Miracle-dz/UniFAR-FTUs huggingface dataset:
A systematic method for surveying data visualizations and a resulting genomic epidemiology visualization typology: GEViT

Motivation: Data visualization is an important tool for exploring and communicating findings from genomic and healthcare datasets. Yet, without a systematic way of organizing and describing the design space of data visualizations, researchers may not be aware of the breadth of possible visualization design choices or how to distinguish between good and bad options. Results: We have developed a method that systematically surveys data visualizations using the analysis of both text and images. Our method supports the construction of a visualization design space that is explorable along two axes: why the visualization was created and how it was constructed. We applied our method to a corpus of scientific research articles from infectious disease genomic epidemiology and derived a Genomic Epidemiology Visualization Typology (GEViT) that describes how visualizations were created from a series of chart types, combinations, and enhancements. We have also implemented an online gallery that allows others to explore our resulting design space of visualizations. Our results have important implications for visualization design and for researchers intending to develop or use data visualization tools. Finally, the method that we introduce is extensible to constructing visualizations design spaces across other research areas. Availability: Our browsable gallery is available at http://gevit.net and all project code can be found at https://github.com/amcrisan/gevitAnalysisRelease
Mandatory and recommended vaccinations in Poland in the views of parents

ABSTRACT Background: Vaccinations are currently the key element in the prevention of the spread of infectious diseases. We studied parents’ opinions about mandatory and recommended preventive vaccinations in Poland. Methods: A diagnostic survey using an original questionnaire was done in a group of 300 parents. Results: A total of 3.7% of parents did not vaccinate their children. 90% were aware of the threat potentially posed by infectious diseases, and 73.7% knew that breastfeeding alone does not ensure sufficient protection against them. 28% believed that it is necessary to vaccinate a child against all diseases, 51.7% that the number of vaccinations is insufficient, and 62.7% that vaccine use is safe. 40.7% thought that unvaccinated children should not be able to attend nurseries and kindergartens, as they pose a threat to other children. Postvaccinal adverse events occurred in 21.3% of children, mainly (71.9%) an increase in body temperature above 38°C. 88.3% were informed about possible vaccine-induced complications, most often by nurses (79.7%). 88% of the respondents were aware of the possibility to switch to an alternative immunization program, 92% were informed on the possible administration of recommended vaccines, and 53% took advantage of combined vaccines. Conclusions: Views on vaccinations were mostly varied, depending on the age, sex, education, and financial situation of the respondents. Most of the parents who did not vaccinate their children believed that immunity can be acquired by infection. They were in favor of a limited number of vaccinations, were more critical of the vaccination program in Poland, considered the vaccines used in Poland to be unsafe, and blamed vaccines for multiple developmental defects and autism in children. Parents whose children experienced vaccine-induced adverse reactions were more likely to have doubts before the next vaccination.
Functional observer-based sliding mode control for linear discrete-time-delayed stochastic systems

Abstract Functional observers are the primary solution to sundry estimation problems, wherein full- or reduced-order observer cannot be directly applied. This paper presents a functional observer-based sliding mode control method for the linear discrete-time delayed stochastic system. Stability analysis of sliding function is presented for the delayed stochastic system with a linear matrix inequality approach. The functional observer method for the linear discrete-time-delayed stochastic system is proposed based on the Kronecker product approach. Sliding mode controller is estimated using the functional observer method. Finally, to demonstrate the efficacy of the proposed design, comparison of its performance with some of the well-known existing state feedback controller is presented.
Baseline Detrending for the Photopic Negative Response

Purpose The photopic negative response (PhNR) of the light-adapted electroretinogram (ERG) holds promise as an objective marker of retinal ganglion cell function. We compared baseline detrending methods to improve PhNR repeatability without compromising its diagnostic ability in glaucoma. Methods Photopic ERGs were recorded in 20 glaucoma and 18 age-matched control participants. A total of 50 brief, red-flashes (1.6 cd.s/m2) on a blue background (10 photopic cd/m2) were delivered using the RETeval device. Detrending methods compared were: (1) increasing the high-pass filter from 1 to 10 Hz and (2) estimating and removing the trend with an increasing polynomial (order from 1–10) applied to the prestimulus interval, prestimulus and postsignal interval, or the whole ERG signal. Coefficient of repeatability (COR%), unpaired Student's t-test, and area under the receiver operating characteristic curve (AUC) were used to compare the detrending methods. Results Most detrending methods improved PhNR test–retest repeatability compared to the International Society for Clinical Electrophysiology of Vision (ISCEV) recommended 0.3 to 300 Hz band-pass filter (COR% ± 200%). In particular, detrending with a polynomial (order 3) applied to the whole signal performed the best (COR% ± 44%) while achieving similar diagnostic ability as ISCEV band-pass (AUC 0.74 vs. 0.75, respectively). However, over-correcting with higher orders of processing can cause waveform distortion and reduce diagnostic ability. Conclusions Baseline detrending can improve the PhNR repeatability without compromising its clinical use in glaucoma. Further studies exploring more complex processing methods are encouraged. Translational Relevance Baseline detrending can significantly improve the quality of the PhNR.
IL-15 regulates susceptibility of CD4+ T cells to HIV infection

Significance HIV creates a persistent reservoir, which is largely resistant to current antiretroviral treatment aimed at inhibiting HIV replication. CD4+ T memory lymphocytes, key components of this reservoir, are generally refractory to infection, but stimulation with γc-chain cytokines, such as IL-15, renders these cells more susceptible to HIV. We found that, by inducing cell cycle entry of CD4+ T cells, JAK1 is a key mediator responsible for counteracting the antiviral activity of SAM domain and HD domain-containing protein 1 (SAMHD1). Pharmacological inhibition of these kinases resulted in restoration of SAMHD1 in CD4+ T cells. Protecting these cells during the critical IL-15 surge observed during primary infection has the potential to limit reservoir establishment. HIV integrates into the host genome to create a persistent viral reservoir. Stimulation of CD4+ memory T lymphocytes with common γc-chain cytokines renders these cells more susceptible to HIV infection, making them a key component of the reservoir itself. IL-15 is up-regulated during primary HIV infection, a time when the HIV reservoir established. Therefore, we investigated the molecular and cellular impact of IL-15 on CD4+ T-cell infection. We found that IL-15 stimulation induces SAM domain and HD domain-containing protein 1 (SAMHD1) phosphorylation due to cell cycle entry, relieving an early block to infection. Perturbation of the pathways downstream of IL-15 receptor (IL-15R) indicated that SAMHD1 phosphorylation after IL-15 stimulation is JAK dependent. Treating CD4+ T cells with Ruxolitinib, an inhibitor of JAK1 and JAK2, effectively blocked IL-15–induced SAMHD1 phosphorylation and protected CD4+ T cells from HIV infection. Using high-resolution single-cell immune profiling using mass cytometry by TOF (CyTOF), we found that IL-15 stimulation altered the composition of CD4+ T-cell memory populations by increasing proliferation of memory CD4+ T cells, including CD4+ T memory stem cells (TSCM). IL-15–stimulated CD4+ TSCM, harboring phosphorylated SAMHD1, were preferentially infected. We propose that IL-15 plays a pivotal role in creating a self-renewing, persistent HIV reservoir by facilitating infection of CD4+ T cells with stem cell-like properties. Time-limited interventions with JAK1 inhibitors, such as Ruxolitinib, should prevent the inactivation of the endogenous restriction factor SAMHD1 and protect this long-lived CD4+ T-memory cell population from HIV infection.
RMTL: an R library for multi-task learning

MOTIVATION Multi-task learning (MTL) is a machine learning technique for simultaneous learning of multiple related classification or regression tasks. Despite its increasing popularity, MTL algorithms are currently not available in the widely used software environment R, creating a bottleneck for their application in biomedical research. RESULTS We developed an efficient, easy-to-use R library for MTL (www.r-project.org) comprising 10 algorithms applicable for regression, classification, joint predictor selection, task clustering, low-rank learning and incorporation of biological networks. We demonstrate the utility of the algorithms using simulated data. AVAILABILITY AND IMPLEMENTATION The RMTL package is an open source R package and is freely available at https://github.com/transbioZI/RMTL. RMTL will also be available on cran.r-project.org. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome

Disrupting the LINC complex reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome. Help for HGPS Children with Hutchinson-Gilford progeria syndrome (HGPS), a rare disorder of accelerated aging caused by mutations in lamin, exhibit vascular complications. Kim et al. investigated the mechanism responsible for vascular smooth muscle cell death and aortic disease using HGPS mice. They found that smooth muscle cells expressing progerin (truncated form of lamin produced by mutations in lamin) became apoptotic under stretch. HGPS mice exhibited greater disease burden in the inner curvature of the aorta and at vascular branch regions. Disrupting the transmission of force between the cytoskeleton and nucleus abrogated apoptosis in progerin-expressing smooth muscle cells. These results highlight the role of shear stress in contributing to vascular disease in HGPS. Hutchinson-Gilford progeria syndrome is a disorder of premature aging in children caused by de novo mutations in LMNA that lead to the synthesis of an internally truncated form of prelamin A (commonly called progerin). The production of progerin causes multiple disease phenotypes, including an unusual vascular phenotype characterized by the loss of smooth muscle cells in the arterial media and fibrosis of the adventitia. We show that progerin expression, combined with mechanical stress, promotes smooth muscle cell death. Disrupting the linker of the nucleoskeleton and cytoskeleton (LINC) complex in smooth muscle cells ameliorates the toxic effects of progerin on smooth muscle cells and limits the accompanying adventitial fibrosis.
Severe Traumatic Brain Injury Requiring Surgical Decompression in the Young Adult: Factors Influencing Morbidity and Mortality – A Retrospective Analysis

Introduction: Severe traumatic brain injury (TBI) is a leading cause of morbidity and mortality among young adults. The clinical outcome may also be difficult to predict. We aim to identify the factors predictive of favorable and unfavorable clinical outcomes for youthful patients with severe TBI who have the option of surgical craniotomy or surgical craniectomy. Methods: A retrospective review at a single Level II trauma center was conducted, identifying patients aged 18 to 30 years with isolated severe TBI with a mass-occupying lesion requiring emergent (< 6 hours from time of arrival) surgical decompression. Glasgow Coma Scale (GCS) score on arrival, type of surgery performed, mechanism of injury, length of hospital stay, Glasgow Outcome Score (GOS), mortality, and radiographic findings were recorded. A favorable outcome was a GOS of four or five at 30 days post operation, while an unfavorable outcome was GOS of 1 to 3. Results: Fifty patients were included in the final analysis. Closed head injuries (skull and dura intact), effacement of basal cisterns, disproportional midline shift (MLS), and GCS 3-5 on arrival all correlated with statistically significant higher rate of mortality and poor 30-day functional outcome. All mortalities (6/50 patients) were positive for each of these findings. Conclusions: Closed head injuries, the presenting GCS 3-5, the presence of MLS disproportional to the space occupying lesion (SOL), and effacement of basal cisterns on the initial computed tomography of the head all correlated with unfavorable 30-day outcome. Future prospective studies investigating a larger cohort may provide further insight into patients suffering from severe TBI.
Rethinking Timekeeping for Modern IT Solutions

Advances in processor performance and virtualization technologies, together with complexities of operating systems (OS) and software defined networking, have outpaced legacy network - based solutions for keeping system clocks accurate across geographic locations—in cloud - space and on - premises. Computer time accuracy with respect to Coordinated Universal Time (UTC) is now being codified and enforced by recently adopted regulatory requirements in the financial services sector for governance, risk mitigation, and demonstration of compliance. These factors necessitate a rethinking of timekeeping for modern IT solutions. In this paper, we describe our technical approach to making UTC - accurate computer system clock a fundamental platform capability that is independent from other OS subsystems such as networking. We will also share a series of lessons learnt from building industry standard hardware interfaces to keep general - purpose computing platforms and their virtual machines UTC - accurate, and from our collaboration with industry partners Microsoft and selected server vendors to implement traceability to UTC via the National Institute of Standards and Technology (NIST) for modern IT solutions. We will conclude with our thoughts on how the full complement of Global Positioning System (GPS) positioning data in addition to accurate timekeeping would further benefit IT solutions of the future.
Morphed Learning: Towards Privacy-Preserving for Deep Learning Based Applications

The concern of potential privacy violation has prevented efficient use of big data for improving deep learning based applications. In this paper, we propose Morphed Learning, a privacy-preserving technique for deep learning based on data morphing that, allows data owners to share their data without leaking sensitive privacy information. Morphed Learning allows the data owners to send securely morphed data and provides the server with an Augmented Convolutional layer to train the network on morphed data without performance loss. Morphed Learning has these three features: (1) Strong protection against reverse-engineering on the morphed data; (2) Acceptable computational and data transmission overhead with no correlation to the depth of the neural network; (3) No degradation of the neural network performance. Theoretical analyses on CIFAR-10 dataset and VGG-16 network show that our method is capable of providing 10^89 morphing possibilities with only 5% computational overhead and 10% transmission overhead under limited knowledge attack scenario. Further analyses also proved that our method can offer same resilience against full knowledge attack if more resources are provided.
Differential Sensitivity Analysis for Resistant Malignancies (DISARM) Identifies Common Candidate Therapies across Platinum-Resistant Cancers

Purpose: Despite a growing arsenal of approved drugs, therapeutic resistance remains a formidable and, often, insurmountable challenge in cancer treatment. The mechanisms underlying therapeutic resistance remain largely unresolved and, thus, examples of effective combinatorial or sequential strategies to combat resistance are rare. Here, we present Differential Sensitivity Analysis for Resistant Malignancies (DISARM), a novel, integrated drug screen analysis tool designed to address this dilemma. Experimental Design: DISARM, a software package and web-based application, analyzes drug response data to prioritize candidate therapies for models with resistance to a reference drug and to assess whether response to a reference drug can be utilized to predict future response to other agents. Using cisplatin as our reference drug, we applied DISARM to models from nine cancers commonly treated with first-line platinum chemotherapy including recalcitrant malignancies such as small cell lung cancer (SCLC) and pancreatic adenocarcinoma (PAAD). Results: In cisplatin-resistant models, DISARM identified novel candidates including multiple inhibitors of PI3K, MEK, and BCL-2, among other classes, across unrelated malignancies. Additionally, DISARM facilitated the selection of predictive biomarkers of response and identification of unique molecular subtypes, such as contrasting ASCL1-low/cMYC-high SCLC targetable by AURKA inhibitors and ASCL1-high/cMYC-low SCLC targetable by BCL-2 inhibitors. Utilizing these predictions, we assessed several of DISARM's top candidates, including inhibitors of AURKA, BCL-2, and HSP90, to confirm their activity in cisplatin-resistant SCLC models. Conclusions: DISARM represents the first validated tool to analyze large-scale in vitro drug response data to statistically optimize candidate drug and biomarker selection aimed at overcoming candidate drug resistance.
ODF2 maintains centrosome cohesion by restricting β-catenin accumulation

ABSTRACT The centrosome, as the main microtubule-organizing center, safeguards chromosome segregation by supporting the bipolar spindle. Centrosome aberrations are causally related to chromosome segregation disorders, both characterizing cancer cells. Thus, a restriction to only having one centrosome per cell and cell cycle-dependent duplication of the centrosome is mandatory. Duplicated centrosomes remain physically connected, in order to function as a single entity, until onset of mitosis when centrosome disjunction is licensed by disassembly of linker proteins and accumulation of β-catenin. The crucial role β-catenin plays in centrosome disjunction inevitably demands for restricting its premature accumulation. ODF2 (also known as cenexin) is an essential centrosomal component, but its relevance for the interphase centrosome has not been elucidated. We show here that ODF2 plays a central role in centrosome cohesion. Depletion of ODF2 induces premature centrosome splitting and formation of tripolar spindles that are likely caused by the observed accumulation of centrosomal β-catenin. Our data collectively indicate that ODF2 restricts β-catenin accumulation at the centrosome, thus preventing premature centrosome disjunction. Summary: ODF2 maintains centrosome cohesion by restricting premature accumulation of centrosomal β-catenin, which ensure precise chromosome segregation and centrosome disjunction.
Ryanodine receptor cluster size sets the tone in cerebral smooth muscle

Ryanodine receptors (RyRs) are large intracellular Ca2+ channels that provide the molecular basis of the process termed Ca2+-induced Ca2+ release (1). Ca2+ signaling through RyRs has been shown to be critical for skeletal, cardiac, and smooth muscle physiology (2) as well as for neurons (3) and secretory cells like pancreatic beta cells. RyRs were first seen in the electron microscope as ∼30-nm-size particles (4), and it had been known from EM studies that they form clusters, typically in the narrow “junctional” space between sarcolemma and sarcoplasmic reticulum (SR) membranes. Due to the inherent positive feedback of Ca2+-induced Ca2+ release, the size and shape of RyR clusters are expected to affect their functional activity. Indeed, detailed mathematical modeling suggests that RyR clustering is important for determining the excitability of RyR-mediated Ca2+ release (5, 6) and could, in principle, also affect the amount of Ca2+ released in microscopic release events termed Ca2+ sparks (7). The experimental study of RyR clustering has received a boost with the advent of optical superresolution microscopy, which has made the assessment of RyR cluster size more accessible by using essentially standard immunolabeling protocols. When first applied in cardiac muscle cells, this approach revealed a broad, approximately exponential RyR cluster size distribution (8), which had previously not been fully recognized. In PNAS, Pritchard et al. (9) describe changes in type 2 RyR (RyR2) clustering in smooth muscle of cerebral arteries in the mdx mouse model of Duchenne muscular dystrophy. The study is important because Pritchard et al. (9) identify these nanoscale receptor clustering changes as the likely source of cerebral muscular dysfunction in the mdx mouse. Different from striated muscle in which RyR-mediated Ca2+ release mainly contributes to the cell-wide Ca2+ transient to activate … [↵][1]1Email: c.soeller{at}exeter.ac. uk. [1]: #xref-corresp-1-1
Quality of life and related factors among older people living in rural areas in south-eastern Poland.

INTRODUCTION Quality of life (QOL) is an important aspect of life, reflecting health and conditioning the well-being of older adults. Maintaining the QOL is essential in times of demographic changes which resulting longer life spans, and consequently an increased proportion of older adults in society. OBJECTIVE The aim of the study was to assess the quality of life and its basic determining factors in the elderly living in rural areas of south-eastern Poland. MATERIAL AND METHODS The study was conducted on 973 respondents aged 60-80 years living in rural areas of south-eastern Poland (Podkarpackie Region). The research tool used in the study was the WHOQOL-Bref and a questionnaire on personal characteristics and health. Statistical analysis was performed using Statistica version 10. RESULTS All quality of life domains assessed were above the median values of the scale. The highest values were found in the social domain (67.35 ± 17.31) and the lowest values in the physical domain (58.74 ± 14.80). All the quality of life values decreased with an increase in age and increase in number of chronic diseases in a given person. A higher quality of life was found in subjects who were physically and socially active. CONCLUSIONS The study stresses the impact of modifiable determiners of QOL. Interventions aimed at improving the quality of life of older adults should involve interdisciplinary monitoring of health, early treatment of diagnosed problems, and promotion of physical activity and daily life activities.