Category: Statistics

BMC Cancer. 2022 Jul 25;22(1):815. doi: 10.1186/s12885-022-09919-0.

ABSTRACT

BACKGROUND: Renin-angiotensin system inhibitors (RASIs) are widely used in the treatment of hypertension. However, their impact on the outcome of the combined treatment of rectal cancer is poorly understood. The aim of this study was to assess the effect of RASIs on the survival of rectal cancer patients with associated hypertension after neoadjuvant treatment and radical resection.

METHODS: Between 2008 and 2016, 242 radical (R0) rectal resections for cancer were performed after neoadjuvant treatment in patients with associated hypertension. At the time of treatment, 158 patients were on RASIs, including 35 angiotensin-receptor antagonists (ARB) users and 123 angiotensin-converting enzyme inhibitors (ACEI) users. Eighty-four patients were on drugs other than RASIs (non-RASI users). The survival analysis was performed using the Kaplan-Meier estimator with the log-rank test and the Cox proportional hazards model.

RESULTS: The log-rank test showed a significantly worse overall survival (OS) in the group of ACEI users compared to ARB users (p = 0.009) and non-RASI users (p = 0.013). Disease-free survival (DFS) was better in the group of ARB users compared to ACEI users. However, the difference was not statistically significant (p = 0.064). The Multivariate Cox analysis showed a significant beneficial effect of ARBs on OS (HR: 0.326, 95% CI: 0.147-0.724, p = 0.006) and ARBs on DFS (HR: 0.339, 95% CI: 0.135-0.850, p = 0.021) compared to ACEIs. Other factors affecting OS included age (HR: 1.044, 95% CI: 1.016-1.073, p = 0.002), regional lymph node metastasis (ypN +) (HR: 2.157, 95% CI: 1.395-3.334, p = 0.001) and perineural invasion (PNI) (HR: 3.864, 95% CI: 1.799-8.301, p = 0.001). Additional factors affecting DFS included ypN + (HR: 2.310, 95% CI: 1.374-3.883, p = 0.002) and PNI (HR: 4.351, 95% CI: 1.584-11.954, p = 0.004).

CONCLUSIONS: The use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.

PMID:35879682 | DOI:10.1186/s12885-022-09919-0

BMC Neurol. 2022 Jul 25;22(1):276. doi: 10.1186/s12883-022-02804-0.

ABSTRACT

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis. The underlying mechanism(s) remain largely unknown. Recent evidence has indicated that the gut microbiome may be involved in neurological immune diseases via the “gut-brain axis”. This study aimed to explore the possible relationship between anti-NMDAR encephalitis and the gut microbiome.

METHODS: Fecal specimens were collected from 10 patients with anti-NMDAR encephalitis and 10 healthy volunteers. The microbiome analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The alpha, beta, and taxonomic diversity analyses were mainly based on the QIIME2 pipeline.

RESULTS: There were no statistical differences in epidemiology, medication, and clinical characteristics (except for those related to anti-NMDAR encephalitis) between the two groups. ASV analysis showed that Prevotella was significantly increased, while Bacteroides was reduced in the gut microbiota of the patients, compared with the controls. Alpha diversity results showed a decrease in diversity in the patients compared with the healthy controls, analyzed by the Shannon diversity, Simpson diversity, and Pielou_E uniformity based on the Kruskal-Wallis test (P = 0.0342, 0.0040, and 0.0002, respectively). Beta diversity analysis showed that the abundance and composition of the gut microbiota was significantly different between the two groups, analyzed by weighted and unweighted UniFrac distance (P = 0.005 and 0.001, respectively).

CONCLUSIONS: The abundance and evenness of bacterial distribution were significantly lower and jeopardized in patients with anti-NMDAR encephalitis than in healthy controls. Thus, our findings suggest that gut microbiome composition changes might be associated with the anti-NMDAR encephalitis. It could be a causal agent, or a consequence.

PMID:35879681 | DOI:10.1186/s12883-022-02804-0

BMC Bioinformatics. 2022 Jul 25;23(1):296. doi: 10.1186/s12859-022-04748-1.

ABSTRACT

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150-3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849-911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

PMID:35879655 | DOI:10.1186/s12859-022-04748-1

J Pediatr Orthop. 2022 Jul 22. doi: 10.1097/BPO.0000000000002212. Online ahead of print.

ABSTRACT

BACKGROUND: Brachial plexus birth injuries (BPBI) can result in lasting impairments of external rotation and cross-body adduction (CBA) that disrupt functional activities such as dressing, grooming, or throwing a ball. The purpose of this study was to compare the quantification of shoulder humerothoracic (HT) external rotation (ER), and glenohumeral (GH) CBA by 3 methods – physician visual estimate, goniometer measurement by an occupational therapist, and motion capture.

METHODS: Twenty-six patients with BPBI (average age of 9.9±3.2 y) participated in this study. Mallet scores and visual estimates of passive HT ER and GH CBA were recorded by a physician. The passive measures were repeated by an occupational therapist using a goniometer while motion capture measures were simultaneously collected. Active HT ER was also measured by motion capture. The passive measures were compared with analyses of variance with repeated measures, intraclass correlations, and Bland-Altman plots. External rotation Mallet scores determined by motion capture and by the physician were compared.

RESULTS: The measures of GH CBA were not statistically different and demonstrated good agreement, but substantial variation. For HT ER, all measures were significantly different and demonstrated poor agreement and substantial variation. When the joint angles measured by motion capture were used to determine the Mallet score, 79% of external rotation Mallet scores assigned by the physician were incorrectly categorized, with the physician always scoring the participant higher than predicted motion capture Mallet score.

CONCLUSIONS: Both GH CBA and HT ER measures demonstrated substantial variability between measurement types, but only HT ER joint angles were significantly different. In addition, more than three-quarters of external rotation Mallet scores were misclassified by the physician. Motion capture measurements offer the benefit of less susceptibility to patients’ compensatory and/or out-of-plane movements and should be considered for clinical assessment of shoulder range of motion in children with BPBI. If motion capture is unavailable, the use of a goniometer provides more accurate clinical measures of shoulder motion than visual estimates and care should be taken to minimize and account for compensatory movement strategies.

LEVEL OF EVIDENCE: Level IV Case series.

PMID:35878417 | DOI:10.1097/BPO.0000000000002212

Vet Sci. 2022 Jul 13;9(7):357. doi: 10.3390/vetsci9070357.

ABSTRACT

Histological diagnosis of Canine Mammary Tumours (CMTs) provides the basis for proper treatment and follow-up. Nowadays, its accuracy is poorly understood and variable interpretation of histological criteria leads to a lack of standardisation and impossibility to compare studies. This study aimed to quantify the reproducibility of histological diagnosis and grading in CMTs. A blinded ring test on 36 CMTs was performed by 15 veterinary pathologists with different levels of education, after discussion of critical points on the Davis-Thompson Foundation Classification and providing consensus guidelines. Kappa statistics were used to compare the interobserver variability. The overall concordance rate of diagnostic interpretations of WP on identification of hyperplasia-dysplasia/benign/malignant lesions showed a substantial agreement (average k ranging from 0.66 to 0.82, with a k-combined of 0.76). Instead, outcomes on ICD-O-3.2 morphological code /diagnosis of histotype had only a moderate agreement (average k ranging from 0.44 and 0.64, with a k-combined of 0.54). The results demonstrated that standardised classification and consensus guidelines can produce moderate to substantial agreement; however, further efforts are needed to increase this agreement in distinguishing benign versus malignant lesions and in histological grading.

PMID:35878374 | DOI:10.3390/vetsci9070357

Vet Sci. 2022 Jul 21;9(7):374. doi: 10.3390/vetsci9070374.

ABSTRACT

Immunosuppressive myeloid cells in the tumor microenvironment play a major role in suppressing tumor immunity via the production of arginase, IL-10, and others. The objectives of this study were to determine the ability of all-trans retinoic acid (ATRA) to decrease the expression of arginase and other soluble mediators by canine monocyte-derived macrophages (MDMs) and to determine the inhibitory activity of arginase on canine T-lymphocytes. The immunomodulatory ability of ATRA (2 µM) on canine MDMs was evaluated via reverse transcription quantitative PCR (RT-qPCR), flow cytometry, arginase activity assay, and enzyme-linked immunoassay (ELISA). Arginase effects on T-lymphocyte phenotype and proliferation were then evaluated by flow cytometry. ATRA consistently decreased MDM expression of IL6, TGFB1, NOS2, ARG1, and CIITA transcripts, by approximately 2-4-fold, although this did not reach statistical significance for ARG1 or CIITA. Furthermore, arginase activity was decreased in ATRA-treated MDMs while the MDM phenotype remained unchanged. Arginase decreased the expression of granzyme B on CD8+ T-lymphocytes and inhibited CD4+ and CD8+ T-lymphocyte proliferation. These findings suggested that ATRA could inhibit canine MDM production of soluble inflammatory/immunosuppressive mediators. These data also revealed that arginase decreased canine T-lymphocyte proliferation and granzyme B expression. Further studies are needed to determine whether ATRA could reverse the immunosuppressive effects of myeloid cells on canine T-lymphocytes in vivo.

PMID:35878391 | DOI:10.3390/vetsci9070374

Vet Sci. 2022 Jul 5;9(7):340. doi: 10.3390/vetsci9070340.

ABSTRACT

The term angiomatosis is used to denote a group of well-known to poorly characterized proliferative vascular entities. In animals, cutaneous progressive angiomatosis (CPA) is a disorder with variable prognosis related to the extension and depth of infiltration of the surrounding tissues by vessels. CPA may share some microscopical features with other vascular proliferations such as low-grade well-differentiated capillaritic hemangiosarcoma (HS), making the diagnosis not always straightforward, especially in small biopsies. The aim of this study is to retrospectively assess the most common diagnostic microscopical features of CPA in dogs. In this work, 11 histopathological criteria were analyzed on 31 CPA and 11 primary cutaneous HS in dogs. Features significantly associated with CPA included: lobular growth, interposition of connective tissue and adnexa between the vascular proliferation, presence of nerve fibers, and a mixed vascular proliferative component. Absence of plump/prominent endothelial cells, lack of atypia, and lack of mitoses were also significant factors differentiating CPA from HS. Additional distinctive findings in CPA, although with no statistical association to CPA diagnosis, were vascular shunting, absence of necrosis, and endothelial cell piling up. In conclusion, the combined use of different microscopical clues allowed for the distinction of CPA from HS and was considered useful for the diagnosis of CPA.

PMID:35878357 | DOI:10.3390/vetsci9070340

Vet Sci. 2022 Jun 27;9(7):323. doi: 10.3390/vetsci9070323.

ABSTRACT

Filaggrin is an epidermal protein involved in skin barrier formation and hydration, whose expression is altered in canine atopic dermatitis (CAD). CAD patients also present an abnormal immune response with an altered expression of antimicrobial peptides (AMPs), such as β-defensins and cathelicidins. Sphingolipids and glycosaminoglycans (GAGs) have been reported to improve the skin barrier in several animal species, including dogs. Our objective was to evaluate the in vitro effects of a sphingomyelin-rich lipid extract (LE), a hyaluronic acid-rich GAG matrix, and their combination, on the expression of filaggrin and human β-defensin 2 (hBD-2). Filaggrin expression was quantified in a reconstructed human epidermis (RHE), and hBD-2 in normal human epidermal keratinocyte (NHEK) cultures. LE and GAGs were tested at 0.02 mg/mL, with or without adding a cytokine mix. A significant increase in mean hBD-2, compared to the control (99 pg/mL) was achieved with LE (138 pg/mL) and LE+GAGs (165 pg/mL). Filaggrin increased with GAGs (202% ± 83) and LE (193% ± 44) vs. the stimulated control, but this difference was statistically significant (p < 0.05) only with LE+GAGs (210% ± 39). In conclusion, the tested GAGs and LE enhance filaggrin and AMP expression in vitro, which might benefit CAD patients if applied in vivo.

PMID:35878340 | DOI:10.3390/vetsci9070323

Toxics. 2022 Jul 10;10(7):383. doi: 10.3390/toxics10070383.

ABSTRACT

This study is the first to investigate the ingestion of microplastics (MPs), plasticizers, additives, and particles of micro-litter < 100 μm by larvae of Simuliidae (Diptera) in rivers. Blackflies belong to a small cosmopolitan insect family whose larvae are present alongside river courses, often with a torrential regime, up to their mouths. Specimens of two species of blackfly larvae, Simulium equinum and Simulium ornatum, were collected in two rivers in Central Italy, the Mignone and the Treja. Small microplastics (SMPs, <100 μm), plasticizers, additives, and other micro-litter components, e.g., natural and non-plastic synthetic fibers (APFs) ingested by blackfly larvae were, for the first time, quantified and concurrently identified via MicroFTIR. The pretreatment allowed for simultaneous extraction of the ingested SMPs and APFs. Strong acids or strong oxidizing reagents and the application of temperatures well above the glass transition temperature of polyamide 6 and 6.6 (55-60 °C) were not employed to avoid further denaturation/degradation of polymers and underestimating the quantification. Reagent and procedural blanks did not show any SMPs or APFs. The method’s yield was >90%. Differences in the abundances of the SMPs and APFs ingested by the two species under exam were statistically significant. Additives and plasticizers can be specific to a particular polymer; thus, these compounds can be proxies for the presence of plastic polymers in the environment.

PMID:35878288 | DOI:10.3390/toxics10070383

Toxics. 2022 Jul 3;10(7):368. doi: 10.3390/toxics10070368.

ABSTRACT

Due to increased levels of human activity, various pollutants are frequently detected on the Tibetan Plateau, where the environment is extremely fragile and sensitive. Therefore, this study investigated the sources, pollution, and ecological risks of soil potentially toxic elements (PTEs) in different landscape areas within the Qaidam Basin in the northeastern part of the Qinghai-Tibet Plateau. The contents of seven PTEs (Cd, Cu, Pb, Zn, As, Cr, and Ni) in 32 topsoil samples (0-2 cm) were analyzed in different regions of the Qaidam Basin. The concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were 10.4-29.9 mg/kg, 0.08-4.45 mg/kg, 19-66 mg/kg, 8.2-40 mg/kg, 11.7-30.8 mg/kg, 11.1-31.2 mg/kg, and 32-213 mg/kg, respectively. The correlation between Pb and Cd in unpopulated areas was 0.896 (p < 0.01). The correlations among Pb, Cd, and Zn in agricultural areas, among As, Cd, Cr, and Zn in saline lake areas, and among As, Cd, Cr, Cu, Ni, Pb, and Zn in residential areas were all greater than 0.65 (p < 0.05). The principal component analysis results showed that Pb and Cd in unpopulated areas, Pb, Cd, and Zn in agricultural areas, As, Cd, Cr, Zn, and Pb in saline lake areas, and As, Cd, Cr, Cu, Ni, Pb, and Zn in residential areas were affected by human activities (significant factor >0.70). Based on the geological accumulation index and single-factor pollution index results, the maximum Cd values were found to be 4.93 and 45.88, respectively; Cd was thus the most serious PTE pollutant. The comprehensive pollution index of Nemero showed that moderately and severely polluted areas accounted for 18.89% and 18.46% of the total area, respectively. The results of the potential risk index showed that very strong and strong ecological risk points together accounted for 18.8% of the total points. The spatial variations in PTE pollution and the potential ecological risk index had similar patterns; both increased from the unpopulated areas in the northeastern Qaidam Basin to Golmud city in the south-western Qaidam Basin. These results indicate that human activities negatively impacted the soil ecological environment in the Qaidam Basin during the rapid development of the economy and urbanization and that these negative impacts tended to spread to unpopulated areas. Therefore, it is necessary to emphasize the significant impacts of human activities on environmental quality and formulate preventive measures to reduce PTE pollution in the Qinghai-Tibet Plateau.

PMID:35878273 | DOI:10.3390/toxics10070368