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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： helen M.Knight Merve DemirbugenÖz Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular GeneticsSchool of Life SciencesUniversity of NottinghamNottinghamUK Department of Pharmaceutical Toxicology Faculty of PharmacyAnkara UniversityAnkaraTurkey

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying *** of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding *** emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these *** processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of *** this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive *** studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader ***,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development ***,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain ***,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are *** parahippocampal brain tissue,m^(6)A modification is enri

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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World Journal of Emergency Medicine 2024年第4期15卷 256-262页

作者： Jie Er Janice Soo Yuan helen Zhang Gek Hsiang Lim Fatimah Lateef Department of Emergency Medicine Singapore General HospitalSingapore 168753Singapore Health Services Research Unit Singapore General HospitalSingapore168753Singapore

BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury ***:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June *** records were reviewed and *** analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were ***:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients *** most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a *** majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical *** of 214(78.7%)discharged patients,no re-attendances or mortality were *** the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to ***:Our study highlights significant morbidities in bicycle-related *** is also a high proportion of fractures in the young healthy male *** prevention is paramount and we propose emphasizing helmet use and road user safety.

关键词： Cycling Injuries Emergency department

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Wheat zinc finger protein TaZF interacts with both the powdery mildew AvrPm2 protein and the corresponding wheat Pm2a immune receptor

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Plant Communications 2024年第5期5卷 25-41页

作者： Beatrice Manser helen Zbinden Gerhard Herren Joel Steger Jonatan Isaksson Stephanie Braunlich Thomas Wicker Beat Keller Department of Plant and Microbial Biology University of ZurichZollikerstrasse 1078008 ZurichSwitzerland Agroscope Route de Duillier 501260 NyonSwitzerland BIOREBA AG Christoph Merian-Ring 74153 ReinachSwitzerland

Plant defense responses to pathogens are induced after direct or indirect perception of effector proteins or their activity on host *** fungal–plant interactions,relatively little is known about whether,in addi-tion to avirulence effectors and immune receptors,other proteins contribute to specific *** nucleotide-binding leucine-rich repeat(NLR)immune receptor Pm2a in wheat recognizes the fungal pow-dery mildew effector *** found that the predicted wheat zincfinger TaZF interacts with both the fungal avirulence protein AvrPm2 and the wheat NLR *** further demonstrated that the virulent AvrPm2-H2 variant does not interact with *** silencing in wheat resulted in a reduction but not a loss of Pm2a-mediated powdery mildew *** studies showed that the leucine-rich repeat domain of Pm2a is the mediator of the interaction with *** recruits both Pm2a and AvrPm2 from the cytosol to the nucleus,resulting in nuclear localization of Pm2a,TaZF,and AvrPm2 in *** propose that TaZF acts as a facilitator of Pm2a-dependent AvrPm2 effector *** highlight the importance of identifying effector host targets for characterization of NLR-mediated effector recognition.

关键词： plant immunity plant-fungal interactions pathogen effectors nucleotide-binding leucine-rich repeat immune receptor NLR wheat powdery mildew

Survival outcomes in early-onset oesophageal adenocarcinoma patients:A systematic review and meta-analyses

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World Journal of Gastroenterology 2024年第38期30卷 4221-4231页

作者： Ashleigh Russell Shauna Mitchell Richard C Turkington helen G Coleman Centre for Public Health Queen's University BelfastBelfast BT126BAUnited Kingdom Patrick G Johnston Centre for Cancer Research Queen's University BelfastBelfast BT71NNUnited Kingdom

BACKGROUND The incidence of oesophageal adenocarcinoma(OAC)has been reported to be increasing in many *** this trend,an increase in incidence of early-onset OAC,defined as OAC in adults aged under 50 years,has been *** is unclear whether survival outcomes for early-onset OAC patients differ from older age *** To investigate survival outcomes in early-onset OAC *** Ovid Medline and Embase were searched from inception to January 2022 for relevant studies relating to early-onset OAC and survival *** regarding the overall five-year survival and risk of death of younger and older patients with OAC were extracted and pooled using meta-analyses to produce pooled estimates and 95%CIs where *** Eleven studies which compared survival of early-onset OAC,defined as age at diagnosis ofng results,with studies showing early-onset OAC patients having both better and worse outcomes compared to older age groups.A meta-analysis of five-year survival demonstrated similar outcomes across age groups,with 22%-25%of patients in the young,middle and older age groups alive after five years.A meta-analysis of four studies demon-strated that early-onset OAC patients did not have a significantly increased risk of death compared to middle-aged patients(hazard ratio 1.12,95%CI:0.85-1.47).INTRODUCTION There is concern that the incidence of oesophageal adenocarcinoma(OAC)in patients under 50,described as early-onset OAC,is ***,data regarding survival of younger patients with OAC is ***,while increasing age remains a major non-modifiable risk factor for cancer,the incidence of early-onset cancers,largely accepted to be in adults aged under 50 years,is increasing[1].This includes an observed increase in the incidence of gastrointestinal malignancies such as colorectal,oesophageal,gastric and he

关键词： Early-onset cancer Early-onset oesophageal adenocarcinoma Survival Cancer epidemiology Systematic review Meta-analysis

SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World Journal of Pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Rojas Emelia Bainto helen Harvey Adriana H.Tremoulet Jane C.Burns Kirsten B.Dummer Department of Pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease Research Center La JollaCAUSA Department of Pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA Department of Pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different *** publications exist about specific variants and their correlation with the severity of *** This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-San Diego between May 2020 and March *** epidemiologic data,including viral genomic information,were obtained from public ***,clinical presentation,laboratory values,and outcomes were obtained from electronic medical *** The analysis included 104 pediatric *** MIS-C waves were *** variants in San Diego during the first wave included clades 20A to *** the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20J(Gamma).The third wave had Delta strains(clades 21A,21I,and 21J),and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all *** patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second *** of the patients required mechanical circulatory support,and only two required invasive ventilatory *** was no *** The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical *** the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu helen He Zhu Hao Wang Yaping Li Pengcheng Zhang China State Institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai Institute of Materia Medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

基于深度神经网络模拟复杂多孔介质中两相驱替过程

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石油勘探与开发 2024年第5期51卷 1126-1140页

作者： ASADOLAHPOUR Seyed Reza JIAng Zeyun LEWIS helen 闵超赫瑞瓦特大学能源、地球科学、基础设施与社会学院地球能源工程研究所爱丁堡EH144AS英国西南石油大学理学院成都610500 油气藏地质及开发工程全国重点实验室西南石油大学成都610500

为了预测复杂孔隙结构中毛管压力主导下两相流排驱过程中的流体分布,从仿真多孔介质和岩石CT图像中抽取子样本,并采用孔隙形态模拟器(PMS)生成流体分布,以创建多样化的数据集,将距离图及像素大小、界面张力、接触角、压力作为输入参数,... 详细信息

为了预测复杂孔隙结构中毛管压力主导下两相流排驱过程中的流体分布,从仿真多孔介质和岩石CT图像中抽取子样本,并采用孔隙形态模拟器(PMS)生成流体分布,以创建多样化的数据集,将距离图及像素大小、界面张力、接触角、压力作为输入参数,通过改造、训练、评估卷积神经网络(CNN)、递归神经网络(RNN)和视觉转换器(ViT),优选用于预测流体分布的模型。模拟分析表明,常用的卷积和递归神经网络在捕捉流体连通性方面存在不足。基于ViT构建了一个高维视觉转换器(HD-ViT),该转换器先忽略孔隙的空间位置仅根据其大小进行排驱,再在后处理步骤中追加流体连通要求,这种方法允许在任何坐标方向预设出入口,并使用不同尺寸和不同分辨率的图像进行渗流状态推断。通过在砂岩和碳酸盐岩大图像上验证,并与微流控驱替测试的实验结果比较,证实了HD-ViT模型的有效性、精确性和速度优势,且在捕捉孔隙尺度三维流动方面存在较大的潜力。

关键词：两相驱替流体分布深度神经网络视觉转换器孔隙形态模拟器大数据集

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Predictors and Complications of Prematurity in Two Health Facilities in Fako Division, Southwest Region, Cameroon

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Open Journal of Pediatrics 2024年第3期14卷 630-644页

作者： Naiza Monono Verla Sissi Kamo helen nguepong Vianney Nana Njamen Department of Internal Medicine and Paediatrics Faculty of Health Sciences University of Buea Buea Cameroon Regional Hospital Limbe Southwest Region Cameroon Department of Paediatrics Faculty of Medicine and Biomedical Sciences University of Garoua Garoua Cameroon Department of Obstetrics and Gynaecology Faculty of Health Sciences University of Buea Buea Cameroon

Background: Prematurity is the leading cause of neonatal mortality. Most preterm births can be associated to an identifiable risk factor. In Cameroon, especially in the Southwest Region, there is limited data regarding prematurity associated risk factors. The aim of this study was to evaluate the risk factors and complications of prematurity in two health facilities in the Fako division, the BRH and RHL. Methods: A hospital based retrospective case control study was done from the 1st of January 2021 to 28th of February 2022. We assessed the gestational ages at which preterm birth occurred and their short-term outcome using a structured pretested questionnaire to collect data from files. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 26. Results: The minimum sample size was 137 preterms. 45.5% of cases were born between 34 and increased the risk of having a preterm birth meanwhile being married (AOR: 0.410;95% CI: 0.217 - 0.773;p = 0.006) decreased the risk. Hospital complications were neonatal infection 103 (51.5%), respiratory distress 79 (39.5%) and neonatal jaundice 61 (30.50%). Among the cases, 97 (48.50%) stayed in the hospital for 2 to 4 weeks and 177 (88.5%) were discharged alive. Conclusions: Modifiable factors that increased the risk of prematurity were advanced maternal age, secondary level of education, rural residence, and prenatal alcohol consumption. Being married decreased the risk. The most common hospital complications in both the cases and controls were neonatal infection, respiratory distress syndrome and neonatal jaundice.

关键词： Prematurity Gestational Age Risk Factors Complications Outcome

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在悉尼的街道展现中国音乐的魅力（英文）

新世纪智能 2024年第ZF期 13-14页

作者： helen

On the bustling streets of Sydney,Australia,a young Chinese woman,in elegant hanfu,the traditional attire of China,gracefully holds a dizi,the bamboo flute of China,enchanting passers-by with the melodies of traditional Chinese *** videos of her performances have been making the news since earlier this *** the performer is Dong Min,a talented musician born in 1990.

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