A Survey of MPSoC Management toward Self-Awareness.

Managing Multi-Processor Systems-on-Chip (MPSoCs) is becoming increasingly complex as demands for advanced capabilities rise. This complexity is due to the involvement of more processing elements and resources, leading to a higher degree of heterogeneity throughout the system. Over time, management schemes have evolved from simple to autonomous systems with continuous control and monitoring of various parameters such as power distribution, thermal events, fault tolerance, and system security. Autonomous management integrates self-awareness into the system, making it aware of its environment, behavior, and objectives. Self-Aware Cyber-Physical Systems-on-Chip (SA-CPSoCs) have emerged as a concept to achieve highly autonomous management. Communication infrastructure is also vital to SoCs, and Software-Defined Networks-on-Chip (SDNoCs) can serve as a base structure for self-aware systems-on-chip. This paper presents a survey of the evolution of MPSoC management over the last two decades, categorizing research works according to their objectives and improvements. It also discusses the characteristics and properties of SA-CPSoCs and explains why SDNoCs are crucial for these systems.

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review.

Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.

Meta-Transcriptomic Analysis Uncovers the Presence of Four Novel Viruses and Multiple Known Virus Genera in a Single Hibiscus rosa-sinensis Plant in Colombia.

Hibiscus is not native to Colombia but well suited to its arid soil and dry climates. A single hibiscus plant from Risaralda, showing black spots on upper and lower sides of its leaves, was collected for virome analysis using meta-transcriptomic high-throughput sequencing technology. Bioinformatic analysis identified 12.5% of the total reads in the Ribo-Zero cDNA library which mapped to viral genomes. BLAST searches revealed the presence of carlavirus, potexvirus, and of known members of the genera Betacarmovirus, Cilevirus, Nepovirus, and Tobamovirus in the sample; confirmed by RT-PCR with virus-specific primers followed by amplicon sequencing. Furthermore, in silico analysis suggested the possibility of a novel soymovirus, and a new hibiscus strain of citrus leprosis virus C2 in the mixed infection. Both RNA dependent RNA polymerase and coat protein gene sequences of the potex and carla viruses shared less than 72% nucleotide and 80% amino acid identities with any alphaflexi- and betaflexi-virus sequences available in GenBank, identifying three novel carlavirus and one potexvirus species in the Hibiscus rosa-sinensis plant. The detection of physalis vein necrosis nepovirus and passion fruit green spot cilevirus in hibiscus are also new reports from Colombia. Overall, the meta-transcriptome analysis identified the complex virome associated with the black spot symptoms on hibiscus leaves and demonstrated the diversity of virus genera tolerated in the mixed infection of a single H. rosa-sinensis plant.

Integrating Dermoscopic Images into PACS Using DICOM and Modality Worklist.

Dermatology is one of the medical fields outside the radiology service that uses image acquisition and analysis in its daily medical practice, mostly through digital dermoscopy imaging modality. The acquisition, transfer, and storage of dermatology images has become an important issue to resolve. We aimed to describe our experience in integrating dermoscopic images into PACS using DICOM as a guide for the health informatics and dermatology community. During 2022 we integrated the video dermoscopy equipment through a strategic plan with an 8-step procedure. We used the DICOM standard with Modality Worklist and Storage commitment. Three systems were involved (video dermoscopy software, the EHR, and PACS). We identified critical steps and faced many challenges, such as the lack of a final model of DICOM standard for dermatology images.

How Would I Treat My Own Chronic Thromboembolic Pulmonary Hypertension in the Perioperative Period?

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an incomplete resolution of acute pulmonary embolism, leading to occlusive organized thrombi, vascular remodeling, and associated microvasculopathy with pulmonary hypertension (PH). A definitive CTEPH diagnosis requires PH confirmation by right-heart catheterization and evidence of chronic thromboembolic pulmonary disease on imaging studies. Surgical removal of the organized fibrotic material by pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest represents the treatment of choice. One-third of patients with CTEPH are not deemed suitable for surgical treatment, and medical therapy or interventional balloon pulmonary angioplasty presents alternative treatment options. Pulmonary endarterectomy in patients with technically operable disease significantly improves symptoms, functional capacity, hemodynamics, and quality of life. Perioperative mortality is <2.5% in expert centers where a CTEPH multidisciplinary team optimizes patient selection and ensures the best preoperative optimization according to individualized risk assessment. Despite adequate pulmonary artery clearance, patients might be prone to perioperative complications, such as right ventricular maladaptation, airway bleeding, or pulmonary reperfusion injury. These complications can be treated conventionally, but extracorporeal membrane oxygenation has been included in their management recently. Patients with residual PH post-PEA should be considered for medical or percutaneous interventional therapy.

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Consensus statement on the use of biosimilar drugs in immune-mediated diseases in Spain.

OBJECTIVE: To improve knowledge about biosimilar medicines and to generate a consensus framework on their use. METHODS: Qualitative study. A multidisciplinary group of experts in biosimilar medicines was established (1dermatologist, 1hospital pharmacist, 1rheumatologist, and 1gastroenterologist) who defined the sections and topics of the document. A narrative literature review was performed in Medline to identify articles on biosimilar medicines. Systematic reviews, controlled, pre-clinical, clinical, and real-life studies were selected. Based on the results of the review, several general principles and recommendations were generated. The level of agreement was tested in a Delphi that was extended to 66 health professionals who voted from 1 (totally disagree) to 10 (totally agree). Agreement was defined if at least 70% of the participants voted ≥7. RESULTS: The literature review included 555 articles. A total of 10 general principles and recommendations were voted upon. All reached the level of agreement established. The document includes data on the main characteristics of biosimilar medicines (definition, development, approval, indication extrapolation, interchangeability, financing, and traceability); published evidence (biosimilarity, efficacy, effectiveness, safety, immunogenicity, efficiency, switch); barriers and facilitators to its use; and data on information for patients. CONCLUSIONS: Authorized biosimilar medicines meet all the characteristics of quality, efficacy, and safety. They also significantly help improve patient access to biological therapies and contribute to health system sustainability.

Documento de consenso sobre los medicamentos biosimilares en enfermedades inmunomediadas en España / Consensus statement on the use of biosimilar drugs in immune-mediated diseases in Spain

Objetivo: Mejorar el nivel de conocimiento sobre los medicamentos biosimilares y generar un marco consensuado sobre su uso. Métodos: Estudio cualitativo. Se seleccionó un grupo multidisciplinar de expertos en medicamentos biosimilares (una dermatóloga, un farmacéutico de hospital, un reumatólogo y un gastroenterólogo) que definieron los apartados y los temas del documento. Se realizó una revisión narrativa de la literatura en Medline para identificar artículos sobre los medicamentos biosimilares. Se seleccionaron revisiones sistemáticas de la literatura, estudios controlados pre-clínicos, clínicos y en vida real. Con esta información se generaron varios principios generales y recomendaciones. El grado de acuerdo con los mismos se estableció mediante un Delphi que se extendió a 66 profesionales de la salud que votaron de 1 (totalmente en desacuerdo) a 10 (totalmente de acuerdo). Se definió acuerdo si al menos el 70% de los participantes votaron ≥7. Resultados: La revisión de la literatura incluyó 555 artículos. Se votaron un total de 10 principios generales y recomendaciones. Todos alcanzaron el nivel de acuerdo establecido en el Delphi. El documento incluye datos sobre las características principales de los medicamentos biosimilares (definición, desarrollo, aprobación, extrapolación de indicaciones, intercambiabilidad, financiación y trazabilidad); sobre la evidencia publicada (biosimilitud, eficacia, efectividad, seguridad, inmunogenicidad, eficiencia, switch); sobre barreras y facilitadores a su uso, y datos sobre la información para pacientes. Conclusiones: Los medicamentos biosimilares autorizados reúnen todas las características de calidad, eficacia y seguridad. Además, ayudan significativamente a mejorar el acceso de los pacientes a las terapias biológicas y contribuyen a la sostenibilidad de los sistemas sanitarios. (AU)

Objective: To improve knowledge about biosimilar medicines and to generate a consensus framework on their use. Methods: Qualitative study. A multidisciplinary group of experts in biosimilar medicines was established (1dermatologist, 1hospital pharmacist, 1rheumatologist, and 1gastroenterologist) who defined the sections and topics of the document. A narrative literature review was performed in Medline to identify articles on biosimilar medicines. Systematic reviews, controlled, pre-clinical, clinical, and real-life studies were selected. Based on the results of the review, several general principles and recommendations were generated. The level of agreement was tested in a Delphi that was extended to 66 health professionals who voted from 1 (totally disagree) to 10 (totally agree). Agreement was defined if at least 70% of the participants voted ≥7. Results: The literature review included 555 articles. A total of 10 general principles and recommendations were voted upon. All reached the level of agreement established. The document includes data on the main characteristics of biosimilar medicines (definition, development, approval, indication extrapolation, interchangeability, financing, and traceability); published evidence (biosimilarity, efficacy, effectiveness, safety, immunogenicity, efficiency, switch); barriers and facilitators to its use; and data on information for patients. Conclusions: Authorized biosimilar medicines meet all the characteristics of quality, efficacy, and safety. They also significantly help improve patient access to biological therapies and contribute to health system sustainability. (AU)

Versatile Biodegradable Poly(acrylic acid)-Based Hydrogels Infiltrated in Porous Titanium Implants to Improve the Biofunctional Performance.

This research work proposes a synergistic approach to improve implants' performance through the use of porous Ti substrates to reduce the mismatch between Young's modulus of Ti (around 110 GPa) and the cortical bone (20-25 GPa), and the application of a biodegradable, acrylic acid-based polymeric coating to reduce bacterial adhesion and proliferation, and to enhance osseointegration. First, porous commercially pure Ti substrates with different porosities and pore size distributions were fabricated by using space-holder techniques to obtain substrates with improved tribomechanical behavior. On the other hand, a new diacrylate cross-linker containing a reduction-sensitive disulfide bond was synthesized to prepare biodegradable poly(acrylic acid)-based hydrogels with 1, 2, and 4% cross-linker. Finally, after the required characterization, both strategies were implemented, and the combination of 4% cross-linked poly(acrylic acid)-based hydrogel infiltrated in 30 vol % porosity, 100-200 µm average pore size, was revealed as an outstanding choice for enhancing implant performance.

Emerging Strategies to Improve the Design and Manufacturing of Biocompatible Therapeutic Materials.

Currently, the field of medicine is drastically advancing, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the liberation, absorption, distribution, metabolism, and excretion (LADME) properties of the derived formulations, with a consequent enhancement in the treatment efficacy, a reduction in the secondary effects, and an increase in compliance with the dosage guidelines. Additionally, the use of biocompatible scaffolds is translating into the possibility of regenerating biological tissues. Personalized medicine is also benefiting from the advantages offered by additive manufacturing. However, all these areas have in common the need to develop novel materials or composites that fulfill the requirements of each application. Therefore, the aim of this Special Issue was to identify novel materials/composites that have been developed with specific characteristics for the designed biomedical application.

Perioperative Management in Pulmonary Endarterectomy.

Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH), provided lesions are proximal enough in the pulmonary vasculature to be surgically accessible and the patient is well enough to benefit from the operation in the longer term. It is a major cardiothoracic operation, requiring specialized techniques and instruments developed over several decades to access and dissect out the intra-arterial fibrotic material. While in-hospital operative mortality is low (<5%), particularly in high-volume centers, careful perioperative management in the operating theater and intensive care is mandatory to balance ventricular performance, fluid balance, ventilation, and coagulation to avoid or treat complications. Reperfusion pulmonary edema, airway hemorrhage, and right ventricular failure are the most problematic complications, often requiring the use of extracorporeal membrane oxygenation to bridge to recovery. Successful PEA has been shown to improve both morbidity and mortality in large registries, with survival >70% at 10 years. For patients not suitable for PEA or with residual PH after PEA, balloon pulmonary angioplasty and/or PH medical therapy may prove beneficial. Here, we describe the indications for PEA, specific surgical and perioperative strategies, postoperative monitoring and management, and approaches for managing residual PH in the long term.

Obtaining of Mg-Zn Co-Doped GaN Powders via Nitridation of the Ga-Mg-Zn Metallic Solution and Their Structural and Optical Properties.

Mg-Zn co-dopedGaN powders via the nitridation of a Ga-Mg-Zn metallic solution at 1000 °C for 2 h in ammonia flow were obtained. XRD patterns for the Mg-Zn co-dopedGaN powders showed a crystal size average of 46.88 nm. Scanning electron microscopy micrographs had an irregular shape, with a ribbon-like structure and a length of 8.63 µm. Energy-dispersive spectroscopy showed the incorporation of Zn (Lα 1.012 eV) and Mg (Kα 1.253 eV), while XPS measurements showed the elemental contributions of magnesium and zinc as co-dopant elements quantified in 49.31 eV and 1019.49 eV, respectively. The photoluminescence spectrum showed a fundamental emission located at 3.40 eV(364.70 nm), which was related to band-to-band transition, besides a second emission found in a range from 2.80 eV to 2.90 eV (442.85-427.58 nm), which was related to a characteristic of Mg-doped GaN and Zn-doped GaN powders. Furthermore, Raman scattering demonstrated a shoulder at 648.05 cm-1, which could indicate the incorporation of the Mg and Zn co-dopants atoms into the GaN structure. It is expected that one of the main applications of Mg-Zn co-doped GaN powders is in obtaining thin films for SARS-CoV-2 biosensors.

Membrane Vesicles of Toxigenic Clostridioides difficile Affect the Metabolism of Liver HepG2 Cells.

Clostridioides difficile infection (CDI) appears to be associated with different liver diseases. C. difficile secretes membrane vesicles (MVs), which may be involved in the development of nonalcoholic fatty liver disease (NALFD) and drug-induced liver injury (DILI). In this study, we investigated the presence of C. difficile-derived MVs in patients with and without CDI, and analyzed their effects on pathways related to NAFLD and DILI in HepG2 cells. Fecal extracellular vesicles from CDI patients showed an increase of Clostridioides MVs. C. difficile-derived MVs that were internalized by HepG2 cells. Toxigenic C. difficile-derived MVs decreased mitochondrial membrane potential and increased intracellular ROS compared to non-toxigenic C. difficile-derived MVs. In addition, toxigenic C. difficile-derived MVs upregulated the expression of genes related to mitochondrial fission (FIS1 and DRP1), antioxidant status (GPX1), apoptosis (CASP3), glycolysis (HK2, PDK1, LDHA and PKM2) and ß-oxidation (CPT1A), as well as anti- and pro-inflammatory genes (IL-6 and IL-10). However, non-toxigenic C. difficile-derived MVs did not produce changes in the expression of these genes, except for CPT1A, which was also increased. In conclusion, the metabolic and mitochondrial changes produced by MVs obtained from toxigenic C. difficile present in CDI feces are common pathophysiological features observed in the NAFLD spectrum and DILI.

The Metagenomic Composition and Effects of Fecal-Microbe-Derived Extracellular Vesicles on Intestinal Permeability Depend on the Patient's Disease.

The composition and impact of fecal-microbe-derived extracellular vesicles (EVs) present in different diseases has not been analyzed. We determined the metagenomic profiling of feces and fecal-microbe-derived EVs from healthy subjects and patients with different diseases (diarrhea, morbid obesity and Crohn's disease (CD)) and the effect of these fecal EVs on the cellular permeability of Caco-2 cells. The control group presented higher proportions of Pseudomonas and Rikenellaceae_RC9_gut_group and lower proportions of Phascolarctobacterium, Veillonella and Veillonellaceae_ge in EVs when compared with the feces from which these EVs were isolated. In contrast, there were significant differences in 20 genera between the feces and EV compositions in the disease groups. Bacteroidales and Pseudomonas were increased, and Faecalibacterium, Ruminococcus, Clostridium and Subdoligranum were decreased in EVs from control patients compared with the other three groups of patients. Tyzzerella, Verrucomicrobiaceae, Candidatus_Paracaedibacter and Akkermansia were increased in EVs from the CD group compared with the morbid obesity and diarrhea groups. Fecal EVs from the morbid obesity, CD and, mainly, diarrhea induced a significant increase in the permeability of Caco-2 cells. In conclusion, the metagenomic composition of fecal-microbe-derived EVs changes depending on the disease of the patients. The modification of the permeability of Caco-2 cells produced by fecal EVs depends on the disease of the patients.

Prehabilitation Before Gastrointestinal Cancer Surgery: Protocol for an Implementation Study.

BACKGROUND: Surgery remains the standard curative treatment for early-stage colorectal and upper gastrointestinal cancer. Reduced preoperative functional capacity, nutritional status, and psychological well-being are associated with poor postoperative outcomes. Prehabilitation aims to improve preoperative functional reserves through physical, nutritional, and psychological interventions. Yet, how it transitions from a trial setting to being integrated into a real-world health setting is unknown. OBJECTIVE: The primary aim is to evaluate the implementation of a multimodal (supervised exercise, nutrition, and nursing support) prehabilitation program into standard care for patients with gastrointestinal cancer (colorectal and upper gastrointestinal cancer) scheduled for curative intent surgery. The secondary aim is to determine the impact of a multimodal prehabilitation program on functional capacity, nutritional and psychological status, and surgical outcomes. METHODS: This is an implementation study that will investigate a multimodal prehabilitation intervention, in a nonblinded, nonrandomized, single-group, pre-post design. Patients diagnosed with colorectal and upper gastrointestinal cancer scheduled for potentially curative intent surgery at Concord Repatriation General Hospital, with ≥14 intervention days prior to surgery and are medically cleared to exercise will be eligible. The study will be evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Evaluation Framework. RESULTS: The protocol was approved in December 2019 by the Concord Repatriation General Hospital Human Research Ethics Committee (reference number 2019/PID13679). Recruitment commenced in January 2020. In response to the COVID-19 pandemic, recruitment was paused in March 2020 and reopened in August 2020 with remote or telehealth intervention adaptations. Recruitment ended on December 31, 2021. Over the 16-month recruitment period, a total of 77 participants were recruited. CONCLUSIONS: Prehabilitation represents an opportunity to maximize functional capacity and improve surgical outcomes. The study will provide guidance and contribute to the evidence on the integration of prehabilitation into standard care using adaptive models of health care delivery including telehealth. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTR 12620000409976; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378974&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/41101.

Highlights from the International Chronic Thromboembolic Pulmonary Hypertension Congress 2021.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by chronic organised fibrotic clots, despite adequate anticoagulation. The pulmonary hypertension is also caused by concomitant microvasculopathy which may progress without timely treatment. Timely and accurate diagnosis requires the combination of imaging and haemodynamic assessment. Optimal therapy should be individualised to each case and determined by an experienced multidisciplinary CTEPH team with the ability to offer all current treatment modalities. This report summarises current knowledge and presents key messages from the International CTEPH Conference, Bad Nauheim, Germany, 2021. Sessions were dedicated to 1) disease definition; 2) pathophysiology, including the impact of the hypertrophied bronchial circulation, right ventricle (dys)function, genetics and inflammation; 3) diagnosis, early after acute pulmonary embolism, using computed tomography and perfusion techniques, and supporting the selection of appropriate therapies; 4) surgical treatment, pulmonary endarterectomy for proximal and distal disease, and peri-operative management; 5) percutaneous approach or balloon pulmonary angioplasty, techniques and complications; and 6) medical treatment, including anticoagulation and pulmonary hypertension drugs, and in combination with interventional treatments. Chronic thromboembolic pulmonary disease without pulmonary hypertension is also discussed in terms of its diagnostic and therapeutic aspects.

Hypersaline environments as natural sources of microbes with potential applications in biotechnology: The case of solar evaporation systems to produce salt in Alicante County (Spain).

Extremophilic microbes show a unique metabolism due to the adaptations they display to deal with extreme environmental parameters characterizing the extreme ecosystems that they inhabit (high salt concentration, high temperatures, and extreme pH values, high exposure to solar radiation etc.). Halophilic microorganisms characterised and isolated from saltmarshes, brines, salted ponds, salty lagoons etc. have recently attracted attention due to their potential biotechnological applications (as whole cells used for different purposes like wastewater treatments, or their biomolecules: enzymes, antibiotics, carotenoids, bioplastics). Alicante county (southeast of Spain) accounts for a significant number of salty environments like coastal or inland salty ponds from where sodium chloride (NaCl)is obtained, marshes, salty lagoons, etc. The best system characterised so far from a microbiological point of view is "Salinas de Santa Pola", also termed "Salinas Bras del Port". However, there are many other salty environments to be explored, like the natural park of Torrevieja and la Mata lagoons, salty lagoon located in Calpe city or inland salted ponds like those located in the northwest of the county. This review summarises the most relevant biotechnological applications of halophilic microbes described up to now. In addition, special attention is focused on ecosystems such as the lagoons of Torrevieja or inland salt marshes as natural environments whose microbial biodiversity is worthy of being studied in search of new strains and species with the aim to analyze their potential biotechnological applications (pharmaceutical, food industry, biomedicine, etc.).