Bone quality assessment in patients with healing mandibular fracture sites: a computed tomography investigation.

The objective of this retrospective study was to assess the bone quality of healing mandibular fracture sites by measuring the Hounsfield units (HU) on computed tomographic (CT) images obtained presurgery and postsurgery in patients treated with rigid internal fixation (RIF). The HU values of healing fracture sites were compared to those of corresponding nonfractured (control) sites on the opposing side and cervical vertebrae sites in the same patients. In total, 31 patients with 45 mandibular fractures treated with RIF underwent presurgical and postsurgical CT examinations. The scans performed after surgery (1, 3, 6, 12, or 18 months) were taken only when there was a need for radiographic evaluation due to a complaint of discomfort from the patient or when the surgeon needed to verify the postsurgical outcome, and each patient underwent only a single postsurgical CT. At the presurgical CT examination, the HU values were lower in the fracture sites than in the control sites. At 3 months postsurgery, the HU values in the fracture sites had increased as the mandibular bone healed. At 6 months postsurgery, the HU values in the fracture sites were higher than those of the control sites. At 12 and 18 months postsurgery, the HU values of both sites were similar. The HU values of the cervical vertebrae remained constant with time. These results suggest that, in patients who have been treated with RIF for mandibular bone fracture, HU values measured by CT vary across time, expressing the physiologic bone healing process.

"We Don't Want to Screen for the Sake of Screening": A Qualitative Evaluation of a Social Needs Screening and Referral Intervention in the NICU.

BACKGROUND: Low uptake of social determinants of health (SDH) screening and referral interventions within neonatal intensive care units (NICUs) is partly due to limited understanding of the best procedures to integrate this practice into routine clinical workflows. PURPOSE: To examine the feasibility and acceptability of an SDH screening and referral intervention in the NICU from the perspective of neonatal nurses; and to identify factors affecting implementation outcomes. METHODS: We conducted 25 semistructured interviews with NICU nurses. We used the Promoting Action on Research Implementation in Health Services (PARiHS) framework to guide interview questions and codebook development for directed content analysis. Themes were mapped onto the 3 PARiHS domains of context, evidence, and facilitation. FINDINGS: Analysis yielded 8 themes. Context: Nurses felt that stressors experienced by NICU families are magnified in a safety net environment. Nurses shared varying viewpoints of the roles and responsibilities for social care in the NICU, and feared that scarcity of community resources would make it difficult to address families' needs. Evidence: The intervention was perceived to increase identification of adverse SDH and provision of resources; and to potentially jump-start better caregiver and infant health trajectories. Facilitation: Procedures that improved acceptability included dynamic training and champion support, regular feedback on intervention outcomes, and strategies to reduce stigma and bias. CONCLUSION: We identified contextual factors, concrete messaging, and training procedures that may inform implementation of SDH screening and referral in NICU settings.

Dynamic Glycoprotein Hyposialylation Promotes Chemotherapy Evasion and Metastatic Seeding of Quiescent Circulating Tumor Cell Clusters in Breast Cancer.

Most circulating tumor cells (CTC) are detected as single cells, whereas a small proportion of CTCs in multicellular clusters with stemness properties possess 20- to 100-times higher metastatic propensity than the single cells. Here we report that CTC dynamics in both singles and clusters in response to therapies predict overall survival for breast cancer. Chemotherapy-evasive CTC clusters are relatively quiescent with a specific loss of ST6GAL1-catalyzed α2,6-sialylation in glycoproteins. Dynamic hyposialylation in CTCs or deficiency of ST6GAL1 promotes cluster formation for metastatic seeding and enables cellular quiescence to evade paclitaxel treatment in breast cancer. Glycoproteomic analysis reveals newly identified protein substrates of ST6GAL1, such as adhesion or stemness markers PODXL, ICAM1, ECE1, ALCAM1, CD97, and CD44, contributing to CTC clustering (aggregation) and metastatic seeding. As a proof of concept, neutralizing antibodies against one newly identified contributor, PODXL, inhibit CTC cluster formation and lung metastasis associated with paclitaxel treatment for triple-negative breast cancer. SIGNIFICANCE: This study discovers that dynamic loss of terminal sialylation in glycoproteins of CTC clusters contributes to the fate of cellular dormancy, advantageous evasion to chemotherapy, and enhanced metastatic seeding. It identifies PODXL as a glycoprotein substrate of ST6GAL1 and a candidate target to counter chemoevasion-associated metastasis of quiescent tumor cells. This article is featured in Selected Articles from This Issue, p. 1949.

Patient Perspectives of the Hospital Discharge Process: A Qualitative Study.

Care transitions after hospitalization require communication across care teams, patients, and caregivers. As part of a quality improvement initiative, we conducted qualitative interviews with a diverse group of 53 patients who were recently discharged from a hospitalization within a safety net hospital to explore how patient preferences were included in the hospital discharge process and differences in the hospital discharge experience by race/ethnicity. Four themes emerged from participants regarding desired characteristics of interactions with the discharge team: (1) to feel heard, (2) inclusion in decision-making, (3) to be adequately prepared to care for themselves at home through bedside teaching, (4) and to have a clear and updated discharge timeline. Additionally, participants identified patient-level factors the discharge planning team should consider, including the social context, family involvement, health literacy, and linguistic barriers. Lastly, participants identified provider characteristics, such as a caring and empathetic bedside manner, that they found valuable in the discharge process. Our findings highlight the need for shared decision-making in the discharge planning process to improve both patient safety and satisfaction.

Computational ranking-assisted identification of Plexin-B2 in homotypic and heterotypic clustering of circulating tumor cells in breast cancer metastasis.

Metastasis is the cause of over 90% of all deaths associated with breast cancer, yet the strategies to predict cancer spreading based on primary tumor profiles and therefore prevent metastasis are egregiously limited. As rare precursor cells to metastasis, circulating tumor cells (CTCs) in multicellular clusters in the blood are 20-50 times more likely to produce viable metastasis than single CTCs. However, the molecular mechanisms underlying various CTC clusters, such as homotypic tumor cell clusters and heterotypic tumor-immune cell clusters, are yet to be fully elucidated. Combining machine learning-assisted computational ranking with experimental demonstration to assess cell adhesion candidates, we identified a transmembrane protein Plexin- B2 (PB2) as a new therapeutic target that drives the formation of both homotypic and heterotypic CTC clusters. High PB2 expression in human primary tumors predicts an unfavorable distant metastasis-free survival and is enriched in CTC clusters compared to single CTCs in advanced breast cancers. Loss of PB2 reduces formation of homotypic tumor cell clusters as well as heterotypic tumor-myeloid cell clusters in triple-negative breast cancer. Interactions between PB2 and its ligand Sema4C on tumor cells promote homotypic cluster formation, and PB2 binding with Sema4A on myeloid cells (monocytes) drives heterotypic CTC cluster formation, suggesting that metastasizing tumor cells hijack the PB2/Sema family axis to promote lung metastasis in breast cancer. Additionally, using a global proteomic analysis, we identified novel downstream effectors of the PB2 pathway associated with cancer stemness, cell cycling, and tumor cell clustering in breast cancer. Thus, PB2 is a novel therapeutic target for preventing new metastasis.

Implementing Social Risk Screening and Referral to Resources in the NICU.

OBJECTIVE: Social risk screening is recommended by the American Academy of Pediatrics, but this practice is underutilized in NICUs. To address this gap in social care, we aimed to increase rates of: (1) systematic social risk screening and (2) connection with community resources, each to ≥50% over a 14-month period. METHODS: We conducted a quality improvement initiative from November 2020 to January 2022. We adapted a screening tool and used Plan-Do-Study-Act cycles to integrate screening and referral to resources into clinical workflow. Primary outcome measures included the percentage of (1) families screened and (2) connection with resources. We examined screening by maternal race/ethnicity and primary language. Process measures were (1) time from admission to screening and (2) percentage of referrals provided to families reporting unmet needs and requesting assistance. We used statistical process control to assess change over time and χ2 tests to compare screening by race/ethnicity and language. RESULTS: The rates of systematic screening increased from 0% to 49%. Among 103 families screened, 84% had ≥1, and 64% had ≥2 unmet needs, with a total of 221 needs reported. Education, employment, transportation, and food were the most common needs. Screening rates did not vary by race/ethnicity or language. Among families requesting assistance, 98% received referrals. The iterative improvement of a written resource guide and community partnerships led to increased rates of connection with resources from 21% to 52%. CONCLUSION: Leveraging existing staff, our social risk screening and referral intervention built the capacity to address the high burden of unmet needs among NICU families.

Beyond income: material hardship and the health and healthcare of premature children.

OBJECTIVES: To estimate national prevalence of household hardships (food insufficiency, financial hardship, and difficulty paying medical bills) among children born term and preterm; and examine associations of household hardships with preterm children's outcomes (health status, emergency room visits, and unmet healthcare needs). METHODS: We studied 24,026 children aged 0-3 years born term, preterm with moderately low birth weight (1501-2499 grams) and preterm with very low birth weight (VLBW; ≤1500 grams). Using propensity score matching to control for correlates of poverty, we examined associations of hardships and child outcomes. RESULTS: Compared with term, households with preterm VLBW children had >2-fold higher odds of financial hardship (aOR:2.63; 95% CI: 1.26-5.46) and >5-fold higher odds of difficulty paying bills (aOR:5.60; 95% CI: 2.35-10.35). Matching for sociodemographics, special healthcare needs, income and receipt of public benefits, hardships were independently associated with adverse preterm children's outcomes. CONCLUSIONS: Addressing household hardships is needed to optimize preterm child outcomes.

Association of Primary Language with Provision of Mother's Milk Among Very-Low-Birthweight Infants in Massachusetts.

Background: Racial/ethnic inequities in mother's milk provision for hospitalized preterm infants persist. The extent to which primary language contributes to these racial/ethnic inequities is unknown. Objective: Examine associations of maternal race/ethnicity and primary language with (1) any/exclusive mother's milk at hospital discharge and (2) the time to cessation of mother's milk provision during the hospitalization. Methods: We examined 652 mother/very-low-birthweight (VLBW) infant dyads at 9 level 3 neonatal intensive care units in Massachusetts from January 2017 to December 2018. We abstracted maternal race/ethnicity and language from medical records, and examined English and non-English-speaking non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic mothers of any race. We examined associations of race/ethnicity and language with (1) any/exclusive mother's milk at discharge (yes/no) using mixed-effects logistic regression and (2) cessation of mother's milk during the hospitalization using cox proportional hazard models, adjusting for gestational age, birthweight, and accounting for clustering by plurality and hospital. Results: Fifty-three percent were English-speaking NHW, 22% English-speaking NHB, 4% non-English-speaking NHB, 14% English-speaking Hispanic, and 7% non-English-speaking Hispanic. Compared with English-speaking NHW, NHB mothers (English adjusted odds ratio [aOR] 0.28 [0.17, 0.44]; and non-English-speaking aOR 0.55 [0.19, 0.98]), and non-English-speaking Hispanic mothers (aOR 0.29 [0.21, 0.87]) had lower odds of any mother's milk at discharge. In time-to-event analyses, non-English-speaking Hispanic (adjusted hazard ratio [aHR] 4.37 [2.20, 6.02]) and English-speaking NHB mothers (aHR 3.91 [1.41, 7.61] had the earliest cessation of mother's milk provision. Conclusion: In Massachusetts, maternal primary language was associated with inequities in mother's milk provision for VLBW infants with a differential effect for NHB and Hispanic mothers.

Efeitos da suplementação de óleo de abacate sobre o perfil lipídico e índices aterogênicos em intervenção duplo-cego e randomizada em pacientes com síndrome metabólica / Effects of avocado oil supplementation on lipid profile and atherogenic indices in a double-blind and randomised intervention in patients with metabolic syndrome

Introdução: A síndrome metabólica é definida como um conjunto de condições clínicas que acometem cerca de 25% da população mundial e 29,6% dos brasileiros. Essa síndrome está relacionada ao aumento dos desfechos cardiovasculares, que podem ser preditos através do perfil lipídico. Compostos bioativos, tais como os ácidos graxos monoinsaturados (MUFA), são fortes aliados na prevenção desses desfechos. Um alimento importante por conter compostos bioativos e MUFA em abundância é o abacate. Há, porém, poucos estudos avaliando o efeito do óleo puro/virgem de abacate sobre o perfil lipídico em humanos com síndrome metabólica, e seus efeitos sobre os índices aterogênicos inexistem. Objetivo: O estudo buscou avaliar a suplementação de óleo de abacate sobre os níveis lipídicos e índices aterogênicos em pacientes portadores de síndrome metabólica. Método: 31 indivíduos adultos e obesos foram randomizados em grupo controle (óleo de soja) e grupo intervenção (óleo de abacate). Estes foram avaliados nos períodos pré e pós-intervenção (12 semanas) através de anamnese clínica e avaliação nutricional. Resultados: Observou-se que tanto o grupo controle quanto o grupo intervenção tinham a ingestão de lipídeos e gordura saturada maior que o recomendável. Quanto ao perfil lipídico e índices aterogênicos, não foi observada diferença significativa entre os períodos pré e pós. Conclusão: Os resultados podem ter se dado pela ausência do controle alimentar, sobrecarga de medicamentos, duração da intervenção, modo de administração e dose do suplemento. Logo, são necessários estudos futuros sobre os efeitos do óleo de abacate nessa população, que controlem melhor essas variáveis.

Introduction: Metabolic syndrome is defined as a set of clinical conditions that affect approximately 25% of the world's population and 29.6% of Brazilians. This syndrome is related to increased cardiovascular outcomes, which may be predicted by the lipid profile. Bioactive compounds, such as monounsaturated fatty acids (MUFAs), are strong allies in preventing these outcomes. Avocado is an important food because it contains abundant bioactive compounds and MUFAs. However, few studies evaluated the effects of pure/virgin avocado oil on the lipid profile in humans with metabolic syndrome, and its effects on atherogenic indices are not known. Objective:This study evaluated avocado oil supplementation on lipid levels and atherogenic indices in patients with metabolic syndrome. Method: Thirty-one obese adults were randomised into a control group (soybean oil) and an intervention group (avocado oil). These groups were evaluated in the pre- and post-intervention periods (12 weeks) via clinical anamnesis and nutritional assessment. Results: The control group and the intervention group had higher intakes of lipids and saturated fat than recommended. For the lipid profile and atherogenic indices, no significant difference was observed between the pre- and postintervention periods. Conclusion: These results may have been due to the absence of dietary control, medication overload, intervention duration, mode of administration and dose of the supplement. Therefore, future studies on the effects of avocado oil are needed in this population to better control these variables.

Structure of the Solid-State Electrolyte Li3+2xP1-xAlxS4: Lithium-Ion Transport Properties in Crystalline vs Glassy Phases.

The search for new solid electrolyte materials and an understanding of fast-ion conductivity are crucial for the development of safe and high-power all-solid-state battery technology. Herein, we present the synthesis, structure, and properties of a crystalline lithium-ion conductor, Li3.3Al0.15P0.85S4 (i.e., Li9.9Al0.45P2.55S12), found in the compositional range Li3+2xP1-xAlxS4 (x = 0.15, 0.20, and 0.33). 31P magic-angle spinning nuclear magnetic resonance (MAS-NMR) aided in identifying the successful introduction of Al into the lattice. At high values of x (>0.15), crystalline Li5AlS4 and a glassy amorphous component exsolve to yield a multiphase mixture. The crystal structure of Li3.3Al0.15P0.85S4 was elucidated by single-crystal X-ray diffraction and powder neutron diffraction, demonstrating that it belongs to the thio-LISICON family with the Pnma space group, a = 12.9572(13) Å, b = 8.0861(8) Å, c = 6.1466(6) Å, and V = 644.00(11) Å3. The Li+-ion conductivity and diffusivity in this bulk material (which contains about 10 wt % of an amorphous phase, as prepared) were studied by electrochemical impedance spectroscopy and 7Li pulsed-field gradient nuclear magnetic resonance spectroscopy (PFG-NMR). The total ionic conductivity of Li3.3Al0.15P0.85S4 is 0.22(2) mS·cm-1 at room temperature with an activation energy of 0.30(1) eV. A two-component analysis method based on the Kärger equations was developed to analyze the diffusive exchange between the bulk and amorphous phases of Li3.3Al0.15P0.85S4 detected via the PFG-NMR signal attenuation curves. This approach was employed to quantitatively compare different sample morphologies (glass powder, crystalline powder, and crystalline pellets of Li3.3Al0.15P0.85S4) and assess the influence of the macroscopic state on microscopic ion transport, as supported by NMR relaxation measurements.

Direitos Sexuais e Reprodutivos nos Protocolos Profissionais sobre HIV/Aids / Sexual Rights and Reproductive Rights in Professional Protocols on HIV/AIDS / Derechos Sexuales y Reproductivos en Protocolos Profesionales sobre VIH/SIDA

O trabalho em saúde no campo do HIV/Aids requer uma abordagem interdisciplinar e tem como desafios fundamentais a adesão da população aos métodos e medidas de prevenção e tratamento, assim como a efetivação do acesso e da integralidade na assistência, o enfrentamento à discriminação e à estigmatização das populações-chave e das pessoas que vivem com HIV. Além disso, ele mobiliza questões complexas relacionados à sexualidade e ao exercício da autonomia cidadã. Tendo isso em vista, analisamos neste trabalho dezoito protocolos clínicos que instruem a atuação profissional na assistência ao HIV/Aids, pautando temas a serem abordados e procedimentos para qualificar o atendimento. Realizamos uma revisão integrativa buscando elucidar o entendimento dos diretos sexuais e reprodutivos presente nestes documentos. Com a síntese dos resultados obtidos, organizamos três categorias a partir das quais são desenvolvidos a temática dos direitos sexuais e reprodutivos: vulnerabilidade; autonomia; gênero e diversidade sexual. Concluímos que os tópicos da vulnerabilidade, reiteradamente abordado, e da sexualidade, que coloca progressivamente em questão a desnaturalização dos papéis sociais de gênero, buscam convergir aspectos sociais, culturais e individuais, indicando um aprimoramento das práticas de promoção de autonomia e a efetivação dos direitos sexuais e reprodutivos na assistência ao HIV/Aids.

Health work in the field of HIV/AIDS requires an interdisciplinary approach and has as fundamental challenges the population's adherence to prevention and treatment methods and measures, as well as the effective access and integrality in assistance, and the struggle against discrimination and stigmatization of key-populations and people living with HIV. In addition, it mobilizes complex issues related to sexuality and the exercise of citizenship autonomy. Considering this, we analyzed in this work eighteen clinical protocols that guide professional performance in HIV/AIDS care, organizing themes and procedures to qualify the care. We performed an integrative review to elucidate the understanding of sexual and reproductive rights present in these documents. With the synthesis of the results obtained, we organized three categories from which the theme of sexual and reproductive rights is developed: vulnerability; autonomy; gender and sexual diversity. We conclude that the topics of vulnerability, repeatedly addressed, and sexuality, which progressively questions the naturalization of social gender roles, try to converge social, cultural and individual aspects, indicating an improvement of practices that promotes sexual and reproductive autonomy and enforcement of rights in HIV/AIDS care.

El trabajo en salud en el campo del VIH/SIDA requiere un abordaje interdisciplinario y tiene como desafíos fundamentales la adhesión de la población a los métodos y medidas de prevención y tratamiento, así como el acceso efectivo y la atención integral, combatiendo la discriminación y estigmatización de las poblaciones-clave y de las personas que viven con el VIH. Además, moviliza temas complejos relacionados con la sexualidad y el ejercicio de la autonomía ciudadana. Considerando eso, analizamos dieciocho protocolos clínicos que orientan la actuación profesional en la atención al VIH/SIDA, orientando temas a ser abordados y procedimientos para calificar la atención. Realizamos una revisión integrativa buscando elucidar la comprensión de los derechos sexuales y reproductivos presente en estos documentos. Con la síntesis de los resultados obtenidos, organizamos tres categorías con las cuales se desarrolla la temática de los derechos sexuales y reproductivos: vulnerabilidad; autonomía; género y diversidad sexual. Concluimos que los temas vulnerabilidad, repetidamente abordado, y sexualidad, que progresivamente cuestiona la naturalización de los roles sociales de género, buscan converger aspectos sociales, culturales e individuales, indicando una mejora de las prácticas de promoción de la autonomía y la efectuación de los derechos sexuales y reproductivos en la atención del VIH/SIDA.

National Prevalence of Social Determinants of Health Screening Among US Neonatal Care Units.

OBJECTIVES: The extent that universal social determinants of health (SDH) screening in clinical encounters, as recommended by the American Academy of Pediatrics, has been implemented in inpatient pediatric settings is unknown. We aimed to determine the national prevalence and predictors of standardized SDH screening in US level 2 to 4 neonatal care units (NICUs), describe characteristics of SDH screening programs, and ascertain beliefs of clinical leaders about this practice in the NICU setting. METHODS: We randomly selected 100 hospitals with level 2 to 4 NICUs among each of 5 US regions (n = 500) and surveyed clinical leaders from January to November 2021 regarding standardized SDH screening. Responses were weighted for number of level 2 to 4 NICUs in each region and nonresponse. RESULTS: Overall response rate was 34% (28%-40% by region). Twenty-three percent of US level 2 to 4 NICUs reported standardized SDH screening. We found no associations of hospital characteristics, such as region, size, or safety-net status, with implementation of this practice. Existing programs conducted systematic screening early in the hospitalization (84%), primarily led by social workers (92%). We identified practice variation regarding the type of screening tool, but there was substantial overlap among domains incorporated in the screening. Reported barriers to implementation included perceived lack of resources, inadequate referrals, and lack of an inpatient screening tool. CONCLUSIONS: The prolonged neonatal hospitalization provides opportunities to systematically address SDH. Yet, only 23% of US level 2 to 4 NICUs have implemented this practice. To scale-up implementation, quality improvement may support adaptation of screening and referral processes to the NICU context.

Machine learning-assisted elucidation of CD81-CD44 interactions in promoting cancer stemness and extracellular vesicle integrity.

Tumor-initiating cells with reprogramming plasticity or stem-progenitor cell properties (stemness) are thought to be essential for cancer development and metastatic regeneration in many cancers; however, elucidation of the underlying molecular network and pathways remains demanding. Combining machine learning and experimental investigation, here we report CD81, a tetraspanin transmembrane protein known to be enriched in extracellular vesicles (EVs), as a newly identified driver of breast cancer stemness and metastasis. Using protein structure modeling and interface prediction-guided mutagenesis, we demonstrate that membrane CD81 interacts with CD44 through their extracellular regions in promoting tumor cell cluster formation and lung metastasis of triple negative breast cancer (TNBC) in human and mouse models. In-depth global and phosphoproteomic analyses of tumor cells deficient with CD81 or CD44 unveils endocytosis-related pathway alterations, leading to further identification of a quality-keeping role of CD44 and CD81 in EV secretion as well as in EV-associated stemness-promoting function. CD81 is coexpressed along with CD44 in human circulating tumor cells (CTCs) and enriched in clustered CTCs that promote cancer stemness and metastasis, supporting the clinical significance of CD81 in association with patient outcomes. Our study highlights machine learning as a powerful tool in facilitating the molecular understanding of new molecular targets in regulating stemness and metastasis of TNBC.

Bayesian paired comparison with the bpcs package.

This article introduces the bpcs R package (Bayesian Paired Comparison in Stan) and the statistical models implemented in the package. This package aims to facilitate the use of Bayesian models for paired comparison data in behavioral research. Bayesian analysis of paired comparison data allows parameter estimation even in conditions where the maximum likelihood does not exist, allows easy extension of paired comparison models, provides straightforward interpretation of the results with credible intervals, has better control of type I error, has more robust evidence towards the null hypothesis, allows propagation of uncertainties, includes prior information, and performs well when handling models with many parameters and latent variables. The bpcs package provides a consistent interface for R users and several functions to evaluate the posterior distribution of all parameters to estimate the posterior distribution of any contest between items and to obtain the posterior distribution of the ranks. Three reanalyses of recent studies that used the frequentist Bradley-Terry model are presented. These reanalyses are conducted with the Bayesian models of the bpcs package, and all the code used to fit the models, generate the figures, and the tables are available in the online appendix.

Linguistic Disparities in Child Health and Presence of a Medical Home Among United States Latino Children.

OBJECTIVE: The impact of household language on Latino-White and Latino intragroup disparities in child health and having a medical home in the United States is poorly understood. This study aimed to examine these disparities 1) between Whites and Latinos (overall and stratified by English-primary-language [EPL] and non-English-primary-language [NEPL] households); 2) within Latinos, stratified by household language; and 3) potential moderation of disparities by social determinants. METHODS: Cross-sectional analysis of nationally representative sample of children 0 to 17 years old from the 2016-2018 National Survey of Children's Health. We evaluated associations of child race/ethnicity and household language with child health and presence of a medical home. Multivariable logistic regression was used to compare groups of interest, adjusting for sociodemographic factors and health needs. Moderation was assessed using interaction terms for household income, parental educational attainment, and child insurance coverage. RESULTS: Among 81,514 children, 13.5% were NEPL Latino, and 19.4% were EPL Latino. Compared with EPL Whites, both EPL and NEPL Latinos had reduced odds of excellent/very good health (adjusted odds ratio [aOR]: 0.70; 95% confidence interval [CI]: 0.58-0.84; and aOR: 0.42; 95% CI: 0.33-0.53) and presence of a medical home (aOR: 0.62; 95% CI: 0.56-0.69; and aOR: 0.45; 95% CI: 0.37-0.54), respectively. Among Latinos, NEPL (vs EPL) was also associated with reduced odds of excellent/very good health (aOR: 0.61; 95% CI: 0.46-0.83), and presence of a medical home (aOR: 0.66; 95% CI: 0.48-0.78); these associations were magnified by adverse social determinants. CONCLUSIONS: Striking Latino-White and within-Latino medical-home disparities persist in the United States, particularly for NEPL Latino children. Interventions should target social determinants and the rich sociocultural and linguistic diversity of the Latino population.

Maternal language disparities in neonatal intensive care unit outcomes.

OBJECTIVE: To examine associations of maternal primary language with neonatal intensive care unit (NICU) outcomes (mother's milk at discharge, necrotizing enterocolitis [NEC], late-onset sepsis, weight gain) DESIGN: We performed a retrospective cohort study of mother-infant dyads (<34 weeks' gestation) in 9 NICUs (1/2016-12/2019), examining associations of maternal language (English [ref], Spanish, Other) with NICU outcomes, adjusting for birth weight for gestational age z-score, race/ethnicity, maternal age, and clustering by hospital. RESULTS: Among 1402 mothers, 85% spoke English, 7% spoke Spanish, and 7% spoke another language. Compared to English, infants with Spanish-speaking mothers had slower growth (-0.34 z-score units [-0.58, -0.10]). Infants with other non-English-speaking mothers had increased mother's milk at discharge (aOR 1.48 [1.18, 1.85]), NEC (aOR 1.43 [1.05, 1.95]), late-onset sepsis (aOR 2.84) [1.67, 4.83] and slower growth (-0.17 z-score units [-0.29, -0.05]). CONCLUSIONS: After adjustments, preterm infants with non-English-speaking mothers had worse outcomes than infants with English-speaking mothers.

ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer.

Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.

EGFR inhibition blocks cancer stem cell clustering and lung metastasis of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive and metastatic breast cancer subtypes lacking targeted therapy. Our recent work demonstrated that circulating tumor cell (CTC) clusters and polyclonal metastasis of TNBC are driven by aggregation of CD44+ cancer stem cells (CSC) and associated with an unfavorable prognosis, such as low overall survival. However, there is no existing therapeutic that can specifically block CTC or CSC cluster formation. Methods: Using patient-derived xenograft (PDX) models, we established an ex vivo tumor cell clustering assay for a pilot screening of blockade antibodies. After identifying EGFR as a target candidate, we modulated the gene expression and inhibited its kinase activity to determine its functional importance in tumor cell clustering and therapeutic inhibition of lung metastasis. We also examined the molecular regulation network of EGFR and a potential connection to CSC marker CD44 and microRNAs, which regulate CTC clustering. Results: We report here that EGFR inhibition successfully blocks circulating CSC (cCSC) clustering and lung metastasis of TNBC. EGFR enhances CD44-mediated tumor cell aggregation and CD44 stabilizes EGFR. Importantly, blocking EGFR by a novel anti-EGFR monoclonal antibody (clone LA1) effectively blocked cell aggregation in vitro and reduced lung metastasis in vivo. Furthermore, our data demonstrated that the tumor suppressor microRNA-30c serves as another negative regulator of cCSC clustering and lung metastasis by targeting CD44 as well as its downstream effector EGFR. Conclusion: Our studies identify a novel anti-EGFR therapeutic strategy to inhibit cCSC aggregation and therefore abolish cCSC cluster-mediated metastasis of TNBC.

COVID-19: neonatal-perinatal perspectives.

The coronavirus disease 2019 (COVID-19) pandemic, resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe and widespread illness in adults, including pregnant women, while rarely infecting neonates. An incomplete understanding of disease pathogenesis and viral spread has resulted in evolving guidelines to reduce transmission from infected mothers to neonates. Fortunately, the risk of neonatal infection via perinatal/postnatal transmission is low when recommended precautions are followed. However, the psychosocial implications of these practices and racial/ethnic disparities highlighted by this pandemic must also be addressed when caring for mothers and their newborns. This review provides a comprehensive overview of neonatal-perinatal perspectives of COVID-19, ranging from the basic science of infection and recommendations for care of pregnant women and neonates to important psychosocial, ethical, and racial/ethnic topics emerging as a result of both the pandemic and the response of the healthcare community to the care of infected individuals.