Differential mechanism between Listeria monocytogenes strains with different virulence contaminating ready-to-eat sausages during the simulated gastrointestinal tract.

Listeria monocytogenes exhibits varying levels of pathogenicity when entering the host through contaminated food. However, little is known regarding the stress response and environmental tolerance mechanism of different virulence strains to host gastrointestinal (GI) stimuli. This study analyzed the differences in the survival and genes of stress responses among two strains of L. monocytogenes 10403S (serotype 1/2a, highly virulent strain) and M7 (serotype 4a, low-virulence strain) during simulated gastrointestinal digestion. The results indicated that L. monocytogenes 10403S showed greater acid and bile salt tolerance than L. monocytogenes M7, with higher survival rates and less cell deformation and cell membrane permeability during the in vitro digestion. KEGG analysis of the transcriptomes indicated that L. monocytogenes 10403S displayed significant activity in amino acid metabolism, such as glutamate and arginine, associated with acid tolerance. Additionally, L. monocytogenes 10403S demonstrated a higher efficacy in promoting activities that preserve bacterial cell membrane integrity and facilitate flagellar protein synthesis. These findings will contribute valuable practical insights into the tolerance distinctions among different virulence strains of L. monocytogenes in the GI environment.

A Proposal to Reflect Survival Difference and Modify the Staging System for Lung Adenocarcinoma and Squamous Cell Carcinoma: Based on the Machine Learning.

Objective: To propose modifications to refine prognostication over anatomic extent of the current tumor, node, and metastasis (TNM) staging system of non-small cell lung cancer (NSCLC) for a better distinction, and reflect survival differences of lung adenocarcinoma and squamous cell carcinoma. Study Design: Three large cohorts were included in this study. The training cohort consisted of 124,788 patients in the Surveillance, Epidemiology, and End Results (SEER) database (2006-2015). The validation cohort consisted of 4,247 patients from the Zhongshan Hospital, Fudan University (FDZSH; 2005-2014), and People's Hospital, Peking University (PKUPH; 2000-2017). The algorithm generated a hierarchical clustering model based on the unsupervised learning for survival data using Kaplan-Meier curves and log-rank test statistics for recursive partitioning and selection of the principal groupings. Results: In the modified staging system, adenocarcinoma cases are usually at a lower stage than the squamous cell carcinoma cases of the same TNM, reflecting a better outcome of adenocarcinoma than that of squamous cell carcinoma. The C-index of the modified staging system was significantly superior to that of the staging system [SEER cohort: 0.722, 95% CI, (0.721-0.723) vs. 0.643, 95% CI, (0.640-0.647); FDZSH cohort: 0.720, 95% CI, (0.709-0.731) vs. 0.519, 95% CI, (0.450-0.586); and PKUPH cohort: 0.730, 95% CI, (0.705-0.735) vs. 0.728, 95% CI, (0.703-0.753)]. Conclusion: Survival differences between lung adenocarcinoma and squamous cell carcinoma have been reflected accurately and reliably in the modified staging system based on the machine learning. It may refine prognostication over anatomic extent.

Effect of hydric stress on locomotion and morphology of tadpoles from temporary ponds.

Many frog species reproduce in temporary ponds maintained exclusively by rainfall, thereby being exposed to drought and possibly mortality of eggs and tadpoles. Some tadpoles, however, can survive for up to 5 days out of water but few data are available regarding the effects of dehydration on their development. The aim of this study was to evaluate whether hydric stress affects the locomotor capacity and the morphology in tadpoles of two leptodactylid frog species showing different reproductive modes (Leptodactylus fuscus and Physalaemus nattereri), examining specifically: (a) difference in survival rate and body mass between tadpoles at different hydration levels, (b) the hydric stress effect on locomotor performance, (c) difference in external morphology, and (d) visceral volume among tadpoles suffering hydric stress. Tadpoles for both species were divided into two groups, one staying in 100 ml of water and the other maintained on absorbent paper with 4 ml of water for 12, 24, and 72 hr (n = 20 each). Significant differences in weight loss were found between the groups of both species, the treatment losing more weight in all stress levels. Almost half of P. nattereri tadpoles died within 36 hr of hydric stress. We found no difference in locomotor performance between groups of L. fuscus tadpoles, but significant differences in locomotor performance, tail morphometry, and visceral volume between groups of P. nattereri tadpoles. Our results suggest that hydric stress has a significant effect on locomotion and morphology of P. nattereri tadpoles but not in L. fuscus.

Comparison of Patient Survival Between Hemodialysis and Peritoneal Dialysis Among Patients Eligible for Both Modalities.

BACKGROUND: Although peritoneal dialysis (PD) costs less to the health care system compared to in-center hemodialysis (HD), it is an underused therapy. Neither modality has been consistently shown to confer a clear benefit to patient survival. A key limitation of prior research is that study patients were not restricted to those eligible for both therapies. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All adult patients developing end-stage renal disease from January 2004 to December 2013 at any of 7 regional dialysis centers in Ontario, Canada, who had received at least 1 outpatient dialysis treatment and had completed a multidisciplinary modality assessment. PREDICTOR: HD or PD. OUTCOMES: Mortality from any cause. RESULTS: Among all incident patients with end-stage renal disease (1,579 HD and 453 PD), PD was associated with lower risk for death among patients younger than 65 years. However, after excluding approximately one-third of all incident patients deemed to be ineligible for PD, the modalities were associated with similar survival regardless of age. This finding was also observed in analyses that were restricted to patients initiating dialysis therapy electively as outpatients. The impact of modality on survival did not vary over time. LIMITATIONS: The determination of PD eligibility was based on the judgment of the multidisciplinary team at each dialysis center. CONCLUSIONS: HD and PD are associated with similar mortality among incident dialysis patients who are eligible for both modalities. The effect of modality on survival does not appear to change over time. Future comparisons of dialysis modality should be restricted to individuals who are deemed eligible for both modalities to reflect the outcomes of patients who have the opportunity to choose between HD and PD in clinical practice.

Partitioned log-rank tests for the overall homogeneity of hazard rate functions.

In survival analysis, it is routine to test equality of two survival curves, which is often conducted by using the log-rank test. Although it is optimal under the proportional hazards assumption, the log-rank test is known to have little power when the survival or hazard functions cross. To test the overall homogeneity of hazard rate functions, we propose a group of partitioned log-rank tests. By partitioning the time axis and taking the supremum of the sum of two partitioned log-rank statistics over different partitioning points, the proposed test gains enormous power for cases with crossing hazards. On the other hand, when the hazards are indeed proportional, our test still maintains high power close to that of the optimal log-rank test. Extensive simulation studies are conducted to compare the proposed test with existing methods, and three real data examples are used to illustrate the commonality of crossing hazards and the advantages of the partitioned log-rank tests.

Integrated genomic analysis of survival outliers in glioblastoma.

Background: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). Methods: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients. Results: LTS GB showed frequent chromosomal gains in 4q12 (platelet derived growth factor receptor alpha and KIT) and 12q14.1 (cyclin-dependent kinase 4), and deletion in 19q13.33 (BAX, branched chain amino-acid transaminase 2, and cluster of differentiation 33). STS GB showed frequent deletion in 9p11.2 (forkhead box D4-like 2 and aquaporin 7 pseudogene 3) and 22q11.21 (Hypermethylated In Cancer 2). LTS GB showed 2-fold more frequent copy number deletions compared with STS GB. Gene expression differences showed the STS cohort with altered transcriptional regulators: activation of signal transducer and activator of transcription (STAT)5a/b, nuclear factor-kappaB (NF-κB), and interferon-gamma (IFNG), and inhibition of mitogen-activated protein kinase (MAPK1), extracellular signal-regulated kinase (ERK)1/2, and estrogen receptor (ESR)1. Expression-based biological concepts prominent in the STS cohort include metabolic processes, anaphase-promoting complex degradation, and immune processes associated with major histocompatibility complex class I antigen presentation; the LTS cohort features genes related to development, morphogenesis, and the mammalian target of rapamycin signaling pathway. Whole genome methylation analyses showed that a methylation signature of 89 probes distinctly separates LTS from STS GB tumors. Conclusion: We posit that genomic instability is associated with longer survival of GB (possibly with vulnerability to standard therapy); conversely, genomic and epigenetic signatures may identify patients where up-front entry into alternative, targeted regimens would be a preferred, more efficacious management.

Tuberculosis and survival in past populations: A paleo-epidemiological appraisal.

Historical assessments of the last two centuries consistently placed tuberculosis as the leading cause of mortality. However, for earlier periods, we can only calculate the frequencies of archaeological bone lesions, which tell us little about the real impact of the disease on mortality. These lesions are usually observed in individuals who have developed immune resistance, which is visible as healed osteo-articular lesions. This study aimed to test the differential impacts of tuberculosis, cribra orbitalia and cribra femoris on adult survival and sex-based survival. We analyzed 28 French adult samples from the Antiquity and the Early Middle Ages. The age-at-death of 1480 individuals was estimated using cementochronology. Survival curves and median age-at-death were calculated to test new hypotheses that challenge the parasitic and deficiency theories of bone stress markers. Comparisons between carriers and non-carriers provided new information concerning the plausible causes of bone stress markers related to infections and TB. The most likely hypothesis is skeletal demineralization and osteoclastic resorption, which are usually observed close to tubercular granuloma or distant from active lesions. The bone marrow niche of Mycobacterium tuberculosis within CD271(+) BM-MSCs stem cells is the proposed explanation for the localized cortical resorption that is observed in bone stress markers.

Rural-urban differences in acute myocardial infarction mortality: Evidence from Nebraska.

AIMS: Acute myocardial infarction (AMI) remains a major cause of death and disability in the United States and worldwide. Despite the importance of surveillance and secondary prevention, the incidence of and mortality from AMI are not continuously monitored, and little is known about survival outcomes after 30 days of AMI hospitalization or associated risk factors, especially in the rural areas. The current study examines rural-urban differences in both in- and out-hospital survival outcomes for AMI patients. METHODS: We performed a retrospective analysis using hospital discharge data in Nebraska for January 2005 to December 2009 and Nebraska death certificate records through October 2011. Multivariate logistic regression was used to estimate the rural-urban difference in 30-day mortality. A Cox proportional hazard model was used to predict out-of-hospital and overall survival rate. RESULTS: In the 30-day mortality model, after controlling for age, comorbidities, and rehabilitation, patients in urban areas were less likely to die than patients in rural areas (odds ratio: 0.709, 95% confidence interval: 0.626-0.802). In the overall survival model, patients in urban areas had a lower hazard of AMI death (hazard ratio: 0.86, 95% confidence interval: 0.806-0.931) than patients in rural areas. Patients with a previous history of heart failure had a significantly higher likelihood of 30-day mortality, while atrial fibrillation, heart failure, and chronic kidney disease were associated with lower overall survival. Patients who attended at least 1 cardiac rehabilitation session had significantly lower 30-day and overall mortality (p < 0.0001). CONCLUSIONS: This study confirms previous findings on rural-urban disparities in 30-day mortality following AMI hospitalization, and reports new findings on overall rural-urban mortality disparity. The study also found an association between cardiac rehabilitation and reduced mortality, a finding never before reported at the population level. Further efforts are needed to develop systems in rural hospitals and communities to ensure that AMI patients receive recommended care.