bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic Peripheral Neuropathy in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Tadesse Degena Bahrey , Gebrewahd Gebremeskel Tukue , Hailay Abrha , Aberhe Woldu , Mebrahtom Guesh , Zereabruk Kidane , Gebreayezgi Guesh , Mariye Teklewoini , Haile Teklehaimanot Gereziher , Gebremeskel Gebreamlak Gebremedhn , Demoz Gebre Teklemariam
Published: February 2021

Background. Currently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. Methods. This study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index (

I

2

). The reviewers examined the publication bias by the funnel plot. Results. The search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara. Conclusions. More than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients’ blood glucose.
Shield Reliability Analysis-Based Transfer Impedance Optimization Model for Double Shielded Cable of Electric Vehicle
Authors: Wu Xiaoshan , Shi Xiaohui , Jia Jin , Zhao Heming , Li Xu
Published: February 2021

Due to the high-voltage and high-current operating characteristics of the electric drive system of electric vehicles, it forms strong electromagnetic interference during the working process. The shielding effectiveness of the high-voltage connection cable that connects the components of the electric drive system is directly related to its electromagnetic interference emissions. Therefore, the modeling and analysis of the shielding effectiveness of the connection cable is very important for the development of a connection cable with good shielding effectiveness. Firstly, the transfer impedance value representing the shielding effectiveness of the shielded cable is analyzed, and the difference between the single-layer shield and the double-layer shield cable is compared. The influence of double-layer shielded high-voltage connection cables commonly used in electric vehicles on the shielding layer DC resistance and keyhole inductance is clarified. Secondly, the transfer impedance optimization model ZT_D-Desmoulins is obtained by combining with the single-layer shielded cable Desmoulins model and considering the influence of shielded layer DC resistance and keyhole inductance. Finally, three double-layer shielded cables of different types were selected for the triaxial test. The error rates of the test data and the ZT_D-Desmoulin optimization model are all lower than 20% in each frequency band, which verified the correctness, universality, and great engineering application value of the optimization model.
Optimizing Ontology Alignment through Linkage Learning on Entity Correspondences
Authors: Xue Xingsi , Yang Chaofan , Jiang Chao , Tsai Pei-Wei , Mao Guojun , Zhu Hai
Published: February 2021

Data heterogeneity is the obstacle for the resource sharing on Semantic Web (SW), and ontology is regarded as a solution to this problem. However, since different ontologies are constructed and maintained independently, there also exists the heterogeneity problem between ontologies. Ontology matching is able to identify the semantic correspondences of entities in different ontologies, which is an effective method to address the ontology heterogeneity problem. Due to huge memory consumption and long runtime, the performance of the existing ontology matching techniques requires further improvement. In this work, an extended compact genetic algorithm‐based ontology entity matching technique (ECGA‐OEM) is proposed, which uses both the compact encoding mechanism and linkage learning approach to match the ontologies efficiently. Compact encoding mechanism does not need to store and maintain the whole population in the memory during the evolving process, and the utilization of linkage learning protects the chromosome’s building blocks, which is able to reduce the algorithm’s running time and ensure the alignment’s quality. In the experiment, ECGA‐OEM is compared with the participants of ontology alignment evaluation initiative (OAEI) and the state‐of‐the‐art ontology matching techniques, and the experimental results show that ECGA‐OEM is both effective and efficient.
A Training‐Optimization‐Based Method for Constructing Domain‐Specific Sentiment Lexicon
Authors: Du Maokang , Li Xiaoguang , Luo Longyan
Published: February 2021

Sentiment analysis has been widely used in text mining of social media to discover valuable information from user reviews. Sentiment lexicon is an essential tool for sentiment analysis. Recent research studies indicate that constructing sentiment lexicons for special domains can achieve better results in sentiment analysis. However, it is not easy to construct a sentiment lexicon for a specific domain because most current methods highly depend on general sentiment lexicons and complex linguistic rules. In this paper, the construction of sentiment lexicon is transformed into a training‐optimization process. In our scheme, the accuracy of sentiment classification is used as the optimization objective. The candidate sentiment lexicons are regarded as the individuals that need to be optimized. Then, two genetic algorithms are specially designed to adjust the values of sentiment words in lexicon. Finally, the best individual evolved in the presented genetic algorithms is selected as the sentiment lexicon. Our method only depends on some labelled texts and does not need any linguistic knowledge or prior knowledge. It provides a simple and easy way to construct a sentiment lexicon in a specific domain. Experiment results show that the proposed method has good flexibility and can generate high‐quality sentiment lexicon in specific domains.
The Disinfectant Effect of Modified Hydrothermal Nanotitania Extract on Candida albicans
Authors: Noor Nor Farid Mohd , Yusoff Mohamad Ezany , Rahman Mohd Azizi Abdul , Alam Mohammad Khursheed , Harun Ahmad Mukifza
Published: February 2021

Candida albicans is a pathogenic yeast typically associated with diseases such as HIV, AIDS, and other immunocompromised conditions. It is rarely the cause of fatalities and is commonly treated with drugs administered orally or intravenously. In this experiment, Candida albicans was tested with an extract of modified hydrothermal nanotitania to identify whether the material is capable of inhibiting the organism’s growth. The extract was mixed with the Candida albicans in a culture media preparation to determine whether the organisms were able to grow. The test showed that modified hydrothermal nanotitania inhibits the growth of this organism.
Verification of CENDL-3.2 Nuclear Data on VENUS-3 Shielding Benchmark by ARES Transport Code
Authors: Hu Jiaju , Zhang Bin , Zong Zhiwei , Liu Cong , Chen Yixue
Published: February 2021

The recently released CENDL-3.2 nuclear data library is deemed as an important achievement in the field of nuclear data research in China. To verify the applicability of the library to the shielding calculation of PWR and analyze the influence of multigroup cross-section parameters on the shielding calculation, ARES-MACXS module is used to process the MATXS format multigroup library based on CENDL-3.2 to generate multigroup working cross sections for PWR shielding calculation. VENUS-3 experimental facility has a clear and complete geometry. It is often used to test the ability of the advanced transport calculation method of calculating RPV fast neutron flux and to evaluate the accuracy of cross-section library. Different cross-section parameters are chosen for ARES to calculate VENUS-3 benchmark, and equivalent neutron flux of 58Ni(n,p)58Co, 115In(n,n′)115mIn and 27Al(n,α)24Na detectors is calculated according to the data provided by the benchmark report. The numerical results demonstrate that almost all the relative deviations between the calculated results and the experimental results are within 20%, which satisfies the requirement of shielding calculation. CENDL-3.2 is suitable for PWR shielding calculation. The comparison of various cross-section parameters results indicates that multigroup cross-section parameters have large effects on the transport calculation results.
Poly(1,5-Diaminonaphthalene)-Modified Screen-Printed Device for Electrochemical Lead Ion Sensing
Authors: Nguyen Mai T. T. , Nguyen Huy L. , Nguyen Dung T.
Published: February 2021

Poly(1,5-diaminonaphthalene) has been electropolymerized on the screen-printed device with a three-electrode configuration. The modified electrodes have been developed as the new electrode for electrochemical determination of trace levels of lead ions (Pb2+). The poly(1,5-diaminonaphthalene) film prevents the deposition of Pb2+ into the surface defects of the bare carbon screen-printed electrode and possesses sensitivity to heavy metal ions thanks to amine and secondary amino groups on the polymer chain. The square wave anodic stripping voltammetry was applied to detect Pb2+ ions, showing a sharp stripping peak with the linear range from 0.5 μg·L-1 to 5.0 μg·L-1 (

R

2

=
0.9929

). The limit of detection was found to be 0.30 μg·L-1. The sensors were applied to the analysis of Pb2+ in the tap water sample matrix with satisfactory results.
[Retracted] Earthquake Disaster Rescue Model Based on Complex Adaptive System Theory
Authors: Chen Fujiang , Liu Jingang , Chen Junying
Published: February 2021

China is located in the intersection area of two seismic zones. Due to this special geographical location, earthquake disasters occur frequently in China. Earthquake emergency rescue work is one of the key construction works of disaster prevention and mitigation in China. This paper mainly studies the earthquake disaster rescue model based on the complex adaptive system theory and establishes the earthquake disaster rescue model by analyzing the complex adaptive system theory and combining the earthquake rescue process. In this paper, through the task allocation mechanism task, the disaster rescue task is divided into simple task and complex task, and the executive task subject is divided into single task subject and multitask subject. On the basis of considering the shortest emergency rescue time goal and the goal of maximizing the deployment utility of rescue team, the reasonable deployment of a rescue team is realized through a complex adaptive system, that is, the deployment utility of the rescue team is maximized. In this paper, the simulation experiment and comparison of the earthquake disaster rescue model based on the complex adaptive system theory are carried out. The experimental results show that the model used in this paper is better than the other two models in terms of algorithm convergence, rescue number, and overall score; in different scenarios, the relative survival probability of the model in this paper is 58.92%, 67.85%, and 77.46%, and the proportion of the wounded rescued is 66.31%, 76.45%, and 83.06%, which were higher than those of the other two models. The earthquake disaster rescue model based on the complex adaptive system theory proposed in this paper provides an effective theoretical basis and method system for postdisaster emergency rescue decision making and enhances and improves the emergency response ability to deal with large‐scale geological disaster events.
To Explore MR Imaging Radiomics for the Differentiation of Orbital Lymphoma and IgG4‐Related Ophthalmic Disease
Authors: Yuan Ye , Chu Guangyu , Gong Tingting , Du Lianze , Xie Lizhi , Yuan Qinghai , Han Qinghe
Published: February 2021

Among orbital lymphoproliferative disorders, about 55% of diagnosed cancerous tumors are orbital lymphomas, and nearly 50% of benign cases are immunoglobulin G4‐related ophthalmic disease (IgG4‐ROD). However, due to nonspecific characteristics, the differentiation of the two diseases is challenging. In this study, conventional magnetic resonance imaging‐based radiomics approaches were explored for clinical recognition of orbital lymphomas and IgG4‐ROD. We investigated the value of radiomics features of axial T1‐ (T1WI‐) and T2‐weighted (T2WI), contrast‐enhanced T1WI in axial (CE‐T1WI) and coronal (CE‐T1WI‐cor) planes, and 78 patients (orbital lymphoma, 36; IgG4‐ROD, 42) were retrospectively reviewed. The mass lesions were manually annotated and represented with 99 features. The performance of elastic net‐based radiomics models using single or multiple modalities with or without feature selection was compared. The demographic features showed orbital lymphoma patients were significantly older than IgG4‐ROD patients (p < 0.01), and most of the patients were male (72% in the orbital lymphoma group vs. 23% in the IgG4‐ROD group; p = 0.03). The MR imaging findings revealed orbital lymphomas were mostly unilateral (81%, p = 0.02) and wrapped eyeballs or optic nerves frequently (78%, p = 0.02). In addition, orbital lymphomas showed isointense in T1WI (100%, p < 0.01), and IgG4‐ROD was isointense (60%, p < 0.01) or hyperintense (40%, p < 0.01) in T1WI with well‐defined shape (64%, p < 0.01). The experimental comparison indicated that using CE‐T1WI radiomics features achieved superior results, and the features in combination with CE‐T1WI‐cor features and the feature preselection method could further improve the classification performance. In conclusion, this study comparatively analyzed orbital lymphoma and IgG4‐ROD from demographic features, MR imaging findings, and radiomics features. It might deepen our understanding and benefit disease management.
Model and Experiment on Resistance Loss of Wet Chordal Grid with Spray Pressure and Structural Parameters
Authors: Guo Hua , Wang Haiqiao , Wu Zhirong
Published: February 2021

To reduce the dedusting resistance of wet vibrating string grille precipitators during dedusting in mine ventilation roadways, we investigated the dedusting resistance characteristics of water fog and water film coupling and determined the relationship between dedusting resistance and spray pressure, vibrating grid filling rate, and wind speed. A mathematical resistance coefficient model is established using hydrodynamics theory and capillary mechanics. The theoretical relationship of dedusting resistance is deduced. The results show that when wind speed is constant, the spray pressure and dedusting resistance are higher and the resistance is smaller with a high filling rate compared with a low filling rate. Constant spray pressure allows faster wind speeds and reverse pressure gradient forces to increase when dust flows around the wet vibrating wire, which makes the pressure distribution asymmetrical around the steel wire and increases resistance. Dust removal resistance of the resonance chord with a high filling rate is substantially lower than that with a low filling rate under the same working conditions. On the basis of satisfying the dedusting efficiency, the resonance chord dedusting system does not affect normal production and resistance is low. The spray pressure is controlled at 0.3–0.7 MPa and the optimal wind speed is 3–4 m/s. According to the theoretical calculation and experimental data, the optimal filling rate of a vibrating string grid plate is 77.8%, spray pressure is 0.7 MPa, and wind speed is 3.5 m/s. Dust removal with low resistance and improved economic benefit can thus be obtained.
Scoping Review and Bibliometric Analysis of the Most Influential Publications in Achalasia Research from 1995 to 2020
Authors: Xia Huifang , Tan Shali , Huang Shu , Gan Peiling , Zhong Chunyu , Lü Muhan , Peng Yan , Zhou Xian , Tang Xiaowei
Published: February 2021

Objective. To identify and evaluate characteristics of the most influential articles in achalasia research during the period 1995‐2020. Methods. Articles in Scopus, Web of Science Core Collection (WoSCC), and PubMed were scanned from 1995 to 2020 with achalasia as the keyword. We retrieved the articles that met all criteria by descending order after using EndNote to remove the duplicated references. Our bibliometric analysis highlighted publication year, country, journals, and networks of keywords. Results. Fifteen percent of the top 100 most‐cited articles were published in Annals of Surgery. They were performed in 15 countries, and most (n = 55) were from the USA. The number of citations of the 482 articles ranged from 30 to 953, 38 of which had been published in American Journal of Gastroenterology. Those articles were from 31 countries, and most of the studies (n = 217) had been performed in the USA. Most of articles (n = 335) were clinical research. Treatments were hotspots in the field of achalasia in the past years. The most influential title words were “achalasia,” “esophagomyotomy,” “pneumatic dilation,” and “lower esophageal sphincter.” Conclusion. Our study offers a historical perspective on the progress of achalasia research and identified the most significant evolution in this field. Results showed treatment was the most influence aspect in achalasia.
Epigallocatechin Gallate Protects against MNNG-Induced Precancerous Lesions of Gastric Carcinoma in Rats via PI3K/Akt/mTOR Pathway
Authors: Zhu Feiye , Xu Yanli , Pan Jieli , Li Meiya , Chen Fangming , Xie Guanqun
Published: February 2021

Objective. To evaluate the therapeutic effect of epigallocatechin gallate (EGCG) on precancerous lesions of gastric carcinoma (PLGC) and to determine whether EGCG protects against PLGC by regulating PI3K/Akt/mTOR pathway. Methods. Twenty-four male Wistar rats were randomly divided into 3 groups: normal control group (NC), PLGC model group (MC), and group of PLGC rats treated with EGCG (MC + EGCG). 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) and sodium salicylate were combined and used to establish the PLGC rat animal model. The therapeutic effect of EGCG on PLGC was evaluated by body weight and pathological lesions of gastric mucosa in PLGC rats. Quantitative polymerase chain reaction (qPCR) was applied to measure the mRNA expressions of PI3K, Akt, and mTOR. The protein expressions of cleaved caspase-3, PTEN, PI3K, p-PI3K, Akt, p-Akt, p-mTOR, and mTOR were determined by automated western immunoblotting. Results. The body weight decreased in PLGC rats while EGCG significantly increased body weight. The gastric mucosa of PLGC rats exhibited the pathological lesions of atrophy, intestinal metaplasia, and atypical hyperplasia while EGCG could ameliorate the pathological lesions. EGCG could upregulate the expressions of cleaved caspase-3 and PTEN and reduce the expressions of PI3K, Akt, and mTOR. Conclusions. EGCG ameliorated pathological lesions of PLGC and exerted the effect of apoptosis promotion in PLGC rats. The apoptotic pathway triggered by EGCG may be related to inhibition of PI3K/Akt/mTOR pathway. It provided a theoretical basis for the PLGC treatment and gastric cancer prevention.
Multiperiod Dynamic Pricing and Inventory Control Decisions for an Omnichannel BOPS Retailer with Reference Price Effects
Authors: Li Yuan
Published: February 2021

This paper utilizes the consumers’ reference price in prospect theory to analyze an omnichannel retailer’s multiperiod pricing and inventory management problem in which consumers can cancel their orders before payment and return the products after payment if the products do not meet their expectation. The omnichannel retailer’s optimal equilibrium pricing and ending inventory level are derived under reference price effects by maximizing the discounted total profit over the infinite planning horizon, where the optimal decisions we discussed under two scenarios: loss neutrality and loss aversion. The analysis shows that the convergence of the pricing and ending inventory level toward their equilibrium is from above or below, depending on the relative location of the initial reference price with respect to the unique equilibrium price. Moreover, a set of sensitivity analyses is discussed to characterize the impacts of system parameters on the optimal decisions. This research fills the gap of behavioral operation in the field of omnichannel joint pricing and inventory management.
miR-31 Displays Subtype Specificity in Lung Cancer
Authors: Davenport Mackenzie L. , Echols John B. , Silva Austin D. , Anderson Joshua C. , Owens Philip , Yates Clayton , Wei Qing , Harada Shuko , Hurst Douglas R. , Edmonds Mick D.
Published: February 2021

miRNA rarely possess pan-oncogenic or tumor-suppressive properties. Most miRNAs function under tissue-specific contexts, acting as either tumor suppressors in one tissue, promoting oncogenesis in another, or having no apparent role in the regulation of processes associated with the hallmarks of cancer. What has been less clear is the role of miRNAs within cell types of the same tissue and the ability within each cell type to contribute to oncogenesis. In this study, we characterize the role of one such tissue-specific miRNA, miR-31, recently identified as the most oncogenic miRNA in lung adenocarcinoma, across the histologic spectrum of human lung cancer. Compared with normal lung tissue, miR-31 was overexpressed in patient lung adenocarcinoma, squamous cell carcinoma, and large-cell neuroendocrine carcinoma, but not small-cell carcinoma or carcinoids. miR-31 promoted tumor growth in mice of xenografted human adenocarcinoma and squamous cell carcinoma cell lines, but not in large- or small-cell carcinoma lines. While miR-31 did not promote primary tumor growth of large- and small-cell carcinoma, it did promote spontaneous metastasis. Mechanistically, miR-31 altered distinct cellular signaling programs within each histologic subtype, resulting in distinct phenotypic differences. This is the first report distinguishing diverse functional roles for this miRNA across the spectrum of lung cancers and suggests that miR-31 has broad clinical value in human lung malignancy.

Significance:

These findings demonstrate the oncogenic properties of miR-31 in specific subtypes of lung cancer and highlight it as a potential therapeutic target in these subtypes.
“3G” Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy
Authors: An Omer , Song Yangyang , Ke Xinyu , So Jimmy Bok-Yan , Sundar Raghav , Yang Henry , Rha Sun Young , Lee Ming Hui , Tay Su Ting , Ong Xuewen , Tan Angie Lay Keng , Ng Matthew Chau Hsien , Tantoso Erwin , Chen Leilei , Tan Patrick , Yong Wei Peng
Published: February 2021

Gastric cancer cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic gastric cancer. To achieve greater benefits, selection of patients eligible for this treatment is critical. Although gene expression profiling has been widely used as a genomic classifier to identify molecular subtypes of gastric cancer and to stratify patients for different chemotherapy regimens, its prediction accuracy can be improved. Adenosine-to-inosine (A-to-I) RNA editing has emerged as a new player contributing to gastric cancer development and progression, offering potential clinical utility for diagnosis and treatment. Using a systematic computational approach followed by both in vitro validations and in silico validations in The Cancer Genome Atlas (TCGA), we conducted a transcriptome-wide RNA editing analysis of a cohort of 104 patients with advanced gastric cancer and identified an RNA editing (GCRE) signature to guide gastric cancer chemotherapy. RNA editing events stood as a prognostic and predictive biomarker in advanced gastric cancer. A GCRE score based on the GCRE signature consisted of 50 editing sites associated with 29 genes, predicting response to chemotherapy with a high accuracy (84%). Of note, patients demonstrating higher editing levels of this panel of sites presented a better overall response. Consistently, gastric cancer cell lines with higher editing levels showed higher chemosensitivity. Applying the GCRE score on TCGA dataset confirmed that responders had significantly higher levels of editing in advanced gastric cancer. Overall, this newly defined GCRE signature reliably stratifies patients with advanced gastric cancer and predicts response from chemotherapy.

Significance:

This study describes a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, providing a new tool to improve patient stratification and response to therapy.
Acute Kidney Injury Instigates Malignant Renal Cell Carcinoma via CXCR2 in Mice with Inactivated Trp53 and Pten in Proximal Tubular Kidney Epithelial Cells
Authors: Zhou Xunian , Xiao Fei , Sugimoto Hikaru , Li Bingrui , McAndrews Kathleen M. , Kalluri Raghu
Published: February 2021

Renal cell carcinoma (RCC) is one of the most common urologic malignancies with the highest mortality rates worldwide. However, relevant mouse models that recapitulated the genetic alterations found in RCC have been lacking. In this study, we crossed Trp53 and Pten conditional knockout mice with Ggt1-Cre mice to generate a Ggt1-Cre; Trp53LoxP/LoxP; PtenLoxP/LoxP; YFPLoxP/LoxP (GPPY) mouse model, which resulted in the formation of dysplastic lesions involving kidney tubular epithelial cells (TEC), with only approximately 25% of mice developing RCC at an advanced age. Combining CRISPR/Cas9-mediated Vhl knockout in these mice increased the frequency of dysplasia, but failed to increase the incidence of RCC. Assessments of whether ischemic injury of TECs in the GPPY kidney without Vhl knockout influences the emergence of RCC revealed that advanced RCC predominantly emerged in the contralateral, noninjured kidney with 100% penetrance at a younger age, but rarely in the injured kidney due to severely damaged ischemic TEC. Injured TEC released CXCL1 into the microenvironment that traveled systemically to activate fibroblasts and recruit neutrophils to enable emergence of RCC in the contralateral kidney. Fibroblasts responded to CXCL1 via CXCR2 and recruited tumor-associated neutrophils, which in turn mediated tumor-promoting inflammation and angiogenesis. Treatment with anti-CXCR2 antibodies abolished the emergence of malignant RCC. Collectively, these results demonstrate a defining functional role of systemic inflammation and microenvironment in the emergence of malignant cancer from preestablished dysplastic precursor lesions.

Significance:

These results identify a role for CXCL1/CXCR2 and the tumor microenvironment in the development of RCC.
Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C–Mutant Non–Small Cell Lung Cancer
Authors: Arbour Kathryn C. , Rizvi Hira , Plodkowski Andrew J. , Hellmann Matthew D. , Knezevic Andrea , Heller Glenn , Yu Helena A. , Ladanyi Marc , Kris Mark G. , Arcila Maria E. , Rudin Charles M. , Lito Piro , Riely Gregory J.
Published: February 2021

Purpose:

KRAS mutations are identified in approximately 30% of patients with non–small cell lung cancer (NSCLC). Novel direct inhibitors of KRAS G12C have shown activity in early-phase clinical trials. We hypothesized that patients with KRAS G12C mutations may have distinct clinical characteristics and responses to therapies.

Experimental Design:

Through routine next-generation sequencing, we identified patients with KRAS-mutant NSCLC treated at Memorial Sloan Kettering Cancer Center (New York, NY) from 2014 to 2018 and reviewed tumor characteristics, overall survival, and treatment outcomes.

Results:

We identified 1,194 patients with KRAS-mutant NSCLC, including 770 with recurrent or metastatic disease. KRAS G12C mutations were present in 46% and KRAS non-G12C mutations in 54%. Patients with KRAS G12C had a higher tumor mutation burden (median, 8.8 vs. 7 mut/Mb; P = 0.006) and higher median PD-L1 expression (5% vs. 1%). The comutation patterns of STK11 (28% vs. 29%) and KEAP1 (23% vs. 24%) were similar. The median overall survivals from diagnosis were similar for KRAS G12C (13.4 months) and KRAS non-G12C mutations (13.1 months; P = 0.96). In patients with PD-L1 ≥50%, there was not a significant difference in response rate with single-agent immune checkpoint inhibitor for patients with KRAS G12C mutations (40% vs. 58%; P = 0.07).

Conclusions:

We provide outcome data for a large series of patients with KRAS G12C–mutant NSCLC with available therapies, demonstrating that responses and duration of benefit with available therapies are similar to those seen in patients with KRAS non-G12C mutations. Strategies to incorporate new targeted therapies into the current treatment paradigm will need to consider outcomes specific to patients harboring KRAS G12C mutations.
Diffuse Glioma Heterogeneity and Its Therapeutic Implications
Authors: Nicholson James G. , Fine Howard A.
Published: February 2021

Diffuse gliomas represent a heterogeneous group of universally lethal brain tumors characterized by minimally effective genotype-targeted therapies. Recent advances have revealed that a remarkable level of genetic, epigenetic, and environmental heterogeneity exists within each individual glioma. Together, these interconnected layers of intratumoral heterogeneity result in extreme phenotypic heterogeneity at the cellular level, providing for multiple mechanisms of therapeutic resistance and forming a highly adaptable and resilient disease. In this review, we discuss how glioma intratumoral heterogeneity and malignant cellular state plasticity drive resistance to existing therapies and look to a future in which these challenges may be overcome.

Significance:

Glioma intratumoral heterogeneity and malignant cell state plasticity represent formidable hurdles to the development of novel targeted therapies. However, the convergence of genotypically diverse glioma cells into a limited set of epigenetically encoded transcriptional cell states may present an opportunity for a novel therapeutic strategy we call “State Selective Lethality.” In this approach, cellular states (as opposed to genetic perturbations/mutations) are the subject of therapeutic targeting, and plasticity-mediated resistance is minimized through the design of cell state “trapping agents.”
An Optimized Extract, Named Self-Growth Colony, from Platelet-Rich Plasma Shows Robust Skin Rejuvenation and Anti-Ageing Properties: A Novel Technology in Development of Cosmetics
Authors: Chan Gallant Kar Lun , Guo Maggie Suisui , Dai Diana Kun , Lai Queenie Wing Sze , Fung Kelly Wing Chi , Zheng Brody Zhongyu , Wu Kevin Qiyun , Man Brian King Ki , Dong Tina Tingxia , Tsim Karl Wah Keung
Published: February 2021

Introduction: Inspired by application of platelet-rich plasma (PRP) in skin treatment during injuries, an extracting method was developed here to recover high amounts of cytokines and growth factors from PRP; this prepared extract was named as self-growth colony (SGC). Methods: In optimization of SGC preparation, various parameters were tested, for example, centrifugation force, freeze-thaw, sonication, and inclusion of calcium chelator. The amounts of cytokines and growth factors, including platelet factor 4, β-thromboglobulin, epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, were measured by ELISA assay. Results: By comparing to PRP, the prepared SGC contained a significant higher amount of measured growth factors. In addition, the degradation of growth factors within SGC during the storage was calibrated, which showed better stability as compared to that of PRP preparation. Having possible application in skin care, the optimized SGC was chemically standardized by using the enrichment of growth factors. Application of SGC in cultured keratinocytes stimulated the wound healing of injured cultures. In line to this notion, SGC was applied onto human skin, and thereafter the robust improvement of skin properties was revealed. Conclusions: The potential application of SGC in treating skin rejuvenation and ageing, as well as its elaborated application for medical purpose, that is, wound healing, was illustrated.
Comparison of Sampling Methods for International Normalized Ratio Monitoring in Haemodialysis Patients (INRHaemo Study)
Authors: Rajkumar Theepika , Wong Jeffrey , Harvey Michael , Weidersehn Lachlan , Surmon Laura , Makris Angela
Published: February 2021

Background: Haemorrhagic and thrombotic complications are common in dialysis patients on warfarin; thus, accurate international normalized ratio (INR) monitoring is critical. For expediency and patient comfort, blood sampling from the haemodialysis access or circuit is commonly performed. Point-of-care (POC) INR machines allow both peripheral vein preservation and rapid results, yet are not validated in the haemodialysis population. Methods: A prospective cohort study in haemodialysis patients taking warfarin was undertaken. Three paired samples were drawn over a single session: peripheral blood INR, POC INR, and dialysis INR. Agreement using Bland-Altman analysis and correlation coefficients between the peripheral blood INR, haemodialysis INR, and POC INR were calculated. Inappropriate dosing decisions based on haemodialysis or POC INR were quantified. Results: Amongst 34 patients, agreement between the dialysis INR and peripheral blood INR was high, with the haemodialysis INR differing from the peripheral INR by <±0.2, 85.2% of the time. Correlation between the 2 methods was high (r = 0.914; p < 0.001). POC INR differed from peripheral INR values by <±0.2, 67.6% of the time, with less agreement at higher INR values. Dosing decisions were incongruent between the dialysis and peripheral INR in 6%, whilst the POC and peripheral INR disagreed in 26%. Conclusions: There was good agreement and correlation between the peripheral blood, haemodialysis access/circuit, and POC INR values. POC INR was less reliable at higher values, and dosing decisions differed from the peripheral INR in a quarter of cases.
SINE-B1 Distribution and Chromosome Rearrangements in the South American Proechimys gr. goeldii (Echimyidae, Rodentia)
Authors: Araújo Naiara P. , Sena Radarane S. , Bonvicino Cibele R. , Kuhn Gustavo C.S. , Svartman Marta
Published: February 2021

Proechimys species are remarkable for their extensive chromosome rearrangements, representing a good model to understand genome evolution. Herein, we cytogenetically analyzed 3 different cytotypes of Proechimys gr. goeldii to assess their evolutionary relationship. We also mapped the transposable element SINE-B1 on the chromosomes of P. gr. goeldii in order to investigate its distribution among individuals and evaluate its possible contribution to karyotype remodeling in this species. SINE-B1 showed a dispersed distribution along chromosome arms and was also detected at the pericentromeric regions of some chromosomes, including pair 1 and the sex chromosomes, which are involved in chromosome rearrangements. In addition, we describe a new cytotype for P. gr. goeldii, reinforcing the significant role of gross chromosomal rearrangements during the evolution of the genus. The results of FISH with SINE-B1 suggest that this issue should be more deeply investigated for a better understanding of its role in the mechanisms involved in the wide variety of Proechimys karyotypes.
Longitudinal Reproducibility of CO2-Triggered BOLD MRI for the Hemodynamic Evaluation of Adult Patients with Moyamoya Angiopathy
Authors: Roder Constantin , Klose Uwe , Hurth Helene , Brendle Cornelia , Tatagiba Marcos , Ernemann Ulrike , Khan Nadia , Hauser Till-Karsten
Published: February 2021

Background and Purpose: Hemodynamic evaluation of moyamoya patients is crucial to decide the treatment strategy. Recently, CO2-triggered BOLD MRI has been shown to be a promising tool for the hemodynamic evaluation of moyamoya patients. However, the longitudinal reliability of this technique in follow-up examinations is unknown. This study aims to analyze longitudinal follow-up data of CO2-triggered BOLD MRI to prove the reliability of this technique for long-term control examinations in moyamoya patients. Methods: Longitudinal CO2 BOLD MRI follow-up examinations of moyamoya patients with and without surgical revascularization have been analyzed for all 6 vascular territories retrospectively. If revascularization was performed, any directly (by the disease or the bypass) or indirectly (due to change of collateral flow after revascularization) affected territory was excluded based on angiography findings (group 1). In patients without surgical revascularization between the MRI examinations, all territories were analyzed (group 2). Results: Eighteen moyamoya patients with 39 CO2 BOLD MRI examinations fulfilled the inclusion criteria. The median follow-up between the 2 examinations was 12 months (range 4–29 months). For 106 vascular territories analyzed in group 1, the intraclass correlation coefficient was 0.784, p < 0.001, and for group 2 (84 territories), it was 0.899, p < 0.001. Within the total follow-up duration of 140 patient months, none of the patients experienced a new stroke. Conclusions: CO2 BOLD MRI is a promising tool for mid- and long-term follow-up examinations of cerebral hemodynamics in moyamoya patients. Systematic prospective evaluation is required prior to making it a routine examination.
Repeat Vaginal Natural Orifice Transluminal Endoscopic Surgery: A First Feasibility Study
Authors: Nulens Katrien , Van Genechten Ilse , Baekelandt Jan
Published: February 2021

Objectives: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an emerging minimally invasive technique in benign gynaecologic surgery whereby surgical access to the peritoneal cavity is achieved through natural orifices, namely through a vaginal colpotomy. Experience in repeat vNOTES cases is limited and so far, repeat vNOTES cases have not been described in the literature. The purpose of this study was to demonstrate the feasibility of vNOTES hysterectomy in women with a history of previous vNOTES adnexal surgery. Design: We performed a retrospective cohort study of the first 11 repeat vNOTES cases in our centre. All vNOTES procedures, primary adnexal surgery as well as repeat vNOTES hysterectomy, were performed by one surgeon (J.B.). Materials, Setting, Methods: Between March 2016 and May 2020, 11 patients underwent a vNOTES hysterectomy after prior vNOTES adnexectomy or cystectomy in Imelda Hospital, Bonheiden, Belgium. Relevant patient characteristics and outcome data were collected after written informed consent. Results: Median age was 49 years (range 44–65) at the moment of the first vNOTES procedure. Two patients had one or more caesarean sections in history, and 2 women were nulliparous. Median interval between primary and repeat vNOTES procedure was 15 months (range 0.8–37 months). All patients underwent a vaginally assisted NOTES hysterectomy (VANH) as repeat vNOTES procedure. Performing a colpotomy and entering the peritoneal cavity after prior vNOTES was technically feasible in all cases. All VANHs were successfully performed. There were 3 minor complications after repeat vNOTES, of which one was anaesthesia-related. The 2 complications associated with the surgical procedure were both cystitis. In one of these 2 patients, there were high post-void residues, which were easily managed by bladder training. There were no conversions to laparoscopy or laparotomy, neither serious nor life-threatening complications. No ureteric, bladder, or intestinal injuries have occurred. Limitations: The retrospective design and small sample size are the main limitations of this study. Moreover, the follow-up period of the most recently operated patients was too short to draw conclusions on long-term outcomes, including sexual function. Conclusions: In all patients in this case series, vNOTES hysterectomy after prior vNOTES adnexal surgery was successfully performed. Large-scale prospective trials with long-term follow-up are needed to evaluate the safety and feasibility of multiple consecutive vNOTES procedures in 1 patient.
Incidence of Psoriasis in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Matched Cohort Study
Authors: Moon Jung Min , Lee Jin Yong , Koh Seong-Joon , Park Hyunsun , Kang Sungchan , Soh Hosim , Lee Hyun Jung , Im Jong Pil , Kim Joo Sung
Published: February 2021

Background: Emerging data suggest that inflammatory bowel disease (IBD) and psoriasis are associated, sharing common genetic predispositions and immunological mechanisms. However, concrete data on psoriasis risk in IBD patients compared to the general population are limited. Objective: We investigated the risk of developing psoriasis in IBD patients compared to controls without IBD. Methods: Using the Korean National Health Insurance Database, patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) between 2005 and 2008 were age- and sex-matched 1:4 to non-IBD subjects from 2003 to 2018. IBD patients were defined by combining the International Classification of Diseases 10th revision code and at least one prescription of IBD-specific medications. Disease phenotypes, including psoriasis severity and psoriatic arthritis, were also identified. We investigated newly diagnosed psoriasis from 2009 to 2018. Incidence rates and risk of psoriasis were assessed with multivariate Cox regression models. Subgroup analyses for age and sex, and sensitivity analysis involving tumor necrosis factor (TNF) inhibitor-naïve patients were performed. Results: During nearly a decade of follow-up, 20,152 IBD patients were identified (14,619 [72.54%] UC and 5,533 [27.46%] CD). Among them, 439 patients were newly diagnosed with psoriasis (incidence rate of 217.68 per 100,000 person-years and 228.62 per 100,000 person-years for UC and CD, respectively). The psoriasis risk was higher in IBD patients than in the matched controls (adjusted hazard ratio, aHR, 2.95, 95% confidence interval, CI, 2.60–3.33). Moreover, IBD patients aged <30 years were at an increased risk (aHR 3.35, 95% CI 2.58–4.35), a trend that was unchanged across all psoriasis phenotypes. Sensitivity analysis of TNF inhibitor-naïve patients revealed consistent results. Conclusions: IBD patients were more likely to develop psoriasis compared to non-IBD subjects, including younger patients at an elevated risk regardless of TNF inhibitor use. This advocates the interplay between IBD and psoriasis; thus, inspection of cutaneous manifestation and dermatological consultation may be helpful in IBD patients at risk.
Galantamine-Memantine Combination and Kynurenine Pathway Enzyme Inhibitors in the Treatment of Neuropsychiatric Disorders
Authors: Bai Michael Y. , Lovejoy David B. , Guillemin Gilles J. , Kozak Rouba , Stone Trevor W. , Koola Maju Mathew
Published: February 2021

The kynurenine pathway (KP) is a major route for L-tryptophan (L-TRP) metabolism, yielding a variety of bioactive compounds including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and picolinic acid (PIC). These tryptophan catabolites are involved in the pathogenesis of many neuropsychiatric disorders, particularly when the KP becomes dysregulated. Accordingly, the enzymes that regulate the KP such as indoleamine 2,3-dioxygenase (IDO)/tryptophan 2,3-dioxygenase, kynurenine aminotransferases (KATs), and kynurenine 3-monooxygenase (KMO) represent potential drug targets as enzymatic inhibition can favorably rebalance KP metabolite concentrations. In addition, the galantamine-memantine combination, through its modulatory effects at the alpha7 nicotinic acetylcholine receptors and N-methyl-D-aspartate receptors, may counteract the effects of KYNA. The aim of this review is to highlight the effectiveness of IDO-1, KAT II, and KMO inhibitors, as well as the galantamine-memantine combination in the modulation of different KP metabolites. KAT II inhibitors are capable of decreasing the KYNA levels in the rat brain by a maximum of 80%. KMO inhibitors effectively reduce the central nervous system (CNS) levels of 3-HK, while markedly boosting the brain concentration of KYNA. Emerging data suggest that the galantamine-memantine combination also lowers L-TRP, kynurenine, KYNA, and PIC levels in humans. Presently, there are only 2 pathophysiological mechanisms (cholinergic and glutamatergic) that are FDA approved for the treatment of cognitive dysfunction for which purpose the galantamine-memantine combination has been designed for clinical use against Alzheimer’s disease. The alpha7 nicotinic-NMDA hypothesis targeted by the galantamine-memantine combination has been implicated in the pathophysiology of various CNS diseases. Similarly, KYNA is well capable of modulating the neuropathophysiology of these disorders. This is known as the KYNA-centric hypothesis, which may be implicated in the management of certain neuropsychiatric conditions. In line with this hypothesis, KYNA may be considered as the “conductor of the orchestra” for the major pathophysiological mechanisms underlying CNS disorders. Therefore, there is great opportunity to further explore and compare the biological effects of these therapeutic modalities in animal models with a special focus on their effects on KP metabolites in the CNS and with the ultimate goal of progressing to clinical trials for many neuropsychiatric diseases.
Insumo e autoria na produção de material didático de italiano como língua de herança
Authors: Mattos Tatiana Iegoroff de , Ortale Fernanda Landucci , Fornasier Rosângela Maria Laurindo , Corrias Vinicio
Published: February 2021

Neste artigo relatamos o processo de produção de um material didático para o ensino de italiano como língua de herança que está sendo desenvolvido na comunidade de Pedrinhas Paulista, localizada no interior de São Paulo. Para isso, explicitamos as etapas de produção deste material e a configuração básica das unidades didáticas, dando uma dimensão de suas especificidades. Em seguida, levantamos algumas questões relativas aos insumos que têm sido utilizados na sua composição e o que precisa ser feito para garantir os seus direitos autorais. Em virtude disso, apresentamos os tipos de licenças que protegem os conteúdos que encontramos, principalmente daqueles retirados da internet. Nesta trajetória recorremos a autores que estudaram a produção de materiais didáticos, o ensino de italiano como língua de herança, e os insumos autênticos e suas precedências.