Multiplex Networks for Early Diagnosis of Alzheimer's Disease.

Analysis and quantification of brain structural changes, using Magnetic Resonance Imaging (MRI), are increasingly used to define novel biomarkers of brain pathologies, such as Alzheimer's disease (AD). Several studies have suggested that brain topological organization can reveal early signs of AD. Here, we propose a novel brain model which captures both intra- and inter-subject information within a multiplex network approach.

Vγ9Vδ2 T Cells as Strategic Weapons to Improve the Potency of Immune Checkpoint Blockade and Immune Interventions in Human Myeloma.

The advent of immune checkpoint (ICP) blockade has introduced an unprecedented paradigm shift in the treatment of cancer. Though very promising, there is still a substantial proportion of patients who do not respond or develop resistance to ICP blockade. and models are eagerly needed to identify mechanisms to maximize the immune potency of ICP blockade and overcome primary and acquired resistance to ICP blockade.

Salient networks: a novel application to study Alzheimer disease.

Background: Extracting fundamental information from data, thus underlining hidden structures or removing noisy information, is one of the most important aims in different scientific fields especially in biological and medical sciences. In this article, we propose an innovative complex network application able to identify salient links for detecting the effect of Alzheimer's disease on brain connectivity. We first build a network model of brain connectivity from structural Magnetic Resonance Imaging (MRI) data, then we study salient networks retrieved from the original ones.

New tetrahydroisoquinoline-based P-glycoprotein modulators: decoration of the biphenyl core gives selective ligands.

P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our body. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P-gp substrates.

Oxidative stress and neurodegeneration: the involvement of iron.

Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low.

A novel approach to brain connectivity reveals early structural changes in Alzheimer's disease.

Objective: Recent studies have shown that complex networks along with diffusion weighted imaging (DWI) can be efficient and promising techniques for early detection of structural pathological changes in Alzheimer's disease. Besides, connectivity studies, specifically assessing the organization of a graph and its topology, could represent the best chance to discover how brain activity is shaped and driven. Accordingly, we propose a methodology to evaluate how Alzheimer's disease affects brain networks through a novel way to look at graph connectivity.

Complex networks reveal early MRI markers of Parkinson's disease.

Parkinson's disease (PD) is the most common neurological disorder, after Alzheimer's disease, and is characterized by a long prodromal stage lasting up to 20 years. As age is a prominent factor risk for the disease, next years will see a continuous increment of PD patients, making urgent the development of efficient strategies for early diagnosis and treatments. We propose here a novel approach based on complex networks for accurate early diagnoses using magnetic resonance imaging (MRI) data; our approach also allows us to investigate which are the brain regions mostly affected by the disease.

Molecular Insights into hERG Potassium Channel Blockade by Lubeluzole.

Background/aims: Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in preclinical models of ischemic stroke. However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. Since the cardiac cellular effects of lubeluzole have not been described thus far, an explanation for the lubeluzole-induced QT interval prolongation is lacking.

One pot environmental friendly synthesis of gold nanoparticles using Punica Granatum Juice: A novel antioxidant agent for future dermatological and cosmetic applications.

Hypothesis: The interesting properties of Gold Nanoparticles (AuNPs) make them attractive for different application fields such as cosmetology, medicine and clinical nanotechnologies. In this work a fast, easy and eco-friendly method for the AuNPs synthesis is proposed by using the Punica Granatum Juice (PGJ) with potential dermatological and cosmetic applications. The AuNPs antioxidant activity, due to the presence of phenols from the juice, and their use as booster for improving the Sun Protection Factor (SPF) in commercial sunscreen formulations, are thus expounded.

CoVaCS: a consensus variant calling system.

Background: The advent and ongoing development of next generation sequencing technologies (NGS) has led to a rapid increase in the rate of human genome re-sequencing data, paving the way for personalized genomics and precision medicine. The body of genome resequencing data is progressively increasing underlining the need for accurate and time-effective bioinformatics systems for genotyping - a crucial prerequisite for identification of candidate causal mutations in diagnostic screens.

Results: Here we present CoVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation.

Alzheimer's disease diagnosis based on the Hippocampal Unified Multi-Atlas Network (HUMAN) algorithm.

Background: Hippocampal atrophy is a supportive feature for the diagnosis of probable Alzheimer's disease (AD). However, even for an expert neuroradiologist, tracing the hippocampus and measuring its volume is a time consuming and extremely challenging task. Accordingly, the development of reliable fully-automated segmentation algorithms is of paramount importance.

Low-picomolar, label-free procalcitonin analytical detection with an electrolyte-gated organic field-effect transistor based electronic immunosensor.

Herein a label-free immunosensor based on electrolyte-gated organic field-effect transistor (EGOFET) was developed for the detection of procalcitonin (PCT), a sepsis marker. Antibodies specific to PCT were immobilized on the poly-3-hexylthiophene (P3HT) organic semiconductor surface through direct physical adsorption followed by a post-treatment with bovine serum albumin (BSA) which served as the blocking agent to prevent non-specific adsorption. Antibodies together with BSA (forming the whole biorecognition layer) served to selectively capture the procalcitonin target analyte.

Deep learning reveals Alzheimer's disease onset in MCI subjects: Results from an international challenge.

Background: Early diagnosis of Alzheimer's disease (AD) and its onset in subjects affected by mild cognitive impairment (MCI) based on structural MRI features is one of the most important open issues in neuroimaging. Accordingly, a scientific challenge has been promoted, on the international Kaggle platform, to assess the performance of different classification methods for prediction of MCI and its conversion to AD.

New Method: This work presents a classification strategy based on Random Forest feature selection and Deep Neural Network classification using a mixed cohort including the four classes of classification problem, that is HC, AD, MCI and cMCI, to train the model.

Discovery of a new mexiletine-derived agonist of the hERG K channel.

The human Ether-a-go-go Related Gene (hERG) potassium channel plays a central role in the rapid component (I) of cardiac action potential repolarization phase. A large number of structurally different compounds block hERG and cause a high risk of arrhythmias. Among the drugs that block hERG channel, a few compounds have been identified as hERG channel activators.

Selective inhibition of matrix metalloproteinase-2 in the multiple myeloma-bone microenvironment.

Multiple myeloma is a plasma cell malignancy that homes aberrantly to bone causing extensive skeletal destruction. Despite the development of novel therapeutic agents that have significantly improved overall survival, multiple myeloma remains an incurable disease. Matrix metalloproteinase-2 (MMP-2) is associated with cancer and is significantly overexpressed in the bone marrow of myeloma patients.

Structure-Activity Relationship Studies on 6,7-Dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline Derivatives as Multidrug Resistance Reversers.

A series of derivatives were synthesized and studied with the aim to investigate the structure-activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar. Then, different aryl-substituted amides were inserted, and to explore the effects of varying the amide function, the corresponding isosteric ester derivatives and some alkylamine analogues were synthesized. The new compounds were studied to evaluate their P-gp interaction profile and selectivity toward the two other ABC transporters, multidrug-resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP).

Topological Measurements of DWI Tractography for Alzheimer's Disease Detection.

Neurodegenerative diseases affect brain morphology and connectivity, making complex networks a suitable tool to investigate and model their effects. Because of its stereotyped pattern Alzheimer's disease (AD) is a natural benchmark for the study of novel methodologies. Several studies have investigated the network centrality and segregation changes induced by AD, especially with a single subject approach.

Resilient landscapes in Mediterranean urban areas: Understanding factors influencing forest trends.

Urban and peri-urban forests are recognized as basic elements for Nature-Based Solutions (NBS), as they preserve and may increase environmental quality in urbanized contexts. For this reason, the amount of forest land per inhabitant is a pivotal efficiency indicator to be considered in the sustainable governance, land management, planning and design of metropolitan areas. The present study illustrates a multivariate analysis of per-capita forest area (PFA) in mainland Attica, the urban region surrounding Athens, Greece.

DTI measurements for Alzheimer's classification.

Diffusion tensor imaging (DTI) is a promising imaging technique that provides insight into white matter microstructure integrity and it has greatly helped identifying white matter regions affected by Alzheimer's disease (AD) in its early stages. DTI can therefore be a valuable source of information when designing machine-learning strategies to discriminate between healthy control (HC) subjects, AD patients and subjects with mild cognitive impairment (MCI). Nonetheless, several studies have reported so far conflicting results, especially because of the adoption of biased feature selection strategies.

Mercury Exposure and Heart Diseases.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities.

Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (logD): Evaluation and comparison to existing practices.

In drug discovery, lipophilicity is a key parameter for drug optimization. Lipophilicity determinations can be both work and time consuming, especially for non-UV active compounds. Herein, an improved and simple 1H NMR-based method is described to estimate the lipophilicity at physiological pH (logD) in 1-octanol and DO buffer.

Design and Synthesis of New Selective P-gp Substrates and Inhibitors.

P-glycoprotein is an ATP-binding cassette transporter involved in drug absorption, distribution and excretion. It pumps a wide range of xenobiotic compounds out of the cells and plays a crucial role in Multi Drug Resistance. Moreover, recent studies have demonstrated that changes in P-gp function and/or expression at the blood brain barrier are implicated in the pathogenesis of neurological disorders such as therapy-refractory epilepsy, Alzheimer's and Parkinson's disease.