The QUEST initiative anemia study in ESRD: rationale and study protocol

No abstrac

New-onset myasthenia gravis after mRNA SARS-CoV-2 vaccination: a case series

Background Myasthenia gravis (MG) is an autoimmune disease that targets acetylcholine receptor (AChR) of the neuromuscular junction. New-onset MG after SARS-CoV-2 vaccination has rarely been reported. Case presentation We report about three patients who presented new-onset myasthenia gravis after receiving mRNA SARSCoV-2 vaccination. The patients were all males and older than 55 years. All the patients presented with ocular and bulbar symptoms. The interval between vaccine administration and MG onset ranged from 3 days after the frst dose to 10 days after the second dose. All the patients had elevated serum AChR antibodies and responded to pyridostigmine. Two out of three patients were successfully treated with IVIG or plasma exchange and with long-term immunosuppression. Conclusions MG is a rare disease; clinicians should be aware of possible new-onset MG after SARS-CoV-2 vaccination, especially with the current recommendation of booster doses. The hyperstimulation of the innate immune system or the exacerbation of a subclinical pre-existing MG could be possible explanations

Análisis y comparación de la Competencia Transversal Análisis y Resolución de Problemas en asignaturas de Grado

[EN] The last syllabus of the grades of the Polytechnic University of Valencia (UPV) has changed the perspective of the universitary teaching and has highlighted the importance of the specific and the transversal competences. Therefore, there is a need for grading the transversal competences throughout the degrees and masters of the UPV. Moreover, these transversal competences must be assessed in several subjects. Due to the lack of experience in evaluating these skills, UPV has elaborated scoring rubrics to help professors to assess them. In this work, we review the assessment of the transversal competence "Problem identification and solving” of four subjects of different degrees and courses. In two subjects, special activities have been performed for the evaluation of this competence and scoring rubrics have been used. In the other two subjects, the mark of this skill has been obtained from other marks of the subject. Moreover, we have compared the mark of this skill with the final mark of the subject. Our results show that there is a high correlation between the two marks in the four subjects.[ES] En los últimos planes de estudios de los grados de la Universidad Politécnica de Valencia (UPV) ha cambiado el enfoque de la docencia y se ha resaltado el papel de las competencias, tanto específicas como transversales. Actualmente es necesario evaluar competencias transversales en todos los grados y másteres de la UPV y estas deben ser evaluadas en distintas asignaturas. Ante la falta de experiencia en su evaluación, la UPV ha elaborado rúbricas para ayudar al profesorado en dicha tarea. En este artículo revisamos la evaluación de la competencia transversal “Análisis y resolución de problemas” en cuatro asignaturas de distintos cursos y grados. En dos de estas asignaturas se han realizado actividades especiales para la evaluación de esta competencia y se han utilizado rúbricas para ello. En las otras dos asignaturas, se ha optado por utilizar las calificaciones de los actos de evaluación más relacionados con ella. Además, se ha comparado la calificación de esta competencia con la nota de la asignatura y los resultados muestran que para las cuatro asignaturas existe una alta correlación entre ambas.Alvarez Blanco, S.; Bosch Roig, I.; Jordan Lluch, C.; Lloret Mauri, J.; Mendoza Roca, JA.; Romero Pérez, L.; Sanabria Codesal, E.... (2016). Análisis y comparación de la Competencia Transversal Análisis y Resolución de Problemas en asignaturas de Grado. En In-Red 2016. II Congreso nacional de innovación educativa y docencia en red. Editorial Universitat Politècnica de València. https://doi.org/10.4995/INRED2016.2016.4348OC

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy

IntroductionCerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-beta (A beta) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since A beta is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. MethodsThe study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. ResultsWe observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOE epsilon 2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOE epsilon 4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. DiscussionThis study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral beta-amyloidosis

Living in darkness: Exploring adaptation of Proteus anguinus in 3 dimensions by X-ray imaging

Background: Lightless caves can harbour a wide range of living organisms. Cave animals have evolved a set of morphological, physiological, and behavioural adaptations known as troglomorphisms, enabling their survival in the perpetual darkness, narrow temperature and humidity ranges, and nutrient scarcity of the subterranean environment. In this study, we focused on adaptations of skull shape and sensory systems in the blind cave salamander, Proteus anguinus, also known as olm or simply proteus—the largest cave tetrapod and the only European amphibian living exclusively in subterranean environments. This extraordinary amphibian compensates for the loss of sight by enhanced non-visual sensory systems including mechanoreceptors, electroreceptors, and chemoreceptors. We compared developmental stages of P. anguinus with Ambystoma mexicanum, also known as axolotl, to make an exemplary comparison between cave- and surface-dwelling paedomorphic salamanders. Findings: We used contrast-enhanced X-ray computed microtomography for the 3D segmentation of the soft tissues in the head of P. anguinus and A. mexicanum. Sensory organs were visualized to elucidate how the animal is adapted to living in complete darkness. X-ray microCT datasets were provided along with 3D models for larval, juvenile, and adult specimens, showing the cartilage of the chondrocranium and the position, shape, and size of the brain, eyes, and olfactory epithelium. Conclusions: P. anguinus still keeps some of its secrets. Our high-resolution X-ray microCT scans together with 3D models of the anatomical structures in the head may help to elucidate the nature and origin of the mechanisms behind its adaptations to the subterranean environment, which led to a series of troglomorphisms

Childhood aggression and the co-occurrence of behavioural and emotional problems

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychop

A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5(m)C content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy

Euclid Preparation. XXVIII. Forecasts for ten different higher-order weak lensing statistics

Recent cosmic shear studies have shown that higher-order statistics (HOS) developed by independent teams now outperform standard two-point estimators in terms of statistical precision thanks to their sensitivity to the non-Gaussian features of large-scale structure. The aim of the Higher-Order Weak Lensing Statistics (HOWLS) project is to assess, compare, and combine the constraining power of ten different HOS on a common set of $Euclid$-like mocks, derived from N-body simulations. In this first paper of the HOWLS series, we computed the nontomographic ($\Omega_{\rm m}$, $\sigma_8$) Fisher information for the one-point probability distribution function, peak counts, Minkowski functionals, Betti numbers, persistent homology Betti numbers and heatmap, and scattering transform coefficients, and we compare them to the shear and convergence two-point correlation functions in the absence of any systematic bias. We also include forecasts for three implementations of higher-order moments, but these cannot be robustly interpreted as the Gaussian likelihood assumption breaks down for these statistics. Taken individually, we find that each HOS outperforms the two-point statistics by a factor of around two in the precision of the forecasts with some variations across statistics and cosmological parameters. When combining all the HOS, this increases to a $4.5$ times improvement, highlighting the immense potential of HOS for cosmic shear cosmological analyses with $Euclid$. The data used in this analysis are publicly released with the paper.Comment: 33 pages, 24 figures, main results in Fig. 19 & Table 5, version published in A&