Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, -3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and -3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis.

The advent of near-term digital quantum computers could offer us an exciting opportunity to investigate quantum many-body phenomena beyond that of classical computing. To make the best use of the hardware available, it is paramount that we have methods that accurately simulate Hamiltonian dynamics for limited circuit depths. In this paper, we propose a method to classically optimize unitary brickwall circuits to approximate quantum time evolution operators. Our method is scalable in system size through the use of tensor networks. We demonstrate that, for various three-body Hamiltonians, our approach produces quantum circuits that can outperform trotterization in both their accuracy and the quantum circuit depth needed to implement the dynamics, with the exact details being dependent on the Hamiltonian. We also explain how to choose an optimal time step that minimizes the combined errors of the quantum device and the brickwall circuit approximation. Published by the American Physical Society 2024

Evidence for a stochastic gravitational wave (GW) background, plausibly originating from the merger of supermassive black holes (SMBHs), is accumulating with observations from pulsar timing arrays. An outstanding question is how inspiraling SMBHs get past the “final parsec” of separation, where they have a tendency to stall before GW emission alone can make the binary coalesce. We argue that dynamical friction from the dark matter (DM) spike surrounding the black holes is sufficient to resolve this puzzle, if the DM has a self-interaction cross section of order cm2/g. The same effect leads to a softening of the GW spectrum at low frequencies as suggested by the current data. For collisionless cold DM, the friction deposits so much energy that the spike is disrupted and cannot bridge the final parsec, while for self-interacting DM, the isothermal core of the halo can act as a reservoir for the energy liberated from the SMBH orbits. A realistic velocity dependence, such as generated by the exchange of a massive mediator like a dark photon, is favored to give a good fit to the GW spectrum while providing a large enough core. A similar velocity dependence has been advocated for solving the small-scale structure problems of cold DM. Published by the American Physical Society 2024

To address: What are the experiences of 2SLGBTQQIA+ parents using parenting supports and services to meet their children's early childhood development needs (<5 years of age)? Whittemore and Knafl's (2005) integrative review methodology. Electronic databases were searched from 2000 to October 14, 2022 for empirical studies or reviews addressing the research question. The title and abstract of 12,158 articles were screened for inclusion in the review by two independent researchers; 175 of these articles underwent full-text review. Studies selected were critically appraised using a Joanna Briggs Institute Critical Appraisal tool. Relevant key findings were extracted from each study and entered into N-VIVO-12. Thematic content analysis was employed and PRISMA guidelines were adhered to. A total of 18 articles (15 qualitative and three multi-method studies) met the inclusion criteria and were selected for the review. Seven themes were revealed from analysis of the studies: (1) 2SLGBTQQIA+ Status kept a secret; (2) Forced to come out; (3) Heteronormative messaging; (4) Feeling excluded; (5) Stigmatised; (6) Parents act as educators; and (7) Positive experiences. This integrative review provides nurses with insight into the experiences of 2SLGBTQQIA+ parents using health care services for their young child. This article highlights what changes nurses need to make to their practice to ensure appropriate, inclusive care for clients of diverse sexual and gender identities and their families. Health care providers, especially nurses, have an opportunity to improve the experiences of these families and positively impact their health and well-being. Additionally, there is a need for research with the 2SLGBTQQIA+ parent community and the use of rigorous methodological techniques, including clearly linking participants' gender and sexual identities with study findings, to improve our understanding of 2SLGBTQQIA+ parent experiences. Although there was no direct patient contribution to the work since it was an integrative review of the literature, indirectly patient contributions are incorporated from the original research results of studies incorporated into this review.

To determine whether fluid-fluid exchange (endodrainage) or external needle drainage can result in retinal displacement following minimal gas vitrectomy (MGV) with no fluid-air exchange for rhegmatogenous retinal detachment repair. Two patients with macula-off rhegmatogenous retinal detachment underwent MGV with and without segmental buckle. First case had MGV with segmental buckle (MGV-SB), along with endodrainage, whereas the second case had MGV only with external fluid drainage. At the completion of surgery, the patient was immediately log rolled to face down for 6 hours followed by positioning to the break. Both patients achieved retinal reattachment, and postoperative widefield fundus autofluorescence imaging demonstrated a low-integrity retinal attachment with retinal displacement. Iatrogenic fluid drainage techniques, such as fluid-fluid exchange or external needle drainage during MGV (without fluid-air exchange), may result in retinal displacement. Allowing the retinal pigment epithelial pump to reabsorb the fluid naturally may reduce the risk of retinal displacement.

Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.

Abstract Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset (N &amp;gt; 9,000, 9–11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p &amp;lt; .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p &amp;lt; .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

Background Intracranial aneurysms (IAs) are more common in women than in men; however, there is still limited knowledge on sex‐dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors, and histopathology. Methods This cross‐sectional, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors, and histology between sexes. Results We included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). A total of 363 patients (36.97%) had multiple IAs, the proportion of which was significantly higher in women. In women, the internal carotid artery (40.79%) was the most frequent location for IAs, whereas in men most were found along the anterior carotid artery territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes; however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex‐dependent differences. Histologically, wall‐type classification analysis showed significantly more severe aneurysm wall types in men. Conclusion IA prevalence in women is significantly higher than in men. Women more often present with multiple IAs, whereas men were more often diagnosed with ruptured IAs. Sex‐specific differences in IA location were identified, whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex‐dependent manifestations in IAs.

Traumatic injury surveillance can be enhanced by describing injury severity trends. This study reports trends in work-related injury severity for males and females over the period 2004-2017 in Ontario, Canada. A weighted measure of workers' compensation benefit expenditures was used to define injury severity, obtained from the linkage of workers' compensation claims to emergency department (ED) records where the main injury or illness was attributed to work. Denominator counts were obtained from Statistics Canada's Labor Force Survey. Trends in the annual incidence of injury, classified as low, moderate, or high severity, were examined using regression modeling, stratified by age and sex. Over a 14-year observation period, there were 1,636,866 ED records included in the analyses. Overall, 57.6% of occupational injury records were classified as low severity, 29.5% as moderate severity, and 12.8% as high severity conditions. There was an increase in the incidence of high severity injuries among females (annual percent change (APC): 1.52%; 95% CI: 0.77, 2.28), while the incidence of low and moderate severity injuries generally declined for males and females. Among females, injuries attributed to animate mechanical forces and assault increased as causes of low, moderate, and high severity injuries. The incidence of concussion increased for both males (APC: 10.51%; 95% CI: 8.18, 12.88) and females (APC: 16.37%; 95% CI: 13.37, 19.45). The incidence of severe work-related injuries increased among females in Ontario between 2004 and 2017. The methods applied in this surveillance study of traumatic injury severity are plausibly generalizable to applications in other jurisdictions.