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1.
Nature ; 583(7818): 711-719, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32728246

RESUMO

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.


Assuntos
Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Transcriptoma/genética , Processamento Alternativo/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Cromatina/genética , Cromatina/metabolismo , Bases de Dados Genéticas , Feminino , Técnicas de Silenciamento de Genes , Humanos , Espaço Intracelular/genética , Masculino , Ligação Proteica , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Especificidade por Substrato
2.
BMC Bioinformatics ; 25(1): 142, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566005

RESUMO

BACKGROUND: The rapid advancement of new genomic sequencing technology has enabled the development of multi-omic single-cell sequencing assays. These assays profile multiple modalities in the same cell and can often yield new insights not revealed with a single modality. For example, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) simultaneously profiles the RNA transcriptome and the surface protein expression. The surface protein markers in CITE-Seq can be used to identify cell populations similar to the iterative filtration process in flow cytometry, also called "gating", and is an essential step for downstream analyses and data interpretation. While several packages allow users to interactively gate cells, they often do not process multi-omic sequencing datasets and may require writing redundant code to specify gate boundaries. To streamline the gating process, we developed CITEViz which allows users to interactively gate cells in Seurat-processed CITE-Seq data. CITEViz can also visualize basic quality control (QC) metrics allowing for a rapid and holistic evaluation of CITE-Seq data. RESULTS: We applied CITEViz to a peripheral blood mononuclear cell CITE-Seq dataset and gated for several major blood cell populations (CD14 monocytes, CD4 T cells, CD8 T cells, NK cells, B cells, and platelets) using canonical surface protein markers. The visualization features of CITEViz were used to investigate cellular heterogeneity in CD14 and CD16-expressing monocytes and to detect differential numbers of detected antibodies per patient donor. These results highlight the utility of CITEViz to enable the robust classification of single cell populations. CONCLUSIONS: CITEViz is an R-Shiny app that standardizes the gating workflow in CITE-Seq data for efficient classification of cell populations. Its secondary function is to generate basic feature plots and QC figures specific to multi-omic data. The user interface and internal workflow of CITEViz uniquely work together to produce an organized workflow and sensible data structures for easy data retrieval. This package leverages the strengths of biologists and computational scientists to assess and analyze multi-omic single-cell datasets. In conclusion, CITEViz streamlines the flow cytometry gating workflow in CITE-Seq data to help facilitate novel hypothesis generation.


Assuntos
Leucócitos Mononucleares , Software , Humanos , Análise de Sequência de RNA/métodos , Fluxo de Trabalho , Citometria de Fluxo , Proteínas de Membrana , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodos
3.
J Surg Oncol ; 129(6): 1089-1096, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38419204

RESUMO

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors associated with perioperative venous thromboembolism (VTE) in patients undergoing major oncologic surgery using an epidural catheter (EC) for postoperative analgesia with mechanical prophylaxis and without chemoprophylaxis. METHODS: Six hundred and twenty-six patients undergoing major oncologic surgery from 2009 to 2023 were evaluated. VTE was defined as deep vein thrombosis above the level of the knee. Lower extremity venous duplexes (LEVDs) were done preoperatively and postoperatively after the EC was removed. All patients received mechanical thromboprophylaxis, but not chemical prophylaxis, while the EC was in place. A generalized linear multivariable model was constructed to identify risk factors that predict pre and postoperative VTE. RESULTS: 29/626 patients (4.6%) were found to have preoperative VTE. 16/626 (2.6%) were found to have a postoperative VTE when their preoperative LEVD was negative. In comparison to patients without preoperative VTE, those with VTE were more likely to be male, anticoagulated, and have a history of coronary artery disease. Patients in the postoperative VTE group were older, male, anticoagulated, and had a history of VTE. On multivariable analysis, previous history of VTE was the risk factor most strongly associated with both pre and postoperative VTE. CONCLUSION: Oncologic patients undergoing elective abdominopelvic surgery with epidural analgesia should be screened in the perioperative setting with LEVD to identify VTE and possibly prevent PE.


Assuntos
Complicações Pós-Operatórias , Tromboembolia Venosa , Humanos , Masculino , Feminino , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Abdominais/cirurgia , Estudos Retrospectivos , Analgesia Epidural , Neoplasias Pélvicas/cirurgia , Seguimentos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Prognóstico , Adulto
4.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811141

RESUMO

Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells. In the HIV cohort, these dysregulations were evident despite viral suppression for over 10 y. Viral clearance in the HCV cohort partially restored cellular sensitivity to interferon-α, but many immune system alterations persisted for at least 1 y posttreatment. Our findings indicate that in the HIV and HCV cohorts, a broad remodeling and degradation of the immune system can persist for a year or more, even after the removal or drastic reduction of the pathogen load and that this shares some features of chronic inflammation in aging.


Assuntos
Envelhecimento/imunologia , Infecções por HIV/imunologia , Hepatite C/imunologia , Carga Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade , Antivirais/uso terapêutico , Células Cultivadas , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Interferon-alfa/metabolismo , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Sofosbuvir/uso terapêutico
5.
J Public Health Manag Pract ; 30(2): 231-239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38271105

RESUMO

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.


Assuntos
Antraz , Farmácia , Humanos , Antraz/tratamento farmacológico , Antraz/prevenção & controle , Profilaxia Pós-Exposição , Farmacêuticos , Saúde Pública
6.
Radiology ; 307(5): e223088, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37219443

RESUMO

Background Photon-counting CT (PCCT) has been shown to improve cardiovascular CT imaging in adults. Data in neonates, infants, and young children under the age of 3 years are missing. Purpose To compare image quality and radiation dose of ultrahigh-pitch PCCT with that of ultrahigh-pitch dual-source CT (DSCT) in children suspected of having congenital heart defects. Materials and Methods This is a prospective analysis of existing clinical CT studies in children suspected of having congenital heart defects who underwent contrast-enhanced PCCT or DSCT in the heart and thoracic aorta between January 2019 and October 2022. CT dose index and dose-length product were used to calculate effective radiation dose. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated by standardized region-of-interest analysis. SNR and CNR dose ratios were calculated. Visual image quality was assessed by four independent readers on a five-point scale: 5, excellent or absent; 4, good or minimal; 3, moderate; 2, limited or substantial; and 1, poor or massive. Results Contrast-enhanced PCCT (n = 30) or DSCT (n = 84) was performed in 113 children (55 female and 58 male participants; median age, 66 days [IQR, 15-270]; median height, 56 cm [IQR, 52-67]; and median weight, 4.5 kg [IQR, 3.4-7.1]). A diagnostic image quality score of at least 3 was obtained in 29 of 30 (97%) with PCCT versus 65 of 84 (77%) with DSCT. Mean overall image quality ratings were higher for PCCT versus DSCT (4.17 vs 3.16, respectively; P < .001). SNR and CNR were higher for PCCT versus DSCT with SNR (46.3 ± 16.3 vs 29.9 ± 15.3, respectively; P = .007) and CNR (62.0 ± 50.3 vs 37.2 ± 20.8, respectively; P = .001). Mean effective radiation doses were similar for PCCT and DSCT (0.50 mSv vs 0.52 mSv; P = .47). Conclusion At a similar radiation dose, PCCT offers a higher SNR and CNR and thus better cardiovascular imaging quality than DSCT in children suspected of having cardiac heart defects. © RSNA, 2023.


Assuntos
Cardiopatias Congênitas , Tomografia Computadorizada por Raios X , Adulto , Recém-Nascido , Criança , Humanos , Masculino , Lactente , Feminino , Pré-Escolar , Tomografia Computadorizada por Raios X/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Razão Sinal-Ruído , Tórax , Pulmão , Doses de Radiação
7.
Mol Pharm ; 20(10): 5019-5031, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37682633

RESUMO

Grid-based systematic search methods are used to investigate molecule-molecule, molecule-surface, and surface-surface contributions to interparticle interactions in order to identify the crystal faces that most strongly affect particle behavior during powder blend formulation and delivery processes. The model system comprises terbutaline sulfate (TBS) as an active pharmaceutical ingredient (API) and α-form lactose monohydrate (LMH). A combination of systematic molecular modeling and X-ray computed tomography (XCT) is used to determine not only the adhesive and cohesive interparticle energies but, also the agglomeration behavior during manufacturing and de-agglomeration behavior during delivery after inhalation. This is achieved through a detailed examination of the balance between the adhesive and cohesive energies with the XCT results confirming the blend segregation tendencies, through the particle-particle de-agglomeration process. The results reveal that the cohesive interaction energies of TBS-TBS are higher than the adhesive energies between TBS and LMH, but that the cohesive energies of LMH-LMH are the smallest between molecule and molecule, molecule and surface, and surface and surface. This shows how systematic grid-search molecular modeling along with XCT can guide the digital formulation design of inhalation powders in order to achieve optimum aerosolization and efficacy for inhaled medicines. This will lead to faster pharmaceutical design with less variability, higher quality, and enhanced performance.

8.
Support Care Cancer ; 31(2): 111, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633678

RESUMO

PURPOSE: Most breast cancer survivors have challenges with adopting healthy lifestyle behaviors. This may be due to contextual challenges that result from the complex nature of the evidence. To address this gap, we explored the experiences of breast cancer survivors of color and oncology healthcare providers. METHODS: Content analysis with inductive and deductive approaches was used for semi-structured interviews with 26 female breast cancer survivors and 10 oncology healthcare providers from Greater New Haven, Connecticut. RESULTS: Survivors identified substantial confusion on the evidence regarding lifestyle behaviors and breast cancer, stemming from inadequate healthcare provider counseling and an overreliance on informal sources of information. Providers identified lack of evidence-based knowledge as a barrier to counseling on these topics. There was a mixed perspective regarding the consistency of evidence, stemming from a combination of gaps in the available evidence and accessing evidence-based knowledge from a wide range of professional resources. Some providers perceived the guidelines as consistent; others felt guidelines were constantly changing, impacting how and on what they counseled. Therefore, many healthcare providers in oncology care relied on generic messaging on lifestyle behaviors after a cancer diagnosis. CONCLUSIONS: Inconsistent information sources, the rapidly changing evidence, and gaps in the current evidence contribute to generic messaging about lifestyle behaviors and may inhibit a survivor's ability to engage in behavior change. Consistent and uniform healthy lifestyle guidelines for cancer outcomes may address both provider and patient level barriers to knowledge.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Feminino , Humanos , Pessoal de Saúde , Hispânico ou Latino , Estilo de Vida , Negro ou Afro-Americano
9.
BMC Med Educ ; 23(1): 68, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707803

RESUMO

BACKGROUND: Career prospects in academic medicine are strongly linked to scientific authorship and this marker has been widely used as an indicator of gender equity in academia. However, direct comparisons of medical disciplines regarding their proportion of female physicians (FP) in different countries are missing. This study examines the gender parity and gender cooperation using first authorships (FA) and senior authorships (SA) of scientific publications in five medical disciplines and six different OECD countries over a 10-year time-trend. METHODS: Articles from three high-impact journals in each of the medical discipline radiology, urology, surgery, gynecology, and pediatrics from the years 2007/8 and 2017/18 were retrospectively reviewed. The gender and affiliation location of the FA and SA of original research articles and reviews were assigned and compared with the proportion of in each discipline for the United States of America, Canada, United Kingdom, France, Germany, and Japan. Mantel-Haenszel test and multinomial logistic regression models were used to calculate differences in proportions of women authors and FP and to assess trends and proportions of FA and SA. RESULTS: 30,803 articles were evaluated. Equally, with rising proportions of FP in all disciplines, the number of women authors increased across years. The shares of women FAs were either significantly higher (urology/surgery/gynecology) or balanced (pediatrics/radiology) compared to the proportion of FP. In contrast, the shares of women SA were balanced only in disciplines with a low proportion of FP (urology and surgery) and otherwise reduced. Women same-gender cooperation was as common as men same-gender cooperation and preferred over a women-led mixed gender cooperation in disciplines where this seemed to be practicable due to the high proportions of FP. CONCLUSION: In contrast to FA, a significant disparity persists in SA, particularly in disciplines with a high proportion of FP. The discrepancy between FA and SA may reflect, among others, dropout from an academic career in early or mid-academic levels, for example, due to structural inequality; together with the findings on gender preference in authorship collaborations, this may inform future strategies for promoting equal career advancement for women physicians.


Assuntos
Autoria , Bibliometria , Masculino , Humanos , Feminino , Estados Unidos , Criança , Fatores Sexuais , Estudos Retrospectivos , Publicações
10.
Perfusion ; : 2676591231216794, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37977566

RESUMO

INTRODUCTION: Cardiac surgery in patients on chronic renal dialysis is associated with significant morbidity and mortality. Minimally invasive extracorporeal circuits (MiECC) have shown a positive impact on patient outcome in different high-risk populations. This retrospective study compares the outcome of these high-risk patients undergoing heart surgery either with a MiECC or a conventional extracorporeal circulation (CECC). METHODS: This is a single-center experience including 131 consecutive dialysis dependent patients undergoing cardiac surgery between January 2006 and December 2016. A propensity score matching was employed leaving 30 matched cases in each group. RESULTS: After propensity score matching the 30-day mortality was significantly lower in the MiECC group (n = 3 (10%) vs n = 10 (33%) in the CECC group, p = .028). Further, intraoperative transfused units of packed red blood cells were lower in the MiECC group (1.4 ± 1.8 units vs 2.8 ± 1.7, p < .001). CONCLUSIONS: There are evident advantages to using MiECC in dialysis dependent patients, especially regarding mortality. These findings necessitate additional research in MiECC usage in high-risk populations.

11.
Sensors (Basel) ; 23(16)2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37631745

RESUMO

This paper presents a depth-based hybrid method to generate safe flight corridors for a memoryless local navigation planner. It is first proposed to use raw depth images as inputs in the learning-based object-detection engine with no requirement for map fusion. We then employ an object-detection network to directly predict the base of polyhedral safe corridors in a new raw depth image. Furthermore, we apply a verification procedure to eliminate any false predictions so that the resulting collision-free corridors are guaranteed. More importantly, the proposed mechanism helps produce separate safe corridors with minimal overlap that are suitable to be used as space boundaries for path planning. The average intersection of union (IoU) of corridors obtained by the proposed algorithm is less than 2%. To evaluate the effectiveness of our method, we incorporated it into a memoryless planner with a straight-line path-planning algorithm. We then tested the entire system in both synthetic and real-world obstacle-dense environments. The obtained results with very high success rates demonstrate that the proposed approach is highly capable of producing safe corridors for memoryless local planning.

12.
J Radiol Prot ; 43(2)2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37257439

RESUMO

The outdoor222Rn and220Rn concentrations at 320 sampling points at 1 m above the ground in different sites surrounding rare earth element (REE) and uranium mines from northern Vietnam were measured using the RAD7. Results showed that222Rn concentrations were always higher than220Rn concentrations with large variation ranges from 25.7 to 573 Bq m-3and from 18.5 to 385 Bq m-3, respectively. The high correlation between220Rn and228Ra concentrations in surface soil of the studied sites were observed. The highest220Rn and222Rn concentrations are found at the sampling points of the REE NX-Lai Chau site. The220Rn and222Rn activities surrounding the REE mines were found to be higher than those surrounding the uranium mines. The average annual committed effective doses originated from the inhalation of220Rn and222Rn outdoor concentrations is about five times higher than the worldwide average value.


Assuntos
Monitoramento de Radiação , Radônio , Urânio , Radônio/análise , Urânio/análise , Vietnã , Mineração , Medição de Risco
13.
Appl Intell (Dordr) ; 53(12): 15909-15922, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36466775

RESUMO

Domain adaptation is a potential method to train a powerful deep neural network across various datasets. More precisely, domain adaptation methods train the model on training data and test that model on a completely separate dataset. The adversarial-based adaptation method became popular among other domain adaptation methods. Relying on the idea of GAN, the adversarial-based domain adaptation tries to minimize the distribution between the training and testing dataset based on the adversarial learning process. We observe that the semi-supervised learning approach can combine with the adversarial-based method to solve the domain adaptation problem. In this paper, we propose an improved adversarial domain adaptation method called Semi-Supervised Adversarial Discriminative Domain Adaptation (SADDA), which can outperform other prior domain adaptation methods. We also show that SADDA has a wide range of applications and illustrate the promise of our method for image classification and sentiment classification problems.

15.
Curr Issues Mol Biol ; 43(3): 2210-2219, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34940129

RESUMO

Astronauts are always faced with serious health problems during prolonged spaceflights. Previous studies have shown that weightlessness significantly affects the physiological function of female astronauts, including a change in reproductive hormones and ovarian cells, such as granulosa and theca cells. However, the effects of microgravity on these cells have not been well characterized, especially in granulosa cells. This study aimed to investigate the effects of simulated microgravity (SMG) on the proliferation and morphology of porcine granulosa cells (pGCs). pGC proliferation from the SMG group was inhibited, demonstrated by the reduced O.D. value and cell density in the WST-1 assay and cell number counting. SMG-induced pGCs exhibited an increased ratio of cells in the G0/G1 phase and a decreased ratio of cells in the S and G2/M phase. Western blot analysis indicated a down-regulation of cyclin D1, cyclin-dependent kinase 4 (cdk4), and cyclin-dependent kinase 6 (cdk6), leading to the prevention of the G1-S transition and inducing the arrest phase. pGCs under the SMG condition showed an increase in nuclear area. This caused a reduction in nuclear shape value in pGCs under the SMG condition. SMG-induced pGCs exhibited different morphologies, including fibroblast-like shape, rhomboid shape, and pebble-like shape. These results revealed that SMG inhibited proliferation and induced morphological changes in pGCs.


Assuntos
Células da Granulosa/citologia , Células da Granulosa/fisiologia , Simulação de Ausência de Peso , Ausência de Peso , Citoesqueleto de Actina/metabolismo , Animais , Biomarcadores , Ciclo Celular , Proliferação de Células , Células Cultivadas , Feminino , Suínos
16.
Am J Hum Genet ; 103(2): 296-304, 2018 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-30032983

RESUMO

The dynamic shape of the endoplasmic reticulum (ER) is a reflection of its wide variety of critical cell biological functions. Consequently, perturbation of ER-shaping proteins can cause a range of human phenotypes. Here, we describe three affected children (from two consanguineous families) who carry homozygous loss-of-function mutations in LNPK (previously known as KIAA1715); this gene encodes lunapark, which is proposed to serve as a curvature-stabilizing protein within tubular three-way junctions of the ER. All individuals presented with severe psychomotor delay, intellectual disability, hypotonia, epilepsy, and corpus callosum hypoplasia, and two of three showed mild cerebellar hypoplasia and atrophy. Consistent with a proposed role in neurodevelopmental disease, LNPK was expressed during brain development in humans and mice and was present in neurite-like processes in differentiating human neural progenitor cells. Affected cells showed the absence of full-length lunapark, aberrant ER structures, and increased luminal mass density. Together, our results implicate the ER junction stabilizer lunapark in establishing the corpus callosum.


Assuntos
Retículo Endoplasmático/genética , Proteínas de Homeodomínio/genética , Mutação/genética , Adolescente , Animais , Atrofia/genética , Diferenciação Celular/genética , Criança , Corpo Caloso/patologia , Feminino , Humanos , Lactente , Deficiência Intelectual/genética , Masculino , Proteínas de Membrana , Camundongos , Hipotonia Muscular/genética , Fenótipo , Transtornos Psicomotores/genética , Células-Tronco/patologia
17.
Biotechnol Bioeng ; 118(10): 3847-3859, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34129251

RESUMO

Predicting the fate of individual cells among a microbial population (i.e., growth and gene expression) remains a challenge, especially when this population is exposed to very dynamic environmental conditions, such as those encountered during continuous cultivation. Indeed, the dynamic nature of a continuous cultivation process implies the potential diversification of the microbial population resulting in genotypic and phenotypic heterogeneity. The present work focused on the induction of the arabinose operon in Escherichia coli as a model system to study this diversification process in continuous cultivations. As a preliminary step, the green fluorescent protein (GFP) level triggered by an arabinose-inducible ParaBAD promoter was tracked by flow cytometry in chemostat cultivations with glucose-arabinose co-feeding. For a wide range of glucose-arabinose co-feeding concentrations in the chemostats, the simultaneous occurrence of GFP positive and negative subpopulation was observed. In the second set of experiments, continuous cultivation was performed by adding glucose continuously and arabinose based on the capability of individual cells to switch from low GFP to high GFP expression states, performed with a technology setup called segregostat. In the segregostat cultivation mode, on-line flow cytometry analysis was used for adjusting the arabinose/glucose transitions based on the phenotypic switching profiles of the microbial population. This strategy allowed finding an appropriate arabinose pulsing frequency, leading to prolonged maintenance of the induction level with a limited increase in the phenotypic diversity for more than 60 generations. The results suggest that the steady forcing of individual cells into a given phenotypic trajectory may not be the best strategy for controlling cell populations. Instead, allowing individual cells to switch periodically around a predefined threshold seems to be a more robust strategy leading to oscillations, but within a predictable cell population behavior range.


Assuntos
Escherichia coli K12 , Proteínas de Fluorescência Verde/biossíntese , Regiões Promotoras Genéticas , Arabinose/genética , Arabinose/metabolismo , Escherichia coli K12/genética , Escherichia coli K12/crescimento & desenvolvimento , Proteínas de Fluorescência Verde/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética
18.
Malar J ; 20(1): 403, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34656112

RESUMO

BACKGROUND: In 2018, the National Malaria Control Programme in Vietnam switched from prioritizing malaria control to elimination. However, with the ongoing elimination programme, there are still areas where residual malaria transmission persists, including the central highlands. This entomological survey was conducted to evaluate Anopheles diversity and host-seeking activity of Anopheles vectors in two communes with very low malaria transmission in Gia Lai Province. METHODS: Anopheles species were collected in Ia DReh commune and Ia KDam commune, Gia Lai Province in the central highlands of Vietnam. Collections were conducted using human-baited double net trap, light trap and manual aspiration collections around cattle sheds, in the dry and rainy season. Mosquito specimens were identified morphologically, and members of species complexes were distinguished molecularly. Mosquito night-feeding patterns were investigated during the dry and rainy seasons. RESULTS: Overall, 18,835 specimens including 19 taxa were collected in Ia KDam and Ia DReh communes. These included the primary malaria vectors, Anopheles dirus and Anopheles minimus, and other secondary vector species. Anopheles dirus was observed to be an anthropophilic species, whereas An. minimus and a number of secondary vectors were observed to be zoophilic. Anopheles vagus was the dominant species, followed by Anopheles sinensis and Anopheles peditaeniatus. The majority of specimens were collected in the rainy season due to the relatively large number of An. vagus, while An. peditaeniatus, An. dirus, Anopheles kochi, Anopheles monstrosus and Anopheles tessellatus were collected in greater numbers during the dry season. The peak of host-seeking activity for An. dirus, An. sinensis, and An. vagus was between 18.00 and 19.00 h. CONCLUSION: This study provided information on the diversity, seasonal prevalence and behaviour of Anopheles at the study sites. Identifying the diverse mosquito fauna in the central highlands of Vietnam allows species-specific control measures to be implemented by the National Programme to reduce malaria in areas of very low malaria transmission. The peak Anopheles host-seeking activity observed in this study was between 18.00 and 23.00 h, which highlights the need to better characterize Anopheles behaviour in this region of Vietnam to inform on vector control strategies.


Assuntos
Anopheles/fisiologia , Malária/transmissão , Mosquitos Vetores/fisiologia , Animais , Anopheles/classificação , Anopheles/parasitologia , Fazendas , Florestas , Humanos , Malária/epidemiologia , Malária/prevenção & controle , Mosquitos Vetores/classificação , Mosquitos Vetores/parasitologia , Reação em Cadeia da Polimerase/métodos , Estações do Ano , Vietnã/epidemiologia
19.
Eur Radiol ; 31(12): 8887-8896, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34009412

RESUMO

OBJECTIVES: To analyze the development of publication numbers of female authors in high-, medium-, and low-impact radiological journals. METHODS: In this bibliometric analysis, gender of the first (FA) and senior author (SA) was assigned to all original research articles and reviews, published in 10 high-, medium-, and low-impact radiological journals in 2007/8 and 2017/18. The adjusted event rate (AER) and adjusted odds ratio (AOR) were calculated using mixed logistic and multinomial logistic regression models to assess and compare female publications according to impact factor, journal, author position, and combination. RESULTS: The proportion of female FA and female SA in N = 6979 (2007/2008) and N = 7383 (2017/2018) articles increased to 29.1% and 16.1% in 2017/2018, respectively. While most female authorships were continuously observed in medium-impact journals, the strongest increase occurred for both female FA (AOR 2.0; p < .0001) and SA (AOR 2.1; p < .0001) in low-impact journals. Female SA published significantly more often in a low- (AOR 1.5) or medium- (AOR 1.8) than in a high-ranking journal. Among the high-ranking journals, female FA published most frequently in European Radiology (32.4%; 95% CI [29.3-35.8]; p < .0001), female SA in Investigative Radiology (15.9%; 95% CI [13.7-18.4]; p < .0001). Male same-sex authorships decreased (AOR 0.9), but remained at least twice as common as all-female or mixed authorships. CONCLUSION: The increase in female authorship is reflected in all impact areas. Female FA and SA increased most in low-ranking journals but are most common in medium-ranking journals. Female SA remain rare, especially in high impact journals. KEY POINTS: • Compared to the proportion of female radiologists worldwide, female senior authors are underrepresented in all impact areas, in particular in high-impact journals. • Among the included high-ranking radiological journals, female first authors and senior authors were strongest represented in European Radiology and Investigative Radiology, while across all impact areas they mostly published in medium-ranking journals. • Female author combinations were more frequent in low- and medium- than in high-ranking journals, whereas male author combinations remained more common than female senior author collaborations in all impact areas.


Assuntos
Autoria , Radiologia , Bibliometria , Feminino , Humanos , Masculino
20.
Dig Dis Sci ; 66(3): 823-831, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32285322

RESUMO

BACKGROUND/AIMS: The prevalence of acute lower gastrointestinal bleeding (ALGIB) has progressively increased worldwide but there are few studies in Asian populations. This study aimed to develop and validate a scoring system to predict severe ALGIB in Vietnamese. METHODS: Risk factors for severe ALGIB were identified by multiple logistic regression analysis using data from a retrospective cohort of 357 patients admitted to a tertiary hospital. These factors were weighted to develop the severe acute lower gastrointestinal bleeding (SALGIB) score to predict severe ALGIB. The performance of SALGIB was validated in a prospective cohort of 324 patients admitted to 6 other hospitals using area under the receiver operating characteristics curve (AUC) analysis. RESULTS: There were four factors at admission independently associated with severe ALGIB in the derivation cohort: heart rate ≥ 100/min, systolic blood pressure < 100 mmHg, hematocrit < 35%, and platelets ≤ 150 × 103/µL. The SALGIB score determined severe ALGIB with AUC values of 0.91 and 0.86 in the derivation and validation cohorts, respectively. A SALGIB score < 2 associated with low risk of severe ALGIB in both cohorts (3.7% and 1.2%; respectively). CONCLUSIONS: The SALGIB score has good performance in discriminating risk of severe ALGIB in Vietnamese.


Assuntos
Povo Asiático/estatística & dados numéricos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etnologia , Medição de Risco/normas , Avaliação de Sintomas/normas , Doença Aguda , Idoso , Área Sob a Curva , Pressão Sanguínea , Feminino , Hemorragia Gastrointestinal/etiologia , Frequência Cardíaca , Hematócrito , Humanos , Modelos Logísticos , Trato Gastrointestinal Inferior , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Avaliação de Sintomas/métodos , Vietnã/etnologia
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