Tag: nevin manimala

BMC Res Notes. 2023 Jul 30;16(1):159. doi: 10.1186/s13104-023-06438-4.

ABSTRACT

OBJECTIVE: To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking.

RESULT: A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model. We then implemented the linear model to create a GWAS of paternal smoking by subtracting the summary statistics from a GWAS of maternal smoking from the summary statistics of a GWAS of the index individual’s smoking. We used a Monte-Carlo simulation to validate the model and showed that this approach performed similarly in terms of bias to performing a traditional GWAS of paternal smoking. Finally, we validated the summary statistics in a Mendelian randomisation analysis by demonstrating an association of genetically predicted paternal smoking with paternal lung cancer and emphysema.

PMID:37518004 | DOI:10.1186/s13104-023-06438-4

Aging (Albany NY). 2023 Jul 28;15. doi: 10.18632/aging.204910. Online ahead of print.

ABSTRACT

PURPOSE: Chronic inflammation and lipid peroxidation (LPO) are associated with the pathogenesis of hepatocellular carcinoma (HCC), and γ-hydroxy-1, N²-propanodeoxyguanosine (γ-OHPdG) is a promutagenic DNA adduct derived from LPO. This study aimed to examine the relationship between γ-OHPdG and the progression of liver carcinogenesis.

METHODS: Primary HCC specimens were obtained from 228 patients and cirrhosis specimens from 46 patients. The patients were followed up with after surgery via outpatient visits and telephone calls. The levels of γ-OHPdG were determined by immunohistochemical analysis in the carcinomatous tissues together with adjacent and cirrhosis tissues.

RESULTS: γ-OHPdG levels in the cancerous tissues were significantly higher compared to adjacent tissues (P < 0.001) and also higher than the ones from the tissues of cirrhosis patients. Along with tumor size, histological grade, MVI grade, T stage, the percentage of ki67-positive cells and HCC progression, γ-OHPdG levels in cancerous tissues showed a gradually increasing trend. Moreover, prognostic analysis showed that higher γ-OHPdG levels in cancerous tissues were strongly correlated with lower overall survival (P < 0.001), lower intrahepatic recurrence-free survival (P < 0.001) and lower distant metastasis-free survival (P < 0.05). There was a trend, although not statistically significant, of increased levels of γ-OHPdG in cirrhosis cases that advanced to HCC, whereas γ-OHPdG levels reversely correlated with the period of time observed for cirrhosis advanced to HCC.

CONCLUSIONS: These results suggest that γ-OHPdG is a prognostic biomarker for predicting outcomes in HCC, and may serve as a prospective indicator for predicting HCC in cirrhosis patients.

PMID:37517089 | DOI:10.18632/aging.204910

Med Phys. 2023 Jul 30. doi: 10.1002/mp.16657. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the nonlinear nature of the logarithmic operation and the stochastic nature of photon counts (N), sinogram data of photon counting detector CT (PCD-CT) are intrinsically biased, which leads to statistical CT number biases. When raw counts are available, nearly unbiased statistical estimators for projection data were developed recently to address the CT number bias issue. However, for most clinical PCD-CT systems, users’ access to raw detector counts is limited. Therefore, it remains a challenge for end users to address the CT number bias issue in clinical applications.

PURPOSE: To develop methods to correct statistical biases in PCD-CT without requiring access to raw PCD counts.

METHODS: (1) The sample variance of air-only post-log sinograms was used to estimate air-only detector counts, ${\overline{N}}_0$ . (2) If the post-log sinogram data, y, is available, then N of each detector pixel was estimated using $N={\overline{N}}_0{e}^{–y}$ . Once N was estimated, a closed-form analytical bias correction was applied to the sinogram. (3) If a patient’s post-log sinogram data are not archived, a forward projection of the bias-contaminated CT image was used to perform a first-order bias correction. Both the proposed sinogram domain- and image domain-based bias correction methods were validated using experimental PCD-CT data.

RESULTS: Experimental results demonstrated that both sinogram domain- and image domain-based bias correction methods enabled reduced-dose PCD-CT images to match the CT numbers of reference-standard images within [-5, 5] HU. In contrast, uncorrected reduced-dose PCD-CT images demonstrated biases ranging from -25 to 55 HU, depending on the material. No increase in image noise or spatial resolution degradation was observed using the proposed methods.

CONCLUSIONS: CT number bias issues can be effectively addressed using the proposed sinogram or image domain method in PCD-CT, allowing PCD-CT acquired at different radiation dose levels to have consistent CT numbers desired for quantitative imaging.

PMID:37517080 | DOI:10.1002/mp.16657

Med Phys. 2023 Jul 30. doi: 10.1002/mp.16597. Online ahead of print.

ABSTRACT

BACKGROUND: Microvascular invasion (MVI) is a major risk factor, for recurrence and metastasis of hepatocellular carcinoma (HCC) after radical surgery and liver transplantation. However, its diagnosis depends on the pathological examination of the resected specimen after surgery; therefore, predicting MVI before surgery is necessary to provide reference value for clinical treatment. Meanwhile, predicting only the existence of MVI is not enough, as it ignores the degree, quantity, and distribution of MVI and may lead to MVI-positive patients suffering due to inappropriate treatment. Although some studies have involved M2 (high risk of MVI), majority have adopted the binary classification method or have not included radiomics.

PURPOSE: To develop three-class classification models for predicting the grade of MVI of HCC by combining enhanced computed tomography radiomics features with clinical risk factors.

METHODS: The data of 166 patients with HCC confirmed by surgery and pathology were analyzed retrospectively. The patients were divided into the training (116 cases) and test (50 cases) groups at a ratio of 7:3. Of them, 69 cases were MVI positive in the training group, including 45 cases in the low-risk group (M1) and 24 cases in the high-risk group (M2), and 47 cases were MVI negative (M0). In the training group, the optimal subset features were obtained through feature selection, and the arterial phase radiomics model, portal venous phase radiomics model, delayed phase radiomics model, three-phase radiomics model, clinical imaging model, and combined model were developed using Linear Support Vector Classification. The test group was used for validation, and the efficacy of each model was evaluated through the receiver operating characteristic curve (ROC).

RESULTS: The clinical imaging features of MVI included alpha-fetoprotein, tumor size, tumor margin, peritumoral enhancement, intratumoral artery, and low-density halo. The area under the curve (AUC) of the ROC values of the clinical imaging model for M0, M1, and M2 were 0.831, 0.701, and 0.847, respectively, in the training group and 0.782, 0.534, and 0.785, respectively, in the test group. After combined radiomics analyis, the AUC values for M0, M1, and M2 in the test group were 0.818, 0.688, and 0.867, respectively. The difference between the clinical imaging model and the combined model was statistically significant (p = 0.029).

CONCLUSION: The clinical imaging model and radiomics model developed in this study had a specific predictive value for HCC MVI grading, which can provide precise reference value for preoperative clinical diagnosis and treatment. The combined application of the two models had a high predictive efficacy.

PMID:37517073 | DOI:10.1002/mp.16597

Fetal Pediatr Pathol. 2023 Jul 30:1-12. doi: 10.1080/15513815.2023.2241903. Online ahead of print.

ABSTRACT

Introduction: Metachronous mucoepidermoid carcinomas (MMEC) may occur in association with childhood leukemias and lymphomas. We compared molecular abnormalities of MMEC in patients with ALL with the abnormalities found in primary mucoepidermoid carcinomas (MECs) in pediatric cases and young adults. Materials and methods: Immunohistochemical stains for p63 and SOX10, molecular alterations in MAML2 and KMT2A genes detected by FISH and/or next-generation sequencing were studied in 12 pediatric MMECs secondary to ALL and six primary MECs in pediatric patients and young adults. Follow-up information of patients in both groups was obtained. Results: KMT2A rearrangements were detected in pediatric MMECs, and they were associated with remarkable histomorphological changes, including deposits of abundant stromal collagen and intratumoral lymphoid proliferations. No KMT2A rearrangements were found in primary MECs. The prognosis of MMEC in patients with ALL, especially in KMT2A-rearranged cases, was worse than in primary MECs. Kruskal-Wallis test showed a statistically significant difference in overall survival between KMT2A-rearranged MMECs and KMT2A-intact MMECs in cases with ALL (p = 0.027). Conclusion: KMT2A-rearranged MMECs in ALL patients may have inherently more aggressive behavior, even when the histomorphology of MMEC suggests a low-grade malignancy.

PMID:37517063 | DOI:10.1080/15513815.2023.2241903

Arch Dermatol Res. 2023 Jul 30. doi: 10.1007/s00403-023-02679-2. Online ahead of print.

ABSTRACT

Eyebrows are an important feature of facial identity and communications in human beings as well as an important eye defense shield from dust and foreign bodies. To compare the efficacy and safety between 0.01%, 0.03% bimatoprost and minoxidil 2% in gel formulations for eyebrow enhancement. Sixty eligible subjects were female or male, aged 18 years or older with eyebrow hypotrichosis, defined as either a Grade 1 or 2 on the Global Eyebrow Assessment (GEBA) scale. Patients were randomized into 3 groups using block randomization. Group a (20 patients) applied topical 0.03% bimatoprost gel once daily onto both eyebrows, group b (20 patients) applied topical 0.01% bimatoprost gel once daily onto both eyebrows while group c (20 patients) applied topical minoxidil 2% gel once daily onto both eyebrows. A significant improvement in GEBA score was reported in all the three groups after treatment (P ≤ 0.001); however, there was no statistically significant difference between the three groups (P1 = 0.091; P2 = 0.102; P3 = 0.663). Bimatoprost is equally efficacious as minoxidil in enhancement of eyebrows with a more favorable response produced by the 0.03% concentration.

PMID:37517060 | DOI:10.1007/s00403-023-02679-2

J Math Biol. 2023 Jul 30;87(2):34. doi: 10.1007/s00285-023-01965-x.

ABSTRACT

Inversions, also sometimes called reversals, are a major contributor to variation among bacterial genomes, with studies suggesting that those involving small numbers of regions are more likely than larger inversions. Deletions may arise in bacterial genomes through the same biological mechanism as inversions, and hence a model that incorporates both is desirable. However, while inversion distances between genomes have been well studied, there has yet to be a model which accounts for the combination of both deletions and inversions. To account for both of these operations, we introduce an algebraic model that utilises partial permutations. This leads to an algorithm for calculating the minimum distance to the most recent common ancestor of two bacterial genomes evolving by inversions (of adjacent regions) and deletions. The algebraic model makes the existing short inversion models more complete and realistic by including deletions, and also introduces new algebraic tools into evolutionary distance problems.

PMID:37517046 | DOI:10.1007/s00285-023-01965-x

Fa Yi Xue Za Zhi. 2023 Jun 25;39(3):296-304. doi: 10.12116/j.issn.1004-5619.2022.520602.

ABSTRACT

OBJECTIVES: To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage.

METHODS: Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed.

RESULTS: Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6.

CONCLUSIONS: Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.

PMID:37517019 | DOI:10.12116/j.issn.1004-5619.2022.520602

Knee Surg Sports Traumatol Arthrosc. 2023 Jul 30. doi: 10.1007/s00167-023-07509-6. Online ahead of print.

ABSTRACT

PURPOSE: The Attune^® total knee arthroplasty system was introduced in 2013 to address lingering issues of patient dissatisfaction. However, recent literature reports concerns of early tibial tray debonding. The aim of this study was to compare the incidence of radiolucent lines, survivorship and patient reported outcome-measures between the Attune^® system and the well-established Triathlon^® system.

METHODS: This retrospective database review was conducted at a single institution in Cork, Ireland. All primary Attune^® (N = 445) and Triathlon^® (N = 285) systems implanted between 2015 and 2016 were reviewed. Radiolucent lines were assessed for those with a minimum two-year radiological follow-up (Attune^® = 338; Triathlon^® = 231). X-rays were taken post op, at 6 months, 2 years and 5 years. Radiolucent lines were documented using the Modern Knee Society Radiographic System. Five-year survival was assessed using Kaplan-Meier analysis with the Log Rank method to determine statistical significance. The Oxford Knee Score and EQ-5D-5L, were collected pre-op, at 6 months, 2 years and 5 years post-operatively and compared using the Kruskal-Wallis Test.

RESULTS: The Attune^® had a higher proportion of radiolucent lines at the tibial tray [87.1% (54/62) vs 61.4% (27/44); p = 0.001] and at the implant-cement interface [62.9% (39/62) vs 43.2% (19/44); p = 0.02]. Conversely, the Triathlon^® had a higher proportion AT the femur [38.6% (17/44) vs 12.9% (8/62); p = 0.001] and at the cement-bone interface [56.8% (25/44) vs 37.1% (23/62); p = 0.02]. The overall frequency of radiolucent lines was similar in both the Attune^® and Triathlon^® groups [17.8%, (60/338) vs 17.7%, (41/231); p = 0.49]. There was no difference in revision-free survival analysis at 5 years (Attune^® 97.8% vs Triathlon^® 95.8%; p = 0.129). The Attune^® performed better at 5 years in the Oxford Knee Score [Attune^® = 42.6 (SD 5.2) vs Triathlon^® = 41 (SD 6.4); p = 0.001] and in the EQ-5D [Attune^® = 0.773 (SD 0.187) vs Triathlon^® = 0.729 (SD 0.218); p = 0.013]. There was no difference at 5 years in the EQ-VAS [Attune^® = 80.4 (SD 13.7) vs Triathlon^® = 78.5 (SD 15.3); p = 0.25].

CONCLUSION: The Attune^® system exhibited a higher incidence of radiolucent lines at the tibial tray. However, this did not lead to decreased survivorship at medium term follow-up compared to the Triathlon^®. Furthermore, improvements in patient reported outcomes modestly favoured the Attune^® system.

LEVEL OF EVIDENCE: III.

PMID:37516985 | DOI:10.1007/s00167-023-07509-6

J Cancer Res Clin Oncol. 2023 Jul 30. doi: 10.1007/s00432-023-05195-y. Online ahead of print.

ABSTRACT

PURPOSE: In this study, we aimed at profiling of luminal B breast cancer specific gene expression pattern in Indian women using mRNA-seq and validation based on TCGA expression data.

METHODS: RNA isolated from luminal B tumor and adjacent normal tissues was used for library construction and sequencing. Reference-based assemblies of these reads were used for differential gene expression analysis using DeSeq2. The DEGs were evaluated using TCGA expression data. Kaplan-Meier survival method was used to evaluate association between genes showing luminal B specific differential expression pattern and breast cancer prognosis and statistical significance was assessed using log-rank test. Alternate splicing analysis was done using rmats.

RESULTS: Differential expression analysis identified 2371 differentially expressed genes (DEGs) in luminal B breast tumors in comparison with adjacent normal tissues of Indian Women. Of them, 1692 DEGs were validated using TCGA luminal B paired samples. Integration of this data with the DEGs obtained by comparative analysis of unpaired luminal B with luminal A unpaired samples from TCGA resulted in 291 DEGs showing luminal B specific expression pattern. Further, 26 genes of prognostic value were identified. Differential splicing analysis between luminal B tumors and adjacent normal tissues in our cohort led to the identification of 687 genes showing significant differential alternate splicing events.

CONCLUSION: This study profiled gene expression pattern of luminal B tumors of Indian women and identified 26 key genes of prognostic value for luminal B breast cancer. This study also profiled differential alternate splicing and identified important alternate splicing events in luminal B breast cancer.

PMID:37516983 | DOI:10.1007/s00432-023-05195-y