Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroimmune mechanisms in fear and panic pathophysiology

Panic disorder (PD) is unique among anxiety disorders in that the emotional symptoms (e.g., fear and anxiety) associated with panic are strongly linked to body sensations indicative of threats to physiological homeostasis. For example, panic attacks often present with feelings of suffocation that evoke hyperventilation, breathlessness, or air hunger. Due to the somatic underpinnings of PD, a major focus has been placed on interoceptive signaling and it is recognized that dysfunctional body-to-brain communication pathways promote the initiation and maintenance of PD symptomatology. While body-to-brain signaling can occur via several pathways, immune and humoral pathways play an important role in communicating bodily physiological state to the brain. Accumulating evidence suggests that neuroimmune mediators play a role in fear and panic-associated disorders, although this has not been systematically investigated. Currently, our understanding of the role of immune mechanisms in the etiology and maintenance of PD remains limited. In the current review, we attempt to summarize findings that support a role of immune dysregulation in PD symptomology. We compile evidence from human studies and panic-relevant rodent paradigms that indicate a role of systemic and brain immune signaling in the regulation of fear and panic-relevant behavior and physiology. Specifically, we discuss how immune signaling can contribute to maladaptive body-to-brain communication and conditioned fear that are relevant to spontaneous and conditioned symptoms of PD and identify putative avenues warranting future investigation.
Topology of diffusion changes in corpus callosum in Alzheimer's disease: An exploratory case-control study

Aim This study aims to assess the integrity of white matter in various segments of the corpus callosum in Alzheimer's disease (AD) by using metrics derived from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and white matter tract integrity model (WMTI) and compare these findings to healthy controls (HC). Methods The study was approved by the institutional ethics board. 12 AD patients and 12 HC formed the study population. All AD patients were recruited from a tertiary neurology memory clinic. A standardized battery of neuropsychological assessments was administered to the study participants by a trained rater. MRI scans were performed with a Philips Ingenia 3.0T scanner equipped with a 32-channel head coil. The protocol included a T1-weighted sequence, FLAIR and a dMRI acquisition. The dMRI scan included a total of 71 volumes, 8 at b = 0 s/mm2, 15 at b = 1,000 s/mm2 and 48 at b = 2,000 s/mm2. Diffusion data fit was performed using DKI REKINDLE and WMTI models. Results and discussion We detected changes suggesting demyelination and axonal degeneration throughout the corpus callosum of patients with AD, most prominent in the mid-anterior and mid-posterior segments of CC. Axial kurtosis was the most significantly altered metric, being reduced in AD patients in almost all segments of corpus callosum. Reduced axial kurtosis in the CC segments correlated with poor cognition scores in AD patients in the visuospatial, language and attention domains.
Impacts of different fencing periods and grazing intensities on insect diversity in the desert steppe in Inner Mongolia

For the past several decades, both species biodiversity and productivity of desert steppe have been reduced due to excessive use and climate factors. To counteract this, Chinese government has supported large-scale grassland ecological restoration programs since the year 2000. The policy needs a standard for the evaluation of the effects of such restorative measures on the grasslands after decades. Grassland insect diversity plays an important role in the maintenance of plant species and functional diversity. To understand the relation of grazing management and insect diversity, we use a complete two factor design, two fencing periods (3 or 7 years) and three grazing intensities (0, 6, or 12 sheep per ha), to examine the response of the insect diversity to fencing and grazing in desert steppe. We found almost no significant differences in either plant or insect species diversity between the sites fenced for 3 and 7 years, as the pressure of grazing increased, insect diversity decreased to a greater extent at 7-year enclosure sites than at 3-year sites. We recommend the most suitable grazing intensity for the sustainability of biodiversity of the desert steppe in Inner Mongolia is light grazing (8 sheep/ha 0.5 yr−1), and the most suitable fencing period is three years, which suggest that policies that remove livestock from the desert grassland for long periods (7 + years) are not beneficial for maintaining insect diversity, and heavy grazing lead ecological environment weaker and insect diversity decreasing. Thus, periodic livestock grazing is important in the design of management actions to preserve biodiversity.
Cardiopulmonary disease as sequelae of long-term COVID-19: Current perspectives and challenges

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients.
Surgical treatment of cranial cruciate ligament disease in dogs using Tibial Plateau Leveling Osteotomy or Tibial Tuberosity Advancement–A systematic review with a meta-analytic approach

Tibial Plateau Leveling Osteotomy (TPLO) or Tibial Tuberosity Advancement (TTA) are commonly used surgical techniques for correction of cranial cruciate ligament (CCL) rupture in dogs. This systematic review aims to investigate whether one technique is superior to the other. Seventy-two studies on surgical management of CCL rupture have been identified and evaluated in regard of subjective and objective gait analysis criteria, development of osteoarthritis (OA), thigh circumference measurements, goniometry, joint stability, pain and complication rates. Almost half (47.2 %) of the studies were considered of low quality of evidence, leading to high heterogeneity in quality among studies; this posed a major limitation for an evidence-based systematic review of both surgical techniques. Out of 72 studies, there were only eleven blinded randomized clinical trials, of which five were rated with a low overall risk of bias. However, both techniques were considered to be successful management options. Subjective and objective gait analysis revealed no lameness at long-term evaluation for the majority of the patients. However, it appeared that TTA lead to better OA scores up to 6 months postoperatively, while TPLO had a lower rate of surgical site infections. In summary, no method can be clearly preferred, as most of the study evaluated were subpar. Studies with a high level of evidence are therefore urgently needed for such a common surgical procedure.
Overcoming the phenomenological Perpetuum mobile in clinical cognitive neuroscience for the benefit of replicability in research and the societal view on mental disorders

Cognitive neuroscience comes in many facets, and a particularly large branch of research is conducted in individuals with mental health problems. This article outlines why it is important that cognitive neuroscientists re-shape their role in mental health research and re-define directions of research for the next decades. At present, cognitive neuroscience research in mental health is too firmly rooted in categorial diagnostic definitions of mental health conditions. It is discussed why this hampers a mechanistic understanding of brain functions underlying mental health problems and why this is a problem for replicability in research. A possible solution to these problems is presented. This solution affects the strategy of research questions to be asked, how current trends to increase replicability in research can or cannot be applied in the mental health field and how data are analyzed. Of note, these aspects are not only relevant for the scientific process, but affect the societal view on mental disorders and the position of affected individuals as members of society, as well as the debate on the inclusion of so-called WEIRD and non-WEIRD people in studies. Accordingly, societal and science political aspects of re-defining the role of cognitive neuroscientists in mental health research are elaborated that will be important to shape cognitive neuroscience in mental health for the next decades.
Operational calibration of VIIRS reflective solar band sensor data records

The Visible-Infrared Imaging Radiometer Suite (VIIRS) is an instrument on-board the Suomi National Polar-orbiting Partnership (NPP) spacecraft, which launched on October 28, 2011. VIIRS performs measurements in 14 reflective solar bands (RSBs) spanning wavelengths from 412 nm to 2.25 um, which are calibrated by using solar radiance reflected from a Solar Diffuser (SD). The SD reflectance degrades over time, and a Solar Diffuser Stability Monitor (SDSM) is used to track the changes. The ratio between the calculated solar radiance reflected from the SD and the VIIRS measurement of this radiance using the pre-launch calibration coefficients is known as the “F factor. ” The F factor is applied in the ground processing as a scale correction to the pre-launch calibration coefficients used to generate the calibrated radiances and reflectances comprising the Sensor Data Records (SDRs). The F factor is trended over time to track instrument response degradation. The equation for calculating expected solar radiance, and the coefficients used to convert the raw digital numbers measured by the detectors into radiance and reflectance values, are based on parameters stored in various Look-Up Tables (LUTs). This paper will discuss on-orbit RSB calibration for VIIRS, along with a description of the processing methodology, which includes operational LUT updates based on off-line calculations of F factor trending behavior.
Anti-glutathione S-transferase theta 1 antibodies correlate with graft loss in non-sensitized pediatric kidney recipients

Introduction Immunity to Human leukocyte antigen (HLA) cannot explain all cases of ABMR, nor the differences observed in the outcome of kidney recipients with circulating DSAs endowed with similar biologic characteristics. Thus, increasing attention has recently been focused on the role of immunity to non-HLA antigenic targets. Methods We analyzed humoral auto- and alloimmune responses to the non-HLA antigen glutathione S-transferase theta 1 (GSTT1), along with development of de novo (dn)HLA-DSAs, in a cohort of 146 pediatric non-sensitized recipients of first kidney allograft, to analyze its role in ABMR and graft loss. A multiplex bead assay was employed to assess GSTT1 antibodies (Abs). Results We observed development of GSTT1 Abs in 71 recipients after transplantation, 16 with MFI > 8031 (4th quartile: Q4 group). In univariate analyses, we found an association between Q4-GSTT1Abs and ABMR and graft loss, suggesting a potential role in inducing graft damage, as GSTT1 Abs were identified within ABMR biopsies of patients with graft function deterioration in the absence of concomitant intragraft HLA-DSAs. HLA-DSAs and GSTT1 Abs were independent predictors of graft loss in our cohort. As GSTT1 Ab development preceded or coincided with the appearance of dnHLA-DSAs, we tested and found that a model with the two combined parameters proved more fit to classify patients at risk of graft loss. Discussion Our observations on the harmful effects of GSTT1Abs, alone or in combination with HLA-DSAs, add to the evidence pointing to a negative role of allo- and auto-non-HLA Abs on kidney graft outcome.
Identification and characterization of Bacillus thuringiensis and other Bacillus cereus group isolates from spinach by whole genome sequencing

Bacillus thuringiensis (Bt), used as a biological control agent (BCA), can persist on plants, and from there can be introduced into the final food product. In routine food safety diagnostics, these Bt residues cannot be distinguished from natural populations of Bacillus cereus present in plants and all are enumerated as “presumptive B. cereus. ” In this study, information on eventual use of Bt biopesticides, brand, application times and intervals provided by three food processing companies in Belgium, were integrated with quantitative data on presumptive B. cereus measured from fresh to frozen food products. This information together with data on genomic similarity obtained via whole genome sequencing (WGS) and cry gene profiling using a quantitative real-time PCR (qPCR) assay, confirmed that six out of 11 Bt isolates originated from the applied Bt biocontrol products. These identified Bt strains were shown to carry enterotoxin genes (nhe, hbl, cytK-2) and express Hbl enterotoxin in vitro. It was also noted that these Bt biopesticide strains showed no growth at standard refrigeration temperatures and a low or moderate biofilm-forming ability and cytotoxic activity. Our results also showed that the use of Bt as a BCA on spinach plants in the field led to higher residual counts of Bt in spinach (fresh or frozen) in the food supply chain, but the residual counts exceeding at present commonly assumed safety limit of 105 CFU/g was only found in one fresh spinach sample. It is therefore recommended to establish a pre-harvest interval for Bt biopesticide application in the field to lower the likelihood of noncompliance to the generic B. cereus safety limit. Furthermore, WGS was found to be the best way to identify Bt biopesticide isolates at the strain level for foodborne outbreaks and clinical surveillance. The developed qPCR assay for screening on the presence of cry genes in presumptive B. cereus can be applied as a rapid routine test as an amendment to the already existing test on Bt crystal proteins determined via phase-contrast microscopy.
Predicting AT(N) pathologies in Alzheimer’s disease from blood-based proteomic data using neural networks

Background and objective Blood-based biomarkers represent a promising approach to help identify early Alzheimer’s disease (AD). Previous research has applied traditional machine learning (ML) to analyze plasma omics data and search for potential biomarkers, but the most modern ML methods based on deep learning has however been scarcely explored. In the current study, we aim to harness the power of state-of-the-art deep learning neural networks (NNs) to identify plasma proteins that predict amyloid, tau, and neurodegeneration (AT[N]) pathologies in AD. Methods We measured 3,635 proteins using SOMAscan in 881 participants from the European Medical Information Framework for AD Multimodal Biomarker Discovery study (EMIF-AD MBD). Participants underwent measurements of brain amyloid β (Aβ) burden, phosphorylated tau (p-tau) burden, and total tau (t-tau) burden to determine their AT(N) statuses. We ranked proteins by their association with Aβ, p-tau, t-tau, and AT(N), and fed the top 100 proteins along with age and apolipoprotein E (APOE) status into NN classifiers as input features to predict these four outcomes relevant to AD. We compared NN performance of using proteins, age, and APOE genotype with performance of using age and APOE status alone to identify protein panels that optimally improved the prediction over these main risk factors. Proteins that improved the prediction for each outcome were aggregated and nominated for pathway enrichment and protein–protein interaction enrichment analysis. Results Age and APOE alone predicted Aβ, p-tau, t-tau, and AT(N) burden with area under the curve (AUC) scores of 0.748, 0.662, 0.710, and 0.795. The addition of proteins significantly improved AUCs to 0.782, 0.674, 0.734, and 0.831, respectively. The identified proteins were enriched in five clusters of AD-associated pathways including human immunodeficiency virus 1 infection, p53 signaling pathway, and phosphoinositide-3-kinase–protein kinase B/Akt signaling pathway. Conclusion Combined with age and APOE genotype, the proteins identified have the potential to serve as blood-based biomarkers for AD and await validation in future studies. While the NNs did not achieve better scores than the support vector machine model used in our previous study, their performances were likely limited by small sample size.
Advances in Joint Modelling: A Review of Recent Developments with Application to the Survival of End Stage Renal Disease Patients

L'approche mixte, pour la modélisation des processus de survie et des processus longitudinaux, connait de nos jours un succès grandissant, en particulier lorsqu';il existe une interdépendance entre ceux‐ci. Réputés pour leur efficacité, les modèles mixtes sont moins biaisés par rapport aux méthodes classiques naïves, d'où une littérature abondante sur le sujet. L'objet de cette étude est de présenter une revue de la littérature récente sur les modèles mixtes, en l'occurrence ceux utilisés pour l'estimation du temps d'échec dans les processus de survie. Nous présenterons une analyse détaillée de la gamme de modèles de survie utilisés pour la construction des modèles mixtes. Une attention particulière sera accordée aux progrès récents dans le développement des logiciels dédiés à la construction de ces modéles. Une illustration sur l'utilisation des progiciels JM et JoineR, développés dans l'environnement R, sera présentée pour le cas de l'analyse de survie des patients souffrant d'insuffisance rénale en phase terminale. Finalement, nous concluons avec une discussion sur plusieurs pistes de recherche potentielles dans le domaine.
Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis

Evidence of the advantages of Coptidis Rhizoma (CR) for the treatment of ulcerative colitis (UC) is accumulating. However, research revealing the targets and molecular mechanisms of CR against UC is scarce. In this research, a bioinformatics analysis was performed to carry out the physicochemical properties and biological activities of phytochemicals in CR and analyze the binding activities, targets, biological functions and mechanisms of CR against UC. This research shows that the CR’s key phytochemicals, which are named Coptisine, Berberrubine, Berlambine, Berberine, Epiberberine, Obacunone, Worenine, Quercetin, (R)-Canadine, Magnograndiolide, Palmatine and Moupinamide, have ideal physicochemical properties and bioactivity. A total of 1,904 potential phytochemical targets and 17,995 UC-related targets are identified, and we finally acquire 233 intersection targets between key phytochemicals and disease. A protein-protein interaction network of 233 common targets was constructed; and six hub targets were acquired with a degree greater than or equal to median, namely TP53, HSP90AA1, STAT3, ESR1, MYC, and RELA. The enrichment analysis suggested that the core targets may exert an impact on anti-inflammatory, immunoregulatory, anti-oxidant and anti-fibrosis functions mainly through the PI3K/ART signaling pathway, Th17 differentiation signaling pathway, inflammatory bowel disease signaling pathway, etcetera. Also, a molecular docking analysis shows that the key phytochemicals have strong affinity for binding to the core targets. Finally, the interaction network of CR, phytochemicals, targets, GO functions, KEGG pathways and UC is constructed. This study indicates that the key phytochemicals in CR have superior drug likeness and bioactivity, and the molecular mechanism of key phytochemicals against UC may be via the signaling pathway mentioned above. The potential and critical pharmacological mechanisms provide a direction for future research.
A metabotropic glutamate receptor affects the growth and development of Schistosoma japonicum

Schistosomiasis is a zoonotic parasitic disease caused by schistosome infection that severely threatens human health. Therapy relies mainly on single drug treatment with praziquantel. Therefore, there is an urgent need to develop alternative medicines. The glutamate neurotransmitter in helminths is involved in many physiological functions by interacting with various cell-surface receptors. However, the roles and detailed regulatory mechanisms of the metabotropic glutamate receptor (mGluR) in the growth and development of Schistosoma japonicum remain poorly understood. In this study, we identified two putative mGluRs in S. japonicum and named them SjGRM7 (Sjc_001309, similar to GRM7) and SjGRM (Sjc_001163, similar to mGluR). Further validation using a calcium mobilization assay showed that SjGRM7 and SjGRM are glutamate-specific. The results of in situ hybridization showed that SjGRM is mainly located in the nerves of both males and gonads of females, and SjGRM7 is principally found in the nerves and gonads of males and females. In a RNA interference experiment, the results showed that SjGRM7 knockdown by double-stranded RNA (dsRNA) in S. japonicum caused edema, chassis detachment, and separation of paired worms in vitro. Furthermore, dsRNA interference of SjGRM7 could significantly affect the development and egg production of male and female worms in vivo and alleviate the host liver granulomas and fibrosis. Finally, we examined the molecular mechanisms underlying the regulatory function of mGluR using RNA sequencing. The data suggest that SjGRM7 propagates its signals through the G protein-coupled receptor signaling pathway to promote nervous system development in S. japonicum. In conclusion, SjGRM7 is a potential target for anti-schistosomiasis. This study enables future research on the mechanisms of action of Schistosomiasis japonica drugs.
PAG3 promotes the differentiation of bloodstream forms in Trypanosoma brucei and reveals the evolutionary relationship among the Trypanozoon trypanosomes

Introduction Trypanosoma brucei, T. evansi and T. equiperdum are members of the subgenus Trypanozoon and are highly similar morphologically and genetically. The main differences between these three species are their differentiation patterns in the hosts and the role of vectors in their life cycles. However, the mechanisms causing these differences are still controversial. Methods PAG3 gene was accessed by PCR amplification in 26 strains of Trypanozoon and sequences were then analyzed by BLAST accompanied with T. evansitype B group. RNA interference and CRISPR/Cas9 were used for revealing possible role of PAG3 in slender to stumpy transformation. Results The procyclin associated gene 3 (PAG3) can be found in the pleomorphicspecies, T.brucei, which undergoes differentiation of slender forms to the stumpy form. This differentiation process is crucial for transmission to the tsetse fly vector. However, a homologue of PAG3 was not detected in either T. evansi or in the majority of T. equiperdum strains which are allmonomorphic. Furthere xperiments in T. brucei demonstrated that, when PAG3 was down-regulated or absent, there was a significant reduction in the differentiation from slender to stumpy forms. Conclusion Therefore, we conclude that PAG3 is a key nuclear gene involved in the slender to stumpy differentiation pathway of T.brucei in the mammalian host. Loss of this gene might also offer a simple evolutionary mechanism explaining why T. evansi and some T. equiperdum have lost the ability to differentiate and have been driven to adapt to transmission cycles that by pass the tsetse vector or mechanical contact.