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Nevin Manimala Statistics

Association of Ultrasonography Features of Follicular Thyroid Carcinoma With Tumor Invasiveness and Prognosis Based on WHO Classification and TERT Promoter Mutation

Korean J Radiol. 2024 Jan;25(1):103-112. doi: 10.3348/kjr.2023.0461.

ABSTRACT

OBJECTIVE: To investigate the association of ultrasound (US) features of follicular thyroid carcinoma (FTC) with tumor invasiveness and prognosis based on the World Health Organization (WHO) classification and telomerase reverse transcriptase (TERT) promoter mutations.

MATERIALS AND METHODS: This retrospective study included 54 surgically confirmed FTC patients with US images and TERT promoter mutations (41 females and 13 males; median age [interquartile range], 40 years [30-51 years]). The WHO classification consisted of minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTCs. Alternative classifications included Group 1 (MI-FTC and EA-FTC with wild type TERT), Group 2 (WI-FTC with wild type TERT), and Group 3 (EA-FTC and WI-FTC with mutant TERT). Each nodule was categorized according to the US patterns of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American College of Radiology-TIRADS (ACR-TIRADS). The Jonckheere-Terpstra and Cochran-Armitage tests were used for statistical analysis.

RESULTS: Among 54 patients, 29 (53.7%) had MI-FTC, 16 (29.6%) had EA-FTC, and nine (16.7%) had WI-FTC. In both the classifications, lobulation, irregular margins, and final assessment categories showed significant differences (all Ps ≤ 0.04). Furthermore, the incidences of lobulation, irregular margin, and high suspicion category tended to increase with increasing tumor invasiveness and worse prognosis (all Ps for trend ≤ 0.006). In the WHO groups, hypoechogenicity differed significantly among the groups (P = 0.01) and tended to increase in proportion as tumor invasiveness increased (P for trend = 0.02). In the alternative group, punctate echogenic foci were associated with prognosis (P = 0.03, P for trend = 0.03).

CONCLUSION: Increasing tumor invasiveness and worsening prognosis in FTC based on the WHO classification and TERT promoter mutation results were positively correlated with US features that indicate malignant probability according to both K-TIRADS and ACR-TIRADS.

PMID:38184773 | DOI:10.3348/kjr.2023.0461

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The role of implants and implant prostheses on the accuracy and artifacts of cone-beam computed tomography: an in-vitro study

Sci Rep. 2024 Jan 6;14(1):704. doi: 10.1038/s41598-024-51293-3.

ABSTRACT

To assess the accuracy of CBCT in implant-supported prostheses and to evaluate metal artifacts with and without implants or implant prostheses. Accuracy and artifacts were assessed in the dried mandible at three points on the buccal and lingual cortical plates on the mandible’s body near the crest and the base. On the buccal cortical plate, these points were labelled as A, B and C near the crest and D, E and F near the base of the body of the mandible. Similarly, points a to f were marked on the lingual cortical plate corresponding to points A to F. The study had two control groups, C0 for physical linear measurement (PLM) and C1 for radiographic linear measurement (RLM) and artifact assessment. There were seven test groups, TG 1 to 7, progressing from a single implant to implant full-arch prosthesis. For accuracy assessment, PLM was compared to RLM. CBCT artifacts were investigated in images integrated at 0.25 mm, 10 mm, and 20 mm at regions of interest on concentric circles at different intersecting angles by comparing grayscale values at C1 and TG1 to 7. The data were collected and statistically analyzed. A significant difference was observed between C0 and C1, and RLM in test groups at the superior axial plane. Similarly, PLM and test RLM in the sagittal plane at A-B, B-C, and D-E were statistically significant. A significant difference between PLM and RLM was also observed in the vertical plane at A-D, B-E, and C-F. Quantification of CBCT artifacts in the presence of implants or prostheses revealed that full-arch prostheses had the highest mean grayscale value, whereas single implants with a prosthesis had the lowest. The mean grayscale change was greatest around the implant and implant prosthesis. The mean grayscale value was maximum at 20 mm voxel integration scales (VIS) and lowest at 0.25 mm. CBCT is a clinically reliable device. Metal in implants or implant-supported prostheses prevents true assessment of the peri-implant area; therefore, lower VIS is suggested in the presence of implants or implant prostheses.

PMID:38184751 | DOI:10.1038/s41598-024-51293-3

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The death rate of COVID-19 infection in different SARS-CoV-2 variants was related to C-reactive protein gene polymorphisms

Sci Rep. 2024 Jan 6;14(1):703. doi: 10.1038/s41598-024-51422-y.

ABSTRACT

The serum level of C-reactive protein (CRP) is a significant independent risk factor for Coronavirus disease 2019 (COVID-19). A link was found between serum CRP and genetic diversity within the CRP gene in earlier research. This study examined whether CRP rs1205 and rs1800947 polymorphisms were associated with COVID-19 mortality among various severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) variants. We genotyped CRP rs1205 and rs1800947 polymorphisms in 2023 deceased and 2307 recovered patients using the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the recovered and the deceased patients in terms of the minor allele frequency of CRP rs1205 T and rs1800947 G. In all three variants, COVID-19 mortality rates were associated with CRP rs1800947 GG genotype. Furthermore, CRP rs1205 CC and rs1800947 GG genotypes showed higher CRP levels. It was found that the G-T haplotype was prevalent in all SARS-CoV-2 variants. The C-C and C-T haplotypes were statistically significant in Delta and Omicron BA.5 variants, respectively. In conclusion, polymorphisms within the CRP gene may relate to serum CRP levels and mortality among COVID-19 patients. In order to verify the utility of CRP polymorphism correlation in predicting COVID-19 mortality, a replication of these results is needed.

PMID:38184750 | DOI:10.1038/s41598-024-51422-y

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ECP versus ruxolitinib in steroid-refractory chronic GVHD – a retrospective study by the EBMT transplant complications working party

Bone Marrow Transplant. 2024 Jan 6. doi: 10.1038/s41409-023-02174-2. Online ahead of print.

ABSTRACT

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can’t replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.

PMID:38184740 | DOI:10.1038/s41409-023-02174-2

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Functional and structural characteristics in patients with type 3 macular neovascularisation treated with anti-VEGF. Three-year results in real world settings

Eye (Lond). 2024 Jan 6. doi: 10.1038/s41433-023-02918-w. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the long-term anatomical and functional outcomes of anti-Vascular Endothelial Growth Factor intravitreal injections (anti-VEGF IVI) in patients with type 3 macular neovascularisation (MNV) in real-world settings.

METHODS: Retrospective review of patients with type 3 MNV who received anti-VEGF IVI between 2013 and 2020. Primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcome was the development of new-onset of foveal-involving geographic atrophy (GA) and disciform scars.

RESULTS: We identified 59 eyes from 48 British patients that met the inclusion criteria. Treatment with anti- VEGF IVI resulted in a statistically significant reduction in median CMT, which was maintained throughout the study period. At 36 months, 24 eyes showed more than 50 μm reduction in CMT, 7 eyes remained stable and only 2 eyes showed an increase in CMT by more than 50μm compared to the baseline. At year three, deterioration was noticed in most eyes (52.78%) and vision remained stable or improved in 47.22% of the eyes. However, the median BCVA was not statistically significant different compared to baseline. During the study period new onset of macula-involving atrophy or scar was noted in 10.2% and 4.3% of the eyes, respectively.

CONCLUSION: In this real-world study, anatomic and functional improvement were recorded 12-months post anti-VEGF IVI in type 3 MNV. Despite sustained anatomical improvement, vision returned back to baseline levels at 36-months. The development of GA and macular scar was only partially responsible for this outcome suggesting a more severe nature of this form of nAMD.

PMID:38184726 | DOI:10.1038/s41433-023-02918-w

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Effects of AST-120 on mortality in patients with chronic kidney disease modeled by artificial intelligence or traditional statistical analysis

Sci Rep. 2024 Jan 6;14(1):738. doi: 10.1038/s41598-024-51498-6.

ABSTRACT

Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120’s impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p < 0.0001) and a reduced prevalence of ESRD (44.16% vs. 53.17%, p = 0.0005). Propensity score matching at 1:1 and 1:2 revealed no significant differences, except for dialysis and all-cause mortality, where AST-120 users exhibited significantly lower all-cause mortality (p < 0.0001), with a hazard ratio (HR) of 0.395 (95% CI = 0.295-0.522). This difference remained statistically significant even after propensity matching. In terms of model performance, the XGBoost model demonstrated the highest accuracy (0.72), specificity (0.90), and positive predictive value (0.48), while the logistic regression model showed the highest sensitivity (0.63) and negative predictive value (0.84). The area under the curve (AUC) values for logistic regression, DNN, and XGBoost were 0.73, 0.73, and 0.69, respectively, indicating similar predictive capabilities for mortality. In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm.

PMID:38184721 | DOI:10.1038/s41598-024-51498-6

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An innovative staged prosthetic lengthening reconstruction strategy for osteosarcoma-related leg discrepancy

Sci Rep. 2024 Jan 6;14(1):717. doi: 10.1038/s41598-023-50422-8.

ABSTRACT

Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6-15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1-14.2) before the lengthening to 0.3 cm (- 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%-53.3%) before the lengthening to 96.3% (86.7%-100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.

PMID:38184715 | DOI:10.1038/s41598-023-50422-8

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A proof of concept study on reliability assessment of different metal foil length based piezoelectric sensor for electromechanical impedance techniques

Sci Rep. 2024 Jan 6;14(1):699. doi: 10.1038/s41598-023-49762-2.

ABSTRACT

Lead zirconate titanate (PZT) patches gained popularity in structural health monitoring (SHM) for its sensing and cost effective. However, a robust installation of PZT patches is challenging due to the often-complex geometry and non-accessibility of structural parts. For tubular structures, the curved surface can compromise the perfect bonding of PZT patches. To alleviate the above-mentioned challenges, the non-bonded and reusable configuration of sensor received considerable interest in the field of SHM. However, ensuring the repeatability and reproducibility of Electro-Mechanical Impedance (EMI) measurements is crucial to establish the reliability of these techniques. This work investigated the repeatability and reproducibility measures for one of non-bonded configuration of PZT patch i.e., Metal Foil Based Piezo Sensor (MFBPS). In addition, the concept, application, and suitability of MFBPS for impedance-based monitoring technique of Civil infrastructure are critically discussed. This study evaluates the effect of length of MFBPS on piezo coupled admittance signature. Also, this study evaluates repeatability and reproducibility of EMI measurements via statistical tools such as ANOVA and Gage R&R analysis. The statistical index CCDM was used to quantify the deviations of impedance signals. The overall result shows that the repeatability of the EMI measurements improves with a metal foil length of 500 mm. Overall, this investigation offers a useful point of reference for professionals and scholars to ensure the reliability of MFBPS for EMI techniques, a variant of piezoelectric sensor for SHM applications.

PMID:38184698 | DOI:10.1038/s41598-023-49762-2

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OXTR polymorphisms associated with severity and treatment responses of schizophrenia

Schizophrenia (Heidelb). 2024 Jan 6;10(1):7. doi: 10.1038/s41537-023-00413-5.

ABSTRACT

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = -0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

PMID:38184684 | DOI:10.1038/s41537-023-00413-5

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Minimally sufficient experimental design using identifiability analysis

NPJ Syst Biol Appl. 2024 Jan 6;10(1):2. doi: 10.1038/s41540-023-00325-1.

ABSTRACT

Mathematical models are increasingly being developed and calibrated in tandem with data collection, empowering scientists to intervene in real time based on quantitative model predictions. Well-designed experiments can help augment the predictive power of a mathematical model but the question of when to collect data to maximize its utility for a model is non-trivial. Here we define data as model-informative if it results in a unique parametrization, assessed through the lens of practical identifiability. The framework we propose identifies an optimal experimental design (how much data to collect and when to collect it) that ensures parameter identifiability (permitting confidence in model predictions), while minimizing experimental time and costs. We demonstrate the power of the method by applying it to a modified version of a classic site-of-action pharmacokinetic/pharmacodynamic model that describes distribution of a drug into the tumor microenvironment (TME), where its efficacy is dependent on the level of target occupancy in the TME. In this context, we identify a minimal set of time points when data needs to be collected that robustly ensures practical identifiability of model parameters. The proposed methodology can be applied broadly to any mathematical model, allowing for the identification of a minimally sufficient experimental design that collects the most informative data.

PMID:38184643 | DOI:10.1038/s41540-023-00325-1