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Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its in vivo efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the in vitro broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043. Here, we demonstrate that V2043, V2053, and V2067 are all orally bioavailable, well-tolerated, and achieve high sustained plasma levels after single oral daily dosing. All three phospholipid prodrugs are significantly more active than RVn in vitro and significantly reduce SARS-CoV-2 lung titers in prophylaxis and treatment mouse models of SARS-CoV-2 B.1.351 infection. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir in vivo. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain. Methods: Data from adult IPD cases (≥18 years) were collected from six Spanish hospitals in 2019–2021. Strains were serotyped, tested for antibiotic susceptibility and subjected to whole genome sequencing (WGS). Findings were compared with data from previous periods (2008–2016). Results: A total of 655 IPD episodes were examined. Pneumonia was the main focus (515/655), and 366 episodes occurred in adults over 64 years. Although IPD incidence decreased during COVID-19 pandemic, the burden of disease caused by PCV13 serotypes was significant. Notably, serotype 3 persisted (GPSC12-ST180 and GPSC83-ST260), and a new serotype 4 lineage emerged (GPSC162-ST13022). Among non-PCV13 serotypes, serotype 8 expanded (GPSC3-ST53) and a new serotype 12F lineage emerged (GPSC55-ST8060). Most serotypes presented a dominant Global Pneumococcal Sequencing Cluster (GPSC) like GPSC16-ST67 of 9N or GPSC19-ST433 of 22F. Nevertheless, some GPSCs were associated with several serotypes, the most numerous were GPSC3 (serotypes 8, 11A, and 33F) and GPSC6 (serotypes 11A and 14). The overall penicillin non-susceptibility rate was 17.0 %, 14.6 % resistance for meningitis and 1.6 % for pneumonia (15.1 % susceptible at increased exposure [SIE]). Serotypes 11A and 14 (GPSC6-ST156/6521) and 19A (GPSC1-ST320) had penicillin MICs above 1 mg/L. Acquired resistance genes associated with macrolide and/or tetracycline resistance were present in 19.4 % of isolates, particularly among serotypes 6C (GPSC47-ST386/4310) and 19A (GPSC1-ST320). Conclusions: The burden of PCV13 serotypes in adult IPD remains significant, and serotype 3 is the primary contributor. However, the rise of stable lineages associated with non-PCV13 serotypes, particularly 8, 9N, and 22F highlights a shifting epidemiology. The persistence of multidrug-resistant lineages, such as GPSC6-ST156 and GPSC1-ST320, emphasizes the need for continued surveillance. Vaccination of high-risk adults with current and broader coverage PCVs would help to control the burden of pneumonia and IPD among adults.

With the substantial growth of the smart textiles market, electrical properties are becoming a basic requirement for most of the advanced textiles used in the development of wearable solutions and other textile-based smart applications. Depending on the textile substrate, the test method to determine the electrical properties can be different. Unlike smart fibers and yarns, the characterization of the electrical properties of fabrics cannot be tested between two connection points because the result would not represent the behavior of the entire fabric, so the electrical properties must be related to an area. The parameters used to characterize the electrical properties of the fabrics include resistance, resistivity, and conductivity. Although all of them can be used to indicate electrical performance, there are significant differences between them and different methods available for their determination, whose suitability will depend on the function and the textile substrate. This paper revises the main parameters used to characterize the electrical properties of conductive fabrics and summarizes the most common methods used to test them. It also discusses the suitability of each method according to several intervening factors, such as the type of conductive fabric (intrinsically or extrinsically conductive), its conductivity range, other fabric parameters, or the final intended application. For intrinsically conductive woven fabrics, all the methods are suitable, but depending on the requirements of conductivity accuracy, the contact resistance from the measuring system should be determined. For intrinsically conductive knitted fabrics, two-point probe, Van der Pauw, and eddy current methods are the most suitable. And for intrinsically conductive nonwoven fabrics, two-point probe and four-point probe methods are the most appropriate. In the case of extrinsically conductive fabrics, the applied method should depend on the substrate and the properties of the conductive layer.

Background: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. Methods: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. Results: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose + PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose + PAC vs. PAC alone p 0.37). Conclusions: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it. Resumen: Antecedentes: Faltan estudios que analicen alternativas no antibióticas para tratar las infecciones del tracto urinario (ITU) en los pacientes trasplantados renales. La D-Manosa, un azúcar simple, inhibe la adhesión bacteriana al urotelio, al igual que las Proantocianidinas; ambas moléculas podrían actuar como una estrategia sinérgica para prevenir las ITUs; pero su eficacia y seguridad aún no se han evaluado en la población trasplantada renal. Métodos: Este es un ensayo piloto prospectivo y doble ciego. Sesenta receptores de trasplante renal de novo fueron asignados al azar (1:1) para recibir una estrategia profiláctica basada en una formulación de liberación prolongada de 24 horas de D-Manosa más Proantocianidinas (PAC), frente a solo Proantocianidinas (PAC). Los suplementos se tomaron durante los primeros 3 meses después del trasplante renal y luego se realizó un seguimiento durante otros 3 meses. El objetivo principal del estudio fue determinar si la adición de D-Manosa a PAC reducía la incidencia de ITU y/o bacteriuria asintomática en los primeros 6 meses después del trasplante. Resultados: El 27% de los pacientes experimentó un episodio de ITU (cistitis o pielonefritis), mientras que la bacteriuria asintomática fue muy común (57%). Las incidencias según el tipo de ITU o bacteriuria asintomática fueron: 7% frente a 4% para episodio de cistitis (p 0.3), 4% frente a 5% para pielonefritis (p 0.5) y 17% frente a 14% para bacteriuria asintomática (p 0.4) en el grupo de manosa + PAC frente al grupo PAC, respectivamente. La bacteria más frecuente en ambos grupos fue Escherichia coli (28% de todos los episodios), sin embargo las ITU o bacteriuria asintomática debidas a E. coli no fueron diferentes según el grupo de estudio (30% frente a 23% para Manosa + PAC frente a PAC solo, p.0.37). Conclusiones: La terapia no antibiótica es una necesidad para prevenir las ITU después del trasplante renal; sin embargo, el uso de D-Manosa más PAC no parece ser capaz de prevenir las ITU en este grupo especial de pacientes.

The objectives of this paper are to describe the Social Science and Humanities projects involving Spanish participation within the Seventh EU Framework Programme (FP7) (2007-2013), along with the scholarly output generated by these projects, and to compare the findings with the data from FP6 (2002-2006) in order to track their evolution. First, we determine the most significant characteristics of the projects with Spanish participation (duration, funding, topics, type of institution, etc.). Second, we analyse the scholarly production derived from a sample of projects taken from the Scopus database to analyse some bibliometric features. The results show an increase in the leadership and prominence of Spanish institutions, compared to FP6-SSH. In terms of scholarly outputs, none of the sources used (CORDIS, OpenAIRE and SCOPUS) allows a detailed study of scholarly production, although this output is characterized by articles written predominantly in English, published in first-quartile journals. Moreover, data showed that research funding for SSH may have long-term effects, with some outputs acknowledging funding being published a decade after the end of the project.

Klebsiella pneumoniae is an opportunistic bacterium that frequently colonizes the nasopharynx and gastrointestinal tract and can also cause severe infections when invading other tissues, particularly in immunocompromised individuals. Moreover, K. pneumoniae variants exhibiting a hypermucoviscous (HMV) phenotype are usually associated with hypervirulent strains that can produce invasive infections even in immunocompetent individuals. Major carbohydrate structures displayed on the K. pneumoniae surface are the polysaccharide capsule and the lipopolysaccharide, which presents an O-polysaccharide chain in its outermost part. Various capsular and O-chain structures have been described. Of note, production of a thick capsule is frequently observed in HMV variants. Here we examined the surface sugar epitopes of a collection of HMV and non-HMV K. pneumoniae clinical isolates and their recognition by several Siglecs and galectins, two lectin families of the innate immune system, using bacteria microarrays as main tool. No significant differences among isolates in sialic acid content or recognition by Siglecs were observed. In contrast, analysis of the binding of model lectins with diverse carbohydrate-binding specificities revealed striking differences in the recognition by galactose- and mannose-specific lectins, which correlated with the binding or lack of binding of galectins and pointed to the O-chain as the plausible ligand. Fluorescence microscopy and microarray analyses of galectin-9 binding to entire cells and outer membranes of two representative HMV isolates supported the bacteria microarray results. In addition, Western blot analysis of the binding of galectin-9 to outer membranes unveiled protein bands recognized by this galectin, and fingerprint analysis of these bands identified several proteins containing potential O-glycosylation sites, thus broadening the spectrum of possible galectin ligands on the K. pneumoniae surface. Moreover, Siglecs and galectins apparently target different structures on K. pneumoniae surfaces, thereby behaving as non-redundant complementary tools of the innate immune system.

Utilizing recycled fibers as reinforcement in cement-based matrices is an effective means of promoting waste recycling and adopting a circular economy approach in the construction industry. Within this framework, the recycling and potential reutilization of textile residues can improve the pre- and post-cracking performance of cement-based matrices intended for building components with up to intermediate structural responsibilities (i.e., panels and cladding elements for buildings). This research is focused on the mechanical and durability -through forced aging of dry-wet and freeze-thaw cycles- experimental characterization of laminated fabric-reinforced cementitious matrices (FRCMs) containing 4 and 6 nonwoven fabric layers obtained from end-of-life fire-protecting t-shirts. For this purpose, both direct and flexural tensile tests were conducted to characterize the mechanical performance of the composite. The tests on the 6-fabric layers produced panels with Portland Cement (PC) matrix, after 28-day of curing, led to average values of the maximum tensile strength of 3.7 MPa with associated toughness index superior to 25 kJ/m2, and mean modulus of rupture of 11.6 MPa with a fracture energy index of 4.3 kJ/m2. After dry-wet accelerated aging, the post-cracking performance of the developed composites decreased (on average, 40% in toughness and 11% in strength) due to fiber embrittlement. To better understand the performance of aged composites, shredded fibers recovered from protective clothing (mainly consisting of meta-aramid fibers) were immersed in the binary matrix. Accordingly, the mechanical properties of the fibers after 5 and 10 cycles of dry-wet aging were studied. Based on the results, replacing partially PC by silica fume (between 30% and 50%) was seen as a sustainable alternative to improve the performance of the aged fibers by more than 10%.

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world's healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified that 2',3' cyclic-nucleotide 3'-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly. We show that CNP inhibits the generation of new SARS-CoV-2 virions, reducing intracellular titers without inhibiting viral structural protein translation. Additionally, we show that targeting of CNP to mitochondria is necessary for inhibition, blocking mitochondrial depolarization and implicating CNP's proposed role as an inhibitor of the mitochondrial permeabilization transition pore (mPTP) as the mechanism of virion assembly inhibition. We also demonstrate that an adenovirus expressing virus expressing both human ACE2 and CNP inhibits SARS-CoV-2 titers to undetectable levels in lungs of mice. Collectively, this work shows the potential of CNP to be a new SARS-CoV-2 antiviral target.

The aim of this paper is to evaluate the influence of sustainable surface treatments —performed on flax nonwoven fabrics as textile reinforcement— on the durability of calcium aluminate cement (CAC) based composites. Two treatments are considered: an alkaline treatment (for increased stability and adhesion), and a treatment with soybean oil (to reduce fiber degradation). The cement hydration was studied by analysis of back-scattered scanning electron microscopy images, which revealed variations nearby the fibers owing their capacity for water absorption and presence of oil on the surface. A retarding effect on cement hydration was observed on the composites prepared with the oil-treated fabrics. The composites containing the alkali treated fabrics had better mechanical properties and also the highest durability. For these composites it was found an optimized fiber-matrix adhesion and penetrability of the cement to the fabric.

The aim of this paper is to evaluate the influence of sustainable surface treatments —performed on flax nonwoven fabrics as textile reinforcement— on the durability of calcium aluminate cement (CAC) based composites. Two treatments are considered: an alkaline treatment (for increased stability and adhesion), and a treatment with soybean oil (to reduce fiber degradation). The cement hydration was studied by analysis of back-scattered scanning electron microscopy images, which revealed variations nearby the fibers owing their capacity for water absorption and presence of oil on the surface. A retarding effect on cement hydration was observed on the composites prepared with the oil-treated fabrics. The composites containing the alkali treated fabrics had better mechanical properties and also the highest durability. For these composites it was found an optimized fiber-matrix adhesion and penetrability of the cement to the fabric.

AbstractCrossref is an official digital object identifier registration agency launched in 2000 as a joint effort between publishers to allow persistent cross-publisher citation linking in online academic journals. Our study explores the coverage of Crossref for tracking literature in the arts and humanities, which usually has a national or regional focus and targets domestic audiences. An analysis of the coverage of ERIH PLUS journals shows that Crossref indexes more sources than Scopus and includes additional journals from Eastern and Southern Europe and the Global South. Crossref limitations arise when analyzing the amount of metadata deposited by publishers. Just two-thirds of the journals deposit abstracts and ORCIDs and around a third deposit affiliations. The level of metadata completion for individual articles is lower, with major differences depending on the language of the document. Just half of the journals actually deposit references. As a result, Scopus retrieves more citations than Crossref, except for publications in German and French. Crossref represents a promising bibliographic discovery tool in the arts and humanities but is in need of improvement regarding the level of metadata completion.

One of the most common load modes is flexure. The paper measures and models the flexural strength and modulus of a bio-polyethylene reinforced with thermos-mechanical fibers from corn stover. Moreover, the authors use modified rules of mixtures to evaluate the contribution of the reinforcements to the properties of the composite. It was found a high impact of coupling agent content on the strength of the composites, and materials with a 6% of such agent and 50% of reinforcement increased 181% the strength of the matrix, and 464% its modulus. The obtained values are noticeable higher than polypropylene and some of its composites. Micromechanics analysis shows that the effect of natural fiber reinforcement on the flexural properties of a bio-based PE is similar to the effects on a polyolefin. Thus, the use of fully bio-based composites can be proposed as a substitute for some oil-based polymers, partially bio-based materials, and their composites.

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to be one of the largest dangers to human health around the world. The need for effective antiviral and anti-inflammatory treatments is still extremely high as newly emerging variants threaten the efficacy of currently used treatment options. Many compounds are effective at inhibiting SARS-CoV-2 infection in vitro but fail to recapitulate that efficacy in vivo. There is a major demand for antiviral drugs that are efficacious and broadly effective for the treatment of highly pathogenic coronaviruses including SARS-CoV-2, and its close relatives SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). One drug with the potential to join the small subset of broadly active antiviral compounds that is both efficacious in vivo and orally bioavailable is pyronaridine triphosphate, which has now been published to show both in vitro and in vivo efficacy in A549 cells and the K18-hACE2 mouse model, respectively, by functioning as a protease inhibitor of the SARS-CoV-2 papain-like protease (PLpro). In our studies, pyronaridine treatment resulted in significant improvements to lung inflammatory pathology, reducing pro-inflammatory cytokine and chemokine levels, and inhibiting weight loss seen in the mouse model associated with the severity of disease in three highly pathogenic coronavirus infection models, SARS-CoV-1, SARS-CoV-2, and MERS-CoV. Additionally, we found that pyronaridine treatment can safely and effectively be combined with currently used therapeutics molnupiravir and nirmatrelvir (main protease inhibitor component of Paxlovid) in a SARS-CoV-2 in vivo model, and there was evidence of a synergistic effect that further reduced viral titers, inflammatory lung pathology, and inflammatory cytokine and chemokine levels. These results indicate that pyronaridine represents an excellent potential therapeutic candidate for COVID-19 treatment individually, or in combination with other approved antivirals as well as a potential therapeutic option for the treatment of highly pathogenic coronaviruses such as SARS-CoV-1, MERS-CoV, and future coronaviruses yet to emerge. IMPORTANCE Pyronaridine tetraphosphate is on the WHO Essential Medicine List for its importance as a widely available and safe treatment for malaria. We find that pyronaridine is a highly effective antiviral therapeutic across mouse models using multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the highly pathogenic viruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus responsible for previous coronavirus outbreaks. Additionally, we find that pyronaridine additively combines with current COVID-19 treatments such as nirmatrelvir (protease inhibitor in Paxlovid) and molnupiravir to further inhibit SARS-CoV-2 infections. There are many antiviral compounds that demonstrate efficacy in cellular models, but few that show this level of impact in multiple mouse models and represent a promising therapeutic for the current coronavirus pandemic as well as future outbreaks as well.

Abstract The Framework Programmes for Research and Technological Development are funding programmes created by the European Union to support and foster research. This study aims to describe the features and assess the performance of Social Sciences and Humanities research projects funded under the Sixth Framework Programme that was active between 2002 and 2006. The results show that most funded projects were in the fields of economics and political sciences, in line with the use of the Framework Programme to enhance economic development and the integration process in Europe. Research teams showed a high level of collaboration with an average of 7.8 countries and 10.8 institutions involved in each project. However, the large size and diversity of consortia did not translate into a large number of co-authored scholarly journal articles. The results show that research funds in the Social Sciences and Humanities may have long-term effects, with some outputs acknowledging funding being published more than a decade after the end of the project. Qualitative analysis of the acknowledgements in the articles revealed four types of support: direct funding; utilisation of results from former funded projects as the basis for further research; involvement in conferences and networks resulting from funded projects; and utilisation of datasets or other products resulting from former funded projects. The study also illustrates the difficulties in retrieving the outputs resulting from funded projects since the funding information in Scopus is heterogeneous and not standardised. As a result, the type of assessment conducted in this project is time-consuming and requires a significant amount of manpower to clean and standardise the data. Nevertheless, the procedure could be applied to analyse the performance of subsequent European Framework Programmes in building a European Research Area in the Social Sciences and Humanities.

Abstract The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBDSARS-PLPs and RBDMERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBDSARS- or RBDMERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBDSARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBDSARS-PLPs, RBDMERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines.

Abstract Haemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract. Non-typeable H. influenzae are highly heterogeneous, but few studies have analysed the genomic variability of capsulated strains. This study aims to examine the genetic diversity of 37 serotype f isolates from the Netherlands, Portugal, and Spain, and to compare all capsulated genomes available on public databases. Serotype f isolates belonged to CC124 and shared few single nucleotide polymorphisms (SNPs) (n = 10,999), but a high core genome (> 80%). Three main clades were identified by the presence of 75, 60 and 41 exclusive genes for each clade, respectively. Multi-locus sequence type analysis of all capsulated genomes revealed a reduced number of clonal complexes associated with each serotype. Pangenome analysis showed a large pool of genes (n = 6360), many of which were accessory genome (n = 5323). Phylogenetic analysis revealed that serotypes a, b, and f had greater diversity. The total number of SNPs in serotype f was significantly lower than in serotypes a, b, and e (p

ABSTRACT Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing bacteria. Our goal was to identify changes in Haemophilus influenzae and Haemophilus parainfluenzae during azithromycin treatment. Fifteen patients were followed while receiving prolonged azithromycin treatment (Hospital Universitari de Bellvitge, Spain). Four patients (P02, P08, P11, and P13) were persistently colonized by H. influenzae for at least 3 months and two (P04 and P11) by H. parainfluenzae. Isolates from these patients (53 H. influenzae and 18 H. parainfluenzae) were included to identify, by whole-genome sequencing, antimicrobial resistance changes and genetic variation accumulated during persistent colonization. All persistent lineages isolated before treatment were azithromycin-susceptible but developed resistance within the first months, apart from those belonging to P02, who discontinued the treatment. H. influenzae isolates from P08-ST107 acquired mutations in 23S rRNA, and those from P11-ST2480 and P13-ST165 had changes in L4 and L22. In H. parainfluenzae, P04 persistent isolates acquired changes in rlmC, and P11 carried genes encoding MefE/MsrD efflux pumps in an integrative conjugative element, which was also identified in H. influenzae P11-ST147. Other genetic variation occurred in genes associated with cell wall and inorganic ion metabolism. Persistent H. influenzae strains all showed changes in licA and hgpB genes. Other genes (lex1, lic3A, hgpC, and fadL) had variation in multiple lineages. Furthermore, persistent strains showed loss, acquisition, or genetic changes in prophage-associated regions. Long-term azithromycin therapy results in macrolide resistance, as well as genetic changes that likely favor bacterial adaptation during persistent respiratory colonization. IMPORTANCE The immunomodulatory properties of azithromycin reduce the frequency of exacerbations and improve the quality of life of COPD patients. However, long-term administration may alter the respiratory microbiota, such as Haemophilus influenzae, an opportunistic respiratory colonizing bacteria that play an important role in exacerbations. This study contributes to a better understanding of COPD progression by characterizing the clinical evolution of H. influenzae in a cohort of patients with prolonged azithromycin treatment. The emergence of macrolide resistance during the first months, combined with the role of Haemophilus parainfluenzae as a reservoir and source of resistance dissemination, is a cause for concern that may lead to therapeutic failure. Furthermore, genetic variations in cell wall and inorganic ion metabolism coding genes likely favor bacterial adaptation to host selective pressures. Therefore, the bacterial pathoadaptive evolution in these severe COPD patients raise our awareness of the possible spread of macrolide resistance and selection of host-adapted clones.

This paper examines the influence of weaving variables such as yarn count, number of layers, warp and weft ratio, materials of the top layer, weft density and interlocking cell shape, and size on the thermal performance of multilayer interlocked woven fabrics. A split-plot design was used to construct a total of 64 fabric structures, which were assessed for thermal performance in terms of resistance to convective, conductive, and radiative heat. It was found that, for equal weft density and yarn number, protective performance improved with the number of fabric layers and with the presence of air cells between these layers, especially if air was not trapped within and could rather pass freely between the cells. An optimal combination of factors for the thermal response to the three types of heat was established via a Derringer–a much needed desirability function. The results of this paper are useful for identifying the interaction between configuration parameters and thermal performance, and hence for the design of improved heat protective clothing.

The digital transition that drives the new industrial revolution is largely driven by the application of intelligence and data. This boost leads to an increase in energy consumption, much of it associated with computing in data centers. This fact clashes with the growing need to save and improve energy efficiency and requires a more optimized use of resources. The deployment of new services in edge and cloud computing, virtualization, and software-defined networks requires a better understanding of consumption patterns aimed at more efficient and sustainable models and a reduction in carbon footprints. These patterns are suitable to be exploited by machine, deep, and reinforced learning techniques in pursuit of energy consumption optimization, which can ideally improve the energy efficiency of data centers and big computing servers providing these kinds of services. For the application of these techniques, it is essential to investigate data collection processes to create initial information points. Datasets also need to be created to analyze how to diagnose systems and sort out new ways of optimization. This work describes a data collection methodology used to create datasets that collect consumption data from a real-world work environment dedicated to data centers, server farms, or similar architectures. Specifically, it covers the entire process of energy stimuli generation, data extraction, and data preprocessing. The evaluation and reproduction of this method is offered to the scientific community through an online repository created for this work, which hosts all the code available for its download.

With the substantial growth of the smart textiles market, electrical properties are becoming a basic requirement for most of the advanced textiles used in the development of wearable solutions and other textile-based smart applications. Depending on the textile substrate, the test method to determine the electrical properties can be different. Unlike smart fibers and yarns, the characterization of the electrical properties of fabrics cannot be tested between two connection points because the result would not represent the behavior of the entire fabric, so the electrical properties must be related to an area. The parameters used to characterize the electrical properties of the fabrics include resistance, resistivity, and conductivity. Although all of them can be used to indicate electrical performance, there are significant differences between them and different methods available for their determination, whose suitability will depend on the function and the textile substrate. This paper revises the main parameters used to characterize the electrical properties of conductive fabrics and summarizes the most common methods used to test them. It also discusses the suitability of each method according to several intervening factors, such as the type of conductive fabric (intrinsically or extrinsically conductive), its conductivity range, other fabric parameters, or the final intended application. For intrinsically conductive woven fabrics, all the methods are suitable, but depending on the requirements of conductivity accuracy, the contact resistance from the measuring system should be determined. For intrinsically conductive knitted fabrics, two-point probe, Van der Pauw, and eddy current methods are the most suitable. And for intrinsically conductive nonwoven fabrics, two-point probe and four-point probe methods are the most appropriate. In the case of extrinsically conductive fabrics, the applied method should depend on the substrate and the properties of the conductive layer. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is an opportunistic bacterium that frequently colonizes the nasopharynx and gastrointestinal tract and can also cause severe infections when invading other tissues, particularly in immunocompromised individuals. Moreover, K. pneumoniae variants exhibiting a hypermucoviscous (HMV) phenotype are usually associated with hypervirulent strains that can produce invasive infections even in immunocompetent individuals. Major carbohydrate structures displayed on the K. pneumoniae surface are the polysaccharide capsule and the lipopolysaccharide, which presents an O-polysaccharide chain in its outermost part. Various capsular and O-chain structures have been described. Of note, production of a thick capsule is frequently observed in HMV variants. Here we examined the surface sugar epitopes of a collection of HMV and non-HMV K. pneumoniae clinical isolates and their recognition by several Siglecs and galectins, two lectin families of the innate immune system, using bacteria microarrays as main tool. No significant differences among isolates in sialic acid content or recognition by Siglecs were observed. In contrast, analysis of the binding of model lectins with diverse carbohydrate-binding specificities revealed striking differences in the recognition by galactose- and mannose-specific lectins, which correlated with the binding or lack of binding of galectins and pointed to the O-chain as the plausible ligand. Fluorescence microscopy and microarray analyses of galectin-9 binding to entire cells and outer membranes of two representative HMV isolates supported the bacteria microarray results. In addition, Western blot analysis of the binding of galectin-9 to outer membranes unveiled protein bands recognized by this galectin, and fingerprint analysis of these bands identified several proteins containing potential O-glycosylation sites, thus broadening the spectrum of possible galectin ligands on the K. pneumoniae surface. Moreover, Siglecs and galectins apparently target different structures on K. pneumoniae surfaces, thereby behaving as nonredundant complementary tools of the innate immune system. [ABSTRACT FROM AUTHOR]

Tetracycline resistance in streptococci is mainly due to ribosomal protection mediated by the tet(M) gene that is usually located in the integrative and conjugative elements (ICEs) of the Tn916-family. In this study, we analyzed the genes involved in tetracycline resistance and the associated mobile genetic elements (MGEs) in Streptococcus dysgalactiae subsp. equisimilis (SDSE) causing invasive disease. SDSE resistant to tetracycline collected from 2012 to 2019 in a single hospital and from 2018 in three other hospitals were analyzed by whole genome sequencing. Out of a total of 84 SDSE isolates, 24 (28.5%) were resistant to tetracycline due to the presence of tet(M) (n = 22), tet(W) (n = 1), or tet(L) plus tet(W) (n = 1). The tet(M) genes were found in the ICEs of the Tn916-family (n = 10) and in a new integrative and mobilizable element (IME; n = 12). Phylogenetic analysis showed a higher genetic diversity among the strains carrying Tn916 than those having the new IME, which were closely related, and all belonged to CC15. In conclusion, tetracycline resistance in SDSE is mostly due to the tet(M) gene associated with ICEs belonging to the Tn916-family and a new IME. This new IME is a major cause of tetracycline resistance in invasive Streptococcus dysgalactiae subsp. equisimilis in our settings.