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Abstract Background Modular acetabular components for total hip arthroplasty (THA) provide intraoperative flexibility; however, polyethylene liner dissociation may occur. This study aimed to examine the incidence and causes of liner dissociation associated with a specific acetabular component design at a single centre. Materials and methods A retrospective analysis of 7027 patients who underwent primary THA was performed to identify isolated liner dislocations. Patient demographics, clinical presentations, surgical and implant details, and both radiographic and computed tomography (CT) findings were analysed. Patients with liner dislocation were matched to a control group via 2:1 propensity score matching, and a logistic regression analysis was employed to identify associated risk factors. Results A total of 32 patients (0.45%) experienced liner dislocation at a mean 71.47 ± 60.10 months post surgery. Significant factors contributing to dislocations included the use of a conventional compared with a highly crosslinked polyethylene component (p = 0.049) and screw fixation (p = 0.028). Radiographic and CT analysis highlighted the importance of proper component orientation, revealing that patients experiencing dislocations demonstrated significantly lower acetabular cup anteversion angles (p = 0.001) compared with the control group. Impingement and malposition, identified in 41% and 47% of the cases, respectively, further underscored the multifactorial nature of dislocation risks. Conclusions While the overall rate of polyethylene liner dislocation was low, the findings of this study highlight the importance of appropriate cup placement to decrease the risk of dissociation. It further substantiates the influence of impingement and malposition in liner displacement, with increased mechanical stress exerted on the locking mechanism under adverse conditions and the potential risk increase due to screw placement.

ABSTRACT Antibiotic therapy alters bacterial abundance and metabolism in the gut microbiome, leading to dysbiosis and opportunistic infections. Bacteroides thetaiotaomicron (Bth) is both a commensal in the gut and an opportunistic pathogen in other body sites. Past work has shown that Bth responds to β-lactam treatment differently depending on the metabolic environment both in vitro and in vivo. Studies of other bacteria show that an increase in respiratory metabolism independent of growth rate promotes susceptibility to bactericidal antibiotics. We propose that Bth enters a protected state linked to an increase in polysaccharide utilization and a decrease in the use of simple sugars. Here, we apply antibiotic susceptibility testing, transcriptomic analysis, and genetic manipulation to characterize this polysaccharide-mediated tolerance (PM tolerance) phenotype. We found that a variety of mono- and disaccharides increased the susceptibility of Bth to several different β-lactams compared to polysaccharides. Transcriptomics indicated a metabolic shift from reductive to oxidative branches of the tricarboxylic acid cycle on polysaccharides. Accordingly, supplementation with intermediates of central carbon metabolism had varying effects on PM tolerance. Transcriptional analysis also showed a decrease in the expression of the electron transport chain (ETC) protein NQR and an increase in the ETC protein NUO, when given fiber versus glucose. Deletion of NQR increased Bth susceptibility while deletion of NUO and a third ETC protein NDH2 had no effect. This work confirms that carbon source utilization modulates antibiotic susceptibility in Bth and that anaerobic respiratory metabolism and the ETC play an essential role.IMPORTANCEAntibiotics are indispensable medications that revolutionized modern medicine. However, their effectiveness is challenged by a large array of resistance and tolerance mechanisms. Treatment with antibiotics also disrupts the gut microbiome which can adversely affect health. Bacteroides are prevalent in the gut microbiome and yet are frequently involved in anaerobic infections. Thus, understanding how antibiotics affect these bacteria is necessary to implement proper treatment. Recent work has investigated the role of metabolism in antibiotic susceptibility in distantly related bacteria such as Escherichia coli. Using antibiotic susceptibility testing, transcriptomics, and genetic manipulation, we demonstrate that polysaccharides reduce β-lactam susceptibility when compared to monosaccharides. This finding underscores the profound impact of metabolic adaptation on the therapeutic efficacy of antibiotics. In the long term, this work indicates that modulation of metabolism could make Bacteroides more susceptible during infections or protect them in the context of the microbiome.

Avian malaria ( Plasmodium spp.) and related haemosporidian parasites ( Leucocytozoon spp. and Haemoproteus spp.) are widespread in birds, yet studies investigating prevalence and diversity of haemosporidians are lacking for many Nearctic-Neotropical migrants. Furthermore, the impact that infections may have on the condition or behavior of birds during migration is still poorly understood. Here, we used nested PCR and DNA sequencing to determine parasite prevalence and identify genetic lineages of haemosporidians in Canada Warblers ( Cardellina canadensis ) and Black-throated Blue Warblers ( Setophaga caerulescens ) during their migration stopover on the south shore of Lake Ontario. We further evaluated if haemosporidian infections were related to immune condition, as assessed via total white blood cell (WBC) counts and heterophil/lymphocyte (H/L) ratios, or refueling patterns and/or migration timing. We found a haemosporidian prevalence of 51.5% in 66 birds; however, there was a greater haemosporidian prevalence in Black-throated Blue Warblers relative to Canada Warblers. We detected 15 cytochrome b lineages of parasites, including 4 novel lineages. In Black-throated Blue Warblers, infected birds had significantly higher total WBC counts compared to uninfected birds. Across species, females had lower H/L ratios when infected, whereas the opposite trend was observed in males. Plasma metabolites (triglyceride, β-hydroxybutyrate, uric acid) were not associated with infection status, and infection was not related to arrival date at the spring stopover site. Results provide insight into the diversity of haemosporidians that infect two species of migratory warblers and illustrate that blood parasite infections are a routine challenge that these birds face during migration. Although haemosporidian infections may be associated with a heightened immune response in some scenarios, the findings of this correlative study provide no evidence that Canada Warblers and Black-throated Blue Warblers experience physiological or behavioral trade-offs as a result of infections.

Abstract The source and roles of fibroblasts and T-cells during maladaptive remodeling and myocardial fibrosis in the setting of pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a subpopulation of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial and perivascular lesions in SUGEN/Hypoxia (SuHx) rats, and fibroblasts labeled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68-positive cell clusters. IL-1β also activates stemness markers, such as NANOG and SOX2, and genes involved in dedifferentiation, lymphoid cell function and metabolic reprogramming. IL-1β induction of lineage traced primary mouse cardiac fibroblasts causes these cells to lose their fibroblast identity and acquire an immune phenotype. Our results identify IL-1β induced immune-competency in human cardiac fibroblasts and suggest that fibroblast secretome modulation may constitute a therapeutic approach to PAH and other diseases typified by inflammation and fibrotic remodeling.

Abstract NbRe-based superconducting thin films recently received relevant interest in the field of low-temperature electronics. However, for these materials the electrical conduction mechanisms, in particular in the normal state, still need to be investigated in more detail. Here, NbRe and NbReN films of different thicknesses have been deposited on two different substrates, namely monocrystalline Si and $$\text {SiO}_2$$ SiO 2 buffered Si. The films were characterized by DC electrical transport measurements. Moreover, a connection with the charge carriers fluctuation processes has been made by analyzing the electrical noise generated in the normal state region. Despite the films morphology seems not to be affected by the substrate used, a lower noise level has been found for the ones grown on $$\text {SiO}_2$$ SiO 2 , in particular for NbReN. From this study it emerges that both NbRe and NbReN ultrathin films are of very good quality, as far as the low-temperature electrical noise and conduction are concerned, with noise levels competitive with NbN. These results may further support the proposal of using these materials in a nanowire form in the field of superconducting electronics.

Abstract Background Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies. Study design A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at “Scuola Medica Salernitana”, Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls. Results Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease. Conclusions Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.

Resumo: Objetivo: Sob a perspectiva do trabalho de Pearson (1998) e utilizando as ferramentas da linguística de corpus disponíveis para o português brasileiro, a pesquisa apresentada neste artigo busca verificar em que medida a coextensividade entre termo técnico, grupo nominal e item lexical pode ser considerada válida para o português brasileiro. Método: Para a verificação desta coextensividade, um corpus de artigos acadêmicos sobre o domínio experiencial do autocuidado em Diabetes Mellitus foi compilado eletronicamente. Esse corpus foi inserido no software concordanciador AntConc (ANTHONY, 2019) e três palavras-chave foram extraídas com base no corpus de referência CALIBRA (FIGUEREDO; PAGANO; FERREGUETTI, 2014). O contexto de cada uma dessas palavras foi analisado por meio da ferramenta clusters/n-grams do AntConc, considerando os clusters/n-grams com o número mínimo de dez ocorrências. Resultados: A investigação desses clusters/n-grams formados à direita e à esquerda de cada uma das palavras-chave selecionadas mostrou que a coextensividade entre termo técnico, grupo nominal e item lexical nem sempre pode ser identificada, embora a utilização da ferramenta de cluster/n-grams pode ser considerada eficaz para buscar por itens lexicais que estão em coextensividade à ordem do grupo nominal, em razão da existência de pelo menos um grupo nominal em cada cluster/n-gram analisado. Conclusão: Ainda que os programas utilizados em Pearson (1998) não estejam totalmente difundidos para o português brasileiro, a abordagem sistêmico-funcional para o grupo nominal e para o item lexical em conjunto com as ferramentas do software concordanciador utilizado se mostraram eficientes para a análise proposta neste artigo. Palavras-chave: item lexical; grupo nominal; termo técnico; linguística de corpus; sistêmico-funcional; co-extensividade. Abstract: Objective: Drawing on Pearson (1998) and using corpus linguistics tools available for Brazilian Portuguese, we report on a study aimed at exploring to what extent the concepts of technical term, nominal group and lexical item are coextensive in Brazilian Portuguese. Method: A corpus of academic articles on the experiential domain of Diabetes Mellitus self-care was compiled and queried in AntConc, a concordancing software (ANTHONY, 2019). Using as a reference corpus CALIBRA (FIGUEREDO; PAGANO; FERREGUETTI, 2014), three keywords were extracted analysed with AntConc tool clusters/n-grams, considering clusters/n-grams with a minimum number of ten occurrences. Results: Analysis of clusters/n-grams to the right and left of each of the selected keywords showed that technical term, nominal group and lexical item cannot always coextensive. The use of cluster/n-grams tool can be considered effective to search for lexical items that are coextensive to the order of the nominal group, due to the existence of at least one nominal group in each cluster/n-gram analyzed. Conclusion: Although the programs used by Pearson (1998) are not fully available to Brazilian Portuguese, a systemic-functional approach to nominal group and lexical item together with the tools of the concordancing software used in this paper proved to be efficient for the analysis herein proposed. Keywords: lexical item; nominal group; technical term; corpus linguistics; systemic functional theory; coextensiveness.

In most individuals, EBV maintains a life-long asymptomatic latent infection. However, EBV can induce the formation of B cell lymphomas in immune suppressed individuals including people living with HIV (PLWH). Most individuals who acquire HIV are already infected with EBV as EBV infection is primarily acquired during childhood and adolescence. Although antiretroviral therapy (ART) has substantially reduced the incidence of AIDS-associated malignancies, EBV positive PLWH are at an increased risk of developing lymphomas compared to the general population. The direct effect of HIV co-infection on EBV replication and EBV-induced tumorigenesis has not been experimentally examined. Using a humanized mouse model of EBV infection, we demonstrate that HIV co-infection enhances systemic EBV replication and immune activation. Importantly, EBV-induced tumorigenesis was augmented in EBV/HIV co-infected mice. Collectively, these results demonstrate a direct effect of HIV co-infection on EBV pathogenesis and disease progression and will facilitate future studies to address why the incidence of certain types of EBV-associated malignancies are stable or increasing in ART treated PLWH.

The COVID-19 pandemic and the need for social distancing have created a demand for new and innovative solutions in healthcare systems worldwide. One of the strategies that have been implemented are chatbots, which can be helpful in providing reliable health information and preventing people from seeking assistance in healthcare centers and being unnecessarily exposed to the virus. In this context, although a high number of chatbots have been implemented worldwide, little has been discussed about the process and challenges in developing and implementing this technology. This paper reports on an action research, which designed a novel chatbot as a prompt response to the COVID-19 pandemic. The chatbot is intended to be a first layer of interaction with the public, performing triage of patients and providing information about COVID-19 on a large scale and without human contact. Our contribution is twofold: (i) we reflected on the development process and discuss lessons learned and recommendations to support a multidisciplinary development and evolution process of the chatbot; and (ii) we identified some interactive and technological features that can be used as a reference framework for this kind of technology. These contributions can be useful to other researchers and multidisciplinary teams facing similar challenges.

We report on a study exploring automatic edit annotation in a post-editing corpus with a new method for computing edit types. We examine edit type association with quality scores assigned to the machine translation output and the post-edited texts. Finally, we account for shortcomings in our method and point out edit types worth leveraging.

The advanced infrared (IR) and microwave (MW) sounding systems have been providing atmospheric sounding information critical for nowcasting and improving weather forecasts through data assimilation in numerical weather prediction. In recent years, advanced IR and MW sounder systems are being proposed to be onboard CubeSats that are much more cost efficient than traditional satellite systems. An impact study using a regional Observing System Simulation Experiment on a local severe storm (LSS) was carried out to evaluate the alternative of using advanced MW and IR sounders for high-impact weather forecasting in mitigating the potential data gap of the Advanced Technology Microwave Sounder (ATMS) and the Cross-track Infrared Sounder (CrIS) on the Suomi-NPP (SNPP) or Joint Polar Satellite System (JPSS). It was found that either MicroMAS-2 or the CubeSat Infrared Atmospheric Sounder (CIRAS) on a single CubeSat was able to provide a positive impact on the LSS forecast, and more CubeSats with increased data coverage yielded larger positive impacts. MicroMAS-2 has the potential to mitigate the loss of ATMS, and CIRAS the loss of CrIS, on SNPP or JPSS, especially when multiple CubeSats are launched. There are several approximations and limitations to the present study, but these represent efficiencies appropriate to the principal goal of the study — gauging the relative values of these sensors.

Background: Vertebral Haemangiomas (VHs) are frequent and generally asymptomatic benign tumors, involving the spine, usually incidentally found on computed tomography and magnetic resonance. Despite being usually asymptomatic and quiescent lesions, VHs can occasionally manifest aggressive features, leading to clinical manifestations such as back pain and neurological deficits.Case report.We report a case of a 54-year-old man, presented with 5 months history of pain, associated with lower limbs paraesthesia and weakness, gait disturbance and episodes of accidental falls. Radiological evaluation by spine pre- and post-contrast MRI indicated multiple vertebral hypervascular lesions, compatible with haemangiomas, involving from T3 to T11 levels, showing several different features (typical and atypical); aggressive haemangioma radiological pattern may be valuable at T3 and T4 vertebras. A thoracic spine pre- and post-contrast computed tomography confirmed the radiological diagnosis of multiple aggressive haemangiomas. Discussion: Aggressive VH consists in a very rare subset of vertebral haemangiomas characterized by a greater tendency in being symptomatic. They may show atypical radiological features, that make their diagnosis very complex. In the recent years, many strategies for treatment of symptomatic or aggressive VHs have been developed, but the optimal treatment strategy is still controversial. Conclusion: Although aggressive VHs being extremely rare, recognizing radiological features of these lesions is mandatory to achieve a correct diagnosis and appropriate therapeutic targets.

Abstract Pulmonary arterial hypertension (PAH) is a syndrome diagnosed by increased mean pulmonary artery (PA) pressure and resistance and normal pulmonary capillary wedge pressure. PAH is characterized pathologically by distal pulmonary artery remodeling, increased pulmonary vascular resistance, and plexiform lesions (PLs). Right ventricular fibrosis and hypertrophy, leading to right ventricular failure, are the main determinants of mortality in PAH. Recent work suggests that right ventricular fibrosis results from resident cardiac fibroblast activation and conversion to myofibroblasts, leading to replacement of contractile cardiomyocytes with nondistensible tissue incapable of conductivity or contractility. However, the origins, triggers, and consequences of myofibroblast expansion and its pathophysiological relationship with PAH are unclear. Recent advances indicate that signals generated by adaptive and innate immune cells may play a role in right ventricular fibrosis and remodeling. This review summarizes recent insights into the mechanisms by which adaptive and innate immune signals participate in the transition of cardiac fibroblasts to activated myofibroblasts and highlights the existing gaps of knowledge as relates to the development of right ventricular fibrosis.

Abstract Axions, originally proposed to solve the strong CP problem of quantum chromodynamics, emerge now as leading candidates of WISP dark matter. The rich phenomenology associated to the light and stable QCD axion can be described as an effective magnetic field that can be experimentally investigated. For the QUAX experiment, dark matter axions are searched by means of their resonant interactions with electronic spins in a magnetized sample. In principle, axion-induced magnetization changes can be detected by embedding a sample in an rf cavity in a static magnetic field. In this work we describe the operation of a prototype ferromagnetic haloscope, with a sensitivity limited by thermal fluctuations and receiver noise. With a preliminary dark matter search, we are able to set an upper limit on the coupling constant of DFSZ axions to electrons $$g_{aee}

Abstract To identify mechanical properties in heterogeneous materials, the local stress fields have to be estimated. The recent developments in imaging techniques allow reaching precise and spatially dense kinematic fields (e.g. displacement, strain ...). In this paper, an iterative procedure is used to identify the distribution of elastoplastic material parameters and the local stress fields. The formulation and the principle of the method are briefly presented while attention is paid to check its reliability and efficiency on finite element simulation data as reference full-field measurements. The method is also applied to noisy measured displacement fields to assess its robustness.

We compare the daily mean and standard deviation of the difference between the sea surface skin temperature (SST) derived from clear sky Atmospheric InfraRed Sounder (AIRS) data from seven atmospheric window channels between 2002 and 2020 and collocated Canadian Meteorological Centre (CMC) SST data from the tropical oceans. After correcting the mean difference for cloud contamination and diurnal effects, the remaining bias relative to the CMC SST, is reasonably consistent with estimates of the AIRS absolute accuracy based on the uncertainty of the pre-launch calibration. The time series of the bias produces trends well below the 10 mK/yr level required for climate change evaluations. The trends are in the 2 mK/yr range for the five window channels between 790 and 1231 cm−1, and +5 mK/yr for the shortwave channels. Between 2002 and 2020, the time series of the standard deviation of the difference between the AIRS SST and the CMC SST dropped fairly steadily to below 0.4 K in several AIRS window channels, a level previously only seen in gridded SST products relative to the Argo buoys.

The Atmospheric Infrared Sounder (AIRS) on the EOS Aqua Spacecraft was launched on 4 May 2002. The AIRS is designed to measure atmospheric temperature and water vapor profiles and has demonstrated exceptional radiometric and spectral accuracy and stability in orbit. The International System of Units (SI)-traceability of the derived radiances is achieved by transferring the calibration from the Large Area Blackbody (LABB) with SI traceable temperature sensors, to the On-Board Calibrator (OBC) blackbody during preflight testing. The AIRS views the OBC blackbody and four full aperture space views every scan. A recent analysis of pre-flight and on-board data has improved our understanding of the measurement uncertainty of the Version 5 AIRS L1B radiance product. For temperatures greater than 260 K, the measurement uncertainty is better than 250 mK 1-sigma for most channels. SI-traceability and quantification of the radiometric measurement uncertainty is critical to reducing biases in reanalysis products and radiative transfer models (RTMs) that use AIRS data, as well as establishing the suitability of AIRS as a benchmark for radiances established in the early 2000s.

ABSTRACT Increasing evidence shows that exosomes are key regulators in cancer cell-to-cell communication. Several reports on Epstein-Barr virus (EBV)-related malignancies demonstrate that latent membrane protein 1 (LMP1) secreted by exosomes derived from EBV- or LMP1-positive cells can promote cancer progression and metastasis. However, the mechanism by which LMP1 is loaded into exosomes is still poorly understood. Here, we examined whether the process of LMP1 loading into exosomes is linked to the multifunctional molecule of the ubiquitin system—ubiquitin C-terminal hydrolase-L1 (UCH-L1). For the first time, we demonstrate that LMP1 is physically associated with UCH-L1 and that directing of LMP1 to exosomes is mediated by C-terminal farnesylation of UCH-L1. Additionally, we found that the FTI-277 farnesyltransferase inhibitor reduces motility- and anchorage-independent growth of EBV-positive cells in functional assays. On the basis of our results, we conclude that C-terminal farnesylation of UCH-L1 is one of the key mechanisms by which LMP1 is sorted to exosomes. We hypothesize that inhibition of farnesylation with specific small-molecule inhibitors blocks exosome-mediated transfer of prometastatic molecules such as LMP1 during cancer cell-to-cell communications and thereby impedes the process of cancer invasion. IMPORTANCE Exosomes are small vesicles that cells secrete into the extracellular space, and there is increasing evidence that they have pivotal roles in cell-to-cell communication in malignancy. It is reported also that EBV-associated malignant cells, including those derived from nasopharyngeal carcinoma (NPC) and B-cell lymphoma, secrete exosomes. These EBV-related exosomes may contain viral products such as latent membrane protein 1 (LMP1) and may contribute to cancer progression. The aim of this study was to investigate the mechanism by which those viral products are loaded in exosomes. In this study, we show for the first time that ubiquitin C-terminal hydrolase-L1 (UCH-L1) and its C-terminal farnesylation, a posttranslational lipid modification, contribute to this mechanism. Our results also suggest that inhibition of UCH-L1 farnesylation is a potential therapeutic target against cancer metastasis and invasion.