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Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-Perez jose j.Gil-Cosano Esther Ubago-Guisado Francisco j.Llorente-Cantarero juan Francisco pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino jonatan R.Ruiz Luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added ben

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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Vertical Displacement Measurement in a Slow-Moving Sinkhole Using BOTDA

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Photonic Sensors 2024年第1期14卷 23-39页

作者： pascual SEVILLANO javier PRECIADO-GARBAYO jorge SEVIL Francisco GUTIERREZ juan jMARTiNEZ Sonia MARTiN-LOPEZ Miguel GONZALEZ-HERRAEZ Aragon Institute of Engineering Research(I3A) Universidad de ZaragozaZaragoza 50018Spain Electronic Enginering and Communicaton Dpartment EINAUniversidad de ZaragzaZaragza 50018Spain Aragon Photonics Labs. Zaragoza 50009Spain Department of Earth Sciences Universidad de ZaragozaZaragoza 50009Spain Department of Electronics Escuela Politecnica SuperiorUniversidad de AlcalaMadrid 28805Spain

The effectiveness of monitoring and early-warning systems for ground deformation phenomena,such as sinkholes,depends on their ability to accurately resolve the ongoing ground displacement and detect the subtle deformation preceding catastrophic failures.Sagging sinkholes with a slow subsidence rate and diffuse edges pose a significant challenge for subsidence monitoring due to the low deformation rates and limited lateral strain gradients.In this work,we satisfactorily illustrate the practicality of the Brillouin optical time domain analysis(BOTDA)to measure the spatial-temporal patterns of the vertical displacement in such challenging slow-moving sagging sinkholes.To assess the performance of the approach,we compare the strain recorded by the distributed optical fiber sensor with the vertical displacement measured by high-precision leveling.The results show a good spatial correlation with the ability to identify the maximum subsidence point.There is also a good temporal correlation with the detection of an acceleration phase in the subsidence associated with a flood event.

关键词： Distributed fiber optic sensing(DFOS) vertical displacement measurement slow subsidence rate sinkhole hazard early-warning system

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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 hepatitis.Cas13,a CRISPR effector,shows promise as an antiviral agent against singlestranded RNA viruses.Cas13d,a type VI-D effector,exhibits higher efficiency in suppressing RNA viruses compared to other type VI variants.However,its in vivo activity against RNA viruses in mammals remains unknown.

关键词： mortality hepatitis treatment

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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 globally.Despite 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 diagnosis.Furthermore,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 increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We 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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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： Li-hua Zhu Yu-pei liang lian Yang Feng Zhu Li-jun jia He-gen lia Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Laboratory Medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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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 status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At 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 cetuximab.In 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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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María joséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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The relationship between DNA fragmentation and the intensity of morphologically abnormal human spermatozoa

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Asian pacific journal of Reproduction 2024年第1期13卷 22-27页

作者： Mercedes González-Martínez pascual Sánchez-Martín Carmen López-Fernández Stephen D.johnston jaime Gosálvez Clínica Ginemed Unidad de ReproducciónSevillaSpain Department of Biology Universidad Autónoma de MadridCantoblancoMadridSpain School of Environment The University of QueenslandGattonAustralia School of Veterinary Science The University of QueenslandGattonAustralia

Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;Pliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.

关键词： Teratozoospermia Sperm morphology Sperm DNA fragmentation Male factor Human reproduction Human fertility

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Diabetes mellitus, revascularization and outcomes in elderly patients with myocardial infarction-related cardiogenic shock

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journal of Geriatric Cardiology 2020年第10期17卷 604-611页

作者： Miquel Gual Albert Ariza-Solé María García Márquez Cristina Fernández joséL Bernal Francesc Formiga María-Isabel Barrionuevo joséC Sánchez-Salado Victòria Lorente júlia.pascual Isaac Llaó Oriol Alegre Angel Cequier javier Elola Hospital Universitari de Bellvitge L’Hospitalet de LlobregatBarcelonaSpain Fundación Instituto para la Mejora de la Asistencia Sanitaria MadridSpain Hospital Clínico Universitario San Carlos MadridSpain Hospital Universitario 12 de Octubre MadridSpain

Background The prognostic role of diabetes mellitus(DM)in elderly patients with myocardial infarction-related cardiogenic shock(MI-CS)remains controversial.Little information exists about the impact of intensive cardiac care unit(ICCU)and revascularization on outcomes of elderly patients with MI-CS.We aimed to assess the prognostic impact of DM according to age in patients with MI-CS,and to analyze the impact ICCU management and revascularization on in-hospital mortality in MI-CS patients at older ages.Methods Discharge episodes with diagnosis of CS associated with MI were selected from the Spanish National Health System’s Basic Data Set.Centers were classified according to their availability of ICCU.Main outcome measured was in-hospital mortality.Results A total of 23,590 episodes of MI-CS were identified,of whom 12,447(52.8%)were in patients aged≥75 years.The impact of DM on in-hospital mortality was different among age subgroups.While in younger patients,DM was associated to a higher mortality risk(0.52 vs.0.47,OR=1.12,95%CI:1.06–1.18,χ^2justed mortality rate of MI-CS aged≥75 years was lower in patients admitted to hospitals with ICCU(adjusted mortality rate:74.2%vs.77.7%,P<0.001)and in patients undergoing revascularization(74.9%vs.77.3%,P<0.001).Conclusions Prognostic impact of DM in patients with MI-CS was different according to age,with a significantly lower impact at older ages.The availability of ICCU and revascularization were associated with better outcomes in these complex patients.

关键词： Cardiogenic shock Diabetes mellitus Myocardial infarction Revascularization The elderly

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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 psychosocial support, can significantly reduce the

关键词： Economic Costs Drug Resistance Tuberculosis Catastrophic Costs

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