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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 Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With 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 systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C 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 injury. Likewise, an abundance of m6A 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. m6A-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 located. In parahippocampal brain tissue, m6A modification is en

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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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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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

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

沙特阿拉伯Middle East Paper公司:多元化快速发展的生活用纸生产商

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生活用纸 2024年第3期24卷 68-69页

作者： helen Morris 不详

在2023年9月的二十国集团(G20)领导人峰会上,宣布了印度-中东-欧洲经济走廊(IMEC)项目,这一新缩写词的出现确认了该地区贸易集团在未来几年将持续发挥重要作用。IMEC将进一步激励当地年轻人口的增长和旅游繁荣,推动地区经济增长。对于Mi... 详细信息

在2023年9月的二十国集团(G20)领导人峰会上,宣布了印度-中东-欧洲经济走廊(IMEC)项目,这一新缩写词的出现确认了该地区贸易集团在未来几年将持续发挥重要作用。IMEC将进一步激励当地年轻人口的增长和旅游繁荣,推动地区经济增长。对于Middle East Paper Company公司来说,通过多元化经营——进军生活用纸领域正在取得回报。Tissue World杂志资深编辑helen Morris采访了公司首席商务官Ahmed El Fazary。

关键词：多元化经营生活用纸经济走廊地区经济增长缩写词领导人峰会沙特阿拉伯

Continuity of care by a primary midwife(caseload midwifery):a cost analysis using results from the COSMOS randomised controlled trial

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Gynecology and Obstetrics Clinical Medicine 2024年第2期4卷 94-101页

作者： Emily J Callander Hannah Jackson helen L McLachlan Mary-Ann Davey Della A Forster University of Technology Sydney SydneyNew South WalesAustralia The Royal Women's Hospital MelbourneVictoriaAustralia Faculty of Health University of Technology SydneyBroadwayNew South WalesAustralia Judith Lumley Centre La Trobe UniversityMelbourneVictoriaAustralia School of Nursing and Midwifery a Trobe UniversityMelbourneVictoriaAustralia Department of Obstetrics and Gynaecology Monash UniversityClaytonVictoriaAustralia

Introduction Caseload midwifery(continuity of midwifery carer)offers benefits including lower caesarean section rates,lower risks of preterm birth and stilbirth,and improved maternal satisfaction of *** these advantages,concerns about additional costs hinder widespread *** study examinesthecost of caseload midwifery compared with standard maternity care from the perspective of both public hospitals and public *** A cost analysis was conducted using data from a randomised controlled trial of 2314 low-risk pregnant women in Melbourne,*** randomised to caseload care received antenatal,intrapartum and postpartum care from a primary midwife,with some care provided by a‘back-up'*** in standard care received midwifery-led care with varying levels of continuity,junior obstetric care or community-based medical *** cost analysis compared differences in mean costs of health resources to public hospitals and to public ***,a budget impact analysis estimated total costs to the health system between 2023 and *** For public hospitals,there was no significant difference in overall costs between women receiving caseload midwifery(n=1146)versus standard care(n=1151)($SA12363(SD:$A4967)vs$A12323(SD:$A7404);p=0.85).Conversely,public funders incurred lower expenditures for women receiving caseload midwifery($A20330(SD:$A8312))versus standard care($A21637(SD:$A11818);pngs of sA625million to the health system over the next 5 years with expanded access to caseloadmidwifery *** Caseloadmidwifery in low-risk women is cost-neutral to public hospitals and cost-saving to public *** abstract Continuity of midwifery for low-risk women reduces costs to public funders,with no additional costs to hospitals.

关键词： random continuity Continuity

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客舱内饰的不断发展

航空维修与工程 2024年第7期 25-26页

作者： helen Massy 赵平(编译) 不详

随着疫情后航空业的复苏,旅客和航空公司对客舱内饰的改进需求日益凸显,如何在提升旅客体验的同时减少碳排放,已成为航空业客舱设备专家面临的一个持续挑战。航空业内的航空公司、飞机制造商、客舱设备供应商、客舱改装咨询公司等都在... 详细信息

随着疫情后航空业的复苏,旅客和航空公司对客舱内饰的改进需求日益凸显,如何在提升旅客体验的同时减少碳排放,已成为航空业客舱设备专家面临的一个持续挑战。航空业内的航空公司、飞机制造商、客舱设备供应商、客舱改装咨询公司等都在大力推进客舱内饰的改进。

关键词：航空公司飞机制造商航空业旅客体验设备供应商大力推进客舱减少碳排放

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