Category: Statistics

Int J Gynecol Pathol. 2023 Nov 10. doi: 10.1097/PGP.0000000000001001. Online ahead of print.

ABSTRACT

Endometrial stromal tumors (ESTs) are uncommon uterine mesenchymal lesions. Nuclear expression of β-catenin, an indication of activated Wnt/β-catenin signaling pathway, was described in 50% to 92% of low-grade ESTs, including endometrial stromal nodule and low-grade endometrial stromal sarcoma. Activation of the Wnt/β-catenin signaling pathway leads to the translocation of β-catenin into the nucleus and interaction with the T-cell factor/lymphoid enhancer-binding factor-1 (LEF1) family of transcription factors to regulate cell proliferation, differentiation, migration, and survival. Immunohistochemical analysis of β-catenin and LEF1 was performed in 2 endometrial stromal nodules and 20 low-grade endometrial stromal sarcomas and demonstrated 90.9% and 81.8% positive rates for β-catenin and LEF1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of β-catenin and LEF1 were 90.9% versus 81.8%, 81.0% versus 85.7%, 83.3% versus 85.7%, 89.5% versus 81.8%, respectively, in the diagnosis of low-grade ESTs. There is no statistical significance of the performance of β-catenin and LEF1 in all ESTs (P = 0.664) or in primary or metastatic/recurrent settings (P = 0.515 and 0.999, respectively). Only 3 smooth muscle tumors showed focal and weak positivity for LEF1. Our results indicate LEF1 can be a useful marker in aiding a diagnosis of low-grade EST and differentiating from smooth muscle tumors alone or in combination with β-catenin.

PMID:38085960 | DOI:10.1097/PGP.0000000000001001

Genome Biol Evol. 2023 Dec 12:evad213. doi: 10.1093/gbe/evad213. Online ahead of print.

ABSTRACT

Phylogenetics is now fundamental in life sciences, providing insights into the earliest branches of life and the origins and spread of epidemics. However, finding suitable phylogenies from the vast space of possible trees remains challenging. To address this problem, for the first time, we perform both tree exploration and inference in a continuous space where the computation of gradients is possible. This continuous relaxation allows for major leaps across tree space in both rooted and unrooted trees, and is less susceptible to convergence to local minima. Our approach outperforms the current best methods for inference on unrooted trees and, in simulation, accurately infers the tree and root in ultrametric cases. The approach is effective in cases of empirical data with negligible amounts of data, which we demonstrate on the phylogeny of jawed vertebrates. Indeed, only a few genes with an ultrametric signal were generally sufficient for resolving the major lineages of vertebrates. Optimisation is possible via automatic differentiation and our method presents an effective way forwards for exploring the most difficult, data-deficient phylogenetic questions.

PMID:38085949 | DOI:10.1093/gbe/evad213

Chem Rev. 2023 Dec 12. doi: 10.1021/acs.chemrev.3c00440. Online ahead of print.

ABSTRACT

Coordinative chain transfer polymerization, CCTP, is a degenerative chain transfer polymerization process that has a wide range of applications. It allows a highly controlled synthesis of polyolefins, stereoregular polydienes, and stereoregular polystyrene, including (stereo)block as well as statistical copolymers thereof. It also shows a green character by allowing catalyst economy during the synthesis of such polymers. CCTP notably allows the end functionalization of both the commodity and stereoregular specialty polymers aforementionned, control of the composition of statistical copolymers without adjusting the feed, and quantitative formation of 1-alkenes from ethene. A one-pot one-step synthesis of the original multiblock microstructures and architectures by chain shuttling polymerization (CSP) is also an asset of CCTP. This methodology takes advantage of the simultaneous presence of two catalysts of different selectivity toward comonomers that produce blocks of different composition/microstructure, while still allowing the chain transfer. This affords the production of highly performant functional polymers, such as thermoplastic elastomers and adhesives, among others. This approach has been extended to cyclic esters’ and ethers’ ring-opening polymerization, providing new types of multiblock microstructure. The present Review provides the state of the art in the field with a focus on the last 10 years.

PMID:38085864 | DOI:10.1021/acs.chemrev.3c00440

Curr Opin Anaesthesiol. 2023 Dec 1. doi: 10.1097/ACO.0000000000001335. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Randomized clinical trials, now commonplace and regarded as top-tier evidence, are actually a recent development. The first randomized trial took place in 1948, just six decades ago. As anticipated from a relatively young field, rapid progress continues in response to an ever-increasing number of medical questions that demand answers. We examine evolving methodologies in cardiac anesthesia clinical trials, focusing on the transition towards larger sample sizes, increasing use of pragmatic trial designs, and the innovative adoption of real-time automated enrollment and randomization. We highlight how these changes enhance the reliability and feasibility of clinical trials.

RECENT FINDINGS: Recent understanding in clinical trial methodology acknowledges the importance of large sample sizes, which increase the reliability of findings. As illustrated by P value fragility, small trials can mislead despite statistical significance. Pragmatic trials have gained prominence, offering real-world insights into the effectiveness of various treatments. Additionally, the use of real-time automated enrollment and randomization, particularly in situations where obtaining prior consent is impractical is an important methodological advance.

SUMMARY: The landscape of cardiac anesthesia clinical trials is rapidly evolving, with a clear trend towards large sample sizes and innovative approaches to enrollment. Recent developments enhance the quality and applicability of research findings, thus providing robust guidance to clinicians.

PMID:38085861 | DOI:10.1097/ACO.0000000000001335

Curr Opin Anaesthesiol. 2023 Dec 8. doi: 10.1097/ACO.0000000000001334. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: This review examines advances in clinical trial methodologies relevant to cardiac anesthesia. It focuses on innovative approaches, including factorial randomization, composite outcomes, and cluster randomized trials, which enhance the efficiency, practical relevance, and generalizability of trial outcomes.

RECENT FINDINGS: Factorial randomization is becoming popular because the approach allows investigators to simultaneously evaluate two or more interventions. Furthermore, factorial designs can evaluate interactions among treatments, which is highly relevant information that cannot be obtained from separate trials. Composite outcomes are also increasingly utilized, combining multiple individual outcomes into a single measure, which increases statistical power and can better represent relevant physiology. Designing valid composites requires careful consideration of component outcome severity and incidence. Cluster randomized trials, including stepped wedge and multiple crossover designs, are addressing the challenges of group-level effects and shared environments.

SUMMARY: The evolution of clinical trial designs is marked by a shift towards methodologies that enhance efficiency and provide more nuanced insights into treatment effects. These include factorial designs for simultaneous intervention assessment, composite outcomes for comprehensive physiological representation, and cluster trials for group-level effect analysis. Such advancements are shaping the future of clinical research, making it more relevant, efficient, and broadly applicable.

PMID:38085856 | DOI:10.1097/ACO.0000000000001334

Hell J Nucl Med. 2023 Dec 14:s002449912603. doi: 10.1967/s002449912603. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to evaluate the efficacy oflutetium-177-prostate-specific membrane antigen-617 (¹⁷⁷Lu-PSMA-617) with the luteinizing hormone releasing hormone (LHRH) analogues in the first or in the second-line setting formetastatic castration sensitive patients and metastatic castration resistance after progression with LHRH analogues.

SUBJECTS AND METHODS: Sixteen consecutive patients with high volume metastatic prostate cancer undergone ¹⁷⁷Lu-PSMA-617 therapy who were refused chemotherapy and were unable to use new generation anti-androgen drugs because of unavailibility of reimbursement, were included in this retrospective study. Prostate specific antigen (PSA) response (>50% decrease), disease control rate (DCR: complete or partial response), progression-free survival (PFS) and overall survival (OS) were calculated to evaluate according to the clinicopathological features of the patients. Treatment response evaluated by ⁶⁸Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT).

RESULTS: Mean age was 74,6 (SD±8,36). Among them, 7 (43,8%) patients has castration resistant disease, while the remaining has castration sensitive disease. Lutetium-177-PSMA-617 was administered to 10 (62,5%) patients as one of the first-line treatment and 6 patients received the treatment after progression on LHRH as a second-line treatment. Considering all patients, PSA response rate and DCR were 50% and 62% respectively. The median PFS and OS (with 95% CI) were 11,2 months (11-15) and 29 months (25,6-32,4), respectively in patients treated with ¹⁷⁷Lu-PSMA-617 and LHRH analogues. Clinicopathological features and basal PSA level did not have effect on PSA response rates, DCR, OS and PFS. On the other hand, increment in PFS and OS (with 95% CI) was observed in castration resistant disease and in the second-line therapy; for castration resistant disease 16,5 months (12.3-19.7); 30 months (25.3-32.7), for the second-line therapy 14.5 months (12-20.5); 29 months (NR), respectively but statistically not significant. Serious toxicity was observed in a limited number of patients (18,7%), treatment-related death was not observed.

CONCLUSION: Favorable results can be achived with second-line ¹⁷⁷Lu-PSMA-617 treatment in terms of OS and PFS, especially in castration-resistant disease, when chemotherapy and new generation ADT’s cannot be used.

PMID:38085834 | DOI:10.1967/s002449912603

J Proteome Res. 2023 Dec 12. doi: 10.1021/acs.jproteome.3c00512. Online ahead of print.

ABSTRACT

PMart is a web-based tool for reproducible quality control, exploratory data analysis, statistical analysis, and interactive visualization of ‘omics data, based on the functionality of the pmartR R package. The newly improved user interface supports more ‘omics data types, additional statistical capabilities, and enhanced options for creating downloadable graphics. PMart supports the analysis of label-free and isobaric-labeled (e.g., TMT, iTRAQ) proteomics, nuclear magnetic resonance (NMR) and mass-spectrometry (MS)-based metabolomics, MS-based lipidomics, and ribonucleic acid sequencing (RNA-seq) transcriptomics data. At the end of a PMart session, a report is available that summarizes the processing steps performed and includes the pmartR R package functions used to execute the data processing. In addition, built-in safeguards in the backend code prevent users from utilizing methods that are inappropriate based on omics data type. PMart is a user-friendly interface for conducting exploratory data analysis and statistical comparisons of omics data without programming.

PMID:38085827 | DOI:10.1021/acs.jproteome.3c00512

Int J Surg. 2023 Dec 4. doi: 10.1097/JS9.0000000000000908. Online ahead of print.

ABSTRACT

BACKGROUND: Undetectable occult liver metastases block the long-term survival of pancreatic ductal adenocarcinoma (PDAC). This study aimed to develop a radiomics-based model to predict occult liver metastases and assess its prognostic capacity for survival.

MATERIALS AND METHODS: Patients who underwent surgical resection and were pathologically proven with PDAC were recruited retrospectively from five tertiary hospitals between January 2015 and December 2020. Radiomics features were extracted from tumors, and the radiomics-based model was developed in the training cohort using LASSO-logistic regression. The model’s performance was assessed in the internal and external validation cohorts using the area under the receiver operating curve (AUC). Subsequently, the association of the model’s risk stratification with progression-free survival (PFS) and overall survival (OS) was then statistically examined using Cox regression analysis and the log-rank test.

RESULTS: A total of 438 patients (mean [standard deviation] age, 62.0 [10.0] years; 255 [58.2%] male) were divided into the training cohort (n = 235), internal validation cohort (n = 100), and external validation cohort (n = 103). The radiomics-based model yielded an AUC of 0.73 (95% confidence interval [CI]: 0.66-0.80), 0.72 (95% CI: 0.62-0.80), and 0.71 (95% CI: 0.61-0.80) in the training, internal validation, and external validation cohorts, respectively, which were higher than the preoperative clinical model. The model’s risk stratification was an independent predictor of PFS (all P < 0.05) and OS (all P < 0.05). Furthermore, patients in the high-risk group stratified by the model consistently had a significantly shorter PFS and OS at each TNM stage (all P < 0.05).

CONCLUSION: The proposed radiomics-based model provided a promising tool to predict occult liver metastases and had great significance in prognosis.

PMID:38085810 | DOI:10.1097/JS9.0000000000000908

Int J Surg. 2023 Dec 4. doi: 10.1097/JS9.0000000000000927. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT).

METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. We examined 367 patients with proximal GC who received NACT followed by PG (n=164) or TG (n=203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed.

RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P>0.05). The TG group had a higher total number of lymph nodes retrived (P<0.001) and longer operative time (P=0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (23.8%, 19/80) (P=0.850). The 5-year OS rates were 68.4% for the PG group and 66.0% for the TG group (P=0.881), while the 5-year RFS rates were 64.8% and 61.9%, respectively (P=0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74%, 0.67%, 1.33%, and 1.74%, respectively.

CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

PMID:38085808 | DOI:10.1097/JS9.0000000000000927

J Neurosci Nurs. 2023 Dec 12. doi: 10.1097/JNN.0000000000000745. Online ahead of print.

ABSTRACT

BACKGROUND: Stroke care partners and caregivers experience emotional and physical burden, and 80% of stroke patients need support after discharge. This study examines the relationship between caregiver preparedness and altruism levels of stroke patients. METHODS: The population of this descriptive and correlational study consisted of the caregivers of stroke patients who were hospitalized at the stroke center of a hospital between January 2021 and August 2021. The sample was determined as 240 with the known sampling formula. The descriptive information form, the Preparedness for Caregiving Scale, and the Altruism Scale were used to collect the study data. RESULTS: The total mean score of the caregivers’ preparedness to provide care was found to be 25.04 (7.36), and the mean total altruism score was 85.78 (9.20). The mean score of Donation, which is one of the subdimensions of the Altruism Scale, was 26.67 (4.08), and that of Helping Status was 59.10 (6.92). No statistically significant relationships were detected between caregivers’ preparedness to provide care scores, Helping Status scores, Donation scores, and total altruism scores in this study (P = .241, P = .245, and P = .129, respectively). CONCLUSION: No statistically significant relationships were detected between the preparedness and altruism levels of the caregivers of the stroke patients in this study.

PMID:38085795 | DOI:10.1097/JNN.0000000000000745