Individual Survival Research Articles

A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.

Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM. A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation. In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells. PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.

Patterns of herbicide resistance in Raphanus raphanistrum revealed by comprehensive testing and statistical analysis.

Raphanus raphanistrum causes $40 million total revenue losses annually in Western Australia partly due to its historically-documented ability to evolve herbicide resistance to multiple modes of action. In this study, 376 field-sampled populations of R. raphanistrum were tested for resistance to 21 herbicides applied at the recommended label rate. Eight treatments were herbicide mixtures with two, three or four modes of action. A total of 7199 individual resistance tests were conducted across 4 years by screening approximately 104 000 individual seeds and seedlings. The mean survival of individuals within a population for all standalone herbicides was 9%, whereas survival was significantly decreased to 3.5% with a herbicide mixture. Some herbicides such as triasulfuron (herbicide Group 2), 2,4-D (Group 4) or diflufenican (Group 12) were highly impacted by resistance, with frequencies of resistant populations being > 50%. Conversely, there was negligible resistance to glyphosate (Group 9) or protoporphyrinogen oxidase (PPO) inhibitors (tiafenacil, saflufenacil + trifludimoxazin, fomesafen: Group 14), and pre-emergence herbicides (i.e., atrazine or mesotrione: Groups 5 and 27, respectively) remained largely effective. Binary, ternary or quaternary mixtures of Groups 4, 6, 12 and 27 herbicides reduced the frequency of high-level resistant populations to 7.1%, 3.8% or 0%, respectively. The cost-effective control of R. raphanistrum remains a challenge due to herbicide resistance. Raphanus raphanistrum management relies heavily on herbicide uses not yet compromised by resistance, such as pre-emergence herbicides (atrazine, fomesafen, mesotrione), glyphosate, and mixtures of two, three or four modes of action including bromoxynil, diflufenican, MCPA, picolinafen, pyrasulfotole and topramezone. Strategies that integrate effective herbicide use patterns, novel modes of action and efficiently-mechanized non-chemical weed control options (i.e., seed destructors) can completely constrain the selection of herbicide resistance in this highly adaptable species. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Uncertain safety: uncovering the religious racial socialization process among Muslim American families during the 2016 election

ABSTRACT Racial socialization refers to the process through which children come to understand their own and others' racial identities, roles, and positions in various contexts, and how race will function in their lives. Although research on the racialization of Islam is growing, the socialization of racialized religious identities is less understood. This article draws on two years of ethnographic and interview data collected among Muslim American families whose children were enrolled in Islamic private schools in suburban Metro Detroit during the 2016 presidential election season. Within this political milieu, second-generation Muslim American parents engaged in what I term religious racial socialization. I show how the process of protecting children from the harms of Islamophobia meant practicing both cultural socialization and preparation for bias with the aid of Islamic schools and mosques. Yet, because the process is incapable of completely buffering against Islamophobia, parents' strategies highlight the tension of individual survival strategies within the context of existing religious-racial hierarchies, offering Muslim American children uncertain safety. The findings from this study contribute to family studies by showing how for some religiously minoritized populations, the processes of racial, religious, and political socialization are not only inextricably linked but are also co-constitutive and mutually reinforcing.

Does the Combination of Metabolic Syndrome and Low Fat-Free Mass Shorten an Individual's Disability-Free Life? A 12-Year Prospective Cohort Study of the Korean Genome and Epidemiology Study (KoGES).

This study aims to explore the combined risk of metabolic syndrome (MetS) and low fat-free mass (FFM) on an individual's disability-free survival (DFS). Disability is defined as a composite of dementia, physical disability, and mortality. Using data from the Korean Genome and Epidemiology Study, we divided 3721 participants aged 40-69 years based on their MetS status and FFM index (FFMI) score. Kaplan-Meier survival analysis and Cox regression were used to analyze differences in DFS between the four groups. From 108 events, MetS group had significantly shorter DFS than the non-MetS group regardless of FFMI (p<0.0001). After adjusting other potential confounding variables, the MetS group had a higher risk of shortened DFS regardless of FFMI, and the MetS group with low FFMI had a 2.06-fold increased risk compared to the non-MetS group with high FFMI (p<0.001). Older age and lower income were also associated with higher risk of shorter DFS (p<0.001). The combination of MetS and low FFMI contribute to a cumulative risk of shortened DFS. Community nurses can perform MetS screening and body composition assessment to predict and control the risk of developing disability over time.

Collective anti-predator escape manoeuvres through optimal attack and avoidance strategies

The collective dynamics of self-organised systems emerge from the decision rules agents use to respond to each other and to external forces. This is evident in groups of animals under attack from predators, where understanding collective escape patterns requires evaluating the risks and rewards associated with particular social rules, prey escape behaviour, and predator attack strategies. Here, we find that the emergence of the ‘fountain effect’, a common collective pattern observed when animal groups evade predators, is the outcome of rules designed to maximise individual survival chances given predator hunting decisions. Using drone-based empirical observations of schooling sardine prey (Sardinops sagax caerulea) attacked by striped marlin (Kajikia audax), we first find the majority of attacks produce fountain effects, with the dynamics of these escapes dependent on the predator’s attack direction. Then, using a spatially-explicit agent-based model of predator-prey dynamics, we show that fountain manoeuvres can emerge from combining an optimal individual prey escape angle with social interactions. The escape rule appears to prioritise maximising the distance to the predator and creates conflict in the effectiveness of predators’ attacks and the prey’s avoidance, explaining the empirically observed predators’ attack strategies and the fountain evasions produced by prey. Overall, we identify the proximate and ultimate explanations for fountain effects and more generally highlight that the collective patterns of self-organised predatory-prey systems can be understood by considering both social escape rules and attack strategies.

Heat domes increase vulnerability of native stingless bees by simultaneously weakening key survival traits

Heatwave events increase in frequency and duration, yet there is a strong gap in assessing their nonlethal effects on tropical insects, including beneficial social species. The stingless bees are a highly diverse group of pantropical pollinators that provide key ecosystem services. Here, we simultaneously analyzed for the first time the effect of sublethal heat stress (HS) during immature (pupal) development on adult morphology (size, shape, symmetry) and immune response of the three castes/sexes in stingless bee colonies: workers, unmated queens (gynes) and males, as well as its impact on the onset of foraging and lifespan in workers. Individuals experimentally heat stressed during development had smaller body size and reduced symmetry as adults compared with control, non-heat stressed (NHS) individuals, though the strength of the effects of HS also varied between castes and sexes. Notably, males were more prone to the effects of HS compared with workers, and less so gynes; HS reduced the immune response of males, though not that of workers or queens. Workers had significantly earlier onset of foraging and a shorter lifespan when exposed as immatures to HS. Under a worst-case scenario, knock-on negative impacts on individual survival caused by HS could compromise colony fitness. In the long-term, heatwaves may also have repercussions for the persistence of stingless bee species, the sustainability of key ancestral activities like meliponiculture and ecosystem services. Measures to ameliorate the effect of climatic warming are urgently needed to protect these pollinators, which represent an iconic world heritage.

Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing.

CDKN2A/B deletions are prognostically relevant in low- and high-grade gliomas. Data on this is derived from heterogeneous series, an accurate estimation of survival risk from homozygous CDKN2A/B deletion is missing. Besides genetic testing, p16-immunohistochemistry (IHC) as a less cost intensive means for indirect detection of CDKN2A/B alterations is possible but not validated in larger datasets. The present meta-analysis aimed to (1) reconstruct individual patient data (IPD) and estimate overall survival (OS) stratified by CDKN2A/B status from all literature and to (2) determine accuracy of p16 testing for CDKNA2/B detection from published studies. For survival analysis according to CDKN2A/B status 460 records were screened, four articles with 714 participants were included. In IDH-wildtype (IDH-wt) gliomas, 57.07% harbored the deletion compared to 9.76% in IDH-mutant (IDH-mut) gliomas. Median OS of patients with IDH-wt gliomas and homozygous CDKN2A/B deletion was 13.0 months compared to 18.0 months with non-deleted CDKN2A/B (p = 0.014, Log-Rank). With homozygous deletion of CDKN2A/B the risk of death was increased by 1.5 (95%-CI 1.1-2.1). Median OS in patients with IDH-mut gliomas without CDKN2A/B deletion was 92.0 months compared to 40.0 months with CDKN2A/B deletion (p < 0.001, Log-Rank). CDKN2A/B deletions were associated with a significantly shorter OS (HR = 3.2; 95%-CI 2.2-5.5). For p16 IHC analysis, 10 eligible studies with 1087 examined samples were included. The cut-off for retention differed between the studies. In 588/662 p16 retained cases CDKN2A/B deletions was not detected, implying a negative predictive value (NPV) of p16 staining of 88.8%. Conversely, 279/425 p16 absent cases showed a CDKN2A/B deletion resulting in a positive predictive value (PPV) of 65.6%. Sensitivity of p16 staining for CDKN2A/B detection was 79.0%, specificity 80.1%. Highest diagnostic accuracy of p16 IHC was reached with a cut-off of > 5% and within IDH-mut glioma.

Individual survival prediction model for patients with leptomeningeal metastasis.

Survival prediction for patients with leptomeningeal metastasis (LM) is crucial for making proper management plans and counseling patients. Prognostic models in this patient domain have been limited, and existing models often include predictors that are not available in resource-limited settings. Our aim was to develop a practical, individualized survival prediction model for patients diagnosed with LM. We collected a retrospective cohort of patients diagnosed with LM from cerebrospinal fluid at Chiang Mai University Hospital from January 2015 to July 2021. Nine candidate predictors included male gender, age>60years, presence of extracranial involvement, types of primary cancer, the time between primary cancer and LM diagnosis, presence of cerebral symptoms, cranial symptoms, spinal symptoms, and abnormal CSF profiles. Flexible parametric survival analysis was used to develop the survival prognostic model for predicting survival at 3, 6, and 12months after diagnosis. The model was evaluated for discrimination and calibration. 161 patients with 133 events were included. The derived individual survival prediction model for patients with LM, or the LMsurv model, consists of three final predictors: types of primary cancer, presence of cerebral symptoms, and presence of spinal symptoms. The model showed acceptable discrimination (Harrell's C-statistics: 0.72; 95% confidence interval 0.68-0.76) and was well calibrated at 3, 6, and 12months. The LMsurv model, incorporating three practical predictors, demonstrated acceptable discrimination and calibration for predicting survival in LM patients. This model could serve as an assisting tool during clinical decision-making. External validation is suggested to confirm the generalizability of the model.

Long-term patterns of forearm asymmetry in females of three syntopic bat species and its effects on individual fitness

Fluctuating asymmetry, the non-directional deviation from bilateral symmetry resulting from developmental instability, can indicate early-life environmental stress. While fluctuating asymmetry can affect individual survival and reproductive success, its effect on fitness differs between species. Here, we analyzed up to 27 years of mark-recapture data from 894 RFID tagged individuals of three forest-living bat species in southern Germany to investigate the degree of fluctuating asymmetry in forearm length. In Bechstein’s bats, Myotis bechsteinii, the species with the highest sample size, we furthermore investigated if fluctuating asymmetry has become more frequent over the study period, a time when juvenile bats have grown larger forearms in response to warmer summers. We also investigated whether fluctuating asymmetry affects individual lifespan and lifetime reproductive success in female Myotis bechsteinii. The degree of fluctuating asymmetry clearly exceeding the measurement error estimated on recaptured individuals was similar in all three species (1.8%). In female Myotis bechsteinii, the frequency of fluctuating asymmetry did not increase over the course of the study and even strong asymmetry had no effect on individual reproductive success and life expectancy. Our data suggest that fluctuating asymmetry is a poor predictor of fitness in the female Myotis bechsteinii studied, and is so far unaffected by the warming environment which is leading to larger individuals in our study population.

Impact of Microtopography and Neighborhood Effects on Individual Survival Across Life History Stages.

Understanding drivers of plant community assembly and individual survival in forest ecosystems is crucial for effective conservation and management. While macro-scale factors influencing vegetation patterns are well documented, the combined impact of microtopographic variations and neighborhood effects at neighborhood scales, particularly in subtropical forests, requires further study. To contribute to this area of research, we established a 9.6 ha dynamic plot in a subtropical evergreen broad-leaved forest to examine the interplay between microtopographic factors and neighborhood effects on individual plant survival across different life stages. We conducted a comprehensive analysis of microtopographic variables and neighborhood effects, with individual plant survival censused through repeated surveys at 5-year intervals. Mixed-effects models were employed to assess the combined influence of these factors across life stages. Our results reveal that both microtopographic factors and neighborhood effects significantly influence plant survival, with their impacts varying across life stages. Water availability, represented by flow direction, emerged as a consistently critical factor throughout all life stages. Elevation and the topographic position index showed significant positive effects on survival, particularly in later life stages, possibly reflecting adaptations to light acquisition and water drainage. The influence of topographic factors intensified with succession, while the impact of neighborhood effects, particularly asymmetric competition and conspecific negative density dependence, changed as plants matured. This study enhances our understanding of forest community assembly, emphasizing the importance of considering abiotic and biotic factors across multiple scales for effective forest conservation and management. It provides insights into mechanisms driving spatial variation in community composition, crucial for preserving biodiversity in heterogeneous forest landscapes.

Analysis of the Psychosocial and Cognitive Effects of Stigma on Bipolar Disorder-A Literature Review

Abstract: Beyond the distress of the disorder, individuals with bipolar disorder also endure long-term stigma. Stigma reflects attitudes towards specific groups without objective evaluation. Certain groups are perceived as unable to meet societal norms due to their limitations. It stems from misconceptions and fear, leading to discrimination, exclusion, and deep shame. Stigma has long posed a significant barrier to the survival and recovery of individuals with mental disorders, including bipolar disorder. Therefore, addressing and reducing the stigma these patients face should be a key focus of our research. Stigma further marginalizes individuals with bipolar disorder, delaying care, damaging relationships, and eventually lowering quality of life. Modern society should adopt a more supportive attitude and work to improve bipolar disorder treatment outcomes. The key approach is eliminating misunderstandings, promoting awareness, and building an inclusive society with the necessary resources. Above all, the most important thing is to correct people's long-held misconceptions about bipolar disorder.

Prognostic Value of Left Ventricular Myocardial Strain Parameters Derived from Cardiac Magnetic Resonance Feature Tracking Technique in Light-Chain Cardiac Amyloidosis Patients: A Pilot Study.

Previous research on the prognostic implications of left ventricular myocardial strain using cardiac magnetic resonance feature tracking (CMR-FT) in light-chain cardiac amyloidosis (AL-CA) has shown promising potential. This study aimed to evaluate the prognostic significance of global and segmental left ventricular myocardial strain in AL-CA patients, specifically analyzing the American Heart Association's 16 segments. A total of 75 consecutive patients (50 men, mean age: 55.6 ± 10.0 years) who underwent CMR examination with histologically confirmed systemic AL-CA were retrospectively enrolled between January 2014 and November 2022. Both global and segmental myocardial strain and the American Heart Association's 16 segments were quantified using CMR-FT on the steady-state free precession (SSFP) cine sequence. A comparative analysis was conducted between survivors and non-survivors based on the defined endpoint. Student t-test or Mann-Whitney U, receiver operating characteristic curve, Kaplan-Meier event-free survival curve, and Cox proportional hazards regression were used. Significance was set at p < 0.05. Following a median follow-up of 34 months, 16 out of 75 patients experienced mortality events. B-type natriuretic peptides (BNP) (p < 0.001), global radial strain (RSglobal) (p = 0.033), and RS in the basal inferior segment (RSbas-inferior) (p = 0.025) remained significant as independent predictors of all-cause mortality. The cut-off values were identified as 24.97% for RSglobal, and 20.97% for RSbas-inferior. Kaplan-Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RSglobal and RSbas-inferior (p = 0.013, p < 0.001, respectively). Radial strain for the global and the basal inferior segment may prove valuable for risk stratification in patients with AL-CA.

Older age but not comorbidity is associated with worse survival in patients with hepatocellular carcinoma

Age and comorbidity are key factors in assessing patient prognosis and informing stopping rules for cancer screening eligibility, but their impact has not been rigorously evaluated in patients with hepatocellular carcinoma (HCC). We conducted a retrospective cohort study of patients diagnosed with HCC at two health systems between January 2010 and February 2023. We used multivariable logistic regression and Cox proportional hazards models to evaluate the associations between older age (≥65 years) and comorbidity burden (Charlson Comorbidity Index) with early-stage presentation, curative treatment receipt, and overall survival. We performed subgroup analyses in patients with early-stage HCC. We identified 2002 patients with HCC (median age 61 years, 76% male, 21% early-stage), with a median survival of 15.7 months. In adjusted analyses, curative treatment receipt was associated with higher comorbidity but not older age. Conversely, overall survival was significantly associated with older age (HR 1.25, 95%CI 1.06 - 1.47) but not high comorbidity (HR 0.92, 95%CI 0.77 - 1.09). Older age continued to be associated with worse survival among patients with early-stage HCC (HR 1.99, 95%CI 1.45 - 2.73) and those who underwent curative treatment (HR 1.52, 95%CI 1.10 - 2.10). Median survival for younger vs. older individuals was 20 vs 14 months overall, 65 vs 49 months for patients with early-stage HCC, and 113 vs. 60 months for those with curative treatment. Older age but not comorbidity burden is associated with worse survival in patients with early-stage HCC. Further studies are needed to define the role of comorbidity in HCC prognostication.

Development and validation of a clinical prediction tool to estimate survival in community-dwelling adults living with dementia: a protocol

IntroductionA clinical prediction tool to estimate life expectancy in community-dwelling individuals living with dementia could inform healthcare decision-making and prompt future planning. An existing Ontario-based tool for community-dwelling elderly individuals does not perform well in people living with dementia specifically. This study seeks to develop and validate a clinical prediction tool to estimate survival in community-dwelling individuals living with dementia receiving home care in Ontario, Canada.Methods and analysisThis will be a population-level retrospective cohort study that will use data in linked healthcare administrative databases at ICES. Specifically, data that are routinely collected from regularly administered assessments for home care will be used. Community-dwelling individuals living with dementia receiving home care at any point between April 2010 and March 2020 will be included (N≈200 000). The model will be developed in the derivation cohort (N≈140 000), which includes individuals with a randomly selected home care assessment between 2010 and 2017. The outcome variable will be survival time from index assessment. The selection of predictor variables will be fully prespecified and literature/expert-informed. The model will be estimated using a Cox proportional hazards model. The model’s performance will be assessed in a temporally distinct validation cohort (N≈60 000), which includes individuals with an assessment between 2018 and 2020. Overall performance will be assessed using Nagelkerke’s R2, discrimination using the concordance statistic and calibration using the calibration curve. Overfitting will be assessed visually and statistically. Model performance will be assessed in the validation cohort and in prespecified subgroups.Ethics and disseminationThe study received research ethics board approval from the Sunnybrook Health Sciences Centre (SUN-6138). Abstracts of the project will be submitted to academic conferences, and a manuscript thereof will be submitted to a peer-reviewed journal for publication. The model will be disseminated on a publicly accessible website (www.projectbiglife.com).Trial registration numberNCT06266325(clinicaltrials.gov).

Establishment and Validation of a Prognostic Nomogram for Predicting Postoperative Overall Survival in Advanced Stage III-IV Colorectal Cancer Patients.

Most colorectal cancer (CRC) patients are at an advanced stage when they are first diagnosed. Risk factors for predicting overall survival (OS) in advanced stage CRC patients are crucial, and constructing a prognostic nomogram model is a scientific method for survival analysis. A total of 2956 advanced stage CRC patients were randomised into training and validation groups at a 7:3 ratio. Univariate and multivariate Cox proportional hazards regression analyses were used to screen risk factors for OS and subsequently construct a prognostic nomogram model for predicting 1-, 3-, 5-, 8- and 10-year OS of advanced stage CRC patients. The performance of the model was demonstrated by the area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Kaplan-Meier curves were used to plot the survival probabilities for different strata of each risk factor. There was no statistically significant difference (p > 0.05) in the 32 clinical variables between patients in the training and validation groups. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that age, location, TNM, chemotherapy, liver metastasis, lung metastasis, MSH6, CEA, CA199, CA125 and CA724 were risk factors for OS. We estimated the AUC values for the nomogram model to predict 1-, 3-, 5-, 8- and 10-year OS, which in the training group were 0.826 (95% CI: 0.807-0.845), 0.836 (0.819-0.853), 0.839 (0.820-0.859), 0.835 (0.809-0.862) and 0.825 (0.779-0.870) respectively; in the validation group, the corresponding AUC values were 0.819 (0.786-0.852), 0.831 (0.804-0.858), 0.830 (0.799-0.861), 0.815 (0.774-0.857) and 0.802 (0.723-0.882) respectively. Finally, the 1-, 3-, 5-, 8- and 10-year OS rates for advanced stage CRC patients were 73.4 (71.8-75.0), 49.5 (47.8-51.4), 43.3 (41.5-45.2), 40.1 (38.1-41.9) and 38.6 (36.6-40.8) respectively. We constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.

Is reinforcement a viable conservation strategy for the endangered perennial herb, Astragalus applegatei?

Reinforcing imperiled plant populations with transplanted individuals is a conservation tool that is increasingly used to counter the negative effects of land use change and habitat fragmentation. A reinforcement project's success is dependent on the survival of planted individuals and the support of the extant population's growth; thus, demographic comparisons of planted and extant individuals within the same population are critical to quantify success. We assessed long‐term demographic data from planted (9 years) and extant (7 years) individuals of a rare perennial herb, Astragalus applegatei, to quantify the success of a reinforcement project. We compared cumulative survival among extant and planted cohorts and constructed generalized mixed‐effect models to understand how age affected survival, flowering, and plant size of both planted and extant individuals. Overall, 9.7% of planted individuals survived after 9–11 years. Although young planted individuals had higher flowering percentages than extant individuals, our models for survival, flowering, and plant size were similar in planted and extant individuals as they aged. Cumulative survival curves among planted cohorts varied while they were similar among extant cohorts. Furthermore, there was evidence of recruitment by planted individuals, an essential benchmark of successful translocation projects. Combined, these results suggest that reinforcement can be a successful conservation tool for A. applegatei under the right conditions and may be used to inform conservation strategies for other imperiled herbaceous perennials.

Longitudinal and time-to-event modeling for the survival of advanced pancreatic ductal adenocarcinoma patients.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers especially at advanced stage. In order to analyze the dynamics of potential prognostic biomarkers and further quantify their relationships with the overall survival (OS) of advanced PDAC patients, we herein developed a parametric time-to-event (TTE) model integrated with longitudinal submodels. Data from 104 patients receiving standard chemotherapies were retrospectively collected for model development, and other 54 patients were enrolled as external validation. The longitudinal submodels were developed with the time-course data of sum of longest diameters (SLD) of tumors, serum albumin (ALB) and body weight (BW) using nonlinear mixed effect models. The model-derived metrics including model parameters and individual predictions at different time points were further analyzed in the TTE model, together with other baseline information of patients. A linear growth-exponential shrinkage model was employed to describe the dynamics of SLD, while logistic models were used to fit the relationship of time prior to death with ALB and BW. The TTE model estimated the ALB and BW changes at the 9th week after chemotherapies as well as the baseline CA19-9 level that showed most significant impact on the OS, and the model-based simulations could provide individual survival rate predictions for patients with different prognostic factors. This study quantitatively demonstrates the importance of physical status and baseline disease for the OS of advanced PDAC patients, and highlights that timely nutrition support would be helpful to improve the prognosis.

Depletion of m6A-RNA in Escherichia coli reduces the infectious potential of T5 bacteriophage.

The importance of RNA modifications has been thoroughly studied in the context of eukaryotic viral infections. However, their role in bacterial hosts during phage infections is largely unexplored. Our research delves into this gap by investigating the effect of host N6-methyladenosine (m6A)-RNA modifications during phage infection. We found that an Escherichia coli mutant depleted of m6A-RNA is less susceptible to T5 infection than the wild type. This finding emphasizes the need to further investigate how RNA modifications affect the fine-tuned regulation of individual bacterial survival in the presence of phages to ensure population survival.

Decoding the Methylation Patterns of ABC Transporters in Colorectal Cancer

Colorectal cancer (CRC) is a significant global health concern, posing a major threat to morbidity and mortality rates. The molecular mechanisms that drive CRC, particularly the DNA methylation patterns in ATP-binding cassette (ABC) genes, have attracted considerable attention because of their potential roles in CRC drug resistance, initiation, and progression. This study aimed to investigate the methylation patterns of ABC genes in CRC using a high-throughput microarray technology. Microarray methylation data from CRC and adjacent normal tissues were subjected to preprocessing, differential methylation analysis, and correlation analysis using the MethSurv tool for a detailed study of methylation patterns. The study revealed global hypomethylation of 43 ABC transporters and two pseudogenes in CRC compared to normal tissues. Receiver operating characteristic curve analysis identified 369 CpG sites as potential biomarkers for CRC diagnosis, with area under the curve values ranging from acceptable to outstanding. Survival analysis demonstrated the correlation between DNA methylation of individual CpG sites and patient survival probability in colon and rectal adenocarcinoma datasets from The Cancer Genome Atlas. The study provides insights into the epigenetic landscape of ABC genes in CRC, highlighting their potential roles in drug resistance, disease initiation, and progression. The findings offer opportunities for developing innovative therapeutic approaches and improving patient outcomes in the fight against CRC. Further research is needed to validate these results and investigate the functional implications of ABC gene methylation in CRC pathogenesis and treatment response.

Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.

Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour. This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers. Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location. Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.