bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid and Automatic Detection of Micronuclei in Binucleated lymphocytes Image
Authors: Shen Xiang , Chen Ying , Li Chaowen , Yang Fucheng , Wen Zhanbo , Zheng Jinlin , Zhou Zhenggan
Published: July 2021

In terms of radiation biological dose estimation, the cytokinesis block micronucleus (CBMN) assay is the internationally recognized dose estimation method. Due to the subjectivity and the time-consuming of manual detection, it cannot meet the needs of rapid standard assay of CBMN. Therefore, in this research work, we combined the convolutional neural network to design a software that can be used for rapid standard automatic detection of micronuclei in Giemsa stained binucleated lymphocytes image. The software analysis workflow is divided into four stages: cell acquisition, adhesive cell masses segmentation, cell type identification, micronucleus counting. After verification, our algorithm can quickly and effectively detect binucleated cells and micronucleus even when the cytoplasm is blurred, multiple micronucleus are attached to each other, or micronucleus is attached to the nucleus. In the test of a large number of random images, the software reached 99.4% of the manual detection in terms of the detection rate of binucleated cell, and the false positive rate of binucleated cell was 14.7%. In terms of micronucleus detection rate, the software reached 115.1% of manual detection, and its false positive rate was 26.2%. The analysis time of each picture is about 0.3s, an order of magnitude faster than conventional method.
Evaluation of Different Machine Learning Models and Novel Deep Learning-based Algorithm for Landslide Susceptibility Mapping
Authors: Zhang Tingyu , Wang Huanyuan , Chen Tianqing , Sun Zenghui , Wang Tao , Luo Dan , Li Chao , Li Yanan , Han Ling
Published: July 2021

The losses and damage caused by landslides are countless in the world every year. However, the existing approaches of landslide susceptibility mapping cannot fully meet the requirement of landslide prevention, and further excavation and innovation are also needed. Therefore, the main aim of this study is to develop a novel deep learning model namely landslide net (LSNet) to assess the landslide susceptibility in Hanyin County, China, meanwhile, support vector machine model (SVM) and kernel logistic regression model (KLR) were employed as reference model. The inventory map was generated based on 259 landslides, the training dataset and validation dataset were respectively prepared using 70% landslides and the remaining 30% landslides. The variance inflation factor (VIF) was applied to optimize each landslide predisposing factor. Three benchmark indices were used to evaluate the result of susceptibility mapping and area under receiver operating characteristics curve (AUROC) was used to compare the models. Result demonstrated that although the processing speed of LSNet model is the slowest, it still significantly outperformed its corresponding benchmark models with validation dataset, and has the highest accuracy (0.950), precision (0.951), F1 (0.951) and AUROC (0.941), which reflected excellent predictive ability in some degree. The achievements obtained in this study can improve the rapid response capability of landslide prevention for Hanyin County.
Impact of COVID-19 on Head and Neck Cancer Advancement Measured by the Increasing Numbers of Acute Dyspnea Cases. What Can be Improved for the Future?
Authors: Rosiak Oskar , Pietruszewska Wioletta , Burduk Paweł , Podlawska Paulina , Zakrzewski Bartosz , Barańska Magda , Kowalczyk Magdalena , Piątkowski Jakub , Solarz Paweł , Staszak Marta , Wierzbicka Małgorzata , Mikaszewski Bogusław
Published: July 2021

Background. The COVID-19 pandemic has altered all aspects of how the healthcare system is organized, and impacted patients with head and neck cancer (HNC), who delayed diagnosis and treatment. The result was the increased admission of patients with severe dyspnea and a need for tracheotomy due to extremely advanced HNC. The aim of this study wasevaluate the characteristics of two multi-center cohorts of HNC patients admitted for dyspnea.Methods..The therapeutic activity of four University Departments of Otolaryngology was studied over two time periods: September-February 2019/2020 and 2020/2021.Results. A group of 136 HNC patients who underwent tracheotomy in two time cohorts, pre-COVID-19 (N=59) and COVID-19 (N=77), were analyzed. The mean tracheotomy incidence proportion was 1.82% (SD: 1.12) for the pre-COVID-19 and 3.79% (SD: 2.76) for the COVID-19 period. A rise in emergency dyspnea was observed in the COVID-19 cohort. In the pre-COVID-19 period, 66% of patients presented with symptoms for more than a month in comparison to 78% of patients in COVID-19 times (p=0.04). The number of tracheotomies performed under general anesthesia dropped in favor of local anesthesia during COVID-19 (64% vs. 56% respectively) due to extremely advanced HNC. In the COVID-19 cohort, most patients received a telemedicine consultation (N=55, 71%) compared to the pre-COVID-19 period (N=14, 24%).Conclusions. There should be a reorganization of the referral system, an adjustment of treatment capacity for an increased number of HNC patients, and a reserve for more extensive resection and reconstruction surgeries in ENT departmentsto not hamper future HNC treatment if there is another pandemic wave.
Explainable multi-view framework for dissecting intercellular signaling from highly multiplexed spatial data
Authors: Tanevski Jovan , Gabor Attila , Flores Ricardo Ramirez , Schapiro Denis , Saez-Rodriguez Julio
Published: July 2021

The advancement of technologies to measure highly multiplexed spatial data requires the development of scalable methods that can leverage the spatial information. We present MISTy, a flexible, scalable and explainable machine learning framework for extracting interactions from any spatial omics data. MISTy builds multiple views focusing on different spatial or functional contexts to dissect different effects, such as those from direct neighbours versus those from distant cells. MISTy can be applied to different spatially resolved omics data with dozens to thousands of markers, without the need to perform cell-type annotation. We evaluate the performance of MISTy on an in silico dataset and demonstrate its applicability on three breast cancer datasets, two measured by imaging mass cytometry and one by Visium spatial transcriptomics. We show how we can estimate interactions coming from different spatial contexts that we can relate to tumor progression and clinical features. Our analysis also reveals that the estimated interactions in triple negative breast cancer are associated with clinical outcomes which could improve patient stratification. Finally, we demonstrate the flexibility of MISTy to integrate different kinds of views by modeling activities of pathways estimated from gene expression in a spatial context to analyse intercellular signaling.
Geographical Clustering Analysis of Birth Defects in Guangxi
Authors: Peng Zhenren , Wei Jie , Qin Jie , Chen Biyan , Huang Xiuning , Song Pengshu , Liang Lifang , Qiu Xiaoxia , Liang Junrong , Wei Hongwei , He Sheng
Published: July 2021

Birth defects (BD) is a big public health issue in Guangxi Zhuang Autonomous Region of China. The overall prevalence of BD in Guangxi is about 1% and higher than most other provinces of China. However, the geographical clustering variations in BD of Guangxi has not been described. Therefore, the aim of this study was to explore and detect the spatial clustering patterns of BD prevalence across a well-defined geographic space. The data were obtained from Guangxi birth defects monitoring network (GXBDMN) from 2016 to 2020, which collected socio-demographic and clinical information from perinatal infants between 28 weeks of gestation and 7 days postnatal. The spatial autocorrelation analysis and hot spot analysis will be used to explore the geographical clustering of BD prevalence in 70 counties and 41 districts of Guangxi in this study. A total of 44,418 perinatal infants were born with BD from 2016 to 2020. The overall prevalence of BD was 122.47/10,000 [95% confidence interval (CI): 121.34-123.60/10,000]. The local indicators of spatial association (LISA) statistic and Gi* statistic showed that the spatial clustering patterns of BD prevalence changed over time, and the largest High-High clustering area and hot spot area were both identified in the city of Nanning. Therefore, the spatial clustering patterns of BD prevalence in Guangxi is very significant. Spatial cluster analysis can provide reliable and accurate spatial distribution patterns in BD control and prevention.
Designing And Simulation Analysis Of A Rocket In Ansys
Authors: Asthana Yashraj
Published: July 2021

In this era of science, man is not limited to the earth, instead, is touching the soil of other planets too. Science has made it possible for humans to reach anywhere anytime by any means. One of the greatest inventions is Transportation. This transportation is not only limited to earth but is possible in the Space also. There are Space Vehicles or space crafts indulged in these operations. Energy is needed to operate them. The amount of this energy can be varied depending upon the structure of the vehicle and the forces opposing its movement. So, analysis is important to justify its structure and to calculate the forces exerted on it. Thus, this research includes analysis of a Rocket in Ansys software and determination of drag force acting on it and average pressure acting on it due to the environmental factors. Subjected to these factors we will design and manufactured the required Rocket for our mission.
The World’s Deadliest Outbreak During the COVID-19 Pandemic: A Proposed Analytical Approach to Estimate Excess Mortality in Ecuador During the First Year of the Pandemic.
Authors: Fernandez-Naranjo Raul Patricio , Vasconez Eduardo , Simbaña-Rivera Katherine , Lister Alex , Landazuri Samanta , Ortiz-Prado Esteban
Published: July 2021

Background: Latin America is the most affected region by the COVID-19 pandemic in terms of excessive mortality. Diagnostic and health care capabilities are limited in this region, deficiencies resulting in poor contact tracing, insufficient medical treatment and an unprecedented number of deaths. One of the key issues to estimate the pandemic's actual impact is to track deaths as one of the most reliable indicators when SARS-CoV-2 under-diagnosis is evident.Objective: This study's objective was to estimate the number of deaths attributed to COVID-19 based on excess mortality data in Ecuador.Methodology: An ecological study of all-cause mortality recorded in Ecuador during the year 2020. In order to calculate the total excess death relative to the historical average for the same dates in 2017, 2018 and 2019, a Poisson fitting analysis was used to identify trends on officially recorded all-caused deaths and those attributed to COVID-19. A bootstrapping technique based on central tendency measures was used to emulate the sampling distribution of our expected deaths estimator μdeaths by simulating the data generation and model fitting processes.Results: In Ecuador, during the first year of the pandemic, at least 115,070 deaths were recorded. At least 42,453 of those were catalogued as excessive mortality when comparing with the last 3-years average (2017-2019). Ecuador is the country with the highest recorded excess mortality in the world with 6 / 100,000 deaths per capita in one single day while Peru had 2 / 100,000. This value represents an additional 408% of the expected fatalities. The province with the highest number of excess deaths was Santa Elena on Ecuador's coast, with more than 154% increment versus previous years.Conclusions: Adjusting for population size and time, the hardest-hit country due to the COVID-19 pandemic was Ecuador. The mortality excess rate shows that the SARS-CoV-2 virus spread rapidly in the country, especially in the coastal province of Santa Elena and Guayas. Our results and the new proposed methodology could help to address the actual death toll situation during the early phase of the pandemic in Ecuador.
Head-to-Head Comparison of [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-617 in Dynamic PET/CT Evaluation of the Same Group of Recurrent Prostate Cancer Patients
Authors: Wang Guochang , Hong Haiyan , Zang Jie , Liu Qingxing , Jiang Yuanyuan , Fan Xinrong , Zhu Zhaohui , Zhu Lin , Kung Hank F.
Published: July 2021

Purpose: This study was prospectively designed to evaluate the early dynamic organ distribution and tumor detection ability of [68Ga]Ga-P16-093, which was compared with [68Ga]Ga-PSMA-617 in the same group of recurrent prostate cancer patients.Methods: Twenty patients with recurrent prostate cancer were enrolled. In two consecutive days, each patient underwent a 60-min dynamic PET/CT scan after intravenous administration of 148–185 MBq (4–5 mCi) [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-617, respectively. Following a low-dose CT scan, serial dynamic PET scans were performed from head to proximate thigh at 9 time points (30 sec/bed at 4, 7, 10, 13 and 16 min, 1 min/bed at 20, 30 and 45 min, and 2 min/bed at 60 min). Standardized uptake values were measured for semi-quantitative comparison.Results: [68Ga]Ga-P16-093 PET/CT revealed a significantly higher tumor uptake at 4 min (SUVmax 7.88 ± 5.26 vs. 6.01 ± 3.88, P < 0.001), less blood pool retention at 4 min (SUVmean 5.12 ± 1.16 vs. 6.14 ± 0.98, P < 0.001) and lower bladder accumulation at 60 min (SUVmean 31.33 ± 27.47 vs. 48.74 ± 34.01, P = 0.042) than [68Ga]Ga-PSMA-617 scan. Significantly higher [68Ga]Ga-P16-093 uptakes were also observed in the parotid gland, liver, spleen and kidney. Besides, [68Ga]Ga-P16-093 exhibited a better detection ability than [68Ga]Ga-PSMA-617 (366 vs. 321, P = 0.009).Conclusions: [68Ga]Ga-P16-093 showed advantages over [68Ga]Ga-PSMA-617 with higher tumor uptakes, tumor-to-blood pool ratio and detection ability, less blood pool and bladder accumulation in recurrent prostate cancer patients.Trial registration [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-617 PET/CT Imaging in the Same Group of Prostate Cancer Patients (NCT04796467, Registered 12 March 2021, retrospectively registered)URL of registry https://clinicaltrials.gov/ct2/show/NCT04796467
DMAG, a Novel Countermeasure for the Treatment of Thrombocytopenia
Authors: Lin Jing , Zeng Jing , Liu Sha , Shen Xin , Jiang Nan , Wu Yue-Song , Li Hong , Wang Long , Wu Jianming
Published: July 2021

Background: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods: In this study, giemsa staining, phalloidin staining and flow cytometry were firstly used to identify the effects of 3,3'-Di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Next, network pharmacology approachs were carried out to identify the targets of DMAG. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrich-ment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, Molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets.Results: DMAG significantly promoted megakaryocyte differentiation and maturation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF and PLEK. Conclusion: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.
Beyond “Sex Prediction”: Estimating and Interpreting Multivariate Sex Differences and Similarities in the Brain
Authors: Sanchis-Segura Carla , Aguirre Naiara , Cruz-Gómez Álvaro Javier , Félix Sonia , Forn Cristina
Published: July 2021

Previous studies have shown that machine-learning (ML) algorithms can “predict” sex based on brain anatomical/ functional features. The high classification accuracy achieved by ML algorithms is often interpreted as revealing large differences between the brains of males and females and as confirming the existence of “male/female brains”. However, classification and estimation are quite different concepts, and using classification metrics as surrogate estimates of between-group differences results in major statistical and interpretative distortions. The present study illustrates these distortions and provides a novel and detailed assessment of multivariate sex differences in gray matter volume (GMVOL) that does not rely on classification metrics. Moreover, modeling and clustering techniques and analyses of similarities (ANOSIM) were used to identify the brain areas that contribute the most to these multivariate differences, and to empirically assess whether they assemble into two sex-typical profiles. Results revealed that multivariate sex differences in GMVOL: 1) are “large” if not adjusted for total intracranial volume (TIV) variation, but “small” when controlling for this variable; 2) differ in size between individuals and also depends on the ML algorithm used for their calculation 3) do not stem from two sex-typical profiles, and so describing them in terms of “male/female brains” is misleading.
Uncovering Early Events in Primary Epstein-Barr Virus Infection Using a Rabbit Model
Authors: Reguraman Narendran , Hassani Asma , Philip Pretty , Khan Prof Gulfaraz
Published: July 2021

Epstein-Barr virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of several malignant and non-malignant conditions. However, a number of fundamental aspects of the biology of EBV and the mechanism(s) by which this virus induces pathology remain unknown. One major obstacle has been the lack of a suitable animal model for EBV infection. In this study, using our recently established rabbit model of EBV infection, we examined the early events following primary EBV infection. We show that, both immunocompetent and immunosuppressed animals were readily susceptible to EBV infection. However, immunosuppressed animals showed marked splenomegaly and widespread infection. Following EBV infection, the virus primarily targeted naïve IgM+, CD20+, CD21+ and CD79a+ B cells. Infected cells expressed varying sets of viral latent/lytic gene products. Notably, co-expression of latent and lytic proteins was not observed. Infected cells in type 0/1 latency (EBER+), were small and proliferating (Ki67+). By contrast, cells in type 2/3 latency (LMP1+), were large, non-proliferating (Ki-67−) and p53+. Although infected B-cells were widely present in splenic follicles, they did not express germinal center marker, BCL-6. Taken together, this study shows for the first time, some of the early events following primary EBV infection in an animal model.
Standardized sampling applied for VOCs emitted by feces using a Micro-Chamber/Thermal Extractor (µ-CTE)
Authors: Ratiu Ileana Andreea , Mametov Radik , Ligor Tomasz , Buszewski Bogusław
Published: July 2021

VOCs (volatile organic compounds) are increasingly wished to be used in diagnosis of diseases. They present strategic advantages, beside classical methods used, such as simplicity and non-invasively of performant sample collection methods/ systems available our days. However, standardized sampling methods are required in order to achieve reproducible results. In the current study we developed a method to be used for feces sampling using a Micro-Chamber/Thermal Extractor (µ-CTE). Design Expert software (with Box–Behnken design) was used to predict the solutions. Therefore by using the simulation experimental plan that was further experimentally verified, a sampling time of 19.6 min, at a sampling temperature of 30.6 °C by using a flow rate of 48.7 mL/min provided the higher response. The developed method was validated by using correlation tests and Network analysis, that both proved the validity of the developed model.
Analysis on Variation and Potential Source Regions of Greenhouse Gases Concentrations at Akedala Station, China
Authors: Zhao Zhujun , He Qing , Zhao Quanwei , Li Hanlin , Lu Zhongqi , Wang Jianlin
Published: July 2021

The research on the variation of greenhouse gases concentrations in typical regions is one of the significant tasks to cope with climate change. Especially at present, the number of extreme weather events is gradually increasing and the trend of global warming is becoming increasingly obvious, the study on variation of greenhouse gases concentrations and their potential source regions can contribute to a scientific formulation of policies regarding greenhouse gas emission reduction as well as to the coordinated development of human and environment. Based on the data of greenhouse gases of Akedala Station from 2009 to 2019, this research studies characteristics of the time series and seasonal trends of greenhouse gases at this station and testes whether abrupt change exists by applying the linear trend analysis method, the contrastive and statistical analysis method and Mann-Kendall method. In addition, Pearson Correlation Coefficient is used to determine the correlation and homology among the four greenhouse gases and backward trajectories model is also used to explore the potential source regions of greenhouse gases at Akedala Station in different seasons. The greenhouse gases concentrations at Akedala Station show a trend of year-on-year growth, with CO2 concentrations ranging from 389.80×10− 6 to 408.79×10− 6 (molar fraction of substances, same below), CH4 concentrations ranging from1890.07×10− 9 to 1976.32×10− 9, N20 concentrations ranging from 321.26×10− 9 to 332.03×10− 9, and SF6 concentrations ranging from 7.04×10− 12 to 10.07×10− 12, the growth rate of which is similar to the decadal average growth rate in the northern hemisphere. There exist obvious seasonal variations, with CO2 concentrations showing high in winter and low in summer and CH4 showing a distinct “W”- shaped trend while N20 and SF6 showing little difference between the four seasons. A relatively strong correlation and homology exist among the four greenhouse gases except in summer, and the analysis based on backward trajectories model shows that the Akedala Station is influenced by the airflow from northwest or southwest throughout the year. Besides, the concentrations of greenhouse gas are closely related to source region of the emissions, biological and non-biological sources, monsoon, and atmospheric photochemical processes.
Two Case Reports of Chorea-acanthocytosis and Review of Literature
Authors: Huang Shuangfeng , Zhang Junliang , Tao Manli , Lv Yaodong , Xu Luyao , Liang Zhigang
Published: July 2021

Background: Chorea-acanthocytosis (ChAc), as the most common subtype of neuroacanthocytosis syndrome, is characterized by the presence of acanthocytes and neurological symptoms. It is thought to be caused by the VPS13A (vacuolar protein sorting-associated protein 13A) mutations. This article reports two confirmed cases of ChAc and summarizes some suggestive features, which provide direction for the diagnosis and treatment of acanthocytosis in the future.Case presentation: Here, we present two cases of ChAc diagnosed based on typical clinical symptoms, neuroimaging features, genetic findings of VPS13A, and response to the symptomatic treatment. Conclusions: Chorea-acanthocytosis is a rare neurodegenerative disease with various early clinical manifestations. The final diagnosis of the ChAc can be established by either genetic analysis or protein expression by Western blotting. Supportive treatments and nursing are helpful to improve the quality of the patient’s life. Nevertheless, it is imperative to investigate the impact of neuroimaging and neuropathological diagnosis in a larger group of ChAc in future studies.
Construction and Validation of a Nomogram for Non-small Cell Lung Cancer Patients with Liver Metastases: A Population-Based Analysis
Authors: Zhao Ruhan , Dai Yunnan , Li Xinyang , Zhu Cuimin
Published: July 2021

Background: Lung cancer is one of the most common malignancies in the United States, and the common metastatic sites in advanced non-small cell lung cancer (NSCLC) are bone, brain, adrenal gland, and liver, respectively, among which patients with liver metastases have the worst prognosis.Methods: We retrospectively analyzed 1963 patients diagnosed with NSCLC combined with liver metastases between 2010 and 2015. Independent prognostic factors for patients with liver metastases from NSCLC were identified by univariate and multivariate Cox regression analysis. Based on this, we developed a nomogram model via R software and evaluated the performance and clinical utility of the model by calibration curve, receiver operating characteristic curves, and decision curve analysis (DCA).Result: The independent prognostic factors for NSCLC patients with liver metastases included age, race, gender, grade, T stage, N stage, brain metastases, bone metastases, surgery, chemotherapy, and tumor size. The area under the curve predicting OS at 6, 9, and 12 months was 0.793, 0.787, and 0.784 in the training cohort, and 0.767, 0.771, and 0.773 in the validation cohort, respectively. Calibration curves of the nomogram showed high agreement between the outcomes predicted by the nomogram and the actual observed outcomes, and the DCA further demonstrated the value of the clinical application of the nomogram.Conclusion: By analyzing the Surveillance, Epidemiology, and End Results database, we established and verified a prognostic nomogram for NSCLC patients with liver metastases, to personalize the prognosis of patients. At the same time, the prognostic nomogram has a satisfactory accuracy and the results are a guide for the development of patient treatment plans.
Purification of Native Histidine-Rich Protein 2 (Nhrp2) from Plasmodium Falciparum Culture Supernatant, Infected Rbcs, and Parasite Lysate
Authors: Singh Balwan , McCaffery Jessica N , Kong Amy , Ah Yong , Wilson Scott , Chatterjee Sayan , Tomar Deepak , Aidoo Michael , Udhayakumar Venkatachalam , Rogier Eric
Published: July 2021

Background: Despite the widespread use of histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs), purified native HRP2 antigen is not standardly used in research applications or assessment of RDTs used in the field.Methods: This report describes purification of native HRP2 (nHRP2) from the HB3 P. falciparum culture strain. As this culture strain lacks pfhrp3 from its genome, it is an excellent source of HRP2 protein only, and does not produce the closely-related HRP3. The nHRP2 protein was isolated from culture supernatant, infected red blood cells (iRBCs), and whole parasite lysate using nickel-metal chelate chromatography. Biochemical characterization of nHRP2 from HB3 culture was conducted by SDS-PAGE and western blotting, and nHRP2 was assayed by RDT, ELISA, and bead-based immunoassay.Results: Purified nHRP2 was identified by SDS-PAGE and western blot as a ~60 kDa protein that bound anti-HRP-2 monoclonal antibodies. Mouse anti-HRP2 monoclonal antibody was found to produce high optical density readings between dilutions of 1:100 and 1:3,200 by ELISA with assay signal observed up to a 1:200,000 dilution. nHRP2 yield from HB3 culture by bead-based immunoassay revealed that both culture supernatant and iRBC lysate were practical sources of large quantities of this antigen, producing a total yield of 292.4 µg of nHRP2 from two pooled culture preparations. Assessment of nHRP2 recognition by RDTs revealed that Carestart Pf HRP2 and HRP2/pLDH RDTs detected purified nHRP2 when applied at concentrations between 20.6 to 2060 ng/mL, performing within a log-fold dilution of commercially-available recombinant HRP2. The band intensity observed for the nHRP2 dilutions was equivalent to that observed for P. falciparum culture strain dilutions of 3D7 and US06 F Nigeria XII between 12.5 and 1,000 parasites/µl.Conclusions: Purified nHRP2 could be a valuable reagent for laboratory applications as well as assessment of new and existing RDTs prior to their use in clinical settings. These results establish that it is possible to extract microgram quantities of the native HRP2 antigen from HB3 culture and that this purified protein is well recognized by existing monoclonal antibody lines and RDTs.
A highly active repeating fast radio burst in a complex local environment
Authors: Li Di , Niu C.H. , Aggarwal Kshitij , Zhang Xian , Chatterjee Shami , Tsai Chao-Wei , Yu Wenfei , Law Casey , Burke-Spolaor Sarah , Cordes James , Zhang Yongkun , Ocker Stella , Yao Jumei , Wang P. , Feng Yi , Niino Yuu , Bochenek Christopher , Cruces Marilyn , Connor Liam , Jiang Ji-an , Dai Shi , Luo Rui , Li Guodong , Miao C.C. , Niu J.R. , Anna-Thomas Reshma , Stern Daniel , Wang Weiyang , Yuan Mao , Yue Youling , Zhou D.J. , Yan Zhen , Zhu Weiwei , Zhang Bing
Published: July 2021

The central engine of fast radio bursts (FRB) is not yet understood. Due to the interaction between the pulse and the intervening plasma, the dispersion sweep of FRBs provides a unique probe of its environment and the ionized baryon content of the intergalactic medium. Active repeaters has been shown to be associated with persistent radio source (PRS), and dense, energetic, magnetized plasmas. Here we report the discovery and localization of a new, extremely active repeater, FRB 190520, which is co-located with a compact PRS and identified with a dwarf host galaxy of high star formation at a redshift z=0.241. The estimated host galaxy contribution DMhost≈912+69−108pc cm−3 is nearly an order of magnitude higher than the average of FRB host galaxies and much larger than the contribution from the intergalactic medium, suggesting caution in inferring redshifts for FRBs without accurate host galaxy identifications. This represents the second source after FRB 121102 with confirmed association between FRB and compact PRS. The dense, complex host galaxy environment and the association with PRS may point to a distinctive origin or an earlier evolutionary stage for highly active repeating FRBs.
Current Status and Problems of Preoperative Assessment for Elderly Cancer Surgery Patients in Japan: A Nationwide Survey
Authors: Inoue Daisuke , Yamamoto Makoto , Arima Hisatomi , Tamura Kazuo , Yoshida Yoshio
Published: July 2021

Elderly cancer patients requiring surgical treatment are increasing, and the deterioration of quality of life and shortening of healthy life expectancy due to postoperative complications represent major problems. This study investigated the current status of medical treatment, including perioperative evaluations, for elderly cancer patients requiring surgical treatment at cancer treatment facilities nationwide. A total of 436 cancer care facilities around Japan were invited to participate in this web-based survey regarding management of cancer patients ≥65 years old who had undergone surgical treatment in 2018. A total of 919 department heads from 245 facilities agreed to participate. Although most respondents answered that performance status, preoperative examinations, and comorbidities were important when deciding on a treatment plan, age, Geriatric Assessment (GA), and guidelines were "not important" for >10% of all respondents. GA was familiar to 195 department heads (21%), and awareness of GA was significantly lower among respondents from medical education institutions than the other types of hospitals (18.5% vs 26.3%; P = 0.006). This large survey revealed that the use of GA is not widespread, and its awareness in medical education institutions remains low. We believe that accumulating evidence of geriatric oncology surgery is an urgent issue in Japan.
Both Intraoperative Medial and Lateral Soft Tissue Balances Influence Intraoperative Rotational Knee Kinematics in Bi-Cruciate Stabilized Total Knee Arthroplasty: A Retrospective Investigation.
Authors: Takagi Kentaro , Inui Hiroshi , Taketomi Shuji , Yamagami Ryota , Kono Kenichi , Kawaguchi Kohei , Sameshima Shin , Kage Tomofumi , Tanaka Sakae
Published: July 2021

BackgroundTibial internal rotation following total knee arthroplasty (TKA) is important in achieving favorable postoperative clinical outcomes. Studies have reported the effect of intraoperative soft tissue balance on tibial internal rotation in conventional TKA, however, its effect on bi-cruciate stabilized (BCS) TKA has not reported enough. Furthermore, although studies have shown that both medial and lateral soft tissue balances are important for a good tibial internal rotation, no studies have evaluated the effects of soft tissue balance at medial or lateral compartments separately on tibial internal rotation in BCS TKA. The purpose of this study was to clarify the relationship between medial or lateral component gaps and rotational knee kinematics in BCS TKA.MethodsOne hundred fifty-eight knees that underwent BCS TKA were included in this study. They were divided into two groups according to the medial or lateral joint laxities, which was defined as the value of component gap minus the selected thickness of the tibial component at 30°, 60°, and 90° flexion, respectively: Group M-stable (medial joint laxity, ≤2 mm) or Group M-loose (medial joint laxity, ≥3 mm) and Group L-stable (lateral joint laxity, ≤3 mm) or Group L-loose (lateral joint laxity, ≥4 mm). The intraoperative rotational knee kinematics was compared between Group M-stable and Group M-loose or between Group L-stable and Group L-loose at each angle, respectively.ResultsThe rotational angular difference between 30° flexion and maximum flexion was significantly larger in Group M-stable at 30° flexion than that in Group M-loose at 30° flexion. The rotational angular difference between 60° flexion and maximum flexion was significantly larger in Group L-loose at 60° flexion than that in Group L-stable at 60° flexion. The rotational angular difference between 60° flexion and maximum flexion was significantly larger in Group L-loose at 90° flexion than that in Group L-stable at 90° flexion.ConclusionSurgeons should pay attention to the importance of medial joint stability at midflexion and lateral joint laxities at midflexion and 90° flexion on a good tibial internal rotation from midflexion to deep flexion in BCS TKA.
The Emergence of Extended-Spectrum β-Lactamase Producing and Hybrid Pathotypes of Escherichia Coli Isolates from Diarrheic Human Cases: A New Public Health Concern in Iran
Authors: Asadi Zahra , Ghanbarpour Reza , Kalantar-Neyestanaki Davood , Alizade Hesam
Published: July 2021

Background: Intra-intestinal pathogenic strains of Escherichia coli are responsible for mild to severe gastrointestinal lesions, which are mediated by various virulence factors. In this study, we have focused on a comprehensive set of E. coli pathotypes, including STEC, EPEC, EHEC, ETEC, and some hybrid pathotypes including, STEC/ ETEC, EHEC/ ETEC, and EPEC/ ETEC.Methods: Totally, 467 stool samples were obtained from gastrointestinal patients during four years (2016 to 2020). Four pathotypes of E. coli (EPEC, ETEC, EHEC, STEC) were screened due to six virulence genes, including eae, stx1, stx2, st, and lt using the conventional PCR method. Finally, detected E. coli pathotypes were subjected to determine phenotypic and genotypic β-lactam resistance properties.Result: In this study 59/467 (12.63%) strains belonged four pathotypes including STEC (20/59; 50.8%), EPEC (11/59; 18.6%), ETEC (8/59 13.5%), EHEC (5/59; 8.4%) and three novel hybrid pathotypes including STEC/ETEC (3/59; 5%), EHEC/ETEC (1/59; 1.6%), and EPEC/ETEC (1/59; 1.6%). Totally 23/59 (38.9%) isolates were identified as ESBL-producing. Conclusion: Transmission of virulence and antibiotic resistance genes among E. coli strains lead to the emergence of antimicrobial-resistant hybrid pathogenic strains, which is an important health concern. According to food-born and fecal-oral transmission of these E. coli strains, standard methods should be performed to eliminate the possible contamination of food, equipment, and living environment to manure and feces.
SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19
Authors: Stanevich Oksana , Alekseeva Evgeniia , Sergeeva Maria , Fadeev Artem , Komissarova Kseniya , Ivanova Anna , Simakova Tamara , Vasilyev Kirill , Shurygina Anna-Polina , Stukova Marina , Safina Ksenia , Nabieva Elena , Garushyants Sofya , Klink Galya , Bakin Evgeny , Zabutova Jullia , Kholodnaia Anastasia , Lukina Olga , Skorokhod Irina , Ryabchikova Viktoria , Medvedeva Nadezhda , Lioznov Dmitry , Danilenko Daria , Chudakov Dmitriy , Komissarov Andrey , Bazykin Georgii
Published: July 2021

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties, but the mode of selection underlying this process remains unclear. While escape from humoral immunity certainly plays a role in intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin’s lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented binding of known immunogenic SARS-CoV-2 HLA class I antigens, suggesting that virus immunoediting is largely driven by cytotoxic CD8 T cell clones. The two changes with the strongest effect, nsp3:T504A and nsp3:T504P, were experimentally assessed in a cytotoxic assay of the patient's CD8 T cells. Both these changes were associated with immune escape, with a stronger effect observed for nsp3:T504P, the change which ultimately got fixed. Together, these results suggest that CD8 T cell escape may be an underappreciated contributor to SARS-CoV-2 evolution in humans.
Age Increased Cancer-specific Mortality Risk of Thyroid Cancer With Lung Metastasis
Authors: Huang Xiu , Xia Qing , Qu Shen , Peng Aimei , Yang Jie
Published: July 2021

Background: To investigate the relationship between age and cancer-specific mortality in thyroid cancer (TC) with lung-metastasis.Methods: 1,418 patients with initial distant metastases from Surveillance, Epidemiology and End Results databases were investigated. Patients with median follow-up time of 8 months [interquartile range (IQR), 2–27] and median age of 66 years (IQR, 55-76) were divided into five groups by age and the association between age and TC-specific mortality was analyzed.Results: The TC-specific mortality rates were 32.78% (118/360), 46.71% (156/334), 53.93% (199/369), 58.96% (158/268) and 82.76% (72/87) for patients with age of ≤55 years,56-65 years, 66-75 years, 76-85 years and >85 years. Kaplan-Meier curves showed that TC-specific mortality rate was associated with increased age (p < 0.001). Compared with patients ≤55 years, patients of 56-65 years, 66-75 years, 76-85 years and >85 years had significantly higher hazard ratios (HRs) of 1.69(1.26-2.26), 1.97 (1.47-2.64), 2.18(1.59-2.99) and 3.24(2.08-5.06) after adjustments for gender, tumor size and radiation therapy (all p < 0.001).In TC with initial lung-metastasis, compared with patients ≤55 years, patients of 56-65 years, 66-75 years, 76-85 years and >85 years had significantly higher adjusted HRs of 1.68(1.20-2.36, p=0.003), 2.18(1.57-3.02), 2.16(1.51-3.08) and 2.91(1.79-4.75) (p < 0.001). Similar results could be obtained in papillary thyroid cancer.Conclusions: The TC-specific mortality increased with age in TC patients with initial lung-metastasis, which suggested that further risk stratification based on age was necessary for TC over 55 years with lung-metastasis. Individual treatment strategy maybe recommended for patients over 85 years.
Lidocaine suppressed the movement of A549 cells by the CXCR4 signal
Authors: Cui Yanan
Published: July 2021

Background

Lidocaine is a local anesthetic that wildly used in surgical treatment and postoperative medical care for lung cancers. We hypothesized that lidocaine at clinical plasma concentration can inhibit CXCL12/CXCR4 axis-regulated cytoskeletal remodeling thereby reduce the migration of Non-small-cell lung cancers (NSCLC) cells.
Methods

We determined the effect of lidocaine at clinical plasma concentration on CXCL12-induced cell viability, apoptosis, cell death, monolayer cell wound healing rate, individual cell migration indicators, expression of CXCR4, CD44, and ICAM-1, intracellular Ca2+ level, and filamentous actin level alteration of NSCLC cells A549 and CXCR4-knocked down A549 cells using CCK-8, Bcl-2 ELISA, Cell death ELISA, wound healing assay, chemotaxis assay, western blotting, QPCR, Fura-2-based intracellular Ca2+ assay, and Fluorescein Phalloidin staining respectively.
Results

Lidocaine did not affect cell viability, apoptosis, and cell death but inhibited CXCL12-induced migration, intracellular Ca2+ releasing, and filamentous actin increase. Lidocaine decreased expression of CXCR4, increased CD44, but had no effect on ICAM-1. CXCL12 induced the increase of CD44 and ICAM-1 but did not affect CD44 in the presence of lidocaine. The knockdown of CXCR4 eliminated all the effects of lidocaine. The overexpression of CXCR4 promoted migration but the migration was inhibited by lidocaine.
Conclusion

Lidocaine at clinical plasma concentrations inhibited CXCL12-induced CXCR4 activation, thereby reduced the intracellular Ca2+-dependent cytoskeleton remodeling, resulting in slower migration of A549 cells.
Quantitation of Macropinocytosis in Glioblastoma Based on High-Content Analysis
Authors: Wang Bo , Yao Xuan , Dong Qiang , Wang Xiao-fang , Yin Hang , Li Qiao , Wang Xiao-qing , Liu Yang , Pan Ya-Wen , Yuan Guo-qiang
Published: July 2021

Background: Macropinocytosis serves as an internalization pathway for extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because manual acquisition in combination with visual evaluation of images is laborious, making it difficult for high-throughput applications. So, there is a need to develop sensitive and specific methods. Methods: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Meanwhile, cell proliferation was tested by means of CCK8. Results: The term “macropinosome index” was defined to estimate macropinocytosis and allow comparison between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote Glioblastoma (GBM) cells survival in glutamine deficient conditions which resemble tumor microenvironment. Conclusions: HCA represents a novel, non-subjective and high-throughput assay for macropinocytosis assessment. Besides, Gln deprivation increased the macropinosome index in GBM cells, which points to the possible exploitation of this process in the design of GBM therapies.
nPTD Classification: An Updated Classification of Gastric Cancer Location for Function Preserving Gastrectomy Based on Physiological Lymphatic Flow
Authors: Kinami Shinichi , Nakamura Naohiko , Miyashita Tomoharu , Kitakata Hidekazu , Fushida Sachio , Fujimura Takashi , Itoh Tohru , Takamura Hiroyuki
Published: July 2021

Background: The correlation between tumor location and lymphatic flow distribution in gastric cancer has been previously reported, and PTD (Proximal – Transitional – Distal) classification, proposed. We updated and developed the nPTD classification.Method: We retrospectively studied gastric cancer patients who underwent the dye method sentinel node biopsy from 1993 to 2020. The inclusion criteria were a single lesion type 0 cancer of ≤5 cm in the long axis, clinically node-negative, and invasion within the proper muscle layer pathologically. In this study, the distribution of dyed lymphatic flow was evaluated for each occupied area of the tumor.Results: We selected 416. The tumors located watershed of the right and left gastroepiploic artery near greater curvature had extensive lymphatic flow; therefore, a newly circular region with a diameter of 5 cm is set on the watershed on greater curvature between P and T zone as the ‘n’ zone. In addition, for cancers located in the lesser P curvature, lymphatic flow to the greater curvature was not observed. Therefore, the P zone is divided into two: the lesser curvature side (PL) and the greater curvature side (PG).Conclusions: The advantage of the nPTD classification is that it provides not only proper nodal dissection, but also adequate function-preserving gastrectomy. If the tumor is localized within the PL, the proximal gastrectomy resection area can be further reduced. In contrast, for cancers located in the ‘n’ zone, near-total gastrectomy is required because of the extensive lymphatic flow.
18F-FDG PET/CT findings in post COVID Multisystem inflammatory syndrome in adults (MIS-A)
Authors: MARAMATTOM BOBY VARKEY , Philips Geetha , Santhamma Shagos Gopalan Nair
Published: July 2021

We describe 18 fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET-CT) findings in a patient that inadvertently betrayed features of MIS-A. The findings were suggestive of an exaggerated Systemic inflammatory response syndrome (SIRS)- a prequel to MIS-A. MIS-A has been recently described in 2020 as a post-infectious or para-infectious sequela of COVID-19. Within 12 weeks of symptomatic or asymptomatic COVID-19 illness (diagnosed by serum SARS CoV2 antibodies), patients present with an illness requiring hospitalization that can rapidly progress to myocardial dysfunction and cardiogenic shock. (1) As with any illness, there is a period of ‘quiet before the storm’. Identification of patients early in the course of the illness and prompt treatment can improve clinical outcomes in MIS-A.
Anhydrous Topical Ointment for Management of Infected Wounds
Authors: Sanguramath Rajashekharayya A. , Laadan Boaz , Franco Ariel
Published: July 2021

Optimal prevention of microbial infection at the wound site is a priority clinical consideration required to facilitate normal healing process. Topical antimicrobials are commonly used for treatment and prevention of local wound infections. Herein, an anhydrous, hydrophilic, non-greasy, and non-occlusive antimicrobial ointment was formulated by incorporating two main active ingredients, CuO(1−x)ZnOx and (±)-α-bisabolol. CuO(1−x)ZnOx nanocomposite was added to provide a broad-spectrum antimicrobial activity through the release of reactive oxygen species. (±)-α-Bisbolol was added to expedite the wound healing process. Prepared ointment showed very high killing efficacy against a spectrum of bacteria ( ̴6Log reduction) and a pathogenic yeast ( ̴5Log reduction) within 2h of exposure. Results described here would be of great benefit to professionals as wells as for personal use in treating infected wounds.