Takshan/R1 huggingface dataset:
Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors.

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.
Laparoscopic instrument use in laryngeal surgery: transoral resection of a supraglottic haemangioma.

BACKGROUND: Adult laryngeal haemangiomas are rare vascular tumours that have been managed by a variety of surgical techniques. METHODS: This paper describes a case of near-fatal acute airway obstruction secondary to such a lesion, followed by our approach to surgical resection using a laparoscopic bipolar tissue-sealing device. RESULTS: This technique resulted in successful excision of the lesion, with no evidence of recurrence at one year of follow up. CONCLUSION: Laparoscopic bipolar instruments can be used for the resection of moderate to large laryngeal haemangiomas as an alternative to laser excision.
Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit.

OBJECTIVE: Numerous factors can cause delays in transfer to an intensive care unit for critically ill emergency department patients. The impact of delays is unknown. We aimed to determine the association between emergency department "boarding" (holding admitted patients in the emergency department pending intensive care unit transfer) and outcomes for critically ill patients. DESIGN: This was a cross-sectional analytical study using the Project IMPACT database (a multicenter U.S. database of intensive care unit patients). Patients admitted from the emergency department to the intensive care unit (2000-2003) were included and divided into two groups: emergency department boarding >or=6 hrs (delayed) vs. emergency department boarding <6 hrs (nondelayed). Demographics, intensive care unit procedures, length of stay, and mortality were analyzed. Groups were compared using chi-square, Mann-Whitney, and unpaired Student's t-tests. SETTING: Emergency department and intensive care unit. PATIENTS: Patients admitted from the emergency department to the intensive care unit (2000-2003). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Main outcomes were intensive care unit and hospital survival and intensive care unit and hospital length of stay. During the study period, 50,322 patients were admitted. Both groups (delayed, n = 1,036; nondelayed, n = 49,286) were similar in age, gender, and do-not-resuscitate status, along with Acute Physiology and Chronic Health Evaluation II score in the subgroup for which it was recorded. Among hospital survivors, the median hospital length of stay was 7.0 (delayed) vs. 6.0 days (nondelayed) (p < .001). Intensive care unit mortality was 10.7% (delayed) vs. 8.4% (nondelayed) (p < .01). In-hospital mortality was 17.4% (delayed) vs. 12.9% (nondelayed) (p < .001). In the stepwise logistic model, delayed admission, advancing age, higher Acute Physiology and Chronic Health Evaluation II score, male gender, and diagnostic categories of trauma, intracerebral hemorrhage, and neurologic disease were associated with lower hospital survival (odds ratio for delayed admission, 0.709; 95% confidence interval, 0.561-0.895). CONCLUSIONS: Critically ill emergency department patients with a >or=6-hr delay in intensive care unit transfer had increased hospital length of stay and higher intensive care unit and hospital mortality. This suggests the need to identify factors associated with delayed transfer as well as specific determinants of adverse outcomes.
Hyperglycaemia, oxidative stress and inflammatory markers.

INTRODUCTION: The increasing prevalence of hyperglycaemia implicates a state of oxidative stress and inflammation. Traditional and emerging biomarkers associated with increasing hyperglycaemia were assessed to clarify their role they play in hyperglycaemia. RESULTS: 309 participants attending a rural diabetic screening program were categorised into control and quintile groups based upon glucose levels: 1st quintile - <4.5 mmol/L and 4th, 5th quintile - >6.1 mmol/L. Significant results were obtained for anthropometric data and biochemical markers - glucose, HbA1c and total cholesterol (P < 0.001); oxidative stress: glutathione (P < 0.001), glutathione:glutathione disulfide and 8-hydroxy-2-deoxyguanosine (P < 0.05). Interleukin -1β and inflammatory marker ratios IL-6/IL-10, IL-1β/IL-10, MCP-1/IL-10, IGF-1/IL-10 and IL-6/IL-1β were significant (P < 0.05). CONCLUSION: This study provided further evidence that inflammatory and oxidative stress biomarkers may contribute to diagnostic information associated with preclinical increases in BGL. Further we have provided a unique study in the analysis of ratios of inflammatory biomarkers and correlations with increasing BGL.
A Longitudinal Imaging Genetics Study of Neuroanatomical Asymmetry in Alzheimer's Disease.

BACKGROUND: Contralateral brain structures represent a unique, within-patient reference element for disease, and asymmetries can provide a personalized measure of the accumulation of past disease processes. Neuroanatomical shape asymmetries have recently been associated with the progression of Alzheimer's disease (AD), but the biological basis of asymmetric brain changes in AD remains unknown. METHODS: We investigated genetic influences on brain asymmetry by identifying associations between magnetic resonance imaging-derived measures of asymmetry and candidate single nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies for AD diagnosis and for brain subcortical volumes. For analyzing longitudinal neuroimaging data (1241 individuals, 6395 scans), we used a mixed effects model with interaction between genotype and diagnosis. RESULTS: Significant associations between asymmetry of the amygdala, hippocampus, and putamen and SNPs in the genes BIN1, CD2AP, ZCWPW1, ABCA7, TNKS, and DLG2 were found. CONCLUSIONS: The associations between SNPs in the genes TNKS and DLG2 and AD-related increases in shape asymmetry are of particular interest; these SNPs have previously been associated with subcortical volumes of amygdala and putamen but have not yet been associated with AD pathology. For AD candidate SNPs, we extend previous work to show that their effects on subcortical brain structures are asymmetric. This provides novel evidence about the biological underpinnings of brain asymmetry as a disease marker.
Accurate prediction of protein contact maps by coupling residual two-dimensional bidirectional long short-term memory with convolutional neural networks.

Motivation: Accurate prediction of a protein contact map depends greatly on capturing as much contextual information as possible from surrounding residues for a target residue pair. Recently, ultra-deep residual convolutional networks were found to be state-of-the-art in the latest Critical Assessment of Structure Prediction techniques (CASP12) for protein contact map prediction by attempting to provide a protein-wide context at each residue pair. Recurrent neural networks have seen great success in recent protein residue classification problems due to their ability to propagate information through long protein sequences, especially Long Short-Term Memory (LSTM) cells. Here, we propose a novel protein contact map prediction method by stacking residual convolutional networks with two-dimensional residual bidirectional recurrent LSTM networks, and using both one-dimensional sequence-based and two-dimensional evolutionary coupling-based information. Results: We show that the proposed method achieves a robust performance over validation and independent test sets with the Area Under the receiver operating characteristic Curve (AUC) > 0.95 in all tests. When compared to several state-of-the-art methods for independent testing of 228 proteins, the method yields an AUC value of 0.958, whereas the next-best method obtains an AUC of 0.909. More importantly, the improvement is over contacts at all sequence-position separations. Specifically, a 8.95%, 5.65% and 2.84% increase in precision were observed for the top L∕10 predictions over the next best for short, medium and long-range contacts, respectively. This confirms the usefulness of ResNets to congregate the short-range relations and 2D-BRLSTM to propagate the long-range dependencies throughout the entire protein contact map 'image'. Availability and implementation: SPOT-Contact server url: http://sparks-lab.org/jack/server/SPOT-Contact/. Supplementary information: Supplementary data are available at Bioinformatics online.
Ensemble Methods for MiRNA Target Prediction from Expression Data.

BACKGROUND: microRNAs (miRNAs) are short regulatory RNAs that are involved in several diseases, including cancers. Identifying miRNA functions is very important in understanding disease mechanisms and determining the efficacy of drugs. An increasing number of computational methods have been developed to explore miRNA functions by inferring the miRNA-mRNA regulatory relationships from data. Each of the methods is developed based on some assumptions and constraints, for instance, assuming linear relationships between variables. For such reasons, computational methods are often subject to the problem of inconsistent performance across different datasets. On the other hand, ensemble methods integrate the results from individual methods and have been proved to outperform each of their individual component methods in theory. RESULTS: In this paper, we investigate the performance of some ensemble methods over the commonly used miRNA target prediction methods. We apply eight different popular miRNA target prediction methods to three cancer datasets, and compare their performance with the ensemble methods which integrate the results from each combination of the individual methods. The validation results using experimentally confirmed databases show that the results of the ensemble methods complement those obtained by the individual methods and the ensemble methods perform better than the individual methods across different datasets. The ensemble method, Pearson+IDA+Lasso, which combines methods in different approaches, including a correlation method, a causal inference method, and a regression method, is the best performed ensemble method in this study. Further analysis of the results of this ensemble method shows that the ensemble method can obtain more targets which could not be found by any of the single methods, and the discovered targets are more statistically significant and functionally enriched. The source codes, datasets, miRNA target predictions by all methods, and the ground truth for validation are available in the Supplementary materials.
Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk.

BACKGROUND: Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS: Eighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling. The concentrations of apoE in HDL that contain or lack apoCIII were measured in a prospective study in Denmark including 1,949 incident CHD cases during 9 years. RESULTS: HDL containing apoE but not apoCIII is disproportionately secreted into the circulation, actively expands while circulating, and is quickly cleared. These are key metabolic steps in reverse cholesterol transport, which may protect against atherosclerosis. ApoCIII on HDL strongly attenuates these metabolic actions of HDL apoE. In the epidemiological study, the relation between HDL apoE concentration and CHD significantly differed depending on whether apoCIII was present. HDL apoE was associated significantly with lower risk of CHD only in the HDL subspecies lacking apoCIII. CONCLUSIONS: ApoE and apoCIII on HDL interact to affect metabolism and CHD. ApoE promotes metabolic steps in reverse cholesterol transport and is associated with lower risk of CHD. ApoCIII, when coexisting with apoE on HDL, abolishes these benefits. Therefore, differences in metabolism of HDL subspecies pertaining to reverse cholesterol transport are reflected in differences in association with CHD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01399632. FUNDING: This work was supported by NIH grant R01HL095964 to FMS and by a grant to the Harvard Clinical and Translational Science Center (8UL1TR0001750) from the National Center for Advancing Translational Science.