Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type.

Importance: Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. Objective: To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. Design, Setting, and Participants: This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Exposures: Bypass surgery and conservative management. Main Outcomes and Measures: Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. Results: A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). Conclusions and Relevance: The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

Cost-benefit analysis of human adenovirus vaccine development in a Korean military setting.

BACKGROUND: Human adenovirus (HAdV) is a prevalent causative agent of acute respiratory disease (ARD) and is frequently responsible for outbreaks, particularly in military environments. Current vaccines do not effectively cover HAdV subtypes commonly found among Korean military personnel, highlighting the need for a new targeted vaccine. This study presents a cost-benefit analysis to evaluate the economic viability of developing and implementing such a vaccine within a military context. METHODS: We adopted a societal perspective for this cost-benefit analysis, which included estimating costs associated with vaccine development, production, and distribution over a projected timeline. We assumed a development period of five years, after which vaccine production and administration were initiated in the sixth year. The cost associated with vaccine development, production, and dispensation was considered. The benefits were calculated based on both direct and indirect cost savings from preventing HAdV infections through vaccination. All financial figures were expressed in 2023 US dollars. A sensitivity analysis was conducted to explore the impact of varying factors such as vaccination rate, incidence of infection, vaccine efficacy, and discount rate. RESULTS: For the base case scenario, we assumed a vaccination rate of 100 %, an incidence rate of 0.02, and a vaccine efficacy of 95 %, applying a 3 % discount rate. Initially, in the sixth year, the benefit-cost ratio stood at 0.71, suggesting a cost disadvantage at the onset of vaccination. However, this ratio improved to 1.32 in the following years, indicating a cost benefit from the seventh year onward. The cumulative benefit-cost ratio over a decade reached 2.72. The outcomes from the sensitivity analysis were consistent with these findings. CONCLUSION: Our cost-benefit analysis demonstrates that the introduction of an HAdV vaccine for the Korean military is economically advantageous, with substantial cost benefits accruing from the seventh year after the commencement of vaccination.

The effect of inhaler prescription on the development of lung cancer in COPD: a nationwide population-based study.

BACKGROUND: COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD. METHODS: A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded. RESULTS: Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86-3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01-1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01-1.39), along with older age and male sex, were independently associated with the development of lung cancer. CONCLUSION: Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.

Design, Synthesis, and Biological Evaluation of New 2,6,7-Substituted Purine Derivatives as Toll-like Receptor 7 Agonists for Intranasal Vaccine Adjuvants.

TLR7/8 agonists are versatile immune stimulators capable of treating various diseases such as viral infections, autoimmune, and cancer. Despite the structural similarity of TLR7/8, their immune stimulation mechanisms and time-course responses significantly differ. In this study, a new series of TLR7-selective agonists was synthesized utilizing the economical building block 2,6-dichloropurine. Compound 27b showed the most potent activity on hTLR7 with an EC50 of 17.53 nM and demonstrated high hTLR7 selectivity (224 folds against TLR8). 27b effectively stimulated the secretion of proinflammatory cytokines in mouse macrophages and enhanced intranasal vaccine efficacy against influenza A virus in vivo. Assessment of humoral and mucosal antibody titers confirmed that 27b elevates IgG and IgA levels, protecting against both homologous and heterologous influenza viral infections. These findings suggest that 27b is a promising candidate as a vaccine adjuvant to prevent viral infections or as a robust immunomodulator with prolonged activity for treating immune-suppressed diseases.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Traumatic spinal cord injury in South Korea for 13 years (2008-2020).

Traumatic spinal cord injury (TSCI) has significant physical, psychological, and socioeconomic impacts. However, the epidemiological characteristics and treatment patterns of TSCI in South Korea remain unclear. This study aimed to investigate TSCI incidence and treatment behaviors in South Korea from 2008 to 2020. We included data from 30,979 newly diagnosed TSCI patients obtained from the Health Insurance Review and Assessment Service (HIRA). Treatment trends, location of surgery, surgical method, comorbidities, factors affecting hospital stay, and risk factors affecting readmission were analyzed. Patients were divided into the surgery group [n = 7719; (25%)] and the non-surgery group [n = 23,260; (75%)]. Surgical cases involved cervical (64%), thoracic (17%), and lumbar/sacral (19%) lesions. Anterior fusion (38%), posterior fusion (54%), and corpectomy (8%) were the surgical methods. Surgical treatments increased annually. Factors influencing hospital stay included male sex, older age, and higher Charlson comorbidity index (CCI). Female sex and higher CCI scores were associated with readmission. In conclusion, a quarter of all TSCI patients underwent surgery, with an upward trend. Risk factors for longer hospital stays were thoracic spine injury, older age, higher CCI, and male sex. Risk factors for readmission included age range of 40-59 years, lumbar/sacral spine injuries, CCI score of 2, and female sex.

The discovery of an anti-inflammatory monoterpenoid, neoroseoside from the Zea mays.

A new monoterpenoid, neoroseoside (1), along with two previously reported compounds, 2″-O-α-l-rhamnosyl-6-C-fucosylluteolin (2) and farobin A (3) were isolated from the Zea mays. The structure of compound 1 was determined through the analysis spectroscopic data, including mass spectrometry (MS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) data. The absolute configurations of 1 were deduced from the comparing the values of optical rotations and from the interpretation of electronic circular dichroism (ECD) spectra. Compounds 2 and 3 displayed moderate antibacterial activity against Streptococcus mutans ATCC 25175 (inhibition rates 24 % and 28 %, respectively) and Streptococcus sobrinus ATCC 33478 (inhibition rate of 26 %), at a concentration of 100 µg/mL, whereas compound 1 did not have any significant antibacterial activities. The compounds 1-3 also showed anti-inflammatory activity on cytokine IL-6 and TNF-α.

SGLT2i impact on HCC incidence in patients with fatty liver disease and diabetes: a nation-wide cohort study in South Korea.

This study evaluated the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer development, particularly in hepatocellular carcinoma (HCC), in individuals with concomitant fatty liver disease (FLD) and type 2 diabetes mellitus (T2DM). Using data from Korea's Health Insurance Review and Assessment Service, we performed Kaplan-Meier and Cox regression analyses in patients with non-alcoholic fatty liver disease (NAFLD) and T2DM (NAFLD-T2DM cohort) and those with chronic viral hepatitis (CVH) alongside FLD and T2DM (FLD-T2DM-CVH cohort). In the propensity score (PS) matched NAFLD-T2DM cohort (N = 107,972), SGLT2i use was not associated with the occurrence of overall cancer, including HCC. However, old age, male sex, liver cirrhosis, and hypothyroidism were identified as independent risk factors for HCC occurrence, whereas statin and fibrate usage were associated with reduced HCC risk in this cohort in multivariate Cox analysis. In the PS-matched FLD-T2DM-CVH cohort (N = 2798), a significant decrease in HCC occurrence was observed among SGLT2i users (P = 0.03). This finding remained consistent in the multivariate Cox regression analysis (Hazard ratio = 2.21, 95% confidence interval = 1.01-4.85, P = 0.048). In conclusion, SGLT2i may be a beneficial option for diabetes management in patients with concomitant T2DM, FLD, and CVH while affirming the overall safety of SGLT2i in other types of cancer.

2,4,6-Triphenyl-1-hexene, an Anti-Melanogenic Compound from Marine-Derived Bacillus sp. APmarine135.

Although melanin protects against ultraviolet radiation, its overproduction causes freckles and senile lentigines. Recently, various biological effects of metabolites derived from marine microorganisms have been highlighted due to their potential for biological and pharmacological applications. In this study, we discovered the anti-melanogenic effect of Bacillus sp. APmarine135 and verified the skin-whitening effect. Fractions of APmarine135 showed the melanin synthesis inhibition effect in B16 melanoma cells, and 2,4,6-triphenyl-1-hexene was identified as an active compound. The melanogenic capacity of 2,4,6-triphenyl-1-hexene (1) was investigated by assessing the intracellular melanin content in B16 cells. Treatment with 5 ppm of 2,4,6-triphenyl-1-hexene (1) for 72 h suppressed the α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin increase to the same level as in the untreated control group. Additionally, 2,4,6-triphenyl-1-hexene (1) treatment suppressed the activity of tyrosinase, the rate-limiting enzyme for melanogenesis. Moreover, 2,4,6-triphenyl-1-hexene (1) treatment downregulated tyrosinase, Tyrp-1, and Tyrp-2 expression by inhibiting the microphthalmia-associated transcription factor (MITF). Furthermore, 2,4,6-triphenyl-1-hexene (1) treatment decreased the melanin content in the three-dimensional (3D) human-pigmented epidermis model MelanoDerm and exerted skin-whitening effects. Mechanistically, 2,4,6-triphenyl-1-hexene (1) exerted anti-melanogenic effects by suppressing tyrosinase, Tyrp-1, and Tyrp-2 expression and activities via inhibition of the MITF. Collectively, these findings suggest that 2,4,6-triphenyl-1-hexene (1) is a promising anti-melanogenic agent in the cosmetic industry.

Dienogest attenuates STAT3 activation in ovarian endometriotic cysts.

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.

Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

BACKGROUNDS: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. METHODS: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. RESULTS: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. CONCLUSION: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp.

This study aims to explore the potential inhibition effects of staurosporine isolated from a Streptomyces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimicrobial and antihypertensive activities. This research focuses on investigating the effects of staurosporine on suppressing the growth and development of nasal polyps and elucidating the underlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF-ß1 in the presence of staurosporine. The levels of α-smooth muscle actin (α-SMA), collagen type-I (Col-1), fibronectin, and phosphorylated (p)-Smad 2 were investigated using Western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-ß1 stimulated the production of Col-1, fibronectin, and α-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-ß1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine's role in nasal polyp management and provide insights into its mechanisms of action.

Methylanthranilate, a Food Fragrance Attenuates Skin Pigmentation through Downregulation of Melanogenic Enzymes by cAMP Suppression.

Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm™. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.

Prevalence and Burden of Human Adenovirus-Associated Acute Respiratory Illness in the Republic of Korea Military, 2013 to 2022.

BACKGROUND: Human adenovirus (HAdV) is a common cause of acute respiratory disease (ARD) and has raised significant concerns within the Korean military. Here, we conducted a comprehensive epidemiological analysis of HAdV-associated ARD by evaluating its prevalence, clinical outcomes, and prognosis. METHODS: We reviewed data from multiple sources, including the New Defense Medical Information System, Defense Medical Statistical Information System, Ministry of National Defense, Army Headquarters, Navy Headquarters, Air Force Headquarters, and Armed Forces Medical Command. We analyzed data of patients who underwent polymerase chain reaction (PCR) testing for respiratory viruses between January 2013 and July 2022 in all 14 Korean military hospitals. The analysis included the PCR test results, demographic characteristics, health care utilization, and prognosis including types of treatments received, incidence of pneumonia, and mortality. RESULTS: Among the 23,830 individuals who underwent PCR testing at Korean military hospitals, 44.78% (10,670 cases) tested positive for respiratory viruses. Across all military types and ranks, HAdV was the most prevalent virus, with a total of 8,580 patients diagnosed, among HAdV, influenza virus, human metapneumovirus, human parainfluenza virus, and human respiratory syncytial virus. HAdV-infected patients exhibited higher rates of healthcare use compared to non-HAdV-infected patients, including a greater number of emergency visits (1.04 vs. 1.02) and outpatient visits (1.31 vs. 1.27), longer hospitalizations (8.14 days vs. 6.84 days), and extended stays in the intensive care unit (5.21 days vs. 3.38 days). Furthermore, HAdV-infected patients had a higher proportion of pneumonia cases (65.79% vs. 48.33%) and greater likelihood of receiving advanced treatments such as high flow nasal cannula or continuous renal replacement therapy. CONCLUSION: Our findings indicate that HAdV posed a significant public health concern within the Korean military prior to the coronavirus disease 2019 (COVID-19) pandemic. Given the potential for a resurgence of outbreaks in the post-COVID-19 era, proactive measures, such as education, environmental improvements, and the development of HAdV vaccines, are crucial for effectively preventing future outbreaks.

Justicia procumbens prevents hair loss in androgenic alopecia mice.

The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/ß-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of ß-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3ß and ß-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss.

Secondary Malignancies in Multiple Myeloma in Korean Patients: A Nationwide Population-Based Study.

Purpose: This study investigated the incidence of secondary malignancy in multiple myeloma (MM) patients compared with that in the general population using a population-based database covering all residents in Korea. Materials and Methods: Based on the national health insurance system in Korea, all people primarily diagnosed with MM between January 1, 2010 to December 31, 2018 were identified. A total of 9,985 MM patients aged ≥20 years in Korea were included. Results: Among them, 237 (2.4%) developed secondary malignancies by 2018. The standardized incidence rates (SIRs) of all secondary malignancies in MM patients were 0.87 (95% confidence interval [CI]=0.76-0.98), with a higher incidence of hematologic malignancies than in the general population with an SIR of 3.80 (95% CI=2.61-5.00). The incidence rates of both lymphoid malignancy (SIR=3.56; 95% CI=2.31-4.82) and myeloid malignancy (SIR=3.78; 95% CI=1.16-6.39) were higher in MM patients than in the general population. In contrast, a lower incidence of solid cancer was observed in MM patients than in the general population (SIR=0.76, 95% CI=0.65-0.86). There was no significant difference in survival in MM patients without secondary malignancies, with hematologic malignancy, and with solid cancer (p-value=0.413). Conclusion: MM patients had a greater risk of secondary malignancies, especially hematologic malignancies, than the general population. Future studies with a focus on analyzing patients' history, treatment details, and genetic information in various stages of MM patients are needed to better understand the mechanism behind this increased risk.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Phosphocode-dependent glutamyl-prolyl-tRNA synthetase 1 signaling in immunity, metabolism, and disease.

Ubiquitously expressed aminoacyl-tRNA synthetases play essential roles in decoding genetic information required for protein synthesis in every living species. Growing evidence suggests that they also function as crossover mediators of multiple biological processes required for homeostasis. In humans, eight cytoplasmic tRNA synthetases form a central machinery called the multi-tRNA synthetase complex (MSC). The formation of MSCs appears to be essential for life, although the role of MSCs remains unclear. Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is the most evolutionarily derived component within the MSC that plays a critical role in immunity and metabolism (beyond its catalytic role in translation) via stimulus-dependent phosphorylation events. This review focuses on the role of EPRS1 signaling in inflammation resolution and metabolic modulation. The involvement of EPRS1 in diseases such as cancer is also discussed.

Denosumab-associated jaw bone necrosis in cancer patients: retrospective descriptive case series study.

BACKGROUND: Denosumab (DMB) is a bone antiresorptive agent used to treat osteoporosis or metastatic cancer of the bones. However, denosumab-associated osteonecrosis of the jaw (DRONJ) has become a common complication in cancer patients. The prevalence of osteonecrosis of the jaw (ONJ) in cancer patients is estimated to be similar for both bisphosphonate-related cases (1.1 to 1.4%) and denosumab-related cases (0.8 to 2%), with the addition of adjunctive therapy with anti-angiogenic agents reportedly increasing its prevalence to 3%. (Spec Care Dentist 36(4):231-236, 2016). The aim of this study is to report on DRONJ in cancer patients treated with DMB (Xgeva®, 120mg). CASE PRESENTATION: In this study, we identified four cases of ONJ among 74 patients receiving DMB therapy for metastatic cancer. Of the four patients, three had prostate cancer and one had breast cancer. Preceding tooth extraction within 2 months of the last DMB injection was found to be a risk factor for DRONJ. Pathological examination revealed that three patients had acute and chronic inflammation, including actinomycosis colonies. Among the four patients with DRONJ referred to us, three were successfully treated without complications and had no recurrence following surgical treatment, while one did not follow up. After healing, one patient experienced a recurrence at a different site. Sequestrectomy in conjunction with antibiotic therapy and cessation of DMB use proved to be effective in managing the condition, and the ONJ site healed after an average 5-month follow-up period. CONCLUSION: Conservative surgery, along with antibiotic therapy and discontinuation of DMB, was found to be effective in managing the condition. Additional studies are needed to investigate the contribution of steroids and anticancer drugs to jaw bone necrosis, the prevalence of multicenter cases, and whether there is any drug interaction with DMB.