Publications by authors named "Carlos Castro"

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

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Knowledge about seafloor depth, or bathymetry, is crucial for various marine activities, including scientific research, offshore industry, safety of navigation, and ocean exploration. Mapping the central Arctic Ocean is challenging due to the presence of perennial sea ice, which limits data collection to icebreakers, submarines, and drifting ice stations. The International Bathymetric Chart of the Arctic Ocean (IBCAO) was initiated in 1997 with the goal of updating the Arctic Ocean bathymetric portrayal.

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Article Synopsis
  • The study investigates the interaction between Ang-(1-7) and the ET-1 system in the context of pulmonary hypertension, suggesting that Ang-(1-7) opposes harmful effects of ET-1.
  • Research methods include various models (in vivo in mice, ex vivo in isolated arteries, and in vitro in human cells) that demonstrate Ang-(1-7) treatment reduces pulmonary vascular damage and promotes vasodilation.
  • Findings reveal a complex signaling network involving MasR and ETR that protects against vascular injury, highlighting the potential for enhancing this pathway to improve vascular health.
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  • Standard first-line treatments for PNH involve anti-C5 therapies like eculizumab and ravulizumab, but these can lead to persistent anemia and quality of life issues due to frequent infusions.
  • Iptacopan, a new oral medication targeting complement factor B, showed promising results in phase 3 trials (APPLY-PNH and APPOINT-PNH), improving hemoglobin levels and offering a safe alternative with no major side effects.
  • This oral therapy helps patients avoid infusions, potentially reducing medical costs and enhancing quality of life, while ongoing studies will further evaluate its long-term safety, including risks like infections and thrombosis.
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Acute myeloid leukemia (AML) is the most common and lethal leukemia in adults. AML consists of many genetic subtypes, which limits broad applicability of targeted therapy. We discovered that the hematopoiesis-restricted tetraspanin CD37 is expressed on the majority of primary AML blasts and thus may represent a common therapeutic target for AML regardless of subtype.

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This study investigates the thermochemical decomposition and gasification performance of biochars produced from blends of waste lignocellulosic biomass and waste insulation electrical cables at varying temperatures. Characterization tests revealed changes, particularly in ash content (27.5 %-34 %) and elemental composition, with nitrogen content increasing notably in biochar samples compared to the original feedstock.

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DNA origami nanotechnology has great potential in multiple fields including biomedical, biophysical, and nanofabrication applications. However, current production pipelines lead to single-use devices incorporating a small fraction of initial reactants, resulting in a wasteful manufacturing process. Here, we introduce two complementary approaches to overcome these limitations by recycling the strand components of DNA origami nanostructures (DONs).

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  • Exercise training induces physiological cardiac hypertrophy, which is influenced by the protective actions of the renin-angiotensin system, particularly the Mas receptor.
  • A study on rats showed that blocking the Mas receptor with A-779 led to higher blood pressure and prevented the beneficial cardiac adaptations that normally occur with exercise.
  • The results suggest that normal Mas receptor activity is crucial for maintaining healthy heart muscle structure and function during exercise-induced changes.
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Mechanical forces play key roles in biological processes such as cell migration and sensory perception. In recent years molecular force sensors have been developed as tools for force measurements. Here we use all-atom steered molecular dynamics simulations to predict and study the relationship between design parameters and mechanical properties for three types of molecular force sensors commonly used in cellular biological research: two peptide- and one DNA-based.

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Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals.

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The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses.

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DNA origami nanostructures (DOs) are promising tools for applications including drug delivery, biosensing, detecting biomolecules, and probing chromatin substructures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing, visualizing, and controlling biomolecular processes within live cells. We present an approach to deliver DOs into live-cell nuclei.

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Choosing Wisely is an initiative by the American Board of Internal Medicine (ABIM) and ABIM Foundation to deter unnecessary medical treatments and procedures. Faced with the burden of modern technologies and treatments, it is crucial to identify practices lacking value in daily care. The Latin American and Caribbean Society (SLACOM), comprising cancer control experts, deems it vital to tailor this initiative for enhancing cancer care in the region.

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Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood.

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Severe aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel's recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate.

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Lupins ( spp.) are legumes with high relevance for the sustainability of agricultural systems as they improve the soil quality, namely, through the fixation of atmospheric nitrogen, and have good adaptability to different climates and soil conditions. Besides, they possess high nutritive value, especially due to the high protein content of the seeds.

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The identification of crops that simultaneously contribute to the global protein supply and mitigate the effects of climate change is an urgent matter. Lupins are well adapted to nutrient-poor or contaminated soils, tolerate various abiotic stresses, and present relevant traits for acting as ecosystem engineers. Lupins are best studied for their seeds, but their full foraging potential needs further evaluation.

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Patients with paroxysmal nocturnal hemoglobinuria (PNH) experience complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Pegcetacoplan, a C3 inhibitor, demonstrated sustained improvements in hematologic and clinical parameters in the phase 3 PEGASUS trial in patients with PNH who remained anemic despite C5 inhibitor therapy. The present post hoc analysis describes 26 hemolysis adverse events (AEs) experienced in 19 patients during pegcetacoplan therapy in PEGASUS and baseline patient characteristics potentially associated with increased hemolysis risk.

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Many experimental and computational efforts have sought to understand DNA origami folding, but the time and length scales of this process pose significant challenges. Here, we present a mesoscopic model that uses a switchable force field to capture the behavior of single- and double-stranded DNA motifs and transitions between them, allowing us to simulate the folding of DNA origami up to several kilobases in size. Brownian dynamics simulations of small structures reveal a hierarchical folding process involving zipping into a partially folded precursor followed by crystallization into the final structure.

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Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Prepuberty has been considered as a later susceptible window of development, and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the prepuberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHRs).

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Article Synopsis
  • Iptacopan, an oral factor B inhibitor, shows promise in treating paroxysmal nocturnal hemoglobinuria patients suffering from persistent hemolytic anemia, especially those not responding to anti-C5 therapy.
  • In two phase 3 trials, iptacopan significantly improved hemoglobin levels in patients with low baseline hemoglobin (under 10 g/dL), with many experiencing increases of at least 2 g/dL without needing blood transfusions.
  • The results revealed that 85% of patients in the first trial and nearly all in the second trial experienced a notable increase in hemoglobin levels, leading to reduced fatigue and dependency on transfusions.
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DNA origami nanodevices achieve programmable structure and tunable mechanical and dynamic properties by leveraging the sequence-specific interactions of nucleic acids. Previous advances have also established DNA origami as a useful building block to make well-defined micron-scale structures through hierarchical self-assembly, but these efforts have largely leveraged the structural features of DNA origami. The tunable dynamic and mechanical properties also provide an opportunity to make assemblies with adaptive structures and properties.

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To date, studies on the thermodynamic and kinetic processes that underlie biological function and nanomachine actuation in biological- and biology-inspired molecular constructs have primarily focused on photothermal heating of ensemble systems, highlighting the need for probes that are localized within the molecular construct and capable of resolving single-molecule response. Here we present an experimental demonstration of wavelength-selective, localized heating at the single-molecule level using the surface plasmon resonance of a 15 nm gold nanoparticle (AuNP). Our approach is compatible with force-spectroscopy measurements and can be applied to studies of the single-molecule thermodynamic properties of DNA origami nanomachines as well as biomolecular complexes.

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Biomolecular systems are dependent on a complex interplay of forces. Modern force spectroscopy techniques provide means of interrogating these forces, but they are not optimized for studies in constrained environments as they require attachment to micron-scale probes such as beads or cantilevers. Nanomechanical devices are a promising alternative, but this requires versatile designs that can be tuned to respond to a wide range of forces.

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Background: In Colombia, the average age of first sexual intercourse is between 14 and 15, and it has one of the highest fertility rates among adolescents in Latin America, which reflects poor access to health services and a lack of knowledge about contraception. Some laws support comprehensive sex education as a learning process that families and schools should provide. The objective of this work was to assess the frequency of adequate knowledge and attitudes of acceptance towards contraception in students, their associated factors, sexual behaviours in sexually active students, and experiences with sex education.

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