Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer.

The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTX exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules.

Intake, digestibility, and behavior of horses fed açaí kernel (Euterpe oleracea Mart.) as a substitute of Mombaça grass (Megathyrsus maximus).

In this study, we analyzed the effects of including açaí kernel, in the experimental diets fed to horses on the intake and digestibility of their nutrient and the resultant effects on the behavior of horses. The experiments were conducted in Federal Rural University of Amazonia. Five mares with no defined breeds, were allocated to five treatments (the replacement of Mombaça grass (Megathyrsus maximus) with crushed açaí kernel at 0, 18.

Real-world effectiveness and safety of switching to dolutegravir/lamivudine among people living with HIV-1 aged over 50 years who are virologically suppressed.

Objectives: People living with HIV face several challenges as they age, including the potential for polypharmacy and increased susceptibility to drug-related adverse effects. Thus, effective and well-tolerated regimens with minimal or no drug interactions would be useful in this population. We present real-world effectiveness and safety data for individuals aged >50 years who achieved virological suppression (HIV-1 RNA <50 copies/mL) and switched to dolutegravir/lamivudine (DTG/3TC).

Large-scale analysis of whole genome sequencing data from formalin-fixed paraffin-embedded cancer specimens demonstrates preservation of clinical utility.

Whole genome sequencing (WGS) provides comprehensive, individualised cancer genomic information. However, routine tumour biopsies are formalin-fixed and paraffin-embedded (FFPE), damaging DNA, historically limiting their use in WGS. Here we analyse FFPE cancer WGS datasets from England's 100,000 Genomes Project, comparing 578 FFPE samples with 11,014 fresh frozen (FF) samples across multiple tumour types.

Precision Cancer Medicine 2.0-Oncology in the postgenomic era.

Genomic medicine has transformed the lives of patients with cancer by enabling individualised and evidence-based clinical decision-making. Despite this progress, the implementation of precision cancer medicine is limited by its dependence on isolated biomarkers. The development of bulk and single-cell multiomic technologies has revealed the enormous complexity of the cancer ecosystem.

Applicability of the Neuman Systems Model to the Gerontology Nursing practice: a scoping review.

Objective: to map scientific productions on the application of the Neuman Systems Model to the Nursing practice focused on health care for aged people.

Method: a scoping review based on the methodology proposed by the Joanna Briggs Institute. Seven electronic databases were consulted.

A deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an indirect two-step approach consisting of (1) DeepPT, a deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response to targeted and immune therapies from the inferred expression values. We show that DeepPT successfully predicts transcriptomics in all 16 The Cancer Genome Atlas cohorts tested and generalizes well to two independent datasets.

Gait analysis of patients undergoing knee endoprosthesis: functional differences between tibia and femur resections.

With the improvement in survival of patients undergoing knee reconstructive surgeries, the functional parameter became widely studied heading optimize and minimize motor sequelae. In patients undergoing knee endoprosthesis, proximal tibial or distal femoral resections affect the functioning of the knee extensor mechanism, with possible repercussions on gait. Seventeen patients were selected, divided into two groups, undergoing distal femoral or proximal tibial resection, and gait analysis examination was performed.

Development and validation of a reliable DNA copy-number-based machine learning algorithm (CopyClust) for breast cancer integrative cluster classification.

The Integrative Cluster subtypes (IntClusts) provide a framework for the classification of breast cancer tumors into 10 distinct groups based on copy number and gene expression, each with unique biological drivers of disease and clinical prognoses. Gene expression data is often lacking, and accurate classification of samples into IntClusts with copy number data alone is essential. Current classification methods achieve low accuracy when gene expression data are absent, warranting the development of new approaches to IntClust classification.

Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy.

Clustering of HR + /HER2- breast cancer in an Asian cohort is driven by immune phenotypes.

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent.

Effects of supplementing cassava root silage to grazing dairy cows on nutrient utilization, milk production and composition in the tropics.

The current study evaluated the effects of supplementing cassava root silage (CRS) to dairy cows grazing on Megathyrsus maximus cv Mombasa on nutrient intake and digestibility, as well as on milk production and composition. Ten primiparous Girolando cows with average body weight ± (SEM) of 373.45 ± (63.

Leishmania and HIV co-infection: first naturally Leishmania strain presenting decreased susceptibility to miltefosine, recovered from a patient in Portugal.

Background: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals.

Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019.

Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals.

Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure.

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers.

Access to infertility care in Brazil: validation of a questionnaire for a bioethical discussion.

Background: The World Health Organization characterizes infertility as a disease since 2009; however, in many countries, reproductive health is not prioritized. Characterizing a target population and knowing the barriers to accessing reproductive care may allow for a broadening of the discussion on how to provide equal opportunities. The objective of this study was to develop and validate a questionnaire that seeks to identify socioeconomic and cultural characteristics of Brazilian infertile couples to open the discussion on the principle of fair access to health.

The Power and Promise of Patient-Derived Xenografts of Human Breast Cancer.

In 2016, a group of researchers engaged in the development of patient-derived xenografts (PDXs) of human breast cancer provided a comprehensive review of the state of the field. In that review, they summarized the clinical problem that PDXs might address, the technical approaches to their generation (including a discussion of host animals and transplant conditions tested), and presented transplantation success (take) rates across groups and across transplantation conditions. At the time, there were just over 500 unique PDX models created by these investigators representing all three clinically defined subtypes (ER, HER2, and TNBC).

Vitamin B supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy. Consequently, spatially resolved omics-level analyses are gaining traction. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization.

Prediction of cancer treatment response from histopathology images through imputed transcriptomics.

Advances in artificial intelligence have paved the way for leveraging hematoxylin and eosin (H&E)-stained tumor slides for precision oncology. We present ENLIGHT-DeepPT, an approach for predicting response to multiple targeted and immunotherapies from H&E-slides. In difference from existing approaches that aim to predict treatment response directly from the slides, ENLIGHT-DeepPT is an indirect two-step approach consisting of (1) DeepPT, a new deep-learning framework that predicts genome-wide tumor mRNA expression from slides, and (2) ENLIGHT, which predicts response based on the DeepPT inferred expression values.

FOXC2 promotes vasculogenic mimicry and resistance to anti-angiogenic therapy.

Vasculogenic mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with a tumor-derived vascular system that directly connects to host blood vessels, and their presence is generally associated with poor patient prognosis. Here we show that the transcription factor, Foxc2, promotes VM in diverse solid tumor types by driving ectopic expression of endothelial genes in tumor cells, a process that is stimulated by hypoxia.

Obesity-associated changes in molecular biology of primary breast cancer.

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients.