Takshan/R1 huggingface dataset:
Predicting RNA-protein binding sites and motifs through combining local and global deep convolutional neural networks.

Motivation: RNA-binding proteins (RBPs) take over 5-10% of the eukaryotic proteome and play key roles in many biological processes, e.g. gene regulation. Experimental detection of RBP binding sites is still time-intensive and high-costly. Instead, computational prediction of the RBP binding sites using patterns learned from existing annotation knowledge is a fast approach. From the biological point of view, the local structure context derived from local sequences will be recognized by specific RBPs. However, in computational modeling using deep learning, to our best knowledge, only global representations of entire RNA sequences are employed. So far, the local sequence information is ignored in the deep model construction process. Results: In this study, we present a computational method iDeepE to predict RNA-protein binding sites from RNA sequences by combining global and local convolutional neural networks (CNNs). For the global CNN, we pad the RNA sequences into the same length. For the local CNN, we split a RNA sequence into multiple overlapping fixed-length subsequences, where each subsequence is a signal channel of the whole sequence. Next, we train deep CNNs for multiple subsequences and the padded sequences to learn high-level features, respectively. Finally, the outputs from local and global CNNs are combined to improve the prediction. iDeepE demonstrates a better performance over state-of-the-art methods on two large-scale datasets derived from CLIP-seq. We also find that the local CNN runs 1.8 times faster than the global CNN with comparable performance when using GPUs. Our results show that iDeepE has captured experimentally verified binding motifs. Availability and implementation: https://github.com/xypan1232/iDeepE. Supplementary information: Supplementary data are available at Bioinformatics online.
Canine invasive mammary carcinomas as models of human breast cancer. Part 1: natural history and prognostic factors.

PURPOSE: Dogs have been proposed as spontaneous animal models of human breast cancer, based on clinicopathologic similarities between canine and human mammary carcinomas. We hypothesized that a better knowledge of the natural history and prognostic factors of canine invasive mammary carcinomas would favor the design of preclinical trials using dogs as models of breast cancer. METHODS: The 2-year outcome of 350 female dogs with spontaneous invasive mammary carcinoma was studied. The investigated prognostic factors included age at diagnosis, pathologic tumor size, pathologic nodal stage, lymphovascular invasion, histological grade, and expression of Estrogen Receptor alpha (ERα), Progesterone Receptor, Ki-67, Human Epidermal Growth Factor Receptor 2, basal cytokeratins 5/6, and Epidermal Growth Factor Receptor. Multivariate survival analyses were performed using the Cox proportional hazards model. RESULTS: The overall survival after mastectomy was 11 months. Within 1 year post mastectomy, 41.5% of dogs (145/350) died from their mammary carcinoma. By multivariate analysis, the significant prognostic factors for overall survival included a pathologic tumor size larger than 20 mm [HR 1.47 (95% confidence interval 1.15-1.89)], a positive nodal stage [pN+, HR 1.89 (1.43-2.48)], a histological grade III [HR 1.32 (1.02-1.69)], ERα negativity [HR 1.39 (1.01-1.89)], a high Ki-67 proliferation index [HR 1.32 (1.04-1.67)], and EGFR absence [HR 1.33 (1.04-1.69)]. CONCLUSION: The short natural history of spontaneous canine invasive mammary carcinomas and high rate of cancer-related death allow for rapid termination of preclinical investigations. The prognostic factors of invasive mammary carcinomas are remarkably similar in dogs and humans, highlighting the similarities in cancer biology between both species.
Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation.

BACKGROUND: To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de-escalation in stereotactic body radiotherapy for non-small cell lung carcinomas (NSCLC). METHODS: For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re-normalized to the median gross tumor volume dose (GTV-based prescription) to assess the impacts of PTV and normal tissue dose reduction. RESULTS: With PTV-based prescription, GTV mean dose was much higher with the optimized PIL at 60% with significant reduction of normal lung receiving 30 to 10 Gy (V 30-10Gy ), and observable but insignificant dose reduction to spinal cord, esophagus, ribs, and others compared with 85% PIL. Mean doses to the normal lung between PTV and GTV was higher with 60-70% PIL than 85%. The dose gradient index was 5.0 ± 1.1 and 6.1 ± 1.4 for 60 and 85% PIL (p < 0.05), respectively. Compared with the reference 85% PIL plan using PTV-base prescription, significant decreases of all normal tissue doses were observed with 60% and 70% PIL by GTV-based prescription. Yet, the resulting biological effective (BED) mean doses of PTV remain sufficiently high, ranging 104.2 to 116.9 Gy α/β = 10. CONCLUSIONS: Optimizing the PIL with VMAT has notable advantage of improving the dosimetric quality of lung SBRT and offers the potential of dose de-escalation for surrounding tissues while increasing the GTV dose simultaneously. The clinical implication of re-normalizing plans from PTV-prescription at 60-70% to the GTV median dose requires further investigations.
Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

Bestrahlungsplanung für Wirbelsäulen-Radiochirurgie : Eine kompetitive Multiplattform-Benchmark-Studie. PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.
A Score to Identify Patients with Brain Metastases from Colorectal Cancer Who May Benefit from Whole-brain Radiotherapy in Addition to Stereotactic Radiosurgery/Radiotherapy.

AIM: To design a tool to predict the probability of new cerebral lesions after stereotactic radiosurgery/radiotherapy for patients with 1-3 brain metastases from colorectal cancer. PATIENTS AND METHODS: In 21 patients, nine factors were evaluated for freedom from new brain metastases, namely age, gender, Karnofsky performance score (KPS), tumor type, number, maximum total diameter of all lesions and sites of cerebral lesions, extra-cranial metastases, and time from cancer diagnosis to irradiation. RESULTS: Freedom from new lesions was positively associated with KPS of 90-100 (p=0.013); maximum total diameter ≤15 mm showed a trend for positive association (p=0.09). Points were assigned as: KPS 70-80=1 point, KPS 90-100=2 points, maximum diameter ≤15 mm=2 points and maximum diameter >15 mm=1 point. Six-month rates of freedom from new lesions were 29%, 45% and 100% for those with total scores of 2, 3 and 4 points, respectively, with corresponding 12-month rates of 0%, 45% and 100% (p=0.027). CONCLUSION: This study identified three risk groups regarding new brain metastases after stereotactic irradiation. Patients with 2 points could benefit from additional whole-brain radiotherapy.
The SBRT database initiative of the German Society for Radiation Oncology (DEGRO): patterns of care and outcome analysis of stereotactic body radiotherapy (SBRT) for liver oligometastases in 474 patients with 623 metastases.

BACKGROUND: The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. METHODS: From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. RESULTS: In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. CONCLUSION: After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.
Investigation of the XCAT phantom as a validation tool in cardiac MRI tracking algorithms.

PURPOSE: To describe our magnetic resonance imaging (MRI) simulated implementation of the 4D digital extended cardio torso (XCAT) phantom to validate our previously developed cardiac tracking techniques. Real-time tracking will play an important role in the non-invasive treatment of atrial fibrillation with MRI-guided radiosurgery. In addition, to show how quantifiable measures of tracking accuracy and patient-specific physiology could influence MRI tracking algorithm design. METHODS: Twenty virtual patients were subjected to simulated MRI scans that closely model the proposed real-world scenario to allow verification of the tracking technique's algorithm. The generated phantoms provide ground-truth motions which were compared to the target motions output from our tracking algorithm. The patient-specific tracking error, ep, was the 3D difference (vector length) between the ground-truth and algorithm trajectories. The tracking errors of two combinations of new tracking algorithm functions that were anticipated to improve tracking accuracy were studied. Additionally, the correlation of key physiological parameters with tracking accuracy was investigated. RESULTS: Our original cardiac tracking algorithm resulted in a mean tracking error of 3.7 ± 0.6 mm over all virtual patients. The two combinations of tracking functions demonstrated comparable mean tracking errors however indicating that the optimal tracking algorithm may be patient-specific. CONCLUSIONS: Current and future MRI tracking strategies are likely to benefit from this virtual validation method since no time-resolved 4D ground-truth signal can currently be derived from purely image-based studies.
Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT.

Direkte Dosiskorrelation von MRT-morphologischen Veränderungen von gesundem Lebergewebe nach robotergestützter Leber-SBRT. PURPOSE: For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters. PATIENTS AND METHODS: MRI data at 6-17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3-5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/β-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue. RESULTS: Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy2, 97.5 ± 54.7 Gy3, and 66.5 ± 32.0 Gy8 significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy2, 97.4 ± 41.0 Gy3, and 65.7 ± 24.2 Gy8 significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy2, 79.3 ± 35.3 Gy3, and 56.6 ± 20.9 Gy8 significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2. CONCLUSIONS: Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1-11.3 Gy per fraction (EQD2 79-97 Gy3) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.
Integrated Decentralized Training for Health Professions Education at the University of KwaZulu-Natal, South Africa: Protocol for the I-DecT Project.

BACKGROUND: The Integrated Decentralized Training (i-DecT) project was created to address the current need for health care in South Africa among resource poor climates in rural and periurban settings. The University of KwaZulu-Natal (UKZN) in South Africa has embarked on a program within the School of Health Sciences (SHS) to decentralize the clinical learning platform in order to address this disparity. Framed in a pragmatic stance, this proposal is geared towards informing the roll out of decentralized clinical training (DCT) within the province of KwaZulu-Natal. There currently remains uncertainty as to how the implementation of this program will unfold, especially for the diverse SHS, which includes specialities like audiology, dentistry, occupational therapy, optometry, pharmacy, physiotherapy, speech-language pathology, and sport science. Consequently, there is a need to carefully monitor and manage this DCT in order to ensure that the participating students have a positive learning experience and achieve expected academic outcomes, and that the needs of the communities are addressed adequately. OBJECTIVE: The study aims to explore the factors that will influence the roll-out of the DCT by developing an inclusive and context-specific model that will adhere to the standards set by the SHS for the DCT program at UKZN. METHODS: Key role players, including but not limited to, the South African Ministry of Health policy makers, clinicians, policy makers at UKZN, clinical educators, academicians, and students of UKZN within the SHS will participate in this project. Once the infrastructural, staffing and pedagogical enablers and challenges are identified, together with a review of existing models of decentralized training, a context-specific model for DCTl will be proposed based on initial pilot data that will be tested within iterative cycles in an Action Learning Action Research (ALAR) process. RESULTS: The study was designed to fit within the existing structures, and emerging framework and memorandum of understanding between the partners of this initiative, namely, the Ministry of Health and UKZN in order to develop health care professionals that are competent and prepared for the changing dynamics of healthcare in a developing world. CONCLUSIONS: It is envisioned that this study, the first to include a combination of health professionals in a DCT platform at UKZN, will not only contribute to effective service delivery, but may also serve to promote an interprofessional cooperation within the SHS and tertiary institutions in similar settings.
Predicting the Risk of Developing New Cerebral Lesions After Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastases from Renal Cell Carcinoma.

AIM: To create an instrument for estimating the risk of new brain metastases after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) alone in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In 45 patients with 1-3 brain metastases, seven characteristics were analyzed for association with freedom from new brain metastases (age, gender, performance score, number and sites of brain metastases, extra-cerebral metastasis, interval from RCC diagnosis to SRS/FSRT). RESULTS: Lower risk of subsequent brain lesions after RT was associated with single metastasis (p=0.043) and supratentorial involvement only (p=0.018). Scoring points were: One metastasis=1, 2-3 metastases=0, supratentorial alone=1, infratentorial with/without supratentorial=0. Scores of 0, 1 and 2 points were associated with 6-month rates of freedom from subsequent brain lesions of 25%, 74% and 92% (p=0.008). After combining groups with 1 and 2 points, 6-month rates were 25% for those with 0 points and 83% for those with 1-2 points (p=0.002). CONCLUSION: Two groups were identified with different risks of new brain metastases after SRS or FSRT alone. High-risk patients may benefit from additional whole-brain irradiation.
Development of an evidence-based clinical algorithm for practice in hypotonia assessment: a proposal.

BACKGROUND: Assessing muscle tone in children is essential during the neurological assessment and is often essential in ensuring a more accurate diagnosis for appropriate management. While there have been advances in child neurology, there remains much contention around the subjectivity of the clinical assessment of hypotonia, which is often the first step in the diagnostic process. OBJECTIVE: In response to this challenge, the objective of the study is to develop and validate a prototype of a decision making process in the form of a clinical algorithm that will guide clinicians during this assessment process. METHODS: Design research within a pragmatic stance will be employed in this study. Multi-phase stages of assessment, prototyping and evaluation will occur. These will include processes that include a systematic review, processes of reflection and action as well as validation methods. Given the mixed methods nature of this study, use of NVIVO or ATLAS-ti will be used in the analysis of qualitative data and SPSS for quantitative data. RESULTS: Initial results from the systematic review revealed a paucity of scientific literature that documented the objective assessment of hypotonia in children. The review identified the need for more studies with greater methodological rigor in order to determine best practice with respect to the methods used in the assessment of low muscle tone in the paediatric population. CONCLUSIONS: It is envisaged that this proposal will contribute to a more accurate clinical diagnosis of children with low muscle tone in the absence of a gold standard. We anticipate that the use of this tool will ultimately assist clinicians towards moving to evidenced based practice whilst upholding best practice in the care of children with hypotonia.
Measuring Acquired Capability for Suicide within an Ideation-to-Action Framework.

Objective: Despite the large literature on risk factors for suicide-related outcomes, few studies have examined risk for acting on suicidal thoughts among suicide ideators. The current study aimed to fill this gap by examining the role of acquired capability, as well as its hypothesized facilitator, painful and provocative events (PPEs), as motivators for behavior among individuals along the suicide continuum. Method: Undergraduates reporting suicidal ideation, suicide plans, suicide attempts without intent to die, or suicide attempts with intent to die (N=546) completed a measure of acquired capability for suicide, as well as assessments of exposure to PPEs. Results: Our findings demonstrated that acquired capability for suicide did not distinguish between individuals falling along the ideation-to-action spectrum. Among the several PPEs assessed, the frequency of non-suicidal self-injury, and the presence of childhood emotional abuse, physical abuse, and physical neglect each significantly differentiated between groups, with individuals having a history of a suicide attempt with the intent to die reporting the highest levels. Conclusions: These findings implicate the PPEs that may be most important to assess in determining suicide risk, and, further, call into question the utility of acquired capability in differentiating between individuals along the suicide continuum.