Nevin Manimala

Gerontol Geriatr Educ. 2023 Nov 12:1-12. doi: 10.1080/02701960.2023.2280061. Online ahead of print.

ABSTRACT

Researchers conducted a four-week pilot sexual health education intervention to investigate changes among older adults’ attitudes about and comfort with sexuality. Six adults between the ages of 74-83 participated in a pilot intervention on sexual health and were administered a pretest and posttest on comfort with and attitudes about sexuality. The intervention included information on personal history of sexuality, sex education, masturbation, sexuality and bodily change in older adulthood, safe sex, healthy relationships, and talking to health care providers. Descriptive statistics for average responses in the pretest and posttest before and after the intervention were used to highlight differences among the participants. Implications for gerontologists, geriatric providers, and education and research regarding older adults are shared.

PMID:37952185 | DOI:10.1080/02701960.2023.2280061

Bioinformatics. 2023 Nov 11:btad683. doi: 10.1093/bioinformatics/btad683. Online ahead of print.

ABSTRACT

MOTIVATION: The LINCS L1000 project has collected gene expression profiles for thousands of compounds across a wide array of concentrations, cell lines, and time points. However, conventional analysis methods often fall short in capturing the rich information encapsulated within the L1000 transcriptional dose-response data.

RESULTS: We present DOSE-L1000, a database that unravels the potency and efficacy of compound-gene pairs and the intricate landscape of compound-induced transcriptional changes. Our study employs the fitting of over 140 million generalized additive models and robust linear models, spanning the complete spectrum of compounds and landmark genes within the LINCS L1000 database. This systematic approach provides quantitative insights into differential gene expression and the potency and efficacy of compound-gene pairs across diverse cellular contexts. Through examples, we showcase the application of DOSE-L1000 in tasks such as cell line and compound comparisons, along with clustering analyses and predictions of drug-target interactions. DOSE-L1000 fosters applications in drug discovery, accelerating the transition to omics-driven drug development.

AVAILABILITY: DOSE-L1000 is publicly available at https://doi.org/10.5281/zenodo.8286375.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:37952162 | DOI:10.1093/bioinformatics/btad683

Environ Sci Technol. 2023 Nov 12. doi: 10.1021/acs.est.3c01259. Online ahead of print.

ABSTRACT

Water-soluble organic matter (WSOM) formed through aqueous processes contributes substantially to total atmospheric aerosol, however, the impact of water evaporation on particle concentrations is highly uncertain. Herein, we present a novel approach to predict the amount of evaporated organic mass induced by sample drying using multivariate polynomial regression and random forest (RF) machine learning models. The impact of particle drying on fine WSOM was monitored during three consecutive summers in Baltimore, MD (2015, 2016, and 2017). The amount of evaporated organic mass was dependent on relative humidity (RH), WSOM concentrations, isoprene concentrations, and NO_x/isoprene ratios. Different models corresponding to each class were fitted (trained and tested) to data from the summers of 2015 and 2016 while model validation was performed using summer 2017 data. Using the coefficient of determination (R²) and the root-mean-square error (RMSE), it was concluded that an RF model with 100 decision trees had the best performance (R² of 0.81) and the lowest normalized mean error (NME < 1%) leading to low model uncertainties. The relative feature importance for the RF model was calculated to be 0.55, 0.2, 0.15, and 0.1 for WSOM concentrations, RH levels, isoprene concentrations, and NO_x/isoprene ratios, respectively. The machine learning model was thus used to predict summertime concentrations of evaporated organics in Yorkville, Georgia, and Centerville, Alabama in 2016 and 2013, respectively. Results presented herein have implications for measurements that rely on sample drying using a machine learning approach for the analysis and interpretation of atmospheric data sets to elucidate their complex behavior.

PMID:37952161 | DOI:10.1021/acs.est.3c01259

J Hand Surg Am. 2023 Nov 10:S0363-5023(23)00502-6. doi: 10.1016/j.jhsa.2023.09.010. Online ahead of print.

ABSTRACT

PURPOSE: Ulnar variance (UV) is a radiographic measurement relating the articular surface heights of the distal radius and ulna. Abnormal UV increases the risk for wrist pathology; however, it only provides a static measurement of an inherently dynamic bony relationship that changes with wrist position and loading. The purpose of this study was to investigate how full-body weight-bearing affects UV using weight-bearing computed tomography (WBCT).

METHODS: Ten gymnasts completed two 45-second scans inside a WBCT machine while performing a handstand on a flat platform (H) and parallettes (P). A non-weight-bearing CT scan was collected to match clinical practice (N). Differences in UV between weight-bearing conditions were evaluated separately for dominant and nondominant sides, and then, UV was compared between weight-bearing conditions on pooled dominant/nondominant data.

RESULTS: Pooled analyses comparing weight-bearing conditions revealed a significant increase in UV for H versus N (0.58 mm) and P versus N (1.00 mm), but no significant change in UV for H versus P (0.43 mm). Significant differences in UV were detected for H versus N, P versus N, and H versus P for dominant and nondominant extremities. The change from N to H was significantly greater in the dominant versus nondominant side, but greater in the nondominant side from N to P.

CONCLUSIONS: Ulnar variance changed with the application of load and position of the wrist. Differences in UV were found between dominant and nondominant extremities.

CLINICAL RELEVANCE: Upper extremity loading patterns are affected by hand dominance as defined by a cartwheel and suggest skeletal consequences from repetitive load on a dominantly used wrist. Although statistically significant, subtle changes detected in this investigational study do not necessarily bear clinical significance. Future WBCT research can lead to improved diagnostic measures for wrist pathologies affected by active loading and rotational wrist behavior.

PMID:37952145 | DOI:10.1016/j.jhsa.2023.09.010

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

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

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

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

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

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 IDH1^R132H 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