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In adult patients, treatment of skeletal crossbite requires combined treatment by fixed or removable appliances and orthognathic surgery. In cases of dentoalveolar crossbite, expansion can be achieved with fixed multibrackets and removable transparent aligners. Various researchers have already assessed the Invisalign system's predictability for arch expansion. However, most of this research was conducted using older appliances, making it necessary to assess the characteristics of the updated system SmartTrack. A sample of 114 patients with transverse malocclusion were treated with SmartTrack. The predictability of the system's software (Clincheck) was assessed by comparing planned measurements (width of canines, premolars and molars rotations and inclinations) with the real measurements achieved at the end of the first treatment phase. Measurements were imported to Clincheck software to create three data sets; T1: initial measurements at start of treatment; T2: Clincheck predicted measurements at end of first treatment phase; T3: measurements taken at start of the second treatment phase. Widths underwent significant advances as a result of treatment. For all widths, virtual planning obtained prognoses of greater expansion than actually achieved: a mean of 0.63 mm more expansion at the canine level (p<0.001), 0.77 mm at first premolar (p<0.001), 0.81 at second premolar (p<0.001), 0.69 mm at first molar (p<0.001), and 0.25 mm at second molar (p = 0.183). All the treatment plan's estimations, with the exception of the second molar, were significantly higher than the actual outcomes. Aligners are an effective tool for producing arch expansion, being more effective in premolar area and less effective in canine and second molar area. Predictability was reasonable for expansion movement. Overcorrection should be considered at the virtual planning stage in order to obtain the expected outcomes.

CD8 + T cells contribute to tuberculosis (TB) infection control by inducing death of infected macrophages. Mycobacterium tuberculosis ( Mtb ) infection is associated with increased PD-1/PD-L1 expression and alternative activation of macrophages. We aimed to study the role of PD-1 pathway and macrophage polarization on Mtb -specific CD8 + T cell-induced macrophage death. We observed that both PD-L1 on CD14 + cells and PD-1 on CD8 + T cells were highly expressed at the site of infection in pleurisy TB patients’ effusion samples (PEMC). Moreover, a significant increase in CD8 + T cells’ Mtb -specific degranulation from TB-PEMC vs. TB-PBMC was observed, which correlated with PD-1 and PDL-1 expression. In an in vitro model, M1 macrophages were more susceptible to Mtb -specific CD8 + T cells’ cytotoxicity compared to M2a macrophages and involved the transfer of cytolytic effector molecules from CD8 + T lymphocytes to target cells. Additionally, PD-L1 blocking significantly increased the in vitro Ag-specific CD8 + T cell cytotoxicity against IFN-γ-activated macrophages but had no effect over cytotoxicity on IL-4 or IL-10-activated macrophages. Interestingly, PD-L1 blocking enhanced Mtb -specific CD8 + T cell killing of CD14 + cells from human tuberculous pleural effusion samples. Our data indicate that PD-1/PD-L1 pathway modulates antigen-specific cytotoxicity against M1 targets in-vitro and encourage the exploration of checkpoint blockade as new adjuvant for TB therapies.

The ability of Mycobacterium tuberculosis (Mtb) to persist inside host cells relies on metabolic adaptation, like the accumulation of lipid bodies (LBs) in the so-called foamy macrophages (FM), which are favorable to Mtb. The activation state of macrophages is tightly associated to different metabolic pathways, such as lipid metabolism, but whether differentiation towards FM differs between the macrophage activation profiles remains unclear. Here, we aimed to elucidate whether distinct macrophage activation states exposed to a tuberculosis-associated microenvironment or directly infected with Mtb can form FM. We showed that the triggering of signal transducer and activator of transcription 6 (STAT6) in interleukin (IL)-4-activated human macrophages (M(IL-4)) prevents FM formation induced by pleural effusion from patients with tuberculosis. In these cells, LBs are disrupted by lipolysis, and the released fatty acids enter the β-oxidation (FAO) pathway fueling the generation of ATP in mitochondria. Accordingly, murine alveolar macrophages, which exhibit a predominant FAO metabolism, are less prone to become FM than bone marrow derived-macrophages. Interestingly, direct infection of M(IL-4) macrophages with Mtb results in the establishment of aerobic glycolytic pathway and FM formation, which could be prevented by FAO activation or inhibition of the hypoxia-inducible factor 1-alpha (HIF-1α)-induced glycolytic pathway. In conclusion, our results demonstrate that Mtb has a remarkable capacity to induce FM formation through the rewiring of metabolic pathways in human macrophages, including the STAT6-driven alternatively activated program. This study provides key insights into macrophage metabolism and pathogen subversion strategies.

Recently, new strategies for treating class III malocclusions have appeared. Skeletal anchorage appears to reduce the dentoalveolar effects while maximising the orthopaedic effect in growing patients. The purpose of this systematic review and meta-analysis is to examine the effectiveness of bone anchorage devices for interceptive treatment of skeletal class III malocclusions. Searches were made in the Pubmed, Embase, Scopus and Cochrane databases, as well as in a grey literature database, and were complemented by hand-searching. The criteria for eligibility were: patients who had undergone orthodontic treatment with skeletal anchorage (miniplates and miniscrews). Patients with syndromes or craniofacial deformities or who had undergone maxillofacial surgery were excluded. The following variables were recorded for each article: author, year of publication, type of study, sample size, dropouts, demographic variables, treatment carried out, radiographic study (2D or 3D), follow-up time, and quality of the articles on the Newcastle-Ottawa Scale. The means and confidence intervals of the following variables were employed: Wits, overjet, ANB, SNA and SNB. Initially, 239 articles were identified. After removing the duplicates and applying the selection criteria, 9 were included in the qualitative synthesis and 7 in the quantitative synthesis (meta-analysis). It may be concluded that skeletal anchorage is an effective treatment for improving skeletal Class III malocclusion, but when compared with other traditional treatments such as disjunction and face mask, there is no clear evidence that skeletal anchorage improves the results.

This paper presents a deep learning approach for predicting rail corrugation based on on-board rolling-stock vertical acceleration and forward velocity measurements using One-Dimensional Convolutional Neural Networks (CNN-1D). The model’s performance is examined in a 1:10 scale railway system at two different forward velocities. During both the training and test stages, the CNN-1D produced results with mean absolute percentage errors of less than 5% for both forward velocities, confirming its ability to reproduce the corrugation profile based on real-time acceleration and forward velocity measurements. Moreover, by using a Gradient-weighted Class Activation Mapping (Grad-CAM) technique, it is shown that the CNN-1D can distinguish various regions, including the transition from damaged to undamaged regions and one-sided or two-sided corrugated regions, while predicting corrugation. In summary, the results of this study reveal the potential of data-driven techniques such as CNN-1D in predicting rails’ corrugation using online data from the dynamics of the rolling-stock, which can lead to more reliable and efficient maintenance and repair of railways.

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

The majority of studies on oxidative phosphorylation in immune cells have been performed in mouse models, necessitating human translation. To understand the impact of oxidative phosphorylation (OXPHOS) deficiency on human immunity, we studied children with primary mitochondrial disease (MtD). scRNAseq analysis of peripheral blood mononuclear cells was performed on matched children with MtD (N = 4) and controls (N = 4). To define B cell function we performed phage display immunoprecipitation sequencing on a cohort of children with MtD (N = 19) and controls (N = 16). Via scRNAseq, we found marked reductions in select populations involved in the humoral immune response, especially antigen presenting cells, B cell and plasma populations, with sparing of T cell populations. , a marker of bioenergetic stress, was significantly elevated in populations that were most depleted. , a miRNA contained in the intron of , was co-expressed. Knockdown studies of demonstrated its role in promoting survival by modulating apoptosis. To determine the functional consequences of our findings on humoral immunity, we studied the antiviral antibody repertoire in children with MtD and controls using phage display and immunoprecipitation sequencing. Despite similar viral exposomes, MtD displayed antiviral antibodies with less robust fold changes and limited polyclonality. Overall, we show that children with MtD display perturbations in the B cell repertoire which may impact humoral immunity and the ability to clear viral infections.

Mechanical vibration devices such as AcceleDent have been marketed as non-invasive adjuncts capable of accelerating orthodontic tooth movement. The proposed mechanism involves the stimulation of cellular activity and bone remodeling. The aim of this study was to determine whether the use of AcceleDent, in combination with clear aligner therapy, produces a measurable increase in the surface temperature of intraoral tissues. Twenty-two adult patients (mean age: 39 ± 15 years) undergoing orthodontic treatment with clear aligners (Invisalign) participated in this crossover study. Infrared thermography (A35, FLIR, Wilsonville, USA) was used to record temperature measurements of gingival and dental surfaces. Each participant underwent two experimental conditions on separate days: (1) wearing the AcceleDent device while active (vibrating) and (2) wearing the same device inactive (non-vibrating). After a 20-minute thermal acclimatization period, the device was applied for 20 min before imaging. No statistically significant differences were observed in surface temperature between the vibrating and non-vibrating conditions (Gingiva: p  = 0.69; Tooth: p  = 0.76). Likewise, no significant differences were detected at baseline between the two sessions (Gingiva: p  = 0.35; Tooth: p  = 0.57). The use of AcceleDent vibration during clear aligner therapy does not result in an increase in the surface temperature of gingival or dental tissues, as measured by infrared thermography. This study provides evidence that AcceleDent vibration does not produce thermal changes in intraoral tissues, suggesting it is thermally safe for use alongside clear aligners. Infrared thermography may serve as a non-invasive tool to monitor physiological effects of orthodontic devices.

The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic classification, which accompanies and complements the most-recent genotypic classification. This phenotypic classification is aimed for clinicians at the bedside and focuses on clinical features and laboratory phenotypes of specific IEI. In this classification, 485 IEI underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity and auto-inflammation are described, including 55 novel monogenic defects and 1 autoimmune phenocopy. Therefore, all 485 diseases of the genetic classification are presented in this paper in the form of colored tables with essential clinical or immunological phenotype entries.

Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide.