Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Five Quality Needs for Rheumatology (Text Analysis and Literature Review)

Background: While the use of the term “quality” in industry relates to the basic idea of making processes measurable and standardizing processes, medicine focuses on achieving health goals that go far beyond the mere implementation of diagnostic and therapeutic processes. However, the quality management systems used are often simple, self-created concepts that concentrate on administrative processes without considering the quality of the results, which is essential for the patient. For several rheumatic diseases, both outcome and treatment goals have been defined. This work summarizes current mainstreams of strategies with published quality efforts in rheumatology. Methods: PubMed, Cochrane Library, and Web of Science were used to search for studies, and additional manual searches were carried out. Screening and content evaluation were carried out using the PRISMA-P 2015 checklist. After duplicate search in the Endnote reference management software (version X9.1), the software Rayyan QCRI (https://rayyan.qcri.org) was applied to check for pre-defined inclusion and exclusion criteria. Abstracts and full texts were screened and rated using Voyant Tools (https://voyant-tools.org/). Key issues were identified using the collocate analysis. Results: The number of selected publications was small but specific (14 relevant correlations with coefficients >0.8). Using trend analysis, 15 publications with relative frequency of keywords >0.0125 were used for content analysis, revealing 5 quality needs. The treat to target (T2T) initiative was identified as fundamental paradigm. Outcome parameters required for T2T also allow quality assessments in routine clinical work. Quality care by multidisciplinary teams also focusing on polypharmacy and other quality aspects become essential, A global software platform to assess quality aspects is missing. Such an approach requires reporting of multiple outcome parameters according to evidence-based clinical guidelines and recommendations for the different rheumatic diseases. All health aspects defined by the WHO (physical, mental, and social health) have to be integrated into the management of rheumatic patients. Conclusion: For the future, quality projects need goals defined by T2T based initiatives in routine clinical work, secondary quality goals include multidisciplinary cooperation and reduction of polypharmacy. Quality indicators and standards in different health systems will provide new information to optimize patients' care in different health systems.
Aberrant Functional Connectivity of the Posterior Cingulate Cortex in Type 2 Diabetes Without Cognitive Impairment and Microvascular Complications

Objective We aimed to investigate the alterations of brain functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without clinical evidence of cognitive impairment and microvascular complications (woCIMC-T2DM) using resting-state functional MRI (rs-fMRI) and to determine whether its value was correlated with clinical indicators. Methods A total of 27 T2DM and 26 healthy controls (HCs) were prospectively examined. Cognitive impairment was excluded using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scales, and microvascular complications were excluded by fundus photography, microalbuminuria, and other indicators. The correlation maps, derived from rs-fMRI with posterior cingulate cortex (PCC) as the seed, were compared between T2DM patients and HCs. Pearson’s correlation analysis was performed to determine the relationship between the FC of PCC and the clinical indicators. Results Compared with HC, woCIMC-T2DM patients showed significantly decreased FCs with PCC (PCC-FCs) in the anterior cingulate cortex (ACC), right superior frontal gyrus, right medial frontal gyrus, and right angular gyrus. Meanwhile, increased PCC-FCs was observed in the right superior temporal gyrus and calcarine fissure (CAL). The FC of PCC-ACC was negatively correlated with glycosylated hemoglobin (HbA1c) and diabetes duration, and the FC of PCC-CAL was significantly positively correlated with HbA1c and diabetes duration. Conclusion The FC, especially of the PCC with cognitive and visual brain regions, was altered before clinically measurable cognitive impairment and microvascular complications occurred in T2DM patients. In addition, the FC of the PCC with cognitive and visual brain regions was correlated with HbA1c and diabetes duration. This indicates that clinicians should pay attention not only to blood glucose control but also to brain function changes before the occurrence of adverse complications, which is of great significance for the prevention of cognitive dysfunction and visual impairment.
Improved Motion Classification With an Integrated Multimodal Exoskeleton Interface

Human motion intention detection is an essential part of the control of upper-body exoskeletons. While surface electromyography (sEMG)-based systems may be able to provide anticipatory control, they typically require exact placement of the electrodes on the muscle bodies which limits the practical use and donning of the technology. In this study, we propose a novel physical interface for exoskeletons with integrated sEMG- and pressure sensors. The sensors are 3D-printed with flexible, conductive materials and allow multi-modal information to be obtained during operation. A K-Nearest Neighbours classifier is implemented in an off-line manner to detect reaching movements and lifting tasks that represent daily activities of industrial workers. The performance of the classifier is validated through repeated experiments and compared to a unimodal EMG-based classifier. The results indicate that excellent prediction performance can be obtained, even with a minimal amount of sEMG electrodes and without specific placement of the electrode.
Fis Connects Two Sensory Pathways, Quorum Sensing and Surface Sensing, to Control Motility in Vibrio parahaemolyticus

Factor for inversion stimulation is a global regulator that is highly expressed during exponential phase growth and undetectable in stationary phase growth. Quorum sensing (QS) is a global regulatory mechanism that controls gene expression in response to changes in cell density and growth phase. In Vibrio parahaemolyticus, a marine species and a significant human pathogen, the QS regulatory sRNAs, Qrr1 to Qrr5, are expressed during exponential growth and negatively regulate the high cell density QS master regulator OpaR. OpaR is a positive regulator of capsule polysaccharide (CPS) formation, which is required for biofilm formation, and is a repressor of lateral flagella required for swarming motility. In V. parahaemolyticus, we show that Fis is a positive regulator of the qrr sRNAs expression. In an in-frame fis deletion mutant, qrr expression was repressed and opaR expression was induced. The Δfis mutant produced CPS and biofilm, but swarming motility was abolished. Also, the fis deletion mutant was more sensitive to polymyxin B. Swarming motility requires expression of both the surface sensing scrABC operon and lateral flagella laf operon. Our data showed that in the Δfis mutant both laf and scrABC genes were repressed. Fis controlled swarming motility indirectly through the QS pathway and directly through the surface sensing pathway. To determine the effects of Fis on cellular metabolism, we performed in vitro growth competition assays, and found that Δfis was outcompeted by wild type in minimal media supplemented with intestinal mucus as a sole nutrient source. The data showed that Fis positively modulated mucus components L-arabinose, D-gluconate and N-acetyl-D-glucosamine catabolism gene expression. In an in vivo colonization competition assay, Δfis was outcompeted by wild type, indicating Fis is required for fitness. Overall, these data demonstrate a global regulatory role for Fis in V. parahaemolyticus that includes QS, motility, and metabolism.
Editorial: Host-Pathogen Interactions During Pneumococcal Infection

1 Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Japan, 2 Department of Bacteriology, The Jikei University School of Medicine, Tokyo, Japan, 3 Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, Tokyo, Japan, 4 Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Japan, 5 Department of Pediatrics, University of California (UC), San Diego, La Jolla, CA, United States, 6 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California (UC), San Diego, La Jolla, CA, United States, 7 Biomedical Sciences Graduate Program, University of California (UC), San Diego, La Jolla, CA, United States
Inhibition of PKR by Viruses

Cells respond to viral infections through sensors that detect non-self-molecules, and through effectors, which can have direct antiviral activities or adapt cell physiology to limit viral infection and propagation. Eukaryotic translation initiation factor 2 alpha kinase 2, better known as PKR, acts as both a sensor and an effector in the response to viral infections. After sensing double-stranded RNA molecules in infected cells, PKR self-activates and majorly exerts its antiviral function by blocking the translation machinery and inducing apoptosis. The antiviral potency of PKR is emphasized by the number of strategies developed by viruses to antagonize the PKR pathway. In this review, we present an update on the diversity of such strategies, which range from preventing double-stranded RNA recognition upstream from PKR activation, to activating eIF2B downstream from PKR targets.
Interconnected Gene Networks Underpin the Clinical Overlap of HNRNPH1-Related and Rubinstein–Taybi Intellectual Disability Syndromes

The transcriptome of induced pluripotent stem cell (iPSC)-neurons (iNeurons) generated from patients with neurodevelopmental disorders (NDDs) is a quantitative phenotype that provides the biological context for unveiling themolecular pathways disrupted in the “diseased” cells. RNASeq of iNeurons from individuals with Rubinstein–Taybi syndrome (RSTS, MIM# 180849, and #613684), an intellectual disability (ID) disorder caused by monoallelic pathogenic variants in the genes encoding CBP/p300 lysine acetyltransferases (Hennekam, 2006), revealed that RSTS-univocal downregulated genes (DRGs) encoding a coherent network of RNA-binding proteins (RBPs) are implicated in RNA processing and ribosome complex biogenesis (Calzari et al., 2020). Variation or misregulation of several genes for heterogeneous nuclear ribonuclear proteins (hnRNP), a wellcharacterized family of RBPs implicated in RNA splicing and processing (Geuens et al., 2016), has been linked to neurological and neurodevelopmental disorders supporting a variably shared molecular pathogenesis of disease subtypes that enhances the identification of new family-related NDD genes (Gillentine et al., 2021). Interestingly, like hnRNPs, lysine acetyltransferases have been identified as a gene family involved in RNA processing reaching the FDR significance from metaanalyses of>10.000 NDD exomes (Coe et al., 2019; Gillentine et al., 2021). We discuss herein RSTS and HNRNPH1-related syndromic ID based on their interconnected gene networks and shared phenotypic spectra.
Label-Free Quantitative Proteome Analysis Reveals the Underlying Mechanisms of Grain Nuclear Proteins Involved in Wheat Water-Deficit Response

In this study, we performed the first nuclear proteome analysis of wheat developing grains under water deficit by using a label-free based quantitative proteomic approach. In total, we identified 625 unique proteins as differentially accumulated proteins (DAPs), of which 398 DAPs were predicted to be localized in nucleus. Under water deficit, 146 DAPs were up-regulated and mainly involved in the stress response and oxidation-reduction process, while 252 were down-regulated and mainly participated in translation, the cellular amino metabolic process, and the oxidation-reduction process. The cis-acting elements analysis of the key nuclear DAPs encoding genes demonstrated that most of these genes contained the same cis-acting elements in the promoter region, mainly including ABRE involved in abscisic acid response, antioxidant response element, MYB responsive to drought regulation and MYC responsive to early drought. The cis-acting elements related to environmental stress and hormones response were relatively abundant. The transcription expression profiling of the nuclear up-regulated DAPs encoding genes under different organs, developmental stages and abiotic stresses was further detected by RNA-seq and Real-time quantitative polymerase chain reaction, and more than 50% of these genes showed consistency between transcription and translation expression. Finally, we proposed a putative synergistic responsive network of wheat nuclear proteome to water deficit, revealing the underlying mechanisms of wheat grain nuclear proteome in response to water deficit.
Effects of Pasture Type on Metabolism, Liver and Kidney Function, Antioxidant Status, and Plant Secondary Compounds in Plasma of Grazing, Jersey Dairy Cattle During Mid-lactation

Some pasture species are rich in phytochemicals, able to improve milk yield and quality and to reduce the environmental impacts of livestock farming. The phytochemicals interact with the different gene networks within the animal, such as nuclear factor erythroid 2-related factor 2 (NRF2), but their overall impact on animal health remains to be fully understood. The objective of this study was to identify the effects of pasture Legumes and non-leguminous Forbs containing high bioactive compounds on metabolism and activity of the liver, antioxidant response, kidney function, and inflammation of dairy cows using a large array of blood parameters associated with metabolism and the innate immune system. For this purpose, 26 parameters and the concentration of certain bioactive compounds were assessed in blood plasma, collected from the Jersey cows grazing either Grass, Legume, or Forb-based pastures. In addition, serum collected from all the cows was utilized to detect the changes in NRF2 activation in bovine mammary alveolar cells (MACT) and hepatocytes. Compared with Grass, the cows that grazed both Forb and Legume pastures had lower β-hydroxybutyric acid (BHB) and creatinine and larger vitamin E and the ferric reducing ability of the plasma, supporting an improved antioxidative status for these animals. Compared with both Grass and Legume, the cows that graze Forb pasture had lower urea and urea to creatinine ratio, and lower creatinine, indicating a better kidney function. The cows grazing Legume pasture had greater hematocrit, bilirubin, cholesterol, albumin, β-carotene, retinol, and thiol groups but lower ceruloplasmin, paraoxonase, and myeloperoxidase (MPO) than those grazed Grass and Forb pastures, indicating a positive effect of Legume pasture on the liver, oxidative stress, and red blood cells. The plasma of cows in the various pastures was enriched with various isoflavonoids, especially the cows grazed on Forb and Legume pastures, which likely contributed to improving the antioxidative status of those cows. However, this effect was likely not due to the higher activation of NRF2. Overall, these results indicate that Forb and Legume pastures rich in secondary metabolites do not strongly affect the metabolism but can improve the status of the liver and the kidney and improve the efficiency of N utilization and antioxidant response, compared with the Grass pasture.
Branched-Chain Amino Acids Catabolism Pathway Regulation Plays a Critical Role in the Improvement of Leukopenia Induced by Cyclophosphamide in 4T1 Tumor-Bearing Mice Treated With Lvjiaobuxue Granule

Background: Cyclophosphamide is a common tumor chemotherapy drug used to treat various cancers. However, the resulting immunosuppression leads to leukopenia, which is a serious limiting factor in clinical application. Therefore, the introduction of immunomodulators as adjuvant therapy may help to reduce the hematological side effects of cyclophosphamide. Lvjiaobuxue granule has been widely used in the clinical treatment of gynecological diseases such as anemia and irregular menstruation. Recently, it has been found to increase the function of white blood cells, but its mechanism of action is still unclear. We aimed to reveal the mechanisms of Lvjiaobuxue granule against acute leukopenia by an integrated strategy combining metabolomics with network pharmacology. Methods: Subcutaneously inoculated 4T1 breast cancer cells to prepare tumor-bearing mice, intraperitoneal injection of cyclophosphamide to establish a 4T1 tumor-bearing mice leukopenia animal model, using pharmacodynamic indicators, metabolomics, network pharmacology and molecular biology and other technical methods. To comprehensively and systematically elucidate the effect and mechanism of Lvjiaobuxue granule in improving cyclophosphamide-induced leukopenia in 4T1 tumor-bearing mice. Results: Lvjiaobuxue granule can improve the blood routine parameters and organ index levels of the leukopenia model of 4T1 tumor-bearing mice. Metabolomics studies revealed that 15 endogenous metabolites in the spleen of mice were considered as potential biomarkers of Lvjiaobuxue granule for their protective effect. Metabonomics and network pharmacology integrated analysis indicated that Lvjiaobuxue granule exerted the leukocyte elevation activity by inhibiting the branched-chain amino acids (BCAAs) degradation pathway and increasing the levels of valine, leucine and isoleucine. The results of molecular biology also showed that Lvjiaobuxue granule can significantly regulate the key enzymes in the catabolism of BCAAs, which further illustrates the importance of BCAAs in improving leukopenia. Conclusion: Lvjiaobuxue granule exerts obvious pharmacological effects on the leukopenia model of 4T1 tumor-bearing mice induced by cyclophosphamide, which could be mediated by regulating the branched-chain amino acid degradation pathway and the levels of valine, leucine and isoleucine.
T-Cell Immunotherapy for Pediatric High-Grade Gliomas: New Insights to Overcoming Therapeutic Challenges

Despite decades of research, pediatric central nervous system (CNS) tumors remain the most debilitating, difficult to treat, and deadliest cancers. Current therapies, including radiation, chemotherapy, and/or surgery, are unable to cure these diseases and are associated with serious adverse effects and long-term impairments. Immunotherapy using chimeric antigen receptor (CAR) T cells has the potential to elucidate therapeutic antitumor immune responses that improve survival without the devastating adverse effects associated with other therapies. Yet, despite the outstanding performance of CAR T cells against hematologic malignancies, they have shown little success targeting brain tumors. This lack of efficacy is due to a scarcity of targetable antigens, interactions with the immune microenvironment, and physical and biological barriers limiting the homing and trafficking of CAR T cells to brain tumors. In this review, we summarize experiences with CAR T–cell therapy for pediatric CNS tumors in preclinical and clinical settings and focus on the current roadblocks and novel strategies to potentially overcome those therapeutic challenges.
Epidemiology, Pathophysiology, and Management of Native Atrioventricular Valve Regurgitation in Heart Failure Patients

Atrioventricular regurgitation is frequent in the setting of heart failure. It is due to atrial and ventricular remodelling, as well as rhythmic disturbances and loss of synchrony. Once atrioventricular regurgitation develops, it can aggravate the underlying heart failure, and further participate and aggravate its own severity. Its presence is therefore concomitantly a surrogate of advance disease and a predictor of mortality. Heart failure management, including medical therapy, cardiac resynchronization therapy, and restoration of sinus rhythm, are the initial steps to reduce atrioventricular regurgitation. In the current review, we analyse the current data assessing the epidemiology, pathophysiology, and impact of non-valvular intervention on atrioventricular regurgitation including medical treatment, cardiac resynchronization and atrial fibrillation ablation.
Hourly Mapping of the Layer Height of Thick Smoke Plumes Over the Western U.S. in 2020 Severe Fire Season

A series of huge smoke plume events from the largest wildfire season recorded in California’s modern history has occurred in 2020. Here, a research algorithm was modified to retrieve the aerosol optical centroid height (AOCH) and aerosol optical depth (AOD) from Earth Polychromatic Imaging Camera (EPIC) measurements. The research focus is to gain insights of the algorithm’s feasibility in heavy smoke conditions to study the diurnal variation of AOCH; this is only made possible via EPIC due to its unique position at Lagrange-1 point and its equipment of O2 B-band at which the vegetated surface reflectance is low. Vicarious calibration is applied to the EPIC 443, 680 and 688 nm channels based on the Tropospheric Monitoring Instrument (TROPOMI) observation. This new calibration leads to a better agreement of AOCH values between EPIC retrievals and the counterparts derived from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) aerosol extinction vertical profile. The hourly variation of AOCH up to 0.45 km on September 7 is shown to have important implications for estimating hourly change of surface PM2.5, although more quantitative studies are needed in the future.
Characterization of Phytochrome-Interacting Factor Genes in Pepper and Functional Analysis of CaPIF8 in Cold and Salt Stress

As a subfamily of basic helix-loop-helix (bHLH) transcription factors, phytochrome-interacting factors (PIFs) participate in regulating light-dependent growth and development of plants. However, limited information is available about PIFs in pepper. In the present study, we identified six pepper PIF genes using bioinformatics-based methods. Phylogenetic analysis revealed that the PIFs from pepper and some other plants could be divided into three distinct groups. Motif analysis revealed the presence of many conserved motifs, which is consistent with the classification of PIF proteins. Gene structure analysis suggested that the CaPIF genes have five to seven introns, exhibiting a relatively more stable intron number than other plants such as rice, maize, and tomato. Expression analysis showed that CaPIF8 was up-regulated by cold and salt treatments. CaPIF8-silenced pepper plants obtained by virus-induced gene silencing (VIGS) exhibited higher sensitivity to cold and salt stress, with an obvious increase in relative electrolyte leakage (REL) and variations in the expression of stress-related genes. Further stress tolerance assays revealed that CaPIF8 plays different regulatory roles in cold and salt stress response by promoting the expression of the CBF1 gene and ABA biosynthesis genes, respectively. Our results reveal the key roles of CaPIF8 in cold and salt tolerance of pepper, and lay a solid foundation for clarifying the biological roles of PIFs in pepper and other plants.
Kinetic Dependencies of the Photorefractive Effect in Lithium Niobate Crystals

The kinetic dependence of the photorefractive effect in the congruent lithium niobate crystal is determined in the work. The adequacy of the model for calculating the photoelectric fields from the indicatrix of photoinduced light scattering is shown. Two methods for determining the induced birefringence by interferograms and on the parameters of photoinduced light scattering are compared.