Harvard College Observatory

ABSTRACT Single‐sex STEM programs—defined here as voluntary, gender‐segregated extracurricular or supplemental activities (e.g., summer camps, workshops, robotics clubs, internships, or citizen science initiatives)—have experienced heightened popularity and scrutiny amid efforts to increase diversity in STEM fields. Empirical evidence regarding their efficacy has been inconsistent. Using a nationally representative dataset of 15,725 US undergraduates, we employed rigorous Propensity Score Weighting (PSW) to estimate the effects of attending single‐sex STEM programs during high school on STEM affinity outcomes (i.e., STEM interest, identity, and career intentions). Our findings demonstrated that attending single‐sex STEM programs was associated with a closing of gender gaps. After PSW adjustment, the interaction between being female and attending a single‐sex program was strongly positive for STEM interest ( β = 0.465, p < 0.001), STEM identity ( β = 0.496, p < 0.001), and, most notably, STEM career intentions ( β = 1.778, p < 0.001; odds ratio = 5.92). Sensitivity analysis showed these effects were highly robust to unmeasured confounding ( E ‐values up to 6.03). Conversely, boys attending all‐boys programs exhibited significantly lower STEM affinity in all three outcomes, compared with boys in coed programs or girls in single‐sex programs. Overall, single‐sex STEM programs provided substantial gains for girls while having mixed‐to‐negative implications for boys. We suggest expanding access to all‐girls STEM programs and critically investigating the pedagogical features driving these differential effects.

Reflection-based lensing is used to focus or collimate extreme ultraviolet (EUV)/x rays (x-ray optics) propagating in grazing incidence small-angle x-ray scattering (GISAXS) inside poly-capillary glass. In the process, the refractive index of silica is slightly less than that of vacuum (1.0) for EUV/x rays, leading to total external reflection with a critical angle slightly less than 90°. Here, we examine the feasibility of widening the total external reflection window by coating the capillary interior surface with a silicon nanofilm that assumes the shape of the polycapillary, which may enhance the collection and collimation power. We use slow dynamic self-assembly via circulation of the nanoparticles through the capillary. Electromagnetic scattering computations are conducted using the model of a flat glass substrate decorated with closely packed Si nanoparticles. Optical, luminescent, and SEM imaging techniques, as well as spectroscopy, show that the polycapillary coating is uniform and luminescent under UV irradiation. The computations show that, for visible wavelengths, a 3 nm silicon nanoparticle film reduces the grazing reflectivity at the visible/UV band-to-band transitions E1 and E2. For EUV/x ray, there is a significant reflectivity enhancement of ∼10% due to a larger index dip below that of vacuum, affording a smaller critical angle. Widening the external reflection regime promises superior collection and focusing power, improving the intensity and resolution. Being luminescent under UV makes it useful for imaging, therapy, and other clinical procedures, while also enabling the development of more compact and versatile instruments.

Accessing brain magnetic resonance imaging (MRI) can be challenging, especially for underserved patients, which may lead to disparities in neurological diagnosis. This mixed-methods study enrolled adults with one of four neurological disorders: mild cognitive impairment or dementia of the Alzheimer type, multiple sclerosis (MS), Parkinson disease (PD), or stroke. Participants were enrolled at the Massachusetts General Hospital outpatient clinic in Boston (01/2021-08/2025) and underwent a point-of-care, low-field portable MRI (pMRI) using a 0.064 T scanner (Hyperfine) and pre- and post-scan surveys. For comparison, all participants had received a standard clinical brain MRI of at least 1.5T. Of the 130 participants (54% male, 46% female), the mean age was 60.6 years (standard deviation (SD) = 17.5). 71% reported at least one barrier to MRI care. The median interval between pMRI and standard MRI brain imaging was 48.5 days (25th, 75th percentiles: 26, 112.5). Participants rated pMRI as highly tolerable, with 93% reporting comfort scores ≥ 7 (on a 10-point scale), and 78% indicating willingness to undergo future pMRI. Mean comfort ratings were significantly higher for pMRI (8.4) compared to traditional MRI (7.5; p < 0.05), though the effect size was moderate (η2 = 0.096). No differences in tolerability or comfort were observed across disease, age, or sex groups. Common barriers to standard MRI access included transportation, cost, and scheduling, particularly among low-income or unemployed participants. Qualitative feedback emphasized the need for better physical accommodations but broadly supported the acceptability and potential uses of pMRI. These findings support the feasibility, tolerability, and high patient acceptability of pMRI.

Periodontal and craniofacial tissue defects are complex regenerative targets as the reconstitution of tissue heterogeneity, interconnection and function is essential for favorable clinical outcomes. Periodontal tissues are additionally challenged by the bacterial and immunological factors associated with oral regeneration. Hydrogels are extracellular matrix-like hydrated polymer networks that represent a diverse class of regenerative materials. Current applications of hydrogels for periodontal and craniofacial tissue regeneration include either independent or combined approaches including serving as scaffolds to support cell migration, proliferation, differentiation and matrix deposition at the defective site, and/or the delivery of biomolecular therapies. The aim of this review is to highlight and classify the hydrogel strategies currently used in the clinical area for the regeneration of periodontal and craniofacial tissues. In addition, we provide a perspective on emerging hydrogel technologies and regenerative strategies under development that may be utilized to address unmet clinical needs.

Brain barriers, cerebrospinal fluid (CSF) dynamics, and peripheral factors are implicated as significant contributors to Alzheimer's disease (AD). The choroid plexus (ChP) is a blood-brain interface that produces CSF and forms the blood-CSF barrier. However, how ChP pathology develops across the lifespan and contributes to AD has not been systematically characterized. Here, we report a multi-modal ChP atlas integrating single-nucleus transcriptomics from 49 individuals, AI-assisted quantitative histopathology across >500 postmortem samples age 16 to 105, spatial transcriptomics, and functional studies in 5xFAD mice. We identify fibrosis, calcification, and macrophage abnormalities as hallmarks of ChP aging, with AD pathology conferring additional effects, including expansion of a pro-inflammatory fibroblast-macrophage signaling niche. In 5xFAD mice, macrophage dysfunction is associated with impaired epithelial barrier maintenance and repair. Together, these data provide a foundational resource for understanding ChP dysfunction in aging and AD and propose the macrophage-fibroblast-epithelial barrier axis as a driver of ChP pathology.

Double-strand breaks (DSBs) are the most cytotoxic DNA damages that arise from endogenous processes (oxidative metabolism as well as external stressors); unrepaired DSBs are consistently found in the hippocampus and cortex of Alzheimer's disease (AD) brains and are thought to contribute to neuronal dysfunction and degeneration. A molecular axis involving histone deacetylase 6 (HDAC6) and an E3 ubiquitin ligase ring finger protein 168 (RNF168) is required for ubiquitination of phosphorylated histone variant H2A.X and the subsequent downstream repair pathway. Herein, we propose that disruption of the HDAC6-RNF168-H2A.X axis is a core mechanism underlying defective DSB repairs in AD and discuss the potential of selectively targeting HDAC6 to restore genomic stability in vulnerable neurons.

As New Zealand faces the challenges of an ageing population and widening inequality, it is useful to ask: what is the long-run economic role of KiwiSaver, is it an inclusive institution, and how can it be strengthened for future generations? This article explores the economic benefits of KiwiSaver beyond individual retirement outcomes in the future. It examines whether KiwiSaver contributes to national savings, reduces long-term fiscal pressures, and supports intergenerational inequality by promoting early asset-building. Considering case studies from Singapore, Australia and the Netherlands, the article highlights how starting earlier, contributing more and investing better can build economic resilience, increase capital accumulation, and reduce social polarisation by supporting intergenerational equity. The findings of this research and focus on the need for long-term stewardship allows us to think deeply about how today’s contributions to KiwiSaver can shape a better future for the younger generations in the year 2100.

Lineage plasticity drives treatment resistance in lung adenocarcinoma (LUAD) as cancer cells adopt new identities. In this issue of Genes & Development, Fort and colleagues (doi:10.1101/gad.352742.125) report HNF4α as a key regulator of hybrid identity states and tumor progression in NKX2-1-positive LUAD. Using murine and human models, they show that HNF4α promotes gastrointestinal/liver-like programs and suppresses pulmonary identity by modulating cell identity-specific binding of NKX2-1. In addition, RAS/MEK signaling was implicated in maintenance of this hybrid identity state by regulating NKX2-1 chromatin binding in LUAD. These findings nominate HNF4α as a driver of LUAD plasticity and a potential therapeutic target to overcome resistance.

BackgroundResearch on cognition and pain is limited in Low and Middle-income Countries (LMICs) and understanding how chronic conditions and pain treatment may moderate this association is underexplored. This study aimed to explore the relationship between pain and cognition and the moderating effect of hypertension, diabetes, HIV, pain treatment, and depressive symptoms.MethodsWe analyzed data from 3803 individuals enrolled in the HAALSI study, a longitudinal population study of older adults in Agincourt, South Africa. Pain was measured with the Brief Pain Inventory. Cognition was assessed using a composite of orientation questions, a memory test, and the Trails Making Test B. Chronic conditions were assessed using biological measures, and depressive symptoms were measured using the CES-D scale. Linear regression models were used to investigate the relationship.ResultsBaseline and longitudinal pain were significantly associated with poorer episodic memory (ß = −0.17 [P < .001]; ß = −0.18 [P < .001]). Hypertension amplified the negative effect of pain on episodic memory, while diabetes and HIV did not moderate the relationship between pain and cognition (ß = −0.10 [.006]). Pain treatment was associated with poorer cognitive performance. Depressive symptoms moderated the relationship between pain and both cognition and executive function (EF) (P = .02). The negative effect of pain on episodic memory was observed in individuals with both acute and persisting pain, while it only affected EF in those with acute pain.ConclusionsThese findings highlight the importance of examining factors that may moderate the relationship between pain and cognition and strategies to mitigate the effect pain has on cognition, particularly in LMICs.

Firearms are the leading cause of death in US children and adolescents, but little is known about whether the overall legal landscape was associated with excess mortality after a landmark US Supreme Court decision in 2010. To measure excess mortality due to firearms among US children aged 0 to 17 years after the McDonald v Chicago US Supreme Court decision (2010). An excess mortality analysis was conducted using the US Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (WONDER) database before and after McDonald v Chicago, the landmark 2010 US Supreme Court decision on firearms regulation. States were divided into 3 groups based on legal actions taken before and since 2010, most permissive, permissive, and strict. Firearm mortality trends before (1999-2010) and after (2011-2023) were determined and compared across the 3 groups for all intents and by intent (homicide and suicide). Subgroup analysis by observed race and ethnicity was conducted. For each US state, pre-and post-McDonald v Chicago all-intent pediatric firearm mortality incident rates were compared. These data were analyzed January 2011 through December 2023. The pre- and post-McDonald v Chicago legal landscape. Excess mortality during the post-McDonald v Chicago period. During the post-McDonald v Chicago period (2011-2023), there were 6029 excess firearm deaths (incidence rate [IR], 158.6 per million population; 95% CI, 154.8-162.5) in the most permissive group. In the permissive group, there were 1424 excess firearm deaths (IR, 107.5 per million person-years; 95% CI, 103.8-111.3). In the strict group, there were -55 excess firearm deaths (IR, -2.5 per million person-years; 95% CI, -5.8 to 0.8). Non-Hispanic Black populations had the largest increase in firearm mortality in the most permissive and permissive state groupings. Four states (California, Maryland, New York, and Rhode Island) had decreased pediatric firearm mortality after McDonald v Chicago, all of which were in the strict firearms law group. States in the most permissive and permissive firearm law categories experienced greater pediatric firearm mortality during the post-McDonald v Chicago era. Future work should focus on determining which types of laws conferred the most harm and which offered the most protection.