bluuebunny/crossref_metadata_2025 huggingface dataset:
Peningkatan Kadar Lipoprotein-Associated Phospholipase A2 Meningkatkan Kejadian Stroke Iskemik Akut
Authors: Indra Syarif
Published: January 2021

Introduction: Stroke is a major health problem in the world, and associated with mortality, disability, and economic burden. Stroke is the second leading cause of death in the world after heart disease and cause of disability in adults. Several recent studies show that levels of Lp-PLA2 contribute to high serum lead to ischemic stroke, whereas some others do not get the association. Aims: studies an association between serum Lp-PLA2 with incident ischemic stroke. Method: This study is a descriptive analytic comparative with cross sectional design in the Neurology ward RS. DR. M. Djamil Padang between October 2013 to April 2014 with total of 88 subjects consisting of 44 subjects ischemic stroke patients and 44 healthy control group who participated in the study. Statistical analysis is used parametric test with unpaired t test, test for normality with the Kolmogorov-Smirnov test, and logistic regression analysis. Result: P value 0.05 was considered statistically significant. The mean age of subjects in the group of ischemic stroke patients was 57.30 ±8.86 years old. Female in patients with ischemic stroke group was 23 people (52,3%). Mean levels of Lp-PLA2 serum in patiens with ischemic stroke group was 103.49±48.00 ng/mL. A significan association between serum levels of Lp-PLA2 with incident ischemic stroke with p<0.05. Conclusion: There was a significant relation in elevation of serum Lp-PLA2 levels with incident of ischemic stroke.
Clinical, Dermoscopic and Histhopatological Findings in Diagnosis of Nevus Spilus
Authors: Risa Amillia , Asri Ennesta , Izrul Irdawaty , Tofrizal Alimudin
Published: January 2021

Introduction: Nevus spilus (NS) are seen in 0.2% to 2.3% of the population and have 0,13% to 0,2% risk for malignant transformation. Clinical, dermoscopic, and histhopatological features were describe in this case report in order to be easily recognize NS. Although NS is a benign cutaneous anomaly it has potential malignant transformation and requires regular follow up. Case Report: A case of nevus spilus in 23 years-old female was reported. There were multiple asymptomatic brownish pigmented spots over brownish patch on left cheek which gradually increased in number and size since 1 year ago. Dermatologic state: brown macules and dark brown papules in a speckled, overlying background café au lait macule. Dermoscopy revealed reticular pattern in background light brown and dark reticuloglobular pattern in dark speckled. Histopathology showed elongation of rete ridges with grouping of melanocyte cells at the tip, and proliferation of nevus cells. Conclution: Patient was planned to treat with Nd-Yag laser.
Hubungan Tingkat Pengetahuan Tentang Antibiotik dengan Sikap dan Tindakan Penggunaan Antibiotik Tanpa Resep pada Mahasiswa/i Universitas HKBP Nommensen Medan
Authors: Sianturi Mega Oktavia , Ompusunggu Henny Erina Saurmauli , . Djohan .
Published: January 2021

Introduction: Antibiotics are drugs that are used to prevent and treat infections caused by bacteria. Inappropriate use of antibiotics can cause various problems, such as bacterial resistance to antibiotics. One of the causes of bacterial resistance to antibiotics is the irrational in non prescription use of antibiotics. Aims: to determine the association of knowledge level about antibiotics with attitude and action level in non prescription use of antibiotics in Universitas HKBP Nommensen students. Method: There was 210 active students of Universitas HKBP Nommensen were included as respondents in this cross sectional study. The level of knowledge, attitudes and actions of respondents were measured using a questionnaire. Chi Square test was used to analyzed the association of knowledge with attitude and action of respondents. Result: There was no significant association of knowledge level about antibiotics with attitude and action level in non prescription use of antibiotics in Universitas HKBP Nommensen students (p > 0,005). Conclusion: Knowledge is not a dominant factor influencing both attitude and action in non prescription use of antibiotics.
Influence of Fluorine Doping of Activated Carbon Fibers on Their Water Vapor Adsorption Characteristics
Authors: Velasco Leticia F. , Kim Kyung Hoon , Lee Young-Seak , Lodewyckx Peter
Published: January 2021

The characterization of fluorinated carbon fibers by water sorption has been broadly investigated in this work. In brief, a pitch-based activated carbon fiber (ACF) was submitted to a fluorination process under different conditions of partial pressure (F2:N2 ratio) and temperature. This led to samples with varied fluorine content and C-F type bonding. The effect of the fluorination treatment on the textural properties of the ACF was studied by means of nitrogen and carbon dioxide adsorption at −196 and 0°C, respectively, while the changes induced in the surface chemistry of the materials were analyzed by XPS. Also, the affinity and stability of the materials toward water was evaluated by single and cycling isotherms. The obtained results show that a mild fluorination not only can preserve most of the textural properties of the parent ACF, but enhance the water uptake at the first stages of the water sorption process, together with a shift in the upswing of the water isotherms toward lower relative humidities. This indicates that fluorination under certain conditions can actually enhance the surface hydrophilicity of carbon materials with specific properties. On the contrary, higher partial pressures led to highly fluorinated fibers with lower porosity and more hydrophobic character. Moreover, they presented a lower chemical stability as demonstrated by a change in the shape of the water isotherms after two consecutive measurements. The kinetics of water sorption in the ACFs provided further insights into the different sorption phenomena involved. Hence, water sorption can definitely help to tailor the water affinity, stability and performance of fluorinated porous carbon materials under humid conditions.
Overview of Biologically Active Nucleoside Phosphonates
Authors: Groaz Elisabetta , De Jonghe Steven
Published: January 2021

The use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P–O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.
Effect of BaF2 Variation on Spectroscopic Properties of Tm3+ Doped Gallium Tellurite Glasses for Efficient 2.0 μm Laser
Authors: Yuan Jian , Wang Weichao , Ye Yichen , Deng Tingting , Ou Deqian , Cheng Junyang , Yuan Shengjin , Xiao Peng
Published: January 2021

The effects of substitution of BaF2 for BaO on physical properties and 1. 8 μm emission have been systematically investigated to improve spectroscopic properties in Tm3+ doped gallium tellurite glasses for efficient 2.0 μm fiber laser. It is found that refractive index and density gradually decrease with increasing BaF2 content from 0 to 9 mol.%, due to the generation of more non-bridging oxygens. Furthermore, OH− absorption coefficient (αOH) reduces monotonically from 3.4 to 2.2 cm−1 and thus emission intensity near 1.8 μm in gallium tellurite glass with 9 mol.% BaF2 is 1.6 times as large as that without BaF2 while the lifetime becomes 1.7 times as long as the one without BaF2. Relative energy transfer mechanism is proposed. The maximum emission cross section and gain coefficient at around 1.8 μm of gallium tellurite glass containing 9 mol.% BaF2 are 8.8 × 10−21 cm2 and 3.3 cm−1, respectively. These results indicate that Tm3+ doped gallium tellurite glasses containing BaF2 appear to be an excellent host material for efficient 2.0 μm fiber laser development.
Global Lysine Crotonylation Alterations of Host Cell Proteins Caused by Brucella Effector BspF
Authors: Zhu Jinying , Dong Qiao , Dong Changpeng , Zhang Xi , Zhang Huan , Chen Zeliang
Published: January 2021

In Brucella spp., the type IV secretion system (T4SS) is essential for bacterial intracellular survival and inhibition of the host innate immune response. The Brucella T4SS secretes 15 different effectors to escape host immunity and promote intracellular replication. Among them, BspF has a GNAT-family acetyltransferase domain, implying its acetyltransferase activity. We confirmed that BspF has acetyltransferase activity (data not shown) and de-crotonyltransferase activity. However, BspF overexpressed in HEK-293T cells can also enhance octamer crotonylation in vitro. Then we enriched crotonylated proteins and conducted LC-MS to study the crotonylation changes of proteins in HEK-293T cells caused by BspF overexpression. A total of 5,559 crotonylation sites were identified on 1,525 different proteins, of which 331 sites on 265 proteins were significantly changed. We found that Rab9A and RAP1B in proteomics data have a great impact on Brucella survival, so we speculate that BspF may influence the function of host proteins by altering crotonylation, thereby promoting the intracellular propagation of Brucella.
Prevalence and Risk Factors of Sensory Symptoms in Diabetes Patients in Taiwan
Authors: Tseng Chin-Hsiao , Chong Choon-Khim , Sheu Jau-Jiuan
Published: January 2021

Background

Diabetic sensory neuropathy has rarely been studied in the Asian populations. This study investigated the prevalence and risk factors of sensory symptoms (SS) in the Taiwanese diabetes patients.

Methods

A total of 1,400 diabetes patients received a health examination together with a structured questionnaire interview for three categories of abnormal sensation of numbness or tingling pain, electric shock, and skin thickness sensation on seven anatomical sites on upper limbs and six sites on lower limbs. Prevalence of SS was defined using nine different criteria, with the least stringent criterion of “any positive symptom on at least 1 site” and the most stringent criterion of “any positive symptom on at least bilateral and symmetrical 2 sites involving the lower limb.” Logistic regression was used to estimate the odds ratios and their 95% confidence interval for SS by the different definitions. Fasting plasma glucose and hemoglobin A1c were entered in separate models to avoid hypercollinearity.

Results

The prevalence of SS was 14.4 and 54.0% when using the most stringent and least stringent criterion, respectively. Women consistently had a significantly higher prevalence than men did. Among the three categories of symptoms, numbness or tingling pain was the most common, and fingers and toes were the most commonly involved anatomical sites. For any symptoms, 37.1% of the patients had any symptoms on the upper limbs and 41.7% had any symptoms on the lower limbs. Female sex, diabetes duration, hemoglobin A1c, and hypertension were associated with SS in all models.

Conclusions

Taiwanese diabetes patients may have a high prevalence of SS if a structured questionnaire is used for screening. Female sex, diabetes duration, hemoglobin A1c, and hypertension are associated with SS.
Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort
Authors: Diener Christian , Reyes-Escogido María de Lourdes , Jimenez-Ceja Lilia M. , Matus Mariana , Gomez-Navarro Claudia M. , Chu Nathaniel D. , Zhong Vivian , Tejero M. Elizabeth , Alm Eric , Resendis-Antonio Osbaldo , Guardado-Mendoza Rodolfo
Published: January 2021

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world’s population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity.

Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment—predominantly metformin—reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.
Serum Ratio of Free Triiodothyronine to Thyroid-Stimulating Hormone: A Novel Index for Distinguishing Graves’ Disease From Autoimmune Thyroiditis
Authors: Wu Zhiyong , Zhu Yu , Zhang Min , Wang Chen , Zhou Lingli , Liu Wei , Yang Wenjia , Li Meng , Zhang Simin , Ren Qian , Han Xueyao , Ji Linong
Published: January 2021

Objective

Graves’ disease (GD) and autoimmune thyroiditis (AIT) are two major causes of thyrotoxicosis that require correct diagnosis to plan appropriate treatment. The objectives of this study were to evaluate the usefulness of thyroid-related parameters for distinguishing GD from AIT and identify a novel index for differential diagnosis of thyrotoxicosis.

Design

This retrospective study was performed using electronic medical records in Peking University People’s Hospital (Beijing, China).

Methods

In total, 650 patients with GD and 155 patients with AIT from December 2015 to October 2019 were included in cohort 1. Furthermore, 133 patients with GD and 14 patients with AIT from December 2019 to August 2020 were included in cohort 2 for validation of the novel index identified in cohort 1. All patients were of Chinese ethnicity and were newly diagnosed with either GD or AIT. Thyroid-related clinical information was collected before intervention by reviewing the patients’ electronic medical records. Receiver operating characteristic curve analysis was used to identify the optimal cutoff for distinguishing GD from AIT.

Results

In cohort 1, thyroid-stimulating hormone (TSH) receptor antibody was identified as the best indicator for distinguishing GD from AIT. The area under the receiver operating characteristic curve was 0.99(95% confidence interval: 0.98–0.99, p<0.0001)and the optimal cutoff was 0.84 IU/l (98% sensitivity and 99% specificity). The free triiodothyronine (FT3)/TSH ratio (FT3/TSH) was the second –best for distinguishing GD from AIT, the area under the receiver operating characteristic curve of FT3/TSH was 0.86 (95% confidence interval: 0.84–0.88, p<0.0001); its optimal cutoff was 1.99 pmol/mIU (79% sensitivity and 80% specificity). Its effectiveness was confirmed in cohort 2 (81% sensitivity and 100% specificity).

Conclusions

The FT3/TSH ratio is a new useful index for differential diagnosis of thyrotoxicosis, especially when combined with TRAb.
Partial Retention of Legacy Trees Protect Mycorrhizal Inoculum Potential, Biodiversity, and Soil Resources While Promoting Natural Regeneration of Interior Douglas-Fir
Authors: Simard Suzanne W. , Roach W. Jean , Beauregard Jacob , Burkart Julia , Cook Dominique , Law Danica , Murphy-Steed Arianna , Schacter Teah , Zickmantel Aidan , Armstrong Gaelin , Fraser Kaya M. , Hart Lia , Heath Oliver R. J. , Jones Liam , Sachs Nava S. , Sachs Hannah R. , Snyder Eva N. , Tien Morgan , Timmermans Joseph
Published: January 2021

Clearcutting reduces proximity to seed sources and mycorrhizal inoculum potential for regenerating seedlings. Partial retention of legacy trees and protection of refuge plants, as well as preservation of the forest floor, can maintain mycorrhizal networks that colonize germinants and improve nutrient supply. However, little is known of overstory retention levels that best protect mycorrhizal inoculum while also providing sufficient light and soil resources for seedling establishment. To quantify the effect of tree retention on seedling regeneration, refuge plants, and resource availability, we compared five harvesting methods with increasing retention of overstory trees (clearcutting (0% retention), seed tree (10% retention), 30% patch retention, 60% patch retention, and 100% retention in uncut controls) in an interior Douglas-fir-dominated forest in British Columbia. Regeneration increased with proximity to legacy trees in partially cut forests, with increasing densities of interior Douglas-fir, western redcedar, grand fir, and western hemlock seedlings with overstory tree retention. Clearcutting reduced cover of ectomycorrhizal refuge plants (from 80 to 5%) while promoting arbuscular mycorrhizal plants the year after harvest. Richness of shrubs, herbs, and mosses declined with increasing harvesting intensity, but tree richness remained at control levels. The presence of legacy trees in all partially cut treatments mitigated these losses. Light availability declined with increasing overstory cover and proximity to leave trees, but it still exceeded 1,000 W m−2 in the clearcut, seed tree and 30% retention treatments. Increasing harvesting intensity reduced aboveground and belowground C stocks, particularly in live trees and the forest floor, although forest floor losses were also substantial where thinning took place in the 60% retention treatment. The loss of forest floor carbon, along with understory plant richness with intense harvesting was likely associated with a loss of ectomycorrhizal inoculum potential. This study suggests that dispersed retention of overstory trees where seed trees are spaced ~10–20 m apart, and aggregated retention where openings are <60 m (2 tree-lengths) in width, will result in an optimal balance of seed source proximity, inoculum potential, and resource availability where seedling regeneration, plant biodiversity, and carbon stocks are protected.
Improvements in Gene Editing Technology Boost Its Applications in Livestock
Authors: Perisse Iuri Viotti , Fan Zhiqiang , Singina Galina N. , White Kenneth L. , Polejaeva Irina A.
Published: January 2021

Accelerated development of novel CRISPR/Cas9-based genome editing techniques provides a feasible approach to introduce a variety of precise modifications in the mammalian genome, including introduction of multiple edits simultaneously, efficient insertion of long DNA sequences into specific targeted loci as well as performing nucleotide transitions and transversions. Thus, the CRISPR/Cas9 tool has become the method of choice for introducing genome alterations in livestock species. The list of new CRISPR/Cas9-based genome editing tools is constantly expanding. Here, we discuss the methods developed to improve efficiency and specificity of gene editing tools as well as approaches that can be employed for gene regulation, base editing, and epigenetic modifications. Additionally, advantages and disadvantages of two primary methods used for the production of gene-edited farm animals: somatic cell nuclear transfer (SCNT or cloning) and zygote manipulations will be discussed. Furthermore, we will review agricultural and biomedical applications of gene editing technology.
Innate Cells: The Alternative Source of IL-17 in Axial and Peripheral Spondyloarthritis?
Authors: Rosine Nicolas , Miceli-Richard Corinne
Published: January 2021

Spondyloarthritis (SpA) is a chronic inflammatory rheumatism characterized by inflammation of sacroiliac joints, peripheral joints, and spine. The Assessment of SpondyloArthritis Society describes three disease forms: axial (axSpA), peripheral, and enthesitic SpA. Each may be associated with extra-articular manifestations: psoriasis, inflammatory bowel disease, and acute anterior uveitis. Genome-wide association studies performed in axSpA and psoriatic arthritis (PsA) have shown a shared genetic background, especially the interleukin 23 (IL-23)/IL-17 pathway, which suggests pathophysiological similarities. The convincing positive results of clinical trials assessing the effect of secukinumab and ixekizumab (anti-IL-17A monoclonal antibodies) in axSpA and PsA have reinforced the speculated crucial role of IL-17 in SpA. Nevertheless, and obviously unexpectedly, the differential efficacy of anti-IL-23–targeted treatments between axSpA (failure) and PsA (success) has profoundly disrupted our presumed knowledge of disease pathogeny. The cells able to secrete IL-17, their dependence on IL-23, and their respective role according to the clinical form of the disease is at the heart of the current debate to potentially explain these observed differences in efficacy of IL-23/IL-17–targeted therapy. In fact, IL-17 secretion is usually mainly related to T helper 17 lymphocytes. Nevertheless, several innate immune cells express IL-23 receptor and can produce IL-17. To what extent these alternative cell populations can produce IL-17 independent of IL-23 and their respective involvement in axSpA and PsA are the crucial scientific questions in SpA. From this viewpoint, this is a nice example of a reverse path from bedside to bench, in which the results of therapeutic trials allow for reflecting more in depth on the pathophysiology of a disease. Here we provide an overview of each innate immunity-producing IL-17 cell subset and their respective role in disease pathogeny at the current level of our knowledge.
Combination Treatment With Metformin and Tacrolimus Improves Systemic Immune Cellular Homeostasis by Modulating Treg and Th17 Imbalance
Authors: Lee Soon Kyu , Park Min-Jung , Jhun Joo Yeon , Beak Jin-Ah , Choi Jeong Won , Rye Jae-Yoon , Jang Jeong Won , Bae Si Hyun , Yoon Seung Kew , Choi Ho Joong , You Young Kyoung , Cho Mi-La , Choi Jong Young
Published: January 2021

We examined the effect of combination therapy with metformin and tacrolimus on immune parameters including T regulatory (Treg) and type 17 helper T (Th17) cells in vitro and in vivo in mice and in liver transplantation (LT) patients. T cell proliferation and subtypes after in vitro T cell activation or allogeneic stimulation were evaluated. RNA sequencing and microarray analysis were used to evaluate differences in gene expression. Metformin and tacrolimus were administered to mice with graft-versus-host disease (GVHD) and the effects in vivo were assessed. Five LT patients were treated with metformin and the changes in Treg and Th17 cells examined. Combination therapy decreased Type 1 helper T (Th1) and Th17 cells present after in vitro T cell activation, whereas genes associated with Treg were overexpressed. During in vitro allogeneic stimulation, combination therapy increased Treg cells and decreased T cell proliferation and pro-inflammatory markers. In mice with GVHD, combination treatment decreased the clinical and pathological severity of GVHD. In LT patients, addition of metformin increased the peripheral percentage of CD4+Treg and CD8+Treg cells and decreased CD4+Th17. Our study suggests that the addition of metformin to tacrolimus may improve immunological balance by increasing Treg cells and decreasing Th17 cells.
Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome
Authors: Oyelakin Akinsola , Horeth Erich , Song Eun-Ah Christine , Min Sangwon , Che Monika , Marzullo Brandon , Lessard Christopher J. , Rasmussen Astrid , Radfar Lida , Scofield R. Hal , Lewis David M. , Stone Donald U. , Grundahl Kiely , De Rossi Scott S. , Kurago Zoya , Farris A. Darise , Sivils Kathy L. , Sinha Satrajit , Kramer Jill M. , Romano Rose-Anne
Published: January 2021

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized primarily by immune-mediated destruction of exocrine tissues, such as those of the salivary and lacrimal glands, resulting in the loss of saliva and tear production, respectively. This disease predominantly affects middle-aged women, often in an insidious manner with the accumulation of subtle changes in glandular function occurring over many years. Patients commonly suffer from pSS symptoms for years before receiving a diagnosis. Currently, there is no effective cure for pSS and treatment options and targeted therapy approaches are limited due to a lack of our overall understanding of the disease etiology and its underlying pathology. To better elucidate the underlying molecular nature of this disease, we have performed RNA-sequencing to generate a comprehensive global gene expression profile of minor salivary glands from an ethnically diverse cohort of patients with pSS. Gene expression analysis has identified a number of pathways and networks that are relevant in pSS pathogenesis. Moreover, our detailed integrative analysis has revealed a primary Sjögren’s syndrome molecular signature that may represent important players acting as potential drivers of this disease. Finally, we have established that the global transcriptomic changes in pSS are likely to be attributed not only to various immune cell types within the salivary gland but also epithelial cells which are likely playing a contributing role. Overall, our comprehensive studies provide a database-enriched framework and resource for the identification and examination of key pathways, mediators, and new biomarkers important in the pathogenesis of this disease with the long-term goals of facilitating earlier diagnosis of pSS and to mitigate or abrogate the progression of this debilitating disease.
Screening of FDA-Approved Drug Library Identifies Adefovir Dipivoxil as Highly Potent Inhibitor of T Cell Proliferation
Authors: Voss Linda , Guttek Karina , Reddig Annika , Reinhold Annegret , Voss Martin , Schraven Burkhart , Reinhold Dirk
Published: January 2021

Repositioning of approved drugs for identifying new therapeutic purposes is an alternative, time and cost saving strategy to classical drug development. Here, we screened a library of 786 FDA-approved drugs to find compounds, which can potentially be repurposed for treatment of T cell-mediated autoimmune diseases. Investigating the effect of these diverse substances on mitogen-stimulated proliferation of both, freshly stimulated and pre-activated (48 h) peripheral blood mononuclear cells (PBMCs), we discovered Adefovir Dipivoxil (ADV) as very potent compound, which inhibits T cell proliferation in a nanomolar range. We further analyzed the influence of ADV on proliferation, activation, cytokine production, viability and apoptosis of freshly stimulated as well as pre-activated human T cells stimulated with anti-CD3/CD28 antibodies. We observed that ADV was capable of suppressing the proliferation in both T cell stimulation systems in a dose-dependent manner (50% inhibition [IC50]: 63.12 and 364.8 nM for freshly stimulated T cells and pre-activated T cells, respectively). Moreover, the drug impaired T cell activation and inhibited Th1 (IFN-γ), Th2 (IL-5), and Th17 (IL-17) cytokine production dose-dependently. Furthermore, ADV treatment induced DNA double-strand breaks (γH2AX foci expression), which led to an increase of p53-phospho-Ser15 expression. In response to DNA damage p21 and PUMA are transactivated by p53. Subsequently, this caused cell cycle arrest at G0/G1 phase and activation of the intrinsic apoptosis pathway. Our results indicate that ADV could be a new potential candidate for treatment of T cell-mediated autoimmune diseases. Prospective studies should be performed to verify this possible therapeutic application of ADV for such disorders.
Plankton Community Metabolism in Western Australia: Estuarine, Coastal and Oceanic Surface Waters
Authors: Garcia-Corral Lara S. , Duarte Carlos M. , Agusti Susana
Published: January 2021

Net community production (NCP) is a community level process informing on the balance between production and consumption, determining the role of plankton communities in carbon and nutrient balances fueling the marine food web. An assessment of net and gross community production (NCP, GPP) and community respiration (CR) in 86 surface plankton communities sampled between 15° and 36° South along coastal Western Australia (WA) revealed a prevalence of net autotrophic metabolism (GPP/CR > 1), comprising 81% of the communities sampled. NCP, GPP, and CR decreased with decreasing nutrient and chlorophyll-a concentrations, from estuarine, to coastal and oceanic waters. CR, standardized per unit chlorophyll-a, increased with temperature, with higher activation energies (Ea) than GPP per unit chlorophyll-a (Ea 1.07 ± 0.18 eV and 0.65 ± 0.15 eV, respectively) either across ecosystem types and for coastal and estuary communities alone, indicating plankton CR to increase much faster with warming than GPP. These results characterize surface plankton communities across Western Australia as CO2 sinks, the stronger thermal-dependence of respiration that gross primary production rates suggests that their role may weaken with future warming.
Preoperatively Estimating the Malignant Potential of Mediastinal Lymph Nodes: A Pilot Study Toward Establishing a Robust Radiomics Model Based on Contrast-Enhanced CT Imaging
Authors: Dong Mengshi , Hou Gang , Li Shu , Li Nan , Zhang Lina , Xu Ke
Published: January 2021

Purpose

To establish and validate a radiomics model to estimate the malignancy of mediastinal lymph nodes (LNs) based on contrast-enhanced CT imaging.

Method

In total, 201 pathologically confirmed mediastinal LNs from 129 patients were enrolled and assigned to training and test sets. Radiomics features were extracted from the region of interest (ROI) delineated on venous-phase CT imaging of LN. Feature selection was performed with least absolute shrinkage and selection operator (LASSO) binary logistic regression. Multivariate logistic regression was performed with the backward stepwise elimination. A model was fitted to associate mediastinal LN malignancy with selected features. The performance of the model was assessed and compared to that of five other machine learning algorithms (support vector machine, naive Bayes, random forest, decision tree, K-nearest neighbor) using receiver operating characteristic (ROC) curves. Calibration curves and Hosmer-Lemeshow tests were used to assess the calibration degree. Decision curve analysis (DCA) was used to assess the clinical usefulness of the logistic regression model in both the training and test sets. Stratified analysis was performed for different scanners and slice thicknesses.

Result

Among the six machine learning methods, the logistic regression model with the eight strongest features showed a significant association with mediastinal LN status and the satisfactory diagnostic performance for distinguishing malignant LNs from benign LNs. The accuracy, sensitivity, specificity and area under the ROC curve (AUC) were 0.850/0.803, 0.821/0.806, 0.893/0.800, and 0.922/0.850 in the training/test sets, respectively. The Hosmer-Lemeshow test showed that the P value was > 0.05, indicating good calibration, and the calibration curves showed good agreement between the classifications and actual observations. DCA showed that the model would obtain more benefit when the threshold probability was between 30% and 90% in the test set. Stratified analysis showed that the performance was not affected by different scanners or slice thicknesses. There was no significant difference (DeLong test, P > 0.05) between any two subgroups, which showed the generalization of the radiomics score across different factors.

Conclusion

The model we built could help assist the preoperative estimation of mediastinal LN malignancy based on contrast-enhanced CT imaging, with stability for different scanners and slice thicknesses.
Emodin Inhibits Inflammation, Carcinogenesis, and Cancer Progression in the AOM/DSS Model of Colitis-Associated Intestinal Tumorigenesis
Authors: Zhang Yunsha , Pu Weiling , Bousquenaud Mélanie , Cattin Sarah , Zaric Jelena , Sun Li-kang , Rüegg Curzio
Published: January 2021

Colorectal cancer (CRC) is one of the most common cancer worldwide. Chronic inflammation contributes to CRC development and progression. Emodin, is a natural anthraquinone derivative with anti-oxidant, anti-inflammatory, and anti-tumor activities. We used the AOM/DSS model of colitis-associated intestinal tumorigenesis to characterize the effect of Emodin on inflammation and tumorigenesis at weeks 3, 5, and 14 after initiation with AOM. At all three time points, Emodin (50 mg/kg) reduced inflammatory cell (i.e. CD11b+ and F4/80+) recruitment, cytokine (i.e. TNFα, IL1α/β, IL6, CCL2, CXCL5) and pro-inflammatory enzymes (i.e. COX-2, NOS2) expression in the tumor microenvironment, while promoting recruitment of CD3+ T lymphocytes at 14 weeks. Emodin decreased the incidence of premalignant lesions (adenoma) at week 3, the incidence of dysplastic lesions and carcinomas at week 5, and the incidence, size and the invasiveness of carcinomas at week 14. Emodin also reduced the acute clinical intestinal symptoms (i.e. bleeding and diarrhea) during DSS treatment. In vitro, Emodin inhibited the expression of pro-inflammatory mediators by LPS-stimulated RAW 264.7 macrophages, and reduced viability, adhesion, migration, and fibroblasts-induced invasion of SW620 and HCT116 colon cancer cells. In conclusion, this work demonstrates that Emodin suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression. These results instigate further studies on Emodin as a natural agent for the prevention or treatment of colorectal cancer.
The Molecular Landscape and Biological Alterations Induced by PRAS40-Knockout in Head and Neck Squamous Cell Carcinoma
Authors: Chen Gang , Li Zhexuan , Chen Changhan , Liu Jiajia , Zhu Weiming , She Li , Huang Huimei , Qin Yuexiang , Liu Guancheng , Wang Juncheng , Liu Yong , Huang Donghai , Tang Qinglai , Zhang Xin , Zhu Gangcai
Published: January 2021

PRAS40 (Prolin-rich Akt substrate of 40 kDa) is a critical protein, which directly connects PI3K/Akt and mTORC1 pathway. It plays an indispensable role in the development of various diseases. However, the relationship between PRAS40 and head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, our study indicated that high expression of PRAS40 mRNA is a favorable prognostic factor in HNSCC patients by analyzing 498 clinical and mRNA data. Moreover, we confirmed that CRISPR/Cas9 induced PRAS40-knockout would promote colony formation, cell migration, and invasion in several HNSCC cell lines. RNA-seq was employed to investigate the further possible mechanisms involving the above regulations by PRAS40 in HNSCC cells. The molecular landscape contributed by 253 differentially expressed mRNA after PRAS40-knockout was enriched in TGF-beta, PI3K-Akt, P53, mTOR, NF-κB signaling pathway. Partial molecular alternations within these pathways were validated by qPCR or Western blotting. Besides, we found that high expression of PRAS40 in HNSC patients would present more CD8+ T and T follicular helper cells, but less Th17 cells than the patients with low expression of PRAS40. The altered molecular pathways and tumor-infiltrating immune cells might associate with the mechanism of PRAS40 being a suppressor in HNSCC cells, which would provide a potential prognostic predictor and therapeutic target in HNSCC patients.
MYBL2-Driven Transcriptional Programs Link Replication Stress and Error-prone DNA Repair With Genomic Instability in Lung Adenocarcinoma
Authors: Morris Benjamin B. , Wages Nolan A. , Grant Patrick A. , Stukenberg P. Todd , Gentzler Ryan D. , Hall Richard D. , Akerley Wallace L. , Varghese Thomas K. , Arnold Susanne M. , Williams Terence M. , Coppola Vincenzo , Jones David R. , Auble David T. , Mayo Marty W.
Published: January 2021

It has long been recognized that defects in cell cycle checkpoint and DNA repair pathways give rise to genomic instability, tumor heterogeneity, and metastasis. Despite this knowledge, the transcription factor-mediated gene expression programs that enable survival and proliferation in the face of enormous replication stress and DNA damage have remained elusive. Using robust omics data from two independent studies, we provide evidence that a large cohort of lung adenocarcinomas exhibit significant genome instability and overexpress the DNA damage responsive transcription factor MYB proto-oncogene like 2 (MYBL2). Across two studies, elevated MYBL2 expression was a robust marker of poor overall survival and disease-free survival outcomes, regardless of disease stage. Clinically, elevated MYBL2 expression identified patients with aggressive early onset disease, increased lymph node involvement, and increased incidence of distant metastases. Analysis of genomic sequencing data demonstrated that MYBL2 High lung adenocarcinomas had elevated somatic mutation burden, widespread chromosomal alterations, and alterations in single-strand DNA break repair pathways. In this study, we provide evidence that impaired single-strand break repair, combined with a loss of cell cycle regulators TP53 and RB1, give rise to MYBL2-mediated transcriptional programs. Omics data supports a model wherein tumors with significant genomic instability upregulate MYBL2 to drive genes that control replication stress responses, promote error-prone DNA repair, and antagonize faithful homologous recombination repair. Our study supports the use of checkpoint kinase 1 (CHK1) pharmacological inhibitors, in targeted MYBL2 High patient cohorts, as a future therapy to improve lung adenocarcinoma patient outcomes.
Long Non-Coding RNA-PAICC Promotes the Tumorigenesis of Human Intrahepatic Cholangiocarcinoma by Increasing YAP1 Transcription
Authors: Xia Long , Chen Xiaolong , Yang Jiarui , Zhu Shuguang , Zhang Lei , Yin Qi , Hong Yueyu , Chen Haoqi , Chen Guihua , Li Hua
Published: January 2021

Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary tumor with poor prognosis, and it lacks reliable prognostic biomarkers and effective therapeutic targets. Long non-coding RNAs (lncRNAs) have been documented to be involved in the progression of various cancers. However, the role of lncRNAs in ICC remains largely unknown. In the present work, we used bioinformatics analysis to identify the differentially expressed lncRNAs in human ICC tissues, among which lncRNA-PAICC was found to be an independent prognostic marker in ICC. Moreover, lncRNA-PAICC promoted the proliferation and invasion of ICC cells. Mechanistically, lncRNA-PAICC acted as a competitive endogenous RNA (ceRNA) that directly sponged the tumor suppressive microRNAs miR-141-3p and miR-27a-3p. The competitive binding property was essential for lncRNA-PAICC to promote tumor growth and metastasis through activating the Hippo pathway. In summary, our results highlighted the important role of the lncRNA-PAICC-miR-141-3p/27a-3p-Yap1 axis in ICC, which offers a novel perspective on the molecular pathogenesis and may serve as a potential target for antimetastatic molecular therapies of ICC.
Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas
Authors: He Yu-qin , Zhang Xi-wei , Zhu Yi-ming , Ni Xiao-guang , Huang Ze-hao , An Chang-ming , Yi Jun-lin , Liu Shao-yan
Published: January 2021

Introduction

We aimed to analyze the relationship between the changed status of vocal cord mobility and survival outcomes.

Methods

Seventy-eight patients with dysfunctional vocal cords and hypopharyngeal carcinomas accepted non-surgical treatment as the initial therapy between May 2009 and December 2016. Vocal cord mobility was assessed before and after the initial non-surgical treatment. The cord mobility status was classified as normal, impaired, and fixed. Patients with improved mobility (IM) (n =56) were retrospectively analyzed for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) and compared with 22 patients with non-improved mobility (non-IM).

Results

Fifty-six (71.8%) patients had improved cord mobility after the initial non-surgical treatment. The non-improved cord mobility was significantly associated with shortened DFS (P=0.005), RFS (P=0.002), and OS (P<0.001). If non-improved cord mobility was regarded as an indicator for local-regional recurrence within 1 year, the sensitivity and the specificity were 60.9%, 87.5% respectively. The multivariate analysis showed that improved cord mobility (P=0.006) and salvage surgery (P=0.015) were both independent protective factors for OS.

Conclusion

Changes in cord mobility are a key marker for predicting prognosis. Non-improved cord mobility may indicate a high possibility of a residual tumor, therefore, patients whose cord mobility remains dysfunctional or worsens after non-surgical treatment might need an aggressive salvage strategy.
The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside
Authors: Feng Yimei , Chen Xiaoli , Cassady Kaniel , Zou Zhongmin , Yang Shijie , Wang Zheng , Zhang Xi
Published: January 2021

The mTOR pathway plays a central role in many cellular processes, such as cellular growth, protein synthesis, glucose, and lipid metabolism. Aberrant regulation of mTOR is a hallmark of many cancers, including hematological malignancies. mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases—either alone or in combination with other treatment regimens. This review highlights experimental evidence underlying the molecular mechanisms of mTOR inhibitors and summarizes their evolving role in the treatment of hematologic disease, including leukemia, lymphoma, myeloma, immune hemocytopenia, and graft-versus-host disease (GVHD). Based on data presented in this review, we believe that mTOR inhibitors are becoming a trusted therapeutic in the clinical hematologist’s toolbelt and should be considered more routinely in combination therapy for the management of hematologic disease.
Second Look After Retromuscular Repair With the Combination of Absorbable and Permanent Meshes
Authors: Robin Valle de Lersundi Alvaro , Munoz-Rodriguez Joaquín , Lopez-Monclus Javier , Blazquez Hernando Luis Alberto , San Miguel Carlos , Minaya Ana , Perez-Flecha Marina , Garcia-Urena Miguel Angel
Published: January 2021

Objective: The aim of this study is to describe the macroscopic features and histologic details observed after retromuscular abdominal wall reconstruction with the combination of an absorbable mesh and a permanent mesh.

Methods: We have considered all patients that underwent abdominal wall reconstruction (AWR) with the combination of two meshes that required to be reoperated for any reason. Data was extracted from a prospective multicenter study from 2012 to 2019. Macroscopic evaluation of parietal adhesions and histological analysis were carried out in this group of patients.

Results: Among 466 patients with AWR, we identified 26 patients that underwent a reoperation after abdominal wall reconstruction using absorbable and permanent mesh. In eight patients, the reoperation was related to abdominal wall issues: four patients were reoperated due to recurrence, three patients required an operation for chronic mesh infection and one patient for symptomatic bulging. A miscellanea of pathologies was the cause for reoperation in 18 patients. During the second surgical procedures made after a minimum of 3 months follow-up, a fibrous tissue between the permanent mesh covering and protecting the peritoneum was identified. This fibrous tissue facilitated blunt dissection between the permanent material and the peritoneum. Samples of this tissue were obtained for histological examination. No case of severe adhesions to the abdominal wall was seen. In four cases, the reoperation could be carried out laparoscopically with minimal adhesions from the previous procedure.

Conclusions: The reoperations performed after the combination of absorbable and permanent meshes have shown that the absorbable mesh acts as a protective barrier and is replaced by a fibrous layer rich in collagen. In the cases requiring new hernia repair, the layer between peritoneum and permanent mesh could be dissected without special difficulty. Few intraperitoneal adhesions to the abdominal wall were observed, mainly filmy, easy to detach, facilitating reoperations.
Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice
Authors: Peng Xinyan , Dai Chongshan , Zhang Min , Das Gupta Subhajit
Published: January 2021

Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.