Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach.

Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI's MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes.

Major declines in NE Atlantic plankton contrast with more stable populations in the rapidly warming North Sea.

Plankton form the base of marine food webs, making them important indicators of ecosystem status. Changes in the abundance of plankton functional groups, or lifeforms, can affect higher trophic levels and can indicate important shifts in ecosystem functioning. Here, we extend this knowledge by combining data from Continuous Plankton Recorder and fixed-point stations to provide the most comprehensive analysis of plankton time-series for the North-East Atlantic and North-West European shelf to date.

Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab.

Emicizumab is a bispecific monoclonal antibody that substitutes for the function of missing or deficient factor VIII (FVIII) in people with hemophilia A (PwHA). Long-term safety and efficacy of emicizumab have been demonstrated in several clinical trials. Nevertheless, in the first of these, three cases of thrombotic microangiopathy (TMA) occurred in PwHA treated with emicizumab receiving high doses of activated prothrombin complex concentrate (aPCC), a bypassing agent used for treating breakthrough bleeds when FVIII neutralizing antibodies (inhibitors) make FVIII replacement ineffective.

An approach to identify early damage biomarker candidates in metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease. Deficient activity of arylsulfatase A causes sulfatides to accumulate in cells of different tissues, including those in the central and peripheral nervous systems, leading to progressive demyelination and neurodegeneration. Although there is some association between specific arylsulfatase A alleles and disease severity, genotype-phenotype correlations are not fully understood.

Artificial intelligence assessment of the potential of tocilizumab along with corticosteroids therapy for the management of COVID-19 evoked acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS), associated with high mortality rate, affects up to 67% of hospitalized COVID-19 patients. Early evidence indicated that the pathogenesis of COVID-19 evoked ARDS is, at least partially, mediated by hyperinflammatory cytokine storm in which interleukin 6 (IL-6) plays an essential role. The corticosteroid dexamethasone is an effective treatment for severe COVID-19 related ARDS.

Female Sex, Age, and Unfavorable Response to Tumor Necrosis Factor Inhibitors in Patients With Axial Spondyloarthritis: Results of Statistical and Artificial Intelligence-Based Data Analyses of a National Multicenter Prospective Registry.

Objective: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy.

Methods: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied.

Stochastic and Deterministic Processes Regulate Phytoplankton Assemblages in a Temperate Coastal Ecosystem.

Assessing the relative contributions of the interacting deterministic and stochastic ecological processes for phytoplankton community assembly is crucial in understanding and predicting community organization and succession at different temporal and spatial scales. In this study, we hypothesized that deterministic and stochastic ecological processes regulating phytoplankton, present seasonal and repeating patterns. This hypothesis was explored during a 5-year survey (287 samples) conducted at a small spatial scale (~15km) in a temperate coastal ecosystem (eastern English Channel).

Identification of the Potential Molecular Mechanisms Linking RUNX1 Activity with Nonalcoholic Fatty Liver Disease, by Means of Systems Biology.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease; nevertheless, no definitive diagnostic method exists yet, apart from invasive liver biopsy, and nor is there a specific approved treatment. Runt-related transcription factor 1 (RUNX1) plays a major role in angiogenesis and inflammation; however, its link with NAFLD is unclear as controversial results have been reported. Thus, the objective of this work was to determine the proteins involved in the molecular mechanisms between RUNX1 and NAFLD, by means of systems biology.

Ceruletide and Alpha-1 Antitrypsin as a Novel Combination Therapy for Ischemic Stroke.

Ischemic stroke is a primary cause of morbidity and mortality worldwide. Beyond the approved thrombolytic therapies, there is no effective treatment to mitigate its progression. Drug repositioning combinational therapies are becoming promising approaches to identify new uses of existing drugs to synergically target multiple disease-response mechanisms underlying complex pathologies.

Molecular phylogeny and synonymy of Balechina gracilis comb. nov. (=Gymnodinium gracile), a widespread polymorphic unarmored dinoflagellate (Dinophyceae).

Gymnodinium gracile, described from the coasts of Denmark in 1881, is one of the first described unarmored dinoflagellates. Individuals that morphologically fit with the original description were isolated from the English Channel (North-East Atlantic). The SSU rRNA gene sequences were identical to the sequences identified as Balechina pachydermata and Gymnodinium amphora from the Mediterranean Sea and Brazil.

In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm.

From January 2020, COVID-19 is spreading around the world producing serious respiratory symptoms in infected patients that in some cases can be complicated by the severe acute respiratory syndrome, sepsis and septic shock, multiorgan failure, including acute kidney injury and cardiac injury. Cost and time efficient approaches to reduce the burthen of the disease are needed. To find potential COVID-19 treatments among the whole arsenal of existing drugs, we combined system biology and artificial intelligence-based approaches.

Molecular phylogeny of the parasitic dinoflagellate Syltodinium listii (Gymnodiniales, Dinophyceae) and generic transfer of Syltodinium undulans comb. nov. (= Gyrodinium undulans).

The parasitic dinoflagellate Syltodinium listii was investigated from the open waters of the English Channel, southern North Sea and the NW Mediterranean Sea. Syltodinium listii has been unreported since its original description in the North Sea. Cells of S.

Aging Increases Hippocampal DUSP2 by a Membrane Cholesterol Loss-Mediated RTK/p38MAPK Activation Mechanism.

Numerous studies suggest that the increased activity of p38MAPK plays an important role in the abnormal immune and inflammatory response observed in the course of neurodegenerative diseases such as Alzheimer's disease. On the other hand, high levels of p38MAPK are present in the brain during normal aging, suggesting the existence of mechanisms that keep the p38MAPK-regulated pro-inflammatory activity within physiological limits. In this study, we show that high p38MAPK activity in the hippocampus of old mice is in part due to the reduction in membrane cholesterol that constitutively occurs in the aging brain.

Quality of Life and Alleviation of Symptoms After Breast Reduction for Macromastia in Obese Patients: Is Surgery Worth It?

Background: Breast hypertrophy can cause a variety of symptoms and affect lifestyle and quality of life. Breast reduction, being the most effective treatment, is sometimes difficult to establish as standard treatment in obese patients (difficulties to differentiate symptoms from macromastia or from obesity, higher rate of complications).

Aim: To evaluate the effect of reduction mammaplasty (quality of life and symptoms) in obese patients comparing with non-obese.

Effect of emersion/immersion cycles on the elemental and isotopic compositions of the organic matter from surface sediments of an intertidal mud bank (French Guiana): a preliminary study.

Rationale: In various marine environments, the combination of elemental ratios and stable isotopic compositions is usually used to trace the sources of organic matter (OM) in sediments. However, in intertidal areas, the sediments might be temporarily exposed to air during a more or less prolonged duration and the impact of this exposure on the latter parameter is unknown.

Methods: The spatial variations of atomic Total Organic Carbon (TOC) and Total Nitrogen (TN) ratios, and δ(13)C and δ(15)N values, were measured on surface sediments of French Guiana, at the beginning and the end of five consecutive days of emersion during equinoctial tides, as well as at the beginning of a new emersion phase after returning to a normal tidal cycle.

Onset of the spring bloom in the northwestern Mediterranean Sea: influence of environmental pulse events on the in situ hourly-scale dynamics of the phytoplankton community structure.

Most of phytoplankton influence is barely understood at the sub meso scale and daily scale because of the lack of means to simultaneously assess phytoplankton functionality, dynamics and community structure. For a few years now, it has been possible to address this objective with an automated in situ high frequency sampling strategy. In order to study the influence of environmental short-term events (nutrients, wind speed, precipitation, solar radiation, temperature, and salinity) on the onset of the phytoplankton bloom in the oligotrophic Bay of Villefranche-sur-Mer (NW Mediterranean Sea), a fully remotely controlled automated flow cytometer (CytoSense) was deployed on a solar-powered platform (EOL buoy, CNRS-Mobilis).

Signaling networks in MS: a systems-based approach to developing new pharmacological therapies.

The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors.

Amazon River carbon dioxide outgassing fuelled by wetlands.

River systems connect the terrestrial biosphere, the atmosphere and the ocean in the global carbon cycle. A recent estimate suggests that up to 3 petagrams of carbon per year could be emitted as carbon dioxide (CO2) from global inland waters, offsetting the carbon uptake by terrestrial ecosystems. It is generally assumed that inland waters emit carbon that has been previously fixed upstream by land plant photosynthesis, then transferred to soils, and subsequently transported downstream in run-off.

[A comparative study of bacterioplankton structure in Argentinian Sea waters by the 454-tag pyrosequencing method].

The present study provides the first information about diversity and abundance of microbial communities in two environments of the Argentinian Sea by the 454 - tag pyrosequencing technique. We observed more than 4,600 unique bacterial sequences from 36,188 tag amplicons, forming 280 phylotypes. In addition, nearly 2,700 unique sequences from more than 47,700 tags identified as Archaea, defined only 5 different phylotypes.

Coastal bacterioplankton community diversity along a latitudinal gradient in Latin America by means of V6 tag pyrosequencing.

The bacterioplankton diversity of coastal waters along a latitudinal gradient between Puerto Rico and Argentina was analyzed using a total of 134,197 high-quality sequences from the V6 hypervariable region of the small-subunit ribosomal RNA gene (16S rRNA) (mean length of 60 nt). Most of the OTUs were identified into Proteobacteria, Bacteriodetes, Cyanobacteria, and Actinobacteria, corresponding to approx. 80% of the total number of sequences.

An optimised protocol to prepare Phaeocystis globosa morphotypes for scanning electron microscopy observation.

A preparation protocol for scanning electron microscopy (SEM) was adapted and tested to the observation of Phaeocystis globosa morphotypes. For extra colonial cells, critical point drying (CPD) gave satisfactory results while for intra colonial cells, preservation with Lugol's iodine and/or glutaraldehyde followed by air-drying appeared as the most suitable method.