Category: Statistics

Cell Rep. 2021 Jul 20;36(3):109422. doi: 10.1016/j.celrep.2021.109422.

ABSTRACT

Tumor-associated tertiary lymphoid structures (TA-TLS) are associated with enhanced patient survival and responsiveness to cancer therapies, but the mechanisms underlying their development are unknown. We show here that TA-TLS development in murine melanoma is orchestrated by cancer-associated fibroblasts (CAF) with characteristics of lymphoid tissue organizer cells that are induced by tumor necrosis factor receptor signaling. CAF organization into reticular networks is mediated by CD8 T cells, while CAF accumulation and TA-TLS expansion depend on CXCL13-mediated recruitment of B cells expressing lymphotoxin-α₁β₂. Some of these elements are also overrepresented in human TA-TLS. Additionally, we demonstrate that immunotherapy induces more and larger TA-TLS that are more often organized with discrete T and B cell zones, and that TA-TLS presence, number, and size are correlated with reduced tumor size and overall response to checkpoint immunotherapy. This work provides a platform for manipulating TA-TLS development as a cancer immunotherapy strategy.

PMID:34289373 | DOI:10.1016/j.celrep.2021.109422

Zhonghua Zhong Liu Za Zhi. 2021 Jul 23;43(7):801-805. doi: 10.3760/cma.j.cn112152-20190927-00635.

ABSTRACT

Objective: To analyze the association between low-frequency variants of ARID1A gene and primary liver cancer using latent category model. Methods: The low-frequency variants of ARID1A gene was combined according to different functional areas, and the combined variables were analyzed by using the latent class model to obtain the latent variables. Then the logistic regression was used to analyze the association between low-frequency variants of ARID1A gene and primary liver cancer. Results: The low-frequency variants of ARID1A gene were divided into three categories by the latent class model. The class 1 was mainly unmutated population, the proportion was 94.2% (2 454/2 603). The class 2 was mainly transcriptional regulatory domain mutation, take 4.8% (124/2 603). The class 3 was dominantly exon mutation, about 1.0% (27/2 603). Using class 1 as a reference, it was found that mutations in the transcriptional regulatory domain could reduce the risk of liver cancer (OR=0.601, 95% CI=0.364-0.992, P=0.046). Conclusion: The latent class model can identify low-frequency variants of gene associated with liver cancer and can be extended to more genetic association studies of low-frequency variants related to complex diseases.

PMID:34289576 | DOI:10.3760/cma.j.cn112152-20190927-00635

Zhonghua Zhong Liu Za Zhi. 2021 Jul 23;43(7):806-809. doi: 10.3760/cma.j.cn112152-20200901-00784.

ABSTRACT

Objective: To investigate the risk factors of peritoneal metastasis in primary appendiceal tumor. Methods: The clinic data of 71 patients with primary appendiceal tumor admitted in the Sixth Affiliated Hospital of Sun Yat-sen University between Dec 2012 and Jan 2019 were enrolled retrospectively. Multivariate logistic regression analysis were carried out to evaluate the risk factors of appendiceal tumor with peritoneal metastasis. Results: Of the 71 patients, 33 were peritoneal metastasis (peritoneal metastasis group) and 38 were non-peritoneal metastasis (no peritoneal metastasis group). Twenty-one patients in the peritoneal metastasis group had increased preoperative cancer embryo antigen (CEA), while 3 cases in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Sixteen cases in peritoneal metastasis group had increased preoperative carbohydrate antigen 199, while only 2 cases in the non-peritoneal metastasis group, the difference was statistically significant (P<0.001). The pathological type of 30 cases in the peritoneal metastasis group was adenocarcinoma (including mucus adenocarcinoma and colon adenocarcinoma), while 12 cases of adenocarcinoma in the non-peritoneal metastasis group, with statistically significant difference (P<0.001). Twelve cases in the peritoneal metastasis group had lymph node metastasis, while 3 cases in the non-peritoneal metastasis group, the difference is statistically significant (P=0.003). Preoperative CEA elevation and pathological type is adenocarinoma were independent risk factors for peritoneal metastasis of appendiceal cancer (P<0.05). Conclusions: The propensity of peritoneal metastasis in primary appendiceal tumor is high and the outcome is poor. Patients with increased preoperative CEA, adenocarcinoma histopathology are more inclined to have peritoneal metastasis.

PMID:34289577 | DOI:10.3760/cma.j.cn112152-20200901-00784

J Speech Lang Hear Res. 2021 Jul 21:1-14. doi: 10.1044/2021_JSLHR-20-00533. Online ahead of print.

ABSTRACT

Purpose We report the results of a systematic review and meta-analysis investigating the relationship between perceptual anchoring and dyslexia. Our goal was to assess the direction and degree of the effect between perceptual anchoring and reading ability in typical and atypical (i.e., dyslexic) readers. Method We performed a literature search of experiments explicitly assessing perceptual anchoring and reading ability using PsycInfo (Ovid, 1860-2020), MEDLINE (Ovid, 1860-2019), EMBASE (Ovid, 1883-2019), and PubMed for all available years up to June (2020). Our eligibility criteria consisted of English language articles, and, at minimum, one experimental group identified as dyslexic-either by reading assessment at the time or by previous diagnosis. We assessed for risk of bias using an adapted version of the Newcastle-Ottawa Scale. Eight studies were included in this review and meta-analysis (n = 422 participants). Results The overall effect was negative, moderate, and statistically significant; g = -0.70, 95% confidence interval [-1.10, -0.29]: a negative effect size indicating less perceptual anchoring in dyslexic versus nondyslexic groups. Visual assessment of funnel plot and Egger’s test suggest minimal bias but with significant heterogeneity; Q (7) = 17.03, prediction interval [-1.79, 0.40]. Conclusions Of the included studies, we find evidence for a moderate perceptual anchoring deficit in individuals with dyslexia. The primary limitation of the current review is the small number of included studies. The variability of effect sizes appears consistent with the inherent variability within subtypes of dyslexia.

PMID:34289307 | DOI:10.1044/2021_JSLHR-20-00533

Zhonghua Zhong Liu Za Zhi. 2021 Jul 23;43(7):762-768. doi: 10.3760/cma.j.cn112152-20200509-00430.

ABSTRACT

Objective: To investigate the effects of long-chain non-coding RNA ASB16 antisense RNA1 (ASB16-AS1) on the proliferation, migration and invasion of esophageal cancer cells by targeting microRNA (miR )-1258. Methods: Forty pairs of esophageal cancer tissues and matched adjacent tissues (distance of tumor margin>3 cm) resected in Xinxiang Central Hospital from May 2016 to July 2017 were collected. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expressions of ASB16-AS1 and miR-1258 in esophageal cancer tissues and adjacent tissues. The small interfering RNA negative control (si-NC), ASB16-AS1 small interfering RNA (si-ASB16-AS1), miR-negative control mimics (miR-NC), miR-1258 mimics (miR-1258), si-ASB16-AS1 and anti-miR-NC, si-ASB16-AS1 and anti-miR-1258, si-ASB16-AS1 and anti-miR-1258 were transfected into Eca109 cells, respectively. Methyl thiazolyl tetrazolium (MTT) was utilized to detect the cell viability. Transwell assays were applied to detect cell migration and invasion. Double luciferase reporting experiment and qRT-PCR were used to confirm the relationship between ASB16-AS1 and miR-1258. Results: The expression levels of ASB16-AS1 and miR-1258 in esophageal cancer tissues were 2.95±0.27 and 0.62±0.06, respectively. Compared with 1.00±0.06 and 1.00±0.07 in adjacent tissues, the difference was statistically significant (P<0.05). The cell viability of the si-NC group at 48 h and 72 h were 0.81±0.07 and 1.15±0.11, while those of si-ASB16-AS1 group were 0.46±0.04 and 0.62±0.06 (P<0.05). The numbers of cell migration and invasion in the si-NC group were 86.32±8.24 and 71.29±7.15, respectively, while those of si-ASB16-AS1 group were 43.22±4.31 and 32.36±3.58, respectively, the differences were statistically significant (P<0.05). The cell viability of the miR-NC group at 48 h and 72 h were 0.84±0.08, 1.18±0.12, while those of miR-1258 group were 0.55±0.05, 0.71±0.07 (P<0.05). The migration and invasion numbers of the miR-NC group were (83.15±8.31) and (75.33±7.51), while those of miR-1258 group were (49.58±4.23) and (38.42±3.84), respectively, the differences were statistically significant (P<0.05). The cell viability of the si-ASB16-AS1+ anti-miR-NC group at 48 h and 72 h were 0.45±0.04, 0.61±0.06, while those of si-ASB16-AS1+ anti-miR-1258 group were 0.72±0.07, 0.98±0.08; The migration and invasion numbers of cells in the si-ASB16-AS1+ anti-miR-NC group were 44.36±4.41 and 31.69±3.85, respectively, while those of si-ASB16-AS1+ anti-miR-1258 group were 72.65±7.27 and 61.22±6.14, respectively, and the differences were statistically significant (P<0.05). ASB16-AS1 targeted negative regulation of miR-1258 expression. Conclusions: ASB16-AS1 upregulates in esophageal cancer. ASB16-AS1 promotes the proliferation, migration and invasion of esophageal cancer cells by targeting miR-1258.

PMID:34289570 | DOI:10.3760/cma.j.cn112152-20200509-00430

Zhonghua Zhong Liu Za Zhi. 2021 Jul 23;43(7):795-800. doi: 10.3760/cma.j.cn112152-20190111-00006.

ABSTRACT

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi–squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

PMID:34289575 | DOI:10.3760/cma.j.cn112152-20190111-00006

J Audiol Otol. 2021 Jul;25(3):146-151. doi: 10.7874/jao.2021.00038. Epub 2021 Jul 10.

ABSTRACT

BACKGROUND AND OBJECTIVES: The relationship between hearing aid (HA) use and improvement in cognitive function is not fully known. This study aimed to determine whether HAs could recover temporal resolution or hearing in noise functions. Materials and.

METHODS: We designed a prospective study with two groups: HA users and controls. Patients older than 45 years, with a pure tone average threshold of worse than 40 dB and a speech discrimination score better than 60% in both ears were eligible. Central auditory processing tests and hearing in noise tests (HINTs) were evaluated at the beginning of the study and 1, 3, 6, and 12 months after the use of a monaural HA in the HA group compared to the control group. The changes in the evaluation parameters were statistically analyzed using the linear mixed model.

RESULTS: A total of 26 participants (13 in the HA and 13 in the control group) were included in this study. The frequency (p<0.01) and duration test (p=0.02) scores showed significant improvements in the HA group after 1 year, while the HINT scores showed no significant change.

CONCLUSIONS: After using an HA for one year, patients performed better on temporal resolution tests. No improvement was documented with regard to hearing in noise.

PMID:34289535 | DOI:10.7874/jao.2021.00038

Zhonghua Zhong Liu Za Zhi. 2021 Jun 23;43(6):646-656. doi: 10.3760/cma.j.cn112152-20210108-00030.

ABSTRACT

Objective: To investigate the role of CUL4B-RING E3 ubiquitin ligase (CRL4B) complex in pancreatic tumorigenesis and the molecular mechanism. Methods: Pancreatic cells were divided into control group (transfected with negative control lentivirus), shCUL4B group (transfected with CUL4B lentivirus), shDDB1 group [transfected with DNA damage binding protein 1 (DDB1) lentivirus], and shCUL4B+ siSFRP1 group (transfected with CUL4B lentivirus and SFRP1-siRNA). RNA-seq was performed in pancreatic cancer cell lines with CUL4B and DDB1 knocked down respectively, to identify the target genes regulated by CRL4B complex. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of target genes. Chromatin immunoprecipitation (ChIP) assay was used to identify the target genes directly regulated by CUL4B and DDB1. Western blot was used to detect the protein expression levels of the epithelial-mesenchymal transition (EMT) markers. The EdU cell proliferation test was used to detect cell proliferation ability. The scratch repair test and Transwell cell invasion test were used to detect cell migration and invasion ability. Finally, the sequencing data of pancreatic cancer-related tumor samples and normal samples in GEO, TCGA and GTEx databases were used to analyze the expression correlations of CUL4B, DDB1 and their downstream target genes. Results: RNA-seq results showed that target genes regulated by CRL4B complex involved in a number of malignant tumor-related signaling pathways. qRT-PCR results verified that the mRNA expression levels of the target genes of CUL4B or DDB1 knockdown groups were higher than those of the control group, and the difference was statistically significant (P<0.05). ChIP-PCR results showed that CRL4B complex directly bound to the promoter regions of the target genes, NME1 and SFRP1, and the enrichment of monoubiquitination of lysine at 119 of histone H2A (H2AK119ub1) in the promoter region of target gene was reduced after CUL4B knockdown. The proliferation rate in PANC-1 cell line of the control group was (32.10±3.58)%, higher than (13.95±1.66)% in the shCUL4B group and (22.38±0.77)% in the shCUL4B+ siSFRP1 group (P<0.05). The proliferation rate in AsPC-1 cell line of the control group was (35.47±7.80)%, higher than (19.60±3.58)% in the shCUL4B group and (30.09±0.81)% in the shCUL4B+ siSFRP1 group (P<0.05). The scratch repair experiment showed that the migration rate of PANC-1 cell line control group was (53.18±3.70)%, higher than that (17.46±2.62)% in the shCUL4B group and (44.99±9.18)% in the shCUL4B + siSFRP1 group (P<0.05). Western blot showed the expression levels of epithelial markers including α-catenin and γ-catenin in the control group were 1.00±0.03 and 1.01±0.11, respectively, lower than 1.44±0.01 and 1.21±0.06 in the shCUL4B group (P<0.05). The expression levels of mesenchymal markers including fibronectin and vimentin in the control group were 1.01±0.14 and 1.02±0.18, respectively, higher than 1.53±0.13 and 1.22±0.07 in the shCUL4B+ siSFRP1 group (P<0.05). The cell metastasis rate of the control group was (100.00±3.96)%, higher than the (35.49±0.34)% in the shCUL4B group and (107.06±2.77)% in the shCUL4B+ siSFRP1 group, the difference was statistically significant (P<0.05). The expressions of CUL4B and DDB1 were significantly upregulated in the pancreatic cancer tissues, and were negatively correlated with the expression of SFRP1 (r=-0.342 and r=-0.264, respectively). Conclusions: CRL4B complex inhibits the transcription of target gene SFRP1 and promotes the development of pancreatic cancer. Moreover, CRL4B complex is upregulated in pancreatic cancer, which provide a potential of therapeutic target for pancreatic cancer.

PMID:34289556 | DOI:10.3760/cma.j.cn112152-20210108-00030

J Intern Med. 2021 Jul 21. doi: 10.1111/joim.13348. Online ahead of print.

ABSTRACT

BACKGROUND: Coronary heart disease occurs more frequently among patients with chronic obstructive pulmonary disease (COPD) compared to those without COPD. While some research suggests that long-acting bronchodilators might confer an additional risk of acute coronary syndrome (ACS), information from real-world clinical practice about the cardiovascular impact of using two versus one long-acting bronchodilator for COPD is limited. We undertook a population-based nested case-control study to estimate the risk of ACS in users of both a long-acting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) relative to users of a LAMA.

METHODS: The study was based on the primary care PREDICT Cardiovascular Disease Cohort and linked data from regional laboratories and the New Zealand Ministry of Health’s national data collections. The underlying cohort (n = 29,993) comprised patients aged 45-84 years, who initiated treatment with a LAMA and/or LABA for COPD between 1 February 2006 and 11 October 2016. 1490 ACS cases were matched to 13,550 controls by date of birth, sex, date of cohort entry (first long-acting bronchodilator dispensing), and COPD severity.

RESULTS: Relative to current use of LAMA therapy, current use of LAMA and LABA dual therapy was associated with a significantly higher risk of ACS (adjusted OR = 1.72; [95% CI: 1.28-2.31]).

CONCLUSION: Dual long-acting bronchodilator therapy, rather than LAMA mono-therapy, could increase the risk of ACS by more than 50%. This has important implications for decisions about the potential benefit/harm ratio of COPD treatment intensification, given the modest benefits of dual therapy.

PMID:34289189 | DOI:10.1111/joim.13348

Int J Nurs Educ Scholarsh. 2021 Jul 20;18(1). doi: 10.1515/ijnes-2021-0033.

ABSTRACT

OBJECTIVES: The aim of this study was to test if the e-learning activity that we developed could improve student nurses’ knowledge of continence and mobility and whether or not students would find the style of learning beneficial.

METHODS: A quasi-experimental pre-post-test design was used to test if the continence and mobility e-learning activity could improve student nurses’ knowledge about assessing and managing the needs of continence and mobility. An 18-item true/false knowledge of continence quiz was completed by 116 student nurses and a Likert style feedback learning survey was completed by 135 nursing students.

RESULTS: There was a statistically significant increase in students’ knowledge about continence and its relationship to mobility following the e-learning activity. The e-learning activity also enhanced students’ knowledge, confidence and perceptions about older people.

CONCLUSIONS: The e-learning activity we developed has the potential to improve nursing students’ knowledge about continence and mobility in an enjoyable manner.

PMID:34289268 | DOI:10.1515/ijnes-2021-0033