bluuebunny/crossref_metadata_2025_split huggingface dataset:
The progression of chronic tinnitus over the years
Authors: Simões Jorge P. , Neff Patrick K. A. , Langguth Berthold , Schlee Winfried , Schecklmann Martin 
Published: February 2021

AbstractLittle is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers.
Deep learning based automated diagnosis of bone metastases with SPECT thoracic bone images
Authors: Lin Qiang , Li Tongtong , Cao Chuangui , Cao Yongchun , Man Zhengxing , Wang Haijun 
Published: February 2021

AbstractSPECT nuclear medicine imaging is widely used for treating, diagnosing, evaluating and preventing various serious diseases. The automated classification of medical images is becoming increasingly important in developing computer-aided diagnosis systems. Deep learning, particularly for the convolutional neural networks, has been widely applied to the classification of medical images. In order to reliably classify SPECT bone images for the automated diagnosis of metastasis on which the SPECT imaging solely focuses, in this paper, we present several deep classifiers based on the deep networks. Specifically, original SPECT images are cropped to extract the thoracic region, followed by a geometric transformation that contributes to augment the original data. We then construct deep classifiers based on the widely used deep networks including VGG, ResNet and DenseNet by fine-tuning their parameters and structures or self-defining new network structures. Experiments on a set of real-world SPECT bone images show that the proposed classifiers perform well in identifying bone metastasis with SPECT imaging. It achieves 0.9807, 0.9900, 0.9830, 0.9890, 0.9802 and 0.9933 for accuracy, precision, recall, specificity, F-1 score and AUC, respectively, on the test samples from the augmented dataset without normalization.
Defining the epitope of a blood–brain barrier crossing single domain antibody specific for the type 1 insulin-like growth factor receptor
Authors: Sheff Joey , Wang Ping , Xu Ping , Arbour Melanie , Masson Luke , van Faassen Henk , Hussack Greg , Kemmerich Kristin , Brunette Eric , Stanimirovic Danica , Hill Jennifer J. , Kelly John , Ni Feng 
Published: February 2021

AbstractLigand-activated signaling through the type 1 insulin-like growth factor receptor (IGF1R) is implicated in many physiological processes ranging from normal human growth to cancer proliferation and metastasis. IGF1R has also emerged as a target for receptor-mediated transcytosis, a transport phenomenon that can be exploited to shuttle biotherapeutics across the blood–brain barrier (BBB). We employed differential hydrogen–deuterium exchange mass spectrometry (HDX-MS) and nuclear magnetic resonance (NMR) to characterize the interactions of the IGF1R ectodomain with a recently discovered BBB-crossing single-domain antibody (sdAb), VHH-IR5, in comparison with IGF-1 binding. HDX-MS confirmed that IGF-1 induced global conformational shifts in the L1/FnIII-1/-2 domains and α-CT helix of IGF1R. In contrast, the VHH-IR5 sdAb-mediated changes in conformational dynamics were limited to the α-CT helix and its immediate vicinity (L1 domain). High-resolution NMR spectroscopy titration data and linear peptide scanning demonstrated that VHH-IR5 has high-affinity binding interactions with a peptide sequence around the C-terminal region of the α-CT helix. Taken together, these results define a core linear epitope for VHH-IR5 within the α-CT helix, overlapping the IGF-1 binding site, and suggest a potential role for the α-CT helix in sdAb-mediated transcytosis.
Multivariate spatio-temporal approach to identify vulnerable localities in dengue risk areas using Geographic Information System (GIS)
Authors: Withanage Gayan P. , Gunawardana Malika , Viswakula Sameera D. , Samaraweera Krishantha , Gunawardena Nilmini S. , Hapugoda Menaka D. 
Published: February 2021

AbstractDengue is one of the most important vector-borne infection in Sri Lanka currently leading to vast economic and social burden. Neither a vaccine nor drug is still not being practiced, vector controlling is the best approach to control disease transmission in the country. Therefore, early warning systems are imminent requirement. The aim of the study was to develop Geographic Information System (GIS)-based multivariate analysis model to detect risk hotspots of dengue in the Gampaha District, Sri Lanka to control diseases transmission. A risk model and spatial Poisson point process model were developed using separate layers for patient incidence locations, positive breeding containers, roads, total buildings, public places, land use maps and elevation in four high risk areas in the district. Spatial correlations of each study layer with patient incidences was identified using Kernel density and Euclidean distance functions with minimum allowed distance parameter. Output files of risk model indicate that high risk localities are in close proximity to roads and coincide with vegetation coverage while the Poisson model highlighted the proximity of high intensity localities to public places and possibility of artificial reservoirs of dengue. The latter model further indicate that clustering of dengue cases in a radius of approximately 150 m in high risk areas indicating areas need intensive attention in future vector surveillances.
Longitudinal analysis of safety and medication adherence of patients in the Fingolimod patient support program: a real-world observational study
Authors: Bourdin Aline , Schneider Marie Paule , Locatelli Isabella , Schluep Myriam , Bugnon Olivier , Berger Jérôme 
Published: February 2021

AbstractThe Fingolimod Patient Support Program (F-PSP) is an interprofessional specialty pharmacy service designed to ensure responsible use of fingolimod by promoting patient safety and medication adherence. This study aims to evaluate the safety and medication adherence of patients who joined the F-PSP between 2013 and 2016. Sociodemographic and medical characteristics, patient safety data (patient-reported symptoms, discontinuations due to adverse events (AEs), repeated first-dose monitoring), and medication adherence (implementation, persistence, reasons for discontinuation, influence of covariates, barriers and facilitators) were described. Sixty-seven patients joined the F-PSP. Patients reported a high frequency of symptoms. Due to AEs, 7 patients discontinued fingolimod, 3 took therapeutic breaks, and 1 reduced the regimen temporarily. Three patients repeated the first-dose monitoring. Patients had a high medication adherence over the 18-month analysis period: implementation decreased from 98.8 to 93.7%, and fingolimod persistence was 83.2% at 18 months. The patients’ level of education, professional situation, and living with child(ren) influenced implementation. Patients reported more facilitators of medication adherence than barriers. The F-PSP seems valuable for supporting individual patients (ensuring responsible use of fingolimod and inviting patients for shared-decision making) and public health (indirectly gathering real-world evidence).
HLA diversity in the Argentinian Umbilical Cord Blood Bank: frequencies according to donor’s reported ancestry and geographical distribution
Authors: Fernández Souto Daniela , Rosello Julieta , Lazo Laura , Veloso Florencia , Gamba Cecilia , Kuperman Silvina , Roca Valeria 
Published: February 2021

AbstractUmbilical cord blood (UCB) is a suitable source for hematopoietic stem cell transplantation. The study of HLA genes by next generation sequencing is commonly used in transplants. Donor/patient HLA matching is often higher within groups of common ancestry, however “Hispanic” is a broad category that fails to represent Argentina’s complex genetic admixture. Our aim is to describe HLA diversity of banked UCB units collected across the country taking into consideration donor’s reported ancestral origins as well as geographic distribution. Our results showed an evenly distribution of units mainly for 2 groups: of European and of Native American descent, each associated to a defined geographic location pattern (Central vs. North regions). We observed differences in allele frequency distributions for some alleles previously described in Amerindian populations: for Class I (A*68:17, A*02:11:01G, A*02:22:01G, B*39:05:01, B*35:21, B*40:04, B*15:04:01G, B*35:04:01, B*51:13:01) and Class II (DRB1*04:11:01, DRB1*04:07:01G/03, DRB1*08:02:01, DRB1*08:07, DRB1*09:01:02G, DRB1*14:02:01, DRB1*16:02:01G). Our database expands the current knowledge of HLA diversity in Argentinian population. Although further studies are necessary to fully comprehend HLA heterogeneity, this report should prove useful to increase the possibility of finding compatible donors for successful allogeneic transplant and to improve recruitment strategies for UCB donors across the country.
MTBP phosphorylation controls DNA replication origin firing
Authors: Ferreira Pedro , Höfer Verena , Kronshage Nora , Marko Anika , Reusswig Karl-Uwe , Tetik Bilal , Dießel Christoph , Köhler Kerstin , Tschernoster Nikolai , Altmüller Janine , Schulze Nina , Pfander Boris , Boos Dominik 
Published: February 2021

AbstractFaithful genome duplication requires regulation of origin firing to determine loci, timing and efficiency of replisome generation. Established kinase targets for eukaryotic origin firing regulation are the Mcm2-7 helicase, Sld3/Treslin/TICRR and Sld2/RecQL4. We report that metazoan Sld7, MTBP (Mdm2 binding protein), is targeted by at least three kinase pathways. MTBP was phosphorylated at CDK consensus sites by cell cycle cyclin-dependent kinases (CDK) and Cdk8/19-cyclin C. Phospho-mimetic MTBP CDK site mutants, but not non-phosphorylatable mutants, promoted origin firing in human cells. MTBP was also phosphorylated at DNA damage checkpoint kinase consensus sites. Phospho-mimetic mutations at these sites inhibited MTBP’s origin firing capability. Whilst expressing a non-phospho MTBP mutant was insufficient to relieve the suppression of origin firing upon DNA damage, the mutant induced a genome-wide increase of origin firing in unperturbed cells. Our work establishes MTBP as a regulation platform of metazoan origin firing.
Beta cell function, insulin resistance and vitamin D status among type 2 diabetes patients in Western Kenya
Authors: Said Jamil , Lagat David , Kimaina Allan , Oduor Chrispine 
Published: February 2021

AbstractSerum vitamin D status exerts effects on glucose-insulin-homeostatic states underlying Diabetes-Mellitus, Type 2 (T2DM). This has been described in white and Asian population where low Vitamin D levels predicted future impairments in beta cell function and worsening of insulin resistance. This study aimed to examine the relationship between serum vitamin D, insulin resistance and beta cell function in a sub population of black Kenyan T2DM patients. The primary objective was to determine the levels of serum 25 hydroxy (25-OH) vitamin D, and estimate the insulin resistance, and beta cell function among T2DM patients at Moi Teaching and Referral Hospital (MTRH). This was a cross sectional study. 124 T2DM patients attending the MTRH Diabetes clinic between February and May 2016 were enrolled. Patients on insulin therapy and/or thiazolidinediones were excluded. Anthropometric, clinical and demographic data was obtained. Samples were drawn for estimation of serum 25-OH vitamin D, fasting insulin levels and fasting blood glucose levels. HOMA (Homeostatic model of assessment) model was used to estimate Beta cell secretion (HOMA-B) and insulin resistance (HOMA-IR); while the Disposition index {(DI) hyperbola product of insulin sensitivity (1/HOMA-IR) and beta cell secretion} was used to estimate the beta cell function. The relationships between serum vitamin D, insulin resistance and beta cell function were explored using a linear regression model. The study participants had a mean age of 56.2 (± 9.2) years, and a mean BMI of 26.9 kg/m2 (4.3). Forty nine percent (n = 61) were males. Vitamin D deficiency was present in 71.1% (n = 88) of the respondents. Relatively low levels of insulin resistance and higher levels of beta cell dysfunction were observed {median HOMA-IR of 2.3 (0.7, 6.5) and Disposition Index (DI) of 25.5 (14.3, 47.2)}. Vitamin D levels exhibited a low positive correlation with DI [r = 0.22 (95% CI: 0.03, 0.37)], but was not significantly correlated with HOMA-IR [r = 0.07(95% CI: − 0.11, 0.25)]. These results indicate that beta cell dysfunction rather than insulin resistance as the predominant defect among black T2DM patients seeking care at the MTRH diabetes clinic. Vitamin D deficiency is also prevalent among them and exhibits a low positive correlation with beta cell dysfunction. There was no correlation observed between Vitamin D deficiency and insulin resistance.
Quantifying the inundation impacts of earthquake-induced surface elevation change by hydrological and hydraulic modeling
Authors: Ouyang Mao , Ito Yuka , Tokunaga Tomochika 
Published: February 2021

AbstractCurrent estimates of flood hazards are often based on the assumption that topography is static. When tectonic and/or anthropogenic processes change the land surface elevation, the spatial patterns of floods might also change. Here, we employ the hydrological and hydraulic modeling to simulate floods in the Kujukuri Plain, Japan, in the years 2004 and 2013, when two severe floods occurred. In between the two floods, land surface elevations were changed by the 2011 Tohoku-Oki earthquake. The effects of land surface elevation changes on inundation areas were quantified by changing input topographies. Our results showed that, without taking into account land surface elevation changes, around 10% of inundation areas were underestimated at the time of flood events in the year 2013. The spatial distribution of inundation locations varied with local topographical features, for example, the areas with backmarsh and valley fill deposits were sensitive to the extent of inundation by land surface elevation changes. The sub-watershed near the coastal shoreline having below-zero meter elevation areas showed that the earthquake-induced land surface elevation changes exacerbated an additional 22% inundation area. This study suggests that the inundation areas will increase in catchments suffering severe settlements, which highlights the necessity of taking into account the spatio-temporal changes of land surface elevations on the assessment of flood hazards.
Diabetic vascular hyperpermeability: optical coherence tomography angiography and functional loss assessments of relationships among retinal vasculature changes
Authors: Arima Mitsuru , Nakao Shintaro , Kaizu Yoshihiro , Wada Iori , Yamaguchi Muneo , Fujiwara Kohta , Akiyama Masato , Stitt Alan W. , Sonoda Koh-Hei 
Published: February 2021

AbstractOur study assessed the influence of vascular permeability on vascular flow density (FD)-correlated retinal sensitivity (RS) in DR. In this cross-sectional, prospective, consecutive study, RS in the extrafoveal macula of DR patient was measured by microperimetry. FD was measured in the total, superficial, and deep capillary plexus layers (TCP, SCP, and DCP) by optical coherence tomography angiography. All measurement points were classified into four categories according to intensity of fluorescein leakage and FD, and the RS reduction was compared. A stratified analysis by retinal thickness (RT) was also performed. Fourteen eyes (14 patients) were enrolled. FDs at 207 RS measurement points were analyzable. For TCP, SCP and DCP, the leakage did not decrease RS at points where FD was maintained. The greater the leakage, the smaller the RS reduction at points with low FD in TCP (P = .020). Points with high leakage showed a significant smaller RS reduction than points with low leakage (P = .001 for TCP, P = .040 for SCP, and P = .046 for DCP) only in areas with low RT and low FD. Our results suggested that vascular hyperpermeability may inhibit the RS reduction in the non-edematous ischemic diabetic retina.
Zero-crossing patterns reveal subtle epileptiform discharges in the scalp EEG
Authors: Pyrzowski Jan , Le Douget Jean- Eudes , Fouad Amal , Siemiński Mariusz , Jędrzejczak Joanna , Le Van Quyen Michel 
Published: February 2021

AbstractClinical diagnosis of epilepsy depends heavily on the detection of interictal epileptiform discharges (IEDs) from scalp electroencephalographic (EEG) signals, which by purely visual means is far from straightforward. Here, we introduce a simple signal analysis procedure based on scalp EEG zero-crossing patterns which can extract the spatiotemporal structure of scalp voltage fluctuations. We analyzed simultaneous scalp and intracranial EEG recordings from patients with pharmacoresistant temporal lobe epilepsy. Our data show that a large proportion of intracranial IEDs manifest only as subtle, low-amplitude waveforms below scalp EEG background and could, therefore, not be detected visually. We found that scalp zero-crossing patterns allow detection of these intracranial IEDs on a single-trial level with millisecond temporal precision and including some mesial temporal discharges that do not propagate to the neocortex. Applied to an independent dataset, our method discriminated accurately between patients with epilepsy and normal subjects, confirming its practical applicability.
Tolerance engineering in Deinococcus geothermalis by heterologous efflux pumps
Authors: Boulant Erika , Cambon Emmanuelle , Vergalli Julia , Bernard Rémi , Neulat-Ripoll Fabienne , Nolent Flora , Gorgé Olivier , Girleanu Maria , Favier Anne-Laure , Leonetti Jean-Paul , Bolla Jean Michel 
Published: February 2021

AbstractProducing industrially significant compounds with more environmentally friendly represents a challenging task. The large-scale production of an exogenous molecule in a host microfactory can quickly cause toxic effects, forcing the cell to inhibit production to survive. The key point to counter these toxic effects is to promote a gain of tolerance in the host, for instance, by inducing a constant flux of the neo-synthetized compound out of the producing cells. Efflux pumps are membrane proteins that constitute the most powerful mechanism to release molecules out of cells. We propose here a new biological model, Deinococcus geothermalis, organism known for its ability to survive hostile environment; with the aim of coupling the promising industrial potential of this species with that of heterologous efflux pumps to promote engineering tolerance. In this study, clones of D. geothermalis containing various genes encoding chromosomal heterologous efflux pumps were generated. Resistant recombinants were selected using antibiotic susceptibility tests to screen promising candidates. We then developed a method to determine the efflux efficiency of the best candidate, which contains the gene encoding the MdfA of Salmonella enterica serovar Choleraesuis. We observe 1.6 times more compound in the external medium of the hit recombinant than that of the WT at early incubation time. The data presented here will contribute to better understanding of the parameters required for efficient production in D. geothermalis.
Head-to-head comparison of clustering methods for heterogeneous data: a simulation-driven benchmark
Authors: Preud’homme Gregoire , Duarte Kevin , Dalleau Kevin , Lacomblez Claire , Bresso Emmanuel , Smaïl-Tabbone Malika , Couceiro Miguel , Devignes Marie-Dominique , Kobayashi Masatake , Huttin Olivier , Ferreira João Pedro , Zannad Faiez , Rossignol Patrick , Girerd Nicolas 
Published: February 2021

AbstractThe choice of the most appropriate unsupervised machine-learning method for “heterogeneous” or “mixed” data, i.e. with both continuous and categorical variables, can be challenging. Our aim was to examine the performance of various clustering strategies for mixed data using both simulated and real-life data. We conducted a benchmark analysis of “ready-to-use” tools in R comparing 4 model-based (Kamila algorithm, Latent Class Analysis, Latent Class Model [LCM] and Clustering by Mixture Modeling) and 5 distance/dissimilarity-based (Gower distance or Unsupervised Extra Trees dissimilarity followed by hierarchical clustering or Partitioning Around Medoids, K-prototypes) clustering methods. Clustering performances were assessed by Adjusted Rand Index (ARI) on 1000 generated virtual populations consisting of mixed variables using 7 scenarios with varying population sizes, number of clusters, number of continuous and categorical variables, proportions of relevant (non-noisy) variables and degree of variable relevance (low, mild, high). Clustering methods were then applied on the EPHESUS randomized clinical trial data (a heart failure trial evaluating the effect of eplerenone) allowing to illustrate the differences between different clustering techniques. The simulations revealed the dominance of K-prototypes, Kamila and LCM models over all other methods. Overall, methods using dissimilarity matrices in classical algorithms such as Partitioning Around Medoids and Hierarchical Clustering had a lower ARI compared to model-based methods in all scenarios. When applying clustering methods to a real-life clinical dataset, LCM showed promising results with regard to differences in (1) clinical profiles across clusters, (2) prognostic performance (highest C-index) and (3) identification of patient subgroups with substantial treatment benefit. The present findings suggest key differences in clustering performance between the tested algorithms (limited to tools readily available in R). In most of the tested scenarios, model-based methods (in particular the Kamila and LCM packages) and K-prototypes typically performed best in the setting of heterogeneous data.