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Cryptic exon inclusion in TDP-43 proteinopathies:opportunities and challenges

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Neural Regeneration Research 2025年第7期20卷 2003-2004页

作者： lorena Decker Sonja Menge Axel Freischmidt Department of Neurology Ulm UniversityUlmGermany

TDP-43 proteinopathies and cryptic exons:Transactive response DNA binding protein of 43 kDa(TDP-43)is a ubiquitously expressed RNA/DNA binding protein crucial for coding and non-coding RNA metabolism including transcription,splicing,transport,translation,and ***-43 shuttles between the nucleus and cytoplasm,but is predominantly localized in the *** diseases(NDs)may be accompanied by nuclear loss and possible cytoplasmic accumulation and aggregation of TDP-43 in vulnerable neurons and *** neuropathology is the hallmark of most individuals suffering from amyotrophic lateral sclerosis(ALS),frontotemporal dementia(FTD)with TDP-43-immunoreactive pathology(FTD-TDP),limbic-predominant age-related TDP-43 encephalopathy(LATE)and Perry syndrome,but also coexists with the primary pathology in subsets of patients suffering from other NDs,such as Alzheimer’s disease,Lewy body dementias,or Huntington’s *** in the gene encoding TDP-43(TARDBP)are the cause of ALS and/or FTD in some rare cases substantiating the importance of this protein in aging *** is still controversial if loss of nuclear,or increased cytoplasmic and/or aggregating TDP-43 is more harmful to neurons(Nag and Schneider,2023).Recently,the role of nuclear TDP-43 in repressing the inclusion of intronic sequences,named cryptic exons(CEs),into mature mRNAs gained much attention.

关键词： Huntington metabolism TDP

Alzheimer’s visual variant: a report of a diagnosis easily missed on ophthalmic examination

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1571-1575页

作者： Jorge Cárdenas-Belaunzarán lorena Wheelock-Gutierrez Karen ACerrillo-Avila Department of Neuro-Ophthalmology Association to Prevent Blindness in MexicoI.A.P.Mexico City 04030Mexico Independent Researcher Mexico City 04040Mexico

Dear Editor,We present a case of posterior cortical atrophy(PCA),which is a syndromic entity caused by different neurodegenerative diseases,mainly Alzheimer’s disease,but it has been described in several other *** frequency is reported to be as high as 5%of all cases;however,it remains widely under-recognized among ophthalmologists and optometrists due to scarce reports in visual health-related journals[1].

关键词： diagnosis Alzheimer diseases

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Wishing

小学生时代（大嘴英语） 2024年第7期 66-67页

作者： Maggie Murphy Gina lorena Maldonado(图) 不详

Quality-adjusted life years and surgical waiting list:Systematic review of the literature

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1155-1164页

作者： Roberto de la Plaza Llamas lorena Ortega Azor Marina Hernández Yuste Ludovica Gorini Raquel Aránzazu Latorre-Fragua Daniel Alejandro Díaz Candelas Farah Al Shwely Abduljabar Ignacio Antonio Gemio del Rey Department of General and Digestive Surgery Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Surgery Medical and Social SciencesFaculty of Medicine and Health SciencesUniversity of AlcaláAlcaláde Henares 28871MadridSpain

BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and *** waiting lists(SWLs)represent a pressing problem in public *** QALY measure has rarely been used in the context of *** would be interesting to know how many QALYs are lost by patients on *** To investigate the relationship between QALYs and SWLs in a systematic review of the scientific *** The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses *** unlimited search was carried out in PubMed,updated on January 19,*** on the following variables were investigated and analyzed:Specialty,country of study,procedure under study,scale used to measure QALYs,the use of a theoretical or real-life model,objectives of the study and items measured,the economic value assigned to the QALY in the country in question,and the results and conclusions *** Forty-eight articles were selected for the *** data were found regarding QALYs lost on *** specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery,with 15 articles *** country in which the most studies of QALYs were carried out was the United States(n=21),followed by the United Kingdom(n=9)and Canada(n=7).The most studied procedure was organ transplantation(n=39),including 15 kidney,14 liver,5 heart,4 lung,and 1 ***(n=4),cataract surgery(n=2),bariatric surgery(n=1),mosaicplasty(n=1),and septoplasty(n=1)completed the surgical interventions ***-nine of the models used were theoretical(the most frequently applied being the Markov model,n=34),and nine were *** survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions,but in 32 articles the survey was not specified.T

关键词： Quality-adjusted life year Waitlist Quality of life Surgery Systematic review

Patient Safety in the Use of Mechanical Restraints: Regulatory Compliance among Hospitals in the City of Buenos Aires and Proposal for Its Improvement

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Open Journal of Emergency Medicine 2024年第2期12卷 33-39页

作者： Martín Javier Mazzoglio y Nabar Sergio Giordano Edgardo Knopoff lorena Onofrio Oscar Agustín Porta Romina Rodríguez Emergency Service Torcuato de Alvear Psychiatric Emergency Hospital Buenos Aires Argentina Department of Psychiatry and Mental Health Faculty of Medicine University of Buenos Aires Buenos Aires Argentina

Introduction: Mechanical or physical restraint is an exceptional therapeutic resource to immobilize a subject and thus guarantee the safety of the patient and/or third parties in the face of high-risk behaviors, but it entails multiple crossings (bioethical, philosophical, medical, psychological, legal). Framed in the so-called “safety culture” developed by the WHO, based on the Protocol for its implementation of the CABA and attentive to its frequent use in CABA by different hospital services (medical clinic, geriatrics, intensive care and medical guards) we consider it necessary its study in terms of compliance with the risks it entails and its management. Objectives: Identify regulatory compliance with the GCABA Mechanical restraint (MR) Protocol from a patient safety perspective, as well as describe the clinical and medicolegal aspects, and propose the usefulness of a tool for its management and control. Methodology: Observational, descriptive, transversal and prospective work through the analysis of Clinical Records with indication of MR using a rubric-type form. 177 cases were analyzed between September-November 2023 from three hospitals of the Government of the City of Buenos Aires, statistical parameters were applied and graphs were made. Results: Only 12.99% complied with the Protocol. In the mental health specialized hospital compliance was almost 5 times greater than in the general one, and in the emergency services compliance was 12 times greater than in Inpatient services. We found that the start or end time of MR was not recorded and only 43% described the causes/justifications for the indication (mostly in Emergency and Specialized hospitals), with the MR average time being shorter in Emergency. Conclusions: Only 1.3 out of 10 patients reliably completed the Protocol and it was mostly in the mental health specialized hospital and the emergency services. The results show non-compliance behavior in the application and management of the risk that the use

关键词： Mechanical Containment Patient Safety Injuries in Custody Buenos Aires City Check List

From Simulation to Reality: A Comprehensive Study on the Efficacy of a Rotating Monopolar and Bipolar Radiofrequency System through In-Silico Modeling and Pre-Clinical and Clinical Validation

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Journal of Biomedical Science and Engineering 2024年第6期17卷 107-128页

作者： Gregorio Viera Mármol Ana lorena Urbano Bojorge Alicia Robledo Jorge José Antonio Ferrández Martínez Olalla Calvo Lozano High Technology Products S.L.U. (Sinclair) Barcelona Spain

Background: Skin aging is an unavoidable process aggravated by environmental agents. Among other energy devices, non-invasive radiofrequency (RF) technology is widely used for skin tightening and body contouring as it is simpler and more affordable than other technologies that also minimize pain and side-effects. However, most of the current RF devices do not provide automatic skin temperature control and it is difficult to achieve controlled, deep, and harmless thermal increase, so treatment performance and safety is dependent on the operator’s movements and expertise. Objective: To show the potential of numerical simulations for optimizing the design of monopolar and bipolar RF electrodes that are capable of providing homogeneous, deep and controlled heating. Materials and methods: In-silico models were developed and analyzed using Comsol Multiphysics software to simulate the RF effect produced in tissue by rotating monopolar and bipolar electrodes with different geometries from the Sculpt & Shape RF device (Sinclair, Spain), operating at frequencies of 0.5 and 1 MHz. Ex-vivo and in-vivo proof-of-concept tests were carried out to validate the simulations. Finally, treatments were performed on 16 subjects and a total of 78 body areas to assess the clinical results generated by the RF electrodes for skin tightening and body contouring. Results: In-silico studies emulated the superficial and deep dispersion of heat due to the release of RF energy into human skin tissue. The rotating electrodes (monopolar and bipolar) and the selected RF frequency (0.5 and 1 MHz) determined the homogeneity of the thermal distribution, the penetration depth (between 4.37 mm and 25.0 mm) and the heating dynamics (between 30 and 100 seconds to reach the target skin temperature), which were confirmed by ex-vivo and in-vivo tests. In addition, real treatments on facial and body areas using skin temperatures of between 43˚C and 44˚C showed consistent results with good clinical efficacy for

关键词： Comsol Multiphysics Simulations Radiofrequency Skin Tightening Fat Reduction Body Contouring Cellulite

Restoring expression of Stathmin-2:a novel strategy to treat TDP-43 proteinopathies

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3553-3554页

作者： Sonja Menge lorena Decker Axel Freischmidt Department of Neurology Ulm University89081 UlmGermany

In a recent study published in Science,Baughn et *** that TDP-43 acts as a steric block in STMN2 pre-mRNA processing preventing inclusion of a deleterious cryptic exon,and present strategies for substituting this function to compensate for the loss of nuclear TDP-43 in a variety of neurodegenerative diseases(NDs)including amyotrophic lateral sclerosis(ALS).1 Stathmin-2(STMN2)is a microtubule-associated protein speci-fically expressed in neurons and required for axon outgrowth and maintenance,as well as for axon regeneration after injury in vitro.

关键词： Stathmin diseases

Chemical-Abrasion U-Pb zircon geochronology reveals 150 Myr of partial melting events in the Archean crust of the São Francisco Craton

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Geoscience Frontiers 2022年第5期13卷 169-189页

作者： lorena Martins Cristiano Lana Ariela Mazoz Tiago Novo Applied Isotope Research Group Departamento de GeologiaEscola de MinasUniversidade Federal de Ouro PretoMorro do CruzeiroOuro PretoMG35400-000Brazil Universidade Federal de Minas Gerais Programa de Pós-Graduação em GeologiaIGC-CPMTCCampus PampulhaAv.Antônio Carlos 6627Belo HorizonteMG31270-901Brazil

Field observations and CA-LA-ICP-MS U–Pb zircon ages and Hf isotope compositions obtained from migmatitic orthogneisses and granitoids from the Belo Horizonte Complex,southern São Francisco Craton,indicate a major period of partial melting and production of felsic rocks in the *** observations show that the complex is an important site for studying partial melting processes of Archean crystalline *** of the complex exposes fine-grained stromatic migmatites that are intruded by multiple leucogranitic veins and sheeted *** migmatites and leucogranite sheets are crosscut by several phases of granitoid batholiths and small granitic bodies;both of which are closely associated with the host banded *** abrasion followed by detailed cathodoluminescence imaging revealed a wide variety of zircon textures that are consistent with a long-lived period of partial melting and crustal *** of U-Pb and Hf isotopes disclose the complex as part of a much wider crustal segment,encompassing the entire southern part of the São Francisco *** of available U-Pb ages suggests that this crustal segment was consolidated sometime between 3000 Ma and 2900 Ma and that it experienced three main episodes of partial melting before stabilization at 2600 *** partial melting episodes took place between 2750 Ma and 2600 Ma as a result of tectonic accretion and peeling off the lithospheric mantle and lower *** process is likely responsible for the emplacement of voluminous potassic granitoids across the entire São Francisco *** believe that the partial melting of Meso-Archean crystalline crust and production of potassic granitoids are linked to a fundamental shift in the tectonics of the craton,which was also responsible for the widespread intrusion of large syenitic bodies in the northern part of the craton,and the construction of layered mafic–ultramafic intrusions to the south of the BHC.

关键词： Archean São Francisco Craton Crustal reworking U-Pb geochronology Lu-Hf isotopes

Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

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Journal of Cancer Therapy 2024年第4期15卷 164-178页

作者： María I. Pamies Ramón Diana Ibarra Anguita Paula Rodríguez Payá Alvaro Muñoz Abad David Sánchez García María Valero Revert Beatriz Grau Mirete Mariano Martínez Marín Alicia Calero Amaro lorena Rodríguez Cazalla Javier Gallego Plazas Medical Oncology Department Elche University Hospital Elche (Alicante) Spain General Surgery Department Elche University Hospital Elche (Alicante) Spain General Surgery Department Vega Baja Hospital Orihuela (Alicante) Spain

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which a

关键词： Real-World Evidence Localized Pancreatic Cancer