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Indication of oxygen therapy in fibrotic interstitial lung diseases is not standardized and its specific requirements are not well defined. The objective of this study was to evaluate ambulatory oxygen therapy features in lung fibrotic patients. Clinical and exploratory data, including 6-minute walking test and pulmonary hypertension, from one hundred and seven patients with fibrotic interstitial lung disease that received ambulatory oxygen treatment were studied. In up to 40% of cases the prescription of oxygen therapy was made after performing a 6-minute walking test. Patients who required ambulatory oxygen only during exercise presented a mild to moderate reduction of the predicted % FVC (62.1 ± 19) and DLCO (49 ± 14.4) while patients who had respiratory failure at rest (mean PaO2 51.9 ± 6.7) presented a moderate reduction of %FVC (56.8 ± 15.6) but a severe decrease of %DLCO (31.67 ± 12). Pulmonary hypertension (PH) was evaluated in 47.7% of patients and occurred in 60.8% of them. In conclusion, there is no pulmonary functional predictor of oxyhaemoglobin desaturation during exercise. PH is frequently associated with interstitial lung diseases, mainly when respiratory failure at rest appears. The heterogeneity of the patients and limitation of retrospective studies could be the cause of the tributes for potential benefits of oxygen treatment in interstitial lung diseases.

Con el propósito de contribuir a la discusión teórica y política sobre la capacidad agencial de las mujeres en condiciones de subalternidad, el presente artículo se basa en un trabajo de investigación empírica sobre los procesos y experiencias migratorias de mujeres latinoamericanas y africanas residentes en Mallorca, España. Demuestra que a pesar de la condicionalidad de la segmentación por género y raza del mercado laboral y el uso político del velo, las mujeres inmigrantes dan cuenta de acciones concretas de resistencias identitarias y políticas desde los márgenes en una búsqueda por una ciudadanía real.

Manuel Alcántara Sáez y Carlos Arnulfo Melo (eds.). Editorial Universidadde Salamanca. 2008, 380 pp.

Se reporta el caso de un varón de 36 años con neurorretinitis por Bartonella henselae, cuyo seguimiento periódico fue realizado con tomografía de coherencia óptica (TCO). El inicio de la enfermedad se caracterizó por disminución de agudeza visual (AV) unilateral, indolora, de inicio brusco en ojo derecho (OD), asociado a cuadro febril. El examen fundoscópico mostró edema en polo posterior, extendiéndose desde el disco óptico hasta la región macular en OD. La TCO confirmó el engrosamiento macular y del disco óptico así como la presencia de fluido macular subretinal. Los estudios sistémicos fueron normales con excepción del hemograma por presencia de leucocitosis y serología positiva a Bartonella henselae. El seguimiento tomográfico permitió valorar la disminución del edema macular, con la correspondiente mejora de la agudeza visual y ausencia de complicaciones asociadas. Este reporte describe la utilidad del seguimiento con TCO en un paciente con neurorretinitis por Bartonella henselaeThe case of a 36 year-old male with neuroretinitis caused by Bartonella henselae is reported, whose periodic follow-up was done through optical coherence tomography (OCT). The onset of this disease was characterized by unilateral low visual acuity (VA), painless, of sudden onset, in the right eye (RE), associated to l febrile symptom. The funduscopic examination showed edema in the posterior pole which extended from the optical disc to the macular region in the RE. The OCT confirmed macular and optical disc thickening, as well as the presence of subretinal macular fluid. Systemic studies were normal except for a blood count due to the presence of leukocytosis and positive for Bartonella henselae. The follow up with CT Scan helped to evaluate the decrease in macular edema, with the subsequent improvement of visual acuity and absence of related complications. This report describes the utility of the follow up with OCT in a patient with neuroretinitis caused by Bartonella henselae

Ured američkog predsjednika George W. Busha je 2001. godine u potpunosti napustio mogućnost usvajanja Kyoto Proktokola. Ovo, zajedno s nedostatkom primjerene politike i zakonodavstva potrebnog za rješavanje pitanja globalnog zatopljenja, uz prisutne posljedice klimatskih promjena, uzrokovale su pomicanje kreiranja odgovorajuće legislative sa zakonodavne i izvršne vlasti na sudove, doprinoseći tako važnom razvoju parničenja vezanog za klimatske promjene. Predmetno parničenje nije samo američki već i svjetski fenomen. Moguće ga je pronaći i u Europi, i to unatoč činjenici postojanja naprednih pravnih režima za zaštitu okoliša i klimatske promjene. Međutim, vjerodostojnost ove izjave je upitna, posebno kada se uzme u obzir nivo učinkovitosti i primjene Europske Direktive za odgovornost za štete u okolišu (EU Environmental Liability Directive - Direktiva) u parnicama vezanima za klimatske promjene. Naime, Direktiva ne predstavlja potpuni i sveobuhvatni režim odgovornosti kojim bi se osigurala adekvatna regulativa za odgovornosti proizišle iz područja zaštite okoliša. Neki su mišljenja da bi se Direktiva trebala zvati Environmental Responsibility Directive (Napomena: Engleski jezik pravi razliku između rječi “liability” i “responsibility”). Cilj ovog članka je utvrditi nivo adekvatnosti primjene Direktive u parnicama vazanima za klimatske promjene, njezine limite u takvoj primjeni i potencijalne probleme. U tu svrhu, autor ispituje postojeći pravni režim kao i slučajeve parničenja vezanog za klimatske promjene u SAD-u, ali i na nivou Europske Unije. Članak završava kratkom studijom parničenja vezanog uz klimatske promjene i postojeći pravni režim u Hrvatskoj (uključujući i samu Direktivu). Konačni zaključak je da je mogućnost primjene Direktive u parnicama vezanima za klimatske promjene ograničena.

Los regímenes democráticos de América Latina han superado en una gran mayoría la fase de consolidación democrática, lo que actualmente sitúa su análisis en una cuestión de calidad. Si bien la calidad de la democracia es un concepto que parte indudablemente de los principios poliárquicos (Alcántara, 2008), éste abarca múltiples elementos entre los que la Administración Electoral juega un papel determinante como garantizadora de unas verdaderas elecciones limpias, libres e imparciales. La Administración Electoral en la región latinoamericana se presenta en diversos modelos que se articulan en un continuo cuyos extremos están marcados por la total independencia formal-legal de los Organismos de Gestión Electoral –OGE- y la dependencia de éstos respecto de los Poderes del Estado. Considerando que la literatura al respecto apuesta por la independencia de estos OGE para su correcto desempeño (Hartlyn, McCoy y Mustillo, 2008), en este trabajo se pretende llevar a cabo un análisis desde la perspectiva de los ciudadanos y legisladores argentinos del modelo de administración electoral argentino, que se caracteriza por cierta dependencia de sus OGE respecto del Ejecutivo y del Poder Judicial (López Pintor, 2000), para observar si esta dependencia tiene relación con el acusado descenso de la participación electoral en las últimas elecciones presidenciales de octubre de 2007, cuyo porcentaje (76,20%) es el menor desde el regreso a la democracia.

La estenosis esofágica congénita, una entidad rara de causa desconocida cuyos reportes han aumentado en los últimos años, requiere un alto índice de sospecha para su diagnóstico y tratamiento adecuado. Se puede clasificar en tres tipos ba - sados en la etiología de la estenosis: restos traqueobronquia - les, hipertrofia fibromuscular y diafragma membranoso. Los síntomas varían dependiendo de la localización y la severi - dad de la estenosis. Las alternativas terapéuticas se basan en la sospecha clínica del tipo histológico de la lesión, pudiendo ser la dilatación con balón o la resección del segmento este - nótico. El diagnostico definitivo es histológico.

FUNDAMENTO: As crianças picadas por escorpião, pressintam ativação maciça do sistema nervoso simpática com vários graus de disfunção sistólica ventricular esquerda. OBJETIVO: Testar um protocolo de resgate em crianças com grave disfunção ventricular esquerda causada por picada de escorpião. Métodos: Quatro crianças após serem picadas por escorpião foram submetidas a: Encubação endotraqueal e suporte respiratório, eletrocardiograma, radiografia de tórax, ecocardiograma e determinação sérica da norepinefrina e troponina I. As análises foram repetidas após 12, 24 e 48 horas. As seguintes medicações intravenosas foram administradas: dobutamina 4-6 μg/kg/min; amiodarona 3 mg/kg durante duas horas, com dose de manutenção de 5 mg/kg/dia; e furosemida 0,5 mg/kg. Amiodarona, dobutamina e furosemida foram administradas durante as primeiras 48 horas. Bloqueadores beta-adrenérgicos e inibidores da enzima conversora da angiotensina foram administrados até 48 após a internação, uma vez que o estado clínico havia melhorado e a fração de ejeção ventricular esquerda encontrava-se acima de 0,35%. RESULTADOS: Na admissão, a dosagem da norepinefrina foi 1.727,50± 794,96 pg/ml, a de troponina I 24,53 ± 14,09 ng/ml e a fração de ejeção do ventrículo esquerdo foi 0,20 ± 0,056. Após 12 horas, os níveis séricos de norepinefrina e de troponina I diminuíram para a metade dos valores iniciais e a fração de ejeção aumentou para 0,32 ± 0,059. Durante as 24 e 48 horas subseqüentes, a fração de ejeção elevou-se para 0,46 ± 0,045 (pFUNDAMENTO: Los niños con picaduras de escorpión sufren activación masiva del sistema nervioso simpático con varios grados de disfunción sistólica ventricular izquierda. OBJETIVO: Probar un protocolo de rescate en niños con disfunción ventricular severa izquierda ocasionada por picadura de escorpión. MÉTODOS: Cuatro niños tras un escorpión picarlas se sometieron a: incubación endotraqueal y soporte respiratorio, electrocardiograma, radiografía de tórax, ecocardiograma y determinación sérica de la norepinefrina y troponina I. Los análisis se repitieron tras 12, 24 y 48 horas. Las siguientes medicaciones intravenosas se administraron: dobutamina 4-6 mcg/kg/min; amiodarona 3 mg/kg durante dos horas, con dosis de mantenimiento de 5 mg/kg/día; y furosemida 0.5 mg/kg. Amiodarona, dobutamina y furosemida se administraron durante las primeras 48 horas. Bloqueante betaadrenergicos e inhibidores de la enzima convertidora de la angiotensina se administraron hasta 48 tras la internación, una vez que el estado clínico había mejorado y la fracción de eyección ventricular izquierda se hallaba superior a un 0,35%. RESULTADOS: Al ingreso, la dosificación de la norepinefrina fue 1727,50± 794,96 pg/ml, la de troponina I 24,53 ± 14,09 ng/ml y la fracción de eyección del ventrículo izquierdo fue 0,20 ± 0,056. Tras 12 horas, los niveles séricos de norepinefrina y de troponina I disminuyeron para la mitad de los valores iniciales y la fracción de eyección aumentó para 0,32 ± 0,059. Durante las 24 y 48 horas subsiguientes, la fracción de eyección se elevó para 0,46 ± 0,045 (pBACKGROUND: Children with scorpion envenomation have massive sympathetic activation and variable degrees of left ventricular systolic dysfunction. OBJECTIVE: To evaluate a rescue protocol for children with severe left ventricular dysfunction secondary to scorpion envenomation. METHODS: Four children, after scorpion envenomation, were subjected to a rescue protocol for acute left ventricular dysfunction: Endotracheal intubation and respiratory assistance, electrocardiograms, chest x-Ray, echocardiograms and blood samples for norepinephrine and troponin I serum levels. Samples and echocardiograms were repeated at 12, 24 and 48 hours. Intravenous medications: Dobutamine: 4-6 μg/kg/min. Amiodarone: 3 mg/kg during a 2 hour period. Maintenance: 5 mg/kg/day. Furosemide: 0.5 mg/kg/dose. Diuretics were given when the systemic blood pressure was above percentile fifty. Amiodarone, Dobutamine and Furosemide were administered during the first 48 hours. Beta-adrenergic blockers and angiotensin converting enzyme were given, at 48 hours after admission, once the left ventricular Ejection fraction > 0.35 and the clinical status had improved. RESULTS: On admission, norepinephrine was 1,727.50 ±794.96 pg/ml, troponin I 24.53 ± 14.09 ng/ml and left ventricular ejection fraction 0.20 ± 0.056. At twelve hours, norepinephrine and troponin I serum levels were down to half of the initial values and the ejection fraction increased to 0.32 ± 0.059. During the next 24 and 48 hours, the ejection fraction rose to 0.46 ± 0.045, (p

El supuesto de racionalidad es central en la teoría económica actual, es el pilar sobre el cual se construye el homo economicus de la teoría convencional. Este trabajo parte del enfoque de la racionalidad en Adam Smith, y busca aportar a la discusión de las características del sujeto racional y de sus implicaciones para el análisis económico. Reexamina el significado de la racionalidad a la luz de diversos autores y argumenta que los fundamentos de la obra de Adam Smith siguen vigentes.

Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq). Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

La investigación teórica-empírica ofrece hallazgos sobre novedosas formas de organización familiar en la región del noroeste argentino. El estudio se centra en la relación trabajo-familia desde una perspectiva que incorpora la división sexual del trabajo familiar como un componente determinante de las estructuras familiares y de sus lógicas de funcionamiento. Se realizó un estudio de caso con familias vinculadas a dos producciones agroindustriales con alto porcentaje de empleo femenino.

Primary abnormalities of the autonomic nervous system had been postulated as the pathogenic mechanisms of myocardial damage, in patients with Chagas disease. However, recent investigations indicate that these abnormalities are secondary and amenable to treatment with beta-adrenergic blockers. Moreover, muscarinic cardiac autoantibodies appear to enhance parasympathetic activity on the sinus node. Therefore, the purpose of this paper is to analyze how knowledge on Chagas' disease evolved from being initially considered as a primary cardioneuromyopathy to the current status of a congestive cardiomyopathy of parasitic origin.

Many genomes have been sequenced to high-quality draft status using Sanger capillary electrophoresis and/or newer short-read sequence data and whole genome assembly techniques. However, even the best draft genomes contain gaps and other imperfections due to limitations in the input data and the techniques used to build draft assemblies. Sequencing biases, repetitive genomic features, genomic polymorphism, and other complicating factors all come together to make some regions difficult or impossible to assemble. Traditionally, draft genomes were upgraded to "phase 3 finished" status using time-consuming and expensive Sanger-based manual finishing processes. For more facile assembly and automated finishing of draft genomes, we present here an automated approach to finishing using long-reads from the Pacific Biosciences RS (PacBio) platform. Our algorithm and associated software tool, PBJelly, (publicly available at https://sourceforge.net/projects/pb-jelly/) automates the finishing process using long sequence reads in a reference-guided assembly process. PBJelly also provides "lift-over" co-ordinate tables to easily port existing annotations to the upgraded assembly. Using PBJelly and long PacBio reads, we upgraded the draft genome sequences of a simulated Drosophila melanogaster, the version 2 draft Drosophila pseudoobscura, an assembly of the Assemblathon 2.0 budgerigar dataset, and a preliminary assembly of the Sooty mangabey. With 24× mapped coverage of PacBio long-reads, we addressed 99% of gaps and were able to close 69% and improve 12% of all gaps in D. pseudoobscura. With 4× mapped coverage of PacBio long-reads we saw reads address 63% of gaps in our budgerigar assembly, of which 32% were closed and 63% improved. With 6.8× mapped coverage of mangabey PacBio long-reads we addressed 97% of gaps and closed 66% of addressed gaps and improved 19%. The accuracy of gap closure was validated by comparison to Sanger sequencing on gaps from the original D. pseudoobscura draft assembly and shown to be dependent on initial reference quality.

In 2001, the administration of the U.S. president George W. Bush completely pulled out from the possibility to adopt the Kyoto Protocol. This, as well as the lack of the adequate policy and legislation necessary to tackle the issue of global warming and impacts of climate change caused the shift of creating the appropriate legislative regime from the regulatory and executive levels of political power to the courts, hence causing important development of the climate change litigation. Subject litigation is not only the U.S. but also a global phenomenon. It can be encountered in Europe in spite of its very advanced environmental and climate change legal regimes. The validity of this statement is however questionable, particularly with respect to the level of effectiveness and applicability of the EU Environmental Liability Directive (the “ELD”) in the climate change litigation. Unfortunately, ELD does not provide for the complete and comprehensive liability regime that would ensure proper liability regulation related to the environmental issues. In fact, some say that its name should be Environmental Responsibility Directive. The aim of this paper is to determine the level of the applicability of the ELD in the climate change litigation, its limits and potential problems. For that purpose, the author examines the existing legislative regimes and climate change litigation cases in the U.S. and at the EU level. The paper will end with a short study on the status of the climate change litigation and potentially applicable regime in Croatia (including the ELD). Overall conclusion is that the applicability of the ELD in the climate change litigation is very limited.

Se examinaron 41 503 fichas de donantes o potenciales donantes para conocer la prevalencia de algunos agentes de transmisión parenteral, en el Banco de Sangre Central de Corrientes. Se halló que la prevalencia de hepatitis B fue de 0,38 %; de hepatitis C, de 0,41 % y la de VIH, de 0,03 %. Se comprobó que las cifras obtenidas resultaron mayores que las reportadas en el Boletín Epidemiológico Nacional, lo que puede deberse a la no detección de los afectados asintomáticos o a la incompleta notificación.41 503 cards of donors or potential donors were examined to know the prevalence of some parenteral transmission agents in the Central Blood Bank of Corrientes. It was found that the prevalence of hepatitis B was 0.38 %; hepatitis C, 0.41 %; and HIV, 0.03 %. It was proved that the figures obtained were higher than the reported in the National Epidemiological Bulletin, which may result from the non-detection of the affected asymptomatic subjects or from an incomplete notification.

Background: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD)., Objective: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered., Methods: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory., Results: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p  = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p  = 0.038) and AD dementia (OR = 15.75, p  = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p  = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p  = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p  = 0.027)., Conclusions: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Proactive risk analyses identify potential risks before they occur, enabling us to pinpoint the most vulnerable aspects of our treatment process, thus promoting safer treatments. The proactive risk matrix methodology assesses the risk from potential errors and failures (initiating events) by evaluating and integrating their frequency, the severity of their potential consequences and the probability of failure of the barriers designed to prevent these consequences. Based on this methodology, the MARRTA project derived a theoretical risk model of advanced radiotherapy treatments and developed software to implement the model and facilitate the risk analysis., Methods: A multidisciplinary team built the risk model by identifying initiating events in a generic advanced radiotherapy process, along with their preventive and mitigating barriers, categorized by nature and effectiveness. Each initiating event was assigned a frequency, a consequence, and the corresponding failure probability of the barriers in place. By integrating these three parameters, a calculated risk was associated to each given initiating event. This initial risk model was then incorporated into the developed software and distributed to 18 Spanish hospitals for testing. Feedback from these hospitals was used to refine and update the model and software., Results: The final risk model (reference risk model) identifies 110 potential initiating events, 60 barriers, 54 frequency reducers and 13 consequence reducers., Conclusions: The MARRTA model and software provide a novel means to easily apply the risk matrix methodology for comprehensive and straightforward risk analysis, as it allows the reference model to be customized to the specific features of each radiotherapy department., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Rationale and Objectives: This study aims to evaluate the performance of generative pre-trained transformer (GPT)-4o in the complete official European Board of Radiology (EBR) exam, designed to assess radiology knowledge, skills, and competence., Materials and Methods: Questions based on text, image, or video and in the format of multiple choice, free-text reporting, or image annotation were uploaded into GPT-4o using standardized prompting. The results were compared to the average scores of radiologists taking the exam in real time., Results: In Part 1 (multiple response questions and short cases), GPT-4o outperformed both the radiologists' average scores and the maximum pass score (70.2% vs. 58.4% and 60%, respectively). In Part 2 (clinically oriented reasoning evaluation), the performance of GPT-4o was below both the radiologists' average scores and the minimum pass score (52.9% vs. 66.1% and 55%, respectively). The accuracy on questions involving ultrasound images was higher compared to other imaging modalities (accuracy rate, 87.5-100%). For video-based questions, the performance was 50.6%. The model achieved the highest accuracy on most likely diagnosis questions but showed lower accuracy in free-text reporting and direct anatomical assessment in images (100% vs. 31% and 28.6%, respectively)., Conclusion: The abilities of GPT-4o in the official EBR exam are particularly noteworthy. This study demonstrates the potential of large language models to assist radiologists in assessing and managing cases from diagnosis to treatment or follow-up recommendations, even with zero-shot prompting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2-3 standard deviations above the mean for age, gender, and ethnic group. Several copy-number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1-qter, among many others. In this study, we have applied 850K SNP-arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well-established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation., Material and Methods: This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups., Results: Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82)., Conclusions: Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Microlab Salmonella is an all-in-one solution for detection of Salmonella O Groups A-E that integrates, in a single disposable device, all elements to perform the analysis: a ready-to-use enrichment broth, a lateral flow immunochromatography test, and a chemical agent for bacterial inactivation. Microlab Salmonella can be easily used on-site and does not require specific laboratory equipment or technical skills. The device is sealed during the analysis, avoiding risks of contamination, and is therefore safe to use in food production environments., Objective: This report details the method validation study for raw ground beef, raw turkey (thermal processed, marinated), fresh cheese, deli ham, and pasteurized liquid egg., Methods: Matrix studies and inclusivity/exclusivity, product consistency/stability, and robustness testing were conducted to assess the method's performance., Results: Inclusivity/exclusivity testing showed that the Microlab Salmonella method was able to detect Salmonella O Group A-E isolates while excluding the non-Salmonella strains. In the matrix studies, the differences between the candidate and reference methods were not statistically significant. Minor variations in test parameters (enrichment time, time to read results, and enrichment temperature) did not affect the performance of the Microlab assay. There were no statistically significant differences between recently manufactured lots and those that were halfway through their expiration period or between those that were close to expiring., Conclusions: The reported data confirm that Microlab Salmonella is reliable for detecting Salmonella in raw ground beef, raw turkey (thermal processed, marinated), fresh cheese, pasteurized liquid egg, and deli ham., Highlights: Microlab Salmonella is validated to detect Salmonella in select food matrixes. Microlab Salmonella integrates the steps of enrichment, detection, and inactivation in a single device., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3-triazole, using a building block strategy. The design of these structures was guided by Lead-Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising "lead-like" candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5-fluorouracil, across a panel of six different tumor cell lines. Moreover, compared with our group's previous hybrid compounds, these new structures exhibit similar activity while offering simpler synthesis and greater potential for structural diversification, a fact that was previously an issue. Further investigations on the most active compounds included assessments of reproductive cell survival, inhibition of cell migration, and effects on nuclear morphology, indicating potential diverse mechanisms of action for these compounds. Pharmacokinetic properties were also calculated for the whole series of compounds using the pkCSM online software., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (N ADHD =312, N NoADHD =305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., Ruminococcus&#95;torques&#95;group (LogOdds=0.17, p fdr =4.42 × 10 -2 ), which was more abundant in adults with ADHD, and Eubacterium&#95;xylanophilum&#95;group (LogOdds= -0.12, p fdr =6.9 × 10 -3 ), which was less abundant in ADHD. Ruminococcus&#95;torques&#95;group was further associated with hyperactivity/impulsivity symptoms and Eisenbergiella with inattention and hyperactivity/impulsivity (p fdr <0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties., Competing Interests: Declaration of competing interest J.A.R.Q was on the speakers’ bureau and/or acted as consultant for Biogen, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen- Cilag, Shire, Oryzon, Roche, Psious, and Rubió. BF has received educational speaking fees from Medice. IT receives funding from the Dutch organisation of research (ZONMW project numbers 80-86200-98-20006, 80-85200-98-20006, 60-63600-98-903) VR has served as a speaker for Rubió and Shire/Takeda in the last 5 years. She has received travel awards from Shire/Takeda for participating in psychiatric meetings. JKB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. BJ, PV, DM, PvE, MR, JV, MB, AAV and MH have nothing further to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem cardiorespiratory control centres. The primary neurons that release serotonin reside in the brainstem cardiorespiratory control centres and may be affected by FGR. At two time points in the last trimester of sheep brain development, 110 and 127 days of gestation (0.74 and 0.86 of gestation), we assessed histopathological alterations in the brainstem cardiorespiratory control centres of the pons and medulla in early-onset FGR versus control fetal sheep. The FGR cohort were hypoxaemic and asymmetrically growth restricted. Compared to the controls, the brainstem of FGR fetuses exhibited signs of neuropathology, including elevated cell death and reduced cell proliferation, grey and white matter deficits, and evidence of oxidative stress and neuroinflammation. FGR brainstem pathology was predominantly observed in the medullary raphé nuclei, hypoglossal nucleus, nucleus ambiguous, solitary tract and nucleus of the solitary tract. The FGR groups showed imbalanced brainstem serotonin and serotonin 1A receptor abundance in the medullary raphé nuclei, despite evidence of increased serotonin staining within vascular regions of placentomes collected from FGR fetuses. Our findings demonstrate both early and adaptive brainstem neuropathology in response to placental insufficiency. KEY POINTS: Early-onset fetal growth restriction (FGR) was induced in fetal sheep, resulting in chronic fetal hypoxaemia. Growth-restricted fetuses exhibit persistent neuropathology in brainstem nuclei, characterised by disrupted cell proliferation and reduced neuronal cell number within critical centres responsible for the regulation of cardiovascular and respiratory functions. Elevated brainstem inflammation and oxidative stress suggest potential mechanisms contributing to the observed neuropathological changes. Both placental and brainstem levels of 5-HT were found to be impaired following FGR., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Women are at a higher risk of sexual assault, partly due to societal sexism. This scoping review addresses the question: What is known about the psychosocial consequences of sexual assault on women? To understand these impacts, various studies were reviewed. Searches were conducted in Web of Science, PubMed, Scopus, PsycArticles, and PsycINFO between April and May 2022. The methodology followed Arksey and O'Malley's (2005) framework. PRISMA guidelines were used for screening and the Scoping Reviews Checklist was employed to ensure the quality of the review process. As a result, 1744 studies were identified, and 21 were selected based on inclusion and exclusion criteria, with publication years ranging from 1997 to 2021. The total sample of women analyzed across these studies was 20,071 (M = 955.76; σ = 2236.53). These 21 studies examined the psychosocial consequences of sexual assault on women's lives. The primary psychosocial outcomes identified were depressive symptoms (n = 13), anxiety symptoms (n = 11), post-traumatic stress disorder (n = 11), alcohol dependence (n = 6), and sleep disorders (n = 3). In conclusion, this review enhances our understanding of the effects of sexual assault on women and identifies areas for future research to further understand and address this phenomenon. This work can ultimately guide efforts to improve the well-being of survivors., (© 2024. The Author(s).)

Background: Cutaneous melanoma is the most aggressive form of skin cancer, responsible for most skin cancer-related deaths. Recent advances in artificial intelligence, jointly with the availability of public dermoscopy image datasets, have allowed to assist dermatologists in melanoma identification. While image feature extraction holds potential for melanoma detection, it often leads to high-dimensional data. Furthermore, most image datasets present the class imbalance problem, where a few classes have numerous samples, whereas others are under-represented., Methods: In this paper, we propose to combine ensemble feature selection (FS) methods and data augmentation with the conditional tabular generative adversarial networks (CTGAN) to enhance melanoma identification in imbalanced datasets. We employed dermoscopy images from two public datasets, PH2 and Derm7pt, which contain melanoma and not-melanoma lesions. To capture intrinsic information from skin lesions, we conduct two feature extraction (FE) approaches, including handcrafted and embedding features. For the former, color, geometric and first-, second-, and higher-order texture features were extracted, whereas for the latter, embeddings were obtained using ResNet-based models. To alleviate the high-dimensionality in the FE, ensemble FS with filter methods were used and evaluated. For data augmentation, we conducted a progressive analysis of the imbalance ratio (IR), related to the amount of synthetic samples created, and evaluated the impact on the predictive results. To gain interpretability on predictive models, we used SHAP, bootstrap resampling statistical tests and UMAP visualizations., Results: The combination of ensemble FS, CTGAN, and linear models achieved the best predictive results, achieving AUCROC values of 87% (with support vector machine and IR=0.9) and 76% (with LASSO and IR=1.0) for the PH2 and Derm7pt, respectively. We also identified that melanoma lesions were mainly characterized by features related to color, while not-melanoma lesions were characterized by texture features., Conclusions: Our results demonstrate the effectiveness of ensemble FS and synthetic data in the development of models that accurately identify melanoma. This research advances skin lesion analysis, contributing to both melanoma detection and the interpretation of main features for its identification., (© 2024. The Author(s).)

Chronic obstructive pulmonary disease (COPD) is an etiologically complex disease characterized by acute exacerbations and stable phases. We aimed to identify biological functions modulated in specific COPD conditions, using whole blood samples collected in the AERIS clinical study (NCT01360398). Considered conditions were exacerbation onset, severity of airway obstruction, and presence of respiratory pathogens in sputum samples. With an integrative multi-network gene community detection (MNGCD) approach, we analyzed expression profiles to identify communities of correlated genes. The approach combined different layers of gene interactions for each explored condition/subset of samples: gene expression similarity, protein-protein interactions, transcription factors, and microRNAs validated regulons. Heme metabolism, interferon-alpha, and interferon-gamma pathways were modulated in patients at both exacerbation and stable-state visits, but with the involvement of distinct sets of genes. An important gene community was enriched with G2M checkpoint, E2F targets, and mitotic spindle pathways during exacerbation. Targets of TAL1 regulator and hsa-let-7b - 5p microRNA were modulated with increasing severity of airway obstruction. Bacterial infections with Moraxella catarrhalis and, particularly, Haemophilus influenzae triggered a specific cellular and inflammatory response in acute exacerbations, indicating an active reaction of the host to infections. In conclusion, COPD is a complex multifactorial disease that requires in-depth investigations of its causes and features during its evolution and whole blood transcriptome profiling can contribute to capturing some relevant regulatory mechanisms associated with this disease. In this work, we explored multi-network modeling that integrated diverse layers of regulatory gene networks and enhanced our comprehension of the biological functions implicated in the COPD pathogenesis., (© 2024. GSK.)

Background: The role of integrase strand transfer inhibitors (INSTI) in the cardiovascular risk of people with HIV is controversial., Objectives: To assess the association of INSTI to subclinical atherosclerosis progression measured with the carotid intima-media thickness (cIMT)., Methods: Prospective study in virologically suppressed people with HIV receiving INSTI- or NNRTI-based regimens. cIMT was measured at baseline, 48 and 96 weeks. cIMT progression was analysed both as a continuous and categorical variable, defined as cIMT increase ≥ 10% and/or new carotid plaque. Adjustments through Cox proportional hazard regression and linear mixed models, and propensity score matching were conducted., Results: 190 participants were recruited and 173 completed the 96 week follow-up. 107 (56.3%) were receiving an INSTI-containing, 128 (67.4%) a NNRTI-containing and 45 (23.7%) a NNRTI plus an INSTI-containing regimen. The overall median (IQR) 2-year change of cIMT was 0.029 (-0.041 to 0.124) mm; 87 (45.8%) participants experienced a cIMT increase ≥ 10%, of whom 54 (28.4%) developed a new carotid plaque. Adjusted Cox regression showed no differences between INSTI and NNRTI groups in the categorical 2-year progression of cIMT, both including or excluding participants receiving INSTI + NNRTI. Similar results were observed for the continuous cIMT increase through adjusted linear mixed models. Propensity score matching showed no significant differences in the 2 year cIMT change between treatment groups [0.049 mm (-0.031-0.103) in the INSTI group versus 0.047 mm (-0.023-0.115) in the NNRTI group; P = 0.647]. cIMT progression was associated with traditional cardiovascular risk factors., Conclusions: INSTI-based regimens are not associated with increased progression of subclinical atherosclerosis when compared to NNRTI., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC)., Methods: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR -mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review., Results: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR -related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib., Conclusions: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR -mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: Much research on the treatment of paranoia has involved cognitive-behavioural interventions that address explicit social cognition processes. However, much of human cognition is preverbal or implicit, raising the possibility that such social judgements are implicated in paranoia. One type of implicit social cognition that has been investigated concerning paranoia is implicit self-esteem with some evidence that it may be possible to change implicit self-esteem using techniques based on conditioning theory. Therefore, the primary purpose of this research is to further evaluate the potential of this approach. At the same time, as a secondary purpose, we introduce a novel way of measuring social cognition that, we argue, has utility for investigating the psychological processes involved in paranoia., Method: We conducted two proof-of-concept studies of a novel brief intervention based on evaluative conditioning, targeting implicit cognition. The first study was conducted with a large non-clinical sample, while the second study included a small series of psychotic patients. As part of our proof-of-concept evaluation of the potential of evaluative conditioning, we attempted to probe for neurophysiological changes following the intervention using magnetoencephalography in an exploratory way in the clinical sample., Results: Our results revealed that both non-clinical and clinical participants in the experimental group showed a significant change in how they evaluated themselves in the social cognition task, which could be related to the perception of social information in a less threatening way. In addition, clinical participants in the experimental group showed changes in brain activity during the social cognition task, particularly in regions involved in emotional reactivity and mentalization processes., Discussion: Our results are encouraging, suggesting that implicit cognition is manipulable, that such manipulation affects underlying neurophysiological mechanisms, and that there may be an impact on paranoid symptoms. However, much more work is required to determine whether this approach can produce meaningful clinical change and be delivered in routine clinical settings. Finally, it is important to note that we are not claiming the clinical effectiveness of our intervention, which is in a very early stage of development. Our goal here is to demonstrate clinical possibilities that warrant further investigation., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Trucharte, Carmen, Pacios, Bruña, Espinosa, Peinado, Pascual, Martinez, Maestu and Bentall.)

Background: Human epidermal growth factor receptor 2 (HER2)-low has emerged as a potential new entity in breast cancer (BC). Data on this subset are limited, and prognostic results are controversial, evidencing the need of further data in a BC real-world cohort., Methods: Patients with HER2-negative stage I-III BC diagnosed between 2006 and 2016 were retrospectively reviewed in a single cohort from the Catalan Institute of Oncology Badalona. Demographics and clinicopathological characteristics were examined via medical charts/electronic health records. We aim to describe and compare HER2-0/HER2-low populations through Chi-square or Fisher test, and explore its prognostic impact using Kaplan-Meier curves and Cox regression models., Results: From a cohort of 1755 BC patients, 1401 invasive HER2-negative, stage I-III cases were evaluated. 87% were hormone receptor (HR)-positive versus 13% triple negative (TNBC). Overall, 43% were HER2-0 and 57% HER2-low (61% immunohistochemistry (IHC) 1+ and 39% IHC 2+). Comparing HER2-low versus HER2-0, HER2-low showed higher proportion of estrogen receptor (ER)-positive (91.6% vs 79.9%, p  ⩽ 0.001) and progesterone receptor (PR)-positive (79.8% vs 68.9%, p  ⩽ 0.001) cases. HER2-0 exhibited higher proportion of TNBC (20.1% vs 8.4%, p  = 0.001), grade III tumors (28.8% vs 23.5%, p  = 0.039), and higher Ki67 median value (26.47% vs 23.88%, p  = 0.041). HER2-low was associated with longer time to distant recurrence (TTDR) compared to HER2-0 (67.8 vs 54.1 months; p  = 0.015) and better BC-related survival (19.2 vs 16.3 years; p  = 0.033). In the multivariable analysis, HER2-low was not an independent prognostic factor for TTDR and BC-related survival. ER expression showed a strong association with longer TTDR (Hazard Ratio: 0.425, p  ⩽ 0.001) and improved BC-related survival (Hazard Ratio: 0.380, p  ⩽ 0.001). PR expression was also associated with longer TTDR (Hazard Ratio: 0.496, p  ⩽ 0.001), and improved BC-related survival (Hazard Ratio: 0.488, p  ⩽ 0.001). Histological grade III was significantly associated with shorter TTDR (Hazard Ratio: 1.737, p  = 0.002). Positive nodal status was the strongest factor correlated with worse BC-related survival (Hazard Ratio: 2.747, p  ⩽ 0.001)., Conclusion: HER2-low was significantly associated with HR-positive disease, whereas HER2-0 group had higher incidence of TNBC, histological grade III and higher Ki67%. Although HER2-low group was associated with longer TTDR and improved BC-related survival, these findings could be explained by the greater proportion of favorable prognostic features in this subgroup compared to HER2-0., Competing Interests: A.P. declares being invited as speaker for GSK, Eisai, and Lilly, travel expenses and congress assistance from Lilly, Gilead, Dr. Reddys, and Pfizer. Member of GEICAM, SEOM, ESMO, and SOLTI societies. A.B.P. declares no conflicts of interest. A.L. declares being invited as speaker for Eisai, Lilly, and Novartis, and travel expenses from Roche, Gilead, and Novartis. Member of GEICAM, SEOM, ESMO, and SOLTI societies. B.C. declares being invited as speaker for BMS, Merck, and MSD. Training grants from BMS, Merck, and MSD. Advisory board: BMS, Merck, and MSD. Member of GEICAM, SEOM, ESMO, and SOLTI societies, and member of the board of directors from TTCC. V.Q. declares being invited as speaker for AstraZeneca, Novartis, Pfizer, and Roche. Advisory board for Roche. Educational activities from GSK, Lilly, and Pfizer and travel expenses from Pfizer and Roche. Member of GEICAM, SEOM, and SOLTI societies. I.T. declares being invited as speaker for Astra Zeneca. Training grants from Novartis, Lilly, ROCHE, and MSD. Member of GEICAM, SEOM, ESMO, and SOLTI societies. E.F declares travel expenses from Pfizer, Lilly, Novartis, and Roche. Speaking fees from Pfizer and advisory board from Novartis. A.F.D. declares being invited as speaker for MSD and Angelini Pharma; and travel expenses from MSD, Lilly, Roche, Merck, and BMS. M.B. declares advisory funding from Eisai, AstraZeneca, Pfizer, Novartis, and travel expenses from Novartis and AstraZeneca. L.B. declares no conflicts of interest. M.R. declares advisory funding from GSK and AstraZeneca, and travel expenses from MSD and AstraZeneca. G.S. declares no conflicts of interest. C.M. declares no conflicts of interest. P.R.M. declares no conflicts of interest. L.P declares no conflicts of interest. E.B. declares no conflicts of interest. A.M.C. declares no conflicts of interest. M.M. declares being invited as speaker for Pfizer, Novartis, and Lilly. Institution research grants from Pfizer and Gilead. Consultant advisory board from Novartis, Lilly, and Menarini. Travel expenses and congress assistance from Gilead, Pfizer, and Roche., (© The Author(s), 2024.)

A novel assay was developed based on a turn-off fluorescent probe using the in situ generation of carbon dots (CDs) by means of UV/H 2 O 2 advanced oxidation of carbohydrates for the detection of bisphenol A (BPA) in food. Different parameters involved in the synthesis of CDs for the direct recognition of BPA have been optimised and a sensing mechanism is outlined. The presence of H 2 O 2 during CD synthesis causes a fluorescence enhancement due to the action of highly oxidant HO · radicals formed throughout the photochemical reaction. Phenolic compounds such as BPA can be easily degraded by the UV/H 2 O 2 oxidation process, acting as a HO · free radical scavengers. This results in a decrease in the fluorescence that can be related to the BPA concentration. Under optimal conditions, a detection limit of 15 µg/kg of BPA and a quantification limit of 46 µg/kg of BPA in food samples were obtained. The repeatability and reproducibility, expressed as relative standard deviation and obtained for two concentration levels (30 µg/kg and 200 µg/kg, n = 5), were less than 2.0% and 6.4%, respectively. The proposed procedure was applied to the analysis of five samples of canned foods (sweet corn, peas, mushrooms, cockles and natural tuna), obtaining concentrations in the range 29.8-49.9 µg/kg of sample. Recovery studies were conducted at two concentration levels (100 and 400 µg BPA/kg of sample), resulting in recoveries in the range 99-101%. Method validation against two certified reference materials was also successfully performed. The experimental results demonstrate that the novel approach is suitable for the detection and quantification of BPA in canned foods., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Tumor hypoxia is a dynamic phenomenon marked by fluctuations in oxygen levels across both rapid (seconds to minutes) and slow (hours to days) time scales. While short hypoxia cycles are relatively well understood, the mechanisms behind longer cycles remain largely unclear. In this paper, we present a novel mechanistic mathematical model that explains slow hypoxia cycles through feedback loops involving vascular expansion and regression, oxygen-regulated tumor growth, and toxic cytokine production. Our study reveals that, for the emergence of slow hypoxia cycles, endothelial cells must adapt by decreasing receptor activation as ligand concentration increases. Additionally, the interaction between tumor cells and toxic cytokines influences frequency and intensity of these cycles. By examining the effects of pharmacological interventions, specifically poly (ADP-ribose) polymerase inhibitors, we also demonstrate how targeting cell proliferation can help regulate oxygen levels. Our findings enhance the understanding of hypoxia regulation and suggest PARP proteins as promising therapeutic targets., (© 2024. The Author(s).)

Malignant melanoma is an aggressive cancer, with a high risk of metastasis and mortality rates, characterized by cancer cell heterogeneity and complex tumor microenvironment (TME). Single cell biology is an ideal and powerful tool to address these features at a molecular level. However, this approach requires enzymatic cell dissociation that can influence cellular coverage. By contrast, single nucleus RNA sequencing (snRNA-seq) has substantial advantages including compatibility with frozen samples and the elimination of a dissociation-induced, transcriptional stress response. To better profile and understand the functional diversity of different cellular components in melanoma progression, we performed snRNA-seq of 16,839 nuclei obtained from tumor samples along the growth of murine syngeneic melanoma model carrying a BRAFV600E mutation and collected 9 days or 23 days after subcutaneous cell injection. We defined 11 different subtypes of functional cell clusters among malignant cells and 5 different subsets of myeloid cells that display distinct global transcriptional program and different enrichment in early or advanced stage of tumor growth, confirming that this approach was useful to accurately identify intratumor heterogeneity and dynamics during tumor evolution. The current study offers a deep insight into the biology of melanoma highlighting TME reprogramming through tumor initiation and progression, underlying further discovery of new TME biomarkers which may be potentially druggable.

Stressful events, from daily stressors to traumatic experiences, are common and occur at any age. Despite the high prevalence of trauma, not everyone develops stress-related disorders like major depressive disorder (MDD) and post-traumatic stress disorder (PTSD), a variation attributed to resilience, the ability to adapt and avoid negative consequences of significant stress. This review examines the locus coeruleus-norepinephrine (LC-NE) system, a critical component in the brain's stress response. It discusses the LC-NE system's anatomical and functional complexity and its role in individual variability in stress responses. How different etiological factors and stress modalities affect the LC-NE system, influencing both adaptive stress responses and psychopathologies, are discussed and supported by evidence from human and animal studies. It also explores molecular and cellular adaptations in the LC that contribute to resilience, including roles of neuropeptide, inflammatory cytokines, and genetic modulation, and addresses developmental and sex differences in stress vulnerability. The need for a multifaceted approach to understand stress-induced psychopathologies is emphasized and pave the way for more personalized interventions for stress-related disorders., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC., Methods: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches., Results: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment., Conclusions: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction., (© 2024. The Author(s).)

Objective: Shoulder pain, primarily due to rotator cuff tendinopathy, significantly impacts function and quality of life, with considerable socioeconomic implications. Physiotherapy myofascial trigger point therapy (MPT) is traditionally used, but therapeutic exercise (TE) has gained attention for its potential administrative and implementation benefits. The aim of this study was to evaluate the efficacy of TE compared with MPT in treating shoulder tendinopathies., Methods: A single-blind randomised controlled trial was conducted comparing TE and MPT. Outcome measures included pain intensity with the Numerical Rating Scale, pressure pain threshold (PPT) and range of motion (ROM), assessed before and after 10 treatment sessions. A total number of 72 participants (TE group n=36 age 49.22±15.29/MTP group n=36 age 49.03±19.12) participated in the study., Interventions: Participants in both groups were evaluated before treatment and after 10 sessions. A total of 10 sessions were conducted over 5 weeks of intervention., Results: Both interventions showed improvements in pain intensity and ROM, with no significant differences between the groups in most measures except PPT, where TE demonstrated a greater decrease in pressure-induced pain., Conclusion: TE could serve as an alternative to manual therapy, offering cost-benefit advantages, especially in administration via telecare and group sessions, highlighting its broader application in physiotherapy., Trial Registration Number: NCT06241404., Competing Interests: None declared., (Copyright © 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.)

Introduction: Specific home tasks and the use of splints seem to positively affect altered structures and functions, as well as the activities and participation, of children with unilateral cerebral palsy (UCP). However, how did families experience the implementation of these therapies?, Objective: To describe the experiences as they were perceived by the families of children with UCP before, during, and after a specific task intervention in the home environment, either with or without upper limb splinting., Methods: A qualitative, descriptive, phenomenological study was conducted in a natural environment. Fourteen families caring for children with UCP who participated in a previous randomized controlled trial were included. Data from unstructured and semi-structured interviews were analyzed through a thematic analysis., Results: Fourteen families (17 parents, age 37-47 years) caring for children with UCP (14 children, ages 6-10 years, 64% female) were interviewed. The following three themes emerged: "The project itself", in which families explained that they enrolled because of their trust in therapists; "Results obtained", where the main improvement was the integration of the assisting hand in the body schema; and "Lights and shadows", where families showed what they learned as positive points and some negative aspects related to the assessments and splints., Conclusions: The perceptions of the parents after the specific task intervention in the home environment showed a greater integration of the most affected side. Nevertheless, although the support of a splint on the hand can have beneficial results in terms of performance, other drawbacks leading to the disuse of the splint were highlighted.

Slide electrification experiments were performed on low-density polyethylene films ( PE ) and PE sprayed with five amphiphilic compounds, including antistatic and slip additives. Drops of aqueous solutions were delivered on the films and after sliding spontaneously acquired a net electrical charge ( Q drop ), which is dependent on the pH and ionic strength. The slide electrification was detected in pristine PE films and those with five additives. An acid-base equilibrium model, based on the adsorption of hydroxides and protons on surface sites, accounted for the dependence of Q drop on pH, allowing recovery of the acid-base equilibrium constants and the density of adsorption sites. The model was modified to account for ionic strength effects through activity factors. The surface conductivity, wettability, and friction coefficients were strongly modified by the additives. However, the observed trends are different from those observed in slide electrification, which better correlated with zeta potential determinations. This suggests that the interaction mechanisms among surface water, the considered additives, and the polymer, which are involved in slide electrification and the generation of zeta potential, are different from those associated with other surface processes involving surface water. Although additives are required for changing surface resistivity, friction coefficients, and wettability, the generation of sliding electrical charges in polyethylene is a spontaneous and highly effective process. For one specific additive, a simultaneous decrease in friction coefficients, zeta potential, and Q drop was observed, assigned to the blockade of hydroxide adsorption sites and water repulsion by the compound.

Background: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown., Aims: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain., Methods: Multicenter, ambispective, observational nationwide registry., Results: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device., Conclusions: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibiotics in the environment are considered emerging pollutants, with special relevance and concern due to the proliferation of antibiotic-resistant bacteria and genes. Therefore, finding ways to remediate antibiotics-contaminated soil and water through the use of bio-adsorbents is imperative. In this research, we investigate three by-products (hemp waste, oak ash, and mussel shell) as potential low-cost bio-adsorbents for the antibiotics Ciprofloxacin (CIP), Clarithromycin (CLA), and Trimethoprim (TRI), using batch-type and stirred flow chamber experiments to study their retention and release. The results indicate that hemp waste has higher sorption capacity for CIP and TRI (20891.8 and 2481.6 μmol L -1 , respectively), while oak ash yields the highest retention for CLA (3078.4 μmol L -1 ). In addition, it was shown that the pH value significantly influences the sorption of these pollutants onto hemp waste. Among the three antibiotics, CLA was the most mobile, given the release experiments (903.9-1758.9 μmol kg -1 ), while ciprofloxacin (440.3-542.4 μmol kg -1 ) and trimethoprim (639.4-1652.1 μmol kg -1 ) are released less. Overall, the results of this research (the first of this kind including these antibiotics and sorbents simultaneously) suggest that while the individual antibiotics retention on each of the three by-products may not be entirely satisfactory, its potential combination (among them and/or with other low-cost sorbents) could significantly contribute to addressing antibiotics environmental pollution, favouring recycling and promoting a circular economy, which is a matter of global relevance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Given his role as Editor, Dr. Núñez-Delgado was not involved in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Prof. Raf Dewil., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gold nanorods (GNRs) are of special interest in nanotechnology and biomedical applications due to their biocompatibility, anisotropic shape, enhanced surface area, and tunable optical properties. The use of GNRs, for example, as sensors and mechanical actuators, relies on the ability to remotely control their orientation as well as their translational and rotational motion, whether individually or in groups. Achieving such particle control by using optical tools is challenging and exceeds the capabilities of conventional laser tweezers. We present a tool that addresses this complex manipulation problem by using a curve-shaped laser trap, enabling the optical capture and programmable transport of single and multiple GNRs along any trajectory. This type of laser trap combines confinement and propulsion optical forces with optical torque to transport the GNRs while simultaneously controlling their rotation (spinning) and orientation. The proposed system facilitates the light-driven control of GNRs and the quantitative characterization of their motion dynamics including transport speed, spinning frequency, orientation, and confinement strength. We experimentally demonstrate that remote control of the GNRs can be achieved both near a substrate surface (2D trapping) and deep within the sample (3D all-optical trapping). The motion dynamics of two sets of off-resonant GNRs, possessing similar aspect ratios but different resonance wavelengths, are analyzed to highlight the role played by their optical and mechanical properties in the optical manipulation process. The experimental results are supported by a theoretical model describing the observed motion dynamics of the GNRs. This optical manipulation tool can significantly facilitate applications of light-driven nanorods.

In the context of climate change, it is of utmost importance to replace the use of fossil fuels as raw material in areas of industrial interest, for example, in the production of chemical inputs. In this context, a viable option is biomass, since by subjecting it to chemical processes such as pyrolysis, it is possible to obtain platform molecules that are the basis for the generation of value-added chemical products. Acetals are molecules obtained from biomass derivatives, which have various applications in cosmetic chemistry, in the pharmaceutical industry as intermediates or final compounds, food additives, among others. Different catalysts have been used in the acetalization reaction, including MOFs, which have the advantage of being porous materials with high surface area values. The large surface area translates into a greater number of catalytically active sites available for the reaction. Among the MOFs that have been used for this purpose is MOF-808, which is characterized by having a lower number of ligands attached to its metal cluster, therefore, it has a greater exposure of the metals that make up its structure. In this context, the work carried out studied the catalytic performance of MOF-808 when its Zr(IV) metal centers are replaced by Hf(IV) and Ce(IV) atoms in the acetalization reaction of benzaldehyde with methanol. The MOFs obtained by solvothermal synthesis were characterized by powder X-ray diffraction, N 2 adsorption and desorption, FT-IR spectroscopy, acid-base potentiometric titration, XPS and thermogravimetric analysis. The results of the catalysis indicate that the MOF with the best performance was MOF-808-Ce, which achieved conversions greater than 80% in a period of ten minutes. MOF-808-Ce exhibits a higher number of defects and therefore a higher availability of catalytic sites for the reaction to occur, which explains the better performance. Finally, the performance of MOF-808 in the acetalization of benzaldehyde with methanol was also supported by density functional theory (DFT) calculations.

Apolipoprotein E4 ( APOE4 ) is the leading genetic risk factor for Alzheimer's disease. While most studies examine the role of APOE4 in aging, imaging, and cognitive assessments reveal that APOE4 influences brain structure and function as early as infancy. Here, we examined human-relevant cellular phenotypes across neurodevelopment using induced pluripotent stem cell (iPSC) derived cortical and ganglionic eminence organoids (COs and GEOs). In COs, we showed that APOE4 decreased BRN2+ and SATB2+ cortical neurons, increased astrocytes and outer radial glia, and was associated with increased cell death and dysregulated GABA-related gene expression. In GEOs, APOE4 accelerated maturation of neural progenitors and neurons. Multi-electrode array recordings in assembloids revealed that APOE4 disrupted network formation and altered response to GABA, resulting in heightened excitability and synchronicity. Together, our data provides new insights into how APOE4 may influence cortical neurodevelopmental processes and network formation in the human brain.

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL., (© 2024. The Author(s).)