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Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner Mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi katalin Bartyik Krisztina Míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss Miklós Garami István Peták Oncompass Medicine Hungary Kft Retek Str.34Budapest 1024Hungary Division of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary Department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(rithm for therapeutic decision ***,a molecular tumor board(MTB)evaluated the results to provide therapy *** Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the evidence *** approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

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Preservation of the Intercostobrachial Nerve during Axillary Dissection for Breast Cancer at the Surgical Oncology Unit of Cancer Department of Dakar University

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Advances in Breast Cancer Research 2022年第1期11卷 63-68页

作者： Sidy ka Michel Auguste Mouelle mohammed Ezzet Charfi Jaafar Thiam Souleymane Dieng Salif Balde Moustapha Dieng Ahmadou Dem Centre Hospitalier Universitaire Le Dantec Dakar Sénégal

The intercostobrachial nerve (ICBN) is responsible for the sensory innervation of a part of the inner side of the arm. Injury of the intercostobrachial nerve is a complication of axillary dissection during lymph node dissection. Objective: This study aimed to determine the effect of preservation of the intercostobrachial nerve on postoperative sensory disturbances. Methods: This is a prospective, single-center study which was carried out in 90 patients followed in the oncology department of the Aristide Le Dantec hospital in Dakar, suffering from breast cancer and having undergone breast surgery associated with axillary dissection, for a period of 6 months. The patients were divided into two groups depending on whether the intercostobrachial nerve (ICBN) was preserved or not. The two groups were compared in terms of the incidence of sensory disturbances. Results: Sixty patients without nerve preservation and 30 patients with nerve preservation were included in the study, i.e., 90 patients in total.

关键词： Axillary Dissection Intercostobrachial Nerve Pain Hypoesthesia

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Exposure of Mercury from Gold Ming Area: A Case Study in Tendo and Aby Lagoon in Côte d’Ivoire

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Journal of Environmental Protection 2022年第9期13卷 613-627页

作者： Stéphane Jean Claon Serge Kouakou Kouassi Séka Arsène M’bassidje Laurent Kipré Séri Luc Kouakou Kouadio Joseph Allico Djaman Public Health and Hydrology Laboratory Félix Houphou&euml t-Boigny University Abidjan C&ocirc te d’Ivoire Water Quality Control and Analysis Laboratory National Drinking Water Office Abidjan C&ocirc te d’Ivoire Biology and Health Laboratory Félix Houphou&euml t-Boigny University Abidjan C&ocirc te d’Ivoire Environmental Sciences Laboratory Nanguy Abrogoua University Abidjan C&ocirc te d’Ivoire Department of Medical and Fundamental Biochemistry Institut Pasteur of C&ocirc te d’Ivoire Abidjan C&ocirc te d’Ivoire

Lagoons of West African countries are seriously threatened by rapid artisanal and small-scale gold mining (ASGM) that exposes lagoons to mercury pollution. In this study, the mercury level in the sediments of the Tendo and Aby lagoons in Côte d’Ivoire had been evaluated. A total of 87 samples from 25 stations located on Tendo and Aby lagoons were analyzed by atomic fluorescence spectrometry. The mean Hg concentrations obtained in the sediments of Tendo and Aby lagoons were 0.89 ± 0.26 mg⋅kg-1 and 0.70 ± 0.18 mg⋅kg-1, respectively. Hg concentrations evaluated in the bays of Tendo and Aby during the dry season were 1.38 ± 0.45 mg⋅kg-1 and 1.07 ± 0.31 mg⋅kg-1, respectively. The minimum and maximum total Hg concentrations in the sediments from 25 stations were 0.04 and 3.56 mg⋅kg-1, respectively. Mercury contamination in lagoons during ASGM poses risks of pollution for the lagoon ecosystem and also poses health risks for the population living near these lagoons.

关键词： ASGM Mercury Sediments Côte d’Ivoire Pollution

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Epileptic seizure detection using EEG signals and extreme gradient boosting

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The Journal of Biomedical Research 2020年第3期34卷 228-239页

作者： Paul Vanabelle Pierre De Handschutter riem El Tahry mohammed Benjelloun Mohamed Boukhebouze Data Science Department Centre of Excellence in Informationand Communication TechnologiesCharleroi 6041Belgium Computer Science Unit Faculty of EngineeringUniversity of MonsMons 7000Belgium Refractory Epilepsy Centre University Hospital of Saint-LucBrussels 1200Belgium Institute of Neuroscience Catholic University of LouvainBrussels 1200Belgium

The problem of automated seizure detection is treated using clinical electroencephalograms(EEG) and machine learning algorithms on the Temple University Hospital EEG Seizure Corpus(TUSZ).Performances on this complex data set are still not encountering *** purpose of this work is to determine to what extent the use of larger amount of data can help to improve the *** methods are explored:a standard partitioning on a recent and larger version of the TUSZ,and a leave-one-out approach used to increase the amount of data for the training ***,a fast implementation of the gradient boosting classifier,is the ideal algorithm for these *** performances obtained are in the range of what is reported until now in the literature with deep learning *** give interpretation to our results by identifying the most relevant features and analyzing performances by seizure *** show that generalized seizures tend to be far better predicted than focal *** also notice that some EEG channels and features are more important than others to distinguish seizure from background.

关键词： epileptic seizure electroencephalograms Temple University Hospital EEG Seizure Corpus machine learning XGBoost

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Effect of herpesvirus infection on pancreatic duct cell secretion

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World Journal of Gastroenterology 2005年第38期11卷 5997-6002页

作者： Péter Hegyi Balázs rdg Zoltán Rakonczai Jr Tamás Takács János Lonovics Annamária Szabolcs Réka Sári András Tóth Julius G Papp András Varró Mária K Kovács Mike A Gray Barry E Argent Zsolt Boldogki First Department of Medicine Department of Biology Division of Cardiovascular Pharmacology School of Cell and Molecular Biosciences

AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal ***: The virulent Ba-DupGreen (BDG) and nonvirulent ka-RREpOlacgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/interlobular ducts were infected with BDG virus (107 PFU/mL for 6 h) or with KEG virus (1010 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 *** rate of HCO3- secretion [base efflux -J(B-)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L)and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3--buffered ringer solution at 37 ℃ (n = 5ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning ***: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -J(B-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -J(B-). After alkali loading the ducts, -J(B-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected ***: Incubation with the BDG or KEG strains of PRV results in an effective infection o

关键词：疱疹病毒胰腺细胞胰管分泌病毒感染

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Practical strategies for modulating foam cell formation and behavior

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World Journal of Clinical Cases 2014年第10期2卷 497-506页

作者： Elisabeth Uitz Babak Bahadori Mark F McCarty mohammed H Moghadasian Department of Internal Medicine 2 University Hospital of St. Poelten Karl Landsteiner Private University of Health and Life Sciences Catalytic Longevity Carlsbad CA 92009 United States Department of Human Nutritional Sciences University of Manitoba Winnipeg R2H 2A6 Manitoba Canada

Although high density lipoprotein(HDL)-mediated reverse cholesterol transport is crucial to the prevention and reversal of atheroma, a recent meta-analysis makes evident that current pharmaceutical strategies for modulating HDL cholesterol levels lower cardiovascular risk only to the extent that they concurrently decrease low density lipoprotein(LDL) cholesterol. This corresponds well with findings of a recent Mendelian randomization analysis, in which genetic polymorphisms associated with HDL cholesterol but no other known cardiovascular risk factors failed to predict risk for myocardial infarction. Although it is still seems appropriate to search for therapies that could improve the efficiency with which HDL particles induce reverse cholesterol transport, targeting HDL cholesterol levels per se with current measures appears to be futile. Itmay therefore be more promising to promote reverse cholesterol transport with agents that directly target foam cells. Macrophage expression of the cholesterol transport proteins adenosine triphosphate binding cassette transporter A1, adenosine triphosphate binding cassette transporter G1, and scavenger receptor class B member 1 is transcriptionally up-regulated by activated liver X receptors(LXR), whereas nuclear factor(NF)-kappa B antagonizes their expression. Taurine, which inhibits atherogenesis in rodent studies, has just been discovered to act as a weak agonist for LXRalpha. Conversely, it may be possible to oppose NF-kappa B activation in macrophages with a range of measures. Induction of heme oxygenase-1, which can be attained with phase 2 inducer phytochemicals such as lipoic acid and green tea catechins, promotes reverse cholesterol transport in macrophages and inhibits atherogenesis in rodents, likely due to, in large part, NF-kappa B antagonism. Inhibition of macrophage nicotinamide adenine dinucleotide phosphate(NADPH) oxidase activity with the spirulina-derived bilirubin-mimetic phycocyanobilin may also oppose NF-ka

关键词： Atherosclerosis Cholesterol Inflammation Phytochemical Nutraceutical Atherogenesis Plaque Cytokine Antioxidant

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Doppler Study of Uterine Artery and Ultrasonography of Endometrial Thickness in Perimenopausal and Postmenopausal Bleeding

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Open Journal of Obstetrics and Gynecology 2022年第4期12卷 309-322页

作者： Shaimaa Belal Manal Abdel-Wanees Al-Sayed Hany Mahmoud Abd El Hamid Hesham mohammed Hamed Department of Obstetrics and Gynecology Faculty of Medicine Helwan University Helwan Cairo Egypt Department of Obstetrics and Gynecology Al-Sahel Teaching Hospital Cairo Egypt

Background: Transvaginal color Doppler sonography of the uterine artery has been reported useful for evaluation of abnormal uterine bleeding in peri-/post-menopausal women. It may differentiate physiological from malignant endometrial changes. Objective: Evaluating the endometrial thickness and uterine artery Doppler as an initial diagnostic tool to identify patients with abnormal endometrial pathology. Methods: This is a prospective case control study consisted of total 50 women with peri-(n = 35) and post-(n = 15) menopausal bleeding, with 20 women consisting control group (no bleeding) (peri-(n = 10) and post-menopausal (n = 10)). Double layer endometrial thickness and uterine-artery-Doppler waveforms were measured, with the latter being S/D ratio, ri and PI. These were related to histological findings (endometrial biopsy). Result: Patients with abnormal uterine bleeding (both peri- and postmenopausal) had a significantly higher mean endometrial thickness than the control women. Study group showed a significantly lower value of all Doppler indices (S/D ratio, ri and PI). In study group, patients with malignant endometrial pathology showed significantly thicker endometrium and significantly lower Doppler indices than those with benign pathology. Conclusion: The combination of endometrial thickness and uterine artery color Doppler pattern might predict uterine endometrial malignancy, although whether it can discriminate (screen) patients requiring endometrial biopsy is not evident. Further study is needed.

关键词： Doppler Study Uterine Artery Ultrasonography Endometrial Thickness

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考虑电力业务重要性的电力通信网关键节点识别

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电工技术学报 2019年第11期34卷 2384-2394页

作者：李昌超康忠健于洪国郑世超 ri Kihong 中国石油大学(华东)信息与控制工程学院

为了能够准确辨识出电力通信网的关键节点,给出了一种识别电力通信网关键节点的分析方法。首先,通过分析电力业务对电力通信网的要求和对电力网的影响,建立多层评估模型,采用量化赋值的方式对评价指标进行量化处理,提出针对非对称不完... 详细信息

为了能够准确辨识出电力通信网的关键节点,给出了一种识别电力通信网关键节点的分析方法。首先,通过分析电力业务对电力通信网的要求和对电力网的影响,建立多层评估模型,采用量化赋值的方式对评价指标进行量化处理,提出针对非对称不完全层次结构的层次分析法和基于云模型原理的改进熵权法,建立电力业务综合重要度评估体系;其次,结合实际电力业务分布情况建立加权网络,通过改进的权值降低法识别网络关键节点;最后,通过对两个实际电力通信网络的仿真验证了该方法的正确性。

关键词：电力网电力通信网电力业务网络拓扑加权网络

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一种识别电力系统关键输电线路的方法

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电力自动化设备 2020年第4期40卷 63-70页

作者：康忠健李昌超于洪国郑世超 ri Kihong 中国石油大学(华东)控制科学与工程学院山东青岛266580

电网关键输电线路的辨别有利于预防电网灾难事故,提高电力系统的安全稳定性。通过评估支路开断后系统潮流所受冲击的强弱,给出一种识别电力系统关键输电线路的方法。首先,基于等相角线理论,定义相角分割区,依据相角分割区和电气距离对... 详细信息

电网关键输电线路的辨别有利于预防电网灾难事故,提高电力系统的安全稳定性。通过评估支路开断后系统潮流所受冲击的强弱,给出一种识别电力系统关键输电线路的方法。首先,基于等相角线理论,定义相角分割区,依据相角分割区和电气距离对系统输电线路进行分区,基于广义熵指数理论,定义潮流增长率广义熵指数指标,评估支路开断后潮流冲击分布的均衡度;然后,从网络拓扑结构的角度,定义边的katz-Bonacich中心性指标评估输电线路位置的重要性,并定义评估系统对潮流冲击抵抗能力的余度指标;最后,基于云模型原理,对各评估指标进行云模型转换,以云图的形式展现评估结果。通过对IEEE 30节点系统和新英格兰10机39节点系统进行仿真,验证了所提方法的正确性。

关键词：电力系统输电线路广义熵指数相角分割区 katz-Bonacich中心性负载率

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A SARS-CoV-2-specific CAR-T-cell model identifies felodipine,fasudil,imatinib,and caspofungin as potential treatments for lethal COVID-19

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Cellular & Molecular Immunology 2023年第4期20卷 351-364页

作者： in Xia Lun-zhi Yuan Ya-hong Hu Jun-yi Liu Guo-sheng Hu Ruo-yao Qi Tian-ying Zhang Hua-long Xiong Zao-zao Zheng Hong-wei Lin Jia-mo Zhang Chao Yu Ming Zhou Jian Ma Tong Cheng ri-rong Chen Yi Guan Ning-shao Xia Wen Liu State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical SciencesXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiang’an South RoadXiamenFujian 361102China State Key Laboratory of Emerging Infectious Diseases School of Public HealthLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019(COVID-19)severity and ***,drugs that are effective against inflammation to treat lethal COVID-19 are still urgently ***,we constructed a SARS-CoV-2 spike protein-specific CAR,and human T cells infected with this CAR(SARS-CoV-2-S CAR-T)and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients,causing cytokine storm and displaying a distinct memory,exhausted,and regulatory T-cell ***1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in *** on this"two-cell"(CAR-T and THP1 cells)model,we screened an FDA-approved drug library and found that felodipine,fasudil,imatinib,and caspofungin were effective in suppressing the release of cytokines,which was likely due to their ability to suppress the NF-kB pathway in ***,fasudi,imatinib,and caspofungin were further demonstrated,although to different extents,to attenuate lethal inflammation,ameliorate severe pneumonia,and prevent mortality in a SARS-CoV-2-infected Syrian hamster model,which were also linked to their suppressive role in *** summary,we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput *** drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe,inexpensive,and easily accessible for immediateuseinmostcountries.

关键词： COVID-19 SARS-CoV-2 CAR-T anti-inflammation NF-kB pathway

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