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Invited Mini Review Metabolic Bone Disease of Prematurity: Overview and Practice Recommendations
No full textMetabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum Ca, phosphorus, and alkaline phosphatase to identify infants at risk. If these laboratories are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of PO4 can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines. Metabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum Ca, phosphorus, and alkaline phosphatase to identify infants at risk. If these laboratories are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of PO4 can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines
Unraveling Vascular and Parenchymal Microenvironment Changes in Patients with Mixed CAA/AD Pathology: A Spatial Transcriptomic In‐Depth Analysis
No full textBackground:
Cerebral amyloid angiopathy (CAA), defined as the accumulation of amyloid in cerebral blood vessels causing alterations in the blood brain barrier (BBB) and the gliovascular unit, occurs in over 85% of Alzheimer’s disease (AD) cases, positioning CAA as one of the strongest vascular contributors to age‐related cognitive decline. However, the specific mechanisms in the microvasculature that become altered due to amyloid deposition and its downstream effects on the brain are complex and incompletely understood. A spatial transcriptomic analysis comparing pathways affected in the gliovascular niche differently in the presence of vascular amyloid could provide critical insight into the mechanisms underlying cerebrovascular changes involved in the deposition of Amyloid in the cerebrovasculature.
Method:
Using NanoString’s GeoMx Human Whole Transcriptome Atlas, which measures over 18,000 protein‐coding genes at each region of interest (ROI) in tissue sections, we evaluated mixed CAA/AD pathology patients. We evaluated and performed selected pair wise comparisons between 4 types of ROI: 1) Astrocytes surrounding vascular amyloid, 2) astrocytes surrounding amyloid‐free vasculature, 3) astrocytes surrounding parenchymal amyloid, & 4) astrocytes in an amyloid‐free parenchymal zone.
Result:
Conducting pairwise comparisons among the four types of Regions of Interest (ROIs) unveiled distinctive transcriptomic signatures across ROI categories. Notably, gene expression profiles in regions of vasculature positive for Aβ‐amyloid differed significantly from those in amyloid‐free vasculature, showcasing pronounced gene expression changes. While the signatures corresponding to both Parenchymal amyloid and vascular amyloid have a similar transcriptional signature, they differ in certain pathways. Through meticulous data mining, we identified a co‐expression cluster of genes intricately linked to vascular amyloid deposition. Further analysis involved determining Differentially Expressed Genes (DEGs) based on ROI types, yielding a comprehensive list of potential targets indicative of the perturbations induced by vascular amyloid deposition versus parenchymal amyloid deposition.
Conclusion:
In summary, the identified differential (parenchymal vs vascular) genes underscore a clear association with alterations in the neurovascular microenvironment, indicating a discernible shift in vasculature dynamics attributed to amyloid presence. This observation emphasizes the significance of comprehending the changes within the vascular unit to address Cerebral Amyloid Angiopathy (CAA) thoroughly to develop comprehensive strategies to tackle CAA‐related challenges
CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors
No full textMicrowave ablation (MWA) triggers a weak systemic immune response that leads to the abscopal regression of distant metastases while killing local tumors, known as the abscopal effect. Combining MWA with chimeric antigen receptor (CAR)-T cells demonstrates promise in enhancing the abscopal effect in antigen-homogeneous tumors. However, the loss of the antigen recognized by CAR or intrinsic antigenic heterogeneity in solid tumors poses a major obstacle. SIRPα variant (CV1)-secreting CAR-T (sCAR-T) cells elicit an abscopal effect on distant tumors with antigen heterogeneity in mice receiving local MWA. Mechanistically, sCAR-T cells can locally eliminate antigen-positive tumors and secrete CV1, whereas the secreted CV1 can activate macrophages that migrate to non-ablated tumor sites in response to post-MWA chemokines, eliciting a macrophage-dependent abscopal effect that enables phagocytosis of antigen-heterogeneous cancer cells. This macrophage-dependent abscopal effect instigated by MWA and sCAR-T cells offers a clinically translatable strategy in metastatic solid tumors with antigen heterogeneity
Microbiome-mediated modulation of immune memory to P. yoelii affects the resistance to secondary cerebral malaria challenge
Get PDFMalaria is caused by protozoan parasites in the genus Plasmodium. Over time individuals slowly develop clinical immunity to malaria, but this process occurs at variable rates, and the mechanism of protection is not fully understood. We have recently demonstrated that in genetically identical C57BL/6N mice, gut microbiota composition dramatically impacts the quality of the humoral immune response to Plasmodium yoelii and subsequent protection against a lethal secondary challenge with Plasmodium berghei ANKA in C57BL/6N mice. Here, we utilize this genetically identical, gut microbiome-dependent model to investigate how the gut microbiota modulate immunological memory, hypothesizing that the gut microbiome impacts the formation and functionality of immune memory. In support of this hypothesis, P. yoelii hyperparasitemia-resistant C57BL/6N mice exhibit increased protection against P. berghei ANKA-induced experimental cerebral malaria (ECM) compared to P. yoelii hyperparasitemia-susceptible C57BL/6N mice. Despite differences in protection against ECM, P. yoelii-resistant and -susceptible mice accumulate similar numbers of memory B cells (MBCs) and memory T cells. Following challenge with P. berghei ANKA, P. yoelii-resistant mice generated more rapid germinal center reactions; however, P. yoelii-resistant and -susceptible mice had similar titers of P. yoelii- and P. berghei-specific antibodies. In contrast, P. yoelii-resistant mice had an increased number of regulatory T cells in response to secondary challenge with P. berghei ANKA, which may dampen the immune-mediated breakdown of the blood-brain barrier and susceptibility to P. berghei-induced ECM. These findings demonstrate the ability of the gut microbiome to shape immune memory and the potential to enhance resistance to severe malaria outcomes
Frontal Theta Event‐Related Oscillations During a Continuous Performance Test: The Influence of Trauma Type and Fluid Intelligence Polygenic Score
No full textBackground: Trauma exposure during adolescence can lead to impaired executive function and altered neural development in related cognitive control networks. Studies have shown that adolescents with a family history of alcohol use disorders have a disproportionately high rate of trauma exposure, as well as impaired response inhibition, making them particularly vulnerable to cognitive impairment and poor mental health outcomes in adulthood. While studies have suggested that this may be due partly to genetic influences, no study to our knowledge has investigated the influences of trauma exposure and polygenic scores (PGS) for cognitive function on later cognitive function.
Methods: This study used data from trauma-exposed individuals in the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 912), comprising offspring from alcohol-dependent high-risk and comparison families, to investigate main and interaction effects of PGS for cognitive function (fluid intelligence score, UK Biobank study) and trauma exposure (nonsexual assaultive, nonassaultive, sexual assaultive) on performance measures and frontal theta event-related oscillations (EROs) during a continuous performance test (CPT).
Results: A significant interaction between fluid intelligence PGS and nonsexual assaultive trauma was observed for CPT ERO power (B = 0.094, p < 0.01), such that individuals with a lower PGS who experienced a nonsexual assaultive traumatic exposure had lower frontal theta ERO power during the cued no-go condition of the CPT.
Conclusion: These findings suggest that a polygenic predisposition for higher fluid intelligence may be associated with differences in neural response inhibition depending on trauma type
Women and Philanthropy: A Literature Review (2025)
No full textThis updated literature review from the Women’s Philanthropy Institute (WPI) synthesizes nearly a decade of new research on gender and philanthropy since the publication of WPI’s inaugural review in 2015. It provides a comprehensive overview of what is known about women’s giving and volunteering, their motivations and behaviors, and their growing influence as nonprofit and philanthropic leaders.
The report explores key themes including women’s historical and contemporary roles in philanthropy, gender differences in giving and volunteering patterns, giving to women’s and girls’ organizations, and the impact of women’s leadership on nonprofit governance and outcomes. It highlights the influence of social and political events on women’s giving, the expansion of collective giving models such as giving circles, and the development of tools like the Women & Girls Index that track philanthropic support for women’s and girls’ causes.
The review concludes by identifying gaps and priorities for future research, including approaches that more fully consider intersectional identities; longitudinal studies of giving across life stages and generations; international comparative research; and investigations into the long-term effects of women’s philanthropic leadership and collective giving models. Together, these insights advance a nuanced understanding of women’s philanthropy and provide a roadmap for scholars, funders, and practitioners to further strengthen the field
Improvement of pulmonary edema and respiratory status after transcatheter PDA closure in the smallest and most premature infants
No full textObjective: We evaluated the effect of transcatheter PDA closure (TCDC) on pulmonary edema by chest x-ray and respiratory status in preterm infants and identified factors contributing to clinical improvement.
Study design: A retrospective review of TCDC in 68 premature infants from January 2017 to June 2021. Chest x-rays were reviewed to assess pulmonary edema. Multiple clinical characteristics were also evaluated.
Results: 40% of patients weaned respiratory support. x-ray haziness change was not significantly different between groups (p = 0.086), however trended toward significance. 59% had decreased haziness and 16% had a marked decrease. Smaller, younger infants were more likely to wean support and have improved edema.
Conclusion: Chest x-ray haziness improved after TCDC, with smaller infants and earlier closure having more improvement. Infants with lung disease had less noticeable improved edema, indicating the difficulty to assess the hemodynamic significance of their PDA prior to closure. Further studies are needed to identify which neonates benefit most from TCDC
Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction
No full textBackground: With an in-depth understanding of cardiac cell differentiation, cell therapy derived from stem cells has shown promising therapeutic effects in the treatment of myocardial infarction (MI). Although many types of cardiac or noncardiac cells have been found to play protective roles in MI, the specific role of endocardial cells (ECCs) in MI has not been reported.
Methods: The current study was designed to determine whether human embryonic stem cell (hESC)-derived endocardial cells (hESC-ECCs) could be protective against MI. We first developed a cell delivery system by constructing a photosensitive interpenetrating network hydrogel consisting of gelatin methacryloyl (GelMA) and silk fibroin methacryloyl (SilMA). The sorted hESC-ECCs were loaded into the delivery system and then injected into the pericardium cavity of the MI rats.
Results: These results show that the cell delivery system has good biocompatibility. Moreover, the delivered endocardial cells improved cardiac function and delayed capillary atrophy after MI. Further mechanistic analysis revealed that hESC-ECCs protect the mitochondria of cardiomyocytes from damage under oxidative stress and potentially promote the angiogenesis of cardiac endothelial cells.
Conclusion: Our results demonstrated that hESC-ECCs have the potential to serve as a cell therapy strategy for MI treatment by maintaining cardiomyocyte survival and facilitating angiogenesis
Temporal variability of brain–behavior relationships in fine-scale dynamics of edge time series
No full textMost work on functional connectivity (FC) in neuroimaging data prefers longer scan sessions or greater subject count to improve reliability of brain-behavior relationships or predictive models. Here, we investigate whether systematically isolating moments in time can improve brain-behavior relationships and outperform full scan data. We assess how behavioral relationships vary over time points that are less visible in full FC based on co-fluctuation amplitude. Additionally, we perform optimizations using a temporal filtering strategy to identify time points that improve brain-behavior relationships. Analyses were performed on resting-state fMRI data of 352 healthy subjects from the Human Connectome Project and across 58 different behavioral measures. Templates were created to select time points with similar patterns of brain activity and optimized for each behavior to maximize brain-behavior relationships from reconstructed functional networks. With 10% of scan data, optimized templates of select behavioral measures achieved greater strength of brain-behavior correlations and greater transfer of behavioral associations between groups of subjects than full FC across multiple cross-validation splits of the dataset. Therefore, selectively filtering time points may allow for development of more targeted FC analyses and increased understanding of how specific moments in time contribute to behavioral prediction