Alloparental care and division of labour are hallmarks of insect societies1. Social insect workers typically care for brood within the nest when they are young and transition to foraging outside the nest as they age2-5. This provides a powerful paradigm to study the neural basis of parenting and age-related behavioural change. Although previous work has interrogated aspects of these dynamics6-14, the underlying neural and molecular mechanisms remain poorly understood. Here, using an unbiased pharmacological screen of neuropeptides, we show that two ancestral regulators of feeding, neuropeptide F (NPF) and allatostatin A (AstA), modulate brood-care behaviour in the clonal raider ant. Through functional manipulations, we show that NPF increases brood-care behaviour, whereas AstA has the opposite effect. Furthermore, we find that the levels of NPF and AstA in the brain change naturally as ants age, suggesting that these changes underlie the age-related changes in brood-care behaviour. Finally, we show that, as in solitary species15,16, NPF and AstA remain sensitive to nutritional state, and nutritional state affects brood-care behaviour accordingly. Our results reveal that evolution has co-opted molecular mechanisms that regulated feeding ancestrally to enable cooperative brood care and age-associated division of labour.
We present FOMO260K, a large-scale, heterogeneous dataset of 260,927 brain Magnetic Resonance Imaging (MRI) scans from 77,589 MRI sessions and 55,378 subjects, aggregated from 910 publicly available sources. The dataset includes both clinical- and research-grade images, multiple MRI sequences, and a wide range of anatomical and pathological variability, including scans with large brain anomalies. Minimal preprocessing was applied to preserve the original image characteristics while reducing entry barriers for new users. Companion code for self-supervised pretraining and finetuning is provided, along with pretrained models. FOMO260K is intended to support the development and benchmarking of self-supervised learning methods in medical imaging at scale.
Neonatal Intensive Care Units (NICU) are often designed to primarily optimize the health of critically ill newborns. However, prolonged hospitalizations and stressors, in particular for diverse families can lead to alienation. In this Perspective, we explore how NICUs can be designed to center the diversity of families care for in the NICU including, but not limited to, racial and ethnic diversity, LGBTQ+ headed families, non-traditional families, families with disabled caregivers, families who prefer a language other than English, and those with low health literacy. Through thoughtful and inclusive designed spaces, we highlight how a NICU can become a place of healing for families and infants and foster a sense of inclusion and belonging.
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Language discordance in surgical care is a structural driver of inequity that affects patient safety, trust, and outcomes. Emerging interpreter technologies, including artificial intelligence (AI) and remote video interpretation (RVI), are rapidly entering clinical settings. However, implementation decisions are often made without understanding how patients themselves perceive these modalities or whether they view them as replacements or complementary tools within their care. To explore Spanish-speaking surgical patients' perceptions of AI- and RVI-based interpreter technologies, and to understand how clinical context influences modality preferences, the author team conducted a descriptive concurrent mixed-methods study within a U.S. academic health system, enrolling 23 adult patients with Spanish language preference across the surgical continuum. The patients did not choose a single preferred modality; instead, they expressed context-dependent needs. AI was viewed as advantageous for its speed, privacy, and literal translation in straightforward or time-sensitive scenarios. RVI was favored for emotionally complex conversations and cultural nuance. Across narratives, patient agency emerged as a dominant theme. These findings support the development of a multifaceted language access infrastructure in which AI and remote human interpreters are deployed synergistically based on clinical sensitivity, urgency, and patient preference.
Recent theoretical and empirical advancements in well-being science can have meaningful implications for medical care when considering existential issues faced by people with incurable or life-limiting cancer diagnoses. We propose that certain elements of flourishing, such as meaning and purpose, deep personal relationships, and cultivating virtue, can be uniquely realized if targeted appropriately toward the end of life. Qualitative thematic analysis of semistructured interviews was conducted to explore the experiences and unmet psychological needs of people living with the blood cancer multiple myeloma and, precursor, smoldering myeloma to identify key themes related to the potential for flourishing at the end of life. Interview data was obtained from 25 participants (multiple myeloma n = 24, smoldering myeloma n = 4) and 10 health professionals with clinical expertise supporting or treating patients with multiple myeloma. Participants reported personal growth following their diagnosis through acceptance, meaning-making, and connection, yet reported the loneliness of dying with cancer with a desire to have discussions about death with their clinicians in addition to them maintaining treatment. On the contrary, health professionals were hesitant to discuss death with their patients, balancing hope in treatments with preparation for dying. We argue that the hesitation to discuss death thwarts the opportunity to flourish and that existing solutions such as dignity therapy, meaning-centered psychotherapy, early palliative care, and multidisciplinary support can close this gap without diminishing hope in treatments.
Alzheimer's disease (AD) is characterized by neuroinflammation, yet the impact of concurrent systemic infections on the AD brain remains poorly understood. We investigated the molecular mechanisms underlying the central nervous system response to systemic infections in AD by analyzing RNA sequencing data generated in the prefrontal cortex from 202 post-mortem donors (113 AD, 89 controls), where we stratified by the presence of a respiratory infection at the time of death. We identified 763 significant differentially expressed genes (DEGs) between AD and controls without infection, which were enriched for oxidative phosphorylation and neurodegenerative pathways. In contrast, 122 DEGs distinguished AD from controls during infection, with 57 genes uniquely altered in AD in the presence of infection, including MAPK4, VAV3, and POU3F4, implicating infection-dependent mechanisms of vascular and immune regulation. Pathway activity analysis revealed that infection in AD suppresses some immune and vascular pathways, while enhancing transcriptional and developmental programs. Weighted gene co-expression network analysis uncovered three key modules: one module strongly associated with AD, enriched for aging and signal transduction; one module linked to both AD and infection, highlighting cytoskeletal remodeling and host-pathogen interactions; and one module specific to infection, enriched in astrocytes, pericytes, and endothelial cells, implicating blood-brain barrier dysfunction. These findings suggest that systemic respiratory infections reshape transcriptional programs in the AD brain, dampening immune effector pathways and engaging vascular and host-pathogen processes in blood-brain-barrier-associated cell types. Our results highlight the complex interplay between systemic infection, neuroinflammation, and vascular responses in AD.
Inhaled pathogens, pollutants and therapeutics interact with the dynamic architecture of the alveoli, yet how individual particles move and deposit at cellular resolution remains unclear. Here, utilizing the crystal ribcage platform, we track aerosol transport in ex vivo, actively ventilated lungs using real-time fluorescence imaging with single-particle resolution, capturing droplet trajectories, free-flight motion, impact orientation and deposition timescales within functional alveoli. These measurements show that intra-alveolar transport is directional and shaped by airway-guided flow and tissue motion. At larger scales, aerosols do not disperse uniformly throughout the lung's volume but instead concentrate into geometrically constrained clusters of alveoli, forming a conserved mosaic-like compartmentalization while neighbouring alveoli remain largely unexposed. The pattern persists across particle types and species and varies with particle properties and lung age. In models of emphysema, fibrosis and metastasis, airway remodelling alters both the geometry and amount of deposition. These multiscale insights reveal how single-particle transport and airway structure together shape alveolar exposure, immune activation, development and therapeutic accessibility.
The SMART (Stereotactic MR-Guided Adaptive Radiation Therapy) protocol for prostate SBRT has demonstrated favorable clinical outcomes using a 3T-MRI for delineation and a 0.35 T MR-Linac for adaptation, addressing challenges associated with low-field MRI delineation. However, this workflow necessitates three distinct simulation scans (CT, 3T-MRI, and 0.35T-MRI), resulting in logistical complexity and inefficiency. To address these limitations, we have developed and validated an end-toend MR-only workflow to eliminate the need for a planning CT scan (pCT), thereby streamlining treatment delivery and reducing patient burden. A workflow was developed wherein ten prostate cancer patients were simulated on a 3T Siemens MAGNETOM Vida MRI scanner. Consistent with the SMART protocol, high-resolution T2-weighted BLADE/DWI sequences were used for definitive urethra/dominant intraprostatic lesion (DIPL) delineation, and additionally a T1weighted DIXON VIBE sequence was acquired to generate a synthetic CT (sCT) using an FDA-approved deep-learning-based algorithm. This single 3T-simulation dataset was used to plan and subsequently deliver treatment on the ViewRay Systems MRIdian 0.35T MR-Linac. To validate this CT-free pathway, pCT-based plans were retrospectively recalculated on the sCTs. Dosimetric agreement was assessed using DVH analysis and 3D gamma index analysis. Clinical implementation of the full workflow was successful. Dosimetric validation demonstrated high fidelity between sCT and pCT calculations. Computed γ-indices were 96.80±1.33% (2% dose deviation (DD), 2 mm dose-to-agreement (DTA), 10% threshold, local dose normalization) and 99.98±0.03% (3%DD,2mm DTA, 10%, global). Mean absolute differences in PTV D95% were small (0.06±0.14 Gy). Integrating high-field 3T MR simulation with 0.35 T MR-Linac delivery via an sCT pathway is clinically feasible and dosimetrically robust. MRI-only simulation reduces patient burden and improves workflow efficiency, while maintaining the high-quality 3T delineation and MR-guidance that defines the SMART approach.
The corporatization of medicine that sociologist Paul Starr predicted in his 1982 landmark work, The Social Transformation of American Medicine, has come to pass in many ways and is reshaping the delivery of American health care for both good and bad. Although the corporate focus on cost and efficiency is welcome at a time of constrained resources, the more pernicious impacts of corporatization must be managed to keep the health care industry focused on the health of our patients and our communities. The corporation is here to stay. The challenge is to make peace with that reality and work within it to reap its potential benefits while maintaining health care as a social good.
Adolescence has been proposed as a second sensitive period of development with heightened sensitivity to socio-cultural processing. However, age-specific relationships between adverse social experiences and internalising symptoms are unclear. In this study, we used self-reported data at yearly intervals from age 10 to 21 years from the UK Household Longitudinal (UKHLS) Study. We investigated individual differences in how internalising symptoms change with age and whether there are differences in sensitivity to adverse social experiences (bullying and social exclusion). We captured the relationship between bullying and internalising symptoms from age 10 to 15 years (N = 10,285) and social exclusion and internalising symptoms from age 16 to 21 years (N = 11,623) by leveraging latent growth curve models with time-varying covariates. More bullying was associated with greater internalising symptoms, and there was evidence for age-specific sensitivity at yearly intervals from age 10-15 years (estimates = .541-.714, standardised estimates: .270-.400, ps < .001, FDR corrected ps < .05). From ages 16-21, higher feelings of social exclusion were associated with greater internalising symptoms (est = .312, p < .001), and the strength of this relationship remained stable over time. This evidence shows that vulnerability to adverse social experiences varies over age, and more so between age 10-15 years. The findings highlight: 1) the role of adverse social experiences in internalising symptoms with yearly precision, 2) the relevance of age-specific vulnerabilities to adverse social experiences, 3) and the importance of considering sensitivities beyond age 18 years.
The aim of this study was to evaluate the association of oral menopausal hormone therapy (estrogen only [E-only] or estrogen and progestin [E+P]), as compared to placebo on postmenopausal headache severity among females with and without a history of migraine in the Women's Health Initiative Hormone Therapy (WHI-HT) trials. Migraine is three times more common among females than males and is a major source of pain and disability among women throughout the life course. Previous observational research found a positive association between menopausal hormone therapy (MHT) use and migraine prevalence, but the longitudinal association of MHT with postmenopausal migraine severity is unclear. We examined changes in self-reported headache severity between baseline and year 1 in 22,876 females (average age 64 years) across the United States enrolled in the WHI-HT trials between 1993 and 1998. We conducted a secondary, stratified analysis of data of two parallel, randomized, placebo-controlled clinical trials to estimate the association of MHT and headache severity overall and stratified by history of migraine at baseline. Additionally, we assessed the association between MHT and headache trajectory, based on whether headaches worsened over the follow-up period. At baseline, the prevalence of a lifetime migraine diagnosis was 10%. Among participants with a history of migraine, randomization to E-only MHT was not associated with more severe headache at 1 year (adjusted odds ratio [aOR] = 1.14, 95% confidence interval [CI]: 0.90-1.44), or worsening headache trajectory (adjusted risk ratio [aRR] = 0.98, 95% CI: 0.71-1.34) after 1 year. Randomization to E+P MHT was modestly associated with more severe headache, although estimates did not reach statistical significance (aOR = 1.21, 95% CI: 0.98-1.50). E+P MHT was significantly associated with worsening headache trajectory (aRR= 1.53, 95% CI: 1.14-2.03). Among those without a migraine history, E-only MHT was not strongly associated with moderate-to-severe headache severity (aOR: 1.11, 95% CI: 1.01-1.21) or worsening headache trajectory (aRR = 1.08 95% CI: 0.96-1.22) after 1 year. However, E+P MHT was associated with modestly increased odds of moderate-to-severe headache severity (aOR = 1.14, 95% CI: 1.06-1.23) and a higher likelihood of worsening headache trajectory (aRR = 1.18, 95% CI: 1.07-1.30) after 1 year. In this study of MHT in the WHI hormone therapy trial participants, E-only MHT was not associated with increased odds of more severe postmenopausal headache severity. Among those with a history of migraine, E+P MHT was associated with more severe and worsening postmenopausal headache. Further research on the effect of newer MHT formulations on postmenopausal headache is warranted. Menopausal hormone therapy is widely used, but its impact on headache severity, especially among those with a history of migraine, is unclear. We analyzed data from randomized trials and found that estrogen‐only therapy was not linked to worse headaches, while combined estrogen plus progestin therapy was associated with worsening headaches, particularly among women with prior migraine. These findings suggest that menopausal hormone therapy types differ in their association with headache outcomes.
Tools that help patients to digitally manage their health and health care have become increasingly important in recent years. The patient portal is the most well-established and widely used digital health tool through which patients may access their electronic medical record. Organizational efforts to promote awareness and use of the patient portal have primarily been directed at patients, yet millions of Americans with complex and costly health needs and disabilities manage their health with one or more care partners from among their family and friends. The presence and capacity of care partners can have profound effects on care quality and resource use, but their involvement is not well supported in care delivery. Care partners have been generally excluded from digital health initiatives and are often unable to access the information they need to coordinate or execute the patient's care plan. In this article, the authors take stock of the current landscape of care partner engagement through the patient portal, given its widespread availability and use. They describe the launch of the Coalition for Care Partners to stimulate collaborative initiatives to advance research, policy, and practice in this arena, and present an agenda to advance the field.
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WNK2 is a known tumor suppressor in a set of solid tumors, including glioblastoma multiforme and pancreatic ductal adenocarcinoma. WNK2 functions are largely unknown beyond the kinase domain (KD)-dependent inhibition of ERK1/2 signaling. Waldenström's Macroglobulinemia (WM) is an indolent, yet incurable, B cell lymphoma characterized by highly recurrent MYD88 (MYD88MUT) and CXCR4 (CXCR4MUT) mutations that trigger sustained NF-κB and ERK1/2 signaling. Although not expressed in healthy B cells, WNK2 is a top dysregulated gene in MYD88MUT WM. To study WNK2 regulation and signaling, we performed multi-omics analyses, including bulk and PacBio Iso-Seq RNA-Seq and methylome, in 264 untreated WM and functional studies in cell lines and primary WM cells. Aberrant expression of WNK2 emerged as a near universal feature of early-stage WM and a hallmark of plasma cell-like MYD88MUT WM. We identified novel isoforms that carried a shared aberrant splicing event, either contained or lacked the KD and were highly expressed by the tumor cells, unlike the canonical full-length isoforms. Functionally, WNK2/S-NK1, the most expressed of the KD-lacking isoforms in WM, triggered a pro-inflammatory cascade that activated ERK1/2 and NF-κB signaling. We observed a similar, cancer-specific upregulation of WNK2 in a set of solid tumors, including the highly aggressive cholangiocarcinoma. Our findings reveal an undocumented oncogenic function for WNK2 driven by novel, cancer-specific isoforms and provide a framework for its further investigation as a determinant of disease progression in MYD88MUT WM and a novel therapeutic target in hematological and solid tumor oncology.
Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.
From disparities in the number of exhibiting artists to auction opportunities, there is evidence of women's under-representation in visual art. Here we explore the exhibition history and auction sales of 65,768 contemporary artists in 20,389 institutions, revealing gender differences in the artist population, exhibitions and auctions. We distinguish between two criteria for gender equity: gender-neutrality, when artists have gender-independent access to exhibition opportunities, and gender-balanced, that strives for gender parity in representation, finding that 58% of institutions are gender-neutral but only 24% are gender-balanced, and that the fraction of man-overrepresented institutions increases with institutional prestige. We define artist's co-exhibition gender to capture the gender inequality of the institutions that an artist exhibits. Finally, we use logistic regression to predict an artist's access to the auction market, finding that co-exhibition gender has a stronger correlation with success than the artist's gender. These results help unveil and quantify the institutional forces that relate to the persistent gender imbalance in the art world.
Primary enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles, known as congenital cerebral ventriculomegaly (CCV), is a hallmark of congenital hydrocephalus. CCV is also enigmatically but frequently associated with autism and other neurodevelopmental disorders. To gain insight into the developmental genetic regulation of the human CSF-ventricular system, we conducted an integrated, multiomic study of about 2700 trio-based exomes from patients with primary CCV. We found that about 25% of cases were associated with rare, damaging de novo variants in mutation-intolerant genes, many of which are linked to other dominant Mendelian disorders. Thirty-five exome-wide significant CCV genes and dozens of other high-confidence CCV genes converged on pathways involved in ATP-dependent Brahma-related gene 1/Brahma-associated factor chromatin remodeling, histone H3 lysine 4 methylation, and phosphoinositide 3-kinase signaling. Knockout of selected CCV genes in mouse models supported that de novo variants in CCV genes caused ventriculomegaly by impairing both CSF dynamics and cortical cytoarchitecture through dysregulation of neuroprogenitor cell growth and maturation in the ventricular and subventricular zones. These findings indicated that genetic and epigenetic programs coordinate the "hand-in-glove" development of the CSF-ventricular system with that of the cerebral cortex and establish a genetic connection between CCV and neurodevelopmental disorders, potentially explaining why some patients with hydrocephalus continue to exhibit CCV and neurodevelopmental disorders despite CSF shunting. We suggest that combined brain imaging and whole-exome sequencing could enable early detection of, and intervention for, autism and other neurodevelopmental disorders.
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In chronic rhinosinusitis (CRS) patients, psychological status influences whether symptoms are indicative of CT results and affects short-term outcomes after endoscopic sinus surgery (ESS). Our objective was to assess the impact of psychological status on 5-year outcomes following ESS. CRS patients undergoing ESS prospectively completed 22-item sinonasal outcome test (SNOT-22) surveys preoperatively and postoperatively at 3 months and annually for 5 years. Patients were stratified into high and low psychological dysfunction groups based on SNOT-22 psychological domain scores, and outcomes were compared. Of 1069 patients enrolled, 557 were in the high psychological dysfunction (HPD) cohort and 512 were in the low psychological dysfunction (LPD) cohort. 5-year outcome data were available for 205 patients in the HPD and 196 patients in the LPD group. Patients with HPD were more likely to be female and have a history of prior sinus surgery, allergy, and headaches. HPD patients had significantly higher SNOT-22 scores (61.1 vs. 32.8, p < 0.001) at baseline. Both groups had significant improvement at each postoperative timepoint and similar relative improvement (45.2% vs. 44.5% reduction at 5 years), although the HPD patients had significantly greater symptom severity at 5 years (33.5 vs. 18.2, p < 0.001). Multivariable regression revealed that preoperative psychological domain scores independently predicted higher postoperative non-psychological SNOT-22 scores (β = 0.29; 95% CI: 0.11-0.47; p = 0.001). ESS provides long-term benefit to patients regardless of psychological dysfunction severity. However, patients with HPD experienced significantly worse symptoms before ESS and for up to 5 years postoperatively. Preoperative psychological score independently predicts postoperative symptom severity.