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Adaptive optics two-photon microscopy enables near-diffraction-limited and functional retinal imaging in vivo

Light(Science & Applications) 2020年第1期9卷 1298-1308页

作者： Zhongya Qin Sicong He Chao Yang Jasmine Sum-Yee Yung Congping Chen christopher Kai-Shun Leung Kai Liu Jianan Y.Qu Department of Electronic and Computer Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Division of Life Science The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong KongChina State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and TechnologyClear Water BayKowloonHongKongChina Center of Systems Biology and Human Health The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina

In vivo fundus imaging offers non-invasive access to neuron structures and biochemical processes in the ***,optical aberrations of the eye degrade the imaging resolution and prevent visualization of subcellular retinal *** developed an adaptive optics two-photon excitation fluorescence microscopy(AO-tPEFM)system to correct ocular aberrations based on a nonlinear fluorescent guide star and achieved subcellular resolution for in vivo fluorescence imaging of the mouse *** accurate wavefront sensing and rapid aberration correction,AOtPEFM permits structural and functional imaging of the mouse retina with submicron ***,simultaneous functional calcium imaging of neuronal somas and dendrites was ***,the timelapse morphological alteration and dynamics of microglia were characterized in a mouse model of retinal *** addition,precise laser axotomy was achieved,and degeneration of retinal nerve fibres was *** highresolution AO-tPEFM is a promising tool for non-invasive retinal imaging and can facilitate the understanding of a variety of eye diseases as well as neurodegenerative disorders in the central nervous system.

关键词： optics functional photon

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Safety and immunogenicity of a third dose of mRNA-1273 vaccine among cancer patients

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Cancer Communications 2023年第7期43卷 749-764页

作者： Anna Giuliano Barbara Kuter Shari Pilon-thomas Junmin Whiting Qianxing Mo Brett Leav Bradley Sirak christopher Cubitt christopher Dukes Kimberly Isaacs-Soriano Kayoko Kennedy Somedeb Ball Ning Dong Akriti Jain Patrick Hwu Jeffrey Lancet Department of Cancer Epidemiology Moffitt Cancer CenterTampaFloridaUSA Moderna CambridgeMassachusettsUSA Department of Immunology Moffitt Cancer CenterTampaFloridaUSA Department of Biostatistics and Bioinformatics Moffitt Cancer CenterTampaFloridaUSA Immune Monitoring Core Moffitt Cancer CenterTampaFloridaUSA Non-therapeutic Research Office(NtRO) Moffitt Cancer CenterTampaFloridaUSA Department of Malignant Hematology Moffitt Cancer CenterTampaFloridaUSA

Background:Compared to the general population,cancer patients are at higher risk of morbidity and mortality following SARS-CoV-2 *** immune response to a two-dose regimen ofmRNA vaccines in cancer patients is generally lower than in immunocompetent *** doses may meaningfully augment immune response in this *** conducted an observational study with the primary objective of determining the immunogenicity of vaccine dose three(100μg)of mRNA-1273 among cancer patients and a secondary objective of evaluating safety at 14 and 28 ***:the mRNA-1273 vaccine was administered~7 to 9 months after administering two vaccine doses(i.e.,the primary series).Immune responses(enzyme-linked immunosorbent assay[ELISA])were assessed 28 days post-dose *** events were collected at days 14(±5)and 28(+5)post-dose *** exact or X^(2)tests were used to compare SARS-CoV-2 antibody positivity rates,and paired t-tests were used to compare SARS-CoV-2 antibody geometric mean titers(GMts)across different time ***:Among 284 adults diagnosed with solid tumors or hematologic malignancies,dose three of mRNA-1273 increased the percentage of patients seropositive for SARS-CoV-2 antibody from 81.7%pre-dose three to 94.4%28 days post-dose *** increased 19.0-fold(15.8-22.8).Patients with lymphoid cancers or solid tumors had the lowest and highest antibody titers post-dose three,*** responses after dose three were reduced among those who received anti-CD20 antibody treatment,had lower total lymphocyte counts and received anticancer therapy within 3 *** patients seronegative for SARS-CoV-2 antibody pre-dose three,69.2%seroconverted after dose three.A majority(70.4%)experienced mostly mild,transient adverse reactions within 14 days of dose three,whereas severe treatment-emergent events within 28 days were very rare(three of the mRNA-1273 vaccine was well-tolerated and augmented SAR

关键词： Cancer Coronavirus disease 2019 Immunogenicity Observational study Vaccination

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Survival benefit with extended lymphadenectomy for advanced renal malignancy: A population-based analysis

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Asian Journal of Urology 2020年第1期7卷 29-36页

作者： Dean Laganosky christopher P.Filson Dattatraya Patil Viraj A.Master Department of Urology Emory University School of MedicineAtlantaGAUSA Winship Cancer Institute AtlantaGAUSA Atlanta VA Medical Center DecaturGAUSA

Objective:We used population-based data to examine the possible benefit of extended lymphadenectomy for patients with renal malignancy in the setting of more advanced ***:the Surveillance,Epidemiology,and End Results(SEER)database was utilized to identify non-metastatic,t3-t4 renal cancer patients from 2004-2015 treated with removal of≥1 lymph node at the time of ***-parametric bivariate statistics were used to assess associations between covariates of interest and extended lymphadenectomy(≥10 lymph nodes removed).Cancer-specific survival(CSS)and overall survival(OS)benefit was evaluated using Kaplane-Meier ***:Of the 4397 patients identified,816(18.6%)underwent extended *** patients with t3a disease,5-year CSS and OS benefit with extended lymphadenectomy did not reach statistical significance(CSS:hazard ratio[HR]0.98,95%confidence interval[CI]0.77-1.24;OS:HR 0.96,95%CI 0.77-1.20).Conversely,for those with t3b-t3c disease,extended lymphadenectomy led to statistically significant improvements in both 5-year CSS and OS compared to non-extended lymphadenectomy(CSS:HR 0.78,95%CI 0.61-0.99;OS:HR 0.72,95%CI 0.58-0.90).Finally,for those with t4 disease,use of extended lymphadenectomy had OS benefit after 5 years(OS:HR 0.51,HR 0.29-0.90,p = 0.02).Conclusion:Based on population-level data,extended lymphadenectomy was associated with improved survival in select patients with advanced renal malignancy treated with surgical *** the basis of these real-world findings in the face of conflicting randomized trial results will be key,moving forward.

关键词： Extended lymphadenectomy Lymph node dissection Advanced renal malignancy Renal cell carcinoma

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Vitamin B_(12)-auxotrophy in dinoflagellates caused by incomplete or absent cobalamin-independent methionine synthase genes(metE)

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Fundamental Research 2022年第5期2卷 727-737页

作者： Siheng Lin Zhangxi Hu Xiaoying Song christopher JGobler Ying Zhong tang CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Ecology and Environmental Science Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China School of Marine and Atmospheric Sciences Stony Brook UniversityNY11790USA Department of Biological Sciences and Biotechnology Minnan Normal UniversityZhangzhou 363000China

Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean *** than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can control dinoflagellate HABs,yet the genetic basis of B_(12) auxotrophy in dinoflagellates in the framework of the ecology of dinoflagellates and particularly HABs,which was the objective of this ***,we investigated the presence,phylogeny,and transcription of two methionine synthase genes(B_(12)-dependent metH and B_(12)-independent metE)via searching and assembling transcripts and genes from transcriptomic and genomic databases,cloning 38 cDNA isoforms of the two genes from 14 strains of dinoflagellates,measuring the expression at different scenarios of B_(12),and comprehensive phylogenetic analyses of more than 100 *** found that 1)metH was present in all 58 dinoflagellates accessible and metE was present in 40 of 58 species,2)all metE genes lacked N-terminal domains,3)metE of dinoflagellates were phylogenetically distinct from other known metE genes,and 4)expression of metH in dinoflagellates was responsive to exogenous B_(12) levels while expression of metE was not responding as that of genuine metE *** conclude that most,hypothetically all,dinoflagellates have either non-functional metE genes lacking N-terminal domain for most species,or do not possess metE for other species,which provides the genetic basis for the widespread nature of B_(12) auxotrophy in *** work elucidated a fundamental aspect of the nutritional ecology of dinoflagellates.

关键词： Harmful algal blooms(HABs)Dinoflagellates Vitamin B_(12) (cobalamin) Auxotrophy Methionine synthase genes Phytoplankton ecology

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transient elastography improves detection of liver cirrhosis compared to routine screening tests

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World Journal of Gastroenterology 2015年第3期21卷 953-960页

作者： thomas Gobel Janine Schadewaldt-tümmers Lucas Greiner christopher Poremba Dieter Haussinger Andreas Erhardt Klinik für Gastroenterologie Hepatologie und InfektiologieUniversitatsklinikum Düsseldorf40225 DüsseldorfGermany Klinik für Gastroenterologie Hepatologie und DiabetologiePetrus-Krankenhaus Wuppertal42283 WuppertalGermany Pathologie München-Nord Ernst-Platz-StraBe 280992 MünchenGermany

AIM:to investigate the diagnostic significance oftransient elastography(tE) in a daily routine clinical setting in comparison to clinical signs,laboratory parameters and ***:tE,ultrasound,laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily ***:Sensitivity of tE for the detection of liver cirrhosis was 90.4%,compared to 80.1% for ultrasound,58.0% for platelet count and 45.1% for cutaneous liver signs(P th histology).AUROC for tE was 0.760(95%CI:0.694-0.825).Combination of tE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825(95%CI:0.768-0.882).tE correlated with laboratory parameters of cirrhosis progression like albumin(r =-0.43),prothrombin time(r =-0.44),and bilirubin(r = 0.34; P ticularly,in patients with Child Pugh score A or normal platelet count tE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1%(P transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.

关键词： transient elastography Fibroscan Liver cirrhosis Liver disease Chronic hepatitis

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Designing user-centric transport strategies for urban road space redistribution

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Communications in transportation Research 2023年第1期3卷 230-248页

作者： Manu Sasidharan Mehran Eskandari torbaghan Yasmin Fathy christopher D.F.Rogers Nicole Metje Jennifer Schooling Department of Engineering University of CambridgeCambridgeCB21PZUK School of Engineering University of BirminghamBirminghamEdgbastonB152TTUK

Cities worldwide are geared to promote economic growth,improve accessibility,address environmental issues,and enhance the quality of ***,the processes that lead to the design of urban roads,particularly the space distribution,reflect the inequalities existing in the fabric of our *** often have shorter travel time and more space than passengers of other ***,the existing transport appraisal and planning tools that frame sustainable transport policies fall short of considering the dimension of social ***,our urban transport systems are essential areas for advancing sustainability through a transport justice-based approach to planning that can pivot the distribution of infrastructure investments over different social groups and transport *** study proposes such an approach by which such suitable urban transport strategies can be identified,co-created with users and appraised while considering the commuters’***,the interaction between the multidimensional characteristics of sustainability and the principles of transport justice are *** proposed approach is applied to London and *** results show that a transparent and holistic approach to integrating users within transport planning is an effective way to reflect diverse needs and local circumstances and thereby ensure a just transition to sustainable urban transport *** results from the case studies highlight a strong rationale for the centrality of justice in any urban transport planning and policy making efforts,particularly in the allocation of road space.

关键词： Urban transport Sustainability Road space allocation Cost-benefit analysis

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mtORC1 signaling:what we still don’t know

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分子细胞生物学报:英文版 2011年第4期3卷 206-220页

作者： Xuemin Wang christopher G.Proud School of Biological Sciences Life Sciences BuildingUniversity of SouthamptonSouthampton SO171BJUK

the mammalian target of rapamycin(mtOR)is a protein kinase that plays key roles in cellular *** forms complexes with additional *** best-understood one is mtOR complex 1(mtORC1).the regulation and cellular functions of mtORC1 have been the subjects of intense study;despite this,many questions remain to be *** include questions about the actual mechanisms by which mtORC1 signaling is stimulated by hormones and growth factors,which involves the small GtPase Rheb,and by amino acids,which involves other GtPase *** control of Rheb and the mechanism by which it activates mtORC1 remain incompletely *** it has been known for many years that rapamycin interferes with some functions of mtORC1,it is not known how it does this,or why only some functions of mtORC1 are ***1 regulates diverse cellular *** mtORC1 substrates are now known,although in several cases their physiological roles are poorly or incompletely *** the case of several processes,although it is clear that they are regulated by mtORC1,it is not known how mtORC1 does ***,mtORC1 is implicated in ageing,but again it is unclear what mechanisms account for *** the importance of mtORC1 signaling both for cellular functions and in human disease,it is a high priority to gain further insights into the control of mtORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.

关键词： mtORC1 protein synthesis cell signaling transcription cell growth autophagy metabolism

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Narrow band imaging evaluation of duodenal villi in patients with and without celiac disease:A prospective study

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World Journal of Gastrointestinal Endoscopy 2019年第2期11卷 145-154页

作者： James H tabibian Jean F Perrault Joseph A Murray Konstantinos A Papadakis Felicity t Enders christopher J Gostout Division of Gastroenterology and Hepatology Mayo Clinic Division of Gastroenterology Olive View-UCLA Medical Center Division of Biomedical Statistics and Informatics Mayo Clinic

BACKGROUND Duodenal biopsies are commonly obtained during esophagogastroduodenoscopy(EGD) but are very often histopathologically normal. therefore, a more strategic method for evaluating the duodenal mucosa and avoiding unnecessary biopsies is *** to examine the clinical utility of narrow band imaging(NBI) for evaluating duodenal villous *** We performed a prospective cohort study of adult patients at Mayo Clinic Rochester from 2013-2014 who were referred for EGD with duodenal biopsies. A staff endoscopist scored, in real-time, the NBI-based appearance of duodenal villi into one of three categories(normal, partial villous atrophy, or complete villous atrophy), captured ≥ 2 representative duodenal NBI images, and obtained mucosal biopsies therein. Images were then scored by an advanced endoscopist and gastroenterology fellow, and biopsies(gold standard) by a pathologist, in a masked fashion using the same three-category classification. Performing endoscopist, advanced endoscopist, and fellow NBI scores were compared to histopathology to calculate performance characteristics [sensitivity, specificity,positive and negative, negative predictive value(NPV), and accuracy]. Inter-rater agreement was assessed with Cohen's ***112 patients were included. the most common referring indications were dyspepsia(47%), nausea(23%), and suspected celiac disease(14%). Duodenal histopathology scores were: 84% normal, 11% partial atrophy, and 5% complete atrophy. Performing endoscopist NBI scores were 79% normal, 14% partial atrophy, and 6% complete atrophy compared to 91%, 5%, and 4% and 70%, 24%,and 6% for advanced endoscopist and fellow, respectively. NBI performed favorably for all raters, with a notably high(92%-100%) NPV. NBI score agreement was best between performing endoscopist and fellow(κ = 0.65).CONCLUSION NBI facilitates accurate, non-invasive evaluation of duodenal villi. Its high NPV renders it especially useful for foregoing biopsies of hi

关键词： Endoscopy Digestive tract Mucosa Celiac disease Minimally-invasive imaging Esophagogastroduodenoscopy

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Presence of extensive intraductal component in patients undergoing breast conservative surgery predicts presence of residual disease in subsequent completion mastectomy

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Chinese Medical Journal 2009年第8期122卷 900-905页

作者： christopher C. E Yiu Wings t. Y. Loo C. K. Lam Louis W. C. Chow UNIMED Medical Institute Comprehensive Centre for Breast Diseases Hong Kong China Clinical trial Centre Li Ka Shing Faculty of Medicine University of Hong Kong China

Background Local recurrence remains a serious problem among patients undergoing breast conservative surgery. this study aimed at identifying risk factors for residual disease after breast conservative surgery. Methods this retrospective study was based on patients with invasive breast cancer who have received breast conservative surgery and subsequent completion mastectomy. All patients had a clear resection margin in the initial operation. We analyzed the association between the presence of residual disease during completion mastectomy and the following risk factors： t staging, young age, and presence of extensive intraductal component （EIC）, a close margin, lymphovascular permeation （LVP）, positivity of estrogen receptor, progesterone receptor, and c-erbB-2. Results Residual disease was encountered in 21 （45.7%） of 46 patients; EIC was present in 28 patients （60.9%）, of whom 17 had residual disease. Presence of EIC during breast conservation surgery was associated with a higher risk of residual disease during completion mastectomy （P=0.011）. Other variables were not statistically significant risk factors for presence of residual disease. No local recurrence was recorded in our cohort, and the disease-free survival and overall survival after completion mastectomy were similar for patients who had residual disease and those who had not. Conclusions the presence of EIC is a significant risk factor for residual disease in patients after breast conservative surgery. Our findings may suggest the indicated value of completion mastectomy in patients with EIC during initial breast conservative surgery to decrease the risk of subsequent local failure.

关键词： extensive intraductal component breast conservative surgery residual disease completion mastectomy

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thermally-actuated microfluidic membrane valve for point-of-care applications

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Microsystems & Nanoengineering 2021年第3期7卷 197-208页

作者： Muhsincan Sesen christopher J.Rowlands Department of Bioengineering Imperial College LondonLondonSW72AZUK

Microfluidics has enabled low volume biochemistry reactions to be carried out at the point-of-care.A key component in microfluidics is the microfluidic *** valves are not only useful for directing flow at intersections but also allow mixtures/dilutions to be tuned real-time and even provide peristaltic pumping *** the transition from chip-in-a-lab to lab-on-a-chip,it is essential to ensure that microfluidic valves are designed to require less peripheral equipment and that they are *** this paper,a thermally-actuated microfluidic valve is *** valve itself is fabricated with off-the-shelf components without the need for sophisticated cleanroom *** is shown that multiple valves can be controlled and operated via a power supply and an Arduino microcontroller;an important step towards transportable microfluidic devices capable of carrying out analytical assays at the *** is been calculated that a single actuator costs less than$1,this highlights the potential of the presented valve for scaling *** valve operation is demonstrated by adjusting the ratio of a water/dye mixture in a continuous flow microfluidic chip with Y-junction channel *** power required to operate one microfluidic valve has been characterised both theoretically and *** operation of the valve has been demonstrated for 65 h with 585 *** presented valve is capable of actuating rectangular microfluidic channels of 500μm×50μm with an expected temperature increase of up to 5°*** fastest actuation times achieved were 2 s for valve closing(heating)and 9 s for valve opening(cooling).

关键词： fluid valve Arduino

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