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Abstract Chimeric antigen receptor T (CAR-T) cells show remarkable efficacy for some hematological malignancies. However, CAR targets that are expressed at high level and selective to tumors are scarce. Several strategies have been proposed to tackle the on-target off-tumor toxicity of CAR-T cells that arise from suboptimal selectivity, but these are complicated, with many involving dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40. Our system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which we show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. Simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag may further enhance safety by enabling permanent in vivo depletion of the switchable CAR-T cells when necessary. In summary, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the range of CAR targets.

The objectives of fusion surgery for spinal deformities include decompressing neural elements and achieving balanced spinal alignment. Particularly, in cases where spinal deformities coexist with osteoporosis, successful surgery requires careful consideration due to the susceptibility to fixation failure and non-union. Various efforts are being made to restore spinal alignment through surgery in osteoporotic patients. The administration of osteoporosis medications before and after surgery is effective for bony union. Additionally, appropriate selection of fusion range, rigid internal fixation, and utilization of bone substitutes play significant roles in successful fusion surgery. Although surgical treatment for spinal deformities accompanied by osteoporosis remains still challenging, we can anticipate successful outcomes with effective strategies and ongoing advancements in the future.

Background: We identified the uptake of people living with HIV (PLWH) using health-screening services and compared the screening rate with the general population, to identify factors associated with the use of screening services by PLWH. Methods: This population-based study used data from the Korean National Health Insurance, a single mandatory health insurance system covering all residents. The uptake rates for screening for general health, gastric cancer, and colorectal cancer, which were provided by a national health screening program with free of charge or minimal cost in Korea from 2010–2020. Factors associated with general health, gastric cancer, and colorectal cancer screening were also explored. Results: Screening uptake rates for general health, gastric cancer, and colorectal cancer in PLWH increased from 2010–2019 but decreased in 2020. The standardized screening ratio showed lower screening rates for general health, gastric cancer, and colorectal cancer in PLWH with 0.80 (95 % confidence interval (CI) = 0.77–0.83), 0.64 (95 % CI = 0.61–0.67), and 0.67 (95 % CI = 0.64–0.71) in 2019. Increased age, Charlson Comorbidity Index, and years since HIV diagnosis were associated with increased screening uptake in PLWH. Otherwise, PLWH recipients of medical aid programs received less for each screening compared to PLWH who paid insurance premiums higher than 50 %. An increased medication possession ratio of highly active antiretroviral therapy was associated with decreased general health and gastric cancer screening uptake but increased colorectal cancer screening uptake. Conclusions: Significant disparities in health-screening uptake were observed in PLWH compared to the general population in a nationwide organized screening setting without cost barriers.

Abstract Half‐Heusler compounds are promising materials for thermoelectric applications due to their high zT at elevated temperatures. However, their intrinsic high thermal conductivity limits their efficiency. Doping with Hf or Zr can improve the zT of these materials. Recently, a high zT of 1.5 at 1200 K achieved in p‐type Nb1‐xHfxFeSb has attracted much attention. While the effect of doping Hf in thermal conductivity is studied thoroughly, the effect of Hf doping on band parameters is not fully evaluated. This study investigates the effect of Hf and Zr doping on the electronic band parameters and thermoelectric properties of NbFeSb using the Single Parabolic Band model. The results show that Hf doping increases the weighted mobility of the samples, while Zr doping has no significant effect. Hf doping with x = 0.14 is predicted to improve the zT of NbFeSb by 35% at 300 K (0.19 → 0.26). These results show the intricate effects of Hf and Zr doping on the electronic and thermal properties of NbFeSb.

In this study, a 4D trajectory weather (4DT-Wx) prototype system was developed and evaluated for effective weather information integration in trajectory-based operation (TBO) environments. The system has two key distinguishing features: multi-model-based trajectory services and buffer zone information provision. We constructed a distributed processing system using Apache Spark, enabling the efficient processing of large-scale weather data. The performance evaluation demonstrated excellent scalability and efficiency in processing large-scale data. An analysis of the buffer configurations highlighted that buffer zone information is valuable in decision-making processes and has the potential to enhance the system performance. The system’s practical applicability is presented through visualizations of the extracted weather information. This system is expected to enhance aviation safety and operational efficiency, providing a foundation for addressing increasingly complex weather conditions and flight scenarios in the future. The approach presented in this study marks a significant step toward effective TBO implementation and the advancement of future air traffic management. The evaluation of the 4DT-Wx system analyzed the accuracy of weather data processing and the performance of distributed processing, finding that the temperature (T) estimation had the highest accuracy, and that the parallel processing using Apache Spark was most effectively modeled by Ahmed et al.’s model. The findings suggest the potential for further optimization in integrating various weather models and developing algorithms to enhance their utilization.

PurposeTo understand the current practice of radiation oncologists (ROs) and orthopedic surgeons (OSs) regarding spine metastasis.MethodsIn 2022, an internet-based survey was conducted for ROs and OSs who treat spinal metastasis in Korea. Respondents were asked to choose the treatment option for two clinical scenarios. Scenario 1 involved a case displaying symptoms of leg weakness due to spinal cord compression and Scenario 2 involved a case with back pain due to pathologic compression fracture. The survey also included a question that required respondents to rank the importance of 11 clinical factors that affect treatment decisions.ResultsForty-nine ROs and 30 OSs responded to the survey. There were significant differences in treatment choices between two groups for both scenarios (P = 0.001). In Scenario 1, more OSs chose surgical resection than ROs (43.3% vs. 16.7%), while more ROs chose radiotherapy than OSs (83.3% vs. 53.3%). In Scenario 2, a similar proportion of OSs and ROs chose radiotherapy (OSs, 71.4% vs. ROs, 67.3%), while more OSs opted for prophylactic fixation after radiotherapy than ROs (95.0% vs. 42.4%). The top three factors influencing treatment decisions were general performance status, life expectancy, and spinal instability for both ROs and OSs. In both Scenarios 1 and 2, the treatment decisions of ROs changed significantly when clinical conditions related to these top three factors were altered.ConclusionAlthough ROs and OSs share the same factors influencing treatment decisions for spinal metastases, notable differences exist in their actual treatment preferences, with ROs preferring radiotherapy and OSs opting for surgical resection. Multidisciplinary discussions may be necessary to reduce the gap in decision-making.

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was −3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes.

Objective: This study aimed to evaluate the effectiveness of pembrolizumab among patients with programmed death-ligand 1 (PD-L1) positive platinum resistant recurrent ovarian cancer (PROC). Methods: We retrospectively reviewed the medical records of patients diagnosed with PROC and treated with pembrolizumab monotherapy. All patients were PD-L1 positive. Fixed does of pembrolizumab 200 mg was administered intravenously every three weeks. The primary endpoint was the objective response rate. Results: In total, 8 patients were included in this study. Median number of pembrolizumab cycles was 3 (range, 1-45). The objective response rate was 37.5%, with one complete response and 2 partial responses. The treatment was generally well tolerated. None of the patients experienced treatment discontinuation or treatment-related death due to adverse events. Conclusion: Pembrolizumab monotherapy showed modest antitumor activity against PROC. Pembrolizumab monotherapy is an alternative treatment option for patients with PROC. [ABSTRACT FROM AUTHOR]