Search

Abstract BackgroundThe long-term economic impact of frailty measured at the beginning of elderhood is unknown. ObjectiveThe objective of our study was to examine the association between an individual’s frailty index at 66 years of age and their health care costs and utilization over 10 years. MethodsThis retrospective cohort study included 215,887 Koreans who participated in the National Screening Program for Transitional Ages at 66 years of age between 2007‐2009. Frailty was categorized using a 39-item deficit accumulation frailty index: robust (

IntroductionEffective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone.MethodsWe investigated this hypothesis using two NSG mouse models bearing GSU or CAPAN-2 solid tumors. The mice were treated with engineered CAR-T cells targeting guanyl cyclase-C (GCC) or mesothelin as monotherapy or in combination with LDRT. Additionally, we extended this approach to a C57BL/6 mouse model implanted with MC38-gp100+ cells, followed by adoptive transfer of pmel+ T cells before and after LDRT. Tumor growth and survival outcomes were monitored in all models. Furthermore, we employed atomic force microscopy (AFM) in a small cohort to assess the effects of radiotherapy on tumor stiffness and plasticity, exploring the role of tumor nanomechanics as a potential biomarker for treatment efficacy.ResultsOur results demonstrated enhanced tumor control and prolonged survival in mice treated with LDRT followed by T-cell therapy across all models. The combination of LDRT with CAR-T or pmel+ T-cell therapy led to superior tumor suppression and survival compared to monotherapy, highlighting the synergistic impact of the combined approach. Additionally, AFM analysis revealed significant changes in tumor stiffness and plasticity in response to LDRT, suggesting that the nanomechanical properties of the tumor may be predictive of therapeutic response.DiscussionThe findings of this study highlight the transformative potential of incorporating LDRT as a precursor to adoptive T-cell therapy in solid tumors. By promoting CAR-T and pmel+ T-cell infiltration into the tumor microenvironment, LDRT enhanced tumor control and improved survival outcomes, offering a promising strategy to overcome the challenges associated with CAR-T therapy in solid tumors. Additionally, the changes in tumor nanomechanics observed through AFM suggest that tumor stiffness and plasticity could be biomarkers for predicting treatment outcomes. These results support further investigation into the clinical application of this combined approach to improve the efficacy of cell-based therapies in patients with solid tumors.

Background/Aims While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. Methods Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff’s perceptions of antibiotics in cancer patients with EOL. Results Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. Conclusions Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient’s right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

This paper addresses the potential for technology to support husbandry and enrichment opportunities that enhance the welfare of zoo and sanctuary-housed nocturnal and crepuscular species. This topic was investigated through the medium of a multidisciplinary workshop (Moon Jam) that brought together species experts, zoo designers, Animal-Computer Interaction researchers and post-graduate students in collaborative discussions and design sessions. We explain the context through an examination of existing research and current practices, and report on specific challenges raised and addressed during the Moon Jam, highlighting and discussing key themes that emerged. Finally, we offer a set of guidelines to support the integration of technology into the design of animal husbandry and enrichment that support wellbeing, to advance the best practices in keeping and managing nocturnal and crepuscular animals.

In this paper the authors construct estimates of electricity consumption changes at the metropolitan level across the continental U.S., during the initial two months of the COVID-19 pandemic, demonstrating variations in electricity consumption patterns based on several factors.

Background: Although investigating patterns of cancer mortality is important in understanding the effect of cancer on population health, knowledge regarding mortality in cancer patients with disability is scarce. This study examined the association between disability status and all-cause mortality in older patients with colorectal cancer. Methods: Data were obtained from the 2008–2019 National Health Insurance Service claims data. The study population included patients with colorectal cancer aged 60 years or above. The outcome measure was all-cause 5-year and overall mortality. A survival analysis was performed using the Cox proportional hazards model to analyze the association between all-cause mortality and disability status. Subgroup analysis was conducted based on disability severity. Results: The study population consisted of 6340 patients, and disability was reported in 15.8% of the included individuals. Participants with disability had a higher risk of both all-cause 5-year (hazard ratio (HR) 1.21, 95% confidence interval (95% CI) 1.07–1.37) and overall mortality (HR 1.15, 95% CI 1.03–1.28). These findings were particularly significant in individuals with severe rather than mild disability. Conclusion: Older colorectal cancer patients with disabilities showed a higher risk of overall and 5-year all-cause mortality, which was evident in individuals with severe disabilities. The findings indicated disparities in mortality according to disability status. Further, we suggest that policies that can mediate such disparities must be strengthened.

Background Korea operates the Personal Assistance Service (PAS) program, a social service program that assists with the daily activities and coping needs of individuals with disabilities. In January 2013, the eligibility to enroll in the PAS program was expanded to include all individuals with severe disabilities. Objective As supporting individuals with disabilities is important in reducing disparities related to the uptake of health screening, this study investigated whether eligibility expansion of the PAS program was associated with increased participation in the National Health Screening Program (NHSP) among adults with severe disabilities. Methods Nationwide data from Korea that included 24 701 individuals were used. The treatment group included individuals with severe disabilities, while the control group included those with mild disabilities. The difference-in-difference approach was used to estimate differences in participation in the NHSP between the two groups before and after the intervention period. A negative binomial distribution model was applied in the analysis with adjustment for all independent variables. Results The expansion of the PAS program was directly related to an increase in NHSP uptake by people with severe disabilities (increase by 0.044 times compared to the control group following the implementation of the policy). Conclusions Expanding the eligibility for the PAS program was associated with an increase in NHSP participation among individuals with severe disabilities. These findings suggest the importance of supporting individuals with disabilities by increasing participation in health screenings to reduce potential related health disparities. [ABSTRACT FROM AUTHOR]

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone. Methods: We investigated this hypothesis using two NSG mouse models bearing GSU or CAPAN-2 solid tumors. The mice were treated with engineered CAR-T cells targeting guanyl cyclase-C (GCC) or mesothelin as monotherapy or in combination with LDRT. Additionally, we extended this approach to a C57BL/6 mouse model implanted with MC38-gp100+ cells, followed by adoptive transfer of pmel+ T cells before and after LDRT. Tumor growth and survival outcomes were monitored in all models. Furthermore, we employed atomic force microscopy (AFM) in a small cohort to assess the effects of radiotherapy on tumor stiffness and plasticity, exploring the role of tumor nanomechanics as a potential biomarker for treatment efficacy. Results: Our results demonstrated enhanced tumor control and prolonged survival in mice treated with LDRT followed by T-cell therapy across all models. The combination of LDRT with CAR-T or pmel+ T-cell therapy led to superior tumor suppression and survival compared to monotherapy, highlighting the synergistic impact of the combined approach. Additionally, AFM analysis revealed significant changes in tumor stiffness and plasticity in response to LDRT, suggesting that the nanomechanical properties of the tumor may be predictive of therapeutic response. Discussion: The findings of this study highlight the transformative potential of incorporating LDRT as a precursor to adoptive T-cell therapy in solid tumors. By promoting CAR-T and pmel+ T-cell infiltration into the tumor microenvironment, LDRT enhanced tumor control and improved survival outcomes, offering a promising strategy to overcome the challenges associated with CAR-T therapy in solid tumors. Additionally, the changes in tumor nanomechanics observed through AFM suggest that tumor stiffness and plasticity could be biomarkers for predicting treatment outcomes. These results support further investigation into the clinical application of this combined approach to improve the efficacy of cellbased therapies in patients with solid tumors. [ABSTRACT FROM AUTHOR]

Metastatic castrate-resistant prostate cancer (mCRPC) is associated with poor prognosis. DNA damage response (DDR) genes are commonly altered in mCRPC rendering them as promising therapeutic targets. Poly (ADP ribose) polymerase inhibitors (PARPi) demonstrated antitumor activity in mCRPC patients with DDR gene mutations through synthetic lethality. Multiple clinical trials with PARPi monotherapy exhibited encouraging clinical outcomes in selected patients with mCRPC. More recently, three Phase III randomized clinical trials (RCTs) combining PARPi with androgen receptor signaling inhibitors (ARSIs) demonstrated improved antitumor activity compared to ARSI monotherapy in mCRPC patients as the first-line therapy. Clinical benefit was more pronounced in patients harboring DDR alterations, specifically BRCA1/2. Interestingly, antitumor activity was also observed irrespective of DDR gene mutations, highlighting BRCAness phenotype with androgen receptor blockade resulting in synergistic activity between ARSIs and PARPi. In this review, we discuss the clinical efficacy and safety data of the combination of PARPi plus ARSI in all Phase 3 randomized controlled trials (RCTs), emphasizing strategies for patient selection and highlighting emerging trends based on clinical trial data. [ABSTRACT FROM AUTHOR]

Abstract Neuroblastoma (NB) is the most common extracranial tumor in children resulting in substantial morbidity and mortality. A deeper understanding of the NB tumor microenvironment (TME) remains an area of active research but there is a lack of reliable and biomimetic experimental models. This study utilizes a 3D bioprinting approach, in combination with NB spheroids, to create an in vitro vascular model of NB for exploring the tumor function within an endothelialized microenvironment. A gelatin methacryloyl (gelMA) bioink is used to create multi‐channel cubic tumor analogues with high printing fidelity and mechanical tunability. Human‐derived NB spheroids and human umbilical vein endothelial cells (HUVECs) are incorporated into the biomanufactured gelMA and cocultured under static versus dynamic conditions, demonstrating high levels of survival and growth. Quantification of NB‐EC integration and tumor cell migration suggested an increased aggressive behavior of NB when cultured in bioprinted endothelialized models, when cocultured with HUVECs, and also as a result of dynamic culture. This model also allowed for the assessment of metabolic, cytokine, and gene expression profiles of NB spheroids under varying TME conditions. These results establish a high throughput research enabling platform to study the TME‐mediated cellular‐molecular mechanisms of tumor growth, aggression, and response to therapy.

Simple Summary: The behaviours and needs of nocturnal animals can be overlooked by humans, potentially because of our poor night vision and diurnal waking hours. Despite certain challenges in studying many nocturnal animals, appropriate provisions for their welfare should be supported in both wild and managed environments. To investigate this issue and explore ways to offer technology-enhanced welfare, husbandry practices and enrichment opportunities for nocturnal species, we conducted a multidisciplinary workshop (Moon Jam). During the event, species experts provided animal welfare briefs that related to specific challenges for nocturnal animals in different contexts. Teams of participants addressed these challenges in collaborative design sessions, producing a collection of hand-crafted models to share their ideas. An important aspect of the workshop was to be inclusive of all the stakeholders involved, including zoo management teams, animal stewards and zoo visitors, as well as the individual species. In this paper, we present our reflections on managed nocturnal animal welfare, framing these within current practices and Moon Jam workshop outputs. We contribute a set of guidelines for those involved with caring for zoo-housed nocturnal species, emphasizing the provision of technology-enhanced husbandry and enrichment opportunities. This paper addresses the potential for technology to support husbandry and enrichment opportunities that enhance the welfare of zoo and sanctuary-housed nocturnal and crepuscular species. This topic was investigated through the medium of a multidisciplinary workshop (Moon Jam) that brought together species experts, zoo designers, Animal-Computer Interaction researchers and post-graduate students in collaborative discussions and design sessions. We explain the context through an examination of existing research and current practices, and report on specific challenges raised and addressed during the Moon Jam, highlighting and discussing key themes that emerged. Finally, we offer a set of guidelines to support the integration of technology into the design of animal husbandry and enrichment that support wellbeing, to advance the best practices in keeping and managing nocturnal and crepuscular animals. [ABSTRACT FROM AUTHOR]

Previous research into the possibility of learning in paramecia in this laboratory has shown that these organisms can learn to go to and remain in a specific location based on cathode shock reinforcement. The present experiment was designed to determine whether paramecia could retain (remember) the learned brightness discrimination task. The results indicate that the retention interval for this task in paramecia is shorter than 1 minute. It is possible that paramecia can remember this task for longer than a second but shorter than the 1-minute interval that was used during test. It is also possible that remembering for more than a few seconds requires a nervous system, which paramecia do not have.

Protein aggregates of cofilin and actin have been found in neurons under oxygen–glucose deprivation. However, the regulatory mechanism behind the expression of Cfl1 during oxygen–glucose deprivation remains unclear. Here, we found that heterogeneous nuclear ribonucleoproteins (hnRNP) Q and hnRNP A1 regulate the translation of Cfl1 mRNA, and formation of cofilin–actin aggregates. The interaction between hnRNP A1 and Cfl1 mRNA was interrupted by hnRNP Q under normal conditions, while the changes in the expression and localization of hnRNP Q and hnRNP A1 increased such interaction, as did the translation of Cfl1 mRNA under oxygen–glucose deprived conditions. These findings reveal a new translational regulatory mechanism of Cfl1 mRNA in hippocampal neurons under oxygen–glucose deprivation.

In most cases of ingested foreign bodies, endoscopy is the first treatment of choice. Moreover, emergency endoscopic removal is required for sharp and pointed foreign bodies such as animal or fish bones, food boluses, and button batteries due to the increased risks of perforation, obstruction, and bleeding. Here, we presented two cases that needed emergency endoscopic removal of foreign bodies without sufficient fasting time. Foreign bodies could not be visualized by endoscopy due to food residue; therefore, fluoroscopic imaging was utilized for endoscopic removal of foreign bodies in both cases.

Jejunal variceal bleeding is less common compared with esophagogastric varices in patients with portal hypertension. However, jejunal variceal bleeding can be fatal without treatment. Treatments include surgery, transjugular intrahepatic porto-systemic shunt (TIPS), endoscopic sclerotherapy, percutaneous coil embolization, and balloon-occluded retrograde transvenous obliteration (BRTO). Percutaneous coil embolization can be considered as an alternative treatment option for those where endoscopic sclerotherapy, surgery, TIPS or BRTO are not possible. Complications of percutaneous coil embolization have been reported, including coil migration. Herein, we report a case of migration of the coil into the jejunal lumen after percutaneous coil embolization for jejunal variceal bleeding. The migrated coil was successfully removed using surgery.