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We present orally administrable prodrugs (OSC-GCDIs) of guanidino oseltamivir carboxylate (GOC) based on guanidine cyclic diimide (GCDI) to treat influenza viruses. By concealing the guanidine group, which significantly limits the intestinal absorption, its prodrugs OSC-GCDIs demonstrate dramatic improvement of oral bioavailability. The most promising antiviral substance OSC-GCDI(P) readily forms covalent adducts with serum proteins via a degradable linker after the intestinal absorption. Subsequently, the active species, GOC, is released from the conjugate in a sustained manner, which greatly contributes to improving pharmacokinetic properties. Because of the remarkable improvements in both oral bioavailability and longevity of its active metabolite, OSC-GCDI(P) demonstrates outstanding therapeutic efficacy against both wild-type and oseltamivir-resistant (H275Y) influenza virus strains in a mouse infection model, even with a single oral administration.

Various technology-based interventions exist to support writing for students with learning disabilities (LD). However, it is not enough to simply provide access to technology. How it is implemented by teachers may affect student outcomes. In this study, three special education teachers used a technology-based graphic organizer (TBGO) with embedded self-regulated strategies and technology supports to improve the persuasive paragraph writing of 43 6th-8th grade students with LD. Teachers followed scripted lesson plans when delivering instruction. Quality of their instruction or process fidelity while implementing a technology-based intervention was determined. Students wrote a paragraph in response to a persuasive prompt using a Microsoft Word document at pretest, using TBGO at posttest with TBGO, and using a Microsoft Word document at posttest without TBGO. There were significant differences in the number of words, transition words, and essay parts measures between pretest and posttest with TBGO as well as between pretest and posttest without TBGO. Gain scores on the essay parts measure showed no correlation with the students' typing rate. However, there was a significant correlation found between those gain scores and teachers' process fidelity scores. Differences between teachers' implementation along with practical implications for the integration of technology tools in writing instruction are discussed.

Background: Although extramusculoskeletal manifestations, such as uveitis and psoriasis, in patients with axial spondyloarthritis (SpA) are well-documented, studies on the occurrence of glomerulonephritis in this population are scarce. Objectives: This study aimed to assess the incidence rate and risk factors for glomerulonephritis in patients with axial SpA using a nationwide population-based cohort in Korea. Design: Nationwide population-based study. Methods: This study included patients diagnosed with axial SpA between 2016 and 2019 from Korea's National Health Insurance Database. Patients with a diagnosis of preexisting kidney disease prior to their axial SpA diagnosis and those diagnosed with glomerulonephritis within 1 year of their axial SpA diagnosis were excluded. For the remaining patients, the incidence rates of glomerulonephritis and Cox proportional hazard ratios were analyzed. Results: Among the 11,796 patients, 58 had glomerulonephritis, resulting in an incidence rate of 1.82 per 1000 person-years. After adjusting for age and sex, the hazard ratio for patients with a Charlson Comorbidity Index score of ⩾1 was 2.03 (confidence interval (CI), 1.14–3.63; p = 0.017). When adjusting for age, sex, and comorbidities, the hazard ratio for patients with hypertension was 2.37 (CI, 1.20–4.69; p = 0.014). Among the 58 patients, 4 (6.9%) were diagnosed with glomerulonephritis, as confirmed via kidney biopsy. Conclusion: The incidence rate of glomerulonephritis in Korean patients with axial SpA is lower than that in patients with other musculoskeletal manifestations. In addition, the presence of comorbidities, including hypertension, is a significant risk factor for glomerulonephritis in patients with axial SpA. Despite the low occurrence, careful monitoring for glomerulonephritis in patients with axial SpA is essential. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and current treatments are limited by high toxicity and low survival rates, highlighting the need for new therapeutic approaches. Natural killer (NK) cells can identify and eliminate cancer cells without prior antigen exposure. Radiotherapy directly targets tumors and increases activating ligands on tumor cells, promoting NK cell interactions. Cetuximab, an EGFR-targeting antibody, enhances NK cell cytotoxicity. Additionally, anti-PD-1 antibodies may further boost NK cell function by blocking inhibitory signals. The study aimed to enhance HNSCC treatment efficacy by combining radiotherapy and targeted therapy with expanded NK cells. Methods: NK cells were isolated, activated, and expanded from healthy donors. The FaDu and SCC-47 cell lines were inoculated into NOD/SCID mice. The mice were treated with PD-1 inhibitors, cetuximab, and radiation, followed by intravenous injection of NK cells. Results: Radiation increased ligands that regulate NK cell sensitivity. The combination of cetuximab, radiotherapy, and expanded NK cells significantly suppressed cancer progression and improved survival rates. However, adding anti-PD-1 antibodies did not further enhance outcomes. Conclusion: This study suggests that a multimodal approach combining cetuximab, radiotherapy, and NK cells can significantly improve HNSCC therapy efficacy, offering a novel and promising treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) of subphrenic hepatocellular carcinomas (HCCs) using ultrasound (US) guidance presents a challenge. Purpose: To evaluate local tumor progression (LTP) and overall survival (OS) after RFA of right posterior subphrenic HCCs, and to identify the risk factors for LTP and OS after RFA. Material and Methods: We screened patients who underwent US-guided RFA for a single HCC <3 cm in the right posterior subphrenic area. Cumulative rates of LTP and OS were compared between multiple- and single-electrode treatments and artificial pleural effusion versus no-effusion groups using Kaplan–Meier curves and the log-rank test. The risk factors for LTP and OS were assessed. Results: A total of 36 patients were included. The cumulative 5-year and 10-year LTP rates were 32.9% and 39.6%, respectively, and the corresponding OS rates were 72.2% and 48.7%, respectively. The multiple-electrode group had significantly lower cumulative LTP rates compared to the single-electrode group (P < 0.001). The group receiving artificial pleural effusion showed a trend towards lower LTP rates than the no-effusion group (P = 0.076). The albumin-bilirubin (ALBI) grade was the only risk factor for LTP (hazard ratio [HR] = 4.17, 95% confidence interval [CI] = 1.26–14.55; P = 0.020). A lower albumin level was a risk factor for mortality (HR = 0.24, 95% CI = 0.07–0.79; P = 0.020). Conclusion: US-guided RFA with multiple electrodes and artificial pleural effusion tends to be linked with lower LTP rates. The ALBI grade and serum albumin level are risk factors for LTP and OS, respectively. [ABSTRACT FROM AUTHOR]

Cryptogenic new‐onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole‐genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208 [ABSTRACT FROM AUTHOR]

Objective: Leucine‐rich glioma‐inactivated 1 (LGI1)‐antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e. Methods: Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status. Results: A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP‐associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes. Interpretation: LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression. [ABSTRACT FROM AUTHOR]

Background: Clinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear. Methods: Kidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN. Results: Among a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p =.008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p =.026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN. Conclusions: Approximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation. [ABSTRACT FROM AUTHOR]