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A novel homozygous missense variant in ARSK causes mPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： miao Sun Cornelia K.Kaminsky Philip Deppe mai-Brittllse Frederic m.Vaz Barbara Plecko Torben Lubke linda m.Randolph Division of Genomic medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UmC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria Division of medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

mucopolysaccharidoses(mPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

major,trace element and Sr-Nd isotope evidence for a sublithospheric mantle source for the Umkondo large igneous province

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Geoscience Frontiers 2024年第1期15卷 263-285页

作者： Ben Hayes Lewis D.Ashwal Khulekani B.Khumalo linda m.Iaccheri School of Geosciences University of the WitwatersrandJohannesburg2050South Africa

The mesoproterozoic(1.11 Ga)Umkondo large igneous province(LIP)in southern Africa and Antarctica was emplaced in<5 myr and is dominated by low-Ti tholeiitic doleritic-gabbroic *** is of particular interest because it ... 详细信息

The mesoproterozoic(1.11 Ga)Umkondo large igneous province(LIP)in southern Africa and Antarctica was emplaced inmyr and is dominated by low-Ti tholeiitic doleritic-gabbroic *** is of particular interest because it is the least studied LIP in southern Africa with both sublithospheric and lithospheric mantle sources proposed and it coincides with the early assembly of Rodinia,so it has importance in understanding the nature of magmatism and tectonics in and around the Kalahari craton during the *** this study,we compiled a large database of existing(~750)and new(~100)major and trace element data for the Umkondo province,as well as 42 new Sr-Nd isotopic measurements,to provide constraints on its magma sources and geochemical *** element compositional variations in the low-Ti tholeiites are explained by low-pressure(1 kbar)three-phase fractional crystallisation(olivine,clinopyroxene and plagioclase)of a parent magma with~10 wt.%mgO in oxidising conditions(QFm+1).Inverse models show that the low-Ti tholeiitic magmas were derived as residual melts after the crystallization of 12%-33%olivine from primary komatiitic-basaltic magmas(up to~20 wt.%mgO)in equilibrium with mantle olivine(Fo90).Low Sm/Yb and TiO2/Yb-Nb/Yb indicate that the primary magmas were derived by 2%-20%shallow(40-50 km)partial melting of spinel *** Sm/Yb is restricted to dyke swarms and may imply limited magma production from deeper(up to~70 km)garnet lherzolite-like *** low-Ti tholeiites of the Umkondo province are enriched in large ion lithophile elements(Rb-Sr-Cs-K)and depleted in high-field strength elements(Zr-Hf-Nb-Ta),indicating the involvement of crustal material and/or the subcontinental lithospheric *** is supported by covariations in Th/Nb,Nb/Yb,Nb/La and Ce/Sm with generally negativeΔ***-Nd isotopes lend support to the notion that the Umkondo magmas were derived from depleted and/or enriched sublithospheric mantle sources and subs

关键词： Umkondo large igneous province Low-Ti magma Continental tholeiites Sublithospheric mantle sources Kalahari craton Rodinia

Unequal Distribution of Innovation Efforts for Neglected Tropical Diseases: The Role of Funding Evaluation Criteria

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Health 2024年第5期16卷 490-520页

作者： Anne m. G. Neevel Kenneth D. S. Fernald linda H. m. van de Burgwal Athena Institute Faculty of Science Vrije Universiteit Amsterdam Amsterdam Netherlands

Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. Societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, curre

关键词： Neglected Tropical Diseases Funding Decision Evaluation Criteria Health Research Funding Research Impact

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad Norevik Aleksi m.Huuha Ragnhild N.RФsbjФrgen linda Hildegard Bergersen Kamilla Jacobsen Rodrigo miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco N.moreira Asgeir Kobro-Flatmoen menno P.Witter Nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of Neurology and Clinical Neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil Centre of molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems Neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen Centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(mcGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(pmyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation Neurons Plasma transfusion

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求职面试秘决

空中英语教室（初级版．大家说英语） 2024年第3期 44-45,56页

作者： linda m.Chung 不详

雇主们在招聘面试上经常会提出一些相同的要求。一个常见的要求是:“请向我介绍你自己。”你可以说一说自己成长的地方以及你的学历,也可以分享一些你的个人兴趣,例如你最喜欢的事。雇主可能会问:“你为什么想要应征这份工作?”你的答... 详细信息

雇主们在招聘面试上经常会提出一些相同的要求。一个常见的要求是:“请向我介绍你自己。”你可以说一说自己成长的地方以及你的学历,也可以分享一些你的个人兴趣,例如你最喜欢的事。雇主可能会问:“你为什么想要应征这份工作?”你的答案可以展现出你对这份工作以及这家公司的了解。在面试之前,先了解这家公司以及其提供的产品与各项服务。说出你为什么适合这份工作,还有你最喜欢这份工作以及这家公司的什么地方。

关键词：求职面试招聘面试个人兴趣雇主公司

Cellular metabolism: A key player in cancer ferroptosis

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Cancer Communications 2024年第2期44卷 185-204页

作者： Xianjie Jiang Qiu Peng mingjing Peng linda Oyang Honghan Wang Qiang Liu Xuemeng Xu Nayiyuan Wu Shiming Tan Wenjuan Yang Yaqian Han Jinguan Lin Longzheng Xia Yanyan Tang Xia Luo Jie Dai Yujuan Zhou Qianjin Liao Hunan Key Laboratory of Cancer metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanP.R.China Public Service Platform of Tumor Organoids Technology ChangshaHunanP.R.China Department of Head and Neck Surgery Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunanP.R.China Hengyang medical School University of South ChinaHengyangHunanP.R.China

Cellular metabolism is the fundamental process by which cells maintain growth and *** produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular *** metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell *** is a recently discovered form of iron-dependent programmed cell *** inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor ***,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well ***,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this ***,we provided a detailed overview of agents used to induce cancer *** explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell *** combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

关键词： cancer therapy cellular metabolism ferroptosis inducer ferroptosis

Risk profiling in patients undergoing penile prosthesis implantation

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Asian Journal of Andrology 2020年第1期22卷 8-14页

作者： linda m Huynh mohamad m Osman Faysal A Yafi Department of Urology University of CaliforniaIrvine Medical CenterOrangeCA 92868USA

Penile prosthesis implantation is the gold standard of surgical therapy for patients with medication-refractory erectile ***,this umbrella definition includes significant heterogeneity and associated risk profiles that should be candidly discussed and addressed *** associated with operative success and patient satisfaction are often surgery specific;however,risk profiling via patient selection,preoperative optimization,proper device selection,and intraoperative consideration are highly *** examples of common risk profiles include comorbidity(ies)such as cardiovascular disease,diabetes mellitus,prior abdominal surgery,Peyronie's disease,and psychological risk ***,integration of surgeon-and patient-amenable characteristics is key to decreasing risk of infection,complication,and need for ***,patient risk profiling provides a unique context for proper device selection and evidence-based intraoperative considerations.

关键词： patient selection penile prosthesis risk factors

利妥昔单抗联合GDP方案治疗非霍奇金淋巴瘤患者的效果及对免疫功能的影响

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临床医学研究与实践 2024年第23期9卷 38-41页

作者：钟林达河南科技大学第一附属医院血液内科河南洛阳471000

目的探讨利妥昔单抗联合吉西他滨+顺铂+地塞米松(GDP)方案治疗非霍奇金淋巴瘤患者的效果及对免疫功能的影响。方法选取2020年3月至2022年8月我院收治的106例非霍奇金淋巴瘤患者,根据治疗方案不同将其分为对照组(53例)和观察组(53例)。... 详细信息

目的探讨利妥昔单抗联合吉西他滨+顺铂+地塞米松(GDP)方案治疗非霍奇金淋巴瘤患者的效果及对免疫功能的影响。方法选取2020年3月至2022年8月我院收治的106例非霍奇金淋巴瘤患者,根据治疗方案不同将其分为对照组(53例)和观察组(53例)。对照组采用GDP方案治疗,观察组在对照组基础上加用利妥昔单抗治疗。比较两组的治疗效果。结果观察组的疾病控制率(DCR)为96.23%,高于对照组的84.91%,差异具有统计学意义(Pm(Igm)、补体C3、补体C4、血管内皮生长因子(VEGF)及胸苷激酶-1(TK-1)水平均低于对照组,差异具有统计学意义(P0.05)。结论利妥昔单抗联合GDP方案治疗非霍奇金淋巴瘤患者效果显著,可改善免疫功能,降低血清肿瘤标志物水平,且用药安全性高。

关键词：非霍奇金淋巴瘤利妥昔单抗免疫功能

Projection on Segre varieties and determination of holomorphic mappings between real submanifolds Dedicated to Professor Sheng GONG on the occasion of his 75th birthday

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Science China mathematics 2006年第11期49卷 1611-1624页

作者： BAOUENDI m S EBENFELT Peter ROTHSCHILD linda P Department of mathematics University of California at San Diego La JollaCA 92093-0112USA

It is shown that a germ of a holomorphic mapping sending a real-analytic generic submanifold of finite type into another is determined by its projection on the Segre variety of the target manifold. A necessary and sufficient condition is given for a germ of a mapping into the Segre variety of the target manifold to be the projection of a holomorphic mapping sending the source manifold into the target. An application to the biholomorphic equivalence problem is also given.

关键词： Segre variety, generic submanifold, Segre mappings, finite type, biholomorphic equivalence.