MMIR: an open-source software for the registration of multimodal histological images.

BACKGROUND: Multimodal histology image registration is a process that transforms into a common coordinate system two or more images obtained from different microscopy modalities. The combination of information from various modalities can contribute to a comprehensive understanding of tissue specimens, aiding in more accurate diagnoses, and improved research insights. Multimodal image registration in histology samples presents a significant challenge due to the inherent differences in characteristics and the need for tailored optimization algorithms for each modality. RESULTS: We developed MMIR a cloud-based system for multimodal histological image registration, which consists of three main modules: a project manager, an algorithm manager, and an image visualization system. CONCLUSION: Our software solution aims to simplify image registration tasks with a user-friendly approach. It facilitates effective algorithm management, responsive web interfaces, supports multi-resolution images, and facilitates batch image registration. Moreover, its adaptable architecture allows for the integration of custom algorithms, ensuring that it aligns with the specific requirements of each modality combination. Beyond image registration, our software enables the conversion of segmented annotations from one modality to another.

Stroke care and collaborative academic research in Latin America.

OBJECTIVE: A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). MATERIALS AND METHODS: A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. RESULTS: The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage-ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. CONCLUSIONS: Regional networks foster the conduct of multicenter studies -particularly randomized controlled trials-, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.

On the Colloidal Behavior of Cellulose Nanocrystals as a Hydrophobization Reagent for Mineral Particles.

In the search for more sustainable alternatives to the chemical reagents currently used in froth flotation, the present work offers further insights into the behavior of functionalized cellulose nanocrystals as mineral hydrophobization agents. The study corroborates that hexylamine cellulose nanocrystals (HACs) are an efficient collector for the flotation of quartz and also identifies some particular characteristics as a result of their colloidal nature, as opposed to the water-soluble reagents conventionally used. To investigate the individual and collective effects of the frother and HACs on the attachment of particles and air bubbles, an automated contact timer apparatus was used. This induction timer measures particle-bubble attachment probabilities (Patt) without the influence of macroscopic factors present in typical flotation experiments. This allowed the study of the combined influence of nanocellulose and frother concentration on Patt for the first time. While HACs readily adsorb on quartz modifying its wettability, the presence of a frother leads to a drastic reduction in Patt up to 70%. The improved recovery of quartz in flotation cells might thus be attributed to froth stabilization by HACs, perhaps acting as a Pickering foam stabilizer. Among the main findings, a tendency of HACs to form mineral agglomerates was identified and further explained using the extended DLVO theory in combination with measured adsorption rates in a quartz crystal microbalance. Therefore, this study distinguishes for the first time the antagonistic effect of frothers on Patt and their synergies with HACs on the stabilization of orthokinetic froths through the hydrophobization mechanism unlike those of typical water-soluble collectors.

Environmental remediation of sulfidic tailings with froth flotation: Reducing the consumption of additional resources by optimization of conditioning parameters and water recycling.

The removal of sulfidic species in tailings using froth flotation is a promising approach to prevent phenomena such as acid mine drainage. However, flotation requires the consumption of reagents and water that represent additional expenses. Despite the strong interest of scientists and industry alike on tailings remediation, there is no study on the minimization of resource consumption to promote the implementation of desulfurization with froth flotation. Following a systematic analysis based on Design of Experiments (DoE), this work aims to determine the implications of a decrease in the consumption of flotation reagents and fresh water. It was found that: i) recovery of sulfidic species is strongly influenced by collector concentration and the use of a preliminary re-dispersion step; ii) higher frother concentrations have a negative impact on sulfur grade in the concentrate; and iii) the interactions between the conditioning variables hereby explored have no significant impact on flotation performance. Composition analysis showed that flotation further aids in the removal of hazardous species, such as As, Co and Zn. Finally, the use of recycled water appears possible since flotation performance remained unchanged over 10 flotation cycles, despite the observed accumulation of metallic ions and organic species in the process water.

[Emergency endovascular management of ischemic stroke. Experience in 104 patients]. / Experiencia en el tratamiento endovascular del accidente cerebrovascular isquémico agudo en un centro chileno.

BACKGROUND: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. AIM: To report patients with ischemic stroke treated with endovascular methods. MATERIAL AND METHODS: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. RESULTS: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. CONCLUSIONS: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.

[Risk matrix for estimating imported outbreaks of measles or rubella in ChileMatriz de risco para estimar surtos importados de sarampo ou rubéola aplicada ao Chile]. / Matriz de riesgo para estimar brotes importados de sarampión o rubéola aplicada a Chile.

OBJECTIVE: Develop a risk matrix to evaluate the ongoing risk of measles and rubella outbreaks associated with imported cases in Chile. METHODS: The risk assessment tools were developed in the following stages: preparation and approval of biological, programmatic, and demographic variables; weighting of the selected variables by a panel of experts; calculation of the risk index; specialization; and knowledge transfer. RESULTS: Of the 346 Chilean communes analyzed, 34% were in the high-risk interval for experiencing a measles and rubella outbreak with the introduction of the virus, 59%, in the average-risk interval, and 3%, in the low-risk interval. The remaining percentage corresponded to communes lacking data in at least one of the 13 variables required for calculating the risk index. CONCLUSION: Use of this tool will enable subnational teams to use their own data to evaluate the risk of outbreaks in their area and take corrective action for a rapid response to any importation of these viruses in the post-elimination phase.

OBJETIVO: Desenvolver uma matriz de risco para avaliar o risco contínuo de surtos de sarampo e rubéola associados com a importação de casos no Chile. MÉTODOS: As ferramentas de avaliação de riscos foram desenvolvidas nas seguintes etapas: preparação e aprovação das variáveis biológicas, programáticas e demográficas, consideração das variáveis selecionadas por painel de especialistas, cálculo do índice de risco, especialização e transferência de conhecimento. RESULTADOS: Das 346 comunidades analisadas, 34% estavam dentro da faixa de alto risco de ter um surto de sarampo e rubéola com a introdução do vírus, 59% na faixa de risco intermediário e 3% na faixa de baixo risco. O percentual restante correspondeu a comunidades com dados insuficientes em pelo menos uma das 13 variáveis necessárias ao cálculo do índice de risco. CONCLUSÃO: A utilização desta ferramenta permitirá às equipes subnacionais lançar mão de dados próprios para avaliar o risco de surtos e realizar medidas corretivas para responder rapidamente a qualquer importação de vírus na fase posterior à eliminação.

A Data Augmentation Methodology to Reduce the Class Imbalance in Histopathology Images.

Deep learning techniques have recently yielded remarkable results across various fields. However, the quality of these results depends heavily on the quality and quantity of data used during the training phase. One common issue in multi-class and multi-label classification is class imbalance, where one or several classes make up a substantial portion of the total instances. This imbalance causes the neural network to prioritize features of the majority classes during training, as their detection leads to higher scores. In the context of object detection, two types of imbalance can be identified: (1) an imbalance between the space occupied by the foreground and background and (2) an imbalance in the number of instances for each class. This paper aims to address the second type of imbalance without exacerbating the first. To achieve this, we propose a modification of the copy-paste data augmentation technique, combined with weight-balancing methods in the loss function. This strategy was specifically tailored to improve the performance in datasets with a high instance density, where instance overlap could be detrimental. To validate our methodology, we applied it to a highly unbalanced dataset focused on nuclei detection. The results show that this hybrid approach improves the classification of minority classes without significantly compromising the performance of majority classes.

Circular And Sustainable: Evaluating Lithium-Ion Battery Recycling using a Combined Statistical Entropy and Life Cycle Assessment Methodology.

While there has been a growing interest on the concept of Circular Economy (CE), its correlation with sustainability remains controversial. In this work, the combination of Statistical Entropy Analysis (SEA) and Life Cycle Assessment (LCA) is proposed as a new methodology to evaluate recycling processes from the perspective of materials circularity and environmental impacts using a Li-ion battery recycling process as a case study. This work addresses the need of quantitative circularity indicators, as SEA evaluates the concentration of materials at a systems level, while LCA measures the environmental impact of recycling processes in comparison with virgin raw materials production. It was found that process optimization points can be found by simultaneously accounting for materials recovery and the LCA categories of global warming potential, ozone depletion and mineral resource scarcity. Furthermore, a strong correlation was found for the first time between the recovery of critical elements and the environmental impact of raw materials production. The proposed methodology thus offers a robust analysis of a product lifecycle that aids in its design and optimization from the CE perspective.

A study on recovery strategies of graphite from mixed lithium-ion battery chemistries using froth flotation.

The growing electric vehicle industry has increased the demand for raw materials used in lithium-ion batteries (LIBs), raising concerns about material availability. Froth flotation has gained attention as a LIB recycling method, allowing the recovery of low value materials while preserving the chemical integrity of electrode materials. Furthermore, as new battery chemistries such as lithium titanate (LTO) are introduced into the market, strategies to treat mixed battery streams are needed. In this work, laboratory-scale flotation separation experiments were conducted on two model black mass samples: i) a mixture containing a single cathode (i.e., NMC811) and two anode species (i.e., LTO and graphite), simulating a mixed feedstock prior to hydrometallurgical treatment; and ii) a graphite-TiO2 mixture to reflect the expected products after leaching. The results indicate that graphite can be recovered with > 98 % grade from NMC811-LTO-graphite mixtures. Additionally, it was found that flotation kinetics are dependent on the electrode particle species present in the suspension. In contrast, the flotation of graphite from TiO2 resulted in a low grade product (<96 %) attributed to the significant entrainment of ultrafine TiO2 particles. These results suggest that flotation of graphite should be preferably carried out before hydrometallurgical treatment of black mass.

Enhanced electrochemical discharge of Li-ion batteries for safe recycling.

The recycling of spent lithium-ion batteries (LIBs) is crucial to sustainably manage resources and protect the environment as the use of portable electronics and electric vehicles (EVs) increases. However, the safe recycling of spent LIBs is challenging, as they often contain residual energy. Left untreated, this can trigger a thermal runaway and result in disasters during the recycling process. For efficient recycling, it is important to withdraw any leftover energy from LIBs, regardless of the processing method that follows the discharge. The electrochemical discharge method is a quick and inexpensive method to eliminate this hazard. This method works by immersing batteries in an aqueous inorganic salt solution to discharge LIBs completely and efficiently. Previously, research focus has been on different inorganic salt solutions that release toxic or flammable gaseous products during discharge. In contrast, we present an entirely new approach for electrochemical discharge - the utilization of an Fe(ii)-Fe(iii) redox couple electrolyte. We show that this medium can be used for efficient LIB deep discharge to a voltage of 2.0 V after rebound, a level that is low enough for safe discharge. To accomplish this, periodic discharge methods were used. In addition, no corrosion on the battery casing was observed. The pH behavior at the poles was also investigated, and it was found that without convection, gas evolution during discharge cannot be avoided. Finally, it was discovered that the battery casing material plays a vital role in electrochemical discharge, and its industrial standardization would facilitate efficient recycling.

The role of angiogenesis inhibitors associated with tyrosine kinase inhibitors in the first-line treatment for EGFR-mutated advanced lung cancer.

Tyrosine kinase inhibitors (TKIs) are the standard treatment for epidermal growth factor receptor mutant (EGFRm) advanced non-small cell lung cancer (NSCLC). Combining TKIs with an angiogenesis inhibitor has shown promise in pre-clinical studies. A systematic search of clinical trials found that combining erlotinib (a first-generation TKI) with bevacizumab or ramucirumab (angiogenesis inhibitors) improved progression-free survival (PFS) in EGFRm advanced NSCLC patients compared to TKI alone. However, no significant benefit in overall survival (OS) was observed in trials. Similar efficacy was seen in patients with specific EGFR mutations. Third generation TKIs were used as second-line therapy for patients with the T790M mutation. The combination treatment was associated with a higher incidence of severe adverse events. Overall, combining erlotinib or another TKI with an angiogenesis inhibitor is a safe and effective alternative for first-line treatment in EGFRm advanced NSCLC, particularly in countries without access to osimertinib and for patients with the EGFR L858R mutation.

Use of PD-1 blockade in refractory/relapsed natural killer T-cell lymphomas: a systematic review and synthesis of case reports.

Natural killer/T-cell lymphoma (NK/T-cellL) is an aggressive non-Hodgkin's lymphoma with limited treatment options for patients who experience disease progression or recurrence after second-line treatment. The use of new therapies, such as pembrolizumab, which involves immune checkpoint blockade mechanisms, is proposed. This systematic review followed the MOSE guidelines and searched PUBMED/MEDLINE, EMBASE, and Scopus databases. Fourteen articles were found, reporting on the use of pembrolizumab anti PD-1 in NK/T-cellL patients. The objective response rate was 84.50%, with disease-free survival ranging from two to 48 months. The complete response rate was 61.6%, and the quality of the reported studies was evaluated to be of high and moderate confidence bias levels in case reports and high bias in clinical trials. Pembrolizumab and others anti PD-1 are treatment options for refractory/recurrent NK/T-cellL, regardless of PD-L1 expression, with good short- and long-term results and low adverse events.

A simple methodology for the quantification of graphite in end-of-life lithium-ion batteries using thermogravimetric analysis.

A new method based on thermogravimetric analysis was developed to measure the graphite content in battery material mixture. This approach exploits the thermochemical reduction of cathodic Li-transition metal oxides with anodic graphite at elevated temperatures under an inert atmosphere. Using known composition artificial mixtures, a linear correlation between cathode mass loss and sample graphite content was observed. The method was validated using industrial black mass samples and characterized traditionally to estimate and rationalize potential error sources. Thermal degradation profiles of industrial battery waste reflected those in the artificial system, demonstrating its applicability. This work also demonstrates that thermogravimetric degradation profiles can distinguish between a cathode consisting of single or multiple Li-metal oxides. Although accuracy depends on active component mixture content and impurities, it is demonstrated that the method is useful for a fast graphite content estimation. Unlike other graphite characterization techniques, the method proposed is simple and inexpensive.

A multi-dimensional indicator for material and energy circularity: Proof-of-concept of exentropy in Li-ion battery recycling.

Recycling processes are an important stage in the raw material life cycle, as it enables the transition from a linear economy into a circular one. However, the currently available indicators of productivity in recycling technologies respond to the needs of a linear economy. In this work, a parameter called "exentropy" is proposed, offering the possibility to simultaneously account for mass preservation and the energy efficiency of transformative stages. As a proof-of-concept of this indicator, the analysis of a lithium-ion battery recycling process under various concentrations of a leaching reagent (i.e., 0.1M, 1M, and 2M) is presented. It is shown that, when the energy or mass dimensions are considered independently, the processes considered optimal may have conflicting characteristics. In contrast, the multi-dimensional analysis identified the process option offering the best compromise for both material and energy preservation, an aspect closer to the goals of the circular economy.

Effectiveness and safety of the bevacizumab and erlotinib combination versus erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis.

Background: The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC. Methods: Using eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis. Results: The bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54-0.73, p < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64-0.97, p = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78-1.10, p = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76-6.88, p = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs. Conclusions: The bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results. Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.

[Limbic encephalitis with positive anti-N-methyl-D-aspartate antibodies. Report of one case]. / Encefalitis autoinmune reversible y anticuerpos anti-receptores de N-metil-D-aspartato.

BACKGROUND: Limbic encephalitis is a subacute syndrome characterized by memory impairment, confusion, seizures, hypothalamic dysfunction and psychiatric symptoms. It has been associated to tumors located outside of the central nervous system. In 2007, anti-N-methyl-D-aspartate receptors (NMDAr) antibodies were found in serum and CSF of patients with this particular type of encephalitis. We report a 25-year-old female who, following upper respiratory tract symptoms, developed serious behavioral and consciousness impairment that progressed to coma. Cerebrospinal fluid (CSF) analysis showed a lymphocyte pleocytosis, the electroencephalogram was altered with a slow encephalopathic rhythm and a brain magnetic resonance imaging was normal. Infectious etiologies were ruled out. CSF and serum anti NMDA receptors antibodies were positive.

Software tools and platforms in Digital Pathology: a review for clinicians and computer scientists.

At the end of the twentieth century, a new technology was developed that allowed an entire tissue section to be scanned on an objective slide. Originally called virtual microscopy, this technology is now known as Whole Slide Imaging (WSI). WSI presents new challenges for reading, visualization, storage, and analysis. For this reason, several technologies have been developed to facilitate the handling of these images. In this paper, we analyze the most widely used technologies in the field of digital pathology, ranging from specialized libraries for the reading of these images to complete platforms that allow reading, visualization, and analysis. Our aim is to provide the reader, whether a pathologist or a computational scientist, with the knowledge to choose the technologies to use for new studies, development, or research.

The World Stroke Academy: A World Stroke Organization global pathway to improve knowledge in stroke care.

BACKGROUND: The World Stroke Academy (WSA) (www.world-stroke-academy.org) is the educational platform of the World Stroke Organization (WSO). It facilitates educational activities (e.g. webinars and eLearning modules) and supports the WSO mission by providing high-quality stroke education to healthcare professionals. It provides evidence-based educational materials in a variety of formats to meet the needs of the WSO membership. AIM: This article introduces the WSA, its core activities, and outlines how to access the many educational resources it offers. RESULTS: The WSA offers high-quality peer reviewed stroke education material and uses outcome metrics to assess and improve the quality of medical training of healthcare professionals. This article also highlights the importance of identifying knowledge and knowledge-to-action gaps through the creation of special projects and initiatives. It describes three areas in which the WSA has carried out recent educational initiatives, namely: life after stroke, women in stroke, and stroke checklist/pre-printed stroke orders. CONCLUSION: WSA material is freely available, and we would encourage the global stroke community to use, and contribute to, its resources.