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Translational challenges in amyotrophic lateral sclerosis therapy with macrophage migration inhibitory factor

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Neural Regeneration Research 2025年第9期20卷 2583-2584页

作者： Leenor Alfahel Aleksandar Rajkovic adrian Israelson Department of Physiology and Cell Biology Faculty of Health SciencesBen-Gurion University of the NegevBeer ShevaIsraelThe School of Brain Sciences and CognitionBen-Gurion University of the NegevBeer ShevaIsrael

Macrophage migration inhibitory factor(MIF):MIF acts as a pleiotropic inflammatory mediator,playing regulatory roles in innate and adaptive immunity,neuroinflammation,neuroendocrine functions,and nervous system development(Matejuk et al.,2024).In recent years,MIF has attra cted significant inte rest from research groups as a potential target for the treatment of various neurodegenerative diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,and glioblastoma(Matejuk et al.,2024).

关键词： immunity sclerosis

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Evaluating the potential of(epi)genotype‑by‑low pass nanopore sequencing in dairy cattle:a study on direct genomic value and methylation analysis

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2276-2289页

作者： Oscar Gonzalez‑Recio adrian Lopez‑Catalina Ramon Peiro‑Pastor Alicia Nieto‑valle Monica Castro Almudena Fernandez Dpt.Mejora Genetica Animal INIA-CSICCtra La Coruna Km 7.528040 MadridSpain. ETSIAAB Universidad Politecnica de Madrid.Ciudad Universitaria S/N28040 MadridSpain.

Background Genotype-by-sequencing has been proposed as an alternative to SNP genotyping arrays in genomic selection to obtain a high density of markers along the *** requires a low sequencing depth to be cost effective,which may increase the error at the genotype *** generation nanopore sequencing technology offers low cost sequencing and the possibility to detect genome methylation,which provides added value to *** aim of this study was to evaluate the performance of genotype-by-low pass nanopore sequencing for estimating the direct genomic value in dairy cattle,and the possibility to obtain methylation marks *** Latest nanopore chemistry(LSK14 and Q20)achieved a modal base calling accuracy of 99.55%,whereas previous kit(LSK109)achieved slightly lower accuracy(99.1%).The direct genomic value accuracy from genotype-by-low pass sequencing ranged between 0.79 and 0.99,depending on the trait(milk,fat or protein yield),with a sequencing depth as low as 2×and using the latest chemistry(LSK114).Lower sequencing depth led to biased estimates,yet with high rank *** LSK109 and Q20 achieved lower accuracies(0.57-0.93).More than one million high reliable methylated sites were obtained,even at low sequencing depth,located mainly in distal intergenic(87%)and promoter(5%)*** This study showed that the latest nanopore technology in useful in a LowPass sequencing framework to estimate direct genomic values with high *** may provide advantages in populations with no available SNP chip,or when a large density of markers with a wide range of allele frequencies is *** addition,low pass sequencing provided nucleotide methylation status of>1 million nucleotides at≥10×,which is an added value for epigenetic studies.

关键词： Genomic selection Genomic values Low pass sequencing Low sequencing imputation Polygenic risk score

Genetic predisposition to colorectal cancer:Where we stand and future perspectives

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World Journal of Gastroenterology 2014年第29期20卷 9828-9849页

作者： Laura valle Hereditary Cancer Program Catalan Institute of OncologyIDIBELL08908 BarcelonaSpain

The development of colorectal cancer(CRC)can be influenced by genetic factors in both familial cases and sporadic *** CRC has been associated with genetic changes in high-,moderate-and low-penetrance susceptibility ***,despite the availability of current gene-identification techniques,the genetic causes of a considerable proportion of hereditary cases remain ***-wide association studies of CRC have identified a number of common lowpenetrance alleles associated with a slightly increased or decreased risk of *** accumulation of low-risk variants may partly explain the familial risk of CRC,and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance *** the predisposition to develop CRC will require investigators to address the following challenges:the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis;the classification of variants of unknown significance in known CRC-predisposing genes;and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation *** performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of lowand moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene *** challenges and future perspectives in the field of CRC predisposition are also discussed.

关键词： Hereditary colorectal cancer Familial colorectal cancer High penetrance Low penetrance Cancer syndromes Cancer susceptibility Hereditary cancer genes Risk variants Heritability

Challenges and improvement strategies in the hospitalization of chronic multimorbid patients

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World Journal of Clinical Cases 2025年第3期13卷 35-41页

作者： Andres Fontalba-Navas Francisco Pozo Muñoz Rogelio Garcia Cisneros Maria Jose Garcia Larrosa Maria del Mar Callejon Gil Ignacio Garcia Delgado Maria Belen jimenez Martinez Antequera Hospital Northern Málaga Integrated Healthcare AreaAntequera 29200AndalusiaSpain Department of Public Health and Psychiatry University of MálagaMálaga 29010Spain Antequera Hospital Northern Málaga Antequera Integrated Healthcare AreaAntequera 29200MálagaSpain

BACKGROUND Addressing the growing challenge of hospitalizing chronic multimorbid patients,this study examines the strain these conditions impose on healthcare systems at a local level,focusing on a pilot *** diseases and complex patients require comprehensive management strategies to reduce healthcare burdens and improve patient *** proven effective,this pilot model has the potential to be replicated in other healthcare settings to enhance the management of chronic multimorbid *** To evaluate the effectiveness of the high complexity unit(HCU)in managing chronic multimorbid patients through a multidisciplinary care model and to compare it with standard hospital *** The study employed a descriptive longitudinal approach,analyzing data from the Basic Minimum Data Set(BMDS)to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** The study employed a descriptive longitudinal approach,analyzing data from the BMDS to compare hospitalization variables among the HCU,the Internal Medicine Service,and other services at Antequera Hospital throughout *** HCU,designed for patients with complex chronic conditions,integrates a patient-centered model emphasizing multidisciplinary care and continuity *** This study demonstrates the effectiveness of the HCU in managing patients with complex chronic diseases through a multidisciplinary *** coordinated care provided by the HCU results in improved patient outcomes,reduced unnecessary hospitalizations,and better management of patient *** superiority of the HCU compared to standard care is evident in key outcomes such as fewer readmissions and higher patient satisfaction,reinforcing its value as a model of ca

关键词： High complexity unit Chronic multimorbidity Patient-centered care Integrated care Healthcare management

Debate about TGFBR1 and the susceptibility to colorectal cancer

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World Journal of Gastrointestinal Oncology 2012年第1期4卷 1-8页

作者： Laura valle Hereditary Cancer Program Catalan Institute of Oncology IDIBELL 08908 Hospitalet de Llobregat Spain

Recent years have witnessed enormous progress in our understanding of the genetic predisposition to colorectal cancer (CRC). Estimates suggest that all or most genetic susceptibility mechanisms proposed so far, ranging from high-penetrance genes to low-risk alleles, account for about 60% of the population-attributable fraction of CRC predisposition. In this context, there is increasing interest in the gene encoding the transforming growth factor β receptor 1 (TGFBR1 ); first when over a decade ago a common polymorphism in exon 1 (rs11466445, TGFBR1 *6A/9A) was suggested to be a risk allele for CRC, then when linkage studies identified the chromosomal region where the gene is located as susceptibility locus for familial CRC, and more recently when the allele-specific expression (ASE) of the gene was proposed as a risk factor for CRC. Published data on the association of TGFBR1 with CRC, regarding polymorphisms and ASE and including sporadic and familial forms of the disease, are often contradictory. This review gives a general overview of the most relevant studies in order to clarify the role of TGFBR1 in the field of CRC genetic susceptibility.

关键词： Transforming growth factor β receptor 1 Transforming growth factor β receptor 1*6A 9q linkage peak Allele-specific expression Colorectal cancer risk

An Efficient Representation of Quadtrees and Bintrees for Multiresolution Terrain Models

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Geo-Spatial Information Science 2011年第3期14卷 198-206页

作者： Yusnier valle José Ortiz Center of Geoinformatics and Digital Signals University of Informatics Sciences Dean of the Faculty 1 University of Informatics Sciences

A space-filling curve in 2,3,or higher dimensions can be thought as a path of a continuously moving *** its main goal is to preserve spatial proximity,this type of curves has been widely used in the design and implementation of spatial data structures and nearest neighbor-finding *** paper is essentially focused on the efficient representation of Digital Ele-vation Models(DEM) that entirely fit into the main *** propose a new hierarchical quadtree-like data structure to be built over domains of unrestricted size,and a representation of a quadtree and a binary triangles tree by means of the Hilbert and the Sierpinski space-filling curves,respectively,taking into account the hierarchical nature and the clustering properties of this kind of *** triangulation schemes are described for the space-filling-curves-based approaches to efficiently visualize multiresolu-tion surfaces.

关键词： bintrees quadtrees space-filling curves spatial data structures digital terrain models

Results on non-SUSY searches for physics beyond standard model in pp collisions at CMS

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Frontiers of physics 2013年第3期8卷 257-269页

作者： adrian Perieanu Physikalisches Institut B RWTH-Aachen Germany

In this paper a review of the results on searches for pnysics beyond the standard model in pp collisions with the CMS experiment at √s = 7 and 8 TeV is presented. Aspects of the analyses and their achieved limits on ... 详细信息

关键词： beyond standard model gauge bosons leptoquarks extra dimensions

Neural Network for Estimating Daily Global Solar Radiation Using Temperature, Humidity and Pressure as Unique Climatic Input Variables

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Smart Grid and Renewable Energy 2016年第3期7卷 94-103页

作者： Victor adrian jimenez Amelia Barrionuevo adrian Will Sebastiá n Rodrí guez Grupo de Investigació n en Tecnologí as Informá ticas Avanzadas Facultad Regional Tucum&aacute n Universidad Tecnol&oacute gica Nacional Tucum&aacute n Argentina Facultad de Ciencias Exactas y Tecnología Universidad Nacional de Tucum&aacute n Tucum&aacute n Argentina

Solar radiation is one of the most important parameters for applications, development and research related to renewable energy. However, solar radiation measurements are not a simple task for several reasons. In the cases where data are not available, it is very common the use of computational models to estimate the missing data, which are based mainly on the search for relationships between weather variables, such as temperature, humidity, precipitation, cloudiness, sunshine hours, etc. But, many of these are subjective and difficult to measure, and thus they are not always available. In this paper, we propose a method for estimating daily global solar radiation, combining empirical models and artificial neural networks. The model uses temperature, relative humidity and atmospheric pressure as the only climatic input variables. Also, this method is compared with linear regression to verify that the data have nonlinear components. The models are adjusted and validated using data from five meteorological stations in the province of Tucumán, Argentina. Results show that neural networks have better accuracy than empirical models and linear regression, obtaining on average, an error of 2.83 [MJ/m2] in the validation dataset.

关键词： Daily Solar Radiation Estimation Empirical Solar Radiation Model Feedforward Backpropagation Neural Network Regression Analysis