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quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)expression.This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of pneumonia.Remarkably,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G.The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient.Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

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Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 794-805页

作者： Muhammad Zulfiqah Sadikan Nurul Alimah Abdul Nasir Mohammad Johari Ibahim Igor Iezhitsa Renu Agarwal Department of Pharmacology Faculty of MedicineManipal University College Malaysia(MUCM)Bukit BaruMelaka 75150Malaysia centre for Neuroscience Research(NeuRon) Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia Department of Medical Education Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia Department of Biochemistry and Molecular medicine Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSungai BulohSelangor 47000Malaysia School of medicine International Medical UniversityBukit JalilKuala Lumpur 57000Malaysia Department of Pharmacology and Bioinformatics Volgograd State Medical UniversityVolgograd 400131Russia

AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.

关键词： housekeeping genes stability real-time reverse transcription polymerase chain reaction retinal tissue streptozotocin-induced diabetic rats

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Health behavior outcomes in stroke survivors prescribed wearables for atrial fibrillation detection stratified by age

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Journal of Geriatric Cardiology 2024年第3期21卷 323-330页

作者： Joanne Mathew Jordy Mehawej Ziyue Wang Taylor Orwig Eric Ding Andreas Filippaios Syed Naeem Edith Mensah Otabil Alex Hamel Kamran Noorishirazi IrinaRadu Jane Saczynski David D.McManus Khanh-Van Tran Division of Cardiovascular medicine Department of MedicineUniversity of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA Department of Internal medicine Central Michigan UniversityMount PleasantUSA Department of Pharmacy and Health Systems Sciences School of PharmacyNortheastern UniversityBostonUSA Department of Population and quantitative Health Sciences University of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA

BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older adults.We examine the health behavior outcomes of stroke survivors prescribed smartwatches for AF detection stratified by age.METHODS We analyzed data from the Pulsewatch study,a randomized controlled trial that enrolled patients(≥50 years)with a history of stroke or transient ischemic attack and CHA2DS2-VASc≥2.Intervention participants were equipped with a cardiac patch monitor and a smartwatch-app dyad,while control participants wore the cardiac patch monitor for up to 44 days.We evaluated health behavior parameters using standardized tools,including the Consumer Health Activation Index,the Generalized Anxiety Disorder questionnaire,the 12-Item Short Form Health Survey,and wear time of participants categorized into three age groups:Group 1(ages 50-60),Group 2(ages 61-69),and Group 3(ages 70-87).We performed statistical analysis using a mixedeffects repeated measures linear regression model to examine differences amongst age groups.RESULTS Comparative analysis between Groups 1,2 and 3 revealed no significant differences in anxiety,patient activation,perception of physical health and wear time.The use of smartwatch technology was associated with a decrease in perception of mental health for Group 2 compared to Group 1(β=-3.29,P=0.046).CONCLUSION Stroke survivors demonstrated a willingness to use smartwatches for AF monitoring.Importantly,among these study participants,the majority did not experience negative health behavior outcomes or decreased engagement as age increased.

关键词： prescribed stratified wear

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Sustainable food waste management using modified fuzzy improved analytic hierarchy process:a study of Malaysia

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Waste Disposal and Sustainable Energy 2024年第1期6卷 63-84页

作者： Chun Yuan Choo Syariza Abdul-Rahman Abdul Malek Yaakob Emy E.A-Jalil Department of Decision Science School of Quantitative SciencesUniversiti Utara Malaysia06010SintokKedahMalaysia Institute of Strategic Industrial Decision Modeling School of Quantitative SciencesCollege of Arts and SciencesUniversiti Utara Malaysia06010SintokKedahMalaysia Technology and Supply Chain Excellence Institute School of Technology Management and LogisticsUniversiti Utara Malaysia06010SintokKedahMalaysia

Food waste generation is a pressing issue that requires urgent attention and concerted efforts worldwide.The staggering amount of food wasted each year not only wastes valuable resources but also exacerbates environmental,economic,and social challenges.Food Waste Management(FWM)consists of a complex array of criteria and sub-criteria,and treatments which seems interdependent.There is a need to evaluate the FWM with the help of important criteria and sub-criteria and treatments to address this challenge.In this study,we identified four important criteria,21 sub-criteria,and four alternatives of FWM for the case of Malaysia using the integrated approach of literature review and expert opinions.Further,we employed the approach of Modified Fuzzy Improved Analytical Hierarchy Process(IAHP)to corroborate the interrelationships among the identified criteria and sub-criteria,and their associated treatments.This study undertakes linear normalization methods to transform data into comparable numerical values and the Geometric Mean method to handle uncertainty in human judgments.Moreover,the Centroid method is employed to convert fuzzy weights into crisp sets for ease of interpretation.The results indicate that environmental is the most essential criterion,followed by social,economic,and technical.In addition,air and water pollution is identified as the most critical sub-criteria.Black Soldier Fly is discovered as the most sustainable FWM treatment,since it performs the best while meeting all the criteria and sub-criteria assessed.Sensitivity analysis demonstrates that the outputs from the proposed method are robust and reliable.The finding suggests a proper and robust approach to help decision-makers select suitable FWM treatments to tackle various criteria and alternatives especially when handling inconsistent and uncertain judgments during evaluation.

关键词： Multi-criteria decision-making Sustainable food waste management Improved Analytical Hierarchy Process Fuzzy method Sensitivity analysis

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quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

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World Journal of Hepatology 2024年第4期16卷 550-565页

作者： Wattana Leowattana Pathomthep Leowattana Tawithep Leowattana Department of Clinical Tropical medicine Mahidol UniversityRachatawee 10400BangkokThailand Department of medicine Srinakharinwirot UniversityWattana 10110BangkokThailand

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

关键词： quantitative hepatitis B core antibody quantitative hepatitis B surface antigen Chronic hepatitis B management Novels viral biomarkers

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In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 102-119页

作者： Shengnan Huang Chenyang Zhou Chengzhi Song Xiali Zhu Mingsan Miao Chunming Li Shaofeng Duan Yurong Hu Academy of Chinese Medical Sciences Henan University of Chinese MedicineZhengzhou 450046China School of Pharmaceutical Sciences Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou UniversityZhengzhou 450001China Center for quantitative Biology Peking UniversityBeijing 100871China School of Pharmaceutical Sciences Henan University of Chinese MedicineZhengzhou 450046China Department of Pharmacy Chongqing University Cancer HospitalChongqing 400030China School of Pharmaceutical Sciences Henan UniversityZhengzhou 450046China

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

关键词： Post-sur gical tumor recurrence In situl hydrogel Immunotherapy Tumor micr oenvir onment Manganese(II) Nitic oxide

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Forward robust portfolio selection: The binomial case

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Probability, Uncertainty and quantitative Risk 2024年第1期9卷 107-122页

作者： Harrison Waldon Oaford-Man Institute of quantitative Finance University of OafordEagle House Walton Well RoadOrfordOX26EDUK

We introduce a new approach for optimal portfolio choice under model ambiguity by incorporating predictable forward preferences in the framework of Angoshtari et al.[2].The investor reassesses and revises the model ambiguity set incrementally in time while,also,updating his risk preferences forward in time.This dynamic alignment of preferences and ambiguity updating results in time-consistent policies and provides a richer,more accurate learning setting.For each investment period,the investor solves a worst-case portfolio optimization over possible market models,which are represented via a Wasserstein neighborhood centered at a binomial distribution.Duality methods from Gao and Kleywegt[10];Blanchet and Murthy[8]are used to solve the optimization problem over a suitable set of measures,yielding an explicit optimal portfolio in the linear case.We analyze the case of linear and quadratic utilities,and provide numerical results.

关键词： Forward robust portfolio selection Binomial case Optimal portfolio Forward performance processes Linear utilities Quadratic utilities Robust forward performance criteria

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A pH-responsive nanoparticle delivery system containing dihydralazine and doxorubicin-based prodrug for enhancing antitumor efficacy

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Aggregate 2024年第1期5卷 436-450页

作者： Lianxue Zhang Jianxiang Huang Damiano Buratto Panli Han Zaixing Yang Ruhong Zhou Institute of quantitative Biology Shanghai Institute for Advanced StudyCollege of Life SciencesZhejiang UniversityHangzhouChina State Key Laboratory of Radiation medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)Soochow UniversitySuzhouChina Cancer Center Zhejiang UniversityHangzhouChina Department of Chemistry Columbia UniversityNew YorkNew YorkUSA

The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP transportation.Therefore,the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance.Herein,we propose a potential solution using a dihydralazine(HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive,cyclic RGD peptide-modified prodrug based on doxorubicin(cRGD-Dex-DOX).With a combined experimental and theoretical approach,we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues.HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α(HIF1α),α-smooth muscle actin,and fibronectin through the dilation of tumor blood vessels.These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors,suggesting that such a system may offer an effective“multifunctional therapy”through both improving the chemotherapeutic effect and enhancing the immune response to tumors.In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens,with the lowest side effects as well.

关键词： antitumor dihydralazine drug delivery system tumor stromal microenvironment vasculature

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quantitative assessment of the impact of a triage physician on the Accreditation Council for Graduate Medical Education resident milestones in the emergency department

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World Journal of Emergency medicine 2024年第3期15卷 220-222页

作者： Julie Cueva Duncan Grossman Vishnu Muppala Arlene Chung Mahlaqa Butt Jefferson Drapkin Antonios Likourezos Errel Khordipour Department of Emergency medicine Maimonides Medical CenterNew York 11219USA

The “door-to-doctor” time for patients to be seen by a physician is an increasingly studied metric.Hospitals may shorten this time by implementing a triage physician (TP).The exact role of a TP may vary across departments.TPs put in preliminary orders for lab work,imaging,and treatment,and decide treatment location for further evaluation.As the prevalence of TPs grows,its effect on resident education in academic emergency departments (EDs) remains unclear.We implemented a TP in the spring of 2016 and assessed resident physicians before and after implementation.

关键词： physician doctor treatment

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Coordinate-wise monotonic transformations enable privacy-preserving age estimation with 3D face point cloud

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Science China(Life Sciences) 2024年第7期67卷 1489-1501页

作者： Xinyu Yang Runhan Li Xindi Yang Yong Zhou Yi Liu Jing-Dong J.Han School of Life Sciences Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Beijing Key Lab of Traffic Data Analysis and Mining School of Computer and Information TechnologyBeijing Jiaotong UniversityBeijing 100044China Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy concerns.Here we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic transformations.We first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and generalizability.We show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial aging.Through visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is accessible.Our study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.

关键词： face point cloud age estimation face verification privacy coordinate-wise monotonic transformation

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