Miracle-dz/UniFAR-FTUs huggingface dataset:
Visualizing Structure and Vascular Interactions: Macular Nonperfusion in Three Capillary Plexuses.

BACKGROUND AND OBJECTIVE To assess the relationship between retinal vascular and structural changes in the superficial, middle, and deep capillary plexuses (SCP, MCP, DCP) using optical coherence tomography angiography (OCTA) and en face OCT. PATIENTS AND METHODS Patients with diabetic retinopathy were imaged using the Cirrus HD-OCT with AngioPlex. Using manual segmentation of the retinal layers, the authors compared OCTA to en face OCT images to examine corresponding patterns in each of the three capillary plexuses. RESULTS Areas of decreased perfusion and capillary dropout on OCTA were found to be associated with three corresponding lesions on en face OCT: hyporeflectivity, cystic edema, and hard exudates. Vascular changes in individual capillary plexuses corresponded with structural changes in their respective perfused retinal layers. CONCLUSIONS Using manual segmentation on OCTA, the authors provide a framework to visualize the relationship between vascular pathology on OCTA and structural changes on en face OCT within specific capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e182-e190. ].
Therapeutic Approaches Targeting Inflammation in Cardiovascular Disorders

Cardiovascular disease is a leading cause of morbidity and mortality in the Western world and represents an enormous global health burden. Significant advances have been made in the conservative, medical and surgical management across the range of cardiovascular diseases however the inflammatory components of these diseases have traditionally been neglected. Inflammation is certainly a key component of atherosclerosis, a chronic inflammatory condition, but it is at least correlative and predictive of risk in many other aspects of cardiovascular medicine ranging from heart failure to outcomes following reperfusion strategies. Inflammation therefore represents significant potential for future risk stratification of patients as well as offering new therapeutic targets across cardiovascular medicine. This review explores the role of inflammation in several of the major aspects of cardiovascular medicine focusing on current and possible future examples of the targeting of inflammation in prognosis and therapy. It concludes that future directions of cardiovascular research and clinical practice should seek to identify cohorts of patients with a significant inflammatory component to their cardiovascular condition or reaction to cardiovascular intervention. These patients might benefit from therapeutic strategies mounted against the inflammatory components implicated in their condition.
Thrombolysis Enhancing by Magnetic Manipulation of Fe3O4 Nanoparticles

In this paper, an effective method of accelerating urokinase-administrated thrombolysis through a rotating magnetic field (RMF) of guided magnetic nanoparticles (NPs) in the presence of low-dose urokinase is proposed. The dispersed Fe3O4 NPs mixed with urokinase were injected into microfluidic channels occluded by thrombus prepared in vitro. These magnetic NPs aggregated into elongated clusters under a static magnetic field, and were then driven by the RMF. The rotation of Fe3O4 aggregates produced a vortex to enhance the diffusion of urokinase to the surface of the thrombus and accelerate its dissolution. A theoretical model based on convective diffusion was constructed to describe the thrombolysis mechanism. The thrombus lysis speed was determined according to the change of the thrombus dissolution length with time in the microfluidic channel. The experimental results showed that the thrombolysis speed with rotating magnetic NPs is significantly increased by nearly two times compared with using the same dose of pure urokinase. This means that the magnetically-controlled NPs approach provides a feasible way to achieve a high thrombolytic rate with low-dose urokinase in use.
PPE37 Is Essential for Mycobacterium tuberculosis Heme-Iron Acquisition (HIA), and a Defective PPE37 in Mycobacterium bovis BCG Prevents HIA

Mycobacterium tuberculosis, one of the world’s leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and M. tuberculosis possesses two different systems to acquire iron from its environment: siderophore-mediated iron acquisition (SMIA) and heme-iron acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. ABSTRACT Mycobacterium tuberculosis, one of the world’s leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and M. tuberculosis possesses two different systems to acquire iron from its environment: siderophore-mediated iron acquisition (SMIA) and heme-iron acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. We have discovered that Mycobacterium bovis BCG, the tuberculosis vaccine strain, is severely deficient in HIA, and we exploited this phenotypic difference between BCG and M. tuberculosis to identify genes involved in HIA by complementing BCG’s defect with a fosmid library. We identified ppe37, an iron-regulated PPE family gene, as being essential for HIA. BCG complemented with M. tuberculosis ppe37 exhibits HIA as efficient as that of M. tuberculosis, achieving robust growth with <0.2 µM hemin. Conversely, deletion of ppe37 from M. tuberculosis results in a strain severely attenuated in HIA, with a phenotype nearly identical to that of BCG, requiring a 200-fold higher concentration of hemin to achieve growth equivalent to that of its parental strain. A nine-amino-acid deletion near the N terminus of BCG PPE37 (amino acids 31 to 39 of the M. tuberculosis PPE37 protein) underlies BCG’s profound defect in HIA. Significant genetic variability exists in ppe37 genes across different M. tuberculosis strains, with more than 60% of sequences from completely sequenced M. tuberculosis genomes having mutations that result in altered PPE37 proteins; furthermore, these altered PPE37 proteins are nonfunctional in HIA. Our findings should allow delineation of the relative roles of HIA and SMIA in M. tuberculosis pathogenesis.
New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance

Chemoresistance is a complicated process developed by most cancers and accounts for the majority of relapse and metastasis in cancer. The main mechanisms of chemoresistance phenotype include increased expression and/or activated drug efflux pumps, altered DNA repair, altered metabolism of therapeutics as well as impaired apoptotic signaling pathways. Aberrant sphingolipid signaling has also recently received considerable attention in chemoresistance. Sphingolipid metabolites regulate main biological processes such as apoptosis, cell survival, proliferation, and differentiation. Two sphingosine kinases, SphK1 and SphK2, convert sphingosine to sphingosine‐1‐phosphate, an antiapoptotic bioactive lipid mediator. Numerous evidence has revealed the involvement of activated SphK1 in tumorigenesis and resistance, however, contradictory results have been found for the role of SphK2 in these functions. In some studies, overexpression of SphK2 suppressed cell growth and induced apoptosis. In contrast, some others have shown cell proliferation and tumor promotion effect for SphK2. Our understanding of the role of SphK2 in cancer does not have a sufficient integrity. The main focus of this review will be on the re‐evaluation of the role of SphK2 in cell death and chemoresistance in light of our new understanding of molecular targeted therapy. We will also highlight the connections between SphK2 and the DNA damage response. Finally, we will provide our insight into the regulatory mechanisms of SphKs by two main categories, micro and long, noncoding RNAs as the novel players of cancer chemoresistance.
The Influence of Stored Energy on Grain Boundary Chemistry and Intergranular Corrosion Development in AA2024-T3 Alloy

Following our previous research, the correlation between the micro-chemistry of grain boundary and the distribution of stored energy in AA2024-T3 alloy is investigated, using the combination of transmission Kikuchi diffraction and transmission electron microscopy. It is found that the difference of dislocation density, namely stored energy, between two neighboring grains significantly affects the micro-chemistry of the grain boundary. Further, it is revealed that intergranular corrosion development in the AA2024-T3 alloy is mainly attributed to the combined effect of grain boundary chemistry and stored energy distribution.
Genetic polymorphisms of diabetes‐related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project

To examine 143 diabetes risk single nucleotide polymorphisms (SNPs), identified from genome‐wide association studies, in association with breast cancer (BC) incidence and subsequent mortality. A population‐based sample of Caucasian women with first primary invasive BC (n = 817) and controls (n = 1021) were interviewed to assess diabetes status. Using the National Death Index, women with BC were followed for >18 years during which 340 deaths occurred (139 BC deaths). Genotyping was done using DNA extracted from blood samples. We used unconditional logistic regression to estimate age‐adjusted odds ratios and 95% confidence intervals (CIs) for BC incidence, and Cox regression to estimate age‐adjusted hazard ratios and CIs for all‐cause and BC‐specific mortality. Twelve SNPs were associated with BC risk in additive genotype models, at α = 0.05. The top three significant SNPs included SLC30A8‐rs4876369 (P = 0.0034), HHEX‐rs11187146 (P = 0.0086), and CDKN2A/CDKN2B‐rs1333049 (P = 0.0094). Diabetes status modified the associations between rs4876369 and rs2241745 and BC incidence, on the multiplicative interaction scale. Six SNPs were associated with all‐cause (CDKAL1‐rs981042, P = 0.0032; HHEX‐rs1111875, P = 0.0361; and INSR‐rs919275, P = 0.0488) or BC‐specific (CDKN2A/CDKN2B‐rs3218020, P = 0.0225; CDKAL1‐rs981042, P = 0.0246; and TCF2/HNF1B‐rs3094508, P = 0.0344) mortality in additive genotype models, at α = 0.05. Genetic polymorphisms that increase the risk of developing diabetes may also increase the risk of developing and dying from BC.
EEG Neurofeedback Training in Children With Attention Deficit/Hyperactivity Disorder: A Cognitive and Behavioral Outcome Study

Background. Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder with symptoms of inattention, impulsivity, and hyperactivity. EEG neurofeedback training (NFT) is a new intervention modality based on operant conditioning of brain activity, which helps reduce symptoms of ADHD in children. Methods and Procedures. To examine the efficacy of NFT in children with ADHD, an experimental longitudinal design with pre-post comparison was adopted. A total of 30 children in the age range of 6 to 12 years diagnosed as ADHD with or without comorbid conditions were assigned to treatment group (TG; n = 15) and treatment as usual group (TAU; n = 15). TG received EEG-NFT along with routine clinical management and TAU received routine clinical management alone. Forty sessions of theta/beta NFT at the C3 scalp location, 3 to 4 sessions in a week for a period of 3.5 to 5 months were given to children in TG. Children were screened using sociodemographic data and Binet-Kamat test of intelligence. Pre-and postassessment tools were neuropsychological tests and behavioral scales. Follow-up was carried out on 8 children in TG using parent-rated behavioral measures. Results. Improvement was reported in TG on cognitive functions (sustained attention, verbal working memory, and response inhibition), parent- and teacher-rated behavior problems and on academic performance rated by teachers. Follow-up of children who received NFT showed sustained improvement in ADHD symptoms when assessed 6 months after receiving NFT. Conclusion. The present study suggests that NFT is an effective method to enhance cognitive deficits and helps reduce ADHD symptoms and behavior problems. Consequently, academic performance was found to be improved in children with ADHD. Improvement in ADHD symptoms induced by NFT were maintained at 6-month follow-up in children with ADHD.
Modulated Convolutional Networks

Despite great effectiveness of very deep and wide Convolutional Neural Networks (CNNs) in various computer vision tasks, the significant cost in terms of storage requirement of such networks impedes the deployment on computationally limited devices. In this paper, we propose new modulated convolutional networks (MCNs) to improve the portability of CNNs via binarized filters. In MCNs, we propose a new loss function which considers the filter loss, center loss and softmax loss in an end-to-end framework. We first introduce modulation filters (M-Filters) to recover the unbinarized filters, which leads to a new architecture to calculate the network model. The convolution operation is further approximated by considering intra-class compactness in the loss function. As a result, our MCNs can reduce the size of required storage space of convolutional filters by a factor of 32, in contrast to the full-precision model, while achieving much better performances than state-of-the-art binarized models. Most importantly, MCNs achieve a comparable performance to the full-precision Resnets and WideResnets. The code will be available publicly soon.
Post‐cataract surgery endophthalmitis: The role of prophylactic antibiotic eye drops

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Multielemental Analysis Associated with Chemometric Techniques for Geographical Origin Discrimination of Tea Leaves (Camelia sinensis) in Guizhou Province, SW China

This study aimed to construct objective and accurate geographical discriminant models for tea leaves based on multielement concentrations in combination with chemometrics tools. Forty mineral elements in 87 tea samples from three growing regions in Guizhou Province (China), namely Meitan and Fenggang (MTFG), Anshun (AS) and Leishan (LS) were analyzed. Chemometrics evaluations were conducted using a one-way analysis of variance (ANOVA), principal component analysis (PCA), linear discriminant analysis (LDA), and orthogonal partial least squares discriminant analysis (OPLS-DA). The results showed that the concentrations of the 28 elements were significantly different among the three regions (p < 0.05). The correct classification rates for the 87 tea samples were 98.9% for LDA and 100% for OPLS-DA. The variable importance in the projection (VIP) values ranged between 1.01–1.73 for 11 elements (Sb, Pb, K, As, S, Bi, U, P, Ca, Na, and Cr), which can be used as important indicators for geographical origin identification of tea samples. In conclusion, multielement analysis coupled with chemometrics can be useful for geographical origin identification of tea leaves.
Phase 1 Study of Edasalonexent (CAT-1004), an Oral NF-κB Inhibitor, in Pediatric Patients with Duchenne Muscular Dystrophy

Background: Edasalonexent is an orally administered small molecule designed to inhibit NF-κB, which is activated from infancy in Duchenne muscular dystrophy and is central to causing muscle damage and preventing muscle regeneration. Objective: Evaluate the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of three doses of edasalonexent in ambulatory males ≥4 to <8 years of age with genetically confirmed Duchenne muscular dystrophy. Methods: This was a 1-week, open-label, multiple-dose study with 3 sequential ascending doses (33, 67 and 100 mg/kg/day) of edasalonexent administered under different dietary conditions to 17 males with a mean age of 5.5 years. Results: All doses of edasalonexent were well tolerated, with no serious adverse events, no drug discontinuations and no dose reductions. The majority of adverse events were mild, and the most common adverse events were gastrointestinal (primarily diarrhea). Edasalonexent was rapidly absorbed with peak levels observed 2–6 hours after dosing and exposures appeared to increase nearly proportionally to dose for the 2 lower and all 3 doses under low-fat and high-fat meal conditions, respectively. Only minor plasma accumulation of edasalonexent was observed with 7 days of dosing. After treatment with edasalonexent for 7 days, levels of NF-κB-regulated genes and serum proteins were decreased. Conclusions: This first report of edasalonexent oral administration for one week in male pediatric patients with Duchenne muscular dystrophy showed that treatment was well tolerated and inhibited NF-kB pathways.
Psychometric properties of the Group Climate Instrument (GCI) in individuals with mild intellectual disability or borderline intellectual functioning

Abstract Background This study examined the psychometric properties of the Group Climate Instrument (GCI) in a sample of N = 189 adults (79% men) with mild intellectual disability or borderline intellectual functioning who were residents of a treatment facility in the Netherlands. Method Construct validity of the GCI was examined by means of confirmatory factor analysis. Also, reliability and convergent validity of the GCI were examined. We also examined the variability in perception of the living group climate between and within living groups by computing intraclass correlation coefficients. Results The model contained four first‐order factors (support, growth, group atmosphere and repression) and a second‐order factor overall climate, providing preliminary support for construct validity of the GCI. Reliability coefficients were good for all factors. Preliminary evidence for convergent validity was found in significant moderate associations between subscales and single item ratings for the factors of group climate. The intraclass correlation coefficients indicated that a considerate proportion of variance can be attributed to between‐group differences. Conclusions The GCI might be used to assess perception of the living group climate for individuals with mild intellectual disability or borderline intellectual functioning in psychiatric and forensic care settings, although further development of the GCI and replication of our findings seem necessary.
Evoked hypoalgesia is accompanied by tonic pain and immune cell infiltration in the dorsal root ganglia at late stages of diabetic neuropathy in mice

Diabetic peripheral neuropathy is a major debilitating late complication of diabetes, which significantly reduces the quality of life in patients. Diabetic peripheral neuropathy is associated with a wide spectrum of sensory abnormalities, where in loss of sensation or hypoalgesia to applied external stimuli is paradoxically accompanied by debilitating tonic spontaneous pain. In numerous studies on animal models of diabetic peripheral neuropathy, behavioural measurements have been largely confined to analysis of evoked withdrawal to mechanical and thermal stimuli applied to dermatomes, whereas spontaneous, on-going pain has not been widely studied. In the Streptozotocin model of type 1 diabetes, we employed the Conditioned Place Preference test to assess tonic pain. Our results indicate that both phases, that is, early evoked hypersensitivity (i.e. 5–7 weeks post-Streptozotocin) as well as late stage hypoalgesia (i.e. 17–20 weeks post-Streptozotocin) are accompanied by significant tonic pain in mice with diabetic peripheral neuropathy. We also report on the temporal relation between on-going pain and neuropathological changes in the dorsal root ganglia of mice with diabetic peripheral neuropathy up to 6 months post-Streptozotocin. Neither early hypersensitivity nor late hypoalgesia were associated with markers of cellular stress in the dorsal root ganglia. Whereas significant neutrophil infiltration was observed in the dorsal root ganglia over both early and late stages post-Streptozotocin, T-cell infiltration in the dorsal root ganglia was prominent at late stages post-Streptozotocin. Thus, longitudinal analyses reveal that similar to patients with chronic diabetic peripheral neuropathy, mice show tonic pain despite sensory loss after several months in the Streptozotocin model, which is accompanied by neuroimmune interactions in the dorsal root ganglia.
The Digital Divide in Health-Related Technology Use: The Significance of Race/Ethnicity

Background and Objectives Technology can enhance the health and quality of life of diverse populations and may play an important role in reducing health disparities. Although a "digital divide" between the young and the old has been noted, it is unclear whether the use of technology for managing health differs by race/ethnicity among older adults. This study uses nationally representative data from community-dwelling older Americans to characterize racial/ethnic differences in health-related technology use. Design and Methods Data came from 1,336 white, black, and Hispanic adults aged 54 and older who completed the 2014 technology module of the Health and Retirement Study. Racial/ethnic differences in overall health-related technology use were assessed using Poisson regression. Then, F-tests were used to assess differences in the use of phone calls, text messages, E-mails, social media, health management sites, health-related mobile applications, web searches, and brain games for health purposes. Results Compared to whites, older blacks and Hispanics were less likely to use technology for health-related purposes after accounting for demographic characteristics, education, and health conditions. They were also less likely to make or receive phone calls, use health management sites, search the web for health information, and use brain games for their health. Discussion and Implications Older racial and ethnic minorities are less likely than whites to use certain technologies when managing their health. These findings highlight the importance of understanding the patterns of health-related technology use across racially and ethnically diverse populations to appropriately tailor interventions aimed at improving minority health and eliminating health disparities.