Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

Imaging reveals increased structural and functional plasticity in human visual pathways after retinal gene therapy. Vision restoration shines a light on human brain plasticity Much of our understanding about the plasticity of the human visual system comes from animal studies. Owing to the success of retinal gene therapy, it is now possible to study this process in humans with Leber’s congenital amaurosis (LCA) after their vision has been restored. Using a multimodal imaging approach, Ashtari et al. assessed both functional and structural changes in the visual pathways of a group of patients who underwent retinal gene therapy for this blinding disease in comparison with a group of sighted controls. Their results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated compared to the untreated eye of LCA patients. Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber’s congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy.
An unsupervised artificial immune classifier for multi/hyperspectral remote sensing imagery

A new method in computational intelligence namely artificial immune systems (AIS), which draw inspiration from the vertebrate immune system, have strong capabilities of pattern recognition. Even though AIS have been successfully utilized in several fields, few applications have been reported in remote sensing. Modern commercial imaging satellites, owing to their large volume of high-resolution imagery, offer greater opportunities for automated image analysis. Hence, we propose a novel unsupervised machine-learning algorithm namely unsupervised artificial immune classifier (UAIC) to perform remote sensing image classification. In addition to their nonlinear classification properties, UAIC possesses biological properties such as clonal selection, immune network, and immune memory. The implementation of UAIC comprises two steps: initially, the first clustering centers are acquired by randomly choosing from the input remote sensing image. Then, the classification task is carried out. This assigns each pixel to the class that maximizes stimulation between the antigen and the antibody. Subsequently, based on the class, the antibody population is evolved and the memory cell pool is updated by immune algorithms until the stopping criterion is met. The classification results are evaluated by comparing with four known algorithms: K-means, ISODATA, fuzzy K-means, and self-organizing map. It is shown that UAIC is an adaptive clustering algorithm, which outperforms other algorithms in all the three experiments we carried out.
Energy-efficient peer selection mechanism for BitTorrent content distribution

In this paper, we evaluate the energy consumption of BitTorrent based peer to peer (P2P) content distribution systems in bypass IP/WDM core networks and compare it to client-server (C/S) systems. A Mixed Integer Linear Programming (MILP) model is developed to carry out the comparison. Our results for homogeneous peers with similar upload capacities show that the original BitTorrent, based on random peer selection, has comparable energy consumption to the C/S model. The results also reveal that the power-minimized BitTorrent model achieves 30% energy savings compared to the C/S model as it converges to locality. Furthermore, a heterogeneous BitTorrent system with two upload capacity classes is investigated and the results show a 50% reduction in energy consumption compared to a C/S model. For real-time implementation, we develop a simple heuristic based on the model insights. Comparable power savings are achieved with a reduction of only 13% in the download rate.
Multispectral bathymetry using a simple physically based algorithm

A simple method for estimating water depths from multispectral imagery is described and is applied to several IKONOS data sets for which independent measurements of the water depth are available. The methodology is based on a physical model for the shallow-water reflectance, and is capable of correcting for at least some range of water-quality and bottom-reflectance variations. Corrections for sun-glint effects are applied prior to the application of the bathymetry algorithm. The accuracy of the depth algorithm is determined by comparison with ground-truth measurements, and comparisons between the observed and calculated radiances are presented for one case to illustrate how the algorithm corrects for water-attenuation and/or bottom-reflectance variations
Does Cryolipolysis Lead to Skin Tightening? A First Report of Cryodermadstringo.

Skin laxity occurs over time as collagen and elastin fibers break down. The breakdown is exacerbated by environmental factors, such as ultraviolet radiation, pollution, and stress. The rate of collagen and elastin degradation accelerates with time, while the rate of new collagen and elastin formation slows. For facial and neck laxity, several treatment methods exist, such as surgical lifts, minimally-invasive filler injections, and nonsurgical devices employing radiofrequency, laser, infrared, and ultrasound energy.1⇓⇓-4 To treat skin laxity on the body, the same treatment methods are available, although they are not as commonly used. Cryolipolysis (CoolSculpting System; Zeltiq Aesthetics, Pleasanton, CA) is a noninvasive method for selective fat reduction on the body. This nonsurgical procedure uses controlled cooling to reduce subcutaneous fat without inducing damage to surrounding tissues. Cleared by the Food and Drug Administration for fat reduction in 2010, cryolipolysis is an established procedure to safely and effectively reduce fat. A retrospective study on cryolipolysis discussed its clinical safety and efficacy, as well as its potential for business growth, in a plastic surgery practice.5 As shown in the aforementioned article, significant fat reduction can be achieved nonsurgically by cryolipolysis. Patients in flank and buttocks examples in the article also showed evidence of significant skin tightening.5 While cryolipolysis is well established as a nonsurgical method for fat reduction, it has …
From the Southern Association for Vascular Surgery Preoperative prediction of mortality within 1 year after elective thoracic endovascular aortic aneurysm repair

Objective: Thoracic endovascular aortic repair (TEVAR) is known to have a survival benefit over open repair in patients with descending thoracic aneurysms and has become a mainstay of therapy. Because death before 1 year after TEVAR likely indicates an ineffective therapy, we have created a predictive model for death within 1 year using factors available in the preoperative setting. Methods: A registry of 526 TEVARs performed at the University of Florida between September 2000 and November 2010 was queried for patients with degenerative descending thoracic aneurysm as their primary pathology. Procedures with emergent or urgent indications were excluded. Preoperatively available variables, such as baseline comorbidities, anatomic-, and procedure-specific planning details, were recorded. Univariate predictors of death were analyzed with multivariable Cox proportional hazards to identify independent predictors of 30-day (death within 30 days) and 1-year mortality (death within 1 year) after TEVAR. Results: A total of 224 patients were identified and evaluated. The 30-day mortality rate was 3% (n 7) and the 1-year mortality rate was 15% (n 33). Multivariable predictors of 1-year mortality (hazard ratios [95% confidence interval]) included: age >70 years (5.8 [2.1-16.0]; P .001), adjunctive intraoperative procedures (eg, brachiocephalic or visceral stents, or both, concomitant arch debranching procedures; 4.5 [1.9-10.8]; P .001), peripheral arterial disease (3.0 [1.4-6.7]; P .006), coronary artery disease (2.4 [1.1-4.9]; P .02), and chronic obstructive pulmonary disease (1.9 [1.0-3.9]; P .06). A diagnosis of hyperlipidemia was protective (0.4 [0.2-0.7]; P .006). When patients were grouped into those with one, two, three, or four or more of these risk factors, the predicted 1-year mortality was 1%, 3%, 10%, 27%, and 54%, respectively. Conclusions: Factors are available in the preoperative setting that are predictive of death within 1 year after TEVAR and can guide clinical decision making regarding the timing of repair. Patients with multiple risk factors, such as age >70 years, coronary artery disease, chronic obstructive pulmonary disease, and a need for an extensive procedure involving adjunctive therapies, have a high predicted mortality within 1 year and may be best served by waiting for a larger aneurysm size to justify the risk of intervention. (J Vasc Surg 2012;56:1266-73.)
Attenuation in Nonrainy Conditions at Millimeter Wavelengths: Assessment of a Procedure

A large database of radio-soundings, brightness temperatures, and satellite beacon data was used to verify the ability of radiometers in estimating the attenuation in nonprecipitating conditions at millimeter wavelengths. The mass absorption models proposed by Liebe and Rosenkranz have been used coupled with the Helsinki University of Technology (TKK) cloud-detection model to derive coefficients for the calculation of the attenuation due to integrated water vapor and liquid water contents. Comparison of predicted and measured attenuation cumulative distribution functions in the 20-50-GHz band confirms radiometers as a unique tool for retrieving attenuation in nonrainy condition and shows the very good performance of the TKK model for propagation applications.
A Method to Assess the Quality of Studies That Examine the Toxicity of Engineered Nanomaterials

As reports on the safety of various nanomaterials have yielded conflicting results, assessment of the reliability of each study is required to objectively interpret overall safety of the nanomaterial. A 2-step method to assess the quality of nanotoxicity studies is described. The first step uses a publicly available tool to rank the reliability of the study based on adequacy of design and documentation of methods, materials, and results, providing a “study score. ” The second step determines the completeness of physicochemical characterization of the nanomaterial/nanomaterials assessed within the study, providing a “nanomaterial score. ” This approach is encouraged to promote the notion that for studies conducted with nanomaterials, the combination of a reliable study and sufficient nanomaterial characterization is of significantly greater value than either of these alone. It is anticipated that the use and evolution of this approach will assist with the design and interpretation of studies assessing nanomaterial toxicity.
Final Report of the Amended Safety Assessment of Sodium Laureth Sulfate and Related Salts of Sulfated Ethoxylated Alcohols

Sodium laureth sulfate is a member of a group of salts of sulfated ethoxylated alcohols, the safety of which was evaluated by the Cosmetic Ingredient Review (CIR) Expert Panel for use in cosmetics. Sodium and ammonium laureth sulfate have not evoked adverse responses in any toxicological testing. Sodium laureth sulfate was demonstrated to be a dermal and ocular irritant but not a sensitizer. The Expert Panel recognized that there are data gaps regarding use and concentration of these ingredients. However, the overall information available on the types of products in which these ingredients are used and at what concentrations indicates a pattern of use. The potential to produce irritation exists with these salts of sulfated ethoxylated alcohols, but in practice they are not regularly seen to be irritating because of the formulations in which they are used. These ingredients should be used only when they can be formulated to be nonirritating.
Elderly Fallers: A Baseline Audit of Admissions to a Day Hospital for Elderly People

Falls in elderly people are a major problem for health and social services because of the incidence of injury and the fear of falling as a disabling consequence (McKee 1998). It seemed that many admissions to a South Buckinghamshire day hospital for elderly people were as a result of falls. A retrospective and concurrent caseload audit was carried out of medical and occupational therapy notes. The aim of the audit was to establish the incidence of falls among the day hospital population, with a view to improving the quality of the service. The data collected included age, diagnosis, functional ability and consequential actions. These items were included by consensus agreement following a literature review. Fifty-six of 196 elderly people admitted over the 12-month period had fallen at least once. Of these, 73% had no apparent predisposing factor for their fall and 39% were not carrying out any obvious activity at the time; 59% had an increase in social support due to decreased confidence and mobility after the fall. A multidisciplinary team approach was reinforced and the management of patients' problems on an individual basis was to be continued. The adoption of the audit data collection form as a checklist to facilitate future assessment was recommended.
Genetic interrogation of circulating multiple myeloma cells at single-cell resolution

Circulating tumor cells provide a practical and noninvasive way to monitor multiple myeloma. Single-cell approach to multiple myeloma Multiple myeloma is a cancer of plasma cells in the bone marrow, and it remains very difficult to treat. Unfortunately, it is hard to tell when a patient is developing chemotherapy resistance because monitoring response to treatment in this cancer normally requires a bone marrow biopsy, an invasive and painful procedure that cannot be repeated frequently. Lohr et al. now demonstrate that circulating tumor cells in peripheral blood of multiple myeloma patients can provide the same genetic information as bone marrow samples, and sometimes more. This finding suggests that noninvasive monitoring of peripheral blood samples in multiple myeloma should be useful for tracking patients’ response to therapy and optimizing the treatment approach for each patient. Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow. We demonstrate that CTCs provide the same genetic information as bone marrow MM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.
Immune correlates of vaccine protection against HIV-1 acquisition

Vaccine-induced non–broadly neutralizing antibodies are associated with protection against HIV-1 acquisition. The partial efficacy reported in the RV144 HIV vaccine trial in 2009 has driven the HIV vaccine field to define correlates of risk associated with HIV-1 acquisition and connect these functionally to preventing HIV infection. Immunological correlates, mainly including CD4+ T cell responses to the HIV envelope and Fc-mediated antibody effector function, have been connected to reduced acquisition. These immunological correlates place immunological and genetic pressure on the virus. Indeed, antibodies directed at conserved regions of the V1V2 loop and antibodies that mediate antibody-dependent cellular cytotoxicity to HIV envelope in the absence of inhibiting serum immunoglobulin A antibodies correlated with decreased HIV risk. More recently, researchers have expanded their search with nonhuman primate studies using vaccine regimens that differ from that used in RV144; these studies indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge as well. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition.
Broadly neutralizing human monoclonal JC polyomavirus VP1–specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy

Human monoclonal antibodies broadly neutralize multiple PML-causing JC polyomavirus variants. Opportunity knocks for JC polyomavirus therapy JC polyomavirus (JCPyV) can be found in the urinary tract in most adults, resulting in a persistent but asymptomatic infection. However, in immunocompromised individuals, JCPyV opportunistically infects the brain, resulting in the debilitating and frequently fatal disease progressive multifocal leukoencephalopathy (PML). No treatments are currently available for PML, but two papers now identify and exploit a gap in the immune response to JCPyV. Ray et al. report that JCPyV strains found in the cerebrospinal fluid of PML patients have mutations that prevent antibody neutralization and that these blind spots can be overcome with vaccination. Jelcic et al. suggest that broadly neutralizing antibodies derived from a patient who recovered from PML may fill this gap. In immunocompromised individuals, JC polyomavirus (JCPyV) may mutate and gain access to the central nervous system resulting in progressive multifocal leukoencephalopathy (PML), an often fatal opportunistic infection for which no treatments are currently available. Despite recent progress, the contribution of JCPyV-specific humoral immunity to controlling asymptomatic infection throughout life and to eliminating JCPyV from the brain is poorly understood. We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti–VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show “recognition holes”; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell repertoire of individuals who recovered from PML could be a source for the molecular cloning of broadly neutralizing antibodies for passive immunization. We generated a series of memory B cell–derived JCPyV VP1–specific human monoclonal antibodies from HDs and a patient with NAT-associated PML–immune reconstitution inflammatory syndrome (IRIS). These antibodies exhibited diverse binding affinity, cross-reactivity with the closely related BK polyomavirus, recognition of PML-causing VP1 variants, and JCPyV neutralization. Almost all antibodies with exquisite specificity for JCPyV, neutralizing activity, recognition of all tested JCPyV PML variants, and high affinity were derived from one patient who had recovered from PML. These antibodies are promising drug candidates for the development of a treatment of PML.
Toxicity Assessment of 4-Amino-2-Nitrotoluene

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.