus how the gut microbiota may explain part of the missing heritability of T2D found by GWAS analysis. We also discuss future directions in this field and how approaches such as FMT, prebiotics, and probiotics supplementation are being considered as potential therapeutics for T2D.
The Interrelation Between Language Anxiety and Self-Determined Motivation; A Mixed Methods Approach

The relationship between language anxiety and self-determined motivation has been examined from various aspects in the applied linguistics domain. However, the direction of the relationship tend to disagree. Some studies report positive correlation whereas others (and in most cases) show negative correlation. To address this issue, the present study attempted to evaluate in depth the relationship between these two variables. We first qualitatively examined the types of language anxiety students face during learning, and then assessed how motivational variables based on self-determination theory can predict these identified types of anxiety. The results showed that sense of competence and relatedness negatively predicted certain types of anxiety while controlled motivation positively predicted only the general language anxiety. However, perception of autonomy and autonomous motivation did not predict any sub-types of language anxiety while sense of relatedness positively predicted psychological anxiety. The findings are discussed in terms of their theoretical and educational implications for language learning.
Case Report: Inflammation and Endothelial Injury Profiling of COVID-19 Pediatric Multisystem Inflammatory Syndrome (MIS-C)

Introduction: COVID-19 is associated with a novel multi-system inflammatory syndrome that shares some characteristics with Kawasaki's Disease. The syndrome manifestation is delayed relative to COVID-19 onset, with a spectrum of clinical severity. Clinical signs may include persistent fever, gastrointestinal symptoms, cardiac inflammation and/or shock. Case Presentation: We measured 59 inflammatory and endothelial injury plasma analytes in an adolescent girl that presented with malaise, fever, cough, strawberry tongue and jaundice. Her COVID-19 status was positive with detection of 2 SARS-CoV-2 viral genes using polymerase chain reaction. She was treated with intravenous immunoglobulin prior to blood draw, but our plasma measurements suggested a unique analyte expression pattern associated with inflammation, endothelial injury and microvascular glycocalyx degradation. Conclusions: COVID-19 is associated with a multi-system inflammatory syndrome and a unique inflammatory and endothelial injury signature. Summary: Analyte markers of inflammation and endothelial cell injury might serve as putative biomarkers and/or be investigated further as potential therapeutic targets.
A Validated Nomogram That Predicts Prognosis of Autoimmune Encephalitis: A Multicenter Study in China

The aim of this retrospective study was to derive and validate a reliable nomogram for predicting prognosis of autoimmune encephalitis (AE). A multi-center retrospective study was conducted in four hospitals in China, using a random split-sample method to allocate 173 patients into either a training (n = 126) or validation (n = 47) dataset. Demographic, radiographic and therapeutic presentation, combined with clinical features were collected. A modified Rankin Scale (mRS) at discharge was the principal outcome variable. A backward-stepwise approach based on the Akaike information criterion was used to test predictors and construct the final, parsimonious model. Multivariable analysis was conducted using logistic regression to develop a prognosis model and validate a nomogram using an independent dataset. The performance of the model was assessed using receiver operating characteristic curves and a Hosmer-Lemeshow test. The final nomogram model considered age, viral prodrome, consciousness impairment, memory dysfunction and autonomic dysfunction as predictors. Model validations displayed a good level of discrimination in the validation set: area under the Receiver operator characteristic curve = 0.72 (95% Confidence Interval: 0.56–0.88), Hosmer–Lemeshow analysis suggesting good calibration (chi-square: 10.33; p = 0.41). The proposed nomogram demonstrated considerable potential for clinical utility in prediction of prognosis in autoimmune encephalitis.