Glioma subtype classification from histopathological images using in-domain and out-of-domain transfer learning: An experimental study.

We provide in this paper a comprehensive comparison of various transfer learning strategies and deep learning architectures for computer-aided classification of adult-type diffuse gliomas. We evaluate the generalizability of out-of-domain ImageNet representations for a target domain of histopathological images, and study the impact of in-domain adaptation using self-supervised and multi-task learning approaches for pretraining the models using the medium-to-large scale datasets of histopathological images. A semi-supervised learning approach is furthermore proposed, where the fine-tuned models are utilized to predict the labels of unannotated regions of the whole slide images (WSI). The models are subsequently retrained using the ground-truth labels and weak labels determined in the previous step, providing superior performance in comparison to standard in-domain transfer learning with balanced accuracy of 96.91% and F1-score 97.07%, and minimizing the pathologist's efforts for annotation. Finally, we provide a visualization tool working at WSI level which generates heatmaps that highlight tumor areas; thus, providing insights to pathologists concerning the most informative parts of the WSI.

Impact of Formalin- and Cryofixation on Raman Spectra of Human Tissues and Strategies for Tumor Bank Inclusion.

Reliable training of Raman spectra-based tumor classifiers relies on a substantial sample pool. This study explores the impact of cryofixation (CF) and formalin fixation (FF) on Raman spectra using samples from surgery sites and a tumor bank. A robotic Raman spectrometer scans samples prior to the neuropathological analysis. CF samples showed no significant spectral deviations, appearance, or disappearance of peaks, but an intensity reduction during freezing and subsequent recovery during the thawing process. In contrast, FF induces sustained spectral alterations depending on molecular composition, albeit with good signal-to-noise ratio preservation. These observations are also reflected in the varying dual-class classifier performance, initially trained on native, unfixed samples: The Matthews correlation coefficient is 81.0% for CF and 58.6% for FF meningioma and dura mater. Training on spectral differences between original FF and pure formalin spectra substantially improves FF samples' classifier performance (74.2%). CF is suitable for training global multiclass classifiers due to its consistent spectrum shape despite intensity reduction. FF introduces changes in peak relationships while preserving the signal-to-noise ratio, making it more suitable for dual-class classification, such as distinguishing between healthy and malignant tissues. Pure formalin spectrum subtraction represents a possible method for mathematical elimination of the FF influence. These findings enable retrospective analysis of processed samples, enhancing pathological work and expanding machine learning techniques.

Tales of me: storytelling identity work, authenticity, and impression management during new CEOs' work role transitions.

Introduction: This study aims to understand how new CEOs construct, revise, and maintain in their narrative, repertoire stories that represent their identity as it is associated with their new occupational role. Methods: For this purpose, we conducted a qualitative study using the Grounded Theory method, involving 47 CEOs from different sectors residing in Brazil. Results: Our results allowed for the construction of a central category called Storytelling Identity Work, which refers to stories that individuals tell about themselves, and enable them to propose and redefine who they are during major life transitions. This paper seeks to explain: (a) under what conditions this phenomenon tends to occur; (b) what characterizes the success of Storytelling Identity Work and; (c) what leads to the revision or retention of stories in the self. Our results show that storytelling identity work tends to be used by new CEOs during their transition period into the role, and when their new position involves higher levels of visibility and alteration of prestige levels in comparison to their previous position. They also suggest that storytelling identity work tends to be more successful when the stories are co-constructed and validated with other significant individuals and when they enable new CEOs to feel "sufficiently authentic" and "sufficiently impressive." Finally, we theorize that such feelings, along with a sense of coherence between the story being told and other narratives consciously or unconsciously being narrated by the interviewees throughout their lives, lead to the retention of the story within the individual's self. Discussion: This article innovates by connecting the literature on personal storytelling with identity work and exploring processes that are not only useful during the process of transitioning into the role of new CEOs but also influence the constitution of the narrative repertoire and, consequently, the identity of these individuals.

The great pretenders? Individuals' responses to threats to their remote worker identities.

Introduction: This study aims to understand (a) how remote workers respond to threats to their identity and (b) the conditions in which each coping response tends to occur more frequently. Methods: To this end, we pursued a grounded theory approach, conducting interviews with 71 individuals who chose to work remotely. Results: Our model and theoretical propositions create insights into how remote workers respond to negative stigma from a range of origins. While some responses lead to restructuring the remote workers' identity (identity restructuring responses), others involve keeping the enactment of such identity (identity-preserving responses) or maintaining a paradoxical relationship between restructuring and preserving the identity (paradoxical identity work responses). We also theorise on the conditions under which each response is more likely to occur. Discussion: We expand the predominant focus on the meso and macro aspects of this type of work to the micro-interactions in which these individuals engage, thus highlighting how identity is made, performed, created, and enacted, within specific boundary conditions. In addition, by reflecting upon remote workers' identity threats in light of the wider macro context. We also explore the conditions under which specific kinds of responses tend to emerge.

Correlative light and electron microscopy to explore the lytic immunological synapse between natural killer cells and cancer cells.

Cytotoxic lymphocytes, such as natural killer (NK) cells and cytotoxic T cells, can recognize and kill tumor cells by establishing a highly specialized cell-cell contact called the immunological synapse. The formation and lytic activity of the immunological synapse are accompanied by local changes in the organization, dynamics and molecular composition of the cell membrane, as well as the polarization of various cellular components, such as the cytoskeleton, vesicles and organelles. Characterization and understanding of the molecular and cellular processes underlying immunological synapse formation and activity requires the combination of complementary types of information provided by different imaging modalities, the correlation of which can be difficult. Correlative light and electron microscopy (CLEM) allows for the accurate correlation of functional information provided by fluorescent light microscopy with ultrastructural features provided by high-resolution electron microscopy. In this chapter, we present a detailed protocol describing each step to generate cell-cell conjugates between NK cells and cancer cells, and to analyze these conjugates by CLEM using separate confocal laser-scanning and transmission electron microscopes.

Algorithmic management, preferences for autonomy/security and gig-workers' wellbeing: A matter of fit?

The objective of this study was to understand how gig-workers interpret the effects of their laboral activity on their wellbeing. We developed a grounded theory based on interviews with 57 Brazilian gig-workers. The results show that (1) workers and gig-work organizations have preferences for work relationships with more autonomy or security; (2) when there is a congruence of preferences, the worker experiences greater wellbeing, and when the preferences diverge, there are episodes of preference violations that, when repeated, reduce worker wellbeing; and (3) however, not everything is a matter of fit: when both individuals and organizations have the same preference (for example, for more autonomy and less security), worker wellbeing may be vulnerable to abuse, for example, in terms of an unsustainable workload. Our study draws attention to an integrated discussion of the benefits and harms of algorithmic management, which allows overcoming a polarized view in which it would be seen only as beneficial or harmful to workers.

Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses.

Small extracellular vesicle (sEV, or exosome) communication among cells in the tumor microenvironment has been modeled mainly in cell culture, whereas their relevance in cancer pathogenesis and progression in vivo is less characterized. Here we investigated cancer-microenvironment interactions in vivo using mouse models of chronic lymphocytic leukemia (CLL). sEVs isolated directly from CLL tissue were enriched in specific miRNA and immune-checkpoint ligands. Distinct molecular components of tumor-derived sEVs altered CD8+ T-cell transcriptome, proteome, and metabolome, leading to decreased functions and cell exhaustion ex vivo and in vivo. Using antagomiRs and blocking antibodies, we defined specific cargo-mediated alterations on CD8+ T cells. Abrogating sEV biogenesis by Rab27a/b knockout dramatically delayed CLL pathogenesis. This phenotype was rescued by exogenous leukemic sEV or CD8+ T-cell depletion. Finally, high expression of sEV-related genes correlated with poor outcomes in CLL patients, suggesting sEV profiling as a prognostic tool. In conclusion, sEVs shape the immune microenvironment during CLL progression. SIGNIFICANCE: sEVs produced in the leukemia microenvironment impair CD8+ T-cell mediated antitumor immune response and are indispensable for leukemia progression in vivo in murine preclinical models. In addition, high expression of sEV-related genes correlated with poor survival and unfavorable clinical parameters in CLL patients. See related commentary by Zhong and Guo, p. 5. This article is highlighted in the In This Issue feature, p. 1.

Occupational callings: A double-edged sword for burnout and stress / Chamados ocupacionais: uma faca de dois gumes para o burnout e o estresse / Llamamientos ocupacionales: un cuchillo de doble filo para el burnout y el estrés

We evaluate the bivalent relationship between perceiving a calling and burnout syndrome and occupational stress. We suggest that although callings are negatively associated with burnout and stress, they produce a positive effect on both, having the perception of paradoxical tensions as a mediator. For this purpose, we conducted a quantitative survey of 539 individuals. The results showed a direct effect, according to which the more individuals perceive an occupational calling, the smaller the symptoms of burnout and stress. We also found an opposite indirect effect: the more individuals perceive a calling, the greater the symptoms of burnout and stress caused by increased paradoxical tensions that are experienced by individuals. Our findings show the importance of problematizing the idea of occupational callings as a necessarily positive antecedent for career development.

Neste estudo, avalia-se a relação bivalente entre perceber um chamado com a síndrome de burnout e o estresse ocupacional. Sugere-se que apesar dos chamados estarem negativamente associados com o burnout e o estresse, eles podem gerar um aumento nessas variáveis, por meio da percepção de tensões paradoxais. Para isto, realizou-se uma pesquisa quantitativa com 539 indivíduos. Em consonância com a literatura, os resultados apontaram que, diretamente, quanto mais os indivíduos percebem um chamado a uma ocupação, menores são os sintomas de burnout e de estresse. Mostrou também que, indiretamente, quanto mais os indivíduos percebem um chamado, maiores serão os sintomas de burnout e de estresse, provocado pelo aumento de tensões paradoxais que vivenciadas pelos indivíduos.

En este estudio, evaluaremos la relación bivalente entre percibir una llamada con síndrome de burnout y estrés laboral. Sugerimos que aunque los llamamientos se asocian negativamente con el agotamiento y el estrés, pueden generar un aumento en estas variables, a través de la percepción de tensiones paradójicas. Para esto, se llevó a cabo una investigación cuantitativa con 539 individuos. En línea con la literatura, los resultados mostraron que directamente, mientras más individuos perciben un llamamiento a una ocupación, menores son los síntomas de agotamiento y estrés. Evidenció también , indirectamente, que cuanto más un individuo percibe un llamamiento, mayores son los síntomas de burnout y estrés, causados por el aumento de las tensiones paradójicas vivenciadas por los individuos.

Differentiation of primary CNS lymphoma and glioblastoma using Raman spectroscopy and machine learning algorithms.

Objective and Methods: Timely discrimination between primary CNS lymphoma (PCNSL) and glioblastoma is crucial for diagnosis and therapy, but also determines the intraoperative surgical course. Advanced radiological methods allow for their distinction to a certain extent but ultimately, biopsies are still necessary for final diagnosis. As an upcoming method that enables tissue analysis by tracking changes in the vibrational state of molecules via inelastic scattered photons, we used Raman Spectroscopy (RS) as a label free method to examine specimens of both tumor entities intraoperatively, as well as postoperatively in formalin fixed paraffin embedded (FFPE) samples. Results: We applied and compared statistical performance of linear and nonlinear machine learning algorithms (Logistic Regression, Random Forest and XGBoost), and found that Random Forest classification distinguished the two tumor entities with a balanced accuracy of 82.4% in intraoperative tissue condition and with 94% using measurements of distinct tumor areas on FFPE tissue. Taking a deeper insight into the spectral properties of the tumor entities, we describe different tumor-specific Raman shifts of interest for classification. Conclusions: Due to our findings, we propose RS as an additional tool for fast and non-destructive tumor tissue discrimination, which may help to choose the proper treatment option. RS may further serve as a useful additional tool for neuropathological diagnostics with little requirements for tissue integrity.

When a Calling Goes Unanswered: Exploring the Role of Workplace Personalizations as Calling Enactments.

Individuals are sometimes unable to realize their callings in their formal careers. The literature has highlighted that such unanswered callings produce negative outcomes in the individual's career and personal life and that coping strategies, such as job and leisure crafting, can help them buffer such consequences. We developed a grounded theory regarding how people cope with their unanswered callings through a previously unexplored strategy in the calling literature: workplace personalization. Our study revealed that through this strategy, individuals retain the aspects of an unanswered calling in their self-concept and then reduce the consequences of not realizing the calling. Some participants enjoy some of the benefits of perceiving a calling, even without performing it in a formal work role. This phenomenon occurs because workplace personalization can be used to represent unanswered callings performed in the past and present, or that are intended to be performed in the future. This form of enactment produces interpersonal and intrapersonal processes that help buffer the negative consequences of not realizing a calling.

Entrapment of the sural nerve on gastrocnemius muscle: histological analysis / Compresión del nervio sural en el músculo gastrocnemio: análisis histológico

Anatomical variations in the formation of the sural nerve are common, although the topographical localization of this nerve is constant. In this report, we describe the histological analysis of anomalous course of the medial sural cutaneous nerve which descended through the gastrocnemius via a tunnel formed within the muscle and fascia. This anatomical curiosity are clinically important when evaluating sensory axonal loss in distal axonal neuropathies since sural nerve mononeuropathy is less likely to occur.

Las variaciones anatómicas en la formación del nervio sural son comunes, aunque la localización topográfica de este nervio es constante. En este reporte se describe el análisis histológico del nervio cutáneo sural medial de curso anómalo, que descendió a través de los músculos gastrognemios en un túnel formado en el músculo y la fascia. Esta curiosidad anatómica es de importancia clínica cuando se evalúa la pérdida sensitiva distal en neuropatías axonales, desde mononeuropatía del nervio sural a otras de menor frecuencia.

Structure and concentration of elastic system fibers in the trachea of the rat / Estructura y concentración del sistema de fibras elásticas en la tráquea de la rata

The extracellular matrix is a key element in the tracheal morphology and physiology, both in normal and pathological states, yet little is known regarding its composition and organization. Herein we carried out a detailed study of the morphological organization and volumetric density of elastic system fibers in the trachea of Wistar rats. Six Wistar rats at the age of 45 days were used. The trachea was excised following anesthesia with Thiopental and perfusion through the left ventricle with buffered saline followed by formalin solution. Samples were fixed in formaline, embedded in paraffin, and histologically processed. The elastic system fibers were evaluated at light microscopy by using Weigert's resorcin-fuchsin technique after oxidation with oxone. Morphometric studies were performed by the point-counting method. Quantities were expressed ( percent, mean) as volumetric densities and were determined on 25 random fields for each animal. Elastic system fibers were identified beneath the tracheal mucosa showing mainly a longitudinal profile. There were also some bundles of oblique fibers in this region, forming an irregular network of elastic tissue. Close to the inner surface of the cartilaginous ring, a well defined circular layer is present. The volumetric density of the elastic system fibers in the trachea of Wistar rats is 2.46 +/- 0.99 percent. The data in the present study provides original information regarding the elastic system fibers of the rat trachea, which might be used as a model for studying human major airway morphology. The results reported herein provide the basis for continuous investigations on tracheal extracellular matrix by stereology.

La matriz extracelular es un elemento clave en la morfología y fisiología de la tráquea, tanto en estados normales como patológicos. Sin embargo, poco se sabe acerca de su composición y organización. Se llevó a cabo un estudio detallado de la organización morfológica y la densidad volumétrica de fibras del sistema elástico en la tráquea de ratas Wistar. Se utilizaron seis ratas Wistar edad de 45 días de vida. La tráquea fue extraída después de anestesia con tiopental y la perfusión a través del ventrículo izquierdo con solución salina tamponada seguido de solución de formalina. Las muestras fueron fijadas en formalina e incluidas en parafina y se procesaron histológicamente. Las fibras del sistema elástico fueron evaluadas en microscopía de luz utilizando la técnica de Weigert, resorcina-fucsina después de la oxidación con Oxone. Los estudios morfométricos fueron realizados por el método de conteo de puntos. Las cantidades se expresaron ( por ciento, media) como la densidad volumétrica y se determinaron en 25 campos al azar para cada animal. Las fibras elásticas del sistema fueron identificadas por bajo la mucosa traqueal que muestra principalmente un perfil longitudinal. También se encontraron algunos haces de fibras oblicuas en esta región, formando una red irregular de tejido elástico. Cerca de la superficie interna del anillo cartilaginoso, una capa bien definida circular está presente. La densidad volumétrica de las fibras del sistema elástico en la tráquea de ratas Wistar fue de 2,46 +/- 0,99 por ciento. Los datos del presente estudio proporcionan información inicial sobre las fibras del sistema elástico de la tráquea de rata, que puede ser utilizado como un modelo para el estudio de la morfología de las vías respiratorias humanas. Los resultados reportados en este documento constituyen la base de investigaciones continuas en la tráquea de la matriz extracelular por estereología.

Structural analysis of the corpora cavernosa in patients with ischaemic priapism.

STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To evaluate, using quantitative and qualitative methods, the changes in the corpora cavernosa of patients with ischaemic priapism. PATIENTS AND METHODS: We obtained samples of corpora cavernosa from seven patients with ischaemic priapism (mean age 38 years, range 28-44) who had a cavernous-glandular shunt. The control tissues were fragments of corpora cavernosa obtained from autopsies of seven age-matched men who died from causes unrelated to the urogenital tract. Histochemical and immunohistochemical techniques were used to assess and quantify the extracellular matrix and smooth muscle fibres. The volumetric density of smooth muscle, elastic fibres and collagen were determined in corpora cavernosa. RESULTS: From the stereological analysis the mean (sd) values of volumetric density were: for collagen, control 34.76 (4.64), priapism 39.64 (2.91) (P = 0.002); elastic system fibres, controls 28.10 (2.85), priapism 36.10 (3.06) (P = 0.001); smooth muscle fibres, controls 43.37 (4.96), priapism 26.48 (5.00) (P < 0.001). There were significantly more fibrous elements of the connective tissue and significantly fewer smooth muscle fibres in the corpora cavernosa of patients with ischaemic priapism than in controls. CONCLUSION: Ischaemic priapism is associated with early and significant changes in the components of the extracellular matrix and smooth muscle fibres of the corpora cavernosa. This could explain the frequent occurrence of erectile dysfunction found in patients with ischaemic priapism.

Depoimentos sobre a construcao coletiva e participativa de um novo modelo para a saude / Staments about collective and participative construction of a new health model

Rompendo com a visao tradicional dos Postinhos de Saude, a Prefeitura do Municipio de Londrina, atraves da Secretaria de Saude, com a participacao da comunidade e do Centro de Ciencias da Saude da Universidade Estadual de Londrina, atraves do PROUNI, inaugurou uma nova concepcao arquitetonica, uma nova forma de envolvimento da populacao com os equipamentos publicos de saude e uma nova forma de interacao docente-assistencial. Apresenta a visao dos profissionais dos servicos de saude, dos alunos e dos professores sobre o significado da construcao deste novo modelo para a saude