Weakly-supervised deep learning models enable HER2-low prediction from H &E stained slides.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a new subtype of tumor, for which novel antibody-drug conjugates have shown beneficial effects. Assessment of HER2 requires several immunohistochemistry tests with an additional in situ hybridization test if a case is classified as HER2 2+. Therefore, novel cost-effective methods to speed up the HER2 assessment are highly desirable. METHODS: We used a self-supervised attention-based weakly supervised method to predict HER2-low directly from 1437 histopathological images from 1351 breast cancer patients. We built six distinct models to explore the ability of classifiers to distinguish between the HER2-negative, HER2-low, and HER2-high classes in different scenarios. The attention-based model was used to comprehend the decision-making process aimed at relevant tissue regions. RESULTS: Our results indicate that the effectiveness of classification models hinges on the consistency and dependability of assay-based tests for HER2, as the outcomes from these tests are utilized as the baseline truth for training our models. Through the use of explainable AI, we reveal histologic patterns associated with the HER2 subtypes. CONCLUSION: Our findings offer a demonstration of how deep learning technologies can be applied to identify HER2 subgroup statuses, potentially enriching the toolkit available for clinical decision-making in oncology.

Small biopsies for pancreatic lesions: Is there still room for fine needle aspiration?

Pancreatic carcinoma is an aggressive tumour with increasing incidence in both sexes worldwide. Early detection is, therefore, essential for patient management. A recent advancement involves the utilization of larger, thicker gauge needles, which enable the collection of core-type biopsies (FNB). Here, we investigated the role of fine needle aspiration and cytopathology in the diagnostic workflow of pancreatic lesions. A search query was designed to search for articles in the PubMed database comparing FNA and FNB for biopsy of pancreatic lesions, and detailed data were extracted from selected studies. Statistical analyses were performed using the R package meta version 6.2. Twenty-one studies made the final cut for data extraction. Overall, median age was 64.3 years (±6.1; 47.6-71.5), male: female proportion 53.9 (±11.3; 27.6-67.4), lesion size 3.1 cm (±0.5; 1.9-4.2 cm) and percentage of malignant cases 78.3% (±26.8; 2.1-100). FNA and FNB diagnostic yield was 85.8% (±10.3; 70.0-100.0) and 89.2% (±7.7; 70.0-98.6), respectively. Average accuracy was 89.5% (±11.7; 63.0-100.0) for FNA and 90.8% (±7.1; 77.0-100.0) for FNB. Adverse effects rate was 1.0% (±1.3; 0-4.3) for FNA and 2.2% (±4.4; 0-16.1) for FNB. None of the selected variables had a significant statistical difference between both methods. FNA and FNB perform similarly for diagnostic material acquisition in pancreatic lesions. The best outcome comes from the association of both techniques, emphasizing the value of combining cytological and histological morphology for the most accurate analysis.

Accuracy of fine-needle aspiration of lymph nodes: A cancer center's experience.

INTRODUCTION: Lymph node fine needle aspiration (LN-FNA) is a minimally invasive method of evaluating lymphadenopathy. Nonetheless, its use is not widely accepted due to the lack of guidelines and a cytopathological categorisation that directly relates to management. We report our experience with LN FNA at a large Cancer Center in Latin America. METHODS: We retrospectively collected cytological cases of lymph node FNA from the department of pathology at AC Camargo Cancer Center performed over a 2-year period. Data extracted included LN location, age, sex and final cytological diagnosis. Patients that had undergone neoadjuvant chemotherapy and/or cases for which the surgery specimen location was not clearly reported were excluded. For those cases with surgical reports, risk of malignancy was calculated for each diagnostic category, along with overall performance of cytology. False positive cases were reviewed to assess any possible misinterpretation or sampling errors. RESULTS: A total of 1730 LN-FNA were distributed as follows: 62 (3.5%) non-diagnostic (ND); 1123 (64.9%) negative (NEG), 19 (1.1%) atypical (ATY), 53 (3.1%) suspicious for malignancy (SUS), and 473 (27.3%) positive (POS). Surgical reports were available for 560 cases (32.4%). Risk of malignancy (ROM) for each category was 33.3% for ND, 29.9% for NEG, 25% for ATY, 74.2% for SUS and 99.6% for POS. Overall sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were 78.5%, 99.4%, 70.2% and 99.6%, respectively. CONCLUSION: Lymph node FNA is a very specific and accurate exam, which is reliable in the detection of lymph node metastasis and other causes of lymphadenopathy.

Moving to healthier landscapes: Forest restoration decreases the abundance of Hantavirus reservoir rodents in tropical forests.

Hantavirus Cardiopulmonary Syndrome (HCPS) is a disease with high human lethality rates, whose transmission risk is directly related to the abundance of reservoir rodents. In the Brazilian Atlantic forest, the main reservoirs species, Oligoryzomys nigripes and Necromys lasiurus, are thought to increase in abundance with deforestation. Therefore, forest restoration may contribute to decrease HCPS transmission risk, a topic still unexplored, especially in tropical regions. Aiming at filling this research gap, we quantified the potential of forest restoration, as required by the current environmental legislation, to reduce the abundance of Hantavirus reservoir rodents in the Brazilian Atlantic Forest. Using a dataset on small mammal communities sampled at 104 sites, we modeled how the abundance of these two rodent species change with the percentage of forest cover and forest edge density. From the best model, we extrapolated rodent abundance to the entire Atlantic Forest, considering two scenarios: current and restored forest cover. Comparing the estimated abundance between these two scenarios, we show that forest restoration can reduce the abundance of O. nigripes up to 89.29% in 43.43% of Atlantic forest territory. For N. lasiurus, abundance decreased up to 46% in 44% of the Atlantic forest. To our knowledge, this is the first study linking forest restoration and zoonotic diseases. Our results indicate that forest restoration would decrease the chance of HCPS transmission in ~45% of the Atlantic forest, making the landscape healthier to ~2,8 million people living within this area. This positive effect of restoration on disease regulation should be considered as an additional argument to encourage and promote forest restoration in tropical areas around the world.

Deep Learning Predicts Underlying Features on Pathology Images with Therapeutic Relevance for Breast and Gastric Cancer.

DNA repair deficiency (DRD) is an important driver of carcinogenesis and an efficient target for anti-tumor therapies to improve patient survival. Thus, detection of DRD in tumors is paramount. Currently, determination of DRD in tumors is dependent on wet-lab assays. Here we describe an efficient machine learning algorithm which can predict DRD from histopathological images. The utility of this algorithm is demonstrated with data obtained from 1445 cancer patients. Our method performs rather well when trained on breast cancer specimens with homologous recombination deficiency (HRD), AUC (area under curve) = 0.80. Results for an independent breast cancer cohort achieved an AUC = 0.70. The utility of our method was further shown by considering the detection of mismatch repair deficiency (MMRD) in gastric cancer, yielding an AUC = 0.81. Our results demonstrate the capacity of our learning-base system as a low-cost tool for DRD detection.

Conservation economics. Response to Comment on "Using ecological thresholds to evaluate the costs and benefits of set-asides in a biodiversity hotspot".

Finney claims that we did not include transaction costs while assessing the economic costs of a set-aside program in Brazil and that accounting for them could potentially render large payments for environmental services (PES) projects unfeasible. We agree with the need for a better understanding of transaction costs but provide evidence that they do not alter the feasibility of the set-aside scheme we proposed.

Association of the "IUCN vulnerable" spiny rat Clyomys bishopi (Rodentia: Echimyidae) with palm trees and armadillo burrows in southeastern Brazil.

The globally vulnerable Clyomys bishopi, a semi-fossorial and colonial rodent, is apparently limited to cerrado (savannah-like vegetation) physiognomies in São Paulo State, Brazil. The aim of the study was to verify whether the presence of C. bishopi is associated to the occurrence of palm trees (Attalea gearensis, Syagrus loefgrenii) and armadillo burrows. Thirty six quadrats were placed in different physiognomies of cerrado vegetation at Itirapina Ecological Station, southeastern Brazil to survey the number of C. bishopi burrows of individuals of palm trees and burrows of armadillos. There was a strong dependence and association between the number of C. bishopi burrows and all measured variables (Contingency tables and Spearman rank correlations). It is suggested that this rodent can be found in great numbers where palm trees are abundant. The use of armadillo burrows possibly makes the movement of the rodents easier inside their own galleries.

Using ecological thresholds to evaluate the costs and benefits of set-asides in a biodiversity hotspot.

Ecological set-asides are a promising strategy for conserving biodiversity in human-modified landscapes; however, landowner participation is often precluded by financial constraints. We assessed the ecological benefits and economic costs of paying landowners to set aside private land for restoration. Benefits were calculated from data on nearly 25,000 captures of Brazilian Atlantic Forest vertebrates, and economic costs were estimated for several restoration scenarios and values of payment for ecosystem services. We show that an annual investment equivalent to 6.5% of what Brazil spends on agricultural subsidies would revert species composition and ecological functions across farmlands to levels found inside protected areas, thereby benefiting local people. Hence, efforts to secure the future of this and other biodiversity hotspots may be cost-effective.

Immigration rates in fragmented landscapes--empirical evidence for the importance of habitat amount for species persistence.

BACKGROUND: The total amount of native vegetation is an important property of fragmented landscapes and is known to exert a strong influence on population and metapopulation dynamics. As the relationship between habitat loss and local patch and gap characteristics is strongly non-linear, theoretical models predict that immigration rates should decrease dramatically at low levels of remaining native vegetation cover, leading to patch-area effects and the existence of species extinction thresholds across fragmented landscapes with different proportions of remaining native vegetation. Although empirical patterns of species distribution and richness give support to these models, direct measurements of immigration rates across fragmented landscapes are still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brazilian Atlantic forest marsupial Gray Slender Mouse Opossum (Marmosops incanus) as a model species and estimating demographic parameters of populations in patches situated in three landscapes differing in the total amount of remaining forest, we tested the hypotheses that patch-area effects on population density are apparent only at intermediate levels of forest cover, and that immigration rates into forest patches are defined primarily by landscape context surrounding patches. As expected, we observed a positive patch-area effect on M. incanus density only within the landscape with intermediate forest cover. Density was independent of patch size in the most forested landscape and the species was absent from the most deforested landscape. Specifically, the mean estimated numbers of immigrants into small patches were lower in the landscape with intermediate forest cover compared to the most forested landscape. CONCLUSIONS/SIGNIFICANCE: Our results reveal the crucial importance of the total amount of remaining native vegetation for species persistence in fragmented landscapes, and specifically as to the role of variable immigration rates in providing the underlying mechanism that drives both patch-area effects and species extinction thresholds.

Beyond the fragmentation threshold hypothesis: regime shifts in biodiversity across fragmented landscapes.

Ecological systems are vulnerable to irreversible change when key system properties are pushed over thresholds, resulting in the loss of resilience and the precipitation of a regime shift. Perhaps the most important of such properties in human-modified landscapes is the total amount of remnant native vegetation. In a seminal study Andrén proposed the existence of a fragmentation threshold in the total amount of remnant vegetation, below which landscape-scale connectivity is eroded and local species richness and abundance become dependent on patch size. Despite the fact that species patch-area effects have been a mainstay of conservation science there has yet to be a robust empirical evaluation of this hypothesis. Here we present and test a new conceptual model describing the mechanisms and consequences of biodiversity change in fragmented landscapes, identifying the fragmentation threshold as a first step in a positive feedback mechanism that has the capacity to impair ecological resilience, and drive a regime shift in biodiversity. The model considers that local extinction risk is defined by patch size, and immigration rates by landscape vegetation cover, and that the recovery from local species losses depends upon the landscape species pool. Using a unique dataset on the distribution of non-volant small mammals across replicate landscapes in the Atlantic forest of Brazil, we found strong evidence for our model predictions--that patch-area effects are evident only at intermediate levels of total forest cover, where landscape diversity is still high and opportunities for enhancing biodiversity through local management are greatest. Furthermore, high levels of forest loss can push native biota through an extinction filter, and result in the abrupt, landscape-wide loss of forest-specialist taxa, ecological resilience and management effectiveness. The proposed model links hitherto distinct theoretical approaches within a single framework, providing a powerful tool for analysing the potential effectiveness of management interventions.

Absence of atypical haplotype and presence of Senegal haplotype sickle cell disease in African-descent population in the northern Brazil / Ausência do haplótipo atípico e presença do haplótipo Senegal da doença falciforme em uma população afrodescendente na região norte do Brasil

Introduction: Sickle cell anemia (SCA) is the most severe form of sickle cell disease; it presents variants that are called haplotypes βS. There are five major haplotypes βS gene: Arab-Indian/Saudi, Senegal, Benin, Bantu, and Camaroon. Objective: Characterize the presence of haplotypes in patients with SCA in Amapá. Methods: 46 sample were studied, all samples were amplified and analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: Bantu (61.2%), followed by Benin (26.5%) and Senegal (12.2%). Conclusion: We identified three haplotypes characteristic of African ethnicity, with the presence of Senegal. In our study we found the presence of atypical haplotype, suggesting concentration and semi-isolation of the founding groups with little mixing. .

Introdução: A anemia falciforme (AF) é a forma mais grave da doença falciforme; apresenta formas variantes que são chamadas de haplótipos βS. Existem cinco principais haplótipos desse gene: árabe-indiano/saudi, Senegal, Benin, Bantu e Camarões. Objetivos: Caracterizar a presença dos haplótipos em pacientes com AF no Amapá. Métodos: Foram estudadas 46 amostras, todas amplificadas e analisadas pela técnica de reação em cadeia da polimerase-polimorfismo de tamanho de fragmentos de restrição (PCR-RFLP). Resultados: Bantu (61,2%) seguido de Benin (26,5%) e Senegal (12,2%). Conclusão: Foram identificados três haplótipos característicos da etnia africana, com a presença do Senegal. Em nosso estudo não encontramos a presença de haplótipos atípicos, sugerindo a concentração e semi-isolamento de grupos fundadores com pouca miscigenação. .

Infecciones invasivas por Haemophilus influenzae tipo b (Hib) en Tucumán-Argentina / Invasive infections caused by haemophilus influenzae type b in children in Tucumáan-Argentina, before vaccination

Objetivo: Investigar los "aspectos epidemiológicos" de la patología invasiva Hib (PI Hib) con especial referencia a la meningitis, en niños menores de 5 años. Categorizar el problema dentro de la salud pública en Tucumán. Material y métodos: El estudio se llevó a cabo desde enero de 1985 a diciembre de 1992 en el Hospital del Niño Jesús. Se incluyó a todo paciente con sospecha clínica de PI Hib y confirmada por cultivo o serología obtenida de materiales representativos. Resultados: Se registraron 264 casos de PI Hib: 218 (82,5 por ciento) meningitis y 46 (17,5 por ciento) formas extrameníngeas. El 89 por ciento de las meningitis tuvieron foco único. Las formas extrameníngeas se distribuyeron entre bacteriemias, supuración pleuro-pulmonar, neumonías, celulitis, artritis y otras. La meningitis Hib (M Hib) es endémica en Tucumán, con un aumento en los meses de invierno. El Hib representa el 70 por ciento de las meningitis extrahospitalarias bacterianas. La incidencia anual promedio, en niños menores de 5 años, de la PI Hib fue 20,4/100.000 y de M Hib 16,7/100.000, en menores de 1 año la incidencia de M Hib fue 63/100.000; el 77,5 por ciento de las meningitis suceden a esta edad. La tasa de letalidad: 20,1 por ciento. La resistencia a ampicilina osciló entre 0-17,4 por ciento y la de ampicilina-cloranfenicol entre 2,7-8,7 por ciento. Conclusiones: Al cabo de ocho años de estudio la M Hib mostró en Tucumán un sostenido aumento; es la primera causa de mortalidad dentro de las enfermedades prevenibles por vacunas en niños menores de 2 años y la octava causa de mortalidad infantil

Hallazgo del mosquito Haemagogus equinus (Theobald, 1903) en el área metropolitana de Bucaramanga, Santander / Presence of the mosquito Haemagogus equinus (Theobald, 1903) in the metropolitan area of Bucaramanga, Santander

Utilizando un sistema de vigilancia entomológica, se registra por primera vez en Colombia el hallazgo del mosquito Haemagogus equinus, eficiente vector del virus de la fiebre amarilla selvática, en criaderos artificiales (llantas). Se recolectaron 181 larvas de H. equinus en cuatro ovilarvitrampas encontradas positivas, localizadas en el área metropolitana de Bucaramanga

Association of the IUCN vulnerable spiny rat Clyomys bishopi (Rodentia: Echimyidae)with palm trees and armadillo burrows in southeastern Brazil

The globally vulnerable Clyomys bishopi ,a semi-fossorial and colonial rodent,is apparently limited to cerrado (savannah-like vegetation)physiognomies in São Paulo State,Brazil.The aim of the study was to verify whether the presence of C.bishopi is associated to the occurrence of palm trees (Attalea gearensis, Syagrus loefgrenii )and armadillo burrows.Thirty six quadrats were placed in different physiognomies of cerrado vegetation at Itirapina Ecological Station,southeastern Brazil to survey the number of C.bishopi burrows of individuals of palm trees and burrows of armadillos.There was a strong dependence and association between the number of C.bishopi burrows and all measured variables (Contingency tables and Spearman rank correlations).It is suggested that this rodent can be found in great numbers where palm trees are abundant.The use of armadillo burrows possibly makes the movement of the rodents easier inside their own galleries

El roedor colonial Clyomys bishopi está aparentemente limitado a vegetación de semi-sabana (cerrado)en el estado de São Paulo,Brasil.El objetivo de este estudio fue verificar si la presencia de C.bishopi está asociada a la individuos de las palmeras Attalea gearensis,Syagrus loefgrenii y madrigueras de armadillos.El estudio fue realizado en la Estación Ecológica de Itirapina,en el sureste de Brasil.Treinta y seis cuadrantes fueron dispuestos en diferentes fisionomías del la vegetación del cerrado para encuestar el número de madrigueras de C.bishopi, árboles individuales de palma y madrigueras de armadillos.Se calcularon tablas de contingencia y correlaciones de Sperman para evaluar, respectivamente, la dependencia y asociación entre el número de madrigueras de C.bishopi y las otras variables.Se encontró una fuerte dependencia y asociación entre el número de madrigueras de C.bishopi y todas las variables medidas.Esto sugiere que este roedor alcanza grandes poblaciones cuando hay palmeras en abundancia. El uso de madrigueras de armadillos posiblemente facilita el movimiento de los roedores dentro de sus propias galerías