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1.
Crit Care Explor ; 6(9): e1133, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39268149

RESUMO

OBJECTIVE: Pulse oximetry, a ubiquitous vital sign in modern medicine, has inequitable accuracy that disproportionately affects minority Black and Hispanic patients, with associated increases in mortality, organ dysfunction, and oxygen therapy. Previous retrospective studies used self-reported race or ethnicity as a surrogate for skin tone which is believed to be the root cause of the disparity. Our objective was to determine the utility of skin tone in explaining pulse oximetry discrepancies. DESIGN: Prospective cohort study. SETTING: Patients were eligible if they had pulse oximetry recorded up to 5 minutes before arterial blood gas (ABG) measurements. Skin tone was measured using administered visual scales, reflectance colorimetry, and reflectance spectrophotometry. PARTICIPANTS: Admitted hospital patients at Duke University Hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sao2-Spo2 bias, variation of bias, and accuracy root mean square, comparing pulse oximetry, and ABG measurements. Linear mixed-effects models were fitted to estimate Sao2-Spo2 bias while accounting for clinical confounders.One hundred twenty-eight patients (57 Black, 56 White) with 521 ABG-pulse oximetry pairs were recruited. Skin tone data were prospectively collected using six measurement methods, generating eight measurements. The collected skin tone measurements were shown to yield differences among each other and overlap with self-reported racial groups, suggesting that skin tone could potentially provide information beyond self-reported race. Among the eight skin tone measurements in this study, and compared with self-reported race, the Monk Scale had the best relationship with differences in pulse oximetry bias (point estimate: -2.40%; 95% CI, -4.32% to -0.48%; p = 0.01) when comparing patients with lighter and dark skin tones. CONCLUSIONS: We found clinical performance differences in pulse oximetry, especially in darker skin tones. Additional studies are needed to determine the relative contributions of skin tone measures and other potential factors on pulse oximetry discrepancies.


Assuntos
Estado Terminal , Oximetria , Pigmentação da Pele , Humanos , Oximetria/métodos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos de Coortes , Adulto , Gasometria/métodos , População Branca
2.
Crit Care Clin ; 40(4): 827-857, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39218488

RESUMO

This narrative review focuses on the role of clinical prediction models in supporting informed decision-making in critical care, emphasizing their 2 forms: traditional scores and artificial intelligence (AI)-based models. Acknowledging the potential for both types to embed biases, the authors underscore the importance of critical appraisal to increase our trust in models. The authors outline recommendations and critical care examples to manage risk of bias in AI models. The authors advocate for enhanced interdisciplinary training for clinicians, who are encouraged to explore various resources (books, journals, news Web sites, and social media) and events (Datathons) to deepen their understanding of risk of bias.


Assuntos
Inteligência Artificial , Cuidados Críticos , Humanos , Cuidados Críticos/normas , Viés , Tomada de Decisão Clínica
4.
medRxiv ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39211868

RESUMO

Background: Although hypothesized to be the root cause of the pulse oximetry disparities, skin tone and its use for improving medical therapies have yet to be extensively studied. Studies previously used self-reported race as a proxy variable for skin tone. However, this approach cannot account for skin tone variability within race groups and also risks the potential to be confounded by other non-biological factors when modeling data. Therefore, to better evaluate health disparities associated with pulse oximetry, this study aimed to create a unique baseline dataset that included skin tone and electronic health record (EHR) data. Methods: Patients admitted to Duke University Hospital were eligible if they had at least one pulse oximetry value recorded within 5 minutes before an arterial blood gas (ABG) value. We collected skin tone data at 16 different body locations using multiple devices, including administered visual scales, colorimetric, spectrophotometric, and photography via mobile phone cameras. All patients' data were linked in Duke's Protected Analytics Computational Environment (PACE), converted into a common data model, and then de-identified before publication in PhysioNet. Results: Skin tone data were collected from 128 patients. We assessed 167 features per skin location on each patient. We also collected over 2000 images from mobile phones measured in the same controlled environment. Skin tone data are linked with patients' EHR data, such as laboratory data, vital sign recordings, and demographic information. Conclusions: Measuring different aspects of skin tone for each of the sixteen body locations and linking them with patients' EHR data could assist in the development of a more equitable AI model to combat disparities in healthcare associated with skin tone. A common data model format enables easy data federation with similar data from other sources, facilitating multicenter research on skin tone in healthcare. Description: A prospectively collected EHR-linked skin tone measurements database in a common data model with emphasis on pulse oximetry disparities.

5.
PLOS Digit Health ; 3(7): e0000454, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38991014

RESUMO

INTRODUCTION: The Brazilian Multilabel Ophthalmological Dataset (BRSET) addresses the scarcity of publicly available ophthalmological datasets in Latin America. BRSET comprises 16,266 color fundus retinal photos from 8,524 Brazilian patients, aiming to enhance data representativeness, serving as a research and teaching tool. It contains sociodemographic information, enabling investigations into differential model performance across demographic groups. METHODS: Data from three São Paulo outpatient centers yielded demographic and medical information from electronic records, including nationality, age, sex, clinical history, insulin use, and duration of diabetes diagnosis. A retinal specialist labeled images for anatomical features (optic disc, blood vessels, macula), quality control (focus, illumination, image field, artifacts), and pathologies (e.g., diabetic retinopathy). Diabetic retinopathy was graded using International Clinic Diabetic Retinopathy and Scottish Diabetic Retinopathy Grading. Validation used a ConvNext model trained during 50 epochs using a weighted cross entropy loss to avoid overfitting, with 70% training (20% validation), and 30% testing subsets. Performance metrics included area under the receiver operating curve (AUC) and Macro F1-score. Saliency maps were calculated for interpretability. RESULTS: BRSET comprises 65.1% Canon CR2 and 34.9% Nikon NF5050 images. 61.8% of the patients are female, and the average age is 57.6 (± 18.26) years. Diabetic retinopathy affected 15.8% of patients, across a spectrum of disease severity. Anatomically, 20.2% showed abnormal optic discs, 4.9% abnormal blood vessels, and 28.8% abnormal macula. A ConvNext V2 model was trained and evaluated BRSET in four prediction tasks: "binary diabetic retinopathy diagnosis (Normal vs Diabetic Retinopathy)" (AUC: 97, F1: 89); "3 class diabetic retinopathy diagnosis (Normal, Proliferative, Non-Proliferative)" (AUC: 97, F1: 82); "diabetes diagnosis" (AUC: 91, F1: 83); "sex classification" (AUC: 87, F1: 70). DISCUSSION: BRSET is the first multilabel ophthalmological dataset in Brazil and Latin America. It provides an opportunity for investigating model biases by evaluating performance across demographic groups. The model performance of three prediction tasks demonstrates the value of the dataset for external validation and for teaching medical computer vision to learners in Latin America using locally relevant data sources.

6.
Cell ; 187(13): 3303-3318.e18, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906101

RESUMO

Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a "filament identification" (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4ALDH2 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1ACSS2. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.


Assuntos
Gametogênese , Mitocôndrias , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Aldeído Desidrogenase/metabolismo , Aldeído Desidrogenase/química , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Coenzima A Ligases/metabolismo , Microscopia Crioeletrônica , Citoplasma/metabolismo , Tomografia com Microscopia Eletrônica , Meiose , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Esporos Fúngicos/metabolismo , Modelos Moleculares , Estrutura Quaternária de Proteína
7.
Dev Cell ; 59(13): 1764-1782.e8, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38906138

RESUMO

Sexually reproducing eukaryotes employ a developmentally regulated cell division program-meiosis-to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FoF1-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4ALDH2, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4ALDH2 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.


Assuntos
Gametogênese , Meiose , Proteoma , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Fosforilação , Proteoma/metabolismo , Gametogênese/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteômica/métodos , Mitocôndrias/metabolismo , Regulação Fúngica da Expressão Gênica , Saccharomycetales/metabolismo , Saccharomycetales/genética
8.
Sci Data ; 11(1): 535, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789452

RESUMO

Pulse oximeters measure peripheral arterial oxygen saturation (SpO2) noninvasively, while the gold standard (SaO2) involves arterial blood gas measurement. There are known racial and ethnic disparities in their performance. BOLD is a dataset that aims to underscore the importance of addressing biases in pulse oximetry accuracy, which disproportionately affect darker-skinned patients. The dataset was created by harmonizing three Electronic Health Record databases (MIMIC-III, MIMIC-IV, eICU-CRD) comprising Intensive Care Unit stays of US patients. Paired SpO2 and SaO2 measurements were time-aligned and combined with various other sociodemographic and parameters to provide a detailed representation of each patient. BOLD includes 49,099 paired measurements, within a 5-minute window and with oxygen saturation levels between 70-100%. Minority racial and ethnic groups account for ~25% of the data - a proportion seldom achieved in previous studies. The codebase is publicly available. Given the prevalent use of pulse oximeters in the hospital and at home, we hope that BOLD will be leveraged to develop debiasing algorithms that can result in more equitable healthcare solutions.


Assuntos
Gasometria , Oximetria , Humanos , Saturação de Oxigênio , Unidades de Terapia Intensiva , Etnicidade , Oxigênio/sangue
9.
J Biomed Inform ; 153: 104643, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621640

RESUMO

OBJECTIVE: Health inequities can be influenced by demographic factors such as race and ethnicity, proficiency in English, and biological sex. Disparities may manifest as differential likelihood of testing which correlates directly with the likelihood of an intervention to address an abnormal finding. Our retrospective observational study evaluated the presence of variation in glucose measurements in the Intensive Care Unit (ICU). METHODS: Using the MIMIC-IV database (2008-2019), a single-center, academic referral hospital in Boston (USA), we identified adult patients meeting sepsis-3 criteria. Exclusion criteria were diabetic ketoacidosis, ICU length of stay under 1 day, and unknown race or ethnicity. We performed a logistic regression analysis to assess differential likelihoods of glucose measurements on day 1. A negative binomial regression was fitted to assess the frequency of subsequent glucose readings. Analyses were adjusted for relevant clinical confounders, and performed across three disparity proxy axes: race and ethnicity, sex, and English proficiency. RESULTS: We studied 24,927 patients, of which 19.5% represented racial and ethnic minority groups, 42.4% were female, and 9.8% had limited English proficiency. No significant differences were found for glucose measurement on day 1 in the ICU. This pattern was consistent irrespective of the axis of analysis, i.e. race and ethnicity, sex, or English proficiency. Conversely, subsequent measurement frequency revealed potential disparities. Specifically, males (incidence rate ratio (IRR) 1.06, 95% confidence interval (CI) 1.01 - 1.21), patients who identify themselves as Hispanic (IRR 1.11, 95% CI 1.01 - 1.21), or Black (IRR 1.06, 95% CI 1.01 - 1.12), and patients being English proficient (IRR 1.08, 95% CI 1.01 - 1.15) had higher chances of subsequent glucose readings. CONCLUSION: We found disparities in ICU glucose measurements among patients with sepsis, albeit the magnitude was small. Variation in disease monitoring is a source of data bias that may lead to spurious correlations when modeling health data.


Assuntos
Glicemia , Unidades de Terapia Intensiva , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia/análise , Etnicidade/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Retrospectivos , Negro ou Afro-Americano , Hispânico ou Latino
10.
Sensors (Basel) ; 24(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38676025

RESUMO

Wireless communication systems have grown rapidly, moving towards being highly compact, intelligent, and flexible to adapt to changing operating requirements. Multifunctional and highly versatile antennas are key in this development to ensure system quality. Reconfigurable antennas, particularly regarding polarization, allow frequency reuse and enable the mitigation of fading effects. This work presents a square microstrip patch antenna operating in the ISM 5.8 GHz band with reconfigurable polarization by controlling its feeding. This antenna has four different states through the application of a symmetrical DC voltage that controls an RF circuit with PIN diodes. As a result, the microstrip patch can operate with three different polarizations: linear polarization and both circular polarizations (right-handed and left-handed). The antenna was fabricated to validate the proposed concept. The good agreement between the measurement and the simulation results was possible to observe regarding its polarization behaviour, impedance adaptation and radiation pattern.

11.
medRxiv ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38562711

RESUMO

Background: Health research that significantly impacts global clinical practice and policy is often published in high-impact factor (IF) medical journals. These outlets play a pivotal role in the worldwide dissemination of novel medical knowledge. However, researchers identifying as women and those affiliated with institutions in low- and middle-income countries (LMIC) have been largely underrepresented in high-IF journals across multiple fields of medicine. To evaluate disparities in gender and geographical representation among authors who have published in any of five top general medical journals, we conducted scientometric analyses using a large-scale dataset extracted from the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), The British Medical Journal (BMJ), The Lancet, and Nature Medicine. Methods: Author metadata from all articles published in the selected journals between 2007 and 2022 were collected using the DimensionsAI platform. The Genderize.io API was then utilized to infer each author's likely gender based on their extracted first name. The World Bank country classification was used to map countries associated with researcher affiliations to the LMIC or the high-income country (HIC) category. We characterized the overall gender and country income category representation across the medical journals. In addition, we computed article-level diversity metrics and contrasted their distributions across the journals. Findings: We studied 151,536 authors across 49,764 articles published in five top medical journals, over a long period spanning 15 years. On average, approximately one-third (33.1%) of the authors of a given paper were inferred to be women; this result was consistent across the journals we studied. Further, 86.6% of the teams were exclusively composed of HIC authors; in contrast, only 3.9% were exclusively composed of LMIC authors. The probability of serving as the first or last author was significantly higher if the author was inferred to be a man (18.1% vs 16.8%, P < .01) or was affiliated with an institution in a HIC (16.9% vs 15.5%, P < .01). Our primary finding reveals that having a diverse team promotes further diversity, within the same dimension (i.e., gender or geography) and across dimensions. Notably, papers with at least one woman among the authors were more likely to also involve at least two LMIC authors (11.7% versus 10.4% in baseline, P < .001; based on inferred gender); conversely, papers with at least one LMIC author were more likely to also involve at least two women (49.4% versus 37.6%, P < .001; based on inferred gender). Conclusion: We provide a scientometric framework to assess authorship diversity. Our research suggests that the inclusiveness of high-impact medical journals is limited in terms of both gender and geography. We advocate for medical journals to adopt policies and practices that promote greater diversity and collaborative research. In addition, our findings offer a first step towards understanding the composition of teams conducting medical research globally and an opportunity for individual authors to reflect on their own collaborative research practices and possibilities to cultivate more diverse partnerships in their work.

12.
medRxiv ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38464170

RESUMO

Importance: Pulse oximetry, a ubiquitous vital sign in modern medicine, has inequitable accuracy that disproportionately affects Black and Hispanic patients, with associated increases in mortality, organ dysfunction, and oxygen therapy. Although the root cause of these clinical performance discrepancies is believed to be skin tone, previous retrospective studies used self-reported race or ethnicity as a surrogate for skin tone. Objective: To determine the utility of objectively measured skin tone in explaining pulse oximetry discrepancies. Design Setting and Participants: Admitted hospital patients at Duke University Hospital were eligible for this prospective cohort study if they had pulse oximetry recorded up to 5 minutes prior to arterial blood gas (ABG) measurements. Skin tone was measured across sixteen body locations using administered visual scales (Fitzpatrick Skin Type, Monk Skin Tone, and Von Luschan), reflectance colorimetry (Delfin SkinColorCatch [L*, individual typology angle {ITA}, Melanin Index {MI}]), and reflectance spectrophotometry (Konica Minolta CM-700D [L*], Variable Spectro 1 [L*]). Main Outcomes and Measures: Mean directional bias, variability of bias, and accuracy root mean square (ARMS), comparing pulse oximetry and ABG measurements. Linear mixed-effects models were fitted to estimate mean directional bias while accounting for clinical confounders. Results: 128 patients (57 Black, 56 White) with 521 ABG-pulse oximetry pairs were recruited, none with hidden hypoxemia. Skin tone data was prospectively collected using 6 measurement methods, generating 8 measurements. The collected skin tone measurements were shown to yield differences among each other and overlap with self-reported racial groups, suggesting that skin tone could potentially provide information beyond self-reported race. Among the eight skin tone measurements in this study, and compared to self-reported race, the Monk Scale had the best relationship with differences in pulse oximetry bias (point estimate: -2.40%; 95% CI: -4.32%, -0.48%; p=0.01) when comparing patients with lighter and dark skin tones. Conclusions and relevance: We found clinical performance differences in pulse oximetry, especially in darker skin tones. Additional studies are needed to determine the relative contributions of skin tone measures and other potential factors on pulse oximetry discrepancies.

13.
J Biomed Inform ; 152: 104631, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38548006

RESUMO

Selection bias can arise through many aspects of a study, including recruitment, inclusion/exclusion criteria, input-level exclusion and outcome-level exclusion, and often reflects the underrepresentation of populations historically disadvantaged in medical research. The effects of selection bias can be further amplified when non-representative samples are used in artificial intelligence (AI) and machine learning (ML) applications to construct clinical algorithms. Building on the "Data Cards" initiative for transparency in AI research, we advocate for the addition of a participant flow diagram for AI studies detailing relevant sociodemographic and/or clinical characteristics of excluded participants across study phases, with the goal of identifying potential algorithmic biases before their clinical implementation. We include both a model for this flow diagram as well as a brief case study explaining how it could be implemented in practice. Through standardized reporting of participant flow diagrams, we aim to better identify potential inequities embedded in AI applications, facilitating more reliable and equitable clinical algorithms.


Assuntos
Pesquisa Biomédica , Equidade em Saúde , Humanos , Inteligência Artificial , Algoritmos , Aprendizado de Máquina
14.
medRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38343827

RESUMO

Introduction: The Brazilian Multilabel Ophthalmological Dataset (BRSET) addresses the scarcity of publicly available ophthalmological datasets in Latin America. BRSET comprises 16,266 color fundus retinal photos from 8,524 Brazilian patients, aiming to enhance data representativeness, serving as a research and teaching tool. It contains sociodemographic information, enabling investigations into differential model performance across demographic groups. Methods: Data from three São Paulo outpatient centers yielded demographic and medical information from electronic records, including nationality, age, sex, clinical history, insulin use, and duration of diabetes diagnosis. A retinal specialist labeled images for anatomical features (optic disc, blood vessels, macula), quality control (focus, illumination, image field, artifacts), and pathologies (e.g., diabetic retinopathy). Diabetic retinopathy was graded using International Clinic Diabetic Retinopathy and Scottish Diabetic Retinopathy Grading. Validation used Dino V2 Base for feature extraction, with 70% training and 30% testing subsets. Support Vector Machines (SVM) and Logistic Regression (LR) were employed with weighted training. Performance metrics included area under the receiver operating curve (AUC) and Macro F1-score. Results: BRSET comprises 65.1% Canon CR2 and 34.9% Nikon NF5050 images. 61.8% of the patients are female, and the average age is 57.6 years. Diabetic retinopathy affected 15.8% of patients, across a spectrum of disease severity. Anatomically, 20.2% showed abnormal optic discs, 4.9% abnormal blood vessels, and 28.8% abnormal macula. Models were trained on BRSET in three prediction tasks: "diabetes diagnosis"; "sex classification"; and "diabetic retinopathy diagnosis". Discussion: BRSET is the first multilabel ophthalmological dataset in Brazil and Latin America. It provides an opportunity for investigating model biases by evaluating performance across demographic groups. The model performance of three prediction tasks demonstrates the value of the dataset for external validation and for teaching medical computer vision to learners in Latin America using locally relevant data sources.

16.
J Biol Chem ; 300(3): 105767, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367672

RESUMO

Approximately 5 to 15% of nonmedullary thyroid cancers (NMTC) present in a familial form (familial nonmedullary thyroid cancers [FNMTC]). The genetic basis of FNMTC remains largely unknown, representing a limitation for diagnostic and clinical management. Recently, germline mutations in DNA repair-related genes have been described in cases with thyroid cancer (TC), suggesting a role in FNMTC etiology. Here, two FNMTC families were studied, each with two members affected with TC. Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing, revealing two germline CHEK2 missense variants (c.962A > C, p.E321A and c.470T > C, p.I157T), which segregated with TC in each FNMTC family. p.E321A, located in the CHK2 protein kinase domain, is a rare variant, previously unreported in the literature. Conversely, p.I157T, located in CHK2 forkhead-associated domain, has been extensively described, having conflicting interpretations of pathogenicity. CHK2 proteins (WT and variants) were characterized using biophysical methods, molecular dynamics simulations, and immunohistochemistry. Overall, biophysical characterization of these CHK2 variants showed that they have compromised structural and conformational stability and impaired kinase activity, compared to the WT protein. CHK2 appears to aggregate into amyloid-like fibrils in vitro, which opens future perspectives toward positioning CHK2 in cancer pathophysiology. CHK2 variants exhibited higher propensity for this conformational change, also displaying higher expression in thyroid tumors. The present findings support the utility of complementary biophysical and in silico approaches toward understanding the impact of genetic variants in protein structure and function, improving the current knowledge on CHEK2 variants' role in FNMTC genetic basis, with prospective clinical translation.


Assuntos
Quinase do Ponto de Checagem 2 , Síndromes Neoplásicas Hereditárias , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Quinase do Ponto de Checagem 2/química , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndromes Neoplásicas Hereditárias/genética , Estudos Prospectivos , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Domínios Proteicos , Masculino , Feminino , Pessoa de Meia-Idade
17.
Materials (Basel) ; 16(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38068069

RESUMO

Composite materials are used in a substantial number of products. Environmental concerns highlight the need for the inclusion of recovered waste in their formulation, thus reducing their carbon footprint. These solutions raise the need to confirm the mechanical characteristics of these materials, avoiding unwanted failures. In this work, the authors present an experimental study on the drilling effects on fibrous-particulate hybrid composites made of glass/carbon fabrics and three different micro-inclusions: silica particles, recycled carbon fibre powder and cement. The mechanical features of the plates are confirmed by thrust force monitoring during drilling and by flexural testing. The range of results confirm the mechanical outcomes due to machining. The plates with monolithic carbon fabric or with carbon fabric plies in the outer plies returned higher mechanical characteristics. The plates with micro-inclusions had enhanced the flexural strength by 23% and 10%, in 40% and 60% fabric plates, respectively. The results demonstrate that the use of alternative formulations with micro-inclusions from recovered waste can contribute both to the reduction of the mechanical degradation of drilled hybrid composites and to environmental purposes by avoiding the increase in landfill waste.

18.
Yale J Biol Med ; 96(3): 293-312, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37780990

RESUMO

Background: Low-resolution administrative databases can give biased results, whereas high-resolution, time-stamped variables from clinical databases like MIMIC-IV might provide nuanced insights. We evaluated racial-ethnic disparities in life-sustaining ICU-treatments (Invasive Mechanical Ventilation (IMV), Renal Replacement Therapy (RRT), and Vasopressors (VP)) among patients with sepsis. Methods: In this observational retrospective cohort study, patients fulfilling sepsis-3 criteria were categorized by treatment assignment within the first 4 days. The outcomes were treatment allocations. The likelihood of receiving treatment was calculated by race-ethnicity (Racial-ethnic group (REG) or White group (WG)) using 5-fold sub-sampling nested logistic regression and XGBoost. Results: In 23,914 admissions, 82% were White, 42% were women. REG were less likely to receive IMV across all eligibility days (day 1 odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83-0.94, day 4 OR 0.80, 95% CI 0.72 - 0.87). There were no differences in RRT (day 1 OR 1.00, 95% CI 0.96-1.09, day 4 OR 1.00, 95% CI 0.94-1.06). REG were also less likely to be treated with VP at days 1 to 3 (day 1 OR 0.87, 95% CI 0.76-0.94), but not at day 4 (OR 0.95, 95% CI 0.87-1.01). These findings remained robust when relaxing eligibility criteria for treatment allocation. Conclusion: Our findings reveal significant disparities in the use of invasive life-saving ICU treatments among septic patients from racial and ethnic minority backgrounds, particularly with respect to IMV and VP use. These disparities underscore not only the need to address inequality in critical care settings, but also highlight the importance of high-resolution data.


Assuntos
Cuidados Críticos , Etnicidade , Disparidades em Assistência à Saúde , Sepse , Feminino , Humanos , Masculino , Registros Eletrônicos de Saúde , Unidades de Terapia Intensiva , Grupos Minoritários , Estudos Retrospectivos , Sepse/terapia
19.
medRxiv ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37873163

RESUMO

Objective: Health inequities can be influenced by demographic factors such as race and ethnicity, proficiency in English, and biological sex. Disparities may manifest as differential likelihood of testing which correlates directly with the likelihood of an intervention to address an abnormal finding. Our retrospective observational study evaluated the presence of variation in glucose measurements in the Intensive Care Unit (ICU). Methods: Using the MIMIC-IV database (2008-2019), a single-center, academic referral hospital in Boston (USA), we identified adult patients meeting sepsis-3 criteria. Exclusion criteria were diabetic ketoacidosis, ICU length of stay under 1 day, and unknown race or ethnicity. We performed a logistic regression analysis to assess differential likelihoods of glucose measurements on day 1. A negative binomial regression was fitted to assess the frequency of subsequent glucose readings. Analyses were adjusted for relevant clinical confounders, and performed across three disparity proxy axes: race and ethnicity, sex, and English proficiency. Results: We studied 24,927 patients, of which 19.5% represented racial and ethnic minority groups, 42.4% were female, and 9.8% had limited English proficiency. No significant differences were found for glucose measurement on day 1 in the ICU. This pattern was consistent irrespective of the axis of analysis, i.e. race and ethnicity, sex, or English proficiency. Conversely, subsequent measurement frequency revealed potential disparities. Specifically, males (incidence rate ratio (IRR) 1.06, 95% confidence interval (CI) 1.01 - 1.21), patients who identify themselves as Hispanic (IRR 1.11, 95% CI 1.01 - 1.21), or Black (IRR 1.06, 95% CI 1.01 - 1.12), and patients being English proficient (IRR 1.08, 95% CI 1.01 - 1.15) had higher chances of subsequent glucose readings. Conclusion: We found disparities in ICU glucose measurements among patients with sepsis, albeit the magnitude was small. Variation in disease monitoring is a source of data bias that may lead to spurious correlations when modeling health data.

20.
medRxiv ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37873267

RESUMO

Background: Variability in the provision of intensive care unit (ICU)-interventions may lead to disparities between socially defined racial-ethnic groups. Research Question: We used causal inference to examine the use of invasive mechanical ventilation (IMV), renal replacement therapy (RRT), and vasopressor agents (VP) to identify disparities in outcomes across race-ethnicity in patients with sepsis. Study Design and Methods: Single-center, academic referral hospital in Boston, Massachusetts, USA. Retrospective analysis of treatment effect with a targeted trial design categorized by treatment assignment within the first 24 hours in the MIMIC-IV dataset (2008- 2019) using targeted maximum likelihood estimation. Of 76,943 ICU stays in MIMIC-IV, 32,971 adult stays fulfilling sepsis-3 criteria were included. The primary outcome was in-hospital mortality. Secondary outcomes were hospital-free days, and occurrence of nosocomial infection stratified by predicted mortality probability ranges and self-reported race-ethnicity. Average treatment effects by treatment type and race-ethnicity, Racial-ethnic group (REG) or White group (WG), were estimated. Results: Of 19,419 admissions that met inclusion criteria, median age was 68 years, 57.4% were women, 82% were White, and mortality was 18.2%. There was no difference in mortality benefit associated with the administration of IMV, RRT, or VP between the REG and the WG. There was also no difference in hospital-free days or nosocomial infections. These findings are unchanged with different eligibility periods. Interpretation: There were no differences in the treatment outcomes from three life-sustaining interventions in the ICU according to race-ethnicity. While there was no discernable harm from the treatments across mortality risk, there was also no measurable benefit. These findings highlight the need for research to understand better the risk-benefit of life-sustaining interventions in the ICU.

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