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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko Jeremic lydia jiménez-díaz Juan d.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early Ad.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1166-1179页

作者： Sebastián díaz-López Jerónimo jiménez-Castro Carlos Enrique Robles-Barraza Carlos Ayala-de Miguel Manuel Chaves-Conde Medical Oncology department Hospital Universitario ValmeSeville 41014AndalucíaSpain

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

关键词： Mixed neuroendocrine non-neuroendocrine neoplasms Mixed adenoneuroendocrine carcinomas Mixed tumours Gastroenteropancreatic Treatment Etiology diagnosis

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús Ana Belen Martínez-Padilla Lourdes Sánchez-Salido Anne Baron-Van Evercooren Beatriz García-díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONANd) MálagaSpain Unidad Clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain Sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.during the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

Reuse of port industrial heritage in tourist cities:Shipyards as case studies

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Frontiers of Architectural Research 2024年第1期13卷 164-183页

作者： María J.Andrade Eduardo jiménez-Morales Rachel Rodríguez-Ramos Pablo Martínez-Ramírez department of Art and Architecture School of ArchitectureMalaga UniversityMalaga 29013Spain

The progressive deindustrialisation of many western cities since the 1980s has led to many industrial zones linked to port activities being abandoned or falling into disuse.Cities such as Barcelona,Naples,Lisbon,Amsterdam,and Hamburg have port industrial complexes of high tangible and intangible heritage value that could totally or partially disappear,resulting in an irreparable loss of their scientific,architectural,social,technological,and historical values.With that in mind,Adaptive Reuse(AR)of the built heritage allows the industrial memory of the ports to be preserved by turning them into new functional centres within the existing urban structure.That occurs in the context of the contemporary challenges of those cities,such as touristification,the circular economy and climate change,while guaranteeing the life cycle of those buildings.This article analyses two case studies—the Nederlandsche Scheepsbouw Maatschappij(NdSM)and the Rotterdamsche droogdok Maatschappij(RdM)shipyards,both in the Netherlands—in order to contribute to the knowledge of AR of Port Industrial Heritage.They are two examples of good practices in port industrial heritage interventions,where the factors behind their acclaim can be easily highlighted.A multi-scale methodology is therefore used and tailored to the case of port industrial heritage,based on analysing previous studies of the heritage in different spheres and on different scales.A relationship matrix tool is thus defined.It enables a comparative study to be conducted,using key variables and indicators,and considering qualitative and quantitative data.That provides extensive output information for each case study,which is summarised in the most favourable factors for the success of the AR of this port industrial heritage.

关键词： Industrial heritage Port-city Adaptive reuse Best practices Circular economy HUL Touristification

Small molecules to target tau amyloid aggregation

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Neural Regeneration Research 2024年第3期19卷 509-511页

作者： Zoe Manglano-Artuñedo Samuel Peña-díaz Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain

Protein aggregation has been linked with many neurodegenerative diseases,such as Alzheimer’s disease(Ad)or Parkinson’s disease.Ad belongs to a group of heterogeneous and incurable neurodegenerative disorders collectively known as tauopathies.They comprise frontotemporal dementia,Pick’s disease,or corticobasal degeneration,among others.The symptomatology varies with the specific tau protein variant involved and the affected brain region or cell type.However,they share a common neuropathological hallmark-the formation of proteinaceous deposits named neurofibrillary tangles.Neurofibrillary tangles,primarily composed of aggregated tau(Zhang et al.,2022),disrupt normal neuronal functions,leading to cell death and cognitive decline.

关键词： tau degeneration aggregation

Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan Antonio López-Villodres Beatriz García-díaz departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma Bionand) MálagaSpain

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual role.First,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action potentials.Second and not less important,OLs provide trophic support to neurons and axons.Thus,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

Predicting grain size-dependent superplastic properties in friction stir processed ZK30 magnesium alloy with machine learning methods

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Journal of Magnesium and Alloys 2024年第5期12卷 1931-1943页

作者： Farid Bahari-Sambran Fernando Carre?o C.M.Cepeda-jiménez Alberto Orozco-Caballero Physical Metallurgy department CENIM-CSIC department of Mechanical Engineering Chemistry and Industrial Design Polytechnic University of Madrid

The aim of this work is to predict, for the first time, the high temperature flow stress dependency with the grain size and the underlaid deformation mechanism using two machine learning models, random forest（RF） and artificial neural network（ANN）. With that purpose, a ZK30 magnesium alloy was friction stir processed（FSP） using three different severe conditions to obtain fine grain microstructures（with average grain sizes between 2 and 3 μm） prone to extensive superplastic response. The three friction stir processed samples clearly deformed by grain boundary sliding（GBS） deformation mechanism at high temperatures. The maximum elongations to failure, well over 400% at high strain rate of 10-2s-1, were reached at 400 ℃ in the material with coarsest grain size of 2.8 μm, and at 300 ℃ for the finest grain size of 2 μm. Nevertheless, the superplastic response decreased at 350 ℃ and 400 ℃ due to thermal instabilities and grain coarsening, which makes it difficult to assess the operative deformation mechanism at such temperatures. This work highlights that the machine learning models considered, especially the ANN model with higher accuracy in predicting flow stress values, allow determining adequately the superplastic creep behavior including other possible grain size scenarios.

关键词： Machine learning Artificial intelligence Magnesium alloys Superplasticity Friction stir processing Grain coarsening

Ca-based materials derived from calcined cigarette butts for CO_(2)capture and thermochemical energy storage

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Journal of Environmental Sciences 2024年第6期140卷 230-241页

作者： Nabil Amghar Virginia Moreno Pedro E.Sánchez-jiménez Antonio Perejón Luis A.Pérez-Maqueda Instituto de Ciencia de Materiales de Sevilla C.S.I.C.-Universidad de SevillaC.Américo Vespucio4941092 SevillaSpain Instituto de Tecnología de Materiales(ITM) Universitat Politècnica de València(UPV)Plaza Ferrándiz y Carbonell 1AlcoyAlicante 03801Spain departamento de Química Inorgánica Facultad de QuímicaUniversidad de Sevilla41012 SevillaSpain

Cigarette butts(CBs)are one of the most common types of litter in the world.due to the toxic substances they contain,the waste generated poses a harmful risk to the environment,and therefore there is an urgent need for alternative solutions to landfill storage.Thus,this work presents a possible revalorization of this waste material,which implies interesting environmental benefits.CBs were used as sacrificial templates for the preparation of CaO-based materials by impregnation with calcium and magnesium nitrates followed by flaming combustion.These materials presented enhanced porosity for their use in the Calcium Looping process applied either to thermochemical energy storage or CO_(2)capture applications.The influence of the concentration of Ca and Mg in the impregnating solutions on the multicycle reactivity of the samples was studied.An improved multicycle performance was obtained in terms of conversion for both applications.

关键词： Cigarette butts Calcium-Looping CO_(2)Capture Thermochemical energy storage

Metastatic pancreatic and lung cancer patient in complete remission following immunotherapy: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2233-2240页

作者： Joaquina Martínez-Galán Cristina jiménez-Luna Isabel Rodriguez Elisabeth Maza Carlos García-Collado Antonio Rodríguez-Fernández Javier Luis López-Hidalgo Octavio Caba department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain Instituto de Investigación Biosanitaria Ibs.GranadaGranada 18012Spain Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Pharmacogenetics Unit Virgen de las Nieves University HospitalGranada 18014Spain department of Medicina Nuclear Virgen de las Nieves University HospitalGranada 18014Spain department of Anatomía Patológica Virgen de las Nieves University HospitalGranada 18014Spain

BACKGROUNd Metastatic pancreatic ductal adenocarcinoma(PdAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PdAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PdAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PdAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PdAC.To our knowledge,this is the first reported case of a patient with metastatic PdAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PdAC patients most likely to benefit from this immunotherapy.

关键词： Pancreatic ductal adenocarcinoma Lung cancer Immunotherapy Pembrolizumab Programmed cell death protein-1 Case report