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Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm 'HYENA' to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking based on tumor whole-genome and transcriptome sequencing data. HYENA detects genes whose elevated expression is associated with somatic SVs by using a rank-based regression model. We systematically analyze 1146 tumors across 25 types of adult tumors and identify a total of 108 candidate oncogenes including many non-coding genes. A long non-coding RNA TOB1-AS1 is activated by various types of SVs in 10% of pancreatic cancers through altered 3-dimensional genome structure. We find that high expression of TOB1-AS1 can promote cell invasion and metastasis. Our study highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression.
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INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, nâ =â 98 646) who received continuous androgen deprivation therapy (nâ =â 29 453), died of prostate cancer (2013-2018, nâ =â 3864), and received life-prolonging therapy for mCRPC (nâ =â 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs. RESULTS: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (nâ =â 447) or started BTA only after first bone radiotherapy (nâ =â 401). More patients received denosumab (nâ =â 825, 77%) than zoledronic acid (nâ =â 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (ORâ =â 1.0, Pâ =â .023), de novo metastases (ORâ =â 1.4, Pâ =â .005), medical oncologist involvement (ORâ =â 2.0, Pâ =â .007), diagnosis 2012-2017 versus 2007-2011 (ORâ =â 0.75, Pâ =â .034), and academic center (ORâ =â 0.061, Pâ =â .007). CONCLUSION: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.
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OBJECTIVE: To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection. BACKGROUND: Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens. METHODS: An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers. RESULTS: A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD. CONCLUSIONS: A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Predicción , Cirugía Torácica Asistida por Video , Microambiente TumoralRESUMEN
Primary care (PC) is a unique clinical specialty and research discipline with its own perspectives and methods. Research in this field uses varied research methods and study designs to investigate myriad topics. The diversity of PC presents challenges for reporting, and despite the proliferation of reporting guidelines, none focuses specifically on the needs of PC. The Consensus Reporting Items for Studies in Primary Care (CRISP) Checklist guides reporting of PC research to include the information needed by the diverse PC community, including practitioners, patients, and communities. CRISP complements current guidelines to enhance the reporting, dissemination, and application of PC research findings and results. Prior CRISP studies documented opportunities to improve research reporting in this field. Our surveys of the international, interdisciplinary, and interprofessional PC community identified essential items to include in PC research reports. A 2-round Delphi study identified a consensus list of items considered necessary. The CRISP Checklist contains 24 items that describe the research team, patients, study participants, health conditions, clinical encounters, care teams, interventions, study measures, settings of care, and implementation of findings/results in PC. Not every item applies to every study design or topic. The CRISP guidelines inform the design and reporting of (1) studies done by PC researchers, (2) studies done by other investigators in PC populations and settings, and (3) studies intended for application in PC practice. Improved reporting of the context of the clinical services and the process of research is critical to interpreting study findings/results and applying them to diverse populations and varied settings in PC.Annals "Online First" article.
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Lista de Verificación , Proyectos de Investigación , Humanos , Consenso , Informe de Investigación , Atención Primaria de SaludRESUMEN
NAPCRG celebrated 50 years of leadership and service at its 2022 meeting. A varied team of primary care investigators, clinicians, learners, patients, and community members reflected on the organization's past, present, and future. Started in 1972 by a small group of general practice researchers in the United States, Canada, and the United Kingdom, NAPCRG has evolved into an international, interprofessional, interdisciplinary, and intergenerational group devoted to improving health and health care through primary care research. NAPCRG provides a nurturing home to researchers and teams working in partnership with individuals, families, and communities. The organization builds upon enduring values to create partnerships, advance research methods, and nurture a community of contributors. NAPCRG has made foundational contributions, including identifying the need for primary care research to inform primary care practice, practice-based research networks, qualitative and mixed-methods research, community-based participatory research, patient safety, practice transformation, and partnerships with patients and communities. Landmark documents have helped define classification systems for primary care, responsible research with communities, the central role of primary care in health care systems, opportunities to revitalize generalist practice, and shared strategies to build the future of family medicine. The future of health and health care depends upon strengthening primary care and primary care research with stronger support, infrastructure, training, and workforce. New technologies offer opportunities to advance research, enhance care, and improve outcomes. Stronger partnerships can empower primary care research with patients and communities and increase commitments to diversity and quality care for all. NAPCRG offers a home for all partners in this work.
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Investigación Participativa Basada en la Comunidad , Atención a la Salud , Humanos , Estados Unidos , Canadá , Calidad de la Atención de Salud , Atención Primaria de SaludRESUMEN
Pupillometry has been found to be correlated with activity of cholinergic and noradrenergic neuromodulator systems. These systems regulate the level of cortical arousal and therefore perception, attention, and memory. Here, we tested how different types of pupil size variance (prestimulus baseline and prestimulus hippus power) may correlate with behavioral and event-related potentials (ERPs). We recorded pupil size and ERPs while participants were presented with a series of words and then asked whether the words had been in the initial list when they were later presented intermixed with unpresented words. We found that a smaller prestimulus baseline pupil size during the study phase was associated with better memory performance. Study items also evoked a larger P3 response at presentation and a greater old/new memory ERP effect at test when prestimulus pupil size was small rather than large. Prestimulus hippus power was found to be a between-subjects factor affecting the robustness of memory encoding with less power being associated with a greater old/new memory ERP effect. These results provide evidence relating memory and ERPs to variables defined on pupil size that are thought to reflect varying states of parasympathetic and sympathetic arousal.
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Electroencefalografía , Pupila , Nivel de Alerta/fisiología , Atención , Potenciales Evocados , Humanos , Pupila/fisiologíaRESUMEN
The central nervous system (CNS) is endowed with a specialized cerebrospinal fluid (CSF)/lymph network which removes toxic molecules and metabolic by-products from the neural parenchyma; collectively, this has been named the glymphatic system. It allows CSF located in the subarachnoid space which surrounds the CNS to enter the depths of the brain and spinal cord by means of Virchow-Robin perivascular and perivenous spaces. CSF in the periarterial spaces is transferred across the astrocytic end feet which line these spaces aided by AQ4 channels; in the interstitium, the fluid moves via convection through the parenchyma to be eventually discharged into the perivenous spaces. As it passes through the neural tissue, the interstitial fluid flushes metabolic by-products and extracellular toxins and debris into the CSF of the perivenous spaces. The fluid then moves to the surface of the CNS where the contaminants are absorbed into true lymphatic vessels in the dura mater from where it is shunted out of the cranial vault to the cervical lymph nodes. Pineal melatonin released directly into the CSF causes the concentration of this molecule to be much higher in the CSF of the third ventricle than in the blood. After the ventricular melatonin enters the subarachnoid and Virchow-Robin spaces it is taken into the neural tissue where it functions as a potent antioxidant and anti-inflammatory agent. Experimental evidence indicates that it removes pathogenic toxins, e.g., amyloid-ß and others, from the brain to protect against neurocognitive decline. Melatonin levels drop markedly during aging, coincident with the development of several neurodegenerative diseases and the accumulation of the associated neurotoxins.
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Melatonina , Encéfalo/fisiología , Líquido Cefalorraquídeo/metabolismo , Melatonina/metabolismoRESUMEN
PURPOSE: The aim of the study was to evaluate cystic thymic masses by using computed tomography (CT) and magnetic resonance (MR) scoring systems to differentiate nonneoplastic thymic cysts from cystic thymic neoplasms. METHODS: This retrospective multisite study included adult patients who underwent CT and MR imaging of the chest between 2007 and 2020 with any of the following impressions on cross-sectional imaging studies: "thymic mass with cystic component," "unilocular or multilocular cystic thymic lesion," "complex thymic cyst," "thymic cyst with hemorrhage." Two blinded radiologists reviewed and recorded specific imaging features as well as overall impressions on both CT and MR using a Likert scale scoring system. Data were analyzed, and diagnostic accuracy of CT and MR was compared using areas under the receiver operating characteristic curves (AUC). RESULTS: Fifty-six patients were included, of which 45 (80%) had benign masses. Total of 21 patients (38%) had indeterminate scores on CT of which 3 (14%) were malignant, while only 6 (11%) had indeterminate scores on MR and 1 was malignant. Magnetic resonance scoring system (AUC, 0.95) performed better than CT scoring system (AUC, 0.86) in distinguishing benign versus malignant lesions (P = 0.06). Lack of enhancement within the mass was completely predictive of benign etiology (P < 0.001). Wall thickness of an enhancing cyst was predictive of malignancy, with AUC 0.93. CONCLUSIONS: Magnetic resonance yielded higher specificity allowing a larger number of lesions to be confidently assigned a benign diagnosis. This could help in averting unnecessary follow-up, biopsies, or surgery. The authors recommend follow-up imaging with MR for prevascular masses, even those appearing "solid" on CT.
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Quiste Mediastínico , Timoma , Neoplasias del Timo , Adulto , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Quiste Mediastínico/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias del Timo/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
The early identification of youth at risk for restraint incidents is an important next step to reducing the likelihood of such incidents. Yet, the extant research has not comprehensively investigated the idiographic factors that contribute to the restraint of youth in psychiatric residential treatment facilities (PRTFs). The current study investigated client-level predictors of restraint incidents, with specific emphasis on youth client trauma history and traumatic stress symptoms as assessed at admission. Participants were children and adolescents (N = 150; 55.3% female, 66.7% White, 33.3% Black or biracial) aged 6-17 (M = 11.8 years) admitted to a PRTF in the northeastern United States. A negative binomial regression with maximum likelihood estimation was conducted to examine the relative contributions of age, gender, length of stay, number of psychiatric diagnoses, body mass index (BMI), and traumatic stress symptoms at intake to the frequency of restraint incidents. The model was significant, χ2 (6, N = 150) = 30.326, p < .001, and both length of stay, ß = .005, p < .001, IRR = 1.005, and traumatic stress symptoms at intake, ß = .072, p = .007, IRR = 1.074, were identified as significant predictors within the model. Although length of stay is an obvious predictor of restraint incidents, the current study is the first of which we are aware to identify traumatic stress symptoms at intake as a potential indicator of restraint frequency following admission. Clinical implications of these results are discussed.
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Tratamiento Domiciliario , Trastornos por Estrés Postraumático , Adolescente , Niño , Femenino , Hospitalización , Humanos , Masculino , Restricción Física , Trastornos por Estrés Postraumático/psicologíaRESUMEN
One of the most challenging issues in the routing protocols for underwater wireless sensor networks (UWSNs) is the occurrence of void areas (communication void). That is, when void areas are present, the data packets could be trapped in a sensor node and cannot be sent further to reach the sink(s) due to the features of the UWSNs environment and/or the configuration of the network itself. Opportunistic routing (OR) is an innovative prototype in routing for UWSNs. In routing protocols employing the OR technique, the most suitable sensor node according to the criteria adopted by the protocol rules will be elected as a next-hop forwarder node to forward the data packets first. This routing method takes advantage of the broadcast nature of wireless sensor networks. OR has made a noticeable improvement in the sensor networks' performance in terms of efficiency, throughput, and reliability. Several routing protocols that utilize OR in UWSNs have been proposed to extend the lifetime of the network and maintain its connectivity by addressing void areas. In addition, a number of survey papers were presented in routing protocols with different points of approach. Our paper focuses on reviewing void avoiding OR protocols. In this paper, we briefly present the basic concept of OR and its building blocks. We also indicate the concept of the void area and list the reasons that could lead to its occurrence, as well as reviewing the state-of-the-art OR protocols proposed for this challenging area and presenting their strengths and weaknesses.
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Algoritmos , Tecnología Inalámbrica , Reproducibilidad de los Resultados , Redes de Comunicación de Computadores , ComunicaciónRESUMEN
Partial information decomposition allows the joint mutual information between an output and a set of inputs to be divided into components that are synergistic or shared or unique to each input. We consider five different decompositions and compare their results using data from layer 5b pyramidal cells in two different studies. The first study was on the amplification of somatic action potential output by apical dendritic input and its regulation by dendritic inhibition. We find that two of the decompositions produce much larger estimates of synergy and shared information than the others, as well as large levels of unique misinformation. When within-neuron differences in the components are examined, the five methods produce more similar results for all but the shared information component, for which two methods produce a different statistical conclusion from the others. There are some differences in the expression of unique information asymmetry among the methods. It is significantly larger, on average, under dendritic inhibition. Three of the methods support a previous conclusion that apical amplification is reduced by dendritic inhibition. The second study used a detailed compartmental model to produce action potentials for many combinations of the numbers of basal and apical synaptic inputs. Decompositions of the entire data set produce similar differences to those in the first study. Two analyses of decompositions are conducted on subsets of the data. In the first, the decompositions reveal a bifurcation in unique information asymmetry. For three of the methods, this suggests that apical drive switches to basal drive as the strength of the basal input increases, while the other two show changing mixtures of information and misinformation. Decompositions produced using the second set of subsets show that all five decompositions provide support for properties of cooperative context-sensitivity-to varying extents.
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Extracellular vesicles (EVs) are a heterogeneous population of membrane-enclosed nanoparticles released by cells. They play a role in intercellular communication and are involved in numerous physiological and pathological processes. Cells release subpopulations of EVs with distinct composition and inherent biological function which overlap in size. Current size-based isolation methods are, therefore, not optimal to discriminate between functional EV subpopulations. In addition, EVs overlap in size with several other biological nanoparticles, such as lipoproteins and viruses. Proteomic analysis has allowed for more detailed study of EV composition, and EV isolation approaches based on this could provide a promising alternative for purification based on size. Elucidating EV heterogeneity and the characteristics and role of EV subpopulations will advance our understanding of EV biology and the role of EVs in health and disease. Here, we discuss current knowledge of EV composition, EV heterogeneity and advances in affinity based EV isolation tools.
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Vesículas Extracelulares , Nanopartículas , ProteómicaRESUMEN
To examine ion solvation, exchange, and speciation for minority components in molten salts (MS) typically found as corrosion products, we propose a multimodal approach combining extended X-ray absorption fine structure (EXAFS) spectroscopy, optical spectroscopy, ab initio molecular dynamics (AIMD) simulations, and rate theory of ion exchange. Going beyond conventional EXAFS analysis, our method can accurately quantify populations of different coordination states of ions with highly disordered coordination environments via linear combination fitting of the EXAFS spectra of these coordination states computed from AIMD to the experimental EXAFS spectrum. In a case study of dilute Ni(II) dissolved in the ZnCl2+KCl melts, our method reveals heterogeneous distributions of coordination states of Ni(II) that are sensitive to variations in temperature and melt composition. These results are fully explained by the difference in the chloride exchange dynamics at varied temperatures and melt compositions. This insight will enable a better understanding and control of ion solubility and transport in MS.
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NEW FINDINGS: What is the central question of this study? The (dystrophin-deficient) muscles of mdx mice generate less contractile force per cross-sectional area (specific force) than those of healthy wild-type mice: what is the influence of muscle specific kinase (MuSK) upon the properties of the tibialis anterior (TA) muscle in mdx mice? What is the main finding and its importance? Injection of adeno-associated viral vector encoding MuSK into the TA muscle of young mdx mice increased the specific force of the muscle, suggesting the MuSK signalling system has the potential to restore healthy growth to dystrophin-deficient muscles. ABSTRACT: In the mdx mouse model of Duchenne muscular dystrophy, muscle fibres are fragile and prone to injury and degeneration. Compared to wild-type mice, muscles of mdx mice also develop less specific force (contractile force/cross-sectional area). We recently reported that injecting adeno-associated viral vector encoding muscle specific kinase (AAV-MuSK) into muscles of mdx mice increased utrophin expression and made the muscles more resistant to acute stretch-induced injury. Here we injected AAV-MuSK unilaterally into the tibialis anterior muscle of mdx mice at a younger age (4 weeks), and recorded contraction force from the muscles in situ at 12 weeks of age. Compared to contralateral empty-vector control muscles, muscles injected with AAV-MuSK produced 28% greater specific force (P = 0.0005). They did not undergo the compensatory hypertrophy that normally occurs in muscles of mdx mice. Injection of AAV encoding rapsyn (a downstream effector of MuSK signalling) caused no such improvement in muscle strength. Muscles injected with AAV-MuSK displayed a 10% reduction in the number of fibres with centralized nuclei (P = 0.0015). Our results in mdx mice suggest that elevating the expression of MuSK can reduce the incidence of muscle fibre regeneration and improve the strength of dystrophin-deficient muscles.
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Distrofia Muscular de Duchenne , Animales , Distrofina/metabolismo , Ratones , Ratones Endogámicos mdx , Contracción Muscular/fisiología , Fuerza Muscular , Músculo Esquelético/fisiología , Distrofia Muscular de Duchenne/metabolismoRESUMEN
BACKGROUND: Despite broad efforts to improve the reporting of biomedical research, no reporting guideline exists for primary care (PC) research. Little is known about current reporting practices or how well reports meet the needs of varied users in PC. OBJECTIVE: To map the published literature on PC research reporting: quality, strengths and weaknesses, recommendations and efforts to improve reporting. METHODS: Scoping review of literature across seven major databases and search engines to identify all articles on PC research reporting published in English, 2000-20. An additional secondary search of references of these 25 articles and consideration of expert panel suggestions. Structured data extraction by multiple reviewers using a predetermined form. RESULTS: Search yielded 2847 unique titles, of which 126 underwent full-text review and 25 met inclusion criteria. Publications included opinion pieces (9), systematic reviews (5), methods articles (2), literature reviews (4), qualitative studies (4) and surveys (1). Studies focussed on a variety of topics and research methods. All publications identified the need for improved reporting and recommended items to include in reports. Most commonly, publications cited the need for more detailed reporting on the context of study interventions, clinical settings and health care systems. Most publications endorsed the use of reporting guidelines and recognized the unique needs of PC research reporting. CONCLUSIONS: Published research and opinion identify unique needs for PC research reports and support new guidance to improve the validity, generalizability and application of study findings.
Doctors and health scientists recognize the need to improve the way they report their research. Despite the key role of primary care (PC) in strong health care systems, none of the many reporting guidelines focuses on PC research. To understand what is known about reporting PC research, we systematically searched all scientific articles published in English 200020. We studied the 25 key articles, which dealt with a great variety of patients, populations, medical problems and research methods. These articles identified needs for improvement and suggested items to include or ways to communicate research findings more effectively to the variety of readers who must put new research into practice to improve patient care and community health. These readerspracticing clinicians, researchers, patients, teachers and policymakersneed more practical details to understand the context and setting where the research took place and the patients were treated. Readers need better reporting of context to help them judge how they can apply the new research knowledge in their own practices. This review helped identify items to include and ways to improve research reports that can help develop new guidelines for PC research reports.
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Atención a la Salud , Atención Primaria de Salud , Humanos , Investigación Cualitativa , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
Much attention has been focused lately on the Opportunistic Routing technique (OR) that can overcome the restrictions of the harsh underwater environment and the unique structures of the Underwater Sensor Networks (UWSNs). OR enhances the performance of the UWSNs in both packet delivery ratio and energy saving. In our work; we propose a new routing protocol; called Energy Efficient Depth-based Opportunistic Routing with Void Avoidance for UWSNs (EEDOR-VA), to address the void area problem. EEDOR-VA is a reactive OR protocol that uses a hop count discovery procedure to update the hop count of the intermediate nodes between the source and the destination to form forwarding sets. EEDOR-VA forwarding sets can be selected with less or greater depth than the packet holder (i.e., source or intermediate node). It efficiently prevents all void/trapped nodes from being part of the forwarding sets and data transmission procedure; thereby saving network resources and delivering data packets at the lowest possible cost. The results of our extensive simulation study indicate that the EEDOR-VA protocol outperforms other protocols in terms of packet delivery ratio and energy consumption.
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For many families, the possibility that their child may have scoliosis causes great anxiety because their child may be deformed for life, may need to wear a brace for years, or may need to undergo a large and dangerous operation. For most families, these fears are groundless. Up to 3% of the population has a spinal curvature, most of which are small curves that may not need referral or repeated imaging. Many adolescents with scoliosis do well and do not need to wear a brace or have surgery.
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Escoliosis , Adolescente , Tirantes , Niño , Familia , Humanos , Atención Primaria de Salud , Escoliosis/diagnóstico , Escoliosis/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Gene regulation by control of transcription initiation is a fundamental property of living cells. Much of our understanding of gene repression originated from studies of the Escherichia coli lac operon switch, in which DNA looping plays an essential role. To validate and generalize principles from lac for practical applications, we previously described artificial DNA looping driven by designed transcription activator-like effector dimer (TALED) proteins. Because TALE monomers bind the idealized symmetrical lac operator sequence in two orientations, our prior studies detected repression due to multiple DNA loops. We now quantitatively characterize gene repression in living E. coli by a collection of individual TALED loops with systematic loop length variation. Fitting of a thermodynamic model allows unequivocal demonstration of looping and comparison of the engineered TALED repression system with the natural lac repressor system.
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Proteínas de Escherichia coli , Efectores Tipo Activadores de la Transcripción , ADN Bacteriano , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulación Bacteriana de la Expresión Génica , Operón Lac/genética , Represoras Lac/genética , Represoras Lac/metabolismo , Conformación de Ácido NucleicoRESUMEN
OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1âmg compared to <1âmg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1âmg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Ganglio Linfático Centinela/diagnóstico por imagen , Ganglio Linfático Centinela/patología , Espectroscopía Infrarroja Corta/métodos , Colorantes , Humanos , Verde de Indocianina , Estudios RetrospectivosRESUMEN
PURPOSE: General practitioners (GPs) are part of the US physician workforce, but little is known about who they are, what they do, and how they differ from family physicians (FPs). We describe self-identified GPs and compare them with board-certified FPs. METHODS: Analysis of data on 102,604 Doctor of Medicine and Doctor of Osteopathy physicians in direct patient care in the United States in 2016, who identify themselves as GPs or FPs. The study used linking databases (American Medical Association Masterfile, American Board of Family Medicine [ABFM], Area Health Resource File, Medicare Public Use File) to examine personal, professional, and practice characteristics. RESULTS: Of the physicians identified, 6,661 self-designated as GPs and 95,943 self-designated as FPs. Of the self-designated GPs, 116 had been ABFM certified and were excluded from the study. Of the remaining 102,488 physicians, those who self-designated as GPs but were never ABFM certified constituted the GP group (n = 6,545, 6%). Self-designated FPs that were ABFM certified made up the FP group (n = 79,449, 78%). The remaining self-designated FPs not ABFM certified constituted the uncertified group (n = 16,494, 16%). GPs differed from FPs in every characteristic examined. Compared with FPs, GPs are more likely to be older, male, Doctors of Osteopathy, graduates of non-US medical schools, and have no family medicine residency training. GPs practice location is similar to FPs, but GPs are less likely to participate in Medicare or to work in hospitals. CONCLUSIONS: GPs in the United States are a varied group that differ from FPs. Researchers, educators, and policy makers should not lump GPs together with FPs in data collection, analysis, and reporting.