Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustained Post-Developmental T-Bet Expression Is Critical for the Maintenance of Type One Innate Lymphoid Cells In Vivo

Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic intraepithelial ILC1, colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets. SIGNIFICANCE STATEMENT IFNγ is a key mediator of pathology in the standard model of murine colitis induced by dextran sodium sulphate (DSS), and its expression has been observed in patients with inflammatory bowel disease. Several immune cells can produce IFNγ during colitis, but among those, the relevance of innate lymphoid cells expressing T-bet is unknown. T-bet-expressing ILC1 are predominately resident in mucosal tissues and as such may play a critical role at the onset of inflammation. In this study we employed a mouse model to induce Tbx21 (encoding T-bet) deletion in adult mice resulting in the loss of intestinal ILC1. This long-term loss of ILC1 correlated to milder DSS-elicited colitis and indicates that ILC1 may play a pathogenic role during colitis.
Influence of the metallized coils on human leg blood circulation

The aim of the study was to find out if magnetic field generated by the human body affects a human blood flow. The idea is based on Lenz’s law where the blood flow induces an opposing alternating magnetic field (OAMF). In the experiment the OAMF will be modulated by repeating heart contractions (pulses). In an experiment with metallized coils it was found that wearing metal coils affects blood flow and it differs from when coils were not worn.
Characterizing the middle-age neurophysiology using EEG/MEG

Middle adulthood – the period of life between 40 and 60 years of age – is accompanied by important physical and emotional changes, as well as cognitive and neuronal ones. Nevertheless, middle age is often overlooked in neuroscience under the assumption that this is a time of relative stability, although cognitive decline, as well as changes in brain structure and function are well-established by the age of 60. Here we characterized the middle-aged brain in the context of healthy younger and older adults by assessing resting-state electrophysiological and neuromagnetic activity in two different samples (N = 179, 631). Alpha and beta oscillations – two key ageing signatures – were analyzed in terms of spectral power and burst events. While posterior alpha power and burst rate features changed linearly with age, similarly to behavioral measures, sensorimotor beta power and burst rate properties varied non-linearly, with inflection points during middle age. The findings suggest that ageing is characterized by distinct spatial and temporal brain dynamics, some critically arising in middle age.
Secular Students’ Perceptions of Christian Rhetoric: What College Students Do and Do Not Want from Conversations with Christians

Abstract A phenomenological study was conducted to understand how secular, Generation Z, college students have experienced Christian rhetoric. The study’s findings revealed Christian rhetorical praxis lacked intellectual vulnerability, empathetic imagination and a willingness to engage in steeped embodied discourse. This article contends these elements are essential for winsomely engaging in Christian discourse.
Access to knowledge and knowledge production: the case of China

ABSTRACT This paper estimates knowledge production functions for the Chinese economy using provincial-level data over the years 2008 through 2016. First, the number of R&D personnel, funding, and the accessibility to global knowledge stock all have positive and significant effects on both general patent application, and invention patent application. Second, the knowledge accumulation effect on knowledge production efficiency is substantial. Third, the state-owned sector has an important role in fundamental innovation. Most importantly, accessibility to knowledge is important in realizing the benefit of the non-rivalry of knowledge. Hence, it is pivotal that the Chinese government adopt an open innovation approach and keep moving along its plan of reform and opening up [All sources are published on-line except for NSO, which is available upon request].
Fecal Methylmercury Correlates With Gut Microbiota Taxa in Pacific Walruses (Odobenus rosmarus divergens)

Objectives Methylmercury metabolism was investigated in Pacific walruses (Odobenus rosmarus divergens) from St. Lawrence Island, Alaska, United States. Methods Total mercury and methylmercury concentrations were measured in fecal samples and paired colon samples (n = 16 walruses). Gut microbiota composition and diversity were determined using 16S rRNA gene sequencing. Associations between fecal and colon mercury and the 24 most prevalent gut microbiota taxa were investigated using linear models. Results In fecal samples, the median values for total mercury, methylmercury, and %methylmercury (of total mercury) were 200 ng/g, 4.7 ng/g, and 2.5%, respectively, while in colon samples, the median values for the same parameters were 28 ng/g, 7.8 ng/g, and 26%, respectively. In fecal samples, methylmercury was negatively correlated with one Bacteroides genus, while members of the Oscillospirales order were positively correlated with both methylmercury and %methylmercury (of total mercury). In colon samples, %methylmercury (of total mercury) was negatively correlated with members of two genera, Romboutsia and Paeniclostridium. Conclusions Median %methylmercury (of total mercury) was 10 times higher in the colon compared to the fecal samples, suggesting that methylmercury was able to pass through the colon into systemic circulation. Fecal total mercury and/or methylmercury concentrations in walruses were comparable to some human studies despite differences in seafood consumption rates, suggesting that walruses excreted less mercury. There are no members (at this time) of the Oscillospirales order which are known to contain the genes to methylate mercury, suggesting the source of methylmercury in the gut was from diet and not in vivo methylation.
Heterotypic Tumor Spheroids in Agitation-Based Cultures: A Scaffold-Free Cell Model That Sustains Long-Term Survival of Endothelial Cells

Endothelial cells (ECs) are an important component of the tumor microenvironment, playing key roles in tumor development and progression that span from angiogenesis to immune regulation and drug resistance. Heterotypic tumor spheroids are one of the most widely used in vitro tumor microenvironment models, presenting improved recapitulation of tumor microenvironments compared to 2D cultures, in a simple and low-cost setup. Heterotypic tumor spheroid models incorporating endothelial cells have been proposed but present multiple limitations, such as the short culture duration typically obtained, the use of animal-derived matrices, and poor reproducibility; the diversity of culture conditions employed hinders comparison between studies and standardization of relevant culture parameters. Herein, we developed long-term cultures of triple heterotypic spheroids composed of the HCC1954 tumor cell line, human fibroblasts, and ECs. We explored culture parameters potentially relevant for EC maintenance, such as tumor cell line, seeding cell number, cell ratio, and agitation vs. static culture. In HCC1954-based spheroids, we observed maintenance of viable EC for up to 1 month of culture in agitation, with retention of the identity markers CD31 and von Willebrand factor. At the optimized tumor cell:fibroblast:EC ratio of 1:3:10, HCC1954-based spheroids had a higher EC area/total spheroid area at 1 month of culture than the other cell ratios tested. EC maintenance was tumor cell line-dependent, and in HCC1954-based spheroids it was also dependent on the presence of fibroblasts and agitation. Moreover, vascular endothelial growth factor (VEGF) supplementation was not required for maintenance of EC, as the factor was endogenously produced. ECs co-localized with fibroblasts, which accumulated preferentially in the core of the spheroids and secreted EC-relevant extracellular matrix proteins, such as collagen I and IV. This simple model setup does not rely on artificial or animal-derived scaffolds and can serve as a useful tool to explore the culture parameters influencing heterotypic spheroids, contributing to model standardization, as well as to explore molecular cross talk of ECs within the tumor microenvironment, and potentially its effects on drug response.
Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas. Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association. Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III. Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs.
Floral Distribution of a Sub-Bituminous Coal Dumpsite in Enugu, Nigeria

The remnant floral diversity of a naturally reclaimed area proximal to an abandoned mine was assessed. The coal mine site, the Incident zone (IZ) and an unsullied site, the Control zone (CZ), were sampled. Using a 5 m2 quadrat, the floristic composition was determined by the occurrence, distribution analysis, and species diversity indices. The study revealed a degraded vegetation type and recorded a total of 60 species, 53 genera and 27 families. Both the IZ and CZ shared 26.67% species similarity, while 36.67% are were unique to each zone. Five species were dominant (Ageratum conyzoides, Panicum maximum, Calopogonium mucunoides, Chromolaena odorata). While the dominant genera vary between IZ (Borreria, Dioscorea, Ipomoea, and Phyllanthus) and CZ (Desmodium, Euphorbia, and Ipomoea), Asteraceae and Poaceae were the dominant families in both zones. Forbs were the most dominant life forms in both zones; Cyclosorus sp. and Adiantum sp. were only found on the IZ, whereas, Kyllinga erecta and Mariscus alternifolius were exclusive to the CZ. Our results reflect that species composition and vegetation paradigm in the study area could be influenced by coal mining, farming, infrastructural installations and climate. Hence, we suggest future studies to investigate how the species adapt to the environment. Although most of the species encountered belonged to lower-risk conservation, the conservation of the species to this area is imperative.
Classification of 41 Hand and Wrist Movements via Surface Electromyogram Using Deep Neural Network

Surface electromyography (sEMG) is a non-invasive and straightforward way to allow the user to actively control the prosthesis. However, results reported by previous studies on using sEMG for hand and wrist movement classification vary by a large margin, due to several factors including but not limited to the number of classes and the acquisition protocol. The objective of this paper is to investigate the deep neural network approach on the classification of 41 hand and wrist movements based on the sEMG signal. The proposed models were trained and evaluated using the publicly available database from the Ninapro project, one of the largest public sEMG databases for advanced hand myoelectric prosthetics. Two datasets, DB5 with a low-cost 16 channels and 200 Hz sampling rate setup and DB7 with 12 channels and 2 kHz sampling rate setup, were used for this study. Our approach achieved an overall accuracy of 93.87 ± 1.49 and 91.69 ± 4.68% with a balanced accuracy of 84.00 ± 3.40 and 84.66 ± 4.78% for DB5 and DB7, respectively. We also observed a performance gain when considering only a subset of the movements, namely the six main hand movements based on six prehensile patterns from the Southampton Hand Assessment Procedure (SHAP), a clinically validated hand functional assessment protocol. Classification on only the SHAP movements in DB5 attained an overall accuracy of 98.82 ± 0.58% with a balanced accuracy of 94.48 ± 2.55%. With the same set of movements, our model also achieved an overall accuracy of 99.00% with a balanced accuracy of 91.27% on data from one of the amputee participants in DB7. These results suggest that with more data on the amputee subjects, our proposal could be a promising approach for controlling versatile prosthetic hands with a wide range of predefined hand and wrist movements.
Exosomes in Intestinal Inflammation

Exosomes are 30–150 nm sized vesicles released by a variety of cells, and are found in most physiological compartments (feces, blood, urine, saliva, breast milk). They can contain different cargo, including nucleic acids, proteins and lipids. In Inflammatory Bowel Disease (IBD), a distinct exosome profile can be detected in blood and fecal samples. In addition, circulating exosomes can carry targets on their surface for monoclonal antibodies used as IBD therapy. This review aims to understand the exosome profile in humans and other mammals, the cargo contained in them, the effect of exosomes on the gut, and the application of exosomes in IBD therapy.
Right Inferior Parietal Lobule Activity Is Associated With Handwriting Spontaneous Tempo

Handwriting is a complex activity including motor planning and visuomotor integration and referring to some brain areas identified as “writing centers. ” Although temporal features of handwriting are as important as spatial ones, to our knowledge, there is no evidence of the description of specific brain areas associated with handwriting tempo. People with multiple sclerosis (PwMS) show handwriting impairments that are mainly referred to as the temporal features of the task. The aim of this work was to assess differences in the brain activation pattern elicited by handwriting between PwMS and healthy controls (HC), with the final goal of identifying possible areas specific for handwriting tempo. Subjects were asked to write a sentence at their spontaneous speed. PwMS differed only in temporal handwriting features from HC and showed reduced activation with a subset of the clusters observed in HC. Spearman’s correlation analysis was performed between handwriting temporal parameters and the activity in the brain areas resulting from the contrast analysis, HC > PwMS. We found that the right inferior parietal lobule (IPL) negatively correlated with the duration of the sentence, indicating that the higher the right IPL activity, the faster the handwriting performance. We propose that the right IPL might be considered a “writing tempo center. ”
MicroRNAs Regulating Tumor Immune Response in the Prediction of the Outcome in Patients With Breast Cancer

MicroRNAs (miRNAs) are key regulators in immune surveillance and immune escape as well as modulators in the metastatic process of breast cancer cells. We evaluated the differential expression of plasma miR-10b, miR-19a, miR-20a, miR-126 and miR-155, which regulate immune response in breast cancer progression and we investigated their clinical relevance in the outcomes of breast cancer patients. Plasma samples were obtained from early (eBC; n = 140) and metastatic (mBC; n = 64) breast cancer patients before adjuvant or first-line chemotherapy, respectively. Plasma miRNA expression levels were assessed by qRT-PCR. We revealed a 4-miRNA panel consisted of miR-19a, miR-20a, miR-126, and miR-155 able to discriminate eBC from mBC patients with an AUC of 0.802 (p < 0.001). Survival analysis in eBC patients revealed that low miR-10b and miR-155 expression was associated with shorter disease free survival (disease free survival; p = 0.012 and p = 0.04, respectively) compared to high expression. Furthermore, miR-126 expression was associated with shorter overall survival (overall survival; p = 0.045). In multivariate analysis the number of infiltrated axillary lymph nodes and low miR-10b expression independently predicted for shorter DFS (HR: 2.538; p = 0.002 and HR: 1.943; p = 0.033, respectively) and axillary lymph nodes and low miR-126 for shorter OS (HR: 3.537; p = 0.001 and HR: 2.558; p = 0.018). In the subgroup of triple negative breast cancer (TNBC) patients, low miR-155 expression independently predicted for shorter DFS (HR: 5.056; p = 0.037). Accordingly in mBC, patients with low miR-10b expression had shorter progression free survival and OS compared to patients with high expression (p = 0.0017 and p = 0.042, respectively). In multivariate analysis, recurrent disease and low miR-10b expression independently predicted for shorter PFS (HR: 2.657; p = 0.001 and HR: 1.920; p = 0.017, respectively), whereas performance status two independently predicted for shorter OS (HR: 2.031; p = 0.03). In summary, deregulated expression of circulating miRNAs involved in tumor and immune cell interactions evaluated before adjuvant and 1st-line chemotherapy can distinguish disease status and emerge as independent predictors for outcomes of breast cancer patients.
Potential Disease-Modifying Effects of Lithium Carbonate in Niemann-Pick Disease, Type C1

Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1. Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety. Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months (p = 0.005). Improvement in swallowing capacity was observed in treated patients (p = 0.014). No serious adverse events were recorded in the patients receiving lithium. Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding. Clinical Trial Registration: ClinicalTrials.gov, NCT03201627.
Learning Set Formation and Reversal Learning in Mice During High-Throughput Home-Cage-Based Olfactory Discrimination

Rodent behavioral tasks are crucial to understanding the nature and underlying biology of cognition and cognitive deficits observed in psychiatric and neurological pathologies. Olfaction, as the primary sensory modality in rodents, is widely used to investigate cognition in rodents. In recent years, automation of olfactory tasks has made it possible to conduct olfactory experiments in a time- and labor-efficient manner while also minimizing experimenter-induced variability. In this study, we bring automation to the next level in two ways: First, by incorporating a radio frequency identification-based sorter that automatically isolates individuals for the experimental session. Thus, we can not only test animals during defined experimental sessions throughout the day but also prevent cagemate interference during task performance. Second, by implementing software that advances individuals to the next test stage as soon as performance criteria are reached. Thus, we can prevent overtraining, a known confounder especially in cognitive flexibility tasks. With this system in hand, we trained mice on a series of four odor pair discrimination tasks as well as their respective reversals. Due to performance-based advancement, mice normally advanced to the next stage in less than a day. Over the series of subsequent odor pair discriminations, the number of errors to criterion decreased significantly, thus indicating the formation of a learning set. As expected, errors to criterion were higher during reversals. Our results confirm that the system allows investigating higher-order cognitive functions such as learning set formation (which is understudied in mice) and reversal learning (which is a measure of cognitive flexibility and impaired in many clinical populations). Therefore, our system will facilitate investigations into the nature of cognition and cognitive deficits in pathological conditions by providing a high-throughput and labor-efficient experimental approach without the risks of overtraining or cagemate interference.