Dataset from the bell and dean paper on the structure of vitreous silica.

Digitized data is presented based on the 1966 and 1972 seminal papers by R. J. Bell and P. Dean, which in turn are based on a physical ball and stick model of vitreous silica. The original Bell and Dean paper supports the random network theory for glass structure proposed by Zachariasen in 1932. The data were collected and digitized by verifying the data set in the Appendix of the Bell and Dean paper. One error in location was corrected. The dataset provides a convenient method to determine specific information about bond locations and angles of silica and oxygen atoms if researchers want to test theories of glass structure or fracture in amorphous materials.

Decoding pathology: the role of computational pathology in research and diagnostics.

Traditional histopathology, characterized by manual quantifications and assessments, faces challenges such as low-throughput and inter-observer variability that hinder the introduction of precision medicine in pathology diagnostics and research. The advent of digital pathology allowed the introduction of computational pathology, a discipline that leverages computational methods, especially based on deep learning (DL) techniques, to analyze histopathology specimens. A growing body of research shows impressive performances of DL-based models in pathology for a multitude of tasks, such as mutation prediction, large-scale pathomics analyses, or prognosis prediction. New approaches integrate multimodal data sources and increasingly rely on multi-purpose foundation models. This review provides an introductory overview of advancements in computational pathology and discusses their implications for the future of histopathology in research and diagnostics.

DNA-binding protein-A: a multitool in tubular epithelial cells.

Acute kidney injury is still associated with high morbidity and mortality. Reichardt et al. investigated DNA-binding protein-A (Ybx3) in acute kidney injury induced by ischemia-reperfusion injury and found that mice lacking Ybx3 have altered mitochondrial function and increased antioxidant activity, making them more resistant to ischemia-reperfusion injury-acute kidney injury. The study highlights a new role of the multifaceted protein DNA-binding protein-A, which could be potentially therapeutically exploited.

Sex-related differences in young binge drinkers on the neurophysiological response to stress in virtual reality.

Background: Stress is one of the main environmental factors involved in the onset of different psychopathologies. In youth, stressful life events can trigger inappropriate and health-damaging behaviors, such as binge drinking. This behavior, in turn, can lead to long-lasting changes in the neurophysiological response to stress and the development of psychological disorders late in life, e.g., alcohol use disorder. Our aim was to analyze the pattern of neurophysiological responses triggered with the exposition to a stressful virtual environment in young binge drinkers. Methods: AUDIT-3 (third question from the full AUDIT) was used to detect binge drinking (BD) in our young sample (age 18-25 years). According to the score, participants were divided into control (CO) and BD group. Next, a standardized virtual reality (VR) scenario (Richie's Plank) was used for triggering the stress response while measuring the following neurophysiological variables: brain electrical activity by electroencephalogram (EEG) and cortisol levels through saliva samples both measurements registered before and after the stressful situation. Besides, heart rate (HR) with a pulsometer and electrodermal response (EDA) through electrodes placed on fingers were analyzed before, during and after the VR task. Results: Regarding the behavior assessed during the VR task, BD group spent significantly less amount of time walking forward the table and a tendency toward more time walking backwards. There was no statistically significant difference between the BD and the CO group regarding time looking down, but when we controlled the variable sex, the BD women group displayed higher amount of time looking down than the rest of the groups. Neurophysiological measurements revealed that there was not any statistically significant difference between groups in any of the EEG registered measures, EDA response and cortisol levels. Sex-related differences were found in HR response to VR scenario, in which BD women displayed the highest peak of response to the stressor. Also, the change in heartbeat was higher in BD women than men. Conclusion: Unveiling the neurophysiological alterations associated with BD can help us to prevent and detect early onset of alcohol use disorder. Also, from our data we conclude that participants' sex can modulate some stress responses, especially when unhealthy behaviors such as BD are present. Nevertheless, the moment of registration of the neurophysiological variables respect to the stressor seems to be a crucial variable.

A new approach to urinalysis: effectiveness of a contingency management program among adolescent offenders in Spain.

Background: When addressing antisocial behaviour among adolescents, programs based on the paradigm of positive psychology through enhancing self-efficacy have demonstrated their effectiveness in furthering the positive development of young people with a history of antisocial behaviour. Nevertheless, there has been little research into the effectiveness of these type of programs in mitigating substance abuse among juvenile offenders. The aim of this paper is to analyse the effectiveness of a contingency management program in reducing the prevalence of relapses into drug consumption among adolescents who have committed serious crimes. Methods: The study consisted of a sample of 91 male adolescents, between 15 and 19 years, in juvenile detention, who were divided into two treatment groups. For both groups, biological testing was used to detect drug consumption upon their re-turn from leave permits from the Centre. Results: The quasi-experimental group had significantly lower rates of relapse than the quasi-control group. Furthermore, being part of the quasi-experimental group was a significant predictor of reduced rates of relapses. Conclusion: The results suggest that the incorporation of treatment strategies which reinforce feelings of self-efficacy and adequate orientation towards the future, as a complement to disciplinary sanctions, are effective in reducing relapses in drug use among adolescent offenders.

Histopathological biomarkers for predicting the tumour accumulation of nanomedicines.

The clinical prospects of cancer nanomedicines depend on effective patient stratification. Here we report the identification of predictive biomarkers of the accumulation of nanomedicines in tumour tissue. By using supervised machine learning on data of the accumulation of nanomedicines in tumour models in mice, we identified the densities of blood vessels and of tumour-associated macrophages as key predictive features. On the basis of these two features, we derived a biomarker score correlating with the concentration of liposomal doxorubicin in tumours and validated it in three syngeneic tumour models in immunocompetent mice and in four cell-line-derived and six patient-derived tumour xenografts in mice. The score effectively discriminated tumours according to the accumulation of nanomedicines (high versus low), with an area under the receiver operating characteristic curve of 0.91. Histopathological assessment of 30 tumour specimens from patients and of 28 corresponding primary tumour biopsies confirmed the score's effectiveness in predicting the tumour accumulation of liposomal doxorubicin. Biomarkers of the tumour accumulation of nanomedicines may aid the stratification of patients in clinical trials of cancer nanomedicines.

The immunostimulatory roles of gold nanoparticles in immunization and vaccination against Brucella abortus antigens.

One effective antigen carrier proposed for use in immunization and vaccination is gold nanoparticles. Prior work has shown that gold nanoparticles themselves have adjuvant properties. Currently, gold nanoparticles are used to design new diagnostic tests and vaccines against viral, bacterial, and parasitic infections. We investigated the use of gold nanoparticles as immunomodulators in immunization and vaccination with an antigen isolated from Brucella abortus. Gold nanoparticles with a diameter of 15 nm were synthesized for immunization of animals and were then conjugated to the isolated antigen. The conjugates were used to immunize white BALB/c mice. As a result, high-titer (1:10240) antibodies were produced. The respiratory and proliferative activities of immune cells were increased, as were the serum interleukin concentrations. The minimum antigen amount detected with the produced antibodies was âˆ¼ 0.5 pg. The mice immunized with gold nanoparticles complexed with the B. abortus antigen were more resistant to B. abortus strain 82 than were the mice immunized through other schemes. This fact indicates that animal immunization with this conjugate enhances the effectiveness of the immune response. The results of this study are expected to be used in further work to examine the protective effect of gold nanoparticles complexed with the B. abortus antigen on immunized animals and to develop test systems for diagnosing brucellosis in the laboratory and in the field.

tRigon: an R package and Shiny App for integrative (path-)omics data analysis.

BACKGROUND: Pathomics facilitates automated, reproducible and precise histopathology analysis and morphological phenotyping. Similar to molecular omics, pathomics datasets are high-dimensional, but also face large outlier variability and inherent data missingness, making quick and comprehensible data analysis challenging. To facilitate pathomics data analysis and interpretation as well as support a broad implementation we developed tRigon (Toolbox foR InteGrative (path-)Omics data aNalysis), a Shiny application for fast, comprehensive and reproducible pathomics analysis. RESULTS: tRigon is available via the CRAN repository ( https://cran.r-project.org/web/packages/tRigon ) with its source code available on GitLab ( https://git-ce.rwth-aachen.de/labooratory-ai/trigon ). The tRigon package can be installed locally and its application can be executed from the R console via the command 'tRigon::run_tRigon()'. Alternatively, the application is hosted online and can be accessed at https://labooratory.shinyapps.io/tRigon . We show fast computation of small, medium and large datasets in a low- and high-performance hardware setting, indicating broad applicability of tRigon. CONCLUSIONS: tRigon allows researchers without coding abilities to perform exploratory feature analyses of pathomics and non-pathomics datasets on their own using a variety of hardware.

[Advances in computational quantitative nephropathology]. / Fortschritte in der computergestützten quantitativen Nephropathologie.

BACKGROUND: Semiquantitative histological scoring systems are frequently used in nephropathology. In computational nephropathology, the focus is on generating quantitative data from histology (so-called pathomics). Several recent studies have collected such data using next-generation morphometry (NGM) based on segmentations by artificial neural networks and investigated their usability for various clinical or diagnostic purposes. AIM: To present an overview of the current state of studies regarding renal pathomics and to identify current challenges and potential solutions. MATERIALS AND METHODS: Due to the literature restriction (maximum of 30 references), studies were selected based on a database search that processed as much data as possible, used innovative methodologies, and/or were ideally multicentric in design. RESULTS AND DISCUSSION: Pathomics studies in the kidney have impressively demonstrated that morphometric data are useful clinically (for example, for prognosis assessment) and translationally. Further development of NGM requires overcoming some challenges, including better standardization and generation of prospective evidence.

Detection of PatIent-Level distances from single cell genomics and pathomics data with Optimal Transport (PILOT).

Although clinical applications represent the next challenge in single-cell genomics and digital pathology, we still lack computational methods to analyze single-cell or pathomics data to find sample-level trajectories or clusters associated with diseases. This remains challenging as single-cell/pathomics data are multi-scale, i.e., a sample is represented by clusters of cells/structures, and samples cannot be easily compared with each other. Here we propose PatIent Level analysis with Optimal Transport (PILOT). PILOT uses optimal transport to compute the Wasserstein distance between two individual single-cell samples. This allows us to perform unsupervised analysis at the sample level and uncover trajectories or cellular clusters associated with disease progression. We evaluate PILOT and competing approaches in single-cell genomics or pathomics studies involving various human diseases with up to 600 samples/patients and millions of cells or tissue structures. Our results demonstrate that PILOT detects disease-associated samples from large and complex single-cell or pathomics data. Moreover, PILOT provides a statistical approach to find changes in cell populations, gene expression, and tissue structures related to the trajectories or clusters supporting interpretation of predictions.

Synthesis and properties of nano-cadmium oxide and its size-dependent responses by barley plant.

Present study included technological methods that made it possible to synthesize CdO nanoparticles and carry out their qualitative and quantitative diagnostics, confirming the as-prepared CdO nanoparticles (NPs) were spherical and had a size of 25 nm. Then, under the conditions of the model experiment the effect of CdO in macro and nanosized particles on absorption, transformation, and structural and functional changes occurring in cells and tissues of Hordeum vulgare L. (spring barley) during its ontogenesis was analyzed. Different analytical techniques were used to detect the transformation of CdO forms: Fourier-transform infrared spectroscopy (FTIR), Dynamic light scattering (DLS), X-ray fluorescence analysis (XRF), Scanning electron microscopy (SEM-EDXMA and TEM), X-ray diffraction (XRD), and X-ray absorption fine structure, consists of XANES - X-ray absorption near edge structure, and EXAFS - Extended X-ray absorption fine structure. Quantitative differences in the elemental chemical composition of barley root and leaf samples were observed. The predominant root uptake of Cd was revealed. CdO-NPs were found to penetrate deeply into barley plant tissues, where they accumulated and formed new mineral phases such as Cd5(PO4)3Cl and CdSO4 according to XRD analysis. The molecular-structural state of the local Cd environment in plant samples corresponding to Cd-O and Cd-Cd. The toxicity of CdO-NPs was found to significantly affect the morphology of intracellular structures are the main organelles of photosynthesis therefore, destructive changes in them obviously reduce the level of metabolic processes ensuring the growth of plants. This study is an attempt to show results how it is possible to combine some instrumental techniques to characterize and behavior of NPs in complex matrices of living organisms.

Banff Digital Pathology Working Group: Image Bank, Artificial Intelligence Algorithm, and Challenge Trial Developments.

The Banff Digital Pathology Working Group (DPWG) was established with the goal to establish a digital pathology repository; develop, validate, and share models for image analysis; and foster collaborations using regular videoconferencing. During the calls, a variety of artificial intelligence (AI)-based support systems for transplantation pathology were presented. Potential collaborations in a competition/trial on AI applied to kidney transplant specimens, including the DIAGGRAFT challenge (staining of biopsies at multiple institutions, pathologists' visual assessment, and development and validation of new and pre-existing Banff scoring algorithms), were also discussed. To determine the next steps, a survey was conducted, primarily focusing on the feasibility of establishing a digital pathology repository and identifying potential hosts. Sixteen of the 35 respondents (46%) had access to a server hosting a digital pathology repository, with 2 respondents that could serve as a potential host at no cost to the DPWG. The 16 digital pathology repositories collected specimens from various organs, with the largest constituent being kidney (n = 12,870 specimens). A DPWG pilot digital pathology repository was established, and there are plans for a competition/trial with the DIAGGRAFT project. Utilizing existing resources and previously established models, the Banff DPWG is establishing new resources for the Banff community.

Sodium pyruvate improves the plasma amino acid profile in rats with L-arginine-induced acute pancreatitis.

Plasma amino acid levels are altered upon many pathological conditions including acute pancreatitis. It is unclear whether amino acids can be used as specific biomarker of acute pancreatitis severity or recovery. Development of acute pancreatitis is associated with mitochondrial dysfunction and decreased cytosolic ATP level. Sodium pyruvate is considered as a potential treatment of pancreatitis due to its ability to sustain mitochondrial oxidative and ATP-productive capacity in vitro. This study investigated the effect of sodium pyruvate on pancreatic morphology and plasma amino acid levels in rats with acute pancreatitis. Acute pancreatitis in rats was induced by administration of L-arginine (5 g/kg) Experimental treatment group received sodium pyruvate (1 g/kg) for 4 days. On day 8 of the experiment, animals were killed, blood was collected and plasma amino acid concentration was determined with high-performance liquid chromatography. Histological examination showed large areas of fibrosis in the pancreas of animals treated with L-arginine irrespectively of sodium pyruvate administration. Sodium pyruvate improved the plasma amino acid levels. Rats with acute pancreatitis had significantly lower levels of most essential and non-essential amino acids and increased glutamate and aspartate in plasma. Administration of sodium pyruvate completely or partially restored the levels of methionine, phenylalanine, tryptophan, leucine, isoleucine, aspartate, asparagine and ornithine levels, while increasing glutamine and serine to levels significantly higher than control. Plasma lysine, alanine, arginine and taurine remained unaffected in all experimental groups. Sodium pyruvate may be considered for use as a maintenance therapy in acute pancreatitis.

Finerenone Added to RAS/SGLT2 Blockade for CKD in Alport Syndrome. Results of a Randomized Controlled Trial with Col4a3-/- Mice.

SIGNIFICANCE STATEMENT: We hypothesized that triple therapy with inhibitors of the renin-angiotensin system (RAS), sodium-glucose transporter (SGLT)-2, and the mineralocorticoid receptor (MR) would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression in Col4a3 -deficient mice, a model of Alport syndrome. Late-onset ramipril monotherapy or dual ramipril/empagliflozin therapy attenuated CKD and prolonged overall survival by 2 weeks. Adding the nonsteroidal MR antagonist finerenone extended survival by 4 weeks. Pathomics and RNA sequencing revealed significant protective effects on the tubulointerstitium when adding finerenone to RAS/SGLT2 inhibition. Thus, triple RAS/SGLT2/MR blockade has synergistic effects and might attenuate CKD progression in patients with Alport syndrome and possibly other progressive chronic kidney disorders. BACKGROUND: Dual inhibition of the renin-angiotensin system (RAS) plus sodium-glucose transporter (SGLT)-2 or the mineralocorticoid receptor (MR) demonstrated additive renoprotective effects in large clinical trials. We hypothesized that triple therapy with RAS/SGLT2/MR inhibitors would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression. METHODS: We performed a preclinical randomized controlled trial (PCTE0000266) in Col4a3 -deficient mice with established Alport nephropathy. Treatment was initiated late (age 6 weeks) in mice with elevated serum creatinine and albuminuria and with glomerulosclerosis, interstitial fibrosis, and tubular atrophy. We block-randomized 40 male and 40 female mice to either nil (vehicle) or late-onset food admixes of ramipril monotherapy (10 mg/kg), ramipril plus empagliflozin (30 mg/kg), or ramipril plus empagliflozin plus finerenone (10 mg/kg). Primary end point was mean survival. RESULTS: Mean survival was 63.7±10.0 days (vehicle), 77.3±5.3 days (ramipril), 80.3±11.0 days (dual), and 103.1±20.3 days (triple). Sex did not affect outcome. Histopathology, pathomics, and RNA sequencing revealed that finerenone mainly suppressed the residual interstitial inflammation and fibrosis despite dual RAS/SGLT2 inhibition. CONCLUSION: Experiments in mice suggest that triple RAS/SGLT2/MR blockade may substantially improve renal outcomes in Alport syndrome and possibly other progressive CKDs because of synergistic effects on the glomerular and tubulointerstitial compartments.

Stokes and Anti-Stokes Luminescent Rare-Earth-Doped Tantalum Oxide Nanoparticles.

Doping of nano- and microparticles of oxides with rare earth elements (REEs) is used to fine-tune their structural, optical, and electrochemical properties. On the way to establish the structure-property relationship, we dope tantalum oxide (Ta2O5) particles with REEs to study their effect on the oxide structure and luminescence. Ta2O5 is highly perspective in medicine, catalysis, and optics, but its crystal structure is insufficiently studied. Two synthesis approaches (sol-gel and solvothermal) were used to obtain powders with different textures. Experimental and theoretical studies of amorphous and crystallized tantalum oxide NPs by means of X-ray powder diffraction, Rietveld analysis, EXAFS/XANES spectroscopy, and density functional theory calculations were performed. All samples (doped and undoped) crystallized in orthorhombic phase with no admixtures. It was demonstrated that Ta2O5 is a promising wide-spectrum luminescent material: by combining REEs, both Stokes and anti-Stokes luminescence in the visible region were obtained. By means of optical absorption spectroscopy, it was shown that the prepared samples could be classified as wide band gap semiconductors.

Prediction of heart transplant rejection from routine pathology slides with self-supervised deep learning.

Aims: One of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system. Methods and results: We collected 1079 histopathology slides from 325 patients from three transplant centres in Germany. We trained an attention-based deep neural network to predict rejection in the primary cohort and evaluated its performance using cross-validation and by deploying it to three cohorts. For binary prediction (rejection yes/no), the mean area under the receiver operating curve (AUROC) was 0.849 in the cross-validated experiment and 0.734, 0.729, and 0.716 in external validation cohorts. For a prediction of the ISHLT grade (0R, 1R, 2/3R), AUROCs were 0.835, 0.633, and 0.905 in the cross-validated experiment and 0.764, 0.597, and 0.913; 0.631, 0.633, and 0.682; and 0.722, 0.601, and 0.805 in the validation cohorts, respectively. The predictions of the artificial intelligence model were interpretable by human experts and highlighted plausible morphological patterns. Conclusion: We conclude that artificial intelligence can detect patterns of cellular transplant rejection in routine pathology, even when trained on small cohorts.

Patients Response to Interventional Care for Chronic Pain Study (PRICS): A Cross-Sectional Survey of Community-Based Pain Clinics in Ontario, Canada.

BACKGROUND: Non-image guided injection treatments ("nerve blocks") are commonly provided in community pain clinics in Ontario for chronic non-cancer pain (CNCP) but remain controversial. AIM: We explored patients' perspectives of nerve blocks for CNCP. METHODS: We administered a 33-item cross-sectional survey to patients living with CNCP pain attending four community-based pain clinics in Ontario, Canada. The survey captured demographic information and asked about patient experiences with nerve blocks. RESULTS: Among 616 patients that were approached, 562 (91%) provided a completed survey. The mean age of respondents was 53 (SD 12), 71% were female, and the majority (57%) reported living with CNCP for more than a decade. Fifty-eight percent had been receiving nerve blocks for their pain for >3 years, 51% on a weekly frequency. Since receiving nerve blocks, patients self-reported a median improvement in pain intensity of 2.5 points (95% CI -2.5 to -3.0) on an 11-point numeric rating scale and 66% reported stopping or reducing prescription medications, including opioids. The majority who were not retired (62%) were receiving disability benefits and were unable to work in any capacity. When asked what impact cessation of nerve blocks would have, most employed patients (52%) reported they would be unable to work, and the majority indicated their ability to function across multiple domains would decrease. CONCLUSION: Our respondents who received nerve blocks for CNCP attribute important pain relief and functional improvement to this intervention. Randomized trials and clinical practice guidelines are urgently needed to optimize the evidence-based use of nerve blocks for CNCP.

Language Barriers in Organismal Biology: What Can Journals Do Better?

In the field of organismal biology, as in much of academia, there is a strong incentive to publish in internationally recognized, highly regarded, English-language journals to promote career advancement. This expectation has created a linguistic hegemony in scientific publishing, whereby scholars for whom English is an additional language face additional barriers to achieving the same scientific recognition as scholars who speak English as a first language. Here, we surveyed the author guidelines of 230 journals in organismal biology with impact factors of 1.5 or greater for linguistically inclusive and equitable practices and policies. We looked for efforts that reflect first steps toward reducing barriers to publication for authors globally, including the presence of statements that encouraged submissions from authors of diverse nationalities and backgrounds, policies regarding manuscript rejection based on perceived inadequacies of the English language, the existence of bias-conscious reviewer practices, whether translation and editing resources or services are available, allowance for non-English abstracts, summaries, or translations, and whether journals offer license options that would permit authors (or other scholars) to translate their work and publish it elsewhere. We also directly contacted a subset of journals to verify whether the information on their author guidelines page accurately reflects their policies and the accommodations they would make. We reveal that journals and publishers have made little progress toward beginning to recognize or reduce language barriers. Counter to our predictions, journals associated with scientific societies did not appear to have more inclusive policies compared to non-society journals. Many policies lacked transparency and clarity, which can generate uncertainty, result in avoidable manuscript rejections, and necessitate additional time and effort from both prospective authors and journal editors. We highlight examples of equitable policies and summarize actions that journals can take to begin to alleviate barriers to scientific publishing.

ResumenEn el campo de la biología organísmica, al igual que en el mundo académico en general, existe un gran incentivo para publicar en revistas científicas de lengua inglesa que son reconocidas internacionalmente y que poseen gran prestigio con el fin de avanzar profesionalmente. Esta expectativa ha creado una hegemonía lingüística en la publicación científica en la que los académicos para quienes el inglés es una lengua adicional se enfrentan a barreras adicionales para lograr el mismo reconocimiento científico que los académicos que hablan inglés como primera lengua. En este estudio examinamos las instrucciones para autores de 230 revistas de biología organísmica con Factor de Impacto igual o superior a 1.5 en busca de prácticas y políticas lingüísticamente inclusivas y equitativas. Buscamos iniciativas que reflejen pasos iniciales hacia la reducción de barreras de publicación para autores a nivel mundial. Estas incluyen la presencia de anuncios que incentiven el envío de trabajos por autores de diversas nacionalidades, políticas relacionadas al rechazo de manuscritos debido a la percepción de insuficiencias en el inglés, prácticas de revisión conscientes de prejuicios, disponibilidad de recursos o servicios de traducción y edición, la publicación de resúmenes o traducciones en idiomas adicionales al inglés y la disponibilidad de licencias que permitan a los autores (u otros académicos) traducir su trabajo y publicarlo en otro lugar. También contactamos directamente a un subconjunto de revistas para comprobar si la información que aparece en las instrucciones para autores refleja con exactitud sus políticas y los ajustes que harían. Comprobamos que las revistas y los editores han avanzado poco en el reconocimiento o reducción de barreras lingüísticas y en la promoción de igualdad lingüística. Al contrario de nuestras predicciones, las revistas asociadas a sociedades científicas no parecen tener políticas más inclusivas en comparación con las revistas que no pertenecen a ninguna sociedad. Muchas políticas carecen de transparencia y claridad, lo que puede generar incertidumbre, dar lugar a rechazos evitables de manuscritos y exigir tiempo y esfuerzo adicionales tanto a los futuros autores como a los editores de las revistas. También destacamos ejemplos de políticas equitativas y resumimos las medidas que las revistas pueden adoptar para empezar a aliviar los obstáculos de publicación científica.

Reorganization of Brain Networks as a Substrate of Resilience: An Analysis of Cytochrome c Oxidase Activity in Rats.

The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims to evaluate the effects of environmental enrichment (EE) on resilience in this experimental model of depression. We also aim to assess changes in brain connectivity using cytochrome c oxidase histochemistry in cerebral regions related to cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. Five groups of rats were used: UCMS, EE, EE + UCMS (enrichment + stress), BG (basal level of brain activity), and CONT (behavioral tests only). We assessed the hedonic responses elicited by sucrose solution using a consumption test; the anxiety level was evaluated using the elevated zero maze test, and the unconditioned fear responses were assessed by the cat odor test. The behavioral results showed that the UCMS protocol induces elevated anhedonia and anxiety. But these responses are attenuated previous exposure to EE. Regarding brain activity, the UCMS group showed greater activity in the habenula compared to the EE + UCMS group. EE induced a functional reorganization of brain activity. The EE + UCMS and UCMS groups showed different patterns of connections between brain regions. Our results showed that EE favors greater resilience and could reduce vulnerability to disorders such as depression and anxiety, modifying metabolic brain activity.