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Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.
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AIM: To compare the biomechanical properties of three different sternal closure techniques in a 3D-printed bone model of a sternum from a 30-kg dog. METHODS: Median sternotomy was performed on a total of 90 three-dimensional (3D) copies of a polycarbonate (PC) model of a sternum, generated from the CT images of the sternum of a 30-kg German Shepherd dog. Three different methods were used to repair the sternotomies: polydioxanone suture (group PDS, n = 30), stainless steel bone staples (group SS, n = 30), and nitinol bone staples (group NS, n = 30). Each repair method was tested by applying tensile force in one of three ways (longitudinally, laterally, or torsionally) resulting in a sample size of n = 10 for each repair method-loading combination. In all experiments, the loads at 1-mm and 2-mm gap formation, failure, and the displacement at the failure point were measured. RESULTS: In lateral distraction and longitudinal shear tests, NS and SS staple repairs required application of significantly greater force than PDS across all displacement criteria (1 and 2 mm). NS exhibited significantly greater failure load than PDS. In torsion tests, NS required significantly greater application of force compared to SS or PDS at all displacement criteria (1 and 2 mm) and exhibited a greater failure load than PDS. In terms of displacement at failure point, PDS suture showed more displacement than SS or NS across all experiments (laterally, longitudinally, torsionally). CONCLUSIONS: In this study, bone staples were mechanically superior to PDS suture in median sternotomy closure using 3D-printed bone model in terms of 1-mm, 2-mm displacement loads, and displacement at failure. NS had a higher failure load than PDS under lateral, longitudinal, and torsional distraction. CLINICAL RELEVANCE: These study results imply that bone staples can be considered as an alternative surgical method for median sternotomy closure in dogs.
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Impresión Tridimensional , Esternotomía , Suturas , Animales , Suturas/veterinaria , Perros , Fenómenos Biomecánicos , Esternotomía/veterinaria , Esternotomía/métodos , Grapado Quirúrgico/veterinaria , Grapado Quirúrgico/métodos , Grapado Quirúrgico/instrumentación , Esternón/cirugía , Modelos Anatómicos , Técnicas de Sutura/veterinariaRESUMEN
The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.
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Pediatría , Humanos , Malasia , Niño , Pediatría/ética , Pediatría/normas , Investigación Biomédica/ética , Investigación Biomédica/normasRESUMEN
Although not as common as solitary lesions, multiple schwannomas do occur, even in single nerve lesions. We report a rare case of a 47-year-old female patient who presented with multiple schwannomas with inter-fascicular invasion in the ulnar nerve above the cubital tunnel. Preoperative MRI revealed a 10-cm multilobulated tubular mass along the ulnar nerve above the elbow joint. During excision under 4.5° loupe magnification, we separated three ovoid yellow-colored neurogenic tumors of different sizes, but there were still remaining lesions as it was difficult to completely separate lesions from the ulnar nerve due to the risk of iatrogenic nerve ulnar nerve injury. The operative wound was closed. Postoperative biopsy confirmed the diagnosis of the three schwannomas. During the follow-up, the patient recovered without neurological symptom or limitations in range of motion, and there were no neurological abnormalities. At 1year after surgery, small lesions remained in the most proximal part. However, the patient had no clinical symptoms and was satisfied with the surgical results. Although a long-term follow-up is necessary for this patient, we were able to obtain good clinical and radiological results.
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Articulación del Codo , Neurilemoma , Femenino , Humanos , Persona de Mediana Edad , Nervio Cubital/patología , Nervio Cubital/cirugía , Estudios de Seguimiento , Codo , Neurilemoma/diagnóstico , Neurilemoma/patología , Neurilemoma/cirugíaRESUMEN
Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.
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Osteoporosis , Fracturas de la Columna Vertebral , Asia/epidemiología , Humanos , Tamizaje Masivo , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Osteoporosis/terapia , Nivel de AtenciónRESUMEN
The risks for hip fracture and vertebral fracture, but not the risk for distal radius fracture, were significantly higher in the blindness group than in the control group with a maximum 12-year follow-up. PURPOSE: To evaluate the influence of visual impairment on the risk for osteoporotic fractures at common sites: hip, thoracic/lumbar vertebra, and distal radius. METHODS: This longitudinal follow-up study used a database of a national sample cohort from 2002 to 2013 provided by the Korean National Health Insurance Service. Of a total of 1,125,691 subjects, 3918 patients with visual impairment and age ≥ 50 years were enrolled in a 1:4 ratio; 15,672 control participants were matched for age, sex, income, and region of residence. Stratified Cox proportional-hazards models were used to evaluate the crude and adjusted (for steroid medication, rheumatoid arthritis, depression, osteoporosis, diabetes mellitus, and stroke history) hazard ratios (HRs) for each fracture site. Fracture diagnoses were based on the ICD-10 codes: hip fracture (S720, S721, S722), vertebral fracture (S220, S320), and distal radius fracture (S525). RESULTS: The HRs for hip and vertebral fracture were significantly higher in the blindness group (adjusted HR = 2.46, p < 0.001 for hip fracture; adjusted HR = 1.42, p = 0.020 for thoracic/lumbar vertebral fracture) than in the matched control group. However, the HR for distal radius fracture was not higher in the blindness group. The HRs for all three fracture sites were not significantly higher in the non-blindness visual impairment group after adjustment. CONCLUSION: The risks for hip fracture and vertebral fracture were significantly higher in the blindness group. However, the risk for distal radius fracture was not related to visual impairment including blindness.
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Fracturas de Cadera , Fracturas Osteoporóticas , Fracturas del Radio , Fracturas de la Columna Vertebral , Ceguera , Estudios de Seguimiento , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas del Radio/epidemiología , Factores de Riesgo , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiologíaRESUMEN
The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:⢠The FLS business case.⢠Planning the FLS patient pathway.⢠The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:⢠78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.⢠87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.⢠26.1% of respondents stated that their FLS has sustainable funding.⢠The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.
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Osteoporosis , Fracturas Osteoporóticas , Asia/epidemiología , Humanos , Osteoporosis/prevención & control , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Prevención SecundariaRESUMEN
Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. INTRODUCTION: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. METHODS: Clinical perspective and updated literature search. RESULTS: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. CONCLUSIONS: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.
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Algoritmos , Osteoporosis Posmenopáusica , Fracturas Osteoporóticas , Anciano , Densidad Ósea , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Medición de Riesgo , Factores de RiesgoRESUMEN
The article 'Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures',written by J. A. Kanis, was originally published Online First without Open Access. After publication in volume [#], issue [#] and page [#-#], the author decided to opt for Open Choice and to make the article an Open Access publication.
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We propose a DSP scheme with soft-output maximum likelihood sequence equalizer (sMLSE) and low-overhead (8.51%) low density parity check (LDPC) code for C-band PAM-4 transmission. In order to apply LDPC code in conjunction with MLSE, the conventional hard-output MLSE is modified to have a soft-output value by using the Max-log BCJR algorithm. The feasibility of this approach is experimentally investigated in a 56 Gb/s C-band PAM-4 system. In order to investigate the advantages of the proposed scheme, we compare the performance of the sMLSE-LDPC code to that of MLSE-RS code. Relatively, additional OSNR gain of 0.6 dB ~2.1 dB is achieved. The variation of the relative OSNR gain depends on the burst errors, which originate from the power fading effect. By using an interleaver that spreads burst errors in time, one can see that the relative OSNR gain is improved as 1.6 dB ~2.1 dB. Using the proposed scheme with the interleaver, one can see that the 30 km transmission of 56 Gb/s PAM-4 in the C-band was experimentally demonstrated.
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In a heterogeneous environment containing multiple patches that may deplete and renew, a forager should be able to detect the quality of food resources within and among patches and choose to exploit them to best maximize returns. From the predator's perspective, the behavioral responses of the prey in a patch will be perceived as depletion when they retreat to refuge and renewal when they reemerge. A predator encountering responsive prey should manage predation risk, and thus behavioral resource depression, by optimally timing its return time to the patch based on prey behavior. We evaluated the foraging decisions of a predator that encountered patches differing in size of the refuge and prey density. We used little egrets and goldfish as predators and prey in an environment that contained three patches (pools). We manipulated prey density and refuge size and availability (using covers) and observed predator foraging behavior. When the egret had previously caught a fish it did not discriminate between the pools, and the return time was similar for all cover types. The fish densities also did not affect the egret decisions to return to pools. However, when it failed to catch fish, it returned sooner to the pool containing the small cover than the larger one. Additionally, after failing to catch fish in patches containing the highest prey density, the egrets subsequently preferred to return to such patches sooner. We show experimentally that previous failures influence the foraging decisions of a predator choosing how quickly to return to a previously visited patch.
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Aves , Conducta Predatoria , Animales , PecesRESUMEN
Although infiltrating macrophages influence many pathological processes after spinal cord injury (SCI), the intrinsic molecular mechanisms that regulate their function are poorly understood. A major hurdle has been dissecting macrophage-specific functions from those in other cell types as well as understanding how their functions change over time. Therefore, we used the RiboTag method to obtain macrophage-specific mRNA directly from the injured spinal cord in mice and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process, and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.SIGNIFICANCE STATEMENT The intrinsic molecular mechanisms that regulate macrophage function after spinal cord injury (SCI) are poorly understood. We obtained macrophage-specific mRNA directly from the injured spinal cord and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.
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Metabolismo de los Lípidos/fisiología , Macrófagos/metabolismo , Traumatismos de la Médula Espinal/patología , Animales , Trasplante de Médula Ósea , Antígenos CD36/genética , Antígenos CD36/metabolismo , Movimiento Celular/genética , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica/genética , Hemaglutininas/metabolismo , Antígenos Comunes de Leucocito/genética , Antígenos Comunes de Leucocito/metabolismo , Metabolismo de los Lípidos/genética , Locomoción , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , ARN Ribosómico/administración & dosificación , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Transducción de Señal/genética , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/cirugíaRESUMEN
Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.
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Alternativas a las Pruebas en Animales/normas , Pruebas Cutáneas/normas , Pruebas de Toxicidad/normas , Cooperación Internacional , Estándares de ReferenciaRESUMEN
The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat.
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Encéfalo/diagnóstico por imagen , Fatiga/fisiopatología , Calor , Imagen por Resonancia Magnética , Encéfalo/fisiopatología , Ejercicio Físico , Fiebre/fisiopatología , HumanosRESUMEN
Background: Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population. Patients and methods: This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2. The primary endpoint was the objective response rate. Results: A total of 18 patients were enrolled in this study between July 2013 and October 2015. Patients were aged 35-71 years; three had a performance status of 2, and the majority were a heavily pretreated population (≥ two different previous chemotherapy regimens in 72% of the patients). Among the 17 evaluable patients, three had a partial response (objective response rate = 18%) and eight had a stable disease (disease control rate = 65%). Among these patients, the partial response or disease stabilization was durable for more than 6 months in eight patients. Vandetanib also showed a progression-free survival of 4.5 months, and an overall survival of 11.6 months during a median follow-up duration of 14 months. The safety profile was comparable with previous studies of vandetanib. Most vandetanib-related adverse events were mild with prevalent hypertension and rash (in >70% of patients). Grade 3 toxicity included hypertension (n = 3), QT prolongation (2), and elevation of aminotransferases (1), and as a consequence the dose was reduced in four patients. There were no adverse events associated with grade 4 or 5 toxicity. Conclusion: Vandetanib is moderately active in pretreated patients with advanced NSCLC-harboring RET rearrangements.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Piperidinas/uso terapéutico , Proteínas Proto-Oncogénicas c-ret/genética , Quinazolinas/uso terapéutico , Adenocarcinoma/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Resultado del Tratamiento , Carga TumoralRESUMEN
Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.
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Carcinoma/genética , Transformación Celular Neoplásica/genética , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Adulto , Femenino , Reordenamiento Génico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Proteínas de Unión al ARN/genética , Factores de Transcripción , TranscriptomaRESUMEN
OBJECTIVE: Few studies have compared the risk of recurrent falls across different types of analgesic use, and with limited adjustment for potential confounders (e.g., pain/depression severity). We assessed analgesic use and the subsequent risk of recurrent falls, among participants with or at risk of knee osteoarthritis (OA). METHODS: A longitudinal analysis included 4231 participants aged 45-79 years at baseline with 4-year follow-up from the Osteoarthritis Initiative (OAI) cohort study. We grouped participants into six mutually exclusive subgroups based on annually assessed analgesic use in the following hierarchical order of analgesic/central nervous system (CNS) potency: use of (1) opioids, (2) antidepressants, (3) other prescription pain medications, (4) over-the-counter (OTC) pain medications, (5) nutraceuticals, and (6) no analgesics. We used multivariable modified Poisson regression models with a robust error variance to estimate the effect of analgesic use on the risk of recurrent falls (≥2) in the following year, adjusted for demographics and health status/behavior factors. RESULTS: Opioid use increased from 2.7% at baseline to 3.6% at the 36-month visit (>80% using other analgesics/nutraceuticals), while other prescription pain medication use decreased from 16.7% to 11.9% over this time period. Approximately 15% of participants reported recurrent falls. Compared to those not using analgesics, participants who used opioids and/or antidepressants had a 22-25% increased risk of recurrent falls (opioids: RRadjusted = 1.22, 95% CI = 1.04-1.45; antidepressants: RRadjusted = 1.25, 95% CI = 1.10-1.41). CONCLUSION: Participants with or at risk of knee OA who used opioids and antidepressants with/without other analgesics/nutraceuticals may have an increased risk of recurrent falls after adjusting for potential confounders. Use of opioids and antidepressants warrants caution.
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Accidentes por Caídas/estadística & datos numéricos , Analgésicos/efectos adversos , Osteoartritis de la Rodilla/tratamiento farmacológico , Anciano , Analgésicos Opioides/efectos adversos , Antidepresivos/efectos adversos , Factores de Confusión Epidemiológicos , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/epidemiología , Recurrencia , Medición de Riesgo/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiologíaRESUMEN
"Partially tethering" a thin film of a polymer melt by covalently attaching to the substrate a fraction of the chains in an unentangled melt dramatically increases the relaxation time of the surface height fluctuations. This phenomenon is observed even when the film thickness, h, is 20 times the unperturbed chain radius, Rg,tethered, of the tethered chains, indicating that partial tethering is more influential than any physical attraction with the substrate. Furthermore, a partially tethered layer of a low average molecular weight of 5k showed much slower surface fluctuations than did a reference layer of pure untethered chains of much greater molecular weight (48k), so the partial tethering effect is stronger than the effects of entanglement and increase in glass transition temperature, Tg, with molecular weight. Partial tethering offers a means of tailoring these fluctuations which influence wetting, adhesion, and tribology of the surface.
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In this study, 21 simple sequence repeat (SSR) markers were used to evaluate the genetic diversity and population structure among 77 Perilla accessions from high-latitude and middle-latitude areas of China. Ninety-five alleles were identified with an average of 4.52 alleles per locus. The average polymorphic information content (PIC) and genetic diversity values were 0.346 and 0.372, respectively. The level of genetic diversity and PIC value for cultivated accessions of Perilla frutescens var. frutescens from middle-latitude areas were higher than accessions from high-latitude areas. Based on the dendrogram of unweighted pair group method with arithmetic mean (UPGMA), all accessions were classified into four major groups with a genetic similarity of 46%. All accessions of the cultivated var. frutescens were discriminated from the cultivated P. frutescens var. crispa. Furthermore, most accessions of the cultivated var. frutescens collected in high-latitude and middle-latitude areas were distinguished depending on their geographical location. However, the geographical locations of several accessions of the cultivated var. frutescens have no relation with their positions in the UPGMA dendrogram and population structure. This result implies that the diffusion of accessions of the cultivated Perilla crop in the northern areas of China might be through multiple routes. On the population structure analysis, 77 Perilla accessions were divided into Group I, Group II, and an admixed group based on a membership probability threshold of 0.8. Finally, the findings in this study can provide useful theoretical knowledge for further study on the population structure and genetic diversity of Perilla and benefit for Perilla crop breeding and germplasm conservation.