Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy.

UNLABELLED It is generally accepted that growth factors play an important role in the pathogenesis of proliferative diabetic retinopathy. Since platelet-derived growth factor AB (PDGF AB) is known to be involved in many angiogenetic and proliferative processes, it was the aim of our study to elucidate the role of PDGF AB in the angiogenetic process in proliferative diabetic retinopathy. We measured PDGF AB concentrations in the vitreous of 23 patients with proliferative diabetic retinopathy, 4 of them with additional rubeosis iridis as an indicator of very high vasoproliferative activity. Control measurements were done in 19 patients without diabetic or ischemic eye diseases and also in 4 non-diabetic patients with ischemic proliferative retinopathy with rubeosis iridis. To exclude PDGF remnants in the vitreous due to vitreous bleeding we additionally measured platelet factor 4 concentrations as a stable marker of activated thrombocytes in the vitreous. RESULTS Significantly elevated concentrations of PDGF AB were found in the vitreous of patients with proliferative diabetic retinopathy, with higher levels in individuals with additional rubeosis iridis compared to controls. However, concentrations of PDGF AB were also elevated in ischemic non-diabetic retinopathy, supporting the concept that ischemia might be a strong stimulator of growth factor production in the retina. Platelet factor 4 was not detectable in any of the vitreous samples included in the study. In summary, our results indicate that the growth factor PDGF plays an important role in the pathogenesis of proliferative diabetic retinopathy, probably in synergistic action with other growth factors like IGF I, IGF II, VEGF and TNF alpha.
Normal plasma choline responses to ingested lecithin

we examined plasma choline changes after ingestion of diets composed of common foodstuffs, with choline contents bracketing the average daily intake in the American diet, and ingestion of diets supplemented with exogenous purified lecithin. A diet with low choline content did not increase plasma choline concentrations; a diet with high choline content doubled plasma choline levels. A lecithin-supplemented (25 gm; 80% phosphatidylcholine) low-choline diet increased plasma choline levels 400%, these findings indicate that normal diets cause only small elevations in plasma choline; purified lecithin supplements are likely to have greater effects in treating neurologic diseases.
Genital antibody response to a parenteral gonococcal pilus vaccine

A parenteral gonococcal pilus vaccine which has previously been shown to be safe and antigenic also results in the production of specific local genital antibody. All three major antibody classes were present in the local secretions, but immunoglobulin A predominated, a portion of which is dimeric 11S immunoglobulin A. This mucosal antibody is also capable of blocking the attachment of gonococci to epithelial cells. The antibody cross-reacted with five heterologous pili in a solid-phase radioimmunoassay. These results are encouraging and suggest that a gonococcal pilus vaccine may be efficacious in preventing gonorrhea.
Long-Term Efficacy and Safety of Empagliflozin Monotherapy in Drug-Naïve Patients with Type 2 Diabetes in Indian Subgroup: Results from a 76-week Extension Trial of Phase III, Double-Blind, Randomized Study

Background and Objectives: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article. Materials and Methods: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs). Results: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (−0.81, 95% confidence interval (CI) −1.33, −0.28; P = 0.0029) and E25 (−1.11, 95% CI − 1.60, −0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (−1.41, 95% CI − 2.51, −0.31; P = 0.0125) and E25 (−1.50, 95% CI − 2.54, −0.46; P = 0.0051) but nonsignificant with S100 (−0.75 95% CI − 1.86, −0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs. Conclusion: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.
Factors associated with incident human immunodeficiency virus-dementia.

BACKGROUND Antecedents to human immunodeficiency virus-dementia (HIV-D) are poorly understood. OBJECTIVE To identify risk factors for HIV-D. METHODS Subjects who are positive for HIV who have CD4+ counts either below 200/microL or below 300/microL with evidence of cognitive impairment were enrolled in this study. Neurologic, cognitive, functional, and laboratory assessments were done semiannually for up to 30 months. Human immunodeficiency virus-dementia was diagnosed using American Academy of Neurology criteria for probable HIV-1-associated dementia complex. RESULTS One hundred forty-six nondemented patients were enrolled, 45 of whom subsequently met criteria for incident HIV-D. In univariate analyses using the Cox proportional hazards regression model, the following variables were significantly associated with time to develop dementia: cognitive: abnormal scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests; attention-memory, psychomotor, and executive function domain scores; and the diagnosis of minor cognitive/motor disorder; neurologic and medical: increased abnormalities on the neurologic examination, extrapyramidal signs, history of HIV-related medical symptoms; functional: higher reported role or physical function difficulties. Depression was also a strong risk factor, along with sex, hematocrit, hemoglobin, and beta2-microglobulin levels. In a multivariate model that used cognitive domain scores, covariates with significant hazard ratios included depression, executive dysfunction, and the presence of minor cognitive/motor disorder. CONCLUSION Cognitive deficits, minor cognitive/motor disorder, and depression may be early manifestations of HIV-D.
Multiview 3D reconstruction and human point cloud classification

An efficient method for human point cloud classification to semantic parts is presented. Using multiview frames, the 3D point cloud is extracted by 3D reconstruction and structure from motion methods. Bundle adjustment method is used for obtaining camera position and 3D point cloud by minimizing the reprojection error. For semantically classifying this point cloud to human limbs the conditional random field (CRF) and the mean field approximation are used. For reducing computational complexity in message passing stage (because of a huge number of nodes related to 3d point cloud), the over-segmentation method and the voxel cloud connectivity segmentation (VCCS) that voxelisizes the 3D point cloud to the over segmented parts are used. Here, we use the fully connected CRF graph on voxels instead of single point cloud points. The pair wise potentials for this CRF are combinations of Gaussian kernels of normal, positions, and colors. Gaussian kernels are appearance, shape, smoothness and Geodesic distance. Appearance kernel is inspired by the observation that nearby pixels with similar color are likely to be in the same class. The smoothness kernel removes small isolated regions. The shape kernel is a Gaussian kernel of normal differences. The Geodesic kernel is shortest path with Dijkstra algorithm between meshes. The inference function is a weighted combination of Gaussians. The unary potentials are prior probability for each limb that have the related label. The 6D pose invariant features such as FFPH for obtaining the discriminative features in whole body parts are used for unary potentials in CRF model. The experimental results show the efficiency of the proposed method.
Robust voltage control model for active distribution network considering PVs and loads uncertainties

In active distribution networks (ADNs), the output of Photovoltaics (PVs) and loads cannot be accurately estimated because of insufficient measurements and highly frequent fluctuation of PVs. Therefore, it is necessary to implement the voltage control considering the uncertainties of PVs and loads. In this paper, a robust voltage control (R-VC) considering these uncertainties is proposed for ADNs. Firstly, the deterministic voltage control (D-VC) model based on distflow is developed for three-phase ADNs. Then, probability density function (PDF) curve for PVs and loads is discretized represented by different scenarios, and a simultaneous backward reduction method is used to reduce the scenarios. Finally the robust voltage optimization control model with reduced scenarios is proposed. Case studies show that the proposed method is robust and can capture the uncertainties.
Estimation of compressible or incompressible deformable motions for density images

When deformable motion is considered, the conventional "smoothness" constraint are not suitable. Since the deformation information lies on the derivatives of the displacement components, an ill-chosen minimization over the spatial derivatives of the now field can distort the estimated vector field. So we propose to use the small displacement theory of elasticity to define a new penalty function for 2D or 3D deformable motion estimation. This penalty function depends on two parameters. The study of these parameters shows the ability of the proposed functional to take into account compressible or incompressible deformations.
Attention, Comprehension, Execution: Effects of Different Designs of Biofeedback Display

The rapid development of biosensors and wearable devices has led to an increasing number of quantified self applications with physiological data. However, conventional graph-style visual representations which have been commonly used for behavior monitoring and control may not be the most applicable biofeedback methods. This is because biosensor data is not intuitive and is hard to manipulate directly and precisely, especially in computer-mediated collaborative interactions. In this work, we explore four different designs, i.e., graphical, illustrative, artistic and ambient representations, by visualizing physiological data in individual settings. Following the Research through Design model, we compare these four designs in terms of their abilities to facilitate biofeedback interpretation through a within-subject controlled experiment with 24 participants. The results suggest that users' visual perception is affected by different design styles.
Accuracy of Laboratory Data Communication on ICU Daily Rounds Using an Electronic Health Record*

Objectives: Accurately communicating patient data during daily ICU rounds is critically important since data provide the basis for clinical decision making. Despite its importance, high fidelity data communication during interprofessional ICU rounds is assumed, yet unproven. We created a robust but simple methodology to measure the prevalence of inaccurately communicated (misrepresented) data and to characterize data communication failures by type. We also assessed how commonly the rounding team detected data misrepresentation and whether data communication was impacted by environmental, human, and workflow factors. Design: Direct observation of verbalized laboratory data during daily ICU rounds compared with data within the electronic health record and on presenters’ paper prerounding notes. Setting: Twenty-six-bed academic medical ICU with a well-established electronic health record. Subjects: ICU rounds presenter (medical student or resident physician), interprofessional rounding team. Interventions: None. Measurements and Main Results: During 301 observed patient presentations including 4,945 audited laboratory results, presenters used a paper prerounding tool for 94.3% of presentations but tools contained only 78% of available electronic health record laboratory data. Ninty-six percent of patient presentations included at least one laboratory misrepresentation (mean, 6.3 per patient) and 38.9% of all audited laboratory data were inaccurately communicated. Most misrepresentation events were omissions. Only 7.8% of all laboratory misrepresentations were detected. Conclusion: Despite a structured interprofessional rounding script and a well-established electronic health record, clinician laboratory data retrieval and communication during ICU rounds at our institution was poor, prone to omissions and inaccuracies, yet largely unrecognized by the rounding team. This highlights an important patient safety issue that is likely widely prevalent, yet underrecognized.
Estimated Effectiveness and Cost-Effectiveness of Federally Funded Prevention Efforts on Gonorrhea Rates in the United States, 1971–2003, Under Various Assumptions About the Impact of Prevention Funding

Background: Reported gonorrhea incidence rates in the United States declined by 75% from 1975 to 2003 after implementation of a federally funded gonorrhea control program in the mid-1970s. The purpose of this study was to (1) estimate national gonorrhea rates that might have occurred from 1971 to 2003 had there been no federally funded sexually transmitted disease (STD) prevention activities and (2) calculate crude estimates of the cost-effectiveness of these prevention activities. Methods: Hypothetical gonorrhea rates had there been no federally funded prevention efforts from 1971 to 2003 were estimated based on (1) the amount of federal funding allocated to state and local health departments for STD prevention and (2) a published estimate of the impact of funding on STD rates in the United States. Standard methods of cost-effectiveness analysis were used to calculate the cost per case of gonorrhea prevented. Results: Under base case assumptions about the impact of prevention funding on gonorrhea rates drawn from a published study, prevention efforts were cost saving, meaning that the program costs were less than the averted costs of treating gonorrhea and its associated sequelae. Over the 33-year period, an estimated 32 million cases of gonorrhea were averted by prevention efforts. Conclusion: STD prevention efforts appeared to be cost saving when considering only the benefits of gonorrhea prevention. If other benefits were considered (such as the prevention of other STDs), the estimated effectiveness and cost-effectiveness of STD prevention in the United States would be even greater.
Identification of Discrete Domains within Gonococcal Transferrin-Binding Protein A That Are Necessary for Ligand Binding and Iron Uptake Functions

ABSTRACT The availability of free iron in vivo is strictly limited, in part by the iron-binding protein transferrin. The pathogenicNeisseria spp. can sequester iron from this protein, dependent upon two iron-repressible, transferrin-binding proteins (TbpA and TbpB). TbpA is a TonB-dependent, integral, outer membrane protein that may form a β-barrel exposing multiple surface loops, some of which are likely to contain ligand-binding motifs. In this study we propose a topological model of gonococcal TbpA and then test some of the hypotheses set forth by the model by individually deleting three putative loops (designated loops 4, 5, and 8). Each mutant TbpA could be expressed without toxicity and was surface exposed as assessed by immunoblotting, transferrin binding, and protease accessibility. Deletion of loop 4 or loop 5 abolished transferrin binding to whole cells in solid- and liquid-phase assays, while deletion of loop 8 decreased the affinity of the receptor for transferrin without affecting the copy number. Strains expressing any of the three mutated TbpAs were incapable of growth on transferrin as a sole iron source. These data implicate putative loops 4 and 5 as critical determinants for receptor function and transferrin-iron uptake by gonococcal TbpA. The phenotype of the ΔL8TbpA mutant suggests that high-affinity ligand interaction is required for transferrin-iron internalization.
The potential of proteasome inhibitors in cancer therapy

Background: The ubiquitin-proteasome system has become a promising novel molecular target in cancer due to its critical role in cellular protein degradation, its interaction with cell cycle and apoptosis regulation and its unique mechanism of action. Objective: This review focuses both on preclinical results and on data from clinical trials with proteasome inhibitors in cancer. Methods: Results in hematological malignancies and solid tumors were included, and important data presented in abstract form were considered in this review. Results/conclusion: Bortezomib as first-in-class proteasome inhibitor has proven to be highly effective in some hematological malignancies, overcomes conventional chemoresistance, directly induces cell cycle arrest and apoptosis, and also targets the tumor microenvironment. It has been granted approval by the FDA for relapsed multiple myeloma, and recently for relapsed mantle cell lymphoma. Combination chemotherapy regimens have been developed providing high remission rates and remission quality in frontline treatment or in the relapsed setting in multiple myeloma. The combination of proteasome inhibition with novel targeted therapies is an emerging field in oncology. Moreover, novel proteasome inhibitors, such as NPI-0052 and carfilzomib, have been developed. This review summarizes our knowledge of the ubiquitin-proteasome system and recent data from cancer clinical trials.
InAs/InSb nanowire heterostructures grown by chemical beam epitaxy

We report the Au-assisted chemical beam epitaxy growth of defect-free zincblende InSb nanowires. The grown InSb segments are the upper sections of InAs/InSb heterostructures on InAs(111)B substrates. We show, through HRTEM analysis, that zincblende InSb can be grown without any crystal defects such as stacking faults or twinning planes. Strain-map analysis demonstrates that the InSb segment is nearly relaxed within a few nanometers from the interface. By post-growth studies we have found that the catalyst particle composition is AuIn2, and it can be varied to a AuIn alloy by cooling down the samples under TDMASb flux.
Excess cholesterol inhibits glucose‐stimulated fusion pore dynamics in insulin exocytosis

Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β‐cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β‐cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β‐cells and contribute to β‐cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β‐cell function remain largely unknown. Here, we used total internal reflection fluorescence microscopy to address, at the single‐granule level, the role of cholesterol in regulating fusion pore dynamics during insulin exocytosis. We focused particularly on the effects of cholesterol overload, which is relevant to type 2 diabetes. We show that excess cholesterol reduced the number of glucose‐stimulated fusion events, and modulated the proportion of full fusion and kiss‐and‐run fusion events. Analysis of single exocytic events revealed distinct fusion kinetics, with more clustered and compound exocytosis observed in cholesterol‐overloaded β‐cells. We provide evidence for the involvement of the GTPase dynamin, which is regulated in part by cholesterol‐induced phosphatidylinositol 4,5‐bisphosphate enrichment in the plasma membrane, in the switch between full fusion and kiss‐and‐run fusion. Characterization of insulin exocytosis offers insights into the role that elevated cholesterol may play in the development of type 2 diabetes.
Bilayer Implants

Objective To compare the regenerative capacity of 2 distinct bilayer implants for the restoration of osteochondral defects in a preliminary sheep model. Methods Critical sized osteochondral defects were treated with a novel biomimetic poly-ε-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months postoperation, repair tissue (n = 5 each) was analyzed for histology and biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo. Results Histological scores, electromechanical quantitative parameter values, dsDNA and sGAG contents measured at the repair sites were statistically lower than those obtained from the contralateral surfaces. Electromechanical mappings and higher dsDNA and sGAG/weight levels indicated better regeneration for Treatment No. 1. However, these differences were not significant. For both treatments, Arthro-BST revealed early signs of degeneration of the cartilage surrounding the repair site. The International Cartilage Repair Society II histological scores of the repair tissue were significantly higher for Treatment No. 1 (10.3 ± 0.38 SE) compared to Treatment No. 2 (8.7 ± 0.45 SE). The parameters cell morphology and vascularization scored highest whereas tidemark formation scored the lowest. Conclusion There was cell infiltration and regeneration of bone and cartilage. However, repair was incomplete and fibrocartilaginous. There were no significant differences in the quality of regeneration between the treatments except in some histological scoring categories. The results from Arthro-BST measurements were comparable to traditional invasive/destructive methods of measuring quality of cartilage repair.
Similar calcification process in acute and chronic human brain pathologies

Cellular microcalcification observed in a diversity of human pathologies, such as vascular dementia, Alzheimer's disease, Parkinson's disease, astrogliomas, and posttraumatic epilepsy, also develops in rodent experimental models of central nervous system (CNS) neurodegeneration. Central to the neurodegenerative process is the inability of neurons to regulate intracellular calcium levels properly, and this is extensible to fine regulation of the CNS. This study provides evidence of a common pattern of brain calcification taking place in several human pathologies, and in the rat with glutamate‐derived CNS lesions, regarding the chemical composition, physical characteristics, and histological environment of the precipitates. Furthermore, a common physical mechanism of deposit formation through nucleation, lineal growth, and aggregation is presented, under the modulation of protein deposition and elemental composition factors. Insofar as calcium precipitation reduces activity signals at no energy expense, the presence in human and rodent cerebral brain lesions of a common pattern of calcification may reflect an imbalance between cellular signals of activity and energy availability for its execution. If this is true, this new step of calcium homeostasis can be viewed as a general cellular adaptative mechanism to reduce further brain damage. © 2005 Wiley‐Liss, Inc.