Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Histone Deacetylase Inhibition Mitigates Ischemia/Reperfusion Brain Injury by Reducing Microglia Activation and Modulating Their Phenotype

Histone deacetylase inhibitors (HDACi) are a promising therapeutic intervention for stroke. The involvement of the anti-inflammatory effects of HDACi in their neuroprotection has been reported, but the underlying mechanisms are still uncertain. Given the post-stroke inflammation is a time-dependent process, starting with acute and intense inflammation, and followed by a prolonged and mild one, we proposed whether target the early inflammatory response could achieve the neuroprotection of HDACi? To test this hypothesis, a single dose of suberoylanilide hydroxamic acid (SAHA) (50 mg/kg), a pan HDACi, was intraperitoneally (i.p.) injected immediately or 12 h after ischemia onset in a transient middle cerebral artery occlusion (tMCAO) mouse model. Compared with delayed injection, immediate SAHA treatment provided more protection, evidenced by smaller infarction volume, and a better outcome. This protection was accompanied by suppression of pro-inflammatory cytokines and reduction of activated microglia in the early stage of post-stroke inflammation. Moreover, SAHA treatment suppressed M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) in LPS-challenged mouse microglia, and enhanced CD206 (M2 marker) but decreased CD86 (M1 markers) levels in microglia isolated from the ipsilateral hemisphere of MCAO mice. Collectively, our data suggested that the protection of SAHA on ischemic brain injury was closely associated with its inhibition on the early inflammatory response, and this inhibition was related to its reducing microglia activation and priming the activated microglia toward a more protective phenotype.
Visitors to a Tropical Marine Beach Show Evidence of Immunoconversions to Multiple Waterborne Pathogens

Determining infections from environmental exposures, particularly from waterborne pathogens is a challenging proposition. The study design must be rigorous and account for numerous factors including study population selection, sample collection, storage, and processing, as well as data processing and analysis. These challenges are magnified when it is suspected that individuals may potentially be infected by multiple pathogens at the same time. Previous work demonstrated the effectiveness of a salivary antibody multiplex immunoassay in detecting the prevalence of immunoglobulin G (IgG) antibodies to multiple waterborne pathogens and helped identify asymptomatic norovirus infections in visitors to Boquerón Beach, Puerto Rico. In this study, we applied the immunoassay to three serially collected samples from study participants within the same population to assess immunoconversions (incident infections) to six waterborne pathogens: Helicobacter pylori, Campylobacter jejuni, Toxoplasma gondii, hepatitis A virus, and noroviruses GI. I and GII.4. Further, we examined the impact of sampling on the detection of immunoconversions by comparing the traditional immunoconversion definition based on two samples to criteria developed to capture trends in three sequential samples collected from study participants. The expansion to three samples makes it possible to capture the IgG antibody responses within the survey population to more accurately assess the frequency of immunoconversions to target pathogens. Based on the criteria developed, results showed that when only two samples from each participant were used in the analysis, 25.9% of the beachgoers immunoconverted to at least one pathogen; however, the addition of the third sample reduced immunoconversions to 6.5%. Of these incident infections, the highest levels were to noroviruses followed by T. gondii. Moreover, many individuals displayed evidence of immunoconversions to multiple pathogens. This study suggests that detection of simultaneous infections is possible, with far reaching consequences for the population. The results may lead to further studies to understand the complex interactions that occur within the body as the immune system attempts to ward off these infections. Such an approach is critical to our understanding of medically important synergistic or antagonistic interactions and may provide valuable and critical information to public health officials, water treatment personnel, and environmental managers.
Efficient Mining of Variants From Trios for Ventricular Septal Defect Association Study

Ventricular septal defect (VSD) is a fatal congenital heart disease showing severe consequence in affected infants. Early diagnosis plays an important role, particularly through genetic variants. Existing panel-based approaches of variants mining suffer from shortage of large panels, costly sequencing, and missing rare variants. Although a trio-based method alleviates these limitations to some extent, it is agnostic to novel mutations and computational intensive. Considering these limitations, we are studying a novel variants mining algorithm from trio-based sequencing data and apply it on a VSD trio to identify associated mutations. Our approach starts with irrelevant k-mer filtering from sequences of a trio via a newly conceived coupled Bloom Filter, then corrects sequencing errors by using a statistical approach and extends kept k-mers into long sequences. These extended sequences are used as input for variants needed. Later, the obtained variants are comprehensively analyzed against existing databases to mine VSD-related mutations. Experiments show that our trio-based algorithm narrows down candidate coding genes and lncRNAs by about 10- and 5-folds comparing with single sequence-based approaches, respectively. Meanwhile, our algorithm is 10 times faster and 2 magnitudes memory-frugal compared with existing state-of-the-art approach. By applying our approach to a VSD trio, we fish out an unreported gene—CD80, a combination of two genes—MYBPC3 and TRDN and a lncRNA—NONHSAT096266.2, which are highly likely to be VSD-related.
Ethical and Statistical Considerations in Models of Moral Judgments

This work extends recent advancements in computational models of moral decision making by using mathematical and philosophical theory to suggest adaptations to state of the art. It demonstrates the importance of model assumptions and considers alternatives to the normal distribution when modeling ethical principles. We show how the ethical theories, utilitarianism and deontology can be embedded into informative prior distributions. We continue to expand the state of the art to consider ethical dilemmas beyond the Trolley Problem and show the adaptations needed to address this complexity. The adaptations made in this work are not solely intended to improve recent models but aim to raise awareness of the importance of interpreting results relative to assumptions made, either implicitly or explicitly, in model construction.
Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice

Chinese herbal medicines used in combination have long-term been shown to be mild remedies with “integrated effects. ” However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.
Understanding Cancer Through the Lens of Epigenetic Inheritance, Allele-Specific Gene Expression, and High-Throughput Technology

Epigenetic information is characterized by its stable transmission during mitotic cell divisions and plasticity during development and differentiation. This duality is in contrast to genetic information, which is stable and identical in all cells in an organism with exception of immunoglobulin gene rearrangements in lymphocytes and somatic mutations in cancer cells. Allele-specific analysis of gene expression and epigenetic modifications provides a unique approach to studying epigenetic regulation in normal and cancer cells. Extension of Knudson's two-hits theory to include epigenetic alteration as a means to inactivate tumor suppressor genes provides better understanding of how genetic mutations and epigenetic alterations jointly contribute to cancer development. High-throughput technology has greatly accelerated cancer discovery. Large initiatives such as TCGA have shown that epigenetic components are frequent targets of mutations in cancer and these discoveries provide new insights into understanding cancer etiology and generate new opportunities for cancer therapeutics.
Assisting Operators in Heavy Industrial Tasks: On the Design of an Optimized Cooperative Impedance Fuzzy-Controller With Embedded Safety Rules

Human-robot cooperation is increasingly demanded in industrial applications. Many tasks require the robot to enhance the capabilities of humans. In this scenario, safety also plays an important role in avoiding any accident involving humans, robots, and the environment. With this aim, the paper proposes a cooperative fuzzy-impedance control with embedded safety rules to assist human operators in heavy industrial applications while manipulating unknown weight parts. The proposed methodology is composed by four main components: (i) an inner Cartesian impedance controller (to achieve the compliant robot behavior), (ii) an outer fuzzy controller (to provide the assistance to the human operator), (iii) embedded safety rules (to limit force/velocity during the human-robot interaction enhancing safety), and (iv) a neural network approach (to optimize the control parameters for the human-robot collaboration on the basis of the target indexes of assistance performance defined for this purpose). The main achieved result refers to the capability of the controller to deal with uncertain payloads while assisting and empowering the human operator, both embedding in the controller safety features at force and velocity levels and minimizing the proposed performance indexes. The effectiveness of the proposed approach is verified with a KUKA iiwa 14 R820 manipulator in an experimental procedure where human subjects evaluate the robot performance in a collaborative lifting task of a 10 kg part.
Systematic Analysis of Intestinal MicroRNAs Expression in HCC: Identification of Suitable Reference Genes in Fecal Samples

Hepatocellular carcinoma (HCC) is an extremely fatal malignancy. Intestinal microRNAs, which can be detected in fecal samples in humans may be involved in the pathological process of HCC. Therefore, screening for functional intestinal microRNAs in fecal samples and investigating their potential roles in the molecular progression of HCC are necessary. Quantitative real-time PCR (qRT-PCR) has been widely used in microRNA expression studies. However, few genes have been reported as reference genes for intestinal microRNAs in fecal samples. In order to obtain a more accurately analyzed intestinal microRNAs expression, we first searched for reliable reference genes for intestinal microRNAs expression normalization during qRT-PCR, using three software packages (GeNorm, NormFinder, and Bestkeeper). Next we screened and predicted the target genes of the differentially intestinal microRNAs of control and HCC mice through quantitative RT-PCR or miRtarBase. Finally, we also analyzed the mRNA targets for enrichment of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the DAVID Bioinformatic Resources database. This study has successfully screened relatively suitable reference genes and we have discovered that the differential intestinal microRNAs play significant roles in the development of HCC. The top reference genes identified in this study could provide a theoretical foundation for the reasonable selection of a suitable reference gene. Furthermore, the detection of intestinal microRNAs expression may serve as a promising therapeutic target for the diagnosis and treatment of HCC.
Inhibition of Brain Area and Functional Connectivity in Idiopathic Sudden Sensorineural Hearing Loss With Tinnitus, Based on Resting-State EEG

This study aimed to identify the mechanism behind idiopathic sudden sensorineural hearing loss (ISSNHL) in patients with tinnitus by investigating aberrant activity in areas of the brain and functional connectivity. High-density electroencephalography (EEG) was used to investigate central nervous changes in 25 ISSNHL subjects and 27 healthy controls. ISSNHL subjects had significantly reduced activity in the left frontal lobe at the alpha 2 frequency band compared with controls. Linear lagged connectivity and lagged coherence analysis showed significantly reduced functional connectivity between the temporal gyrus and supramarginal gyrus at the gamma 2 frequency band in the ISSNHL group. Additionally, a significantly reduced functional connectivity was found between the central cingulate gyrus and frontal lobe under lagged phase synchronization analysis. These results strongly indicate inhibition of brain area activity and change in functional connectivity in ISSNHL with tinnitus patients.
Biobanking for Viral Hepatitis Research

Introduction: Viral hepatitis is a worldwide, important health issue. The optimal management of viral hepatitis infections faces numerous challenges. In this paper, we describe how biobanking of biological samples derived from viral hepatitis patients collected both in-hospital and during community outreach screenings provides a unique collection of samples. Materials and Methods: All samples and materials were provided with a study code within the SLIMS system Study protocols and an informed consent form were approved by the Antwerp University Hospital/University of Antwerp Ethical Committee. Systematic biobanking was initiated in October 2014. Collected sample types include: (1) serum and plasma of all newly diagnosed HBV, HCV, HDV, and HEV positive patients; (2) left-over serum and plasma samples from all PCR analyses for HBV and HCV performed in the context of routine clinical care; (3) left-over liver tissue not needed for routine histological diagnosis after liver biopsy; and (4) additional virus-specific, appropriate sample types using a scientific rationale-based approach. A community outreach screening program was performed in three major Belgian cities. Serum, EDTA, Tempus Blood RNA and BD Vacutainer CPT were collected. CPT tubes were centrifuged on-site and mononuclear cells collected within 24 h. Results: Concerning community screening: 298 individuals supplied all 4 sample types. Samples were stored at −150°C and were logged in the biobank SLIMS database. Samples were used for HBV-related immunological and biomarker studies. DNA isolated from plasma samples derived from chronic HBV patients was used to investigate Single Nucleotide Polymorphism rs 1790008. Serum samples collected from chronic hepatitis C patients were used to assess the efficacy of HCV treatment. Peripheral Blood Mononuclear Cells (PBMC) isolated from chronic HBV patients and healthy controls were used for different immunological study purposes. Virus isolated from biobanked stool of a chronic hepatitis E patient was used to establish a mouse model for Hepatitis E infections, allowing further HEV virology studies. Conclusion: The establishment of a biobank with samples collected both in-hospital and during community-outreach screening resulted in a unique, continuously expanding collection of biological samples which provides an excellent platform for prompt answers to clinically and translational relevant research questions.
Flow mechanism in twin-wire blade forming. Part ll

In a one-sided twin-wire model gap former, the KTH-former, the behaviour of pulp fibre flocs in the presence of blade forming pressure pulses has been studied at different blade loads and wire permeabilities. Pulp fibre flocs were injected into the headbox and recorded with a high speed video camera when passing a forming blade in the forming zone. With a visual evaluation method the fibre flocs were found to be elongated and some of them ruptured during the acceleration when the flocs passed the forming blade. Floc strain and floc breaking ratio increased with blade load because of a higher acceleration. Flocs partially pinned to the permeable wire will elongate and tend to rupture more due to the mix-to-wire speed difference upstream of the forming blade. Some differences for rupture using different pulp qualities are quantified.
The Influence of Social Networks and Norms on Breastfeeding in African American and Caucasian Mothers: A Qualitative Study.

Background: Social networks and subjective norms (individuals' perceptions of what other people think) can be influential in decision-making. Although there are data about the importance of support in initiation and duration of breastfeeding, no studies have explored the influence of women's social networks and the norms within those networks on breastfeeding. Research Aim: To investigate, through qualitative methods, the influence of mothers' social networks and subjective norms, both within and outside of her network, with regard to breastfeeding practices. Materials and Methods: Twenty-eight mothers participated in focus groups or individual interviews. Probing questions concerning breastfeeding intent, initiation, continuation, and support with regard to social networks and subjective norms were asked. Themes were developed in an iterative manner from coded data. Results: General themes that emerged were the importance of breastfeeding experience within one's social network, the influence of the infant's father, handling disagreement within one's network, and the effects of social norms that exist outside of one's network. Mothers described support for breastfeeding from network members as especially important when breastfeeding was not the norm within the network. Conclusion: Breastfeeding behavior is influenced by a mother's social network. Even when breastfeeding is not normative within one's social network, by relying on one network member to support them, mothers may be able to resist the opposing norms of their social network. Since breastfeeding is known to be beneficial to infants and mothers, education or interventions to improve breastfeeding rates may be more effective if they include individual network members who can provide strong support to new mothers.
Urinary Amino-Terminal Pro-C-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes.

BACKGROUND Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. METHODS ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. RESULTS The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. CONCLUSIONS Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.
Resource Management and Tuples in CⱯ

C∀ is a modern, non-object-oriented extension of the C programming language. This thesis addresses several critical deficiencies of C, notably: resource management, a limited functionreturn mechanism, and unsafe variadic functions. To solve these problems, two fundamental language features are introduced: tuples and constructors/destructors. While these features exist in prior programming languages, the contribution of this work is engineering these features into a highly complex type system. C is an established language with a dedicated user-base. An important goal is to add new features in a way that naturally feels like C, to appeal to this core user-base, and due to huge amounts of legacy code, maintaining backwards compatibility is crucial.
The relationship between hearing loss and insomnia for patients with tinnitus*

Abstract Objective: It is possible that tinnitus, hearing loss and insomnia are all linked to oxidative stress. If so, there should be a relationship between insomnia and hearing loss among patients with tinnitus. The aim of this study was to assess the relationship between insomnia and hearing thresholds for patients with tinnitus. Design: This was a retrospective study. Study sample: Data were gathered from records of 1066 consecutive patients (≥18 years old) with tinnitus who were seen in an audiology clinic in the UK. Results: Seventy percent of patients experienced some form of insomnia as measured via the Insomnia Severity Index (ISI). Thirty eight percent of patients had hearing loss. Regression models showed that the average hearing threshold across ears and frequencies (0.5–4 kHz), adjusted for age and gender, did not predict ISI scores: regression coefficient (b) = 0.02 (95% confidence interval, CI: –0.013 to 0.05, p = 0.25). Moreover, the ISI scores did not predict the severity of hearing loss: b = 0.07 (95% CI: –0.05 to 0.18, p = 0.25). Conclusion: The data do not support the idea that high levels of oxidative stress, which are associated with insomnia, have a strong influence on hearing loss among patients with tinnitus.