Search

Abstract Atmospheric new particle formation (NPF) is a naturally occurring phenomenon, during which high concentrations of sub-10 nm particles are created through gas to particle conversion. The NPF is observed in multiple environments around the world. Although it has observable influence onto annual total and ultrafine particle number concentrations (PNC and UFP, respectively), only limited epidemiological studies have investigated whether these particles are associated with adverse health effects. One plausible reason for this limitation may be related to the absence of NPF identifiers available in UFP and PNC data sets. Until recently, the regional NPF events were usually identified manually from particle number size distribution contour plots. Identification of NPF across multi-annual and multiple station data sets remained a tedious task. In this work, we introduce a regional NPF identifier, created using an automated, machine learning based algorithm. The regional NPF event tag was created for 65 measurement sites globally, covering the period from 1996 to 2023. The discussed data set can be used in future studies related to regional NPF.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.

The dynamics of a two-wheeled vehicle represent a higher level of complexity, with a high variety of rider practices, peculiarly during the bend-taking maneuver. This complexity is one reason why research on motorcyclists’ practiced trajectories is limited compared to cars. Another reason is the low representation of motorcycles in the land motor vehicle fleet.The dataset was collected within the framework of the French ANR research project VIROLO++. The objective was twofold. One concerns the analysis of the interactions between a rider and the motorcycle during a bend-taking maneuver. The second aims at studying the precise trajectory of a motorcycle.Multi-sensor instrumentation of a motorcycle (Honda CBF1000) has been achieved for precise trajectory reconstruction as well as the analysis of the interactions between the rider and the motorcycle during a ride. Real experiments were conducted on the “La Ferté Gaucher'' racetrack. The collected data include the precise location and attitude of the motorcycle and rider. Several sensors providing redundant data have been embedded to validate measurements. Two RTK GPS receivers were installed at the rear of the motorcycle to provide ground truth. A preliminary analysis was performed to validate the consistency of the dataset and the relevance of the sensors according to the aimed study.

Abstract One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.

Abstract Background Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days. Conclusions This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.

The franciscana dolphin (Pontoporia blainvillei) is a small cetacean endemic to the coastal waters of the southwestern Atlantic Ocean. Due to its restricted distribution, it is subject to high bycatch mortality in the gillnets used for commercial and artisanal fishing. The rehabilitation of the franciscana is still a major challenge, as most attempts to rehabilitate stranded animals have failed. This study aims to present the case of the rehabilitation of a franciscana dolphin calf, stranded in San Clemente del Tuyú, Argentina, at the beginning of the predation period. The feeding strategy and nutritional profile at different stages during the 88 days of rehabilitation are meticulously detailed. Its diet was prepared by hand based on studies of milk composition, the feeding ecology of franciscana in Argentinean waters, and previous records of the Fundación Mundo Marino Rehabilitation Center. The diets were designed to meet the nutritional needs of franciscana dolphins. In addition, the hematological, cytological, and fecal analyses recorded during the rehabilitation are presented. Although the animal could not be released, due to its death, this report provides baseline information that can improve the ability of veterinarians to care for debilitated, live-stranded dolphins. This information may also be useful in the implementation and development of healthcare protocols for this species.

Despite being the largest group in the Salesian Family, with 100,000 affiliated members worldwide, the Past Pupils of Don Bosco Movement has to date lacked a biography of their charismatic founder, the Turin-born Carlo Gastini (1833–1902), the 120th anniversary of whose death was commemorated in 2022. A family man, bookbinder and teacher, as well as occasional poet and actor, he was the first boarder at the Oratory of Saint Francis de Sales. Little was known about him, beyond three specific anecdotes. However, from 1847 to 1902, he was linked to Valdocco as a pupil (first as a day pupil and then as a boarder), seminarian, parishioner, worker and entertainer. His life was parallel to that of Don Bosco himself, who was a second father to him, and to the development of his own congregation, the Salesian Family and even Italy as a nation. The culmination of his gratitude since 1849 was the charismatic foundation, in 1870, of the Past Pupils of Don Bosco Movement, which celebrated its 150th anniversary in 2020. Its basis was simple: create an instrument of mutual help among his former colleagues, just as Don Bosco had taught them to do when they were students at the Oratory. Creating a cohesive group centred on values ​​is a proposal for facing difficulties together. In Spain, the Movement found one of its deepest-rooted abodes.

The franciscana dolphin is a small, vulnerable species often caught in artisanal gillnets. This study aims to provide a comprehensive assessment of their acoustic capabilities by using advanced equipment to collect a large dataset of wideband, continuous recordings. We examined the detailed acoustic signals of franciscana dolphins, comparing the sounds from rehabilitated dolphins in captivity with those of wild dolphins near fishing nets. Significant differences in acoustic characteristics were found between neonates and older dolphins, with juvenile and wild dolphins showing similar features. For the first time, repetition patterns in click production were identified, highlighting the importance of understanding the context of these sounds in regards to feeding and communication. This study emphasizes the need for detecting neonates for species protection and suggests the potential for developing acoustic classifiers specific to different age groups. Our findings offer valuable insights for conservation efforts and the development of protection strategies for franciscana dolphins.

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score >- 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Abstract Arthropod-borne virus (arbovirus) and arthropod-specific virus (ASV) are viruses circulating amongst hematophagous arthropods that are broadly transmitted in ecological systems. Arbovirus may replicate in both vertebrates and invertebrates and some are known to be pathogenic to animals or humans. ASV only replicate in invertebrate arthropods yet they are basal to many types of arboviruses. We built a comprehensive dataset of arbovirus and ASV by curating globally available data from the Arbovirus Catalog, the arbovirus list in Section VIII-F of the Biosafety in Microbiological and Biomedical Laboratories 6th edition, Virus Metadata Resource of International Committee on Taxonomy of Viruses, and GenBank. Revealing the diversity, distribution and biosafety recommendation of arbovirus and ASV at a global scale is essential to the understanding of potential interactions, evolution, and risks associated with these viruses. Moreover, the genomic sequences associated with the dataset will enable the investigation of genetic patterns distinguishing the two groups, as well as aid in predicting the vector/host relationships of the newly discovered viruses.

The purpose of this study is to compare IVC Celect and ALN filters in regard to their efficacy, retrievability, and one-year follow-up after retrieval. Materials and Methods: This is a prospective randomized study, conducted in three centers between April 2020 and May 2021. A total of 115 participants were randomized, of which 15 participants were excluded for various reasons. Each group of 50 participants was finally assigned a type of filter (Celect n = 50 and ALN = 50). Tilt angles at placement and retrieval, rates of overall filter retrieval, complications, complex retrieval, and clinical follow-up at 12 months were compared. Results: One hundred participants (59 men and 41 women) were included. The mean age was 62.4 ± 13.3, with no significant differences between both groups (p 0.503). The mean of dwelling time was 44.7 ± 93 days. (p 0.520) Filter retrieval was successful in all participants (100%). The main complication in CT prior to removal was tilt >15° (31%) and filter tip embedment (16%). No significant differences were observed in the type of retrieval (standard or complex) between both filters (p 0.24); however, fluoroscopy time was significantly longer in the complex removal of the Celect filter: 29.1 ± 12 min vs. 17.5 ± 10.3 (p 0.005). After one year, no recurrent pulmonary embolism was observed in both types of filters. Conclusions: The ALN filter had a significantly lower rate of tip and filter tip embedding, with no differences in complexity or removal success rate. There were significant differences in the fluoroscopy time consumed for standard and complex retrievals between both filters, with less time for the ALN filter.

Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo.

Este artículo presenta los resultados de un estudio exploratorio y empírico sobre la protesta digital k-pop desplegada durante el Paro Nacional de 2021 en Colombia. Utilizando métodos mixtos y un corpus de 134 144 tuits, se indagó sobre las dinámicas que caracterizan esta forma de activismo político digital y el repertorio de tácticas empleadas por los participantes de esta acción colectiva. Además, por medio de un análisis de contenido multimodal a una muestra aleatoria de 1840 tuits publicados con el hashtag #RepudioAlVándalo, se caracterizaron las imágenes y textos utilizados para controlar el flujo de información y capturar la atención pública en la plataforma digital Twitter. Los resultados de la investigación revelan que las tácticas de resistencia algorítmica, secuestro de hashtags y spam se desplegaron en la acción k-pop de forma efectiva y que consiguieron sabotear los públicos-hashtag que buscaban estigmatizar a los manifestantes y apoyar el uso de la fuerza contra la protesta. A manera de conclusión, se reflexiona sobre la efectividad del movimiento global-local k-pop, la evolución de las tácticas de activismo político digital y su problemática asociación con la terminología de la guerra de la información.

ObjectivesThis study aimed to report the prevalence and identify potential risk factors of chronic conditions among West African migrants living in the greater Barcelona area, Spain, and explore the relationship between years of residence in Spain and chronic disease burden.MethodsThis cross-sectional study included 436 adult African migrants who participated in a community-based hepatitis B virus (HBV) screening and vaccination program (HBV-COMSAVA) in the greater Barcelona area from 21 November 2020 to 22 January 2022. Data were analyzed using standard descriptive statistics and bivariable and multivariable logistic regression.ResultsHBV, non-communicable diseases (NCDs) and metabolic risk factors, and multimorbidity prevalence were 9.17, 20.87, and 4.13%, respectively. Being male or having been previously tested for HBV were associated with higher odds of HBV positivity. Associated risk factors for NCDs and metabolic risk factors included living in Spain for >5 years, being female, and being aged ≥50 years.ConclusionThe high prevalence of chronic conditions in migrant populations supports a need for early detection strategies and tailored public health interventions that aim to reduce the disease burden imposed on migrants and on health systems in host countries.

Summary: The relevance of extracellular matrix (ECM) remodeling is reported in white adipose tissue (AT) and obesity-related dysfunctions, but little is known about the importance of ECM remodeling in brown AT (BAT) function. Here, we show that a time course of high-fat diet (HFD) feeding progressively impairs diet-induced thermogenesis concomitantly with the development of fibro-inflammation in BAT. Higher markers of fibro-inflammation are associated with lower cold-induced BAT activity in humans. Similarly, when mice are housed at thermoneutrality, inactivated BAT features fibro-inflammation. We validate the pathophysiological relevance of BAT ECM remodeling in response to temperature challenges and HFD using a model of a primary defect in the collagen turnover mediated by partial ablation of the Pepd prolidase. Pepd-heterozygous mice display exacerbated dysfunction and BAT fibro-inflammation at thermoneutrality and in HFD. Our findings show the relevance of ECM remodeling in BAT activation and provide a mechanism for BAT dysfunction in obesity.

Background: The purpose of this review is to explore the evidence and efficacy of two trends in early childhood intervention services: the family-centered model and the use of tele-intervention. Methods: A systematic review was carried out following the PRISMA methodology and using three databases: Web of Science, PubMed and Scopus. The studies included were those aimed at children from 0 to 6 years of age, focused on early intervention, and which alluded to the family-centered model and/or tele-intervention. Results: a total of 33 studies were included. Five main themes were identified: (1) The participation of children and family is facilitated and improved by the family-centered model of care; (2) the feeling of competence, self-efficacy, satisfaction and empowerment in professionals and families have a positive impact on quality of life; (3) the use of tele-intervention as a tool for prevention and intervention; (4) preparation for telepractice can improve the development of commitment; (5) tele-intervention as a possible solution to contextual barriers. Conclusions: Tele-intervention in pediatrics is presented as a tool inherent to the family-centered model since its implementation involves several common strategies. Future lines of research should explore the use of this tool as a possible solution to contextual barriers.

Background: Benign esophageal strictures arise from various etiologies, mostly severe esophagitis. Although endoscopic balloon dilation is still the first-line therapy, refractory or recurrent strictures do occur and remain a challenge to the endoluminal treatment. The aim of this report was to communicate a recurrent esophageal stricture resolution in a cat treated with balloon dilatation and steroids injection in Ciudad de Buenos Aires, Argentina. Case Description: A 1-year-old spayed mix-breed female cat consulted to the Veterinary Endoscopy Service, for recurring regurgitation after two previous esophageal dilations. The cat had received doxycycline for Mycoplasma spp. infection and 20 days after the treatment consulted for dysphagia and regurgitation. Upper esophagogastroscopy (UGE) was performed with an Olympus CV-160 8,7 mm diameter endoscope, an annular 7 mm stricture was observed 3 cm caudal to the cranial esophagus sphincter. Three balloon dilatations procedures were performed with a Boston Scientific CRE balloon 8-10-12 mm of one minute each. Because of ongoing clinical signs, another UGE was performed 15 days from the first procedure: a 3 mm stricture was encounter, balloon dilatation was repeated with 6-10-12 mm diameter and a four quadrant triamcinolone was injected in the submucosa. Clinically the cat could eat with no alterations until day 20, where it started with mild dysphagia. Another UE was performed, the known stricture conserved a 11 mm diameter and balloon dilatation 12-15-16,5 mm with triamcinolone injection was repeated 30 days after the previous procedure. The cat could eat kibbles with no clinical signs in a 11-month follow-up. Conclusion: The alternative of triamcinolone injection after balloon dilatation presented in this clinical report was successful and it could be a therapeutic option for recurrent esophageal strictures in cats as it is in human medicine.

Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.

Coronavirus disease 2019 (COVID-19) is a highly communicable viral infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), which has spread rapidly throughout the world. From a computer science point of view, research efforts have focused on the use of approaches such as machine learning and curve fitting to predict or simulate disease behavior. However, the mathematical characterization of the spread of COVID-19 is a topic that has not yet been explored by these techniques. In this work, we propose a novel metaheuristic framework called META-COVID19, which merges the Generalized Boltzmann distribution and the family of Jacobi polynomials to automatically characterize the COVID-19 spread without prior knowledge of the data and without involving a human expert. In general terms, the algorithm receives as input a time series of daily reported cases and the output is a polynomial mathematical model. Our framework only needs a single parameter, which is the number of Jacobi polynomials to analyze during the iterative process, and it is capable of proposing polynomials whose adjustment error is close to 1E-3. Finally, we show the applicability of the polynomial models found by META-COVID19, through a theoretical mathematical analysis in order to know attributes of the spread of COVID-19 in different periods of time, allowing to generate better strategies to face it in the future.

The aeronautical industry is one of the last groups which has decided to join the distributed architecture trend in order to increase both the safety and efficiency of future aircraft. However, the actual power system used in aircrafts has certain limitations that makes it difficult to achieve this objective due to its high centralisation. This paper proposes a novel methodology for the design of a new modular power electronic device that is based on semiconductor technology, which provides the equipment and functionality that makes the full decentralisation of the aircraft DC power system possible in the near future. The proposed and developed device can be adapted to the requirements of the system where it is going to be implanted, as it is possible to add as many devices as the system needs and have as many modules as needed. All the modules are bidirectional, which makes the system more redundant and fault tolerant, as the number of possible paths to feed the loads is increased. Tests were carried out with 5 devices (4 modules per device), 3 power supplies and 2 loads, where the correct operation of the system (path search, load feed and failure management) was proved.

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.

The indoor Visual Simultaneous Localization And Mapping (V-SLAM) dataset with various acquisition modalities has been created to evaluate the impact of acquisition modalities on the Visual SLAM algorithm’s accuracy. The dataset contains different sequences acquired with different modalities, including RGB, IR, and depth images in passive stereo and active stereo modes. Each sequence is associated with a reference trajectory constructed with an Structure From Motion (SFM) and Multi View Stereo (MVS) library for comparison. Data were collected using an intrinsically calibrated Intel RealSense D435i camera. The RGB/IR and depth data are spatially aligned, and the stereo images are rectified. The dataset includes various areas, some with low brightness, with changes in brightness, wide, narrow and texture.

Vibrio europaeus is an emergent pathogen affecting clams, oysters and scallops produced in the most important countries for bivalve aquaculture. Studies concerning virulence factors involved in the virulence of V. europaeus are very scarce despite its global significance for aquaculture. Zinc-metalloproteases have been described as a major virulence factor in some Vibrio spp., although their contribution and role in the virulence of V. europaeus is not clear. To address this, we have studied an extracellular zinc-metalloprotease (VemA) encoded by V. europaeus, which was identified as a vibriolysin, highly conserved in this species and homologous in other pathogenic and non-pathogenic species. Virulence challenge experiments demonstrated that infection processes were faster when Manila clam larvae and juveniles were infected with the wildtype rather than with a mutant defective in the vemA gene (ΔvemA). V. europaeus was able to resist the bactericidal action of mucus and displayed a chemotaxis ability favoured by VemA to colonize the body mucus of clams and form a biofilm. The overall results suggest that VemA, although it is not a major virulence factor, plays a role in the colonization of the Manila clam mucus, and thus boosts the infection process as we observed in virulence challenge experiments.

Marine plastic pollution is projected to increase globally in the next few decades. This holds true for South America where the number of species that interacts with plastics is increasing. In this study, we explore for the first time the potential of certain charismatic species of marine turtles, mammals and seabirds as indicators of plastic pollution in the Río de la Plata (RdP), one of the largest and most important estuarine areas of the Southwest Atlantic. Through a revision of published studies integrated with unpublished data, we summarize studies on the interaction of charismatic marine species with plastics in the region and evaluate their role as indicators of plastic pollution in the RdP based on aspects of their local ecology and key attributes (i.e., biological/ecological, methodological, and conservation attributes) of indicator species. We found that at least 45 charismatic marine species interact –whether by ingestion or entanglement– with plastics in the region. Eight of these species were selected as potential indicators given their occurrence, probability of sampling and interaction with plastics in the RdP, namely: Chelonia mydas, Caretta caretta, Dermochelys coriacea, Pontoporia blainvillei, Arctocephalus australis, Otaria flavescens, Larus dominicanus, and Spheniscus magellanicus. The species shared some key attributes of indicator species, e.g., they are relatively well studied, but differed in critical aspects such as their home range and mobility. We discuss whether the species’ attributes are strengths or weaknesses according to the available knowledge on their ecology in the RdP, and propose a multispecies indicator of plastic pollution given that those strengths and weaknesses can be compensated among species. Monitoring plastic pollution through a combination of species would enable a better understanding of plastic pollution in this relevant area.

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

RESUMEN Objetivos: Determinar la efectividad del tratamiento de la hepatitis C crónica definida como la respuesta viral sostenida a las 12 semanas (RVS12) tras la finalización del tratamiento con fármacos antivirales de acción directa (AAD) (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir y grazoprevir/elbasvir) en pacientes atendidos en la consulta de farmacia ambulatoria. Métodos: estudio retrospectivo que incluye los pacientes atendidos por farmacia que iniciaron tratamiento con AAD entre el 1 de diciembre de 2017 y el 31 de mayo de 2018. Se registraron datos demográficos, de la enfermedad, grado de adherencia y consultas sobre el tratamiento (interacciones, efectos adversos y otras). Resultados: Se incluyeron 205 pacientes con diferentes genotipos de hepatitis C, estados de fibrosis y grados de morbilidad. La efectividad fue del 99,5%, similar a la reportada en los ensayos clínicos. Conclusiones: Estos resultados se asemejan a los obtenidos en las consultas de farmacia en Estados Unidos, funcionando desde hace más de diez años.

Emerging technologies in the context of Autonomous Vehicles (AV) have drastically evolved the industry’s qualification requirements. AVs incorporate complex perception and control systems. Teaching the associated skills that are necessary for the analysis of such systems becomes a very difficult process and existing solutions do not facilitate learning. In this study, our efforts are devoted to proposingan open-source scale model vehicle platform that is designed for teaching the fundamental concepts of autonomous vehicles technologies that are adapted to undergraduate and technical students. The proposed platform is as realistic as possible in order to present and address all of the fundamental concepts that are associated with AV. It includes all on-board components of a stand-alone system, including low and high level functions. Such functionalities are detailed and a proof of concept prototype is presented. A set of experiments is carried out, and the results obtained using this prototype validate the usability of the model for the analysis of time- and energy-constrained systems, as well as distributed embedded perception systems.

Background Canine tracheal collapse is a complex airway pathology without promising treatment results. Currently nitinol stents are the best surgical option; however, some professionals are doubting if stent placement is the best option due to the associated complications. Objective Determine the technical feasibility, safety, and long-term follow-up after the implantation of a new tracheal stent designed for canine tracheal collapse. Methods Thirteen healthy, adult female New Zealander rabbits were involved in this pilot study.A new intra-tracheal device (Reference number 902711 patent registered as CasMin-Twine) was implanted in ten animals. Deployment was performed under general anesthesia, making a puncture incision via a 21 Gauge needle in the intra-tracheal space where the stent was introduced with a screwing process. The device was fixed to the tracheal wall with a non-absorbable suture. Computerized Tomography (CT) and an endoscopy to study structural abnormalities were performed after 30, 90 and 365 days after stent placement. Results Technical and clinical success was 100%. There was no significant change in behavior or respiratory disorders. CT studies showed no significant alterations. After the 30 days, 60% of the animals showed partial endothelization in the endoscopy study, and only one animal still presented partial endothelization after 12 months. Mucus accumulation was only present in 40% of cases and classified as low, without respiratory consequences. Only one animal presented a single granuloma at caudal stent tip. Conclusions This new tracheal stent (CasMin-Twine) is an effective and safe procedure with promising results, and also shows the possibility of removing the device after endothelization has been produced. New studies should be carried out to evaluate the effectiveness in patients with tracheomalacia. Clinical Significance/Impact This new product can give veterinarians a new option of treatment for this complicated pathology. Minimizing specific equipment for its deployment, CasMin-Twine will be more accessible for all professionals.

One of the repeating themes around the provision of the knowledge and skills needed for delivering sustainable communities is the idea of a “common language” for all built environment professionals. This suggestion has been repeated regularly with each new political and professional review within and between different sectors responsible for the delivery of sustainable communities. There have been multiple efforts to address academic limitations, industry fragmentation and promote more interdisciplinary working and sector collaboration. This research explored the role of skills for sustainable communities, particularly within the higher education (HE) sector, and the responses to support the development of a “common language of sustainability” that can be shared between different sectors, professional disciplines and stakeholders. As an interdisciplinary group of academics and practitioners working with the HE sector in the North East of England, we evaluate the progression of sector collaboration to develop a quintuple helix model for HE. We use this as a suitable framework for systematically “mapping” out the mixed sector (academic, public, business, community and environmental organisations) inputs and influences into a representative sample of HE degree modules that are delivered from foundation and undergraduate to postgraduate levels, including examples of part-time and distance-learning modules. We developed a cascade of models which demonstrate increasing levels of collaboration and their potential positive impact on the effectiveness of education on sustainable communities. The methodological assessments of modules were followed by semi-structured group reflective analysis undertaken through a series of online workshops (recorded during the Covid19 lockdown) to set out a collective understanding of the generic skills needed for the delivery of sustainable communities. These generic skills for sustainable communities are presented as a pedagogical progression model of teaching activities and learning outcomes applied to the levels within HE. We propose sustainability education principles and progressions with the hope that they can have an impact on the design or review of current degree modules and programmes. The paper informs future sustainability research to be grounded in holism and systems thinking; better understanding of values, ethics, influencing and political impact; and procedural authenticity.

Autonomous driving systems tightly rely on the quality of the data from sensors for tasks such as localization and navigation. In this work, we present an integrity monitoring framework that can assess the quality of multimodal data from exteroceptive sensors. The proposed multisource coherence-based integrity assessment framework is capable of handling highway as well as complex semi-urban and urban scenarios. To achieve such generalization and scalability, we employ a semantic-grid data representation, which can efficiently represent the surroundings of the vehicle. The proposed method is used to evaluate the integrity of sources in several scenarios, and the integrity markers generated are used for identifying and quantifying unreliable data. A particular focus is given to real-world complex scenarios obtained from publicly available datasets where integrity localization requirements are of high importance. Those scenarios are examined to evaluate the performance of the framework and to provide proof-of-concept. We also establish the importance of the proposed integrity assessment framework in context-based localization applications for autonomous vehicles. The proposed method applies the integrity assessment concepts in the field of aviation to ground vehicles and provides the Protection Level markers (Horizontal, Lateral, Longitudinal) for perception systems used for vehicle localization.

Behavioural and psychological symptoms of dementia (BPSD), including fear-anxiety- and depressive-like behaviour, are present in Alzheimer’s disease (AD), together with memory decline. I2-imidazoline receptors (I2-IRs) have been associated with neuropsychiatric and neurodegenerative disorders, further, I2-IR ligands have demonstrated a neuroprotective role in the central nervous system (CNS). In this study, we assessed the effect of the I2-IR ligand MCR5 on both cognitive and non-cognitive symptoms in the Senescence accelerated mice prone 8 (SAMP8) mouse model. Oral administration of I2-IR ligand MCR5 (5 mg/kg/day for four weeks) in 10-month SAMP8 mice ameliorated both BPSD-like phenotype and cognitive decline by attenuating depressive-like behaviour, reducing fear-anxiety-like behaviour and improving cognitive performance using different tasks. Interaction of I2-IR ligand MCR5 with serotoninergic system did not account for behavioural or cognitive improvement, although changes in molecular pathways underlying depression and anxiety phenotype were observed. MCR5 increased levels of p-AKT, phosphorylated glycogen synthase kinase 3 β (GSK3β) at Ser9 and phosphorylated mammalian target of rapamycin complex 1 (mTORC1) levels in SAMP8 treated mice compared to SAMP8 control. Moreover, MCR5 treatment altered N-methyl-d-aspartate receptor (NMDA) 2B phosphorylation, and decreased the protein levels of phosphorylated cyclin-dependent kinase 5 (p-CDK5) and dopamine- and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein of Mr 32 kDa phosphorylated at Thr75 (p-DARPP32), with a parallel increase in protein kinase A (PKA) and p-cAMP response element-binding (pCREB) levels. Consistent with these changes MCR5 attenuated neuroinflammation by decreasing expression of pro-inflammatory markers such as Tumor necrosis factor-alpha (Tnf-α), Interleukin 1β (Il-1β), Interleukin 6 (Il-6), and promoted synaptic plasticity by increasing levels of postsynaptic density protein 95 (PSD95) as well as ameliorating tropomyosin-related kinase B (TrkB) and nerve growth factor receptor (NGFR) signalling. Collectively, these results increase the potential of highly selective I2-IR ligands as therapeutic agents in age-related BPSD and cognitive alterations.

Genomic analysis of the kelp fly Fucellia costalis (Family Anthomyiidae) from Asilomar beach, Pacific Grove, California, resulted in the assembly of its complete mitogenome. The mitogenome is 16,175 bp in length, A + T biased (78.1%), contains 37 genes, a large 1356 bp control region, and has a high-level of gene synteny to other Muscoidea. Phylogenetic analysis of F. costalis fully resolves it in a clade with two members of the Anthomyiidae, Delia platura (8.2% pairwise genetic distance) and D. antiqua (9.2% distance), in a sister position to Scathophaga stercoraria (7.8% distance) from the Scathophagidae. The phylogenetic position and genetic distances of F. costalis support the continued recognition of the subfamily Fucellinae. This identification and data extends the distributional range of F. costalis northward from California to Vancouver Island, Canada.

The shrimp Litopenaeus vannamei, one of the most important species in world aquaculture, has seriously affected by infectious myonecrosis virus (IMNV) that causes up to 70% mortalities. With the aim of improving the development of new strategies for rapid and reliable diagnosis, we isolated IMNV, from L. vannamei farmed in Brazil, through a discontinuous sucrose gradient, and sequenced cDNA fragment encoding the major capsid protein from this virus. Nucleotides sequences corresponding to the viral capsid protein was obtained by RT-PCR and confirmed by automatic sequencing. Comparison with sequences which encode the capsid protein obtained from Indonesia isolates showed a high identity.

As glucose-dependent insulinotropic polypeptide (GIP) possesses pro-adipogenic action, the suppression of the GIP hypersecretion seen in obesity might represent a novel therapeutic approach to the treatment of obesity. However, the mechanism of GIP hypersecretion remains largely unknown. In the present study, we investigated GIP secretion in two mouse models of obesity: High-fat diet-induced obese (DIO) mice and leptin-deficient Lepob/ob mice. In DIO mice, plasma GIP was increased along with an increase in GIP mRNA expression in the lower small intestine. Despite the robust alteration in the gut microbiome in DIO mice, co-administration of maltose and the α-glucosidase inhibitor (α-GI) miglitol induced the microbiome-mediated suppression of GIP secretion. The plasma GIP levels of Lepob/ob mice were also elevated and were suppressed by fat transplantation. The GIP mRNA expression in fat tissue was not increased in Lepob/ob mice, while the expression of an interleukin-1 receptor antagonist (IL-1Ra) was increased. Fat transplantation suppressed the expression of IL-1Ra. The plasma IL-1Ra levels were positively correlated with the plasma GIP levels. Accordingly, although circulating GIP levels are increased in both DIO and Lepob/ob mice, the underlying mechanisms differ, and the anti-obesity actions of α-GIs and leptin sensitizers may be mediated partly by the suppression of GIP secretion.

This paper proposes a Track-before-Detect framework for a multibody motion segmentation (named TbD-SfM). Our contribution relies on a tightly coupled tracking before detection strategy intended to reduce the complexity of existing Multibody Structure from Motion approaches. Efforts were done towards an algorithm variant closer and aimed to a further embedded implementation for dynamic scene analysis while enhancing processing time performances. This generic motion segmentation approach can be transposed to several transportation sensor systems since no constraints are considered on segmented motions (6-DOF model). The tracking scheme is analyzed and its performance is evaluated under thorough experimental conditions including full-scale driving scenarios from known and available datasets. Results on challenging scenarios including the presence of multiple and simultaneous moving objects observed from a moving camera are reported and discussed.

Stearoyl-CoA desaturase 1 (SCD1) is a lipogenic enzyme important for the regulation of membrane lipid homeostasis; dysregulation likely contributes to obesity associated metabolic disturbances. SCD1 catalyses the Δ9 desaturation of 12-19 carbon saturated fatty acids to monounsaturated fatty acids. To understand its influence in cellular lipid composition we investigated the effect of genetic ablation of SCD1 in 3T3-L1 adipocytes on membrane microdomain lipid composition at the species-specific level. Using liquid chromatography/electrospray ionisation-tandem mass spectrometry, we quantified 70 species of ceramide, mono-, di- and trihexosylceramide, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, bis(monoacylglycero)phosphate, phosphatidylinositol and cholesterol in 3T3-L1 adipocytes in which a 90% reduction in scd1 mRNA expression was achieved with siRNA. Cholesterol content was unchanged although decreases in other lipids resulted in cholesterol accounting for a higher proportion of lipid in the membranes. This was associated with decreased membrane lateral diffusion. An increased ratio of 24:0 to 24:1 in ceramide, mono- and dihexosylceramide, and sphingomyelin likely also contributed to this decrease in lateral diffusion. Of particular interest, we observed a decrease in phospholipids containing arachidonic acid. Given the high degree of structural flexibility of this acyl chain this will influence membrane lateral diffusion, and is likely responsible for the transcriptional activation of Lands' cycle enzymes lpcat3 and mboat7. Of relevance these profound changes in the lipidome were not accompanied by dramatic changes in gene expression in mature differentiated adipocytes, suggesting that adaptive homeostatic mechanisms to ensure partial maintenance of the biophysical properties of membranes likely occur at a post-transcriptional level.

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

Type 2 Diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting the notion that a crosstalk between mitochondria and the insulin signaling cascade could be involved in the etiology of T2D and insulin resistance. In this study we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered, and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses, and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the genome-wide association study meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found modest enrichment of genes associated with T2D amongst our linker genes (p = 0.0549), including three already validated T2D SNPs and 15 additional SNPs, which, when combined, were collectively associated to increased fasting glucose levels according to MAGIC genome wide meta-analysis (p = 8.12×10(-5)). This study highlights the potential of combining systems biology, experimental, and genome-wide association data mining for identifying novel genes and related variants that increase vulnerability to complex diseases.

microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

Identification of early mechanisms that may lead from obesity towards complications such as metabolic syndrome is of great interest. Here we performed lipidomic analyses of adipose tissue in twin pairs discordant for obesity but still metabolically compensated. In parallel we studied more evolved states of obesity by investigating a separated set of individuals considered to be morbidly obese. Despite lower dietary polyunsaturated fatty acid intake, the obese twin individuals had increased proportions of palmitoleic and arachidonic acids in their adipose tissue, including increased levels of ethanolamine plasmalogens containing arachidonic acid. Information gathered from these experimental groups was used for molecular dynamics simulations of lipid bilayers combined with dependency network analysis of combined clinical, lipidomics, and gene expression data. The simulations suggested that the observed lipid remodeling maintains the biophysical properties of lipid membranes, at the price, however, of increasing their vulnerability to inflammation. Conversely, in morbidly obese subjects, the proportion of plasmalogens containing arachidonic acid in the adipose tissue was markedly decreased. We also show by in vitro Elovl6 knockdown that the lipid network regulating the observed remodeling may be amenable to genetic modulation. Together, our novel approach suggests a physiological mechanism by which adaptation of adipocyte membranes to adipose tissue expansion associates with positive energy balance, potentially leading to higher vulnerability to inflammation in acquired obesity. Further studies will be needed to determine the cause of this effect.