Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-22 regulates immunity, inflammation and tissue homeostasis at mucosal sites

At mucosal sites, a single layer of epithelial cells separates the connective tissues of the mammalian body from the external environment. The gastrointestinal tract is the largest mucosal surface exposed to the environment and is colonized with an estimated 300 trillion beneficial commensal bacteria. These properties of mucosal sites help facilitate critical biological processes, including nutrient absorption, gas exchange and excretion of wastes, yet also renders mucosal sites particularly vulnerable to infection and inflammation. In order to maintain a state of health, complex immunoregulatory networks have evolved at mucosal sites to promote immunity, limit inflammation and maintain tissue homeostasis. Interleukin (IL)-22 is a member of the IL-10 cytokine family that is produced by both innate and adaptive immune cells, and acts directly on the mucosal epithelium to promote anti-microbial, reparative and inflammatory responses. Chapter 2 of this thesis examines the role and regulation of IL-22 production by innate lymphoid cells (ILCs) in promoting immunity to the enteric bacterial pathogen Citrobacter rodentium. The data identify that following infection, IL-23 promotes an IL-22+ CD4+ ILC response that is necessary and sufficient to promote enteric immunity, limit bacteria dissemination and prevent host morbidity and mortality. In addition to pathogenic bacteria, loss of containment and peripheral dissemination of beneficial commensal bacteria results in dysregulated systemic immune cell homeostasis, and is a hallmark of numerous chronic human diseases. Chapter 3 of this thesis demonstrates a novel role for IL-22-producing ILCs in containing intestinal commensal bacteria, limiting peripheral dissemination and induction of systemic inflammation. Finally, studies have identified both pathologic proinflammatory and beneficial tissue-protective functions for IL-22 in distinct models of infection and inflammation. Chapter 4 of this thesis identifies that the pathologic proinflammatory versus tissue-protective properties of IL-22 in a model of airway inflammation are regulated by Th17 cell-derived IL-17A. Collectively, studies presented in this thesis identify novel regulatory and functional aspects of IL-22 and ILCs, and demonstrate a critical role for this pathway in the immunoregulation of tissue homeostasis at mucosal sites. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Immunology First Advisor David Artis
Osmoregulatory Physiology of Pupfish (Cyprinodon spp.) in Freshwater

of a dissertation at the University of Miami. Dissertation supervised by Professor Martin Grosell. No. of pages in text. (148) Active uptake of Na + at the gill by fish is fundamental to their osmoregulation and thus survival in freshwater environments. Studies to date have demonstrated several different mechanisms by which fish can accomplish this important physiological function. This dissertation provides a comparative characterization of Na + uptake in the coastal pupfish, Cyprinodon variegatus variegatus (Cvv), the closely related Lake Eustis pupfish, C. v. hubbsi (Cvh), and the endangered desert pupfish, C. macularius (Cm). When acclimated to slightly saline freshwater (7 mM Na + ) all three fish use a low affinity Na + /H + exchanger (NHE) for apical Na + uptake. Cvv also uses a Na + :K + :2Cl cotransporter under these conditions, the first time this has been functionally demonstrated in a freshwater fish. When acclimated to 2 mM Na + , all three fish strictly rely on a low affinity NHE for Na + uptake. Only Cvh, which naturally occurs in eight dilute freshwater lakes in central Florida, was able to acclimate to 0.1 mM Na + and under these conditions switches to a high affinity NHE for Na + uptake. In other fish studied to date that use a high affinity NHE in dilute freshwater, the NHE operates in a metabolon with an Rh glycoprotein (ammonia transporter) that provides H + for the operation of NHE in this thermodynamically constrained environment. This dissertation confirmed that Cvh does not use an NHE-Rh metabolon, but instead acquires H + from carbonic anhydrase mediated hydration of CO2 to allow for NHE operation in dilute freshwater. This is the first time this has been demonstrated in a fish exposed to low Na + water. Finally, because Cvh only occurs in eight lakes in central Florida, all of which are suffering from habitat loss and water quality degradation through urban development, this dissertation evaluated whether Cvh should be designated a separate species from Cvv, allowing for greater environmental protection. While there is no clear consensus on the definition of a species, within the regulatory framework of the Endangered Species Act, this dissertation demonstrated heritable physiological differences between Cvv and Cvh, partial preand post-zygotic isolation between the two subspecies, and likely monophyletic origin for Cvh, all of which support the designation of Cvh as an evolutionarily significant unit, and likely a separate species.
SDN2GO: An Integrated Deep Learning Model for Protein Function Prediction

The assignment of function to proteins at a large scale is essential for understanding the molecular mechanism of life. However, only a very small percentage of the more than 179 million proteins in UniProtKB have Gene Ontology (GO) annotations supported by experimental evidence. In this paper, we proposed an integrated deep-learning-based classification model, named SDN2GO, to predict protein functions. SDN2GO applies convolutional neural networks to learn and extract features from sequences, protein domains, and known PPI networks, and then utilizes a weight classifier to integrate these features and achieve accurate predictions of GO terms. We constructed the training set and the independent test set according to the time-delayed principle of the Critical Assessment of Function Annotation (CAFA) and compared it with two highly competitive methods and the classic BLAST method on the independent test set. The results show that our method outperforms others on each sub-ontology of GO. We also investigated the performance of using protein domain information. We learned from the Natural Language Processing (NLP) to process domain information and pre-trained a deep learning sub-model to extract the comprehensive features of domains. The experimental results demonstrate that the domain features we obtained are much improved the performance of our model. Our deep learning models together with the data pre-processing scripts are publicly available as an open source software at https://github.com/Charrick/SDN2GO.
First Experience in Korea of Stereotactic Partial Breast Irradiation for Low-Risk Early-Stage Breast Cancer

Purpose: Accelerated partial breast irradiation (A-PBI) in Korean women has been considered impracticable, owing to small breast volume and lack of high-precision radiotherapy experience. We present the first experience of stereotactic-PBI (S-PBI) with CyberKnife M6 to investigate feasibility of use and early toxicities in Korean women with early breast cancers. Materials and Methods: A total of 104 breasts receiving S-PBI at our institution between September 2017 and October 2018 were reviewed. Patients were selected based on the American Society for Radiation Oncology (ASTRO), American Brachytherapy Society, American Society of Breast Surgeons, and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology guidelines. A dose of 30 Gy in 5 fractions (NCT01162200) was used. Gold fiducials were routinely inserted near the tumor bed for tracking. Constraints regarding organs-at-risk followed the NSABP-B39/RTOG 0413 protocol. Results: Median follow-up was for 13 months. Patients were categorized as “suitable” (71.2%) or “cautionary” (28.8%) according to 2017 the ASTRO guidelines. No tracking failure of inserted gold fiducials occurred. Median planning target volume (PTV) and PTV-to-whole breast volume ratio was 73.6 mL (interquartile range, 58.8–103.9 mL) and 17.0% (13.3–19.1%), respectively. Median PTV V95%, PTV Dmax, and ipsilateral breast V50% were 97.8% (96.2–98.8%), 105.3% (104.2–106.4%), and 35.5% (28.3–39.8%), respectively. No immediate post-S-PBI toxicity ≥ grade 2 was reported, except grade 2 induration in three breasts. All patients remain disease-free to date. Conclusion: The first use of S-PBI in Korean women was feasible and safe for selected early breast cancer. Based on these results, we have initiated a prospective study (NCT03568981) to test S-PBI in whole-breast irradiation for low-risk early breast cancer.
Frequency-Tagging Electroencephalography of Superimposed Social and Non-Social Visual Stimulation Streams Reveals Reduced Saliency of Faces in Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) have difficulties with social communication and interaction. The social motivation hypothesis states that a reduced interest in social stimuli may partly underlie these difficulties. Thus far, however, it has been challenging to quantify individual differences in social orientation and interest, and to pinpoint the neural underpinnings of it. In this study, we tested the neural sensitivity for social versus non-social information in 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ, while children were engaged in an orthogonal task. We recorded electroencephalography (EEG) during fast periodic visual stimulation (FPVS) of social versus non-social stimuli to obtain an objective implicit neural measure of relative social bias. Streams of variable images of faces and houses were superimposed, and each stream of stimuli was tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). This frequency-tagging method allows disentangling the respective neural responses evoked by the different streams of stimuli. Moreover, by using superimposed stimuli, we controlled for possible effects of preferential looking, spatial attention, and disengagement. Based on four trials of 60 s, we observed a significant three-way interaction. In the control group, the frequency-tagged neural responses to faces were larger than those to houses, especially in lateral occipito-temporal channels, while the responses to houses were larger over medial occipital channels. In the ASD group, however, faces and houses did not elicit significantly different neural responses in any of the regions. Given the short recording time of the frequency-tagging paradigm with multiple simultaneous inputs and the robustness of the individual responses, the method could be used as a sensitive marker of social preference in a wide range of populations, including younger and challenging populations.
The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection

The RTS,S/AS01 vaccine provides partial protection against Plasmodium falciparum infection but determinants of protection and/or disease are unclear. Previously, anti-circumsporozoite protein (CSP) antibody titers and blood RNA signatures were associated with RTS,S/AS01 efficacy against controlled human malaria infection (CHMI). By analyzing host blood transcriptomes from five RTS,S vaccination CHMI studies, we demonstrate that the transcript ratio MX2/GPR183, measured 1 day after third immunization, discriminates protected from non-protected individuals. This ratiometric signature provides information that is complementary to anti-CSP titer levels for identifying RTS,S/AS01 immunized people who developed protective immunity and suggests a role for interferon and oxysterol signaling in the RTS,S mode of action.
Biosurfactants : Properties, commercial production and application

Biosurfactants or microbial surfactants are surface-active biomolecules that are produced by a variety of microorganisms. Biosurfactants have gained importance in the fields of enhanced oil recovery, environmental bio-remediation, food processing and pharmaceuticals owing to their unique properties such as higher biodegradability and lower toxicity. Interest in the production of biosurfactants has steadily increased during the past decade. However, large-scale production of these molecules has not been realized because of low yields in production processes and high recovery and purification costs. This article describes some practical approaches that have been adopted to make the bio-surfactant production process economically attractive. These include the use of cheaper raw materials, optimized and efficient bioprocesses and overproducing mutant and recombinant strains for obtaining maximum productivity. Here, we discuss the role and applications of biosurfactants focusing mainly on medicinal and therapeutic perspectives. With these specialized and cost-effective applications in biomedicine, we can look forward to biosurfactants as the molecules of the future.
Implied Volatility Structure in Turbulent and Long-Memory Markets

We consider fractional stochastic volatility models that extend the classic Black–Scholes model for asset prices. The models are general and motivated by recent empirical results regarding the behavior of realized volatility. While such models retain the semimartingale property for the asset price the associated European option pricing problem becomes complex, with no explicit solution. In a number of canonical scaling regimes it is possible, however, to derive asymptotic and sparse representations for the option price and the associated implied volatility, that are parameterized by a few effective parameters and that involve power law dependencies on time to maturity. These effective parameters may depend in a complicated way on the volatility model, but they can be easily estimated from the observation of a few option prices. The effective parameters associated with a particular underlying asset can be calibrated with respect to liquid contracts written on this asset and then used for pricing less liquid contracts written on the same underlying asset. Therefore, the effective parameters provide a robust link between financial products written on a particular underlying asset.
Biochar Application Alleviated Negative Plant-Soil Feedback by Modifying Soil Microbiome

Negative plant-soil feedback (NPSF) frequently cause replant failure in agricultural ecosystems, which has been restricting the sustainable development of agriculture. Biochar application has appealing effects on soil improvement and potential capacity to affect NPSF, but the process is poorly understood. Here, our study demonstrated that biochar amendment can effectively alleviate the NPSF and this biochar effect is strongly linked to soil microorganism in a sanqi (Panax notoginseng) production system. High-throughput sequencing showed that the bacterial and fungal communities were altered with biochar amendment, and bacterial community is more sensitive to biochar amendment than the fungal community. Biochar amendment significantly increased the soil bacterial diversity, but the fungal diversity was not significantly different between biochar-amended and non-amended soils. Moreover, we found that biochar amendment significantly increased the soil pH, electrical conductivity, organic matter, available phosphorus, available potassium, and C/N ratio. The correlation analysis showed that these increased soil chemical variables have a significantly positive correlation with the bacterial diversity. Further analysis of the soil microbial composition demonstrated that biochar soil amendment enriched the beneficial bacterium Bacillus and Lysobacter but suppressed pathogens Fusarium and Ilyonectria. In addition, we verified that biochar had no direct effect on the pathogen Fusarium solani, but can directly enrich biocontrol bacterium Bacillus subtilis. In short, biochar application can mitigate NPSF is mostly due to the fact that biochar soil amendment modified the soil microbiome, especially inhibited pathogens by enriching beneficial bacterium with antagonistic activity against pathogen.
Proteomics Unravels Emodin Causes Liver Oxidative Damage Elicited by Mitochondrial Dysfunction

Emodin is one of the main active compounds in many Chinese traditional herbs. Due to its potential toxic effect on the liver, the possible injury mechanism needs to be explored. In the present study, we investigated liver injury mechanisms of emodin on rats by the technology of proteomics. Firstly, 4530 proteins were identified from the liver of rats treated with emodin by label free proteomics. Inside, 892 differential proteins were selected, presenting a downward trend. Bioinformatics analysis showed that proteins interfered with by emodin were mainly involved in oxidation-reduction biological processes and mitochondrial metabolic pathways, such as mitochondrial fatty acid β-oxidation, citric acid cycle, and oxidative phosphorylation, which were further confirmed by western blot. The decrease in maximal respiration, ATP production, spare respiratory capacity, and coupling efficiency and increase in proton leakage were detected by seahorse XFe 24 analyzer, which confirmed the damage of mitochondrial function. The down-regulated expressions in antioxidant proteins were verified by western blot and a significant increase of ROS levels were detected in emodin group, which showed that emodin disrupted redox homeostasis in livers. Molecular docking revealed that the main targets of emodin might be acadvl and complex IV. Generally, emodin could induce oxidative stress in livers by directly targeting acadvl/complex IV and inhibiting fatty acid β-oxidation, citric acid cycle, and oxidative phosphorylation taken place in mitochondria.
Novelty Manipulations, Memory Performance, and Predictive Coding: the Role of Unexpectedness

Novelty is central to the study of memory, but the wide range of experimental manipulations aimed to reveal its effects on learning produced inconsistent results. The novelty/encoding hypothesis suggests that novel information undergoes enhanced encoding and thus leads to benefits in memory, especially in recognition performance; however, recent studies cast doubts on this assumption. On the other hand, data from animal studies provided evidence on the robust effects of novelty manipulations on the neurophysiological correlates of memory processes. Conceptualizations and operationalizations of novelty are remarkably variable and were categorized into different subtypes, such as stimulus, context, associative or spatial novelty. Here, we summarize previous findings about the effects of novelty on memory and suggest that predictive coding theories provide a framework that could shed light on the differential influence of novelty manipulations on memory performance. In line with predictive coding theories, we emphasize the role of unexpectedness as a crucial property mediating the behavioral and neural effects of novelty manipulations.
Validation of the Toronto Empathy Questionnaire (TEQ) Among Medical Students in China: Analyses Using Three Psychometric Methods

This study aimed to validate the simplified Chinese version of the Toronto Empathy Questionnaire (cTEQ) for use with the Chinese population. The original English version of the TEQ was translated into simplified Chinese based on international criteria. Psychometric analyses were performed based on three psychometric methods: classical test theory (CTT), item response theory (IRT), and Rasch model theory (RMT). Differential item functioning analysis was adopted to check possible item bias caused by responses from different subgroups based on sex and ethnicity. A total of 1296 medical students successfully completed the TEQ through an online survey; 75.2% of respondents were female and the average age was 19 years old. Forty students completed the questionnaire 2 weeks later to assess the test–retest reliability of the questionnaire. Confirmatory factor analysis supported a 3-factor structure of the cTEQ. The CTT analyses confirmed that the cTEQ has sound psychometric properties. However, IRT and RMT analyses suggested some items might need further modifications and revisions.
Model-Informed Precision Dosing of Vancomycin in Hospitalized Children: Implementation and Adoption at an Academic Children’s Hospital

Background Model-informed precision dosing (MIPD) can serve as a powerful tool during therapeutic drug monitoring (TDM) to help individualize dosing in populations with large pharmacokinetic variation. Yet, adoption of MIPD in the clinical setting has been limited. Overcoming technologic hurdles that allow access to MIPD at the point-of-care and placing it in the hands of clinical specialists focused on medication dosing may encourage adoption. Objective To describe the hospital implementation and usage of a MIPD clinical decision support (CDS) tool for vancomycin in a pediatric population. Methods Within an academic children’s hospital, MIPD for vancomycin was implemented via a commercial cloud-based CDS tool that utilized Bayesian forecasting. Clinical pharmacists were recognized as local champions to facilitate adoption of the tool and operated as end-users. Integration within the electronic health record (EHR) and automatic transmission of patient data to the tool were identified as important requirements. A web-link icon was developed within the EHR which when clicked sends users and needed patient-level clinical data to the CDS platform. Individualized pharmacokinetic predictions and exposure metrics for vancomycin are then presented in the form of a web-based dashboard. Use of the CDS tool as part of TDM was tracked and users were surveyed on their experience. Results After a successful pilot phase in the neonatal intensive care unit, implementation of MIPD was expanded to the pediatric intensive care unit, followed by availability to the entire hospital. During the first 2+ years since implementation, a total of 853 patient-courses (n = 96 neonates, n = 757 children) and 2,148 TDM levels were evaluated using the CDS tool. For the most recent 6 months, the CDS tool was utilized to support 79% (181/230) of patient-courses in which TDM was performed. Of 26 users surveyed, > 96% agreed or strongly agreed that automatic transmission of patient data to the tool was a feature that helped them complete tasks more efficiently; 81% agreed or strongly agreed that they were satisfied with the CDS tool. Conclusions Integration of a vancomycin CDS tool within the EHR, along with leveraging the expertise of clinical pharmacists, allowed for successful adoption of MIPD in clinical care.