Miracle-dz/UniFAR-FTUs huggingface dataset:
Response of Nitrate Processing to Bio-labile Dissolved Organic Matter Supply Under Variable Oxygen Conditions in a Sandy Beach Seepage Face

Supply of bio-labile dissolved organic matter (DOM) has been assumed to be a key factor for the intensity of nitrate (NO3–) removal in permeable coastal sediments. In the present study, a series of flow through reactor experiments were conducted using glucose as a N-free bio-labile DOM source to permeable sediments from a sandy beach seepage face to identify its effect on benthic NO3– removal. The results revealed a shift from the dominance of NO3– production to removal processes when NO3– input concentration increased from 10 to 80 μM under oxic conditions. Sediment microbiota information suggests that nitrification (e.g., Nitrosomonas and Nitrososphaera) and denitrification (e.g., Marinobacter and Bacillus) were dominant pathways for benthic NO3– production and removal in the studied sediment. Compared with the active response of sediment microbiota to NO3– additions, the supply of glucose (approximately 300 μM final concentration added) did not significantly change the NO3– removal efficiency under aerobic conditions (dissolved oxygen saturation approximately 100%). Similarly, an insignificant increase of NO3– removal rate after glucose amendment of the circulating water was obtained when dissolved oxygen (DO) saturation decreased to approximately 70% in the input solution. When DO at the input solution was decreased to 30% saturation (sub-oxic conditions), the removal rate of NO3– in the group amended with glucose increased, suggesting that glucose stimulated denitrifiers. These results revealed that NO3– removal relied mainly on the anaerobic environment at particle surfaces, with a dependence on the sedimentary organic matter as an electron supplier under bulk aerobic conditions, while the bio-labile DOM was consumed mainly by aerobic respiration instead of stimulating NO3– reduction. However, the respiration triggered by the over-supply of bio-labile DOM reduced the DO in the porewater, likely depressing the activity of aerobic reactions in the permeable sediment. At this point, the benthic microbiota, especially potential denitrifiers, shifted to anaerobic reactions as the key to support nitrogen metabolism. The glucose amendment benefited NO3– reduction at this point, under sub-oxic conditions.
Different Effects of Total Bilirubin on 90-Day Mortality in Hospitalized Patients With Cirrhosis and Advanced Fibrosis: A Quantitative Analysis

Introduction: Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality via evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Methods: Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the “TB-mortality correlation curves. ” The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Results: Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. Conclusion: This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
E183K Mutation in Chalcone Synthase C2 Causes Protein Aggregation and Maize Colorless

Flavonoids give plants their rich colors and play roles in a number of physiological processes. In this study, we identified a novel colorless maize mutant showing reduced pigmentation throughout the whole life cycle by EMS mutagenesis. E183K mutation in maize chalcone synthase C2 (ZmC2) was mapped using MutMap strategy as the causal for colorless, which was further validated by transformation in Arabidopsis. We evaluated transcriptomic and metabolic changes in maize first sheaths caused by the mutation. The downstream biosynthesis was blocked while very few genes changed their expression pattern. ZmC2-E183 site is highly conserved in chalcone synthase among Plantae kingdom and within species’ different varieties. Through prokaryotic expression, transient expression in maize leaf protoplasts and stable expression in Arabidopsis, we observed that E183K and other mutations on E183 could cause almost complete protein aggregation of chalcone synthase. Our findings will benefit the characterization of flavonoid biosynthesis and contribute to the body of knowledge on protein aggregation in plants.
Cognitive Profiles of Amyotrophic Lateral Sclerosis Differ in Resting-State Functional Connectivity: An fMRI Study

Background Half of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity. Methods Healthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson’s correlation. Results At a liberal alpha level of uncorrected p < 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of pFDR< 0.001. Conclusion Resting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting.
Nano Based Approach for the Treatment of Neglected Tropical Diseases

Neglected tropical diseases (NTDs) afflict more than one billion peoples in the world’s poorest countries. The World Health Organization (WHO) has recorded seventeen NTDs in its portfolio, mainly caused by bacterial, protozoal, parasitic, and viral infections. Each of the NTDs has its unique challenges on human health such as interventions for control, prevention, diagnosis, and treatment. Research for the development of new drug molecules against NTDs has not been undertaken by pharmaceutical industries due to high investment and low-returns, which results in limited chemotherapeutics in the market. In addition, conventional chemotherapies for the treatment of NTDs are unsatisfactory due to its low efficacy, increased drug resistance, short half-life, potential or harmful fatal toxic side effects, and drug incompetence to reach the site of parasite infection. In this context, active chemotherapies are considered to be re-formulated by overcoming these toxic side effects via a tissue-specific targeted drug delivery system. This review mainly emphasizes the recent developments of nanomaterial-based drug delivery systems for the effective treatment of NTDs especially sleeping sickness, leishmaniasis, chagas disease, soil-transmitted helminthiasis, african trypanosomiasis and dengue. Nanomaterials based drug delivery systems offer enhanced and effective alternative therapy through the re-formulation approach of conventional drugs into site-specific targeted delivery of drugs.
Editorial: Repurposed Drugs Targeting Cancer Signaling Pathways: Clinical Insights to Improve Oncologic Therapies

The analyses of drug development from different standpoints show how resource-intensive this process is, with two main disadvantages: time and cost. It takes 11 to 14 years to develop a pharmaceutical product, with a financial cost currently estimated around 161-1,800 million dollars (1). Bypassing these limitations has made drug repositioning one of the most burgeoning areas in pharmacology over the past decade. Drug repositioning finds new applications of existing drugs by testing them against diseases unrelated to their initial use; so, the availability of complete data on pharmacology, formulation, safety, and adverse effects reduces development time and cost. However, it also has disadvantages: managing patents, intellectual property, investment, market demand, and even production technology (2). Regardless, drug repositioning poses a fascinating challenge with the potential to improve human health, in particular for the treatment of various types of cancer, but also a complex challenge in the legal and regulatory fields (3). Drug repurposing has captivated the cancer research community due to the increasing demand for new anticancer drugs. Although there are several treatments, such as chemotherapy and targeted therapies, cancer is characterized by the eventual development of resistance or lack of response to these drugs and medications, making the design of new drugs against cancer a flourishing area of study. In this regard, drug repositioning is an attractive research area that has gained tremendous popularity. Oncology has taken advantage of existing, well-characterized, widely-used, non-cancer drugs and successfully tested them as anticancer agents (4–6). To get an overall picture, we searched the Medline (pubmed.ncbi.nlm.nih.gov) and ClinicalTrials.gov (clinicaltrials.gov) databases for
Metabolic Control of Smoldering Neuroinflammation

Compelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation.
Enhanced Information Flow From Cerebellum to Secondary Visual Cortices Leads to Better Surgery Outcome in Degenerative Cervical Myelopathy Patients: A Stochastic Dynamic Causal Modeling Study With Functional Magnetic Resonance Imaging

Degenerative cervical myelopathy (DCM) damages the spinal cord, resulting in long-term neurological impairment including motor and visual deficits. Given that visual feedback is crucial in guiding movements, the visual disorder may be a cause of motor deficits in patients with DCM. It has been shown that increased functional connectivity between secondary visual cortices and cerebellum, which are functionally related to the visually guided movements, was correlated with motor function in patients with DCM. One possible explanation is that the information integration between these regions was increased to compensate for impaired visual acuity in patients with DCM and resulted in better visual feedback during motor function. However, direct evidence supporting this hypothesis is lacking. To test this hypothesis and explore in more detail the information flow within the “visual-cerebellum” system, we measured the effective connectivity (EC) among the “visual-cerebellum” system via dynamic causal modeling and then tested the relationship between the EC and visual ability in patients with DCM. Furthermore, the multivariate pattern analysis was performed to detect the relationship between the pattern of EC and motor function in patients with DCM. We found (1) significant increases of the bidirectional connections between bilateral secondary visual cortices and cerebellum were observed in patients with DCM; (2) the increased self-connection of the cerebellum was positively correlated with the impaired visual acuity in patients; (3) the amplitude of effectivity from the cerebellum to secondary visual cortices was positively correlated with better visual recovery following spinal cord decompression surgery; and (4) the pattern of EC among the visual-cerebellum system could be used to predict the pre-operative motor function. In conclusion, this study provided direct evidence that the increased information integration within the “visual-cerebellum” system compensated for visual impairments, which might have importance for sustaining better motor function in patients with DCM.
Thermal Stress Affects Gonadal Maturation by Regulating GnRH, GnRH Receptor, APGWamide, and Serotonin Receptor Gene Expression in Male Pacific Abalone, Haliotis discus hannai During Breeding Season

Temperature has crucial effects on gonadal development and reproduction of abalone. To understand the impact of thermal stress on molecular and physiological processes triggering the regulation of reproduction, changes in the mRNA expression of neuroendocrine genes encoding two abalone gonadotropin-releasing hormone (Hdh-GnRH, Hdh-GnRH-like peptide), GnRH receptor (Hdh-GnRH-R), Hdh-APGWamide, serotonin receptor (5-HThdh), and a heat shock protein HSP70 were examined in ganglia and testis of male Pacific abalone (Haliotis discus hannai). Abalone were exposed to low water temperature (LWT) and high water temperature (HWT) in early and peak breeding seasons for 7 days. Then, gonadosomatic index (GSI) was calculated, relative gene expression was measured by qRT-PCR, and levels of testosterone in hemolymph were also measured by ELISA during the peak breeding season. GSI did not show any significant changes during the early breeding season. However, it was significantly decreased in LWT- or HWT-exposed abalone compared to the normal water temperature (NWT) group during the peak breeding season. In the early breeding season, changes of mRNA expression of all five genes were significant between LWT and HWT groups on day-7. In the peak breeding season, compared to the NWT group, the mRNA expressions of different genes were significantly decreased in different tissues both in LWT and HWT groups of abalone, such as Hdh-GnRH-like peptide in the cerebral ganglion (CG) and testis; Hdh-GnRH in the pleuropedal ganglion (PPG) and branchial ganglion (BG); Hdh-GnRH-R in the CG, PPG, and testis; and Hdh-APGWamide in the PPG and testis. Interestingly, the expression of 5-HThdh was significantly increased in the HWT group but decreased in the LWT group. Expression of HSP70 was significantly increased in the testis after exposure to HWT. Hemolymph levels of testosterone were significantly decreased in the HWT group compared to those in the NWT group. Altogether, these results denote that thermal stress has a repressive effect on gonadal maturation and reproduction by regulating the expression of Hdh-GnRH-like peptide, Hdh-GnRH, Hdh-GnRH-R, Hdh-APGWamide, 5-HThdh, and HSP70 genes and levels of hemolymph testosterone.
Effectiveness of Virtual/Augmented Reality–Based Therapeutic Interventions on Individuals With Autism Spectrum Disorder: A Comprehensive Meta-Analysis

In recent years, the application of virtual reality (VR) for therapeutic purposes has escalated dramatically. Favorable properties of VR for engaging patients with autism, in particular, have motivated an enormous body of investigations targeting autism-related disabilities with this technology. This study aims to provide a comprehensive meta-analysis for evaluating the effectiveness of VR on the rehabilitation and training of individuals diagnosed with an autism spectrum disorder. Accordingly, we conducted a systematic search of related databases and, after screening for inclusion criteria, reviewed 33 studies for more detailed analysis. Results revealed that individuals undergoing VR training have remarkable improvements with a relatively large effect size with Hedges g of 0.74. Furthermore, the results of the analysis of different skills indicated diverse effectiveness. The strongest effect was observed for daily living skills (g = 1.15). This effect was moderate for other skills: g = 0.45 for cognitive skills, g = 0.46 for emotion regulation and recognition skills, and g = 0.69 for social and communication skills. Moreover, five studies that had used augmented reality also showed promising efficacy (g = 0.92) that calls for more research on this tool. In conclusion, the application of VR-based settings in clinical practice is highly encouraged, although their standardization and customization need more research.
Physiologically Based Pharmacokinetics Model in Pregnancy: A Regulatory Perspective on Model Evaluation

Physiologically based pharmacokinetics (PBPK) modelling is widely used in medicine development and regulatory submissions. The lack of clinical pharmacokinetic data in pregnancy is widely acknowledged; therefore, one area of current interest is in the use of PBPK modelling to describe the potential impact of anatomical and physiological changes during pregnancy on the medicine's pharmacokinetics. PBPK modelling could possibly represent a predictive tool to support the medicine benefit–risk decision and inform dose adjustment in this population and also to investigate medicine levels in the foetus to support the risk assessment to the foetus. In the context of regulatory application, there are, however, a number of considerations around model evaluation, and this should be tailored to the model purpose, in order to inform the confidence in the model for the intended application. A number of gestational age-related physiological changes are expected to alter the pharmacokinetics of medicines during pregnancy, and there are uncertainties on some parameters; therefore, well-qualified models are needed to improve assurance in the model prediction before this approach can be used to inform with confidence high-impact decisions as part of regulatory submissions.
Strategies for Constructing College Students' Entrepreneurial Value Judgments Based on Educational Psychology

Against the background of economic globalization, the strategies for constructing college students' entrepreneurial value judgment are explored, providing college graduates with more employment options and thereby keeping up with the trend of the times. The documentary analysis and questionnaire survey methods are adopted to investigate contemporary college students' entrepreneurial value judgments, and the investigation results are organized. According to documentary materials, the discovered problems are analyzed to put forward strategies for constructing college students' entrepreneurial value judgments based on educational psychology. Results show that only 14.1% of college graduates choose to start a business; 48.7% do not understand or recognize the entrepreneurial values; 14.8% believe teaching activities on constructing entrepreneurial value judgments are insufficient, and the entrepreneurial atmosphere is lacking. Regarding the above investigation results, strategies for constructing college students' entrepreneurial value judgments are proposed, involving the construction environment, construction system, construction method, and construction mechanism. Hence, considering contemporary college students' entrepreneurial values, the proposed strategies for constructing college students' entrepreneurial judgments are suitable and valuable, providing a practical reference for enriching and perfecting the college innovation and entrepreneurship education systems.
Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

Breast cancer is the second leading cause of death among women worldwide, and while hormone receptor positive subtypes have a clear and effective treatment strategy, other subtypes, such as triple negative breast cancers, do not. Development of new drugs, antibodies, or immune targets requires significant re-consideration of current preclinical models, which frequently fail to mimic the nuances of patient-specific breast cancer subtypes. Each subtype, together with the expression of different markers, genetic and epigenetic profiles, presents a unique tumor microenvironment, which promotes tumor development and progression. For this reason, personalized treatments targeting components of the tumor microenvironment have been proposed to mitigate breast cancer progression, particularly for aggressive triple negative subtypes. To-date, animal models remain the gold standard for examining new therapeutic targets; however, there is room for in vitro tools to bridge the biological gap with humans. Tumor-on-chip technologies allow for precise control and examination of the tumor microenvironment and may add to the toolbox of current preclinical models. These new models include key aspects of the tumor microenvironment (stroma, vasculature and immune cells) which have been employed to understand metastases, multi-organ interactions, and, importantly, to evaluate drug efficacy and toxicity in humanized physiologic systems. This review provides insight into advanced in vitro tumor models specific to breast cancer, and discusses their potential and limitations for use as future preclinical patient-specific tools.