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1.
Pediatr Res ; 96(1): 165-171, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38413766

RESUMEN

BACKGROUND: Acquired neonatal intestinal diseases have an array of overlapping presentations and are often labeled under the dichotomous classification of necrotizing enterocolitis (which is poorly defined) or spontaneous intestinal perforation, hindering more precise diagnosis and research. The objective of this study was to take a fresh look at neonatal intestinal disease classification using unsupervised machine learning. METHODS: Patients admitted to the University of Florida Shands Neonatal Intensive Care Unit January 2013-September 2019 diagnosed with an intestinal injury, or had imaging findings of portal venous gas, pneumatosis, abdominal free air, or had an abdominal drain placed or exploratory laparotomy during admission were included. Congenital gastroschisis, omphalocele, intestinal atresia, malrotation were excluded. Data was collected via retrospective chart review with subsequent hierarchal, unsupervised clustering analysis. RESULTS: Five clusters of intestinal injury were identified: Cluster 1 deemed the "Low Mortality" cluster, Cluster 2 deemed the "Mature with Inflammation" cluster, Cluster 3 deemed the "Immature with High Mortality" cluster, Cluster 4 deemed the "Late Injury at Full Feeds" cluster, and Cluster 5 deemed the "Late Injury with High Rate of Intestinal Necrosis" cluster. CONCLUSION: Unsupervised machine learning can be used to cluster acquired neonatal intestinal injuries. Future study with larger multicenter datasets is needed to further refine and classify types of intestinal diseases. IMPACT: Unsupervised machine learning can be used to cluster types of acquired neonatal intestinal injury. Five major clusters of acquired neonatal intestinal injury are described, each with unique features. The clusters herein described deserve future, multicenter study to determine more specific early biomarkers and tailored therapeutic interventions to improve outcomes of often devastating neonatal acquired intestinal injuries.


Asunto(s)
Enfermedades Intestinales , Aprendizaje Automático no Supervisado , Humanos , Recién Nacido , Estudios Retrospectivos , Femenino , Masculino , Unidades de Cuidado Intensivo Neonatal , Enterocolitis Necrotizante/diagnóstico , Análisis por Conglomerados , Enfermedades del Recién Nacido
2.
J Child Psychol Psychiatry ; 65(8): 1098-1107, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38287782

RESUMEN

BACKGROUND: Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. METHODS: Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist). RESULTS: We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes. CONCLUSIONS: Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.


Asunto(s)
Aprendizaje Automático , Primer Trimestre del Embarazo , Proteómica , Temperamento , Humanos , Femenino , Temperamento/fisiología , Preescolar , Embarazo , Masculino , Primer Trimestre del Embarazo/sangre , Conducta Infantil/fisiología , Adulto , Efectos Tardíos de la Exposición Prenatal/fisiopatología
3.
BMC Pregnancy Childbirth ; 24(1): 366, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750438

RESUMEN

BACKGROUND: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy. METHODS: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters. RESULTS: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: ß 6.1, p = 0.01, MAP: ß 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: ß 9.6, p = 0.01, DBP: ß 8.1, p < 0.001, and MAP: ß 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP. CONCLUSIONS: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety.


Asunto(s)
Ansiedad , Presión Sanguínea , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Femenino , Embarazo , Proyectos Piloto , Estudios Prospectivos , Adulto , Presión Sanguínea/fisiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Sueño/fisiología , Complicaciones del Embarazo/psicología , Encuestas y Cuestionarios , Actigrafía
4.
BMC Pregnancy Childbirth ; 24(1): 490, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033276

RESUMEN

BACKGROUND: Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth. METHODS: This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks' gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy. RESULTS: 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02). CONCLUSION: Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.


Asunto(s)
Leucocitos , Periodo Posparto , Preeclampsia , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Estudios de Casos y Controles , Adulto , Preeclampsia/sangre , Nacimiento Prematuro/epidemiología , Proyectos Piloto , Complicaciones del Embarazo/sangre , Telómero , Estudios de Cohortes , Población Urbana/estadística & datos numéricos , Acortamiento del Telómero , Adulto Joven
7.
Clin Perinatol ; 51(2): 461-473, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705652

RESUMEN

Preterm birth (PTB) and its associated morbidities are a leading cause of infant mortality and morbidity. Accurate predictive models and a better biological understanding of PTB-associated morbidities are critical in reducing their adverse effects. Increasing availability of multimodal high-dimensional data sets with concurrent advances in artificial intelligence (AI) have created a rich opportunity to gain novel insights into PTB, a clinically complex and multifactorial disease. Here, the authors review the use of AI to analyze 3 modes of data: electronic health records, biological omics, and social determinants of health metrics.


Asunto(s)
Inteligencia Artificial , Registros Electrónicos de Salud , Nacimiento Prematuro , Humanos , Nacimiento Prematuro/epidemiología , Recién Nacido , Embarazo , Femenino , Determinantes Sociales de la Salud , Mortalidad Infantil
8.
Clin Perinatol ; 51(2): 391-409, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705648

RESUMEN

The complexity of preterm birth (PTB), both spontaneous and medically indicated, and its various etiologies and associated risk factors pose a significant challenge for developing tools to accurately predict risk. This review focuses on the discovery of proteomics signatures that might be useful for predicting spontaneous PTB or preeclampsia, which often results in PTB. We describe methods for proteomics analyses, proteomics biomarker candidates that have so far been identified, obstacles for discovering biomarkers that are sufficiently accurate for clinical use, and the derivation of composite signatures including clinical parameters to increase predictive power.


Asunto(s)
Biomarcadores , Nacimiento Prematuro , Proteómica , Humanos , Femenino , Embarazo , Biomarcadores/metabolismo , Preeclampsia/diagnóstico , Preeclampsia/metabolismo , Recién Nacido , Valor Predictivo de las Pruebas
9.
JAMA Surg ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837145

RESUMEN

Importance: General-domain large language models may be able to perform risk stratification and predict postoperative outcome measures using a description of the procedure and a patient's electronic health record notes. Objective: To examine predictive performance on 8 different tasks: prediction of American Society of Anesthesiologists Physical Status (ASA-PS), hospital admission, intensive care unit (ICU) admission, unplanned admission, hospital mortality, postanesthesia care unit (PACU) phase 1 duration, hospital duration, and ICU duration. Design, Setting, and Participants: This prognostic study included task-specific datasets constructed from 2 years of retrospective electronic health records data collected during routine clinical care. Case and note data were formatted into prompts and given to the large language model GPT-4 Turbo (OpenAI) to generate a prediction and explanation. The setting included a quaternary care center comprising 3 academic hospitals and affiliated clinics in a single metropolitan area. Patients who had a surgery or procedure with anesthesia and at least 1 clinician-written note filed in the electronic health record before surgery were included in the study. Data were analyzed from November to December 2023. Exposures: Compared original notes, note summaries, few-shot prompting, and chain-of-thought prompting strategies. Main Outcomes and Measures: F1 score for binary and categorical outcomes. Mean absolute error for numerical duration outcomes. Results: Study results were measured on task-specific datasets, each with 1000 cases with the exception of unplanned admission, which had 949 cases, and hospital mortality, which had 576 cases. The best results for each task included an F1 score of 0.50 (95% CI, 0.47-0.53) for ASA-PS, 0.64 (95% CI, 0.61-0.67) for hospital admission, 0.81 (95% CI, 0.78-0.83) for ICU admission, 0.61 (95% CI, 0.58-0.64) for unplanned admission, and 0.86 (95% CI, 0.83-0.89) for hospital mortality prediction. Performance on duration prediction tasks was universally poor across all prompt strategies for which the large language model achieved a mean absolute error of 49 minutes (95% CI, 46-51 minutes) for PACU phase 1 duration, 4.5 days (95% CI, 4.2-5.0 days) for hospital duration, and 1.1 days (95% CI, 0.9-1.3 days) for ICU duration prediction. Conclusions and Relevance: Current general-domain large language models may assist clinicians in perioperative risk stratification on classification tasks but are inadequate for numerical duration predictions. Their ability to produce high-quality natural language explanations for the predictions may make them useful tools in clinical workflows and may be complementary to traditional risk prediction models.

11.
medRxiv ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38746318

RESUMEN

Molecular studies of Alzheimer's disease (AD) implicate potential links between autoimmunity and AD, but the underlying clinical relationships between these conditions remain poorly understood. Electronic health records (EHRs) provide an opportunity to determine the clinical risk relationship between autoimmune disorders and AD and understand whether specific disorders and disorder subtypes affect AD risk at the phenotypic level in human populations. We evaluated relationships between 26 autoimmune disorders and AD across retrospective observational case-control and cohort study designs in the EHR systems at UCSF and Stanford. We quantified overall and sex-specific AD risk effects that these autoimmune disorders confer. We identified significantly increased AD risk in autoimmune disorder patients in both study designs at UCSF and at Stanford. This pattern was driven by specific autoimmunity subtypes including endocrine, gastrointestinal, dermatologic, and musculoskeletal disorders. We also observed increased AD risk from autoimmunity in both women and men, but women with autoimmune disorders continued to have a higher AD prevalence than men, indicating persistent sex-specificity. This study identifies autoimmune disorders as strong risk factors for AD that validate across several study designs and EHR databases. It sets the foundation for exploring how underlying autoimmune mechanisms increase AD risk and contribute to AD pathogenesis.

12.
Obstet Gynecol ; 143(6): 803-810, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663016

RESUMEN

OBJECTIVE: To evaluate whether antepartum hospitalization was associated with differences in sleep duration or disrupted sleep patterns. METHODS: This was a prospective cohort study with enrollment of pregnant people aged 18-55 years with singleton gestations at 16 weeks of gestation or more between 2021 and 2022. Each enrolled antepartum patient was matched by gestational age to outpatients recruited from obstetric clinics at the same institution. Participants responded to the ISI (Insomnia Severity Index) and wore actigraph accelerometer watches for up to 7 days. The primary outcome was total sleep duration per 24 hours. Secondary outcomes included sleep efficiency (time asleep/time in bed), ISI score, clinical insomnia (ISI score higher than 15), short sleep duration (less than 300 minutes/24 hours), wakefulness after sleep onset, number of awakenings, and sleep fragmentation index. Outcomes were evaluated with multivariable generalized estimating equations adjusted for body mass index (BMI), sleep aid use, and insurance type, accounting for gestational age correlations. An interaction term assessed the joint effects of time and inpatient status. RESULTS: Overall 58 participants were included: 18 inpatients and 40 outpatients. Inpatients had significantly lower total sleep duration than outpatients (mean 4.4 hours [SD 1.6 hours] inpatient vs 5.2 hours [SD 1.5 hours] outpatient, adjusted ß=-1.1, 95% CI, -1.8 to -0.3, P =.01). Awakenings (10.1 inpatient vs 13.8, P =.01) and wakefulness after sleep onset (28.3 inpatient vs 35.5 outpatient, P =.03) were lower among inpatients. There were no differences in the other sleep outcomes, and no interaction was detected for time in the study and inpatient status. Inpatients were more likely to use sleep aids (39.9% vs 12.5%, P =.03). CONCLUSION: Hospitalized pregnant patients slept about 1 hour/day less than outpatients. Fewer awakenings and reduced wakefulness after sleep onset among inpatients may reflect increased use of sleep aids in hospitalized patients.


Asunto(s)
Pacientes Internos , Pacientes Ambulatorios , Humanos , Femenino , Embarazo , Adulto , Estudios Prospectivos , Pacientes Ambulatorios/estadística & datos numéricos , Adulto Joven , Pacientes Internos/estadística & datos numéricos , Complicaciones del Embarazo , Adolescente , Trastornos del Inicio y del Mantenimiento del Sueño , Persona de Mediana Edad , Sueño/fisiología , Hospitalización/estadística & datos numéricos , Actigrafía
13.
Eur J Obstet Gynecol Reprod Biol ; 297: 8-14, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38554481

RESUMEN

OBJECTIVE: Physical activity is linked to lower anxiety, but little is known about the association during pregnancy. This is especially important for antepartum inpatients, who are known to have increased anxiety yet may not be able to achieve target levels of physical activity during hospitalization. We compared physical activity metrics between pregnant inpatients and outpatients and explored correlations with anxiety. MATERIALS AND METHODS: This was a prospective cohort between 2021 and 2022 of pregnant people aged 18-55 years carrying singleton gestations ≥ 16 weeks. Three exposure groups were matched for gestational age: 1) outpatients from general obstetric clinics; 2) outpatients from high-risk Maternal-Fetal Medicine obstetric clinics; and 3) antepartum inpatients. Participants wore Actigraph GT9X Link accelerometer watches for up to 7 days to measure physical activity. The primary outcome was mean daily step count. Secondary outcomes were metabolic equivalent tasks (METs), hourly kilocalories (kcals), moderate to vigorous physical activity (MVPA) bursts, and anxiety (State-Trait Anxiety Inventory [STAI]). Step counts were compared using multivariable generalized estimating equations adjusting for maternal age, body-mass index, and insurance type as a socioeconomic construct, accounting for within-group clustering by gestational age. Spearman correlations were used to correlate anxiety scores with step counts. RESULTS: 58 participants were analyzed. Compared to outpatients, inpatients had significantly lower mean daily steps (primary outcome, adjusted beta -2185, 95 % confidence interval [CI] -3146, -1224, p < 0.01), METs (adjusted beta -0.18, 95 % CI -0.23, -0.13, p < 0.01), MVPAs (adjusted beta -38.2, 95 % CI -52.3, -24.1, p < 0.01), and kcals (adjusted beta -222.9, 95 % CI -438.0, -7.8, p = 0.04). Over the course of the week, steps progressively decreased for inpatients (p-interaction 0.01) but not for either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30, p = 0.02). CONCLUSION: We present antenatal population norms and variance for step counts, metabolic equivalent tasks, moderate to vigorous physical activity bursts, and kcals, as well as correlations with anxiety. Antepartum inpatients had significantly lower physical activity than outpatients, and lower step counts correlated with higher anxiety levels. These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people.


Asunto(s)
Ansiedad , Ejercicio Físico , Humanos , Femenino , Embarazo , Adulto , Estudios Prospectivos , Ejercicio Físico/psicología , Adulto Joven , Pacientes Internos/psicología , Pacientes Internos/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Adolescente , Persona de Mediana Edad , Complicaciones del Embarazo/psicología
14.
Eur J Obstet Gynecol Reprod Biol ; 300: 224-229, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39032311

RESUMEN

BACKGROUND: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging. STUDY DESIGN: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6 months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6 months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma). RESULTS: Of 67 included people, 50 (74.6 %) had vaginal and 17 (25.4 %) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2 bp cesarean versus 6267.8 bp vaginal, p = 0.01) as well as in the later draws (5586.6 versus 5945.6 bp, p = 0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95 % confidence interval [CI] -891.1, -101.1, p = 0.01) and beyond (adjusted beta -396.8; 95 % CI -727.2, -66.4. p = 0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction. CONCLUSION: Maternal LTLs in postpartum week 1 were nearly 500 bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.

15.
Sci Rep ; 14(1): 2977, 2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316895

RESUMEN

Links between human milk (HM) and infant development are poorly understood and often focus on individual HM components. Here we apply multi-modal predictive machine learning to study HM and head circumference (a proxy for brain development) among 1022 mother-infant dyads of the CHILD Cohort. We integrated HM data (19 oligosaccharides, 28 fatty acids, 3 hormones, 28 chemokines) with maternal and infant demographic, health, dietary and home environment data. Head circumference was significantly predictable at 3 and 12 months. Two of the most associated features were HM n3-polyunsaturated fatty acid C22:6n3 (docosahexaenoic acid, DHA; p = 9.6e-05) and maternal intake of fish (p = 4.1e-03), a key dietary source of DHA with established relationships to brain function. Thus, using a systems biology approach, we identified meaningful relationships between HM and brain development, which validates our statistical approach, gives credence to the novel associations we observed, and sets the foundation for further research with additional cohorts and HM analytes.


Asunto(s)
Ácidos Grasos Omega-3 , Madres , Lactante , Femenino , Animales , Humanos , Leche Humana , Ácidos Docosahexaenoicos , Ácidos Grasos , Lactancia Materna
16.
Nat Aging ; 4(3): 379-395, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38383858

RESUMEN

Identification of Alzheimer's disease (AD) onset risk can facilitate interventions before irreversible disease progression. We demonstrate that electronic health records from the University of California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction of AD onset and (2) prioritization of biological hypotheses, and (3) contextualization of sex dimorphism. We trained random forest models and predicted AD onset on a cohort of 749 individuals with AD and 250,545 controls with a mean area under the receiver operating characteristic of 0.72 (7 years prior) to 0.81 (1 day prior). We further harnessed matched cohort models to identify conditions with predictive power before AD onset. Knowledge networks highlight shared genes between multiple top predictors and AD (for example, APOE, ACTB, IL6 and INS). Genetic colocalization analysis supports AD association with hyperlipidemia at the APOE locus, as well as a stronger female AD association with osteoporosis at a locus near MS4A6A. We therefore show how clinical data can be utilized for early AD prediction and identification of personalized biological hypotheses.


Asunto(s)
Enfermedad de Alzheimer , Masculino , Humanos , Femenino , Enfermedad de Alzheimer/diagnóstico , Registros Electrónicos de Salud , Apolipoproteínas E/genética , San Francisco
17.
bioRxiv ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38496400

RESUMEN

Postoperative cognitive decline (POCD) is the predominant complication affecting elderly patients following major surgery, yet its prediction and prevention remain challenging. Understanding biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This longitudinal study involving 26 elderly patients undergoing orthopedic surgery aimed to characterize the impact of peripheral immune cell responses to surgical trauma on POCD. Trajectory analyses of single-cell mass cytometry data highlighted early JAK/STAT signaling exacerbation and diminished MyD88 signaling post-surgery in patients who developed POCD. Further analyses integrating single-cell and plasma proteomic data collected before surgery with clinical variables yielded a sparse predictive model that accurately identified patients who would develop POCD (AUC = 0.80). The resulting POCD immune signature included one plasma protein and ten immune cell features, offering a concise list of biomarker candidates for developing point-of-care prognostic tests to personalize perioperative management of at-risk patients. The code and the data are documented and available at https://github.com/gregbellan/POCD . Teaser: Modeling immune cell responses and plasma proteomic data predicts postoperative cognitive decline.

18.
Acad Pathol ; 11(2): 100113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562568

RESUMEN

Stanford Health Care, which provides about 7% of overall healthcare to approximately 9 million people in the San Francisco Bay Area, has undergone significant changes due to the opening of a second hospital in late 2019 and, more importantly, the COVID-19 pandemic. We examine the impact of these events on anatomic pathology (AP) cases, aiming to enhance operational efficiency in response to evolving healthcare demands. We extracted historical census, admission, lab tests, operation, and AP data since 2015. An approximately 45% increase in the volume of laboratory tests (P < 0.0001) and a 17% increase in AP cases (P < 0.0001) occurred post-pandemic. These increases were associated with progressively increasing (P < 0.0001) hospital census. Census increase stemmed from higher admission through the emergency department (ED), and longer lengths of stay mostly for transfer patients, likely due to the greater capability of the new ED and changes in regional and local practice patterns post-pandemic. Higher census led to overcapacity, which has an inverted U relationship that peaked at 103% capacity for AP cases and 114% capacity for laboratory tests. Overcapacity led to a lower capability to perform clinical activities, particularly those related to surgical procedures. We conclude by suggesting parameters for optimal operations in the post-pandemic era.

19.
Nat Biotechnol ; 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168992

RESUMEN

Adoption of high-content omic technologies in clinical studies, coupled with computational methods, has yielded an abundance of candidate biomarkers. However, translating such findings into bona fide clinical biomarkers remains challenging. To facilitate this process, we introduce Stabl, a general machine learning method that identifies a sparse, reliable set of biomarkers by integrating noise injection and a data-driven signal-to-noise threshold into multivariable predictive modeling. Evaluation of Stabl on synthetic datasets and five independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used sparsity-promoting regularization methods while maintaining predictive performance; it distills datasets containing 1,400-35,000 features down to 4-34 candidate biomarkers. Stabl extends to multi-omic integration tasks, enabling biological interpretation of complex predictive models, as it hones in on a shortlist of proteomic, metabolomic and cytometric events predicting labor onset, microbial biomarkers of pre-term birth and a pre-operative immune signature of post-surgical infections. Stabl is available at https://github.com/gregbellan/Stabl .

20.
Heliyon ; 10(7): e29050, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38623206

RESUMEN

Background: Anesthesiology plays a crucial role in perioperative care, critical care, and pain management, impacting patient experiences and clinical outcomes. However, our understanding of the anesthesiology research landscape is limited. Accordingly, we initiated a data-driven analysis through topic modeling to uncover research trends, enabling informed decision-making and fostering progress within the field. Methods: The easyPubMed R package was used to collect 32,300 PubMed abstracts spanning from 2000 to 2022. These abstracts were authored by 737 Anesthesiology Principal Investigators (PIs) who were recipients of National Institute of Health (NIH) funding from 2010 to 2022. Abstracts were preprocessed, vectorized, and analyzed with the state-of-the-art BERTopic algorithm to identify pillar topics and trending subtopics within anesthesiology research. Temporal trends were assessed using the Mann-Kendall test. Results: The publishing journals with most abstracts in this dataset were Anesthesia & Analgesia 1133, Anesthesiology 992, and Pain 671. Eight pillar topics were identified and categorized as basic or clinical sciences based on a hierarchical clustering analysis. Amongst the pillar topics, "Cells & Proteomics" had both the highest annual and total number of abstracts. Interestingly, there was an overall upward trend for all topics spanning the years 2000-2022. However, when focusing on the period from 2015 to 2022, topics "Cells & Proteomics" and "Pulmonology" exhibit a downward trajectory. Additionally, various subtopics were identified, with notable increasing trends in "Aneurysms", "Covid 19 Pandemic", and "Artificial intelligence & Machine Learning". Conclusion: Our work offers a comprehensive analysis of the anesthesiology research landscape by providing insights into pillar topics, and trending subtopics. These findings contribute to a better understanding of anesthesiology research and can guide future directions.

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