Nevin Manimala

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

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

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

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

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

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 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

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 One. 2022 Jan 10;17(1):e0262414. doi: 10.1371/journal.pone.0262414. eCollection 2022.

ABSTRACT

BACKGROUND: Postpartum urinary Catheter-Related Infections (CRIs) are a significant cause of maternal sepsis. Several studies done have reported the presence of mixed populations of bacteria with a significant increase in Extended-Spectrum Beta-Lactamase (ESBL) Enterobacteriaceae spps, Methicillin-Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant (MDR) bacteria in urine and blood cultures of catheterized patients despite the use of prophylactic antibiotics. This study aimed at determining the bacterial species diversity and susceptibility patterns of indwelling urinary catheters from postpartum mothers attending Mbale Regional Referral Hospital (MRRH).

METHODS: A cross-sectional study employing quantitative and qualitative was carried out in MRRH among postpartum mothers with urinary catheters and their care-takers. The purposive non-random sampling strategy was used to collect data using an interviewer-administered questionnaire for the quantitative data collection and in-depth interviews for qualitative data collection. All the data collection tools used were developed, pretested and validated. At the point of de-catheterization, Catheter tips from enrolled participants were cut about 2-3cm below the balloon aseptically into test-tube containing peptone water, sonication technique employed, and incubation done 24hours then cultured to ensure phenotypic identification. An antibiotic sensitivity test was performed using the disc diffusion method following Clinical and Laboratory Standards Institute (CLSI) guidelines. Quantitative data collected was entered in Microsoft Excel and then exported to STATA14 for statistical analysis. Thematic analysis was used to analyse and organise qualitative data by an inductive coding method using Nvivo 12 software.

RESULTS: In this study, 208 postpartum mothers participated, the majority of whom were caesarean section mothers of age range 20-24 years and 17 care-takers with a median age of 32 years. The prevalence of catheter tips bacterial colonisation was 98% despite 88.5% of the participants being on broad-spectrum antibiotics. The average duration of catheterisation was 2 days. All bacteria isolates were potential uro-pathogens with a mean occurrence of 2 bacteria species in each urinary catheter tip. The rates of MDR to commonly used antibiotics were high. The urinary catheter size of greater than F14 and duration of catheterization greater than 2 days were significantly associated with the number of bacterial species isolated from each sample. The maintenance care and knowledge of care-urinary catheter care among the care-takers was found sub-optimal.

CONCLUSION: There was a high prevalence of catheter colonisation with bacterial spps diversity averaging 2 spps per sample despite use of broad spectrum antibiotics. The MDR rates were high, which calls for routine culture and sensitivity. Health workers practicing obstetric medicine need to pay attention to catheter sizes during catheterisation and its duration. Health education should be part of antenatal and postnatal care education.

PMID:35007300 | DOI:10.1371/journal.pone.0262414

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