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Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8(+) and CD4(+) T cell priming. However, the precise molecular mechanism by which IFNs regulate maturation and immunogenicity of DCs in vivo has not been studied in depth. Here we show that, after in vivo stimulation with the TLR ligand poly IC, IFNs dominate transcriptional changes in DCs. In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity. In addition, metabolic pathways, particularly the switch from oxidative phosphorylation to glycolysis, are also regulated by IFNs and required for DC maturation. These data provide evidence for a metabolic reprogramming concomitant with DC maturation and offer a novel mechanism by which IFNs modulate DC maturation.

Severe trauma induces a widespread response of the immune system. This \"genomic storm\" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.

Future wireless systems integrating communication and sensing will require handling an enormous amount of data with extremely low latency. Intense video streaming data traffic, pervasive-augmented and virtual reality services, advanced haptic-tactile interaction and holography-type communications, in fact, reveal a trend towards experience-based networks and multi-sense media, which require seamless connectivity and ultra-high capacity. Using current 5G technologies to take mentioned challenges, might not represent the desired solution and a completely new paradigm is needed. Recently, to support this change, scientists have been focusing on the concept of Smart Electromagnetic Environments (SEE), based on deploying a number of smart nodes, whose electromagnetic response needs to be finely adapted to the changing operative conditions. In this framework, a pivotal role is played by reconfigurable intelligent metasurfaces, allowing the implementation of smart skins, reflecting intelligent surfaces, smart repeaters, and intelligent antennas. This paper aims at offering an insightful review of the role of intelligent metasurfaces in advancing the concept of SEE. Different application domains will be illustrated: advanced signal processing at the physical layer, a new generation of smart antennas whose intelligence is enabled by the physical layer, and practical implementation of reflecting intelligent surfaces. With an in-depth analysis of these areas, this review sheds light on how intelligent metasurfaces drive innovation in wireless communication shaping the future of SEEs.

Obesity is among the leading causes of elevated cardiovascular disease mortality and morbidity. Adipose tissue dysfunction, insulin resistance and inflammation are recognized as important risk factors for the development of cardiovascular disorders in obesity. Hypoxia appears to be a key factor in adipose tissue dysfunction affecting not only adipocytes but also immune cell function. Here we examined the effect of hypoxia-induced transcription factor HIF1α activation on classical dendritic cell (cDCs) function during obesity. We found that deletion of Hif1 α on cDCs results in enhanced adipose-tissue inflammation and atherosclerotic plaque formation in a mouse model of obesity. This effect is mediated by HIF1α-mediated increased lipid synthesis, accumulation of lipid droplets and alter synthesis of lipid mediators. Our findings demonstrate that HIF1α activation in cDCs is necessary to control vessel wall inflammation.

BACKGROUNDEpicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT's immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients.METHODSWe recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients' clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups.RESULTSFlow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls.CONCLUSIONAdaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile.FUNDINGBarts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419.

Background Staged bilateral Magnetic Resonance–guided Focused Ultrasound (MRgFUS) thalamotomy is an incisionless option for medication‐refractory essential tremor (ET). While the efficacy and safety of unilateral MRgFUS are established, evidence for bilateral treatment remains limited. Objective To evaluate the efficacy and safety of staged bilateral MRgFUS in a prospective single‐centre observational cohort and to perform a systematic review and meta‐analysis of the literature. Methods Consecutive ET patients undergoing second‐side MRgFUS were prospectively assessed. The primary efficacy endpoint was the longitudinal change in Clinical Rating Scale for Tremor (CRST) A + B scores for the treated hand after FUS2, while safety was evaluated by collecting and grading adverse events (AEs). A systematic review identified published bilateral MRgFUS series; efficacy data were meta‐analysed, while AEs were reported descriptively. Results Fifteen patients (60% men; mean age 74.1 ± 8.9 years) underwent FUS2 28.9 ± 22.5 months after first‐side treatment. At the 12‐month evaluation, CRST A + B decreased from 21.0 to 8.8 (−58%), CRST C from 7.3 to 1.9 (−74.2%), and QUEST from 30.5 to 9.5 (−68.7%). Head and voice tremor were reduced by 73.8% and 40.3%, respectively. AEs were predominantly mild (95.2%) and transient (88%). Cognition at 1 year was globally preserved, with a selective decline in verbal episodic memory. Meta‐analysis confirmed significant improvement in tremor severity. Conclusion Staged bilateral MRgFUS thalamotomy was associated with sustained tremor reduction, including midline tremor, functional improvement and acceptability, with a manageable safety profile. Overall, consistent with literature, these findings support its potential role as a therapeutic option in selected ET patients. This study evaluated the efficacy and safety of staged bilateral MR‐guided focused ultrasound (MRgFUS) thalamotomy for medication‐refractory essential tremor (ET) through a prospective cohort and a systematic review with meta‐analysis. Second‐side treatment was associated with sustained tremor reduction, additional functional improvement, and a manageable safety profile at 12 months. Overall, these results support staged bilateral MRgFUS as a therapeutic option in patients with ET. Abbreviations: AEs, Adverse Events; CRST, Clinical Rating Scale for Tremor; CTCAE, Common Terminology Criteria for Averse Events; FUS1, first side MRgFUS thalamotomy; FUS2, second side MRgFUS thalamotomy.

Background:Reproductive health is growing attention is all medical fields. As most rheumatic diseases are diagnosed at young age both in men and women, reproductive health is to be considered for a comprehensive management of our patients.Objectives:To assess whether reproductive health counselling is a valid choice for patients with rheumatic diseases.Methods:In this observational study, a survey about reproductive health (sexuality, contraception, fertility, pregnancy, lactation, transmissibility) in relation to their disease has been administered to patients with immune-mediated diseases aged 18 to 50years, attending a Reproductive Health Counselling Clinic. Their need for information about reproductive health as part of a counselling carried out by dedicated rheumatologists was investigated. A survey about their experience with our clinic is analyzed in this study.Results:From January to September 2023, 271 patients completed the survey (Figure 1), of which 102 (37.6%) asked for counselling. Of these 102 patients, 24 (23.5%) wanted to explore contraception, 49 (48.0%) fertility, 79 (77.5%) transmissibility, 46 (45.1%) drugs used for their rheumatic disease and 41 (40.2%) sexuality. 68.3% of women wanted to address pregnancy and lactation, while 7 men wanted to address conceiving. 35 counselling have already been carried out (22 females, 13 males); 4 of these counselling were televisits. 15 were couple counselling. The topics that patients needed to address during counselling were sexuality (16, 45.7%), fertility (22, 60.0%), contraception (11, 31%), conceiving/pregnancy/lactation (20, 571%), drugs used for their rheumatic disease (18, 51.4%). 7 patients were referred to other specialists, such as gynecologist (4 women), urologist (1 man), sexologist (2 patients). 2 patients were referred to other specialists. 12 women were referred to our rheumatologic-gynecologic multidisciplinary clinic for broodiness. Most of the patients, as shown in Figure 1, reported an optimal satisfaction.Conclusion:Reproductive health counseling conducted by dedicated rheumatologists, in-person or remotely, has proven to be an effective method for conveying useful information and providing appropriate guidance to male and female patients. The level of patients’ satisfaction was found to be high, both in terms of the quality of the information received and the positive impact on reducing fear and stress in relation to these issues, suggesting to implement this tool to improve the management and the quality of life of patients living with rhematic diseases.REFERENCES:NIL.Table 1. Demographic characteristics of patients. CTD, connective tissue disease; RA, rheumatoid arthritis; SpA, spondyloarthropathies; b-DMARDs, biological disease-modifying antirheumatic drugs; cs-DMARDs, conventional synthetic disease-modifying antirheumatic drugs; ts-DMARDs, targeted synthetic disease-modifying antirheumatic drugs.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:As reproductive health is gathering attention in Rheumatology and all medical fields, the male perspective on the matter is often overlooked as not directly related to pregnancy and lactation.Objectives:To describe male perception of sexuality, fertility, contraception, conceiving related to their rheumatic disease, and their need to explore these aspects in a dedicated counselling session.Methods:In this cross-sectional observational study, a survey about reproductive health (sexuality, contraception, fertility, conceiving, pregnancy, lactation, transmissibility) in relation to their disease has been administered to consecutive patients with immune-mediated diseases aged 18 to 50years, attending a Reproductive Health Counselling Clinic. Their need for information about reproductive health as part of a counselling carried out by dedicated rheumatologists (on-site or by televisit) was investigated. In this study the male perspective was analysed.Results:From January to September 2023, 103 male patients completed the survey (Table 1). 10% of patients noted a changing in their sexuality after the diagnosis, 20% patients thought their rheumatic disease influences their sexuality and 3.9% believed their partner sexual behavior changed after the diagnosis. Regarding contraception, 37.9% of patients affirmed not to use condoms, while 18% had a female partner that used contraceptives, and most patients had never explored the contraception topic with their partner. 10% and 17% of patients reported their fertility may be influenced by their disease or the drugs taken for it, respectively. From our data, 60% were worried about transmissibility of their disease to children. 37% of patients were worried both for the effect that their disease or the drugs taken for it could have on conceiving, respectively. Figure 1 shows which aspects of reproductive health had already been addressed during any visit and which aspects patients needed to address. It is important to underline that 44% of patients had never addressed any reproductive health issue with any physician, while 39% had already discussed these topics with a rheumatologist, 4% with a urologist and 7% with their general practitioner. 37 patients requested counselling, of which 15 have already been carried out (13 on-site visits, 2 televisits). Most of the patients was satisfied by the counselling (80%) and would recommend it to other patients (86.7%). 1 patient has been referred to a Urologist to address infertility issues.Conclusion:Reproductive health is often overlooked especially in male patients as not directly related to pregnancy or lactation. As almost 50% of male patients had never addressed any of reproductive health related items before (sexuality, fertility, conceiving, contraception, drugs taken for the rheumatic disease), counselling, both in-person or remotely, has proved successful in answering patients’ questions or doubts.REFERENCES:NIL.Table 1.Demographic and clinical characteristics of patientsCTD, connective tissue diseases; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SpA, spondyloarthropathies; b-DMARDs, biological disease-modifying antirheumatic drugs; cs-DMARDs, conventional synthetic disease-modifying antirheumatic drugs; ts-DMARDs, targeted synthetic disease-modifying antirheumatic drugs.Figure 1.Acknowledgements:NIL.Disclosure of Interests:None declared.

BACKGROUNDThymic involution with age leads to reduced T cell output and impaired adaptive immunity. However, the extent to which thymic activity persists later in life and how this contributes to immunological aging remains unclear. This study aimed to assess the presence and function of thymic tissue in older adults and identify factors influencing residual thymopoiesis.METHODSPatients aged 50 or older undergoing cardiothoracic surgery were recruited. Thymic structures within mediastinal adipose tissue were evaluated using histology, immunofluorescence, flow cytometry, T cell receptor (TCR) sequencing, and RNA sequencing. Recent thymic emigrants (RTEs) were quantified in peripheral blood and correlated with transcriptomic, epigenetic, and TCR repertoire data. Primary outcomes included thymic tissue identification, RTE frequency, and immune correlates.RESULTSFunctional thymic tissue was identified in mediastinal adipose tissue of older individuals. The frequency of CD31+CD4+ T cells (RTEs) positively correlated with the presence of thymic tissue. Thymic output showed substantial heterogeneity and was influenced by sex and smoking history. Thymic activity was associated with increased TCR repertoire diversity, improved immune protection against infections, and reduced epigenetic aging. Detailed profiling uncovered functional and phenotypic heterogeneity within naive CD4+ T cell subsets shaped by thymic activity.CONCLUSIONThis study demonstrates that thymic function can persist into later life and is modulated by factors such as sex and smoking. These findings suggest that thymic activity during aging is heterogeneous and influenced by more than chronological age alone, with potential implications for immune competence in older adults.

T cell activation is associated with a profound and rapid metabolic response to meet increased energy demands for cell division, differentiation and development of effector function. Glucose uptake and engagement of the glycolytic pathway are major checkpoints for this event. Here we show that the low-affinity, concentration-dependent glucose transporter 2 (Glut2) regulates the development of CD8 + T cell effector responses in mice by promoting glucose uptake, glycolysis and glucose storage. Expression of Glut2 is modulated by environmental factors including glucose and oxygen availability and extracellular acidification. Glut2 is highly expressed by circulating, recently primed T cells, allowing efficient glucose uptake and storage. In glucose-deprived inflammatory environments, Glut2 becomes downregulated, thus preventing passive loss of intracellular glucose. Mechanistically, Glut2 expression is regulated by a combination of molecular interactions involving hypoxia-inducible factor-1 alpha, galectin-9 and stomatin. Finally, we show that human T cells also rely on this glucose transporter, thus providing a potential target for therapeutic immunomodulation. In this study, Fu et al. provide mechanistic insight into how GLUT2 fine-tunes environmental nutrient sensing with T cell activation, which optimizes metabolic adaptation during acquisition of T cell effector function.