Miracle-dz/UniFAR-FTUs huggingface dataset:
Radiobiological doses, tumor, and treatment features influence on outcomes after epiescleral brachytherapy. A 20-year retrospective analysis from a single-institution: part II

Purpose To assess the influence of the radiobiological doses, tumor, and treatment features on retinopathy, cataracts, retinal detachment, optic neuropathy, vitreous hemorrhage, and neovascular glaucoma at the authors’ institution after brachytherapy for posterior uveal melanoma. Material and methods Medical records of 243 eyes with uveal melanoma, treated by iodine brachytherapy between 1996 and 2016 at a single center were analyzed. Clinical and radiotherapy data were extracted from a dedicated database. Biologically effective dose (BED) was included in survival analysis performed using Kaplan-Meier and Cox regressions. Relative survival rates were estimated, and univariate/multivariate regression models were constructed for predictive factors of each item. Hazard ratio and confidence interval at 95% were determined. Variables statistically significant were analyzed and compared by log-rank tests. Results The median follow-up was 73.9 months (range, 3-202 months). Cumulative probabilities of survival by Kaplan-Meier analysis at 3 and 5 years, respectively, were: 59% and 48% for retinopathy; 71% and 55% for cataracts; 63% and 57% for retinal detachment; 88% and 79% for optic neuropathy; 87% and 83% for vitreous hemorrhage; 92% and 89% for neovascular glaucoma, respectively. Using multivariate analysis, statistically significant risk factors were: age, tumor apical height, dose to foveola, and location of anterior border for retinopathy; age, dose to lens, type of plaque, and tumor shape, for cataracts; age, tumor apical height, and size of the plaque for retinal detachment; age, plaque shape, longest basal dimension, and BED to optic nerve for optic neuropathy; age, tumor apical height, and tumor shape for vitreous hemorrhage; tumor apical height and BED to foveola for neovascular glaucoma. Conclusions Tumor factors in addition to radiation treatment may contribute to secondary effects. Enhanced clinical optimization should evaluate radiobiological doses delivered to the tumor volume and surrounding normal ocular structures.
Comparative analysis of prokaryotic and eukaryotic transcription factors using machine-learning techniques

The DNA-protein interactions play vital roles in the central dogma of molecular biology. Proper interactions between DNA and protein would lead to the onset of various biological phenomena like transcription, translation, and replication. However, the mechanisms of these well-known processes vary between prokaryotic and eukaryotic organisms. The exact molecular mechanisms of these processes are unknown. Therefore, it is of interest to report the comparative estimate of the different properties of the DNA binding proteins from prokaryotic and eukaryotic organisms. We analyzed the different sequence-based features such as the frequency of amino acids and amino acid groups in the proteins of prokaryotes and eukaryotes by statistical measures. The general pattern of differences between the various DNA binding proteins for the development of a prediction system to discriminate between these proteins between prokaryotes and eukaryotes is documented.
A review of the effects of baclofen and of THC:CBD oromucosal spray on spasticity-related walking impairment in multiple sclerosis

ABSTRACT Introduction: Multiple sclerosis (MS) is a complex disease with a heterogeneous and unpredictable clinical course. Mobility impairment after progressive paralyses and muscle tone spasticity is common. Areas covered: The prevalence, assessment, and pharmacological management of gait impairment and spasticity in MS and their effects on health-related quality of life (HRQoL) are discussed. The roles of oral and intrathecal baclofen and of delta-9-tetrahydrocannabinol/cannabidiol (THC:CBD) oromucosal spray in treating MS spasticity-related gait impairment are reviewed. Expert commentary: Mobility impairment and spasticity are experienced by approximately 90% and 80% of MS patients, respectively, during the disease course. Prevalence and severity of gait impairment and spasticity increase as disease progresses. The symptoms are related and both impact negatively on HRQoL. Oral baclofen and tizanidine are generally used for first-line treatment of MS spasticity but are ineffective in approximately 40% of cases. Second-line therapy includes add-on THC:CBD spray for patients with resistant MS spasticity. Results of studies evaluating baclofen for treating MS spasticity gait impairment are equivocal. In studies of patients with resistant MS spasticity, THC:CBD spray consistently improved the timed 10-meter walk test and significantly improved multiple spatial-temporal and kinematic gait parameters. THC:CBD oromucosal spray warrants further investigation as a treatment for MS spasticity-related gait impairment.
Finding Explanations of Entity Relatedness in Graphs: A Survey

Analysing and explaining relationships between entities in a graph is a fundamental problem associated with many practical applications. For example, a graph of biological pathways can be used for discovering a previously unknown relationship between two proteins. Domain experts, however, may be reluctant to trust such a discovery without a detailed explanation as to why exactly the two proteins are deemed related in the graph. This paper provides an overview of the types of solutions, their associated methods and strategies, that have been proposed for finding entity relatedness explanations in graphs. The first type of solution relies on information inherent to the paths connecting the entities. This type of solution provides entity relatedness explanations in the form of a list of ranked paths. The rank of a path is measured in terms of importance, uniqueness, novelty and informativeness. The second type of solution relies on measures of node relevance. In this case, the relevance of nodes is measured w.r. t. the entities of interest, and relatedness explanations are provided in the form of a subgraph that maximises node relevance scores. This paper uses this classification of approaches to discuss and contrast some of the key concepts that guide different solutions to the problem of entity relatedness explanation in graphs.
Sequence clustering in bioinformatics: an empirical study.

Sequence clustering is a basic bioinformatics task that is attracting renewed attention with the development of metagenomics and microbiomics. The latest sequencing techniques have decreased costs and as a result, massive amounts of DNA/RNA sequences are being produced. The challenge is to cluster the sequence data using stable, quick and accurate methods. For microbiome sequencing data, 16S ribosomal RNA operational taxonomic units are typically used. However, there is often a gap between algorithm developers and bioinformatics users. Different software tools can produce diverse results and users can find them difficult to analyze. Understanding the different clustering mechanisms is crucial to understanding the results that they produce. In this review, we selected several popular clustering tools, briefly explained the key computing principles, analyzed their characters and compared them using two independent benchmark datasets. Our aim is to assist bioinformatics users in employing suitable clustering tools effectively to analyze big sequencing data. Related data, codes and software tools were accessible at the link http://lab.malab. cn/∼lg/clustering/.
Revisit of the eigenfilter method for the design of FIR filters and wideband beamformers*

ABSTRACT The least squares-based eigenfilter method has been applied to the design of both finite impulse response (FIR) filters and wideband beamformers successfully. It involves calculating the resultant filter coefficients as the eigenvector of an appropriate Hermitian matrix, and offers lower complexity and less computation time with better numerical stability as compared to the standard least squares method. In this paper, we revisit the method and critically analyse the eigenfilter method by revealing a serious performance issue in the passband of the designed FIR filter and the mainlobe of the wideband beamformer, which occurs due to a formulation problem. A solution is then proposed to mitigate this issue by imposing an additional constraint to control the response at the passband/mainlobe, and design examples for both FIR filters and wideband beamformers are provided to demonstrate the effectiveness of the proposed method.
Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV.

BACKGROUND Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa. METHODS In this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO). RESULTS We found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA). CONCLUSIONS The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.
Uwaga na twórczość! Poznawcze aspekty kreatywności

Głównym problemem badawczym jest różnicowanie stanu uwagi w czasie wykonywania zadań konwergencyjnych i dywergencyjnych. Zadania dywergencyjne wiązane są z procesami twórczymi. Zadania te wymagają różnorodnych i często nowych rozwiązań. Niezbędne jest wówczas aktywowanie w pamięci roboczej informacji słabo połączonych z siecią pamięci długotrwałej. Kluczowym procesem w aktywowaniu informacji w pamięci jest uwaga. Postawiona została hipoteza mówiąca, że zadania dywergencyjne są wykonywane przy większej ekstensyfikacji uwagi niż zadania konwergencyjne. Procedura badawcza wykorzystana w przeprowadzonym eksperymencie opierała się na jednoczesnym wykonywaniu zadania konwergencyjnego (odtwarzania zapamiętanej melodii) lub dywergencyjnego (improwizacja w oparciu o zapamiętaną melodię), przy jednoczesnym rozwiązywaniu testu mierzącego ekstensywność uwagi. Uzyskane wyniki wspierają postawioną hipotezę. Procesy twórcze zależą od stanu uwagi i jej aktywnego działania.
Salivary metabolite profiling distinguishes patients with oral cavity squamous cell carcinoma from normal controls

Oral cavity squamous cell carcinoma (OCC) and oropharyngeal squamous cell carcinoma (OPC) are among the most common cancers worldwide and are associated with high mortality and morbidity. The purpose of this study is to identify potential biomarkers to distinguish OCC/OPC from normal controls and to distinguish OCC patients with and without nodal metastasis. We tested saliva samples from 101 OCC, 58 OPC, and 35 normal controls using four analytical platforms (NMR, targeted aqueous by LC-MS/MS, global aqueous and global lipidomics by LC-Q-TOF). Samples from OCC and normal controls were divided into discovery and validation sets. Using linear regression adjusting for age, sex, race and experimental batches, we found the levels of two metabolites (glycine and proline) to be significantly different between OCC and controls (FDR < 0.1 for both discovery and validation sets) but did not find any appreciable differences in metabolite levels between OPC and controls or between OCC with and without nodal metastasis. Four metabolites, including glycine, proline, citrulline, and ornithine were associated with early stage OCC in both discovery and validation sets. Further study is warranted to confirm these results in the development of salivary metabolites as diagnostic markers.
Sequence-Subset Distance and Coding for Error Control in DNA-Based Data Storage

The process of DNA-based data storage (DNA storage for short) can be mathematically modelled as a communication channel, termed DNA storage channel, whose inputs and outputs are sets of unordered sequences. To design error correcting codes for DNA storage channel, a new metric, termed the sequence-subset distance, is introduced, which generalizes the Hamming distance to a distance function defined between any two sets of unordered vectors and helps to establish a uniform framework to design error correcting codes for DNA storage channel. We further introduce a family of error correcting codes, referred to as sequence-subset codes, for DNA storage and show that the error-correcting ability of such codes is completely determined by their minimum distance. We derive some upper bounds on the size of the sequence-subset codes including a tight bound for a special case, a Singleton-like bound and a Plotkin-like bound. We also propose some constructions, including an optimal construction for that special case, which imply lower bounds on the size of such codes.
Blinded Sample Size Recalculation in Longitudinal Clinical Trials Using Generalized Estimating Equations

In clinical trials in which outcomes are measured repeatedly during the follow-up phase, data analysis is frequently performed using generalized estimating equations (GEEs). Sample size calculation is then especially challenging since in addition to the treatment effect, the intrasubject correlation and the variability of the model error term have to be specified. In this article, the authors investigated by Monte Carlo simulations whether a blinded midcourse estimation of these quantities in an internal pilot study design is feasible in such trials and whether nominal type I and type II error rates are preserved when the estimates are used for sample size recalculation. The actual type I error rates of the blinded sample size recalculation procedure turned out to agree well with the nominal levels. Furthermore, the simulated power was observed to be near the target value as long as the sample size of the internal pilot study was sufficiently high and the bound effects induced by the range of the correlation were limited. The proposed procedure is a helpful tool to achieve robustness of the power with respect to initial misspecifications in the planning stage in clinical trials analyzed by GEE.
The Relation Between Capillary Transit Times and Hemoglobin Saturation Heterogeneity. Part 2: Capillary Networks

Brain metabolism is highly dependent on continuous oxygen supply. Cortical microvascular networks exhibit heterogeneous blood flow, leading to non-uniform tissue oxygenation and capillary hemoglobin saturation. We recently proposed capillary outflow saturation heterogeneity (COSH) to represent effects of heterogeneity on oxygen supply to tissue regions most vulnerable to hypoxia, and showed that diffusive oxygen exchange among red blood cells within capillaries and among capillaries (diffusive interaction) significantly reduces COSH in simplified geometrical configurations. Here, numerical simulations of oxygen transport in capillary network geometries derived from mouse somatosensory cortex are presented. Diffusive interaction was found to reduce COSH by 41 to 62% compared to simulations where diffusive interaction was excluded. Hemoglobin saturation drop across the microvascular network is strongly correlated with red blood cell transit time, but the coefficient of variation of saturation drop is approximately one third lower. Unexpectedly, the radius of the tissue cylinder supplied by a capillary correlates weakly with the anatomical tissue cylinder radius, but strongly with hemoglobin saturation. Thus, diffusive interaction contributes greatly to the microcirculation's ability to achieve tissue oxygenation, despite heterogeneous capillary transit time and hematocrit distribution. These findings provide insight into the effects of cerebral small vessel disease on tissue oxygenation and brain function.
Quantum rejection sampling

Rejection sampling is a well-known method to sample from a target distribution, given the ability to sample from a given distribution. The method has been first formalized by von Neumann [1951] and has many applications in classical computing. We define a quantum analogue of rejection sampling: given a black box producing a coherent superposition of (possibly unknown) quantum states with some amplitudes, the problem is to prepare a coherent superposition of the same states, albeit with different target amplitudes. The main result of this article is a tight characterization of the query complexity of this quantum state generation problem. We exhibit an algorithm, which we call quantum rejection sampling, and analyze its cost using semidefinite programming. Our proof of a matching lower bound is based on the automorphism principle that allows to symmetrize any algorithm over the automorphism group of the problem. Our main technical innovation is an extension of the automorphism principle to continuous groups that arise for quantum state generation problems where the oracle encodes unknown quantum states, instead of just classical data. Furthermore, we illustrate how quantum rejection sampling may be used as a primitive in designing quantum algorithms, by providing three different applications. We first show that it was implicitly used in the quantum algorithm for linear systems of equations by Harrow et al. [2009]. Second we show that it can be used to speed up the main step in the quantum Metropolis sampling algorithm by Temme et al. [2011]. Finally, we derive a new quantum algorithm for the hidden shift problem of an arbitrary Boolean function and relate its query complexity to “water-filling” of the Fourier spectrum.
Comparing length and frequency effects in children across modalities

Although it is well established that beginning readers rely heavily on phonological decoding, the overlap of the phonological pathways used in visual and auditory word recognition is not clear. Especially in transparent languages, phonological reading could use the same pathways as spoken word processing. In the present study, we report a direct comparison of lexical decision performance in the visual and auditory modality in beginning readers of a transparent language. Using lexical decision, we examine how marker effects of length and frequency differ in the two modalities and how these differences are modulated by reading ability. The results show that both frequency and length effects are stronger in the visual modality, and the differences in length effects between modalities are more pronounced for poorer readers than for better readers. This suggests that visual word recognition in beginning readers of a transparent language initially is based on phonological decoding and subsequent matching in the phonological lexicon, especially for poor readers. However, some orthographic processing seems to be involved already. We claim that the relative contribution of the phonological and orthographic route in beginning readers can be measured by the differences in marker effects between auditory and visual lexical decision.
Facilitators and inhibitors of transition for older people who have relocated to a long‐term care facility: A systematic review

Moving into a long-term care facility to live permanently is a significant life event for older people. Care facilities need to support older people to make a healthy transition following relocation. To help achieve this, we need to understand what facilitates and inhibits the transition process from the perspective of older people, their families, and care facility staff. Our review generated new knowledge to inform this understanding. We addressed the question: what factors facilitate and inhibit transition for older people who have relocated to a long-term care facility? Five electronic databases, PsychINFO, British Nursing Index, CINAHL, MEDLINE and Web of Science were searched for the period January 1990 to October 2017. Grey literature searches were conducted using Google Scholar, and Social Science Research Network. Data were extracted for individual studies and a narrative synthesis was conducted informed by Meleis's Theory of Transition. Thirty-four studies (25 qualitative, 7 quantitative and 2 mixed methods) met the inclusion criteria. Data synthesis identified that transition following relocation was examined using a variety of terms, timelines and study designs. Potential personal and community focused facilitators and inhibitors mapped to four themes: resilience of the older person, interpersonal connections and relationships, this is my new home, and the care facility as an organisation. These findings can inform the development of interventions for these target areas. They highlight also that further research is warranted to understand the organisational culture of long-term care facilities, how this influences transition, and how it might be shaped to create and sustain a caring culture for older people.
Discovering Causal Relationships in Grapevine Expression Data to Expand Gene Networks. A Case Study: Four Networks Related to Climate Change

In recent years the scientific community has been heavily engaged in studying the grapevine response to climate change. Final goal is the identification of key genetic traits to be used in grapevine breeding and the setting of agronomic practices to improve climatic resilience. The increasing availability of transcriptomic studies, describing gene expression in many tissues and developmental, or treatment conditions, have allowed the implementation of gene expression compendia, which enclose a huge amount of information. The mining of transcriptomic data represents an effective approach to expand a known local gene network (LGN) by finding new related genes. We recently published a pipeline based on the iterative application of the PC-algorithm, named NES2RA, to expand gene networks in Escherichia coli and Arabidopsis thaliana. Here, we propose the application of this method to the grapevine transcriptomic compendium Vespucci, in order to expand four LGNs related to the grapevine response to climate change. Two networks are related to the secondary metabolic pathways for anthocyanin and stilbenoid synthesis, involved in the response to solar radiation, whereas the other two are signaling networks, related to the hormones abscisic acid and ethylene, possibly involved in the regulation of cell water balance and cuticle transpiration. The expansion networks produced by NES2RA algorithm have been evaluated by comparison with experimental data and biological knowledge on the identified genes showing fairly good consistency of the results. In addition, the algorithm was effective in retaining only the most significant interactions among the genes providing a useful framework for experimental validation. The application of the NES2RA to Vitis vinifera expression data by means of the BOINC-based implementation is available upon request (valter.cavecchia@cnr.it).