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We conducted tensile tests on Mg AZ31 samples with in-situ EBSD acquisition at 250°C and 10-3 s-1 to characterize the evolution of dynamic recrystallization (DRX) and its effect on the mechanical behavior. To investigate the entire deformation range up to failure at 65-67% engineering strain, step-wise experiments were conducted with in-situ EBSD acquisition at 2-5% strain intervals. Both in-situ microstructural observations and statistical analysis of microstructural properties document continuous DRX with nucleation by association of bulging and subgrain rotation starting at strains as low as 6%. However, the microstructure evolves slowly, mainly by development of substructure (polygonization), with DRX limited to isolated clusters, until 35% strain. This long incubation period is followed by acceleration of DRX, with faster grain boundary migration allowing for development of a DRX-necklace structure, whose spatial heterogeneity controls the final strain localization at strains > 60%. The microstructural evolution contrasts with the bulk mechanical behavior, which displays a linear decrease in the hardening rate between 15 and 60% strain. Comparison of the observed texture evolution with predictions by polycrystal plasticity simulations without DRX shows that DRX-induced changes in texture counteract the geometrical hardening due to the texture evolution resulting from dislocation glide. Microstructural softening is, nevertheless, required to compensate for hardening due to increase in the dislocation density. The intensity of this softening has to steadily increase with strain to explain the decrease in hardening rate between 15% and 60% strain. The apparent discrepancy between the kinetics of the microstructural evolution and the mechanical behavior implies, however, that the bulk softening does not depend solely on the DRX volume fraction, but also on its spatial organization.

Diarrhea in patients infected with the human immunodeficiency virus (HIV) represents a challenge for the clinician. Its differential diagnosis includes infectious causes (bacteria, viruses, fungi, and parasites) as well as non-infectious ones. Among the infectious causes are microorganisms that can affect both immunocompetent and immunocompromised hosts, making the differential diagnosis broad. The presentation can be acute or chronic, with the latter having a greater impact on morbidity and quality of life for patients. The diagnostic approach should be sequential, first with non-invasive laboratory methods, progressing to endoscopic studies with biopsy in those individuals for whom reaching a diagnosis is difficult.

Derrick Lopez,1 Juan Lu,1,2 Frank M Sanfilippo,1 Judith M Katzenellenbogen,1 Tom Briffa,1 Lee Nedkoff1,3 1Cardiovascular Epidemiology Research Centre, School of Population and Global Health, The University of Western Australia, Crawley, Western Australia, Australia; 2Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia; 3Victor Chang Cardiac Research Institute, Sydney, New South Wales, AustraliaCorrespondence: Derrick Lopez, School of Population and Global Health (M431), The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia, 6009, Australia, Email Derrick.Lopez@uwa.edu.auPurpose: Measures of disease burden using hospital administrative data are susceptible to over-inflation if the patient is transferred during their episode of care. We aimed to identify and compare measures of coronary heart disease (CHD) and myocardial infarction (MI) episodes using six algorithms that account for transfers.Patient and Methods: We used person-linked hospitalisations for CHD and MI for 2000– 2016 in Western Australia based on the interval between discharge and subsequent admission (date, datetime algorithms), pathway (admission source, discharge destination) and any combination to generate machine learning models (random forest [RF], gradient boosting machine [GBM]). The date and datetime algorithms used deidentified patient identifiers to identify records belonging to the same individual. We calculated counts, age-standardised rates (ASR) and age-adjusted trends for CHD and MI for each algorithm.Results: Counts of CHD increased from 11,733 in 2000 to 13,274 in 2016, while MI increased from 2605 to 4480 using the date algorithm. Correspondingly ASR for CHD decreased from 2086.2 to 1463.1 while MI increased from 468.2 to 498.1 per 100,000 person-years. ASR for CHD and MI for datetime algorithm were consistently 1– 2% higher than the date algorithm. Differences in ASR of CHD and MI counts increased over time with the admission source, RF and GBM algorithms relative to the date algorithm. Age-adjusted trends in CHD and MI episode rates using RF and GBM differed significantly from all other algorithms. Only 86.7% and 87.6% of MI episodes identified by the date algorithm were identified by the admission source and discharge destination algorithms, respectively.Conclusion: The date and datetime algorithms produced the most valid measures of CHD and MI episodes. Findings underscore the importance of identifying admission and discharge dates/times belonging to the same individual in enumerating these episodes.Keywords: patient transfer, rates, trends, Western Australia

Chemical Biology can be defined as the design and the development of molecular tools to decipher or modulate biological processes of interest so that they can be better understood, controlled or modified. It also consists in the observation and analysis of these molecular tools within, and in interaction with, their complex biological environment. Chemical Biology can then lead to highly valuable basic knowledge and be applied in diverse fields such as health and environment. Therefore, Chemical Biology has strong interactions with the design of therapeutic strategies, diagnosis, agrochemicals or Ecology.

Maria Vernet-Tomas,1,2 Ivonne Vazquez,1,3 Francesc Olivares,3 David Lopez,3 Jose Yelamos,2,4 Laura Comerma1– 3 1Breast Diseases Unit, Hospital Del Mar, Barcelona, Spain; 2Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; 3Department of Pathology; Hospital del Mar, Barcelona, Spain; 4Laboratory of Immunology, Department of Pathology; Hospital Del Mar, Barcelona, SpainCorrespondence: Maria Vernet-Tomas, Breast Diseases Unit, Hospital del Mar, Passeig Marítim de la Barceloneta 25- 29, Barcelona, 08003, Spain, Tel +342483132, Email mvernet@hmar.catPurpose: The aim of this study was to determine whether low HLA-I expression and NK cells infiltration are related to prognostic features in breast cancer, as observed in cancers in other locations and non-hormone dependent breast cancers. Particularly, we explored their relation to infiltrated axillary lymph nodes (ALNs), with the aim of finding new predictors helping to decide the extent of axillary surgery.Patients and Methods: We conducted a retrospective correlational analysis of 35 breast cancers from 35 breast cancer patients showing axillary infiltration at diagnosis and with upfront surgery. HLA-I H-score and the number of NK cells x 50 high power fields (HPF) in the biopsy specimen were correlated with pathological variables of the surgical specimen: number of infiltrated ALNs, tumor size, histological type, the presence of ductal carcinoma in situ, focality, histological grade, necrosis, lymphovascular and perineural invasion, Her2Neu status, and the percentages of tumor-infiltrating lymphocytes (TILs), estrogen receptor, progesterone receptor, ki67, and p53.Results: All tumors showed hormone receptor expression and three of them Her2Neu positivity. A positive correlation (p=0.001**) was found between HLA-I H-score and TILs and Ki67 expression. HLA H-score increased with histological grade and was higher in unifocal than in multifocal disease (p=0.044 and p=0.011, respectively). No other correlations were found.Conclusion: High HLA-I H-score values correlated with features of poor prognosis in this cohort of luminal breast tumors, but not with infiltrated ALNs. This finding highlights the differences between luminal breast cancer, and cancers in other locations and non-hormone dependent breast cancers, in which low HLA-I expression tends to be associated with poor prognostic features.Keywords: luminal breast cancer, HLA-I, natural killer cells, prognostic features, axillary lymph nodes

Lorena Piñel Jimenez, Álvaro Martinez Mesa, Esther Sanchez Alvarez, Javier Lopez Garcia, Ana Aguilar Galvez, Nuria Reina Marfil, Belen Gómez Rodríguez, Eva Cabrera Cesar, Jose Luis Velasco Garrido Department of Pulmonology, Hospital Universitario Virgen de la Victoria, Málaga, SpainCorrespondence: Eva Cabrera Cesar, Department of Pulmonology, Hospital Universitario Virgen de la Victoria, Campus de Teatinos, S/N. 29010, Málaga, Spain, Tel +34 646905201, Email evacabreracesar@gmail.comObjective: To describe the clinical management of asthmatic patients and the level of compliance with the Guía Española para el Manejo del Asma (GEMA, Spanish Guidelines for Asthma Management) in the influential al area of Virgen de la Victoria University Hospital, Málaga (Spain).Materials and Methods: Descriptive, cross-sectional study in asthma patients from the Virgen de la Victoria University Hospital influential area, Málaga (Spain). Asthma Control Test (ACT) results, demographic and clinical characteristics, and GEMA indicators of quality asthma care were obtained from each participating patient.Results: Two hundred and eighty-eight patients (64.2% woman, mean age 48.6 years) were included in the study. The evaluation of the level of compliance with the GEMA quality indicators showed that in 20.8% of the patients the diagnosis of asthma was confirmed by spirometry and bronchodilator test, and 52.5% of the patients with suspicion of allergic asthma performed a sensitization test. Among the smoker patients, 76.3% were recommended to stop smoking; 14.2% of the patients received a paper-based educational plan. Regarding asthma treatment, 92.3% of patients with persistent asthma received inhaled glucocorticoids (IGC). IGC and LABA were the most common treatments for asthma, used in combination (ICG + LABA) in 139 (48.3%) patients; 32.6% discontinued SABA treatment during the study period. Asthma was well controlled in 54.9% of the patients (ACT score ≥ 20), and 13.9% of the patients registered exacerbations during the previous year with a mean (SD) of 1.38 (0.74) events.Conclusion: Most of the GEMA quality indicators of asthma care are not followed in real-world clinical practice. Specialists select the best option among the available treatments but there is an unmet need for training plans in other relevant aspects, such as diagnosis and/or disease monitoring.Keywords: asthma, asthma control, indicators of quality care, clinical guidelines, asthma management, compliance with guidelines

Analiza y detalla la propuesta de reforma de la administración de Javier Milei titulada Ley de Bases y Puntos de Partida para la Libertad de los Argentinos, pero conocida como la “ley ómnibus” por la cantidad de temáticas y problemáticas que toca. Una de las reformas propone cambiar el sistema electoral argentino para la elección de los representantes a la Cámara de Diputados de la Nación; en concreto, salir del sistema proporcional de circunscripciones plurinominales (conformadas por cada una de las provincias) para adoptar un sistema de circunscripciones uninominales. Cambio cuyas implicaciones no son solo en lo electoral, sino también en el sistema de partidos políticos. La última elección argentina presentó un escenario de tercios, en virtud de ello se analiza la propuesta tomando como base los autores clásicos para un abordaje integral de esta.

Polypropylene (PP) films are crucial in various industrial applications, from packaging to medical products. However, a common challenge in PP manufacturing is the presence of gel-like defects. These gels are minor defects on the surface of the films that significantly affect the physicochemical, mechanical, and organoleptic properties of the films, compromising the quality of the final product. This first research focuses on developing and validating an in-line optical method to replace the international method ASTM D 3351–93. The main objective was to create a methodology that has the same scope and analytical performance as those reported by ASTM D 3351–93 in such a way that it can compete with it in terms of precision and accuracy, thus allowing end users to this ASTM, such as PP producers, PP marketers, PP film producers, among others internationally, can use this new methodology with necessary analytical support. This analytical methodology integrates the PP extrusion zones, the film processing stages, and the optical zone for reading and processing analytical data. Additionally, it has the advantage of working with a sample size that is even more representative of the population and has less human error since only one operator is required to carry out the test; this method also has much shorter response times. The developed prototype had 14 online stages that allowed representative quantities of samples to be taken and processed thermally and mechanically for ideal optical measurement. For the online method, a 6-point calibration curve is carried out at concentrations of 40, 10, 5, 2, 1 and 0 ppm for the gel or defect sizes of 200, 400, 500, 600, 700, 800 and 900 µm, showing excellent linearity where the correlation coefficient varied between 0.997 and 0.999, the limits of detection (LOD) varied between 0.85 and 2.61 and the limits of quantification (LOQ) ranged between 2.82 and 8.71. The statistical analyzes by ANOVA of the comparison between the ASTM D 3351–93 method and the proposed simultaneous method indicate that the p value of the evaluation of the means was 0.946, which suggests that the means are not statistically different. To complement, the Tukey test was carried out at 95 %, indicating that the methods have statistical equivalence. • Process optimization • Determination of defects or imperfections in PP films

Shani Reich,1 Maria Lopez,2,&ast; Jacqueline Leff,3,&ast; Jordan Herman1 1Clinical Research Center of Florida, Pompano Beach, FL, USA; 2New England Eye Center/Tufts Medical Center, Boston, MA, USA; 3Touro Osteopathic School of Medicine, Touro University, New York, NY, USA&ast;These authors contributed equally to this workCorrespondence: Shani Reich, Tel +1 305 984 7785, Fax + 1 305 570 2642, Email Shani.reich@gmail.comPurpose: To compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the treatment of allergic conjunctivitis in a real-world model of allergen exposure.Methods: This was a prospective comparative trial. Adults with testing-confirmed bilateral allergic conjunctivitis received DEX in the more symptomatic eye and either LOT 2 times daily or OLO once daily for 30 days in the fellow eye. The primary outcome was patient preference for treatment. Clinical outcomes included ocular itching and hyperemia, lid swelling, and watering/tearing. Safety outcomes included intraocular pressure (IOP).Results: Thirty patients participated and completed the study. All received DEX in the eye with worse symptoms and 15 received LOT and the other 15 received OLO in the other eye. Patients preferred DEX (10/15; 66.7%) over LOT (4/15; 26.7%), with one patient having no preference (p = 0.0103). Patients had no preference between DEX (8/15; 53.3%) and OLO (6/15; 40%), with one patient having no preference (p = 0.1044). In the DEX/LOT cohort, ocular itching and hyperemia improved more with DEX than LOT (p ≤ 0.009), while in the DEX/OLO cohort, the DEX eyes showed greater improvement in conjunctival hyperemia (p < 0.0001) but not itching (p = 0.074). No between-group differences were seen in eyelid swelling or tearing/watering in either cohort. Mean change in IOP was similar between the DEX and LOT eyes (p = 0.4921), and mean IOP rose more in the DEX eyes than the OLO eyes (by < 1 mmHg; p = 0.0403).Conclusion: Overall, this real-world study demonstrated that the dexamethasone intracanalicular insert was as effective as a topical antihistamine/mast cell stabilizer and more effective than topical steroids in relieving the signs and symptoms of allergic conjunctivitis. This insert should be considered as an alternative to topical therapy for the treatment of allergic conjunctivitis.Keywords: dexamethasone, dextenza, allergic conjunctivitis

We report room temperature heterodyne detection of a quantum cascade laser beaten with a local oscillator on a unipolar quantum photodetector in two different atmospheric windows, at 4.8 µm and 9 µm. A noise equivalent power of few pW is measured by employing an active stabilization technique in which the local oscillator and the signal are locked in phase. The measured heterodyne noise equivalent power is six orders of magnitude lower than that obtained with direct detection.

There are limited treatment options and no consensus on the management of advanced rare ovarian malignancies. Rare ovarian malignancies can present with peritoneal metastases (PM), featuring a similar presentation to more common ovarian subtypes. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for PM of non-gynecologic origin and, recently, epithelial ovarian cancer. We evaluated the feasibility of CRS/HIPEC in the management of PM from rare ovarian malignancies and report postoperative outcomes on these patients.

Jose P Lopez-Lopez,1,2,&ast; Ana Maria Gonzalez,1,&ast; Paola Lanza,1 Patricio Lopez-Jaramillo1 1MASIRA Research Institute, Universidad de Santander (UDES), Bucaramanga, Santander, Colombia; 2Department of Internal Medicine. Cardiology Unit, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia&ast;These authors contributed equally to this workCorrespondence: Patricio Lopez-Jaramillo, MASIRA Research Institute, Facultad de Ciencias de la Salud, Universidad de Santander (UDES), Bloque G, piso 6, Bucaramanga, Santander, Colombia, Tel +57 315 306 8939, Email jplopezj@gmail.comBackground: Higher medication adherence reduces the risk of new cardiovascular events. However, there are individual and health system barriers that lead to lower adherence. The polypill has demonstrated benefits in cardiovascular morbidity and mortality mainly driven by an increase in adherence. We aim to evaluate the impact of the polypill on adherence to cardiovascular medication, its efficacy and safety in cardiovascular disease (CVD) prevention.Methods: A systematic review following PRISMA guidelines was conducted. Databases were searched from January 2003 to December 2022. We included randomized, pragmatic, or real-world clinical trials and observational studies. The primary outcome was medication adherence, secondary outcomes were efficacy in cardiovascular disease in primary and secondary prevention and safety.Results: From the 490 publications screened, 13 met the inclusion criteria and were incorporated into a comparative table Of those included, 70% were randomized controlled trials (RCTs) and 53.8% focused on secondary prevention. Most of the studies received a high and moderate quality rating. Self-report, pill counting and, the Morisky scale were the most frequent methods to evaluate adherence (84.6%). Compared with standard medication, the polypill improved overall medication adherence by 13%, with percentages ranging from 7.6% to 34.9%. Moreover, a potential benefit was also observed in reducing Major Adverse Cardiovascular Events (MACE), particularly in secondary prevention studies, with hazard ratios ranged between 0.43 to 0.76. Compared to standard care, the profile of side effects was similar.Conclusion: The polypill is an effective, safe, and practical strategy to improve adherence in people at risk of CVD. Although there is a demonstrated benefit in reducing MACE, predominantly in secondary prevention, there are still gaps in its efficacy in primary prevention and reducing total mortality. Therefore, the importance of obtaining long-term results of the polypill effect and how this strategy can be implemented in real practice.Keywords: polypill, cardiovascular disease, hypertension, dyslipidemia, major cardiovascular events

Similar to many small islands within the Wider Caribbean Region, the French West Indies are rich but fragile island ecosystems threatened by global warming, pollutants and other anthropic pressures. To understand integrated and complex human impacts on the environment, the Caribbean Coast Human-Environment Observatory (OHM) is developing disciplinary and interdisciplinary studies related to the local-scale driving factors that affect the coastal evolution in Guadeloupe. We present here results that show the multiple causalities, causal asymmetries, and equifinality of environmental pollution related to chlordecone, glyphosate, arsenic and Sargassum and highlight the need to bring further knowledge and awareness to the local populations on these concerns.

The effect of Radopholus similis, Pratylenchus araucensis, Meloidogyne spp., and their interaction was evaluated in seedlings of Musa AAB ‘Dominico Hartón’. The study was conducted in a nursery in Palestina, Caldas department, Colombia. Forty-day-old plantain seedlings were infected separately with 750, 1,500, 2,250 and 3,000 of each species of nematodes/plant. Two experiments were conducted to evaluate the damage of R. similis, P. araucensis, Meloidogyne spp. and the mixture of 750 R. similis + 750 P. araucensis + 750 Meloidogyne spp. compared with the mixture of different proportions (1,500, 2,250 and 3,000 of each species of nematodes). Noninfected plants were included as a control treatment, for a total of 17 treatments in a randomized complete block design with ten replications. Twelve weeks after inoculation, all nematodes, both alone and in combination, reduced (p < 0.05) plantain dry root and shoot weight. In two experiments, R. similis, P. araucensis, and Meloidogyne spp. alone, each with a population density of 3,000, reduced (p < 0.05) root dry weight by 32.5%, 9.5% and 49%, respectively, and decreased (p < 0.05) shoot dry weight by 21.5%, 23%, and 31.5%, respectively, compared to the control. The interaction of nematodes with the lowest population decreased root (33%) and shoot (21%) weight. We conclude that the growth of ‘Dominico Hartón’ seedlings was affected by plant-parasitic nematodes, but the greatest damage occurred with concomitant nematode infection.

Introduction Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%–25%.Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting.Methods and analysis This open-label randomised controlled study focuses on LCS for patients aged 50–80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant.Ethics and dissemination The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations.Trial registration number NCT05704920.

Rogelio Perez-Padilla,1 Maria Montes de Oca,2 Ireri Thirion-Romero,1 Fernando C Wehrmeister,3 Maria Victorina Lopez,4 Gonzalo Valdivia,5 Jose R Jardim,6 Adriana Muino,4 Ana Maria B Menezes3 On behalf of the PLATINO Group1National Institute of Respiratory Diseases, Mexico City, Mexico; 2Pulmonary Division, Hospital Universitario de Caracas, Universidad Central de Venezuela, and Centro Medico de Caracas, Caracas, Venezuela; 3Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil; 4Universidad de la Republica. Hospital Maciel, Montevideo, Uruguay; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Paulista School of Medicine, Federal University of São Paulo, São Paulo, BrazilCorrespondence: Rogelio Perez-Padilla, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Col. Sección XVI, 14080, CDMX, Mexico City, Mexico, Email perezpad@gmail.comBackground: Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America.Methods: Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5– 9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥ 0.70 with FEV1 < 80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition.Results: At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2– 4 6.5%, and PRISm was: 5.0% (95% CI 4.2– 5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥ 2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2– 3.3) and COPD GOLD 1– 4 categories (HR 1.79, 95% CI 1.3– 2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment.Conclusion: PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.Keywords: preserved ratio impaired spirometry PRISm, airflow obstruction, COPD, lung function decline

Victor Hugo Ahumada Topete,1,&ast; Kevin Jesus de Dios Sanchez,1,&ast; Gustavo Alejandro Casas Aparicio,2 Graciela Hernandez Silva,2 Cesar Emmanuel Lopez Vejar,1 Luz Maria Torres Espíndola,3 Arnoldo Aquino-Galvez,4 Odalis Rodriguez Ganen,5 Manuel de Jesus Castillejos Lopez1 1Hospital Epidemiology and Infectology Unit, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 2Department of Infectious Disease Research, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 3Laboratory of Pharmacology, National Institute of Pediatrics, Mexico City, Mexico; 4Molecular Biology Laboratory, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico; 5Department of Hospital Pharmacy, National Institute of Respiratory Diseases Ismael Cosío Villegas, Mexico City, Mexico&ast;These authors contributed equally to this workCorrespondence: Manuel de Jesus Castillejos Lopez; Arnoldo Aquino Galvez, Email mcastillejos@gmail.com; araquiga@yahoo.comAbstract: The adverse events related to sodium colistimethate have had variability regarding the prevalence of nephrotoxicity, neurotoxicity, and less frequent respiratory depression. In recent years, its use has been relevant due to the increase of multidrug-resistant bacteria since it is considered the last-line drug, being its main adverse event and reason for discrepancies between authors’ nephrotoxicity. The indiscriminate use of antibiotic therapy has generated multiple mechanisms of resistance, the most common being related to Colistin, the bactericidal escape effect. Based on the search criteria, no randomized clinical trials were identified showing safety and efficacy with the use of Colistin, inferring that the application of the appropriate dose is governed by expert opinion and retrospective and prospective observational studies, which confounding factors such as the severity of the patient and the predisposition to develop acute renal failure are constant. In this review, we focus on identifying the mechanism of nephrotoxicity and bacterial resistance, where much remains to be known.Keywords: colistin, colistimethate, nephrotoxicity, neurotoxicity, resistance mechanism, multidrug-resistant gram-negative bacteria, risk factors, high doses, toxicity

The European X-ray Free Electron Laser (European XFEL) is a cutting-edge user facility that generates per second up to 27,000 ultra-short, spatially coherent X-ray pulses within an energy range of 0.26 to more than 20 keV. Specialized instrumentation, including various 2D X-ray detectors capable of handling the unique time structure of the beam, is required. The one-megapixel AGIPD (AGIPD1M) detectors, developed for the European XFEL by the AGIPD Consortium, are the primary detectors used for user experiments at the SPB/SFX and MID instruments. The first AGIPD1M detector was installed at SPB/SFX when the facility began operation in 2017, and the second one was installed at MID in November 2018. The AGIPD detector systems require a dedicated infrastructure, well-defined safety systems, and high-level control procedures to ensure stable and safe operation. As of now, the AGIPD1M detectors installed at the SPB/SFX and MID experimental end stations are fully integrated into the European XFEL environment, including mechanical integration, vacuum, power, control, data acquisition, and data processing systems. Specific high-level procedures allow facilitated detector control, and dedicated interlock systems based on Programmable Logic Controllers ensure detector safety in case of power, vacuum, or cooling failure. The first 6 years of operation have clearly demonstrated that the AGIPD1M detectors provide high-quality scientific results. The collected data, along with additional dedicated studies, have also enabled the identification and quantification of issues related to detector performance, ensuring stable operation. Characterization and calibration of detectors are among the most critical and challenging aspects of operation due to their complex nature. A methodology has been developed to enable detector characterization and data correction, both in near real-time (online) and offline mode. The calibration process optimizes detector performance and ensures the highest quality of experimental results. Overall, the experience gained from integrating and operating the AGIPD detectors at the European XFEL, along with the developed methodology for detector characterization and calibration, provides valuable insights for the development of next-generation detectors for Free Electron Laser X-ray sources.

While Knowledge Graphs (KGs) have long been used as valuable sources of structured knowledge, in recent years, KG embeddings have become a popular way of deriving numeric vector representations from them, for instance, to support knowledge graph completion and similarity search. This study surveys advances as well as open challenges and opportunities in this area. For instance, the most prominent embedding models focus primarily on structural information. However, there has been notable progress in incorporating further aspects, such as semantics, multi-modal, temporal, and multilingual features. Most embedding techniques are assessed using human-curated benchmark datasets for the task of link prediction, neglecting other important real-world KG applications. Many approaches assume a static knowledge graph and are unable to account for dynamic changes. Additionally, KG embeddings may encode data biases and lack interpretability. Overall, this study provides an overview of promising research avenues to learn improved KG embeddings that can address a more diverse range of use cases.

Ruth Milz,1 Carmela Benson,1 Karl Knight,1 Jose Antunes,2 Dean Najarian,3 Paola-Maria Lopez Rengel,4 Steven Wang,1 Ute Richarz,5 Srihari Gopal,1 John M Kane6,7 1Janssen Research & Development LLC, Titusville, NJ, USA; 2Janssen-Cilag, Porto Salvo, Portugal; 3Janssen Scientific Affairs, LLC, Raritan, NJ, USA; 4Janssen Cilag, Madrid, Spain; 5Janssen Global Medical Affairs, Cilag, Zug, Switzerland; 6Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Queens, NY, USA; 7Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USACorrespondence: Ruth Milz, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA, Email rmilz@ITS.JNJ.comAbstract: Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2– 3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic).Keywords: adherence, long-acting injectable, paliperidone palmitate, schizophrenia

Jeffrey A Hutchens, Kevin J Lopez, Eugene P Ceppa Department of Surgery, Division of Surgical Oncology, Indiana University School of Medicine, Indianapolis, IN, USACorrespondence: Eugene P Ceppa, Associate Professor of Surgery, Section Chief of HPB Surgery, Division of Surgical Oncology, Indiana University School of Medicine, 545 Barnhill Dr, EH 541, Indianapolis, IN, 46202, USA, Tel +1-317-944-5013, Fax +1-317-968-1031, Email eceppa@iu.eduAbstract: Mucinous cystic neoplasms (MCNs) are rare tumors of the liver, occasionally seen in the biliary tree. Epidemiologic data are limited by their indolence and recent changes to diagnostic criteria. They are considered premalignant lesions capable of invasive behavior. While their etiology remains unknown, their female predominance, age of onset, and hormonally responsive ovarian-type stroma suggest ectopic organogenesis during embryologic development. MCNs can typically be recognized on imaging; yet, invasiveness is often indeterminate, and percutaneous tissue biopsy has shown limited value. Therefore, complete excision is recommended for all lesions as focal malignant transformation and metastatic disease has been reported.Keywords: mucinous cystic neoplasm, hepatobiliary cystadenoma, hepatobiliary cystadenocarcinoma

This research proposes an innovative method for correcting banding errors in satellite images based on Generative Adversarial Networks (GAN). Small satellites are frequently launched into space to obtain images that can be used in scientific or military research, commercial activities, and urban planning, among other applications. However, its small cameras are more susceptible to radiometric, geometric errors, and other distortions caused by atmospheric interference. The proposed method was compared to the conventional correction technique using experimental data, showing the similar performance (92.64% and 90.05% accuracy, respectively). These experimental results suggest that generative models utilizing Artificial Intelligence (AI) techniques, specifically Deep Learning, are getting closer to achieving automatic correction close to conventional methods. Advantages of the GAN models include automating the task of correcting banding in satellite images, reducing the required time, and facilitating the processing without requiring prior technical knowledge in handling Geographic Information Systems (GIS). Potentially, this technique could represent a valuable tool for satellite image processing, improving the accuracy of the results and making the process more efficient. The research is particularly relevant to the field of remote sensing and can have practical applications in various industries.