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OBJECTIVE: To evaluate a series of prospective life course models testing whether the timing of pubertal development is a pathway through which prepubertal risk factors may influence adulthood cardiometabolic health. METHODS: Subjects were 655 female participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE). Prepubertal risk factors included maternal menarcheal age, child race/ethnicity, child health status indicators, and child adversity indicators. Pubertal timing was indexed by breast development onset (Tanner stage [TS] II), pubic hair onset (TS II) and menarcheal age. Adulthood cardiometabolic risk (CMR) was indexed by a composite of waist circumference, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, C-reactive protein, and high-density lipoprotein. RESULTS: Inspection of paths between the prepubertal risk factors, pubertal timing indicators, and adulthood CMR composite showed later breast development onset (-0.173, p < .01), later pubic hair onset (-0.182, p < .01), and later menarche (-0.145, p < .01) each predicted lower adulthood CMR, and each pubertal timing indicator mediated effects of prepubertal risk factors on adulthood CMR. Specifically, the timing of breast development onset and menarche mediated effects of maternal menarcheal age, Black (vs. White), Asian/PI (vs. White), child BMI percentile, and child SES on adulthood CMR (all ps < .05), and the timing of pubic hair onset mediated effects of maternal menarcheal age, Black (vs. White), and child BMI percentile on adulthood CMR (all ps < .10). CONCLUSION: Findings in the current study contribute to the broader literature by identifying pubertal development and its timing as a potentially important pathway through which early life exposures may shape adulthood cardiometabolic health and disease. These findings have important implications for novel opportunities for increased surveillance and potential intervention focusing on pubertal development as a target to improve health more broadly.

Abstract Design A retrospective, cross-sectional image analysis using a convenience sample. Subjects Five cases selected based on the availability of comprehensive imaging data. Methods This study involved a retrospective review of images from five cases, focusing on the use of retinal monochromatic blue light reflectance (BLR) imaging to detect non-perfusion areas. Two cases of sickle-cell retinopathy demonstrated peripheral retinal non-perfusion identified through widefield fluorescein angiography. Three other cases—one with branch retinal vein occlusion, one with branch retinal artery occlusion, and one presenting paracentral acute middle maculopathy showed focal macular non-perfusion detected by structural OCT and OCTA. The areas of nonperfused retinal tissue, confirmed by fluorescein angiography, OCT, and OCTA, were then correlated with findings from the BLR image. This correlation aimed to identify any potential associations between these imaging modalities. Main outcome measures Enhance understanding of the utilization of retinal monochromatic BLR images as a non-perfusion biomarker. Results The perfusion defects identified through fluorescein angiography were qualitatively correlated with hypo-reflective regions observed in the BLR images. A notable correlation was also observed between the OCTA deep capillary plexus findings and the BLR images. Additionally, areas of retinal thinning identified on structural OCT thickness maps corresponded with the hypo-reflective regions in the BLR images. This indicates the potential of BLR in identifying non-perfused retinal areas. Conclusions This study reinforces the evidence, through OCT, OCTA, and angiographic correlation, that the BLR can effectively identify areas of retinal non-perfusion in a non-invasive manner. Further research is warranted to assess the method’s sensitivity, specificity, and limitations. While the interaction of blue light with the retina, leading to specular reflections and scattering, is established, this research represents a pioneering effort in suggesting which specific retinal structures may be implicated in this phenomenon. This novel insight opens avenues for deeper exploration into the underlying mechanisms and potential clinical applications of utilizing the BLR imaging technique for assessing retinal vascular abnormalities.

BackgroundOver the past decade, progress in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC) has led to the identification of many targeted mutations. This has enhanced PFS and OS in both advanced and early-stage NSCLC. The current standard of care for stage III NSCLC varies, and it may combine chemotherapy with either immunotherapy or radiotherapy. This study evaluated the role of induction targeted therapies in patients with driver mutations and inoperable NSCLC.MethodsThis is a single-center, retrospective study assessing the efficacy of targeted therapy in resectable stage III NSCLC patients who are EGFR or ALK-positive, using patient records, PET-CT, brain MRI staging, and mediastinal lymph node evaluation.ResultsBetween January 2020 and February 2024, we identified four patients with either EML4-ALK fusions (2/4) or EGFR mutations (2/4) who underwent treatment with brigatinib or osimertinib before surgery. All patients experienced clinical benefits. Of the two patients with ALK fusion, one responded almost completely, while the other exhibited a notable partial response. Among the patients with EGFR mutations, one had a complete response and the other displayed a significant partial response. All four patients subsequently underwent lobectomy surgical resection.ConclusionsThis case series highlights the potential of targeted therapies for resectable NSCLC in the neoadjuvant setting. Further research is required to confirm their benefits, assess their safety and efficacy, and determine optimal timing and sequencing.

IntroductionVitamin C (L-ascorbic acid) plays a vital role in human physiology, serving as both an antioxidant and a cofactor in enzymatic reactions. High-dose intravenous Vitamin C can achieve significantly elevated plasma concentrations, potentially enhancing its anticancer effects. This case study explores the synergistic impact of high-dose intravenous vitamin C in combination with bevacizumab and atezolizumab in the treatment of a patient with unresectable hepatocellular carcinoma (HCC).Case presentationA 68-year-old male was diagnosed with unresectable HCC, presenting with elevated liver enzymes and an alpha-fetoprotein (AFP) level of 2018 ng/mL. Initial treatment with atezolizumab and Bevacizumab commenced in February 2022. Although imaging indicated stable disease, AFP levels decreased modestly to 1,526 ng/mL, while liver function tests remained elevated, accompanied by further clinical deterioration and weight loss. Subsequently, intravenous vitamin C (30 grams) was introduced into the treatment regimen. This addition led to a rapid and significant reduction in AFP levels, normalization of liver function tests, and marked improvement in clinical symptoms. The patient continued on this combined regimen of vitamin c, atezolizumab, and bevacizumab. Four months later, CT scans revealed significant tumor shrinkage and necrosis. As of 30 months post-diagnosis, the patient remains on the regimen with normal liver function and an AFP level of 1.8 ng/mL, maintaining normal activities and stable weight.ConclusionTo our knowledge, this is the first reported case of combining high-dose intravenous vitamin C with Bevacizumab and atezolizumab, which proved to be safe and resulted in significant clinical and radiological improvements in unresectable hepatocellular carcinoma (HCC). Further studies are recommended to explore the potential of this combination therapy.

PurposeThe purpose of the current study, The National Institute of Child Health and Human Development (NICHD) Study of Health in Early and Adult Life (SHINE), was to build on the landmark Study of Early Child Care and Youth Development (SECCYD), a longitudinal birth cohort initiated in 1991, by conducting a health-focused follow-up of the now adult participants. This effort has produced an invaluable resource for the pursuit of life course research examining links between early life risk and resilience factors and adulthood health and disease risk.ParticipantsOf the 927 NICHD SECCYD participants available for recruitment in the current study, 705 (76.1%) participated in the study. Participants were between 26 and 31 years and living in diverse geographic locations throughout the USA.Findings to dateIn descriptive analyses, the sample exhibited risk on health status indicators, especially related to obesity, hypertension and diabetes. Of particular concern, the prevalence of hypertension (29.4%) and diabetes (25.8%) exceeded national estimates in similar-age individuals. Health behaviour indicators generally tracked with the parameters of poor health status, showing a pattern of poor diet, low activity and disrupted sleep. The juxtaposition of the sample's relatively young age (mean=28.6 years) and high educational status (55.6% college educated or greater) with its poor health status is noteworthy, suggesting a dissociation between health and factors that are typically health protective. This is consistent with observed population health trends, which show a worsening of cardiometabolic health status in younger generations of Americans.Future plansThe current study, SHINE, lays the groundwork for future analyses in which the uniquely robust measures collected as a part of the original NICHD SECCYD will be leveraged to pinpoint specific early life risk and resilience factors as well as the correlates and potential mechanisms accounting for variability in health and disease risk indicators in young adulthood.

Individual differences in the quality of early experiences with primary caregivers have been reliably implicated in the development of socioemotional adjustment and, more recently, physical health. However, few studies have examined the development of such associations with physical health into the adult years. To that end, the current study used prospective, longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,306, 52% male, 77% White/non-Hispanic) to investigate whether associations between direct observations of maternal sensitivity in the first 3 years of life and repeated assessments of two commonly used, objective indicators of physical health (i.e., body mass and mean arterial blood pressure) remained stable or diminished in magnitude over time. Associations between early maternal sensitivity and lower body mass remained relatively stable from age 54 months to 26 years and were robust to the modeling of autoregressive and second-order stability processes as well as the inclusion of potential demographic confounders. In contrast, although associations between early caregiving and lower mean arterial pressure remained relatively stable from Grade 4 to age 15 years (the oldest age for which mean arterial pressure was assessed thus far), these associations were not robust to the inclusion of covariates and the modeling of second-order stability processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction: Adverse epidermal growth factor receptor (EGFR) dermatological events affect many patients and can impair the patient’s quality of life (QoL), leading to dose reduction or discontinuation of therapy. Objective: To carry out the translation, cross-cultural adaptation, reliability and validity of the Functional Evaluation of Cancer Therapy - Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRI-18) to be utilized in Portuguese. Method: Study to evaluate the cross-cultural adaptation, reliability and construct validation of the FACT-EGFRI-18 translated into Portuguese. To evaluate cross-cultural adaptation, semantic analysis was performed by ten patients and content analysis by experts. Reliability was assessed by internal consistency analysis using Cronbach’s alpha coefficient. Construct validity was determined by the correlation between the translated FACT-EGFRI-18 and the Dermatology Life Quality Index (DLQI) answered by 30 participants with cancer undergoing treatment with EGFR. A descriptive analysis of the study population was performed and Cronbach’s alpha coefficient was calculated to determine the internal consistency of the Portuguese version of the FACTEGFRI- 18 and Pearson’s demonstration coefficient was applied to determine the transparency between the questionnaires. ANOVA test was performed to compare the mean FACT-EGFRI-18 score according to demographic variables. Results: The semantic evaluation showed that all the participants understood the items of the translated questionnaire, which revealed strong internal consistency (Cronbach’s alpha = 0.89) and validity (Pearson's correlation = 0.66). Conclusion: The FACT-EGFRI-18 was easily understood by the patients and the results support its reliability and validity.

Abstract Mast cells (MCs) are immune cells that play roles in both normal and abnormal processes. They have been linked to tumor progression in several types of cancer, including non-small cell lung cancer (NSCLC). However, the exact role of MCs in NSCLC is still unclear. Some studies have shown that the presence of a large number of MCs is associated with poor prognosis, while others have suggested that MCs have protective effects. To better understand the role of MCs in NSCLC, we aimed to identify the initial mechanisms underlying the communication between MCs and lung cancer cells. Here, we recapitulated cell-to-cell contact by exposing MCs to membranes derived from lung cancer cells and confirming their activation, as evidenced by increased phosphorylation of the ERK and AKT kinases. Profiling of the microRNAs that were selectively enriched in the extracellular vesicles (EVs) released by the lung cancer-activated MCs revealed that they contained significantly increased amounts of miR-100-5p and miR-125b, two protumorigenic miRNAs. We explored the pathways regulated by these miRNAs via enrichment analysis using the KEGG database, demonstrating that these two miRNAs regulate p53 signaling, cancer pathways, and pathways associated with apoptosis and the cell cycle.

Abstract Personalized medicine has revolutionized approaches to treatment in the field of lung cancer by enabling therapies to be specific to each patient. However, physicians encounter an immense number of challenges in providing the optimal treatment regimen for the individual given the sheer complexity of clinical aspects such as tumor molecular profile, tumor microenvironment, expected adverse events, acquired or inherent resistance mechanisms, the development of brain metastases, the limited availability of biomarkers and the choice of combination therapy. The integration of innovative next-generation technologies such as deep learning—a subset of machine learning—and radiomics has the potential to transform the field by supporting clinical decision making in cancer treatment and the delivery of precision therapies while integrating numerous clinical considerations. In this review, we present a brief explanation of the available technologies, the benefits of using these technologies in predicting immunotherapy response in lung cancer, and the expected future challenges in the context of precision medicine.

ContextPrepubertal obesity is a well-established predictor of earlier pubertal onset, which is itself a risk factor for poor health and well-being. Identifying specific patterns of weight gain in early life may help explain differential risk for earlier pubertal onset.ObjectiveThe objective of the study was to examine patterns of weight gain across infancy and early childhood in relation to pubertal onset outcomes.Design setting and participantsParticipants were 426 girls in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, a longitudinal birth cohort of children and their families followed between birth and adolescence.Main outcome measuresThree pubertal onset outcomes were examined, including age at menarche and ages at Tanner stage II for dimensions of breast and pubic hair development.ResultsIn infancy (birth to 15 months), greater percent weight gain and higher birthweight predicted earlier pubertal onset for all outcomes (Ps < 0.05). In early childhood (24 months to grade 1), body mass index (BMI) trajectories reflecting BMI values that were persistently high or changed from low to high over time (vs BMI values that were stable at median or low levels), predicted younger ages at menarche and the onset of breast (Ps < 0.05), but not pubic hair (Ps > 0.05), development. All associations were independent of breastfeeding, maternal menarcheal age, and race/ethnicity.ConclusionsDistinct patterns of early life weight gain predict differential risk for earlier onset puberty. Focusing on these patterns for earlier and more targeted intervention may help lessen life course linkages between prepubertal obesity, accelerated pubertal development, and negative postpubertal outcomes.

Increasingly, attachment representations are being assessed via secure base script knowledge - the degree to which individuals show awareness of the temporal-causal schema that summarizes the basic features of seeking and receiving effective support from caregivers during times of need. Limited research has assessed the links between secure base script knowledge and aspects of adult functioning and the role that secure base script knowledge may play in accounting for associations between early caregiving quality and adulthood functioning. We used follow-up assessments of the NICHD Study of Early Child Care and Youth Development cohort (N = 585) to examine whether secure base script knowledge at age 18 years: (a) is associated with later romantic relationship quality, depressive symptoms, and body mass index (BMI) at age 26 years, and (b) mediates expected associations between the quality of maternal and paternal sensitivity across the first 15 years of life and age-26 outcomes. More access to, and elaborated knowledge of the secure base script predicted less extreme hostility with romantic partners, and better emotional and physical health. Moreover, secure base script knowledge mediated the links between early maternal and paternal sensitivity and both later romantic partner hostility and depressive symptoms, but not BMI.

Retrospective self-report assessments of adults' childhood experiences with their parents are widely employed in psychological science, but such assessments are rarely validated against actual parenting experiences measured during childhood. Here, we leveraged prospectively acquired data characterizing mother-child and father-child relationship quality using observations, parent reports, and child reports covering infancy through adolescence. At age 26 years, approximately 800 participants completed a retrospective measure of maternal and paternal emotional availability during childhood. Retrospective reports of childhood emotional availability demonstrated weak convergence with composites reflecting prospectively acquired observations (R2s = .01-.05) and parent reports (R2s = .02-.05) of parenting quality. Retrospective parental availability was more strongly associated with prospective assessments of child-reported parenting quality (R2s = .24-.25). However, potential sources of bias (i.e., depressive symptoms and family closeness and cohesiveness at age 26 years) accounted for more variance in retrospective reports (39%-40%) than did prospective measures (26%), suggesting caution when using retrospective reports of childhood caregiving quality as a proxy for prospective data.

Gravure printing is a type of printing method that uses metal cylinders with engraved cells that hold ink. The ink is transferred directly to the paper or other material by pressing it against the cylinder. The flow associated with gravure printing includes a flow in a liquid bridge formed in the contact region of the cylinders and a thin-film coating flow of the ink. The flow is governed by viscous and capillary forces. In many cases, the flow is unstable, which leads to the formation of instability patterns on the printed surfaces. The analysis of these instabilities is a very challenging problem, especially since industrial inks are usually rheologically complex. In this experimental and theoretical study, the flow of inks on a rotating cylinder is analysed, accounting for the shear-rate-dependent liquid viscosity. A theoretical solution for the film flow allows us to predict the width of the liquid bridge between two cylinders. Moreover, it is shown that the measured characteristic size of the printed pattern is of the same order as the predicted liquid bridge width. We observe a nearly linear dependence of pattern size and liquid bridge width.

ObjectiveTo identify early life adversity (ELA) risk factors for earlier pubertal timing, itself a risk factor for poor cardiometabolic health, and to determine whether such ELA-related risk may be mediated by pre-pubertal body mass index (BMI).MethodsSubjects included 426 female participants in a prospective birth cohort study, the NICHD Study of Early Child Care and Youth Development. Survival analysis models were fit to examine ELA exposures, representing childhood socioeconomic status (SES), maternal sensitivity, mother-child attachment, and negative life events, along with child health indicators and covariates, in relation to pubertal timing outcomes, including age at menarche and ages at Tanner stage II for breast and pubic hair development.ResultsHigher childhood SES emerged as an independent predictor of older age at menarche, showing each one standard deviation increase in childhood SES corresponded to a 1.3% increase in age at menarche (factor change = 1.013; 1.003-1.022; p < .01), but did not predict breast or pubic hair development (ps > .05). In mediation analyses, indirect (mediated) effects of mother-child attachment on the pubertal timing outcomes, via pre-pubertal BMI, were all statistically significant (ps < .05).ConclusionsHigher childhood SES predicted directly, and secure (vs. insecure) mother-child attachment predicted indirectly (via pre-pubertal BMI), later pubertal timing, suggesting these factors may protect girls from earlier pubertal development. By extension, clinical implications are that intervention strategies designed to lessen ELA- and pre-pubertal obesity-related risk may be effective in remediating life course pathways linking ELA, accelerated pubertal development, and cardiometabolic risk.