Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy.

Background: Although stromal tumor-infiltrating lymphocytes (sTILs) have been considered an important prognostic factor in early-stage triple-negative breast cancer (TNBC), there have been limited data on their prognostic value in the absence of adjuvant chemotherapy.

Patients And Methods: A pooled analysis was carried out using four cohorts of TNBC patients not treated with chemotherapy. sTILs were evaluated in the most representative tumoral block of surgical specimens.

A constant postpacing interval in response to overdrive pacing with variable number of beats: An aid in the identification of entrainment for a particular pacing train during macroreentrant atrial tachycardias.

Background: When pacing trains with a constant cycle length (CL) but increasing number of beats are introduced during a macroreentrant atrial tachycardia (MAT), the postpacing interval (PPI) is expected to increase if entrainment does not occur but could be stable if entrainment occurs. We tested the ability of PPI analysis to detect entrainment.

Methods: Synchronized pacing trains with increasing number of beats (1-20) were delivered from the coronary sinus (CS) and lateral right atrium (RA) at a CL 20 ms shorter than the MAT CL.

Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia.

Fanconi anemia (FA) is a DNA repair syndrome generated by mutations in any of the 22 FA genes discovered to date. Mutations in FANCA account for more than 60% of FA cases worldwide. Clinically, FA is associated with congenital abnormalities and cancer predisposition.

CT and MR imaging prior to transcatheter aortic valve implantation: standardisation of scanning protocols, measurements and reporting-a consensus document by the European Society of Cardiovascular Radiology (ESCR).

Transcatheter aortic valve replacement (TAVR) is a minimally invasive alternative to conventional aortic valve replacement in symptomatic patients with severe aortic stenosis and contraindications to surgery. The procedure has shown to improve patient's quality of life and prolong short- and mid-term survival in high-risk individuals, becoming a widely accepted therapeutic option which has been integrated into current clinical guidelines for the management of valvular heart disease. Nevertheless, not every patient at high-risk for surgery is a good candidate for TAVR.

Microenvironment-regulated lncRNA-HAL is able to promote stemness in breast cancer cells.

Multicellular Tumor Spheroids culture (MCTS) is an in vitro model mimicking the characteristics of the tumor microenvironment, such as hypoxia and acidosis, resulting in the presence of both proliferating and quiescent cell populations. lncRNA's is a novel group of regulatory molecules that participates in the acquisition of tumorigenic phenotypes. In the present work we evaluated the oncogenic association of an uncharacterized lncRNA (lncRNA-HAL) in the tumorigenic phenotype induced by the MCTS microenvironment.

Biological variation of resting measures of ventilation and gas exchange in a large healthy cohort.

Purpose: Resting measures of ventilation and gas exchange are impacted by a variety of physiological stressors, such as those resulting from a research intervention or an extreme environment. However, the biological variation of these parameters, an important statistical consideration for identifying a meaningful physiological change, has not been quantified.

Methods: We performed a retrospective analysis of 21 studies completed by the U.

Production of Fungal Phytases from Agroindustrial Byproducts for Pig Diets.

The application of phytases for animal feed in developing countries is limited due to the high cost of these enzymes, determined by the importation fees and the expensive substrates used for their production. In this work, we have used agroindustrial byproducts for the production of extracts containing phytases, which were accessed for their stability focusing on the conditions found in the gastrointestinal tract of pigs. The fungus Acremonim zeae presented higher phytase production in medium containing cornmeal, while the yeast Kluyveromyces marxianus produced 10-fold more phytase when cultivated on rice bran.

SET: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer.

There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SET index to measure gene expression microarray probe sets that were correlated with hormone receptors ( and ) and robust to preanalytical and analytical influences. We tested SET index in biopsies of metastastic HR+/HER2- breast cancer against the treatment outcomes in 140 patients.

The Relationship Between Tumor-Infiltrating Lymphocytes, PD-L1 Expression, Driver Mutations and Clinical Outcome Parameters in Non-Small Cell Lung Cancer Adenocarcinoma in Patients with a Limited to no Smoking History.

Tumor infiltrating lymphocytes (TIL), programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) expression are important prognostic markers. This study aimed to investigate these markers in lung adenocarcinoma (ADC) biopsies from patients with stage IIIB or IV ADC with little or no smoking history, to investigate their prognostic value and to correlate these results with the presence of driver mutations in the tumors. TIL were retrospectively evaluated on hematoxylin and eosin stained slides from 152 tumor samples.

Publisher Correction: Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

In the version of this article originally published, there was an error in Fig. 3j. A label on the heatmap read "TGF-α signaling via NF-κB".

Primary midgut volvulus without intestinal malrotation in a young adult: a case report.

Background: Midgut volvulus is a rare cause of acute abdomen characterized by a twisting of the entire small intestine around its mesenteric pedicle. It is a well-known complication of intestinal malrotation usually occurring in infants and young children. We report a rare case of a midgut volvulus without any underlying condition occurring in a young adult.

Vertical distribution of benthic diatoms in a large reservoir (Alqueva, Southern Portugal) during thermal stratification.

Freshwater diatom communities are known to respond to a wide range of environmental factors, however, the depth gradient is usually neglected and few studies are available, especially in large reservoirs. During the ALqueva hydro-meteorological EXperiment (ALEX) field campaign, diatom communities were studied in the margins and in three platforms (from the surface to the bottom of the reservoir) located in the limnetic zone of the Alqueva reservoir, one of the largest artificial lakes in western Europe. A detailed meteorological and physico-chemical characterization of the reservoir was carried out from June to September in Summer 2014, when the reservoir was stratified, to relate these variables with diatom assemblages.

Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial.

The efficacy of programmed cell death protein 1 (PD-1) blockade in metastatic triple-negative breast cancer (TNBC) is low, highlighting a need for strategies that render the tumor microenvironment more sensitive to PD-1 blockade. Preclinical research has suggested immunomodulatory properties for chemotherapy and irradiation. In the first stage of this adaptive, non-comparative phase 2 trial, 67 patients with metastatic TNBC were randomized to nivolumab (1) without induction or with 2-week low-dose induction, or with (2) irradiation (3 × 8 Gy), (3) cyclophosphamide, (4) cisplatin or (5) doxorubicin, all followed by nivolumab.

Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology.

Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit.

Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration.

Aims: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections.

Neoantigen-directed immune escape in lung cancer evolution.

The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied both between and within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct immune microenvironments.

Stromal Tumor-infiltrating Lymphocytes in NRG Oncology/NSABP B-31 Adjuvant Trial for Early-Stage HER2-Positive Breast Cancer.

We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in National Surgical Adjuvant Breast and Bowel Project B-31 (N = 2130). sTILs were assessed in 1581 eligible B-31 cases utilizing all available hematoxylin and eosin slides. Mean concordance between main reviewer and six other pathologists was 90.

The Cultural Adaptation of a Transition Program for Latino Families of Youth with Autism Spectrum Disorder.

During the transition to adulthood, effective and culturally relevant supports are critical for families of youth with autism spectrum disorder (ASD). There is a dearth of documented program development and research on supports for Spanish-speaking Latino families during this life stage. The present work describes the cultural adaptation process of an evidence-based transition program for Latino families of youth with ASD.

mutations in metastatic lobular breast cancer patients.

Invasive lobular breast cancer (ILC) represents the second most common histology of breast cancer after invasive ductal breast cancer (IDC), accounts for up to 15% of all invasive cases and generally express the estrogen receptor (ER, coded by the gene). mutations have been associated with resistance to endocrine therapy, however these have not been specifically evaluated in ILC. We assessed the frequency of mutations by droplet digital PCR in a retrospective multi-centric series of matched primary tumor and recurrence samples ( = 279) from 80 metastatic ER-positive ILC patients.

Imprint of parity and age at first pregnancy on the genomic landscape of subsequent breast cancer.

Background: Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer subtypes, with parity and young age at first pregnancy being associated with a marked reduction in the risk of developing luminal subtype but not triple negative breast cancer. In this study, we investigated the imprint of parity and age at first pregnancy on the pattern of somatic mutations, somatic copy number alterations, transcriptomic profiles, and tumor immune microenvironment by assessing tumor-infiltrating lymphocytes (TILs) levels of subsequent breast cancer.

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers.

Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC, with implications for current therapies including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+CD8+ T cells (GzmB+CD8+ T cells), a type 1 IFN signature, and elevated expression of multiple immune inhibitory molecules including indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1), and resulted in good outcomes.

The circular RNome of primary breast cancer.

Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently.