Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV) is a novel coronavirus that has rapidly disseminated worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic. As of January 6th, 2021, there were over 86 million global confirmed cases, and the disease has claimed over 1.87 million lives (a ∼2.2% case fatality rate). SARS-CoV-2 is able to infect human cells by binding its spike (S) protein to angiotensin-conversing enzyme 2 (ACE2), which is expressed abundantly in several cell types and tissues. ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7). Virion binding to ACE2 for host cell entry leads to internalization of both via endocytosis, as well as activation of ADAM17/TACE, resulting in downregulation of ACE2 and loss of its protective actions in the lungs and other organs. Although COVID-19 was initially described as a purely respiratory disease, it is now known that infected individuals can rapidly progress to a multiple organ dysfunction syndrome. In fact, all human structures that express ACE2 are susceptible to SARS-CoV-2 infection and/or to the downstream effects of reduced ACE2 levels, namely systemic inflammation and injury. In this review, we aim to summarize the major features of SARS-CoV-2 biology and the current understanding of COVID-19 pathogenesis, as well as its clinical repercussions in the lung, heart, kidney, bowel, liver, and brain. We also highlight potential therapeutic targets and current global efforts to identify safe and effective therapies against this life-threatening condition.
The Effects of Early Nutritional Intervention on Oral Mucositis and Nutritional Status of Patients With Head and Neck Cancer Treated With Radiotherapy

Radiation-induced oral mucositis (RIOM) is a common side effect after radiotherapy (RT) in head and neck cancer (HNC) patients. RIOM patients with severe pain have difficulty in eating, which increases the incidence of malnutrition and affects patients’ quality of life and the process of RT. The mechanism of RIOM is not fully understood, and inflammatory response and oxidative stress appear to be important for RIOM occurrence and development. The nutritional status of patients is very important for their RT tolerance and recovery. Malnutrition, which can lead to anemia, low protein, decreased immunity and other problems, is an important clinical factor affecting tumor progression and treatment. Recent studies have shown that early nutritional intervention can ameliorate oral mucositis and nutritional status of patients with HNC. However, in clinical practice, early nutritional intervention for patients with HNC is not a conventional intervention strategy. Therefore, this review summarized the possible pathogenesis of RIOM, commonly used assessment tools for malnutrition in patients, and recent studies on the effects of early nutritional interventions on RIOM and nutritional status of patients with HNC. We hope to provide the basis and reference for the clinical application of early nutritional intervention models.
Neuropathological Characterization of a Dravet Syndrome Knock-In Mouse Model Useful for Investigating Cannabinoid Treatments

Dravet syndrome (DS) is an epileptic syndrome caused by mutations in the Scn1a gene encoding the α1 subunit of the sodium channel Nav1.1, which is associated with febrile seizures that progress to severe tonic-clonic seizures and associated comorbidities. Treatment with cannabidiol has been approved to reduce seizures in DS, but it may also be active against these comorbidities. The aim of this study was to validate a new mouse model of DS having lower mortality than previous models, which may serve to further evaluate therapies for the long-term comorbidities. This new model consists of heterozygous conditional knock-in mice carrying a missense mutation (A1783V) in Scn1a gene expressed exclusively in neurons of the CNS (Syn-Cre/Scn1aWT/A1783V). These mice have been used here to determine the extent and persistence of the behavioral deterioration in different postnatal days (PND), as well as to investigate the alterations that the disease produces in the endocannabinoid system and the contribution of inflammatory events and impaired neurogenesis in the pathology. Syn-Cre/Scn1aWT/A1783V mice showed a strong reduction in hindlimb grasp reflex at PND10, whereas at PND25, they presented spontaneous convulsions and a greater susceptibility to pentylenetetrazole-induced seizures, marked hyperactivity, deficient spatial working memory, lower levels of anxiety, and altered social interaction behavior. These differences disappeared at PND40 and PND60, except the changes in social interaction and anxiety. The analysis of CNS structures associated with these behavioral alterations revealed an elevated glial reactivity in the prefrontal cortex and the dentate gyrus. This was associated in the dentate gyrus with a greater cell proliferation detected with Ki67 immunostaining, whereas double-labeling analyses identified that proliferating cells were GFAP-positive suggesting failed neurogenesis but astrocyte proliferation. The analysis of the endocannabinoid system of Syn-Cre/Scn1aWT/A1783V mice confirmed reductions in CB1 receptors and MAGL and FAAH enzymes, mainly in the cerebellum but also in other areas, whereas CB2 receptors became upregulated in the hippocampus. In conclusion, Syn-Cre/Scn1aWT/A1783V mice showed seizuring susceptibility and several comorbidities (hyperactivity, memory impairment, less anxiety, and altered social behavior), which exhibited a pattern of age expression similar to DS patients. Syn-Cre/Scn1aWT/A1783V mice also exhibited greater glial reactivity and a reactive response in the neurogenic niche, and regional changes in the status of the endocannabinoid signaling, events that could contribute in behavioral impairment.
Recent R&D Studies Related to Coprocessing of Spent Nuclear Fuel Using N,N-Dihexyloctanamide

Abstract The PUREX process has undergone several modifications to address the issues of high burn up, fewer solvent extraction cycles, and reduced waste arisings. Advanced fuel cycle scenarios have led to a renewed international interest in the development of separation schemes for co-recovering U/Pu from spent fuels. Completely incinerable N,N-dihexyloctanamide (DHOA) has been identified as a promising candidate for the reprocessing of spent fuels. Batch extraction studies were carried out to evaluate DHOA and TBP for the coprocessing (co-extraction and co-stripping) of U and Pu from spent fuel under varying concentrations of nitric acid and of uranium as well as under simulated pressurized heavy water reactor spent fuel feed conditions. At 50 g/L U in 4 M HNO3, DPu values for 1.1 M DHOA and 1.1 M TBP solutions in n-dodecane were 7.9 and 3.8, respectively. In contrast, significantly lower DPu value at 0.5 M HNO3 (4 × 10−3) for DHOA as compared to TBP (4 × 10−2) suggested that it was a better choice for coprocessing of spent nuclear fuel. This behavior was attributed to the change in stoichiometry of extracted species at lower acidity vis-a-vis the higher acidity. These studies suggest that plutonium fraction can be enriched with respect to uranium contamination in the product stream. DHOA displays better extraction behavior of plutonium and stripping behavior of uranium under simulated feed conditions. DHOA appears distinctly better than TBP with respect to fission product/structural material decontamination of U/Pu.
Transcriptomic Signatures and Functional Network Analysis of Chronic Rhinosinusitis With Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment.
Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

SARS-CoV-2 is wreaking havoc around the world. To get the world back on track, hundreds of vaccines are under development. A deeper understanding of how the immune system responds to SARS-CoV-2 re-infection will certainly help. Studies have highlighted various aspects of T cell response in resolving acute infection and preventing re-infections. Lung resident memory T (TRM) cells are sentinels in the secondary immune response. They are mostly differentiated from effector T cells, construct specific niches and stay permanently in lung tissues. If the infection recurs, locally activated lung TRM cells can elicit rapid immune response against invading pathogens. In addition, they can significantly limit tumor growth or lead to pathologic immune responses. Vaccines targeting TRM cells are under development, with the hope to induce stable and highly reactive lung TRM cells through mucosal administration or “prime-and-pull” strategy. In this review, we will summarize recent advances in lung TRM cell generation and maintenance, explore their roles in different diseases and discuss how these cells may guide the development of future vaccines targeting infectious disease, cancer, and pathologic immune response.
The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis

Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial. Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility. Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the CTLA-4 genes and RA for more robust conclusions. Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms. Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.
Identification of Potential Biomarkers and Immune Infiltration Characteristics in Idiopathic Pulmonary Arterial Hypertension Using Bioinformatics Analysis

Objectives: Idiopathic pulmonary arterial hypertension (IPAH) is a rare but severe lung disorder, which may lead to heart failure and early mortality. However, little is known about the etiology of IPAH. Thus, the present study aimed to establish the differentially expressed genes (DEGs) between IPAH and normal tissues, which may serve as potential prognostic markers in IPAH. Furthermore, we utilized a versatile computational method, CIBERSORT to identify immune cell infiltration characteristics in IPAH. Materials and Methods: The GSE117261 and GSE48149 datasets were obtained from the Gene Expression Omnibus database. The GSE117261 dataset was adopted to screen DEGs between IPAH and the control groups with the criterion of |log2 fold change| ≥ 1, adjusted P < 0.05, and to further explore their potential biological functions via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, and Gene Set Enrichment Analysis. Moreover, the support vector machine (SVM)-recursive feature elimination and the least absolute shrinkage and selection operator regression model were performed jointly to identify the best potential biomarkers. Then we built a regression model based on these selected variables. The GSE48149 dataset was used as a validation cohort to appraise the diagnostic efficacy of the SVM classifier by receiver operating characteristic (ROC) analysis. Finally, immune infiltration was explored by CIBERSORT in IPAH. We further analyzed the correlation between potential biomarkers and immune cells. Results: In total, 75 DEGs were identified; 40 were downregulated, and 35 genes were upregulated. Functional enrichment analysis found a significantly enrichment in heme binding, inflammation, chemokines, cytokine activity, and abnormal glycometabolism. HBB, RNASE2, S100A9, and IL1R2 were identified as the best potential biomarkers with an area under the ROC curve (AUC) of 1 (95%CI = 0.937–1.000, specificity = 100%, sensitivity = 100%) in the discovery cohort and 1(95%CI = 0.805–1.000, specificity = 100%, sensitivity = 100%) in the validation cohort. Moreover, immune infiltration analysis by CIBERSORT showed a higher level of CD8+ T cells, resting memory CD4+ T cells, gamma delta T cells, M1 macrophages, resting mast cells, as well as a lower level of naïve CD4+ T cells, monocytes, M0 macrophages, activated mast cells, and neutrophils in IPAH compared with the control group. In addition, HBB, RNASE2, S100A9, and IL1R2 were correlated with immune cells. Conclusion: HBB, RNASE2, S100A9, and IL1R2 were identified as potential biomarkers to discriminate IPAH from the control. There was an obvious difference in immune infiltration between patient with IPAH and normal groups.
Clinical Perspectives on Liquid Biopsy in Metastatic Colorectal Cancer

Liquid biopsy, which generally refers to the analysis of biological components such as circulating nuclear acids and circulating tumor cells in body fluids, particularly in peripheral blood, has shown good capacity to overcome several limitations faced by conventional tissue biopsies. Emerging evidence in recent decades has confirmed the promising role of liquid biopsy in the clinical management of various cancers, including colorectal cancer, which is one of the most prevalent cancers and the second leading cause of cancer-related deaths worldwide. Despite the challenges and poor clinical outcomes, patients with metastatic colorectal cancer can expect potential clinical benefits with liquid biopsy. Therefore, in this review, we focus on the clinical prospects of liquid biopsy in metastatic colorectal cancer, specifically with regard to the recently discovered various biomarkers identified on liquid biopsy. These biomarkers have been shown to be potentially useful in multiple aspects of metastatic colorectal cancer, such as auxiliary diagnosis of metastasis, prognosis prediction, and monitoring of therapy response.
Assessing Intervention Effects in Sentence Processing: Object Relatives vs. Subject Control

Object relative clauses are harder to process than subject relative clauses. Under Grillo’s (2009) Generalized Minimality framework, complexity effects of object relatives are construed as intervention effects, which result from an interaction between locality constraints on movement (Relativized Minimality) and the sentence processing system. Specifically, intervention of the subject DP in the movement dependency is expected to generate a minimality violation whenever processing limitations render the moved object underspecified, resulting in compromised comprehension. In the present study, assuming Generalized Minimality, we compared the processing of object relatives with the processing of subject control in ditransitives, which, like object relatives, instantiates a syntactic dependency across an intervening DP. This comparison is justified by the current debate on whether Control should be analyzed as movement: if control involves movement of the controller DP, as proposed by Hornstein (1999), a parallel between the processing of object relatives and subject control in ditransitives may be anticipated on the basis of intervention. In addition, we explored whether general cognitive factors contribute to complexity effects ascribed to movement across a DP. Sixty-nine adult speakers of European Portuguese read sentences and answered comprehension probes in a self-paced reading task with moving-window display, comprising four experimental conditions: Subject Relatives; Object Relatives; Subject Control; Object Control. Furthermore, participants performed four supplementary tasks, serving as measures of resistance to interference, lexical knowledge, working memory capacity and lexical access ability. The results from the reading task showed that whereas object relatives were harder to process than subject relatives, subject control was not harder to process than object control, arguing against recent movement accounts of control. Furthermore, we found that whereas object relative complexity effects assessed by response times to comprehension probes interacted with Reading Span, object relative complexity effects assessed by comprehension accuracy and reading times did not interact with any of the supplementary tasks. We discuss these results in light of Generalized Minimality and the hypothesis of modularity in syntactic processing (Caplan and Waters, 1999).
Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study

The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion. The expression of HMGB1, TLR4, Nf-κB, AQP4, IL-2, IL-4, IL-6, and TNF-α in the fetal membrane and placenta was compared between the patient with pregnancy-related ADEM and a woman with a normal pregnancy using Real-time qPCR and western blotting (WB). The patient was diagnosed with ADEM in the early stage of pregnancy after showing limb weakness symptoms. In the third month of gestation, the symptoms worsened, with a disturbance of consciousness and breathing. After the abortion, the patient relapsed with vertigo and visual rotation. Analysis of lymphocyte subsets by flow cytometry showed that B lymphocytes increased, while natural killer T lymphocytes decreased. WB and Real-time qPCR showed that the expression levels of HMGB1, TLR4, Nf-κB, AQP4, and IL-6 in the fetal membrane and placenta were higher in the patient with pregnancy-related ADEM than in the woman with a normal pregnancy, while those of IL-2 were lower in the patient than in the woman with a normal pregnancy. The local immune changes and the activation of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal–fetal interface may be related to the pathogenesis of ADEM.
No Detectable Electroencephalographic Activity After Clinical Declaration of Death Among Tibetan Buddhist Meditators in Apparent Tukdam, a Putative Postmortem Meditation State

Recent EEG studies on the early postmortem interval that suggest the persistence of electrophysiological coherence and connectivity in the brain of animals and humans reinforce the need for further investigation of the relationship between the brain’s activity and the dying process. Neuroscience is now in a position to empirically evaluate the extended process of dying and, more specifically, to investigate the possibility of brain activity following the cessation of cardiac and respiratory function. Under the direction of the Center for Healthy Minds at the University of Wisconsin-Madison, research was conducted in India on a postmortem meditative state cultivated by some Tibetan Buddhist practitioners in which decomposition is putatively delayed. For all healthy baseline (HB) and postmortem (PM) subjects presented here, we collected resting state electroencephalographic data, mismatch negativity (MMN), and auditory brainstem response (ABR). In this study, we present HB data to demonstrate the feasibility of a sparse electrode EEG configuration to capture well-defined ERP waveforms from living subjects under very challenging field conditions. While living subjects displayed well-defined MMN and ABR responses, no recognizable EEG waveforms were discernable in any of the tukdam cases.