Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of common IL-10 promoter gene variants with the susceptibility to head and neck cancer in Tunisia

Background/aim We investigated the association of three IL-10 promoter single-nucleotide polymorphisms and altered IL-10 plasma levels with the risk of head and neck cancer (HNC). Materials and methods Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA). Results Carriage of rs1800896 A/A genotype was more frequent in the HNC and NPC cases, but was less frequent in the controls than the LC patients. Significant differences in IL-10 levels were observed between the rs1800896A/G genotype-carrying NPC patients and the controls. Positive association with NPC and LC was observed for rs1800871C/C, and carriage of rs1800872A/A genotype, and A allele were associated with higher risk of HNC and NPC, but not LC. GT rs1800896-rs1800871 haplotype was more frequent among the HNC and NPC patients than the controls in contrast to GC haplotype, which has a protective effect. Positive association was found between TA haplotype and LC. Conclusion Our results demonstrate that IL-10-1082, IL-10-819, and IL-10-592 variants, and haplotypes GC and GT constitute biomarkers for early detection of HNC, especially NPC subtype. IL-10 -819T/C and TA haplotype may be used as biomarkers for early detection of LC.
Genetic profiling for disease stratification in chronic obstructive pulmonary disease and asthma

Purpose of review In asthma and chronic obstructive pulmonary disease (COPD), the movement towards genetic profiling with a push towards ‘personalized medicine’ has been hindered by complex environment--gene interactions and lack of tools to identify clear causal genetic traits. In this review, we will discuss the need for genetic profiling in asthma and COPD, what methods are currently used in the clinics and the recent finding using new sequencing methods. Recent findings Over the past 10–15 years, genome-wide association studies analysis of common variants has provide little in the way of new genetic profiling markers for asthma and COPD. Whole exome/genome sequencing has provided a new method to identify lowly abundant alleles, which might have a much higher impact. Although, low population numbers due to high costs has hindered early studies, recent studies have reached genome wide significance. Summary The use of genetic profiling of COPD in the clinic is current limited to the identification of Alpha-1 antitrypsin deficiency, while being absent in asthma. Advances in sequencing technology provide new avenues to identify disease causes or therapy response altering variants that in the short-term will allow for the development of screening procedures for disease to identify patients at risk of developing asthma or COPD.
A Modified Random Survival Forests Algorithm for High Dimensional Predictors and Self-Reported Outcomes

ABSTRACT We present an ensemble tree-based algorithm for variable selection in high-dimensional datasets, in settings where a time-to-event outcome is observed with error. This work is motivated by self-reported outcomes collected in large-scale epidemiologic studies, such as the Women’s Health Initiative. The proposed methods equally apply to imperfect outcomes that arise in other settings such as data extracted from electronic medical records. To evaluate the performance of our proposed algorithm, we present results from simulation studies, considering both continuous and categorical covariates. We illustrate this approach to discover single nucleotide polymorphisms that are associated with incident Type 2 diabetes in the Women’s Health Initiative. A freely available R package icRSF has been developed to implement the proposed methods. Supplementary material for this article is available online.
Factors affecting quality of life in children and adolescents with hypermobile Ehlers‐Danlos syndrome/hypermobility spectrum disorders

Hypermobile Ehlers‐Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12–20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain‐Frequency‐Severity‐Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population.
High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice

Background: Dietary intake of fruit and vegetables is associated with lower incidence of hypertension, but the mechanisms involved have not been elucidated. Here, we evaluated the effect of a high-fiber diet and supplementation with the short-chain fatty acid acetate on the gut microbiota and the prevention of cardiovascular disease. Methods: Gut microbiome, cardiorenal structure/function, and blood pressure were examined in sham and mineralocorticoid excess–treated mice with a control diet, high-fiber diet, or acetate supplementation. We also determined the renal and cardiac transcriptome of mice treated with the different diets. Results: We found that high consumption of fiber modified the gut microbiota populations and increased the abundance of acetate-producing bacteria independently of mineralocorticoid excess. Both fiber and acetate decreased gut dysbiosis, measured by the ratio of Firmicutes to Bacteroidetes, and increased the prevalence of Bacteroides acidifaciens. Compared with mineralocorticoid-excess mice fed a control diet, both high-fiber diet and acetate supplementation significantly reduced systolic and diastolic blood pressures, cardiac fibrosis, and left ventricular hypertrophy. Acetate had similar effects and markedly reduced renal fibrosis. Transcriptome analyses showed that the protective effects of high fiber and acetate were accompanied by the downregulation of cardiac and renal Egr1, a master cardiovascular regulator involved in cardiac hypertrophy, cardiorenal fibrosis, and inflammation. We also observed the upregulation of a network of genes involved in circadian rhythm in both tissues and downregulation of the renin-angiotensin system in the kidney and mitogen-activated protein kinase signaling in the heart. Conclusions: A diet high in fiber led to changes in the gut microbiota that played a protective role in the development of cardiovascular disease. The favorable effects of fiber may be explained by the generation and distribution of one of the main metabolites of the gut microbiota, the short-chain fatty acid acetate. Acetate effected several molecular changes associated with improved cardiovascular health and function.
Three-dimensional optical trapping and orientation of microparticles for coherent X-ray diffraction imaging

Significance Obtaining a fundamental understanding of crystal growth and chemical reactions in solution is of broad and enduring interest for materials discovery, structural biology, and catalysis. The recent availability of bright, coherent X-ray sources can enable these fluctuation-driven processes to be monitored in situ through the technique of coherent X-ray diffractive imaging (CXDI), in which the 3D internal structure of microscopic objects is determined with nanometer resolution from the fine structure of diffraction peaks. So far, Bragg CXDI has required immobilization of particles on a substrate, which modifies their structure and chemical activity. Here, we demonstrate Bragg CXDI on a single particle that is trapped and oriented in solution using optical tweezers and thus obtain its 3D structure and strain map. Optical trapping has been implemented in many areas of physics and biology as a noncontact sample manipulation technique to study the structure and dynamics of nano- and mesoscale objects. It provides a unique approach for manipulating microscopic objects without inducing undesired changes in structure. Combining optical trapping with hard X-ray microscopy techniques, such as coherent diffraction imaging and crystallography, provides a nonperturbing environment where electronic and structural dynamics of an individual particle in solution can be followed in situ. It was previously shown that optical trapping allows the manipulation of micrometer-sized objects for X-ray fluorescence imaging. However, questions remain over the ability of optical trapping to position objects for X-ray diffraction measurements, which have stringent requirements for angular stability. Our work demonstrates that dynamic holographic optical tweezers are capable of manipulating single micrometer-scale anisotropic particles in a microfluidic environment with the precision and stability required for X-ray Bragg diffraction experiments—thus functioning as an “optical goniometer. ” The methodology can be extended to a variety of X-ray experiments and the Bragg coherent diffractive imaging of individual particles in solution, as demonstrated here, will be markedly enhanced with the advent of brighter, coherent X-ray sources.
Sancus 2.0

The Sancus security architecture for networked embedded devices was proposed in 2013 at the USENIX Security conference. It supports remote (even third-party) software installation on devices while maintaining strong security guarantees. More specifically, Sancus can remotely attest to a software provider that a specific software module is running uncompromised and can provide a secure communication channel between software modules and software providers. Software modules can securely maintain local state and can securely interact with other software modules that they choose to trust. Over the past three years, significant experience has been gained with applications of Sancus, and several extensions of the architecture have been investigated—both by the original designers as well as by independent researchers. Informed by these additional research results, this journal version of the Sancus paper describes an improved design and implementation, supporting additional security guarantees (such as confidential deployment) and a more efficient cryptographic core. We describe the design of Sancus 2.0 (without relying on any prior knowledge of Sancus) and develop and evaluate a prototype FPGA implementation. The prototype extends an MSP430 processor with hardware support for the memory access control and cryptographic functionality required to run Sancus. We report on our experience using Sancus in a variety of application scenarios and discuss some important avenues of ongoing and future work.
Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine &ggr;-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

Background— The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine &ggr;-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension. Methods and Results— Plasma levels of H2S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8–12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H2S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H2S production. Conclusions— These results imply that endogenous H2S is required for healthy placental vasculature and that a decrease in CSE/H2S activity may contribute to the pathogenesis of preeclampsia. (Circulation. 2013;127:2514-2522.)
Gli Proteins: Regulation in Development and Cancer

Gli proteins are transcriptional effectors of the Hedgehog signaling pathway. They play key roles in the development of many organs and tissues, and are deregulated in birth defects and cancer. We review the molecular mechanisms of Gli protein regulation in mammals, with special emphasis on posttranslational modifications and intracellular transport. We also discuss how Gli proteins interact with co-activators and co-repressors to fine-tune the expression of Hedgehog target genes. Finally, we provide an overview of the regulation of developmental processes and tissue regeneration by Gli proteins and discuss how these proteins are involved in cancer progression, both through canonical regulation via the Hedgehog pathway and through cross-talk with other signaling pathways.
Validation of lesion simulations in clinical CT data for anonymized chest and abdominal CT databases

PURPOSE To make available to the medical imaging community a computed tomography (CT) image database composed of hybrid datasets (patient CT images with digitally inserted anthropomorphic lesions) where lesion ground truth is known a priori. It is envisioned that such a dataset could be a resource for the assessment of CT image quality, machine learning, and imaging technologies [e.g., computer aided detection (CAD) and segmentation algorithms]. ACQUISITION AND VALIDATION METHODS This HIPPA compliant, IRB waiver of approval study consisted of utilizing 120 chest and 100 abdominal clinically acquired adult CT exams. One image series per patient exam was utilized based on coverage of the anatomical region of interest (either the thorax or abdomen). All image series were de-identified. Simulated lesions were derived from a library of anatomically informed digital lesions (93 lung and 50 liver lesions) where six and four digital lesions with nominal diameters ranging from 4 to 20 mm were inserted into lung and liver image series, respectively. Locations for lesion insertion were randomly chosen. A previously validated lesion simulation and virtual insertion technique were utilized. The resulting hybrid images were reviewed by three experienced radiologists to assure similarity with routine clinical imaging in a diverse adult population. DATA FORMAT AND USAGE NOTES The database is composed of four datasets that contain 100 patient cases each, for a total of 400 image series accompanied by Matlab.mat tables that provide descriptive information about the virtually inserted lesions (i.e., size, shape, opacity, and insertion location in physical (world) coordinates and voxel indices). All image and metadata are stored in DICOM format on the Quantitative Imaging Data Warehouse (https://qidw.rsna.org/#collection/57d463471cac0a4ec8ff8f46/folder/5b23dceb1cac0a4ec800a770? dialog=login), in two sets: (a) QIBA CT Hybrid Dataset I which contains Lung I and Liver I datasets, and (b) QIBA CT Hybrid Dataset II which contains Lung II and Liver II datasets. The QIDW is supported by the Radiological Society of North America (RSNA). Registration is required upon initial log in. POTENTIAL APPLICATIONS By simulating lesion opacity (full solid, part solid and ground glass), size, and texture, the relationship between lesion morphology and segmentation or CAD algorithm performance can be investigated without the need for repetitive patient exams. This database can also serve as a reference standard for device and reader performance studies.
Tetra‐arsenic tetra‐sulfide ameliorates lupus syndromes by inhibiting IL‐17 producing double negative T cells

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra‐arsenic tetra‐sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus‐prone mice treated with As4S4 has showed improved monocytosis, decreased serum interleukin (IL)‐6 and suppressed skin, liver and renal lesions with well‐tolerance. In this study, we explored the effect and mechanism of As4S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4S4 treatment groups and dosed with As4S4 or placebo for 8 weeks. We found that As4S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL‐17, IL‐10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4S4 treated MRL/lpr mice. Taken together, As4S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL‐17, which may be produced by DN T cells. As4S4 may represent a new therapy for SLE.
Neural Adaptive Event-Triggered Control for Nonlinear Uncertain Stochastic Systems With Unknown Hysteresis

In this paper, the uncertain direct of the hysteretic system component will be considered. Besides, the effect of stochastic disturbance inevitably exists in many practical systems, which would cause the instability. Simultaneously, it is significant to guarantee the perfect error tracking performance for the uncertain nonlinear hysteresis systems when operation suffers the failure. To ensure the maintaining acceptable system performance in reality, the new properties of the Nussbaum function are proposed, and an auxiliary virtual controller is designed through the neural network (NN) universal approximator. Furthermore, it is challenged to save the system-limited transmutation resource for nonlinear systems, especially for stochastic nonlinear systems, with unknown hysteresis input and actuator failures. The coupling effect of the system communication resource constrains has to arise the issue of the mutual coupling function, which makes that the tracking control design is more complicated. Using the proposed event-triggered controller and back-stepping technology, a new optimization algorithm is proposed to ensure that the states of the closed-loop system and the tracking error remain bounded in probability. Finally, to illustrate the effectiveness of our proposed adaptive NN control method with the event-triggered strategy, some numerical examples are provided.
Quad-Rotor Helicopter Autonomous Navigation Based on Vanishing Point Algorithm

Quad-rotor helicopter is becoming popular increasingly as they can well implement many flight missions in more challenging environments, with lower risk of damaging itself and its surroundings. They are employed in many applications, from military operations to civilian tasks. Quad-rotor helicopter autonomous navigation based on the vanishing point fast estimation (VPFE) algorithm using clustering principle is implemented in this paper. For images collected by the camera of quad-rotor helicopter, the system executes the process of preprocessing of image, deleting noise interference, edge extracting using Canny operator, and extracting straight lines by randomized hough transformation (RHT) method. Then system obtains the position of vanishing point and regards it as destination point and finally controls the autonomous navigation of the quad-rotor helicopter by continuous modification according to the calculated navigation error. The experimental results show that the quad-rotor helicopter can implement the destination navigation well in the indoor environment.
Chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is the modern term used to refer to the cumulative long term neurological consequences of repetitive concussive and subconcussive blows to the head (1). CTE is a neurodegenerative tauopathy that has been speculated to exist among some former athletes involved in collision sports (like boxing and American football), as well as being observed in some military veterans who were exposed to combat ‘blastinjury’ (2). The condition is often referred to by a number of names in the medical and non-medical literature including dementia pugilistica and “punch drunk” syndrome.
Deconstructing the eradication of new world screwworm in North America: retrospective analysis and climate warming effects

Before its eradication from North America, the subtropical‐tropical new world screwworm fly Cochliomyia hominivorax (Coquerel) invaded southwestern temperate areas of the U.S.A. , where it caused myiasis in wildlife and livestock. Outbreaks of the fly occurred during years when adult migrants were carried northward on North American monsoon winds from the northern areas of Mexico and south Texas. We deconstruct, retrospectively, the biology and the effect of weather on the eradication of the fly in North America. Screwworm was found to be an ideal candidate for eradication using the sterile insect technique (SIT) because females mate only once, whereas males are polygynous, and, although it has a high reproductive potential, field population growth rates are low in tropical areas. In northern areas, eradication was enhanced by cool‐cold weather, whereas eradication in tropical Mexico and Central America is explained by the SIT. Despite low average efficacy of SIT releases (approximately 1.7%), the added pressure of massive SIT releases reduced intrinsically low fly populations, leading to mate‐limited extinction. Non‐autochthonous cases of myiasis occur in North America and, if the fly reestablishes, climate warming by 2045–2055 will expand the area of favourability and increase the frequency and severity of outbreaks.