Sex-related differences in amyotrophic lateral sclerosis: A 2-[F]FDG-PET study.

Purpose: We investigated sex-related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC).

Methods: We collected two equal-sized groups of male (m-ALS) and female ALS (f-ALS) patients (n = 130 each), who underwent 2-[F]FDG-PET at diagnosis, matched for site of onset, cognitive status and King's stage. We included 168 age-matched healthy controls, half female (f-HC) and half male (m-HC).

Network Analysis of miRNA and Cytokine Landscape in Human Hematopoiesis.

The differentiation/maturation trajectories of different blood cell types stemming from a CD34 common ancestor takes place in different biologically relevant multidimensional spaces. Here, we generated microRNA and cytokine profiles from highly purified populations of hematopoietic progenitors/precursors derived from cord blood hematopoietic stem/progenitor cells. MicroRNA and cytokine landscapes were then analyzed to find their mutual relationships under the hypothesis that the highly variable miRNome corresponds to the 'force field' driving the goal of a stable phenotype (here corresponding to the cytokine abundance pattern) typical of each cell kind.

Upper Bound for the Ground State Energy of a Dilute Bose Gas of Hard Spheres.

We consider a gas of bosons interacting through a hard-sphere potential with radius in the thermodynamic limit. We derive an upper bound for the ground state energy per particle at low density. Our bound captures the leading term and shows that corrections are smaller than , for a sufficiently large constant .

Topical application of a hyaluronic acid-based hydrogel integrated with secretome of human mesenchymal stromal cells for diabetic ulcer repair.

This preclinical proof-of-concept study aimed to evaluate the effectiveness of secretome therapy in diabetic mice with pressure ulcers. We utilized a custom-made hyaluronic acid (HA)-based porous sponge, which was rehydrated either with normal culture medium or secretome derived from human mesenchymal stromal cells (MSCs) to achieve a hydrogel consistency. Following application onto skin ulcers, both the hydrogel-only and the hydrogel + secretome combination accelerated wound closure compared to the vehicle group.

Stability/Flexibility: the tightly coupled homeostasis generator is at the same time the driver of change.

There is "no Flexibility without Stability and no Stability without Flexibility": this is a crucial feature common to any system interacting with its environment. This tight link between two apparently opposite features is at the basis of the time-honoured concept of homeostasis (the tendency of any adaptive system to go back to its "comfort zone" contrasting the incoming perturbations) and is widely recognized since long time. On the contrary, the fact that the escape from a stable attractor state is a consequence of the same homeostasis mechanisms is often overlooked.

Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

Objective: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB).

Methods: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study.

Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy.

Stem cell-derived small extracellular vesicles embedded into methacrylated hyaluronic acid wound dressings accelerate wound repair in a pressure model of diabetic ulcer.

Over the past years, the development of innovative smart wound dressings is revolutionizing wound care management and research. Specifically, in the treatment of diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In the present work, a methacrylated hyaluronic acid (MeHA) bioink is employed to manufacture 3D printed patches to deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs).

From Cell States to Cell Fates: Control of Cell State Transitions.

We examine the coordinated behavior of thousands of genes in cell fate transitions through genome expression as an integrated dynamical system using the concepts of self-organized criticality and coherent stochastic behavior. To quantify the effects of the collective behavior of genes, we adopted the flux balance approach and developed it in a new tool termed expression flux analysis (EFA). Here we describe this tool and demonstrate how its application to specific experimental genome-wide expression data provides new insights into the dynamics of the cell-fate transitions.

The Search for System's Parameters: Statistical and Dynamical Description from Complex Network Analysis.

The integration of physical and biological science styles is the key for facing the deluge of molecular level information that is becoming a real threat for knowledge advancement. In this work, I will indicate a possible integration path based on the network formalization of molecular knowledge by two different (here named flux and dynamical) perspectives. Some theoretical and applicative cases are presented, focusing on the different physical models implicit in the two network analysis approaches.

Special Issue "Advances in Genome Regulation in Cancer".

Cancer is globally increasing [...

Wheel Running Adversely Affects Disease Onset and Neuromuscular Interplay in Amyotrophic Lateral Sclerosis Slow Progression Mouse Model.

Background: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial role. In some epidemiological studies, both recreational or professional sport exercise has been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise have not been fully elucidated in either patients or animal models.

Methods: To better reproduce the influence of this environmental factor in the pathogenesis of ALS, we exposed SOD1 low-copy male mice to multiple exercise sessions at asymptomatic and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3 months.

Is cancer an intelligent species?

Some relevant emerging properties of intelligent systems are "adaptation to a changing environment," "reaction to unexpected situations," "capacity of problem solving," and "ability to communicate." Single cells have remarkable abilities to adapt, make adequate context-dependent decision, take constructive actions, and communicate, thus theoretically meeting all the above-mentioned requirements. From a biological point of view, cancer can be viewed as an invasive species, composed of cells that move from primary to distant sites, being continuously exposed to changes in the environmental conditions.

Synchronization between Attractors: Genomic Mechanism of Cell-Fate Change.

Herein, we provide a brief overview of complex systems theory approaches to investigate the genomic mechanism of cell-fate changes. Cell trajectories across the epigenetic landscape, whether in development, environmental responses, or disease progression, are controlled by extensively coordinated genome-wide gene expression changes. The elucidation of the mechanisms underlying these coherent expression changes is of fundamental importance in cell biology and for paving the road to new therapeutic approaches.

Systems Biology and Omics Approaches for Complex Human Diseases.

For many years, there has been general interest in developing virtual cells or digital twin models [...

Network-Based Prediction of Side Effects of Repurposed Antihypertensive Sartans against COVID-19 via Proteome and Drug-Target Interactomes.

The potential of targeting the Renin-Angiotensin-Aldosterone System (RAAS) as a treatment for the coronavirus disease 2019 (COVID-19) is currently under investigation. One way to combat this disease involves the repurposing of angiotensin receptor blockers (ARBs), which are antihypertensive drugs, because they bind to angiotensin-converting enzyme 2 (ACE2), which in turn interacts with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. However, there has been no in silico analysis of the potential toxicity risks associated with the use of these drugs for the treatment of COVID-19.

Globally invariant behavior of oncogenes and random genes at population but not at single cell level.

Cancer is widely considered a genetic disease. Notably, recent works have highlighted that every human gene may possibly be associated with cancer. Thus, the distinction between genes that drive oncogenesis and those that are associated to the disease, but do not play a role, requires attention.

"Combo" Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is characterized by a cascade of events that lead to sensory and motor disabilities. To date, this condition is irreversible, and no cure exists. To improve myelin repair and limit secondary degeneration, we developed a multitherapy based on nanomedicines (NMeds) loaded with the promyelinating agent triiodothyronine (T3), used in combination with systemic ibuprofen and mouse nerve growth factor (mNGF).

A novel network approach to multiscale biological regulation.

Modeling systems at multiple interacting scales is probably the most relevant task for pursuing a physically motivated explanation of biological regulation. In a new study, Smart and Zilman develop a convincing, albeit preliminary, model of the interplay between the cell microscale and the macroscopic tissue organization in biological systems.

Computational analysis of the sequence-structure relation in SARS-CoV-2 spike protein using protein contact networks.

The structure of proteins impacts directly on the function they perform. Mutations in the primary sequence can provoke structural changes with consequent modification of functional properties. SARS-CoV-2 proteins have been extensively studied during the pandemic.

Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change.

Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers.

Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution.

The biological complexity of cancer represents a tremendous clinical challenge, resulting in the frequent failure of current treatment protocols. In the rapidly evolving scenario of a growing tumor, anticancer treatments impose a drastic perturbation not only to cancer cells but also to the tumor microenvironment, killing a portion of the cells and inducing a massive stress response in the survivors. Consequently, treatments can act as a double-edged sword by inducing a temporary response while laying the ground for therapy resistance and subsequent disease progression.

Reconstruction of the Temporal Correlation Network of All-Cause Mortality Fluctuation across Italian Regions: The Importance of Temperature and Among-Nodes Flux.

All-cause mortality is a very coarse grain, albeit very reliable, index to check the health implications of lifestyle determinants, systemic threats and socio-demographic factors. In this work, we adopt a statistical-mechanics approach to the analysis of temporal fluctuations of all-cause mortality, focusing on the correlation structure of this index across different regions of Italy. The correlation network among the 20 Italian regions was reconstructed using temperature oscillations and traveller flux (as a function of distance and region's attractiveness, based on GDP), allowing for a separation between infective and non-infective death causes.

Awareness: An empirical model.

In this work, we face the time-honored problem of the contraposition/integration of analytical and intuitive knowledge, and the impact of such interconnection on the onset of awareness resulting from human decision-making processes. Borrowing the definitions of concepts like intuition, tacit knowledge, uncertainty, metacognition, and emotions from the philosophical, psychological, decision theory, and economic points of view, we propose a skeletonized mathematical model grounded on Markov Decision Processes of these multifaceted concepts. Behavioral patterns that emerged from the solutions of the model enabled us to understand some relevant properties of the interaction between explicit (mainly analytical) and implicit (mainly holistic) knowledge.