Open-radiomics: A Collection of Standardized Datasets and a Technical Protocol for Reproducible Radiomics Machine Learning Pipelines

Purpose: As an important branch of machine learning pipelines in medical imaging, radiomics faces two major challenges namely reproducibility and accessibility. In this work, we introduce open-radiomics, a set of radiomics datasets along with a comprehensive radiomics pipeline based on our proposed technical protocol to investigate the effects of radiomics feature extraction on the reproducibility of the results. Materials and Methods: Experiments are conducted on BraTS 2020 open-source Magnetic Resonance Imaging (MRI) dataset that includes 369 adult patients with brain tumors (76 low-grade glioma (LGG), and 293 high-grade glioma (HGG)). Using PyRadiomics library for LGG vs. HGG classification, 288 radiomics datasets are formed; the combinations of 4 MRI sequences, 3 binWidths, 6 image normalization methods, and 4 tumor subregions. Random Forest classifiers were used, and for each radiomics dataset the training-validation-test (60%/20%/20%) experiment with different data splits and model random states was repeated 100 times (28,800 test results) and Area Under Receiver Operating Characteristic Curve (AUC) was calculated. Results: Unlike binWidth and image normalization, tumor subregion and imaging sequence significantly affected performance of the models. T1 contrast-enhanced sequence and the union of necrotic and the non-enhancing tumor core subregions resulted in the highest AUCs (average test AUC 0.951, 95% confidence interval of (0.949, 0.952)). Although 28 settings and data splits yielded test AUC of 1, they were irreproducible. Conclusion: Our experiments demonstrate the sources of variability in radiomics pipelines (e.g., tumor subregion) can have a significant impact on the results, which may lead to superficial perfect performances that are irreproducible

Improving Deep Learning Models for Pediatric Low-Grade Glioma Tumors Molecular Subtype Identification Using 3D Probability Distributions of Tumor Location

Background and Purpose: Pediatric low-grade glioma (pLGG) is the most common type of brain tumor in children, and identification of molecular markers for pLGG is crucial for successful treatment planning. Convolutional Neural Network (CNN) models for pLGG subtype identification rely on tumor segmentation. We hypothesize tumor segmentations are suboptimal and thus, we propose to augment the CNN models using tumor location probability in MRI data. Materials and Methods: Our REB-approved retrospective study included MRI Fluid-Attenuated Inversion Recovery (FLAIR) sequences of 143 BRAF fused and 71 BRAF V600E mutated tumors. Tumor segmentations (regions of interest (ROIs)) were provided by a pediatric neuroradiology fellow and verified by a senior pediatric neuroradiologist. In each experiment, we randomly split the data into development and test with an 80/20 ratio. We combined the 3D binary ROI masks for each class in the development dataset to derive the probability density functions (PDF) of tumor location, and developed three pipelines: location-based, CNN-based, and hybrid. Results: We repeated the experiment with different model initializations and data splits 100 times and calculated the Area Under Receiver Operating Characteristic Curve (AUC). The location-based classifier achieved an AUC of 77.90, 95% confidence interval (CI) (76.76, 79.03). CNN-based classifiers achieved AUC of 86.11, CI (84.96, 87.25), while the tumor-location-guided CNNs outperformed the formers with an average AUC of 88.64 CI (87.57, 89.72), which was statistically significant (Student's t-test p-value 0.0018). Conclusion: We achieved statistically significant improvements by incorporating tumor location into the CNN models. Our results suggest that manually segmented ROIs may not be optimal.Comment: arXiv admin note: text overlap with arXiv:2207.1477

Are women better police officers? Evidence from survey experiments in Uganda

Can the feminization of public services improve quality and lower corruption? The underlying logic of such efforts is the belief that women have higher ethical standards than men. To answer this question, we examine the links between gender and policing practice using data from twelve vignette cases assessed by 600 Ugandan police officers. Our empirical strategy is based on a randomized framing experiment, which is designed to isolate the effect of gender from institutional factors and social norms. We find that the gender of the police officer depicted in the cases and victim gender are not related to the judgment of police malpractice, nor to suggested disciplinary measures. However, respondent gender matters for the reporting of misconduct and the perception of the official institutional policy of the police. Men are stricter when assessing cases along these dimensions. The results indicate that simply feminizing the police force is unlikely to enhance service quality

Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept

For some molecular players in red blood cells (RBCs), the functional indications and molecular evidence are discrepant. One such protein is transient receptor potential channel of canonical subfamily, member 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse RBCs and its absence in human RBCs. We transfused TRPC6 knockout RBCs into wild-type mice and performed functional tests. We observed the “rescue” of TRPC6 within 10 days; however, the “rescue” was slower in splenectomized mice. The latter finding led us to mimic the mechanical challenge with the cantilever of an atomic force microscope and simultaneously carry out imaging by confocal (3D) microscopy. We observed the strong interaction of RBCs with the opposed surface at around 200 pN and the formation of tethers. The results of both the transfusion experiments and the atomic force spectroscopy suggest mechanically stimulated protein transfer to RBCs as a protein source in the absence of the translational machinery. This protein transfer mechanism has the potential to be utilized in therapeutic contexts, especially for hereditary diseases involving RBCs, such as hereditary xerocytosis or Gardos channelopathy

Analysis and classification of oncology activities on the way to workflow based single source documentation in clinical information systems

BACKGROUND: Today, cancer documentation is still a tedious task involving many different information systems even within a single institution and it is rarely supported by appropriate documentation workflows. METHODS: In a comprehensive 14 step analysis we compiled diagnostic and therapeutic pathways for 13 cancer entities using a mixed approach of document analysis, workflow analysis, expert interviews, workflow modelling and feedback loops. These pathways were stepwise classified and categorized to create a final set of grouped pathways and workflows including electronic documentation forms. RESULTS: A total of 73 workflows for the 13 entities based on 82 paper documentation forms additionally to computer based documentation systems were compiled in a 724 page document comprising 130 figures, 94 tables and 23 tumour classifications as well as 12 follow-up tables. Stepwise classification made it possible to derive grouped diagnostic and therapeutic pathways for the three major classes - solid entities with surgical therapy - solid entities with surgical and additional therapeutic activities and - non-solid entities. For these classes it was possible to deduct common documentation workflows to support workflow-guided single-source documentation. CONCLUSIONS: Clinical documentation activities within a Comprehensive Cancer Center can likely be realized in a set of three documentation workflows with conditional branching in a modern workflow supporting clinical information system

Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly

Draft genome sequences of two Bulgarian Bacillus anthracis strains

Bacillus anthracis strains previously isolated from Bulgaria form a unique subcluster within the A1.a cluster that is typical for isolates from southeastern Europe. Here, we report the draft genome sequences of two Bulgarian B. anthracis strains belonging to the A branch (A.Br.) 008/009 canonical single nucleotide polymorphism (SNP) group of the major A branch

1,12-Diferrocenyldodecane at 100 K

1,12-Diferrocenyldodecane, [Fe2(C5H5)2(C22H32)], was synthesized from ferrocene and 1,12-dodecanedioyl chloride, followed by Clemmensen reduction. The single-crystal structure was determined at 100 K by X-ray diffraction and the spectroscopic and cyclic voltammetric data of 1,12-diferrocenyldodecane and its precursor are reported

Effect of Cell Age and Membrane Rigidity on Red Blood Cell Shape in Capillary Flow

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and altered viscoelastic membrane properties, the evolution of their shape-adapting abilities during senescence remains unclear. In this study, we investigated the effect of RBC properties on the microcapillary in vitro flow behavior and their characteristic shapes in microfluidic channels. For this, we fractioned RBCs from healthy donors according to their age. Moreover, the membranes of fresh RBCs were chemically rigidified using diamide to study the effect of isolated graded-membrane rigidity. Our results show that a fraction of stable, asymmetric, off-centered slipper-like cells at high velocities decreases with increasing age or diamide concentration. However, while old cells form an enhanced number of stable symmetric croissants at the channel centerline, this shape class is suppressed for purely rigidified cells with diamide. Our study provides further knowledge about the distinct effects of age-related changes of intrinsic cell properties on the single-cell flow behavior of RBCs in confined flows due to inter-cellular age-related cell heterogeneity