Tag: statistics

J Cancer Res Clin Oncol. 2023 Mar 4. doi: 10.1007/s00432-023-04664-8. Online ahead of print.

ABSTRACT

PURPOSE: In testicular neoplasms, the interrelationship of elevations of the novel serum tumor marker microRNA-371a-3p (M371) and traditional markers with other clinical features is still incompletely understood. The present study evaluated marker expression rates in relation to various other clinical parameters.

METHODS: The following data were retrospectively registered from 641 consecutive patients with testicular neoplasms: histology, such as seminoma (n = 365), nonseminoma (n = 179), benign tumor (n = 79), other malignant tumor (n = 18); patients age (years); clinical stage (CS1, CS2a/b, CS2c, CS3); and preoperative elevation of beta HCG, AFP, LDH, M371 (yes/no). Descriptive statistical methods were employed with comparisons of various subgroups to disclose associations of marker expression rates with age, histology and CS, and of age with histology.

RESULTS: The histologic subgroups revealed significantly different expression rates of tumor markers. M371 performed best with expression rates of 82.69% and 93.58% in seminoma and in nonseminoma, respectively. In germ cell tumors, all markers had significantly higher expression rates in metastasized stages than in localized disease. All markers except LDH have significantly higher expression rates in younger than in older patients. Nonseminoma is most prevalent in the youngest age category, seminoma predominates in patients > 40 years, other malignancies were restricted to patients > 50 years.

CONCLUSION: The study documented significant associations of serum marker expression rates with histology, age and clinical staging, with highest rates in nonseminomas, young age and advanced clinical stages. M371 showed significantly higher expression rates than other markers suggesting its superior clinical usefulness.

PMID:36869885 | DOI:10.1007/s00432-023-04664-8

Horm Mol Biol Clin Investig. 2023 Mar 6. doi: 10.1515/hmbci-2022-0104. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study sought to examine the relationship of betatrophin with certain key enzymes, namely lactate dehydrogenase-5 (LDH5), citrate synthase (CS), and acetyl-CoA carboxylase-1 (ACC1), in insulin-resistant mice.

METHODS: Eight-week-old male C57BL6/J mice were used in this study (experimental group n=10 and control group n=10). S961 was administered using an osmotic pump to induce insulin resistance in the mice. The betatrophin, LDH5, CS, and ACC1 expression levels were determined from the livers of the mice using the real-time polymerase chain reaction (RT-PCR) method. Moreover, biochemical parameters such as the serum betatrophin, fasting glucose, insulin, triglyceride, total cholesterol, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were analyzed.

RESULTS: The betatrophin expression and serum betatrophin (p=0.000), fasting glucose, insulin, triglyceride (p≤0.001), and total cholesterol (p=0.013) levels were increased in the experimental group. In addition, the CS gene expression level was statistically significantly decreased in the experimental group (p=0.01). Although strong correlation was found between the expression and serum betatrophin and triglyceride levels, no correlation was found between the betatrophin gene expression and the LDH5, ACC1, and CS gene expression levels.

CONCLUSIONS: The betatrophin level appears to play an important role in the regulation of triglyceride metabolism, while insulin resistance increases both the betatrophin gene expression and serum levels and decreases the CS expression level. The findings suggest that betatrophin may not regulate carbohydrate metabolism through CS and LDH5 or lipid metabolism directly through the ACC1 enzyme.

PMID:36869875 | DOI:10.1515/hmbci-2022-0104

Biometrics. 2023 Mar 4. doi: 10.1111/biom.13849. Online ahead of print.

ABSTRACT

We consider theoretical and practical issues for innovatively using a large number of covariates in clinical trials to achieve various design objectives without model misspecification. Specifically, we propose a new family of semiparametric covariate-adjusted response-adaptive randomization (CARA) designs and we use the target maximum likelihood estimation (TMLE) to analyze the correlated data from CARA designs. Our approach can flexibly achieve multiple objectives and correctly incorporate the effect of a large number of covariates on the responses without model misspecification. We also obtain the consistency and asymptotic normality of the target parameters, allocation probabilities, and allocation proportions. Numerical studies demonstrate that our approach has advantages over existing approaches, even when the data-generating distribution is complicated. This article is protected by copyright. All rights reserved.

PMID:36869863 | DOI:10.1111/biom.13849

Epilepsia. 2023 Mar 4. doi: 10.1111/epi.17574. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to assess determinants of seizure outcome following pediatric hemispherotomy in a contemporary cohort.

METHODS: We retrospectively analyzed the seizure outcomes of 457 children who underwent hemispheric surgery in five European epilepsy centers between 2000 and 2016. We identified variables related to seizure outcome through multivariable regression modeling with missing data imputation and optimal group matching and further investigated the role of surgical technique by Bayes factor (BF) analysis.

RESULTS: 177 (39%) children underwent vertical and 280 (61%) lateral hemispherotomy. 344 (75%) children achieved seizure freedom at a mean follow-up of 5.1 years (range 1 to 17.1). We identified acquired etiology other than stroke (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.1-18.0), hemimegalencephaly (OR 2.8, CI 1.1-7.3), contralateral MRI findings (5.5, CI 2.7-11.1), prior resective surgery (OR 5.0, CI 1.8-14.0), and left hemispherotomy (OR 2.3, CI 1.3-3.9), as significant determinants of seizure recurrence. We found no evidence for an impact of the hemispherotomy technique on seizure outcome (the Bayes factor for a model including the hemispherotomy technique over the null model was 1.1), with comparable overall major complication rates for different approaches.

SIGNIFICANCE: Knowledge about independent determinants of seizure outcome following pediatric hemispherotomy will improve the counseling of patients and families. In contrast to previous reports, we found no statistically-relevant difference in seizure-freedom rates between the vertical and horizontal hemispherotomy techniques when accounting for different clinical features between groups.

PMID:36869851 | DOI:10.1111/epi.17574

Brief Bioinform. 2023 Mar 3:bbad071. doi: 10.1093/bib/bbad071. Online ahead of print.

ABSTRACT

Alignment is the cornerstone of many long-read pipelines and plays an essential role in resolving structural variants (SVs). However, forced alignments of SVs embedded in long reads, inflexibility of integrating novel SVs models and computational inefficiency remain problems. Here, we investigate the feasibility of resolving long-read SVs with alignment-free algorithms. We ask: (1) Is it possible to resolve long-read SVs with alignment-free approaches? and (2) Does it provide an advantage over existing approaches? To this end, we implemented the framework named Linear, which can flexibly integrate alignment-free algorithms such as the generative model for long-read SV detection. Furthermore, Linear addresses the problem of compatibility of alignment-free approaches with existing software. It takes as input long reads and outputs standardized results existing software can directly process. We conducted large-scale assessments in this work and the results show that the sensitivity, and flexibility of Linear outperform alignment-based pipelines. Moreover, the computational efficiency is orders of magnitude faster.

PMID:36869850 | DOI:10.1093/bib/bbad071

Brief Bioinform. 2023 Mar 3:bbad045. doi: 10.1093/bib/bbad045. Online ahead of print.

ABSTRACT

The rapid development of single-cell RNA sequencing (scRNA-seq) technology allows us to study gene expression heterogeneity at the cellular level. Cell annotation is the basis for subsequent downstream analysis in single-cell data mining. As more and more well-annotated scRNA-seq reference data become available, many automatic annotation methods have sprung up in order to simplify the cell annotation process on unlabeled target data. However, existing methods rarely explore the fine-grained semantic knowledge of novel cell types absent from the reference data, and they are usually susceptible to batch effects on the classification of seen cell types. Taking into consideration the limitations above, this paper proposes a new and practical task called generalized cell type annotation and discovery for scRNA-seq data whereby target cells are labeled with either seen cell types or cluster labels, instead of a unified ‘unassigned’ label. To accomplish this, we carefully design a comprehensive evaluation benchmark and propose a novel end-to-end algorithmic framework called scGAD. Specifically, scGAD first builds the intrinsic correspondences on seen and novel cell types by retrieving geometrically and semantically mutual nearest neighbors as anchor pairs. Together with the similarity affinity score, a soft anchor-based self-supervised learning module is then designed to transfer the known label information from reference data to target data and aggregate the new semantic knowledge within target data in the prediction space. To enhance the inter-type separation and intra-type compactness, we further propose a confidential prototype self-supervised learning paradigm to implicitly capture the global topological structure of cells in the embedding space. Such a bidirectional dual alignment mechanism between embedding space and prediction space can better handle batch effect and cell type shift. Extensive results on massive simulation datasets and real datasets demonstrate the superiority of scGAD over various state-of-the-art clustering and annotation methods. We also implement marker gene identification to validate the effectiveness of scGAD in clustering novel cell types and their biological significance. To the best of our knowledge, we are the first to introduce this new and practical task and propose an end-to-end algorithmic framework to solve it. Our method scGAD is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/aimeeyaoyao/scGAD.

PMID:36869836 | DOI:10.1093/bib/bbad045

J Crohns Colitis. 2023 Mar 4:jjad038. doi: 10.1093/ecco-jcc/jjad038. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn’s disease (CD) with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD.

METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD (iCREST-CD).

RESULTS: Perianal lesions were present in 324 (48.2%) of 672 patients with newly diagnosed CD. 71.9% (233/324) were male. The prevalence of perianal lesions was higher in patients aged <40 years versus ≥40 years, and it decreased with age. Perianal fistula (59.9%) and abscess (30.6%) were the most common perianal lesions. In multivariate analyses, male sex, age <40 years, and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent (33.3% vs 21.6%) and, work productivity and activity impairment-work time missed (36.3% vs 29.5%) and activity impairment (51.9% vs 41.1%) were numerically higher in patients with than those without perianal lesions.

CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location, and behaviour are significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities.

PMID:36869815 | DOI:10.1093/ecco-jcc/jjad038

J Endovasc Ther. 2023 Mar 4:15266028231157636. doi: 10.1177/15266028231157636. Online ahead of print.

ABSTRACT

PURPOSE: To systematically review existing evidence on outcomes of endovascular repair of abdominal atherosclerotic penetrating aortic ulcers (PAUs).

MATERIAL AND METHODS: Cochrane Central Registry of Registered Trials (CENTRAL), MEDLINE (via PubMed), and Web of Science databases were systematically searched. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P 2020). The protocol was registered in the international registry of systematic reviews (PROSPERO CRD42022313404). Studies reporting on technical and clinical outcomes of endovascular PAU repair in 3 or more patients were included. Random effects modeling was used to estimate pooled technical success, survival, reinterventions, and type 1 and type 3 endoleaks. Statistical heterogeneity was assessed using the I² statistic. Pooled results are reported with 95% confidence intervals (CIs). Study quality was assessed using an adapted version of the Modified Coleman Methodology Score.

RESULTS: Sixteen studies including 165 patients with a mean/median age ranging from 64 to 78 years receiving endovascular therapy for PAU between 1997 and 2020 were identified. Pooled technical success was 99.0% (CI: 96.0%-100%). In all, 30-day mortality was 1.0% (CI: 0%-6.0%) with an in-hospital mortality of 1.0% (CI: 0.0%-13.0%). There were no reinterventions, type 1, or type 3 endoleaks at 30 days. Median/mean follow-up ranged from 1 to 33 months. Overall, there were 16 deaths (9.7%), 5 reinterventions (3.3%), 3 type 1 (1.8%), and 1 type 3 endoleak (0.6%) during follow-up. The quality of studies was rated low according to the Modified Coleman score at 43.4 (+/- 8.5) of 85 points.

CONCLUSION: There is low-level evidence on outcomes of endovascular PAU repair. While in the short-term endovascular repair of abdominal PAU seems safe and effective, mid-term and long-term data are lacking. Recommendations with regard to treatment indications and techniques in asymptomatic PAU should be made cautiously.

CLINICAL IMPACT: This systematic review demonstrated that evidence on outcomes of endovascular abdominal PAU repair is limited. While in the short-term endovascular repair of abdominal PAU seems safe and effective, mid-term and long-term data are lacking. In the context of a benign prognosis of asymptomatic PAU and lacking standardization in current reporting, recommendations with regard to treatment indications and techniques in asymptomatic PAUs should be made cautiously.

PMID:36869667 | DOI:10.1177/15266028231157636

Womens Health (Lond). 2023 Jan-Dec;19:17455057231155302. doi: 10.1177/17455057231155302.

ABSTRACT

OBJECTIVES: Community doulas, who provide culturally concordant, nonclinical support during and after pregnancy, are increasingly promoted as an evidence-based intervention to advance birth equity. As valued members of their communities, community doulas often provide extensive physical and emotional pregnancy, birth, and postpartum support at low or no cost to clients. However, neither community doulas’ scope of work nor the distribution of time among their different work activities has been clearly defined or enumerated; therefore, this project sought to describe the work activities and time use of doulas in one community-based doula organization.

METHODS: In a quality improvement project, we reviewed case management system client data and collected 1 month of time diary data from eight doulas employed full-time at SisterWeb San Francisco Community Doula Network. We calculated descriptive statistics for activities community doulas reported in their time diaries and each visit/interaction logged in the case management system.

RESULTS: SisterWeb doulas spent about half of their time in direct client care. For every hour that doulas spent with a client in prenatal and postpartum visits, on average, they spent an additional 2.15 h communicating with and supporting their clients in other ways. Overall, we estimate that SisterWeb doulas spend an average of 32 h providing care for a client receiving the standard course of care, including intake, prenatal visits, support during childbirth, and postpartum visits.

CONCLUSIONS: Results highlight the wide variety of work that SisterWeb community doulas do beyond direct client care. Acknowledgment of community doulas’ broad scope of work and appropriate compensation for all activities is necessary if doula care is to be advanced as a health equity intervention.

PMID:36869648 | DOI:10.1177/17455057231155302

Ann Med. 2023 Dec;55(1):800-807. doi: 10.1080/07853890.2022.2160490.

ABSTRACT

OBJECTIVE: Delayed extubation was commonly associated with increased adverse outcomes. This study aimed to explore the incidence and predictors and to construct a nomogram for delayed extubation after thoracoscopic lung cancer surgery.

METHODS: We reviewed medical records of 8716 consecutive patients undergoing this surgical treatment from January 2016 to December 2017. Using potential predictors to develop a nomogram and using a bootstrap-resampling approach to conduct internal validation. For external validation, we additionally pooled 3676 consecutive patients who underwent this procedure between January 2018 and June 2018. Extubation performed outside the operating room was defined as delayed extubation.

RESULTS: The rate of delayed extubation was 1.60%. Multivariate analysis identified age, BMI, FEV₁/FVC, lymph nodes calcification, thoracic paravertebral blockade (TPVB) usage, intraoperative transfusion, operative time and operation later than 6 p.m. as independent predictors for delayed extubation. Using these eight candidates to develop a nomogram, with a concordance statistic (C-statistic) value of 0.798 and good calibration. After internal validation, similarly good calibration and discrimination (C-statistic, 0.789; 95%CI, 0.748 to 0.830) were observed. The decision curve analysis (DCA) indicated the positive net benefit with the threshold risk range of 0 to 30%. Goodness-of-fit test and discrimination in the external validation were 0.113 and 0.785, respectively.

CONCLUSION: The proposed nomogram can reliably identify patients at high risk for the decision to delayed extubation after thoracoscopic lung cancer surgery. Optimizing four modifiable factors including BMI, FEV₁/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.Key Messages:This study identified eight independent predictors for delayed extubation, among which lymph node calcification and anaesthesia type were not commonly reported.Using these eight candidates to develop a nomogram, we could reliably identify high-risk patients for the decision to delayed extubation.Optimizing four modifiable factors, including BMI, FEV₁/FVC, TPVB usage, and operation later than 6 p.m. may reduce the risk of delayed extubation.

PMID:36869647 | DOI:10.1080/07853890.2022.2160490