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Las alteraciones morfológicas de la próstata, por las que se realiza cribado son la hiperplasia prostática benigna (HPB) y el cáncer de próstata (CaP). La HPB es el tumor benigno más frecuente en varones mayores de 50 años, se caracteriza por el aumento del volumen de la glándula y usualmente acompañado de síntomas urinarios. El CaP es la segunda causa de muerte relacionada con cáncer en Estados Unidos y Europa en mayores de 70 años, su incidencia por debajo de los 50 es rara. El cribado o pruebas de detección, tiene como meta el hallar el cáncer antes de la aparición de síntomas, el cribado no se realiza en pacientes por sospechar que tienen cáncer, sino como un método de pesquisa. El objetivo de este artículo, es efectuar una revisión a los referentes teóricos, y proponer un nuevo algoritmo diagnóstico de alteraciones morfológicas de la próstata, basado en la evidencia.

Introduction. High-dose antibiotic regimens are commonly employed to improve outcomes in critically ill patients with severe infections; however, their direct impact on antimicrobial resistance (AMR) remains underexplored. Methods. This systematic review analyzed randomized controlled trials (RCTs) published between 2020 and 2024, focusing on high-dose regimens for gram-negative bacterial infections, cellulitis, and ventilated hospital-acquired bacterial pneumonia (vHABP). A comprehensive search was conducted using the Web of Science and PubMed databases, yielding four studies that met the inclusion criteria. Results. The results suggest that while high-dose regimens reduce treatment failure and improve clinical outcomes, they are associated with higher adverse effects and may contribute to antibiotic-resistant bacteria. Notably, none of the studies directly assessed the molecular or epidemiological mechanisms linking high-dose regimens to AMR, underscoring a significant gap in the current literature. Conclusion. Further research is required to elucidate these mechanisms and establish evidence-based guidelines that balance immediate clinical benefits with long-term public health concerns.

Archivo histórico de Kipus: Revista Andina de Letras y Estudios Culturales, 2002 y 2003.

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDR-TB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDR-TB hotspots.

Background Lung ultrasound (LUS) has proven to be useful in the evaluation of lung involvement in COVID-19. However, its effectiveness for predicting the risk of severe disease is still up for debate. The aim of the study was to establish the prognostic accuracy of serial LUS examinations in the prediction of clinical deterioration in hospitalised patients with COVID-19. Methods Prospective single-centre cohort study of patients hospitalised for COVID-19. The study protocol consisted of a LUS examination within 24 h from admission and a follow-up examination on day 3 of hospitalisation. Lung involvement was evaluated by a 14-area LUS score. The primary end-point was the ability of LUS to predict clinical deterioration defined as need for intensive respiratory support with high-flow oxygen or invasive mechanical ventilation. Results 200 patients were included and 35 (17.5%) of them reached the primary end-point and were transferred to the intensive care unit (ICU). The LUS score at admission had been significantly higher in the ICU group than in the non-ICU group (22 (interquartile range (IQR) 20–26) versus 12 (IQR 8–15)). A LUS score at admission ≥17 was shown to be the best cut-off point to discriminate patients at risk of deterioration (area under the curve (AUC) 0.95). The absence of progression in LUS score on day 3 significantly increased the prediction accuracy by ruling out deterioration with a negative predictive value of 99.29%. Conclusion Serial LUS is a reliable tool in predicting the risk of respiratory deterioration in patients hospitalised due to COVID-19 pneumonia. LUS could be further implemented in the future for risk stratification of viral pneumonia.

Introduction: stenotrophomonas maltophilia is a clinically relevant opportunistic and nosocomial pathogen with increasing concerns regarding antibiotic resistance. Accurate diagnosis and identification are crucial for effective treatment, and misidentification can occur, thereby emphasizing the need for appropriate laboratory testing and surveillance. This review aimed to evaluate the epidemiology, pathogenesis, diagnosis, treatment, and antimicrobial resistance of Stenotrophomonas spp. Materials and Methods. A systematic literature review was conducted using the PubMed Central Database. Inclusion criteria included studies published in open-access scientific journals within the last five years, reporting information on Stenotrophomonas spp. epidemiology, pathogenesis, diagnosis, treatment, and/or antimicrobial resistance. The synthesis of the results involved a narrative synthesis of the findings from the included studies. Results. A total of 25 articles met the inclusion criteria and provided valuable insights into Stenotrophomonas spp. infections. The distribution of reported cases by country, sample type, and antimicrobial resistance patterns was summarized. The prevalence of resistance to various antibiotics was also assessed, highlighting the need for continuous surveillance. Conclusion. This analysis revealed the presence of antimicrobial resistance in Stenotrophomonas spp., particularly in S. maltophilia. The high prevalence of antibiotic resistance underscores the importance of ongoing surveillance and control measures to combat antibiotic resistance. The diverse distribution of S. maltophilia across different sample types emphasizes the need for accurate diagnosis and identification. Addressing antimicrobial resistance in Stenotrophomonas spp. is essential for global public health.

El infinito en un junco, ensayo de Irene Vallejo

Background: Interstitial lung sequelae are increasingly being reported in survivors of COVID-19 pneumonia. An early detection of these lesions may help prevent the development of irreversible lung fibrosis. Lung ultrasound (LUS) has shown high diagnostic accuracy in interstitial lung disease (ILD) and could likely be used as a first-line test for post-COVID-19 lung sequelae.Methods: Single-center observational prospective study. Follow-up assessments of consecutive patients hospitalized for COVID-19 pneumonia were conducted 2–5 months after the hospitalization. All patients underwent pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and LUS. Radiological alterations in HRCT were quantified using the Warrick score. The LUS score was obtained by evaluating the presence of pathological B-lines in 12 thoracic areas (range, 0–12). The correlation between the LUS and Warrick scores was analyzed.Results: Three hundred and fifty-two patients who recovered from COVID-19 pneumonia were recruited between July and September 2020. At follow-up, dyspnea was the most frequent symptom (69.3%). FVC and DLCO alterations were present in 79 (22.4%) and 234 (66.5%) patients, respectively. HRCT showed relevant interstitial lung sequelae (RILS) in 154 (43.8%) patients (Warrick score ≥ 7). The LUS score was strongly correlated with the HRCT Warrick score (r = 0.77) and showed a moderate inverse correlation with DLCO (r = −0.55). The ROC curve analysis revealed that a LUS score ≥ 3 indicated an excellent ability to discriminate patients with RILS (sensitivity, 94.2%; specificity, 81.8%; negative predictive value, 94.7%).Conclusions: LUS could be implemented as a first-line procedure in the evaluation of Post-COVID-19 interstitial lung sequelae. A normal LUS examination rules out the presence of these sequelae in COVID-19 survivors, avoiding the need for additional diagnostic tests such as HRCT.

Si bien el establecimiento de relaciones diplomáticas —a nivel de embajadas— se dio en 1969, las relaciones bilaterales ruso-peruanas se remontaban aproximadamente un siglo atrás. Reticente a reconocer, en sus inicios, la independencia de los países de la otrora América española, el Imperio ruso experimentó, bajo el reinado del zar Alejandro II, un cambio en su política exterior respecto a las jóvenes naciones sudamericanas.

En el centenario del nacimiento de Mario Benedetti, prolífico y destacado escritor uruguayo, en este texto se hace un recuento de su memoria y de sus aportes a la literatura latinoamericana del siglo XX. Un autor que como pocos del continente supo granjearse en vida el cariño y respeto de propios y extraños, aun cuando no compartieran su ideología y sus posturas políticas y literarias. Como pocos autores también consiguió que su vasta producción (más de ochenta libros de muy diversos géneros) llegue a tanta gente de Uruguay y del mundo.

Miguel Riofrío. El hombre y el escritor, 151 ensayo de Hernán Rodríguez Castelo

Due to low labeling efficiency and structural heterogeneity in fluorescence-based single-molecule localization microscopy (SMLM), image alignment and quantitative analysis is often required to make accurate conclusions on the spatial relationships between proteins. Cryo-electron microscopy (EM) image alignment procedures have been applied to average structures taken with super-resolution microscopy. However, unlike cryo-EM, the much larger cellular structures analyzed by super-resolution microscopy are often heterogeneous, resulting in misalignment. And the light-microscopy image library is much smaller, which makes classification challenging. To overcome these two challenges, we developed a method to deform semi-flexible ring-shaped structures and then align the 3D structures without classification. These algorithms can register semi-flexible structures with an accuracy of several nanometers in short computation time and with greatly reduced memory requirements. We demonstrated our methods by aligning experimental Stochastic Optical Reconstruction Microscopy (STORM) images of ciliary distal appendages and simulated structures. Symmetries, dimensions, and locations of protein complexes in 3D are revealed by the alignment and averaging for heterogeneous, tilted, and under-labeled structures.

El acné constituye una enfermedad inflamatoria crónica que afecta principalmente a adolescentes y adultos jóvenes, cuya principal manifestación clínica es la presencia de lesiones dermatológicas. Se realizó un estudio descriptivo, transversal con el objetivo de caracterizar la automedicación en pacientes con diagnóstico de acné que asistieron a consulta externa de Dermatología, en el Hospital Provincial General Docente de Riobamba, durante el periodo comprendido entre diciembre 2017 y mayo 2018. Cuya población estuvo constituida por 200 pacientes con diagnóstico de acné, con edades comprendidas entre 14 y 20 años. La media de la edad de los participantes fue de 17,03 años, prevaleciendo el grupo etario de 17 a 20 años (58,50 %). 119 pacientes (59,50 %) declararon administrarse diversos tratamientos medicamentosos, para combatir el acné sin prescripción facultativa. Con respecto al nivel de escolaridad de los pacientes de la población de estudio, los datos permitieron apreciar que entre los pacientes que se automedicaban prevalecieron aquellos con nivel medio vencido (77,31 % de estos); mientras que en el caso de los que no lo hacían predominaron los que tenían nivel básico (43,21 %), seguidos de los de nivel superior, para un 30,86 %. La prueba de Chi Cuadrado permitió establecer la dependencia entre esas dos últimas variables.

La fe en la vida se confirma a través del lenguaje, de las palabras que son las que nos dan el testimonio fiel de lo que es la vida humana. La palabra es el instrumento de lo vivido, es el medio que se enlaza entre el yo y el tú como sujetos actuantes. A través del yo y del tú, de la otredad, las palabras viven atentas, navegan por doquier, nos esperan siempre, nos retan, nos dan cuenta de la existencia humana: del amor pero también del desamor; de la alegría pero también del sufrimiento; de la esperanza pero también de la desazón; de la piedad pero también de la indiferencia; de la solidaridad pero también de la insensibilidad; la palabra para hablar pero también para escribir; la palabra nuestra frente a la palabra del otro; la palabra que nos recrea pero también que nos maltrata; pero, ante todo, la palabra como símbolo de la fecundidad para que la vida tenga el más pleno sentido de humanidad.

En el centenario de la muerte del escritor uruguayo José Enrique Rodó, el autor rememora la relación que tuvo con el escritor y polemista ecuatoriano Juan Montalvo. Los presenta a ambos como los escritores más destacados del siglo XIX en sus respectivos países, como ejemplos paradigmáticos del intelectual comprometido con tu tiempo. Ahonda en el pensamiento de estos autores que tienen singular vigencia en nuestros días. Un ensayo desmitificador y exaltador, a su vez, de la vida y obra de estos brillantes autores latinoamericanos que murieron lejos de sus países, en la pobreza y el olvido.

Uno de los descubrimientos intelectuales más gratos que me han ocurrido a mis sesenta y dos mayos es la narrativa del escritor argentino Antonio Di Benedetto (Mendoza 1922-Buenos Aires 1986). Lo descubrí gracias a la película de su compatriota Lucrecia Martel, Zama, basada en la novela del mismo nombre, cuyo autor es Di Benedetto. La película me llevó a la novela y la novela a otros libros de este formidable autor, un tanto opacado por los monstruos de la literatura argentina: Borges, Cortázar, Arlt, Piglia, entre otros. Así es como llegué a El Silenciero (la primera edición apareció en 1964), libro con el cual me he identificado de manera soprendente, hasta preocupante, diría. Llegó un momento que parecía que no lo estaba leyendo sino escribiendo. Que los ruidos que escuchaba el personaje eran los ruidos que yo escuchaba. Que esos ruidos me estaban volviendo loco (o esquizofrénico, para utilizar una palabra más elegante y más científica).

Modern electric power distribution systems are progressively integrating electronic power converters. However, the design of electronic-power-converter-based systems is not a straightforward task, as the interactions among the different converters can lead to dynamic degradation or instabilities. In addition, electric power distribution systems are expected to consist of commercial-off-the-shelf converters, which implies limited information about the dynamic behavior of the devices. Large-signal blackbox modeling approaches have been proposed in order to obtain accurate dynamic models of commercial converters that can be used for system-level analyses. However, most of the works are focused on DC-DC converters. In this work, a large-signal blackbox model is proposed to model grid-connected three-phase DC-AC converters. An experimental setup has been used to demonstrate the limitations of small-signal models and the capability of the proposed modeling approach to capture the dynamic behavior of the converter when large perturbations are applied. Finally, the automation of the model identification process is discussed.

Uno de los descubrimientos intelectuales más gratos que me han ocurrido a mis sesenta y dos mayos es la narrativa del escritor argentino Antonio Di Benedetto (Mendoza 1922-Buenos Aires 1986). Lo descubrí gracias a la película de su compatriota Lucrecia Martel, Zama, basada en la novela del mismo nombre, cuyo autor es Di Benedetto.

El presente artículo expone las circunstancias en las que se produjo un brusco cambio de sucesión durante el reinado de Andrónico II Paleólogo (12821328), quien en el año 1321, tras la muerte de su hijo mayor y heredero Miguel IX (1320), excluyó de la sucesión imperial al hijo de éste último, Andrónico III, colocando en su lugar a su segundo vástago, Constantino, y principalmente al hijo bastardo de éste, Miguel Katharos, situación que sería el preámbulo a la Primera Guerra Civil entre los Paleólogos.The present article exposes the circumstances in which an abrupt change in the succession which took place during the reign of Andronikos II Palaiologos (1282-1328), who in the year 1321, after the decease of his eldest son and heir Michael IX (1320), excluded from the imperial succession the latter's son, Andronikos III, putting in his place his second son, Constantine, and above all the latter's bastard, Michael Katharos, a situation that would be the preamble to the First Civil War between the Palaiologoi.

Se hace una invocación a que se debe recuperar la fe en el pueblo que por naturaleza es creador, cuyas culturas pueden ser el motor que ayude a sacarnos de este abandono. Culturas que sabrán dar la personalidad necesaria para no sucumbir ante los modelos que nos llegan arrolladores desde afuera

Es el año 78 del siglo pasado. Un grupo de aspirantes a poetas nos reunimos religiosamente todos los sábados en un bar de la Facultad de Jurisprudencia de la Universidad Central del Ecuador o en un aula de esa misma Facultad o en la casa de Pepe Torres y su esposa Margarita, quienes de manera generosa acogen a ese tropel de seres desiguales que parecen (parecemos) salidos de un cuadro impresionista.

En este texto, el autor presenta un recuento que es celebración de los años azarosos que le tocó compartir, en el ejercicio de la diplomacia, con el escritor y diplomático Francisco Proaño Arandi en los años 80 en varios países del continente. Se testimonia la experiencia intensa vivida en la Nicaragua sandinista; y en Cuba, enfrentando situaciones que, para Galarza, resultan inolvidables y vitales en medio de la heroicidad cotidiana de un pueblo del que prefiere siempre “hablar bien”. Reconstrucción de diálogos literarios en los que en su momento se definió el título de la novela de Proaño: Antiguas caras en el espejo. Esta crónica es un viaje a la memoria y un testimonio de una pasión compartida: la literatura y la práctica profesional de la diplomacia con sus paradojas, desolación y, a veces, reivindicaciones; crónica que nos participa de algunos hechos que hoy son parte de la historia, pero también de la amistad fraterna entre escritores que nunca han dejado de saber amigos.

El presente estudio analizó las concentraciones de cadmio y plomo en diecisiete sitios distribuidos a lo largo y ancho de la ciudad de Quito, además de un sector en la ciudad de Sangolquí, y dos más en las parroquias de Carapungo y Calderón. La metodología utilizada es el Biomonitoreo, la cual emplea organismos vivos, en este caso briofitas (musgo), debido a que al no contar con una pared celular se facilita la absorción de los contaminantes del aire. Este musgo fue recolectado en el refugio de vida silvestre el Molinuco para asegurar niveles mínimos de contaminación y luego fue sembrado en los sitios establecidos dentro de las ciudades, permaneciendo en éstos por cincuenta días. Posteriormente, las concentraciones de contaminantes se determinaron en el laboratorio mediante un equipo de absorción atómica marca Varian, modelo spectrAA 50. Finalmente, se empleó una ecuación matemática que transforma la concentración en ppm del musgo a microgramos por metro cúbico de aire Los resultados encontrados indican la presencia de Plomo en todos los puntos analizados, el Cadmio se halla sólo en las cercanías del intercambiador de Zámbiza.

Background: Organizing pneumonia (OP), an interstitial lung disease, has been observed in patients with inflammatory demyelinating diseases (IDDs) treated with anti-CD20, particularly after COVID-19, but data are limited., Aim: To provide a detailed characterization of COVID-19-associated OP in IDD patients treated with anti-CD20., Methods: Bi-centric retrospective cohort study including patients with multiple sclerosis (MS), aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who received anti-CD20 and were diagnosed with COVID-19-associated OP between March 2020 and October 2023., Results: Nineteen patients were included (mean age 46.8 years; 52.6% female; 63% rituximab, 37% ocrelizumab). Sixteen had MS, two MOGAD, and one AQP4 + NMOSD. Intermittent fever was the predominant symptom. Hospitalization occurred in all but one patient, without fatalities. Chest CT consistently showed OP patterns. Thirteen patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR in bronchoalveolar lavage. Treatments included corticosteroids, antivirals, monoclonal antibodies, and convalescent plasma. Fourteen patients postponed infusions; nine resumed post-recovery (median 11.9 months), two switched due to hypogammaglobulinemia, and three stopped. After a mean follow-up of 1.5 years, lung abnormalities and clinical manifestations resolved in 18 patients; however, 13 experienced long-COVID., Conclusions: In anti-CD20-treated patients with recurrent fever and distinctive CT features, COVID-19-associated OP should be considered., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R Carvajal is currently being funded by a Research grand from the European Charcot Foundation. In 2023, he received a grant by “Vall d′Hebron Institut de Recerca.” In 2021, he received an ECTRIMS Fellowship training performed during 2021–2022. He has also received speaking honoraria from Roche, Novartis, Biogen, Merck, and Sanofi.B Rodríguez-Acevedo has received speaking honoraria from Merck and honoraria for consulting services from Novartis.L García-Vasco has received honoraria as a speaker from Merck and Novartis; and received support for attending meetings and congresses from BMS, Horizon, Janssen, Novartis and Sanofi.A Zabalza has a predoctoral grant Rio Hortega, from the Instituto de Salud CarlosIII, Spain (CM22/00237), received travel expenses for scientific meetings from Biogen-Idec, Merck Serono and Novartis; speaking honoraria from Eisai; and a study grant from Novartis.H Ariño has received grant from Instituto de Salud Carlos III, Spain; JR22/00072.L Bollo is supported by a 1-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof. Xavier Montalban in 2022.N Cabello-Clotet has received support for attending meetings and congresses and honoraria as a speaker from Gilead, GSK Janssen, and MSD.A Cobo-Calvo has received grant from Instituto de Salud Carlos III, Spain; JR19/00007.M Comabella has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, and Novartis.A García-Sarreón is currently an ECTRIMS clinical fellowship awardee for 2023–2024 and receives support from ECTRIMS.S Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed and MSD; as well as research support from Novartis.A Pappolla has received funding travel from Roche and speaking honoraria from Novartis. He performed an ECTRIMS Clinical Training Fellowship program during 2021, and is currently performing an MSIF-ARSEP Fellowship program.J Rio has received speaking honoraria and personal compensation for participating on Advisory Boards from Biogen-Idec, Genzyme, Janssen, Merck- Serono, Novartis, Teva, Roche, and Sanofi-Aventis.P Tagliani has received support during one year as an ECTRIMS clinical fellowship awardee in 2019–2020.C Tur is currently being funded by a Miguel Servet contract, awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (CP23/00117). She has also received a 2020 Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008), awarded by “la Caixa” Foundation (ID 100010434), a 2021 Merck’s Award for the Investigation in MS awarded by Fundación Merck Salud (Spain), a 2021 Research Grant (PI21/01860) awarded by the ISCIII, Ministerio de Ciencia e Innovación de España, and a FORTALECE research grant (FORT23/00034) also by the ISCIII, Ministerio de Ciencia e Innovación de España. In 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society. She is a member of the Editorial Board of Neurology Journal and Multiple Sclerosis Journal. She has also received honoraria from Roche, Novartis, Merck, Immunic Therapeutics, and Bristol Myers Squibb. She is a steering committee member of the O’HAND trial and of the Consensus group on Follow-on DMTs.A Vidal-Jordana has received support has received support for contracts Juan Rodes (JR16/00024) and from Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, and Merck.A Vilaseca has received a Rio Hortega grant (CM22/00247) by Institute of Health Carlos III (ISCIII).A Villar has engaged in consulting and/or participated as a speaker in events organized by Boehringer Ingelheim, Roche, Janssen, and Glaxo, with travel expenses covered by Boehringer Ingelheim, Roche, Glaxo, Chiesi, and Novartis for participation in scientific meetings. In addition, research support has been received from Janssen and GlaxoSmithKline.J Sastre-Garriga serves as co-Editor for Europe on the editorial board of Multiple Sclerosis Journal and as Editor-in-Chief in Revista de Neurología, receives research support from Fondo de Investigaciones Sanitarias (19/950) and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis and Merck.C Oreja-Guevara has received honoraria for speaking and serving on advisory boards from Biogen Idec., F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck, Janssen, BMS, Novartis and Teva.M Tintoré has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Immunic Therapeutics, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bioand Teva Pharmaceuticals. Data Safety Monitoring Board for Parexel and UCB Biopharma, Relapse Adjudication Committee for IMCYSE SA.X Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS.G Arrambide has received speaking honoraria and consulting services or participation in advisory boards from Sanofi, Roche and Horizon Therapeutics/Amgen; and travel expenses for scientific meetings from Novartis, Roche, ECTRIMS and EAN.J Castillo, A Falcó-Roget, I Galan, I Gómez-Estévez, G Granados, G Mato-Chain, D La Puma, L Midaglia, A Nieto-García, M Rodríguez, and I Sansano report no disclosures.

Accurately estimating gross primary productivity (GPP) is crucial for simulating the carbon cycle and addressing the challenges of climate change. However, estimating GPP is challenging due to the absence of direct measurements at scales larger than the leaf level. To overcome this challenge, researchers have developed indirect methods such as remote sensing and modeling approaches. This study estimated GPP in a humid páramo ecosystem in the Andean Mountains using machine learning models (ML), specifically Random Forest (RF) and Support Vector Regression (SVR), and compared them with traditional models. The study's objective was to analyze the strength and complex nonlinear relationships that govern GPP and to perform an uncertainty analysis for future climate projections. The methodology used to estimate GPP showed that ML-based models outperformed traditional models. The performance of ML models varied significantly among seasons, with the correlation coefficient (R) ranging from 0.24 to 0.86. The RF model performed better in capturing the temporal changes and magnitude of GPP in the less humid season, displaying the highest R (0.86), lowest root mean squared error (0.37 g C*m -2 ), and percentage bias (-3%). Additionally, the analysis indicates that solar radiation is the primary predictor of GPP in the páramo biome, rather than water. The study presents a method for deriving daily GPP fluxes and evaluates the impact of various variables on GPP estimates. This information can be employed in the development of vegetation prediction models., Competing Interests: Declarations. 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., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Background: Prostate cancer is the second most common neoplasm in men, with projections estimating over one million new cases by 2045. Differentially expressed genes can significantly enhance the diagnosis, treatment, monitoring, and prognosis of this disease., Purpose: to systematically review and analyze validated differentially expressed mRNAs in prostate cancer patients to propose a robust molecular profile for clinical diagnostics., Methods: A systematic review was conducted following PRISMA guidelines, searching literature databases for mRNAs with validated differential expression in adult prostate cancer patients. Identified mRNAs were analyzed using STRING, Cytoscape, and DrugBank to explore protein-protein interactions and potential drug targets., Results: A total of 5003 participants from Europe, Asia, America, and Oceania were included, and 144 mRNAs ( p < 0.05) were reported across 75 primary articles, predominantly validated using RT-qPCR with tissue samples. Among these, at least 36 mRNAs were identified as targets for cancer-related drugs. Enrichment analysis revealed the top pathways were associated with cancer, including specific prostate cancer terms. Key nodes emerged as hubs in the protein-protein interaction network., Conclusion: Based on our comprehensive in silico analysis of validated differentially expressed mRNAs, we propose a molecular profile of twenty-five mRNAs with significant potential for clinical diagnosis of prostate cancer. These findings offer a valuable foundation for developing precision oncology strategies to improve patient outcomes.

Objective: The objective of this study was to investigate which of two short questionnaires, the Asthma Control Test (ACT) or the COPD Assessment Test (CAT), correlates better with severity variables and whether they share similar determinants in patients with asthma-COPD overlap. Method: This observational, cross-sectional, multicentric study included smokers and former smokers of more than 10 pack-years, with non-fully reversible airflow obstruction and either a concomitant diagnosis of asthma or signs of type 2 inflammation, from 15 centres in Spain. Results: A total of 157 patients were included, 109 (69.4%) were men, the mean age was 63.3 (SD: 9) years and the mean FEV1 (%) was 59.7% (SD: 20.5%). The mean CAT score was 14.5 (SD: 8.7), and the mean ACT score was 17.9 (SD: 5.2). Both scores showed good correlations (r = 0.717; p < 0.001). In the multivariate analysis, the Hospital Anxiety and Depression Scale and mMRC dyspnoea scores were independently and significantly associated with both the CAT and ACT scores; however, age was only significantly associated with the CAT, and the EQ-5D scores and the number of exacerbations in the previous year were only significantly associated with the ACT scores. The ACT had a slightly better predictive value for exacerbations than the CAT (AUC = 0.70 (95% CI: 0.62 to 0.79 vs. 0.65 (95% CI: 0.56 to 0.74))). Conclusions: There is a good correlation between ACT and CAT scores in patients with ACO. However, severe patients scored worse on the CAT than the ACT. Anxiety, depression and dyspnoea were significantly associated with both the CAT and ACT scores. The ACT was a slightly better predictor of exacerbations than the CAT in this population.

Cancer and infectious diseases are two of the world's major public health problems. Gemcitabine (GEM) is an effective chemotherapeutic agent against several types of cancer. In this study, we developed macrocapsules incorporating GEM into a chitosan matrix blended with magnetite and zeolite by ionic gelation. Physicochemical characterization was performed using HRTEM-ED, XRD, FESEM-EDS, FT-IR, TGA, encapsulation efficiency (%E.E.), and release profiles at pHs 7.4 and 5.0. Cell viability tests against A549 and H1299 cell lines, and microbiological properties against staphylococcal strains were performed. Our results revealed the successful production of hemispherical capsules with an average diameter of 1.22 mm, a rough surface, and characteristic FT-IR material interaction bands. The macrocapsules showed a high GEM encapsulation efficiency of over 86% and controlled release over 24 h. Cell viability assays revealed that similar cytotoxic effects to free GEM were achieved with a 45-fold lower GEM concentration, suggesting reduced dosing requirements and potentially fewer side effects. Additionally, the macrocapsules demonstrated potent antimicrobial activity, reducing Staphylococcus epidermidis growth by over 90%. These results highlight the macrocapsules dual role as a chemotherapeutic and antimicrobial agent, offering a promising strategy for treating lung cancer in patients at risk of infectious diseases or who are immunosuppressed.

Purpose: To develop and test a deep learning (DL) algorithm for detecting referable glaucoma in the Los Angeles County (LAC) Department of Health Services (DHS) teleretinal screening program., Methods: Fundus photographs and patient-level labels of referable glaucoma (defined as cup-to-disc ratio [CDR] ≥ 0.6) provided by 21 trained optometrist graders were obtained from the LAC DHS teleretinal screening program. A DL algorithm based on the VGG-19 architecture was trained using patient-level labels generalized to images from both eyes. Area under the receiver operating curve (AUC), sensitivity, and specificity were calculated to assess algorithm performance using an independent test set that was also graded by 13 clinicians with one to 15 years of experience. Algorithm performance was tested using reference labels provided by either LAC DHS optometrists or an expert panel of 3 glaucoma specialists., Results: 12,098 images from 5,616 patients (2,086 referable glaucoma, 3,530 non-glaucoma) were used to train the DL algorithm. In this dataset, mean age was 56.8 ± 10.5 years with 54.8% females and 68.2% Latinos, 8.9% Blacks, 2.7% Caucasians, and 6.0% Asians. 1,000 images from 500 patients (250 referable glaucoma, 250 non-glaucoma) with similar demographics (p ≥ 0.57) were used to test the DL algorithm. Algorithm performance matched or exceeded that of all independent clinician graders in detecting patient-level referable glaucoma based on LAC DHS optometrist (AUC = 0.92) or expert panel (AUC = 0.93) reference labels. Clinician grader sensitivity (range: 0.33-0.99) and specificity (range: 0.68-0.98) ranged widely and did not correlate with years of experience (p ≥ 0.49). Algorithm performance (AUC = 0.93) also matched or exceeded the sensitivity (range: 0.78-1.00) and specificity (range: 0.32-0.87) of 6 LAC DHS optometrists in the subsets of the test dataset they graded based on expert panel reference labels., Conclusions: A DL algorithm for detecting referable glaucoma developed using patient-level data provided by trained LAC DHS optometrists approximates or exceeds performance by ophthalmologists and optometrists, who exhibit variable sensitivity and specificity unrelated to experience level. Implementation of this algorithm in screening workflows could help reallocate eye care resources and provide more reproducible and timely glaucoma care.

Purpose: To assess patterns in gonioscopy during initial glaucoma evaluations in the United States., Design: Retrospective, case-control study., Methods: Patients undergoing initial glaucoma evaluation between 2009-2020 were identified in the Optum Clinformatics DataMart. Initial evaluation was defined as follows: (1) glaucoma suspect, anatomical narrow angle (ANA), or primary/secondary glaucoma diagnosed by an ophthalmologist; (2) continuously observable during a 36-month lookback period; (3) no history of glaucoma medications, laser, or surgical procedures; and (4) optical coherence tomography (OCT) or visual field performed within 6 months of initial diagnosis. Logistic regression models were developed to identify factors associated with no record of gonioscopy based on Current Procedural Terminology (CPT) codes., Results: Among 198,995 patients, 20.4% and 29.5% had recorded gonioscopy on the day of diagnosis or within 6 months, respectively. On multivariable analysis, odds of recorded gonioscopy within 6 months of initial evaluation was lower (P < .001) among non-Hispanic Whites (OR=0.84) but similar for Blacks (OR=1.02) and Hispanics (OR=0.96) compared with Asians. Age ≥60 years (OR<0.82), pseudophakia/aphakia (OR=0.58), or residence outside of the Northeast region (OR=0.66-0.84) conferred lower odds of recorded gonioscopy (P < .001). Angle closure glaucoma (OR=0.85), secondary glaucoma (OR=0.31), or open angle glaucoma/suspect (OR=0.12/0.24, respectively) patients were less likely to have recorded gonioscopy compared to ANA patients (P < .01)., Conclusions: More than 70% patients undergoing initial glaucoma evaluation in the United States do not have a record of gonioscopy, especially elderly, non-Hispanic White, and pseudophakic patients in non-Northeast regions. This pattern does not conform to current practice guidelines and could contribute to misdiagnosed disease and suboptimal outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Problem: A shortage of curriculum-aligned formative multiple-choice questions (FMCQs) remains despite their known learning benefits in preclinical medical education due to limitations on teaching faculty time and other reasons. In response, students often use extramural resources such as commercial or collaborative question banks; however, these options are often expensive and cannot be aligned with the content of each school's unique curriculum. In addition, students need feedback on their learning in a manner that parallels the format of summative assessments. In this pilot, the authors aimed to enhance student learning by creating an intramural formative practice resource that was developed as the curriculum unfolded under the direction of the faculty leading the concurrently running curricular units., Approach: The authors developed a workflow known as Professor-Reviewed Exam Practice (PREP) in 2023. PREP partnered preclinical medical students and faculty to create vignette-style, single best response FMCQs with feedback for every lecture and self-guided learning module in multiple preclinical blocks of The Ohio State University College of Medicine undergraduate medical curriculum., Outcomes: PREP established a sustainable, student-led, faculty-guided workflow that created high-quality, curriculum-aligned FMCQs for student use in the preclinical medical curriculum over a 14-month period. Usage rates were high across multiple preclinical blocks, reflecting high student demand for FMCQs of this nature and their value as a study aid. Survey data showed faculty agreed that their time commitment and role in the PREP workflow was appropriate., Next Steps: Future work will evaluate the benefits of PREP to students by exploring the potential impact of PREP FMCQs on summative assessment performance and if writing FMCQs confers benefits to PREP team members. Faculty survey indicated that performance data from PREP FMCQs could be used to tailor upcoming teaching and learning methods, which is an area for future inquiry., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Research on personal adornments depends on the reliable characterisation of materials to trace provenance and model complex social networks. However, many analytical techniques require the transfer of materials from the museum to the laboratory, involving high insurance costs and limiting the number of items that can be analysed, making the process of empirical data collection a complicated, expensive and time-consuming routine. In this study, we compiled the largest geochemical dataset of Iberian personal adornments (n = 1243 samples) by coupling X-ray fluorescence compositional data with their respective X-ray diffraction mineral labels. This allowed us to develop a machine learning-based framework for the prediction of bead-forming minerals by training and benchmarking 13 of the most widely used supervised algorithms. As a proof of concept, we developed a multiclass model and evaluated its performance on two assemblages from different Portuguese sites with current mineralogical characterisation: Cova das Lapas (n = 15 samples) and Gruta da Marmota (n = 10 samples). Our results showed that decisión-tres based classifiers outperformed other classification logics given the discriminative importance of some chemical elements in determining the mineral phase, which fits particularly well with the decision-making process of this type of model. The comparison of results between the different validation sets and the proof-of-concept has highlighted the risk of using synthetic data to handle imbalance and the main limitation of the framework: its restrictive class system. We conclude that the presented approach can successfully assist in the mineral classification workflow when specific analyses are not available, saving time and allowing a transparent and straightforward assessment of model predictions. Furthermore, we propose a workflow for the interpretation of predictions using the model outputs as compound responses enabling an uncertainty reduction approach currently used by our team. The Python-based framework is packaged in a public repository and includes all the necessary resources for its reusability without the need for any installation., Competing Interests: 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 Sanchez-Gomez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Integrating genetic data into conservation management decisions is a challenging task that requires strong partnerships between researchers and managers. Conservation in Latin America is of crucial relevance worldwide given the high biodiversity levels and the presence of hotspots in this region. Methods: We conducted a survey across Latin America to identify gaps and opportunities between genetic researchers and conservation managers. We aimed to better understand conservation managers' points of view and how genetic research could help conservation practitioners to achieve their goals, by implementing genetic assessments that could effectively inform conservation practices. We distributed an online survey via four regional collaborating organizations and 32 focal points based in 20 Latin American countries. The target respondents were conservation managers of species or areas in Latin America. Results: We collected a total of 468 answered questionnaires from 21 Latin American countries. Most respondents (44%) were from an academic or research institution while non-academics were mainly from non-governmental institutions (30%) and government agencies (25%). Most respondents (65%) have performed or used genetic assessments in their managed area or species, either alone, in partnership, contracting someone else or using published results. For the majority of this group, the genetic results were relevant to their conservation management goals, helping to inform management decisions. Respondents that had not performed genetic assessments (35%) were mainly from the non-academic group, and their main barriers were limited access to funds, genetic lab facilities, and trained personnel to design studies and conduct lab work. Discussion: From the findings, we describe the current situation and provide a general diagnosis of the conservation-genetics gap in Latin America. We describe the gender gap, academic-practitioner co-development of conservation questions and projects, and the nationality and residency of Latin American conservation managers in relation to the countries where they work. We discuss opportunities to co-create research questions and co-develop studies based on conservation practitioners' needs. We offer recommendations for overcoming barriers to integrate genetic information into conservation actions, and advance agendas that fit the needs and realities of the highly heterogeneous, biodiverse and challenging Latin American region., Competing Interests: Author ND was employed by Aquatic and Terrestrial Pioneers Consulting Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Napolitano, Clavijo, Rojas-Bonzi, Miño, González-Maya, Bou, Giraldo, Martino, Miyaki, Aguirre, Cosacov, Milián-García, Prosdocimi, Ramírez-Bravo, Tovar, Velez-Zuazo, Barrios, Herrera-Fernández, Montiel-Villalobos, Oliveira-Miranda, Pool, Santos-Murgas, Segovia-Salcedo, Cecchi, Dans, Dilchand, Lima, Novas, Pelz-Serrano, Pougy, Rodríguez, van der Meer and Zapata-Ríos.)

Negative pressure wound therapy is currently one of the most popular treatment approaches that provide a series of benefits to facilitate healing, including increased local blood perfusion with reduced localized oedema and control of wound exudate. The porous foam dressing is a critical element in the application of this therapy and its choice is based on its ability to manage exudate. Industry standards often employ aqueous solutions devoid of proteins to assess dressing performance. However, such standardized tests fail to capture the intricate dynamics of real wounds, oversimplifying the evaluation process. This study aims to evaluate the technical characteristics of two different commercial polyurethane foam dressings during negative pressure wound therapy. We introduce an innovative experimental model designed to evaluate the effects of this therapy on foam dressings in the presence of viscous exudates. Our findings reveal a proportional increase in dressing fibre occupancy as pressure intensifies, leading to a reduction in dressing pore size. The tests underscore the pressure system's diminished efficacy in fluid extraction with increasing fluid viscosity. Our discussion points to the need of establishing standardized guidelines for foam dressing selection based on pore size and the necessity of incorporating real biological exudates into industrial standards., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Transition metal oxides are a great alternative to less expensive hydrogen evolution reaction (HER) catalysts. However, the lack of conductivity of these materials requires a conductor material to support them and improve the activity toward HER. On the other hand, carbon paste electrodes result in a versatile and cheap electrode with good activity and conductivity in electrocatalytic hydrogen production, especially when the carbonaceous material is agglomerated with ionic liquids. In the present work, an electrode composed of multi-walled carbon nanotubes (MWCNTs) and cobalt ferrite oxide (CoFe 2 O 4 ) was prepared. These compounds were included on an electrode agglomerated with the ionic liquid N-octylpyridinium hexafluorophosphate (IL) to obtain the modified CoFe 2 O 4 /MWCNTs/IL nanocomposite electrode. To evaluate the behavior of each metal of the bimetallic oxide, this compound was compared to the behavior of MWCNTs/IL where a single monometallic iron or cobalt oxides were included (i.e., α-Fe 2 O 3 /MWCNTs/IL and Co 3 O 4 /MWCNTs/IL). The synthesis of the oxides has been characterized by X-ray diffraction (XRD), RAMAN spectroscopy, and field emission scanning electronic microscopy (FE-SEM), corroborating the nanometric character and the structure of the compounds. The CoFe 2 O 4 /MWCNTs/IL nanocomposite system presents excellent electrocatalytic activity toward HER with an onset potential of -270 mV vs. RHE, evidencing an increase in activity compared to monometallic oxides and exhibiting onset potentials of -530 mV and -540 mV for α-Fe 2 O 3 /MWCNTs/IL and Co 3 O 4 /MWCNTs/IL, respectively. Finally, the system studied presents excellent stability during the 5 h of electrolysis, producing 132 μmol cm -2 h -1 of hydrogen gas.

Clinical trials (CTs) are essential for medical advancements but face significant challenges, particularly in professional training and role clarity. Principal investigators, clinical research coordinators (CRCs), nurses, clinical trial pharmacists, and monitors are key players. Each faces unique challenges, such as maintaining protocol compliance, managing investigational products, and ensuring data integrity. Clinical trials' complexity and evolving nature demand specialized and ongoing training for these professionals. Addressing these challenges requires clear role delineation, continuous professional development, and supportive workplace environments to improve retention and trial outcomes. Enhanced training programs and a collaborative approach are essential for the successful conduct of clinical trials and the advancement of medical research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peralta and Sánchez-Santiago.)

Aim: To perform an independent validation of deep learning (DL) algorithms for automated scleral spur detection and measurement of scleral spur-based biometric parameters in anterior segment optical coherence tomography (AS-OCT) images., Methods: Patients receiving routine eye care underwent AS-OCT imaging using the ANTERION OCT system (Heidelberg Engineering, Heidelberg, Germany). Scleral spur locations were marked by three human graders (reference, expert and novice) and predicted using DL algorithms developed by Heidelberg Engineering that prioritise a false positive rate <4% (FPR4) or true positive rate >95% (TPR95). Performance of human graders and DL algorithms were evaluated based on agreement of scleral spur locations and biometric measurements with the reference grader., Results: 1308 AS-OCT images were obtained from 117 participants. Median differences in scleral spur locations from reference locations were significantly smaller (p<0.001) for the FPR4 (52.6±48.6 µm) and TPR95 (55.5±50.6 µm) algorithms compared with the expert (61.1±65.7 µm) and novice (79.4±74.9 µm) graders. Intergrader reproducibility of biometric measurements was excellent overall for all four (intraclass correlation coefficient range 0.918-0.997). Intergrader reproducibility of the expert grader (0.567-0.965) and DL algorithms (0.746-0.979) exceeded that of the novice grader (0.146-0.929) for images with narrow angles defined by OCT measurement of angle opening distance 500 µm anterior to the scleral spur (AOD500)<150 µm., Conclusions: DL algorithms on the ANTERION approximate expert-level measurement of scleral spur-based biometric parameters in an independent patient population. These algorithms could enhance clinical utility of AS-OCT imaging, especially for evaluating patients with angle closure and performing intraocular lens calculations., Competing Interests: Competing interests: BYX and ASH receive research support from Heidelberg Engineering. MS is employed by Heidelberg Engineering., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)