Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Peripheral Nervous System in PD Pathology, Diagnosis, and Treatment

Studies on Parkinson disease (PD) have mostly focused on the central nervous system—specifically, on the loss of mesencephalic dopaminergic neurons and associated motor dysfunction. However, the peripheral nervous system (PNS) is gaining prominence in PD research, with increasing clinical attention being paid to non-motor symptoms. Researchers found abnormal deposition of α-synuclein and neuroinflammation in the PNS. Attempts have been made to use these pathological changes during the clinical diagnosis of PD. Animal studies demonstrated that combined transplantation of autologous peripheral nerves and cells with tyrosine hydroxylase activity can reduce dopaminergic neuronal damage, and similar effects were observed in some clinical trials. In this review, we will systematically explain PNS performance in PD pathology and its clinical diagnostic research, describe PNS experimental results [especially Schwann cell (SC) transplantation in the treatment of PD animal models] and the results of clinical trials, and discuss future directions. The mechanism by which SCs produce such a therapeutic effect and the safety of transplantation therapy are briefly described.
The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

More than fifty c-type lectin receptors (CLR) are known and have been identified so far. Moreover, we know the group of galectins and sialic acid-binding immunoglobulin-type lectins that also belong to the carbohydrate-binding receptors of the immune system. Thus, the lectin receptors form the largest receptor family among the pathogen recognition receptors. Similar to the toll-like receptors (TLRs), the CLR do not only recognize foreign but also endogenous molecules. In contrast to TLRs, which have a predominantly activating effect on the immune system, lectin receptors also mediate inhibitory signals. They play an important role in innate and adaptive immunity for the induction, regulation and shaping of the immune response. The hygiene hypothesis links enhanced infection to protection from allergic disease. Yet, the microbial substances that are responsible for mediating this allergy-protective activity still have to be identified. Microbes contain both ligands binding to TLRs and carbohydrates that are recognized by CLR and other lectin receptors. In the current literature, the CLR are often recognized as the ‘bad guys’ in allergic inflammation, because some glycoepitopes of allergens have been shown to bind to CLR, facilitating their uptake and presentation. On the other hand, there are many reports revealing that sugar moieties are involved in immune regulation. In this review, we will summarize what is known about the role of carbohydrate interaction with c-type lectins and other sugar-recognizing receptors in anti-inflammation, with a special focus on the regulation of the allergic immune response.
RGB Colors and Ecological Optics

Object color space is highly structured due to optical constraints (radiant power non-negative, reflectance factors between zero and unity) and ecological context (daylight illuminant). In this setting trichromacy induces a natural geometry through a unique spectral tripartition. Different from null-context colorimetry, one gains two desirable relations: The colorimetric coordinates are coarse-grained spectral reflectance factors and there is a direct link to color experiences, since RGB–coordinates provide ostensive definitions. The framework allows one to deal with subtractive color mixture, source variation, effects of metamerism and relations between scenes and image data in a unified, structured manner. In ecological contexts, colors are effectively object properties. The formal framework is linear algebra and convex geometry. Applications in human biology, computer graphics, design, etc., are immediate.
The Absence of PTEN in Breast Cancer Is a Driver of MLN4924 Resistance

Background: Numerous studies have indicated that the neddylation pathway is closely associated with tumor development. MLN4924 (Pevonedistat), an inhibitor of the NEDD8-activating E1 enzyme, is considered a promising chemotherapeutic agent. Recently, we demonstrated that neddylation of the tumor suppressor PTEN occurs under high glucose conditions and promotes breast cancer development. It has been shown, however, that PTEN protein levels are reduced by 30–40% in breast cancer. Whether this PTEN deficiency affects the anti-tumor function of MLN4924 is unknown. Methods: In the present study, cell counting kit-8 and colony formation assays were used to detect cell proliferation, and a transwell system was used to quantify cell migration. A tumor growth assay was performed in BALB/c nude mice. The subcellular location of PTEN was detected by fluorescence microscopy. The CpG island of the UBA3 gene was predicted by the Database of CpG Islands and UCSC database. Western blotting and qRT-PCR were used to measure the expression of indicated proteins. The Human Protein Atlas database, the Cancer Genome Atlas and Gene Expression Omnibus datasets were used to validate the expression levels of UBA3 in breast cancer. Results: Our data show that the anti-tumor efficacy of MLN4924 in breast cancer cells was markedly reduced with the deletion of PTEN. PI3K/Akt signaling pathway activity correlated positively with UBA3 expression. Pathway activity correlated negatively with NEDP1 expression in PTEN-positive breast cancer patients, but not in PTEN-negative patients. We also demonstrate that high glucose conditions upregulate UBA3 mRNA by inhibiting UBA3 promoter methylation, and this upregulation results in the overactivation of PTEN neddylation in breast cancer cells. Conclusion: These data suggest a mechanism by which high glucose activates neddylation. PTEN is critical, if not indispensable, for MLN4924 suppression of tumor growth; PTEN status thus may help to identify MLN4924-responsive breast cancer patients.
Proof of Concept: Measuring Aortic Annulus Resistance by Means of Pressure-Volume Curves During Balloon Inflation to Guide Transcatheter Aortic Valve Implantation

This study assessed the basic working principle to measure aortic annulus resistance during balloon inflation for transcatheter aortic valve implantation (TAVI), by acquisition of pressure-volume curve for a guided semi-automatic implantation. A modular bench-system was used which allows the incremental inflation of valvuloplasty balloons by means of a stepper-motor driven linear axis with simultaneous recording of the pressure changes inside the system. Different porcine aortic xenografts were assessed by use of a non-compliant valvuloplasty balloon. In a second step transcatheter aortic stents were implanted inside target sized xenografts. The recorded pressure volume-curves showed that the system can accurately differentiate between different xenografts and assess the quality of the tissue rendering real-time analysis of pressure-volume curves during balloon-inflation possible, which has the potential to optimize the implantation procedure by direct adaptation to the patient specific anatomy and characteristics. Further investigations and development are warranted.
Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain

Background: Chronic non-cancer pain (CNCP) is estimated to affect 20% of the adult population. Current United States and Canadian Chronic non-cancer pain guidelines recommend careful reassessment of the risk-benefit ratio for doses greater than 90 mg morphine equivalent dose (MED), due to low evidence for improved pain efficacy at higher morphine equivalent dose and a significant increase in morbidity and mortality. There are a number of human studies demonstrating cannabis opioid synergy. This preliminary evidence suggests a potential role of cannabis as an adjunctive therapy with or without opioids to optimize pain control. Methods: In 2017, the Canadian Opioid Guidelines Clinical Tool was created to encourage judicious opioid prescribing for CNCP patients and to reevaluate those who have been chronically using high MED. Mirroring this approach, we draw on our clinical experiences and available evidence to create a clinical tool to serve as a foundational clinical guideline for the initiation of medical cannabis in the management of CNCP patients using chronic opioid therapy. Findings: Following principles of harm reduction and risk minimization, we suggest cannabis be introduced in appropriately selected CNCP patients, using a stepwise approach, with the intent of pain management optimization. We use a structured approach to focus on low dose cannabis (namely, THC) initiation, slow titration, dose optimization and frequent monitoring. Conclusion: When low dose THC is introduced as an adjunctive therapy, we observe better pain control clinically with lower doses of opioids, improved pain related outcomes and reduced opioid related harm.
Considering Performance in the Automated and Manual Coding of Sociolinguistic Variables: Lessons From Variable (ING)

Impressionistic coding of sociolinguistic variables like English (ING), the alternation between pronunciations like talkin' and talking, has been a central part of the analytic workflow in studies of language variation and change for over a half-century. Techniques for automating the measurement and coding for a wide range of sociolinguistic data have been on the rise over recent decades but procedures for coding some features, especially those without clearly defined acoustic correlates like (ING), have lagged behind others, such as vowels and sibilants. This paper explores computational methods for automatically coding variable (ING) in speech recordings, examining the use of automatic speech recognition procedures related to forced alignment (using the Montreal Forced Aligner) as well as supervised machine learning algorithms (linear and radial support vector machines, and random forests). Considering the automated coding of pronunciation variables like (ING) raises broader questions for sociolinguistic methods, such as how much different human analysts agree in their impressionistic codes for such variables and what data might act as the “gold standard” for training and testing of automated procedures. This paper explores several of these considerations in automated, and manual, coding of sociolinguistic variables and provides baseline performance data for automated and manual coding methods. We consider multiple ways of assessing algorithms' performance, including agreement with human coders, as well as the impact on the outcome of an analysis of (ING) that includes linguistic and social factors. Our results show promise for automated coding methods but also highlight that variability in results should be expected even with careful human coded data. All data for our study come from the public Corpus of Regional African American Language and code and derivative datasets (including our hand-coded data) are available with the paper.
Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization

Myocardial fibrosis is closely related to high morbidity and mortality. In Inner Mongolia, Gentianella amarella subsp. acuta (Michx.) J.M. Gillett (G. acuta) is a kind of tea used to prevent cardiovascular diseases. Bellidifolin (BEL) is an active xanthone molecule from G. acuta that protects against myocardial damage. However, the effects and mechanisms of BEL on myocardial fibrosis have not been reported. In vivo, BEL dampened isoprenaline (ISO)-induced cardiac structure disturbance and collagen deposition. In vitro, BEL inhibited transforming growth factor (TGF)-β1-induced cardiac fibroblast (CF) proliferation. In vivo and in vitro, BEL decreased the expression of α-smooth muscle actin (α-SMA), collagen Ⅰ and Ⅲ, and inhibited TGF-β1/Smads signaling. Additionally, BEL impeded p38 activation and NR4A1 (an endogenous inhibitor for pro-fibrogenic activities of TGF-β1) phosphorylation and inactivation in vitro. In CFs, inhibition of p38 by SB203580 inhibited the phosphorylation of NR4A1 and did not limit Smad3 phosphorylation, and blocking TGF-β signaling by LY2157299 and SB203580 could decrease the expression of α-SMA, collagen I and III. Overall, both cell and animal studies provide a potential role for BEL against myocardial fibrosis by inhibiting the proliferation and phenotypic transformation of CFs. These inhibitory effects might be related to regulating TGF-β1/Smads pathway and p38 signaling and preventing NR4A1 cytoplasmic localization.
Dopaminergic Projections From the Ventral Tegmental Area to the Nucleus Accumbens Modulate Sevoflurane Anesthesia in Mice

The role of the dopaminergic pathway in general anesthesia and its potential mechanisms are still unknown. In this study, we usedc-Fos staining combined with calcium fiber photometry recording to explore the activity of ventral tegmental area (VTA) dopaminergic neurons(VTA-DA) and nucleus accumbens (NAc) neurons during sevoflurane anesthesia. A genetically encoded dopamine (DA) sensor was used to investigate thefunction of the NAc in sevoflurane anesthesia. Chemogenetics and optogenetics were used to explore the role of the VTA-DA in sevofluraneanesthesia. Electroencephalogram (EEG) spectra, time of loss of righting reflex (LORR) and recovery of righting reflex (RORR) were recorded asassessment indicators. We found that VTA-DA and NAc neurons were inhibited during the induction period and were activated during the recoveryperiod of sevoflurane anesthesia. The fluorescence signals of dopamine decreased in the induction of and increased in the emergence from sevoflurane anesthesia.Activation of VTA-DA and the VTADA-NAc pathway delayed the induction and facilitated the emergence accompanying with thereduction of delta band and the augmentation of the gamma band. These data demonstrate that VTA-DA neurons play a critical role in modulating sevofluraneanesthesia via the VTADA-NAc pathway.
Editorial: Mitochondrial Remodeling and Dynamic Inter-Organellar Contacts in Cardiovascular Physiopathology

Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, Wilf Family Cardiovascular Research Institute and Einstein Institute for Aging Research, New York, NY, United States, Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Fleischer Institute for Diabetes and Metabolism (FIDAM), Montefiore University Hospital, New York, NY, United States, 3 International Translational Research and Medical Education Academic Research Unit (ITME), Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy, Center for Innovation and Stimulation of Drug Discovery (CISTIM), Leuven, Belgium, 5 Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile, 7 Advanced Center of Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas y Facultad de Medicina, Universidad de Chile, Santiago, Chile, Network for the Study of High-Lethality Cardiopulmonary Diseases (REECPAL), Universidad de Chile, Santiago, Chile, Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy, Maria Cecilia Hospital, GVM Care and Research, Cotignola, Italy
RIPK3 Suppresses the Progression of Spontaneous Intestinal Tumorigenesis

Receptor-interacting protein 3 (RIPK3), a member of the family of serine/threonine protein kinases, emerged as a critical regulator of necroptosis. Downregulated expression of RIPK3 is correlated with poor prognosis in multiple tumor types. Here, we show that RIPK3 is involved in the progression of spontaneous intestinal tumorigenesis. As a clinical correlate, reduced expression of RIPK3 is positively associated with histological grade, lymphatic metastasis and poor prognosis in CRC patients. RIPK3-deficient (Ripk3-/- ) mice exhibit increased tumor formation in Apcmin/+ spontaneous intestinal tumorigenesis. Apcmin/+Ripk3-/- tumors promote hyperactivation of IL-6/STAT3 signaling, which exacerbates proliferation and inhibits apoptosis. Blocking IL-6 signaling suppressed tumor formation and reduced STAT3 activation in Apcmin/+Ripk3-/- mice. Thus, our results reveal that RIPK3 is a tumor suppressor in spontaneous intestinal tumorigenesis, and implicate targeting the IL-6/STAT3 signaling axis as a potential therapeutic strategy for intestinal tumor patients with reduced RIPK3.
Lymphoma of the Uvula: Clinical, Morphological, Histopathological, and Genetic Characterization. A Nationwide Danish Study From 1980 to 2019

Background: In the head and neck region the uvula is a rare site for extranodal lymphomas to develop. In this national study, we present six cases and provide an overview of the current literature, characterizing the clinical and histopathological features of lymphomas involving this location. Materials and Methods: Clinical information was obtained retrospectively from patient records in a nationwide Danish study covering from 1980 through 2019. In order to validate the diagnoses, uvular tissue specimens were examined histologically and immunohistochemically and if relevant for subtyping, cytogenetic rearrangements were investigated. Results: We present six cases of lymphomas involving the uvula, of which four of the cases were diagnosed with a B-cell lymphoma (two diffuse large B-cell lymphomas, one extranodal marginal zone B-cell lymphoma and one Mantle cell lymphoma), while two were diagnosed with a T-cell lymphoma (one peripheral T-cell lymphoma and one natural killer/T-cell lymphoma). Presenting symptoms included swelling, pain and ulceration of the uvula. Treatment was comprised of radiotherapy and/or chemotherapy, with T-cell lymphomas showing a poorer outcome than B-cell lymphomas. Conclusion: Lymphoma of the uvula is rare, with few case reports being reported in the literature. The most frequent histological subtypes reported are extranodal marginal zone B-cell lymphoma and peripheral T-cell lymphoma. When encountering a swollen, painful and/or ulcerated uvula, the clinician should always consider malignancy as a possible cause. Lymphoma of the uvula is a possible diagnosis and if this is the case, there is a high risk of disseminated disease at the time of diagnosis.
“Omics” Technologies for the Study of Soil Carbon Stabilization: A Review

Evidence-based decisions governing sustainable agricultural land management practices require a mechanistic understanding of soil organic matter (SOM) transformations and stabilization of carbon in soil. Large amounts of carbon from organic fertilizers, root exudates, and crop residues are input into agricultural soils. Microbes then catalyze soil biogeochemical processes including carbon extracellular transformation, mineralization, and assimilation of resources that are later returned to the soil as metabolites and necromass. A systems biology approach for a holistic study of the transformation of carbon inputs into stable SOM requires the use of soil “omics” platforms (metagenomics, metatranscriptomics, metaproteomics, and metabolomics). Linking the data derived from these various platforms will enhance our knowledge of structure and function of the microbial communities involved in soil carbon cycling and stabilization. In this review, we discuss the application, potential, and suitability of different “omics” approaches (independently and in combination) for elucidating processes involved in the transformation of stable carbon in soil. We highlight biases associated with these approaches including limitations of the methods, experimental design, and soil sampling, as well as those associated with data analysis and interpretation.
High Level of METTL7B Indicates Poor Prognosis of Patients and Is Related to Immunity in Glioma

Glioma is the most common primary intracranial malignant tumor in adults. Although there have been many efforts on potential targeted therapy of glioma, the patient’s prognosis remains dismal. Methyltransferase Like 7B (METTL7B) has been found to affect the development of a variety of tumors. In this study, we collected RNA-seq data of glioma in CGGA and TCGA, analyzed them separately. Then, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, and receiver operating characteristic curve (ROC curve) analysis were used to evaluate the effect of METTL7B on prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) enrichment analyses were used to identify the function or pathway associated with METTL7B. Moreover, the ESTIMATE algorithm, Cibersort algorithm, Spearman correlation analysis, and TIMER database were used to explore the relationship between METTL7B and immunity. Finally, the role of METTL7B was explored in glioma cells. We found that METTL7B is highly expressed in glioma, and high expression of METTL7B in glioma is associated with poor prognosis. In addition, there were significant differences in immune scores and immune cell infiltration between the two groups with different expression levels of METTL7B. Moreover, METTL7B was also correlated with immune checkpoints. Knockdown of METTL7B revealed that METTL7B promoted the progression of glioma cells. The above results indicate that METTL7B affects the prognosis of patients and is related to tumor immunity, speculating that METTL7B may be a new immune-related target for the treatment of glioma.
Abundance Imparts Evolutionary Constraints of Similar Magnitude on the Buried, Surface, and Disordered Regions of Proteins

An understanding of the forces shaping protein conservation is key, both for the fundamental knowledge it represents and to allow for optimal use of evolutionary information in practical applications. Sequence conservation is typically examined at one of two levels. The first is a residue-level, where intra-protein differences are analyzed and the second is a protein-level, where inter-protein differences are studied. At a residue level, we know that solvent-accessibility is a prime determinant of conservation. By inverting this logic, we inferred that disordered regions are slightly more solvent-accessible on average than the most exposed surface residues in domains. By integrating abundance information with evolutionary data within and across proteins, we confirmed a previously reported strong surface-core association in the evolution of structured regions, but we found a comparatively weak association between disordered and structured regions. The facts that disordered and structured regions experience different structural constraints and evolve independently provide a unique setup to examine an outstanding question: why is a protein’s abundance the main determinant of its sequence conservation? Indeed, any structural or biophysical property linked to the abundance-conservation relationship should increase the relative conservation of regions concerned with that property (e.g., disordered residues with mis-interactions, domain residues with misfolding). Surprisingly, however, we found the conservation of disordered and structured regions to increase in equal proportion with abundance. This observation implies that either abundance-related constraints are structure-independent, or multiple constraints apply to different regions and perfectly balance each other.