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The HIF-1α/PlOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy l.Strong Yuxiao Sun lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.fernandes Michael Woodard Juhoon lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby lin Xu Robert J.Tower Benjamin levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PlOD2/lOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-lOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PlOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PlOD2/lOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PlOD2/lOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 883-893页

作者： Brendha Cação Coimbra Marina Alessandra Pereira leonardo Cardili Venancio Avancini ferreira Alves Evandro Sobroza de Mello Ulysses Ribeiro Jr Marcus Fernando Kodama Pertille Ramos Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of Pathology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-l1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-l1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-l1 status in PT and matched lymph node metastases(lNM)of GC patients and to determine the correlation between the PD-l1 status and clinicopathological *** We retrospectively reviewed 284 GC patients who underwent ***-l1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive *** PD-l1+PT staged as pN+were also tested for PD-l1 expression in their ***-l1(-)GC with pN+served as the comparison *** Among 284 GC patients included,45 had PD-l1+PT and 24 of them had pN+.For comparison,44 PD-l1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-l1+PT,54.2%(13/24 cases)were also PD-l1+in the *** PD-l1(-)PT,9.1%(4/44)had PD-l1+in the *** agreement between PT and lNM had a kappa value of *** tumor size and moderate/severe peritumoral inflammatory response were associated with PD-l1 positivity in both *** was no statistical difference in overall survival for PT and lNM according to the PD-l1 status(P=0.166 and P=0.837,respectively).CONClUSION Intra-patient heterogeneity in PD-l1 expression was observed between the PT and matched *** disagreement in PD-l1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

关键词： Gastric cancer lymph node Programmed death ligand 1 Stomach neoplasms Immunohistochemistry Metastasis

A Pooling Method Developed for Use in Convolutional Neural Networks

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Computer Modeling in Engineering & Sciences 2024年第10期141卷 751-770页

作者： Ìsmail Akgül Departmant of Computer Engineering Faculty of Engineering and ArchitectureErzincan Binali Yıldırım UniversityErzincan24002Turkiye

In convolutional neural networks,pooling methods are used to reduce both the size of the data and the number of parameters after the convolution of the *** methods reduce the computational amount of convolutional neural networks,making the neural network more *** pooling,average pooling,and minimum pooling methods are generally used in convolutional neural ***,these pooling methods are not suitable for all datasets used in neural network *** this study,a new pooling approach to the literature is proposed to increase the efficiency and success rates of convolutional neural *** method,which we call MAM(Maximum Average Minimum)pooling,is more interactive than other traditional maximum pooling,average pooling,and minimum pooling methods and reduces data loss by calculating the more appropriate pixel *** proposed MAM pooling method increases the performance of the neural network by calculating the optimal value during the training of convolutional neural *** determine the success accuracy of the proposed MAM pooling method and compare it with other traditional pooling methods,training was carried out on the leNet-5 model using CIFAR-10,CIFAR-100,and MNIST *** to the results obtained,the proposed MAM pooling method performed better than the maximum pooling,average pooling,and minimum pooling methods in all pool sizes on three different datasets.

关键词： Pooling convolutional neural networks deep learning

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál Department of Physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of *** events are significantly slower than the excitatory postsynaptic *** of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto *** are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback *** as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological *** is a growing body of evidence on the roles of slow inward currents on a single neuron or local network *** events often occur in synchro ny on neurons located in the same astrocytic *** synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic *** addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory *** note,there might be important regionspecific differences in the roles and actions triggering slow inward *** greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological *** inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural *** inward currents are significant contributors to paroxysmal depolarizational shifts/interictal *** events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive *** with features overlapping with slow inward currents(excitatory,N-methyl-Dasp

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

ProTSA: A Testing Process for Automotive Software Domain

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Journal of Software Engineering and Applications 2024年第7期17卷 571-615页

作者： Renato Rafael Arcanjo luiz Eduardo Galvão Martins Dirceu lavoiser fernandes Graci Department of Inovation and Science Federal University of Sao Paulo (UNIFESP) Sao Jose dos Campos Brazil Department of Automotive Electronics Faculty of Technology of Sao Paulo (Fatec) Santo Andre Brazil

This study evaluates the development of a testing process for the automotive software domain, highlighting challenges stemming from the absence of adequate processes. The research demonstrates the application of Design Science Research methodology in developing, an automotive software testing process—ProTSA, using six functional testing modules. Additionally, the study evaluates the benefits of implementing ProTSA in a specific Original Equipment Manufacturer (OEM) using an experimental single-case approach with industry professionals’ participation through a survey. The study concludes that combining testing techniques with effective communication and alignment is crucial for enhancing software quality. Furthermore, survey data indicates that implementing ProTSA leads to productivity gains by initiating tests early, resulting in time savings in the testing program and increased productivity for the testing team. Future work will explore implementing ProTSA in cybersecurity, over-the-air software updates, and autonomous vehicle testing processes. .

关键词： Verification and Validation Automotive Software Automotive Systems

Effect of radiative loss mechanisms on FIR thermometric parameters of Nd^(3+)-doped lithium tellurite glasses

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Journal of Rare Earths 2024年第7期42卷 1250-1257,I0002页

作者： C.Y.Morassuti A.P.l Silva l.A.O.Nunes S.M.lima l.H.C.Andrade Optical and Photothermal Spectroscopy Group(GEOF) Center for Studies in Natural Resources(CERNA)State University of Mato Grosso do Sul(UEMS)C.P.351DouradosMSBrazil Renato Archer Information Technology Center Dom Pedro I Highway(SP-65)Km 1436-Chácaras Campos dos AmaraisCampinasSPBrazil Institute of Physics of São Carlos University of São PauloSão CarlosSPBrazil

Nd^(3+)-doped tellurite glasses are promising materials for thermometers based on the fluorescence intensity ratio(FIR)***,at high Nd^(3+)concentrations,energy transfer(ET)processes such as optical reabsorption and cross-relaxation can affect the Nd^(3+)emission,which has been little explored in the ***,the present work investigated the use of Nd^(3+)-doped tellurite glass(samples doped with Nd^(3+)at 0.2 mol%,0.5 mol%,2.0 mol%,and 4.0 mol%)in fluorescence thermometers,in the temperature range from 299 to 371 *** results indicate a strong dependence of the FIR parameters on the Nd^(3+)concentration,due to changes in the emission band profiles caused by optical reabsorption of the Nd^(3+)emissions and cross-relaxation processes.A decrease of the relative sensitivity of the ratio^(4)F_(5/2)→^(4)I_(9/2)/^(4)F_(3/2)→^(4)I_(9/2)is observed for samples doped with higher amounts of Nd^(3+).The maximum relative sensitivity at 299 K is 3.00%/K,which is the highest value among the reported Nd^(3+)ions.

关键词： Nd^(3+)-doped tellurite glass Fluorescence intensity ratio Optical thermometry Judd-Ofelt Rare earths

Unsuccessful tuberculosis treatment outcomes across Brazil's geographical landscape before and during the COVID-19 pandemic:are we truly advancing toward the sustainable development/end TB goal?

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Infectious Diseases of Poverty 2024年第1期13卷 105-106页

作者： Reginaldo Bazon Vaz Tavares Thais Zamboni Berra Yan Mathias Alves Marcela Antunes Paschoal Popolin Antonio Carlos Vieira Ramos Ariela Fehr Tartaro Clara ferreira de Souza Ricardo Alexandre Arcencic Department of Maternal-Infant and Public Health Nursing University of São Paulo at Ribeirão Preto College of Nursing (USP/RPCN) Ribeirão Preto São Paulo Brazil Federal University of Tocantins Palmas Campus (FUT) Palmas Brazil State University of Minas Gerais Passos Campus (SUMG) Passos Brazil

Background Tuberculosis is one of the most significant infectious diseases for global public *** reallocation of healthcare resources and the restrictions imposed by the COVID-19 pandemic have hindered access to TB diag-nosis and *** in unfavorable outcomes of the disease have been observed in *** objective of this study was to analyze the spatial distribution of unfavorable TB treatment outcomes in Brazil before and during the *** An ecological study with spatial analysis was conducted with all 5569 municipalities in *** reported cases of tuberculosis between January 2010 and December 2021,as well as reported cases of COVID-19 from Febru-ary 2020 to December 2021,were *** outcomes studied encompass loss to follow-up,drug-resistant tuber-culosis,and *** Getis Ord GI*technique was employed to assess spatial association,and the Kernel density estimator was used to identify areas with concentrated increases or decreases in *** local Moran's/was used to examine the spatial association between outcomes and cOVID-19 *** study was approved by the Research Ethics Committee of Ribeirao Preto Nursing School,University of Sao *** There were 134,394 cases of loss to follow-up,10,270 cases of drug resistance,and 37,863 *** of high and low values were identified for all three outcomes,indicating significant changes in the spatial distribu-tion *** in concentrations were observed for lost to follow-up cases in the Southeast,while reductions occurred in the Northeast,South,and ***-resistant tuberculosis experienced an increase in the Southern and Southeastern regions and a decrease in the Northeast and ***-related deaths showed notable concentra-tions in the Midwest,Northeast,South,and *** was an increase in high occurrence clusters for deaths after 2020 and 2021 in the *** The pandemic has brought additional chal

关键词： Tuberculosis COVID-19 Spatial analysis Ecological studies

Finding biomarkers of experience in animals

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Journal of Animal Science and Biotechnology 2024年第3期15卷 925-944页

作者： Sarah Babington Alan J.Tilbrook Shane K.Maloney Jill N.fernandes Tamsyn M.Crowley luoyang Ding Archa H.Fox Song Zhang Elise A.Kho Daniel Cozzolino Timothy J.Mahony Dominique Blache School of Agriculture and Environment The University of Western AustraliaCrawleyWA 6009Australia Centre for Animal Science The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia School of Veterinary Science The University of QueenslandGattonQLD 4343Australia School of Human Sciences The University of Western AustraliaCrawleyWA 6009Australia School of Medicine Deakin UniversityGeelongVIC 3217Australia Poultry Hub Australia University of New EnglandArmidaleNSW 2350Australia College of Animal Science and Technology Yangzhou UniversityYangzhou 225009China Centre for Nutrition and Food Sciences The Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a *** is critical to ensure appropriate animal welfare *** behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative *** welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to *** this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human *** proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological *** also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

关键词： Animal experience Animal welfare Biomarker Stress Welfare assessment

Quantum vortices get stretched

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Frontiers of physics 2024年第3期19卷 225-227页

作者： Emanuel A.l.Henn São Carlos Institute of Physics University of São Paulo-PO Box 36913560-970São CarlosBrazil

Since its discovery, superfluidity [1,2] remains one of the most remarkable phenomena in quantum physics. The onset of the quantum regime in liquid helium is visually striking, when the fluid flows without dissipation or detaches from a rotating bucket, remaining still upon soft rotations. The same phenomenon is present in the context of ultracold bosonic quantum gases where, most of the time, superfluidity walks hand-in-hand with the transition to Bose−Einstein condensation [3].

关键词： quantum rotating rotation