Reading the mind in the eyes in patients with idiopathic REM sleep behavior disorder.

OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by vocalizations, jerks, and motor behaviors during REM sleep, often associated with REM-related dream content, which is considered a prodromal stage of α-synucleinopathy. The results of the Reading the Mind in the Eyes (RME) reflecting affective Theory of Mind (ToM) are inconsistent in α-synucleinopathy. The present study tried to investigate the RME in patients with iRBD. METHODS: A total of 35 patients with iRBD and 26 healthy controls were included in the study. All participants were administered the RME and the cognitive assessments according to a standard procedure. The patients with iRBD were further divided into two groups (high or low RME) according to the scores of the RME (> 21, or ≤ 20). RESULTS: The patients with iRBD had worse scores on cognitive tests compared with healthy controls involving global cognitive screening, memory, and visuospatial abilities (p < 0.05), but the scores of the RME were similar between the two groups (20.83 ± 3.38, 20.58 ± 3.43) (p ˃ 0.05). Patients with low RME had more obvious cognitive impairments than healthy controls. After applying Bonferroni correction for multiple tests, the low REM group only performed worse on the Sum of trials 1 to 5 and delayed recall of the RAVLT compared with the healthy control group (p < 0.001, = 0.002). The RME correlated with the scores of cognitive tests involving executive function, attention, memory, and visuospatial function. CONCLUSIONS: The changes in RME had a relationship with cognitive impairments, especially memory, in patients with iRBD.

gcPathogen: a comprehensive genomic resource of human pathogens for public health.

Here, we present the manually curated Global Catalogue of Pathogens (gcPathogen), an extensive genomic resource designed to facilitate rapid and accurate pathogen analysis, epidemiological exploration and monitoring of antibiotic resistance features and virulence factors. The catalogue seamlessly integrates and analyzes genomic data and associated metadata for human pathogens isolated from infected patients, animal hosts, food and the environment. The pathogen list is supported by evidence from medical or government pathogenic lists and publications. The current version of gcPathogen boasts an impressive collection of 1 164 974 assemblies comprising 986 044 strains from 497 bacterial taxa, 4794 assemblies encompassing 4319 strains from 265 fungal taxa, 89 965 assemblies featuring 13 687 strains from 222 viral taxa, and 646 assemblies including 387 strains from 159 parasitic taxa. Through this database, researchers gain access to a comprehensive 'one-stop shop' that facilitates global, long-term public health surveillance while enabling in-depth analysis of genomes, sequence types, antibiotic resistance genes, virulence factors and mobile genetic elements across different countries, diseases and hosts. To access and explore the data and statistics, an interactive web interface has been developed, which can be accessed at https://nmdc.cn/gcpathogen/. This user-friendly platform allows seamless querying and exploration of the extensive information housed within the gcPathogen database.

Intratumoral and peritumoral radiomics model based on abdominal ultrasound for predicting Ki-67 expression in patients with hepatocellular cancer.

Background: Hepatocellular cancer (HCC) is one of the most common tumors worldwide, and Ki-67 is highly important in the assessment of HCC. Our study aimed to evaluate the value of ultrasound radiomics based on intratumoral and peritumoral tissues in predicting Ki-67 expression levels in patients with HCC. Methods: We conducted a retrospective analysis of ultrasonic and clinical data from 118 patients diagnosed with HCC through histopathological examination of surgical specimens in our hospital between September 2019 and January 2023. Radiomics features were extracted from ultrasound images of both intratumoral and peritumoral regions. To select the optimal features, we utilized the t-test and the least absolute shrinkage and selection operator (LASSO). We compared the area under the curve (AUC) values to determine the most effective modeling method. Subsequently, we developed four models: the intratumoral model, the peritumoral model, combined model #1, and combined model #2. Results: Of the 118 patients, 64 were confirmed to have high Ki-67 expression while 54 were confirmed to have low Ki-67 expression. The AUC of the intratumoral model was 0.796 (0.649-0.942), and the AUC of the peritumoral model was 0.772 (0.619-0.926). Furthermore, combined model#1 yielded an AUC of 0.870 (0.751-0.989), and the AUC of combined model#2 was 0.762 (0.605-0.918). Among these models, combined model#1 showed the best performance in terms of AUC, accuracy, F1-score, and decision curve analysis (DCA). Conclusion: We presented an ultrasound radiomics model that utilizes both intratumoral and peritumoral tissue information to accurately predict Ki-67 expression in HCC patients. We believe that incorporating both regions in a proper manner can enhance the diagnostic performance of the prediction model. Nevertheless, it is not sufficient to include both regions in the region of interest (ROI) without careful consideration.

Association between serum amylase levels and CD4 cell counts in newly diagnosed people living with HIV: A case-control study.

Serum amylase is a direct reflection of pancreatic injury. Several clinical studies have indicated that antiretroviral therapy may be the main cause of increased serum amylase in people living with human immunodeficiency virus (PLWH). However, other probable causes including direct human immunodeficiency virus infection, opportunistic infections and neoplasms, alcohol abuse, and use of illicit drugs, which can also affect pancreatic amylase levels were not considered in these studies. In our study, we collected clinical data from newly diagnosed PLWH who had not received antiretroviral therapy, and examined the association between serum amylase levels and CD4 cell counts. Between November 2018 and September 2021, a total of 344 newly diagnosed PLWH and 344 healthy controls were recruited at Ningbo Yinzhou No 2 Hospital. Serum amylase levels, CD4 cell counts and other clinical features were measured. Relationships between serum amylase levels and clinical parameters were evaluated using correlation analysis. Multiple linear regression analyses were performed to identify the independent risk factors. Newly diagnosed PLWH had lower CD4 cell counts and higher serum amylase levels than healthy controls (P < .05). Serum amylase levels were negatively correlated with CD4 cell counts (r = -0.506, P < .001). In multiple linear regression analyses, CD4 cell counts (ß = -0.327, 95% confidence interval = -0.051--0.022, P < .001) were independently associated with serum amylase levels. CD4 cell counts were independently associated with serum amylase levels in newly diagnosed PLWH. Thus, close monitoring of serum amylase may be significant in preventing opportunistic infections of PLWH, since low CD4 cell counts are associated with an increased risk of opportunistic infections.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy.

PURPOSE: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. METHODS: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. RESULTS: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. CONCLUSIONS: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

gcCov: Linked open data for global coronavirus studies.

We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework (RDF) and implement a server to publish linked open data (LOD). As one of the largest and most comprehensive semantic databases about coronaviruses, the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes. These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs. These LOD with 62,168,127 semantic triplets and their visualizations are freely accessible through gcCov at https://nmdc.cn/gccov/.

VarEPS: an evaluation and prewarning system of known and virtual variations of SARS-CoV-2 genomes.

The genomic variations of SARS-CoV-2 continue to emerge and spread worldwide. Some mutant strains show increased transmissibility and virulence, which may cause reduced protection provided by vaccines. Thus, it is necessary to continuously monitor and analyze the genomic variations of SARS-COV-2 genomes. We established an evaluation and prewarning system, SARS-CoV-2 variations evaluation and prewarning system (VarEPS), including known and virtual mutations of SARS-CoV-2 genomes to achieve rapid evaluation of the risks posed by mutant strains. From the perspective of genomics and structural biology, the database comprehensively analyzes the effects of known variations and virtual variations on physicochemical properties, translation efficiency, secondary structure, and binding capacity of ACE2 and neutralizing antibodies. An AI-based algorithm was used to verify the effectiveness of these genomics and structural biology characteristic quantities for risk prediction. This classifier could be further used to group viral strains by their transmissibility and affinity to neutralizing antibodies. This unique resource makes it possible to quickly evaluate the variation risks of key sites, and guide the research and development of vaccines and drugs. The database is freely accessible at www.nmdc.cn/ncovn.

Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review.

Mucinous cystic neoplasms (MCN) are rare premalignant neoplasms of the pancreas typically found as single lesions in the pancreatic body and tail of women in the fifth and sixth decade of life, constituting 2-5% of pancreatic neoplasms. We present a 50-year-old female patient with a large tail mass of the pancreatic body (size of 15 cm × 12 cm) with elevated tumor indicators. Computed tomography and magnetic resonance imaging revealed a large cystic lesion with septa and wall nodules. During the operation, the tumor capsule wall adhered to the left half colon and mesentery and could not be detached. Splenectomy and left hemicolectomy were performed. The postoperative pathological examination of the specimens confirmed a premalignant pancreatic mucous cystic tumor with moderate heterocytosis. The preoperative diagnosis of pancreatic MCN and MCN with invasive carcinoma is discussed, considering the characteristics of this case. Age, tumor size, texture, tumor marker elevation, and cystic wall condition are important characteristics of malignant MCN. Nevertheless, it is still very difficult to determine accurately whether an MCN is malignant or not before an actual pathological examination of the resected specimen.

Danshensu derivative ADTM ameliorates CCl4­induced acute liver injury in mice through inhibiting oxidative stress and apoptosis.

Previous studies reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM), which conferred cardioprotective, neuroprotective and anti-thrombotic effects. Here we aim to investigate the hepatoprotective effect of ADTM on acute liver injury caused by carbon tetrachloride (CCl4) and the underlying molecular mechanisms. ADTM (30 and 60 mg/kg) was given to mice by gavage for two weeks. At the last day mice were injected with 0.3% CCl4, 10 mL/kg, ip for 24 h. Clinical and histological chemistry assays were performed to assess liver injury. Moreover, hepatic oxidative stress and apoptosis related markers were determined by western blotting. As a result, ADTM significantly protected against CCl4-induced liver injury by the decrease of elevated serum transaminases and liver index, and the attenuation of histopathological changes in mice. In addition, ADTM remarkably alleviated hepatic oxidative stress (MDA contents and SOD activity) and apoptosis. Further studies revealed that ADTM significantly inhibited the CCl4-induced upregulation of Bax/Bcl-2, increased the CCl4-induced decrease of AKT phosphorylation and inhibited the expression level of NF-κB p65 in CCl4-intoxicated mice. These findings suggest that ADTM possesses the potential protective effects against CCl4-induced liver injury in mice by exerting antioxidative stress and antiapoptosis.

Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

ABSTRACT Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusions: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Irisin Protects Against Motor Dysfunction of Rats with Spinal Cord Injury via Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase-Nuclear Factor Kappa-B Pathway.

The aim of the present research was to investigate the effects of irisin, a skeletal muscle-derived myokine, on spinal cord injury (SCI) in rats and explore the possible mechanisms. SCI model was constructed in male SD rats. The effects of irisin on SCI rats were assessed via behavior tests including Basso, Beattie, and Bresnahan (BBB) scoring method and inclined plane test, followed by histomorphology tests including HE staining, Nissl staining, and transmission electron microscope examination. Biochemical analyses including PCR, Western blots and ELISA were employed to further evaluate the changes at molecular level of SCI rats. In addition, lipopolysaccharide (LPS)-induced cell damage model was established in PC12 cells to verify the mechanism of irisin's effect on nerve cells in vitro. Results showed that the BBB score and the angle of incline significantly decreased after SCI surgery, however, chronic irisin treatment improved SCI-induced motor dysfunction. HE and Nissl staining assays showed that SCI surgery induced histological injury of spinal cord, which could be reversed by irisin treatment. Morphological abnormality of nerve cells caused by SCI also could be alleviated by irisin. Further biochemical analyses showed that irisin inhibited SCI-induced overexpression of Interleukin-1ß (IL-1ß), Interleukin- 6 (IL-6), tumor necrosis factor alpha (TNF-α), inducible nitricoxidesynthase (iNOS) and Cyclooxygenase-2 (COX-2)], as well as nuclear factor kappa-B (NF-κB)p65 in rats, and the positive function of irisin could be reversed by Compound C treatment. In our in vitro study, LPS-induced declines of cell viability and neurite length of PC12 cell were inhibited by irisin treatment, and irisin inhibited LPS-induced overexpression of NF-κBp65, IL-1ß, IL-6, TNF-α, iNOS and COX-2. These changes could be reversed by activated protein kinase (AMPK) siRNA pre-treatment. Taken together, irisin could protect the rats from SCI, and its protection is associated with the regulation of adenosine 5'-monophosphate-activated protein kinase (AMPK)- NF-κB signaling pathway.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Clinical outcomes of curative treatment for colorectal liver metastases combined with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastases: a systematic review and meta-analysis of current evidence.

BACKGROUND: The optimal treatment for colorectal cancer (CRC) with synchronous peritoneal carcinomatosis (PC) and liver metastases (LM) remains controversial. We aimed to investigate clinical outcomes in patients with CRC and concomitant PC and LM who had undergone curative surgery, including resections at both metastatic sites and synchronous intraabdominal chemotherapy. METHODS: We searched PubMed, EMBASE, and Web of Science databases for eligible studies. Studies focusing on the clinical effects of curative surgery and synchronous intraabdominal chemotherapy for patients with CRC and concomitant PC and LM were included. Meta-analysis results were recorded as hazard ratios (HRs), risk ratios (RRs) and mean differences. RESULTS: We included 9 of 998 identified studies in the meta-analysis, involving 746 patients (221 patients with PC + LM, 525 patients with PC). Overall survival (pooled HR 1.68, 95% confidence interval [CI] 1.33-2.13, p < 0.01) and disease-free survival (pooled HR 1.82, 95% CI 1.51-2.20, p < 0.01) were both lower in patients with PC + LM. A higher recurrence rate (RR 1.22, 95% CI 1.04-1.44, p = 0.02) and major postoperative morbidity (RR 1.47, 95% CI 1.19-1.82, p < 0.01) were also observed in patients with PC + LM. CONCLUSION: Liver resection in combination with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with CRC and synchronous hepatic and peritoneal metastases may be associated with worse survival and higher morbidity compared with patients with isolated PC. More restricted patient inclusion criteria should be established to facilitate an optimal prognosis for this patient group.

CORD-19: The Covid-19 Open Research Dataset.

The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.

A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer. The prognostic signature could be reliable to stratify LUAD patients according to risk, which helps the management of the systematic treatments. In this study, a systematic and reliable immune signature was performed to estimate the prognostic stratification in LUAD. METHODS: The profiles of immune-related genes for patients with LUAD were used as one TCGA training set: n = 494, other validation set 1: n = 226 and validation set 2: n = 398. Univariate Cox survival analysis was used to identify the candidate immune-related genes from each cohort. Then, the immune signature was developed and validated in the training and validation sets. RESULTS: In this study, functional analysis showed that immune-related genes involved in immune regulation and MAPK signaling pathway. A prognostic signature based on 10 immune-related genes was established in the training set and patients were divided into high-risk and low-risk groups. Our 10 immune-related gene signature was significantly related to worse survival, especially during early-stage tumors. Further stratification analyses revealed that this 10 immune-related gene signature was still an effective tool for predicting prognosis in smoking or nonsmoking patients, patients with KRAS mutation or KRAS wild-type, and patients with EGFR mutation or EGFR wild-type. Our signature was negatively correlated with B cell, CD4+ T cell, CD8+ T cell, neutrophil, dendritic cell (DC), and macrophage immune infiltration, and immune checkpoint molecules PD-1 and CTLA-4 (P < 0.05). CONCLUSIONS: These findings suggested that our signature was a promising biomarker for prognosis prediction and can facilitate the management of immunotherapy in LUAD.

Sclerosing Angiomatoid Nodular Transformation of the Spleen: Analysis of Clinical and Pathological Features in Five Cases.

Objective: We aimed to summarize the clinical and pathological features of sclerosing angiomatoid nodular transformation (SANT) in spleen among five cases. Methods: Five cases (male: 3; female: 2; mean age: 47.6 years) with SANT confirmed by pathological analysis between July 2010 and November 2019 in our hospital were included in this study. The clinical, imaging, and pathological data were analyzed retrospectively. Results: Three patients presented with mild abdominal pain or discomfort, while the other two were symptom free. Two patients received ultrasonography (US), and all patients underwent a computerized tomography (CT) scan in our hospital. The typical "spoke wheel" pattern was seen in two cases, and central calcification was detected in one case on the CT scans. All patients indicated peripheral enhancement around the SANT lesion during the arterial phase. Open or laparoscopic splenectomy was performed for treatment. No patient showed recurrence in the follow-up. The pathological characteristics of our cases were in line with those of previous literatures. Conclusions: Peripheral enhancement around the SANT lesion during the arterial phase should be taken into consideration for the diagnosis of SANT as an imaging sign on CT scans. Special attention should be paid to the splenic integrality during the laparoscopic approach, due to the probability of malignancy and the fragility of the spleen.

Mitigating Biases in CORD-19 for Analyzing COVID-19 Literature.

On the behest of the Office of Science and Technology Policy in the White House, six institutions, including ours, have created an open research dataset called COVID-19 Research Dataset (CORD-19) to facilitate the development of question-answering systems that can assist researchers in finding relevant research on COVID-19. As of May 27, 2020, CORD-19 includes more than 100,000 open access publications from major publishers and PubMed as well as preprint articles deposited into medRxiv, bioRxiv, and arXiv. Recent years, however, have also seen question-answering and other machine learning systems exhibit harmful behaviors to humans due to biases in the training data. It is imperative and only ethical for modern scientists to be vigilant in inspecting and be prepared to mitigate the potential biases when working with any datasets. This article describes a framework to examine biases in scientific document collections like CORD-19 by comparing their properties with those derived from the citation behaviors of the entire scientific community. In total, three expanded sets are created for the analyses: 1) the enclosure set CORD-19E composed of CORD-19 articles and their references and citations, mirroring the methodology used in the renowned "A Century of Physics" analysis; 2) the full closure graph CORD-19C that recursively includes references starting with CORD-19; and 3) the inflection closure CORD-19I, that is, a much smaller subset of CORD-19C but already appropriate for statistical analysis based on the theory of the scale-free nature of the citation network. Taken together, all these expanded datasets show much smoother trends when used to analyze global COVID-19 research. The results suggest that while CORD-19 exhibits a strong tilt toward recent and topically focused articles, the knowledge being explored to attack the pandemic encompasses a much longer time span and is very interdisciplinary. A question-answering system with such expanded scope of knowledge may perform better in understanding the literature and answering related questions. However, while CORD-19 appears to have topical coverage biases compared to the expanded sets, the collaboration patterns, especially in terms of team sizes and geographical distributions, are captured very well already in CORD-19 as the raw statistics and trends agree with those from larger datasets.