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In order to convey bionic image semantics of the intelligent projection TV efficiently and accurately, and improve the matching of users' perceptual cognitive needs with the bionic image of intelligent projection TV. An image coupling bionic design method was proposed. Firstly, the intelligent projection TV target image was obtained by KJ, Semantic difference method (SD) and K-means clustering method. Secondly, the primary, secondary and general target images were distinguished by anallytic hierarchy process(AHP), and the bionic prototype was selected according to the coupling of the primary target images. Thirdly, by means of morphological analysis and AHP, the decline structure of multi-feature coupled images was established and the judgment matrix was constructed. The contribution of coupled image of biological features was obtained. The main features were integrated into the intelligent projection TV styling to form a visual scheme. Finally, the reliability of image coupling styling method was verified by Delphi and fuzzy comprehensive evaluation method. The research process provides a reference for related product innovation design.

Background: China's sports tourism has seen significant growth since the 2008 Olympics, only to be challenged by the coronavirus disease 2019 pandemic. This study aims to assess the impact of the pandemic on China's tourism and sports tourism, which are highly interrelated., Method: Data and materials from 2019 to mid-2023 were systematically collected and analyzed, focusing on seasonal tourism reports published on official local networks in China., Results: The study reveals a prepandemic annual tourism consumption of 6.63 trillion CNY, a 52.1% decline during the pandemic, and a postpandemic rebound exceeding pre-coronavirus disease levels., Conclusion: The pandemic's impact was profound, yet the resilience of China's tourism sector is evident, with a focus on the recovery's implications for sustainable growth. Despite the pandemic's disruption, China's tourism and sports tourism sectors have demonstrated resilience and potential for continued growth, warranting ongoing attention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Animal agriculture is a leading contributor to greenhouse gas emissions and other harmful environmental impacts, which underscores the need to shift away from the consumption of animal-based products. One promising nudge intervention is making plant-based meals the default option, so we tested this approach at six different university events across four academic institutions for effecting sustainable dietary change. Event attendees pre-selected their meal on one of two randomly assigned RSVP forms: one with a plant-based default and one with a meal with meat default. The results from our randomized controlled trial showed that participants had a 43-percentage point greater probability of selecting the plant-based meal when it was indicated as the default option. This effect was similar across events and academic institutions, which indicates that this default intervention is generalizable and can be successfully implemented at university events. The combined effect of using plant-based defaults at these six events was an estimated reduction of 104,387 kg of CO2 emissions, 299.9 m 2 of land use, 959.0 g of nitrogen use, and 259.5 g of phosphorus use, which represent roughly 45-46.2% reductions in harmful environmental impacts relative to the meals chosen when using a meat default. Given the significance and magnitude of these environmental benefits, our results support the widespread implementation of plant-based defaults for helping universities improve their sustainability., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity. We studied WGD evolution in 65 high-grade serous ovarian cancer (HGSOC) tissue samples from 40 patients, yielding 29,481 tumor cell genomes. We found near-ubiquitous evidence of WGD as an ongoing mutational process promoting cell-cell diversity, high rates of chromosomal missegregation, and consequent micronucleation. Using a novel mutation-based WGD timing method, doubleTime , we delineated specific modes by which WGD can drive tumor evolution: (i) unitary evolutionary origin followed by significant diversification, (ii) independent WGD events on a pre-existing background of copy number diversity, and (iii) evolutionarily late clonal expansions of WGD populations. Additionally, through integrated single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signaling and cGAS-STING pathway activation result from ongoing chromosomal instability and are restricted to tumors that remain predominantly diploid. This contrasted with predominantly WGD tumors, which exhibited significant quiescent and immunosuppressive phenotypic states. Together, these findings establish WGD as an evolutionarily 'active' mutational process that promotes evolvability and dysregulated immunity in late stage ovarian cancer.

Introduction: Only 34% of Canadian surgeons in 2022 were female. The protracted length of surgical residency training, concerns regarding infertility, and increased rates of obstetrical complications have been shown to contribute to the disproportionate lack of females in surgical specialties., Methods: A novel online survey was sent to all surgical residents in Canada. Respondents were asked about perceptions of pregnancy and parenthood during surgical training, and parents were asked about parental leave, accommodations they received, and pregnancy complications. Chi squared tests were used to compare opinions of male and female residents., Results: A total of 272/2,419 (11.2%) responses were obtained, with a high response from females (61.8%) and orthopaedic residents (29.0%). There were 56 women reporting 76 pregnancy events during training, 62.5% of which had complications. Notably, 27.3% of men and 86.7% of women 'agreed' or 'strongly agreed' that surgeons have higher pregnancy complication rates than the general population (p<0.001). Men were much less likely to believe that pregnant residents should be offered modified duties (74.2% of men, 90.0% of women, p = 0.003). Women were much more likely to experience significant stigma or bias due to their status as a parent (43% of women, 0% of men, p<0.001). Women reported negative comments from others at a higher rate (58.5% of women, 40.7% of men, p = 0.013). Women believe there is negative stigma attached to being pregnant during training (62.7% of women, 42.7% of men, p = 0.01). The limitations of our study include a small sample size and response bias., Conclusion: Challenges and negative perceptions exist around pregnancy and parenthood in surgical residency, which disproportionately affect women trainees., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Peters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Older adults with COVID-19 have a high prevalence of complications and mortality during hospitalization. Given the large proportion of older adults requiring admission to an intensive care unit (ICU), we aimed to describe the management and outcomes of older adults with COVID-19 requiring ICU care and identify predictors of hospital mortality., Methods: We included consecutive patients ≥ 65 yr of age who were admitted between 11 March 2020 and 30 June 2021 to one of five Toronto (ON, Canada) ICUs with a primary diagnosis of SARS-CoV-2 infection in a retrospective cohort study. Patient characteristics, ICU treatment, and outcomes were recorded. We used multivariable logistic regression to identify predictors of in-hospital mortality., Results: Of the 273 patients, the median [interquartile range] age was 74 [69-80] yr, 104 (38.1%) were female, and 164 (60.1%) required invasive mechanical ventilation. One hundred and forty-two patients (52.0%) survived their hospital stay. Compared with survivors, nonsurvivors were older (74 [70-82] yr vs 73 [68-78] yr; P = 0.03), and a smaller proportion was female (39/131, 29.8% vs 65/142, 45.8%; P = 0.01). Patients had long hospital (19 [11-35] days) and ICU (9 [5-22] days) stays, with no significant differences in ICU length of stay or duration of invasive mechanical ventilation between the two groups. Higher APACHE II score, increasing age, and the need for organ support were independently associated with higher in-hospital mortality while female sex was associated with lower mortality., Conclusions: Older critically ill COVID-19 patients had long ICU and hospital stays, and approximately half died in hospital. Further research is needed to identify individuals who will benefit most from an ICU admission and to evaluate posthospitalization outcomes., (© 2023. Canadian Anesthesiologists' Society.)

Purpose of Review: Aquatic foods are increasingly being recognized as a diverse, bioavailable source of nutrients, highlighting the importance of fisheries and aquaculture for human nutrition. However, studies focusing on the nutrient supply of aquatic foods often differ in the nutrients they examine, potentially biasing their contribution to nutrition security and leading to ineffective policies or management decisions., Recent Findings: We create a decision framework to effectively select nutrients in aquatic food research based on three key domains: human physiological importance, nutritional needs of the target population (demand), and nutrient availability in aquatic foods compared to other accessible dietary sources (supply). We highlight 41 nutrients that are physiologically important, exemplify the importance of aquatic foods relative to other food groups in the food system in terms of concentration per 100 g and apparent consumption, and provide future research pathways that we consider of high importance for aquatic food nutrition. Overall, our study provides a framework to select focal nutrients in aquatic food research and ensures a methodical approach to quantifying the importance of aquatic foods for nutrition security and public health., (© 2023. The Author(s).)

Importance: Cannabis use is increasingly viewed by adolescents as not harmful. Youths with cannabis use disorder (CUD) are recognized by clinicians as being at risk for adverse outcomes, yet little is known about the associations between subclinical cannabis use (ie, nondisordered cannabis use [NDCU]) and adverse psychosocial events., Objective: To describe the prevalence and demographics of NDCU and to compare associations of cannabis use with adverse psychosocial events among adolescents with no cannabis use, NDCU, and CUD., Design, Setting, and Participants: This cross-sectional study used a nationally representative sample derived from the 2015 to 2019 National Survey on Drug Use and Health. Participants were adolescents aged 12 to 17 years, separated into 3 distinct groups: nonuse (no recent cannabis use), NDCU (recent cannabis use below diagnostic threshold), and CUD. Analysis was conducted from January to May 2022., Exposures: CUD, NDCU, or cannabis nonuse. NDCU was defined as endorsing recent cannabis use but not meeting the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) CUD criteria. CUD was defined using DSM-5 criteria., Main Outcomes and Measures: The main outcomes were prevalence of adolescents meeting criteria for NDCU and associations between adverse psychosocial events and NDCU, adjusted for sociodemographic characteristics., Results: The 68 263 respondents (mean [SD] age, 14.5 [1.7] years; 34 773 [50.9%] males) included in the analysis represented an estimated yearly mean of 25 million US adolescents during 2015 to 2019. Among respondents, 1675 adolescents (2.5%) had CUD, 6971 adolescents (10.2%) had NDCU, and 59 617 adolescents (87.3%) reported nonuse. Compared with nonusers, individuals with NDCU had approximately 2 to 4 times greater odds of all adverse psychosocial events examined, including major depression (adjusted odds ratio [aOR], 1.86; 95% CI, 1.67-2.08), suicidal ideation (aOR, 2.08; 95% CI, 1.88-2.29), slower thoughts (aOR, 1.76; 95% CI, 1.58-1.96), difficulty concentrating (aOR, 1.81; 95% CI, 1.65-2.00), truancy (aOR, 1.90; 95% CI, 1.67-2.16), low grade point average (aOR, 1.80; 95% CI, 1.62-2.00), arrest (aOR, 4.15; 95% CI, 3.17-5.43), fighting (aOR, 2.04; 95% CI, 1.80-2.31), and aggression (aOR, 2.16; 95% CI, 1.79-2.62). Prevalence of adverse psychosocial events was greatest for adolescents with CUD (range, 12.6% to 41.9%), followed by NDCU (range, 5.2% to 30.4%), then nonuse (range, 0.8% to 17.3%)., Conclusions and Relevance: In this cross-sectional study of US adolescents, past-year NDCU was approximately 4 times as prevalent as past-year CUD. A stepwise gradient association was observed for odds of adverse psychosocial events between adolescent NDCU and CUD. In the context of US normalization of cannabis use, prospective research into NDCU is necessary.

Objective: To determine which radiographic measures used to define the severity of hip dysplasia are associated with hip joint translation and to investigate relationships between position, body mass index, and joint translation., Materials and Methods: This is a cross-sectional retrospective study evaluating 10 validated radiographic measures of dysplasia on weight-bearing AP pelvis and supine 45-degree bilateral Dunn radiographs of 93 young adults with symptomatic hip dysplasia presenting to a single academic institution between October 2016 and May 2019. We determined the difference between standing and supine measurements for each hip and the correlation of each measure with the patient's body mass index., Results: Femoral head extrusion index was 2.49% lower on supine X-ray (p = 0.0020). Patients with higher body mass index had higher center gap distance (p = 0.0274), femoral head extrusion (p = 0.0170), and femoral head lateralization (p = 0.0028) when standing. They also had higher Tönnis angle (p standing  = 0.0076, p supine  = 0.0121) and lower lateral center-edge angle (p standing  = 0.0196, p supine  = 0.0410) in both positions. The difference in femoral head lateralization between standing and supine positions increased with higher body mass index (p = 0.0081)., Conclusion: Translation of the hip joint with position change is demonstrated by decreased femoral head extrusion index on supine X-ray. Patients with higher body mass index had more dysplastic hips, as measured by five of six radiographic outcomes of dysplasia, and experienced more translation with weight-bearing, reflected by increased femoral head lateralization., (© 2022. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

How cell-to-cell copy number alterations that underpin genomic instability 1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer 2 , remains understudied. Here, by applying scaled single-cell whole-genome sequencing 3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells., (© 2022. The Author(s).)

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability 1-4 patterned by distinct mutational processes 5,6 , tumour heterogeneity 7-9 and intraperitoneal spread 7,8,10 . Immunotherapies have had limited efficacy in HGSOC 11-13 , highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumours harboured inflammatory signalling and ongoing immunoediting, reflected in loss of HLA diversity and tumour infiltration with highly differentiated dysfunctional CD8 + T cells. By contrast, foldback-inversion-bearing tumours exhibited elevated immunosuppressive TGFβ signalling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumours and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research., (© 2022. The Author(s).)

Objective: To investigate the urate-lowering efficacy of febuxostat in peritoneal dialysis (PD) patients with hyperuricemia (HUA) and its relationship with residual renal function. Methods: Patients with HUA who underwent PD in Ningbo First Hospital from January 2018 to October 2021 were enrolled and divided into experimental group and control group according to whether to use febuxostat. The clinical baseline data before treatment and clinical indicators during 1-12 months after treatment were collected in two groups, and the adverse reactions during the use of febuxostat were also recorded. The changes of serum uric acid, standard-reaching rate and residual renal function were compared between the two groups during the follow-up. Results: A total of 105 patients were included in the study. There were 55 patients in the experimental group [27 males and 28 females, with a mean age of (54.5±14.8) years] and 50 patients in the control group [32 males and 18 females, with a mean age of (53.8±15.2) years]. No statistically significant difference was detected in clinical baseline data between the two groups (all P >0.05). The serum uric acid of the experimental group [(479±77), (311±69), (286±61), (307±65), (312±57) μmol/L] and control group [(486±59), (454±71), (453±76), (463±70), (459±76) μmol/L] were lower than baseline values at 1, 3, 6 and 12 months after treatment and the differences of two groups were statistically significant (all P <0.05). The serum uric acid in experimental group was significantly lower than that of control group ( P <0.05). At 1, 3, 6 and 12 months after treatment, the standard-reaching rate of serum uric acid in the experimental group was significantly higher than that of the control group (all P <0.05). The decrease of residual estimated glomerular filtration rate (eGFR) and residual renal urea clearance index (Kt/V) in the experimental group were significantly lower than those in the control group at 12 months after treatment (all P <0.05). During the follow-up, the incidence of adverse reactions in the experimental group was 9.09% (5/55). Conclusions: Febuxostat can effectively treat PD patients with hyperuricemia and has a high safety profile. Moreover, it may delay the loss of residual renal function.

Background: The COVID-19 pandemic has affected older adults disproportionately, and delirium is a concerning consequence; however, the relationship between delirium and corticosteroid use is uncertain. The objective of the present study was to describe patient characteristics, treatments and outcomes among older adults hospitalized with COVID-19, with a focus on dexamethasone use and delirium incidence., Methods: We completed this retrospective cohort study at 7 sites (including acute care, rehabilitation and long-term care settings) in Toronto, Ontario, Canada. We included adults aged 65 years or older, consecutively hospitalized with confirmed SARS-CoV-2 infection, between Mar. 11, 2020, and Apr. 30, 2021. We abstracted patient characteristics and outcomes from charts and analyzed them descriptively. We used a logistic regression model to determine the association between dexamethasone use and delirium incidence., Results: During the study period, 927 patients were admitted to the acute care hospitals with COVID-19. Patients' median age was 79.0 years (interquartile range [IQR] 72.0-87.0), and 417 (45.0%) were female. Most patients were frail (61.9%), based on a Clinical Frailty Scale score of 5 or greater. The prevalence of delirium was 53.6%, and the incidence was 33.1%. Use of restraints was documented in 20.4% of patients. In rehabilitation and long-term care settings ( n = 115), patients' median age was 86.0 years (IQR 78.5-91.0), 72 (62.6%) were female and delirium occurred in 17 patients (14.8%). In patients admitted to acute care during wave 2 of the pandemic (Aug. 1, 2020, to Feb. 20, 2021), dexamethasone use had a nonsignificant association with delirium incidence (adjusted odds ratio 1.38, 95% confidence interval 0.77-2.50). Overall, in-hospital death occurred in 262 (28.4%) patients in acute care settings and 28 (24.3%) patients in rehabilitation or long-term care settings., Interpretation: In-hospital death, delirium and use of restraints were common in older adults admitted to hospital with COVID-19. Further research should be directed to improving the quality of care for this population with known vulnerabilities during continued waves of the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

PRAME is a prominent member of the cancer testis antigen family of proteins, which triggers autologous T cell-mediated immune responses. Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME downmodulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL. In turn, PRC2-regulated genes were repressed in isogenic PRAME-KO lymphoma cell lines, and PRAME was found to directly interact with EZH2 as a negative regulator. EZH2 inhibition with EPZ-6438 abrogated these extrinsic and intrinsic effects, leading to PRAME expression and microenvironment restoration in vivo. Our data highlight multiple functions of PRAME during lymphomagenesis and provide a preclinical rationale for synergistic therapies combining epigenetic reprogramming with PRAME-targeted therapies.

The (co)variance components and corresponding phenotypic and genetic parameters for growth traits and wool traits of economic importance were estimated in the Alpine Merino sheep population maintained at Gansu Provincial Sheep Breeding Technology Extension Station in northwestern China. Data from a maximum of 49,474 animals sired by 526 rams and born from 22,531 ewes over 20 years from 2000 to 2019 were used in this study. Birth type, age of dam, birth year, sex and/or management group, and age at measurement were initially fitted as fixed effects in an animal model with various random effects. Genetic groups were defined for all animals by the sire breed and breed genotype interacted with dam-strain flocks and were fitted as one of the random effects. Analyses were conducted using a residual maximum likelihood procedure (ASReml). Seven different animal models were fitted for all traits, and the most appropriate model with relevant random effects was selected through log-likelihood ratio testing. After identifying the appropriate model through single-trait analysis, bivariate analyses were used to obtain the phenotypic and genetic correlations among the traits. The estimates of additive direct heritability for birth weight (BWT), weaning weight (WWT), preweaning growth rate (prwADG), postweaning growth rate (powADG), yearling body weight (YWT), average fibre diameter (AFD), greasy fleece weight (GFW), clean fleece weight (CFW), yield (YLD), yearling wool staple length (YSL), coefficient of variation of average fibre diameter (FDcv) and wool visual fineness counts (VFC) were 0.30, 0.18, 0.18, 0.20, 0.29, 0.20, 0.19, 0.20, 0.35, 0.19, 0.16 and 0.13, respectively, with standard errors ranging from 0.02 to 0.05. The corresponding ratios of genetic group variance to additive genetic variance were significant and, respectively, 0.35, 0.80, 0.62, 0.26, 0.13, 1.06, 0.38, 0.64, 0.09, 0.12, 0.06 and 0.58. These results suggest for these traits that there is potential to exploit both the additive genetic variation and between genetic group variation although for most traits the between group variation was smaller than the variation within groups. Favourable genetic correlations were found among the growth traits, and between growth traits and fleece production traits, and among wool traits GFW, CFW, YSL and YLD. This study provides the required estimates of genetic parameters of both growth and wool traits of the new breed for the design of more effective breeding programmes., (© 2022 Wiley-VCH GmbH.)

Background: The waves of COVID-19 infections in Ontario, Canada, were marked by differences in patient characteristics and treatment. Our objectives were to (i) describe patient characteristics, treatment, and outcomes of hospitalized older adults with COVID-19 between waves 1, 2, and 3, (ii) determine if there was an improvement in in-hospital mortality in waves 2 and 3 after adjusting for covariates., Methods: This retrospective cohort study was done in five acute care hospitals in Toronto, Ontario. Consecutive hospitalized older adults aged ≥65 years with confirmed COVID-19 infection were included. Wave 1 extended from March 11 to July 31, 2020, wave 2 from August 1, 2020 to February 20, 2021, and wave 3 from February 21 to June 30, 2021. Patient characteristics and outcomes were abstracted from charts. A logistic regression model was used to determine the association between COVID-19 and in-hospital mortality in waves 2 and 3 compared with wave 1., Results: Of the 1671 patients admitted to acute care, 297 (17.8%) were admitted in wave 1, 751 (44.9%) in wave 2, and 623 (37.3%) in wave 3. The median age of our cohort was 77.0 years (interquartile range: 71.0-85.0) and 775 (46.4%) were female. The prevalence of frailty declined in progressive waves. The use of dexamethasone, remdesivir, and tocilizumab was significantly higher in waves 2 and 3 compared with wave 1. In the unadjusted analysis, in-hospital mortality was unchanged between waves 1 and 2, but it was lower in wave 3 (18.3% vs. 27.4% in wave 1). After adjustment, in-hospital mortality was unchanged in waves 2 and 3 compared with wave 1., Conclusion: In-hospital mortality in hospitalized older adults with COVID-19 was similar between waves 1 and 3. Further research should be done to determine if COVID-19 therapies have similar benefits for older adults compared with younger adults., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown., Methods: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model., Results: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004)., Conclusions: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Treatments of ALL predispose survivors to obesity, which increases the risk of cardiovascular disease and diabetes. The hallmark of obesity is excess fat mass, and adiposity is a superior predictor of cardiometabolic risk when compared to Body Mass Index (BMI), yet clinical measures of adiposity in children are lacking. The Tri-Ponderal Mass Index (TMI) (kg/m 3 ) is a more accurate adiposity measure compared to BMI z-score in the general pediatric population. This cross-sectional study aimed to validate TMI as an adiposity measure against DEXA scan-derived adiposity, and to compare it to BMI z-score, in pediatric ALL survivors. This study was a retrospective chart review of pediatric ALL survivors diagnosed between 2004 and 2015 at McMaster Children's Hospital, a tertiary pediatric center in Ontario, Canada. One hundred and thirteen patients (Female n = 55, 48.70%) were included, and adiposity was measured using DEXA scans. Exploratory partial correlations and linear regression analyses were adjusted for age, sex, ethnicity, and ALL risk status. Both TMI and BMI z-score correlated with the DEXA-measured fat mass percentage (FM%) (partial correlation TMI versus FM% r = 0.56; p value < 0.0001; BMI z-score versus FM% r = 0.55; p value < 0.0001). In regression analyses, the association of TMI was not inferior to BMI z-score in assessing adiposity (TMI versus FM% estimated unstandardized B 0.80, 95% CI 0.56, 1.02; p value < 0.0001; BMI z-score versus FM% (unstandardized B 0.37, 95% CI 0.26, 0.49; p value < 0.0001). The TMI is a useful clinical adiposity-specific measure in survivors of pediatric ALL., (© 2022. The Author(s).)

Two new glycosidic acids, evolvulic acids B and C ( 1 and 2 ), along with a known one, evolvulic acid A ( 3 ), were isolated from the glycosidic acid fraction afforded by alkaline hydrolysis of crude resin glycosides from Evolvulus alsinoides whole plants. Their structures were characterized by the spectroscopic data and chemical evidences. Compounds 1 and 2 are both defined as tetrasaccharides, composed of D-fucose, D-glucose, L-rhamnose or D-galactose units. Their aglycones are identified to be a distinctive 3 S ,11 R ,14 R -trihydroxyhexadecanoic acid, which is only discovered from E. alsinoides up to now. The cytotoxic and anti-migration activities of compounds 1-3 were also tested.

Progress in defining genomic fitness landscapes in cancer, especially those defined by copy number alterations (CNAs), has been impeded by lack of time-series single-cell sampling of polyclonal populations and temporal statistical models 1-7 . Here we generated 42,000 genomes from multi-year time-series single-cell whole-genome sequencing of breast epithelium and primary triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), revealing the nature of CNA-defined clonal fitness dynamics induced by TP53 mutation and cisplatin chemotherapy. Using a new Wright-Fisher population genetics model 8,9 to infer clonal fitness, we found that TP53 mutation alters the fitness landscape, reproducibly distributing fitness over a larger number of clones associated with distinct CNAs. Furthermore, in TNBC PDX models with mutated TP53, inferred fitness coefficients from CNA-based genotypes accurately forecast experimentally enforced clonal competition dynamics. Drug treatment in three long-term serially passaged TNBC PDXs resulted in cisplatin-resistant clones emerging from low-fitness phylogenetic lineages in the untreated setting. Conversely, high-fitness clones from treatment-naive controls were eradicated, signalling an inversion of the fitness landscape. Finally, upon release of drug, selection pressure dynamics were reversed, indicating a fitness cost of treatment resistance. Together, our findings define clonal fitness linked to both CNA and therapeutic resistance in polyclonal tumours., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Monocytes are an essential cellular component of the innate immune system that support the host's effectiveness to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations are not fully understood. In this study, we investigated whether the composition of the gastrointestinal microbiota is associated with the recovery of monocyte homeostasis after HCT., Methods: We performed a single-center, prospective, pilot study of 18 recipients of either autologous or allogeneic HCT. Serial blood and stool samples were collected from each patient during their HCT hospitalization. Analysis of the gut microbiota was done using 16S rRNA gene sequencing, and flow cytometric analysis was used to characterize the phenotypic composition of monocyte populations., Results: Dynamic fluctuations in monocyte reconstitution occurred after HCT, and large differences were observed in monocyte frequency among patients over time. Recovery of absolute monocyte counts and subsets showed significant variability across the heterogeneous transplant types and conditioning intensities; no relationship to the microbiota composition was observed in this small cohort., Conclusion: In this pilot study, a relationship between the microbiota composition and monocyte homeostasis could not be firmly established. However, we identify multivariate associations between clinical factors and monocyte reconstitution post-HCT. Our findings encourage further longitudinal surveillance of the intestinal microbiome and its link to immune reconstitution., Competing Interests: Dr. Perales reports honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on DSMBs for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec. He serves in a volunteer capacity as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT) and Be The Match (National Marrow Donor Program, NMDP), as well as on the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee. The other authors declare no conflict of interests., (© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.)

Background: Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic procedure in oncology patients. Transfusing to a minimum preprocedural platelet threshold of 50 × 10 9 /L is widely upheld without good quality evidence. The objective was to compare the outcomes of LPs performed with platelets above and below this threshold. An increased risk of adverse events in patients with lower platelet counts was not expected. As a corollary, transfusion reaction rates incurred by transfusing to this recommended threshold are also reported., Methods: A total of 2259 LPs performed on 1137 oncology patients (adult, n = 871, and pediatric, n = 266) were retrospectively analyzed between February 2011 and December 2017. The incidence of LP-related complications for groups above and below the minimum platelet threshold was compared. Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebral spinal fluid. Groups were compared using the 2-Proportion Z-test and Fisher exact test., Results: At time of LP, the total number of events with platelets less than 50 × 10 9 /L and 50 × 10 9 /L or greater were 110 and 2149, respectively. There were no significant differences in LP-associated complications between patients with platelet counts above or below 50 × 10 9 /L (P = .29). Patients with a pre-LP platelet count of less than 50 × 10 9 /L had a higher proportion of traumatic taps (P < .001). Three patients developed transfusion-related adverse events., Conclusion: Patients with platelet counts less than 50 × 10 9 /L did not have a higher incidence of clinically significant post-lumbar puncture complications (P = .29)., (© 2020 AABB.)

Single-cell technologies have revolutionized biomedical research by enabling scalable measurement of the genome, transcriptome, proteome, and epigenome of multiple systems at single-cell resolution. Now widely applied to cancer models, these assays offer new insights into tumour heterogeneity, which underlies cancer initiation, progression, and relapse. However, the large quantities of high-dimensional, noisy data produced by single-cell assays can complicate data analysis, obscuring biological signals with technical artifacts. In this review article, we outline the major challenges in analyzing single-cell cancer genomics data and survey the current computational tools available to tackle these. We further outline unsolved problems that we consider major opportunities for future methods development to help interpret the vast quantities of data being generated.

Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and 'eat-me' signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation-a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited.

Hodgkin lymphoma is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of noncancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding cross-talk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 Hodgkin lymphoma tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the Hodgkin lymphoma-specific immune microenvironment at single-cell resolution. Single-cell expression profiling identified a novel Hodgkin lymphoma-associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3 + T-cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3 + T cells in the direct vicinity of MHC class II-deficient tumor cells. Our findings provide novel insights into TME biology and suggest new approaches to immune-checkpoint targeting in Hodgkin lymphoma. SIGNIFICANCE: We provide detailed functional and spatial characteristics of immune cells in classic Hodgkin lymphoma at single-cell resolution. Specifically, we identified a regulatory T-cell-like immunosuppressive subset of LAG3 + T cells contributing to the immune-escape phenotype. Our insights aid in the development of novel biomarkers and combination treatment strategies targeting immune checkpoints. See related commentary by Fisher and Oh, p. 342 . This article is highlighted in the In This Issue feature, p. 327 ., (©2019 American Association for Cancer Research.)

For the past several decades, only a few studies were conducted on the change in immature rice liposomes during seed development. To evaluate and compare the lipid material of different degrees of developing rice grains, this paper focused on fresh rice seeds from only one most popular species of Dasan divided into five growth periods. The lipid components of fresh rice, especially γ-oryzanol and fatty acids equipped with extremely beneficial phytonutrients, were investigated. The results illustrated that the level of extracted liposome increased gradually along with the development of rice and in the third stage of development, the level of liposome achieved maximum. And then, instead of increasing, it was decreased at later stages of development. Moreover, the antioxidant activity of fresh edible rice (FER) was also evaluated by DPPH and ABTS assay. It was shown that FER has the higher antioxidant activity than the ripened rice seed on lipids, which will improve FER using on the functional foods and help provide certainly theoretical basis in food processing industry., (© 2020 Institute of Food Technologists®.)

Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumor tissues and patient-derived mouse xenografts for scRNA-seq are not well understood., Results: We use low temperature (6 °C) protease and collagenase (37 °C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNA-seq dataset comprising 155,165 cells from patient cancer tissues, patient-derived breast cancer xenografts, and cancer cell lines. We observe substantial variation in standard quality control metrics of cell viability across conditions and tissues. From the contrast between tissue protease dissociation at 37 °C or 6 °C, we observe that collagenase digestion results in a stress response. We derive a core gene set of 512 heat shock and stress response genes, including FOS and JUN, induced by collagenase (37 °C), which are minimized by dissociation with a cold active protease (6 °C). While induction of these genes was highly conserved across all cell types, cell type-specific responses to collagenase digestion were observed in patient tissues., Conclusions: The method and conditions of tumor dissociation influence cell yield and transcriptome state and are both tissue- and cell-type dependent. Interpretation of stress pathway expression differences in cancer single-cell studies, including components of surface immune recognition such as MHC class I, may be especially confounded. We define a core set of 512 genes that can assist with the identification of such effects in dissociated scRNA-seq experiments.

Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches require purified or pre-annotated data and both are prone to batch effects. To overcome these issues, we present CellAssign, a probabilistic model that leverages prior knowledge of cell-type marker genes to annotate single-cell RNA sequencing data into predefined or de novo cell types. CellAssign automates the process of assigning cells in a highly scalable manner across large datasets while controlling for batch and sample effects. We demonstrate the advantages of CellAssign through extensive simulations and analysis of tumor microenvironment composition in high-grade serous ovarian cancer and follicular lymphoma.

Regulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype ("stemness") on the immunological properties of cancer has not been systematically explored. Using gene-expression-based metrics, we evaluated the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers. We found pervasive negative associations between cancer stemness and anticancer immunity. This occurred despite high stemness cancers exhibiting increased mutation load, cancer-testis antigen expression, and intratumoral heterogeneity. Stemness was also strongly associated with cell-intrinsic suppression of endogenous retroviruses and type I IFN signaling, and increased expression of multiple therapeutically accessible immunosuppressive pathways. Thus, stemness is not only a fundamental process in cancer progression but may provide a mechanistic link between antigenicity, intratumoral heterogeneity, and immune suppression across cancers., Competing Interests: The authors declare no conflict of interest.

Mutation signatures in cancer genomes reflect endogenous and exogenous mutational processes, offering insights into tumour etiology, features for prognostic and biologic stratification and vulnerabilities to be exploited therapeutically. We present a novel machine learning formalism for improved signature inference, based on multi-modal correlated topic models (MMCTM) which can at once infer signatures from both single nucleotide and structural variation counts derived from cancer genome sequencing data. We exemplify the utility of our approach on two hormone driven, DNA repair deficient cancers: breast and ovary (n = 755 samples total). We show how introducing correlated structure both within and between modes of mutation can increase accuracy of signature discovery, particularly in the context of sparse data. Our study emphasizes the importance of integrating multiple mutation modes for signature discovery and patient stratification, and provides a statistical modeling framework to incorporate additional features of interest for future studies., Competing Interests: SPS and SA are shareholders and consultants of Contextual Genomics Inc.

Cathepsin S plays an important role in the pathogenesis of several cardiovascular diseases; however, the relationship between serum cathepsin S and cerebral infarction (CI) is still unknown. This study aimed to investigate the relationship between acute phase serum cathepsin S level and cerebral infarction. A total of 202 stroke patients were enrolled into this study, and were divided into cerebral infarction (n = 140) group and non-cerebral infarction group (non-CI, n = 62). Fifty healthy individuals were recruited as the control group. Serum levels of cathepsin S and cystatin C were measured at days 1, 7, and 14 posthospitalization. Compared to the non-CI group, the CI group had significantly higher rates of hypertension, dyslipidemia, and smoking (all P < 0.05). The CI group had significantly higher cathepsin S levels and cathepsin S to cystatin C ratio (CatS/CysC) at both days 1 and 7 posthospitalization (both P < 0.05). Multivariate logistic regression analysis demonstrated that cathepsin S level (day 7) and CatS/CysC (days 1 and 7) were the associated factors with CI (all P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the Area Under Curve (AUC) value of CatS-day7, CatS/CysC-day1, and CatS/CysC-day7 were 0.726 (95% CI: 0.652-0.800, P < 0.001), 0.641 (95% CI: 0.559-0.723, P = 0.001), and 0.721 (95% CI: 0.645-0.797, P = 0.039), respectively. Cathepsin S and CatS/CysC were associated with acute CI, and may have the potential to be the diagnostic biomarkers for CI. Our findings help to better understand the role of serum cathepsin S level in CI., (© 2019 The Authors. Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Huntington's disease is a late onset neurological disorder caused by a trinucleotide CAG repeat expansion mutation in the HTT gene encoding for the protein huntingtin. Despite considerable ongoing research, the wild-type function of huntingtin is not yet fully understood., Objective: To improve knowledge of HTT gene regulation at the transcriptional level and inform future studies aimed at uncovering the HTT gene's normal function., Methods: The HTT gene region was functionally characterized through an in silico analysis using publicly available data sets. ChIP-seq data sets and the online STRING database were used to identify putative transcription factor binding sites (TFBSs) and protein-protein interactions within the HTT promoter region. siRNA-mediated knockdown and ChIP-qPCR of STAT1, a TF identified from the in silico analysis, were used to validate the bioinformatics screen., Results: 16 regions containing potential regulatory genomic markers were identified. TFBSs for 59 transcription factors (TFs) were detected in one or more of the 16 candidate regions. Using these TFs, 15 clusters of protein-protein interactions were identified using STRING. siRNA-mediated knockdown of STAT1 resulted in an increase in HTT expression, and ChIP-qPCR detected enrichment of STAT1 binding at one of the predicted regions. These assays confirmed the utility of the bioinformatic analysis., Conclusions: Putative regulatory regions outside of the immediate HTT promoter region have been identified with specific protein-protein interactions. Future work will focus on in vitro and in vivo studies to examine the effect of modulating identified TFBSs and altering the levels of specific TFs of interest in regulating HTT gene expression.

Hybridization is a key molecular process in biology and biotechnology, but so far there is no predictive model for accurately determining hybridization rate constants based on sequence information. Here, we report a weighted neighbour voting (WNV) prediction algorithm, in which the hybridization rate constant of an unknown sequence is predicted based on similarity reactions with known rate constants. To construct this algorithm we first performed 210 fluorescence kinetics experiments to observe the hybridization kinetics of 100 different DNA target and probe pairs (36 nt sub-sequences of the CYCS and VEGF genes) at temperatures ranging from 28 to 55 °C. Automated feature selection and weighting optimization resulted in a final six-feature WNV model, which can predict hybridization rate constants of new sequences to within a factor of 3 with ∼91% accuracy, based on leave-one-out cross-validation. Accurate prediction of hybridization kinetics allows the design of efficient probe sequences for genomics research.

Background: This research aims to investigate the prospective molecular mechanism of miR-375 in Medullary Thyroid Cancer (MTC)., Material and Methods: The expression level of miR-375 in MTC was explored with microarray data from Gene Expression Omnibus (GEO). To gather the putative target genes of miR-375, we selected eligible datasets in GEO, in which antagomir-375 and premir-375 were transfected to provide the miR-375-related genes. Subsequently, we attained the intersection of the results of GEO microarray data and 12 online target genes prediction database as the prospective target genes. Furthermore, we conducted in silico analysis including gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways annotations and Protein-Protein Interactions (PPI) analysis to provide an overview of the function of miR-375 in MTC. Finally, data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) were used for a validation., Results: Up-regulation could be confirmed with the data from GSE40807. GEO dataset GSE67742 provided 10,596 miR-375-related genes, while 12 online prediction databases showed that 3352 target genes appeared no less than four times. Finally, the intersection of the two groups of genes included 1132 prospective targets. In aspect of functional annotation, negative regulation of transcription from RNA polymerase II promoter (P=9.83E-06), golgi membrane (P=9.98E-05) and pathway of protein binding (P=3.63E-07) were highlighted as the most enriched terms with GO analysis. With regards to PPI network, 162 hub genes that interacted with no less than 10 other different genes was visualized, among which PI3K/Akt signaling pathway was the most enriched pathway as assessed by KEGG. Furthermore, two genes (JAK2 and NGFR) in PI3K/Akt signaling pathway showed down-regulated patterns in both mRNA and protein levels., Conclusion: The higher expression level of miR-375 might play a pivotal role in the tumorigenesis of MTC via targeting multiple key pathways, especially PI3K/Akt pathway. However, the exact molecular mechanism of miR-375 needs to be verified with in-depth investigation in the future., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective: To investigate the expression and the subcellular localization of HDAC9 in different brain regions of mice after cerebral ischemic injury and explore the association between HDAC9 and ischemic stroke., Methods: Twenty-one male C57BL/6 mice were randomly divided into sham-operated group (n=9) and operated group (n=12). In the latter group, the mice with Zea-Longa neurological deficit scores of 2 or 3 following middle cerebral artery occlusion (MCAO) were assigned into MCAO group (n=9). Immunofluorescence was performed to investigate the subcellular localization of HDAC9 in the brain tissues on day 3 after MCAO. Western blotting and qRT-PCR were used to analyze the expression of HDAC9 in different regions of the brain. Results Immunofluorescence showed more intense HDAC9 expressions in the brain tissues around the infarct focus, and in the cells surrounding the infarct, HDAC9 expression was obviously increased in the cytoplasm and reduced in the cell nuclei. Compared with the other brain regions, the ipsilesional cortex with MCAO showed more abundant HDAC9 expressions at both the mRNA and protein levels (P<0.05)., Conclusion: HDAC9 may be closely related to cerebral ischemic injury and participate in the pathophysiological process of ischemic stroke.

We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.

Student creation of educational materials has the capacity both to enhance learning and to decrease costs. Three successive honors-style classes of undergraduate students in a cancer genetics class worked with a new software system, CuboCube, to create an e-textbook. CuboCube is an open-source learning materials creation system designed to facilitate e-textbook development, with an ultimate goal of improving the social learning experience for students. Equipped with crowdsourcing capabilities, CuboCube provides intuitive tools for nontechnical and technical authors alike to create content together in a structured manner. The process of e-textbook development revealed both strengths and challenges of the approach, which can inform future efforts. Both the CuboCube platform and the Cancer Genetics E-textbook are freely available to the community.

Gold nanocages (GNCs) are a promising material that not only converts near infrared (NIR) light to heat for the ablation of tumors but also acts as a radiosensitizer. The combination of hyperthermia and radiotherapy has a synergistic effect that can lead to significant tumor cell necrosis. In the current study, we synthesized GNCs that offered the combined effects of hyperthermia and radiotherapy. This combination strategy resulted in increased tumor cell apoptosis and significant tumor tissue necrosis. We propose that GNCs can be used for clinical treatment and to potentially overcome resistance to radiotherapy by clearly increasing the antitumor effect.

We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers.

Objective: To investigate the clinical and radiologic features of patients with spontaneous cerebral arterial dissections (CADs) presenting with ischemic stroke and to explore the effect of gender and age on those features., Methods: Patients admitted to our stroke center diagnosed as ischemic stroke secondary to CADs from August 2008 to April 2015 were prospectively registered. Patients aged between 15 to 80 years old, who had acute brain infarcts within the territory of a major cerebral artery affected by a dissection confirmed by the neuroradiological examinations, were enrolled in the study. The followings were the exclusion criteria: (1) there were any potential causes for the brain infarcts other than CADs; (2) CADs were the results of a definite cause; (3) the clinical data were incomplete., Results: A total of 118 patients were enrolled in the study with the mean age of (44.2±12.8) years old. There were 87 men (73.7%) and 67 patients (56.8%) aged under 45 years old. Smoking (41.5%), hypertension (25.4%) and hypercholesterolemia (21.2%) were the three leading risk factors for stroke. Hypercholesterolemia was more common in the male patients (25.3% vs 9.7%, P=0.021), whereas hypertension (39.2% vs 14.9%, P=0.005) and diabetes (25.5% vs 4.5%, P=0.002) were more common in the patients aged 45 years or older. Headache or neck pain before or at the onset of stroke was more common in the female patients (67.7% vs 34.5%, P=0.002). A total of 71 patients were found with CADs of the anterior circulation, while 47 patients with that of the posterior circulation. The involvement of the intra and extracranial arteries were documented in 59 and 59 patients, respectively. The middle cerebral artery (MCA) was the most common site in the intracranial dissection and more MCA dissections were observed in the male patients (46.3% vs 11.1%, P=0.016). The dissection of intracranial carotid artery was more common in patients aged under 45 years old (38.7% vs 0, P<0.001). Lumen status of CADs often presented as stenosis (43.2%) and occlusion (41.2%), while less aneurysm (5.9%) and aneurysm with stenosis (9.3%) were observed. Aneurysm was found to be more common in patients aged 45 years or older (11.8% vs 1.5%, P=0.042)., Conclusion: Chinese patients with spontaneous CADs presenting with ischemic stroke have unique clinical and imaging features, which correlated with age and gender.