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The Galactic disc is one of the main components of the Milky Way, which contributes most of the luminosity. Its structure is essential for understanding the formation and evolution of the Milky Way. Using 174 443 K-type dwarf stars observed by both Large Sky Area Multi-Object Fiber Spectroscopic Telescope and Gaia Data Release 3, we study the disc density profile in the local volume within 1200 pc. In the azimuthal dimension, we find strong asymmetric signal of the thin disc. The surface density and the scale height of the southern disc significantly change versus the azimuthal angle at the same Galactocentric distance R. Meanwhile, in the vertical dimension, the scale height of the northern disc has quite different trend than that of the southern one. The scale height of the southern disc shows a decreasing trend with ϕ ∼ −2.5°, and change to an increasing one with ϕ ∼ 5.0°. Meanwhile, the scale height of the northern disc has a consistently smaller increase. Finally, we divide the entire sample into three subsamples based on metallicity and all three subsamples show significant non-axisymmetric and north–south asymmetric signals in the Galactic disc. Furthermore, we find that the scale height of the metal-poor ([Fe/H] < −0.4 dex) subsample in the northern disc is greater than that of the metal-rich ([Fe/H] > −0.1 dex) subsample. However, in the southern disc, the scale height exhibits varying relationships across different metallicity slices. [ABSTRACT FROM AUTHOR]

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4 , which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

The CD1 and MR1 protein families present lipid antigens and small molecules to T cells, complementing well-studied major histocompatibility complex–peptide mechanisms. The CD1a subtype is highly and continuously expressed within the skin, most notably on Langerhans cells, and has been demonstrated to present self and foreign lipids to T cells, highlighting its cutaneous sentinel role. Alteration of CD1a-dependent T-cell responses has recently been discovered to contribute to the pathogenesis of several inflammatory skin diseases. In this review, we overview the structure and role of CD1a and outline the current evidence implicating CD1a in the development of psoriasis, atopic dermatitis and allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P  < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P  < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs. [ABSTRACT FROM AUTHOR]

Background In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly used for treatment in patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrowband ultraviolet B (NB-UVB) has rarely been explored. Objectives To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis. Methods We conducted a retrospective cohort study of data in the Taiwan National Health Insurance Research Database from 1997 to 2013. Cumulative incidences and multivariate analysis were investigated using a competing risk regression model, comparing skin cancer risk between cohorts of people having combination therapy and those using NB-UVB alone, matched for relative confounders. We further conducted a sensitivity analysis for those receiving a higher MTX dose. Standardized incidence ratios (SIRs) were calculated for skin cancer risk. Results We enrolled 3203 participants in each cohort. No significant differences in skin cancers were noted between the two cohorts for the cumulative incidences (log-rank test, P = 0.28) and for the hazard ratio (HRs) [adjusted HR 0.50, 95% confidence interval (CI) 0.15–1.63, P = 0.247] in the competing risk regression model. There were also no significant differences between those receiving higher-dose MTX and UVB alone in the cumulative incidences of skin cancers (P = 0.23) and the HR (adjusted HR = 0.29, 95% CI 0.04–2.21, P = 0.23) in the multivariate analysis. There was no significant difference in the SIR between the two cohorts compared with the general population. Conclusions In the Taiwanese population, MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB. [ABSTRACT FROM AUTHOR]

Background Thyroid cancer, the leading endocrine tumor with a rising global incidence, especially in women, is influenced by both genetic and environmental factors. This study examines the relationship between polygenic risk scores (PRS) and thyroid cancer susceptibility in the Han Chinese population, as well as the impact of genetic variants on clinical outcomes. Methods Analyzing data from 57 257 participants in the Taiwan Precision Medicine Initiative, the study employed the Affymetrix Genome-Wide TWB 2.0 SNP Array for genotyping. PRS were calculated using single nucleotide polymorphisms (SNPs) from prior genome-wide association studies, specifically PGS000087 and PGS000797, and correlated with clinical parameters like age, sex, comorbidities, and treatment methods. Results Among 4063 participants with thyroid tumors (839 malignant, 3224 benign), higher PRS quartiles correlated significantly with increased thyroid cancer incidence. The highest quartile showed a 1.15-fold (PGS000797) and 1.14-fold (PGS000087) greater risk than the lowest quartile. Key findings included an association between higher PRS quartiles and younger onset age, along with a notable link to chronic kidney disease and thyroid hormone levels in specific SNPs. Conclusion The study demonstrates PRS's utility in predicting thyroid cancer risk in the Han Chinese population, with higher PRS associated with increased risk and distinct clinical features. While this study focuses on the Han Chinese population, we recognize the importance of comparing PRS performance across different ancestries to fully understand ethnic genetic diversity in cancer risk assessment. Future studies should aim to include such comparative analysis. [ABSTRACT FROM AUTHOR]

Background Everyday discrimination—experiences of being treated unfairly based on background characteristics like race—is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored. Methods Community-dwelling participants from 3 longitudinal cohort studies (N  = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included. Hospitalizations were identified using Medicare fee-for-service claims, available for an average of 6.2 (SD : 3.7) years of follow-up after baseline. Results In mixed-effects ordinal logistic regression models (outcomes of 0, 1, or 2+ hospitalizations per year) adjusted for age, sex, education, and income, higher discrimination was associated with higher odds of total annual hospitalizations (odds ratio [OR] per point higher = 1.09, 95% confidence intervals [95% CI]: 1.02–1.17). Results were similar when accounting for depressive symptoms. Conclusions Higher exposure to everyday discrimination is associated with higher odds of hospitalization among older African Americans. Mechanisms underlying associations should be explored further to understand how hospitalizations may be reduced in older African Americans. [ABSTRACT FROM AUTHOR]

Deep learning-based multi-omics data integration methods have the capability to reveal the mechanisms of cancer development, discover cancer biomarkers and identify pathogenic targets. However, current methods ignore the potential correlations between samples in integrating multi-omics data. In addition, providing accurate biological explanations still poses significant challenges due to the complexity of deep learning models. Therefore, there is an urgent need for a deep learning-based multi-omics integration method to explore the potential correlations between samples and provide model interpretability. Herein, we propose a novel interpretable multi-omics data integration method (DeepKEGG) for cancer recurrence prediction and biomarker discovery. In DeepKEGG, a biological hierarchical module is designed for local connections of neuron nodes and model interpretability based on the biological relationship between genes/miRNAs and pathways. In addition, a pathway self-attention module is constructed to explore the correlation between different samples and generate the potential pathway feature representation for enhancing the prediction performance of the model. Lastly, an attribution-based feature importance calculation method is utilized to discover biomarkers related to cancer recurrence and provide a biological interpretation of the model. Experimental results demonstrate that DeepKEGG outperforms other state-of-the-art methods in 5-fold cross validation. Furthermore, case studies also indicate that DeepKEGG serves as an effective tool for biomarker discovery. The code is available at https://github.com/lanbiolab/DeepKEGG. [ABSTRACT FROM AUTHOR]

The exploratory nature of phase II trials makes it quite common to include heterogeneous patient subgroups with different prognoses in the same trial. Incorporating such patient heterogeneity or stratification into statistical calculation for sample size can improve efficiency and reduce sample sizes in single-arm phase II trials with binary outcomes. However, such consideration is lacking in randomized phase II trials. In this paper, we propose methods that can utilize some natural order constraints that may exist in stratified population to gain statistical efficiency for randomized phase II designs. For thoroughness and simplicity, we focus on the randomized phase II selection designs in this paper, although our method can be easily generalized to the randomized phase II screening designs. We consider both binary and time-to-event outcomes in our development. Compared with methods that do not use order constraints, our method is shown to improve the probabilities of correct selection or reduce sample size in our simulation and real examples. [ABSTRACT FROM AUTHOR]

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy. [ABSTRACT FROM AUTHOR]

The kernel search optimizer (KSO) is a recent metaheuristic optimization algorithm that is based on kernel theory, eliminating the need for hyper-parameter adjustments, and demonstrating excellent global search capabilities. However, the original KSO exhibits insufficient accuracy in local search, and there is a high probability that it may fail to achieve local optimization in complex tasks. Therefore, this paper proposes a multi-strategy enhanced KSO (MSKSO) to enhance the local search ability of the KSO. The MSKSO combines several control strategies, including chaotic initialization, chaotic local search mechanisms, the high-altitude walk strategy (HWS), and the Levy flight (LF), to effectively balance exploration and exploitation. The MSKSO is compared with ten well-known algorithms on 50 benchmark test functions to validate its performance, including single-peak, multi-peak, separable variable, and non-separable variable functions. Additionally, the MSKSO is applied to two real engineering economic emission dispatch (EED) problems in power systems. Experimental results demonstrate that the performance of the MSKSO nearly optimizes that of other well-known algorithms and achieves favorable results on the EED problem. These case studies verify that the MSKSO outperforms other algorithms and can serve as an effective optimization tool. [ABSTRACT FROM AUTHOR]

Objective Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Methods Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Results Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P  < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P  = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P  = 0.009). Conclusion Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing. [ABSTRACT FROM AUTHOR]

Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life. [ABSTRACT FROM AUTHOR]

Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. Results Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7–235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P  = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P  = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P  = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P  = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P  < 0.001) were associated with disparity between self-reported and IS-denoted flares. Conclusion A diagnosis of IIMs confers an equal risk of flares in the post–COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration. [ABSTRACT FROM AUTHOR]

Background Evidence indicates the health care system disproportionately misses dementia in African American compared to White individuals. In preliminary data, we examined factors related to dementia identification by the health care system among African Americans. Methods We leveraged linked Medicare fee-for-service claims and detailed annual cohort evaluations in African Americans from 4 cohorts at Rush Alzheimer's Disease Center. Results Among 88 African Americans with cognitive impairment (mean = 10 years follow-up), Medicare claims identified dementia <2 years from cohort diagnosis in 55%; 27% were identified 2–9.9 years after cohort diagnosis, and in 18% there was either no claims diagnosis during the study period, or claims identified dementia 10+ years after cohort diagnosis. Claims identification of dementia was related to older age at cohort diagnosis (eg, <2 years between cohort and claims: mean = 82 years; 10+ years/no diagnosis: mean = 77 years, p  = .04), lower Mini-Mental State Examination (MMSE) score (<2 years: mean = 24; 10+ years/no diagnosis: mean = 26, p  = .04), more depressive symptoms (<2 years: mean = 2.1 symptoms; 10+ years/no diagnosis: mean = 1.2, p  = .04), and more comorbidity (<2 years: mean = 5.6 comorbidities; 10+ years/no diagnosis, mean = 3.0, p  = .02). Conclusions Among African Americans, preliminary data indicate the health care system most rapidly identifies dementia in older individuals, with worse cognitive and physical health. The health care system may miss opportunities for early support of African Americans with dementia, and caregivers. [ABSTRACT FROM AUTHOR]

Context Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. Objective We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. Methods This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. Results A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). Conclusion Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Masses in the heart and valves have a broad differential diagnosis including infective and rheumatic causes as well as primary or metastatic tumours. Diagnosis involves delineating the location, shape, and origin of the mass/masses and considering the clinical context. This case outlines the work-up and approach to diagnosing a cardiac mass along with imaging findings of a unique secondary metastatic mass in the left ventricle (LV). Case summary A 69-year-old female with past medical history of metastatic lung cancer treated with radiotherapy and breast cancer treated with mastectomy presented with dyspnoea and fever. Due to concern for infective endocarditis, transthoracic echocardiogram (TTE) was performed revealing 2 cm × 0.72 cm finger-like, echo-lucent, mobile mass, appearing to originate from LV lateral wall, protruding into the LV cavity, along with valvular masses on mitral and tricuspid valves. Initial differential diagnosis included benign pathologies, but due to the clinical suspicion of malignancy, cardiac MRI was performed which revealed a broad-based mass with invasion into the LV lateral wall and delayed gadolinium enhancement, suggestive of metastatic tumour. The patient was given Aspirin to prevent embolization and eventually underwent hospice care. Discussion Atypical appearing cardiac masses can be seen on TTE. Cardiac magnetic resonance imaging (MRI) should be used for definite diagnosis in cases where clinical features do not match the echocardiographic findings. [ABSTRACT FROM AUTHOR]

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3–5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution. [ABSTRACT FROM AUTHOR]

The Himalayan marmot Marmota himalayana is widely distributed across the Qinghai–Tibetan Plateau and lives in social groups, yet the mating system of this highly social marmot species is unknown. In this study, the genetic mating system of Himalayan marmots was investigated using microsatellite markers to determine which mating strategies individuals employ. Results revealed that both monogamous and polygamous mating relationships occur in our study population, indicating that the genetic mating system of this marmot species is promiscuity. This study presents the first genetic evidence on the mating system for Himalayan marmots, yet indicates that further studies employing both a genetic and behavioral framework are needed to better understand the social structure and reproductive biology of this marmot species. [ABSTRACT FROM AUTHOR]

Altered prohormone processing, such as with proinsulin and pro-islet amyloid polypeptide (proIAPP), has been reported as an important feature of prediabetes and diabetes. Proinsulin processing includes removal of several C-terminal basic amino acids and is performed principally by the exopeptidase carboxypeptidase E (CPE), and mutations in CPE or other prohormone convertase enzymes (PC1/3 and PC2) result in hyperproinsulinemia. A comprehensive characterization of the forms and quantities of improperly processed insulin and other hormone products following Cpe deletion in pancreatic islets has yet to be attempted. In the present study we applied top-down proteomics to globally evaluate the numerous proteoforms of hormone processing intermediates in a β-cell-specific Cpe knockout mouse model. Increases in dibasic residue–containing proinsulin and other novel proteoforms of improperly processed proinsulin were found, and we could classify several processed proteoforms as novel substrates of CPE. Interestingly, some other known substrates of CPE remained unaffected despite its deletion, implying that paralogous processing enzymes such as carboxypeptidase D (CPD) can compensate for CPE loss and maintain near normal levels of hormone processing. In summary, our quantitative results from top-down proteomics of islets provide unique insights into the complexity of hormone processing products and the regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Background Facial aging is a multifactorial process involving the skin, fat, muscles, bones, and ligaments. The role of facial ligaments in the facial aging process remains elusive. Objectives The aim of this study was to identify whether age-related changes in facial ligaments exist and how to best quantify such changes when investigating the zygomatic ligament in the rat. Methods A total of 30 male Sprague-Dawley rats (10 young, 10 middle-aged, 10 mature) were investigated to visualize the zygomatic ligament. Samples of the ligaments spanning the zygomatic arch and the skin were taken and histologically examined with hematoxylin-eosin, Masson, Verhoeff's elastic, and picrosirius red staining. Quantification of the Type I/III collagen ratio and collagen content was performed by color deconvolution and electron microscopic imaging. Results With increasing age, collagen fibers inside of the examined ligaments appeared thicker and more closely arranged. The Type I/III collagen ratio was measured to be 1.74 in young animals, 3.93 in middle-aged animals, and 5.58 in mature animals. The ultra-microstructure of the ligament was less coordinated in direction and orientation in young and middle-aged animals than in mature animals, in which collagen fibers were bundled together in a strong and oriented mesh. Conclusions Ligaments appeared thinner, transparent, more elastic, and less robust in young animals, whereas ligaments in mature animals appeared thicker, more fascia-like, less elastic, and more robust. An increase in the Type I/III collagen ratio, indicating greater stiffness and reduced elasticity, was observed with higher age of the investigated animals. These findings indicate that ligaments might increase in stiffness and rigidity with age. [ABSTRACT FROM AUTHOR]

In Crypto'19, Gohr proposed the first deep learning-based key recovery attack on 11-round Speck32/64, which opens the direction of neural-aided cryptanalysis. Until now, neural-aided cryptanalysis still faces two problems: (i) the attack complexity estimations rely purely on practical experiments; (ii) it does not work when there are not enough neutral bits. To the best of our knowledge, we are the first to solve these two problems. In this paper, we propose a Neural-Aided Statistical Attack (NASA) that has the following advantages: (i) NASA supports estimating the theoretical complexity. (ii) NASA does not rely on any special properties including neutral bits. Moreover, we propose three methods for reducing the complexity of NASA. One of the methods, which is based on a newly proposed concept named Informative Bit that reveals an important phenomenon, makes NASA applicable to large-size ciphers. We have performed a series of experiments on round reduced Speck32/64, DES, and Speck96/96. These experiments do not only verify the correctness of NASA, but also further highlight the advantage and potential of NASA. Our work arguably raises a new direction for neural-aided cryptanalysis. [ABSTRACT FROM AUTHOR]

Staminal hairs are the particular appendages of stamens, which may affect pollinator foraging behaviour and pollen transfer. However, experimental evidence of the functions of staminal hairs in pollination remains scarce. Here, we conducted staminal hair manipulation experiments in Tradescantia fluminensis (Commelinaceae) to investigate their effects on visitation and pollen transfer by bees. Our observations revealed that both visitation rates and visit duration of honeybees (Apis cerana) to control flowers were significantly higher than that of hairless flowers. Moreover, removing the staminal hairs significantly decreased pollen deposition by honeybees (A. cerana), but did not affect pollen removal. The staminal hair was similar in length to the stamen and the pistil of T. fluminensis. The staminal hairs provide more footholds for honeybees, and they lay prone on the staminal hairs to collect pollen, which increased the accuracy of pollination through the consistent pollen placement and pick-up on the ventral surface of honeybees. These results showed that the staminal hairs in T. fluminensis may represent an adaptation to attract pollinators and enhance pollination accuracy. [ABSTRACT FROM AUTHOR]

A neutron beam for boron neutron capture therapy (BNCT) of deep-seated tumours is designed to maintain a high flux of epithermal neutrons, while keeping the thermal and fast neutron component as low as possible. These neutrons (thermal and fast) have a high relative biological effectiveness in comparison with high energy photon beams used for conventional X-ray radiotherapy. In the past, neutrons for the purpose of BNCT were generated using nuclear reactors. However, there are various challenges that arise when installing a reactor in a hospital environment. From 2006, the Kyoto University Research Reactor Institute, in collaboration with Sumitomo Heavy Industries, began the development of an accelerator-based neutron source for clinical BNCT in a bid to overcome the shortcomings of a nuclear reactor-based neutron source. Following installation and beam performance testing, in vitro studies were performed to assess the biological effect of the neutron beam. Four different cell lines were prepared and irradiated using the accelerator-based neutron source. Following neutron and gamma ray irradiation, the survival curve for each cell line was calculated. The biological end point to determine the relative biological effectiveness (RBE) was set to 10% cell survival, and the D10 for each cell line was determined. The RBE of the accelerator-based neutron beam was evaluated to be 2.62. [ABSTRACT FROM AUTHOR]

The article presents a study which analysed predictors in a global sample of patients with idiopathic inflammatory myopathies (IIMs) using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Topics include patients included in the study, patient-reported flares following COVID-19 infection among IIM patients, and factors that were found to significantly increase the risk of flares in univariate analysis.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (αSyn) and myelin disruption. However, the mechanism underlying αSyn accumulation in MSA brains remains unclear. Here, we aimed to identify epsin-2 as a potential regulator of αSyn propagation in MSA brains. In the MSA mouse model, PLP-hαSyn mice, and FABP7/αSyn hetero-aggregate-injected mice, we initially discovered that fatty acid-binding protein 7 (FABP7) is related to MSA development and forms hetero-aggregates with αSyn, which exhibit stronger toxicity than αSyn aggregates. Moreover, the injected FABP7/αSyn hetero-aggregates in mice selectively accumulated only in oligodendrocytes and Purkinje neurons, causing cerebellar dysfunction. Furthermore, bioinformatic analyses of whole blood from MSA patients and FABP7 knockdown mice revealed that epsin-2, a protein expressed in both oligodendrocytes and Purkinje cells, could potentially regulate FABP7/αSyn hetero-aggregate propagation via clathrin-dependent endocytosis. Lastly, adeno-associated virus type 5-dependent epsin-2 knockdown mice exhibited decreased levels of αSyn aggregate accumulation in Purkinje neurons and oligodendrocytes, as well as improved myelin levels and Purkinje neuron function in the cerebellum and motor performance. These findings suggest that epsin-2 plays a significant role in αSyn accumulation in MSA, and we propose epsin-2 as a novel therapeutic target for MSA. [ABSTRACT FROM AUTHOR]

The propagation of active galactic nucleus jets depends both on the environment into which they propagate and on their internal structure. To test the impact that different magnetic topologies have on the observable properties of radio galaxies on kpc scales, we conducted a series of magnetohydrodynamic simulations of jets injected with different magnetic field configurations propagating into a gaseous atmosphere modelled on the Perseus cluster. The simulations show that the structure of the field affects the collimation and propagation of the jets on cluster scales and thus the morphology of the radio lobes inflated by the jets, due to both magnetic collimation and the development of dynamical instabilities in jets with different magnetic topologies. In all cases, the simulations show a distinct reversal of the synchrotron spectral age gradient in the radio lobes about a dynamical time after the jets turn off due to large-scale circulation inside the radio lobe, driven primarily by buoyancy, which could provide a way to constrain the age of radio sources in cluster environments without the need for detailed spectral modelling and thus constrain the radio-mode feedback efficiency. We suggest a robust diagnostic to search for such age gradients in multifrequency radio data. [ABSTRACT FROM AUTHOR]

Accretion discs around supermassive black holes not only power active galactic nuclei (AGNs), but also host single and binary embedded stellar-mass black holes (EBHs) that grow rapidly from gas accretion. The merger of these EBHs provides a promising mechanism for the excitation of some gravitational wave events observed by LIGO–Virgo, especially those with source masses considerably larger than isolated stellar-mass black hole binaries. In addition to their mass and mass-ratio distribution, their hitherto enigmatic small spin parameters (χeff) carry important clues and stringent constraints on their formation channels and evolutionary pathways. Here, we show that, between each coalescence, the typical rapid spin of the merged EBHs is suppressed by their subsequent accretion of gas from a turbulent environment, due to its ability to randomize the flow's spin orientation with respect to that of the EBHs on an eddy-turnover time-scale. This theory provides supporting evidence for the prolificacy of EBH mergers and suggests that their mass growth may be dominated by gas accretion rather than their coalescence in AGN discs. [ABSTRACT FROM AUTHOR]

Neural-aided cryptanalysis is a challenging topic, in which the neural distinguisher (⁠|$\mathcal{ND}$|⁠) is a core module. In this paper, we propose a new |$\mathcal{ND}$| considering multiple ciphertext pairs simultaneously. Besides, multiple ciphertext pairs are constructed from different keys. The motivation is that the distinguishing accuracy can be improved by exploiting features derived from multiple ciphertext pairs. To verify this motivation, we have applied this new |$\mathcal{ND}$| to five different ciphers. Experiments show that taking multiple ciphertext pairs as input indeed brings accuracy improvement. Then, we prove that our new |$\mathcal{ND}$| applies to two different neural-aided key recovery attacks. Moreover, the accuracy improvement is helpful for reducing the data complexity of the neural-aided statistic attack. The code is available at https://github.com/AI-Lab-Y/ND_mc. [ABSTRACT FROM AUTHOR]

Background Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P <.001), longer ventilator usage (24.70 vs 14.01 days, P =.002), and longer postoperative hospital stays (40.83 vs 28.37 days, P <.001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P =.913). The 2-year survival was not significantly different between the 2 groups (P =.236). Conclusions Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia. [ABSTRACT FROM AUTHOR]

Thrips hawaiiensis (Morgan) (Thysanoptera: Thripidae) is a sap-sucking pest that seriously damages several crops and reduces their economic value. Exposure to low concentrations of insecticides may have a sublethal effect on surviving insects. In order to provide a reference for the rational application of emamectin benzoate, its sublethal effects on the development and reproduction of T. hawaiiensis were evaluated. Pupal development time was significantly shorter in T. hawaiiensis treated with sublethal concentrations of emamectin benzoate (LC10 and LC20) than in control. Female adult longevity and female total longevity were significantly longer following LC20 treatment than in the control and LC10 treatment groups. Nevertheless, male adult longevity and male total longevity were significantly shorter in the LC10 treatment group than in the control and LC20 treatment groups. The sublethal concentration of emamectin benzoate (LC20) significantly shortened the preadult stages and the mean generation. Meanwhile, it significantly increased the finite rate of increase, intrinsic rate of increase, and net reproductive rate. The fecundity was significantly higher after LC20 treatment than after LC10 and control treatments. Compared with the control group, the LC10 and LC20 groups of T. hawaiiensis adults showed a significantly higher expression of the vitellogenin (Vg) and vitellogenin receptor (VgR) genes, which played a key role in increasing their fecundity. These findings suggest that short-term exposure to sublethal concentrations of emamectin benzoate may lead to a resurgence and secondary outbreak of T. hawaiiensis infestation. The results have practical applications for the management of this important and noxious pest. [ABSTRACT FROM AUTHOR]

Continental deep subduction after the closure of large oceanic basins is commonly ascribed to the gravitational pull of the subducting oceanic slab. However, it is not clear how continental lithosphere adjacent to small oceanic basins was subducted to mantle depths. The Sesia Zone in the Western Alps provides an excellent target for exploration of subduction dynamics in such a tectonic setting. Here we report the first finding of coesite in a jadeite-bearing orthogneiss from the Sesia Zone, providing the first evidence for deep subduction of the continental crust to mantle depths for ultrahigh-pressure (UHP) metamorphism in this zone. Three coesite inclusions were identified by laser Raman spectroscopy in two garnet grains. Based on zircon U-Pb dating and trace element analysis, the UHP metamorphic age was constrained to be 76.0 ± 1.0 Ma. The phase equilibrium modeling yields peak metamorphic pressures of 2.8–3.3 GPa, demonstrating the continental deep subduction to mantle depths of >80 km. The subducted continental crust was a rifted hyperextended continental margin, which was converted to the passive continental margin during seafloor spreading and then deeply subducted during the oblique convergence between the Adria microplate and Eurasian plate in the Late Cretaceous. Because the slab pull could only play a limited role in closing small oceanic basins for continental collision, the distal push of either continental breakup or seafloor spreading is suggested as the major driving force for the deep subduction of continental crust in the Western Alps. Therefore, deep subduction of the continental crust bordering small oceanic basins would have been induced by the far-field stress of compression, whereas that bordering large oceanic basins was spontaneous due to the oceanic slab pull. This provides a new insight into the geodynamic mechanism of continental deep subduction. The ultrahigh-pressure metamorphism in the Sesia zone of Western Alps is firstly reported, demonstrating the deep subduction of continental crust to mantle depths of >80 km. The continental deep subduction is driven by the distal push of either continental breakup or seafloor spreading, rather than by the proximal pull of the subducting oceanic slab. [ABSTRACT FROM AUTHOR]

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5 −/− mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5 −/− mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates. [ABSTRACT FROM AUTHOR]

Background Galectin-3 is a multi-functional lectin protein and a ligand of mucin-1 (CA15-3), and has been linked to renal fibrosis in animal models and renal function in humans. However, no population study has ever explored the associations with both ligand and receptor. We therefore investigate the independent association of renal function with serum galectin-3 and mucin-1 (CA15-3) in untreated Chinese patients. METHODS The study participants were outpatients who were suspected of hypertension, but had not been treated with antihypertensive medication. Serum galectin-3 and mucin-1 (CA15-3) concentrations were both measured by the enzyme-linked immunosorbent assay (ELISA) method. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine by the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results The 1,789 participants included 848 (47.4%) men. Mean (±SD) age was 51.3 ± 10.7 years. Multiple regression analyses showed that eGFR was significantly associated with serum galectin-3 and mucin-1 (CA15-3) concentration (0.68 and 1.32 ml/min/1.73 m2 decrease per 1-SD increase in log transformed serum galectin-3 and mucin-1 (CA15-3) concentration, respectively; P ≤ 0.006). The association of eGFR with serum mucin-1 (CA15-3) concentration was significantly stronger in the overweight (BMI 24.0–27.9 kg/m2) and obese (BMI ≥ 28.0 kg/m2) than in normal weight subjects (BMI < 24.0 kg/m2, P for interaction 0.018). Path analysis showed that serum galectin-3 concentration had both a direct (P = 0.016) and a mucin-1 mediated indirect effect (P = 0.014) on eGFR. Conclusions Both circulating galectin-3 and mucin-1 (CA15-3) were significantly associated with renal function. The role of galectin-3 on renal function might be partially via mucin-1. [ABSTRACT FROM AUTHOR]

Drug resistance is increasingly among the main issues affecting human health and threatening agriculture and food security. In particular, developing approaches to overcome target mutation-induced drug resistance has long been an essential part of biological research. During the past decade, many bioinformatics tools have been developed to explore this type of drug resistance, and they have become popular for elucidating drug resistance mechanisms in a low cost, fast and effective way. However, these resources are scattered and underutilized, and their strengths and limitations have not been systematically analyzed and compared. Here, we systematically surveyed 59 freely available bioinformatics tools for exploring target mutation-induced drug resistance. We analyzed and summarized these resources based on their functionality, data volume, data source, operating principle, performance, etc. And we concisely discussed the strengths, limitations and application examples of these tools. Specifically, we tested some predictive tools and offered some thoughts from the clinician's perspective. Hopefully, this work will provide a useful toolbox for researchers working in the biomedical, pesticide, bioinformatics and pharmaceutical engineering fields, and a good platform for non-specialists to quickly understand drug resistance prediction. [ABSTRACT FROM AUTHOR]

Aims Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. Methods and results A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, Δ F / F 0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, Δ F / F 0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 μM], ranolazine (an INa-Late inhibitor, 10 μM), and N -(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. Conclusion Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment. [ABSTRACT FROM AUTHOR]

Background The association of pelvic radiation with pelvic fracture risk has not been examined in prospective cohort settings with comprehensive fracture risk assessment, cancer-free comparison populations, and long-term follow-up. Our objective is to better characterize pelvic fracture and overall mortality risks in postmenopausal women participating in the Women's Health Initiative. Methods A total of 135 743 Women's Health Initiative participants aged 50 to 79 years enrolled from 40 US clinical centers from 1993 to 1998 who had entry Fracture Risk Assessment Tool scores were eligible. Outcomes included pelvic cancer diagnosis, pelvic fracture occurrence, and mortality. Cox proportional hazards regression models were used to examine associations of pelvic cancer and pelvic radiation with pelvic fracture and mortality risk. Results After 17.7 years (median) follow-up, 4451 pelvic cancers, 10 139 pelvic fractures, and 33 040 deaths occurred. In multivariable analyses, women with incident pelvic cancer, compared with women who remained pelvic cancer free, had higher pelvic fracture risk (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43) and higher overall mortality risk (HR = 2.91, 95% CI = 2.77 to 3.05). Women with pelvic cancer treated with pelvic radiation, compared with women with pelvic cancer not treated with pelvic radiation, had higher pelvic fracture risk (HR = 1.98, 95% CI = 1.41 to 2.78) and higher overall mortality after pelvic cancer (HR = 1.32, 95% CI = 1.15 to 1.52). Conclusions Postmenopausal women with pelvic cancer, especially those receiving pelvic radiation, are at higher pelvic fracture risk and higher overall mortality risk. As therapeutic advances have reduced cancer mortality, attention to and interventions for pelvic fracture prevention may be important in pelvic cancer survivors. [ABSTRACT FROM AUTHOR]