Journals
2025 EN
Thomas Quentin Dominique · Vendrell Julie Adèle · Khellaf Lakhdar
+4 more
Abstract Background Microsatellite instability (MSI) has emerged as a predictive biomarker for immunotherapy response in various cancers, but its role in non–small cell lung cancer (NSCLC) is not fully understood. Methods The authors used the bioinformatics tool MIAmS to assess microsatellite status from next‐generation sequencing (NGS) data using a tailored microsatellite score. Immunohistochemistry (IHC) assays were also performed to evaluate the correspondence between MSI and deficient mismatch repair (dMMR) status. A retrospective analysis of 1547 lung cancer patients was conducted, focusing on those with an MSI phenotype. Clinical characteristics, co‐occurring molecular alterations, tumor mutation burden (TMB), and homologous recombination deficiency (HRD) status were evaluated in this subset. Results Of the 1547 patients analyzed, eight (0.52%) were identified as having MSI through MIAmS, with six (0.39%) of these cases also being dMMR on IHC. All patients with dMMR had an MS score ≥2 and a history of smoking. Most patients showed loss of MLH1 and PMS2 staining on IHC. No correlation was found between MSI status and programmed death‐ligand 1 expression, although all MSI patients exhibited high TMB, averaging 21.4 ± 5.6 mutations per megabase. Discussion MSI/dMMR in lung cancer is exceedingly rare, affecting less than 1% of cases. NGS‐based analysis combined with bioinformatics tools provides a robust method to identify MSI/dMMR patients, potentially guiding immunotherapy decisions. This comprehensive approach integrates molecular genotyping and MSI detection, offering personalized treatment options for lung cancer patients. NGS‐based MSI testing is emerging as the preferred method for detecting microsatellite instability in various tumor types, including rare cancers.
Journals
2025 EN
Ruz Oscar · Diaz Jérôme · Vidrascu Marina
+3 more
ABSTRACT The combination of reduced models of cardiac valve dynamics with a one‐way kinematic uncoupling of blood flow and electromechanics is a widespread approach for reducing the complexity of cardiac hemodynamics simulations. This comes, however, with a number of shortcomings: artificial pressure oscillations, missing isovolumetric phases, and valve laws without precise continuous formulation. This paper is aimed at overcoming these three difficulties while still mitigating computational cost. A novel reduced model of valve dynamics is proposed in which unidirectional flow is enforced in a mathematically sound fashion. Artificial pressure oscillations are overcome by considering a fluid–structure interaction model, which couples bi‐ventricular electromechanics and blood flow in the left cavities. The interface coupling is solved in a partitioned fashion via an unconditionally stable loosely coupled scheme. A priori energy estimates are derived for both the continuous coupled problem and its numerical approximation. The benefits and limitations of the proposed approaches are illustrated in a comprehensive numerical study.
Journals
2025 EN
Fuchshuber Jürgen · Zeldovich Marina · Aranyi Gabor
+5 more
ABSTRACT Background The Clinical Outcomes in Routine Evaluation – Outcome Measures (CORE‐OM) is a pantheoretical diagnostic instrument that has been widely used in mental health research. Nevertheless, the exploration of the factor structure of the CORE‐OM yields diverse results. Aims This study aimed to explore the internal structure of the German CORE‐OM using network analysis and compare several competing factorial structures of the CORE‐OM with traditional confirmatory factor analysis (CFA) to gain a more comprehensive understanding of its structural validity. Method A total sample comprised 4496 (63% female) participants from an outpatient population. In a first step, we used network analysis ( n 1 = 2248) to assess relationships between the items, followed by explorative graph analysis (EGA) to analyse community structure. Finally, we specified five competing models, including the one derived from the EGA, and used CFA in a second sample ( n 2 = 2248) to identify the best‐fitting structure of the instrument. Results The estimated cross‐sectional network demonstrated high correlation stability. The average item predictability was R 2 = 0.42. The EGA identified four distinct communities in the German CORE‐OM (General Problems; Interpersonal Problems; Positive Resources; Self Harm Risk). Confirmatory factor analysis showed that the EGA‐derived models had the most parsimonious fit. Conclusions These findings suggest a refined structure for the CORE‐OM, highlighting key item relationships and offering potential improvements for scoring and clinical use.
Journals
2025 EN
Mungai Margaret · Crabtree Amber · Le Han
+26 more
Abstract OPA1 is a dynamin‐related GTPase that modulates mitochondrial dynamics and cristae integrity. Humans carry eight different isoforms of OPA1 and mice carry five, all of which are expressed as short‐ or long‐form isoforms. These isoforms contribute to OPA1's ability to control mitochondrial energetics and DNA maintenance. However, western blot isolation of all long and short isoforms of OPA1 can be difficult. To address this issue, we developed an optimized western blot protocol based on improving running time to isolate five different isoforms of OPA1 in mouse cells and tissues. This protocol can be applied to study changes in mitochondrial structure and function. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol : Western Blot Protocol for Isolating OPA1 Isoforms in Mouse Primary Skeletal Muscle Cells
Journals
2025 EN
Crabtree Amber · Le Han · Harris Chanel
+23 more
Abstract Proximity ligation assays (PLAs) use specific antibodies to detect endogenous protein‐protein interactions. PLAs are a highly useful biochemical technique that allow two proteins within proximity to be visualized with fluorescent probes amplified by PCR. While this technique has gained prominence, the use of a PLA in mouse skeletal muscle (SkM) is novel. In this article, we discuss how the PLA method can be used in SkM to study the protein‐protein interactions within mitochondria‐endoplasmic reticulum contact sites (MERCs). © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol : Proximity ligation assay for skeletal muscle tissue and myoblast for MERC proteins
Journals
2025 EN
Peng Yong · Sakoleva Thaleia · Rockstroh Nils
+11 more
Abstract A concept of combining photocatalytically generated hydrogen with green enzymatic reductions is demonstrated. The developed photocatalytic formic acid (FA) dehydrogenation setup based on Pt(x)@TiO 2 shows stable hydrogen generation activity, which is two orders of magnitude higher than reported values of state‐of‐the‐art systems. Mechanistic studies confirm that hydrogen generation proceeds via a photocatalytic pathway, which is entirely different from purely thermal reaction mechanisms previously reported. The viability of the presented approach is demonstrated by the synthesis of value‐added compounds 3‐phenylpropanal and (2 R , 5 S )‐dihydrocarvone at ambient pressure and room temperature, which should be applicable for many other hydrogenation processes, e. g., for the preparation of flavours and fragrance compounds, as well as pharmaceuticals.
Journals
2025 EN
Messi Nicole
Abstract The Cambridge Handbook of Undergraduate Research, edited by Harald A. Mieg, Elizabeth L. Ambos, Angela Brew, Judith Lehmann, and Dominique M. Galli (2022), is a pioneering work offering a comprehensive global perspective on undergraduate research (UR). This handbook systematically addresses theoretical foundations, practical implementation strategies, disciplinary approaches and international perspectives on UR. It aims to enhance the understanding and practice of UR by integrating research experiences into undergraduate education, thereby bridging the gap between teaching and research. The book underscores UR's role in including underrepresented students, highlighting its potential to foster equity and diversity in academia. It emphasizes the active engagement of students in research, promoting self‐regulated learning and faculty–student partnerships. Despite its broad scope, the handbook identifies areas needing further attention, such as the limited focus on diverse categories of underrepresented students and ensuring active student participation in introductory research courses. Overall, ‘The Cambridge Handbook of Undergraduate Research’ serves as an essential resource for educators, administrators and policymakers, providing insights to advance UR practices and enhance educational outcomes globally. The reflections and insights presented stimulate further research and innovation, aiming to create inclusive, engaging and effective UR programs in higher education institutions worldwide.
Journals
2025 EN
Tessier Bernadette · Poirier Clément · Fruergaard Mikkel
+4 more
Abstract The present study examines the stratigraphy of two sandspits that both appeared and developed since the middle of the 17th century during the Little Ice Age. The Arçay spit is located along the macrotidal Atlantic coast in South‐West France with a maximum tidal range of 6.5 m. The Pointe du Banc in the English Channel, North‐West France, is located in a hypertidal coastal setting with a tidal range of up to 14 m. The evolution of the two spit systems has been compared using historical maps, ground penetrating radar data and facies analysis and geochronological data from sediment cores. The Pointe du Banc spit developed between 1650 and 1750 CE, in a dominant seaward direction while the main mode of construction of the Arçay spit was in a longshore direction. It is proposed that this difference relates to sediment supply and coastline morphology. At the Pointe du Banc spit, the large tidal range causes a long wind fetch and sustained aeolian sediment supply. Moreover, the spit is located at the apex of a large‐scale embayment where sediment transport from north and south converges. Combined, these factors result in a positive sediment budget and seaward shoreline progradation. At the Arçay spit, high wave obliquity results in a large littoral drift and sustained longshore spit construction. At both locations, low gradient shorefaces may have favoured a net landward‐directed sediment flux that supply sand to the foreshore.
Journals
2025 EN
Garcia Amanda Perozo · Perez Michelle · Galvan Thania
+2 more
ABSTRACT As more psychologists engage with marginalized communities for research, the lack of diversity in the academic workforce and inadequate cultural sensitivity training often leads to relying on trainees from underrepresented communities to bridge these gaps—a phenomenon we term “academic brokering.” Academic brokering disproportionately burdens underrepresented trainees, tasking them with facilitating their mentors’ research by serving as intermediaries between the mentor and the marginalized community to which the mentee belongs, while simultaneously navigating their academic and professional development. This practice introduces significant challenges for trainees, including balancing institutional barriers, cultural expectations, community service pressures, and advocacy efforts. This added burden can exacerbate existing stressors, leading to burnout, impeded productivity, and higher attrition rates among underrepresented trainees. Reliance on academic brokering not only places undue pressure on trainees but also risks compromising the quality and authenticity of research with marginalized communities, as it fails to address the systemic issues of cultural sensitivity and workforce diversity. This paper explores the concept of academic brokering and its impact on trainees, concluding with practical recommendations for increasing diversity in scientific training programs, integrating culturally responsive mentoring, fostering resilience among underrepresented trainees, and advocating for training program–level policies to create more equitable academic environments.
Journals
2025 EN
DeSisto Camille M. M. · Zandry Zico · Feno Telesy
+10 more
ABSTRACT Frugivore‐mediated seed dispersal drives ecological functioning across tropical forests. The biological mechanisms affecting seed dispersal outcomes, as well as the role of specific functional traits in plants and their dispersers, is still not well understood. To address this gap, we conducted germination experiments in eight species of captive and two species of wild lemurs, which disperse different plant species. We (1) quantified the effects of pulp removal, seed priming, and feces effects (nutrient/microbial fertilization) through gut passage as mechanisms, (2) determined the effect of frugivore species on germination, and (3) assessed how individual plant and animal traits affected two seed germination outcomes: success rates and time‐to‐germination. Accounting for phylogenetic non‐independence of plants and estimating phylogenetic signal, we evaluated the effects of lemur gut passage and functional traits in a Bayesian framework. Seed priming during gut passage was the primary mechanism through which lemurs improved germination rates and decreased time‐to‐germination. Gut passage influenced the effect of seed length on germination probability but not time‐to germination. Germination outcomes varied by disperser species and seed size. Furthermore, seeds passed by male lemurs were 40% more likely to germinate than those passed by female lemurs. Germination probability was more similar for closely related plant species compared to those that were more distantly related, while the plant phylogenetic effects on time‐to‐germination were weaker. Moreover, germination depended on experimental setting; for example, lemur gut passage decreased time‐to‐germination in captive, but not wild settings. Our results highlight the complexity of biological mechanisms determining seed dispersal outcomes; ecological and evolutionary factors were important drivers of germination. Considering a diversity of potential effects is critical for advancing a mechanistic understanding of species interactions and their outcomes.