Tag: nevin manimala

BMC Genomics. 2022 May 9;22(Suppl 5):919. doi: 10.1186/s12864-022-08537-1.

ABSTRACT

BACKGROUND: Alternative splicing (AS) increases the diversity of transcriptome and could fine-tune the function of genes, so that understanding the regulation of AS is vital. AS could be regulated by many different cis-regulatory elements, such as enhancer. Enhancer has been experimentally proved to regulate AS in some genes. However, there is a lack of genome-wide studies on the association between enhancer and AS (enhancer-AS association). To bridge the gap, here we developed an integrative analysis on a genome-wide scale to identify enhancer-AS associations in human and mouse.

RESULT: We collected enhancer datasets which include 28 human and 24 mouse tissues and cell lines, and RNA-seq datasets which are paired with the selected tissues. Combining with data integration and statistical analysis, we identified 3,242 human and 7,716 mouse genes which have significant enhancer-AS associations in at least one tissue. On average, for each gene, about 6% of enhancers in human (5% in mouse) are associated to AS change and for each enhancer, approximately one gene is identified to have enhancer-AS association in both human and mouse. We found that 52% of the human significant (34% in mouse) enhancer-AS associations are the co-existence of homologous genes and homologous enhancers. We further constructed a user-friendly platform, named Visualization of Enhancer-associated Alternative Splicing (VEnAS, http://venas.iis.sinica.edu.tw/ ), to provide genomic architecture, intuitive association plot, and contingency table of the significant enhancer-AS associations.

CONCLUSION: This study provides the first genome-wide identification of enhancer-AS associations in human and mouse. The results suggest that a notable portion of enhancers are playing roles in AS regulations. The analyzed results and the proposed platform VEnAS would provide a further understanding of enhancers on regulating alternative splicing.

PMID:35534820 | DOI:10.1186/s12864-022-08537-1

BMC Neurol. 2022 May 9;22(1):172. doi: 10.1186/s12883-022-02692-4.

ABSTRACT

BACKGROUND: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment.

METHODS: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression.

RESULTS: A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2-3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG.

CONCLUSIONS: These results show that conventional treatments for MG are not adequately managing patients’ symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

PMID:35534810 | DOI:10.1186/s12883-022-02692-4

Spine (Phila Pa 1976). 2022 May 1;47(9):E432. doi: 10.1097/BRS.0000000000004292. Epub 2021 Nov 12.

NO ABSTRACT

PMID:35533296 | DOI:10.1097/BRS.0000000000004292

Environ Sci Technol. 2022 May 9. doi: 10.1021/acs.est.1c05632. Online ahead of print.

ABSTRACT

New approach methods are being developed to address the challenges of reducing animal testing and assessing risks to the diversity of species in aquatic environments for the multitude of chemicals with minimal toxicity data. The toxicity-normalized species sensitivity distribution (SSDn) approach is a novel method for developing compound-specific hazard concentrations using data for toxicologically similar chemicals. This approach first develops an SSDn composed of acute toxicity values for multiple related chemicals that have been normalized by the sensitivity of a common species tested with each compound. A toxicity-normalized hazard concentration (HC5n) is then computed from the fifth percentile of the SSDn. Chemical-specific HC5 values are determined by back-calculating the HC5n using the chemical-specific sensitivity of the normalization species. A comparison of the SSDn approach with the single-chemical SSD method was conducted by using data for nine transition metals to generate and compare HC5 values between the two methods. We identified several guiding principles for this method that, when applied, resulted in accurate HC5 values based on comparisons with results from single-metal SSDs. The SSDn approach shows promise for developing statistically robust hazard concentrations when adequate taxonomic representation is not available for a single chemical.

PMID:35533293 | DOI:10.1021/acs.est.1c05632

Transbound Emerg Dis. 2022 May 9. doi: 10.1111/tbed.14591. Online ahead of print.

ABSTRACT

An outbreak of canine leptospirosis commenced in Sydney, Australia in 2017. The aim of this retrospective study was to determine if clusters of leptospirosis occurred during this outbreak, and if these were associated with host factors, to assist investigation of the drivers of emerging leptospirosis in this location site. Within the City of Sydney local government area, 13 cases were reported during the outbreak. Administrative data on the canine population were collected and mapped. Clusters of leptospirosis cases were detected using a retrospective space-time analysis and a discrete Poisson probability statistical model. Sydney dog population registration (55.6%, 95% confidence interval [CI] 51.8-58.1%) was lower than the Australian national average (80%). The distribution of dog types, based on the United Kennel Club standards, was significantly (P<0.0001) different to that of the national profile: there was a distinct preference in Sydney for companion dogs. The age distribution of dogs in Sydney did not reflect a typical right-skewed curve; instead, a relatively uniform distribution was observed between the age group of 1 to 8 years. A primary disease cluster (radius 1.1 km) in the eastern area of the Sydney City Council was identified (4 cases observed between 24 May and 9 August 2019 versus 0.10 cases expected), P = 0.0450. When adjusted for the age, breed type and sex distribution of the population, similar clusters were identified; in the case of age-adjustment, the spatio-temporal cluster identified was larger and of longer duration (seven cases observed between 28 June and 11 November 2019 versus 0.34 cases expected), P = 0.0025. The presence of clusters of canine leptospirosis in the City of Sydney during this outbreak, which persisted after adjustment for demographics (age, sex, breed type), suggest that environmental factors – rather than host or pathogen factors – might be responsible for the emergence of leptospirosis. Environmental factors that potentially might be linked to this outbreak of canine leptospirosis and the clusters observed require investigation. This article is protected by copyright. All rights reserved.

PMID:35533268 | DOI:10.1111/tbed.14591

J Appl Clin Med Phys. 2022 May 9:e13634. doi: 10.1002/acm2.13634. Online ahead of print.

ABSTRACT

PURPOSE: To systematically investigate the performance of the analytical anisotropic algorithm (AAA) within the extremes of small tumor volumes and near-minimum lung and tumor tissue densities in order to identify combinations of these parameters where the use of AAA could result in a therapeutically unacceptable loss of tumor coverage on an energy and fractionation-specific basis.

METHODS: Clinically appropriate volumetric modulated arc therapy (VMAT) treatment plans were generated with AAA for 180 unique combinations of lung density (0.05-0.30 g/cm³ ), tumor density (0.30-1.00 g/cm³ ), tumor diameter (0.5-2.5 cm), and beam energy (6 and 10 MV) and recomputed using the AcurosXB algorithm. Regression analysis was used to identify the strongest predictors of a reduction in biologically effective dose at a clinically relevant level (100 Gy BED10) for commonly utilized 1-5 fraction treatment regimens. Measurements were performed within a phantom mimicking the lower extremes of lung and tumor densities to validate AcurosXB as the approximate ground truth within these scenarios.

RESULTS: The strongest predictors of a statistically significant reduction in tumor coverage were lung density ≤0.15 g/cm³ , tumor diameter ≤10 mm, tumor density equal to 0.30 g/cm³ , and a beam energy of 10 MV. Overestimation of clinical target volume (CTV) D95% and CTV V100Gy (BED10) by AAA can exceed 30%-40% in some scenarios. Measurements supported AcurosXB as highly accurate even for these challenging scenarios.

CONCLUSIONS: The accuracy of AAA rapidly diminishes near the minima of clinical lung density, particularly in combination with small tumors and when using a photon energy of 10 MV. The magnitude of the effect can be more dramatic than previously reported data suggests and could potentially compromise the ablative qualities of treatments performed within these environments, particularly with less aggressive fractionation approaches.

PMID:35533238 | DOI:10.1002/acm2.13634

J Appl Clin Med Phys. 2022 May 9:e13630. doi: 10.1002/acm2.13630. Online ahead of print.

ABSTRACT

PURPOSE: Deep learning-based knowledge-based planning (KBP) methods have been introduced for radiotherapy dose distribution prediction to reduce the planning time and maintain consistent high-quality plans. This paper presents a novel KBP model using an attention-gating mechanism and a three-dimensional (3D) U-Net for intensity-modulated radiation therapy (IMRT) 3D dose distribution prediction in head-and-neck cancer.

METHODS: A total of 340 head-and-neck cancer plans, representing the OpenKBP-2020 AAPM Grand Challenge data set, were used in this study. All patients were treated with the IMRT technique and a dose prescription of 70 Gy. The data set was randomly divided into 64%/16%/20% as training/validation/testing cohorts. An attention-gated 3D U-Net architecture model was developed to predict full 3D dose distribution. The developed model was trained using the mean-squared error loss function, Adam optimization algorithm, a learning rate of 0.001, 120 epochs, and batch size of 4. In addition, a baseline U-Net model was also similarly trained for comparison. The model performance was evaluated on the testing data set by comparing the generated dose distributions against the ground-truth dose distributions using dose statistics and clinical dosimetric indices. Its performance was also compared to the baseline model and the reported results of other deep learning-based dose prediction models.

RESULTS: The proposed attention-gated 3D U-Net model showed high capability in accurately predicting 3D dose distributions that closely replicated the ground-truth dose distributions of 68 plans in the test set. The average value of the mean absolute dose error was 2.972 ± 1.220 Gy (vs. 2.920 ± 1.476 Gy for a baseline U-Net) in the brainstem, 4.243 ± 1.791 Gy (vs. 4.530 ± 2.295 Gy for a baseline U-Net) in the left parotid, 4.622 ± 1.975 Gy (vs. 4.223 ± 1.816 Gy for a baseline U-Net) in the right parotid, 3.346 ± 1.198 Gy (vs. 2.958 ± 0.888 Gy for a baseline U-Net) in the spinal cord, 6.582 ± 3.748 Gy (vs. 5.114 ± 2.098 Gy for a baseline U-Net) in the esophagus, 4.756 ± 1.560 Gy (vs. 4.992 ± 2.030 Gy for a baseline U-Net) in the mandible, 4.501 ± 1.784 Gy (vs. 4.925 ± 2.347 Gy for a baseline U-Net) in the larynx, 2.494 ± 0.953 Gy (vs. 2.648 ± 1.247 Gy for a baseline U-Net) in the PTV_70, and 2.432 ± 2.272 Gy (vs. 2.811 ± 2.896 Gy for a baseline U-Net) in the body contour. The average difference in predicting the D₉₉ value for the targets (PTV_70, PTV_63, and PTV_56) was 2.50 ± 1.77 Gy. For the organs at risk, the average difference in predicting the $D_{max}$ (brainstem, spinal cord, and mandible) and $D_{mean}$ (left parotid, right parotid, esophagus, and larynx) values was 1.43 ± 1.01 and 2.44 ± 1.73 Gy, respectively. The average value of the homogeneity index was 7.99 ± 1.45 for the predicted plans versus 5.74 ± 2.95 for the ground-truth plans, whereas the average value of the conformity index was 0.63 ± 0.17 for the predicted plans versus 0.89 ± 0.19 for the ground-truth plans. The proposed model needs less than 5 s to predict a full 3D dose distribution of 64 × 64 × 64 voxels for a new patient that is sufficient for real-time applications.

CONCLUSIONS: The attention-gated 3D U-Net model demonstrated a capability in predicting accurate 3D dose distributions for head-and-neck IMRT plans with consistent quality. The prediction performance of the proposed model was overall superior to a baseline standard U-Net model, and it was also competitive to the performance of the best state-of-the-art dose prediction method reported in the literature. The proposed model could be used to obtain dose distributions for decision-making before planning, quality assurance of planning, and guiding-automated planning for improved plan consistency, quality, and planning efficiency.

PMID:35533234 | DOI:10.1002/acm2.13630

Dementia (London). 2022 May 9:14713012221094979. doi: 10.1177/14713012221094979. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the perceived and unmet needs for health and social services and their relative importance among families coping with dementia in urban China.

METHODS: We used data from a cross-sectional survey conducted between 2018 and 2019 in two cities in eastern China. Trained staff conducted structured interviews of family caregivers of people living with dementia at home to obtain individual characteristics as well as types of service needs of families coping with dementia. Service needs and utilization in 24 types of services across five domains (daily living, medical/nursing, rehabilitation, mental health, and other) were examined. Descriptive statistics were used to describe characteristics of the dyads and the ranking of services based on the percentage of respondents with perceived/unmet needs.

RESULTS: A total of 170 (87.6%) family caregivers completed the interviews. The mean age of the care recipient was 77.2 years (range: 60-102) and 65.3% were female. The mean age of family caregivers was 58.4 years (range: 28-90), and 57.1% were female. The top five services used by the care recipients were: primary care, medication management, housekeeping, activities of daily living assistance, and adult day service. The five services with the most unmet needs were: legal assistance (42.7%), hospice care (44.7%), respiratory secretion management (expectoration) (57.6%), life enrichment activities (65.4%), and companion care (67.0%). Except for transportation and dressing/grooming, working and nonworking caregivers reported similar relative importance of service needs.

CONCLUSIONS: The findings suggest that people living with dementia and their family require a wide range of services and supports to live in the community. Future research and policy efforts should target the unmet needs of families to improve dementia care in the community and promote aging-in-place.

PMID:35533235 | DOI:10.1177/14713012221094979

J Clin Pediatr Dent. 2022 Mar 1;46(2):137-142. doi: 10.17796/1053-4625-46.2.8.

ABSTRACT

OBJECTIVE: YKL-40, a new biomarker of localized inflammation, is secreted by macrophages and regulates inflammation and immune responses. The aim of this study was to investigate YKL-40 levels in saliva and compare the level of this mediator in healthy and unhealthy oral cavity.

STUDY DESIGN: 80 children (42-girl, 38-boy), aged 6-15 (mean±SD: 9.35±2.08) were included in this cross-sectional study. The children were divided into four groups: Group-I (control, n=20, dmft/DMFT=0), Group-II (n=20, exist of dental caries), Group-III (n=20, exist of advanced dental caries without pulp exposure), and Group-IV (n=20, exist of advanced dental caries with pulp exposure). The dmft/DMFT, dmfs/DMFS, and the number of advanced dental caries according to the ICDAS and pufa/PUFA index were recorded. Saliva was collected and YKL-40 concentrations were measured.

RESULTS: The highest level of YKL-40 was obtained in Group IV, followed by Groups III, II, and I, respectively (p<0.01). There was a positive correlation between YKL-40 and the number of caries There were no statistically significant difference in YKL-40 levels in terms of age and gender (p>0.05).

CONCLUSIONS: The advanced dental caries with pulp exposure may play an important role in the increasing levels of YKL-40 in saliva.

PMID:35533232 | DOI:10.17796/1053-4625-46.2.8

Photobiomodul Photomed Laser Surg. 2022 May 9. doi: 10.1089/photob.2021.0038. Online ahead of print.

ABSTRACT

Background: With laser irradiation emerging as an adjunctive treatment utilized in nonsurgical periodontal therapy, it is important to understand the variance of penetration depth among the different laser wavelengths. Purpose: To evaluate the thermal penetration depth, as a photothermal effect, of carbon dioxide (CO₂)-, erbium: doped yttrium-aluminum-garnett (Er:YAG)-, and erbium, chromium: yttrium-scandium-gallium-garnett (Er,Cr:YSGG)-lasers on the bovine gingiva in an in vitro model. Methods: Four mandibles from freshly slaughtered cows were utilized in this study. Buccal and lingual root debridement was provided using three different laser wavelengths, all in pulsed settings. A CO₂– (10,600 nm), Er:YAG- (2940 nm), and Er,Cr:YSGG- (2780 nm) were utilized to irradiate pockets of two mandibular posterior teeth in each group. Laser power output settings were set to 2 W. The posterior teeth were irradiated for 30 sec buccal and 30 sec lingual of each tooth for all selected treatment test groups. Instrumentation with curettes was performed as a control group. Gingival flaps, including the entire gingiva, were fixed in 10% formalin and stained via Elastin van Gieson. Sections were examined microscopically to evaluate thermal damage and statistically compared using mixed effect model with Tukey adjustment. Results: The CO₂-laser irradiation presented a statistically significant lower mean compared to Er,Cr:YSGG-laser (p < 0.0001). Er,Cr:YSGG-laser had a higher penetration depth compared to Er:YAG-laser (p < 0.0001). There was no statistically significant difference found in penetration depth between CO₂– and Er:YAG-laser irradiation. Conclusions: It can be concluded that all tested pulsed lasers had minimal penetration depth into the gingiva. However, the pulsed CO₂– and Er:YAG-lasers presented lower thermal effects compared to Er,Cr:YSGG-laser in vitro.

PMID:35533016 | DOI:10.1089/photob.2021.0038