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Abstract Aims The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Methods and results Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Conclusions Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Background: Knee osteoarthritis (KOA) is a common degenerative and progressive joint disorder that negatively influences patients’ quality of life. Intra-articular therapies, such as hyaluronic acid (HA) and platelet-rich plasma (PRP), have garnered attention for their potential to manage osteoarthritis OA symptoms effectively. This systematic review aims to identify the effectiveness and safety of HA and PRP treatment modalities in treating KOA. Methods: A literature search was conducted across MEDLINE (PubMed), Web of Science Core Collection, and Science Direct Collection Elsevier. Twenty-three randomized controlled trials, cohort studies, and observational studies were included in the review. The selection criteria focused on studies published in English within the last 10 years, involving subjects with KOA treated with intra-articular injections of HA or PRP and reporting on pain, function, or overall treatment efficacy outcomes. Results: The analysis showed that both HA and PRP significantly improve functionality and reduce pain in KOA patients. High molecular weight HA consistently reduced pain and improved joint mobility in various studies. PRP had better long-term outcomes when combined with HA, leading to greater pain reduction and functional improvement. Both therapies had generally favorable safety profiles, with only minor adverse events reported. However, there were potential biases identified across the studies, such as selection, performance, detection, and reporting biases, which impacted the reliability of the results. Conclusions: Intra-articular treatments with HA and PRP show promise in managing knee osteoarthritis, with personalized treatment plans and further research needed to confirm these findings.

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection. Case presentation We describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae. Conclusions This case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a rare uterine tumor primarily affecting perimenopausal and postmenopausal women, typically aged between 45 and 55 years. Characterized by ambiguous histological features, STUMPs present diagnostic challenges as they cannot be definitively classified as benign or malignant based on morphology alone. This systematic review aims to elucidate the clinical, pathological, immunohistochemical, and treatment-related characteristics of STUMPs through an analysis of the literature from the past 20 years. The study follows PRISMA guidelines, utilizing comprehensive searches of PubMed and Scopus databases, yielding 32 studies that meet the inclusion criteria. From the analysis of these studies, it was revealed that the clinical presentations vary from common symptoms such as abnormal uterine bleeding and pelvic pain to incidental detection of uterine mass. Histologically, STUMPs demonstrate features overlapping with both leiomyomas and leiomyosarcomas, including mild nuclear atypia, low mitotic indices, and focal necrosis. Immunohistochemical markers such as p16 and p53 have been investigated for prognostic significance. Elevated p16 expression, often associated with aggressive behavior, was observed in a subset of STUMPs. Surgical management, typically involving hysterectomy or tumorectomy, is the primary treatment, though the extent of resection is variable. Adjuvant therapies are not routinely recommended, but long-term surveillance is advised, especially for high-risk patients. Recurrence rates for STUMPs are approximately 12%, with factors such as high mitotic counts and coagulative necrosis indicating higher risk. This review highlights the complexity of STUMP diagnosis and management, emphasizing the need for more precise diagnostic criteria and individualized treatment strategies. Understanding the morphological, immunohistochemical, and clinical behavior of STUMPs can improve patient outcomes and guide future research in this diagnostically challenging area.

Abstract Equation of state measurements at Jovian or stellar conditions are currently conducted by dynamic shock compression driven by multi-kilojoule multi-beam nanosecond-duration lasers. These experiments require precise design of the target and specific tailoring of the spatial and temporal laser profiles to reach the highest pressures. At the same time, the studies are limited by the low repetition rate of the lasers. Here, we show that by the irradiation of a thin wire with single-beam Joule-class short-pulse laser, a converging cylindrical shock is generated compressing the wire material to conditions relevant to the above applications. The shockwave was observed using Phase Contrast Imaging employing a hard X-ray Free Electron Laser with unprecedented temporal and spatial sensitivity. The data collected for Cu wires is in agreement with hydrodynamic simulations of an ablative shock launched by highly impulsive and transient resistive heating of the wire surface. The subsequent cylindrical shockwave travels toward the wire axis and is predicted to reach a compression factor of 9 and pressures above 800 Mbar. Simulations for astrophysical relevant materials underline the potential of this compression technique as a new tool for high energy density studies at high repetition rates.

Abstract Do all birds' sex chromosomes follow the same canonical one-way direction of evolution? We combined cytogenetic and genomic approaches to analyze the process of the W chromosomal differentiation in two selected Passeriform species, named the Pale-breasted Thrush Turdus leucomelas and the Rufous-bellied thrush T. rufiventris. We characterized the full catalog of satellite DNAs (satellitome) of T. leucomelas, and the 10 TleSatDNA classes obtained together with 16 microsatellite motifs were in situ mapped in both species. Additionally, using Comparative Genomic Hybridization (CGH) assays, we investigated their intragenomic variations. The W chromosomes of both species did not accumulate higher amounts of both heterochromatin and repetitive sequences. However, while T. leucomelas showed a heterochromatin-poor W chromosome with a very complex evolutionary history, T. rufiventris showed a small and partially heterochromatic W chromosome that represents a differentiated version of its original autosomal complement (Z chromosome). The combined approach of CGH and sequential satDNA mapping suggest the occurrence of a former W-autosomal translocation event in T. leucomelas, which had an impact on the W chromosome in terms of sequence gains and losses. At the same time, an autosome, which is present in both males and females in a polymorphic state, lost sequences and integrated previously W-specific ones. This putative W-autosomal translocation, however, did not result in the emergence of a multiple-sex chromosome system. Instead, the generation of a neo-W chromosome suggests an unexpected evolutionary trajectory that deviates from the standard canonical model of sex chromosome evolution.

Abstract Multiple sex chromosomes usually arise from chromosomal rearrangements which involve ancestral sex chromosomes. There is a fundamental condition to be met for their long-term fixation: the meiosis must function, leading to the stability of the emerged system, mainly concerning the segregation of the sex multivalent. Here, we sought to analyze the degree of differentiation and meiotic pairing properties in the selected fish multiple sex chromosome system present in the wolf-fish Hoplias malabaricus (HMA). This species complex encompasses seven known karyotype forms (karyomorphs) where the karyomorph C (HMA-C) exhibits a nascent XY sex chromosomes from which the multiple X1X2Y system evolved in karyomorph HMA-D via a Y-autosome fusion. We combined genomic and cytogenetic approaches to analyze the satellite DNA (satDNA) content in the genome of HMA-D karyomorph and to investigate its potential contribution to X1X2Y sex chromosome differentiation. We revealed 56 satDNA monomers of which the majority was AT-rich and with repeat units longer than 100 bp. Seven out of 18 satDNA families chosen for chromosomal mapping by fluorescence in situ hybridization (FISH) formed detectable accumulation in at least one of the three sex chromosomes (X1, X2 and neo-Y). Nine satDNA monomers showed only two hybridization signals limited to HMA-D autosomes, and the two remaining ones provided no visible FISH signals. Out of seven satDNAs located on the HMA-D sex chromosomes, five mapped also to XY chromosomes of HMA-C. We showed that after the autosome-Y fusion event, the neo-Y chromosome has not substantially accumulated or eliminated satDNA sequences except for minor changes in the centromere-proximal region. Finally, based on the obtained FISHpatterns, we speculate on the possible contribution of satDNA to sex trivalent pairing and segregation.

Abstract Ultra-intense lasers that ionize atoms and accelerate electrons in solids to near the speed of light can lead to kinetic instabilities that alter the laser absorption and subsequent electron transport, isochoric heating, and ion acceleration. These instabilities can be difficult to characterize, but X-ray scattering at keV photon energies allows for their visualization with femtosecond temporal resolution on the few nanometer mesoscale. Here, we perform such experiment on laser-driven flat silicon membranes that shows the development of structure with a dominant scale of 60 nm in the plane of the laser axis and laser polarization, and 95 nm in the vertical direction with a growth rate faster than 0.1 fs−1. Combining the XFEL experiments with simulations provides a complete picture of the structural evolution of ultra-fast laser-induced plasma density development, indicating the excitation of plasmons and a filamentation instability. Particle-in-cell simulations confirm that these signals are due to an oblique two-stream filamentation instability. These findings provide new insight into ultra-fast instability and heating processes in solids under extreme conditions at the nanometer level with possible implications for laser particle acceleration, inertial confinement fusion, and laboratory astrophysics.

Objetivo. Apresentar a experiência de um serviço de resposta rápida para apoiar a tomada de decisão em saúde. Método São descritos os processos e resultados de um serviço de produção de revisões rápidas e mapas de evidências para apoiar a tomada de decisão no âmbito da Política Nacional de Promoção da Saúde, bem como a percepção dos autores sobre o processo de trabalho. Resultados O serviço de resposta rápida teve início em 2020. Até dezembro de 2023, foram produzidas 54 revisões rápidas e cinco mapas de evidências, abrangendo nove temáticas de Promoção da Saúde. Estes produtos foram desenvolvidos em quatorze etapas por uma equipe composta por coordenador, supervisoras, revisores e bibliotecária. O desenvolvimento das respostas rápidas se configurou um processo de tradução do conhecimento e envolveu a interação contínua entre as equipes demandantes e de produção. O estabelecimento de comunicação efetiva foi um fator crítico para que os produtos fossem entregues em tempo oportuno e alinhados às necessidades dos tomadores de decisão e seus apoiadores. Conclusão Os serviços de resposta rápida podem contribuir para melhorar o uso de evidências na tomada de decisão nas políticas e sistemas de saúde.

Despite improvements in female science enrolment, the gender gap remains in some disciplines. This study examines whether elementary school students (N = 1012, third to sixth graders) display gender-stereotypical interest in learning biology and physics content and how this affects their attitudes towards school science. K-means cluster analysis revealed four interest profiles that resemble career enrolment patterns, with slightly more girls in profiles of high interest in biology over physics (biology interest) and low interest in both disciplines (disinterested), and more boys in high interest in physics over biology (physics interest) and high interest in both disciplines (interested). Students in the interested profile had more positive attitudes towards school science than those in the other profiles. These findings suggest gender segregation in science may be shaped before students make career decisions, calling for attitude-based, gender-inclusive educational interventions from elementary grades.

Knowledge of scientific inquiry (SI) is considered essential to the development of an individual's Scientific Literacy (SL) and therefore, SI is included in many international science education reform documents. Two previous large scale international studies assessed the SI understandings of students entering middle school and secondary students at the end of their formal K-12 science education. The purpose of this international project was to use the VASI-E to collect data on what primary level students have learned about SI in their first few years of school. This study adds to previous research to bridge the landscape of SI understandings now with representation from primary, middle and high school samples. A total of 4,238 students from 35 countries/regions spanning six continents participated in the study. The results show that globally, primary students are not adequately informed about SI for their age group. However, when compared with the students in the previous international studies (grades seven and 12), the primary students' understandings were surprisingly closer to the levels of understanding of SI of the secondary school students than those in the seventh grade study.

Virtual laboratories and simulations have emerged as innovative solutions for science teaching. However, existing resources have various limitations and constraints including cognitive load/mental burden and limited coverage of all necessary steps in scientific inquiry, focusing mainly on the experimental simulation. To bridge this gap and address these challenges, the present study introduces the design and usability evaluation of IndagApp, an innovative educational resource explicitly developed to support inquiry-based science teaching. A convergent mixed methods design and a convenience sampling of 90 pre-service teachers were used. The findings indicate that IndagApp exhibits a high level of technological and pedagogical usability. Feedback from the users was incorporated to improve the app, resulting in its final version, which incorporates best practices from existing literature on authentic inquiry-based science teaching. IndagApp is freely accessible in the Spanish language, and compatible with Android 5.0 + smartphones and tablets, as well as PCs running Windows 7 or above operating systems. This research provides a timely and significant educational resource that may assist educators in enacting reform-oriented teaching practices.

As science education shifts toward integrated STEM (Science, Technology, Engineering, and Mathematics) approaches, guidelines for designing teaching and learning episodes that integrate curricular content and procedures from multiple disciplines become increasingly in demand. The existing plethora of conceptualizations of STEM makes difficult such an endeavor, leading to ill-defined lesson plans focused on only two--mainly science and technology or science and mathematics--out of the four STEM disciplines. The question addressed, therefore, is how the integrated STEM approach could be translated into classroom practices that integrate the four STEM disciplines in a way that is consistent and coherent with elementary education curricula. This manuscript advances a theoretically informed didactic model for the design and implementation of integrated STEM in elementary education. The article discusses how the model uses socio-constructivist principles to establish intentional and explicit connections between STEM disciplines via scientific inquiry, engineering design, and computational thinking practices. The model is rooted in learning theories developed by Piaget, Vygotsky, Ausubel, and Bruner and could serve as a roadmap for educators and researchers designing integrated STEM lessons. Future empirical research testing the model is warranted.

Universities play a crucial role in scientific research by promoting innovation, advancing knowledge, and nurturing future scientific experts and performers. The activities conducted within universities cover a wide spectrum, but strategies prioritize key elements. Crafting these strategies is particularly complex in this field, requiring the involvement of a large number of stakeholders, among which academic and research staff stand out in importance. The paper presents the perceptions of academic staff at the "Grigore T. Popa" University of Medicine and Pharmacy in Iași (UMF Iași) regarding the main axes of university strategy development. Essential aspects are addressed, such as the weighting of academic activities, funding procedures, and incentives provided to encourage and support scientific research activities, the objectives of scientific research strategy, and how research activities are integrated into the university's strategy.

Despite achievements in the remarkable photoelectrochemical (PEC) performance of photoelectrodes based on organometal halide perovskites (OHPs), the scaling up of small-scale OHP-based PEC systems to large-scale systems remains a great challenge for their practical application in solar water splitting. Significant resistive losses and intrinsic defects are major obstacles to the scaling up of OHP-based PEC systems, leading to the PEC performance degradation of large-scale OHP photoelectrodes. Herein, a scalable design of the OHP-based PEC systems by modularization of the optimized OHP photoelectrodes exhibiting a high solar-to-hydrogen conversion efficiency of 10.4% is suggested. As a proof-of-concept, the OHP-based PEC module achieves an optimal PEC performance by avoiding major obstacles in the scaling up of the OHP photoelectrodes. The constructed OHP module is composed of a total of 16 OHP photoelectrodes, and a photocurrent of 11.52 mA is achieved under natural sunlight without external bias. The successful operation of unassisted solar water splitting using the OHP module without external bias can provide insights into the design of scalable OHP-based PEC systems for future practical application and commercialization.

Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1's role in mediating neuronal resiliency in glaucoma.

Carotid body tumors (CBTs) are rare, hypervascular neuroendocrine neoplasms that can lead to significant complications during surgical resection due to the high risk of bleeding. We present the case of a 64-year-old male with a palpable neck mass on the left side, diagnosed as a CBT through imaging studies. Given the tumor's increasing size and rich vascularization, percutaneous preoperative embolization with Onyx under ultrasound and angiographic guide, was performed to minimize intraoperative complications. Forty-eight hours later, the tumor was surgically resected with minimal blood loss and no injury to cranial nerves or the carotid bifurcation.