Miracle-dz/UniFAR-FTUs huggingface dataset:
Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation

To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL‐1β was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor‐α (TNF‐α) and IL‐6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation‐specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O‐Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL‐1β‐induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL‐1β‐induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.
SF2Former: Amyotrophic Lateral Sclerosis Identification From Multi-center MRI Data Using Spatial and Frequency Fusion Transformer

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder involving motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has turned into a prominent class of machine learning programs in computer vision and has been successfully employed to solve diverse medical image analysis tasks. However, deep learning-based methods applied to neuroimaging have not achieved superior performance in ALS patients classification from healthy controls due to having insignificant structural changes correlated with pathological features. Therefore, the critical challenge in deep models is to determine useful discriminative features with limited training data. By exploiting the long-range relationship of image features, this study introduces a framework named S F2Former that leverages vision transformer architecture’s power to distinguish the ALS subjects from the control group. To further improve the network’s performance, spatial and frequency domain information are combined because MRI scans are captured in the frequency domain before being converted to the spatial domain. The proposed framework is trained with a set of consecutive coronal 2D slices, which uses the pre-trained weights on ImageNet by leveraging transfer learning. Finally, a majority voting scheme has been employed to those coronal slices of a particular subject to produce the final classification decision. Our proposed architecture has been thoroughly assessed with multi-modal neuroimaging data (i.e., T1-weighted, R2*, FLAIR) using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of our proposed strategy in terms of classification accuracy compared with several popular deep learning-based techniques. © 2023 Elsevier B. V. All rights reserved. ar X iv :2 30 2. 10 85 9v 1 [ ee ss . I V ] 2 1 Fe b 20 23 2 Kushol et al. / Computerized Medical Imaging and Graphics (2023)
Mudstone porosity and clay fraction in overpressured basins

This thesis demonstrates the use of a mixture of standard and novel petrophysical techniques to estimate physical parameters of mudstone and explores the use of a generic, clay fraction-dependent compaction model in the context of pore pressure evaluation. Mudstones are often highly heterogeneous, yet many authors use a single compaction trend to describe their behaviour. Previous work has shown that the rate of a mudstone's compaction with vertical effective stress is a function of its clay fraction, the proportion of the sediment matrix with a particle diameter of less than 2μm. This observation forms the basis of the generic mudstone compaction model used in this thesis. The use of the generic compaction model is explored in two case studies using characterised mudstone samples and wireline log data from the Gulf of Thailand and Gulf of Mexico. Further mudstone samples from the Central North Sea were characterised. An error analysis showed that the compaction model can provide estimates of pressure to within ±1.8MPa at a burial depth of 3km (equivalent to ±0.5ppg mudweight) when the input parameters are constrained to an attainable level. In both cases studied, standard methods of analysis could not provide reasonable estimates of pressure in mudstone using wireline resistivity and porosity log data compared to pressure measurements in associated sand bodies. The deep sediments of the two wells studied from the Gulf of Thailand are overconsolidated with respect to their current stress state. The generic compaction model was used to determine that the overconsolidated sediments were uplifted by 1,300m and have been reburied beneath 900m of sediment that now overlies a regional unconformity. The generic compaction model was used in conjunction with an artificial neural network technique for the characterisation of mudstones from wireline data to determine pressure estimates in the mudstones of three deepwater wells in the Gulf of Mexico. A pressure transition zone in one well was shown to be associated with a 10% increase of mudstone clay fraction within the zone compared to surrounding rocks. In both case studies disequilibrium compaction was identified as the key overpressure generation mechanism.
Impaired erythropoietin‐producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats

An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin‐producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre‐pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho‐cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.
Quorum-sensing, intra- and inter-species competition in the staphylococci

In Gram-positive bacteria such as Staphylococcus aureus and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the agr-mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on agr functionality is considered and the consequences of agr dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between S. aureus and the CoNS and its anti-infective potential.
The atlastin ER morphogenic proteins promote formation of a membrane penetration site during non-enveloped virus entry

ABSTRACT During entry, non-enveloped viruses penetrate a host membrane to cause infection, although how this is accomplished remains enigmatic. Polyomaviruses (PyVs) are non-enveloped DNA viruses that penetrate the endoplasmic reticulum (ER) membrane to reach the cytosol en route to the nucleus for infection. To penetrate the ER membrane, the prototype PyV simian virus 40 (SV40) induces formation of ER-escape sites, called foci, composed of repeating units of multi-tubular ER junctions where the virus is thought to exit. How SV40 triggers formation of the ER-foci harboring these multi-tubular ER junctions is unclear. Here, we show that the ER morphogenic atlastin 2 (ATL2) and ATL3 membrane proteins play critical roles in SV40 infection. Mechanistically, ATL3 mobilizes to the ER-foci where it deploys its GTPase-dependent membrane fusion activity to promote formation of multi-tubular ER junctions within the ER-foci. ATL3 also engages an SV40-containing membrane penetration complex. By contrast, ATL2 does not reorganize to the ER-foci. Instead, it supports the reticular ER morphology critical for the integrity of the ATL3-dependent membrane complex. Our findings illuminate how two host factors play distinct roles in the formation of an essential membrane penetration site for a non-enveloped virus. IMPORTANCE Membrane penetration by non-enveloped viruses, a critical infection step, remains enigmatic. The non-enveloped PyV simian virus 40 (SV40) penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol en route for infection. During ER-to-cytosol membrane penetration, SV40 triggers formation of ER-associated structures (called ER-foci) that function as the membrane penetration sites. Here, we discover a role of the ATL ER membrane proteins—known to shape the ER morphology—during SV40-induced ER-foci formation. These findings illuminate how a non-enveloped virus hijacks host components to construct a membrane penetration structure. Membrane penetration by non-enveloped viruses, a critical infection step, remains enigmatic. The non-enveloped PyV simian virus 40 (SV40) penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol en route for infection. During ER-to-cytosol membrane penetration, SV40 triggers formation of ER-associated structures (called ER-foci) that function as the membrane penetration sites. Here, we discover a role of the ATL ER membrane proteins—known to shape the ER morphology—during SV40-induced ER-foci formation. These findings illuminate how a non-enveloped virus hijacks host components to construct a membrane penetration structure.
The relationship between APOE genotype, CSF Tau and cognition across the Alzheimer's disease spectrum, moderation and mediation role of insula network connectivity

Abstract Aims To investigate whether insula network connectivity modulates the relationship between apolipoprotein E (APOE) ε4 genotype, cerebrospinal fluid (CSF) biomarkers (Aβ, Tau, and pTau) and cognition across Alzheimer's disease (AD) spectrum. Methods Forty‐six cognitive normal (CN), 35 subjective memory complaint (SMC), 41 mild cognitive impairment (MCI), and 32 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were obtained. Multivariable linear regression analyses were conducted to investigate the main effects and interaction of the APOE genotype and disease status on the insula functional connectivity (IFC) network. Mediation and moderation analysis were performed to investigate whether IFC strengths regulate the association between APOE genotype, CSF biomarkers and cognition. Additionally, the support vector machine (SVM) model integrating APOE genotype, CSF biomarkers, and neuroimaging biomarkers (insula volumes and altered regional IFCs) was used to classify the AD spectrum. Results The interactive effect of the APOE genotype and disease on the insula network was found in the left medial superior frontal gyrus (SFGmed.L), right anterior medial prefrontal cortex (aMPFC.R), and bilateral thalamus (THA.B). The functional connectivities (FCs) in the left insula (LIns) connecting with the left posterior middle temporal gyrus (pMTG.L), SFGmed.L, and right lingual gyrus (LING.R) were correlated with cognition. LIns‐SFGmed.L and LIns‐pMTG.L FCs could moderate the effects of Tau on cognition. Furthermore, LIns‐SFGmed.L FC may suppress the association between APOE genotype and cognition. More importantly, the integrated biomarkers from the SVM model yielded strong powers for classifying the AD spectrum. Conclusions Insula functional connectivity regulated the association between APOE genotype, CSF Tau and cognition and provided stage‐dependent biomarkers for early differentiation of the AD spectrum. The present study used a cross‐sectional design. Follow‐up studies are needed to validate the relationship.
Antiseizure medications as migraine preventatives: a call for action for a teratogenic and neurodevelopmental risk removal

ABSTRACT Introduction A recent study has demonstrated an increased risk of neurodevelopmental disorders, including autism spectrum disorder, in individuals exposed to either valproate or topiramate monotherapy. Regulatory bodies have initiated a review to reassess the safety of topiramate exposure during pregnancy. These novel findings raise concerns regarding the recommendation of antiseizure medications in women of childbearing potential. This manuscript highlights current research defining concerns specific to the use of valproate and topiramate in women of childbearing potential. Areas covered This manuscript summarizes recent findings regarding the safety of valproate and topiramate when compared to alternative therapies for the preventative treatment of migraine in women of childbearing potential. The studies included in this review were selected following a comprehensive literature review of multiple relevant databases. All studies that were published within the past 15 years were considered for inclusion. Expert opinion The use of valproate and topiramate in women of childbearing potential should be highly discouraged. Our recommendations include a review of current prescribing guidelines, further public education regarding the neurodevelopmental and congenital risks associated with the use of valproate and topiramate, and an appeal for further research defining the safety of alternative medications for migraine prevention when intrauterine exposure is possible.
Enhanced lupus progression in alcohol‐administered Fc gamma receptor‐IIb–deficiency lupus mice, partly through leaky gut‐induced inflammation

Alcohol can induce a leaky gut, with translocation of microbial molecules from the gut into the blood circulation. Although the contribution of inflammation to organ‐mediated damage in lupus has been previously demonstrated, the mechanistic roles of alcohol consumption in lupus activation are not known. Herein, we tested the effects of 10‐week lasting alcohol administration on organ damages and immune responses in 8‐week‐old lupus‐prone Fc gamma receptor IIb–deficient (FcγRIIb−/−) mice. Our study endpoints were evaluation of systemic inflammation and assessment of fecal dysbiosis along with endotoxemia. In comparison with alcohol‐administered wild‐type mice, FcγRIIb−/− mice demonstrated more prominent liver damage (enzyme, histological score, apoptosis, malondialdehyde oxidant) and serum interleukin(IL)‐6 levels, despite a similarity in leaky gut (fluorescein isothiocyanate–dextran assay, endotoxemia and gut occludin‐1 immunofluorescence), fecal dysbiosis (microbiome analysis) and endotoxemia. All alcohol‐administered FcγRIIb−/− mice developed lupus‐like characteristics (serum anti‐dsDNA, proteinuria, serum creatinine and kidney injury score) with spleen apoptosis, whereas control FcγRIIb−/− mice showed only a subtle anti‐dsDNA. Both alcohol and lipopolysaccharide (LPS) similarly impaired enterocyte integrity (transepithelial electrical resistance), and only LPS, but not alcohol, upregulated the IL‐8 gene in Caco‐2 cells. In macrophages, alcohol mildly activated supernatant cytokines (tumor necrosis factor‐α and IL‐6), but not M1 polarization–associated genes (IL‐1β and iNOS), whereas LPS prominently induced both parameters (more prominent in FcγRIIb−/− macrophages than wild type). There was no synergy in LPS plus alcohol compared with LPS alone in both enterocytes and macrophages. In conclusion, alcohol might exacerbate lupus‐like activity partly through a profound inflammation from the leaky gut in FcγRIIb−/− mice.
Initial description of the novel handheld wireless ultrasound device TE Air with Doppler and Color Duplex imaging

OBJECTIVE: To test and initially describe a new handheld wireless ultrasound technique (TE Air) for clinical use. METHODS: In this pilot study, the new ultrasound device TE Air from Mindray was used to examine the hepatic and renal vessels of healthy volunteers for first impressions. The probe has a sector transducer with a frequency range of 1.8–4.5 MHz. The B-mode and color-coded doppler sonography (CCDS) scanning methods were used. A high-end device from the same company (Resona 9, Mindray) was used as a reference. The results were evaluated using an image rating scale ranging from 0 to 5, with 0 indicating not assessable and 5 indicating without limitations. RESULTS: Altogether, 61 participants (n = 34 female [55.7%], n = 27 male [44.3%]), age range 18–83 years, mean age 37.9±16.5 years) could be adequately studied using TE AIR and the high-end device. With one exception, the image quality score for TE Air never fell below 3 and had a mean/median scored of 4.97/5.00 for the B-mode, 4.92/5.00 for the color flow (CF) mode, and 4.89/5.00 for the pulse wave (PW) mode of the hepatic vein, 4.90/5.00 for the portal vein, 4.11/4.00 for the hepatic artery, and 4.57/5.00 for the renal segmental artery. A significant difference in the assessment of flow measurement of the hepatic artery and renal segmental arteries was found between TE AIR and the high-end device. CONCLUSIONS: TE Air represents a new dimension in point-of-care ultrasound via wireless handheld devices. Especially, its flow measurement ability offers a relevant advantage over other available handheld models. TE Air provides a formally sufficient image quality in terms of diagnostic significance.
Could Spatial Awareness Affect Situation Awareness: A Conceptual Examination

Purpose: The purpose of this study was to explore the relationship between situation awareness (SA) and the physical environment in patient rooms through building a conceptual model. Background: Nurses work in very complicated and dynamic environments where having high levels of SA could be critical for their performance. Studies have also shown that nurses’ awareness of the physical environment and patient room is a part of their awareness of dynamic situations in which nurses’ spatial awareness may play a role in SA. Despite literature outlining the importance of SA, there is a lack of studies exploring the relationship between the two. Method: A literature review was conducted for the study from nursing and psychology databases. Thirty-three articles, books, and dissertations from a scoping review were included for in-depth review. Results: An in-depth review of the harvested literature indicated that there is in fact a relationship between these two phenomena. Founded on Endsley’s model of SA, the literature review in this study offers a conceptual model that articulates a plausible causal pathway between the physical environment and SA. Conclusions: There are a lot of studies focusing on SA and various aspects of it related to nursing, but almost none mention the physical environment and its impact on SA. The current inquiry suggests that spatial awareness plays a prominent role in SA.
The role of fire in bush encroachment in Ithala Game Reserve.

44 Introduction.45 Aerial photographs . 48 The effects of fire in Ithala Game Reserve . 47 Methods . 49 Study site . 49 Data acquisition and analysis . 51 Rainfall data . 51 Herbivore population estimates.52
Prostaglandin E2, Osmoregulation, and Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Visual Abstract Background Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in preclinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity, and disease progression in human ADPKD. Methods Urinary excretions of PGE2 and its metabolite (PGEM) were measured in a prospective cohort of patients with ADPKD. The associations between urinary PGE2 and PGEM excretions, markers of osmoregulation, eGFR and height-adjusted total kidney volume were assessed using linear regression models. Cox regression and linear mixed models were used for the longitudinal analysis of the associations between urinary PGE2 and PGEM excretions and disease progression defined as 40% eGFR loss or kidney failure, and change in eGFR over time. In two intervention studies, we quantified the effect of starting tolvaptan and adding hydrochlorothiazide to tolvaptan on urinary PGE2 and PGEM excretions. Results In 562 patients with ADPKD (61% female, eGFR 63±28 ml/min per 1.73 m2), higher urinary PGE2 or PGEM excretions were independently associated with higher plasma copeptin, lower urine osmolality, lower eGFR, and greater total kidney volume. Participants with higher baseline urinary PGE2 and PGEM excretions had a higher risk of 40% eGFR loss or kidney failure (hazard ratio, 1.28; 95% confidence interval [CI], 1.13 to 1.46 and hazard ratio, 1.50; 95% CI, 1.26 to 1.80 per two-fold higher urinary PGE2 or PGEM excretions) and a faster change in eGFR over time (−0.39 [95% CI, −0.59 to −0.20] and −0.53 [95% CI, −0.75 to −0.31] ml/min per 1.73 m2 per year). In the intervention studies, urinary PGEM excretion was higher after starting tolvaptan, while urinary PGE2 excretion was higher after adding hydrochlorothiazide to tolvaptan. Conclusions Higher urinary PGE2 and PGEM excretions in patients with ADPKD are associated with impaired osmoregulation, disease severity, and progression.