Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?

In the last decades the survival of metastatic gastrointestinal (GI) cancer patients could have been significantly extended due to the introduction of targeted- and immunotherapy. However, only the minority of patients will experience long-lasting survival. Hence, novel therapeutics are clearly necessary for GI cancer patients.

Synchronization cluster bursting in adaptive oscillator networks.

Adaptive dynamical networks are ubiquitous in real-world systems. This paper aims to explore the synchronization dynamics in networks of adaptive oscillators based on a paradigmatic system of adaptively coupled phase oscillators. Our numerical observations reveal the emergence of synchronization cluster bursting, characterized by periodic transitions between cluster synchronization and global synchronization.

Exploring the origins of switching dynamics in a multifunctional reservoir computer.

The concept of multifunctionality has enabled reservoir computers (RCs), a type of dynamical system that is typically realized as an artificial neural network, to reconstruct multiple attractors simultaneously using the same set of trained weights. However, there are many additional phenomena that arise when training a RC to reconstruct more than one attractor. Previous studies have found that in certain cases, if the RC fails to reconstruct a coexistence of attractors, then it exhibits a form of metastability, whereby, without any external input, the state of the RC switches between different modes of behavior that resemble the properties of the attractors it failed to reconstruct.

Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC).

Background: Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC.

Immunotherapy for Microsatellite-Stable Metastatic Colorectal Cancer: Can we close the Gap between Potential and Practice?

Purpose Of Review: This review will explore various strategies to rendering MSS mCRCs susceptible to ICI. Moreover, we will provide an overview of potential biomarkers that may aid to better patient selection, and discuss ongoing efforts in this area of research.

Recent Findings: Colorectal cancer (CRC) ranks among the top three most common cancers worldwide.

Dynamics of a time-delayed relay system.

We study the dynamics of a piecewise-linear second-order delay differential equation that is representative of feedback systems with relays (switches) that actuate after a fixed delay. The system under study exhibits strong multirhythmicity, the coexistence of many stable periodic solutions for the same values of the parameters. We present a detailed study of these periodic solutions and their bifurcations.

Seeing double with a multifunctional reservoir computer.

Multifunctional biological neural networks exploit multistability in order to perform multiple tasks without changing any network properties. Enabling artificial neural networks (ANNs) to obtain certain multistabilities in order to perform several tasks, where each task is related to a particular attractor in the network's state space, naturally has many benefits from a machine learning perspective. Given the association to multistability, in this paper, we explore how the relationship between different attractors influences the ability of a reservoir computer (RC), which is a dynamical system in the form of an ANN, to achieve multifunctionality.

LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study.

Background: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage.

Treatment Algorithm for Patients With Gastric Adenocarcinoma: Austrian Consensus on Systemic Therapy - An Update.

Over the last decade, therapeutic options for patients with gastric cancer have improved significantly. However, despite these recent advances, mortality is still substantial. Surgery and chemotherapy represent the cornerstones of patient management.

Transitional cluster dynamics in a model for delay-coupled chemical oscillators.

Cluster synchronization is a fundamental phenomenon in systems of coupled oscillators. Here, we investigate clustering patterns that emerge in a unidirectional ring of four delay-coupled electrochemical oscillators. A voltage parameter in the experimental setup controls the onset of oscillations via a Hopf bifurcation.

Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations.

Effective targeted treatment strategies resulted from molecular profiling of lung cancer with distinct prevalent mutation profiles in smokers and non-smokers. Although Rn is the second most important risk factor, data for Rn-dependent driver events are limited. Therefore, a Rn-exposed cohort of lung cancer patients was screened for oncogenic drivers and their survival and genetic profiles were compared with data of the average regional population.

Pollutant source or sink? Adsorption and mobilization of PFOS and PFOA from sediments in a large shallow lake with extended reed belt.

In this study, we i) assessed the occurrence of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in sediments, pore water, and bulk water from three different areas in Lake Neusiedl, Austria, and ii) investigated mechanisms regulating adsorption and remobilization of these substances under different conditions via multiple lab-scale experiments. The adsorption capacity was mainly influenced by sediments' organic matter content, oxide composition, and pre-loading. Results suggest that a further increase of PFAS-concentrations in the open lake can be partly buffered by sediment transport to the littoral zone and adsorption to sediments in the extended reed belt.

Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission.

Objectives: We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).

Methods: Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J.

Systematic data-driven exploration of Austrian wastewater and sludge treatment - implications for phosphorus governance, costs and environment.

Within the new policy framework shaped by the EU Green Deal and the Circular Economy Action Plans, the field of wastewater and sludge treatment in Europe is subject to high expectations and new challenges related to mitigation of greenhouse gas emissions, micropollutant removal and resource recovery. With respect to phosphorus recovery, several technologies and processes have been thoroughly investigated. Nevertheless, a systemic and detailed understanding of the existing infrastructure and of the related environmental and economic implications is missing.

Origin of the Unusual Ground-State Spin = 9 in a Cr Single-Molecule Magnet.

The molecular wheel [Cr(OMe)(OCCMe)], abbreviated {Cr}, with an unusual intermediate total spin = 9 and non-negligible cluster anisotropy, / = -0.045(2) K, is a rare case among wheels based on an even number of 3d-metals, which usually present an antiferromagnetic (AF) ground state ( = 0). Herein, we unveil the origin of such a behavior.

Comprehensive Analysis of R-Spondin Fusions and RNF43 Mutations Implicate Novel Therapeutic Options in Colorectal Cancer.

Purpose: Gene fusions involving R-spondin (RSPOfp) and RNF43 mutations have been shown to drive Wnt-dependent tumor initiation in colorectal cancer. Herein, we aimed to characterize the molecular features of RSPOfp/RNF43 mutated (mut) compared with wild-type (WT) colorectal cancers to gain insights into potential rationales for therapeutic strategies.

Experimental Design: A discovery cohort was classified for RSPOfp/RNF43 status using DNA/RNA sequencing and IHC.

Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort.

Background: Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing.

Methods: In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort.

Results: In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated.

Stereotactic radiofrequency ablation of tumors at the hepatic venous confluence.

Background: Radiofrequency ablation (RFA) is subject to "heat-sink" effects, particularly for treatment of tumors adjacent to major vessels.

Methods: In this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.

Benefit of second-line therapy for advanced esophageal squamous cell carcinoma: a tri-center propensity score analysis.

Background: The level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) ASC alone in aESCC.

Methods: We conducted a tri-center retrospective cohort study ( = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy.

Symmetry kills the square in a multifunctional reservoir computer.

The learning capabilities of a reservoir computer (RC) can be stifled due to symmetry in its design. Including quadratic terms in the training of a RC produces a "square readout matrix" that breaks the symmetry to quell the influence of "mirror-attractors," which are inverted copies of the RC's solutions in state space. In this paper, we prove analytically that certain symmetries in the training data forbid the square readout matrix to exist.

Deregulated glutamate to pro-collagen conversion is associated with adverse outcome in lung cancer and may be targeted by renin-angiotensin-aldosterone system (RAS) inhibition.

Background: The tumor-microenvironment (TME) represents an attractive therapeutic target in NSCLC and plays an important role for efficacy of cancer therapeutics. We hypothesized that upregulation of collagen synthesis might be associated with adverse outcome in NSCLC. Literature evidence suggests that renin-angiotensin system inhibitors (RASi) decrease collagen deposition.

Multifunctionality in a reservoir computer.

Multifunctionality is a well observed phenomenological feature of biological neural networks and considered to be of fundamental importance to the survival of certain species over time. These multifunctional neural networks are capable of performing more than one task without changing any network connections. In this paper, we investigate how this neurological idiosyncrasy can be achieved in an artificial setting with a modern machine learning paradigm known as "reservoir computing.