Editor Profile: Andrey Abramov.

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Professor Andrey Abramov is a cell biologist and biophysicist at University College London's Queen Square Institute of Neurology. He has served as an Editorial Board Member of The FEBS Journal since 2015.

Bridging structural and cell biology with cryo-electron microscopy.

Most life scientists would agree that understanding how cellular processes work requires structural knowledge about the macromolecules involved. For example, deciphering the double-helical nature of DNA revealed essential aspects of how genetic information is stored, copied and repaired. Yet, being reductionist in nature, structural biology requires the purification of large amounts of macromolecules, often trimmed off larger functional units. The advent of cryogenic electron microscopy (cryo-EM) greatly facilitated the study of large, functional complexes and generally of samples that are hard to express, purify and/or crystallize. Nevertheless, cryo-EM still requires purification and thus visualization outside of the natural context in which macromolecules operate and coexist. Conversely, cell biologists have been imaging cells using a number of fast-evolving techniques that keep expanding their spatial and temporal reach, but always far from the resolution at which chemistry can be understood. Thus, structural and cell biology provide complementary, yet unconnected visions of the inner workings of cells. Here we discuss how the interplay between cryo-EM and cryo-electron tomography, as a connecting bridge to visualize macromolecules in situ, holds great promise to create comprehensive structural depictions of macromolecules as they interact in complex mixtures or, ultimately, inside the cell itself.

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer / Impacto de la positividad de la citología del lavado pleural en la recurrencia temprana después de la cirugía por cáncer de pulmón de células no pequeñas

Objective: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). Methods: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. Results: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06–2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04–2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14–2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27–3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25–16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25–5.36, p<0.001). Conclusions: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.(AU)

Measuring stomatal and guard cell metrics for plant physiology and growth using StoManager1.

Automated guard cell detection and measurement are vital for understanding plant physiological performance and ecological functioning in global water and carbon cycles. Most current methods for measuring guard cells and stomata are laborious, time-consuming, prone to bias, and limited in scale. We developed StoManager1, a high-throughput tool utilizing geometrical, mathematical algorithms, and convolutional neural networks to automatically detect, count, and measure over 30 guard cell and stomatal metrics, including guard cell and stomatal area, length, width, stomatal aperture area/guard cell area, orientation, stomatal evenness, divergence, and aggregation index. Combined with leaf functional traits, some of these StoManager1-measured guard cell and stomatal metrics explained 90% and 82% of tree biomass and intrinsic water use efficiency (iWUE) variances in hardwoods, making them substantial factors in leaf physiology and tree growth. StoManager1 demonstrated exceptional precision and recall (mAP@0.5 over 0.96), effectively capturing diverse stomatal properties across over 100 species. StoManager1 facilitates the automation of measuring leaf stomatal and guard cells, enabling broader exploration of stomatal control in plant growth and adaptation to environmental stress and climate change. This has implications for global gross primary productivity (GPP) modeling and estimation, as integrating stomatal metrics can enhance predictions of plant growth and resource usage worldwide. Easily accessible open-source code and standalone Windows executable applications are available on a GitHub repository (https://github.com/JiaxinWang123/StoManager1) and Zenodo (https://doi.org/10.5281/zenodo.7686022).

The implementation of an active inquiry learning centered "7E" teaching mode in the cell biology course enhances the learning effects of postgraduate students.

The primary objective of science postgraduate education is to foster students' capacity for creative thinking and problem-solving, particularly in the context of scientific research quality. In order to achieve this goal, the "7E" teaching mood has been implemented in the cell biology course for postgraduate students to promote student-centered active inquiry learning instead of breaking away from traditional indoctrination-based teaching methods. This study demonstrates that the implementation of the "7E" teaching mode, through content programming, process design, and effect evaluation, effectively meets the needs of the majority of students, fosters their interest in learning, enhances their performance in comprehensive questioning, and enhances their innovative abilities in scientific research. Consequently, this research offers a theoretical framework and practical foundation for the development of the "7E" teaching mode in postgraduate courses, aiming to cultivate highly skilled scientific professionals.

Moving structural biology forward together.

Continuing the celebration of Cell's 50th anniversary, this Focus Issue is an ode to the field of Structural Biology. We present Leading Edge articles highlighting specific approaches and insights that this field offers to answer fundamental and critical biological questions.

The beauty and challenges of studying cell biology in diverse organisms.

Cell Reports Editor Shawnna Buttery interviewed Holly Goodson, Wallace Marshall, and Thibaut Brunet at the annual ASCB/EMBO Cell Bio conference. Shawnna asked how non-traditional organisms help us better understand the fundamentals of cell biology. A transcript of the conversation appears below, and the full conversation is available with the article online.

Celebrating our origins with cell biology.

Cell's 50th anniversary celebrations begin with our special focus issue on cell biology. Foundational and critical to our understanding of life and mechanisms of disease, explore Leading Edge content covering exciting frontiers of this field.

Análise do perfil epidemiológico dos exames citopatológico do colo do útero em Altamira no período de 2014 a 2020: dados a partir do SISCAN / Analysis of the epidemiological profile of cervical cytopathological exams in Altamira in the period from 2014 to 2020: data from SISCAN / Análisis del perfil epidemiológico de los exámenes citopatológicos de cérvix en Altamira en el periodo de 2014 a 2020: datos del SISCAN

OBJETIVO: Este trabalho aborda sobre características referente aos exames citopatológicos do colo do útero em Altamira, coletado no Sistema de Informação do Câncer, dentro do período de 2014 a 2020. Observou-se também a qualidade da interpretação dos principais resultados encontrados, sobre a técnica de coleta e qualidade de exames. O objetivo é analisar o perfil epidemiológico dos exames citopatológicos do colo do útero do município. MÉTODO: A metodologia realizada foi estudo quantitativo, de corte transversal, epidemiológico, descritiva e analítico. RESULTADOS: Verificou- se um crescimento anual na taxa de cobertura do exame do preventivo no período de 2014 a 2019, que está ligado à implementação do Plano de Desenvolvimento Regional Sustentável do Xingu, e que esse crescimento mostra uma diferença estatística significativa entre a taxa de cobertura de Altamira, Pará, Brasil. Observou-se presença de falhas no preenchimento da ficha de notificação é referente ao campo da escolaridade das pacientes que não apresentam registro. Quanto a faixa etária mais frequente que realizam o exame do preventivo está entre 25 a 34 anos e as lesões intraepiteliais do colo uterino mais frequentes são: a de baixo grau que corresponde à população jovem (<34 anos) e de alto grau entre 25 a 44 anos.

OBJECTIVE: This paper deals with characteristics related to cytopathological examinations of the cervix in Altamira, collected in the Cancer Information System, within the period from 2014 to 2020. It was also observed the quality of interpretation of the main results found, on the technique collection and quality of exams. The objective is to analyze the epidemiological profile of cytopathological tests of the cervix in the city. METHOD: The methodology used was a quantitative, cross- sectional, epidemiological study, descriptive and analytical approach. RESULTS: As a result, there was an annual growth in the coverage rate of the preventive exam in the period from 2014 to 2019, which is linked to the implementation of the Xingu Sustainable Regional Development Plan, and that this growth shows a significant statistical difference between the coverage rate of Altamira, Pará, Brazil. It was observed the presence of failures in completing the notification form referring to the field of education of patients who do not have a record. As for the most frequent age group that undergoes the preventive examination, it is between 25 and 34 years old and the most frequent intraepithelial lesions of the uterine cervix are: low-grade, which corresponds to the young population (<34 years) and high-grade, between 25 and 34 years old. 44 years.

OBJETIVO: En este trabajo se abordan las características relacionadas con los exámenes citopatológicos de cérvix en Altamira, recogidos en el Sistema de Información del Cáncer, en el periodo comprendido entre 2014 y 2020. También se observó la calidad de interpretación de los principales resultados encontrados, sobre la técnica de recolección y calidad de los exámenes. El objetivo es analizar el perfil epidemiológico de los exámenes citopatológicos de cuello uterino en la ciudad. MÉTODO: La metodología utilizada fue un estudio cuantitativo, transversal, epidemiológico, de abordaje descriptivo y analítico. RESULTADOS: Como resultado, se observó un crecimiento anual de la tasa de cobertura del examen preventivo en el período de 2014 a 2019, que está vinculado a la implementación del Plan de Desarrollo Regional Sostenible Xingu, y que este crecimiento muestra una diferencia estadística significativa entre la tasa de cobertura de Altamira, Pará, Brasil. Se observó la presencia de fallas en el llenado del formulario de notificación referente al campo de la educación de los pacientes que no tienen un registro. En cuanto al grupo de edad más frecuente que se somete al examen preventivo, es entre 25 y 34 años y las lesiones intraepiteliales del cuello uterino más frecuentes son: de bajo grado, que corresponde a la población joven (<34 años) y de alto grado, entre 25 y 44 años.

The value of SOX10 expression in predicting perineural invasion in gastric cancer / El valor de la expresión de SOX10 en la predicción de la invasión perineural en el cáncer gástrico

Background: SRY-related HMG-box 10 (SOX10) protein has a confirmed role in the regulation of neural cell proliferation and differentiation. It is now suggested that the changes in SOX10 expression may be linked to neural invasion by cancer cells. We aimed to assess the value of SOX10 expression in predicting perineural invasion in gastric cancer. Methods: A cross-sectional study was performed on 40 patients with gastric cancer. To assess perineural invasion, Hematoxylin & Eosin stained slides were examined. The expression of SOX10 was also examined by immunohistochemistry. Results: Our study showed higher perineural invasion in those with SOX10 positivity as compared to those without SOX10 expression (64.0% vs. 6.7%, p=0.001). No association was revealed between other baseline variables and SOX10 positivity. The expression of this marker increased the chance of neural invasion up to 17 times as indicated by the multivariable regression modeling. Multivariable regression modeling indicated that the chance of neural invasion increased up to 17 times in cases of SOX10 positivity. Conclusion: Overexpression of SOX10 is closely associated with the risk of perineural invasion in gastric cancer.(AU)

Antecedentes: La proteína HMG-box 10 (SOX10) relacionada con SRY tiene un papel confirmado en la regulación de la proliferación y diferenciación de células neurales. Ahora se propone que los cambios en la expresión de SOX10 pueden estar relacionados con la invasión neuronal de las células cancerosas. Nuestro objetivo fue evaluar el valor de la expresión de SOX10 en la predicción de la invasión perineural en el cáncer gástrico. Métodos: Este estudio transversal se realizó en 40 pacientes con cánceres gástricos. Para evaluar la invasión perineural, se planificó la evaluación histopatológica mediante tinción con hematoxilina y eosina. El estado de expresión de SOX10 también se examinó mediante la técnica de inmunohistoquímica. Resultados: Nuestro estudio mostró una mayor invasión perineural en aquellos con positividad de SOX10 en comparación con aquellos sin expresión de SOX10 (64,0% versus 6,7%; p=0,001). No se reveló ninguna asociación entre otras variables basales y la positividad de SOX10. La expresión de este marcador aumentó la posibilidad de invasión neural hasta 17 veces, como indica el modelo de regresión multivariable. Conclusión: La sobreexpresión de SOX10 está estrechamente asociada con el riesgo de invasión perineural en el cáncer gástrico.(AU)

Estudio de variantes genéticas en 169 pacientes de cáncer de pulmón no microcítico / Study of genetic variants in 169 non-small cell lung cancer patients

Introducción: El cáncer de pulmón es la principal causa de muerte por cáncer en nuestro país. El cáncer de pulmón de células no pequeñas (CPCNP) representa el paradigma de la medicina personalizada. El objetivo principal de este trabajo es estudiar la frecuencia en nuestro medio de las variantes clínicamente significativas más frecuentemente descritas en CPCNP. Material y métodos: Se estudia la expresión inmunohistoquímica de TTF1, p40 y PD-L1 y la frecuencia de variantes genéticas mediante secuenciación masiva (NGS) con un panel de 52 genes, en 174 muestras incluidas en parafina de CPNCP en 169 pacientes (111 hombres y 52 mujeres) de la provincia de Cádiz. Resultados: La expresión inmunohistoquímica de TTF1, p40 y PD-L1 fue positiva en el 87%, el 0% y el 46% de los adenocarcinomas y en el 0%, el 100% y el 41% de los carcinomas escamosos. En NGS, las variantes de un solo nucleótido (SNV) más frecuentes fueron KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%) y MET (3%). Las variantes en el número de copias (CNV) más frecuentes fueron las amplificaciones en NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) y KRAS (7%). En mujeres, las SNV en EGFR fueron más frecuentes que en hombres (p<0,0001). El adenocarcinoma es el tipo histológico más frecuente con SNV en KRAS (p=0,007361) o en EGFR (p<0,0001). En 16 pacientes (9,47%) se detectaron fusiones génicas, 9 casos en el gen MET. Conclusiones: Detectamos nuevas asociaciones entre expresión inmunohistoquímica y algunas variantes génicas, que podrían tener impacto en el tratamiento de pacientes de CPNCP.(AU)

Introduction: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. Material and methods: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. Results: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. Conclusions: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.(AU)

Underestimated Cervical Cancer among Women over 65 Years Old: Is It Time to Revise the Screening Target Age Group? / Câncer cervical subestimado entre mulheres com mais de 65 anos: É hora de rever a faixa etária alvo do rastreamento?

Abstract Objective To compare cytological and histological results from women > 64 years old who followed the Brazilian national cervical cancer screening guidelines with those who did not. Methods The present observational retrospective study analyzed 207 abnormal cervical smear results from women > 64 years old in a mid-sized city in Brazil over 14 years. All results were reported according to the Bethesda System. The women were divided into those who followed the screening guidelines and those who did not. Results Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytology results were found in 128 (62.2%) cases. Of these, 112 (87.5%) had repeated cytology with positive results. The other 79 (38.1%) with abnormal results should have been referred to colposcopy and biopsy. Out of 41 (51.9%) biopsied women, 23 (29.1%) had a confirmed diagnosis of neoplasia or precursor lesion. In contrast, among the 78 (37.7%) biopsied patients, 40 (51.3%) followed the guideline recommendations, with 9 (22.5%) positive biopsies. Of the 38 (48.7%) women who did not follow the guidelines, there were 24 (63.1%) positive results. Women who did not follow the guidelines demonstrated higher chances of cancer and precursor lesions (odds ratio [OR]: 5.904; 95% confidence interval [CI]: 2.188-15.932; p = 0.0002). Conclusion Women > 64 years old who did not follow the national screening protocol showed significant differences in the frequency of abnormal results and severity of diagnosis compared with those who followed the protocol.

Resumo Objetivo Comparar os resultados citológicos e histológicos de mulheres > 64 anos que seguiram as diretrizes nacionais brasileiras de rastreamento do câncer do colo do útero com aquelas que não as seguiram. Método O presente estudo observacional retrospectivo analisou 207 resultados anormais de esfregaço cervical de mulheres > 64 anos de idade em uma cidade de médio porte no Brasil durante 14 anos. Todos os resultados foram relatados de acordo com o Sistema Bethesda. As mulheres foram divididas entre as que seguiram as diretrizes de rastreamento e as que não o fizeram. Resultados Resultados citológicos com células escamosas atípicas de significado indeterminado e lesão intraepitelial escamosa de baixo grau foram encontrados em 128 (62,2%) casos. Destes, 112 (87,5%) repetiram a citologia com resultados positivos. Os outros 79 (38,1%) com resultados anormais deveriam ter sido encaminhados para colposcopia e biópsia. Das 41 (51,9%) mulheres biopsiadas, 23 (29,1%) tiveram diagnóstico confirmado de neoplasia ou lesão precursora. Em contrapartida, entre as 78 (37,7%) pacientes biopsiadas, 40 (51,3%) seguiram as recomendações da diretriz, com 9 (22,5%) biópsias positivas. Entre as 38 (48,7%) mulheres que não seguiram as orientações, houve 24 (63,1%) resultados positivos. As mulheres que não seguiram as diretrizes demonstraram maiores chances de câncer e lesões precursoras (odds ratio [OR]: 5,904; intervalo de confiança [IC] de 95%: 2,188-15,932; p = 0,0002). Conclusão Mulheres > 64 anos que não seguiram a diretriz nacional de rastreamento apresentaram diferenças significativas na frequência de resultados anormais e gravidade do diagnóstico em comparação com aquelas que seguiram a diretriz.

Robustness and complexity.

When a system robustly corrects component-level errors, the direct pressure on component performance declines. Components become less reliable, maintain more genetic variability, or drift neutrally, creating new forms of complexity. Examples include the hourglass pattern of biological development and the hourglass architecture for robustly complex systems in engineering.

Bioorthogonal Chemistry in Cellular Organelles.

While bioorthogonal reactions are routinely employed in living cells and organisms, their application within individual organelles remains limited. In this review, we highlight diverse examples of bioorthogonal reactions used to investigate the roles of biomolecules and biological processes as well as advanced imaging techniques within cellular organelles. These innovations hold great promise for therapeutic interventions in personalized medicine and precision therapies. We also address existing challenges related to the selectivity and trafficking of subcellular dynamics. Organelle-targeted bioorthogonal reactions have the potential to significantly advance our understanding of cellular organization and function, provide new pathways for basic research and clinical applications, and shape the direction of cell biology and medical research.

Cell wall is a dead metaphor.

It was recently suggested to end the usage of the term cell wall in microbiology (including prokaryotes and fungi) because it represented an inappropriate and potentially misleading metaphor (Casadevall and Gow, 2022). The analysis of the arguments for such a move from the viewpoint of the plant physiologist indicates that the suggestion is based on misunderstandings, first, of the early history of cell biology and its terminology; second, of the development of modern concepts of cell wall function since the late 19th century; and third, of the nature of metaphors and their role in scientific communication. We conclude that misconceptions concerning cell walls may arise due to pedagogical shortcomings in introducing students to our technical terminology rather than from the fact that part of this terminology originated from metaphors.