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Integrating multi-omics data of childhood asthma using a deep association model

Fundamental Research 2024年第4期4卷 738-751页

作者： Kai Wei Fang Qian Yixue lia Tao Zeng Tao Huang Bio-Med Big Data Center CAS Key Laboratory of Computational BiologyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China guoke Ningbo Life Science and Health Industry Research Institute Ningbo 315000China guangzhou National Laboratory Guangzhou 510000China gMU-gIBH Joint School of Life Sciences The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and DiseasesGuangzhou LaboratoryGuangzhou Medical UniversityGuangzhou 510000China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Childhood asthma is one of the most common respiratory diseases with rising mortality and *** multi-omics data is providing a new chance to explore collaborative biomarkers and corresponding diagnostic models of childhood *** capture the nonlinear association of multi-omics data and improve interpretability of diagnostic model,we proposed a novel deep association model(DAM)and corresponding efficient analysis ***,the Deep Subspace Reconstruction was used to fuse the omics data and diagnostic information,thereby correcting the distribution of the original omics data and reducing the influence of unnecessary data ***,the Joint Deep Semi-Negative Matrix Factorization was applied to identify different latent sample patterns and extract biomarkers from different omics data ***,our newly proposed Deep Orthogonal Canonical Correlation Analysis can rank features in the collaborative module,which are able to construct the diagnostic model considering nonlinear correlation between different omics data *** DAM,we deeply analyzed the transcriptome and methylation data of childhood *** effectiveness of DAM is verified from the perspectives of algorithm performance and biological significance on the independent test dataset,by ablation experiment and comparison with many baseline methods from clinical and biological *** DAM-induced diagnostic model can achieve a prediction AUC of o.912,which is higher than that of many other alternative ***,relevant pathways and biomarkers of childhood asthma are also recognized to be collectively altered on the gene expression and methylation *** an interpretable machine learning approach,DAM simultaneously considers the non-linear associations among samples and those among biological features,which should help explore interpretative biomarker candidates and efficient diagnostic models from multi-omics data analysis for human complexdiseases.

关键词： Deepsub space reconstruction Deepnon-negative matrix factorization Deepcanonical correlationanalysis Multi-omics Interpretable machine learning Childhood asthma

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Colorectal cancer screening:A review of current knowledge and progress in research

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World Journal of gastrointestinal Oncology 2024年第4期16卷 1119-1133页

作者： Sara Ramos Lopes Claudio Martins Inês Costa Santos Madalena Teixeira Élia.gamito Ana Luisa Alves Department of gastroenterology Centro Hospitalar de SetúbalSetúbal 2910-446Portugal

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths *** the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial ***,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been *** and early detection are pivotal to improve CRC-related *** is well established that CRC screening not only reduces incidence,but also decreases deaths from *** screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the ***,uncertainties persist regarding the optimal screening method,age intervals and ***,adherence to CRC screening remains globally *** recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these ***,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily *** this review,we aim to cover the current evidence surrounding CRC *** will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

关键词： Colorectal cancer Screening Review Oncology Artificial intelligence

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Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

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World Journal of gastrointestinal Oncology 2024年第1期16卷 234-243页

作者： João gramaça Isabel gomes Fernandes Carolina Trabulo Joana gonçalves Rita gameiro dos Santos Adriano Baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical Oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKgROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational *** RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EgFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT *** the other hand,RAS-mutated patients are not eligible for treatment with anti-EgFR *** SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May *** the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and *** neo-RAS wt patients treated with anti-EgFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EgFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EgFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

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Prevention and treatment of gerbil hepatitis E using the programmable CRISPR-Cas13d system

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genes & Diseases 2024年第4期11卷 94-97页

作者： Chengcheng Zhao Chong lia Sa Li Hanyu Wu Pengyao Ren Tianlong Liu Xiaoxiang Hu Ran Zhang State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China Laboratory of Veterinary Pathology and Nanopathology College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China

In recent years,the global incidence of hepatitis E virus(HEV)has been rising,leading to increased morbidity and mortality associated with ***13,a CRISPR effector,shows promise as an antiviral agent against singlestranded RNA ***13d,a type VI-D effector,exhibits higher efficiency in suppressing RNA viruses compared to other type VI ***,its in vivo activity against RNA viruses in mammals remains unknown.

关键词： mortality hepatitis treatment

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DeepRisk:A deep learning approach for genome-wide assessment of common disease risk

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Fundamental Research 2024年第4期4卷 752-760页

作者： Jiajie Peng Zhijie Bao Jingyi lia Ruijiang Han Yuxian Wang Lu Han Jinghao Peng Tao Wang Jianye Hao Zhongyu Wei Xuequn Shang AI for Science Interdisciplinary Research Center Schoolof Computer ScienceNorthwestern Polyechnical UniversityXi'an 129China Key Laboratoryof Bg Data Sorage and Management Northwestern Polytechnical UniversityMinisty of Industy and Information TechnologyX'an 129Chin College of Intelligence and Computing Tianjin UniversityTianjin 300072China School of Data Science Fudan UniversityShanghai 200433China Research and Development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518000China

The potential for being able to identify individuals at high disease risk solely based on genotype data has garnered significant *** widely applied,traditional polygenic risk scoring methods fall short,as they are built on additive models that fail to capture the intricate associations among single nucleotide polymorphisms(SNPs).This presents a limitation,as genetic diseases often arise from complex interactions between multiple *** address this challenge,we developed DeepRisk,a biological knowledge-driven deep learning method for modeling these complex,nonlinear associations among SNPs,to provide a more effective method for scoring the risk of common diseases with genome-wide genotype *** demonstrated that DeepRisk outperforms existing PRs-based methods in identifying individuals at high risk for four common diseases:Alzheimer's disease,inflammatory bowel disease,type 2diabetes,and breast cancer.

关键词： Disease risk prediction Deep learning Polygenic risk score Common disease risk Disease prevention

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An ethically guided preclinical device for phenotyping H_(2)production in laboratory rodents

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Animal Models and Experimental Medicine 2024年第4期7卷 553-561页

作者： Victor Pascal-Moussellard Emilie Boucher Stéphane Tanguy Philippe Cinquin Pierre-Alain Barraud ChloéDavin Cordélia Salomez-Ihl Dalil Hannani François Boucher Jean-Pierre Alcaraz University grenoble Alpes CNRSUMR 5525VetAgro SupGrenoble INPTIMCGrenobleFrance

Background:Dihydrogen(H_(2))is produced endogenously by the intestinal microbiota through the fermentation of diet *** the past few years,numer-ous studies have demonstrated the significant therapeutic potential of H_(2)in various pathophysiological contexts,making the characterization of its production in labora-tory species of major preclinical ***:This study proposes an innovative solution to accurately monitor H_(2)pro-duction in free-moving rodents while respecting animal welfare *** devel-oped device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained,and the H_(2)concentration was continuously *** the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked,tests were carried out on rats and mice with different metabolic phenotypes,over 12 min to 1-h experiments and repeatedly.H_(2)production rates(HPR)were obtained using an easy calculation algorithm based on a first-order moving ***:HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats,respectively,2.64 and 1.27 nmol.s^(−1)per *** addition,the ingestion of inulin,a dietary fiber,stimulated H_(2)production in *** were 0.46 nmol.s^(−1)for animals under control diet and 1.99 nmol.s^(−1)for animals under inulin ***:The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H_(2)production.

关键词： hydrogen therapy laboratory rodents microbiota molecular hydrogen noninvasive monitoring device

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany göttingen graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory genomics group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing genomics group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Impact of phytoconstituents on oral health practices:a post COVID-19 observation

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Food Science and Human Wellness 2024年第5期13卷 2386-2400页

作者： Harsh Kumar Reena Singh Daljeet Singh Dhanjal Chirag Chopra Natália Cruz-Martins gheyath K.Nasrallah Amin F.Majdalawieh Sivakumar Manickam Shahida Anusha Siddiqui Dinesh Kumar Indu Sharma Varun Sharma School of Bioengineering&Food Technology Shoolini University of Biotechnology and Management SciencesSolan 173229India School of Bioengineering and Biosciences Lovely Professional UniversityPunjab 144402India Faculty of Medicine University of PortoPorto 4200-319Portugal Institute for Research and Innovation in Health(i3S) University of PortoPorto 4200-135Portugal Institute of Research and Advanced Training in Health Sciences and Technologies(CESPU) RuaCentral de GandraGandra 4585-116Portugal TOXRUN-Toxicology Research Unit University Institute of Health SciencesCESPUCRLGandra 4585-116Portugal Biomedical Research Center Qatar UniversityDoha 2713Qatar Department of Biomedical Science College of Health SciencesQatar UniversityDoha 2713Qatar Department of Biology Chemistryand Environmental SciencesCollege of Arts and SciencesAmerican University of SharjahSharjah 26666United Arab Emirates Petroleum and Chemical Engineering Faculty of EngineeringUniversiti Teknologi BruneiBandar Seri Begawan BE1410Brunei Campus Straubing for Biotechnology and Sustainability Technical University of MunichStraubing 94315Germany genetic Heritage group New York UniversityAbu Dhabi 129188United Arab Emirates Bioinformatics Division NMC Genetics India Pvt.Ltd.Gurugram 122001India

Appropriate oral hygiene significantly reduces the possibility of oral ***,dental caries and periodontal diseases are major oral health issues causing chronic diseases due to poor oral ***,herbal compounds have gained interest in maintaining oral *** of burdock root(Arctium),noni fruit(Morinda citrifolia),and neem leaf(Azadirachta indica)are now used as intracanal medicaments in endodontics and *** amboinicus species and other plants produces essential oil likeβ-caryophyllene,p-cymene,andγ-terpinene can exhibit antibacterial activity;highlighting phytoconstituents plays a vital role in oral *** COVID-19 pandemic highlighted the importance of hygiene and sanitization,to curb *** cavity is among the gateways for virus entry into *** is a potential reservoir of SARS-CoV-2,and there is an increased risk of infection if there is any fissure in the *** enables entry of virus into the vascular system through gingival or periodontal pocket,possibly reaching lung periphery then to lung vessels by interacting with endothelial surface receptors triggering pulmonary vasoconstriction and lung damage due to endothelial *** review aims to draw attention to the possible route of SARS-CoV-2 infection via the oral cavity and the importance of oral hygiene against COVID-19.

关键词： COVID-19 SARS-CoV-2 Oral Hygiene Microbiota Phytochemicals

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Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

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Journal of Tuberculosis Research 2024年第2期12卷 91-104页

作者： Júlia Malache António Domingas Pacala Isabelle Munyangaju Isaías Benzana Claudia Mutaquiha Dulce Osório Benedita José Edy Nacarapa Pereira Zindoga Faculdade de Cincias de Sade Universidade Catlica de Moambique Beira Moambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Moambique ISglobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psy

关键词： Economic Costs Drug Resistance Tuberculosis Catastrophic Costs

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An Analysis of the Accounting Costs Associated with 20-Month DR TB Regimens in Maputo City, Mozambique

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Journal of Tuberculosis Research 2024年第2期12卷 73-90页

作者： Júlia Malache António Isaías Benzana Isabelle Munyangaju Benedita José Dulce Osório Edy Nacarapa Claudia Mutaquiha Simeão Nhabinde Pereira Zindoga Universidade Catlica de Moambique Beira Moambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique ISglobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Mozambique Faculdade de Economia Universidade Eduardo Mondlane Maputo Moambique

Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.

关键词： Antitubercular Agents Multidrug-Resistant Healthcare Costs Tuberculosis Mozambique

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