Miracle-dz/UniFAR-FTUs huggingface dataset:
Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures

Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.
Supporting Acquisition of Spelling Skills in Different Orthographies Using an Empirically Validated Digital Learning Environment

This paper discusses how the association learning principle works for supporting acquisition of basic spelling and reading skills using digital game-based learning environment with the Finland-based GraphoLearn (GL) technology. This program has been designed and validated to work with early readers of different alphabetic writing systems using repetition and reinforcing connections between spoken and written units. Initially GL was developed and found effective in training children at risk of reading disorders in Finland. Today GL training has been shown to support learning decoding skills among children independent of whether they face difficulties resulting from educational, social, or biological reasons.
Ecological Fitness of Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus in a Small-Scale Population Dynamics Study

The potential spread of infectious diseases in response to climate change and rising sea surface temperatures in temperate regions has been a growing concern for the past several decades. Extreme heat waves in the North Atlantic and North Sea regions have been correlated with an increase in human Vibrio infections; of particular concern to human health are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus. While these species are well-known to cause disease in humans, most environmental strains are not pathogenic. Studying not only the behavior of the pathogenic strains, but that of non-pathogenic environmental isolates, may better elucidate their ecological relationship in their native microbiome and the dispersal of these species in coastal regions. Using red fluorescent protein-tagged and gentamycin-resistant V. cholerae, V. parahaemolyticus, and V. vulnificus strains, we investigated whether increasing temperatures confer greater competitive fitness to these species when incubated within a natural North Sea water sample still containing its microbiome in a small-scale niche investigation. Increased incubation temperatures alone did not confer a competitive advantage to V. cholerae, V. parahaemolyticus, and V. vulnificus. The microbial community could limit Vibrio growth at all temperatures. To the best of our knowledge, we also demonstrate the first (albeit unintentional) genetic modification of multiple species of marine bacteria through the introduction of a genetically modified V. vulnificus strain into a natural water sample in a contained system.
Olive Fruit Extracts Supplement Improve Antioxidant Capacity via Altering Colonic Microbiota Composition in Mice

Oxidative stress, one of the most common biological dysfunctions, is usually associated with pathological conditions and multiple diseases in humans and animals. Chinese olive fruit (Canarium album L.) extracts (OE) are natural plant extracts rich in polyphenols (such as hydroxytyrosol, HT) and with antioxidant, anti-hyperlipidemia, and anti-inflammatory potentials. This study was conducted to investigate the antioxidant capacity of OE supplementation and its related molecular mechanism in mice. Mice (25.46 ± 1.65 g) were treated with 100 mg/kg body weight (BW) OE or saline solution for 4 weeks, and then the antioxidant and anti-inflammatory capacities of mice were examined. The results showed that OE supplement significantly increased the serum antioxidative enzyme activities of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase and decreased the serum malondialdehyde (MDA) level, indicating that OE treatment enhanced the antioxidant capacity in mice. qPCR results showed that the transcriptional expression of antioxidant SOD1, CAT, Gpx1, and Gpx2 were significantly down-regulated in the small intestine (jejunum and ileum) after OE administration. Meanwhile, OE treatment significantly decreased the T-AOC and increased the MDA level in the small intestine. Furthermore, OE administration dramatically reduced the mRNA expression of pro-inflammatory cytokines (TNF-α and IL-1β), which confirmed its antioxidant and anti-inflammatory capacities with OE administration. Using amplicon sequencing technology, 16S rRNA sequencing results showed that OE supplement significantly increased the colonic Firmicutes/Bacteroidetes ratio, which also had a negative correlation with the serum MDA level and positively correlated with serum GSH-Px activity through Pearson correlation analysis. Besides that, Alloprevotella was negatively correlated with serum T-AOC. Colidextribacter was positively correlated with serum MDA and negatively correlated with serum T-AOC, SOD, and GSH-Px levels. In summary, this study showed that treatment with 100 mg/kg BW polyphenol-rich OE could alter colonic microbiota community, which was strongly associated with improved antioxidant capacity in mice.
Diurnal and Seasonal Variations in the Photosynthetic Characteristics and the Gas Exchange Simulations of Two Rice Cultivars Grown at Ambient and Elevated CO2

Investigating the diurnal and seasonal variations of plant photosynthetic performance under future atmospheric CO2 conditions is essential for understanding plant adaptation to global change and for estimating parameters of ecophysiological models. In this study, diurnal changes of net photosynthetic rate (Anet), stomatal conductance (gs), and photochemical efficiency of PSII (Fv′/Fm′) were measured in two rice cultivars grown in the open-top-chambers at ambient (∼450 μmol mol–1) and elevated (∼650 μmol mol–1) CO2 concentration [(CO2)] throughout the growing season for 2 years. The results showed that elevated (CO2) greatly increased Anet, especially at jointing stage. This stimulation was acclimated with the advance of growing season and was not affected by either stomatal limitations or Rubisco activity. Model parameters in photosynthesis model (Vcmax, Jmax, and Rd) and two stomatal conductance models (m and g1) varied across growing stages and m and g1 also varied across (CO2) treatments and cultivars, which led to more accurate photosynthesis and stomatal conductance simulations when using these cultivar-, CO2-, and stage- specific parameters. The results in the study suggested that further research is still needed to investigate the dominant factors contributing to the acclimation of photosynthetic capacity under future elevated CO2 conditions. The study also highlighted the need of investigating the impact of other environmental, such as nitrogen and O3, and non-environmental factors, such as additional rice cultivars, on the variations of these parameters in photosynthesis and stomatal conductance models and their further impacts on simulations in large scale carbon and water cycles.
Culturally Grounded Scapegoating in Response to Illness and the COVID-19 Pandemic

For years, violence against doctors and healthcare workers has been a growing social issue in China. In a recent series of studies, we provided evidence for a motivated scapegoating account of this violence. Specifically, individuals who feel that the course of their (or their family member's) illness is a threat to their sense of control are more likely to express motivation to aggress against healthcare providers. Drawing on existential theory, we propose that blaming and aggressing against a single individual represents a culturally afforded scapegoating mechanism in China. However, in an era of healthcare crisis (i.e., the global COVID-19 pandemic), it is essential to understand cultural variation in scapegoating in the context of healthcare. We therefore undertook two cross-cultural studies examining how people in the United States and China use different scapegoating responses to re-assert a sense of control during medical uncertainty. One study was conducted prior to the pandemic and allowed us to make an initial validating and exploratory investigation of the constructs of interest. The second study, conducted during the pandemic, was confirmatory and investigated mediation path models. Across the two studies, consistent evidence emerged that, both in response to COVID-related and non-COVID-related illness scenarios, Chinese (relative to U.S.) individuals are more likely to respond by aggressing against an individual doctor, while U.S. (relative to Chinese) individuals are more likely to respond by scapegoating the medical industry/system. Further, Study 2 suggests these culture effects are mediated by differential patterns of primary and secondary control-seeking.
Lipid Extract From a Vegetable (Sonchus Oleraceus) Attenuates Adipogenesis and High Fat Diet-Induced Obesity Associated With AMPK Activation

Scope: Sonchus Oleraceus, named bitter vegetable (BV), has been known to have multiple health benefits such as anti-aging and anti-inflammation. However, the role of BV in the prevention of obesity is unclear. The aim of this study was to examine the effect of BV lipid extracts (BVL) on obesity development. Methods and Results: Following treatments of high fat diet-induced obese mice (C57BL/6J) with BVL (0.3 mg/g of BW per mouse) for a month, mice exhibited a significant reduction in weight gain, blood triglyceride, and fasting blood glucose compared to control mice. Intriguingly, phosphorylated AMPK, a key regulator of nutrient metabolism, was markedly increased in inguinal fat of BVL group. In 3T3-L1 cells, BVL-7 (100 μg/ml), an omega-3 fatty acid-rich fraction from BVL, lowered lipid accumulation, and down-regulated the gene expression of adipocyte markers. The inhibitory effect of BVL occurred at the early stage of adipocyte differentiation, leading to the delay of mitotic clonal expansion. AMPK knockdown by siRNA abolished the inhibitory effect of BVL-7 on adipogenesis, suggesting that AMPK is essential for BVL-regulated adipocyte differentiation. Conclusion: BVL can effectively inhibit adipogenesis through, at least in part, stimulating AMPK pathway and attenuate HFD-induced obesity. Our findings suggest that BVL can be a promising dietary supplement for protection against obesity, and the effective component of BVL can be potentially developed as anti-obesity drugs.
Dissection of Functional Modules of AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN 4 in the Development of the Root Xylem

Xylem development in the Arabidopsis root apical meristem requires a complex cross talk between plant hormone signaling and transcriptional factors (TFs). The key processes involve fine-tuning between neighboring cells, mediated via the intercellular movement of signaling molecules. As an example, we previously reported that AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN (AHL) 4 (AHL4), a member of the 29 AT-hook family TFs in Arabidopsis, moves into xylem precursors from their neighbors to determine xylem differentiation. As part of the effort to understand the molecular functions of AHL4, we performed domain swapping analyses using AHL1 as a counterpart, finding that AHL4 has three functionally distinctive protein modules. The plant and prokaryotes conserved (PPC) domain of AHL4 acts as a mediator of protein–protein interactions with AHL members. The N-terminus of AHL4 is required for the regulation of xylem development likely via its unique DNA-binding activity. The C-terminus of AHL4 confers intercellular mobility. Our characterization of modules in the AHL4 protein will augment our understanding of the complexity of regulation and the evolution of intercellular mobility in AHL4 and its relatives.
Editorial: Celebrating the Diversity of Genetic Research to Dissect the Pathogenesis of Parkinson's Disease

Department of Neurology, University of Florida, Gainesville, FL, United States, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan, 4 Institut National de la Santé et de la Recherche Médicale U1127, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7225, Sorbonne Université, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France, Departments of Neuroscience and Clinical Genomics, Mayo Clinic, Jacksonville, FL, United States, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, Australia, 7 Luxembourg Centre for Systems Biomedicine (LCSB), Esch-sur-Alzette, Luxembourg, Centre for Systems Biomedicine (LCSB), Belvaux, Luxembourg, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
Precipitation Variations in the Flood Seasons of 1910–2019 in Hunan and Its Association With the PDO, AMO, and ENSO

Floods in the middle reaches of the Yangtze River threaten thousands of million people, causing casualties and economic loss. Yet, the prediction of floods in this region is still challenging. To better understand the floods in this region, we investigate the interdecadal-interannual rainfall variation of the flood season (April–September) in Hunan province. The relationship between the rainfall and the Pacific decadal oscillation (PDO), Atlantic Multidecadal Oscillation (AMO), and El Niño-Southern Oscillation (ENSO) are also analyzed. The results show that the precipitation in the flood seasons shows an interdecadal oscillation with a period of about 20 years, which is caused by the joint effect of the PDO and AMO. When the PDO and AMO are in the same phase, the corresponding flood season is characterized by more precipitation, and conversely, it is less precipitation. Further analyses show that in the year after El Niño, when the PDO and AMO are both in the positive phase, it is favorable for the west Pacific subtropical high (WPSH) to be stronger and more southward than normal. Such circulation anomaly is conducive to the water vapor transport to the southern China, and as a result there is more precipitation in Hunan. When the PDO and AMO are both in the negative phase, the WPSH is weaker than normal, but the India-Burma trough is obviously stronger, which is also favorable for the southwesterly water vapor transport to the southern China. However, in the next year of the La Niña year, regardless of the phase combination of the PDO and AMO, the southern coast of China are controlled by a negative geopotential height anomaly and the WPSH retreats to the sea, which is not conducive to the northward transport of water vapor, and the precipitation in Hunan is less than normal. But if only the cold SST background in the previous stage is considered (without reaching the standard of a La Niña event),is more precipitation in most of the Hunan Province. Therefore, at the interannual scale, the PDO and AMO also have a modulating effect on the precipitation signal. However, the interannual-scale ENSO signal has a greater influence on the precipitation in Hunan flood seasons. Our results will give implications for the predications of floods in Hunan.
Neurological and Cognitive Performance After Childhood Encephalitis

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood. Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995–2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire. Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008). Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.
Therapeutic Potential of GABAergic Signaling in Myelin Plasticity and Repair

Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABAA receptors (GABAARs) expressed by OPCs and their potential role in remyelination.
Machine Learning-Augmented Propensity Score Analysis of Percutaneous Coronary Intervention in Over 30 Million Cancer and Non-cancer Patients

Background: It is unknown to what extent the clinical benefits of PCI outweigh the risks and costs in patients with vs. without cancer and within each cancer type. We performed the first known nationally representative propensity score analysis of PCI mortality and cost among all eligible adult inpatients by cancer and its types. Methods: This multicenter case-control study used machine learning–augmented propensity score–adjusted multivariable regression to assess the above outcomes and disparities using the 2016 nationally representative National Inpatient Sample. Results: Of the 30,195,722 hospitalized patients, 15.43% had a malignancy, 3.84% underwent an inpatient PCI (of whom 11.07% had cancer and 0.07% had metastases), and 2.19% died inpatient. In fully adjusted analyses, PCI vs. medical management significantly reduced mortality for patients overall (among all adult inpatients regardless of cancer status) and specifically for cancer patients (OR 0.82, 95% CI 0.75–0.89; p < 0.001), mainly driven by active vs. prior malignancy, head and neck and hematological malignancies. PCI also significantly reduced cancer patients' total hospitalization costs (beta USD$ −8,668.94, 95% CI −9,553.59 to −7,784.28; p < 0.001) independent of length of stay. There were no significant income or disparities among PCI subjects. Conclusions: Our study suggests among all eligible adult inpatients, PCI does not increase mortality or cost for cancer patients, while there may be particular benefit by cancer type. The presence or history of cancer should not preclude these patients from indicated cardiovascular care.
A Decade of Hydrological Drought in Central-Western Argentina

Most of the water used for the development of the main socio-economic activities in Central-Western Argentina (CWA), an arid to semi-arid region, home to most of the Argentinean wine production, relies on surface streamflow from several snow-fed rivers. During the last decade (2010-2020), reduced snow accumulation over the higher elevations of the Andes mountains triggered the occurrence of hydrological drought over CWA, affecting winter tourism, restricting water use for irrigation and domestic use, and leading to socio-political disputes. This study provides a detailed description of the recent hydrological drought conditions through the use of streamflow records from 15 river basins, which were complemented by precipitation, snowpack, and water equivalent thickness measurements to provide a comprehensive picture of the water losses over the last decade. Hydrological drought indices derived from the threshold level method and the standardized streamflow index allowed characterizing the unusualness of this dry period in the context of the last 49 years. The hydrological deficit over the last decade highlighted the challenges faced by the water managers to provide water for irrigation in the main agricultural oases, with a likely overexploitation of the groundwater resources to supplement the limited surface runoff. The hydrological drought severity increased since 2017, with record-breaking levels in several basins, particularly during the period between July 2019 and June 2020 for the rivers located between 35° and 36°S. We identified the main hydrological drought impacts in CWA, as well as the need for improved mitigation strategies to cope with current and future drought conditions. We also analyzed the current limitations in terms of snow and groundwater observations, highlighting the necessity for an effective hydrological drought monitoring system, together with an improved forecast of snow accumulation in the headwaters, which can contribute to better regional water management plans.