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We discuss the HCN + H ^− reaction as a path to the formation of CN ^− , the smallest cyanopolyyne anion observed in several interstellar environments. We first obtain the new ab initio reactive potential energy surface using a full 5D representation, where only the C–N bond is kept fixed, and discuss the neural network procedure employed to yield an accurate fit for the dynamics. The reaction is then investigated by using a quasi-classical trajectory approach to scan the low-temperature range of the dark molecular clouds where the anion has been sighted. Calculations are extended to room temperature to make a successful comparison with existing experimental data. We further present reduced dimensionality modeling of the reaction as a 2D process within a variational-transition state treatment with the inclusion of long-range forces. The dominant role of such forces in producing large reaction rate coefficients is discussed for both treatments, which yield very similar sizes and behavior of such coefficients from 50 to 300 K. The implications of our results for the interstellar medium formation of the CN ^− species via this chemical route are discussed, suggesting its greater significance over the radiative electron attachment paths, whose rate coefficients were found by recent calculations to be orders of magnitude smaller.

The work proposes a modified method for obtaining phycocyanin concentrate including extraction of biomass of the food cyanobacterium Arthrospira platensis and subsequent stages of membrane processing, involving combined use of double microfiltration and single- stage ultrafiltration. Extraction of A. platensis biomass was carried out at a temperature of +40°C for 3 hours in potassium phosphate buffer, and the purity of the extract was 0.61. Double microfiltration of the extract and ultrafiltration increased the purity of the intermediate product to 2.7. The content of C-phycocyanin and allophycocyanin in the dry concentrate was (63.6±1.0)% and (4.3±0.4)%, respectively. The molecular weight distribution of protein and peptide fractions of intermediate and final products was characterized using high-pressure size exclusion liquid chromatography.

Analysing message streams in a dynamic environment is challenging. Various methods and metrics are used to evaluate message classification solutions, but often fail to realistically simulate the actual environment. As a result, the evaluation can produce overly optimistic results, rendering current solution evaluations inadequate for real-world environments. This paper proposes a framework based on the simulation of real-world message streams to evaluate classification solutions. The framework consists of four modules: message stream simulation, processing, classification and evaluation. The simulation module uses techniques and queueing theory to replicate a real-world message stream. The processing module refines the input messages for optimal classification. The classification module categorises the generated message stream using existing solutions. The evaluation module evaluates the performance of the classification solutions by measuring accuracy, precision and recall. The framework can model different behaviours from different sources, such as different spammers with different attack strategies, press media or social network sources. Each profile generates a message stream that is combined into the main stream for greater realism. A spam detection case study is developed that demonstrates the implementation of the proposed framework and identifies latency and message body obfuscation as critical classification quality parameters.

Oxidative stress is characterized by an increase in reactive oxygen species or a decrease in antioxidants in the body. This imbalance leads to detrimental effects, including inflammation and multiple chronic diseases, ranging from impaired wound healing to highly impacting pathologies in the neural and cardiovascular systems, or the bone, amongst others. However, supplying compounds with antioxidant activity is hampered by their low bioavailability. The development of biomaterials with antioxidant capacity is poised to overcome this roadblock. Moreover, in the treatment of chronic inflammation, material-based strategies would allow the controlled and targeted release of antioxidants into the affected tissue. In this review, we revise the main causes and effects of oxidative stress, and survey antioxidant biomaterials used for the treatment of chronic wounds, neurodegenerative diseases, cardiovascular diseases (focusing on cardiac infarction, myocardial ischemia-reperfusion injury and atherosclerosis) and osteoporosis. We anticipate that these developments will lead to the emergence of new technologies for tissue engineering, control of oxidative stress and prevention of diseases associated with oxidative stress.

Free-electron lasers are capable of high repetition rates and it is assumed that protein crystals often do not survive the first X-ray pulse. Here the authors address these issues with a demonstration of multi-hit serial crystallography in which multiple FEL pulses interact with the sample without destroying it.

Interleukin-6 (IL-6) is one of the most important pro-inflammatory markers with immunomodulatory activity associated with schizophrenia. The possible involvement of interleukin-6 in the etiopathogenesis of schizophrenia and the development of different clusters of symptoms remains debatable; the relationship between an increase in interleukin-6 and a number of possible confounding factors, including smoking, has not yet been studied. The aim of this work was the pilot evaluation of the serum IL-6 level in patients with schizophrenia compared with healthy controls, as well as its association with clinical symptoms, socio-demographic factors and smoking. Materials and methods: 43 patients with schizophrenia and 24 healthy volunteers were examined. The determination of IL-6 was carried out by enzyme immunoassay. All patients were assessed using the Positive and Negative Schizophrenia Syndrome Scale (PANSS), The UKUSERS-Clin Therapeutic Side Effects Scale (UKU), Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), Barnes Akathisia Scale (BARS), Personal and Social Functioning Scale (PSP). Results: In patients with schizophrenia in a Russian sample, serum IL-6 levels were significantly associated with smoking status (p = 0.0017), the severity of negative symptoms and symptoms of the PANSS general psychopathology scale (p=0.014 and p=0.038, respectively), disorders of personal and social functioning (PSP, p=0.011), as well as side effects measured using the UKU scale (general, p=0.038, 0041 and extrapyramidal, p=0.018), as well as drug-induced parkinsonism (p=0.043), dyskinesia (p=0.0084) and akathisia (p=0.043). All scores are worse in patients with nicotine addiction. The occurrence of extrapyramidal symptoms (EPS) in response to standard doses of antipsychotics (AP) can serve as a clinical marker of possible immune-inflammatory disturbances in patients with schizophrenia, and the smoking status can act as a provocing factor for increasing of latent inflammation. Replication of the study is required to confirm the findings.

Abstract There is a strong discrepancy between the value of the Hubble parameter $$H_0^P$$ H 0 P obtained from large scale observations such as the Planck mission, and the small scale value $$H_0^R$$ H 0 R , obtained from low redshift supernovae (SNe). The value of the absolute magnitude $$M^{Hom}$$ M Hom used as prior in analyzing observational data is obtained from low-redshift SNe, assuming a homogeneous Universe, but the distance of the anchors used to calibrate the SNe to obtain M would be affected by a local inhomogeneity, making it inconsistent to test the Copernican principle using $$M^{Hom}$$ M Hom , since M estimation itself is affected by local inhomogeneities. We perform an analysis of the luminosity distance of low redshift SNe, using different values of M, $$\{M^P,M^R\}$$ { M P , M R } , corresponding to different values of $$H_0$$ H 0 , $$\{H_0^P,H_0^R\}$$ { H 0 P , H 0 R } , obtained from the model independent consistency relation between $$H_0$$ H 0 and M which can be derived from the definition of the distance modulus. We find that the value of M can strongly affect the evidence of a local inhomogeneity. We analyze data from the Pantheon catalog, finding no significant statistical evidence of a local inhomogeneity using the parameters $$\{M^R,H_0^R\}$$ { M R , H 0 R } , confirming previous studies, while with $$\{M^P,H_0^P\}$$ { M P , H 0 P } we find evidence of a small local void, which causes an overestimation of $$M^R$$ M R with respect to $$M^P$$ M P . An inhomogeneous model with the parameters $$\{M^P,H_0^P\}$$ { M P , H 0 P } fits the data better than a homogeneous model with $$\{M^R,H_0^R\}$$ { M R , H 0 R } , resolving the apparent $$H_0$$ H 0 tension. Using $$\{M^P,H_0^P\}$$ { M P , H 0 P } , we obtain evidence of a local inhomogeneity with a density contrast $$-0.140 \pm 0.042 $$ - 0.140 ± 0.042 , extending up to a redshift of $$z_v =0.056 \pm 0.0002$$ z v = 0.056 ± 0.0002 , in good agreement with recent results of galaxy catalogs analysis (Wong et al. in The local hole: a galaxy under-density covering 90 mpc, 2021).

Practical density functional theory (DFT) owes its success to the groundbreaking work of Kohn and Sham that introduced the exact calculation of the non-interacting kinetic energy of the electrons using an auxiliary mean-field system. However, the full power of DFT will not be unleashed until the exact relationship between the electron density and the non-interacting kinetic energy is found. Various attempts have been made to approximate this functional, similar to the exchange–correlation functional, with much less success due to the larger contribution of kinetic energy and its more non-local nature. In this work, we propose a new and efficient regularization method to train density functionals based on deep neural networks, with particular interest in the kinetic-energy functional. The method is tested on (effectively) one-dimensional systems, including the hydrogen chain, non-interacting electrons, and atoms of the first two periods, with excellent results. For atomic systems, the generalizability of the regularization method is demonstrated by training also an exchange–correlation functional, and the contrasting nature of the two functionals is discussed from a machine-learning perspective. [ABSTRACT FROM AUTHOR]

La educación STEM es un enfoque que busca responder a las demandas de una sociedad altamente digitalizada y con problemas emergentes que no se resuelven desde un solo campo disciplinar. En Colombia han proliferado iniciativas desde distintos sectores, aún aisladas y con pocos reportes en la educación superior, particularmente en la formación inicial de profesores. Por esta razón, este artículo tuvo como objetivo analizar las comprensiones y apropiaciones del enfoque educativo STEM/STEAM en el país desde la formación profesional. Para ello, se realizó una revisión crítica de trabajos de pregrado a partir de las siguientes categorías: finalidades, acrónimos y denominaciones; integración de las disciplinas; objetivos de aprendizaje; y estrategias para su implementación. Como resultado, se encontró una preferencia por el uso del acrónimo STEM, y se resaltó la interdisciplinariedad como el nivel de integración pretendido en el diseño de experiencias de aula, pero al mismo tiempo se reconocieron desafíos para su consecución, así como discusiones aún limitadas acerca de la manera en que podrían constituirse relaciones significativas entre las disciplinas del acrónimo STEM/STEAM.

Introduction Outpatient centers offer specialized care to users with severe psychiatric disorders. The usual group activities of outpatient centers have been shown to be effective in the child and adolescent population. There are significant access limitations to these services and one way to expand coverage is through digital care. However, there are no studies on digital outpatient care services in Chile. The present study is part of the preparatory phase of a future randomized clinical trial to investigate the effectiveness of digital adaptation of outpatient centers interventions. Objectives To explore the experience and subjective perception of the pilot intervention participants by identifying central themes, and to evaluate the participant's satisfaction regarding the intervention. Methods Of the 13 users of the digital group activities, 10 participated in this study. Semi-structured interviews and satisfaction surveys were conducted between August 2020 and January 2021. The interviews were evaluated using content analysis and the surveys were conducted using descriptive statistics. Conclusions Results Participants were particularly appreciative of positive social interactions (with peers and therapists). There is a general perception of having improved socioemotional skills and mood. The digital implementation was satisfactory for most participants, who suggested adding activities that promote deeper interactions with their peers. The core elements of this intervention would be the perception of social support (a possible therapeutic mechanism), along with the feeling of improved social skills and mood (possible main outcome).

Summary: Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. Inhibition of UTX/KDM6B enzymatic activity condenses chromatin structure, prevents MRTF-A binding, blocks activation of the pro-fibrotic transcriptome, and results in an inhibition of fibrosis in lens and lung fibrosis models. Our work reveals UTX/KDM6B as central coordinators of fibrosis, highlighting the potential to target its demethylase activity to prevent organ fibrosis.

SC 100 Estudo Multidimensional dos Centenários de Santa Catarina. Objetivo: analisar as percepções de qualidade de vida de idosos centenários mediante atividades físicas e lazer. N: 124. Critérios de inclusão: cognição preservada e utilizar pedômetro por 7 dias. n:17, média de idade 101,53 (DP=2,00, (ativos ≥1000 e insuficientemente ativos ≤999, passos/semanais). Foram realizadas entrevista e análise de conteúdo sobre atividades de lazer e qualidade de vida. 10 centenários ativos e sete insuficientemente ativos. Lazer: assistir televisão (n=9), insuficientemente ativos (n=6) e ativo (n=3). Insuficientemente ativos e suas atividades de lazer: assistir televisão, escutar rádio e música, ler e jogar baralho. Ativos: visitar familiares, jardinagem, dançar, ir à igreja e cavalgar. Centenários com cognição preservada e ativos apresentam um lazer fora do ambiente domiciliar e maiores relações sociais.

Introduction Non-suicidal self-injury (NSSI) – the deliberate, self-directed damage of body tissue without suicidal intent and for purposes not socially or culturally sanctioned – is a highly prevalent phenomenon in adolescents and young adults. Motivation for the NSSI is known to be heterogenous in different patients. However, biological and especially genetic markers associated with different motivation for the NSSI have not been studied to date. One of the possible candidates are mu- (OPRM1) and kappa-opioid receptor (OPRK1) genes, since opioid system is known to be involved in the NSSI. Another perspective candidate is the DCC gene, encoding the netrin 1 receptor, which plays vital part in the formation of the prefrontal cortex. Objectives We conducted a pilot cross-sectional study to test the impact of the rs1779971 OPRM1, rs6473797 OPRK1 and rs8084280 DCC gene polymorphisms on the characteristics and motivations for the NSSI in young adults. Methods 28 patients of European ancestry with NSSI (89,3%; n=25) women, median age (Q1-Q3) – 23 (21,25-25) years) were included in the pilot sample. The majority of the sample had a diagnosis of bipolar disorder (78,6%; n=20). Characteristics and motivation for the NSSI were measured by the Inventory of Statements about Self-Injury (ISAS). The Childhood Trauma Questionnaire (CTQ) was used to control for adverse childhood experiences, a potent environmental factor, associated with NSSI. Genotyping was performed using RT-PCR. The genetic effect was evaluated using the dominant model. For statistical analysis multiple linear regression with the presence of minor alleles, different types of childhood trauma, diagnosis, age and sex as factors and ISAS scores as dependent variables were used. Results Multiple linear regression showed that minor C allele of rs6473796 OPRK1 gene polymorphism was associated with an increase of the “Affect regulation” (B=2,23; CI95% [0,39–4,06]; p=0,022), “Anti-dissociation” (B=3,31; CI95% [0,18–6,44]; p=0,039) subscales of ISAS scores. Moreover, the minor T allele of the rs8082480 DCC gene polymorphism was associated with a decrease of the “Affect regulation” subscale score (B=-1,74; CI95% [-3,30 – -0,18]; p=0,032). Conclusions To our knowledge, this is the first study on the genetic markers of motivations for NSSI. Our pilot results showed that, controlling for diagnosis, age, sex and childhood trauma, OPRK1 and DCC gene polymorphisms may be associated with the heterogeneity of motivations for NSSI. However, these results require confirmation on the larger samples. Disclosure of Interest None Declared

COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Introduction and Objectives: Cryptogenic chronic hepatitis is an increasing cause of liver transplantation and affects 5-15% of patients with chronic liver diseases. This study aimed to investigate possible underlying causes of presumed cryptogenic liver disease referred to specialized liver centers by general practitioners in Brazil and to propose a new diagnostic algorithm including metabolic-dysfunction-associated fatty liver disease (MAFLD) definition and lysosomal acid lipase deficiency (LAL-D) investigation. Materials and Methods: A retrospective multicentric Brazilian cohort of patients with presumed chronic cryptogenic hepatitis was reanalyzed with respect to their clinical, laboratory and histological data using Czaja´s algorithm (2011). Results: 326 patients [mean age 60 (46-68) years, 42.9% males] were initially included, 35.7% with cirrhosis. Forty-five individuals were excluded due to an incomplete etiological investigation. Using Czaja´s algorithm, diagnosis of nonalcoholic fatty liver disease could be established in 60 patients (21.3%), alpha-1-antitrypsin deficiency in 9 (3.2%), alcoholic liver disease in 7 (2.7%), autoimmune hepatitis in 5 (1.78%), hemochromatosis in 5 (1.78%), biliary-related hepatitis in 4 (1.4%), viral hepatitis in 4 (1.4%), Budd Chiari in 4 (1.4%), glycogenosis in 3 (1%), drug-induced liver injury in 2 (0.7%), and Wilson disease in 1 (0.35%). LAL-D was demonstrated in 3 individuals (1%). One hundred seventy-five patients remained with cryptogenic hepatitis (53.6%) (FIGURE A). During follow-up, 40 of those patients were submitted to liver transplantation and 19 (47.5%) were retrospectively diagnosed with non-alcoholic steatohepatitis after histopathological examination of the explanted liver. By including MAFLD in the first step of the new algorithm, 100 patients would have been diagnosed (34.9%), reducing the number of individuals without a diagnosis by 18.3% (FIGURE B). Conclusions: One-third of patients with initially presumed cryptogenic liver disease were diagnosed with MAFLD. Despite being a rare disease, LAL-D investigation should be considered for individuals with chronic liver disease of unknown etiology. An updated diagnostic algorithm is proposed for those individuals.

Introduction and Objectives: Chronic infection with hepatitis C virus (HCV) still affects millions of people around the world despite the recent development of very effective direct-acting antiviral (DAA) treatment. Even after a high cure rate, patients with advanced fibrosis should remain under surveillance due to the high risk of developing hepatocellular carcinoma. This study aimed to evaluate the prevalence and risk factors for hepatocellular carcinoma development in previously treated chronic HCV patients in an outpatient hepatology clinic at Clinic Hospital of the University of São Paulo of School Medicine in the city of São Paulo. Materials and Methods: This is a retrospective, observational and descriptive study of a series of cases in which 410 HCV patients were treated with three different antiviral regiments: Interferon plus Ribavirin (INF + RBV) or Protease Inhibitors (PI) or DAA, were followed for up to ten years (2011-2021). Demographic, clinical and laboratory data were obtained for electronic medical records. Results: the total sample of this study consists of 402 patients. Table 1 shows the patient demographic and clinical data. Of the 35 patients who developed HCC, 26 (74%) had F4-degree fibrosis. Logistic regression model was performed with the following variables: BMI (p=0.005), positive anti-HBC IgG (p=0.015), combination fibrosis and CHIILD-PUGH score A (p=0.001), B (p=0.012) and C(p< 0.001). Conclusions: In our cohort, obesity and anti-HBc IgG were significantly associated with a high risk of developing HCC. The type of antiviral treatment (IFN or DAA-based) was not associated with the risk of HCC.

Currently, there is little published data on the effects of antidepressants on normal gut microbiota and the consequences of such effects on treatment outcomes.The aim of the study: was to evaluate the growth kinetics of normal human gut microorganisms with antidepressants most common in routine clinical practice.Materials and methods: Research objects were species of microorganisms representing normal gut microbiota: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Candida albicans ATCC 24433, Bifidobacterium 791, Enterococcus faecalis ATCC 29212, Lactobacillus rhamnosus ATCC 53103. All microorganisms were cultivated in Schaedler broth (HiMedia) under aerobic/anaerobic conditions. The active substances of all studied antidepressants (fluvoxamine, fluoxetine, escitalopram, duloxetine, venlafaxine, mirtazapine) were extracted from ground preparations by dimethyl sulfoxide and centrifuged. Each solution of antidepressants was added to a Schaedler broth containing a certain microorganism’s strain and diluted to final concentrations—200 μg/ml, 500 μg/ml, and 700 μg/ml. For a quantitative assessment of the effect, the specific growth rates (μ, h-1) of microorganisms were calculated as the slope of the initial part of the growth curve in coordinates (lnA, t). To evaluate the antidepressant effects on representatives of the normal microbiota in vitro, the following parameters were chosen: specific growth rate and IC50.Results: All antidepressants had an inhibitory effect on the growth of all studied microorganisms. Fluvoxamine and venlafaxine had the least effect on the growth activity of all studied microorganisms. Fluoxetine showed a pronounced effect on growth activity against E. coli, E. feacalis, S. aureus, and the least effect against C. albicans. Escitalopram had a greater effect on the growth rate of E. coli, E. feacalis, B. bifidum, L. rhamnosus, and C. albicans, which puts it among the leaders in terms of its effect on the growth activity of the microorganisms we studied. Mirtazapine, according to the results of our experiment, showed the greatest activity against L. rhamnosus and C. albicans.Conclusions: Our results confirm the effects of antidepressants on the growth activity of the normal gut microbiota individual strains. Further study of the antimicrobial activity of antidepressants may become one of the new directions for optimizing the personalized therapy of patients with depression.

Introducción: el síndrome inflamatorio de reconstitución inmune es una complicación clínica dada en algunas personas infectadas con el virus de la inmunodeficiencia humana (VIH) luego de empezar la terapia antirretroviral; se destaca por la producción de citoquinas proinflamatorias, que se han estudiado como posibles biomarcadores que puedan orientar para el diagnóstico y pronóstico de esta condición clínica. Objetivo: llevar a cabo una revisión actualizada de los avances en los biomarcadores para el diagnóstico de SIRI, resaltando la importancia de las moléculas inflamatorias y los exosomas, tanto en su patogénesis como un posible Gold estándar para la confirmación de este estado inflamatorio. Metodología: se realizó una revisión bibliográfica en bases de datos, como Science Direct, PubMed, Scopus y Medline, partiendo de los siguientes términos MeSH: síndrome inflamatorio de reconstitución, enfermedades del sistema inmune, biomarcadores, fármacos antiVIH, plasma. Conclusión: cada vez existen más avances en la identificación de moléculas que pueden servir como biomarcadores de SIRI, buscando un oportuno diagnóstico, monitoreo de la progresión clínica, mejor respuesta al tratamiento y más hallazgos sobre la fisiopatología, pero persiste la necesidad de encontrar un Gold estándar que proporcione criterios para su sospecha y confirmación.