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.

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.

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.

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 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.

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.

Regional Initiatives to Empower Young Medical Doctors: The Young Stroke Latin American Task Force (ALATAC).

Local and regional cooperation may strengthen efforts to reduce stroke burden in low-resource settings. New generations full of energy, honoring the past achievements of mentors and current stroke leaders, have the potential to stimulate stroke research, and prevention and implement the available evidence-based treatments. This article presents how a local initiative focused on young stroke professionals may promote comprehensive stroke care in the region. We will present the creation of ALATAC, its main purpose and objectives, the structure organization, the committees, ongoing activities, the potential results to be achieved, and how to become a member of this group.

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.

A high number of co-occurring genomic alterations detected by NGS is associated with worse clinical outcomes in advanced EGFR-mutant lung adenocarcinoma: Data from LATAM population.

BACKGROUND: Co-occurring genomic alterations identified downstream main oncogenic drivers have become more evident since the introduction of next-generation sequencing (NGS) analyses at diagnosis and progression. Emerging evidence has stated that co-occurring genomic alterations at diagnosis might represent de novo and primary resistance mechanisms to tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutant (EGFRm) non-small lung cancer (NSCLC). In this study, we assessed the prognostic role of co-occurring genomic alterations in advanced EGFRm NSCLC. METHODS: A cohort of 111 patients with advanced NSCLC harboring EGFR-sensitive mutations detected by PCR was analyzed in 5 Latin American oncological centers from January 2019 to December 2020. All eligible patients received upfront therapy with EGFR-TKI. Co-occurring genomic alterations were determined at diagnosis in every patient by the NGS (FoundationOneCDx) comprehensive platform, which evaluates 324 known cancer-related genes. RESULTS: EGFR exon19 deletion was the most frequent oncogenic driver mutation (60.4 %) detected by NGS. According to the NGS assay, 31 % and 68.3 % of patients had 1-2 and ≥ 3 co-occurring genomic alterations, respectively. The most frequent co-occurring genomic alterations were TP53 mutations (64.9 %) followed by CDKN2AB alterations (13.6 %), BRCA2 (13.6 %), and PTEN (12.7 %) mutations. Baseline central nervous system disease was present in 42.7 % of patients. First- or second-generation EGFR TKIs (gefitinib, afatinib, or erlotinib) were the most common treatment in 67.5 % of patients, while osimertinib was administered in 27.9 % of cases. The median PFS in all evaluated patients was 13.63 months (95 %CI: 11.79-15.52). Using ≥ 3 co-occurring alterations as the cut-off point, patients with ≥ 3 co-occurring genomic alterations showed a median PFS, of 12.7 months (95 %CI: 9.92-15.5) vs 21.3 months (95 %CI: 13.93-NR) in patients with 2 or less co-occurring genomic alterations [HR 3.06, (95 %CI: 1.55-5.48) p = 0.0001]. Also, patients with a TP53 mutation had a shorter PFS, 13.6 (95 %CI: 10.7-15.5) vs 19.2 months (95 %CI: 12.8-NR); in wild type TP53 [HR 2.01 (95 %CI: 1.18-3.74) p = 0.12]. In the multivariate analysis, the number (≥3) of concurrent genomic alterations and ECOG PS of 2 or more were related to a significant risk factor for progression [HR 2.79 (95 %CI: 1.49-5.23) p = 0.001 and HR 2.42 (95 %CI: 1.22-4.80) p = 0.011 respectively]. CONCLUSION: EGFR-mutant NSCLC is not a single oncogene-driven disease in the majority of cases, harboring a higher number of co-occurring genomic alterations. This study finds the number of co-occurring genomic alterations and the presence of TP53 mutations as negative prognostic biomarkers, which confers potentially earlier resistance mechanisms to target therapy.

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.

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.

N-Alkylated Chitin Nanocrystals as a Collector in Malachite Flotation.

The majority of reagents currently used in mineral flotation processes are fossil-based and potentially harmful to the environment. Therefore, it is necessary to find environmentally-friendly alternatives to reduce the impact of mineral processing activities. Chitin nanocrystals are a renewable resource that, due to the natural presence of amino groups on its surface, represents a promising collector for various minerals of economic relevance. This study examines the one-pot functionalization of chitin nanocrystals with aldehyde structures to obtain hydrophobized colloids suitable for mineral flotation. The chemical properties of these nano-colloids were investigated by nuclear magnetic resonance spectroscopy, their colloidal behavior and structure by electrophoretic light scattering and atomic force microscopy, and their wettability through water contact angle measurements. The functionalized N-alkylated chitin nanocrystals possessed a hydrophobic character, were able to dress mineral particles and featured a performance in the flotation of malachite similar to commercial collectors, which proves the high potential of chitin nanocrystals in this field of application.

STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP).

BACKGROUND: Mutations in STK11 (STK11Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. METHODS: This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11Wt/KEAP1Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). RESULTS: Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRASMut + STK11Mut, KRASMut + STK11Mut + KEAP1Mut, STK11Mut + KEAP1Mut, and KRASMut + KEAP1Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRASWt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRASMut cases (p = 0.047). Tumors with KRASMut + KEAP1Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1mut 6.1 months versus STK11Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11Mut 14.2 months versus STK11Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1Mut 12.0 months versus KEAP1Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. CONCLUSIONS: This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.

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.

Targeting BRAF V600E in metastatic colorectal cancer: where are we today?

Colorectal cancer (CRC) is the second most frequent cause of direct cancer death worldwide. The study of the molecular state of oncogenes has predictive and prognostic value in metastatic CRC (mCRC). The B-raf proto-oncogene (BRAF) gene mutation represents the 8%-12% of all mutations in mCRC. The BRAF V600E mutation, considered the most common alteration of BRAF, corresponds to a constitutive kinase with a high activating capacity of the RAS/RAF/MEK/ERK pathway after a cascade of successive phosphorylations in the transcription of genes. BRAF V600E mutation is more prevalent in women, elderly, right-sided colon cancer and Caucasian population. Unfortunately, it is considered a poor predictive and prognosis biomarker. Patients with mCRC BRAF V600E mutated (BRAFm) are generally associated with poor response to chemotherapy and short progression-free survival and overall survival. Recently, randomised clinical trials have studied the combination of different chemotherapy regimens with angiogenic inhibitors in mCRC BRAFm. In addition, new anti-BRAF and immunotherapy agents have also been studied in this population, with positive results. The objective of this review is to acknowledge the biology and molecular pathway of BRAF, critically analyse the clinical trials and the therapy options published until today and evaluate the options of treatment according to the patient's clinical presentation.

Detección de mutaciones del gen EGFR en ADN circulante por medio de biopsia líquida en pacientes con cáncer pulmonar de células no pequeñas: Revisión rápida / Detection of EGFR gene mutations in circulating DNA by liquid biopsy in patients with non-small cell lung cancer: Brief review

RESUMEN El cáncer pulmonar es un problema de salud pública debido a su alta morbimortalidad mundial y en el Perú. En el cáncer pulmonar de células no pequeñas (CPCNP) la detección de mutaciones del receptor del factor de crecimiento epidérmico (EGFR) ha sido útil para elección de la terapéutica de esta enfermedad. El presente artículo tiene como objetivo discutir la información actual y relevante sobre la biopsia liquida como técnica diagnóstica en detección de mutaciones del gen EGFR en pacientes con cáncer pulmonar de células no pequeñas. Las principales guías de cáncer y dos revisiones sistemáticas muestran evidencia a favor de la biopsia líquida en busca de mutaciones del gen EGFR, esto como una alternativa a la biopsia de tejido al inicio de diagnóstico y con una mayor aceptación de uso en el escenario clínico de pacientes con CPCNP con mutaciones sensibles de EGFR. Esta tecnología sanitaria puede ser útil en nuestro país, y proponemos su uso en dos escenarios clínicos.

ABSTRACT Lung cancer is a public health problem due to its high morbidity and mortality worldwide and in Peru. In non-small cell lung cancer, the detection of mutations of the epidermal growth factor receptor (EGFR) has been useful for the choice of therapeutics for this disease. In the present article we aim to discuss current and relevant information on the best diagnostic technique for EGFR in patients with non-small cell lung cancer. The main cancer guidelines and two systematic reviews showed evidence in favor of the diagnosis of EGFR gene mutations on liquid biopsy as an alternative to tissue biopsy at the beginning of diagnosis and with a greater acceptance use, in the clinical setting of NSCLC patients with sensitive EGFR mutations. This healthcare technology may be useful in our country, and we propose its use in two clinical scenarios.

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.