Miracle-dz/UniFAR-FTUs huggingface dataset:
Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

Importance Ranibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed. Objective To evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR. Design, Setting, and Participants Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018. Interventions Eyes were randomly assigned to receive intravitreous ranibizumab (n = 191) or PRP (n = 203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group. Main Outcomes and Measures Mean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety. Results The 5-year visit was completed by 184 of 277 participants (66% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44%) were women, and 160 (52%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2 (10.9) and 5.4 (7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1 (14.3) and 3.0 (10.5) letters, respectively (adjusted difference, 0.6; 95% CI, −2.3 to 3.5; P = .68); the mean visual acuity was 20/25 (approximate Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was −330 (645) vs −527 (635) dB in the ranibizumab (n = 41) and PRP (n = 38) groups, respectively (adjusted difference, 208 dB; 95% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22% vs 38%; hazard ratio, 0.4; 95% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified. Conclusions and Relevance Although loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti–vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR. Trial Registration ClinicalTrials.gov Identifier: NCT01489189
Evidence and Perspectives on the Use of Polymyxin B-Immobilized Fiber Column Hemoperfusion among Critically Ill Patients.

BACKGROUND Sepsis frequently leads to multiple organ failure due to the uncontrolled amplification and spread of inflammation, even if the infectious source is controlled. Lipopolysaccharide (LPS), a typical pathogen-associated molecular pattern (PAMP), is adsorbed by the polymyxin B-immobilized fiber column (PMX). PMX has been used for decades in Europe. Results of a North American randomized controlled trial (RCT) on PMX have recently been announced in a press release; results of large-scale observational studies and meta-analyses have also been reported in the last several years. SUMMARY To date, 3 multicenter RCTs on PMX hemoperfusion have been conducted outside of Japan. All of them enrolled postoperative patients with sepsis or septic shock secondary to intra-abdominal infection. However, confidence in the level of evidence provided by these RCTs is very low. Results from recent propensity-matched analyses and meta-analyses indicate that PMX hemoperfusion may improve survival outcomes among patients with sepsis. LPS is an important causative PAMP in sepsis; it triggers the immune response. PMX adsorbs LPS by using a polymyxin B-immobilized fiber that has high affinity for LPS. Moreover, PMX has other mechanisms of action, such as endogenous cannabinoid and activated neutrophil and monocyte adsorption, monocyte surface antigen alteration, and regulation of apoptosis in renal tubular cells. Furthermore, clinical research shows that PMX hemoperfusion can improve patients' hemodynamic status and pulmonary oxygenation and can sustain its endotoxin adsorption capability beyond 2 h. Improved pulmonary oxygenation among patients with sepsis-associated acute respiratory distress syndrome is linked to the effectiveness of PMX hemoperfusion in treating acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). Key Messages: Meta-analysis indicates that PMX hemoperfusion may improve the survival outcomes of patients with sepsis; LPS adsorption is an important treatment modality in sepsis. Many novel findings on the mechanisms of action of PMX, beyond endotoxin adsorption, have been reported. Additionally, a prolonged duration of PMX hemoperfusion has been shown to be efficacious, and beneficial effects on AE-IPF have been demonstrated. The use of PMX hemoperfusion for the correct duration and at the right time in appropriate patients may lead to favorable therapeutic outcomes.
Impact of number of episodes on neurocognitive trajectory in bipolar disorder patients: a 5-year follow-up study

Abstract Background The neurocognitive trajectory in bipolar disorder (BD) is variable, with controversial findings, and most evidence come from cross-sectional studies. We aimed to examine the course of neurocognitive functioning in a sample of euthymic BD patients in comparison with a control group during a 5-year follow-up. Methods Ninety-nine euthymic bipolar patients and 40 healthy controls were assessed using a comprehensive neurocognitive battery (six neurocognitive domains) at baseline (T1) and then at 5-year follow-up (T2) in a longitudinal study. Results No evidence of a progression in neurocognitive dysfunction was found either in cognitive composite index or in any of the neurocognitive domains for the whole cohort. However, there was a negative correlation between number of manic episodes and hospitalisations due to manic episodes and change in neurocognitive composite index (NCI) during the follow-up. Moreover, patients with higher number of manic and hypomanic episodes have a greater decrease in NCI, working memory and visual memory. History of psychotic symptoms was not related to the trajectory of neurocognitive impairment. Conclusions Our results suggest that, although the progression of cognitive decline is not a general rule in BD, BD patients who have a greater number of manic or hypomanic episodes may constitute a subgroup characterised by the progression of neurocognitive impairment. Prevention of manic and hypomanic episodes could have a positive impact on the trajectory of cognitive function.
Effects of protein oxidation on the texture and water-holding of meat: a review

Abstract Protein oxidation readily occurs in postmortem muscle during storage and processing. Over the past decade new analytical methods have been developed and new aspects of protein oxidation in meat have been studied, such as the reaction mechanism, and impacts on eating quality and nutritional value. It is now evident that amino acid side chains in myofibrillar proteins undergoes modifications due to oxidative stress. In turn this will lead to formation of new protein-protein cross-links in structural proteins, however, also the overall level of fixed-charge groups attached to the peptide backbones is modified. Meat texture and water-holding are important quality attributes and they are affected by the oxidation of structural proteins. Different mechanisms have been suggested to explain the oxidation-induced quality changes, focusing mainly on reduced proteolysis and formation of cross-links. This review explores the current understanding of protein oxidation in fresh meat in relation to texture and water-holding. The consequences of protein oxidation at molecular level in relation to oxidation-induced cross-linking and changes in net charges of myofibrillar proteins, and the impacts on texture and water-holding are discussed.
Genome-wide scans of selection highlight the impact sof biotic and abiotic constraints in natural populations of the model grass Brachypodium distachyon

Grasses are essential plants for ecosystem functioning. Quantifying the selective pressures that act on natural variation in grass species is therefore essential regarding biodiversity maintenance. In this study, we investigate the selection pressures that act on two distinct populations of the grass model Brachypodium distachyon without prior knowledge about the traits under selection. We took advantage of whole-genome sequencing data produced for 44 natural accessions of B. distachyon and used complementary genome-wide scans of selection (GWSS) methods to detect genomic regions under balancing and positive selection. We show that selection is shaping genetic diversity at multiple temporal and spatial scales in this species and affects different genomic regions across the two populations. Gene Ontology annotation of candidate genes reveals that pathogens may constitute important factors of positive and balancing selection in Brachypodium distachyon. We eventually cross-validated our results with QTL data available for leaf-rust resistance in this species and demonstrate that, when paired with classical trait mapping, GWSS can help pinpointing candidate genes for further molecular validation. Thanks to a near-base perfect reference genome and the large collection of freely available natural accessions collected across its natural range, B. distachyon appears as a prime system for studies in ecology, population genomics and evolutionary biology.
Telehealth and Home Dialysis: A New Option for Patients in the United States.

On February 9, 2018, after a brief government shutdown, the Bipartisan Budget Act of 2018 was signed into law ([1][1]). This act contained key elements of the Creating High-Quality Results and Outcomes Necessary to Improve Chronic (CHRONIC) Care Act of 2017, including provisions expanding access to
Quantitative analysis of competitive cytokine signaling predicts tissue thresholds for the propagation of macrophage activation

Competitive TNF-α uptake regulates the propagation of heterogeneous responses of macrophages in tissues. Modeling TNF-α signaling by macrophages The proinflammatory cytokine TNF-α is one of the earliest factors secreted by macrophages in response to bacterial infection. Diffusion of TNF-α throughout tissues disseminates the inflammatory response; however, without mechanisms to limit TNF-α signaling, damaging chronic inflammation would occur. Through single-cell monitoring of the dynamics of gene expression in macrophages and of TNF-α secretion and uptake by macrophages and fibroblasts, Bagnall et al. derived a mathematical model that suggests that TNF-α secreted by macrophages in tissues acts locally to drive immune responses but that it is taken up by surrounding nonimmune cells, such as fibroblasts, to limit its long-range effects in the tissue. Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that individual cells exhibited a wide range (three orders of magnitude) of expression of the gene encoding the proinflammatory cytokine tumor necrosis factor–α (TNF-α). The TLR4-induced TNFA transcriptional response correlated with the extent of NF-κB signaling in the cells and their size. We compared the rates of TNF-α production and uptake in macrophages and mouse embryonic fibroblasts and generated a mathematical model to explore the heterogeneity in the response of macrophages to TLR4 stimulation and the propagation of the TNF-α signal in the tissue. The model predicts that the local propagation of the TLR4-dependent TNF-α response and cellular NF-κB signaling are limited to small distances of a few cell diameters between neighboring tissue-resident macrophages. In our predictive model, TNF-α propagation was constrained by competitive uptake of TNF-α from the environment, rather than by heterogeneous production of the cytokine. We propose that the highly constrained architecture of tissues enables effective localized propagation of inflammatory cues while avoiding out-of-context responses at longer distances.
Building Principles for Constructing a Mammalian Blastocyst Embryo

The self-organisation of a fertilised egg to form a blastocyst structure, which consists of three distinct cell lineages (trophoblast, epiblast and hypoblast) arranged around an off-centre cavity, is unique to mammals. While the starting point (the zygote) and endpoint (the blastocyst) are similar in all mammals, the intervening events have diverged. This review examines and compares the descriptive and functional data surrounding embryonic gene activation, symmetry-breaking, first and second lineage establishment, and fate commitment in a wide range of mammalian orders. The exquisite detail known from mouse embryogenesis, embryonic stem cell studies and the wealth of recent single cell transcriptomic experiments are used to highlight the building principles underlying early mammalian embryonic development.
Elective Orthopaedic and Trauma Patients in Southern Italy are Vitamin D Deficient. A Pilot Study

Many patients present with Vitamin D (Vit d; 25 (OH) D) deficiency on admission to hospital. The present study evaluated the levels of serum concentration of 25 (OH) D in patients undergoing elective arthroplasty of the hip and knee and in patients with proximal femur fracture. A total of 90 patients of both sex were recruited, 20 with osteoarthritis of the knee, 29 with osteoarthritis of the hip, and 41 with a hip fracture. The levels of Vit D were measured twice: on admission and on the fourth day after surgery. In patients undergoing knee arthroplasty, the levels of Vit D were 16.85 ng/ml in the preoperative and 18.235 ng/ml in the postoperative period. In patients undergoing hip arthroplasty, we found levels <4.20 ng/ml for men, while in women 25.20 ng/ml pre-operatively and 22.8 ng/ml post-operatively. In patients with a hip fracture, men progressed from very low levels preoperatively (6.38 ng/ml) with post-operative levels of 18.44 ng /ml. Women exhibited a slight improvement from 12.24 ng/ml pre-operatively to 17.9 ng/ml postoperatively. Patients who are candidates for hip and knee arthroplasty and in hip fracture patients exhibit low Vit D levels. The activation of the inflammatory cascade may induce reduction of Vit D levels, and this fall is associated with impaired bone health.
Metamaterial-inspired microstrip antennas for wireless communication systems

Inspired by the concept of the periodic-type metamaterials, a grid-slotted structure is proposed to enhance the bandwidth from traditional microstrip antennas with single radiating patch. Smaller wave number is achieved by using the periodic grid-slotted structure to couple multiple operating modes. Furthermore, for high spectrum efficiency, a polarized multiple-input-multiple-output antenna is constructed based on the proposed structure. The numerical results show exciting possibilities using metamaterials to promote antenna performance in communication systems.
A low-profile dual-polarized ka-band antenna for wide angle scanning phased arrays

In this paper, a low-profile dual-polarized aperture-coupled microstrip patch antenna is presented. The antenna is well suited for Ka-band active phased array systems requiring wide-angle scanning. The simulated VSWR of the antenna exhibits an impedance bandwidth of over 23.5% and the isolation between the two ports is better than 35 dB over the bandwidth. The cross-polarization levels in both E- and H-plane are better than −20 dB. Also, the center embedded antenna element in the array can scan up to 60 degree from boresight in both the principal planes from 31.5 to 38 GHz.
Extracellular aminopeptidase modulates biofilm development of Pseudomonas aeruginosa by affecting matrix exopolysaccharide and bacterial cell death

Biofilm bacteria are embedded within a self-secreted extracellular matrix that contains a considerable amount of proteins including many extracellular enzymes. However, little is known about the roles of such enzymes in biofilm development. Here, we studied Pseudomonas aeruginosa aminopeptidase (PaAP, encoded by PA2939 that we named the gene as paaP in this study), a quorum-sensing-regulated enzyme and one of the most abundant extracellular proteins in the biofilm matrix of this opportunistic pathogen and environmental bacterium. We found that deletion of paaP in P. aeruginosa increased initial attachment and biofilm formation at early stages of biofilm development. After 24 h growth, loss of PaAP resulted in substantial cell death and biofilm disruption. Bacterial cell death was independent of biofilm matrix polysaccharide Psl, while biofilm disruption was due to the degradation of Psl matrix by dead-bacteria-released glycosyl hydrolase PslG, thereby leading to biofilm dispersion. PaAP functioned extracellularly and aminopeptidase catalytic activity was essential for its effect on biofilm development. Our data reveal an important role of extracellular aminopeptidase in biofilm development, suggesting PaAP as a therapeutic target for preventing P. aeruginosa infection and combating biofilm-related complications.
Cardiovascular adaptations after 10 months of intense school‐based physical training for 8‐ to 10‐year‐old children

This study examined cardiovascular adaptations in 8‐ to 10‐year‐old schoolchildren after 10 months (a full school year) of 3 × 40 minute per week of small‐sided ball games (SSG, including football, basketball, and/or floorball) or circuit strength training (CST). The study involved 291 Danish schoolchildren, 8‐10 years old, cluster‐randomized to SSG (n = 93, 4 schools, 5 classes), CST (n = 83, 4 schools, 4 classes), or a control group (CON, n = 115, 2 schools, 5 classes). Before and after the 10‐month intervention, resting heart rate and blood pressure measurements were performed as well as comprehensive transthoracic echocardiography and peripheral arterial tonometry (PAT). Analysis of baseline‐to‐10‐months changes showed between‐group differences (P < 0.05) after both training interventions in diastolic blood pressure (delta scores: SSG −2.1 ± 6.0 mm Hg; CST −3.0 ± 7.1 mm Hg; CON 0.2 ± 5.3 mm Hg). Moreover, there were between‐group differences in delta scores (P < 0.05) in interventricular septum thickness (SSG 0.17 ± 0.87 mm; CST 0.30 ± 0.94 mm; CON −0.15 ± 0.68 mm), left‐atrial volume index (SSG 0.32 ± 5.13 mL/m2; CON 2.60 ± 5.94 mL/m2), and tricuspid annular plane systolic excursion (SSG −0.4 ± 3.3 mm; CON: 0.1 ± 3.6 mm). No significant between‐group differences were observed for the PAT‐derived reactive hyperemia index. In conclusion, 10 months of 3 × 40 minutes per week of SSG and CST in 8‐ to 10‐year‐old children decreased diastolic blood pressure and elicited discrete cardiac adaptations, suggesting that intense physical exercise in school classes can have effects on cardiovascular health in children.
The yin‐yang of the interaction between myelomonocytic cells and NK cells

NK cells are innate lymphoid cells, which play a key role in the immune response to cancer and pathogens and participate in the shaping of adaptive immunity. NK cells engage in a complex bidirectional interaction with myelomonocytic cells. In particular, macrophages, dendritic cells and neutrophils promote differentiation and effector function of NK cells and, on the other hand, myelomonocytic cells express triggers of checkpoint blockade (eg PD‐L1) and other immunosuppressive molecules, which negatively regulate NK cell function. In addition, NK cells express high levels of IL‐1R8, which acts as a checkpoint for IL‐18 driven differentiation and activation of NK cells. Evidence suggests that targeting the myeloid cell‐NK cell crosstalk unleashes effective anti‐tumour and anti‐viral resistance.
Flow cytometry for minimal residual disease testing in acute leukemia: opportunities and challenges

ABSTRACT Introduction: Flow cytometric quantification of minimal residual disease (MRD) in acute leukemia (AL) represents an indispensable tool to guide modern therapeutic protocols toward a precision medicine approach, being a powerful predictor of the overall response to treatment. This review covers the most challenging aspects and developments of this method, aiming at supporting further its implementation in clinical practices. Area covered: Flow cytometric MRD is based on the discrimination of leukemia cells from their physiological counterparts by the recognition of the leukemia-associated immunophenotypes. Technical and standardization advances along the last decades have been implemented allowing flow cytometric MRD to consolidate its role in modern therapeutic protocols for ALs. However, gaps in sensitivity and data interpretation are still present together with the need for further optimization of MRD-based clinical protocols. In this review, we critically analyze and discuss the most relevant and representative contributions in the field by accurate selection of the literature available in PubMed. Expert commentary: Further research in flow cytometric MRD can bring this technology toward wider and consistent applications in multiple acute leukemia settings rendering this tool a future golden standard and providing clinicians with more reliable and accurate tools for clinical decisions.
La "minéralité du vin" : mots d'experts et de consommateurs

Cet article presente l’etat d’avancement d’un projet en cours visant a definir la notion de MINERALITE DU VIN dans deux types de discours : celui des experts et celui des consommateurs. En tant que rapport d’etape, il s’arrete largement sur le contexte ayant preside a l’etude et conduit a la formulation des hypotheses de recherche. Il presente ensuite les resultats d’un premier temps de l’analyse dont l’objectif etait de circonscrire semantiquement la notion telle que celle-ci se degage du discours ambiant emanant essentiellement de professionnels, semi-professionnels et autres amateurs eclaires s’exprimant dans des types de discours souvent prescriptifs. Ces elements de depart etant poses, le second temps de la demonstration presente le mode d’elaboration d’un questionnaire destine a recueillir, aupres de consommateurs, un corpus de parole sur la notion en jeu avant de commenter brievement les premieres tendances se degageant d’un fragment de ce corpus.
140GHz low-profile and high-gain slot array antennas

This paper proposes two low-profile and high-gain array antennas with broad bandwith at 140GHz. The two antennas compose of the same subarray unit. 32 × 32-element array shows more than 38.7dBi gain with 92% efficency at center frequency and 21.5GHz bandwith(129.3–150.8GHz) and 64 × 64-element array shows more than 43.9dBi gain with 74.6% efficiency at center frequency and 20GHz bandwith(130.0–150.0GHz), respectively. The antennas will be divided into 3 layers for fabrication using milling technology.