Janssen (Switzerland)

ABSTRACT This study examines how the reputation of Christian churches is configured, and which sociodemographic variables and experiences (personal or mediated) relate to it. It provides in‐depth insights into how the Swiss population evaluates Roman Catholic, Reformed Protestant, and Evangelical churches on the basis of various theories, such as organizational reputation, media, and social identity theories, embedded in a religious sociological context. Data from representative online surveys conducted in 2022 and 2023 show that perceived identity and attractiveness are the most critical factors for a general organizational reputation in a religious context. The results show that online and offline news media significantly influence the reputation formation of the Roman Catholic Church. However, social media has a less significant influence on churches in general. They also show that Protestants and Catholics rate each other better than Evangelicals, and religiosity is the most decisive factor in rating churches favorably.

Pyrimidin-4-ones and (3H)-quinazolin-4-ones are widely occurring heterocyclic motifs found in biologically active substances. This report presents a practical and scalable three-step, two-pot synthesis of 2-unsubstituted-3-alkyl/aryl derivatives of these heteroaromatics. During the mechanistic investigation of the hexafluorophosphate azabenzotriazole tetramethyl uronium (HATU)-mediated coupling of 4-hydroxyquinazolines with amines, we found that the N-activated heterocycle underwent nucleophilic attack on the methine atom with subsequent ring opening and ring closing (ANRORC mechanism). Building on the new mechanistic insight, we designed and developed an efficient synthesis of 2-unsubstituted-3-substituted pyrimidin-4-ones through the condensation of β-aminoacrylates with dimethylformamide dimethylacetal (DMF-DMA), followed by cyclization with primary amines. The required β-aminoacrylates were easily obtained in a single step via ZnCl2-mediated decarboxylative Blaise–Reformatsky reaction of nitriles, which was extended to aliphatic substrates using an improved protocol. The methodology described herein is particularly suited to execution on a large scale as it requires no chromatography, utilizes no solvents of very high concern, and has been successfully demonstrated on the liter scale.

BackgroundTreatment resistant Major Depressive Disorder (MDD) can be accompanied by lengthy and ineffective treatment periods that prolong patient suffering, reduce expectations of remission and reinforce negative cognitions (Leuchter 2009). Esketamine (a NMDA receptor antagonist) has been approved in Australia and New Zealand (ANZ) as a third-line antidepressant (AD) treatment to provide clinicians with an additional therapeutic option for this population.Aims and ObjectivesThis analysis describes the changes among subgroups stratified by previous treatment lines in quality of life, depression severity scores and productivity of patients treated with esketamine in a real-world setting across ANZ.MethodParticipants were recruited from an esketamine Early Access Program. To be eligible, patients must have failed 2 or more oral AD treatments of adequate dose and duration and not received neurostimulation treatment within their current depressive episode. Patients received esketamine for 16 weeks in the study. Outcomes were obtained for Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work and Productivity Activity Index (WPAI). Pre- specified subgroups were classified by number of previous therapies in the same depressive episode (2, 3-5 or 6+).ResultsOf 108 total participants, 22.9% had received 2 prior therapies vs 48.6% and 28.5% who had 3- 5 and 6 or more therapies respectively within their current depressive episode. There were statistically significant differences (p<0.01) for all subgroups in HAM-D scores from baseline to week 16. The subgroup with 2 prior therapies exhibited the largest HAM-D improvement of -11.1 points, (SD 6.6) when compared to the 6+ therapy subgroup which obtained a statistically significant smaller HAM-D improvement of -5.2 points (SD 6.3), p <0.01. The improvement in the 3-5 prior therapies group was in the middle of the other 2 subgroups, -8.0 points (SD 6.7) and not significantly different to either of the two other subgroups. The AQOL improvements from baseline were also robust and statistically significant across all sub-groups with the largest improvement seen in patients who had failed no more than two lines of therapy, albeit no statistical significance could be observed within subgroups.Discussion and ConclusionThe improvements in AQOL and HAM-D were significant across all sub-groups, with the highest improvement seen in patients who had received only two prior lines of therapy, which might indicate that patients benefit most from an early esketamine treatment. Taken together, the results suggest that patients might benefit more from esketamine earlier in disease treatment, however further studies are warranted.

Este artigo tem como objetivo analisar as condições de trabalho dos catadores de materiais recicláveis em Belo Horizonte, com base na teoria do reconhecimento de Axel Honneth. A partir dessa perspectiva teórica, busca-se compreender como o reconhecimento social e a valorização do trabalho impactam a constituição da identidade e da autoestima desses trabalhadores. O estudo discute os desafios enfrentados pelos catadores, incluindo o preconceito social e a precarização das condições de trabalho, evidenciando a importância do reconhecimento em suas diversas dimensões — afetiva, jurídica e social — para a promoção da dignidade e da inclusão desses profissionais na sociedade.

Este artigo analisa criticamente os regimes jurídicos migratórios em cinco grandes regiões africanas: Norte da África, África Ocidental, Chifre da África, África Central e Sul da África, com destaque para os países lusófonos. A partir de uma metodologia qualitativa e interpretativa, o texto examina legislações nacionais, tratados internacionais e decisões judiciais, dialogando com autores africanos e brasileiros. O objetivo é revelar como o direito migratório africano ainda carrega marcas profundas da colonialidade do poder, reproduzindo hierarquias raciais e dinâmicas excludentes. Ao mesmo tempo, o capítulo destaca avanços normativos e jurisprudências progressistas que ampliam direitos e promovem a proteção humanitária. Por meio de uma comparação crítica com o modelo brasileiro instituído pela Lei 13.445/2017, o texto identifica convergências, divergências e potenciais de cooperação Sul-Sul. Propõe-se, ao final, a criação de uma Carta Migratória do Sul Global, inspirada em princípios de interculturalidade crítica e pluriversalismo jurídico, como caminho para um direito migratório mais inclusivo, equitativo e emancipador.

Vaccination with Ad26.RSV.preF, an Adenoviral serotype 26 vector encoding RSV F protein stabilized in its prefusion conformation, has previously shown to be immunogenic and protective in RSV seropositive adults and immunogenic in seropositive infants. Human and bovine RSV (bRSV) are genetically highly related and share many aspects of pathogenesis, epidemiology and clinical manifestations at young age. As such, infection of calves with bRSV represents a clinically relevant model with high translational value, enabling preclinical evaluation of Ad26.RSV.preF vaccine efficacy in seronegative young animals. Immunization of young calves with Ad26.RSV.preF induced antibodies neutralizing both human and bovine RSV as well as RSV-specific cellular responses. After bRSV challenge, placebo immunized calves showed viral replication in the respiratory tract, and developed fever and lethargy accompanied with severe respiratory distress, resulting in pre-termination of 7/8 calves. In contrast, all Ad26.RSV.preF immunized calves completed the study with only mild clinical symptoms, strongly and significantly diminished viral loads in nasopharynx and lungs, and only minimal lung pathology. Thus, Ad26.RSV.preF is immunogenic in young calves and efficacious in a stringent heterologous bRSV challenge model, demonstrating induction of broadly protective immunity against severe disease.

Abstract Recent efforts to improve tuberculosis (TB) treatment options have focused on developing molecules with novel mechanisms of action and identifying optimal treatment regimens. Inhibition of Mycobacterium tuberculosis cytochrome bc1 oxidase has emerged as a promising therapeutic target that could potentially contribute to improved TB combination regimens. Using a relapsing mouse model, we demonstrate that cytochrome bc1 inhibitors could serve as effective partner drugs, enhancing regimen sterilisation. We propose several novel regimen strategies for both multidrug-resistant TB (MDR-TB) and drug-sensitive TB (DS-TB), where cytochrome bc1 inhibitors contribute to sterilisation and treatment shortening. Additionally, we show that clinical isolates exhibit heightened susceptibility to cytochrome bc1 inhibitors compared to laboratory-adapted strains, further supporting their translational potential. These findings suggest that cytochrome bc1 inhibitors have significant potential to improve TB treatment outcomes and highlight the need for further studies to evaluate their clinical contribution to novel treatment regimens.

Esta pesquisa buscou analisar as estratégias adotadas por profissionais da psicologia nos cuidados paliativos a pacientes com câncer e a seus familiares, além de avaliar os progressos e limitações nesse campo. A metodologia empregada foi qualitativa e exploratória, com uma revisão bibliográfica integrativa de artigos científicos relevantes e a realização de entrevistas presenciais com duas psicólogas atuantes no contexto oncológico. A análise revelou que um desafio vivenciado pelas psicólogas refere-se à amenização do desespero de uma família ou cuidador que deseja fazer de tudo para que seu ente permaneça vivo, sem considerar, muitas vezes, a vontade do principal envolvido. Outro desafio refere-se à limitação do tempo para auxiliar o paciente dentro de sua individualidade a ressignificar sua vida frente à morte, levando-se em consideração a terminalidade rápida em alguns tipos de câncer. Conclui-se que os cuidados paliativos têm como objetivo oferecer proteção e conforto aos/às pacientes e familiares em momentos difíceis, e o profissional da Psicologia cumpre um importante papel nesse processo, mas deve estar atento sobre como a sobrecarga emocional e as dúvidas sobre como ajudar pacientes terminais podem afetar sua saúde mental.

Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.1–35.0). Patients (N = 248) had received median 4 prior LOT (range, 2–13) at enrollment. 91 unique regimens were used in index LOT. Overall response rate was 31.9% (95% CI, 26.1–38.0), median progression-free survival (PFS) was 4.6 months (95% CI, 3.9–5.6) and median overall survival was 13.8 months (95% CI, 10.8–17.0). 152 patients (61.3%) had subsequent LOTs with 134 unique regimens, of which 78 were used in first subsequent LOT. Median PFS2 (from start of study through first subsequent LOT) was 10.8 months (95% CI, 8.4–13.0). 158 patients died on study, 67.7% due to progressive disease. Additional subgroup analyses and long-term safety summaries are reported. The high number of RWCP treatment regimens utilized and poor clinical outcomes confirm a lack of standardized treatment for TCE patients with RRMM, highlighting the need for new treatments with novel mechanisms.