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Nevin Manimala Statistics

Efficacy of the positioning system when measuring canine intraocular pressures with the Reichert® Tono-Vera® Vet rebound tonometer

Vet Ophthalmol. 2023 Nov 12. doi: 10.1111/vop.13161. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare intraocular pressure (IOP) measurements in dogs taken with the Reichert® Tono-Vera® Vet rebound tonometer with and without the automatic positioning system.

ANIMALS STUDIED: Measurements were taken on 49 eyes from 26 Beagle-derived dogs with variable genetics-four non-glaucomatous and 22 ADAMTS10-mutant dogs affected with different stages of open-angle glaucoma. Seventeen of the 26 dogs were measured 2-4 times on different days with variable intervals since IOP-lowering medications were administered.

PROCEDURES: In each dog, tonometry was performed with the Tono-Vera® Vet using three different methods in a randomized order: (Method 1) Average of three readings with an automatic positioning system; (Method 2) one reading with an automatic positioning system; and (Method 3) average of three readings obtained without the automatic positioning system. Statistical analyses included one-way ANOVA, Tukey pairwise comparisons, and Bland-Altman plots (MiniTab®).

RESULTS: With each of the three tonometry methods, 116 measurements were taken, resulting in 348 total IOP measurements with a range of 12.8-49.9 mmHg. The means and standard deviations for each method were 25.4 ± 6.9 mmHg (Method 1), 26.0 ± 7.2 mmHg (Method 2), and 26.9 ± 7.7 mmHg (Method 3), with no significant differences (p = .27). Mean IOP variances were also not significantly different between tonometry methods (p = .24 to .78).

CONCLUSIONS: Because mean IOPs and their standard deviations were not statistically different between the three tonometry methods, we conclude that Tono-Vera® Vet measurements conducted without the aid of the positioning system still provide reliable results.

PMID:37952123 | DOI:10.1111/vop.13161

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European Health Data & Evidence Network-learnings from building out a standardized international health data network

J Am Med Inform Assoc. 2023 Nov 10:ocad214. doi: 10.1093/jamia/ocad214. Online ahead of print.

ABSTRACT

OBJECTIVE: Health data standardized to a common data model (CDM) simplifies and facilitates research. This study examines the factors that make standardizing observational health data to the Observational Medical Outcomes Partnership (OMOP) CDM successful.

MATERIALS AND METHODS: Twenty-five data partners (DPs) from 11 countries received funding from the European Health Data Evidence Network (EHDEN) to standardize their data. Three surveys, DataQualityDashboard results, and statistics from the conversion process were analyzed qualitatively and quantitatively. Our measures of success were the total number of days to transform source data into the OMOP CDM and participation in network research.

RESULTS: The health data converted to CDM represented more than 133 million patients. 100%, 88%, and 84% of DPs took Surveys 1, 2, and 3. The median duration of the 6 key extract, transform, and load (ETL) processes ranged from 4 to 115 days. Of the 25 DPs, 21 DPs were considered applicable for analysis of which 52% standardized their data on time, and 48% participated in an international collaborative study.

DISCUSSION: This study shows that the consistent workflow used by EHDEN proves appropriate to support the successful standardization of observational data across Europe. Over the 25 successful transformations, we confirmed that getting the right people for the ETL is critical and vocabulary mapping requires specific expertise and support of tools. Additionally, we learned that teams that proactively prepared for data governance issues were able to avoid considerable delays improving their ability to finish on time.

CONCLUSION: This study provides guidance for future DPs to standardize to the OMOP CDM and participate in distributed networks. We demonstrate that the Observational Health Data Sciences and Informatics community must continue to evaluate and provide guidance and support for what ultimately develops the backbone of how community members generate evidence.

PMID:37952118 | DOI:10.1093/jamia/ocad214

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Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study

J Radiat Res. 2023 Nov 10:rrad080. doi: 10.1093/jrr/rrad080. Online ahead of print.

ABSTRACT

The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.

PMID:37952082 | DOI:10.1093/jrr/rrad080

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Predicting early breast cancer recurrence from histopathological images in the Carolina Breast Cancer Study

NPJ Breast Cancer. 2023 Nov 11;9(1):92. doi: 10.1038/s41523-023-00597-0.

ABSTRACT

Approaches for rapidly identifying patients at high risk of early breast cancer recurrence are needed. Image-based methods for prescreening hematoxylin and eosin (H&E) stained tumor slides could offer temporal and financial efficiency. We evaluated a data set of 704 1-mm tumor core H&E images (2-4 cores per case), corresponding to 202 participants (101 who recurred; 101 non-recurrent matched on age and follow-up time) from breast cancers diagnosed between 2008-2012 in the Carolina Breast Cancer Study. We leveraged deep learning to extract image information and trained a model to identify recurrence. Cross-validation accuracy for predicting recurrence was 62.4% [95% CI: 55.7, 69.1], similar to grade (65.8% [95% CI: 59.3, 72.3]) and ER status (66.3% [95% CI: 59.8, 72.8]). Interestingly, 70% (19/27) of early-recurrent low-intermediate grade tumors were identified by our image model. Relative to existing markers, image-based analyses provide complementary information for predicting early recurrence.

PMID:37952058 | DOI:10.1038/s41523-023-00597-0

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Maternal depression and child development at 3 years of age: a longitudinal study in a Brazilian child development promotion program

Pediatr Res. 2023 Nov 11. doi: 10.1038/s41390-023-02876-9. Online ahead of print.

ABSTRACT

BACKGROUND: We tested the hypothesis that children of non-depressed mothers perform better in a developmental test at 3 years than children of depressed mothers.

METHOD: Longitudinal analysis from a trial to assess the impact of a child development promotion program in 30 Brazilian municipalities. Mothers and children were appraised at first-year post-partum, 1 and 3 years after enrollment. Child development was assessed through the Ages and Stages Questionnaire (ASQ3) and maternal depression through the Edinburgh Postnatal Depression Scale (EPDS). Crude and adjusted beta coefficients were obtained by linear regression before and after multiple imputation.

RESULTS: In total, 2098 mother/child dyads were included and 8.2% of the mothers had persistent depressive symptoms. There was a decrease in ASQ3 as the number of follow-ups with EPDS ≥ 10 increased (p for trend <0.001). In adjusted analysis, the direction of the association persisted but lost statistical significance. After multiple imputation, children from mothers with EPDS ≥ 10 in three follow-ups presented a decrease of about 14 points in ASQ3 (adjusted beta coefficient = -13.79; -22.59 to -5.00) (p for trend = 0.001).

CONCLUSIONS: Identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil.

IMPACT: In our population study, almost one in every ten women presented persistent depression symptoms across the first 3 years postpartum. In adjusted analysis there was a detrimental impact of persistent maternal depression on child development at 3 years of age. The persistent exposure to maternal depression across early childhood negatively influences children’s development. Considering its prevalence, identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil.

PMID:37952057 | DOI:10.1038/s41390-023-02876-9

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IDH1R132H mutation increases radiotherapy efficacy and a 4-gene radiotherapy-related signature of WHO grade 4 gliomas

Sci Rep. 2023 Nov 11;13(1):19659. doi: 10.1038/s41598-023-46335-1.

ABSTRACT

The prognosis for the WHO grade 4 IDH-mutant astrocytoma is better than IDH-wildtype glioblastoma (GBM) patients. The purpose of this study is to explore the potential mechanism of how IDH1 mutation can increase the efficacy of radiotherapy and to establish a risk-score model to predict the efficacy of radiotherapy in WHO grade 4 gliomas. First, we conducted experimental study on the effect of IDH1R132H mutation on glioma cells in vitro. Radiosensitivity of glioma cells was detected by γ-H2AX after 5 Gy radiation. Cell proliferation, migration and invasion were determined respectively by CCK-8, EDU, monolayer cell migration scratch assay and Transwell assay. Then we analyzed IDH1 gene status and the survival of WHO grade 4 glioma patients received radiotherapy in our center and verified our results by analyzing CGGA and TCGA database. For the risk-score model, we use CGGA data to find genetic differences between WHO grade 4 IDH-mutant astrocytoma and IDH-wildtype GBM patients, and determined a 4-gene radiotherapy-related signature through survival analysis by R software. Evaluation and verification through different glioma validation sets and different statistical methods. For in vitro experiments, we established glioma cells stably overexpressing IDH1 wild-type and IDH1-mutant proteins. γ-H2AX assay showed that IDH1-mutant glioma cells had higher radiosensitivity than wild-type. CCK-8 and EDU assay showed that proliferation capacity of IDH1-mutant glioma cells declined. Transwell assay and monolayer cell migration scratch assay also showed that IDH1-mutant glioma cells reduced migration and invasion capabilities. Among the 83 WHO grade 4 glioma patients who received radiotherapy in our center, WHO grade 4 IDH-mutant astrocytoma patients had longer OS and PFS versus IDH-wildtype GBM (P = 0.0336, P = 0.0324, respectively). TCGA and CGGA database analysis had the similar results. Through complex analysis of CGGA and TCGA databases, we established a risk-model that can predict the efficacy of radiotherapy for WHO grade 4 glioma patients. The 4-gene radiotherapy-related signature including ADD3, GRHPR, RHBDL1 and SLC9A9. Patients in the high-risk group had worse OS compared to low-risk group (P = 0.0001). High- and low-risk groups of patients receiving radiotherapy have significant survival differences, while patients who did not receive radiotherapy have no survival difference both in CGGA and TCGA databases. WHO grade 4 IDH-mutant astrocytoma is more radiosensitive than IDH-wildtype GBM patients. Our 4-gene radiotherapy-related signature can predict the radiation efficacy of WHO grade 4 glioma patients, and it may provide some reference for clinical treatment options.

PMID:37952042 | DOI:10.1038/s41598-023-46335-1

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Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis

Ann Surg Oncol. 2023 Nov 11. doi: 10.1245/s10434-023-14240-6. Online ahead of print.

ABSTRACT

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin.

PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity.

RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death.

CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

PMID:37952018 | DOI:10.1245/s10434-023-14240-6

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United States Grown and Imported Rice on Sale in Las Vegas: Metal(loid)s Composition and Geographic Origin Discrimination

Biol Trace Elem Res. 2023 Nov 11. doi: 10.1007/s12011-023-03942-3. Online ahead of print.

ABSTRACT

Concentrations of metal(loid)s, Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Se, Sr, V and Zn, were determined in rice on sale in Las Vegas. The rice samples were grown in five different countries, the USA, Thailand, India, Pakistan, and Bangladesh. The elemental concentrations in rice grain were determined using inductively coupled plasma mass spectrometry (ICP-MS) following hot block-assisted digestion. The accuracy of the laboratory procedure was verified by the analysis of rice flour standard reference material (NIST SRM 1568b). The mean metal(loid) contents in rice of various geographic origins were 3.18-5.91 mg kg-1 for Al, 0.05-0.12 mg kg-1 for As, 3.64-41 μg kg-1 for Cd, 5.11-12 μg kg-1 for Co, 0.12-0.14 mg kg-1 for Cr, 1.5-1.91 mg kg-1 for Cu, 3.04-4.98 mg kg-1 for Fe, 4.2-10.4 mg kg-1 for Mn, 0.21-0.41 mg kg-1 for Ni, 0.02-0.07 mg kg-1 for Se, 0.68-0.88 mg kg-1 for Sr, 3.64-5.26 μg kg-1 for V, and 16.6-19.9 mg kg-1 for Zn. respectively. The mean concentration of As in US rice was significantly higher than in Indian, Pakistani, and Bangladeshi rice. On the other hand, it was found a significantly low mean level of Cd in US-grown rice. It was also found that the concentrations of metal(loid)s in black and brown rice on sale in Las Vegas were statistically similar, except for Mn and Se. The geographic origin traceability of rice grain involved the use of ICP-MS analysis coupled with chemometrics that allowed their differentiation based on the rice metal(loid) profile, thus confirming their origins. Data were processed by linear discriminant analysis, and US and Thai rice samples were cross-validated with higher accuracy (100%). This authentication quickly discriminates US rice from the other regions and adds verifiable food safety measures for consumers.

PMID:37952013 | DOI:10.1007/s12011-023-03942-3

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Quantitative analysis of peroxisome tracks using a Hidden Markov Model

Sci Rep. 2023 Nov 11;13(1):19694. doi: 10.1038/s41598-023-46812-7.

ABSTRACT

Diffusion and mobility are essential for cellular functions, as molecules are usually distributed throughout the cell and have to meet to interact and perform their function. This also involves the cytosolic migration of cellular organelles. However, observing such diffusion and interaction dynamics is challenging due to the high spatial and temporal resolution required and the accurate analysis of the diffusional tracks. The latter is especially important when identifying anomalous diffusion events, such as directed motions, which are often rare. Here, we investigate the migration modes of peroxisome organelles in the cytosol of living cells. Peroxisomes predominantly migrate randomly, but occasionally they bind to the cell’s microtubular network and perform directed migration, which is difficult to quantify, and so far, accurate analysis of switching between these migration modes is missing. We set out to solve this limitation by experiments and analysis with high statistical accuracy. Specifically, we collect temporal diffusion tracks of thousands of individual peroxisomes in the HEK 293 cell line using two-dimensional spinning disc fluorescence microscopy at a high acquisition rate of 10 frames/s. We use a Hidden Markov Model with two hidden states to (1) automatically identify directed migration segments of the tracks and (2) quantify the migration properties for comparison between states and between different experimental conditions. Comparing different cellular conditions, we show that the knockout of the peroxisomal membrane protein PEX14 leads to a decrease in the directed movement due to a lowered binding probability to the microtubule. However, it does not eradicate binding, highlighting further microtubule-binding mechanisms of peroxisomes than via PEX14. In contrast, structural changes of the microtubular network explain perceived eradication of directed movement by disassembly of microtubules by Nocodazole-treatment.

PMID:37951993 | DOI:10.1038/s41598-023-46812-7

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Detection and agreement of event-based OCT and OCTA analysis for glaucoma progression

Eye (Lond). 2023 Nov 11. doi: 10.1038/s41433-023-02817-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine event-based glaucoma progression using optical coherence tomography (OCT) and OCT angiography (OCTA).

METHODS: In this retrospective study, glaucoma eyes with ≥2-year and 4-visits of OCT/OCTA imaging were included. Peripapillary capillary density (CD) and retinal nerve fibre layer thickness (RNFL) were obtained from 4.5 mm × 4.5 mm optic nerve head (ONH) scans. Event-based OCT/OCTA progression was defined as decreases in ONH measurements exceeding test-retest variability on ≥2 consecutive visits. Visual field (VF) progression was defined as significant VF mean deviation worsening rates on ≥2 consecutive visits. Inter-instrument agreement on progression detection was compared using kappa(κ) statistics.

RESULTS: Among 147 eyes (89 participants), OCTA and OCT identified 33(22%) and 25(17%) progressors, respectively. They showed slight agreement (κ = 0.06), with 7(5%) eyes categorized as progressors by both. When incorporating both instruments, the rate of progressors identified increased to 34%. Similar agreement was observed in diagnosis- and severity-stratified analyses (κ < 0.10). Compared to progressors identified only by OCT, progressors identified only by OCTA tended to have thinner baseline RNFL and worse baseline VF. VF progression was identified in 11(7%) eyes. OCT and VF showed fair agreement (κ = 0.26), with 6(4%) eyes categorized as progressors by both. OCTA and VF showed slight agreement (κ = 0.08), with 4(3%) eyes categorized as progressors by both.

CONCLUSIONS: OCT and OCTA showed limited agreement on event-based progression detection, with OCT showing better agreement with VF. Both OCT and OCTA detected more progressors than VF. OCT and OCTA may provide valuable, yet different and complementary, information about glaucoma progression.

PMID:37951976 | DOI:10.1038/s41433-023-02817-0