Increased expression levels of PIEZO1 in visceral adipose tissue in obesity and type 2 diabetes are triggered by mechanical forces and are associated with inflammation.

Background: PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1 in visceral AT (VAT) and its relation with inflammation.

Methods: Blood and VAT samples were obtained from 100 volunteers.

Development of an platform for the analysis of contractile and calcium dynamics in single human myotubes.

myotube cultures are widely used as models for studying muscle pathophysiology, but their limited maturation and heterogeneity pose significant challenges for functional analyses. While they remain the gold standard for studying muscle function , myotube cultures do not fully recapitulate the complexity and native features of muscle fibers, which may compromise their ability to predict outcomes. To promote maturation and decrease heterogeneity, we have incorporated engineered structures into myotube cultures, based on a PDMS thin layer with micrometer-sized grooves (μGrooves) placed over a glass substrate.

Artificial Trabecular Meshwork Structure Combining Melt Electrowriting and Solution Electrospinning.

The human trabecular meshwork (HTM) is responsible for regulating intraocular pressure (IOP) by means of gradient porosity. Changes in its physical properties, like increases in stiffness or alterations in the extracellular matrix (ECM), are associated with increases in the IOP, which is the primary cause of glaucoma. The complexity of its structure limits the engineered models to one-layered and simple approaches, which do not accurately replicate the biological and physiological cues related to glaucoma.

q2-metnet: QIIME2 package to analyse 16S rRNA data via high-quality metabolic reconstructions of the human gut microbiota.

Motivation: 16S rRNA gene sequencing is the most frequent approach for the characterization of the human gut microbiota. Despite different efforts in the literature, the inference of functional and metabolic interpretations from 16S rRNA gene sequencing data is still a challenging task. High-quality metabolic reconstructions of the human gut microbiota, such as AGORA and AGREDA, constitute a curated resource to improve functional inference from 16S rRNA data, but they are not typically integrated into standard bioinformatics tools.

Application of Graph Models to the Identification of Transcriptomic Oncometabolic Pathways in Human Hepatocellular Carcinoma.

Whole-tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods.

Extending PROXIMAL to predict degradation pathways of phenolic compounds in the human gut microbiota.

Despite significant advances in reconstructing genome-scale metabolic networks, the understanding of cellular metabolism remains incomplete for many organisms. A promising approach for elucidating cellular metabolism is analysing the full scope of enzyme promiscuity, which exploits the capacity of enzymes to bind to non-annotated substrates and generate novel reactions. To guide time-consuming costly experimentation, different computational methods have been proposed for exploring enzyme promiscuity.

gMCSpy: efficient and accurate computation of genetic minimal cut sets in Python.

Motivation: The identification of minimal genetic interventions that modulate metabolic processes constitutes one of the most relevant applications of genome-scale metabolic models (GEMs). The concept of Minimal Cut Sets (MCSs) and its extension at the gene level, genetic Minimal Cut Sets (gMCSs), have attracted increasing interest in the field of Systems Biology to address this task. Different computational tools have been developed to calculate MCSs and gMCSs using both commercial and open-source software.

BN-BacArena: Bayesian network extension of BacArena for the dynamic simulation of microbial communities.

Motivation: Simulating gut microbial dynamics is extremely challenging. Several computational tools, notably the widely used BacArena, enable modeling of dynamic changes in the microbial environment. These methods, however, do not comprehensively account for microbe-microbe stimulant or inhibitory effects or for nutrient-microbe inhibitory effects, typically observed in different compounds present in the daily diet.

Untethered Ultra-Wideband-Based Real-Time Locating System for Road-Worker Safety.

In order to reduce the accident risk in road construction and maintenance, this paper proposes a novel solution for road-worker safety based on an untethered real-time locating system (RTLS). This system tracks the location of workers in real time using ultra-wideband (UWB) technology and indicates if they are in a predefined danger zone or not, where the predefined safe zone is delimited by safety cones. Unlike previous works that focus on road-worker safety by detecting vehicles that enter into the working zone, our proposal solves the problem of distracted workers leaving the safe zone.

Review and meta-analysis of the genetic Minimal Cut Set approach for gene essentiality prediction in cancer metabolism.

Cancer metabolism is a marvellously complex topic, in part, due to the reprogramming of its pathways to self-sustain the malignant phenotype in the disease, to the detriment of its healthy counterpart. Understanding these adjustments can provide novel targeted therapies that could disrupt and impair proliferation of cancerous cells. For this very purpose, genome-scale metabolic models (GEMs) have been developed, with Human1 being the most recent reconstruction of the human metabolism.

Identification of Concussion Subtypes Based on Intrinsic Brain Activity.

Importance: The identification of brain activity-based concussion subtypes at time of injury has the potential to advance the understanding of concussion pathophysiology and to optimize treatment planning and outcomes.

Objective: To investigate the presence of intrinsic brain activity-based concussion subtypes, defined as distinct resting state quantitative electroencephalography (qEEG) profiles, at the time of injury.

Design, Setting, And Participants: In this retrospective, multicenter (9 US universities and high schools and 4 US clinical sites) cohort study, participants aged 13 to 70 years with mild head injuries were included in longitudinal cohort studies from 2017 to 2022.

Enhancing Global Development of Palliative Care: Insights from Country Experts on ATLANTES Observatory's Role.

Despite a steady increase in palliative care (PC)-oriented research, authentic engagement of stakeholders with findings needs to be more used. This study aimed to explore how ATLANTES Observatory can effectively promote the global development of PC by engaging with stakeholders and addressing their specific needs and priorities. An international e-survey among Observatory collaborators explored key audiences, best ways to reach them, and priority activities.

An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration.

During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 μg/ml), resulting in efficient, sustained osteoinduction in vitro.

Nanofibrous PCL-Based Human Trabecular Meshwork for Aqueous Humor Outflow Studies.

Primary open-angle glaucoma is characterized by the progressive degeneration of the optic nerve, with the high intraocular pressure (IOP) being one of the main risk factors. The human trabecular meshwork (HTM), specifically the juxtacanalicular tissue (JCT), is responsible for placing resistance to the aqueous humor (AH) outflow and the resulting IOP control. Currently, the lack of a proper JCT model and the complexity of three-dimensional models impede advances in understanding the relationship between AH outflow and HTM degeneration.

Synthetic lethality in large-scale integrated metabolic and regulatory network models of human cells.

Synthetic lethality (SL) is a promising concept in cancer research. A wide array of computational tools has been developed to predict and exploit synthetic lethality for the identification of tumour-specific vulnerabilities. Previously, we introduced the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to SL developed for genome-scale metabolic networks.

Bayesian Machine Learning Enables Identification of Transcriptional Network Disruptions Associated with Drug-Resistant Prostate Cancer.

Unlabelled: Survival rates of patients with metastatic castration-resistant prostate cancer (mCRPC) are low due to lack of response or acquired resistance to available therapies, such as abiraterone (Abi). A better understanding of the underlying molecular mechanisms is needed to identify effective targets to overcome resistance. Given the complexity of the transcriptional dynamics in cells, differential gene expression analysis of bulk transcriptomics data cannot provide sufficient detailed insights into resistance mechanisms.

Neuroanatomical and psychological considerations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular 'non-epileptic' brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients - with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue.

Photonic Technology for In Vivo Monitoring of Hypoxia-Ischemia.

Surveillance of physiological parameters of newborns during delivery triggers medical decision-making, can rescue life and health, and helps avoid unnecessary cesareans. Here, the development of a photonic technology for monitoring perinatal asphyxia is presented and validated in vivo in a preclinical stage. Contrary to state of the art, the technology provides continuous data in real-time in a non-invasive manner.

Long-Term Changes in Brain Connectivity Reflected in Quantitative Electrophysiology of Symptomatic Former National Football League Players.

Exposure to repetitive head impacts (RHI) has been associated with long-term disturbances in cognition, mood, and neurobehavioral dysregulation, and reflected in neuroimaging. Distinct patterns of changes in quantitative features of the brain electrical activity (quantitative electroencephalogram [qEEG]) have been demonstrated to be sensitive to brain changes seen in neurodegenerative disorders and in traumatic brain injuries (TBI). While these qEEG biomarkers are highly sensitive at time of injury, the long-term effects of exposure to RHI on brain electrical activity are relatively unexplored.

Palliative care in the Eastern Mediterranean: comparative analysis using specific indicators.

Background: Monitoring the development of palliative care (PC) illustrates the capacity of health systems to respond to the needs of people experiencing serious health-related suffering.

Aim: To analyse comparatively the situation of PC in the countries of the Easter Mediterranean region using context-specific indicators.

Method: An online questionnaire with 15 context-specific PC indicators investigating service provision, use of medicines, policy, education, and vitality was designed.

Technological advances in ocular trabecular meshwork in vitro models for glaucoma research.

Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by the progressive degeneration of the optic nerve. Intraocular pressure (IOP), which is considered to be the main risk factor for glaucoma development, builds up in response to the resistance (resistance to what?) provided by the trabecular meshwork (TM) to aqueous humor (AH) outflow. Although the TM and its relationship to AH outflow have remained at the forefront of scientific interest, researchers remain uncertain regarding which mechanisms drive the deterioration of the TM.

Prediction of degradation pathways of phenolic compounds in the human gut microbiota through enzyme promiscuity methods.

The relevance of phenolic compounds in the human diet has increased in recent years, particularly due to their role as natural antioxidants and chemopreventive agents in different diseases. In the human body, phenolic compounds are mainly metabolized by the gut microbiota; however, their metabolism is not well represented in public databases and existing reconstructions. In a previous work, using different sources of knowledge, bioinformatic and modelling tools, we developed AGREDA, an extended metabolic network more amenable to analyze the interaction of the human gut microbiota with diet.