First contact(in): The complete structure of contactin 2.

In this issue of Structure, Fan et al.1 report the structure of the full contactin 2 ectodomain, representing the first for the contactin family. The work reveals six immunoglobulin domains are essential for intercellular interactions, explores differences in proposed contactin 2 homodimerization mechanisms, and provides an updated model for contactin 2 organization on and between cells.

Methyl-donor supplementation in women with systemic lupus erythematosus with different nutritional status: the protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: DNA hypomethylation in patients with systemic lupus erythematosus (SLE) has been recently documented in the literature. Low levels of DNA methylation have been observed globally and in genes associated with immune and inflammatory pathways in SLE's CD4+T lymphocytes. Given that certain micronutrients can either donate methyl groups within one-carbon metabolism pathways or serve as cofactors for enzymes involved in the DNA methylation process, this randomised, double-blind, placebo-controlled trial aims to investigate whether a 3-month supplementation of folic acid and vitamin B12 will modulate the DNA methylation profile in subcutaneous adipose tissue (primary outcome) of women with SLE and normal weight or excess body weight. As secondary objectives, we will assess gene expression, telomere length and phenotypic characteristics (ie, clinical parameters, body weight and composition, abdominal circumference, food intake and disordered eating attitude, physical activity, lipid profile, serum concentrations of leptin, adiponectin, and cytokines). METHODS AND ANALYSIS: Patients will be classified according to their nutritional status by body mass index in normal weight or excess body weight. Subsequently, patients in each group will be randomly assigned to either a placebo or an intervention group (folic acid (400 mcg) and vitamin B12 (2000 mcg) supplementation). Endpoint evaluations will be conducted using both intention-to-treat and per-protocol analyses. This study has the potential to design new personalised nutritional approaches as adjunctive therapy for patients with SLE. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Ethical Committee from Clinical Hospital of the School of Medicine of the University of Sao Paulo, Brazil (CAAE.: 47317521.8.0000.0068). TRIAL REGISTRATION NUMBER: NCT05097365 (first version).

Ventilation does not affect close-range transmission of influenza virus in a ferret playpen setup.

Sustained community spread of influenza viruses relies on efficient person-to-person transmission. Current experimental transmission systems do not mimic environmental conditions (e.g., air exchange rates, flow patterns), host behaviors, or exposure durations relevant to real-world settings. Therefore, results from these traditional systems may not be representative of influenza virus transmission in humans. To address this pitfall, we developed a close-range transmission setup that implements a play-based scenario and used it to investigate the impact of ventilation rates on transmission. In this setup, four immunologically naive recipient ferrets were exposed to a donor ferret infected with a genetically barcoded 2009 H1N1 virus (H1N1pdm09) for 4 h. The ferrets interacted in a shared space that included toys, similar to a childcare setting. Transmission efficiency was assessed under low and high ventilation, with air exchange rates of ~1.3 h-1 and 23 h-1, respectively. Transmission efficiencies observed in three independent replicate studies were similar between ventilation conditions. The presence of infectious virus or viral RNA on surfaces and in air throughout the exposure area was also not impacted by the ventilation rate. While high viral genetic diversity in donor ferret nasal washes was maintained during infection, recipient ferret nasal washes displayed low diversity, revealing a narrow transmission bottleneck regardless of ventilation rate. Examining the frequency and duration of ferret physical touches revealed no link between these interactions and a successful transmission event. Our findings indicate that exposures characterized by frequent, close-range interactions and the presence of fomites can overcome the benefits of increased ventilation.

Domestic chicken predation and prey sharing by urban capuchin monkeys (Sapajus sp.).

Capuchin monkeys are omnivorous platyrrhines with a high frequency of faunivory and can survive in urban forest fragments. Predation of wild vertebrates (high-quality foods) by capuchin monkeys has been frequently reported in many species of Cebus and Sapajus. However, predation of domestic animals is unknown. We describe a rare episode of predation, consumption, and sharing of an adult domestic chicken (Gallus gallus domesticus) by individuals from a social group of robust capuchin monkeys (Sapajus sp.) living in a small urban park in the city of Foz do Iguaçu, southern Brazil. This relatively large prey is freely farmed at the study site. The capture, slaughter, preparation (removal of feathers from the body), and consumption of the prey by the capuchins lasted 22 min. The dominant adult male ate the chicken's head and tolerated the approach of two juveniles. The juveniles shared the remainder of the prey after the adult abandoned it. These juveniles scared other group members that approached the carcass. We recorded an opportunistic hunt for easily accessible domestic prey, a case of human resource use by urban primates that shared passively the atypical and valuable food. Though a rare event, the predation on a domestic animal indicates a potential source of conflict with humans that can have negative impacts on urban primates.

Erythroblast enucleation at a glance.

Erythroid enucleation, the penultimate step in mammalian erythroid terminal differentiation, is a unique cellular process by which red blood cells (erythrocytes) remove their nucleus and accompanying nuclear material. This complex, multi-stage event begins with chromatin compaction and cell cycle arrest and ends with generation of two daughter cells: a pyrenocyte, which contains the expelled nucleus, and an anucleate reticulocyte, which matures into an erythrocyte. Although enucleation has been compared to asymmetric cell division (ACD), many mechanistic hallmarks of ACD appear to be absent. Instead, enucleation appears to rely on mechanisms borrowed from cell migration, endosomal trafficking and apoptosis, as well as unique cellular interactions within the microenvironment. In this Cell Science at a Glance article and the accompanying poster, we summarise current insights into the morphological features and genetic drivers regulating the key intracellular events that culminate in erythroid enucleation and engulfment of pyrenocytes by macrophages within the bone marrow microenvironment.

Activation of the l-fucose utilization cluster in Campylobacter jejuni induces proteomic changes and enhances Caco-2 cell invasion and fibronectin binding.

Most Campylobacter jejuni isolates carry the fucose utilization cluster (Cj0480c-Cj0489) that supports the metabolism of l-fucose and d-arabinose. In this study we quantified l-fucose and d-arabinose metabolism and metabolite production, and the impact on Caco-2 cell interaction and binding to fibronectin, using C. jejuni NCTC11168 and the closely related human isolate C. jejuni strain 286. When cultured with l-fucose and d-arabinose, both isolates showed increased survival and production of acetate, pyruvate and succinate, and the respective signature metabolites lactate and glycolic acid, in line with an overall upregulation of l-fucose cluster proteins. In vitro Caco-2 cell studies and fibronectin-binding experiments showed a trend towards higher invasion and a significantly higher fibronectin binding efficacy of C. jejuni NCTC11168 cells grown with l-fucose and d-arabinose, while no significant differences were found with C. jejuni 286. Both fibronectin binding proteins, CadF and FlpA, were detected in the two isolates, but were not significantly differentially expressed in l-fucose or d-arabinose grown cells. Comparative proteomics analysis linked the C. jejuni NCTC11168 phenotypes uniquely to the more than 135-fold upregulated protein Cj0608, putative TolC-like component MacC, which, together with the detected Cj0606 and Cj0607 proteins, forms the tripartite secretion system MacABC with putative functions in antibiotic resistance, cell envelope stress response and virulence in Gram negative pathogenic bacteria. Further studies are required to elucidate the role of the MacABC system in C. jejuni cell surface structure modulation and virulence.

Self-sensitized photodegradation and adsorption of aqueous malachite green dye using one-dimensional titanium oxide nanofilaments.

Truly one-dimensional titanium oxide nanofilaments with a lepidocrocite structure (1DLs) were explored in the adsorption and photocatalytic degradation of aqueous malachite green (MG), a toxic polluting dye. Decolorization is monitored by ultraviolet-visible spectroscopy, and mineralization is confirmed by total organic carbon analysis. The 1DL/MG flocs are characterized by scanning electron microscopy and X-ray diffraction. 1DLs, a colloidal nanomaterial, exhibit flocculating behavior while demonstrating high affinity for MG, with a maximum uptake of >680 mg/g rapidly via ion exchange. Additionally, 1DLs decolorize MG under visible light only, unlike most available titania products, via a self-sensitization effect. MG is decolorized by 1DLs by >70% in 30 min under 1 sun exposure of visible light. Counterintuitively, dye adsorption increases as the normalized concentration by mass of 1DL decreases. Demonstrating high adsorption capacity and dye mineralization supports the use of 1DLs in water treatment and self-sensitization for photoelectrochemical devices, like solar cells.

Silicon photonic microresonator-based high-resolution line-by-line pulse shaping.

Optical pulse shaping stands as a formidable technique in ultrafast optics, radio-frequency photonics, and quantum communications. While existing systems rely on bulk optics or integrated platforms with planar waveguide sections for spatial dispersion, they face limitations in achieving finer (few- or sub-GHz) spectrum control. These methods either demand considerable space or suffer from pronounced phase errors and optical losses when assembled to achieve fine resolution. Addressing these challenges, we present a foundry-fabricated six-channel silicon photonic shaper using microresonator filter banks with inline phase control and high spectral resolution. Leveraging existing comb-based spectroscopic techniques, we devise a system to mitigate thermal crosstalk and enable the versatile use of our on-chip shaper. Our results demonstrate the shaper's ability to phase-compensate six comb lines at tunable channel spacings of 3, 4, and 5 GHz. Specifically, at a 3 GHz channel spacing, we showcase the generation of arbitrary waveforms in the time domain. This scalable design and control scheme holds promise in meeting future demands for high-precision spectral shaping capabilities.

Toxicity and Sublethal Effects of Piper hispidinervum Essential Oil on Behavioral and Physiological Responses of Sitophilus zeamais Populations.

This study aimed to evaluate the toxicity of Piper hispidinervum essential oil (PHEO) against 11 Brazilian populations of Sitophilus zeamais (Coleoptera: Curculionidae). The effects of sublethal doses of PHEO on the behavior (walking and flying), respiration, and population growth (ri) of the insect populations were investigated. PHEO toxicity was determined through concentration-mortality bioassays, with mortality curves established using increasing PHEO concentrations ranging from 140.00 to 1000.00 µL kg-1. Behavior was evaluated based on walking distance, walking time, walking speed, walking time proportion, flight height, and flight takeoff success. Respiration was measured via the respiratory rate, while population growth (ri) was assessed through the instantaneous growth rate. All 11 populations of S. zeamais were susceptible to PHEO, showing no signs of resistance. The populations exhibited varying behavioral and physiological responses to sublethal exposure to PHEO, indicating different mitigation strategies. The results confirm that PHEO possesses insecticidal potential for controlling S. zeamais populations. However, the observed behavioral and physiological responses should be considered when establishing control measures in pest management programs for stored products.

Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore? - A rapid scoping review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.

Is a 1-year course of methotrexate in patients with arthralgia at-risk for rheumatoid arthritis cost-effective? A cost-effectiveness analysis of the randomised, placebo-controlled TREAT EARLIER trial.

OBJECTIVES: Rheumatoid arthritis (RA) has a considerable disease burden with life-long physical limitations, reduced work productivity and high societal costs. Trials on arthralgia at-risk for RA are therefore conducted, aiming to intercept evolving RA and reduce the disease burden. A 1-year course of methotrexate in patients with clinically suspect arthralgia (CSA) caused sustained improvements in subclinical joint inflammation and physical impairments. Since the cost-effectiveness of treatment in CSA has never been investigated, we investigated whether methotrexate is cost-effective. METHODS: Cost-effectiveness was assessed using the TREAT EARLIER trial. 236 patients with CSA with subclinical joint inflammation were randomised to 1-year treatment with methotrexate, or placebo, and followed for 2 years. Cost-effectiveness was analysed by computing costs and effects. For costs, both a societal perspective (healthcare-productivity and work-productivity costs) and a healthcare perspective (healthcare costs only) were used. For effects, quality adjusted life years (QALYs) were used. RESULTS: Treatment increased QALYs by 0.041 (95% CI -0.050 to 0.091), and reduced costs with €-4809 (95% CI -12 382 to 2726) over the course of 2 years using a societal perspective, with a probability of 88.1% that treatment was cost-effective. From a healthcare perspective, the cost-difference between treatment and placebo was estimated at €-418 (95% CI -1198 to 225). CONCLUSION: A fixed treatment course in individuals with arthralgia at-risk for RA and MRI-detected subclinical joint inflammation resulted in better work productivity, lower healthcare costs and improved quality of life over the course of 2 years; with the largest gain in productivity costs. This is the first evidence that methotrexate treatment aiming at secondary prevention in arthralgia at-risk for RA is cost-effective.

Seizure Induced by Single-Pulse TMS Delivered to Lesioned Hemisphere in Stroke.

ABSTRACT: Transcranial magnetic stimulation (TMS) is used for therapeutic and research purposes, but it is still important to establish safety guidelines and recommendations mainly related to serious adverse effect (SAE). As part of this, safety reports need to be published. Our report highlights a case of a male patient who was a 30-year-old with a history of hemorrhagic stroke following an accidental seizure episode during a single-pulse TMS.

Improving the Tribological Performance of POM through the Incorporation of Bio-Based Materials.

Polyoxymethylene (POM), an engineering polymer commonly used in tribological applications, is often reinforced with fossil-based fibers such as carbon and/or glass fibers to improve its properties. To find more sustainable solutions, in this study, the tribological performance of POM/short cellulose fiber composites at different sliding conditions is investigated. An improvement in the wear coefficient of roughly 69% is observed at the harshest conditions of 5 MPa and 1 m · s-1 with only 10 wt.% cellulose fibers. The friction behavior is furthermore stabilized through fiber addition, as the unfilled polymer did not show a steady state. No signs of thermo-oxidative degradation are found after tribological testing. This study presents promising results for sustainable wear-resistant polymer materials in tribological applications.

Digital Exclusion, Social Deprivation, and Clinical Outcomes of Patients Undergoing Hyperacuity Home Monitoring.

INTRODUCTION: Digital exclusion is a growing challenge when deploying digital patient care pathways and a potential barrier to widespread implementation, especially in the field of smartphone-based self-monitoring of vision. This retrospective case series seeks to examine the characteristics of individuals who adhere to a smartphone home monitoring programme using the Alleye app for retinal disease, with a focus on digital exclusion, social deprivation and clinical outcomes. METHODS: We conducted a retrospective analysis of 89 patients with retinal pathologies including diabetic retinopathy and retinal vein occlusions at Moorfields Eye Hospital participating in an Alleye home monitoring programme between April 2020 and November 2022. Postcodes were used to determine the Digital Exclusion Risk Index (DERI) and the Index of Multiple Deprivation (IMD) rebased for London. Clinical information from the electronic patient record and Alleye app usage data were extracted for each patient. Associations between the DERI/IMD, clinical parameters and app use were examined using multivariable regression models. RESULTS: Mean DERI was 2.56 (standard deviation [SD] = 0.36), IMD was 6.25 (SD = 2.79), visual acuity (VA) in the better eye at study entry was 83.28 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (SD = 7.92), and mean follow-up was 344.46 days (SD = 260.13). During the observation period, 36% received an intravitreal injection (IVI) and VA fell by at least ten letters in approximately one in four patients. In 87.5% of patients requiring IVI, the use of the app increased. We found no association between clinical parameters and programme adherence for DERI or IMD. CONCLUSIONS: We found no association between high digital exclusion risk and high social deprivation with monitoring adherence to smartphone-based self-monitoring of vision, contrary to the currently available evidence. This suggests that smartphone-based self-monitoring of vision is accessible to population groups of varying digital exclusion and social deprivation risk, and can be safely employed to monitor clinical progression.

Patterns and Risk Factors for Rehospitalizations Within the First 90 Days Following Discharge After Heart Transplantation.

BACKGROUND: Heart transplantation (HT) recipients are at risk for urgent rehospitalizations following discharge. However, data on prevalence, risk factors and clinical outcomes associated with post-HT rehospitalization are limited. METHODS: This study aims to describe patterns of urgent rehospitalizations in HT recipients at a cardiology reference center in Brazil. Rehospitalizations and deaths occurring within the first 90 days following hospital discharge were identified. Regression models were used to identify variables associated with urgent rehospitalizations. RESULTS: A total of 239 patients were included. Of those, 118 (49.4%) presented with a rehospitalization within 90 days following hospital discharge and 5 (2.01%) died. Most patients who were rehospitalized had one new hospital admission (86.0%). The main cause of urgent rehospitalization was infection (55.0%). In the multivariate analysis, elevated C-reactive protein at discharge and the occurrence of intracranial bleeding at index hospitalization were associated with an increased risk of readmission. Longer duration of index hospitalization and use of lower doses of azathioprine were associated with a lower risk of rehospitalization. CONCLUSION: Around half of HT recipients were rehospitalized within the first 90 days after hospital discharge. Understanding factors associated with post-HT rehospitalization may help the implementation of strategies to avoid patient morbidity and hospital costs.

Role of Inflammation and the NF-κB Signaling Pathway in Hirschsprung's Disease.

Hirschsprung's disease (HSCR, incidence 1/5000 live births) is caused by the failure of neural crest-derived precursors to migrate, survive, proliferate, or differentiate during the embryonic development of the Enteric Nervous System (ENS), which could be disrupted by many factors, including inflammatory processes. The NF-κB family controls several biological processes, including inflammation, neurogenesis, and cell migration. With the aim of studying the potential role of NF-κB in HSCR, we have analyzed the expression of the NF-κB main subunits and other NF-κB-related genes by RT-qPCR in HSCR tissue samples (sub-divided into ganglionic and aganglionic segments). We found decreased gene expression of the NF-κB main subunit RELA but also of NFKBIA, TNFA, TFGBR2, and ERBB3 in the pathologic distal aganglionic segments compared to the proximal ganglionic segments. Moreover, we could also confirm the lower protein expression of RelA/p65 in the aganglionic distal segments by immunofluorescence staining. Further, we show that the expression of RelA/p65 protein in the proximal segments concurs with lymphocyte infiltration in the bowel tissue, indicating a pro-inflammatory activation of p65 in the proximal ganglionic HSCR tissue in the patients analyzed. All in all, our findings suggest that the modulation of NF-κB signaling in the neuro-enteric system does obviously contribute to the pathological effects of HSCR.

Autogenous Bilateral Cleft Alveolar Bone Grafting with rhBMP-2 and Cellular Bone Matrix.

Alveolar bone grafting (ABG) in bilateral cleft lip and palate (BCLP) patients provides a reconstructive challenge. We present a novel technique of combining autologous iliac crest bone graft (ICBG) with recombinant human bone morphogenic protein 2 (rhBMP-2) and cellular bone matrix (CBM) for ABG in BCLP patients. Complete bone fill occurred in 90% of patients, with 100% having bilateral canine eruption. No patients required repeat ABG, and no significant complications were reported. The alveolar cleft gap volume significantly decreased with an improvement of 75.87%. ABG with autologous ICBG with rhBMP-2 and CBM is an effective technique for patients with BCLP.

Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.