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We demonstrate the generation of broadband tunable and synchronized pulses exceeding the microjoule level using the new concept of Fiber Optical Parametric Chirped-Pulse Oscillation (FOPCPO). The oscillator is based on a collapsed-ends photonic crystal fiber pumped in the normal dispersion regime by an ytterbium fiber laser delivering highly-chirped pulses. The experimental results are compared with the results of numerical simulations and highlight that the feedback ratio appears as a key parameter for optimizing the system’s efficiency and dynamics.

We demonstrate the generation of broadband tunable and synchronized pulses exceeding the microjoule level using the new concept of fiber optical parametric chirped-pulse oscillation (FOPCPO). The oscillator is based on a collapsed-ends photonic crystal fiber pumped in the normal dispersion regime by a fiber laser.

Abstract Remodelling of mitochondrial metabolism is a hallmark of cancer. Mutations in the genes encoding succinate dehydrogenase (SDH), a key Krebs cycle component, are associated with hereditary predisposition to pheochromocytoma and paraganglioma, through mechanisms which are largely unknown. Recently, the jumonji-domain histone demethylases have emerged as a novel family of 2-oxoglutarate-dependent chromatin modifiers with credible functions in tumourigenesis. Using pharmacological and siRNA methodologies we show that increased methylation of histone H3 is a general consequence of SDH loss-of-function in cultured mammalian cells and can be reversed by overexpression of the JMJD3 histone demethylase. ChIP analysis revealed that the core promoter of IGFBP7, which encodes a secreted protein upregulated after loss of SDHB, showed decreased occupancy by H3K27me3 in the absence of SDH. Finally, we provide the first evidence that the chief (type I) cell is the major methylated histone-immunoreactive constituent of paraganglioma. These results support the notion that loss of mitochondrial function alters epigenetic processes and might provide a signature methylation mark for paraganglioma.

Abstract Background A good level of knowledge in dentists is crucial for an early diagnosis of oral cancer (OC). In Latin America there are a few studies of OC knowledge among dentist, those has been performed in Brazil, Colombia, and Chile, and their results showed low level of OC knowledge. On the other hand, there is no publication in which the level of knowledge of dentists in Mexico has been addressed. Therefore, this study aimed to assess knowledge of OC and to determine the association of the level of knowledge with sociodemographic characteristics among dentists in Mexico. Methods A cross-sectional online survey was designed to obtain information via questionnaire. The questionnaire was developed in the Spanish language, and the content validity was determined. The study was conducted among Mexican dentists with a 23-item questionnaire that was designed to be anonymous. The sample size was calculated using the finite population formula. Based on the responses, the level of knowledge of OC was categorized as very low, low, regular, good, or excellent. Additionally, the association between sociodemographic characteristics and the level of knowledge about OC was evaluated. Results This research was conducted on a sample of 387 dentists. Most of the respondents were general dentists and worked in urban zones. The majority of dentists lacked a specialty (76.7%). Additionally, most of the respondents were students (44.2%). The level of knowledge of the participants was between regular and good (77.8%). On the other hand, concerning self-evaluation, most of the participants considered their knowledge of OC to be regular (50.6%). In addition, there was no association between sociodemographic characteristics and knowledge about OC. Conclusions This research identified some weaknesses in most Mexican dentists’ knowledge of OC.

Abstract Background This study aimed to investigate the trajectory of damage accrual, associated factors, and impact on health-related quality of life (HR-QoL) in a multicenter cohort of patients with Behçet’s syndrome (BS) over 2 years of follow-up. Methods Patients recruited in the BS Overall Damage Index (BODI) validation study were prospectively monitored for 2 years and assessed for damage accrual, defined as an increase ≥1 in the BODI score, and HR-QoL was evaluated by the SF-36 questionnaire. Logistic and multiple linear regression models were built to determine factors associated with damage accrual and impairment in the different SF-36 domains. Results During follow-up, 36 out of 189 (19.0%) patients had an increase ≥1 in the BODI score with a mean (SD) difference of 1.7 (0.8) (p

For broad sectors of Spaniards, fundamentally from the left and from the working world, the Civil Guard is considered, when the Spanish Civil War arrives, as a conservative institution with dubious loyalty to the republican cause. Probably an unfair impression, but it is what it is. In addition, in its more than ninety years of history, although it was a military body, its field of action had always been public order and security in the streets and squares of towns and cities. But as of 1936 it was incorporated as one more combat force at the battle front. And in republican Spain, this incorporation of the Civil Guard to the front becomes a means to accredit the commitment to the cause and dispel the doubts and misgivings that many civil guards aroused in the republican sphere. In this article we analyze the characteristics of this type of incorporation to the front and the consequences it has on the civil guards in the republican zone of the Civil War.

Background: Recurrent pericarditis has been described as an unusual manifestation of autoimmune polyglandular syndrome type 2 (APS 2). Case report: We describe a case of a 44-year-old woman who was admitted to hospital due to 5 pericarditis, 3 of them with cardiac tamponade, and in the etiological study of this pathology she was diagnosed with an APS 2. Conclusion: The association of serositis with APS 2 is exceptional with less than 10 cases reported in the literature. The presence of recurrent pericarditis of unknown cause should make us consider APS 2 in the differential diagnosis.

Abstract Liquid argon time projection chamber detector technology provides high spatial and calorimetric resolutions on the charged particles traversing liquid argon. As a result, the technology has been used in a number of recent neutrino experiments, and is the technology of choice for the Deep Underground Neutrino Experiment (DUNE). In order to perform high precision measurements of neutrinos in the detector, final state particles need to be effectively identified, and their energy accurately reconstructed. This article proposes an algorithm based on a convolutional neural network to perform the classification of energy deposits and reconstructed particles as track-like or arising from electromagnetic cascades. Results from testing the algorithm on experimental data from ProtoDUNE-SP, a prototype of the DUNE far detector, are presented. The network identifies track- and shower-like particles, as well as Michel electrons, with high efficiency. The performance of the algorithm is consistent between experimental data and simulation.

Se evaluó y comparó la eficiencia de dos coagulantes Naturales: Cardón Guajiro (Stenocereus Griseus) y Quitosano para tratamiento de agua residual doméstica. El Cardón se extrajo por un proceso de secado, molienda, tamizado y extracción con metanol anhidro. El Quitosano se consiguió en forma de escamas. Se realizaron pruebas de jarras para determinar rangos y dosis óptimas y analizar los parámetros de estudio a medida que se iban aplicando dichos coagulantes. Con el Cardón se realizaron dos pruebas con concentraciones del 5% y 10%, con el Quitosano se realizaron pruebas a una concentración del 1%. Las dosis de Cardón estuvieron entre 10 y 100 PPM en intervalos de 10, las dosis de Quitosano fueron de 50 a 500 PPM en intervalos de 50. El Cardón a concentración del 5% generó excelentes resultados en los parámetros de estudio. El Quitosano mostró porcentajes de remoción mejores que el Cardón Guajiro.

The aim of this report was to present a case of bilateral choroidal detachment following treatment with topical therapy dorzolamide/timolol without history of previous surgery. An 86-year-old woman, with intraocular pressures of 40.00/36.00 mm Hg, was treated with preservative-free double therapy with dorzolamide/timolol. One week later, she presented with bilateral vision loss and irritative symptoms in the face, scalp, and ears, with well controlled pressures. The anterior exam showed LOCS III N4C3 cataracts, and the fundus and ultrasound exams revealed a bilateral infero-temporal choroidal detachment in the absence of neoplasia or other systemic cause. One week in absence of hypotensive treatment and receiving topical prednisolone, she showed reattachment of the choroidal detachment. Six months after cataract surgery, the patient remains stable, without choroidal effusion regression. Hipotensive treatment following chronic angle closure can lead to choroidal effusion similar to cases of acute angle closure treated with oral carbonic-anhydrase inhibitors. The combined strategy of removing hipotensive treatment and topical corticosteroids could be useful for the initial management of choroidal effusion. Also, performing cataract surgery after choroidal reattachment can help with stabilization.

Abstract Objective: To assess whether depression and quality of life scores correlate with glycosylated hemoglobin A (HbA1c) levels in type 2 diabetes mellitus (T2DM) patients of predominant Mayan ethnicity, from a rural community in the state of Yucatán, Mexico. Materials and methods: Instruments: for depression, CES-D (cutoff ≥ 16); for quality of life, D-39; criterion for poor glycemic control, HbA1c ≥ 8%. Results: Depression was detected in 36.3% of 33 diabetic subjects (10 men, 23 women), and their HbA1c levels (mean ± SD) were higher (10.7 ± 2.5%) than for those without depression (8.6 ± 2.2%, p = 0.015; unpaired Student’s t-test, two-tailed). Depression occurred in 33.3% of diabetics with HbA1c ≥8%, but only in 3.0% of those with HbA1c < 8% (p = 0.027, Fisher’s exact test). HbA1c levels positively correlated with CES-D scores (r2 =0.135; p = 0.035; Pearson). D-39 “Anxiety-Worry” (AW) dimension scores were higher in diabetics with depression (43.3 ± 22.2) than in those without depression (17.7 ± 17.8; p = 0.005, Mann-Whitney U-test). A positive correlation was found between CES-D and AW scores (r2 = 0.304; p = 0.001; Pearson). Conclusions: Considering that depression and anxiety have been related to poor self-care for achieving a good glycemic control, we propose the concomitant use of CES-D and D-39, which are validated and easy-to-apply instruments, as screening tests to detect depression and anxiety in T2DM patients residing in rural communities. Therefore, if patients test positive on one or both instruments, they can be referred to a psychiatrist to confirm the diagnosis and provide appropriate therapy. This would help to promote adherence to diabetes control measures and improve their quality of life. Key words: Diabetes Mellitus, Type 2; Depression; Anxiety; Glycosylated hemoglobin A

Abstract Impairment of kidney function is common in acute‐on‐chronic liver failure (ACLF). Patterns of kidney dysfunction and their impact on kidney and patient outcomes are ill‐defined. Aims of the current study were to investigate patterns of kidney dysfunction and their impact on kidney and patient outcomes in patients with acute decompensation (AD) of cirrhosis, with or without ACLF. This prospective study includes 639 admissions for AD (232 with ACLF; 407 without) in 518 patients. Data were collected at admission and during hospitalization, and patients were followed up for 3 months. Urine samples were analyzed for kidney biomarkers. Most patients with ACLF (92%) had associated acute kidney injury (AKI), in most cases without previous chronic kidney disease (CKD), whereas some had AKI‐on‐CKD (70% and 22%, respectively). Prevalence of AKI in patients without ACLF was 35% (p

Higher Education Institutions play a fundamental role in the integral formation of professionals, in the environmental awareness and education of the university community, by developing and implementing actions that allow them to increase the knowledge they have about the environment, train them in decision making, develop skills and behavioral changes that contribute to promote environmental awareness and the solution of environmental problems. The objective of this research is to design a procedure for the incorporation of the environmental dimension in the decision-making process by the managers of university institutions. For its implementation, the theoretical references of the community environmental education management process were taken into account, as well as the characterization of the environmental situation at the University of Pinar del Rio. As a result, it was possible to design a procedure to incorporate the environmental dimension, which consists of 4 stages and 14 steps that consider the key strategic and support processes that are managed, contributing to enhance the analysis of environmental issues in order to improve the decision-making process and the solution of environmental problems at the University of Pinar del Rio.

Abstract The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p

Abstract DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6 $$\times $$ × 6 $$\times $$ × 6 m $$^3$$ 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019–2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties.

Objective: The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. Methods: Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non–small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. Results: New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P

Abstract Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3 VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97–1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10−12) but not in the rest of breast cancer subtypes.

Abstract Background Ifosfamide is an alkylating agent used in the treatment of a wide range of tumours. Because of known side effects it is usually administered in combination with mesna, a thiol agent with uroprotective activity, to reduce them and increase the therapeutic dose. The most frequently administered regimens for ifosfamide are fractionated doses for 3 to 5 days, high-dose intravenous bolus, and continuous infusion over 24 to 72 h. Hypersensitivity reactions to ifosfamide plus mesna are not frequently described in the literature. Moreover, no reports exist concerning desensitization for this chemotherapy combination. Case presentation A 47-year-old man with stage IV renal sarcoma was treated with the combination of ifosfamide and mesna every 3 weeks in a 4-consecutive-day infusion protocol. During the second cycle of chemotherapy, he presented acute cutaneous symptoms. A 12-step desensitization protocol was proposed in view of the lack of knowledge of the possible hypersensitivity reactions to this combination of chemotherapy agents, and the multiple difficulties found during the study of the case. Conclusions The 12-step desensitization protocol was well tolerated. Therefore, it is an appropriate and safe option in the case of suspected allergy to ifosfamide plus mesna.

Risk management is of vital importance; its knowledge and execution allows controlling and minimizing the negative consequences of its occurrence, achieving economic-financial stability and comprehensive security. In Cuba, it acquires relevance due to Resolution 60 of 2011 on the Standards of the Internal Control System, because in its chapter two it includes risk management and prevention. The objective is to apply the methodology for risk management and prevention in the Agricultural Production Cooperative "Rafael Morales" adjusted to its characteristics and particularities that contribute to a better productive performance and value creation. In the diagnosis carried out, it was found, through surveys and interviews, documentary analysis and observation of the areas, that there was a lack of knowledge on the subject, which leaves it exposed to any eventuality, especially because of its exposure to natural and biological risks. With the implementation of the methodology, a better identification and evaluation of risks was obtained, mainly in the prevention and control of tobacco cultivation and other various crops. In economic terms, losses and their valuation are minimized or reduced in the event of their materialization or occurrence. It can be affirmed that the application of this methodology contributed positively to the development of the Agricultural Cooperative, both from the economic point of view, by reducing risks, and from the social point of view, by protecting the interests of the associates and the community.

Este artículo trata un estudio exploratorio acerca de la publicación de datos abiertos en el periodo 2016-2021 en Colombia; también, aborda la medida de su uso por parte de la población a partir del número de vistas y descargas. De allí surge como objetivo de investigación medir el avance en cantidad de datos abiertos, temáticas publicadas, cuáles entidades oficiales los publican y la interacción de la población con estos contenidos. Los resultados obtenidos muestran que las entidades han hecho un uso adecuado de la “Guía para publicación de datos abiertos” desarrollada por el Ministerio de las Tecnologías de la Información y las Comunicaciones (MinTIC) desde el año 2016, y se cuenta con cumplimiento de los estándares de calidad de los datos presentados de acuerdo con la medición de las “Cinco Estrellas de Berners Lee”. En las conclusiones, se evidencia cómo la búsqueda de información sobre la covid-19 modificó sustancialmente los intereses de la población, siendo la categoría de salud y protección social la más consultada.

Abstract Background Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). Methods A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. Results The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70–56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29–9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19–31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1–29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. Conclusions We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended.

Abstract Purpose To evaluate the impact of optical coherence tomography (OCT) biomarkers on intravitreal dexamethasone (DEX) implant clinical outcomes in patients with macular edema secondary to retinal vein occlusion (RVO-ME). Methods Retrospective study conducted on a cohort of patients with RVO-ME, either naïve or previously treated, who underwent treatment with DEX implant and had a follow-up of 6 months. Anatomic success was defined as a central retinal thickness (CRT) 20 hyperreflective foci (HRF) than in those with 20), or disrupted ELM were significantly associated with worse baseline BCVA.

Abstract Background Clinical management in orthogeriatric units and outcome indicators are similar for extracapsular fragility hip fractures, without discriminating between subtrochanteric and pertrochanteric fractures. Hypothesis Geriatric patients, 75 years or older, with subtrochanteric fractures have worse clinical and functional outcomes than those with pertrochanteric fractures. Materials and methods Retrospective observational study of data prospectively collected by the Spanish Hip Fracture Registry including patients 75 years or older, admitted for extracapsular hip fractures from January 2017 to June 2019. Demographic and baseline status, pre-operative, post-operative and 30-day follow-up data were included. Results A total of 13,939 patients with extracapsular hip fractures were registered: 12,199 (87.5%) pertrochanteric and 1740 (12.5%) subtrochanteric. At admission, patients with subtrochanteric fractures were younger (86.5 ± 5.8 versus 87.1 ± 5.6 years old), had better pre-fracture mobility (3.7 ± 2.7 versus 3.9 ± 2.8) (1-to-10 scale, 1 being independent) and were more likely to be living at home; those with pertrochanteric fractures had worse cognitive function (Pfeiffer 3.3 ± 3.3 versus 3.8 ± 3.5). The subtrochanteric fracture group showed worse post-fracture mobility (7.3 ± 2.7 versus 6.7 ± 2.7) and greater deterioration of mobility (3.7 ± 3.0 versus 2.9 ± 2.7). Among individuals living at home at baseline, those with subtrochanteric fractures were more likely to remain in an assisted facility at 30-day follow-up. In-hospital mortality during acute admission was higher for the subtrochanteric group (5.6% versus 4.5%) (p = 0.028). To our knowledge, this is the first paper highlighting the differences between these two fracture groups in the geriatric population. Conclusions Subtrochanteric fractures in the older population are a different and worse entity, with greater morbimortality and functional decline than pertrochanteric fractures. Despite being younger and fitter at admission, older patients with subtrochanteric fractures have a higher risk of remaining non-weight bearing and undergoing re-operation and institutionalization. Orthogeriatric units should be aware of this and manage subtrochanteric fractures accordingly. Level of evidence: IV.

Spinal cord infarction is a rare entity that can be caused by interventional procedures such as chemoembolization, despite its high level of safety. We present a case of a 51-year-old female with chest pain and hemorrhage from a friable neoplastic lesion of the bilateral breast without improvement after conservative measures. After embolization of the tumor arteries, the patient developed crural paraparesis and global lower extremity hyporeflexia. MRI showed hypersignal in the anterior spinal cord, suggesting ischemia/infarction of the spinal cord in the territory of the anterior spinal artery. Despite the interventional procedures being safe, the inherent risks are always present, and unfortunately some serious ones, such as the one reported in this case. That is why the importance of case-by-case evaluation in order to offer the best treatment and maintain informed consent.

Abstract Aims Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Methods and results We conducted a retrospective, single‐centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin 0.05). Conclusions Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

Abstract Homeostatic renal filtration relies on the integrity of podocytes, which function in glomerular filtration. These highly specialized cells are damaged in 90% of chronic kidney disease, representing the leading cause of end-stage renal failure. Although modest podocyte renewal has been documented in adult mice, the mechanisms regulating this process remain largely unknown and controversial. Using a mouse model of Adriamycin-induced nephropathy, we find that the recovery of filtration function requires up-regulation of the endogenous telomerase component TERT. Previous work has shown that transient overexpression of catalytically inactive TERT (i-TERTci mouse model) has an unexpected role in triggering dramatic podocyte proliferation and renewal. We therefore used this model to conduct specific and stochastic lineage-tracing strategies in combination with high throughput sequencing methods. These experiments provide evidence that TERT drives the activation and clonal expansion of podocyte progenitor cells. Our findings demonstrate that the adult kidney bears intrinsic regenerative capabilities involving the protein component of telomerase, paving the way for innovative research toward the development of chronic kidney disease therapeutics.

Multipactor has become a keylimiting factor of the final performance of satellite communication systems, due to the increase in power levels and/or operating frequency bands. As a result, the critical components of these systems must meet demanding multipactor specifications which should be considered during the design process. This paper describes the different techniques available to predict the multipactor threshold power for radio frequency (RF) and microwave passive hardware under continuous wave (CW) excitation, from cumbersome particle simulations to fast approximate methods based on circuit models. All these techniques have been described and compared together for the first time, including also a detailed description of the configuration issues of commercial particle simulators required to obtain accurate multipactor threshold predictions. The techniques are applied to both wideband and narrowband application examples. The predictions have been compared with measured thresholds of manufactured samples obtained with a novel multipactor test bed, thus allowing to highlight the advantages and limitations of each technique and particle simulator. From this paper, it will be possible to choose the most suitable procedure (and an appropriate simulator, if needed) to obtain multipactor threshold prediction of passive hardware.

Abstract Background Seronegative antiphospholipid syndrome (SN-APS) is often defined as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a different note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifestations without non-criteria features/aPL positivity (controls). Methods Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospitals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared. Results A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2–6.5, p

The Mediterranean basin is drastically affected by intense and frequent droughts, which jeopardize the diversity and survival of its forest, for example, Pinus pinaster forests. The dynamics of the bacterial communities inhabiting the rhizosphere of Pinus pinaster and other plants from a pine dominated forest under contrasting hydric conditions was monitored. The forest was located in Sierra de Oria (southeast Spain), and it was mainly composed by P. pinaster, P. halepensis, woody shrub species and herbaceous plants. 18 trees visually belonging to P. pinaster located along the perimeter and across the forest were selected for the analysis. All the trees were separated at least 50 m each other. Although all of them belonged to P. pinaster morphologically according to visual identification, the genotyping of the roots confirmed that they corresponded to P. pinaster, P. halepensis, and other plant species different from genus Pinus, although in the last case it was not possible to identify the plant species. At a distance less than 50 cm from the trunk, the litter and topsoil were removed, and the soil closely attached to non-suberified roots (rhizosphere soil) was collected (depth of 5-25 cm). Sampling was carried out in two seasons with contrasting temperature and rainfall patterns: on July 18, 2017 (summer) and April 24, 2018 (spring). After rhizosphere soil DNA and RNA extraction (and cDNA synthesis), a metabarcoding approach was followed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene and its derived transcripts by Illumina MiSeq platform. Sequencing reads were bioinformatically processed; specifically, they were filtered, trimmed, clustered into ASV (Amplicon Sequence Variants), and taxonomically identified. As a result, a total of 1,123,209 and 1,089,359 quality sequences were obtained from DNA and RNA-derived libraries, which resulted in 5,241 and 5,231 ASVs, respectively. Total communities (DNA) were mainly dominated by phyla Proteobacteria, Acidobacteria, Actinobacteria, Verrucomicrobia and Bacteroidetes in summer and spring, while potentially active populations (RNA libraries) were rich in Proteobacteria, Acidobacteria, Candidate division WPS-1, Actinobacteria and Verrucomicrobia both in summer and spring. On the other hand, DNA libraries were mainly dominated by genera Sphingomonas and acidobacterial groups Gp4 and Gp6, while potentially active bacteria (RNA) were rich in acidobacterial Gp3, Gp4, Gp6 and Phenylobacterium, although their relative abundance depended on the considered season.This dataset can provide valuable information about bacterial candidates which could be used as bioindicators of drought conditions. In addition to shifts in the bacterial relative abundance due to seasonal changes, the ratio RNA-based cDNA:DNA could be calculated as proxy of the potential activity of bacterial taxa. Moreover, these data could aid in developing bioformulations based on microorganisms which could be resistant to desiccation and involved in the drought resistance mechanisms of the host plant.

En este artículo exploramos una vertiente de la cultura escolar, la que se refiere a la cultura empírica. La investigación se construye con los testimonios orales de profesoras de educación primaria de alrededor de 1970. En los hallazgos apreciamos el valor extrínseco e intrínseco que las maestras atribuían a la elaboración de los trabajos manuales o manualidades, como bordado de servilletas y manteles, tejido de colchas y carpetas, composiciones artísticas, lapiceros y floreros. Estas prácticas son manifestaciones de la cultura empírica con componentes de la cultura académica, que se reconfigura, precisamente, por la cultura forjada por el colectivo docente

La historia evidencia que las mujeres han librado serias batallas por lograr el reconocimiento de su derecho a la educación y, consecutivamente, hacerse de una profesión. Por su parte, la sociología y la historia de las profesiones dan cuenta de cómo ciertos campos laborales se han feminizado; uno de ellos es el ejercicio del magisterio, en el cual las maestras han tenido una presencia destacada. En este contexto, el objetivo del presente trabajo es recuperar los diversos significados de ser profesora, expresados en los testimonios de maestras encargadas de formar a niñas y niños y, por tanto, de forjar parte de la historia de la educación. Siendo profesoras, han destacado como forjadoras de nuevas generaciones de mujeres, históricamente relegadas en el campo profesional. Rescatamos testimonios de profesoras sobre su formación e incursión en el campo de la enseñanza, y, como resultado, inferimos los significados de ser maestras, durante la segunda mitad del siglo XX, en el estado de Guanajuato, México, en el marco de sus historias de vida. El proyecto de investigación que la origina abreva en la historia oral como sustento teórico-metodológico basado en los relatos de vida. Concluimos que el ingreso de las mujeres a la educación formal –desde la elemental hasta la escuela Normal, en este caso– jamás les fue una empresa fácil; como tampoco lo fue acceder a un puesto superior como directoras, supervisoras o jefas de sector. Aun así, las profesoras se asumen como actoras relevantes para impulsar el desarrollo profesional de otras mujeres. Sus trayectos biográficos enteran de su vocación docente, su amor por la formación de niñas y niños, sus logros laborales y su aporte a la cultura magisterial, aunque sus nombres e historia pasen prácticamente desapercibidos.

Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 (“virus”). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors’ response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer.

Cytokines have proven to be effective for cancer therapy, however whilst low-dose monotherapy with cytokines provides limited therapeutic benefit, high-dose treatment can lead to a number of adverse events. Interleukin 7 has shown promising results in clinical trials, but anti-cancer effect was limited, in part due to a low concentration of the cytokine within the tumor. We hypothesized that arming an oncolytic adenovirus with Interleukin 7, enabling high expression localized to the tumor microenvironment, would overcome systemic delivery issues and improve therapeutic efficacy. We evaluated the effects of Ad5/3-E2F-d24-hIL7 (TILT-517) on tumor growth, immune cell activation and cytokine profiles in the tumor microenvironment using three clinically relevant animal models and ex vivo tumor cultures. Our data showed that local treatment of tumor bearing animals with Ad5/3- E2F-d24-hIL7 significantly decreased cancer growth and increased frequency of tumor-infiltrating cells. Ad5/3-E2F-d24-hIL7 promoted notable upregulation of pro-inflammatory cytokines, and concomitant activation and migration of CD4+ and CD8 + T cells. Interleukin 7 expression within the tumor was positively correlated with increased number of cytotoxic CD4+ cells and IFNg-producing CD4+ and CD8+ cells. These findings offer an approach to overcome the current limitations of conventional IL7 therapy and could therefore be translated to the clinic.

Abstract Aim To explore the relation between health literacy (HL) and continuing breastfeeding (BF) at 6 months post‐partum. Design Observational, longitudinal and prospective study between December 2018–May 2019. The STROBE checklist was used. Methods 114 mother/baby pairings from a Spanish Hospital were included. Mothers’ health literacy was studied with the Newest Vital Sign and Short Assessment of Health Literacy for Spanish Adults 50 (SAHLSA‐50). Before hospital discharge, BF efficiency was studied using the LATCH BF score and BF continuity was followed for 6 months. Survival analysis and Cox regression were done. Results Health literacy levels and BF effectiveness were adequate before hospital discharge. At 6 months post‐partum, less than half the sample still exclusively breastfed. The main reason for early exclusive BF cessation was lower than the recommended newborn weight gain. The HL level acted as a protective factor against abandonment of BF.

Introducción y objetivos: Los nonagenarios son un grupo de edad en rápido crecimiento entre los pacientes cardiovasculares, en especial con estenosis aórtica, pero los datos sobre su pronóstico después de la implantación transcatéter de válvula aórtica (TAVI) son escasos. El objetivo de este estudio es analizar las características basales de los nonagenarios tratados con TAVI y determinar si la edad "65; 90 años está relacionada con un peor pronóstico en comparación con los pacientes no nonagenarios. Métodos: Se incluyó a todos los pacientes "65; 75 años inscritos en el registro prospectivo multicéntrico español de TAVI entre 2009 y 2018. Se excluyó a aquellos < 75 años. Resultados: Se inscribieron en el registro español de TAVI 8.073 pacientes "65; 75 años de 46 centros de España; 7.686 de > 75 a 90 años (95,2%) y 387 nonagenarios (4,79%). Se observó un aumento progresivo de los nonagenarios. El acceso transfemoral se utilizó en el 91,6% de los casos, predominantemente en los nonagenarios (91,4 frente a 95,1%; p = 0,01). Los nonagenarios tenían más probabilidades de morir durante la hospitalización (4,3 frente a 7,0%; p = 0,01). Sin embargo, no hubo diferencia en la tasa de mortalidad por cualquier causa al año de seguimiento (8,8 frente a 11,3%; p = 0,07). En el análisis multivariable, la edad "65; 90 años no se asoció de forma independiente con un aumento de la mortalidad por cualquier causa ajustada (HR = 1,37; IC95%, 0,91-1,97; p = 0,14). La creatinina basal y las complicaciones hemorrágicas intrahospitalarias se asociaron a un peor pronóstico a largo plazo en pacientes nonagenarios tratados con TAVI. Conclusiones: Los nonagenarios son una población creciente y de muy alto riesgo, con estenosis aórtica grave, para quienes la TAVI podría representar una estrategia segura y efectiva. Una cuidadosa selección de los pacientes por un equipo multidisciplinario la máxima eficiencia en esta población, en la que la función renal basal y las complicaciones hemorrágicas pueden determinar el pronóstico a largo plazo tras la TAVI.

ABSTRACT Introduction and objectives: Nonagenarians are a fast-growing age group among cardiovascular patients, especially with aortic stenosis, but data about their prognosis after transcatheter aortic valve implantation (TAVI) is scarce. The objective of our study is to analyze the baseline characteristics of nonagenarians treated with TAVI and determine whether age ≥ 90 years is associated with a worse prognosis compared to non-nonagenarian patients. Methods: We included all patients ≥75 years enrolled in the multicenter prospective Spanish TAVI registry between 2009 and 2018. Patients < 75 years were excluded. Results: A total of 8073 elderly patients (≥ 75 years) from 46 Spanish centers were enrolled in the Spanish TAVI registry; 7686 were between ≥ 75 and < 90 years old (95.2%), and 387 were nonagenarian patients (4.79%). A gradual increase of nonagenarians was observed. The transfemoral access was used in 91.6% of the cases, predominantly among the nonagenarian patients (91.4% vs 95.1%, P = .01). Nonagenarians were more likely to die during their hospital stay (4.3% vs 7.0% among nonagenarians, P = .01). However, no difference was seen in the all-cause mortality rates reported at the 1-year follow-up (8.8% vs 11.3%, P =.07). In the multivariate analysis, age ≥ 90 years was not independently associated with a higher adjusted all-cause mortality rate (HR, 1.37, 95%CI, 0.91–1.97, P = .14). The baseline creatinine levels, and the in-hospital bleeding complications were all associated with a worse long-term prognosis in nonagenarians treated with TAVI. Conclusions: Nonagenarians are a very high-risk and growing population with severe AS in whom TAVI may be a safe and effective strategy. Careful patient selection by the TAVI heart team is mandatory to achieve maximum efficiency in this population where the baseline kidney function and bleeding complications may determine the long-term prognosis after TAVI.

Se realizó una comparación del análisis de ciclo de vida conceptual para 2 estibas construidas con madera natural (melinna) y madera plástica (100% polietileno) respectivamente, usando el software SIMAPRO 8.4.0.0 en su versión DEMO 2017 la cual usa como norma la UNE EN ISO 14040. Se determinó el alcance del estudio de cada estiba y su análisis de inventario teniendo en cuenta la disponibilidad de actividades en SIMAPRO 8. Se analizaron diferentes factores para cada estiba, los cuales fueron: caracterización y evaluación de daño, y de manera comparativa los factores: salud humana, ecosistemas y recursos. Los resultados arrojados del análisis comparativo afirmaron que las estibas de madera natural afectan en un 100% a la salud humana, y que por el contrario las estibas de madera plástica afectan un 2%, hablando de los ecosistemas, las estibas naturales afectan un 100% y las construidas con madera plástica un 2%, y por último, en el componente de recursos, las estibas naturales afectan en un 100% y las estibas plásticas un 47%.

En la presente investigación se buscó evaluar la tecnología “Biowish Remediate” en la biodegradación de grasas de origen animal presentes en suelos, lo cual se realizó en tres fases metodológicas: caracterización de parámetros fisicoquímicos y microbiológicos del suelo, tasas de remoción de las grasas y determinación de efectividad de Biowish frente a un fertilizante nitrogenado. Los resultados finales para Biowish en cuanto a degradación de grasas fueron de 1350 mg/Kg de suelo (remoción del 98%), mientras que el Fertilizante dio valores de 20750 mg/Kg (remoción 76%). Además, al caracterizar física, química y microbiológicamente el suelo, se observó que, a pesar de que ambas alternativas se mantuvieron en igualdad de condiciones (aireación, humedad, tiempo y temperatura) para la realización de este estudio, hubo una diferencia significativa entre estas a favor de Biowish en cuanto a remoción de grasas, y en los valores finales de macronutrientes como el fósforo y el potasio.

Genome wide association studies in cancer are used to understand the heritable genetic contribution to disease risk. Here, the authors perform a genome wide association study in European patients with acute myeloid leukemia and identify loci associated with risk of developing the disease.

Abstract Both Saccharomyces and non‐Saccharomyces yeast strains are of great importance for the fermentation industry, especially with the flourishing of craft breweries, which are driving current innovations. Non‐conventional yeasts can produce novel beverages with attractive characteristics such as flavour, texture, and reduced alcohol content; however, they have been poorly explored. A new method for screening the fitness of conventional and non‐conventional yeast libraries utilising robotic platforms and solidified media representing industrial conditions is proposed. As proof of concept, a library formed of 6 conventional and 17 non‐conventional yeast strains was distributed in 96, 384 and 1536 arrays onto a YPD agar medium. Following this, the library was replicated in different conditions mimicking beer and cider fermentation conditions. The colony size was monitored over time, and fitness values measured in maximum pixels/h and maximum biomass were calculated. Significant differences in growth were observed in between the different strains and conditions. As examples, Candida milleri Y‐7245 displayed good performance in wort conditions, and Kazachstania yakushimaensis Y‐48837 stood out for its performance in apple juice. The method is proposed to be used as a pre‐screening step when studying vast yeast libraries. This would enable interested parties to discover potential hits for further study at a low initial cost. Furthermore, this method can be used in other applications where the desired screening media can be solidified.

Male and female mice need to generate spatial maps that integrate vomeronasal signals of territory owners in the hippocampus-dependent memory. The authors show that vomeronasal information influences learning-related activity in the hippocampus via the amygdaloid PMCo, lateral entorhinal cortex, and dorsal CA1.

The aim of this paper is to conduct a revenue management study, generating a theoretical model that establishes the relationship between the factors of a Short-Term Rental apartment offered on the Airbnb marketplace or similar and its optimal rental price set when the property is first put on the market, considering not only the characteristics defined in the platform listing but also the sociodemographic characteristics of the area in which the apartment is located. The research process was structured in six phases as case study for the technology transfer model. First, research planning was conducted to estimate the time, cost, and suitability of the research topic. Second, the study design was determined to establish a technology transfer model focusing on the theory of mixed revenue management. Third, data collection about the city of Madrid was extracted from two technological databases, namely SeeTransparent based mainly on Airbnb (28 internal characteristics of the apartment) and Deskmind Research (9 sociodemographic variables of the area in which the apartment is located). Fourth, the data were prepared to create a new descriptive variable of the apartments based on geolocation. Fifth, the analysis of this study was applied to explore the correlation between the price charged per night, the 28 internal characteristics of the apartments, and the 9 sociodemographic variables of their surrounding areas. Sixth, with this integrated database, the information was transformed into multivariate inferential statistics through Exploratory Factor Analysis and Multiple Linear Regression, creating a technology transfer model (big data algorithm) that allows revenue managers to set the price of an apartment based on known information, prior to having a history of market reactions. This research process and model consider some of the factors affecting the psychological behavior of tourism consumers. Practical implications of the findings indicate that the size/capacity of the apartments used for Short-Term rentals largely determines the initial rental price set (72%). The equipment offered by the apartments has a moderate impact (18%), and the sociodemographic characteristics of the surrounding area have a minor influence (11%).

Resumen: Introducción: una Unidad de Educación Médica (UEM) debe ofrecer distintos servicios educativos y de investigación relacionados a su personal docente y a la Dirección Académica. Con esta finalidad se priorizó un proceso de detección de aspectos educativos que repercuten en el aprendizaje de los estudiantes de Medicina y se exploró la visión de los docentes sobre el papel de una UEM, valorando sus necesidades educativas. Material y Métodos: mediante 2 escalas validadas se identificó el nivel de coherencia interna de la escuela (Escala de Coherencia Interna [ECI], 58 items) presencialmente respondida por 30 profesores. Se exploraron las opiniones y necesidades de sus profesores (escala NESEM, 12 preguntas) respondidas online por 75 de ellos. Para la ECI se catalogaron 3 niveles de puntuaciones: alto (> 4,60), medio (entre 4,20 y 4,59) y bajo (< 4,19). Análisis cuantitativo descriptivo y cualitativo para las preguntas abiertas (NESEM) analizadas independientemente por 2 investigadores agrupando las respuestas en códigos homogéneos y discutiendo discordancias. Resultados: veinticinco profesores contestaron la ECI (83,3%) y 56 la NESEM (74,7%). La ECI muestra niveles altos en casi todos los factores a excepción del grado de implicación y participación en las decisiones de la escuela y aspectos del desarrollo profesional. La percepción de la UEM es positiva y las necesidades educativas de los profesores concuerdan con sus funciones habituales. Conclusión: esta aproximación a la coherencia interna y las necesidades percibidas por los profesores de una facultad de Medicina ofrece una fotografía de gran valor para orientar las tareas más inmediatas de la UEM. Abstract: Introduction: A Medical Education Unit (MEU) must offer different educational and research services related to the teaching staff and the Deanery. With this propose, a process of detecting educational aspects that affect the learning of medical students was prioritized as well as the teachers' vision of the role of an MEU, assessing their educational needs. Materials and Methods: Through 2 validated scales, the level of Internal Coherence of the School was identified (ECI Scale, 58 items) and the opinions and needs of its teachers were explored (NESEM Scale, 12 questions). Sent to 30 and 75 teachers in person and online respectively. Three levels of scores were classified for the ECI: high (>4.60), medium (between 4.20 and 4.59) and low (

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [−2.79 mg/dl (95% CI: −4.25, −1.34) and −5.15 mg/dl (95% CI: −7.38, −2.93), p-values = 0.0002 and

Perfusion fixation is a well-established technique in animal research to improve preservation quality in the study of many tissues, including the brain. There is a growing interest in using perfusion to fix postmortem human brain tissue to achieve the highest fidelity preservation for downstream high-resolution morphomolecular brain mapping studies. Numerous practical barriers arise when applying perfusion fixation in brain banking settings, including the large mass of the organ, degradation of vascular integrity and patency prior to the start of the procedure, and differing investigator goals sometimes necessitating part of the brain to be frozen. As a result, there is a critical need to establish a perfusion fixation procedure in brain banking that is flexible and scalable. This technical report describes our approach to developing an ex situ perfusion fixation protocol. We discuss the challenges encountered and lessons learned while implementing this procedure. Routine morphological staining and RNA in situ hybridization data show that the perfused brains have well-preserved tissue cytoarchitecture and intact biomolecular signal. However, it remains uncertain whether this procedure leads to improved histology quality compared to immersion fixation. Additionally, ex vivo magnetic resonance imaging (MRI) data suggest that the perfusion fixation protocol may introduce imaging artifacts in the form of air bubbles in the vasculature. We conclude with further research directions to investigate the use of perfusion fixation as a rigorous and reproducible alternative to immersion fixation for the preparation of postmortem human brains.