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Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from the phosphatidylethanolamine N-methyltransferase-mediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.

Efforts to manage small and medium-sized pelagic fishes (SMPF) using traditional stock assessment methods are hampered by the elusive relationship between spawning stock biomass and recruitment. We propose to compute a reproductive resilience index (RRI) in three steps: (i) we selected 16 biological traits related to distinct aspects of SMPF reproductive biology and characterized by a continuous (e.g., growth rate) or ordinal variable (e.g., spawning site fidelity) scored from 1 to 5 (1 representing a low contribution of the trait to reproductive resilience); (ii) an expert panel assigned the traits' scores to five exploited species in the southern Humboldt Current Large Marine Ecosystem; (iii) a Bayesian Belief Network (BBN) model was used to estimate an RRI based on the combination of the traits' scores. The BBN was used to explore environmental effects on the species' RRI, as some reproductive traits can show intraspecies variability under external forces (e.g., fishing pressure). Through proving the RRI application to detect variability in species' resilience at local time series, we show how the resulting RRI can be interpreted by fishery managers to improve the current management of SMPF. Key words: trait-based approach, expert knowledge, Bayesian Belief Network, ecological indicator, fishery management Les efforts de gestion des petits et moyens poissons pelagiques (PMPP) par des methodes traditionnelles devaluation des stocks sont limites par la mauvaise definition de la relation entre la biomasse du stock reproducteur et le recrutement. Nous proposons d'etablir un indice de resilience reproductive (IRR) par les trois etapes suivantes : (i) nous avons choisi 16 caracteres biologiques relies a differents aspects de la biologie de reproduction des PMPP et caracterises par une variable continue (p. ex., taux de croissance) ou ordinale (p. ex. fidelite au lieu de frai) notee de 1 a 5 (1 representant une faible contribution du caractere a la resilience reproductive), (ii) un panel d'experts a assigne les notes pour ces caracteres pour cinq especes exploitees dans le grand ecosysteme marin du courant de Humboldt meridional, (iii) un modele de reseau de croyances bayesien (RCB) a ete utilise pour estimer un IRR base sur la combinaison des notes des caracteres. Le RCB a ete utilise pour explorer les effets environnementaux sur l'IRR des especes, certains caracteres reproductifs pouvant presenter une variabilite intraspecifique sous l'effet de forcages externes (p. ex. la pression de peche). En demontrant l'application de l'IRR pour detecter la variabilite de la resilience d'especes pour des series chronologiques locales, nous illustrons comment l'IRR resultant peut etre interprete par les gestionnaires de peches pour ameliorer la gestion actuelle des PMPP. [Traduit par la Redaction] Mots-cles : approche basee sur les caracteres, connaissances d'experts, reseaux de croyances bayesiens, indicateur ecologique, gestion des peches, 1. Introduction In fisheries science, the term productivity refers to those factors that affect both adult biomass and our ability to sustainably capture wild fish stocks (Lowerre-Barbieri et al. 2017). [...]

Tendon and ligament (TL) injuries affect millions of people annually. Biopolymers play a significant role in TL tissue repair, whether the treatment relies on tissue engineering strategies or using artificial tendon grafts. The biopolymer governs the mechanical properties, biocompatibility, degradation, and fabrication method of the TL scaffold. Many natural, synthetic and hybrid biopolymers have been studied in TL regeneration, often combined with therapeutic agents and minerals to engineer novel scaffold systems. However, most of the advanced biopolymers have not advanced to clinical use yet. Here, we aim to review recent biopolymers and discuss their features for TL tissue engineering. After introducing the properties of the native tissue, we discuss different types of natural, synthetic and hybrid biopolymers used in TL tissue engineering. Then, we review biopolymers used in commercial absorbable and non-absorbable TL grafts. Finally, we explain the challenges and future directions for the development of novel biopolymers in TL regenerative treatment.

Abstract Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00–304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48–72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.

This paper examines the impact of CEO characteristics on the International Entrepreneurship (IE) of listed island-based firms (IBFs) during the period 2009-2018. The research considers 164 companies from a sample of eight small islands with securities exchanges including more than one firm headquartered on the island. The selected islands are: Barbados, Cyprus, Fiji, Iceland, Jamaica, Malta, Mauritius, and Trinidad & Tobago. Framed on the upper echelons theory and social network theory, the influence on IE of CEO's tenure, academic background and achievement, family allegiance, and international exposure is studied, taking into account the small island particularities. Through a binary probit model, it is concluded that CEOs' family allegiance, tenure, and academic background (if the CEO majored in Business Administration, Finance, Accounting, or Economics) are negatively related with IE, while CEOs' academic achievement and international exposure are positively associated with IE. Some of these results are atypical in the existing literature; nevertheless, islandness can explain these results. The conclusions attained suggest new theoretical and empirical lines of IE research for IBFs.

The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL-bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3–10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications.

Antecedentes: Una ostomía influye significativamente en la vida de la persona, alterando su esfera biopsicosocial y sexual, y afectando a sus relaciones interpersonales. Material y método: Estudio observacional, descriptivo y transversal. Mediante un cuestionario dirigido a profesionales de un área sanitaria de Madrid, se analizan variables sociodemográficas, conocimientos de los profesionales, derivación del paciente a un especialista según la valoración del profesional encuestado y sentimientos que produce en ellos el tema de estudio. Resultados: El 49% afirma tener conocimientos nulos sobre la sexualidad del paciente ostomizado. El 55.9% de los encuestados considera que el sanitario es quien debe introducir el tema de la sexualidad durante la entrevista clínica. El 48.5 y el 85.2% desconocen tratamientos para la disfunción sexual, masculina y femenina, respectivamente. Conclusión: Los datos demuestran que la formación impartida en los centros universitarios es insuficiente para tratar de forma efectiva este tema en la consulta. Los participantes en el estudio muestran nulo o mínimo conocimiento sobre la esfera sexualidad en el paciente ostomizado Se detectan deficiencias de conocimiento en relación con la sexualidad del ostomizado, dificultad para hablar de sexo con el paciente y valor que da el profesional a la esfera sexual en su paciente, entre otras.

Purpose: The study analyzes the evolution of Business Model Innovation (BMI) in the IT sector, which is mentioned in many available scientific publications. The major output of this paper is concrete customer requirements that invite business model innovations to managed IT services and challenges to establish corresponding business model innovations. Design/Method/Approach: The study identified more than 200 journal articles and conference articles with BMI and IT service providers, and it conducted a mapping review of current research to identify relevant academic theories, implementation strategies, and BMI in the managed IT service sector while highlighting gaps in empirical research. Findings: Most applied are BMI and the framework of dynamic capabilities in business models of IT services. Early movers, who develop a comprehensive platform strategy, can achieve an invulnerable moat and establish a leading market position. Practical Implications: The insights of this study could be applied by large companies, small- and medium-sized companies and start-ups, researchers, etc. They can use the insights to innovate their current business models and improve tailored client solutions. Originality/Value: The study concludes that business model innovations and IT service providers develop areas for future success. Research Limitations/Future Research: The design of the study is based on a systematic literature review and limited to the areas of BMI research in the IT service sector. For further research projects, individual articles can be chosen to perform in-depth analysis. Our trend analysis shows the focus on main technologies. However, this can be compared with the technologies mentioned in the Gartner Hype Cycle. Further research could be conducted to overcome limitations and cover the uncertain content of this research. Paper Type: Conceptual.

Plakophilin 1 (PKP1), a member of the p120ctn subfamily of the armadillo (ARM)-repeat-containing proteins, is an important structural component of cell–cell adhesion scaffolds although it can also be ubiquitously found in the cytoplasm and the nucleus. RYBP (RING 1A and YY1 binding protein) is a multifunctional intrinsically disordered protein (IDP) best described as a transcriptional regulator. Both proteins are involved in the development and metastasis of several types of tumors. We studied the binding of the armadillo domain of PKP1 (ARM-PKP1) with RYBP by using in cellulo methods, namely immunofluorescence (IF) and proximity ligation assay (PLA), and in vitro biophysical techniques, namely fluorescence, far-ultraviolet (far-UV) circular dichroism (CD), and isothermal titration calorimetry (ITC). We also characterized the binding of the two proteins by using in silico experiments. Our results showed that there was binding in tumor and non-tumoral cell lines. Binding in vitro between the two proteins was also monitored and found to occur with a dissociation constant in the low micromolar range (~10 μM). Finally, in silico experiments provided additional information on the possible structure of the binding complex, especially on the binding ARM-PKP1 hot-spot. Our findings suggest that RYBP might be a rescuer of the high expression of PKP1 in tumors, where it could decrease the epithelial–mesenchymal transition in some cancer cells.

The scientific community has shown considerable interest in Industry 4.0 due to its capacity to revolutionise the manufacturing sector through digitalisation and data-driven decision-making. However, the actual implementation of Industry 4.0 within complex industrial settings presents obstacles that are typically beyond the scope of mainstream research articles. In this paper, a comprehensive case-study detailing our collaborative partnership with a leading medical device manufacturer is presented. The study traces its evolution from a state of limited digitalisation to the development of a digital intelligence platform that leverages data and machine learning models to enhance operations across a wide range of critical machines and assets. The main business objective was to enhance the energy efficiency of the manufacturing process, thereby improving its sustainability measures while also saving costs. The project encompasses energy modelling and analytics, Fault Detection and Diagnostics (FDD), renewable energy integration and advanced visualisation tools. Together, these components enable informed decision making in the context of energy efficiency.

Most of the previous studies on the genetic variability in Spanish “Berrenda” breeds have been carried out using DNA microsatellites. The present work aimed to estimate the genetic diversity, population structure, and potential genetic differences among individuals of both Berrenda breeds and groups based on the presence of the Robertsonian chromosomal translocation, rob (1;29). A total of 373 samples from animals belonging to the two breeds, including 169 cases diagnosed as rob (1;29)-positive, were genotyped using an SNP50K chip. The genetic diversity at the breed level did not show significant differences, but it was significantly lower in those subpopulations containing the rob (1;29). Runs of homozygosity identified a region of homozygosity on chromosome 6, where the KIT (KIT proto-oncogene, receptor tyrosine kinase) gene, which determines the typical spotted coat pattern in both breeds, is located. The four subpopulations considered showed minor genetic differences. The regions of the genome that most determined the differences between the breeds were observed on chromosomes 4, 6, 18, and 22. The presence of this Robertsonian translocation did not result in sub-structuring within each of the breeds considered. To improve the reproductive performance of Berrenda breeds, it would be necessary to implement strategies considering the involvement of potential breeding stock carrying rob (1;29).