Category: Statistics

Int J Cancer. 2023 Dec 24. doi: 10.1002/ijc.34821. Online ahead of print.

ABSTRACT

Excess body mass index (BMI) is associated with a higher risk of at least 13 cancers, but it is usually measured at a single time point. We tested whether the overweight-years metric, which incorporates exposure time to BMI ≥25 kg/m² , is associated with cancer risk and compared this with a single BMI measure. We used adulthood BMI readings in the Atherosclerosis Risk in Communities (ARIC) study to derive the overweight-years metric. We calculated associations between the metric and BMI and the risk of cancers using Cox proportional hazards models. Models that either included the metric or BMI were compared using Harrell’s C-statistic. We included 13,463 participants, with 3,876 first primary cancers over a mean of 19 years (SD 7) of cancer follow-up. Hazard ratios for obesity-related cancers per standard deviation overweight-years were 1.15 (95% CI: 1.05-1.25) in men and 1.14 (95% CI: 1.08-1.20) in women. The difference in the C-statistic between models that incorporated BMI, or the overweight-years metric was non-significant in men and women. Overweight-years was associated with the risk of obesity-related cancers but did not outperform a single BMI measure in association performance characteristics.

PMID:38143298 | DOI:10.1002/ijc.34821

Mol Nutr Food Res. 2023 Dec 24:e2300286. doi: 10.1002/mnfr.202300286. Online ahead of print.

ABSTRACT

SCOPE: The glucosinolate glucoraphanin from broccoli is converted to sulforaphane (SFN) or sulforaphane-nitrile (SFN-NIT) by plant enzymes or the gut microbiome. Human feeding studies typically observe high inter-individual variation in absorption and excretion of SFN, however, the source of this variation is not fully known. To address this, a human feeding trial to comprehensively evaluate inter-individual variation in the absorption and excretion of all known SFN metabolites in urine, plasma, and stool, and tested the hypothesis that gut microbiome composition influences inter-individual variation in total SFN excretion has been conducted.

METHODS AND RESULTS: Participants (n = 55) consumed a single serving of broccoli or alfalfa sprouts and plasma, stool, and total urine are collected over 72 h for quantification of SFN metabolites and gut microbiome profiling using 16S gene sequencing. SFN-NIT excretion is markedly slower than SFN excretion (72 h vs 24 h). Members of genus Bifidobacterium, Dorea, and Ruminococcus torques are positively associated with SFN metabolite excretion while members of genus Alistipes and Blautia has a negative association.

CONCLUSION: This is the first report of SFN-NIT metabolite levels in human plasma, urine, and stool following consumption of broccoli sprouts. The results help explain factors driving inter-individual variation in SFN metabolism and are relevant for precision nutrition.

PMID:38143283 | DOI:10.1002/mnfr.202300286

Genome Med. 2023 Dec 25;15(1):107. doi: 10.1186/s13073-023-01252-w.

ABSTRACT

BACKGROUND: Despite the acceleration of somatic driver gene discovery facilitated by recent large-scale tumor sequencing data, the contribution of inherited variants remains largely unexplored, primarily focusing on previously known cancer predisposition genes (CPGs) due to the low statistical power associated with detecting rare pathogenic variant-phenotype associations.

METHODS: Here, we introduce a generalized log-regression model to measure the excess of pathogenic variants within genes in cancer patients compared to control samples. It aims to measure gene-level cancer risk enrichment by collapsing rare pathogenic variants after controlling the population differences across samples.

RESULTS: In this study, we investigate whether pathogenic variants in Mendelian disease-associated genes (OMIM genes) are enriched in cancer patients compared to controls. Utilizing data from PCAWG and the 1,000 Genomes Project, we identify 103 OMIM genes demonstrating significant enrichment of pathogenic variants in cancer samples (FDR 20%). Through an integrative approach considering three distinct properties, we classify these CPG-like OMIM genes into four clusters, indicating potential diverse mechanisms underlying tumor progression. Further, we explore the function of PAH (a key metabolic enzyme associated with Phenylketonuria), the gene exhibiting the highest prevalence of pathogenic variants in a pan-cancer (1.8%) compared to controls (0.6%).

CONCLUSIONS: Our findings suggest a possible cancer progression mechanism through metabolic profile alterations. Overall, our data indicates that pathogenic OMIM gene variants contribute to cancer progression and introduces new CPG classifications potentially underpinning diverse tumorigenesis mechanisms.

PMID:38143269 | DOI:10.1186/s13073-023-01252-w

Ann Surg Oncol. 2023 Dec 24. doi: 10.1245/s10434-023-14734-3. Online ahead of print.

NO ABSTRACT

PMID:38143265 | DOI:10.1245/s10434-023-14734-3

Hum Genet. 2023 Dec 24. doi: 10.1007/s00439-023-02627-0. Online ahead of print.

ABSTRACT

It remains challenging to translate the findings from genome-wide association studies (GWAS) of autoimmune diseases (AIDs) into interventional targets, presumably due to the lack of knowledge on how the GWAS risk variants contribute to AIDs. In addition, current immunomodulatory drugs for AIDs are broad in action rather than disease-specific. We performed a comprehensive protein-centric omics integration analysis to identify AIDs-associated plasma proteins through integrating protein quantitative trait loci datasets of plasma protein (1348 proteins and 7213 individuals) and totally ten large-scale GWAS summary statistics of AIDs under a cutting-edge systematic analytic framework. Specifically, we initially screened out the protein-AID associations using proteome-wide association study (PWAS), followed by enrichment analysis to reveal the underlying biological processes and pathways. Then, we performed both Mendelian randomization (MR) and colocalization analyses to further identify protein-AID pairs with putatively causal relationships. We finally prioritized the potential drug targets for AIDs. A total of 174 protein-AID associations were identified by PWAS. AIDs-associated plasma proteins were significantly enriched in immune-related biological process and pathways, such as inflammatory response (P = 3.96 × 10^-10). MR analysis further identified 97 protein-AID pairs with potential causal relationships, among which 21 pairs were highly supported by colocalization analysis (PP.H4 > 0.75), 10 of 21 were the newly discovered pairs and not reported in previous GWAS analyses. Further explorations showed that four proteins (TLR3, FCGR2A, IL23R, TCN1) have corresponding drugs, and 17 proteins have druggability. These findings will help us to further understand the biological mechanism of AIDs and highlight the potential of these proteins to develop as therapeutic targets for AIDs.

PMID:38143258 | DOI:10.1007/s00439-023-02627-0

Gen Thorac Cardiovasc Surg. 2023 Dec 25. doi: 10.1007/s11748-023-01991-y. Online ahead of print.

ABSTRACT

OBJECTIVES: Although several societies recommend regular chest computed tomography (CT) scans for the surveillance of surgically resected non-small cell lung cancer (NSCLC), there is paucity of evidence to support these statements. This study aimed to clarify whether regular CT scans improved the prognosis of patients with surgically resected NSCLC based on TNM 8th classification.

METHODS: Patients with pathologic Stage 0-III NSCLC who underwent complete surgical resection other than sublobar resection procedures were enrolled in the study. For these patients, clinicopathological data and postoperative surveillance data were collected by the retrospective review of medical records. Patients were categorized into the chest X-ray (CXR) group or the CT group according to whether they were followed-up with basic examinations including CXR or basic examinations plus regular chest CT. Postoperative overall survival was compared between the two groups.

RESULTS: Six hundred sixty five patients were categorized into the CXR (n = 245) and CT (n = 420) groups. The clinicopathological backgrounds did not differ to a statistically significant extent. Recurrence was seen in 68 (27.3%) patients in the CXR group and 117 (27.8%) patients in the CT group. The 5-year overall survival rates of the two groups did not differ to a statistically significant extent (CXR, 76.5%; CT, 78.3%, P = 0.22).

CONCLUSION: Regular chest CT scans may not improve the prognosis of surgically resected NSCLC. Further study is warranted to precisely evaluate the benefit of CT-based postoperative surveillance of NSCLC.

PMID:38143254 | DOI:10.1007/s11748-023-01991-y

Prog Orthod. 2023 Dec 25;24(1):44. doi: 10.1186/s40510-023-00496-x.

ABSTRACT

BACKGROUND: The aim of the study was to compare the accuracy and reproducibility of three different 3D facial scanning systems, relying, respectively, on stereophotogrammetry, structured light and a smartphone app and camera.

METHODS: Thirty subjects have been scanned with three different facial scanning systems, stereophotogrammetry, structured light and a smartphone app and camera. Linear measurements were compared with direct anthropometries measured on the patient’s face, while the study of areas (forehead, tip of the nose, chin, right and left cheek) was evaluated by overlapping scans using the Geomagic Control X program. Statistical analyses were conducted using IBM SPSS v28 software.

RESULTS: The ANOVA test was used to compare linear distances and direct anthropometry measurements, revealing statically significant values for all distances investigated, especially for the Face Hunter scanner, except for the Prn-Pog’ distance (p = 0.092). The three facial scans were superimposed pairwise almost the 100 per cent of the overlapping areas fell within the tolerance limits for all three comparisons analysed. The chin was the most accurately reproduced, with no differences among scanners, while the forehead proved to be the least accurately reproduced by all scanners.

CONCLUSIONS: All three acquisition systems proved to be effective in capturing 3D images of the face, with the exception of the Face Hunter scanner, that produced statistically significant differences in linear measurements for the distances Tr-Na’ and Zyg-Zyg with respect to direct anthropometric measurements.

PMID:38143253 | DOI:10.1186/s40510-023-00496-x

Pharmacotherapy. 2023 Dec 24. doi: 10.1002/phar.2903. Online ahead of print.

ABSTRACT

INTRODUCTION: The introduction of the highly effective modulator therapy elexacaftor-tezacaftor-ivacaftor (ETI) has revolutionized the care of persons with cystic fibrosis (PwCF) with major improvements seen in lung function and body mass index (BMI). Effects of ETI therapy in real-world cohorts on other parameters such as cholesterol levels are largely unknown.

METHODS: A single-center, retrospective chart review study was conducted to assess the change in lipid panels before and after ETI initiation. The study investigated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels using both a univariate and multivariate mixed-effects model to evaluate the change after initiation of ETI in a cohort of PwCF.

RESULTS: There were 128 adult PwCF included in the analysis. Statistically significant changes were seen in both univariate and multivariate analyses for TC, LDL-C, and HDL-C. On multivariate analysis, TC increased by an average of 15.0 mg/dL after ETI initiation (p<0.0001), LDL-C increased by an average of 9.3 mg/dL (p<0.001), and HDL-C increased by an average of 3.8 mg/dL (p < 0.001) after ETI initiation.

CONCLUSION: In this real-world cohort of PwCF, cholesterol parameters increased after initiation with ETI therapy. Further consideration may need to be given for PwCF in regards to screening for cardiometabolic risk factors as PwCF age as well as the potential need for cholesterol-lowering therapies.

PMID:38143243 | DOI:10.1002/phar.2903

Clin Radiol. 2023 Dec 9:S0009-9260(23)00576-7. doi: 10.1016/j.crad.2023.11.022. Online ahead of print.

ABSTRACT

AIM: To identify similarities and differences in the visual (VA) and automated assessment (AA) of systemic sclerosis-related interstitial lung disease (SSc-ILD) at chest computed tomography (CT) in terms of clinical applicability.

MATERIALS AND METHODS: Medline, Embase, and Web of Science were searched to identify all studies investigating VA and AA for SSc-ILD assessment, from inception to 31 July 2022. Exclusion criteria were manuscripts not in English, absence of full-text, reviews, diseases other than ILD in SSc, CT not analysed with both VA and AA, VA and AA not adopted for the same purpose or not compared, overlap syndromes, SSc-ILD data were not extractable separately, and studies with <10 patients.

RESULTS: Ten full-text studies (804 patients) were included. The most adopted VAs were the Warrick or Goh score (four studies each), while densitometry (eight studies) or lung texture analysis (LTA, two studies) were utilised during AA. The main field of investigation was the correlation with baseline pulmonary function tests (PFT, six studies). Warrick VA showed lower correlations compared to densitometry, while Goh VA resulted in similar or stronger coefficients. Compared to LTA, Goh VA obtained lower correlations with lung volumes but stronger coefficients with alveolar diffusibility.

CONCLUSIONS: VA and AA showed heterogeneous results comparing their correlations with PFT, probably depending on the specific analysis adopted for each method. More data are needed on VA versus LTA. Comparisons between VA and AA regarding correlation with PFT follow-up and as prognosticators and for disease monitoring are lacking. AAs in progressive fibrosis diagnosis remain to be tested.

PMID:38143228 | DOI:10.1016/j.crad.2023.11.022

Semin Perinatol. 2023 Dec 19:151873. doi: 10.1016/j.semperi.2023.151873. Online ahead of print.

ABSTRACT

The National Vital Statistics System is the primary source of information on fetal deaths of 20 weeks of gestation or more in the United States. Data are cooperatively produced by jurisdiction vital statistics offices and the National Center for Health Statistics. In order to promote the uniformity of data, the National Center for Health Statistics issues The Model State Vital Statistics Act and Regulations, and produces standard certificates and reports, developed in collaboration with the states, to inform the development of jurisdictional vital records laws and regulations and data collection. While there are challenges in collecting national fetal death data, there are ongoing data quality improvement efforts to address them. Improved national fetal death data and data from other sources will continue to add insights into the risks, causes and prevention of fetal death.

PMID:38143212 | DOI:10.1016/j.semperi.2023.151873