Category: Statistics

Ecol Lett. 2022 Jan 10. doi: 10.1111/ele.13956. Online ahead of print.

ABSTRACT

Studies of oscillatory populations have a long history in ecology. A first-principles understanding of these dynamics can provide insights into causes of population regulation and help with selecting detailed predictive models. A particularly difficult challenge is determining the relative role of deterministic versus stochastic forces in producing oscillations. We employ statistical physics concepts, including measures of spatial synchrony, that incorporate patterns at all scales and are novel to ecology, to show that spatial patterns can, under broad and well-defined circumstances, elucidate drivers of population dynamics. We find that when neighbours are coupled (e.g. by dispersal), noisy intrinsic oscillations become distinguishable from noise-induced oscillations at a transition point related to synchronisation that is distinct from the deterministic bifurcation point. We derive this transition point and show that it diverges from the deterministic bifurcation point as stochasticity increases. The concept of universality suggests that the results are robust and widely applicable.

PMID:35007391 | DOI:10.1111/ele.13956

J Pathol. 2022 Jan 10. doi: 10.1002/path.5864. Online ahead of print.

ABSTRACT

We assessed the utility of quantitative features of colon cancer nuclei, extracted from digitized hematoxylin and eosin-stained whole slide images (WSIs), to distinguish between Stage II from Stage IV colon cancers. Our discovery cohort comprised 100 Stage II and Stage IV colon cancer cases sourced from the University Hospitals Cleveland Medical Center (UHCMC). We performed initial (independent) model validation on 51 (143) Stage II and 79 (54) Stage IV colon cancer cases from UHCMC (The Cancer Genome Atlas’s Colon Adenocarcinoma, TCGA-COAD, cohort). Our approach comprised the following steps, (1) a fully convolutional deep neural network with VGG-18 architecture was trained to locate cancer on WSIs, (2) another deep-learning model based on Mask-RCNN with Resnet-50 architecture was used to segment all nuclei from within the identified cancer region, (3) a total of 26,641 quantitative morphometric features pertaining to nuclear shape, size, and texture were extracted from within and outside tumor nuclei, (4) a random forest classifier was trained to distinguish between Stage II and Stage IV colon cancers using the 5 most discriminatory features selected by the Wilcoxon rank-sum test. Our trained classifier using these top 5 features yielded an AUC of 0.81 and 0.78, respectively, on the held-out cases in UHCMC and TCGA validation sets. For 197 TCGA-COAD cases, the Cox-proportional hazards model yielded a hazard ratio of 2.20 (95% CI: 1.24-3.88) with a concordance index of 0.71 using only top-five features for risk stratification of overall survival. The Kaplan-Meier estimate also showed statistically significant separation between the low-risk and high-risk patients with a log-rank p-value of 0.0097. Finally, unsupervised clustering of the top-five features revealed that Stage IV colon cancers with peritoneal spread were morphologically more similar to Stage II colon cancers with no long-term metastases than Stage IV colon cancers with hematogenous spread. This article is protected by copyright. All rights reserved.

PMID:35007352 | DOI:10.1002/path.5864

Pathol Int. 2022 Jan 10. doi: 10.1111/pin.13195. Online ahead of print.

ABSTRACT

Perineural invasion (PNI) is known as a poor prognostic factor in colorectal cancer (CRC). Although histopathological evaluation of PNI is usually conducted on hematoxylin and eosin (HE)-stained sections (HE-PNI), it remains controversial whether PNI can be precisely evaluated only by HE-staining, and its concise mechanisms causing worse prognosis remains elusive. In this study, we examined the impact of PNI evaluated by S-100-immunostaining (S100-PNI) on postoperative mortality in 279 consecutive CRC patients and further investigated its association with the tumor immune microenvironment. S100-PNI was present in 67.3% of tumors whereas HE-PNI was present in 18.5%. A 5-year cumulative incidence of death in the S100-PNI-positive group was significantly higher than that in the S100-PNI-negative group. Further statistical analyses revealed that S100-PNI was an independent prognostic factor of all-cause mortality in stage I/II but not in stage III/IV. Importantly, S100-PNI was associated with the altered tumor immune microenvironment. Infiltrating immune cell profiling revealed that stromal lymphocytic reaction, which was inversely correlated with postoperative mortality, was significantly reduced in S100-PNI-positive tumors compared to S100-PNI-negative tumors in stage I/II. These results indicated that S100-PNI was a poor prognostic factor in stage I/II CRC with possible association with immunosuppression in the tumor.

PMID:35007380 | DOI:10.1111/pin.13195

Hepatology. 2022 Jan 10. doi: 10.1002/hep.32323. Online ahead of print.

ABSTRACT

The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5cm HCC over time. From 2008 to 2019, 1,289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching (PSM) was used to balance all baseline variables between the two groups in 2008-2019 (n =335 in each group) and 2014-2019 (n =257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (Hazard ratio (HR): 0.88, 95% confidence interval (CI) 0.65-1.19, P =0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95%CI (1.05-1.75), P =0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95%CI (0.56-1.30), P =0.460) and approached statistical significance for DFS (HR 1.33, 95%CI (0.98-1.82), P =0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0cm HCCs (HR 0.88, 95%CI (0.53-1.47), P =0.630) and 4.1-5.0cm HCCs (HR 0.77, 95%CI (0.37-1.60), P =0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both P >0.05), shorter hospitalization and lower cost to LLR (all P <0.001). Conclusion: MWA might be a first-line alternative to LLR for solitary 3-5cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

PMID:35007334 | DOI:10.1002/hep.32323

Rev Esc Enferm USP. 2022 Jan 7;56:e20210330. doi: 10.1590/1980-220X-REEUSP-2021-0330. eCollection 2022.

ABSTRACT

OBJECTIVE: To identify factors associated with the adoption of non-pharmacological preventive measures against covid-19 by healthcare workers within their families.

METHOD: This is an analytical cross-sectional study carried out from October 1st to December 31st, 2020, with 11,513 healthcare workers in Brazil. Data collection through a virtual questionnaire on the platform Survey Monkey. To characterize the participants, descriptive statistical analysis was used with measures of absolute and relative frequency. Using inferential statistics, independent variables and outcome were compared, with hypothesis tests for association (chi-square, Fisher’s exact test), logistic regression, and Woe analysis. A significance level of 95% was used.

RESULTS: Most workers used measures such as hand hygiene, environmental sanitation, food hygiene, use of fabric masks, and physical distancing from family members. The association among variables was significant for the region, especially the South region, female sex, and nursing professionals.

CONCLUSION: Healthcare workers adopt preventive measures against covid-19 within family life, especially the women and nursing professionals, with family isolation being the measure of greatest adherence.

PMID:35007318 | DOI:10.1590/1980-220X-REEUSP-2021-0330

Diabetes. 2022 Jan 7:db210612. doi: 10.2337/db21-0612. Online ahead of print.

ABSTRACT

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of at-risk children, associated with progression to islet autoimmunity. We analysed gene expression by RNAseq in CD4+ and CD8+ T cells, NK cells and B cells, and chromatin accessibility by ATACseq in CD4+ T cells, in five genetically at-risk children with islet autoantibodies who progressed to diabetes over a median of 3 years (‘Progressors’) compared to five children matched for sex, age and HLA-DR who had not progressed (‘Non-progressors). In Progressors, differentially expressed genes (DEGs) were largely confined to CD4+ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 Progressors and 11 Non-progressors. Flow cytometry confirmed progression was associated with expansion of CD4+ cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4+ T cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4+ T cells play a role in promoting progression to type 1 diabetes.

PMID:35007320 | DOI:10.2337/db21-0612

PLoS Negl Trop Dis. 2022 Jan 10;16(1):e0010120. doi: 10.1371/journal.pntd.0010120. Online ahead of print.

ABSTRACT

BACKGROUND: Intestinal parasites and Tuberculosis (TB) co-infection is a major public health problem. The parasitic infection suppresses the cell mediated immunity that protects tuberculosis. Helminthes-induced immune modulation promotes progression to active tuberculosis. However, there is paucity of evidences on the intestinal parasites-tuberculosis co-infection in Ethiopia. This study explores the magnitude and associated factors of intestinal parasitic infection and TB among suspected pulmonary Tuberculosis (PTB) patients.

METHODOLOGY: A cross-sectional study design was conducted in Kuyu General Hospital from December 2019-March 2020. The socio-demographic data and associated factors were collected by structured questionnaire and then spot-spot sputum and fresh stool samples were collected following standard guidelines and were processed. Descriptive analysis was conducted and reported in frequency and percentage. Bivariate analysis was computed and a multivariable analysis was conducted to provide an adjusted odds ratio (AOR). P-value <0.05 at 95% confidence interval was considered as statistically significant.

RESULTS: The burden of intestinal parasites was 20.2% (49/ 242) and 6.1% (20/ 242) of them were helminths infections and 14.1% (29/ 242) were protozoa infections. Of 242 patients, 14.9% (36/242) were sputum smear-positive for acid fast-bacilli. Of 36 smear positive patients, 9(25%) had TB-intestinal parasites co-infection. Dwelling in rural areas and having untrimmed fingernails were statistically significantly associated with intestinal parasites. Having a contact history of Tb patients was significantly associated with pulmonary tuberculosis.

CONCLUSIONS: The magnitude of intestinal parasites and TB among PTB suspected patients were high. Hookworm infection was the predominant helmenthic infection. It is important to consider screening TB patients for intestinal parasites and treat co-infection properly.

PMID:35007304 | DOI:10.1371/journal.pntd.0010120

Rev Esc Enferm USP. 2022 Jan 5;56:e20210252. doi: 10.1590/1980-220X-REEUSP-2020-0252. eCollection 2022.

ABSTRACT

OBJECTIVE: To identify the main nursing diagnoses and interventions in children in the immediate postoperative period of palatoplasty.

METHOD: Documentary and retrospective study, developed in a Brazilian public and tertiary hospital, between August and September 2020. Children who underwent only palatoplasty, between January and December 2019, aged between 10 and 24 months, were included. Those with medical syndromes and/or comorbidities were excluded. The Theoretical Framework of Basic Human Needs and the NANDA International and Nursing Interventions Classification Taxonomies were used. Data underwent descriptive statistical analysis.

RESULTS: The sample consisted of 126 children. Psychobiological needs such as oxygenation, hydration, nutrition, elimination, cutaneous-mucosal and physical integrity, pain and environmental perception predominated. Based on them, nine nursing diagnoses, with four focusing on the problem and five on risk, as well as 17 interventions, were identified.

CONCLUSION: The use of standardized languages to identify affected human needs and, based on them, diagnoses and interventions, favored clinical reasoning for the construction and organization of clinical nursing practice.

PMID:35007314 | DOI:10.1590/1980-220X-REEUSP-2020-0252

PLoS One. 2022 Jan 10;17(1):e0262484. doi: 10.1371/journal.pone.0262484. eCollection 2022.

ABSTRACT

BACKGROUND: Extracellular vesicles are released into body fluids from the majority of, if not all, cell types. Because their secretion and specific cargo (e.g., proteins) varies according to pathology, extracellular vesicles may prove a rich source of biomarkers. However, their biological and pathophysiological functions are poorly understood in hematological malignancies.

OBJECTIVE: Here, we investigated proteome changes in the exosome-rich fraction of the plasma of myelodysplastic syndrome patients and healthy donors.

METHODS: Exosome-rich fraction of the plasma was isolated using ExoQuick™: proteomes were compared and statistically processed; proteins were identified by nanoLC-MS/MS and verified using the ExoCarta and QuickGO databases. Mann-Whitney and Spearman analyses were used to statistically analyze the data. 2D western blot was used to monitor clusterin proteoforms.

RESULTS: Statistical analyses of the data highlighted clusterin alterations as the most significant. 2D western blot showed that the clusterin changes were caused by posttranslational modifications. Moreover, there was a notable increase in the clusterin proteoform in the exosome-rich fraction of plasma of patients with more severe myelodysplastic syndrome; this corresponded with a simultaneous decrease in their plasma.

CONCLUSIONS: This specific clusterin proteoform seems to be a promising biomarker for myelodysplastic syndrome progression.

PMID:35007303 | DOI:10.1371/journal.pone.0262484

PLoS Comput Biol. 2022 Jan 10;18(1):e1009762. doi: 10.1371/journal.pcbi.1009762. Online ahead of print.

ABSTRACT

Activities of transcription factors (TFs) are temporally modulated to regulate dynamic cellular processes, including development, homeostasis, and disease. Recent developments of bioinformatic tools have enabled the analysis of TF activities using transcriptome data. However, because these methods typically use exon-based target expression levels, the estimated TF activities have limited temporal accuracy. To address this, we proposed a TF activity measure based on intron-level information in time-series RNA-seq data, and implemented it to decode the temporal control of TF activities during dynamic processes. We showed that TF activities inferred from intronic reads can better recapitulate instantaneous TF activities compared to the exon-based measure. By analyzing public and our own time-series transcriptome data, we found that intron-based TF activities improve the characterization of temporal phasing of cycling TFs during circadian rhythm, and facilitate the discovery of two temporally opposing TF modules during T cell activation. Collectively, we anticipate that the proposed approach would be broadly applicable for decoding global transcriptional architecture during dynamic processes.

PMID:35007289 | DOI:10.1371/journal.pcbi.1009762