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Multiple prediction models for risk of in-hospital mortality from COVID-19 have been developed, but not applied, to patient cohorts different to those from which they were derived. The MEDLINE, EMBASE, Scopus, and Web of Science (WOS) databases were searched. Risk of bias and applicability were assessed with PROBAST. Nomograms, whose variables were available in a well-defined cohort of 444 patients from our site, were externally validated. Overall, 71 studies, which derived a clinical prediction rule for mortality outcome from COVID-19, were identified. Predictive variables consisted of combinations of patients′ age, chronic conditions, dyspnea/taquipnea, radiographic chest alteration, and analytical values (LDH, CRP, lymphocytes, D-dimer); and markers of respiratory, renal, liver, and myocardial damage, which were mayor predictors in several nomograms. Twenty-five models could be externally validated. Areas under receiver operator curve (AUROC) in predicting mortality ranged from 0.71 to 1 in derivation cohorts; C-index values ranged from 0.823 to 0.970. Overall, 37/71 models provided very-good-to-outstanding test performance. Externally validated nomograms provided lower predictive performances for mortality in their respective derivation cohorts, with the AUROC being 0.654 to 0.806 (poor to acceptable performance). We can conclude that available nomograms were limited in predicting mortality when applied to different populations from which they were derived.

A summary on Psychology as science and profession in Argentina is presented. The report includes a historical review on places, criteria and results of psychologists'education, aspects of their professional practices; quantitative data on universities, graduates and students related to sociodemographic variables; characteristics of research activities, publications, legal frameworks and types of institutions where psychologists work. Some distinctive features of Argentine psychology are mentioned, including problems and developmental perspectives.

ince the beginning of Psychology as an university career, 55853 graduate student have obtained their degree as a psychologist. These professionals studied in 34 universities (7 federal and 27 private universities). 46777 psychologists in activity have been detected up to date. Graduate psychologists who are not in activity are 9076. University psychology students are 56387. In 2005, 12268 have started these studies in the field. Taking into account the amount of graduate psychologists related to national population it yields 154 psychologists every 100.000 citizens or in other way 649 inhabitants per psychologist.

Las pretensiones del autor son: (i) Describir la versión modal de la prueba ontológica propuesta por Charles Hartshorne, una versión que enfatiza la anomalía modal del concepto de Dios, que demuestra que las dos únicas alternativas metafísicas coherentes son el positivismo y un teísmo basado en la noción de “necesidad bajo condiciones tautológicas”, y que vindica esta última opción apelando a una filosofía del proceso inspirada en Whitehead y cuya herramienta conceptual básica es la distinción entre existencia y actualidad. (ii) Evaluar la propuesta de Hartshorne, defendiéndola frente a equivocaciones frecuentes y desarrollándola en al menos dos aspectos, incluyendo un análisis del proyecto de Russell de reducir las proposiciones modales a enunciados de alcance, y proponiendo una concepción iterativa de la modalidad. (iii) Reivindicar la actitud filosófica de Hartshorne, un racionalismo circunspecto que evita el reduccionismo sin temer el conocimiento racional.

Se presentan los resultados de un relevamiento sobre la formación universitaria y la distribución geográfica y ocupacional de los psicólogos en la República Argentina en 2008. Los datos obtenidos muestran que hasta 2008: han egresado de las 40 universidades con carrera de psicología 69004 psicólogos, de ellos, 57631 psicólogos estaban en actividad, a razón de 145 psicólogos cada 100.000 mil habitantes. Estaban estudiando 72533 estudiantes, y durante el año egresaron 4969 psicólogos e ingresaron 14276 estudiantes. Los psicólogos y los estudiantes de psicología representaban aproximadamente un 4% del total de profesionales universitarios y de estudiantes universitarios del país. Género: el 85% son psicólogas. Distribución ocupacional: predomina el ámbito privado sobre el público, y en cuanto al área de trabajo predomina la clínica seguida por educacional, forense, laboral, comunitaria y otras. Se incluye un cuadro comparativo sobre la cantidad de psicólogos en Argentina en relación con otros países.We present the quantitative results of the professional training in Psychology, its geographical and occupational distribution in Argentina until 2008. The data shows that up to 2008 there have been 69004 graduated from the 40 different universities with the Psychology degree. Within the number of graduated people, 57631 psychologists are active, with a ratio of 145 psychologists per 100.000 inhabitants. There are 72533 students. During 2008, 4969 psychologists graduated and 14276 entered to the different universities of Psychology. According to the amount of professionals and students in Argentina, psychologists and students represent a 4% of the population, and 85% are female. Occupational distribution: the private practice predominates over the public services. In respect of the different areas of work, the clinical area predominates over educational, forensic, industrial, community and other areas. Finally, we include a chart of the quantity of psychologists in Argentina compared to the psychologists in other countries.

Las pretensiones del autor son: (i) Mostrar cómo el conservadurismo político se sostiene en una concepción de la naturaleza humana de corte racionalista, que, oponiéndose al modelo antropológico de Hobbes, reconoce tanto el poder de la razón sobre los afectos como una debilidad intrínseca en el hombre que no ha de confundirse con inclinación natural al mal. En este sentido, la política moderada del conservadurismo resulta de su pesimismo mitigado. (ii) Señalar cómo de acuerdo con este paradigma político los criterios de legitimidad política son la protección de las minorías, la preservación de la igualdad de derechos y el mantenimiento de una libertad racional de la que participan por igual todos los miembros del cuerpo político; es decir, cómo la medida de la legitimidad es el imperio de la ley. (iii) Finalmente, subrayar que porque para que exista Estado de derecho la ley no puede estar sujeta a voluntad particular alguna, sea de un individuo o de una mayoría, el conservadurismo es baluarte de una democracia constitucionalista que es condición natural de la naturaleza humana.

El propósito de este artículo es cuestionar la lectura tradicional de las Meditaciones metafísicas, una lectura que, abstrayendo del reto escépticode una reducción de la razón al absurdo al que se enfrenta Descartes,magnifica la prioridad epistémica del argumento del Cogito, y que, haciendocaso omiso de su estrategia anti-escéptica, es incapaz de apreciar que, másque la recopilación de mejores evidencias a favor de las proposicionesnucleares, su función es la de sustraer razones para dudar, de tal forma queel Investigador adquiera una posición ilustrada desde la que los escenariosescépticos carezcan de sentido. Descartes propone una versión modal ometafísica de confiabilismo análoga a la defendida en el panoramacontemporáneo por Ernest Sosa, una posición capaz de superar sincircularidad el escepticismo y que muestra cómo el uso correcto de la razón desemboca en una teoría ontológica que elimina la posibilidad de quenuestras facultades cognitivas no sean fiables.

Multiple prediction models for risk of in-hospital mortality from COVID-19 have been developed, but not applied, to patient cohorts different to those from which they were derived. The MEDLINE, EMBASE, Scopus, and Web of Science (WOS) databases were searched. Risk of bias and applicability were assessed with PROBAST. Nomograms, whose variables were available in a well-defined cohort of 444 patients from our site, were externally validated. Overall, 71 studies, which derived a clinical prediction rule for mortality outcome from COVID-19, were identified. Predictive variables consisted of combinations of patients′ age, chronic conditions, dyspnea/taquipnea, radiographic chest alteration, and analytical values (LDH, CRP, lymphocytes, D-dimer); and markers of respiratory, renal, liver, and myocardial damage, which were mayor predictors in several nomograms. Twenty-five models could be externally validated. Areas under receiver operator curve (AUROC) in predicting mortality ranged from 0.71 to 1 in derivation cohorts; C-index values ranged from 0.823 to 0.970. Overall, 37/71 models provided very-good-to-outstanding test performance. Externally validated nomograms provided lower predictive performances for mortality in their respective derivation cohorts, with the AUROC being 0.654 to 0.806 (poor to acceptable performance). We can conclude that available nomograms were limited in predicting mortality when applied to different populations from which they were derived. [ABSTRACT FROM AUTHOR]

In the last decades, gut microbiota and its role in mammal host development and health have been increasingly investigated. Metabolites produced by gut microbiota can affect intestinal homeostasis and immune system maturity and activation, and in turn, they can influence the health and growth performance of livestock. Therefore, a better understanding of the functional metabolic capability of the gut microbiota would be appreciated by the scientific community. In this study, the BiologTM Ecoplates technology was applied for studying the metabolic potential of the aerotolerant microbial community of pig fecal samples, evaluating the interference of different storage conditions and cell concentrations. The length of time for which a fecal sample maintained detectable and unchanged microbial metabolic activity was also investigated. Two assays aimed to evaluate differences in the metabolic activities between fresh and snap-frozen fecal samples at different dilutions and at different lengths of times of preservation at −80°C were carried out. The biodiversity and the predicted functionality of the entire bacterial community through a targeted metagenomic approach were also explored. The results highlighted that snap freezing of fecal samples preserved the metabolic activity of the microbial community when compared to fresh feces. Sample storage at −80 °C did not significantly affect the metabolic activity of the microbial community, which was stable for 150 days. Furthermore, the highest metabolic activity was detected with 1:2 to 1:5 dilutions of the stock suspension. BiologTM Ecoplates technology is a rapid and useful method to explore microbial communities' metabolism in animal fecal samples contributing to investigate host animal physiology. Key points: • Freezing of samples can preserve the functional activity of the aerotolerant microbial community for 150 days. • The concentration of microbial cells strongly influences metabolic activity detection. • Sequencing coupled with the BiologTMEcoplates could be a strategy to evaluate the metabolic potential of the microbiota of the fecal sample. [ABSTRACT FROM AUTHOR]

Copyright of Revista FAVE is the property of Universidad Nacional del Litoral and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To characterize four novel autochthonous bifidobacteria isolated from monkey faeces and a Bifidobacterium lactis strain isolated from chicken faeces by evaluating their technological and biological/functional potential to be used as probiotics. Different stressors, including food process parameters and storage, can affect their viability and functionality. Methods and Results: The resistance to frozen storage, tolerance to lyophilization and viability during storage, thermal, acidic and simulated gastric resistance, surface hydrophobicity and antimicrobial activity against pathogens were studied. Bifidobacterium lactis Bb12 and INL1 were used as reference strains. The results obtained demonstrated that the new isolates presented strain‐dependent behaviour. Good results were obtained for thermal resistance, frozen storage at −80°C and lyophilized powders maintained at 5°C. Cell viability during refrigerated storage was higher when the strains were resuspended in milk at pH 5·0 than at 4·5. The surface hydrophobicity ranged between 7 and 98% depending on the strain. The simulated gastric resistance was improved for the strains incorporated in cheese. Regarding antimicrobial activity, bifidobacteria isolated from monkey presented higher inhibitory capacity than the reference strains. Conclusion: This research provides a deeper insight into new strains of bifidobacteria isolated from primates and chicken that have not been previously characterized for their potential use in dairy products and confirm the most robust stress tolerance of B. lactis. Significance and Impact of the Study: The possibility of expanding the available bifidobacteria with the potential to be added to a probiotic food necessarily implies characterizing them from different points of view, especially when considering unknown species. For monkey isolates (which showed higher antimicrobial activity against pathogens), more in‐depth knowledge is needed before applying strategies to improve their performance. On the contrary, the chicken isolate B. lactis P32/1 showed similar behaviour to the references B. lactis strains; therefore, it could be considered as a potential probiotic candidate. [ABSTRACT FROM AUTHOR]

Copyright of Arquivo Brasileiro de Medicina Veterinária e Zootecnia is the property of Universidade Federal de Minas Gerais, Escola de Veterinaria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Laguna: Revista de Filosofía is the property of Universidad de La Laguna and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Praxis Filosófica is the property of Universidad del Valle and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sugarcane is one of the most important industries of the Brazilian economy, and its main products are sugar and ethanol. Most of the industrial plants produce both products in an integrated process, in which the sugarcane bagasse is a by-product that can be used as a fuel in the cogeneration system. The bagasse is used as the only fuel of the plant, supplying all energy required for the process, and also producing electricity surplus that may be sold to the grid. In this paper, exergy analysis is used to assess an integrated sugar and ethanol plant with its cogeneration system. The plant was divided into eight sub-systems to evaluate the irreversibility generation in each separately. Data from typical sugarcane factories in Brazil, which produce sugar and ethanol, were used in the process simulation. The analysis has shown that the sub-systems with the highest contribution for the total irreversibility generation of the plant were co-generation, juice extraction and fermentation. Some improvements are proposed, including process thermal integration and the introduction of more efficient equipments for prime mover and steam and electricity generation. The analysis indicated that the total irreversibility could be reduced by 10% should those changes be implemented. [Copyright &y& Elsevier]

Abstract: The rational use of energy became a priority for all industries in Brazil after the energetic rationing in 2001. The aim of this work is to assess a proposal of a power generation system for Companhia Siderúrgica Tubarão, a steel mill plant. The current system is based on a regenerative Rankine cycle using two gases from steel production—blast furnace gas (BFG) and coke oven gas (COG)—to generate electric power and occasionally steam for the process. The proposed system is a combined cycle comprising two gas turbines, two heat recovery steam generators (HRSGs), and a steam turbine. The fuel for the gas turbines is BFG, and the supplementary firing of HRSG uses COG. The proposed HRSGs work at three pressure levels. The system was assessed by means of two thermoeconomic methodologies, Theory of Exergetic Cost and Thermoeconomic Functional Analysis; exergetic and monetary costs of power production were calculated and compared to the respective values of the current system. [Copyright &y& Elsevier]

Fifty (50) selected patients with arteriovenous malformation (AVM) with and without subarachnoid haemorrhage (SAH) were investigated, in respect of occurrence and course of the vasospasm. The diameters of the carotid siphon and its main branches were measured and plotted against the time elapsing between the haemorrhage and the angiographic study. Patients without SAH were used as a reference group. The results suggest intracranial arterial spasm to occur between the third and eleventh day after the onset of SAH. Patients with intracerebral haematoma may show vasospasm from the first day onwards. It seems that the radiologically demonstrated spasm in AVM had no impact on the clinical outcome in this series. [ABSTRACT FROM AUTHOR]

Presents the case of a 39-year-old male who developed a left ventriculo-bronchial fistula after being operated on for idiopathic hypertropic subaortic stenosis. Symptoms of idiopathic hypertropic subaortic stenosis; Medical history of the patient; Advice on the treatment of the fistula.

Background: The long-term effects of COVID-19 remain largely unclear. This study aims to investigate post-acute health consequences and mortality one year after hospital discharge. Methods: All surviving adult patients who were discharged after hospital admission due to acute COVID-19 in the first wave of the pandemic underwent a comprehensive interview. Functional assessment was performed in patients aged over 65. Clinical and hospital records were reviewed and mortality causes assessed. Results: A total of 587 patients with COVID-19 were discharged from hospital, including 266 after hospital admission and 321 from the emergency room. Mortality within the following year occurred in 34/266 (12.8%) and 10/321 (3.1%), respectively, due to causes directly or possibly related to COVID-19 in 20.5% and 25% of patients. Post-COVID-19 syndrome was assessed in 543 patients at one year from discharge. Any clinical complaint was reported by 90.1% of patients who needed hospitalization and 80.4% of those discharged from the emergency room (p = 0.002), with breathlessness (41.6%), tiredness (35.4%), ageusia (30.2%), and anosmia (26.3%) being the most common complaints. Ongoing symptoms attributed to COVID-19 were reported by 66.8% and 49.5% of patients, respectively (p < 0.001). Newly developed COPD, asthma, diabetes, heart failure, and arthritis—as well as worsening of preexisting comorbidities—were found. Conclusions: One-year mortality among survivors of acute COVID-19 was 7.5%. A significant proportion of COVID-19 patients experienced ongoing symptoms at 1 year from onset of the disease. [ABSTRACT FROM AUTHOR]

Background: Risk factors for in-hospital mortality from severe coronavirus disease 2019 (COVID-19) infection have been identified in studies mainly carried out in urban-based teaching hospitals. However, there is little data for rural populations attending community hospitals during the first wave of the pandemic. Methods: A retrospective, single-center cohort study was undertaken among inpatients at a rural community hospital in Spain. Electronic medical records of the 444 patients (56.5% males) admitted due to severe SARS-CoV-2 infection during 26 February 2020–31 May 2020 were reviewed. Results: Mean age was 71.2 ± 14.6 years (rank 22–98), with 69.8% over 65. At least one comorbidity was present in 410 patients (92.3%), with chronic obstructive pulmonary disease (COPD) present in 21.7%. Overall in-hospital mortality was 32%. Multivariate analysis of factors associated with death identified patients' age (with a cumulative effect per decade), COPD as a comorbidity, and respiratory insufficiency at the point of admission. No additional comorbid conditions proved significant. Among analytical values, increased serum creatinine, LDH > 500 mg/dL, thrombocytopenia (<150 × 109/per L), and lymphopenia (<1000 cells/µL) were all independently associated with mortality during admission. Conclusions: Age remained the major determinant for COVID-19-caused mortality; COPD was the only comorbidity independently associated with in-hospital death, together with respiratory insufficiency and analytical markers at admission. [ABSTRACT FROM AUTHOR]

Introduction Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug–gene–population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial.Methods and analysis the PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period and subjects will be followed for a 9-month period.Ethics and dissemination The PREVESTATGx trial received ethical approval on 24 April 2024. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open-access peer-reviewed medical speciality-specific publication.Trial registration number EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO.

BACKGROUND: Non cephalic presentation in childbirth involves various risks to both the mother and the foetus. The incidence in Spain is 3.8% of all full-term pregnancies. The most common technique used to end the gestation in cases of non cephalic presentation is that of caesarian section, and although it provokes a lower rate of morbi-mortality than does vaginal delivery in such situations, there remains the possibility of traumatic injury to the foetal head and neck, while maternal morbidity is also increased. The application of heat (moxibustion) to an acupuncture point, in order to correct non cephalic presentation, has been practised in China since ancient times, but as yet there is insufficient evidence of its real effectiveness. METHODS/DESIGN: The experimental design consists of a multi-centre randomised controlled trial with three parallel arms, used to compare real moxibustion, sham moxibustion and the natural course of events, among pregnant women with a non cephalic presentation and a gestational duration of 33-35 weeks (estimated by echography). The participants in the trial will be blinded to both interventions. The results obtained will be analyzed by professionals, blinded with respect to the allocation to the different types of intervention. In addition, we intend to carry out a economic analysis. DISCUSSION: This trial will contribute to the development of evidence concerning moxibustion in the correction of non cephalic presentations. The primary outcome variable is the proportion of cephalic presentations at term. As secondary outcomes, we will evaluate the proportion of cephalic presentations at week 38 of gestation, determined by echography, together with the safety of the technique, the specificity of moxibustion and the control of the blinding process.This study has been funded by the Health Ministry of the Andalusian Regional Government. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10634508. [ABSTRACT FROM AUTHOR]

METHODS: Retrospective cohort study including 1,211 patients undergoing consecutive SLB from 1998 to 2010. SLB were performed in patients with invasive carcinoma of the breast with clinically negative axilla. Age, tumor size, and histologic grades, estrogen and progesterone receptors expression, HER-2, lymphovascular invasion and size of metastases in lymph nodes were assessed. Tumor sizes were divided according to pathologic staging into pT1(< 2,0mm) and pT2(>2,0mm). Lymph nodes were classified as negative (pN0), positive with micro metastases with diameter ranging from 0,21 mm to 2,0mm(pN1 mi) and positive with macro metastases with diameter greater than 2,0mm(pN1). Statistical analyses were performed by the Likelihood ratio test or Chi-square test for insufficient samples between macro metastases and micro metastases in SLB. Time was considered in months and the overall follow-up time was 125 months and mean time was 65 months. Local regional and distant recurrences were considered as events for disease free survival and Kaplan-Meier survival functions were constructed, testing time between metastases sizes in SLB using the Log-rank test, with a significance level of 5%. RESULTS: Of the studied variables, lymphovascular invasion(p = 0,068) and local regional and distant metastases(p = 0,002) had a statistically significant association with overall survival. Tumor size(p = 0,016); lymph vascular invasion(p = 0,002) and metastases types in sentinel lymph node(p < 0,001) were associated to disease free survival. In the association tests with types of metastases in sentinel lymph node, the following were statistically significant: age(p = 0,004), tumor size(p < 0,001), lymph vascular invasion(p < 0,001) and local regional and distant recurrences. In the interim and final Cox regression analysis, macro metastases were the only statistically relevant factor for disease free survival(p < 0,001). CONCLUSION: The presence of micro metastases(pN1mi) in sentinel lymph node is associated to a prognosis similar to that of negative axilla patients(pN0), indicating that other risk factors for local regional and systemic recurrences should be taken into account. [ABSTRACT FROM AUTHOR]

xCas9 is an evolved variant of the CRISPR-Cas9 genome editing system, engineered to improve specificity and reduce undesired off-target effects. How xCas9 expands the DNA targeting capability of Cas9 by recognising a series of alternative protospacer adjacent motif (PAM) sequences while ignoring others is unknown. Here, we elucidate the molecular mechanism underlying xCas9's expanded PAM recognition and provide critical insights for expanding DNA targeting. We demonstrate that while wild-type Cas9 enforces stringent guanine selection through the rigidity of its interacting arginine dyad, xCas9 introduces flexibility in R1335, enabling selective recognition of specific PAM sequences. This increased flexibility confers a pronounced entropic preference, which also improves recognition of the canonical TGG PAM. Furthermore, xCas9 enhances DNA binding to alternative PAM sequences during the early evolution cycles, while favouring binding to the canonical PAM in the final evolution cycle. This dual functionality highlights how xCas9 broadens PAM recognition and underscores the importance of fine-tuning the flexibility of the PAM-interacting cleft as a key strategy for expanding the DNA targeting potential of CRISPR-Cas systems. These findings deepen our understanding of DNA recognition in xCas9 and may apply to other CRISPR-Cas systems with similar PAM recognition requirements., Competing Interests: KH, LN, MO, JC, GP No competing interests declared, (© 2024, Hossain et al.)

Drug resistance in cancer is determined by genetic mutations and adaptations of tumor cells to drug treatments, raising a challenge in the treatment of cancer. Factors such as prolonged drug exposure, genetic variability among patients, and tumor heterogeneity have been established as contributors to rising incidence of drug resistance, prompting ongoing research into alternative therapies and combination treatments to overcome this challenge. Monoamine oxidases (MAOs), including both isoforms MAO-A and MAO-B, are mitochondrial enzymes responsible for the catabolism of monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. While these enzymes play a pivotal role in the nervous system, their role in tumorigenesis has garnered increasing attention in the last years. Recent studies, in fact, have highlighted the potential of MAO inhibitors (MAOIs) as antitumor agents, emphasizing their use as standalone treatments or in synergy with traditional anticancer therapies, focusing on pathways involved in tumorigenesis. This review aims to provide a comprehensive overview of MAOIs currently under study for their potential antitumor activity, focusing on their structural characteristics, mechanisms of action, and efficacy in preclinical and clinical settings, referencing key articles in the field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A pilot, multicenter and randomised study on the treatment of Barrett´s esophagus with electro conventional scalpel versus argon plasma coagulation in 36 patients consecutives. The disappearance of gastric mucosa was achieved in 83% of cases. Not serious adverse effects.

L-Amino acid transporters (LATs) play a key role in a wide range of physiological processes. Defects in LATs can lead to neurological disorders and aminoacidurias, while the overexpression of these transporters is related to cancer. BasC is a bacterial LAT transporter with an APC fold. In this study, to monitor the cytoplasmic motion of BasC, we developed a single-molecule Förster resonance energy transfer assay that can characterize the conformational states of the intracellular gate in solution at room temperature. Based on combined biochemical and biophysical data and molecular dynamics simulations, we propose a model in which the conserved lysine residue in TM5 supports TM1a to explore both open and closed states within the cytoplasmic gate under apo conditions. This equilibrium can be altered by substrates, mutation of conserved lysine 154 in TM5, or a transport-blocking nanobody interacting with TM1a. Overall, these findings provide insights into the transport mechanism of BasC and highlight the significance of the lysine residue in TM5 in the cytoplasmic gating of LATs., (© The Author(s) 2025. Published by Oxford University Press on behalf of National Academy of Sciences.)

Annulated azecines, mostly partially saturated benzo[d]azecine and dibenzo[c,g]azecine fusion isomers, constitute a unique class of alkaloids and nature-inspired azaheterocyclic compounds with interesting reactivity, physicochemical and biological properties. Due to difficulties associated with the synthesis of the benzazecine (or bioisosteric) scaffold they are not the focus of organic and medicinal chemists' consideration, whereas it is worth noting the range of their pharmacological activities and their potential application in medicinal chemistry. Herein, we reviewed the synthetic methodologies of arene-fused azecine derivatives known up to date and reported about the progress in disclosing their potential in drug discovery. Indeed, their conformational restriction or liberation drives their selectivity towards diverse biological targets, making them versatile scaffolds for developing drugs, including antipsychotic and anticancer drugs, but also small molecules with potential for anti-neurodegenerative treatments, as the recent literature shows., Competing Interests: Declaration of competing interest On behalf of all the co-authors, I declare that the authors of the manuscript entitled “Advances in synthesis of novel benzazecines and their unique pharmacological properties” have no competing interests to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

Geographic isolation and chromosome evolution are two of the major drivers of diversification in eukaryotes in general, and specifically, in plants. On one hand, range shifts induced by Pleistocene glacial oscillations deeply shaped the evolutionary trajectories of species in the Northern Hemisphere. On the other hand, karyotype variability within species or species complexes may have adaptive potential as different karyotypes may represent different recombination rates and linkage groups that may be associated with locally adapted genes or supergenes. Organisms with holocentric chromosomes are ideal to study the link between local adaptation and chromosome evolution, due to their high cytogenetic variability, especially when it seems to be related to environmental variation. Here, we integrate the study of the phylogeography, chromosomal evolution and ecological requirements of a plant species complex distributed in the Western Euro-Mediterranean region (Carex gr. laevigata, Cyperaceae). We aim to clarify the relative influence of these factors on population differentiation and ultimately on speciation. We obtained a well-resolved RADseq phylogeny that sheds light on the phylogeographic patterns of molecular and chromosome number variation, which are compatible with south-to-north postglacial migration. In addition, landscape genomics analyses identified candidate loci for local adaptation, and also strong significant associations between the karyotype and the environment. We conclude that karyotype distribution in C. gr. laevigata has been constrained by both range shift dynamics and local adaptation. Our study demonstrates that chromosome evolution may be responsible, at least partially, for microevolutionary patterns of population differentiation and adaptation in Carex., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)