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BACKGROUND: Establishing collaborations between cohort studies has been fundamental for progress in health research. However, such collaborations are hampered by heterogeneous data representations across cohorts and legal constraints to data sharing. The first arises from a lack of consensus in standards of data collection and representation across cohort studies and is usually tackled by applying data harmonization processes. The second is increasingly important due to raised awareness for privacy protection and stricter regulations, such as the GDPR. Federated learning has emerged as a privacy-preserving alternative to transferring data between institutions through analyzing data in a decentralized manner. METHODS: In this study, we set up a federated learning infrastructure for a consortium of nine Dutch cohorts with appropriate data available to the etiology of dementia, including an extract, transform, and load (ETL) pipeline for data harmonization. Additionally, we assessed the challenges of transforming and standardizing cohort data using the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) and evaluated our tool in one of the cohorts employing federated algorithms. RESULTS: We successfully applied our ETL tool and observed a complete coverage of the cohorts' data by the OMOP CDM. The OMOP CDM facilitated the data representation and standardization, but we identified limitations for cohort-specific data fields and in the scope of the vocabularies available. Specific challenges arise in a multi-cohort federated collaboration due to technical constraints in local environments, data heterogeneity, and lack of direct access to the data. CONCLUSION: In this article, we describe the solutions to these challenges and limitations encountered in our study. Our study shows the potential of federated learning as a privacy-preserving solution for multi-cohort studies that enhance reproducibility and reuse of both data and analyses.
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Demencia , Humanos , Países Bajos , Estudios de Cohortes , Algoritmos , Difusión de la Información/métodos , Investigación BiomédicaRESUMEN
The orchestration of ever larger conformational changes is made possible by the development of increasingly complex foldamers. Aromatic sheets, a rare motif in synthetic foldamer structures, have been designed so as to form discrete stacks of intercalated aromatic strands through the self-assembly of two identical subunits. Ion-mobility ESI-MS confirms the formation of compact dimers. X-ray crystallography reveals the existence of two distinct conformational dimeric states that require large changes to interconvert. Molecular dynamics simulation validates the stability of the two conformations and the possibility of their interconversion.
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The recognition of either homomeric or heteromeric pairs of pentoses in an aromatic oligoamide double helical foldamer capsule was evidenced by circular dichroism (CD), NMR spectroscopy, and X-ray crystallography. The cavity of the host was predicted to be large enough to accommodate simultaneously two xylose molecules and to form a 1:2 complex (one container, two saccharides). Solution and solid-state data revealed the selective recognition of the α-4 C1 -d-xylopyranose tautomer, which is bound at two identical sites in the foldamer cavity. A step further was achieved by sequestering a heteromeric pair of pentoses, that is, one molecule of α-4 C1 -d-xylopyranose and one molecule of ß-1 C4 -d-arabinopyranose despite the symmetrical nature of the host and despite the similarity of the guests. Subtle induced-fit and allosteric effects are responsible for the outstanding selectivities observed.
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BACKGROUND: Chronic inflammation has been implicated in cancer etiology and angiogenesis is stimulated in this disease. In prostate, the crosstalk between malignant epithelial cells and their microenvironment is an essential step of tumorigenesis during which glandular stroma undergo changes designated as reactive stroma. Thus, the aim herewith was to evaluate the effects of associating anti-inflammatory and antiangiogenic therapies on cancer progression, correlating them with steroid hormone receptor (AR and ERα), reactive stroma (vimentin, αSMA, and TGF-ß), and cell proliferation (PCNA) markers expression in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. METHODS: TRAMP mice (12-week old) were divided into the groups: Control (TRCON): received the vehicles used for drug dilution; Celecoxib (TRCEL): received oral doses of the anti-inflammatory drug celecoxib (15 mg/kg) twice daily; Nintedanib (TRNTB): received oral doses of the antiangiogenic drug nintedanib (10 mg/kg) daily; Nintedanib+Celecoxib (TRNTCEL): received the combination of drugs. After 6 weeks, mice were euthanized and ventral prostate samples were harvested for morphological, immunohistochemical, and Western blotting analyses. RESULTS: While celecoxib led to fibromuscular hypertrophy attenuation, nintedanib significantly reduced the incidence of well-differentiated adenocarcinoma (WDAC) foci in relation to controls, both when administered per se or in association to celecoxib. Furthermore, drug combination was associated with unique effects, including lower incidence of HGPIN lesions; lower AR stromal distribution; changes in ERα localization from epithelial nuclei to stroma as well as significant decrease of TGF-ß levels and associated angiogenesis. In parallel, all treatments applied resulted in reduced inflammatory marker and vimentin (VIM) expression. CONCLUSIONS: Celecoxib plus nintedanib is an effective antitumor combination against prostate cancer progression in TRAMP mice, showing remarkable efficacy in relation to isolated therapies. Importantly, this efficacy might be due to drug association effect on driving AR and mainly ERα distribution in the prostatic tissue towards benign patterns. In addition, celecoxib and nintedanib impaired the development of a stromal reaction by reducing the recruitment of reactive stroma cells and maintaining a normal smooth muscle cell-rich prostate stroma in TRAMP mice. Collectively, these findings pointed to the beneficial effects of combining anti-inflammatory and antiangiogenic strategies to prevent or delay prostatic tumorigenesis.
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Inhibidores de la Angiogénesis/farmacología , Antiinflamatorios no Esteroideos/farmacología , Próstata/efectos de los fármacos , Neoplasias de la Próstata/prevención & control , Animales , Celecoxib/farmacología , Progresión de la Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Receptor alfa de Estrógeno/biosíntesis , Indoles/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Próstata/irrigación sanguínea , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/biosíntesis , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/patologíaRESUMEN
The formation of host-guest complexes between seven flavylium cations and water-soluble p-sulfonatocalix[4]arene (SC4) was investigated by UV/vis absorption, fluorescence, and NMR spectroscopies. The results show the cationic guests form complexes with affinities in the submillimolar range. A representative chalcone/flavylium photoswitch was investigated in more detail regarding its pH- and light-triggered interconversion between the two forms. The dramatic affinity differentiation of the SC4 binding of the two switchable species (40 M-1 for the trans-chalcone versus 3.5 × 104 M-1 for the flavylium cation) enables the pH-gated photocontrol of the complexation process. These responsive properties were explored to demonstrate the competitive and selective release of biologically relevant guests from their supramolecular complexes with p-sulfonatocalix[4]arene (SC4), following the principle of AND logic. The guest release can be reverted by the thermally activated reaction of the flavylium ion back to the trans-chalcone.
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Calixarenos/química , Flavonoides/química , Procesos Fotoquímicos , Agua/química , Concentración de Iones de Hidrógeno , EstereoisomerismoRESUMEN
A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl spacers, L, was prepared, and its dinuclear copper(II) and zinc(II) complexes were used as receptors for the recognition in aqueous solution of a phosphorylated peptide derived from a sequence of the STAT3 protein. A detailed study of the acid-base behavior of L and of its complexation properties as well as of the association of the phosphorylated peptide to the receptor was carried out by potentiometry in aqueous solution at 298.2 K and I = 0.10 M in KNO3. The data revealed that the receptor forms stable associations with several protonated forms of the substrate, with constant values ranging from 3.32 to 4.25 log units. The affinity of the receptor for the phosphorylated substrate studied is higher at a pH value where the receptor is mainly in the [Cu2L](4+) form and the pY residue of the substrate is in the dianionic form (pH 6.55). These results, also supported by (31)P NMR studies, showed that the phosphopeptide is bound through the phosphoryl group in a bridging mode. Additionally, the receptor inhibited binding between active (phosphorylated) STAT3 and its target DNA sequence in a dose-dependent manner (IC50 63 ± 3.4 µM) in human nuclear extracts in vitro. Treatment of whole cells with the inhibitor revealed that it is bioactive in living cells and has oncostatic properties that could be interesting for the fight against cancer and other pathologies involving the STAT3 protein.
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Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cobre/química , Cobre/farmacología , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Células HEK293 , Humanos , Modelos Moleculares , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Poliaminas/química , Poliaminas/farmacología , Multimerización de Proteína/efectos de los fármacos , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/metabolismoRESUMEN
A new diethylenetriamine-derived macrocycle known as L, bearing 2-methylquinoline arms and containing m-xylyl spacers, was prepared in good yield by a one-pot [2 + 2] Schiff base condensation procedure, followed by reduction with sodium borohydride. Up to now this is the first hexaazamacrocycle with appended fluorophore units. Single-crystal X-ray diffraction determination of the dinuclear zinc(II) complex of L showed that metal centers are located at about 7.20(2) Å from one another. This complex exhibits only weak fluorescence in aqueous solution, but the addition of 1 equiv of pyrophosphate (PPi) caused a 21-fold enhancement of the fluorescence intensity. The sensor response is linear up to a value of 10 µM HPPi(3-) and has a detection limit of 300 nM. The receptor behaves as a highly selective sensor for pyrophosphate as other anions, including phosphate, phenylphosphate (PhP), adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), failed to induce any fluorescence change and practically do not affect the fluorescence intensity of the sensor in the presence of HPPi(3-). Competition titrations carried out in aqueous solution at pH 7.4 [in 20 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer] by spectrofluorometry revealed a high association constant value of 6.22 log units for binding of PPi by the dinuclear zinc(II) receptor, one of the highest reported values for colorimetric/fluorometric sensors able to work under real aqueous physiological conditions, while association constant values for binding of the other phosphorylated substrates are in the 5.51-4.03 log unit range.
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Searching for receptors selective for the binding of dicarboxylate anions, the copper(II) complexes of the known ditopic octaazacryptand (t2pN8), derived from bistren [tren = tris(2-aminoethyl)amine] linked by p-xylyl spacers, were re-examined, with the expectation of observing a selective binding of oxalate or malonate by bridging the two copper centers of the [Cu2(t2pN8)(H2O)2](4+) receptor. Solution studies involving the supramolecular species formed by the receptor and oxalate (oxa(2-)), malonate (mal(2-)), and succinate (suc(2-)) anions are reported. The determined association constants revealed the unexpected formation of a 3:1:1 Cu/t2pN8/anion stoichiometry for the cascade species with oxa(2-) and mal(2-), and the single crystal X-ray structural characterization confirmed the presence of tricopper(II) complexes, with an unusual binding mode for the dicarboxylate anions. Each of the two copper atoms binds four nitrogen donor atoms of the t2pN8 cryptand and one additional hydroxide group, which bridges to the third copper. The square planar environment of this one is complete with two oxygen atoms from the oxalate (or the malonate). The two copper centers bound to the tren heads are â¼6.5 Å apart, each one at about 3.5 Å from the third Cu center. These studies were complemented by SQUID magnetization measurements and DFT calculations. The magnetic susceptibility measurements of the oxalate cascade complex showed a strong magnetic coupling (J = - 210 cm(-1)) between the Cu centers at a short distance (3.5 Å), while the coupling between the two equivalent Cu atoms (â¼6.5 Å) was only -70 cm(-1). This result was well reproduced by DFT calculations.
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A ditopic polyamine macrobicyclic compound with biphenylmethane spacers was prepared, and its dinuclear copper(II) complex was studied as a receptor for the recognition of dicarboxylate anions of varying chain length in H2O/MeOH (50:50 (v/v)) solution. The acid-base behavior of the compound, the stability constants of its complexes with Cu(2+) ion, and the association constants of the copper(II) cryptate with succinate (suc(2-)), glutarate (glu(2-)), adipate (adi(2-)), and pimelate (pim(2-)) were determined by potentiometry at 298.2 ± 0.1 K in H2O/MeOH (50:50 (v/v)) and at ionic strength 0.10 ± 0.01 M in KNO3. The association constants of the same cryptate as receptor for aromatic dicarboxylate substrates, such as phthalate (ph(2-)), isophthalate (iph(2-)), and terephthalate (tph(2-)), were determined through competition experiments by spectrophotometry in the UV region. Remarkably high values of association constants in the range of 7.34-10.01 log units were found that are, to the best of our knowledge, the highest values of association constants reported for the binding of dicarboxylate anions in aqueous solution. A very well defined peak of selectivity was observed with the binding constant values increasing with the chain length and reaching the maximum for substrates with four carbon atoms between the carboxylate groups. Single-crystal X-ray diffraction determinations of the cascade complexes with adi(2-) and tph(2-) assisted in the understanding of the selectivity of the cryptate toward these substrates. The Hirshfeld surface analyses of both cascade complexes suggest that the establishment of several van der Waals interactions between the substrates and the walls of the receptor also contributes to the stability of the associations.
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Cobre/química , Éteres Corona/química , Ácidos Dicarboxílicos/química , Ácidos Ftálicos/química , Cationes Bivalentes , Éteres Corona/síntesis química , Cristalografía por Rayos X , Concentración de Iones de Hidrógeno , Cinética , Estructura Molecular , Potenciometría , TermodinámicaRESUMEN
A hexamine macrobicycle with pyrrolyl spacers was evaluated as an anion receptor in its protonated forms. The protonation constants of the receptor, as well as its association constants with Cl(-), NO3(-), AcO(-), ClO4(-), H2PO4(-), and SO4(2-) were determined by potentiometry at 298.2 ± 0.1 K in H2O-MeOH (50 : 50 v/v) and at an ionic strength of 0.10 ± 0.01 M in KTsO. These studies revealed that the Hnpyrr(n+) receptor has a very high effective association constant value for the SO4(2-) at pH 4.0 (log Keff = 6.42), and it is selective for the uptake of this anion in the presence of the other studied anionic substrates. In particular, the receptor showed very high SO4(2-)/NO3(-) selectivity. Using the indicator-displacement approach the receptor is able to signal the presence of sulfate by a change of color. Single crystal X-ray diffraction determination of [(H6pyrr)(SO4)(H2O)3](SO4)2·9.3H2O revealed the presence of one sulfate anion inside the receptor cavity and showed that the encapsulation of the anion is favored by an array of nine hydrogen bonding interactions, including N-HO, C-HO and water-mediated ones.
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Éteres Cíclicos/química , Receptores Artificiales/química , Bases de Schiff/química , Sulfatos/análisis , Cristalografía por Rayos X , Éteres Cíclicos/síntesis química , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Cinética , Potenciometría , Receptores Artificiales/síntesis química , Bases de Schiff/síntesis química , Sensibilidad y Especificidad , Soluciones , AguaRESUMEN
Two cyclen (1,4,7,10-tetraazacyclododecane) derivatives bearing trans-bis(2-hydroxybenzyl) arms, the 1,7-(2-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (H2do2ph) and its cross-bridged counterpart (H2cb-do2ph), have been synthesized, aiming toward the possible use of their copper(II) and gallium(III) complexes in nuclear medicine. The protonation of both compounds was studied in aqueous solution as well as their complexes with Cu(2+) and Ga(3+) cations. The complexes of both ligands with Ca(2+) and Zn(2+) metal ions were also studied due to the abundance of these cations in biological media. In mild conditions the complexes of Ca(2+) and Ga(3+) with H2cb-do2ph did not form. The behavior of the two ligands and their complexes was compared by the values of the equilibrium constants, the data of varied spectroscopic techniques, the values of redox potentials of their copper(II) complexes, and the resistance of the complexes to acid dissociation. It was expected that, as found for related pairs of cyclen and cyclam (1,4,8,11-tetraazacyclotetradecane) derivatives, the cross-bridged macrocyclic derivative could be an excellent ligand for the complexation of copper(II). Additionally, the N-2-hydroxybenzyl groups were chosen due to their known ability to coordinate the gallium(III) cation. Due to the small size of the latter cation and its particular propensity to form hexacoordinate complexes, it was also expected that there would be a good ability of both ligands for the uptake of Ga(3+). Surprisingly, the results revealed that the cyclen derivative H2do2ph is the best ligand for the coordination of Cu(2+) and Ga(3+) cations, not only from their thermodynamic stability as expected but also from their kinetic inertness, when compared with its cross-bridged counterpart.
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Cobre/química , Galio/química , Compuestos Heterocíclicos/química , Ciclamas , Espectroscopía de Resonancia por Spin del Electrón , Modelos Moleculares , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja CortaRESUMEN
The Mediterranean basin is highly susceptible to climate change, with soil salinization and the increase in average temperatures being two of the main factors affecting crop productivity in this region. Following our previous studies on describing the detrimental effects of heat and salt stress co-exposure on tomato plants, this study aimed to understand if substrate supplementation with a combination of arbuscular mycorrhizal fungi (AMF) and biochar could mitigate the negative consequences of these stresses. Upon 21 days of exposure, stressed tomato plants grown under supplemented substrates showed increased tolerance to heat (42 °C for 4 h/day), salt (100 mM NaCl), and their combination, presenting increased biomass and flowering rate. The beneficial effects of AMF and biochar were associated with a better ionic balance (i.e. lower sodium accumulation and higher uptake of calcium and magnesium) and increased photosynthetic efficiency. Indeed, these plants presented higher chlorophyll content and improved CO2 assimilation rates. Biochemical data further supported that tomato plants grown with AMF and biochar were capable of efficiently modulating their defence pathways, evidenced by the accumulation of proline, ascorbate, and glutathione, coupled with a lower dependency on energy-costly enzymatic antioxidant players. In summary, the obtained data strongly point towards a beneficial role of combined AMF and biochar as sustainable tools to improve plant growth and development under a climate change scenario, where soil salinization and heat peaks often occur together.
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Carbón Orgánico , Micorrizas , Estrés Salino , Solanum lycopersicum , Micorrizas/fisiología , Solanum lycopersicum/fisiología , Solanum lycopersicum/microbiología , Estrés Salino/fisiología , CalorRESUMEN
INTRODUCTION: Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients. OBJECTIVE: This study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients. METHODS: A cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment. RESULTS: Survey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06). CONCLUSIONS: Patients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.
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Enfermedades Autoinmunes , Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Estudios Transversales , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Persona de Mediana Edad , Adulto , Anciano , Factores de Riesgo de Enfermedad Cardiaca , Autoinforme , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/epidemiología , Medición de Riesgo , Prevalencia , Autoimagen , Factores de RiesgoRESUMEN
Castanea sativa Miller, a high-valuable crop for Mediterranean countries, is facing frequent and prolonged periods of heat and drought, severely affecting chestnut production. Aiming to tackle this problem, this study unraveled the influence of mycorrhizal association with the fungi Paxillus involutus (Batsch) on young chestnut plants' responses to combined heat (42 °C; 4 h/day) and drought (no irrigation until soil moisture reached 25%) over 21 days of stress exposure. Heat stress had no harmful effects on growth, photosynthesis, nor induced oxidative stress in either mycorrhizal (MR) or non-mycorrhizal (NMR) chestnut plants. However, drought (alone or combined) reduced the growth of NMR plants, affecting water content, leaf production, and foliar area, while also hampering net CO2 assimilation and carbon relations. The mycorrhizal association, however, mitigated the detrimental effects of both stresses, resulting in less susceptibility and fewer growth limitations in MR chestnut plants, which were capable of ensuring a proper carbon flow. Evaluation of the oxidative metabolism revealed increased lipid peroxidation and hydrogen peroxide levels in NMR plants under water scarcity, supporting their higher susceptibility to stress. Conversely, MR plants activated defense mechanisms by accumulating antioxidant metabolites (ascorbate, proline and glutathione), preventing oxidative damage, especially under the combined stress. Overall, drought was the most detrimental condition for chestnut growth, with heat exacerbating stress susceptibility. Moreover, mycorrhizal association with P. involutus substantially alleviated these effects by improving growth, water relations, photosynthesis, and activating defense mechanisms. Thus, this research highlights mycorrhization's potential to enhance C. sativa resilience against climate change, especially at early developmental stages.
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BACKGROUND: The shock index (SI), reflecting heart rate (HR) to SBP ratio, is established for predicting adverse outcomes in acute coronary syndrome (ACS) patients. Exploring the age shock index (ASI), obtained by multiplying SI with age, could offer further insights into ACS prognosis. OBJECTIVES: Assess ASI's effectiveness in predicting in-hospital death in individuals with ACS. METHODS: This study encompassed patients with acute myocardial infarction, drawn from a national registry spanning October 2010 to January 2022. The optimal ASI threshold was established using receiver operating characteristic (ROC) curve analysis. The primary outcome was in-hospital mortality. RESULTS: A total of 27 312 patients were enrolled, exhibiting a mean age of 66â ±â 13 years, with 72.3% being male and 47.5% having ST-elevation myocardial infarction. ROC analysis yielded an area under the curve (AUC) of 0.80, identifying the optimal ASI cutoff as 44. Multivariate regression analysis, adjusting for potential confounders, established ASIâ ≥â 44 as an independent predictor of in-hospital death [hazard ratio: 3.09, 95% confidence interval: 2.56-3.71, P â <â 0.001]. Furthermore, ASI emerged as a notably superior predictor of in-hospital death compared to the SI (AUC ASI â =â 0.80 vs. AUC SI â =â 0.72, P â <â 0.0001), though it did not outperform the Global Registry of Acute Coronary Events (GRACE) score (AUC ASI â =â 0.80 vs. AUC GRACE â =â 0.85, P â <â 0.001) or thrombolysis in myocardial infarction (TIMI) risk index (AUC ASI â =â 0.80 vs. AUC TIMI â =â 0.84, P â <â 0.001). CONCLUSION: The ASI offers an expedient mean to promptly identify ACS patients at elevated risk of in-hospital death. Its simplicity and effectiveness could render it a valuable tool for early risk stratification in this population.
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Síndrome Coronario Agudo , Mortalidad Hospitalaria , Sistema de Registros , Humanos , Masculino , Femenino , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Anciano , Persona de Mediana Edad , Medición de Riesgo/métodos , Pronóstico , Factores de Edad , Factores de Riesgo , Frecuencia Cardíaca/fisiología , Valor Predictivo de las Pruebas , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/terapia , Curva ROC , Presión SanguíneaRESUMEN
We present a case of acute heart failure as the first manifestation of Graves' disease. It illustrates some of its cardiovascular complications, particularly atrial fibrillation, pulmonary hypertension and heart failure. This case report highlights the importance of considering hyperthyroidism as a cause of idiopathic pulmonary hypertension, and demonstrates the potential reversibility of its complications.
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Insuficiencia Cardíaca/complicaciones , Hipertensión Pulmonar/complicaciones , Hipertiroidismo/complicaciones , Adulto , Femenino , HumanosRESUMEN
The perceived offset position of a moving target has been found to be displaced forward, in the direction of motion (Representational Momentum; RM), downward, in the direction of gravity (Representational Gravity; RG), and, recently, further displaced along the horizon implied by the visual context (Representational Horizon; RH). The latter, while still underexplored, offers the prospect to clarify the role of visual contextual cues in spatial orientation and in the perception of dynamic events. As such, the present work sets forth to ascertain the robustness of Representational Horizon across varying types of visual contexts, particularly between interior and exterior scenes, and to clarify to what degree it reflects a perceptual or response phenomenon. To that end, participants were shown targets, moving along one out of several possible trajectories, overlaid on a randomly chosen background depicting either an interior or exterior scene rotated -22.5º, 0º, or 22.5º in relation to the actual vertical. Upon the vanishing of the target, participants were required to indicate its last seen location with a computer mouse. For half the participants, the background vanished with the target while for the remaining it was kept visible until a response was provided. Spatial localisations were subjected to a discrete Fourier decomposition procedure to obtain independent estimates of RM, RG, and RH. Outcomes showed that RH's direction was biased towards the horizon implied by the visual context, but solely for exterior scenes, and irrespective of its presence or absence during the spatial localisation response, supporting its perceptual/representational nature.
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In the past decade, there has been a sharp increase in publications describing applications of convolutional neural networks (CNNs) in medical image analysis. However, recent reviews have warned of the lack of reproducibility of most such studies, which has impeded closer examination of the models and, in turn, their implementation in healthcare. On the other hand, the performance of these models is highly dependent on decisions on architecture and image pre-processing. In this work, we assess the reproducibility of three studies that use CNNs for head and neck cancer outcome prediction by attempting to reproduce the published results. In addition, we propose a new network structure and assess the impact of image pre-processing and model selection criteria on performance. We used two publicly available datasets: one with 298 patients for training and validation and another with 137 patients from a different institute for testing. All three studies failed to report elements required to reproduce their results thoroughly, mainly the image pre-processing steps and the random seed. Our model either outperforms or achieves similar performance to the existing models with considerably fewer parameters. We also observed that the pre-processing efforts significantly impact the model's performance and that some model selection criteria may lead to suboptimal models. Although there have been improvements in the reproducibility of deep learning models, our work suggests that wider implementation of reporting standards is required to avoid a reproducibility crisis.
Asunto(s)
Neoplasias de Cabeza y Cuello , Redes Neurales de la Computación , Humanos , Reproducibilidad de los Resultados , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , PronósticoRESUMEN
Two ditopic polyamine macrobicyclic compounds have been studied as receptors for the recognition of dicarboxylate anions of varying chain length in aqueous solution. One of the receptors consists of two tris(2-aminoethyl)amine-derived binding subunits separated by p-xylyl spacers, while the other is a heteroditopic compound, combining two different head units, a tren-derived and a 2,4,6-triethylbenzene-derived one, also separated by p-xylyl spacers. The acid-base behavior of the compounds as well as their binding ability with oxalate (oxa(2-)), malonate (mal(2-)), succinate (suc(2-)), glutarate (glu(2-)), maleate (male(2-)) and fumarate (fum(2-)) anions were studied by potentiometry at 298.2 K in aqueous solution and at ionic strength 0.10 M in KTsO. NMR studies were also performed to obtain structural information in solution on the supermolecules formed by association of the protonated macrobicycles with the dicarboxylate substrates. The results revealed that both compounds are able to form stable associations with the dianionic substrates in competitive aqueous solution, with unprecedented selectivity for fum(2-) over other dicarboxylate competitors, including its cis isomer male(2-). In addition it was found that although the selectivity pattern is unaffected by the introduction of the 2,4,6-triethylbenzene head unit, the affinity toward dicarboxylates is significantly reduced. Therefore, the comparison between the binding behavior of these two receptors showed the effect of the increased rigidity and lipophilicity of the receptor with the 2,4,6-triethylbenzene head unit in the binding properties and the selectivity pattern.
Asunto(s)
Derivados del Benceno/química , Ácidos Dicarboxílicos/química , Fumaratos/química , Compuestos Macrocíclicos/química , Maleatos/química , Oxalatos/química , Poliaminas/química , Cristalografía por Rayos X , Humanos , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Soluciones , AguaRESUMEN
A new heteroditopic macrobicyclic compound (t(2)pN(5)O(3)) containing two separate polyoxa and polyaza compartments was synthesized in good yield through a [1 + 1] "tripod-tripod coupling" strategy. The X-ray crystal structure of H(3)t(2)pN(5)O(3)(3+) revealed the presence of one encapsulated water molecule accepting two hydrogen bonds from two protonated secondary amines and donating a hydrogen bond to one amino group. The acid-base behavior of the compound was studied by potentiometry at 298.2 K in aqueous solution and at ionic strength 0.10 M in KCl. The results revealed unusual protonation behavior, namely a surprisingly low fourth protonation constant contrary to what was expected for the compound. (1)H NMR and DOSY experiments, as well as molecular modeling studies, showed that the water encapsulation and the conformation observed in the solid state are retained in solution. The strong binding of the encapsulated water molecule, reinforced by the cooperative occurrence of a trifurcated hydrogen bond at the polyether compartment of the macrobicycle, account for the very low log K(4)(H) value obtained.