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INTRODUCTION: Over the last several decades, cesarean delivery has been recommended as the safest mode of delivery for breech presentations. The purpose of this study was to evaluate the outcomes of planned vaginal births with planned cesarean births in breech presenting fetuses. METHODS: This retrospective population-based cohort study utilized data from the United States' Period Linked Birth-Infant Death Public Use Files from 2008 to 2017. All term singleton breech deliveries of a live baby without congenital anomalies were identified (n = 546,842) and divided into two cohorts: women who had a planned vaginal birth (n = 116,828), and women who had a planned cesarean section (n = 430,014). Multivariate logistic regression models, adjusted for maternal baseline characteristics, examined the associations between the planned delivery method and neonatal outcomes. RESULTS: It was observed that 26.14 % of the planned vaginal birth cohort had a vaginal delivery. In adjusted analyses, undergoing a planned vaginal birth for breech delivery was associated with an increased risk of adverse neonatal outcomes including infant death, OR 1.32, 95 % CI 1.16-1.52, admission to NICU,1.23, 1.19-1.27, ventilation support at ã 6 h of life, 1.47, 1.42-1.52, ventilation support at ã 6 h of life, 1.19, 1.08-1.31, and Apgar score of ≤3 at 5 min, 2.27, 2.06-2.50. CONCLUSION: In women carrying fetuses in breech presentation, having a planned vaginal birth had a low success rate and was associated with increased risk of neonatal morbidity and mortality. Women should be carefully counselled on the risks associated with breech vaginal delivery as well as the low success rate of vaginal delivery.
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Targeted mass spectrometry (MS) methods are powerful tools for selective and sensitive analysis of peptides identified by global discovery experiments. Selected reaction monitoring (SRM) is currently the most widely accepted MS method in the clinic, due to its reliability and analytical performance. However, due to limited throughput and the difficulty in setting up and analyzing large scale assays, SRM and parallel reaction monitoring (PRM) are typically used only for very refined assays of on the order of 100 targets or less. Here we introduce a new MS platform with a quadrupole mass filter, collision cell, linear ion trap architecture that has increased acquisition rates compared to the analogous hardware found in the Orbitrap™ Tribrid™ series instruments. The platform can target more analytes than existing SRM and PRM instruments - in the range of 5000 to 8000 peptides per hour. This capability for high multiplexing is enabled by acquisition rates of 70-100 Hz for peptide applications, and the incorporation of real-time chromatogram alignment that adjusts for retention time drift and enables narrow time scheduled acquisition windows. Finally, we describe a Skyline external software tool that implements the building of targeted methods based on data independent acquisition chromatogram libraries or unscheduled analysis of heavy labeled standards. We show that the platform delivers ~10x lower LOQs than traditional SRM analysis for a highly multiplex assay and also demonstrate how analytical figures of merit change while varying method duration with a constant number of analytes, or by keeping a constant time duration while varying the number of analytes.
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Cross-linking mass spectrometry (XL-MS) has evolved into a pivotal technique for probing protein interactions. This study describes the implementation of Parallel Accumulation-Serial Fragmentation (PASEF) on timsTOF instruments, enhancing the detection and analysis of protein interactions by XL-MS. Addressing the challenges in XL-MS, such as the interpretation of complex spectra, low abundant cross-linked peptides, and a data acquisition bias, our current study integrates a peptide-centric approach for the analysis of XL-MS data and presents the foundation for integrating data-independent acquisition (DIA) in XL-MS with a vendor-neutral and open-source platform. A novel workflow is described for processing data-dependent acquisition (DDA) of PASEF-derived information. For this, software by Bruker Daltonics is used, enabling the conversion of these data into a format that is compatible with MeroX and Skyline software tools. Our approach significantly improves the identification of cross-linked products from complex mixtures, allowing the XL-MS community to overcome current analytical limitations.
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Reactivos de Enlaces Cruzados , Espectrometría de Masas , Programas Informáticos , Flujo de Trabajo , Reactivos de Enlaces Cruzados/química , Péptidos/química , Péptidos/análisis , HumanosRESUMEN
OBJECTIVE: To estimate incidence and case-fatality rates of amniotic fluid embolism (AFE) and to examine their temporal trends. STUDY DESIGN: Population-based retrospective cohort study using the 2000-2019 Health Care Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). Annual population rates were estimated using HCUP-NIS specific weighting. Descriptive analyses and logistic regression described trends within the cohort. RESULTS: Over the study period, AFE incidence rate remained stable (mean 4.9 cases/100,000 deliveries) and the case-fatality rate declined (mean 17.7 %,95 % CI 16.40-10.09). Highest AFE incidence rates and fatality rates were in women ≥ 35 years, African-Americans, and in urban-teaching hospitals. AFE mortality rates decreased among Hispanics. CONCLUSION: AFE rates remained stable and fatality rates declined over time. Highest rates of AFE occurrence and death were in women who typically have greater risk of experiencing adverse obstetrical outcomes. Continued research into early diagnostic methods and effective treatments are needed to further improve AFE incidence and mortality rates.
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Embolia de Líquido Amniótico , Embarazo , Femenino , Humanos , Estados Unidos/epidemiología , Embolia de Líquido Amniótico/epidemiología , Embolia de Líquido Amniótico/diagnóstico , Embolia de Líquido Amniótico/etiología , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Modelos LogísticosRESUMEN
OBJECTIVE: The incidence of Lyme disease (LD) infections has risen in recent decades. Gestational LD has been associated with adverse pregnancy outcomes; however, the results have been contradictory. The study objective was to examine the effects of gestational LD on obstetrical and neonatal outcomes. METHODS: Using the Healthcare Cost & Utilization Project National (Nationwide) Inpatient Sample from the United States, we conducted a retrospective cohort study of pregnant patients admitted to the hospital between 2016 and 2019. The exposed group consisted of pregnant patients with gestational LD infection (International Classification of Diseases, Tenth Revision [ICD-10] code A692x), while the comparison group consisted of pregnant patients without gestational LD. Descriptive statistics and multivariate logistic regression models, adjusted for baseline maternal characteristics, were used to determine the associations between gestational LD and obstetrical and neonatal outcomes. RESULTS: The cohort included 2 943 575 women, 226 of whom were diagnosed with LD during pregnancy. The incidence of LD was 7.67 per 100 000 pregnancy admissions. The incidence of gestational LD was stable over the study period. Pregnant patients with LD were more likely white, older, to have private health insurance, and to belong to a higher income quartile. Gestational LD was associated with an increased risk of placental abruption (adjusted odds ratio [aOR], 3.45 [95% confidence interval (CI), 1.53-7.80]) and preterm birth (aOR, 1.58 [95% CI, 1.03-2.42]). CONCLUSION: Gestational LD is associated with a higher risk of placental abruption and preterm birth. Pregnancies complicated by LD, while associated with a higher risk of certain adverse outcomes, can be followed in most healthcare settings.
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Enfermedad de Lyme , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Enfermedad de Lyme/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Recién Nacido , Estados Unidos/epidemiología , Incidencia , Adulto Joven , Desprendimiento Prematuro de la Placenta/epidemiología , Nacimiento Prematuro/epidemiologíaRESUMEN
INTRODUCTION: While the literature is replete of clinical studies reporting on the Robin sequence (RS), population-based analyses are scarce with significant variability within the literature in terms of reported incidence, demographic parameters, and outcomes. The authors have conducted a 20-year population-based analysis to guide clinical practice. METHODS: A birth cohort was created from the available datasets in the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID; 2000-2019). Robin sequence patients were identified and further stratified by syndromic status. Incidence, demographic parameters, and outcomes including mortality and tracheostomy rates were computed. A subset analysis comparing the isolated and syndromic cohorts was conducted. Data was analyzed through a χ 2 or t test. RESULTS: The incidence of RS was 5.15:10,000 (95% CI: 4.99-5.31) from a birth cohort of 7.5 million. Overall, 63.3% of the cohort was isolated RS and 36.7% had syndromic RS. Robin sequence patients had a significantly higher rate of cardiac (25.9%) and neurological (8.6%) anomalies compared with the general birth cohort and were most commonly managed in urban teaching hospitals ( P <0.0001). The pooled mortality and tracheostomy rates were 6.6% and 3.6%, respectively. Syndromic status was associated with a longer length of hospital stay (27.8 versus 13.6 d), tracheostomy rate (6.2% versus 2.1%), and mortality (14.1% versus 2.2%) compared with isolated RS ( P <0.0001). CONCLUSIONS: The true incidence of RS is likely higher than previously reported estimates. Isolated RS patients have a low associated mortality and tracheostomy rate and are typically managed in urban teaching hospitals. Syndromic status confers a higher mortality rate, tracheostomy rate, and length of stay compared with nonsyndromic counterparts.
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Síndrome de Pierre Robin , Humanos , Estados Unidos/epidemiología , Estudios Retrospectivos , Síndrome de Pierre Robin/epidemiología , Síndrome de Pierre Robin/cirugía , Síndrome de Pierre Robin/complicaciones , Incidencia , Tiempo de Internación , Pacientes InternosRESUMEN
We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data-independent acquisition, the Thermo Scientific Orbitrap Astral mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific Orbitrap mass spectrometers, which have long been the gold standard for high-resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high-quality quantitative measurements across a wide dynamic range. We also use a newly developed extracellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5000 plasma proteins in a 60 min gradient with the Orbitrap Astral mass spectrometer.
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Péptidos , Proteómica , Proteómica/métodos , Espectrometría de Masas/métodos , Proteoma/metabolismo , Proteínas SanguíneasRESUMEN
Targeted proteomics is widely utilized in clinical proteomics; however, researchers often devote substantial time to manual data interpretation, which hinders the transferability, reproducibility, and scalability of this approach. We introduce DeepMRM, a software package based on deep learning algorithms for object detection developed to minimize manual intervention in targeted proteomics data analysis. DeepMRM was evaluated on internal and public datasets, demonstrating superior accuracy compared with the community standard tool Skyline. To promote widespread adoption, we have incorporated a stand-alone graphical user interface for DeepMRM and integrated its algorithm into the Skyline software package as an external tool.
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Proteómica , Programas Informáticos , Reproducibilidad de los Resultados , Espectrometría de Masas , AlgoritmosRESUMEN
We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data independent acquisition, the Thermo Scientific™ Orbitrap™ Astral™ mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific™ Orbitrap™ mass spectrometers, which have long been the gold standard for high resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high quality quantitative measurements across a wide dynamic range. We also use a newly developed extra-cellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5,000 plasma proteins in a 60-minute gradient with the Orbitrap Astral mass spectrometer.
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The MSstats R-Bioconductor family of packages is widely used for statistical analyses of quantitative bottom-up mass spectrometry-based proteomic experiments to detect differentially abundant proteins. It is applicable to a variety of experimental designs and data acquisition strategies and is compatible with many data processing tools used to identify and quantify spectral features. In the face of ever-increasing complexities of experiments and data processing strategies, the core package of the family, with the same name MSstats, has undergone a series of substantial updates. Its new version MSstats v4.0 improves the usability, versatility, and accuracy of statistical methodology, and the usage of computational resources. New converters integrate the output of upstream processing tools directly with MSstats, requiring less manual work by the user. The package's statistical models have been updated to a more robust workflow. Finally, MSstats' code has been substantially refactored to improve memory use and computation speed. Here we detail these updates, highlighting methodological differences between the new and old versions. An empirical comparison of MSstats v4.0 to its previous implementations, as well as to the packages MSqRob and DEqMS, on controlled mixtures and biological experiments demonstrated a stronger performance and better usability of MSstats v4.0 as compared to existing methods.
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Proteómica , Proyectos de Investigación , Proteómica/métodos , Programas Informáticos , Espectrometría de Masas/métodos , Cromatografía Liquida/métodosRESUMEN
PURPOSE: Severe hypercalcemia resulting from hyperparathyroidism may result in adverse perinatal outcomes. The objective of this study was to evaluate maternal and neonatal outcomes among pregnant women with hyperparathyroidism using a population database. METHODS: A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999-2015. ICD-9 codes were used to identify women diagnosed with hyperparathyroidism during pregnancy. Perinatal outcomes between pregnant women with and without hyperparathyroidism were compared. Multivariate logistic regression, controlling for age, race, income, insurance type, hospital location, and comorbidities, evaluated the effect of hyperparathyroidism on perinatal outcomes. RESULTS: Of 13,792,544 deliveries included over the study period, 368 were to women with hyperparathyroidism. The overall incidence of hyperparathyroidism was 2.7/100,000 births, increasing from 1.6 to 5.2/100,000 births over the study period (p < 0.0001). Women with hyperparathyroidism were older and had more comorbidities, such as obesity, and pre-gestational hypertension and diabetes. Relative to the comparison group, women with hyperparathyroidism were more likely to deliver preterm, OR 1.69 (95% CI 1.24-2.29), to develop preeclampsia, 3.14 (2.30-4.28), and to deliver by cesarean, 1.69 (1.36-2.09). Infants born to mothers with hyperparathyroidism were more likely to be growth restricted, 1.83 (1.08-3.07), and to be diagnosed with a congenital anomaly, 4.21 (2.09-8.48). CONCLUSION: Hyperparathyroidism during pregnancy is associated with a significant increase in adverse perinatal outcomes, including preeclampsia, preterm delivery, fetal growth restriction, and congenital anomalies. As such, pregnancies among women with hyperparathyroidism should be considered high-risk, and specialized care is recommended in order to minimize maternal and neonatal morbidity.
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Hiperparatiroidismo , Preeclampsia , Complicaciones del Embarazo , Recién Nacido , Lactante , Embarazo , Femenino , Humanos , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Preeclampsia/epidemiología , Preeclampsia/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/epidemiologíaRESUMEN
PURPOSE: Vulvodynia and vaginismus are common chronic vulvar pain disorders for which there is a paucity of literature on pregnancy outcomes of affected women. The study objective was to evaluate the associations between vulvodynia and vaginismus and obstetric outcomes. METHODS: We performed a retrospective cohort study including all birth-related admissions from 1999 to October 2015 extracted from the Healthcare Cost and Utilization Project-National Inpatient Sample from the United States. Women with vulvodynia or vaginismus were identified using the appropriate ICD-9 codes. Multivariate logistic regression models, adjusted for baseline maternal characteristics, were performed to evaluate the effect of vulvodynia and vaginismus on obstetrical and neonatal outcomes. RESULTS: A total of 879 obstetrical patients with vulvodynia or vaginismus were identified in our cohort of 13,792,544 patients admitted for delivery in US hospitals between 1999 and 2015, leading to an overall prevalence of 6 cases per 100,000 births. Between 1999 and 2015, the annual prevalence of vulvodynia or vaginismus rose from 2 to 16 cases per 100,000. Vulvodynia and vaginismus were associated with increased risks of eclampsia, chorioamnionitis, post-term pregnancy, cesarean delivery, instrumental vaginal delivery, blood transfusions, prolonged hospital stays, congenital anomalies and intrauterine growth restriction. CONCLUSION: Vulvodynia and vaginismus in pregnancy appears underreported in pregnancy compared to reported population rates. Prevalence of reporting seems to have increased in the last decades and is associated with increased risks of maternal and newborn morbidities. Obstetrical caregivers should be aware of the underreporting of these conditions and the associated adverse effects when counseling obstetrical patients.
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Dispareunia , Vaginismo , Vulvodinia , Embarazo , Recién Nacido , Humanos , Femenino , Estados Unidos/epidemiología , Vaginismo/complicaciones , Vaginismo/epidemiología , Vulvodinia/epidemiología , Estudios Retrospectivos , Parto Obstétrico/efectos adversos , Resultado del Embarazo/epidemiología , Dispareunia/epidemiología , Retardo del Crecimiento FetalRESUMEN
PURPOSE: To identify risk factors associated with bladder injury during cesarean delivery, and to determine the frequency of associated morbidities. METHODS: Data obtained from the United States' Health Care Cost and Utilization Project-Nationwide Inpatient Sample were used to conduct a retrospective population-wide cohort study. ICD-9 codes were used to identify women who underwent a cesarean delivery between 1999 and 2015. Subsequently, women were classified based on whether or not they experienced a bladder injury during delivery. Multivariate logistic regression was used to determine predictors of bladder injury in cesarean deliveries and to examine the associated morbidities while adjusting for baseline maternal demographics and clinical characteristics. RESULTS: Of 4,169,681 cesarean deliveries identified, there were 7,627 (0.2%) bladder injuries for an overall incidence of 18 per 10,000. Women ≥ 35 years were at greater risk of bladder injury 1.5 (1.4-1.6), as were women with endometriosis 2.0 (1.5-2.7) and Crohn's disease 2.7 (1.7-4.2). Risk of bladder injury increased if the cesarean delivery was associated with placenta previa 2.2 (1.9-2.4), previous cesarean delivery 4.3 (4.1-4.6), failed instrumental delivery 4.1 (3.5-4.8), fetal distress 1.7 (1.6-1.8), failed trial of labor after cesarean delivery 1.3 (1.2-1.4), and labor dystocia 1.7 (1.6-1.8). Cesarean hysterectomies presented the greatest risk for bladder injury 37.0 (33.7-40.6). Bladder injury was associated with an increased frequency of sepsis, venous thromboembolism, peritonitis, blood transfusions and longer hospital stays. CONCLUSION: Bladder injury during cesarean deliveries is a rare outcome but it is more common among women with certain demographic and clinical characteristics. Among these cases, strategies to prevent sepsis and venous thromboembolism should be considered.
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Vejiga Urinaria , Tromboembolia Venosa , Embarazo , Femenino , Estados Unidos/epidemiología , Humanos , Masculino , Estudios de Cohortes , Estudios Retrospectivos , Incidencia , Factores de RiesgoRESUMEN
PURPOSE: With improvement in cancer care and fertility preservation, increasing numbers of cancer survivors are requiring obstetrical care. The objective of our study was to evaluate the effect of history of chemotherapy exposure on maternal and neonatal outcomes. METHODS: A retrospective population-based cohort study was conducted using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) to obtain data on maternal and newborn outcomes in a cohort of births occurring between the years 2006 and 2015. The annual and overall prevalence of chemotherapy exposure was calculated among pregnant women, and multivariate logistic regression models were used to estimate the effect of history of exposure to chemotherapy on the risk of adverse maternal and newborn outcomes. RESULTS: Of 7,907,139 birth admissions, 613 had a history of chemotherapy exposure for an overall incidence of 7.75 per 100,000 admissions. The prevalence of chemotherapy exposure in pregnancy increased during the study period (P < 0.001). Women with a history of chemotherapy were more likely to suffer from obstetric and medical complications including pre-eclampsia, chorioamnionitis, postpartum hemorrhage, and venous thromboembolism as well as an increased risk in overall mortality (OR 9.39, 95% CI 1.31-67.32). No differences were observed in the incidence of adverse neonatal outcomes, including stillbirth, intra-uterine growth restriction, or preterm birth. CONCLUSION: Women with history of chemotherapy have higher incidence of pregnancy complications and maternal death, with no differences in fetal or newborn outcomes.
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Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Parto Obstétrico/efectos adversos , Nacimiento Prematuro/epidemiología , Estudios de Cohortes , Complicaciones del Embarazo/epidemiologíaRESUMEN
In spite of its central role in biology and disease, protein turnover is a largely understudied aspect of most proteomic studies due to the complexity of computational workflows that analyze in vivo turnover rates. To address this need, we developed a new computational tool, TurnoveR, to accurately calculate protein turnover rates from mass spectrometric analysis of metabolic labeling experiments in Skyline, a free and open-source proteomics software platform. TurnoveR is a straightforward graphical interface that enables seamless integration of protein turnover analysis into a traditional proteomics workflow in Skyline, allowing users to take advantage of the advanced and flexible data visualization and curation features built into the software. The computational pipeline of TurnoveR performs critical steps to determine protein turnover rates, including isotopologue demultiplexing, precursor-pool correction, statistical analysis, and generation of data reports and visualizations. This workflow is compatible with many mass spectrometric platforms and recapitulates turnover rates and differential changes in turnover rates between treatment groups calculated in previous studies. We expect that the addition of TurnoveR to the widely used Skyline proteomics software will facilitate wider utilization of protein turnover analysis in highly relevant biological models, including aging, neurodegeneration, and skeletal muscle atrophy.
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Proteómica , Programas Informáticos , Proteómica/métodos , Proteolisis , Espectrometría de Masas/métodos , Flujo de Trabajo , Marcaje Isotópico/métodosRESUMEN
Lipidomics studies suffer from analytical and annotation challenges because of the great structural similarity of many of the lipid species. To improve lipid characterization and annotation capabilities beyond those afforded by traditional mass spectrometry (MS)-based methods, multidimensional separation methods such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation and MS (LC-IMS-CID-MS) may be used. Although LC-IMS-CID-MS and other multidimensional methods offer valuable hydrophobicity, structural and mass information, the files are also complex and difficult to assess. Thus, the development of software tools to rapidly process and facilitate confident lipid annotations is essential. In this Protocol Extension, we use the freely available, vendor-neutral and open-source software Skyline to process and annotate multidimensional lipidomic data. Although Skyline ( https://skyline.ms/skyline.url ) was established for targeted processing of LC-MS-based proteomics data, it has since been extended such that it can be used to analyze small-molecule data as well as data containing the IMS dimension. This protocol uses Skyline's recently expanded capabilities, including small-molecule spectral libraries, indexed retention time and ion mobility filtering, and provides a step-by-step description for importing data, predicting retention times, validating lipid annotations, exporting results and editing our manually validated 500+ lipid library. Although the time required to complete the steps outlined here varies on the basis of multiple factors such as dataset size and familiarity with Skyline, this protocol takes ~5.5 h to complete when annotations are rigorously verified for maximum confidence.
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Espectrometría de Movilidad Iónica , Lipidómica , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , LípidosRESUMEN
RING-between-RING (RBR) E3 ligases mediate ubiquitin transfer through an obligate E3-ubiquitin thioester intermediate prior to substrate ubiquitination. Although RBRs share a conserved catalytic module, substrate recruitment mechanisms remain enigmatic, and the relevant domains have yet to be identified for any member of the class. Here we characterize the interaction between the auto-inhibited RBR, HHARI (AriH1), and its target protein, 4EHP, using a combination of XL-MS, HDX-MS, NMR, and biochemical studies. The results show that (1) a di-aromatic surface on the catalytic HHARI Rcat domain forms a binding platform for substrates and (2) a phosphomimetic mutation on the auto-inhibitory Ariadne domain of HHARI promotes release and reorientation of Rcat for transthiolation and substrate modification. The findings identify a direct binding interaction between a RING-between-RING ligase and its substrate and suggest a general model for RBR substrate recognition.
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Proteínas Cullin , Ubiquitina , Dominio Catalítico , Proteínas Cullin/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/química , UbiquitinaciónRESUMEN
OBJECTIVE: To evaluate whether the increased risk of breast cancer is dependent on the formulation of menopausal hormone therapy (HT) used. METHODS: We performed a population-based case-control study of women aged 50 years or older using data from the U.K. Clinical Practice Research Datalink. Women with incident cases of breast cancer were age-matched (1:10) with a control group of women with comparable follow-up time with no history of breast cancer. Exposures were classified as ever or never for the following menopausal HT formulations: bioidentical estrogens, animal-derived estrogens, micronized progesterone, and synthetic progestin. Logistic regression analyses were performed to estimate the adjusted effect of menopausal HT formulation on breast cancer risk. RESULTS: Between 1995 and 2014, 43,183 cases of breast cancer were identified and matched to 431,830 women in a control group. In adjusted analyses, compared with women who never used menopausal HT, its use was associated with an increased risk of breast cancer (odds ratio [OR] 1.12, 95% CI 1.09-1.15). Compared with never users, estrogens were not associated with breast cancer (bioidentical estrogens: OR 1.04, 95% CI 1.00-1.09; animal-derived estrogens: OR 1.01, 95% CI 0.96-1.06; both: OR 0.96, 95% CI 0.89-1.03). Progestogens appeared to be differentially associated with breast cancer (micronized progesterone: OR 0.99, 95% CI 0.55-1.79; synthetic progestin: OR 1.28, 95% CI 1.22-1.35; both OR 1.31, 0.30-5.73). CONCLUSION: Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins. When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.
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Neoplasias de la Mama , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/efectos adversos , Femenino , Humanos , Menopausia , Progesterona/efectos adversos , Progestinas/uso terapéutico , Factores de RiesgoRESUMEN
OBJECTIVES: Pregnancy outcomes in women with inflammatory myopathies (IM) are not well studied. The purpose of this study is to evaluate the effects of IM on maternal and neonatal outcomes. METHODS: We conducted a retrospective cohort study using data from the Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS) from 1999 to 2015. Among all pregnant women who delivered during this period, those with a diagnosis of IM were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding, which included all patients with dermatomyositis and polymyositis. Maternal and neonatal outcomes were compared in pregnant women with and without IM. Multivariate logistic regression analysis was used to estimate the adjusted effects of IM on these outcomes. RESULTS: A total of 13,792,544 pregnant women delivered between 1999 and 2015, of which 308 had a diagnosis of IM, for an overall prevalence of 2 per 100,000 pregnant women, with rates increasing over the study period. Pregnant women with IM were more likely to be older, African American and suffer from other autoimmune connective tissue diseases. IM in pregnancy was associated with greater risk of preeclampsia, caesarean delivery, major postpartum infections, urinary tract infections and longer hospital stay. Neonates born to mothers with IM had greater risk of prematurity, small for gestational age and intrauterine fetal demise. CONCLUSIONS: Pregnant women with IM are at higher risk of adverse maternal and neonatal outcomes and should be closely followed in specialized centers with collaboration between maternal-fetal medicine and rheumatology.
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Miositis , Complicaciones del Embarazo , Femenino , Humanos , Recién Nacido , Miositis/complicaciones , Miositis/diagnóstico , Miositis/epidemiología , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Mujeres Embarazadas , Estudios RetrospectivosRESUMEN
PURPOSE: Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease with an often-unsatisfactory response to treatment. The objective was to evaluate the association between HS and pregnancy, delivery and neonatal outcomes. METHODS: The United States' Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database was used to conduct a retrospective cohort study among all women who delivered between 1999 and 2015. ICD-9 code 705.83 identified those with HS, with the remaining deliveries composing the comparison group. Multivariate logistic regression compared maternal and neonatal outcomes between these two groups, while adjusting for baseline maternal variables. RESULTS: The study included 13,792,544 deliveries, of which 1021 were associated with an HS diagnosis (7.4/100,000 deliveries). During the observation period, there was an upward trend in the prevalence of HS among pregnant women (<0.0001). Pregnant women with HS were more likely to be African-American, to belong to a lower income quartile, and to be insured by Medicaid. They were also more likely to smoke, to be morbidly obese, and to be hypertensive. Compared with women without HS, those with HS had a greater likelihood of developing preeclampsia (OR 1.36, 95% CI 1.08-1.71), delivering by cesarean section (OR 1.78, 95% CI 1.56-2.02), and having a baby with congenital anomalies (OR 2.00, 95% CI 1.10-3.62). CONCLUSIONS: Although HS is a complex skin disorder, pregnancies complicated by HS had comparable outcomes to non-HS pregnancies, with the exception of a greater risk of preeclampsia, cesarean sections, and congenital anomalies. Health-care providers and women should be aware of these HS associated risks.