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Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.

Abstract The popularization of social media has led to a considerable increase in the importance of discursive expressions of violence, especially when directed at vulnerable communities. While social media platforms have created rules to regulate such expressions, little information is available on the perception of the legitimacy of these rules in the general population, regardless of the importance of the former for the latter. It is therefore the objective of this study to analyze the perception of the seriousness of such content and the degree to which the population has established a consensus on the withdrawal of restricted discursive behaviour on three major social media platforms (Facebook, Instagram and Twitter). For this purpose, 918 participants were immersed in an experimental paradigm in three different groups (n 1 = 302; n 2 = 301; n 3 = 315). Each was presented with stimuli containing discursive behaviour that is banned by community guidelines. The stimuli were presented differently to each group (i.e., description of the banned behaviour, description and accompanying example, example only). Our experimental data reveals that the degree of consensus on the need to remove content is quite high, regardless of the style of presentation. It furthermore suggests that the behaviour in question is perceived as very serious, due to the harm that our participants presume it to cause. These results have important implications for the debate on freedom of expression on the Internet and its regulation by private actors.

In this paper, we determine the maximum h max and the minimum h min of the Hilbert vectors of Perazzo algebras A F , where F is a Perazzo polynomial of degree d in n + m + 1 variables. These algebras always fail the Strong Lefschetz Property. We determine the integers n, m, d such that h max (resp. h min ) is unimodal, and we prove that A F always fails the Weak Lefschetz Property if its Hilbert vector is maximum, while it satisfies the Weak Lefschetz Property if it is minimum, unimodal, and satisfies an additional mild condition. We determine the minimal free resolution of Perazzo algebras associated to Perazzo threefolds in P 4 with minimum Hilbert vectors. Finally we pose some open problems in this context. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus prosthetic valve endocarditis (SAPVE) is a serious infection with high mortality. The main objective of this study was to identify factors associated with in-hospital mortality. Methods: From January 2008 to December 2021, consecutive patients from a Spanish cohort of infective endocarditis with a definitive diagnosis of SAPVE were analyzed. Results: During the study period, 219 cases of definitive SAPVE were diagnosed, which accounted for 16.7% of a total of 1309 cases of definitive prosthetic valve endocarditis (PVE). Patients presented advanced age and marked comorbidity. There was a higher incidence of persistent bacteremia, septic shock, stroke, and acute kidney injury than in cases of PVE caused by other microorganisms. Methicillin resistance was not associated with differences in clinical presentation, echocardiographic findings, or mortality. Only 50.6% of the patients with surgical indications (88 patients) underwent surgery. Overall, in-hospital mortality was 47.9%. The variables associated with in-hospital mortality were age (OR:1.03, 95% CI: 1.00-1.05; p = 0.016), heart failure (OR:2.86, 95% CI: 1.53–5.32; p = 0.001), acute kidney injury (OR:2.42, 95%CI:1.28–4.58; p = 0.006), stroke (OR:3.53, 95%CI:1.79–6.96; p < 0.001) and surgery indicated but not performed (OR:2.01, 95%CI:1.06–3.8; p = 0.030). On the other hand, the performance of surgery per se in patients with SAPVE, regardless of whether there was a surgical indication according to the guidelines, was not associated with a reduction in in-hospital mortality. Conclusions: SAPVE is characterized by high mortality, which is more marked in patients who present a surgical indication but do not undergo surgery. [ABSTRACT FROM AUTHOR]

To assess whether older adults who spend a night in emergency departments (ED) awaiting admission are at increased risk of mortality. This was a retrospective review of a multipurpose cohort that recruited all patients ≥ 75 years who visited ED and were admitted to hospital on April 1 to 7, 2019, at 52 EDs across Spain. Study groups were: patients staying in ED from midnight until 8:00 a.m. (ED group) and patients admitted to a ward before midnight (ward group). The primary endpoint was in-hospital mortality, truncated at 30 days, and secondary outcomes assessed length of stay for the index episode. The sample comprised 3,243 patients (median [IQR] age, 85 [81–90] years; 53% women), with 1,096 (34%) in the ED group and 2,147 (66%) in the ward group. In-hospital mortality for patients spending the night in the ED the ED group was 10.7% and 9.5% for patients transferred to a ward bed before midnight the ward group (adjusted OR: 1.12, 95%CI: 0.80–1.58). Sensitivity analyses rendered similar results (ORs ranged 1.06–1.13). Interaction was only detected for academic/non-academic hospitals (p < 0.001), with increased mortality risk for the latter (1.01, 0.33–3.09 vs 2.86, 1.30–6.28). There were no differences in prolonged hospitalization (> 7 days), with adjusted OR of 1.16 (0.94–1.43) and 1.15 (0.94–1.42) depending on whether time spent in the ED was or was not taken into consideration. No increased risk of in-hospital mortality or prolonged hospitalization was found in older patients waiting overnight in the ED for admission. Nonetheless, all estimations suggest a potential harmful effect of staying overnight, especially if a proper bedroom and hospitalist ward bed and hospitalized care are not provided. [ABSTRACT FROM AUTHOR]

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43Cre−ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43fl/fl mice and Cx43Cre−ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia–reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165 ± 0.338 vs. 4.18 ± 0.55 nmol/mg protein, p < 0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43Cre−ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate. [ABSTRACT FROM AUTHOR]

A 3D-printed stereolithographic platform for selective biorecognition is designed to enable convective microscale affinity extraction of microcystin-LR (MC-LR) followed by direct solid-phase optosensing exploiting ratiometric front-face fluorescence spectroscopy. For this purpose, a recombinant monoclonal plantibody (recAb) is covalently attached to a 3D-printed structure for sorptive immunoextraction, whereupon the free and unbound primary amino moieties of the recAb are derivatized with a fluorescent probe. The fluorophore-recAb-MC-LR laden device is then accommodated in the cuvette holder of a conventional fluorometer without any instrumental modification for the recording of the solid-phase fluorescence emission. Using Rodbard's four-parameter sigmoidal function, the 3D-printed bioselective platform features a limit of detection (LOD) of 28 ng L−1 using a sample volume of 500 mL, device-to-device reproducibility down to 12%, and relative recoveries ranging from 91 to 100% in marine waters. Printed prototypes are affordable, just 0.4 € per print and ≤ 10 € per device containing recAb. One of the main assets of the miniaturized immunoextraction device is that it performs comparably well in terms of analytical figures of merit with costly mass spectrometric-based analytical methodologies, such as HPLC–MS/MS. The device is readily applicable to high-matrix samples, such as seawater, as opposed to previous biosensing platforms, just applied to freshwater systems. [ABSTRACT FROM AUTHOR]

Several pathogenic Escherichia coli strains cause diarrhea. Enteroaggregative E. coli (EAEC) strains are one of the diarrheagenic pathotypes. EAEC cells form a "stacked-brick" arrangement over the intestinal epithelial cells. EAEC isolates express, among other virulence determinants, the AggR transcriptional activator and the aggregative adherence fimbriae (AAF). Overexpression of the aggR gene results in increased expression of virulence factors such as the aff genes, as well as several genes involved in specific metabolic pathways such as fatty acid degradation (fad) and arginine degradation (ast). To support the hypothesis that induction of the expression of some of these pathways may play a role in EAEC virulence, in this study we used a murine infection model to evaluate the impact of the expression of these pathways on infection parameters. Mice infected with a mutant derivative of the EAEC strain 042, characterized by overexpression of the aggR gene, showed increased disease symptoms compared to those exhibited by mice infected with the wild type (wt) strain 042. Several of these symptoms were not increased when the infecting mutant, which overexpressed aggR, lacked the fad and ast pathways. Therefore, our results support the hypothesis that different metabolic pathways contribute to EAEC virulence. [ABSTRACT FROM AUTHOR]

In this research, LaFeO3 doped with different concentrations of Ni2+ at Fe sites, ranging from 0.1 to 0.5 with a Δx of 0.1, was studied. The synthesis process involved high-energy milling followed by heat treatment at a low temperature, 1073 K, to induce ferromagnetic order (FM). Moreover, the effects of cation doping on the crystal structure and multiferroic properties were determined. X-ray diffraction analysis and Rietveld refinement confirmed that doped lanthanum ferrite with an orthorhombic structure (Pnma) was obtained for all the studied dopant levels. The magnetic hysteresis loops change from antiferromagnetic (AFM) to weakly ferromagnetic at room temperature when Ni2+ is introduced into the LaFeO3 crystal structure, which is attributed to spin canting due to the difference in ionic radius between the Fe3+ and Ni2+ cations and to the frustration of the magnetic cycloid due to the existence of uncompensated ions. Regarding the dielectric properties, the doped ferrites show semiconductor behavior with high values of relative permittivity as the doping concentration increases. XPS spectra confirmed the existence of adsorbed oxygen associated with oxygen affinity as a mechanism of charge compensation due to vacancies and oxidation from Fe3+ to Fe4+. [ABSTRACT FROM AUTHOR]

Purpose: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). Materials and methods: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. Results: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783–0.842) and 0.849 (0.806–0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. Conclusions: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment. [ABSTRACT FROM AUTHOR]

On February 28th, shortly after the Russian invasion of Ukraine on February 24th, Twitter announced the expansion of its labelling policy for "Russia state-affiliated media", in order to address disinformation in favour of the Russian government.. While this 'soft' approach does not include the removal of content, it entails issues for freedom of expression and information. This article investigates the consequences of this labelling policy for the range and impact of accounts labelled "Russia state-affiliated media" during the Ukrainian war. Using an iterative detection method, a total of 90 accounts of both media outlets and individual journalists with this label were identified. The analysis of these accounts' information and timeline, as well as the comparison of the impact of their tweets before and after February 28th with an ARIMA model, strongly suggests, that this policy, despite its limited scope, could have contributed to a reduction in the impact of the sampled tweets, among other concurrent events. These results provide empirical evidence to guide critical reflection on this content moderation policy. [ABSTRACT FROM AUTHOR]

This study presents a method to improve state-of-the-art concave point detection methods as the first step towards effectively segmenting overlapping objects in images. The approach relies on analysing the curvature of the object contour. This method comprises three main steps. First, the original image is preprocessed to obtain the curvature value at each contour point. Second, the regions with higher curvatures are selected and a recursive algorithm is applied to refine previously selected regions. Finally, a concave point is obtained for each region by analysing the relative position of their neighbourhood. Furthermore, the experimental results indicate that improving the detection of concave points leads to better division of clusters. To evaluate the quality of the concave point detection algorithm, a synthetic dataset was constructed to simulate the presence of overlapping objects. This dataset includes the precise location of concave points, which serve as the ground truth for evaluation. As a case study, the performance of a well-known application, such as the splitting of overlapping cells in images of peripheral blood smears samples from patients with sickle cell anaemia, was evaluated. We used the proposed method to detect concave points in cell clusters and then separated these clusters by ellipse fitting. [ABSTRACT FROM AUTHOR]

Chile is one of the countries with most growing industries worldwide due to their mining and manufacturing industries. Nevertheless, at the same time there is a lack on energy generation and processes efficiency. The objectives of this paper are to estimate the amount of available industrial waste heat derived from the manufacturing industry in Chile, to locate these heat sources geographically, to assess the best technologies to be used to take advantage of this heat, and finally, to estimate the environmental savings of its reuse. Results showed that the sectors with the highest potential for the use of residual heat are food and beverages with an average accumulated potential of 62.9 PJ, basic metals with 21.5 PJ, chemical products with 15.1 PJ, paper products with 10.8 PJ, and non-metallic minerals with 10.6 PJ. With these data, the energy generation in Chile could be more efficient as well as the industrial processes could save more energy, reducing costs and raw materials. [ABSTRACT FROM AUTHOR]

Interpreting chest X-rays is a complex task, and artificial intelligence algorithms for this purpose are currently being developed. It is important to perform external validations of these algorithms in order to implement them. This study therefore aims to externally validate an AI algorithm's diagnoses in real clinical practice, comparing them to a radiologist's diagnoses. The aim is also to identify diagnoses the algorithm may not have been trained for. A prospective observational study for the external validation of the AI algorithm in a region of Catalonia, comparing the AI algorithm's diagnosis with that of the reference radiologist, considered the gold standard. The external validation was performed with a sample of 278 images and reports, 51.8% of which showed no radiological abnormalities according to the radiologist's report. Analysing the validity of the AI algorithm, the average accuracy was 0.95 (95% CI 0.92; 0.98), the sensitivity was 0.48 (95% CI 0.30; 0.66) and the specificity was 0.98 (95% CI 0.97; 0.99). The conditions where the algorithm was most sensitive were external, upper abdominal and cardiac and/or valvular implants. On the other hand, the conditions where the algorithm was less sensitive were in the mediastinum, vessels and bone. The algorithm has been validated in the primary care setting and has proven to be useful when identifying images with or without conditions. However, in order to be a valuable tool to help and support experts, it requires additional real-world training to enhance its diagnostic capabilities for some of the conditions analysed. Our study emphasizes the need for continuous improvement to ensure the algorithm's effectiveness in primary care. [ABSTRACT FROM AUTHOR]

In this work, the enhancement of the magnetocaloric effect by mixing different alkaline-earth-doped lanthanum manganites is reported. The sintering process of the mixed manganites promotes the unexpected presence of a strontium–calcium-co-doped lanthanum manganite phase that enhances the magnetocaloric properties of the composite. Consistent with this result, the composite shows three Curie temperatures at 263 K, 309 K, and 284 K, attributed to the three different phases found. The transition was identified as a second-order phase transition by the Arrott plots. A maximum entropy change of 11.66 J·(kg·K)−1 was obtained for the composite at 18 kOe. It corresponds to a refrigeration cooling power of 484.98 J·kg−1 near room temperature. The results demonstrated the synergistic contribution to the magnetocaloric properties of individual phases, enhancing the magnetocaloric effect by obtaining a composite. [ABSTRACT FROM AUTHOR]

To investigate factors related to the development of hyperactive delirium in patients during emergency department (ED) stay and the association with short-term outcomes. A secondary analysis of the EDEN (Emergency Department and Elderly Needs) multipurpose multicenter cohort was performed. Patients older than 65 years arriving to the ED in a calm state and who developed confusion and/or psychomotor agitation requiring intravenous/intramuscular treatment during their stay in ED were assigned to delirium group. Patients with psychiatric and epileptic disorders and intracranial hemorrhage were excluded. Thirty-four variables were compared in both groups and outcomes were adjusted for age, sex, Charlson Comorbidity Index, Barthel Index and polypharmacy. Hyperactive delirium that needed treatment were developed in 301 out of 18,730 patients (1.6%). Delirium was directly associated with previous episodes of delirium (OR: 2.44, 95% CI 1.24–4.82), transfer to the ED observation unit (1.62, 1.23–2.15), chronic treatment with opiates (1.51, 1.09–2.09) and length of ED stay longer than 12 h (1.41, 1.02–1.97) and was indirectly associated with chronic kidney disease (0.60, 0.37–0.97). The 30-day all-cause mortality was 4.0% in delirium group and 2.9% in non-delirium group (OR: 1.52, 95% CI 0.83–2.78), need for hospitalization 25.6% and 25% (1.09, 0.83–1.43), in-hospital mortality 16.4% and 7.3% (2.32, 1.24–4.35), prolonged hospitalization 54.5% and 48.6% (1.27, 0.80–2.00), respectively, and 90-day post-discharge combined adverse event 36.4% and 35.8%, respectively (1.06, 0.82–2.00). Patients with previous episodes of delirium, treatment with opioids and longer stay in ED more frequently develop delirium during ED stay and preventive measures should be taken to minimize the incidence. Delirium is associated with in-hospital mortality during the index event. [ABSTRACT FROM AUTHOR]

Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromes in cattle, including respiratory disease and is one of the main agents involved in the bovine respiratory disease complex (BRDC). Its infectious cycle is characterized by latent infections with sporadic virus reactivation and transmission. Although the acute disease can be prevented by the use of vaccines, specific therapeutic measures are not available. Ivermectin (IVM) is a semi-synthetic avermectin with a broad-spectrum antiparasitic activity, which has previously shown to have potential as an antiviral drug. In this study, IVM antiviral activity against BoAHV-1 was characterized in two cell lines (MDBK [Madin Darby bovine kidney] and BT [bovine turbinate]), including the measurement of intracellular drug accumulation within virus-infected cells. IVM antiviral activity was assessed at three different drug concentrations (1.25, 2.5 and 5 µM) after incubation for 24, 48 and 72 h. Slight cytotoxicity was only observed with 5 µM IVM. Even the lowest IVM dose was able to induce a significant reduction in virus titers in both cell lines. These findings indicate that the antiviral effects of IVM were evident in our experimental model within the range of concentrations achievable through therapeutic in vivo administration. Consequently, additional in vivo trials are necessary to validate the potential utility of these results in effectively managing BoAHV-1 in infected cattle. [ABSTRACT FROM AUTHOR]

We solve the Ein–Lazarsfeld–Mustopa conjecture for the blow up of a projective space along a linear subspace. More precisely, let X be the blow up of P n at a linear subspace and let L be any ample line bundle on X. We show that the syzygy bundle M L defined as the kernel of the evalution map H 0 (X , L) ⊗ O X → L is L-stable. In the last part of this note we focus on the rigidness of M L to study the local shape of the moduli space around the point [ M L ] . [ABSTRACT FROM AUTHOR]

The Jacobian scheme of a reduced, singular projective plane curve is the zero-dimensional scheme, whose homogeneous ideal is generated by the partials of its defining polynomial. The degree of such a scheme is called the global Tjurina number and, if the curve is not a set of concurrent lines, some upper and lower bounds depending on the degree of the curve and the minimal degree of a Jacobian syzygy, have been given by A.A. du Plessis and C.T.C. Wall. In this paper, we give a complete geometric characterization of conic-line arrangements, with global Tjurina number attaining the upper bound. Furthermore, we characterize conic-line arrangements attaining the lower bound for the global Tjurina number, among all curves with a linear Jacobian syzygy. As an application, we characterize conic-line arrangements with Jacobian scheme equal to an eigenscheme of some ternary tensor, and we study the geometry of their polar maps. [ABSTRACT FROM AUTHOR]

A direct numerical simulation of a three-dimensional diffuser at Reynolds number Re = 10,000 (based on inlet bulk velocity) has been performed using a low-dissipation finite element code. The geometry chosen for this work is the Stanford diffuser, introduced by Cherry et al. (Int. J. Heat Fluid Flow 29:803–811, 2008). Results have been exhaustively compared with the published data with a quite good agreement. Additionally, further turbulent statistics have been provided such as the Reynolds stresses or the turbulent kinetic energy. A proper orthogonal decomposition and a dynamic mode decomposition analyses of the main flow variables have been performed to identify the main characteristics of the large-scale motions. A combined, self-induced movement of the large-scales has been found to originate in the top-right expansion corner with two clear features. A low-frequency diagonal cross-stream travelling wave first reported by Malm et al. (J. Fluid Mech. 699:320–351, 2012), has been clearly identified in the spatial modes of the stream-wise velocity components and the pressure, associated with the narrow band frequency of S t ∈ [ 0.083 , 0.01 ] . This movement is caused by the geometrical expansion of the diffuser in the cross-stream direction. A second low-frequency trait has been identified associated with the persisting secondary flows and acting as a back and forth global accelerating-decelerating motion located on the straight area of the diffuser, with associated frequencies of S t < 0.005 . The smallest frequency observed in this work has been S t = 0.0013 . This low-frequency observed in the Stanford diffuser points out the need for longer simulations in order to obtain further turbulent statistics. [ABSTRACT FROM AUTHOR]

Purpose: Medical image analysis suffers from a sparsity of annotated data necessary in learning-based models. Cardiorespiratory simulators have been developed to counter the lack of data. However, the resulting data often lack realism. Hence, the proposed method aims to synthesize realistic and fully customizable angiograms of coronary arteries for the training of learning-based biomedical tasks, for cardiologists performing interventions, and for cardiologist trainees. Methods: 3D models of coronary arteries are generated with a fully customizable realistic cardiorespiratory simulator. The transfer of X-ray angiography style to simulator-generated images is performed using a new vessel-specific adaptation of the CycleGAN model. The CycleGAN model is paired with a vesselness-based loss function that is designed as a vessel-specific structural integrity constraint. Results: Validation is performed both on the style and on the preservation of the shape of the arteries of the images. The results show a PSNR of 14.125, an SSIM of 0.898, and an overlapping of 89.5% using the Dice coefficient. Conclusion: We proposed a novel fluoroscopy-based style transfer method for the enhancement of the realism of simulated coronary artery angiograms. The results show that the proposed model is capable of accurately transferring the style of X-ray angiograms to the simulations while keeping the integrity of the structures of interest (i.e., the topology of the coronary arteries). [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF). Methods: We analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a QTc = 450 ms as reference. Results: Of 1800 patients meeting entry criteria (median age 84 years (IQR = 77–89), 56% female), their median QTc was 453 ms (IQR = 422–483). The 30-day mortality was 9.7%, while need of hospitalization, in-hospital mortality and prolonged hospitalization were 77.8%, 9.0% and 50.0%, respectively. RCS curves found longer QTc was associated with 30-day mortality if > 561 ms, OR = 1.86 (1.00–3.45), and increased up to OR = 10.5 (2.25–49.1), for QTc = 674 ms. A similar pattern was observed for in-hospital mortality; OR = 2.64 (1.04–6.69), for QTc = 588 ms, and increasing up to OR = 8.02 (1.30–49.3), for QTc = 674 ms. Conversely, the need of hospitalization had a U-shaped relationship: being increased in patients with shorter QTc [OR = 1.45 (1.00–2.09) for QTc = 381 ms, OR = 5.88 (1.25–27.6) for the shortest QTc of 200 ms], and also increasing for prolonged QTc [OR = 1.06 (1.00–1.13), for QTc = 459 ms, and reaching OR = 2.15 (1.00–4.62) for QTc = 588 ms]. QTc was not associated with prolonged hospitalization. Conclusion: In ED AHF patients, initial QTc provides independent short-term prognostic information, with increasing QTc associated with increasing mortality, while both, shortened and prolonged QTc are associated with need of hospitalization. [ABSTRACT FROM AUTHOR]

Background: Self-discharge is a risk factor for readmission and excess mortality. We assess the rate of self-discharge from the emergency department (ED) among presentations for acute recreational drug toxicity and identify factors associated with self-discharge. Methods: From the Euro-DEN Plus database of presentations to the ED with acute recreational drug toxicity, we extracted data from 11 centres in seven European countries from 2014 to 2017. Self-discharge was defined as taking one's own discharge or escaping from the ED before being medically cleared. We used multiple logistic regression analyses to look for factors associated with self-discharge. Results: Among 15,135 included presentations, 1807 (11.9%) self-discharged. Self-discharge rates varied from 1.7 to 17.1% between centres. Synthetic cannabinoids were associated with self-discharge, adjusted odds ratio 1.44 (95% confidence interval 1.10–1.89), as were heroin, 1.44 (1.26–1.64), agitation, 1.27 (1.10–1.46), and naloxone treatment, 1.27 (1.07–1.51), while sedation protected from self-discharge, 0.38 (0.30–0.48). Conclusion: One in eight presentations self-discharged. There was a large variation in self-discharge rates across the participating centres, possibly partly reflecting different discharge procedures and practices. Measures to improve the management of agitation and cautious administration of naloxone to avoid opioid withdrawal symptoms may be approaches worth exploring to reduce self-discharge. [ABSTRACT FROM AUTHOR]

Heatwaves (HWs) are expected to increase both in duration and intensity in the next decades, but little is known about their synoptic and mesoscalar behavior, which is especially important in mid-latitude regions. Most climate research has focused on temperature analysis to characterize HWs. We propose that a combination of temperature and synoptic patterns is a better way to define and understand HWs because including atmospheric circulation patterns provides information about different HW structures that can irregularly affect the territory, and illustrate this approach at the regional and urban scales using the Iberian Peninsula and the Metropolitan Area of Barcelona as case studies. We first select HW events from 1950 to 2020 and apply a multivariate analysis to identify synoptic patterns based on mean sea level pressure, geopotential height at 500 hPa, and maximum daily 2 m temperature. The results indicate that four synoptic patterns reproduce at least 50% of the variance in HWs, namely, "stationary and stable", "dynamic and advective", "stationary and advective", and "dynamic, advective and undulated". Next, we apply the analysis to the Representative Concentration Pathway future scenarios (RCPs) 4.5 and 8.5 from the Coordinated Regional Climate Downscaling Experiment (CORDEX) to determine how these synoptic trends can change in the future. The analysis shows that the four synoptic patterns continue to explain 55 to 60% of the variance in HWs. Future HW events will be characterized by an increase in geopotential height at 500 hPa due to the northward shift of the anticyclonic ridge. This is especially true for RCP8.5, which simulates business as usual incrementing fossil fuel use and additionally shows an increase in atmospheric dynamism in north advections from all directions in comparison with RCP4.5. These findings point to the importance of considering the geopotential height in HW prediction, as well as the direction of advections. [ABSTRACT FROM AUTHOR]

In this work, the photocatalytic activity of bismuth-doped lanthanum ferrite, La1-xBixFeO3 (0 ≤ x ≤ 0.5), synthesized by high-energy ball milling assisted by annealing, is reported. X-ray diffraction and Rietveld refinement confirmed that pure lanthanum ferrite with an orthorhombic structure (Pbnm) was obtained for dopant levels lower than 0.2 mol Bi3+. Higher dopant levels produce the transformation from LaFeO3 to BiFeO3 with the same orthorhombic structure (Pnma), and consequently, a mixture of phases is present in these compositions. The band gap values obtained from diffuse reflectance spectroscopy show a general decrease as bismuth content increases, from 2.10 eV for undoped to 2.00 eV for 0.5 mol doped. For any increase in Bi3+ concentration, all values indicate visible-light absorption. LaFeO3 synthesized powders show high photocatalytic degradation of methylene blue under visible light. Nevertheless, the synthesized bismuth-doped ferrites show a slight decrease, attributed to (i) the modification in the band gap, (ii) the change in the band gap border, and (iii) the presence of a mixture of phases, inducing a heterojunction effect. [ABSTRACT FROM AUTHOR]

This paper presents a broadband dielectric study of the capacitive and resistive formalism of ferroelectric BiFeO3 obtained by high-energy ball milling assisted, and its physical relation to ionized vacancies and dielectric relaxations with mobility charge carriers modulated by frequency and temperature conditions. Rietveld refinement analysis of X-ray diffraction patterns reveals that the almost pure (≈97% wt.) rhombohedral BiFeO3 phase comes along with small amounts of Bi2Fe4O9 as a secondary phase. The gradually reduced semicircles corroborated the ferroelectric nature of BiFeO3 in Nyquist plots and identified the low- and middle-temperature dielectric relaxations. The computed activation energies of 0.459 eV and 0.412 eV, as well as 0.598 eV and 0.569 eV, indicate the presence of singly and doubly ionized oxygen vacancies, respectively. The short-range and long-range mobility charge carriers were determined by the dependence of the normalized imaginary part of impedance (Z''/Z''Max) and modulus (M''/M''Max) on the frequency and the relation f/fMax, respectively. This suggests the relation of low-temperature dielectric relaxation with the grain defects, the short-range mobility, and the singly ionized oxygen vacancies; moreover, the intermediate temperature is linked with the grain boundary, the long-range mobility charge, and doubly ionized oxygen vacancies. [ABSTRACT FROM AUTHOR]

Some recent theories about the origins and maintenance of regular physical activity focus on the rewards of the properties of practicing this activity. Animal and human studies have demonstrated that mesolimbic dopamine plays a crucial role in the involvement in voluntary physical activity. Here, we test this possible role in a sample of 66 right-handed healthy young adults by studying the influence of personality and the volume of reward-related brain areas on individual differences in voluntary physical activity, objectively measured by accelerometer and subjectively self-reported by questionnaire. Our results show that a smaller volume of the right anterior cingulate cortex and lower scores on reward sensitivity contributed to explaining low levels of daily physical activity. Moreover, the volume of the right anterior cingulate cortex correlates positively with self-reported total physical activity. Results are discussed by highlighting the need to use objective measures of daily physical activity, as well as the important role of the anterior cingulate cortex and personality in promoting effortful and invigorating actions to obtain rewards. In a cohort of right-handed young adults, the volume of the right anterior cingulate cortex positively correlates with self-reported physical activity. [ABSTRACT FROM AUTHOR]

An analysis of the sensitivity of the electrical resistance to temperature changes in cobalt-doped lanthanum-strontium manganite was carried out to provide new insight into the effects of the magnetic interactions between cobalt and manganese ions on the electric properties. Cobalt-doped lanthanum-strontium manganites, La0.7Sr0.3CoxMn1−xO3 with x ranging from 0 to 0.1 (Δx = 0.025), were synthesized by high-energy ball milling for 5 h, followed by annealing at 1673 K. X-ray diffraction showed the presence of a rhombohedral phase for all the studied compositions, indicating a decrease in the bandwidth as the cobalt content increased. The Curie temperature, determined by vibrating sample magnetometry, and the insulator-metal transition temperature, determined by electrical measurements, decrease near to room temperature with increases cobalt content up to 0.1 by weakening the double exchange magnetic interaction. The results confirmed that cobalt increased the temperature coefficient of resistance for the doped manganites by up to 15.6% for 0.1 mol of cobalt near room temperature. Therefore, these materials will prove useful for the development of specialized sensing devices such as bolometers. [ABSTRACT FROM AUTHOR]

Potato black dot is a foliar and tuber blemish disease that has become an increasingly economic problem in recent years. Black dot is caused by the fungus Colletotrichum coccodes and is characterised by silver/brown lesions on the tuber skin leading to lower aesthetic quality of potatoes destined for the pre-pack market. Given the consumers' growing demand for washed and pre-packed potatoes, skin blemish diseases (such as black dot and silver scurf), once considered of minor importance, are now serious challenges for the fresh potato industry. The management of C. coccodes is far from satisfactory at either pre- or postharvest stages: firstly, the disease symptoms have not been consistently described on potato plant foliage; and secondly, black dot disease is often confounded with other tuber blemishes during postharvest storage. Good field managing practices in combination with improved postharvest strategies and an accurate detection support tool can be a useful integrated approach to manage potato black dot disease. This review aims to evaluate and critically discuss different novel approaches for better management and detection of potato black dot disease. [ABSTRACT FROM AUTHOR]

In multi-Higgs-doublet models, requiring simultaneously that (i) CP violation only arises spontaneously, (ii) tree level scalar flavour changing couplings are absent and (iii) the fermion mixing matrix is CP violating, can only be achieved in a very specific manner. A general approach with new clarifying insights on the question is presented. Considering the quark sector, that peculiar possibility is not viable on phenomenological grounds. We show that, considering the lepton sector, it is highly interesting and leads to viable models with μ - τ symmetric PMNS matrices. Phenomenological implications of the models, both for Dirac and Majorana (in a type I seesaw scenario) neutrinos, are analysed. [ABSTRACT FROM AUTHOR]

Let (X, L) be a polarized smooth projective variety. For any basepoint-free linear system L V with V ⊂ H 0 (X , O X (L)) , we consider the syzygy bundle M V as the kernel of the evaluation map V ⊗ O X → O X (L) . The purpose of this article is twofold. First, we assume that M V is L-stable and prove that, in a wide family of projective varieties, it represents a smooth point [ M V ] in the corresponding moduli space M . We compute the dimension of the irreducible component of M passing through [ M V ] and whether it is an isolated point. It turns out that the rigidness of [ M V ] is closely related to the completeness of the linear system L V . In the second part of the paper, we address a question posed by Brenner regarding the stability of M V when V is general enough. We answer this question for a large family of polarizations of X = P m × P n . [ABSTRACT FROM AUTHOR]

In this paper, we introduce the notion of a Klyachko diagram for a monomial ideal I in a certain multi-graded polynomial ring, namely the Cox ring R of a smooth complete toric variety, with irrelevant maximal ideal B. We present procedures to compute the Klyachko diagram of I from its monomial generators, and to retrieve the B −saturation Isat of I from its Klyachko diagram. We use this description to compute the first local cohomology module H B 1 (I) . As an application, we find a formula for the Hilbert function of Isat, and a characterization of monomial ideals with constant Hilbert polynomial, in terms of their Klyachko diagram. [ABSTRACT FROM AUTHOR]

In recent decades, many sectors of our society have been digitized, and much of our life has moved to cyberspace, especially in terms of entertainment. Users meet, relate, and cooperate in the new public space that is the internet and form digital communities. Video games play a leading role in the formation of such communities. However, these communities also present antisocial behaviors, ranging from disruptive actions to harassment and hate speech. Such behaviors, encompassed under the umbrella term toxicity, are a major concern for both users and those in charge of moderating these spaces. This article focuses on toxicity in today's leading online video game League of Legends. Three hundred twenty-eight matches were reviewed using a system of two judges to study the prevalence of these problematic behaviors. We find that 70% of matches were affected by disruptive behavior. Nevertheless, only 10.9% of the analyzed matches were exclusively affected by downright harmful behavior. In our view, the results have relevant implications for content moderation policy that are also addressed in this paper. [ABSTRACT FROM AUTHOR]

The emergence of algorithmic tools and Artificial Intelligence and their use in criminal justice has raised a relevant theoretical and political debate. This article unpacks and synthesizes the debate on the role of causality for the scientific method to analyze predictive decision support systems, their practical value and epistemic problems. As a result of this discussion, it is argued that the measured usage of theory and causation-based algorithms is preferable over correlational (i.e., causally opaque) algorithms as support tools in the penal system. At the same time, the usage of the latter is supported when it is critically accompanied by abductive reasoning. Finally, the arguments put forth in this article suggest that the field of criminology needs a deeper epistemological understanding of the scientific value of data-driven tools in order to entertain a serious debate on their use. [ABSTRACT FROM AUTHOR]

Introduction: Spondylodiscitis secondary to colposacropexy is an extremely rare entity. Infection and mesh rejection are the main causes. Removal of the mesh is essential for patient's recovery and it can be a very challenging surgical procedure. Case: A 72-year-old woman presented with severe low back pain in the context of a recent colposacropexy. Magnetic resonance imaging was performed and spondylodiscitis secondary to prolapse correction surgery with mesh was suspected. In order to ensure an adequate recovery, removal of the mesh was required. Conclusions: Spondylodiscitis secondary to colposacropexy should be suspected when the patient starts with moderate lumbar pain and is not correctly controlled with first-level analgesia. Infection or mesh rejection should be considered. Mesh rejection should be suspected when the patient does not improve after antibiotics. Complete removal of the mesh is needed in order to ensure the patient's recovery. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to conduct a meta-analysis of prospective studies assessing the relationship between bundle branch block (BBB) or wide QRS and risk of all-cause mortality in patients with acute heart failure (AHF). Methods and results: We searched the PubMed, Scopus and Web of Science database from inception to February 2022 to identify single centre or multicentre studies including a minimum of 400 patients and assessing the association between BBB or wide QRS and mortality in patients with AHF. Study-specific hazard ratio (HR) estimates were combined using a random-effects meta-analysis. Two meta-analyses were performed: (1) grouping by conduction disturbance and follow-up length and, (2) using the results from the longest follow-up for each study and grouping by the type of BBB. The meta-analysis included 21 publications with a total of 116,928 patients. Wide QRS (considering right (RBBB) and left (LBBB) altogether) was associated with a significant increment in the risk of all-cause mortality (pooled adjusted HR 1.112, 95% CI 1.065–1.160). The increased risk of death was also present when LBBB (HR 1.121, 95% CI 1.042–1.207) and RBBB (HR 1.187, 95% CI 1.045–1.348) were considered individually. There was no difference in risk between LBBB and RBBB (P for interaction = 0.533). Other outcomes including sudden death, rehospitalization and a combination of cardiovascular death or rehospitalization were also increased in patients with BBB or wide QRS. Conclusions: This meta-analysis suggests a modest increase in the risk of all-cause mortality among patients with AHF and BBB or wide QRS, irrespective of the type of BBB. [ABSTRACT FROM AUTHOR]

Oropharyngeal dysphagia (OD) is underdiagnosed and current screening is costly. We aimed: (a) to develop an expert system (ES) based on machine learning that calculates the risk of OD from the electronic health records (EHR) of all hospitalized older patients during admission, and (b) to implement the ES in a general hospital. In an observational, retrospective study, EHR and swallowing assessment using the volume-viscosity swallow test for OD were captured over 24 months in patients > 70 yr admitted to Mataró Hospital. We studied the predictive power for OD of 25,000 variables. ES was obtained using feature selection, the final prediction model was built with non-linear methods (Random Forest). The database included 2809 older patients (mean age 82.47 ± 9.33 yr), severely dependent (Barthel Index 47.68 ± 31.90), with multiple readmissions (4.06 ± 7.52); 75.76% had OD. The psychometrics of the ES built with a non-linear model were: Area under the ROC Curve of 0.840; sensitivity 0.940; specificity, 0.416; Positive Predictive Value 0.834; Negative Predictive Value 0.690; positive likelihood ratio (LH), 1.61 and negative LH, 0.146. The ES screens in 6 s all patients admitted to a 419-bed hospital, identifies patients at greater risk of OD, and shows the risk for OD in the clinician's workstation. It is currently in use at our institution. Our ES provides accurate, systematic and universal screening for OD in real time during hospital admission of older patients, allowing the most appropriate diagnostic and therapeutic strategies to be selected for each patient. [ABSTRACT FROM AUTHOR]

The popularization of social media has led to a considerable increase in the importance of discursive expressions of violence, especially when directed at vulnerable communities. While social media platforms have created rules to regulate such expressions, little information is available on the perception of the legitimacy of these rules in the general population, regardless of the importance of the former for the latter. It is therefore the objective of this study to analyze the perception of the seriousness of such content and the degree to which the population has established a consensus on the withdrawal of restricted discursive behaviour on three major social media platforms (Facebook, Instagram and Twitter). For this purpose, 918 participants were immersed in an experimental paradigm in three different groups (n1 = 302; n2 = 301; n3 = 315). Each was presented with stimuli containing discursive behaviour that is banned by community guidelines. The stimuli were presented differently to each group (i.e., description of the banned behaviour, description and accompanying example, example only). Our experimental data reveals that the degree of consensus on the need to remove content is quite high, regardless of the style of presentation. It furthermore suggests that the behaviour in question is perceived as very serious, due to the harm that our participants presume it to cause. These results have important implications for the debate on freedom of expression on the Internet and its regulation by private actors. [ABSTRACT FROM AUTHOR]

We outline a procedure for applying Hamiltonian Truncation to Quantum Field Theories (QFTs) that have UV divergences. To do this, we derive a novel representation of an Effective Hamiltonian which makes manifest some of its important properties (e.g. the non-perturbative matching of the spectra between the UV theory and the theory described by the Effective Hamiltonian). We check the consistency of our procedure using Conformal Perturbation Theory. Finally we comment on how the Effective Hamiltonian, which incorporates non-local interactions, describes a local QFT. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111–142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111–142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111–142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111–142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of infection and inflammation. Thus, HBA(111–142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during bacterial or viral infection and may play an important role in innate antimicrobial immune responses. [ABSTRACT FROM AUTHOR]

Purpose: Molecular analysis of peritoneal fluid in staging laparoscopy of gastric cancer is performed to improve the detection of free intraperitoneal tumor cells. Nevertheless, its significance is controversial, especially in patients with negative cytology but positive molecular analysis. The aim of this study was to analyze the sensitivity of molecular analysis and its prognostic value. Methods: A retrospective analysis from April 2011 to October 2019 was performed. Cytology (Cyt) and molecular analysis were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) of the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) tumor makers. Results: During the study period, 138 staging laparoscopies were performed. Macroscopic carcinomatosis was found in 12.3%. Of the remaining 87.7%, 9.9% were Cyt + and 11.6% were Cyt- RT-PCR +. Of the latter, 9 responded to chemotherapy and underwent radical surgery. The sensitivity of cytology and molecular analysis was 0.70 and 0.76, respectively (p = 0.67). The 2-year overall survival (OS) of Cyt- RT-PCR + vs. Cyt + was similar (p = 0.1). The 2-year OS of Cyt-RT-PCR + subgroup who underwent radical surgery vs. Cyt-RT-PCR- patients was similar (p = 0.69), but disease-free survival was shorter in the first group (p = 0.005). Conclusion: Our results show that the sensitivity of molecular analysis is similar to that of cytology. The prognostic value of positive molecular analysis was similar to positive cytology in terms of 2-year overall survival, except in the subgroup of operated patients in whom the overall survival was similar to that of those with a negative molecular analysis, albeit with a shorter disease-free survival. [ABSTRACT FROM AUTHOR]

Fenbendazole (FBZ), a benzymidazole (BZD) anthelmintic drug, is used for in-feed medication in pigs. BZD-containing drugs may induce cytochrome P450 isozymes (CYPs), particularly those members of the CYP1A subfamily. The current research evaluated the plasma and liver availability and metabolism of FBZ and its metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), after the administration of the parent drug in feed, and characterized the effect of the sustained administration of the anthelmintic on the catalytic activities of xenobiotic metabolizing enzymes in pig liver. Five female Landrace piglets remained untreated (controls), and other six were treated with a pre-mix of FBZ, combined with feed, for 9 consecutive days as usually is recommended. Blood samples were collected from each treated animal up to day 9 and analyzed by HPLC; all animals were slaughtered for preparation of liver microsomes. Plasma concentration ratios OFZ/FBZ and FBZSO2/OFZ increased significantly (p < 0.05) from the beginning to the end of drug exposure, which may indicate an enhanced conversion of FBZ into its metabolites. FBZ represented 45.8 ± 3.4% of the total anthelmintic molecules in liver tissue. Increased CYP1A-dependent 7-ethoxy (24.5-fold, p = 0.0032) and 7-methoxyresorufin (17.2-fold, p = 0.0006) O-dealkylase activities was observed in liver microsomes from FBZ-treated animals. In addition, a 64% increase (p = 0.042) in the rate of FBZ S-oxidation was observed in pigs treated with the anthelmintic drug compared to that measured in untreated animals. Thus, the continuous FBZ administration may accelerate its own in vivo hepatic metabolism through the CYP1A pathway. [ABSTRACT FROM AUTHOR]