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Within the family of protein kinases there is a subgroup of 'evolutionarily related members of the total human kinome' that are devoid (or have very limited) enzymatic activity. These proteins, so-called pseudokinases, play important functions thanks to their capacity to establish regulatory protein-protein interactions. Specifically, this opinion article focuses on a group of pseudokinases called Tribbles. Tribbles (Trbl) was originally discovered in Drosophila, followed by the subsequent identification of their orthologs in mammals (TRIB1, TRIB2, TRIB3, and STK40). Work over the last decades has shown how these proteins contribute to fine-tuning key signaling pathways involved in the regulation of proliferation, differentiation, inflammation and adaptation to nutritional changes. Accordingly, dysregulation of Tribbles proteins (TRIBs) contributes to the establishment and progression of insulin resistance, obesity, type II diabetes, atherosclerosis and cancer. Here, we will discuss some of the mechanisms by which Tribbles pseudokinases carry out their functions and the crucial importance of cell context in defining the precise role played by each of the TRIBs, with emphasis on TRIB1 and TRIB3, under different physiopathological situations.

Sonic hedgehog-medulloblastoma (SHH-MB) represents a biologically diverse and clinically challenging subgroup, especially in high-risk variants characterized by metastatic dissemination. Despite progress in molecular stratification, current treatments rely on intensive multimodal regimens associated with substantial long-term neurotoxicity. Identifying novel oncogenic mechanisms that can be therapeutically exploited is therefore a critical priority. We combined transcriptomic analyses of patient datasets with immunohistochemistry, RNAscope, and protein profiling to evaluate PTX3 expression in MB subgroups. Functional studies were performed in SHH-MB cell lines following PTX3 knockdown or knockout. Effects on proliferation, migration, and angiogenesis were assessed through multiple in vitro assays. In vivo relevance was tested using subcutaneous and orthotopic xenograft models. Mechanistic insights were obtained through phospho-kinase arrays, Western blotting and GSEA. A high-throughput drug screen and combination studies with specific inhibitors and standard chemotherapy (vincristine/cisplatin/cyclophosphamide; VCC) were performed to assess therapeutic potential. Our results reveal that PTX3 was strongly enriched in SHH-MB subgroup, where it supported proliferation, motility, and angiogenesis. Mechanistically, PTX3 activated a TLR4-dependent IRAK1/PI3K-Akt/GSK-3/β-catenin signaling cascade. Genetic downregulation or pharmacologic blockade of PTX3-TLR4 significantly reduced tumor growth and angiogenesis in vivo. Moreover, the TLR4 inhibitor TAK-242 markedly impacted SHH-MB growth in vitro, and combination therapy of TAK-242 and VCC produced additive/synergistic effects in vitro and significantly prolonged survival in orthotopic SHH-MB-bearing mice. Our findings identify PTX3-TLR4 signaling as key oncogenic driver and a promising therapeutic vulnerability in SHH-MB. Targeting this pathway enhances the efficacy of standard therapy and represents a rationale for mechanism-based combination strategies. Medulloblastoma is the most common cancerous brain tumor in children. One type, called Sonic Hedgehog medulloblastoma, still needs better treatment options. We found that a protein called PTX3 helps these tumors grow by turning on signals that support cancer cell survival and blood vessel formation. When we blocked PTX3 or its partner protein, TLR4, tumor growth slowed, and standard treatment worked better, helping mice bearing medulloblastoma-like tumors live longer. These findings suggest that PTX3 could become a new treatment target. More research is needed, but this approach may help improve future therapies for children with this type of brain tumor.

This high-resolution fast fMRI study explores visual-vestibular network interactions in expanded spatial and temporal detail. Under natural conditions coherent visual motion always occurs during self-motion. Technology applying coherent visual motion on stationary subjects creates visual-vestibular mismatch and allows investigation of system interplay in the MRI. In humans, the process minimizing the intersensory conflict was previously conceptualized as a categorical reciprocal upregulation of one (e.g., visual) and downregulation of the other system (e.g., vestibular), or vice versa. Healthy participants (n = 22) were tested with a two-phase paradigm using different coherent visual dot motion stimulation conditions (stimulation phase) and subsequent variable duration illusory self-motion perception while the visual pattern was stationary, called motion aftereffect (MAE, post-stimulation phase). A matched random dot stimulus, not inducing self-motion perception, served as the control. Signal modulations related to subjective illusory self-motion (MAE duration) were identified in a multivariate temporal model-free way. Visual areas showed uniform positive signal curves with motion stimulation unrelated to self-motion perception (MAE duration), except for V5/MT. In contrast, vestibular areas exhibited fourfold signal patterns along the dimensions of transient versus sustained decreases and in relation to the stimulus phases and presence of correlation with MAE duration. Notably, beside V5/MT, further areas with intermediate signaling were identified. Altogether, in contrast to the visual system, the vestibular network areas exhibited greatly differentiated processing instead of a categorical uniform system "on-off" mode. These novel findings expand our comprehension of the continuous interaction between the visual and vestibular systems, especially with respect to the various dynamical activity changes in vestibular areas, potentially indicating subspecialization of regions that might be essential even for humans moving in the real world.

IntroductionIn Mexico, delays in pediatric cancer diagnosis remain a major barrier to timely care and are partly driven by inefficiencies in referral pathways. This study aimed to evaluate the impact of a direct pathway on referral intervals for patients with suspected childhood cancer treated at a high-specialty hospital in Mexico.MethodsWe conducted a retrospective observational cohort study based on a comprehensive review of medical records of patients referred to a high-specialty hospital in Mexico between 2017 and 2022. Patients' characteristics, along with dates from symptom recognition to diagnosis, were collected. The exposure was the referral pathway: standard versus direct (Golden Code strategy) pathway, which enables access to pediatric oncology through a zero-rejection policy. The primary outcome was the time attributable to oncological referral (TAOR), analyzed as a continuous variable and a dichotomous outcome. Secondary intervals were calculated using standardized definitions. Regression models were used to evaluate factors associated with untimely (>7 days) referral.ResultsA total of 399 patients were included. The direct pathway was associated with a shorter TAOR compared to the standard pathway (median 2.0 vs. 7.0 days; p<0.001). The proportion of timely referrals was substantially higher in the direct pathway (91.3%) than in the standard (50.6%) and reduced the likelihood of an untimely referral (OR = 0.098, 95% CI: 0.055-0.173; p<0.001). No differences were observed in other diagnostic intervals.ConclusionThe direct referral pathway improves the timeliness and consistency of access to pediatric oncology care by reducing referral delays and increasing the proportion of patients evaluated within recommended referral intervals. However, the absence of changes in the secondary intervals, such as time to oncological diagnosis, highlights the need for complementary actions targeting downstream diagnostic processes. Strengthening referral systems represents a feasible and impactful strategy to address delays in pediatric cancer care in middle-income settings. In Mexico, many children and adolescents with suspected cancer experience delays before seeing a cancer specialist. These delays can occur for various reasons, including the organization of the health system. When referrals move slowly through several levels of care, diagnosis and treatment may be postponed. This study examined a program called the Golden Code, which is designed to help children with possible cancer access a pediatric cancer specialist more quickly. The program allows doctors to refer patients directly to a specialized hospital, reducing administrative steps and speeding up appointments. Researchers reviewed the medical records of 399 children and adolescents treated between 2017 and 2022. They compared those referred through the Golden Code program with those referred through the usual system. The results showed that children referred through the Golden Code were seen by a cancer specialist much faster. On average, they had their specialist visit within two days, compared to seven days under the standard referral system. The program greatly reduced the chances of a delayed specialist visit. These findings show that improving how patients are referred within the health system can make an important difference in how quickly children with suspected cancer receive expert evaluation. Although Mexico performs better than some countries with fewer resources, further improvements in referral processes and access to care could help ensure children receive timely diagnosis and treatment.

Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus compounds (OP) known to induce delayed neurotoxicity, called OP-induced delayed neuropathy (OPIDN), which involves multiple pathological processes, including degeneration and demyelination of long axons within the spinal cord and peripheral nerves. In this study, we employed the Schwann cell line (sNF96.2 cells) and adult hens, the classical model animal for OPIDN study, to investigate the mechanism of TOCP-induced myelin damage. The results showed that TOCP (750&#x202f;mg/kg, p.o.) significantly reduced the number of COPII vesicles in the spinal cord and sciatic nerves of hens; on day 2 after the single exposure, the number of vesicles decreased to 27% and 38% of the control group, respectively, while 4-phenylbutyric acid (4-PBA, 150&#x202f;mg/kg, i.p.), an inhibitor of endoplasmic reticulum (ER) restored them to 80% and 75% of the control group, respectively. In sNF96.2 cells, cresyl saligenin phosphate (CBDP), the active metabolite of TOCP, inhibited COPII vesicle transport from the ER to the Golgi apparatus, reducing the transport rate of ManII-SBP-mCherry from 76% to 38% and the relocation rate of GalNAc-T2-GFP in the Golgi apparatus from 91% to 26%. 4-PBA partially reversed the effects (restoring them to 62% and 72%, respectively). These results suggested that TOCP/CBDP impairs COPII vesicle transport at least partially by activating ER stress, and that impaired vesicle transport may be an important mechanism by which TOCP induces neuropathy.

Patients admitted for inflammatory bowel disease (IBD) are often managed by rotating teams of care providers during their hospital stay. This can lead to potential variability in the care they receive. Our team developed a scoring system of six key high-quality care components called the standardized IBD care index (SICI) to standardize care management. A multi-phase implementation was conducted to improve adherence to SICI components. At baseline, compliance with the SICI score was approximately 45%, with a goal of 75% post implementation. After implementation, we were able to exceed our goal of 75% compliance with sustained success for the entirety of the study period. This project demonstrates that standardizing care practices can reduce physician-dependent variability and have measurable improvements in the quality of care provided for IBD patients.

In clinical research, alternatives to venipuncture can reduce participant burden and increase accessibility and sampling opportunities for biomarkers. Residual pancreatic beta-cell function is assessed in clinical research and in diabetes care using fasting and stimulated C-peptide measurements, and changes are assessed over time. Operational, technical, and acceptability considerations of utilizing Tasso+ SST devices for C-peptide collection compared to venipuncture-derived serum samples were investigated. Samples were collected from prospectively enrolled healthy participants via Third Generation Tasso+ SST micro-sampling devices and phlebotomy. Eleven fasted Tasso+ samples collected on-site or remote underwent alternative handling conditions and were evaluated for consistency, quality, and stability. Participants responded to device acceptability questionnaires. The Tasso+ SST micro-sampling device showed excellent concordance with simultaneous venipuncture-derived fasted C-Peptide, with concentration being largely conserved in healthy volunteers despite alternative sample handling. Delayed centrifugation over 72&#x2009;hours caused no consequential degradation of C-peptide when kept at 4&#xb0;C. Questionnaire responses indicate acceptable device usability and associated comfort levels. Fasting C-peptide levels can be accurately collected using micro-sampling collection techniques. Tasso+ C-peptide stability is seen when kept at 4&#xb0;C. Micro-sampling devices can be used with shipping mechanisms (without centrifugation) to decrease participant burden, expand trial populations, and aid biomarker measurements. This study focused on finding an easier way to collect blood samples for measuring C-peptide, a marker used in diabetes research, without needing a traditional needle stick in a vein (venipuncture). Instead, researchers tested a small, easily applied device that collects a small amount of blood from the upper arm. Healthy volunteer participants gave blood samples from both this device (called the Tasso+) and from the standard way (venipuncture). Some of these samples were collected away from a doctor&#x2019;s office. The researchers checked to see if the small device gave accurate and reliable results for C-peptide, even if the samples were handled in different ways. These different ways included delays before processing and being stored in a fridge or freezer. They also asked participants about their experience with using the device.The study showed that transdermal micro-sampling devices, such as the Tasso+, provided C-peptide measurements similar to those from standard blood draws. The C-peptide in the samples stayed stable for up to 3&#x2009;days in the refrigerator, even if not processed right away. Participants found the device easy and comfortable to use.In summary, using this device to collect small amounts of blood is a reliable way for samples related to diabetes to be collected and can help with research with less stress. This can make taking part in studies easier, allow for sample collection at home, and help researchers to include more people in studies while still getting trustworthy results.

Smartphone-wielding citizen scientists and an AI called FLORIST are transforming ecology at the continental scale. In this issue of Cell, when Tibbs-Cortes et al. pair the crowdsourced data with controlled genetics, they discover how switchgrass times its flowering to outwit both frost and heat, depending on latitude.

Transformation in the neurosciences in biomarkers is enabling novel therapeutic strategies targeting earlier stages of disease prior to onset of clinical symptoms. Emerging progress in the area of synucleinopathies, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) have significant implications for clinical trials. Misfolded &#x3b1;-synuclein aggregates (syn-seeds) propagate by templated misfolding of native &#x3b1;-synuclein, driving disease spread. The advent of the &#x3b1;-synuclein seed amplification assay (syn SAA) now enables highly sensitive and specific detection of syn-seeds in cerebrospinal fluid (CSF), allowing in vivo identification of underlying &#x3b1;-synuclein pathology, including in individuals prior to the onset of motor symptoms.To support regulatory alignment, the Critical Path Institute's Critical Path for Parkinson's (CPP) consortium compiled and evaluated the totality of scientific evidence in the area of syn SAA as an in vivo measure of misfolded alpha synuclein in CSF and submitted it to the U.S. Food and Drug Administration (FDA) in a request for a Biomarker Letter of Support (LoS). Within three months of submission, the FDA issued a LoS endorsing CSF syn SAA as a susceptibility and risk biomarker for use in clinical trials targeting &#x3b1;-synuclein-related neurodegenerative diseases, enabling enrichment of participants with underlying pathology and reducing trial risk. These data have enabled the development of biological classification frameworks for synucleinopathies that define disease based on molecular pathology rather than clinical symptoms alone.This review summarizes the regulatory-grade evidence supporting syn SAA and discusses its implications for biologically driven clinical trial design and early-intervention strategies. Enabling precision medicine strategies for synucleinopathiesResearch in Context StatementParkinson's disease and related disorders, such as dementia with Lewy bodies, are caused by the buildup of a misfolded protein called alpha-synuclein in the brain. Until recently, this disease-defining biology could only be confirmed after death, meaning that doctors and researchers had to rely on symptoms alone to diagnose and study these conditions&#x2014;even though symptoms appear years after the disease process has already begun.The alpha-synuclein seed amplification assay (syn SAA) is transforming this landscape. This test can detect tiny amounts of abnormal alpha-synuclein in cerebrospinal fluid, allowing clinicians and researchers to identify the biological presence of Parkinson's-related disease during life and even before symptoms appear. This marks a shift toward precision medicine&#x2014;an approach in which patients are diagnosed, selected for treatment, and monitored based on the specific biology driving their disease rather than symptoms alone.Precision medicine has already reshaped drug development in cancer and is now doing the same in neuroscience. Biomarkers like syn SAA allow clinical trials to enroll the right patients, test therapies earlier, and determine whether a drug is affecting its intended target. This improves trial efficiency, reduces risk, and increases the likelihood that effective therapies reach patients faster.Recognizing this, the U.S. Food and Drug Administration issued a biomarker Letter of Support endorsing syn SAA as a biomarker for clinical trials in Parkinson's-related diseases that share the common biology of synuclein. This milestone signals that neuroscience is entering a new era where biologically defined, precision-based approaches will enable earlier intervention and drive how new treatments are evaluated, approved, and delivered to people living with Parkinson's and related disorders.

Designing molecules with optimized properties remains a fundamental challenge due to the intricate relationship between molecular structure and properties. Traditional computational approaches that address the combinatorial number of possible molecular designs become unfeasible as the molecular size increases, suffering from the so-called "curse of dimensionality" problem. Recent advances in quantum computing hardware present new opportunities to address this problem. Here, we introduce the quantum ensemble variational optimization (QEVO) method for near-term and early fault-tolerant quantum computing platforms. QEVO efficiently maps molecular structures onto an orthonormal basis of binary strings and samples from a superposition state generated by a variational ansatz. The ansatz is iteratively optimized to identify molecular candidates with the desired property. Our numerical simulations demonstrate the potential of QEVO to design drug-like molecules with anticancer properties, operating in combinatorial spaces composed of up to [Formula: see text] solutions, while employing a shallow quantum circuit that requires only a modest number of qubits. We envision that QEVO could be applied to a wide range of complex problems, offering practical solutions to problems with combinatorial complexity.

This issue of Creative Nursing has a theme of Sparking Creativity to Ignite Transformation in Nursing. Most of these 17 articles by authors from Canada, Greece, India, Italy, Japan, New Zealand, Portugal, Sweden, and the United States have already been published Online First. Some didn't fit closely with themes of recent or upcoming issues, but all are of a quality and with such compelling messages that we are proud to have them in our journal. There are many different kinds of articles. Some report modest studies or projects, others review relevant literature on a particular topic, and still others address sweeping issues in nursing. But all of them have one thing in common: the spark of creativity that led us to accept them for publication in our journal called Creative Nursing. This editorial summarizes each article to reveal that spark.

Autistic adults experience significant physical and mental health inequities yet remain underrepresented in clinical research, with few randomised controlled trials to guide care. Randomised controlled trials (RCTs) of selective serotonin reuptake inhibitors (SSRIs) are limited, underpowered, and rarely focused on anxiety. Anticipating recruitment challenges in a large RCT ("STRATA") evaluating sertraline for anxiety in autistic adults, we embedded qualitative research to support recruitment, retention, and monitoring trial acceptability. We organised our findings into the theoretical framework of acceptability (TFA) constructs to assess the acceptability of trial design and delivery for autistic adults. We conducted 64 interviews with autistic adults at different trial stages. Data were analysed thematically and mapped to the seven TFA constructs. Participants considered involvement in a blinded medication RCT acceptable across the TFA domains, which they weighed differently when reflecting on anticipated versus experienced aspects of participation. STRATA was a low-burden, ethically sound, and methodologically coherent study for most participants, who reported minimal trade-offs, potential benefits, and self-efficacy in managing anxiety and research participation. Acceptability of trial participation is dynamic and multidimensional, which can be enhanced by meaningful involvement of autistic people throughout the research cycle, accessible participant information design, and responsive ongoing engagement.Lay AbstractAutistic adults often experience poorer physical and mental health than the general population. Yet they are rarely included in clinical research. There have been very few high-quality studies (RCTs) testing medications for anxiety in this group. Most existing studies are small and focus on other outcomes. They don't provide clear guidance for care. To help address this gap, the STRATA trial tested whether the medication sertraline (an SSRI) can reduce anxiety in autistic adults. Recruiting participants for such trials can be challenging. We included a qualitative study to better understand what helps or hinders people from joining and staying in the trial. We aimed to explore what aspects of the STRATA trial made it easier or more appealing for autistic adults to take part. We used a framework called the theoretical framework of acceptability (TFA) to define acceptability in this context. We interviewed 64 autistic adults at different stages of the trial, including 2 who chose not to take part. Most participants found the trial acceptable when assessed against the seven aspects of the TFA (i.e., how someone feels about taking part, how much effort is needed, whether taking part fits with a person's values, how well someone understands the study, what someone may have to give up, whether the study is likely to help, and how confident someone feels about taking part). In summary, they felt positive about taking part. They thought the study was ethical and easy to understand and believed it could benefit them. Many also felt more confident in managing their anxiety and contributing to research. STRATA is one of the largest studies of its kind; 318 autistic adults took part across the United Kingdom and Australia. The trial had a very high retention rate. Ninety-two per cent of participants stayed until the main outcome point, and 87% completed the full 52&#x2009;weeks. How acceptable clinical trials like STRATA are may change during their course, and researchers need to be responsive. To do this well, researchers should involve autistic people meaningfully throughout the research process and from an early stage. Researchers also need to respect individual communication needs and provide clear and accessible information. These approaches were central to STRATA and supported by other studies.

Anti-programmed death-1 (PD-1)/cytotoxic T lymphocyte antigen-4 antibodies are efficacious in various malignancies. The potential role of dual checkpoint inhibitors in many rare solid tumors is not established. This study presents the results of ipilimumab-nivolumab in salivary gland neoplasm cohorts of the SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) trial. DART is a prospective, open-label, multicenter (1016 US sites), multi-cohort phase II trial of ipilimumab (1&#x2009;mg/kg intravenously (IV) every 6&#x2009;weeks) plus nivolumab (240&#x2009;mg IV every 2&#x2009;weeks). We performed a prospective, multicenter phase II clinical trial of ipilimumab (1&#x2009;mg/kg IV every 6&#x2009;weeks) plus nivolumab (240&#x2009;mg IV every 2&#x2009;weeks) in three salivary gland neoplasm cohorts: major and minor salivary gland and adenoid cystic cancers. Patients with adenoid cystic salivary gland tumors (N&#x2009;=&#x2009;26) and other salivary gland neoplasms (N&#x2009;=&#x2009;34) were evaluable. The most common site of origin was the parotid (31%, N&#x2009;=&#x2009;8 adenoid cystic group; 68%, N&#x2009;=&#x2009;23 remaining histologies). In the adenoid cystic group, objective response rate (ORR), 4% (complete response (CR) 0%, N&#x2009;=&#x2009;0; partial response (PR) 4%, N&#x2009;=&#x2009;1); 6-month progression-free survival (PFS) and overall survival (OS), 32% (95% confidence interval (CI) 18%-57%) and 84% (95% CI 71%-100%), respectively. In the remaining histologic subtypes, the confirmed ORR was 9% (CR, 0%, N&#x2009;=&#x2009;0; PR, 9%, N&#x2009;=&#x2009;3); stable disease (SD) >6&#x2009;months/PR/unconfirmed PR&#x2009;=&#x2009;35%; 6-month PFS and OS, 34% (95% CI 21%-55%) and 88% (95% CI 78%-100%), respectively. The most common toxicities were fatigue (39%) and diarrhea (26%); diarrhea (8%) was the most common grade 3-4 immune-related adverse event. In salivary gland tumors, combined ipilimumab plus nivolumab resulted in only a 4% ORR in adenoid cystic carcinoma and 9% in all other histologies combined, though the latter showed clinical benefit (included SD >6&#x2009;months) in 35% of patients.Trial registration: ClinicalTrials.gov registry: NCT02834013. Testing a dual immunotherapy treatment for rare salivary gland cancers Salivary gland cancers are rare, and there are limited treatment options for patients whose cancer has spread or returned after initial treatment. Immunotherapy helps the immune system fight cancer and has been successful in some other types of cancer. This study tested whether a combination of two immunotherapy drugs&#x2014;one targeting CTLA-4 and the other targeting PD-1&#x2014;could help treat these rare tumors. Patients with advanced salivary gland cancer took part in a clinical trial called DART. They received the two immunotherapy drugs and were monitored to see if their tumors shrank or stopped growing. Researchers also tracked any side effects caused by the treatment. Some patients responded well to the treatment, where their tumors got smaller or stopped growing for a period of time. However, not all patients benefited. Some experienced side effects, as the immune system can also attack healthy cells. This study shows that dual immunotherapy may be a promising option for some people with rare salivary gland cancers, but more research would be needed to understand who is most likely to benefit and how to manage side effects. The findings could help doctors develop better treatment strategies for these rare cancers in the future.

Systemic lupus erythematosus (SLE) or Lupus is often called the "great mimicker" due to its ability to mimic other systemic disorders. SLE is a multisystem autoimmune disorder with varied manifestations, including ocular involvement. Retinal vascular occlusions are an uncommon but potentially vision-threatening presentation of lupus retinopathy. When coexisting systemic features mimic infectious etiologies such as tuberculosis (TB), diagnosis becomes challenging, delaying appropriate immunosuppressive therapy. We report a diagnostically complex case of a 22-year-old female who presented with sudden, painless loss of vision in the right eye.&#xa0;Initially, she was diagnosed elsewhere as macular branch retinal artery occlusion (BRAO) and chorioretinitis. Systemic symptoms-weight loss, low-grade fever, and neuropathy-along with a positive sputum smear and chest radiograph findings, led to a provisional diagnosis of pulmonary tuberculosis with presumed ocular TB. She was started on anti-tubercular therapy (ATT) and oral corticosteroids. Upon further evaluation at our center, additional ocular findings included disc pallor, active vasculitis, and bilateral chorioretinitis. Imaging studies (Fundus Fluorescein Angiography (FFA), Indocyanine Green Angiography (ICGA), Optical Coherence Tomography (OCT)) confirmed retinal vasculitis. A dermatologic evaluation of her facial rash was inconclusive for SLE. However, subsequent worsening of systemic symptoms and neuropsychiatric events prompted re-investigation. Specific MRI findings and immunological tests that revealed strong positivity for anti-Smith, anti-ribonucleoprotein (anti-RNP), anti-Ro-52, and anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies with hypocomplementemia confirmed the diagnosis of neuropsychiatric SLE (NPSLE). ATT was discontinued, and the patient was treated with intravenous steroids and cyclophosphamide and later transitioned to mycophenolate mofetil. Over a year, the patient showed significant systemic and ocular improvement, with best-corrected visual acuity in the affected eye improving from perception of light to 6/60. This case highlights the diagnostic dilemma in distinguishing retinal vasculitis of autoimmune etiology from that due to infectious causes such as tuberculosis, especially in endemic regions. Ocular involvement can be an early sign of systemic SLE, underscoring the need for high clinical suspicion, systemic correlation, and immunological workup in young patients with retinal vascular occlusions. Early recognition of lupus retinopathy and timely immunosuppression are key to preserving vision and preventing systemic morbidity.

Due to the advances in adhesive dentistry and the emphasis on less invasive principles, a treatment option for the restoration of endodontically treated teeth, called endocrown, has been presented. Using finite element as an in vitro simulation evaluation, this study investigated the effect of different restorative materials and the ferrule height on the biomechanical behavior of endocrowns in endodontically treated maxillary and mandibular central incisors. A sound maxillary central incisor and a mandibular central incisor were scanned and fed into Solidworks software for modeling. Endocrowns made of lithium disilicate, zirconia, zirconia-reinforced lithium silicate, and Enamic were modeled by the program. After applying the forces, the maximum von Mises stress values were analyzed in the Ansys software. The maximum von Mises stress on the endocrown, cement, enamel, and dentin of the maxillary central incisor was significantly higher than that on the endocrown, cementum, enamel, and dentin of the mandibular central incisor. It is recommended that a minimum ferrule be used in the central maxillary tooth to reduce the stress on the cementum. In the central mandibular tooth, using endocrowns made of Enamic is recommended because of less stress on the cementum.

Digital technology has brought many advantages to healthcare, but it has also given rise to a new form of worker abuse called "cyberbullying." This type of bullying can happen anytime and can greatly harm workers' mental health. Since "professional quality of life" is vital for how well the healthcare system functions and there is not much research on how this connects to online bullying in Iranian nursing, it is important to look closer at this relationship. This study aimed to assess the association between cyberbullying and professional quality of life among nurses in Southeast Iran. This research utilized a descriptive cross-sectional design and recruited 335 nurses from Kerman University of Medical Sciences affiliated hospitals during 2025. Subjects were enrolled using a convenience sampling approach, and data were collected using the Menesini Cyberbullying Questionnaire and the Professional Quality of Life Scale (ProQOL). Data were analyzed using SPSS Version 24 and descriptive statistics, independent t-tests, analysis of variance, spearman correlation coefficients, and stepwise multivariate regression, with a significance level of less than 0.05. Data analysis indicated a low prevalence of cyberbullying among nurses. The mean scores of compassion satisfaction, burnout, and secondary traumatic stress were 34.71&#x2009;&#xb1;&#x2009;5.47, 16.03&#x2009;&#xb1;&#x2009;3.92, and 31.63&#x2009;&#xb1;&#x2009;4.90, respectively, all of which fell within the moderate range. Inferential findings indicated a significant positive correlation between cyberbullying and compassion fatigue, burnout, and secondary traumatic stress. Furthermore, cyberbullying emerged as a significant positive predictor across all three dimensions of professional quality of life in regression analyses. Additionally, key demographic and occupational factors including educational degree, shift type, employment status, gender, and marital status emerged as significant predictors within their respective models. The findings indicated that cyberbullying was generally low and showed significant statistical associations with compassion fatigue in the analyses. Targeted interventions to enhance nurses' professional quality of life should be prioritized in healthcare settings. Furthermore, longitudinal and interventional studies are needed to better elucidate the temporal and causal relationships among these variables. Nurse administrators should adopt preventive strategies addressing workplace cyberbullying and compassion fatigue to enhance nurses' professional quality of life.

The item cold-start problem remains a major challenge in recommender systems. Existing approaches struggle with three limitations: semantic bias caused by new items that fall outside the pre-training corpus, semantic sparsity caused by limited item attributes, and the absence of interactions, which creates a behavioral gap. To address these challenges, we propose a method called Large Language Model with Retrieval Semantics (LaReS). First, to reduce semantic bias, we introduce self-retrieval contextualization, which retrieves semantically similar warm items as auxiliary knowledge sources. This mechanism grounds cold items in reliable contexts and helps the model infer more reliable item characteristics from warm-item neighbors. Second, to enrich sparse semantics, we propose a large language model-based semantic encoding strategy that transforms augmented textual information into dense, task-specific embeddings. A frozen large language model (LLM) and trainable semantic layers capture deep semantic features beyond simple metadata. Third, to bridge the interaction gap, we implement a joint preference learning framework through multi-objective optimization. This approach distills preference signals from warm items and aligns latent distributions, granting cold items visibility comparable to established items. Experiments and analyses show that LaReS achieves competitive performance in both cold-start and overall recommendation scenarios. For example, LaReS improves cold-start P@5 on MovieLens by 7.98%. The code is available at https://github.com/wuzelong/LaReS.

Uremic pruritus, also called chronic kidney disease-associated Pruritus (CKD-aP), is a symptom of severe and ongoing itching that patients with CKD or end-stage renal disease frequently experience. The purpose of this study was to evaluate the factors associated with moderate-to-severe uremic pruritus in patients receiving chronic hemodialysis. This cross-sectional study was conducted at Dr Sulaiman Al-Habib Hospital in Riyadh, Saudi Arabia, from June to October 2025. The severity of itching was assessed using a single-item scale from 0 to 10, with 0 indicating no itching and 10 indicating maximum itching. Responses of >0 were summed to obtain itching intensity. Among participants, 53 (57.0%) were male. The prevalence of severe itching among participants was 10.8%, with a mean itching scale score of 2.35&#x2005;&#xb1;&#x2005;2.85 out of 10. The noncitizen participants showed higher itching scores than Saudi patients, with a difference that reached the threshold of statistical significance (4.00&#x2005;&#xb1;&#x2005;3.43) and (2.18&#x2005;&#xb1;&#x2005;2.75), respectively. Multivariable logistic regression identified that females were 4 times more likely to have moderate-to-severe itching than males (aOR: 5.64 [95% CI: 1.39-22.99]). The majority of hemodialysis patients had minor uremic pruritus. Further research involving larger samples is also warranted to investigate the factors contributing to uremic pruritus in hemodialysis patients.

Aortic endograft infection (AEGI) is a rare complication of abdominal endovascular aortic repair (EVAR) and thoracic endovascular aortic repair (TEVAR). Surgical explantation with reconstruction is recommended, but data on medical management remain limited. We present our institutional experience with AEGI. To describe the clinical presentation, microbiology, management strategies, and outcomes of patients with AEGI, with the aim of addressing current gaps in the literature and informing future research to improve patient outcomes. Retrospective descriptive study. Adult patients admitted with AEGI at our institution between January 2017 and August 2024 were identified using ICD-10 codes and confirmed using the Management of Aortic Graft Infection Collaboration (MAGIC) diagnostic criteria. Clinical, microbiological, radiographic, treatment, and outcome data were collected and analyzed. We screened 517 patients, and 46 met AEGI criteria (EVAR 54%, TEVAR 46%). Most (63%) presented with late-onset infections (&#x2a7e;3&#x2009;months). Fever (54%) and sepsis (48%) were common presenting symptoms. Computed tomography (CT) (85%) was the primary imaging modality. Blood cultures were positive in 54% of the cases, with Staphylococcus aureus being the most common monomicrobial pathogen (24%), and 24% of cases were polymicrobial. The majority (67%) received combined medical and surgical therapy. Chronic antibiotic suppressive therapy was used in 34 (74%), most often tetracyclines (33%). Overall, treatment success rates were similar between surgical and medical groups (58% vs 60%, p&#x2009;=&#x2009;0.250) with comparable mortality. However, relapses were more frequent in the medical-only group (33% vs 16%, p&#x2009;=&#x2009;0.185). Most patients presented with late-onset AEGI. Fever was absent in nearly half of cases, and blood cultures were positive in only 54%. Overall, surgical and medical therapy had similar success, though relapses were more frequent in those treated medically alone. Aortic stent graft infections are rare but serious and may occur without fever; surgery and antibiotics have similar success, but relapse is more common with antibiotics alone Aortic endografts (also called stent grafts) are devices placed inside the aorta to treat aneurysms or other aortic diseases without open surgery. In rare cases, these devices can become infected. Although uncommon, these infections are serious and can lead to severe illness or death if not treated properly. Diagnosing an infection of an aortic stent graft can be difficult. Patients do not always have typical signs of infection, such as fever or bacteria in the blood. Because the symptoms can be subtle, doctors often need a high level of suspicion and must rely on imaging studies, laboratory tests, and clinical judgment to make the diagnosis. Treatment usually involves either surgery to remove the infected graft, along with antibiotic therapy, or antibiotic therapy alone when surgery is not possible or considered too risky. Surgery is a major operation and may not be suitable for all patients, especially those with other serious medical conditions. In this study, we evaluated patients with aortic endograft infections to better understand how they present and how well different treatments work. We found that both surgical treatment combined with antibiotics and antibiotic treatment alone achieved similar overall success in controlling infection. However, patients treated with antibiotics alone were more likely to experience a relapse of the infection. These findings highlight that aortic endograft infections are challenging to diagnose and treat. Clinicians should consider this diagnosis even when typical signs of infection are absent. While surgery remains an important treatment option, antibiotics alone may still control infection in some patients, although the risk of recurrence appears to be higher.