Tag: nevin manimala

PLoS Comput Biol. 2022 Apr 14;18(4):e1010028. doi: 10.1371/journal.pcbi.1010028. Online ahead of print.

ABSTRACT

Genome wide association studies (GWASs) for complex traits have implicated thousands of genetic loci. Most GWAS-nominated variants lie in noncoding regions, complicating the systematic translation of these findings into functional understanding. Here, we leverage convolutional neural networks to assist in this challenge. Our computational framework, peaBrain, models the transcriptional machinery of a tissue as a two-stage process: first, predicting the mean tissue specific abundance of all genes and second, incorporating the transcriptomic consequences of genotype variation to predict individual abundance on a subject-by-subject basis. We demonstrate that peaBrain accounts for the majority (>50%) of variance observed in mean transcript abundance across most tissues and outperforms regularized linear models in predicting the consequences of individual genotype variation. We highlight the validity of the peaBrain model by calculating non-coding impact scores that correlate with nucleotide evolutionary constraint that are also predictive of disease-associated variation and allele-specific transcription factor binding. We further show how these tissue-specific peaBrain scores can be leveraged to pinpoint functional tissues underlying complex traits, outperforming methods that depend on colocalization of eQTL and GWAS signals. We subsequently: (a) derive continuous dense embeddings of genes for downstream applications; (b) highlight the utility of the model in predicting transcriptomic impact of small molecules and shRNA (on par with in vitro experimental replication of external test sets); (c) explore how peaBrain can be used to model difficult-to-study processes (such as neural induction); and (d) identify putatively functional eQTLs that are missed by high-throughput experimental approaches.

PMID:35421087 | DOI:10.1371/journal.pcbi.1010028

J Cancer Res Clin Oncol. 2022 Apr 14. doi: 10.1007/s00432-022-03997-0. Online ahead of print.

ABSTRACT

PURPOSE: Therapy decision for patients with metastatic renal cell carcinoma (mRCC) is highly dependent on disease monitoring based on radiological reports. The purpose of the study was to compare non-standardized, common practice free text reporting (FTR) on disease response with reporting based on response evaluation criteria in solid tumors modified for immune-based therapeutics (iRECIST).

METHODS: Fifty patients with advanced mRCC were included in the retrospective, single-center study. CT scans had been evaluated and FTR prepared in accordance with center’s routine practice. For study purposes, reports were re-evaluated using a dedicated computer program that applied iRECIST. Patients were followed up over a period of 22.8 ± 7.9 months in intervals of 2.7 ± 1.8 months. Weighted kappa statistics was run to assess strength of agreement. Logistic regression was used to identify predictors for different rating.

RESULTS: Agreement between FTR and iRECIST-based reporting was moderate (kappa 0.38 [95% CI 0.2-0.6] to 0.70 [95% CI 0.5-0.9]). Tumor response or progression according to FTR were not confirmed with iRECIST in 19 (38%) or 11 (22%) patients, respectively, in at least one follow-up examination. With FTR, new lesions were frequently not recognized if they were already identified in the recent prior follow-up examination (odds ratio for too favorable rating of disease response compared to iRECIST: 5.4 [95% CI 2.9-10.1].

CONCLUSIONS: Moderate agreement between disease response according to FTR or iRECIST in patients with mRCC suggests the need of standardized quantitative radiological assessment in daily clinical practice.

PMID:35420348 | DOI:10.1007/s00432-022-03997-0

Environ Sci Pollut Res Int. 2022 Apr 14. doi: 10.1007/s11356-022-20097-1. Online ahead of print.

ABSTRACT

The agriculture sector creates nearly a quarter of the total GHG emissions globally as production and transportation activities in the agriculture sector mostly use fossil fuels, creating carbon emissions. In this regard, it is highly important to study the environmental sustainability of agriculture sector growth by using the theory of environmental Kuznets curve (EKC). Furthermore, this research study is aimed to assess the moderation role of transportation competitiveness in determining the carbon emissions of transportation sector by using agriculture sector value addition. The study uses panel quantile regression technique for data analysis of 121 countries by covering time period from 2008 to 2018. The study results validated the agricultural EKC across four different quantile groups based on carbon emissions of transport sector. The moderation of transportation competitiveness is observed in changing the turning point and flattening of agricultural EKC indicating the early achievement of maturity. The quality of institutions and planned increase of population can help reduce carbon emissions of transportation sector. The moderation of transportation competitiveness implicates the importance of planning and efficiently operating the transportation sector to mitigate carbon emissions.

PMID:35420341 | DOI:10.1007/s11356-022-20097-1

Breast Cancer Res Treat. 2022 Apr 14. doi: 10.1007/s10549-022-06582-8. Online ahead of print.

ABSTRACT

BACKGROUND: There are limited data on breast surgery completion rates and prevalence of care-continuum delays in breast cancer treatment programs in low-income countries.

METHODS: This study analyzes treatment data in a retrospective cohort of 312 female patients with non-metastatic breast cancer in Haiti. Descriptive statistics were used to summarize patient characteristics; treatments received; and treatment delays of > 12 weeks. Multivariate logistic regressions were performed to identify factors associated with receiving surgery and with treatment delays. Exploratory multivariate survival analysis examined the association between surgery delays and disease-free survival (DFS).

RESULTS: Of 312 patients, 249 (80%) completed breast surgery. The odds ratio (OR) for surgery completion for urban vs. rural dwellers was 2.15 (95% confidence interval [CI]: 1.19-3.88) and for those with locally advanced vs. early-stage disease was 0.34 (95%CI: 0.16-0.73). Among the 223 patients with evaluable surgery completion timelines, 96 (43%) experienced delays. Of the 221 patients eligible for adjuvant chemotherapy, 141 (64%) received adjuvant chemotherapy, 66 of whom (47%) experienced delays in chemotherapy initiation. Presentation in the later years of the cohort (2015-2016) was associated with lower rates of surgery completion (75% vs. 85%) and with delays in adjuvant chemotherapy initiation (OR [95%CI]: 3.25 [1.50-7.06]). Exploratory analysis revealed no association between surgical delays and DFS.

CONCLUSION: While majority of patients obtained curative-intent surgery, nearly half experienced delays in surgery and adjuvant chemotherapy initiation. Although our study was not powered to identify an association between surgical delays and DFS, these delays may negatively impact long-term outcomes.

PMID:35420316 | DOI:10.1007/s10549-022-06582-8

Support Care Cancer. 2022 Apr 14. doi: 10.1007/s00520-022-07052-z. Online ahead of print.

ABSTRACT

PURPOSE: Patients receiving cancer treatments experience many treatment-related symptoms. Telehealth is increasingly being used to support symptom management. The overall aim was to determine the effectiveness of nurse-led telehealth symptom management interventions for patients with cancer receiving systemic or radiation therapy compared to usual care on health service use, quality of life, and symptom severity.

METHODS: A systematic review was conducted following the Cochrane Handbook and PRISMA reporting guidelines. Five electronic databases were searched. Two independent reviewers screened articles and extracted data. Meta-analysis was performed if data were clinically and methodologically homogeneous. Subanalysis was conducted on reactive and scheduled telehealth interventions.

RESULTS: Of 7749 citations screened, 10 studies were included (8 randomized control trials, 2 quasi-experimental). Five were reactive telehealth interventions with patient-initiated contact and five evaluated scheduled telehealth interventions initiated by nurses. Compared to usual care (typically patient-initiated calls), nurse-led telehealth interventions for symptom management showed no statistically significant difference in hospitalizations, emergency department visits, or unscheduled clinic visits. Two of three studies of reactive telehealth interventions showed improved quality of life. All telehealth interventions showed reduction in the severity of most symptoms. Pain severity was significantly reduced (standard mean difference – 0.54; 95% CI – 0.88, – 0.19). Significant heterogeneity prevented meta-analysis for most outcomes.

CONCLUSION: Few studies evaluated nurse-led telehealth interventions for cancer symptom management. Compared to usual care, patients exposed to telehealth interventions had reduced symptom severity and no difference in health services use. Future research should focus on better reporting intervention characteristics and consistently measuring outcomes.

PMID:35420331 | DOI:10.1007/s00520-022-07052-z

Eur Radiol. 2022 Apr 14. doi: 10.1007/s00330-022-08771-x. Online ahead of print.

ABSTRACT

OBJECTIVES: Develop and evaluate the performance of deep learning and linear regression cascade algorithms for automated assessment of the image layout and position of chest radiographs.

METHODS: This retrospective study used 10 quantitative indices to capture subjective perceptions of radiologists regarding image layout and position of chest radiographs, including the chest edges, field of view (FOV), clavicles, rotation, scapulae, and symmetry. An automated assessment system was developed using a training dataset consisting of 1025 adult posterior-anterior chest radiographs. The evaluation steps included: (i) use of a CNN framework based on ResNet – 34 to obtain measurement parameters for quantitative indices and (ii) analysis of quantitative indices using a multiple linear regression model to obtain predicted scores for the layout and position of chest radiograph. In the testing dataset (n = 100), the performance of the automated system was evaluated using the intraclass correlation coefficient (ICC), Pearson correlation coefficient (r), mean absolute difference (MAD), and mean absolute percentage error (MAPE).

RESULTS: The stepwise regression showed a statistically significant relationship between the 10 quantitative indices and subjective scores (p < 0.05). The deep learning model showed high accuracy in predicting the quantitative indices (ICC = 0.82 to 0.99, r = 0.69 to 0.99, MAD = 0.01 to 2.75). The automatic system provided assessments similar to the mean opinion scores of radiologists regarding image layout (MAPE = 3.05%) and position (MAPE = 5.72%).

CONCLUSIONS: Ten quantitative indices correlated well with the subjective perceptions of radiologists regarding the image layout and position of chest radiographs. The automated system provided high performance in measuring quantitative indices and assessing image quality.

KEY POINTS: • Objective and reliable assessment for image quality of chest radiographs is important for improving image quality and diagnostic accuracy. • Deep learning can be used for automated measurements of quantitative indices from chest radiographs. • Linear regression can be used for interpretation-based quality assessment of chest radiographs.

PMID:35420306 | DOI:10.1007/s00330-022-08771-x

Eur Radiol. 2022 Apr 14. doi: 10.1007/s00330-022-08768-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess whether systemic-pulmonary collaterals are associated with clinical severity and extent of pulmonary perfusion defects in chronic thromboembolic pulmonary hypertension (CTEPH).

METHODS: This prospective study was approved by a local ethics committee. Twenty-four patients diagnosed with inoperable CTEPH were enrolled between July 2014 and February 2017. Systemic-pulmonary collaterals were detected using pulmonary vascular enhancement on intra-aortic computed tomography (CT) angiography. The pulmonary enhancement parameters were calculated, including (1) Hounsfield unit differences (HUdiff) between pulmonary trunks and pulmonary arteries (PAs) or veins (PVs), namely HUdiff-PA and HUdiff-PV, on the segmental base; (2) the mean HUdiff-PA, mean HUdiff-PV, numbers of significantly enhanced PAs and PVs, on the patient base. Pulmonary perfusion defects were recorded and scored using the lung perfused blood volume (PBV) based on intravenous dual-energy CT (DECT) angiography. Pearson’s or Spearman’s correlation coefficients were used to evaluate correlations between the following: (1) segment-based intra-aortic CT and intravenous DECT parameters (2) patient-based intra-aortic CT parameters and clinical severity parameters or lung PBV scores. Statistical significance was set at p < 0.05.

RESULTS: Segmental HUdiff-PV was correlated with the segmental perfusion defect score (r = 0.45, p < 0.01). The mean HUdiff-PV was correlated with the mean pulmonary arterial pressure (PAP) (r = 0.52, p < 0.01), cardiac output (rho = – 0.41, p = 0.05), and lung PBV score (rho = 0.43, p = 0.04). And the number of significantly enhanced PVs was correlated with the mean PAP (r = 0.54, p < 0.01), pulmonary vascular resistance (r = 0.54, p < 0.01), and lung PBV score (rho = 0.50, p = 0.01).

CONCLUSIONS: PV enhancement measured by intra-aortic CT angiography reflects clinical severity and pulmonary perfusion defects in CTEPH.

KEY POINTS: • Intra-aortic CT angiography demonstrated heterogeneous enhancement within the pulmonary vasculature, showing collaterals from the systemic arteries to the pulmonary circulation in CTEPH. • The degree of systemic-pulmonary collateral development was significantly correlated with the clinical severity of CTEPH and may be used to evaluate disease progression. • The distribution of systemic-pulmonary collaterals is positively correlated with perfusion defects in the lung segments in CTEPH.

PMID:35420297 | DOI:10.1007/s00330-022-08768-6

Catheter Cardiovasc Interv. 2022 Apr 14. doi: 10.1002/ccd.30176. Online ahead of print.

ABSTRACT

INTRODUCTION: The preferred approach for transcatheter aortic valve replacement (TAVR) is transfemoral. There has been widespread adoption of the Perclose Proglide^TM device for vascular closure. Typically, two devices are deployed before upsizing the access sheath in the “preclose technique.” Prior investigations have compared the use of a single device versus double device technique, but none have shown significant clinical benefit to either approach.

METHODS: Five hundred and six patients underwent transfemoral TAVR (TF-TAVR) with single or double Perclose devices for vascular closure from July 2015 to February 2020. A retrospective review was conducted, and propensity-matched analyses were used to account for differences in baseline characteristics.

RESULTS: In the matched analysis, there were 251 patients in the single Perclose group and 238 in the double. There was a statistically significant improvement in overall procedural success using the single closure device (94.6% vs. 88.5%, p = 0.009) This was defined as intraprocedural hemostatic control, lack of contrast extravasation, arterial dissection, occlusion, or stenosis >50% in the final crossover angiogram, as well as unimpaired limb perfusion without claudication throughout the index hospitalization. There was also a significant improvement in arterial dissection rates (0.6% vs. 4.6%, p = 0.004), stenosis >50% (1.3% vs. 4.4%, p = 0.028), and Valve Academic Research Consortium major vascular complications (1.8% vs. 4.9%, p = 0.038).

CONCLUSION: A single Perclose device is a safe means of vascular closure during TF-TAVR and may have important clinical benefits compared to the commonly used two-device technique.

PMID:35420254 | DOI:10.1002/ccd.30176

Arch Endocrinol Metab. 2022 Apr 11:2359-3997000000458. doi: 10.20945/2359-3997000000458. Online ahead of print.

ABSTRACT

OBJECTIVE: Cytological analysis and Bethesda classification of thyroid nodules is the standard method of diagnosing differentiated thyroid carcinoma (DTC). However, even for nodules with a non-malignant cytological diagnosis, there is a not insignificant risk of cancer. There are doubts whether this lack of certainty would influence patient prognosis. Our aim was to compare patients with DTC, classified according to the preoperative cytological diagnosis, regarding their evolution.

METHODS: A retrospective study was carried out with 108 DTC patients submitted to total thyroidectomy (TT) between 2009 and 2015, divided into three groups according to preoperative cytological diagnosis (Bethesda classification): classes I/II, III/IV, and V/VI. Groups were compared for evolution considering response to treatment at last evaluation as well as time disease free. Statistical analysis used ANOVA, chi squared, and Kaplan-Meier curves with p<0.05 considered significant.

RESULTS: Groups differed for time between nodule puncture and TT [in months; V/VI (2.35 ± 2.48) < III/IV (7.32 ± 6.34) < I/II (13.36 ± 8.9); p < 0.0001]. There was no significant difference between groups for evolution at final evaluation (disease free status; classes I/II: 71.4%; classes III/IV: 60%; classes V/VI: 66.6%; p = 0.7433), as well as time disease free (in months; classes I/II: 34.57 ± 25.82; classes III/IV: 38.04 ± 26.66; classes V/VI: 30.84 ± 26.34; p = 0.3841).

CONCLUSION: DTC patients classified according to preoperative cytological diagnosis did not differ for evolution. Although patients with non-malignant cytological diagnoses were submitted to TT later, this did not affect the evolution of the cases.

PMID:35420266 | DOI:10.20945/2359-3997000000458

Vet Comp Oncol. 2022 Apr 14. doi: 10.1111/vco.12821. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the outcome of dogs with soft tissue sarcoma (STS) within the region of the ischiatic tuberosity (ITSTS) treated surgically.

STUDY DESIGN: Multi-institutional retrospective study ANIMALS: Fifty-two client-owned dogs with histologically confirmed STS in the region of the IT treated with surgical resection between March 1st, 2009, and March 1st, 2021, and a minimum follow-up time of six months.

METHODS: Data collected included signalment, preoperative diagnostics, surgical intent/method, complications, histopathology, margins, outcome, and cause of death. Statistical analyses were performed to determine significant factors in treatment and prognosis of ITSTS.

RESULTS: Fifty-two dogs with histopathologically-confirmed ITSTS included resulting in 24 grade I, 20 grade II, and seven grade III tumors. Overall survival time and disease progression were negatively associated with tumor grade while recurrence was positively associated with grade and incomplete margins. Overall survival time and progression-free survival time was not reached for tumors graded as I or II and was 255 and 268 days respectively for grade III. Median time to recurrence was not reached for tumors excised with complete margins and 398 days for incomplete margins. There was a 25% reported surgical complication rate.

CONCLUSION: Ischiatic tuberosity soft tissue sarcoma was not found to be a unique clinical entity in dogs. Treatment recommendations and prognosis were similar to STS in other locations. The outcome was influenced by histologic grade and margins.

CLINICAL SIGNIFICANCE: Ischiatic tuberosity soft tissue sarcoma of dogs does not behave more aggressively than those in other locations. Surgical complications were common but not life-threatening. Overall prognosis, including survival and disease recurrence, appears to depend on histological grade and surgical margins. This article is protected by copyright. All rights reserved.

PMID:35420253 | DOI:10.1111/vco.12821