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Chloroplasts are eukaryotic photosynthetic organelles that drive the global carbon cycle. Despite their importance, our understanding of their protein composition, function, and spatial organization remains limited. Here, we determined the localizations of 1,034 candidate chloroplast proteins using fluorescent protein tagging in the model alga Chlamydomonas reinhardtii. The localizations provide insights into the functions of poorly characterized proteins; identify novel components of nucleoids, plastoglobules, and the pyrenoid; and reveal widespread protein targeting to multiple compartments. We discovered and further characterized cellular organizational features, including eleven chloroplast punctate structures, cytosolic crescent structures, and unexpected spatial distributions of enzymes within the chloroplast. We also used machine learning to predict the localizations of other nuclear-encoded Chlamydomonas proteins. The strains and localization atlas developed here will serve as a resource to accelerate studies of chloroplast architecture and functions.
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Vias Biossintéticas , Chlamydomonas reinhardtii , Proteínas de Cloroplastos , Chlamydomonas reinhardtii/metabolismo , Proteínas de Cloroplastos/metabolismo , Cloroplastos/metabolismo , FotossínteseRESUMO
Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.
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Proteínas Reguladoras de Apoptose , Quirópteros , Inflamassomos , Ribonucleoproteínas , Viroses , Animais , Humanos , Camundongos , Proteínas Reguladoras de Apoptose/metabolismo , Quirópteros/imunologia , COVID-19 , Inflamassomos/imunologia , Ribonucleoproteínas/metabolismo , SARS-CoV-2 , Viroses/imunologia , Fenômenos Fisiológicos ViraisRESUMO
When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery.
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Adaptação Fisiológica/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína , Proteólise , Saccharomyces cerevisiae/enzimologia , Serina Endopeptidases/metabolismo , Estresse Fisiológico/fisiologia , Especificidade por Substrato , Ubiquitina/metabolismoRESUMO
INTRODUCTION: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. METHODS: A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. RESULTS: Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. CONCLUSIONS: A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases.
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Linfonodos , Metástase Linfática , Valor Preditivo dos Testes , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Ultrassonografia , Humanos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/diagnóstico por imagem , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Ultrassonografia/métodos , Adulto , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Idoso , Sensibilidade e Especificidade , Biópsia por Agulha FinaRESUMO
We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists' ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen's kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen's kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies.
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BACKGROUND: Children with neuromuscular early onset scoliosis (EOS) receive numerous radiographic studies both from orthopaedic and other specialties. Ionizing radiation doses delivered by computed tomography (CT) are reportedly 100 times higher than conventional radiography. The purpose of this study was to evaluate the number of radiographic studies ordered for neuromuscular EOS patients during their care. METHODS: Retrospective review at a tertiary children's hospital from January 2010 to June 2021 included all patients with neuromuscular EOS followed by an orthopaedic specialist for a minimum of 3 years. Patients were excluded if the majority of their nonorthopaedic care was provided by outside institutions. RESULTS: Eighteen patients met inclusion criteria with mean follow up of 6.4±2.3 years. A total of 1312 plain radiographs and 35 CT scans were performed. Of the plain radiographs, 34.7% were ordered by orthopaedic providers and 65.3% (857/1312) were ordered by other providers. Of the CT scans, 4 were ordered by orthopaedic providers, while 88.5% (21/35) were ordered by other providers. An average of 74.7 (range: 29 to 124) radiographs and 1.9 (range: 0 to 9) CT scans ordered over the course of each patient's treatment for an average of 13.0±6.0 radiographs and 0.3 CT scans per year. CONCLUSIONS: With an average of 75 radiographs and 1.9 CT scans performed per patient, consideration for steps to limit exposure to ionizing radiation should be made a particularly high priority in this unique subset of patients. This requires interdisciplinary coordination as 65% of the radiographs and over 80% of the CT scans were ordered by nonorthopaedic providers. LEVEL OF EVIDENCE: Level III.
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Escoliose , Tomografia Computadorizada por Raios X , Humanos , Escoliose/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Masculino , Criança , Lactente , Radiografia/métodos , Doses de Radiação , SeguimentosRESUMO
Alpha-synuclein SNCA has been implicated in the etiology of Parkinson's disease (PD); however, the normal function of alpha-synuclein protein and the pathway that mediates its pathogenic effect is yet to be discovered. We investigated the mechanistic role of SNCA in the nucleus utilizing isogenic human-induced pluripotent stem cells-derived neurons from PD patients with autosomal dominant mutations, A53T and SNCA-triplication, and their corresponding corrected lines by genome- and epigenome-editing. Comparisons of shape and integrity of the nuclear envelope and its resistance to stresses found that both mutations result in similar nuclear envelope perturbations that were reversed in the isogenic mutation-corrected cells. Further mechanistic studies showed that SNCA mutation has adverse effects on the nucleus by trapping Ras-related nuclear protein (RAN) and preventing it from transporting key nuclear proteins such as, DNMT3A, for maintaining normal nuclear function. For the first time, we proposed that α-syn interacts with RAN and normally functions in the nucleocytoplasmic transport while exerts its pathogenic effect by sequestering RAN. We suggest that defects in the nucleocytoplasmic transport components may be a general pathomechanistic driver of neurodegenerative diseases.
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Núcleo Celular/genética , DNA (Citosina-5-)-Metiltransferases/genética , Doença de Parkinson/genética , alfa-Sinucleína/genética , Linhagem Celular , Núcleo Celular/patologia , DNA Metiltransferase 3A , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Mutação/genética , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/patologiaRESUMO
Rodent progressive cardiomyopathy (PCM) encompasses a constellation of microscopic findings commonly seen as a spontaneous background change in rat and mouse hearts. Primary histologic features of PCM include varying degrees of cardiomyocyte degeneration/necrosis, mononuclear cell infiltration, and fibrosis. Mineralization can also occur. Cardiotoxicity may increase the incidence and severity of PCM, and toxicity-related morphologic changes can overlap with those of PCM. Consequently, sensitive and consistent detection and quantification of PCM features are needed to help differentiate spontaneous from test article-related findings. To address this, we developed a computer-assisted image analysis algorithm, facilitated by a fully convolutional network deep learning technique, to detect and quantify the microscopic features of PCM (degeneration/necrosis, fibrosis, mononuclear cell infiltration, mineralization) in rat heart histologic sections. The trained algorithm achieved high values for accuracy, intersection over union, and dice coefficient for each feature. Further, there was a strong positive correlation between the percentage area of the heart predicted to have PCM lesions by the algorithm and the median severity grade assigned by a panel of veterinary toxicologic pathologists following light microscopic evaluation. By providing objective and sensitive quantification of the microscopic features of PCM, deep learning algorithms could assist pathologists in discerning cardiotoxicity-associated changes.
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Inteligência Artificial , Cardiomiopatias , Algoritmos , Animais , Cardiomiopatias/induzido quimicamente , Camundongos , Redes Neurais de Computação , Ratos , RoedoresRESUMO
The Barlett Gentile cyberbullying model (BGCM) posits that correlated anonymity perceptions and the belief in the irrelevance of muscularity for online bullying (BIMOB) predict positive cyberbullying attitudes to predict subsequent cyberbullying perpetration. Much research has shown the BGCM to be the only published theory that differentiates traditional and cyberbullying while validly predicting cyberbullying. So far, however, the cross-cultural ubiquity has gone understudied. Thus, 1,592 adult participants across seven countries (USA, Australia, Brazil, China, Germany, Japan, and Singapore) completed measures germane to the BGCM. Supporting the BGCM, the variables were significantly correlated for the entire sample, participants from independent cultures, and participants from interdependent cultures. However, the relationship between BIMOB and positive cyberbullying attitudes as well as the relationship between positive cyberbullying attitudes and cyberbullying perpetration were stronger for independent cultures. These results suggest that the BGCM postulates are mostly universal, but several relations appear to be culturally different. Theoretical implications are discussed.
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Bullying , Vítimas de Crime , Cyberbullying , Adulto , Austrália , China , Comparação Transcultural , Alemanha , Humanos , JapãoRESUMO
Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.
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Dióxido de Carbono/metabolismo , Chlamydomonas reinhardtii/enzimologia , Organelas/enzimologia , Ribulose-Bifosfato Carboxilase/metabolismo , Chlamydomonas reinhardtii/genética , Organelas/genética , Ribulose-Bifosfato Carboxilase/genéticaRESUMO
BACKGROUND: Audiovisual distraction, a non-pharmacological intervention, has been used to manage dental anxiety in prior clinical trials. AIM: Synthesize the available evidences to evaluate the efficacy of audiovisual distraction techniques on the management of dental anxiety in children. DESIGN: Electronic databases (PubMed, Cochrane Central Register of Controlled Trials, and Embase) were searched. We included randomized controlled trials (RCTs), and methodological quality of included trials was assessed using the Cochrane Collaboration's criteria. Information on reported anxiety, pain, behaviors, vital signs (including blood pressure, oxygen saturation, and pulse rate), and children satisfaction was analyzed. RESULTS: Nine studies were included for a systematic review, and none of them had low risk of bias. Significant differences in anxiety were found. According to the study, a majority of results indicated a significant difference in pain and behavior between the audiovisual and control group. Three studies reported children in the audiovisual group preferred usage of an audiovisual device for future dental visits. No significant differences could be found regarding blood pressure. CONCLUSIONS: There is some low-quality evidence suggesting that the usage of audiovisual distraction during dental treatment may relieve children's dental anxiety.
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Recursos Audiovisuais , Ansiedade ao Tratamento Odontológico/terapia , Adolescente , Criança , Pré-Escolar , Humanos , Distorção da Percepção , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Evaluation of the central nervous system (CNS) in the developing mouse presents unique challenges, given the complexity of ontogenesis, marked structural reorganization over very short distances in 3 dimensions each hour, and numerous developmental events susceptible to genetic and environmental influences. Developmental defects affecting the brain and spinal cord arise frequently both in utero and perinatally as spontaneous events, following teratogen exposure, and as sequelae to induced mutations and thus are a common factor in embryonic and perinatal lethality in many mouse models. Knowledge of normal organ and cellular architecture and differentiation throughout the mouse's life span is crucial to identify and characterize neurodevelopmental lesions. By providing a well-illustrated overview summarizing major events of normal in utero and perinatal mouse CNS development with examples of common developmental abnormalities, this annotated, color atlas can be used to identify normal structure and histology when phenotyping genetically engineered mice and will enhance efforts to describe and interpret brain and spinal cord malformations as causes of mouse embryonic and perinatal lethal phenotypes. The schematics and images in this atlas illustrate major developmental events during gestation from embryonic day (E)7.5 to E18.5 and after birth from postnatal day (P)1 to P21.
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Sistema Nervoso Central , Embrião de Mamíferos/anatomia & histologia , Desenvolvimento Embrionário/fisiologia , Animais , Atlas como Assunto , Sistema Nervoso Central/anatomia & histologia , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/crescimento & desenvolvimento , Feminino , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Histocitoquímica , Camundongos , GravidezRESUMO
The 2016 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in San Diego, CA, at the Society of Toxicologic Pathology's (STP) 35th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks, along with select images that were used by the audience for voting and discussion. Some lesions and topics covered during the symposium included malignant glioma and histiocytic sarcoma in the rodent brain; a new statistical method designed for histopathology data evaluation; uterine stromal/glandular polyp in a rat; malignant plasma cell tumor in a mouse brain; Schwann cell proliferative lesions in rat hearts; axillary schwannoma in a cat; necrosis and granulomatous inflammation in a rat brain; adenoma/carcinoma in a rat adrenal gland; hepatocyte maturation defect and liver/spleen hematopoietic defects in an embryonic mouse; distinguishing malignant glioma, malignant mixed glioma, and malignant oligodendroglioma in the rat; comparison of mammary gland whole mounts and histopathology from mice; and discussion of the International Harmonization of Nomenclature and Diagnostic Criteria collaborations.
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Patologia , Toxicologia , Animais , Congressos como Assunto , Técnicas e Procedimentos Diagnósticos , Humanos , Terminologia como AssuntoRESUMO
BACKGROUND: The term social accountability has gained increased interest in medical education, but is relatively unexplored in dentistry. AIMS: The aim of this study is to explore dental students' attitudes towards social accountability. METHODS: A qualitative study utilizing focus groups with University of Otago final year (5th year) Bachelor of Dental Surgery (BDS) students was carried out. A questionnaire designed to measure medical students' attitudes towards social responsibility was used as a guide. Following data collection, framework analysis was used to analyze each of the three focus groups, and repeating themes were noted. RESULTS: Analysis of the focus groups discovered recurring themes, such that participants believed that dentists should be accountable to society in a professional context and that they are responsible for patients who present at their clinic but that there is no professional obligation to help reduce oral health inequalities by working with populations facing inequalities. There was strong agreement that there needs to be change to the dental health care system from a structural and political level to address oral health inequalities, rather than individual dentists assuming greater responsibility. CONCLUSION: Our findings show that dental education may not be accountable to society in the sense that it is not producing graduates who believe that they have an obligation to address the priority oral health concerns of society.
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Atitude do Pessoal de Saúde , Responsabilidade Social , Estudantes de Odontologia/psicologia , Educação em Odontologia/organização & administração , Feminino , Grupos Focais , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Nova Zelândia , Pesquisa Qualitativa , Adulto JovemRESUMO
Although integrating progress monitoring (PM) measures into psychotherapy practice can provide numerous benefits, including improved client outcomes, relatively few clinicians use these measures (e.g., Ionita & Fitzpatrick, 2014). To better understand the reasons for clinicians' reluctance, consensual qualitative research methodology was used to examine the challenges faced by clinicians currently using PM measures. Open-ended, semistructured interviews, with 25 clinicians who chose to use PM measures, revealed that clinicians tended to face challenges involving technical concerns, negative responses from others, and personal barriers such as anxiety. The majority of participants discussed ways to overcome the challenges they experienced, including ensuring the fit of the PM measure, explaining measures to others to help engender a positive response, adapting their own perspective, and increasing their own and others' knowledge of the measures. Implications for practicing psychologists and for knowledge translation efforts are discussed.
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Atitude do Pessoal de Saúde , Transtornos Mentais/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Psicoterapia/estatística & dados numéricos , Adulto , Idoso , Prática Clínica Baseada em Evidências , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Psicoterapia/métodos , Pesquisa Qualitativa , Adulto JovemRESUMO
Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway has been implicated in anti-estrogen resistance in breast cancer. We tested the therapeutic potential of the novel PI3K/mTOR dual inhibitor P7170 in a panel of anti-estrogen-sensitive and anti-estrogen-resistant models of ER+ breast cancer. Estrogen receptor-positive (ER+) breast cancer cells were treated ±P7170. Fresh cores from primary ER+/HER2- tumors from two patients were treated ±P7170 ex vivo. Mice bearing breast cancer xenografts were randomized to treatment with vehicle, fulvestrant, P7170, or combinations, and tumor volumes were measured. Tissues and cells were analyzed for markers of pathway activity, cell viability, and apoptosis. In cell lines, P7170 exhibited IC50 values in the range of 0.9-7 nM and induced apoptosis. P7170 potently inhibited mTOR activity (≤ 25 nM) and inhibited PI3K at higher concentrations (≥ 200 nM). P7170 completely inhibited MCF-7 tumor growth, significantly inhibited growth of fulvestrant-resistant T47D tumors, and suppressed tumor cell proliferation but did not induce apoptosis. While P7170 inhibits PI3K and mTOR in ER+/HER2- human breast cancer cells and tumors ex vivo, in vivo data indicate that the primary mechanism of P7170 anti-tumor action is inhibition of mTOR and cell proliferation. P7170 is a novel agent worthy of further investigation for the treatment of ER+ breast cancer.
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Neoplasias da Mama/genética , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Imidazóis/administração & dosagem , Fosfatidilinositol 3-Quinases/genética , Quinolinas/administração & dosagem , Serina-Treonina Quinases TOR/genética , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias das Glândulas Endócrinas/genética , Neoplasias das Glândulas Endócrinas/patologia , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Fulvestranto , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/administração & dosagem , Receptores de Estrogênio/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We propose a novel detection scheme called Stokes vector direct detection (SV-DD) to realize high electrical spectral efficiency and cost-effective optical communication for short and medium reach. With SV-DD, the signal is modulated in only one polarization and combined with the carrier in the orthogonal polarization for fiber transmission. At reception, the combined signal is detected in Stokes space by three or four photo-detectors. Compared with conventional DD technique, SV-DD is resilient to both chromatic dispersion and signal-to-signal beat noise. Furthermore, SV-DD does not require polarization tracking or narrow band optical filtering for carrier extraction. In this paper, we present for the first time the numerical analysis and experimental demonstration of single-carrier SV-DD. We report 62.5-Gb/s data rate single-carrier SV-DD transmission over 160-km SSMF using 12.5-Gbaud 32-QAM modulation.
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Circulating tumor cells (CTCs) exist in the peripheral blood stream of metastatic cancer patients at rates of approximately 1 CTC per billion background cells. In order to capture and analyze this rare cell population, various techniques exist that range from antibody-based surface marker positive selection to methods that use physical properties of CTCs to negatively exclude background cells from a CTC population. However, methods to capture cells for functional downstream analyses are limited due to inaccessibility of the captured sample or labeling techniques that may be prohibitive to cell function. Here, we present a negative selection method that leverages a Microfluidic Cell Concentrator (MCC) to allow collection and analysis of this rare cell population without needing cell adhesion or other labeling techniques to keep the cells within the chamber. Because the MCC is designed to allow collection and analysis of non-adherent cell populations, multiple staining steps can be applied in parallel to a given CTC population without losing any of the population. The ability of the MCC for patient sample processing of CTCs for enumeration was demonstrated with five patient samples, revealing an average of 0.31 CTCs/mL. The technique was compared to a previously published method - the ELISPOT - that showed similar CTC levels among the five patient samples tested. Because the MCC method does not use positive selection, the method can be applied across a variety of tumor types with no changes to the process.
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Separação Celular/métodos , Técnicas Analíticas Microfluídicas/métodos , Células Neoplásicas Circulantes/patologia , Antígenos de Neoplasias/sangue , Moléculas de Adesão Celular/sangue , Contagem de Células , ELISPOT/métodos , Molécula de Adesão da Célula Epitelial , Humanos , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Metástase Neoplásica , Neoplasias/sangueRESUMO
BACKGROUND: Obesity has become a problem in the USA and identifying modifiable factors at the individual level may help to address this public health concern. A burgeoning literature has suggested that sleep and stress may be associated with obesity; however, little is know about whether these two factors moderate each other and even less is known about whether their impacts on obesity differ by gender. PURPOSE: This study investigates whether sleep and stress are associated with body mass index (BMI) respectively, explores whether the combination of stress and sleep is also related to BMI, and demonstrates how these associations vary across the distribution of BMI values. METHODS: We analyze the data from 3,318 men and 6,689 women in the Philadelphia area using quantile regression (QR) to evaluate the relationships between sleep, stress, and obesity by gender. RESULTS: Our substantive findings include: (1) high and/or extreme stress were related to roughly an increase of 1.2 in BMI after accounting for other covariates; (2) the pathways linking sleep and BMI differed by gender, with BMI for men increasing by 0.77-1 units with reduced sleep duration and BMI for women declining by 0.12 unit with 1 unit increase in sleep quality; (3) stress- and sleep-related variables were confounded, but there was little evidence for moderation between these two; (4) the QR results demonstrate that the association between high and/or extreme stress to BMI varied stochastically across the distribution of BMI values, with an upward trend, suggesting that stress played a more important role among adults with higher BMI (i.e., BMI > 26 for both genders); and (5) the QR plots of sleep-related variables show similar patterns, with stronger effects on BMI at the upper end of BMI distribution. CONCLUSIONS: Our findings suggested that sleep and stress were two seemingly independent predictors for BMI and their relationships with BMI were not constant across the BMI distribution.
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Índice de Massa Corporal , Obesidade/fisiopatologia , Sono/fisiologia , Estresse Psicológico/fisiopatologia , Adulto , Idoso , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Philadelphia , Análise de Regressão , Fatores Sexuais , Fatores Socioeconômicos , Processos Estocásticos , Estresse Psicológico/psicologia , Fatores de TempoRESUMO
INTRODUCTION: The purpose of this study was to investigate whether the use of a dedicated early morning orthopaedic trauma operating room (OR) resulted in shorter wait times, decreased surgical times, decreased length of stay (LOS), and decreased complications in children treated with urgent surgical intervention for supracondylar humerus fractures. METHODS: This retrospective comparative cohort study at a level I pediatric trauma center included patients younger than 12 years with supracondylar humerus fractures urgently treated with closed or open reduction and percutaneous pinning. Index surgical cases from April 28, 2013, to February 26, 2020, were included. Patients with prior humerus fracture, concomitant injuries, open fracture, pulseless supracondylar fracture, or missing data were excluded. Patients were analyzed based on the type of OR: dedicated early morning orthopaedic trauma OR or typical daytime orthopaedic OR. The primary outcome was time from presentation to surgery. Secondary outcomes included surgical time, complications, and LOS. RESULTS: A total of 401 patients with a mean age of 5 ± 2 (range: 1 to 11) years and a mean follow-up of 2.0 ± 2.1 (range: 0.5 to 25.0) months were included, of whom 137 patients (34%) underwent surgery in the early morning dedicated orthopaedic trauma OR. The dedicated early morning orthopaedic OR group had significantly less time from presentation to surgery (7.5 versus 9.4 hours; P = 0.0002) and shorter LOS (21.0 versus 24.0 hours; P = 0.004) compared with children treated in the typical daytime orthopaedic OR. Surgical time (31.1 versus 32.6 minutes; P = 0.40) and complication rates (5.8% versus 4.9%; P = 0.65) were similar between the groups. No revision surgery was required in either group. DISCUSSION: Surgical wait times were diminished with use of the dedicated early morning OR, as was LOS. Surgical times and complication rates were similar between groups. Institutions may consider adopting a dedicated early morning orthopaedic trauma OR to improve surgical wait times and decrease LOS. LEVEL OF EVIDENCE: III.