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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki ignacio sancho-martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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

Navigating medial patellotibial ligament reconstruction:Clinical perspectives and surgical strategies

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World Journal of Clinical Cases 2025年第1期13卷 6-10页

作者： Juan Pablo Zicaro ignacio Garcia-Mansilla Division of Knee Hospital Italiano de Buenos AiresBuenos Aires 1109Argentina

The surgical approach for patellar instability usually refers to reconstruction of the medial patellofemoral ligament associated with an osteotomy of the tibial tuberosity or a trochleoplasty when *** medial patellotibial ligament and the medial patellomeniscal ligament are secondary stabilizers of the *** this,both the medial patellotibial and patellofemoral ligaments aid in patellar rotation and tilt when the knee is flexed beyond 45°.The medial patellotibial ligament plays a particularly important role in the final stages of stretching in extension and between 40 degrees to 90 degrees of *** clinical relevance and surgical indications for medial patellotibial ligament reconstruction associated with medial patellofemoral ligament reconstruction are still *** editorial explores the surgical indications and clinical results for medial patellotibial ligament reconstruction to improve readers’understanding of this technique,especially because reported clinical outcomes have remained sparse.

关键词： Medial patellotibial ligament Patellar instability Reconstruction Surgical

Metabolism of tissue macrophages in homeostasis and pathology

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Cellular & Molecular Immunology 2022年第3期19卷 384-408页

作者： Stefanie K.Wculek Gillian Dunphy ignacio Heras-Murillo Annalaura Mastrangelo David sancho Immunobiology Laboratory Centro Nacional de Investigaciones Cardiovasculares(CNIC)Melchor Fernández Almagro 3Madrid28029Spain

Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy and structural *** emerging field of immunometabolism highlights the importance of cellular metabolism for the maintenance and activities of immune *** are embryo-or adult bone marrow-derived leukocytes that are key for healthy tissue homeostasis but can also contribute to pathologies such as metabolic syndrome,atherosclerosis,fibrosis or *** metabolism has largely been studied in ***,different organs contain diverse macrophage populations that specialize in distinct and often tissue-specific *** context specificity creates diverging metabolic challenges for tissue macrophage populations to fulfill their homeostatic roles in their particular microenvironment and conditions their response in pathological ***,we outline current knowledge on the metabolic requirements and adaptations of macrophages located in tissues during homeostasis and selected diseases.

关键词： Tissue macrophages metabolism homeostasis pathology tissue regeneration

Management of end-stage erectile dysfunction and stress urinary incontinence after radical prostatectomy by simultaneous dual implantation using a single trans-scrotal incision： surgical technique and outcomes

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Asian Journal of Andrology 2015年第5期17卷 792-796,I0008页

作者： Juan I martinez-Salamanca Estefania Linares Espinos ignacio Moncada Luis Del Portillo Joaquin Carballido Department of Urology Hospital Universitario Puerta de Hierro Majadahonda Autonomous University of Madrid Madrid 28222 Spain Hospital Universitario Infanta Sofia Madrid 28702 Spain Hospital La Zarzuela Madrid 28023 Spain

Stress urinary incontinence （SUI） and end-stage erectile dysfunction （ED） after radical prostatectomy （RP） can decrease a patient＇s quality of life （QoL）. We describe a surgical technique involving scrotal incision for simultaneous dual implantation of an artificial urinary sphincter （AUS） and an inflatable penile prosthesis （IPP）. Patients with moderate to severe SUI （〉3 pads per day） and end-stage ED following RP were selected for dual implantation. An upper transverse scrotal incision was made, followed by bulbar urethra dissection and AUS cuff placement. Through the same incision, the corpora cavernosa was exposed, and an IPP positioned. Followed by extraperitoneal reservoirs placement and pumps introduced in the scrotum. Short-term, intra- and post-operative complications; continence status and erectile function; and patient satisfaction and QoL were recorded. A total of 32 patients underwent dual implantation. Early AUS-related complications were： AUS reservoir migration and urethral erosion. One case of distal corporal extrusion occurred. No prosthetic infection was reported. Over 96% of patients were socially the continent （≤1 pad per day） and 〉95% had sufficient erections for intercourse. Limitations of the study were the small number of patients, the lack of the control group using a perineal approach for AUS placement and only a 12 months follow-up. IPP and AUS dual implantation using a single scrotal incision technique is a safe and effective option in patients with SUI and ED after RP. Further studies on larger numbers of patients are warranted.

关键词： artificial urinary sphincter erectile dysfunction penile prosthesis radical prostatectomy single scrotal incision urinary incontinence

Overview of the anterolateral complex of the knee

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World Journal of Clinical Cases 2022年第24期10卷 8474-8481页

作者： ignacio Garcia-Mansilla Juan Pablo Zicaro Ezequiel Fernando martinez Juan Astoul Carlos Yacuzzi MatiasCosta-Paz Knee Surgery Hospital Italiano de Buenos AiresBuenos Aires 1199Argentina

In the last few years,much more information on the anterolateral complex of the knee has become *** has now been demonstrated how it works in conjunction with the anterior cruciate ligament(ACL)controlling anterolateral rotatory *** studies have shown that the anterolateral complex(ALC)has a role as a secondary stabilizer to the ACL in opposing anterior tibial translation and internal tibial *** is of utmost importance that surgeons comprehend the intricate anatomy of the entire anterolateral aspect of the *** most studies have only focused on the anterolateral ligament(ALL),the ALC of the knee consists of a functional unit formed by the layers of the iliotibial band combined with the anterolateral joint *** interest has also been given to imaging evaluation using magnetic resonance and several studies have targeted the evaluation of the ALC in the setting of ACL *** are inconsistent with a lack of association between magnetic resonance imaging evidence of injury and clinical *** ACL reconstruction may not always reestablish knee rotatory stability in patients with associated ALC *** such cases,additional procedures,such as anterolateral reconstruction or lateral tenodesis,may be *** are several techniques available for ALL *** options include the iliotibial band,gracilis or semitendinosus tendon autograft,or allograft.

关键词： Anterolateral complex Knee instability Anterolateral ligament Anterior cruciate ligament reconstruction

Loop-mediated isothermal amplification of single pollen grains

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Journal of Integrative Plant Biology 2014年第8期56卷 741-748页

作者： Ali Bekta ignacio Chapela Department of Environmental Science Policy and Management University of California Berkeley

The polymerase chain reaction （PCR） has been a reliable and fruitful method for many applications in ecology. Nevertheless, unavoidable technical and instrumental require- ments of PCR have limited its widespread application in field situations. The recent development of isothermal DNA amplifica- tion methods provides an alternative to PCR, which circumvents key limitations of PCR for direct amplification in the field. Being able to analyze DNA in the pollen cloud of an ecosystem would provide very useful ecological information, yet would require a field-enabled, high-throughput method for this potential to be realized. Here, we demonstrate the applicability of the loop- mediated DNA amplification method （LAMP）, an isothermal DNA amplification technique, to be used in pollen analysis. Wedemonstrate that LAMP can provide a reliable method to identify species from the pollen cloud, and that it can amplify successfully with sensitivity down to single pollen grains, thus opening the possibility of field-based, high-throughput analysis.

关键词： DNA amplification field-diagnostics loop-mediated DNAamplification method pollen

El nuevo desarrollo sostenible de China

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今日中国（西文版） 2022年第7期 30-31页

作者： JOSE ignacio martinez CORTES 不详

Spinal cord injury drives chronic brain changes

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Neural Regeneration Research 2017年第7期12卷 1044-1047页

作者： ignacio Jure Florencia Labombarda Laboratorio de Bioquimica Neuroendocrina Instituto de Biologia y Medicina Experimental CONICET Buenos Aires Argentina Departamento de Bioqulmica Humana Facultad de Medicina Universidad de Buenos Aires Buenos Aires Argentina

Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury,although cognitive impairments have been reported in these *** cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in *** the hippocampus,neurogenesis is reduced and reactive gliosis *** longterm abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

关键词： spinal cord injury brain neurodegeneration neuroinflammation