Lower Survival Research Articles

Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.

Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.

Immunotherapies for Childhood Cancer.

Children are surviving cancer in greater numbers than ever. Over the last 50 years, substantial advancements in pediatric cancer treatment have resulted in an 85% 5-year survival rate. Nonetheless, a notable 10%-15% of patients encounter relapse or develop refractory disease, leading to significantly lower survival. Recent attempts to further intensify cytotoxic chemotherapy have failed due to either severe toxicities or ineffectiveness, highlighting the need for new treatment strategies. Immunotherapies are emerging and expanding their clinical application to a wide array of cancers, including those affecting children. In pediatric cancers, monoclonal antibodies targeting GD2 have demonstrated durable radiographic and histologic responses in neuroblastoma (NB), and CD19-targeted bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T cells have likewise changed the outlook for refractory acute lymphoblastic leukemia (ALL) in children. This review discusses the clinical development of immunotherapies for pediatric cancers, focusing on pediatric ALL and NB, two major pediatric cancers transformed by immunotherapy, updates on the recent advancements in immunotherapies, and further discusses the future directions of immunotherapy for pediatric cancers.

Time to recovery and predictors among admitted preterm neonates in the neonatal intensive care units of public hospitals of Addis Ababa, Ethiopia, 2021

IntroductionEthiopia implemented measures to reduce preterm mortality, and much is currently being done to avoid preterm death, yet preterm death remains the top cause of infant death. As a result, evaluating median time of recovery and determinants will provide information to planners and policymakers to design strategies to improve preterm survival.MethodsHospital-based retrospective follow-up study was conducted in four selected public hospitals of Addis Ababa from September 2018 to August 2021. Data were collected using a pretested structured questionnaire. Epi-data 4.6 and STATA Version 16 were used for data entry and analysis. Kaplan-Meier survival curve, log-rank test, and median time were computed. To find predictors of time to recovery, a multivariable Cox proportional hazards regression model was fitted, and variables with a p-value less than 0.05 were considered statistically significant.ResultsA total of 466 preterm babies were included in the study of which 261 (56.1%) preterm neonates survived and were discharged from NICUs. The median time to recovery was 10 days (95% CI: 9–12). Low birth weight (Adjusted hazard-ratio [AHR]: 1.91, 95% CI: 1.2–3.06), normal birth weight (AHR: 2.09, 95% CI: 1.16–3.76), late preterm (AHR: 1.91, 95% CI: 1.02–3.55), no hospital-acquired infection (AHR: 2.19, 95% CI: 1.36–3.5), no thrombocytopenia (AHR: 1.96, 95% CI: 1.27–3.02), continuous positive airway pressure (AHR: 0.66, 95% CI: 0.48–0.91), and kangaroo mother care (AHR: 2.04, 95% CI: 1.48–2.81) were found to be independent predictors of time to recovery of preterm babies.Discussion/ConclusionThe recovery rate was found relatively low. Several predictors of preterm recovery time were discovered in the study. The majority of predictors were preventable or treatable. Therefore, emphasis should be given towards prevention and early anticipation, and management of these predictors. Studies to assess the quality of care and cause of low survival rate of preterm infants are recommended.

Racial and ethnic disparities in access to total neoadjuvant therapy for rectal cancer

BackgroundTotal neoadjuvant therapy has revolutionized the treatment of locally advanced rectal cancer and quickly become the new standard of care. Whether patients from all racial and ethnic groups have had equal access to these potential benefits, however, remains unknown. MethodsWe identified all adults diagnosed with locally advanced rectal cancer in California who underwent neoadjuvant chemotherapy and radiation from 2010 to 2020 using the California Cancer Registry. We used logistic regression to estimate the predicted probability of receiving total neoadjuvant therapy as opposed to traditional chemoradiotherapy for each racial and ethnic group and used a time–race interaction to evaluate trends in access to total neoadjuvant therapy over time. We also compared survival by racial and ethnic group and total neoadjuvant therapy status using Kaplan-Meier plots and Cox proportional hazards models. ResultsIn total, 6,856 patients met inclusion criteria. Overall, 36.6% of patients received total neoadjuvant therapy in 2010 compared with 66.3% in 2020. Latino patients were significantly less likely than non-Latino White patients to undergo total neoadjuvant therapy ; however, there was no difference in the rate of growth in total neoadjuvant therapy over time between racial and ethnic groups. Non-Latino Black patients appeared to have lower risk-adjusted survival compared with non-Latino White patients, although not among patients who underwent total neoadjuvant therapy . ConclusionAccess to total neoadjuvant therapy has increased significantly over time in California with no apparent difference in the rate of growth between racial and ethnic groups. We found no evidence of racial or ethnic disparities in survival among patients treated with total neoadjuvant therapy, suggesting that increasing access to high-quality cancer care may also improve health equity.

The associations between the Geriatric Nutritional Risk Index and all-cause, cancer-specific, and cardiovascular mortality in the U.S. population: a large-scale pooled survey

BackgroundPrevious studies have reported a close association between the Geriatric Nutritional Risk Index (GNRI) and various conditions. However, the association between the GNRI and mortality remains unclear. To examine the correlation between the GNRI and all-cause, cancer-specific, and cardiovascular mortality, this study was performed.MethodsWe analyzed elderly participants in the National Health and Nutrition Examination Survey from 2005 to 2016. The GNRI was calculated using body mass index and serum albumin. Kaplan-Meier survival curves were drawn to compare the survival probability between the normal and decreased GNRI groups. Weighted multivariate Cox regression and restricted cubic spline (RCS) models were employed to determine the linear and non-linear associations of the GNRI with all-cause, cancer-specific, and cardiovascular mortality.ResultsA total of 3,276 participants were included in the analysis. The Kaplan-Meier survival curve showed that the decreased GNRI group had a lower survival probability for all-cause mortality and cancer-specific mortality (P < 0.001) but not for cardiovascular mortality (P > 0.05). In the full regression models, the decreased group had a higher risk of all-cause mortality (HR = 1.67, 95% CI = 1.21–2.30, P = 0.002), and cancer-specific mortality (HR = 2.20, 95% CI = 1.32–3.67, P = 0.003) than the normal group. For cardiovascular mortality, no significant association with GNRI (HR = 1.39, 95% CI = 0.60–3.22, P = 0.436) was detected. Notably, the RCS analysis identified a linear downward trend between the GNRI and all-cause, alongside cancer-specific mortalities (all P for overall < 0.05). The time-dependent Receiver Operating Characteristic (ROC) analysis unveiled the predictive power of the GNRI for 5-year all-cause mortality, cancer mortality, and cardiovascular mortality was 0.754, 0.757, and 0.836, respectively, after adjusting for covariates.ConclusionsIndividuals with a decreased GNRI had increased risks of all-cause, and cancer-specific mortality. There were linear associations of the GNRI with all-cause, and cancer-specific mortality. Nutritional status should be carefully monitored, which may improve the overall prognosis for the general population.

Spinosad blocks CHRNA5 mediated EGFR signaling pathway activation to inhibit lung adenocarcinoma proliferation

Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide, with high incidence and low survival rates. Nicotinic acetylcholine receptors play an important role in the progression of LUAD. In this study, a screening of 17 nicotinic acetylcholine receptor allosteric agents revealed that spinosad effectively suppressed the proliferation of LUAD cells. The experiments demonstrated that spinosad induced cell cycle arrest in the G1 phase and stimulated apoptosis, thereby impeding the growth of LUAD and enhancing the responsiveness to gefitinib in vitro and vivo. Mechanistic insights obtained through transcriptome sequencing, Co-IP, and protein immunoblots indicated that spinosad disrupted the interaction between CHRNA5 and EGFR, thereby inhibiting the formation of downstream complexes and activation of the EGFR signaling pathway. The supplementation of exogenous acetylcholine showed to mitigate the inhibition of LUAD cell proliferation induced by spinosad. This study elucidates the therapeutic effects and mechanisms of spinosad in LUAD, and offers a theoretical and experimental foundation for novel LUAD treatments.

In Vivo Mouse Models for Adult Brain Tumors: Exploring Tumorigenesis and Advancing Immunotherapy Development.

Brain tumors, particularly glioblastoma (GBM), are devastating and challenging to treat, with a low 5-year survival rate of only 6.6%. Mouse models are established to understand tumorigenesis and develop new therapeutic strategies. Large-scale genomic studies have facilitated the identification of genetic alterations driving human brain tumor development and progression. Genetically engineered mouse models (GEMMs) with clinically relevant genetic alterations are widely used to investigate tumor origin. Additionally, syngeneic implantation models, utilizing cell lines derived from GEMMs or other sources, are popular for their consistent and relatively short latency period, addressing various brain cancer research questions. In recent years, the success of immunotherapy in specific cancer types has led to a surge in cancer immunology-related research which specifically necessitates the utilization of immunocompetent mouse models. In this review, we provide a comprehensive summary of GEMMs and syngeneic mouse models for adult brain tumors, emphasizing key features such as model origin, genetic alteration background, oncogenic mechanisms, and immune-related characteristics. Our review serves as a valuable resource for the brain tumor research community, aiding in the selection of appropriate models to study cancer immunology.

Characterization and integrated analysis of extrachromosomal DNA amplification in hematological malignancies

The study of extrachromosomal DNA (ecDNA), an element existing beyond classical chromosomes, contributes to creating a more comprehensive map of the cancer genome. In hematological malignancies, research on ecDNA has lacked comprehensive investigation into its frequency, structure, function, and mechanisms of formation. We re-analyzed WGS data from 208 hematological cancer samples across 11 types, focusing on ecDNA characteristics. Amplification of ecDNA was observed in 7 of these cancer types, with no instances found in normal blood cells. Patients with leukemia carrying ecDNA showed a low induction therapy remission rate (<30 %), a high relapse rate (75 %) among those who achieved complete remission, and a significantly lower survival rate compared to the general leukemia population, even those with complex chromosomal karyotypes. Among the 55 identified ecDNA amplicons, 268 genes were detected, of which 38 are known cancer-related genes exhibiting significantly increased copy numbers. By integrating RNA-Seq data, we discovered that the increased copy number, resulting in a higher amount of available DNA templates, indeed leads to the elevated expression of genes encoded on ecDNA. Additionally, through the integration of H3K4me3/H3K27ac chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin with sequencing, and high-throughput chromosome conformation capture data, we identified that ecDNA amplifications can also facilitate efficient, copy number-independent amplification of oncogenes. This process is linked to active histone modifications, improved chromatin accessibility, and enhancer hijacking, all of which are effects of ecDNA amplification. Mechanistically, chromothripsis and dysfunction of the DNA repair pathway can, to some extent, explain the origin of ecDNA.

Towards automatic forecasting of lung nodule diameter with tabular data and CT imaging

Objective:This study aims to forecast the progression of lung cancer by estimating the future diameter of lung nodules. Methods:This approach uses as input the tabular data, axial images from tomography scans, and both data types, employing a ResNet50 model for image feature extraction and direct analysis of patient information for tabular data. The data are processed through a neural network before prediction. In the training phase, class weights are assigned based on the rarity of different types of nodules within the dataset, in alignment with nodule management guidelines. Results:Tabular data alone yielded the most accurate results, with a mean absolute deviation of 0.99 mm. For malignant nodules, the best performance, marked by a deviation of 2.82 mm, was achieved using tabular data applying Lung-RADS class weights during training. The tabular data results highlight the influence of using the initial nodule size as an input feature. These results surpass the literature reference of 348-day volume doubling time for malignant nodules. Conclusion:The developed predictive model is optimized for integration into a clinical workflow after detecting, segmenting, and classifying nodules. It provides accurate growth forecasts, establishing a more objective basis for determining follow-up intervals. Significance:With lung cancer’s low survival rates, the capacity for precise nodule growth prediction represents a significant breakthrough. This methodology promises to revolutionize patient care and management, enhancing the chances for early risk assessment and effective intervention.

Merkel cell carcinoma with adrenal metastasis: a clinical case

Merkel cell carcinoma is a rare primary malignant skin tumor with epithelial and neuroendocrine differentiation, which is usually characterized by an aggressive course with frequent local recurrence and a high metastatic potential. This article presents a clinical case of diagnosing Merkel cell carcinoma with secondary lesions of the adrenal glands, which is a rare localization of distant metastasis of this tumor with a low survival prognosis. Merkel cell carcinoma is difficult to diagnose due to its rare occurrence and can be mistaken for another dermatological disease. The patient's medical history was analyzed, starting from the outpatient stage of medical care until hospitalization for diagnostic surgery. The article is valuable for doctors of any specialty due to the difficulties in differential diagnosis of adrenal incidentalomas.

The absolute lactate levels versus clearance for prognostication of post-cardiotomy patients on veno-arterial ECMO.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving procedure for supporting patients with cardiogenic shock after cardiac surgery. This work aimed to analyse the impact of changes in blood lactate levels on the survival of patients on post-cardiotomy ECMO (PC-ECMO) and whether lactate clearance (LC) performs better than absolute lactate levels. We retrospectively analysed the data of adult patients who received PC-ECMO at our centre between 2016 and 2022. The primary outcome was the in-hospital mortality rate. Arterial lactate levels were measured at ECMO initiation, peak and 12 and 24h after VA-ECMO support. LC was calculated at 12 and 24h. Out of 2368 patients who received cardiac surgeries, 152 (median age, 48years; 57.9% of them were men) received PC-ECMO. Of them, 48 (31.6%) survived and were discharged, while 104 (68.4%) died during the index hospitalization. Non-survivors had higher frequencies of atrial fibrillation (41.35% vs. 12.5%, P<0.001), chronic kidney disease (26.9% vs. 6.3%, P=0.004), prolonged cardiopulmonary bypass (237 vs. 192min, P=0.016) and aortic cross-clamping times (160 vs. 124min, P=0.04) than survivors. Non-survivors had a significantly higher median Sequential Organ Failure Assessment (SOFA) score at ECMO initiation (13.5 vs. 9, P<0.001) and a lower median Survival After Veno-arterial ECMO (SAVE) score (-3 vs. 3, P<0.001) with higher SAVE classes (P<0.001) than survivors. After 12h of VA-ECMO support, the blood lactate level was negatively correlated with LC in survivors (r=-0.755, P<0.001) and non-survivors (r=-0.601, P<0.001). After 24h, the same negative correlation was identified between survivors (r=-0.764, P<0.001) and non-survivors (r=-0.847, P<0.001). Blood lactate levels measured at 12h to determine hospital mortality [>8.2mmol/L, area under the receiver operating characteristic curve (AUROC): 0.868] and 24h (>2.6mmol/L, AUROC: 0.896) had the best performance, followed by LC-T12 (<21.94%, AUROC: 0.807), LC-T24 (<40.3%, AUROC: 0.839) and peak blood lactate (>14.35mmol/L, AUROC: 0.828). The initial pre-ECMO blood lactate (>6.25mmol/L, AUROC: 0.731) had an acceptable ability to discriminate mortality but was less than the following measurements and clearance. Kaplan-Meier curves demonstrated that LC of <21.94% at T12h and <40.3% at T24h was associated with decreased survival (log-rank P<0.001). Cox proportional hazards regression analysis for mortality revealed that LC of <21.94% at T12h had an adjusted hazard ratio (HR) of 2.73 [95% confidence interval (CI): 1.64-5.762, P<0.001] and LC of <40.3% at T24h had an adjusted HR of 1.98 (95% CI: 1.46-4.173, P<0.001). The predictors of hospital mortality after PC-ECMO were the lactate level at 12h [odds ratio (OR): 1.67, 95% CI: 1.121-2.181, P=0.001], initial SOFA score (OR: 1.593, 95% CI: 1.15-2.73, P<0.001), initial blood lactate (OR: 1.21, 95% CI: 1.016-1.721, P=0.032) and atrial fibrillation (OR: 6.17, 95% CI: 2.37-57.214, P=0.003). Bivariate models using lactate levels and clearance at the same points revealed that blood lactate levels performed better than the clearance percentage. Serial measurements of arterial blood lactate and LC help in obtaining early prognostic guidance in adult patients supported by VA-ECMO after cardiac surgery. Absolute lactate levels, compared with LC at the same time points, demonstrated better performance in differentiating mortality.

A disulfidptosis-related lncRNAs cluster to forecast the prognosis and immune landscapes of ovarian cancer

ObjectiveDisulfidptosis is a newly recognized form of regulated cell death that has been linked to cancer progression and prognosis. Despite this association, the prognostic significance, immunological characteristics and treatment response of disulfidptosis-related lncRNAs (DRLs) in ovarian cancer have not yet been elucidated.MethodsThe lncRNA data and clinical information for ovarian cancer and normal samples were obtained from the UCSC XENA. Differential expression analysis and Pearson analysis were utilized to identify core DRLs, followed by LASSO algorithm. Random Survival Forest was used to construct a prognostic model. The relationships between risk scores, RNA methylation, immune cell infiltration, mutation, responses to immunotherapy and drug sensitivity analysis were further examined. Additionally, qRT-PCR experiments were conducted to validate the expression of the core DRLs in human ovarian cancer cells and normal ovarian cells and the scRNA-seq data of the core DRLs were obtained from the GEO dataset, available in the TISCH database.ResultsA total of 8 core DRLs were obtained to construct a prognostic model for ovarian cancer, categorizing all patients into low-risk and high-risk groups using an optimal cutoff value. The AUC values for 1-year, 3-year and 5-year OS in the TCGA cohort were 0.785, 0.810 and 0.863 respectively, proving a strong predictive capability of the model. The model revealed the high-risk group patients exhibited lower overall survival rates, higher TIDE scores and lower TMB levels compared to the low-risk group. Variations in immune cell infiltration and responses to therapeutic drugs were observed between the high-risk and low-risk groups. Besides, our study verified the correlations between the DRLs and RNA methylation. Additionally, qRT-PCR experiments and single-cell RNA sequencing data analysis were conducted to confirm the significance of the core DRLs at both cellular and scRNA-seq levels.ConclusionWe constructed a reliable and novel prognostic model with a DRLs cluster for ovarian cancer, providing a foundation for further researches in the management of this disease.

Osmotic priming-induced cryotolerance uncovers rejuvenation of grapevine cell cultures: morphogenetic changes and gene expression pattern highlighting enhanced embryogenic potential.

Cryopreservation is a reliable technique for the long-term storage and preservation of embryogenic cells, maintaining their viability without loss of their embryogenic capacity. However, the large-scale conservation of grapevine embryogenic lines in cryobanks remains limited. A significant challenge is understanding somatic cell rejuvenation. Here, we investigate the encapsulation/dehydration and encapsulation/vitrification for cryopreserving embryogenic material. Cell rejuvenation and enhanced embryogenic competence were observed after cryopreservation, as evidenced through structural cellular changes observed by histology and electron scanning microscopy. Results showed that cryopreserved samples of 110-Richter, Riesling, and Tempranillo using encapsulation/dehydration had better survival rates, averaging 81%, 62%, and 48%, respectively, while encapsulation/vitrification yielded lower survival rates, averaging 58%, 42%, and 32%, respectively. Cryopreservation also improved post-thaw recovery and regeneration efficiency assessed through regrowth of proembryogenic masses and somatic embryo conversion reaching 54-72% against 11-17% in control samples. Cryopreservation triggered changes in gene expression patterns and exhibited considerable increase at genotype-specific basis of 1.5- to 4.5-fold in SERK1, BBM, and WOX associated to embryogenic competence as well as in ChitIV and LEA involved in stress response. Membrane stability index, hydrogen peroxide, and proline contents were used as indicators of oxidative stress uncovering a key role of an osmotic trans-priming effect leading to cryotolerance. Our finding highlighted that cryopreservation enhances embryogenic capacity in senescent callus and probably acts as a screening process allowing safe maintenance of proembryogenic cells and promoting their recovery. This study provides a high throughput innovation to set up cryolines for cell rejuvenation of grapevine and other important plant species.

Gene signatures of copper metabolism related genes may predict prognosis and immunity status in Ewing’s sarcoma

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

Gene signatures of copper metabolism related genes may predict prognosis and immunity status in Ewing’s sarcoma

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

Integrating otolith and genetic tools to reveal intraspecific biodiversity in a highly impacted salmon population.

Intraspecific biodiversity is vital for species persistence in an increasingly volatile world. By embracing methods that integrate information at different spatiotemporal scales, we can directly monitor and reconstruct changes in intraspecific biodiversity. Here we combined genetics and otolith biochronologies to describe the genotypic and phenotypic diversity of Chinook salmon (Oncorhynchus tshawytscha) in the Yuba River, California, comparing cohorts that experienced a range of hydroclimatic conditions. Yuba River salmon have been heavily impacted by habitat loss and degradation, and large influxes of unmarked hatchery fish each year have led to concern about introgression and uncertainty around the viability of its wild populations, particularly the rarer spring-run salmon. Otolith strontium isotopes showed that Yuba River origin fish represented, on average, 42% (range 7%-73%) of spawners across six return years (2009-2011, 2018-2020), with large interannual variability. The remainder of adult Chinook salmon in the river were primarily strays from the nearby Feather River hatchery, and since 2018 from the Mokelumne River hatchery. Among the Yuba-origin spawners, on average, 30% (range 14%-50%) exhibited the spring-run genotype. The Yuba-origin fish also displayed a variety of outmigration phenotypes that differed in the timing and size at which they left the Yuba river. Early-migrating fry dominated the returns (mean 59%, range 33%-89%), and their contribution rates were negatively correlated with freshwater flows. It is unlikely that fry survival rates are elevated during droughts, suggesting that this trend reflects disproportionately low survival of larger later migrating parr, smolts, and yearlings along the migratory corridor in drier years. Otolith daily increments indicated generally faster growth rates in non-natal habitats, emphasizing the importance of continuing upstream restoration efforts to improve in-river growing conditions. Together, these findings show that, despite a long history of habitat degradation and hatchery introgression, the Yuba River maintains intraspecific biodiversity that should be taken into account in future management, restoration, and reintroduction plans. The finding that genotypic spring-run are reproducing, surviving, and returning to the Yuba River every year suggests that re-establishment of an independent population is possible, although hatchery-wild interactions would need to be carefully considered. Integrating methods is critical to monitor changes in key genetic, physiological, and behavioral traits to assess population viability and resilience.

Integrating otolith and genetic tools to reveal intraspecific biodiversity in a highly impacted salmon population.

Intraspecific biodiversity is vital for species persistence in an increasingly volatile world. By embracing methods that integrate information at different spatiotemporal scales, we can directly monitor and reconstruct changes in intraspecific biodiversity. Here we combined genetics and otolith biochronologies to describe the genotypic and phenotypic diversity of Chinook salmon (Oncorhynchus tshawytscha) in the Yuba River, California, comparing cohorts that experienced a range of hydroclimatic conditions. Yuba River salmon have been heavily impacted by habitat loss and degradation, and large influxes of unmarked hatchery fish each year have led to concern about introgression and uncertainty around the viability of its wild populations, particularly the rarer spring-run salmon. Otolith strontium isotopes showed that Yuba River origin fish represented, on average, 42% (range 7%-73%) of spawners across six return years (2009-2011, 2018-2020), with large interannual variability. The remainder of adult Chinook salmon in the river were primarily strays from the nearby Feather River hatchery, and since 2018 from the Mokelumne River hatchery. Among the Yuba-origin spawners, on average, 30% (range 14%-50%) exhibited the spring-run genotype. The Yuba-origin fish also displayed a variety of outmigration phenotypes that differed in the timing and size at which they left the Yuba river. Early-migrating fry dominated the returns (mean 59%, range 33%-89%), and their contribution rates were negatively correlated with freshwater flows. It is unlikely that fry survival rates are elevated during droughts, suggesting that this trend reflects disproportionately low survival of larger later migrating parr, smolts, and yearlings along the migratory corridor in drier years. Otolith daily increments indicated generally faster growth rates in non-natal habitats, emphasizing the importance of continuing upstream restoration efforts to improve in-river growing conditions. Together, these findings show that, despite a long history of habitat degradation and hatchery introgression, the Yuba River maintains intraspecific biodiversity that should be taken into account in future management, restoration, and reintroduction plans. The finding that genotypic spring-run are reproducing, surviving, and returning to the Yuba River every year suggests that re-establishment of an independent population is possible, although hatchery-wild interactions would need to be carefully considered. Integrating methods is critical to monitor changes in key genetic, physiological, and behavioral traits to assess population viability and resilience.

ENTPD1 (CD39) and NT5E (CD73) expression in human medulloblastoma: an in silico analysis.

Medulloblastoma is the most common malignant tumor in the pediatric population. Its classification has incorporated key molecular variations alongside histological characterization. CD39 (also known as ENTPD1) and CD73 (also known as NT5E), enzymes of the purinergic signaling pathway, act in synergy to generate extracellular adenosine, creating an immunosuppressive tumor microenvironment. Our study examined the expression of mRNA of these genes in previously described transcriptome data sets of medulloblastoma patient samples from the Cavalli Cohort (n = 763). Survival distribution was estimated according to the Kaplan-Meier method using a median cut-off and log-rank statistics (p ≤ 0.05). In non-WNT and non-SHH medulloblastoma Group 4 (n = 264), the high expression of ENTPD1 and NT5E was significantly related to a lower overall survival (p = 2.7e-04; p = 2.6e-03). In the SHH-activated group (n = 172), the high expression of ENTPD1 was significantly related to lower overall survival (p = 7.8e-03), while the high expression of NT5E was significantly related to greater overall survival (p = 0.017). In the WNT group (n = 63), the expressions of ENTPD1 and NT5E were not significantly correlated with overall survival (p = 0.212; p = 0.101). In non-WNT and non-SHH medulloblastoma Group 3 (n = 113), the high expression of ENTPD1 was significantly related to greater survival (p = 0.034), while expression of NT5E was not significantly related to survival of patients (p = 0.124). This in silico analysis indicates that ENTPD1 (CD39) and NT5E (CD73) can be seen as potential prognostic markers and therapeutic targets for primary medulloblastomas in non-WNT and non-SHH Group 4.

Induction of out‐of‐season spawning in an intensively reared walleye (Sander vitreus) broodstock

AbstractThe commercial viability of walleye (Sander vitreus) as an aquaculture species requires that walleye gametes are available year‐round so that multiple cohorts of walleye can be brought to market throughout the year. This study aimed to apply photothermal manipulations to three groups of walleye broodstock to induce out‐of‐season spawning and obtain a year‐round supply of fertilized walleye eggs. We manipulated photothermal regimes for three groups of broodstock to induce spawning in February (early), April (in‐season), and July (late‐season). In autumn, water temperatures were chilled to 8°C in all treatments. The duration of the chill period varied for each treatment with the early, in‐season, and late treatments remaining chilled for 6, 18, and 30 weeks, respectively, before being warmed to induce spawning. Fecundity was significantly lower for late‐season broodstock. Egg size and gonadosomatic index were significantly smaller in the early‐season treatment. Fertilization success was similar for early and in‐season treatments but was 0% for eggs from the late‐season treatment. Larval survival was significantly lower for walleye from early‐season broodstock. Our results suggest that early out‐of‐season spawning for walleye is possible but comes with tradeoffs of smaller egg size and lower larval survival.

Induction of out‐of‐season spawning in an intensively reared walleye (Sander vitreus) broodstock

AbstractThe commercial viability of walleye (Sander vitreus) as an aquaculture species requires that walleye gametes are available year‐round so that multiple cohorts of walleye can be brought to market throughout the year. This study aimed to apply photothermal manipulations to three groups of walleye broodstock to induce out‐of‐season spawning and obtain a year‐round supply of fertilized walleye eggs. We manipulated photothermal regimes for three groups of broodstock to induce spawning in February (early), April (in‐season), and July (late‐season). In autumn, water temperatures were chilled to 8°C in all treatments. The duration of the chill period varied for each treatment with the early, in‐season, and late treatments remaining chilled for 6, 18, and 30 weeks, respectively, before being warmed to induce spawning. Fecundity was significantly lower for late‐season broodstock. Egg size and gonadosomatic index were significantly smaller in the early‐season treatment. Fertilization success was similar for early and in‐season treatments but was 0% for eggs from the late‐season treatment. Larval survival was significantly lower for walleye from early‐season broodstock. Our results suggest that early out‐of‐season spawning for walleye is possible but comes with tradeoffs of smaller egg size and lower larval survival.