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Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning : External Validation and Further Model Development

Background: Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using po

Impact of Neoadjuvant Therapy for Pancreatic Cancer : Transatlantic Trend and Postoperative Outcomes Analysis

BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and short-term outcomes in patients with PDAC unde

Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive

An Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated

The DNA methylation landscape of primary triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcrip

Genetic regulation of RNA splicing in human pancreatic islets

BackgroundNon-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.ResultsWe examine splicing QTLs (sQTLs) in pancreatic islets fro

The deepest X-ray view of high-redshift galaxies : Constraints on low-rate black hole accretion

We exploit the 7 Ms Chandra observations in the Chandra Deep Field-South (CDF-S), the deepest X-ray survey to date, coupled with CANDELS/GOODS-S data, to measure the total X-ray emission arising from 2076 galaxies at 3.5 ≤ z < 6.5. This aim is achieved by stacking the Chandra data at the positions of optically selected galaxies, reaching effective exposure times of ≥109s.We detect significant (>3.

Osannolika händelser och den svenska realistiska romanen : Ett estetiskt och existentiellt bekymmer

Avhandlingens ämne är osannolika händelser i den realistiska romanen. Den övergripande idén är att realismen utmärks av att osannolika händelser hanteras utifrån ett dubbelt perspektiv: både som ett existentiellt och ett estetiskt bekymmer. Som ett existentiellt bekymmer representerar den narrativa fiktionsberättelsens osannolika händelser den ständigt närvarande möjligheten att en oförutsägbar ocThis thesis deals with improbable events in the realistic novel. The overarchingidea is that realism is distinguished by dealing with improbable events on thebasis of a double perspective: both as an existential and as an aesthetic problem.As an existential problem the improbable events of narrative fiction representthe constantly present possibility of an unexpected and unforeseen event suddenly

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systema

Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE) : a randomized multicentre feasibility trial

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care.METHODS: Adults with septic shock in

CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins wer

Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance

Background: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris. Objectives: The purpose of this study was to determine the association between the usage of FFR and all-cause m

Signal-Averaged ECG in the Diagnostic Workup for Arrhythmogenic Cardiomyopathy : Insights From the Nordic ARVC Registry

BACKGROUND: The diagnostic role of signal-averaged ECG (SAECG) in arrhythmogenic right ventricular cardiomyopathy (ARVC) has lately been questioned. We assessed the value of SAECG-derived late ventricular potentials (LP) in ARVC diagnosis and its association with disease manifestations.METHODS AND RESULTS: Patients with definite ARVC diagnosis or genotype-positive family members who underwent SAEC

Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.

Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advan

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels b

Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition,

Painting and firing of late Etruscan votive terracottas

Ancient Italic terracottas were painted before or after firing depending on their function, as suggested by previous analyses. However, concerning the votive terracottas, there seems to have been no anlayses carried out, suggesting either a fired or non fired paint. Methods and problems associated with an ongoing research on some votive terracottas from Tessennano in Southern Etruria are considere

Associations Between Ambient Particle Radioactivity and Blood Pressure: The NAS (Normative Aging Study)

BACKGROUND: The cardiovascular effects of low-level environmental radiation exposures are poorly understood. Although particulate matter (PM) has been linked to cardiovascular morbidity and mortality, and elevated blood pressure (BP), the properties promoting its toxicity remain uncertain. Addressing a knowledge gap, we evaluated whether BP increased with higher exposures to radioactive components

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study

Background: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. Methods: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most