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The activation and functional differentiation of CD8 + T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification; however, the relevance of histone lactylation in the context of CD8 + T cell activation and function is not known. Here, we show the enrichment of H3K18 lactylation (H3K18la) and H3K9 lactylation (H3K9la) in human and mouse CD8 + T cells, which act as transcription initiators of key genes regulating CD8 + T cell function. Further, we note distinct patterns of H3K18la and H3K9la in CD8 + T cell subsets linked to their specific metabolic profiles. Additionally, we find that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways influence CD8 + T cell effector function, including antitumor immunity, in preclinical models. Overall, our study uncovers the potential roles of H3K18la and H3K9la in CD8 + T cells., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The long-term physiological consequences of respiratory viral infections, particularly in the aftermath of the COVID-19 pandemic-termed post-acute sequelae of SARS-CoV-2 (PASC)-are rapidly evolving into a major public health concern 1-3 . While the cellular and molecular aetiologies of these sequelae are poorly defined, increasing evidence implicates abnormal immune responses 3-6 and/or impaired organ recovery 7-9 after infection. However, the precise mechanisms that link these processes in the context of PASC remain unclear. Here, with insights from three cohorts of patients with respiratory PASC, we established a mouse model of post-viral lung disease and identified an aberrant immune-epithelial progenitor niche unique to fibroproliferation in respiratory PASC. Using spatial transcriptomics and imaging, we found a central role for lung-resident CD8 + T cell-macrophage interactions in impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Specifically, IFNγ and TNF derived from CD8 + T cells stimulated local macrophages to chronically release IL-1β, resulting in the long-term maintenance of dysplastic epithelial progenitors and lung fibrosis. Notably, therapeutic neutralization of IFNγ + TNF or IL-1β markedly improved alveolar regeneration and pulmonary function. In contrast to other approaches, which require early intervention 10 , we highlight therapeutic strategies to rescue fibrotic disease after the resolution of acute disease, addressing a current unmet need in the clinical management of PASC and post-viral disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This paper provides a comprehensive overview of the Cancer Public Library Database (CPLD), established under the Korean Clinical Data Utilization for Research Excellence project (K-CURE). The CPLD links data from four major population-based public sources: the Korea National Cancer Incidence Database in the Korea Central Cancer Registry, cause-of-death data in Statistics Korea, the National Health Information Database in the National Health Insurance Service, and the National Health Insurance Research Database in the Health Insurance Review & Assessment Service. These databases are linked using an encrypted resident registration number. The CPLD, established in 2022 and updated annually, comprises 1,983,499 men and women newly diagnosed with cancer between 2012 and 2019. It contains data on cancer registration and death, demographics, medical claims, general health checkups, and national cancer screening. The most common cancers among men in the CPLD were stomach (16.1%), lung (14.0%), colorectal (13.3%), prostate (9.6%), and liver (9.3%) cancers. The most common cancers among women were thyroid (20.4%), breast (16.6%), colorectal (9.0%), stomach (7.8%), and lung (6.2%) cancers. Among them, 571,285 died between 2012 and 2020 owing to cancer (89.2%) or other causes (10.8%). Upon approval, the CPLD is accessible to researchers through the K-CURE portal. The CPLD is a unique resource for diverse cancer research to investigate medical use before a cancer diagnosis, during initial diagnosis and treatment, and long-term follow-up. This offers expanded insight into healthcare delivery across the cancer continuum, from screening to end-of-life care.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

The activation and functional differentiation of CD8 T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification (hPTM); however, the relevance of histone lactylation in the context of CD8 T cell activation and function is not known. Here, we show the enrichment of H3K18-lactylation (H3K18la) and H3K9-lactylation (H3K9la) in human and murine CD8 T cells which act as transcription initiators of key genes regulating CD8 T cell phenotype and function. Further, we note distinct impacts of H3K18la and H3K9la on CD8 T cell subsets linked to their specific metabolic profiles. Importantly, we demonstrate that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways regulates CD8 T cell effector function including anti-tumor immunity in preclinical models. Overall, our study uncovers the unique contributions of H3K18la and H3K9la in modulating CD8 T cell phenotype and function intricately associated with metabolic state.

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets., (© 2024. The Author(s).)

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m 2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m 2 and two at dose of 1.2 mg/m 2 . None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase 2 part of the study at the maximum dose of 1.8 mg/m 2 . One patient developed VOD; this patient had received nivolumab immediately before HSCT while simultaneously experiencing hyperacute graft-vs-host disease (GVHD). Treatment-related mortality (TRM) at 5 years was 12%. With a median follow-up of 48.7 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 84% and 80%, respectively. Compared with a historical cohort who received same conditioning for HSCT but without INO (n = 56), the INO group showed no significant differences in incidence of liver toxicity, engraftment time, TRM, or risk of acute GVHD. Patients with lymphoma who received INO had a trend for a better 5-year OS (93% versus 68%) and PFS (93% versus 58%) than those in the control group. In conclusion, our results showed that INO is safe with no increased risk of VOD when combined with one alkylator-containing regimen of HSCT., (© 2024 Wiley Periodicals LLC.)

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021., Materials and Methods: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea., Results: The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021., Conclusion: In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019-related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.

Purpose: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden., Materials and Methods: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend for prediction., Results: In total, 292,221 new cancer cases and 83,770 cancer deaths are expected to occur in Korea in 2024. The most common cancer site is expected to be the thyroid, followed by the colon and rectum, lung, breast, and stomach. These five cancers are expected to represent 55.7% of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and stomach cancers., Conclusion: The age-standardized incidence rates for female breast and prostate cancers are estimated to continue to increase. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

We investigate the reassembly techniques for utilizing fine graphite particles, smaller than 5 µm, as high-efficiency, high-rate anode materials for lithium-ion batteries. Fine graphite particles of two sizes (0.4-1.2 µm and 5 µm) are utilized, and the mixing ratio of the two particles is varied to control the porosity of the assembled graphite. The packing characteristics of the assembled graphite change based on the mixing ratio of the two types of fine graphite particles, forming assembled graphite with varying porosities. The open porosity of the manufactured assembled graphite samples ranges from 0.94% to 3.55%, while the closed porosity ranges from 21.41% to 26.51%. All the assembled graphite shows improved electrochemical characteristics properties compared with anodes composed solely of fine graphite particles without granulation. The sample assembled by mixing 1.2 µm and 5 µm graphite at a 60:40 ratio exhibits the lowest total porosity (27.45%). Moreover, it exhibits a 92.3% initial Coulombic efficiency (a 4.7% improvement over fine graphite particles) and a capacity of 163.4 mAh/g at a 5C-rate (a 1.9-fold improvement over fine graphite particles).

Traditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days -20 and -13 before transplant. Fludarabine 40 mg/m2 was administered on days -6 to -3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities. This trial was registered at www.clinicaltrials.gov as #NCT02861417., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (-) patients (HR, 4.97; P = 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution-a hydrogen peroxide-sodium bicarbonate mixture-on the surface properties and contact angles of osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. MG-63 osteoblasts were cultured on the specimens, and their adhesion to the specimen surface and proliferation were examined using staining and the MTT assay, respectively. Additional etching with the etching solution caused the formation of nano/micro hierarchical structures, increased surface roughness, and enhanced hydrophilicity. Osteoblast adhesion and proliferation were found to improve on the modified surfaces. The eco-friendly etching method has the potential to enhance the biological properties of Ti implant surfaces and thereby improve dental implant performance.

Purpose: Biphasic calcium phosphate (BCP), a widely used biomaterial for bone regeneration, contains synthetic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), the ratio of which can be adjusted to modulate the rate of degradation. The aim of this study was to evaluate the clinical and radiographic benefits of reconstructing peri-implant bone defects with a newly developed BCP consisting of 40% β-TCP and 60% HA compared to demineralized bovine bone mineral (DBBM)., Methods: This prospective, multicenter, parallel, single-blind randomized controlled trial was conducted at the periodontology departments of 3 different dental hospitals. Changes in clinical (defect width and height) and radiographic (augmented horizontal bone thickness) parameters were measured between implant surgery with guided bone regeneration (GBR) and re-entry surgery. Postoperative discomfort (severity and duration of pain and swelling) and early soft-tissue wound healing (dehiscence and inflammation) were also assessed. Data were compared between the BCP (test) and DBBM (control) groups using the independent t -test and the χ² test., Results: Of the 53 cases included, 27 were in the test group and 26 were in the control group. After a healing period of 18 weeks, the full and mean resolution of buccal dehiscence defects were 59.3% (n=16) and 71.3% in the test group and 42.3% (n=11) and 57.9% in the control group, respectively. There were no significant differences between the groups in terms of the change in mean horizontal bone augmentation (test group: -0.50±0.66 mm vs. control groups: -0.66±0.83 mm, P =0.133), postoperative discomfort, or early wound healing. No adverse or fatal complications occurred in either group., Conclusion: The GBR procedure with the newly developed BCP showed favorable clinical, radiographic, postoperative discomfort-related, and early wound healing outcomes for peri-implant dehiscence defects that were similar to those for DBBM., Trial Registration: Clinical Research Information Service Identifier: KCT0006428., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Academy of Periodontology.)

Due to the high hardness and brittleness of ceramic materials, conventional cutting methods result in poor quality and machining difficulties. Additive manufacturing has also been tried in various ways, but it has many limitations. This study aims to propose a system to monitor surface defects that occur during the printing process based on high-viscosity composite resin that maximizes ceramic powder content in real time using image processing and convolutional neural network (CNN) algorithms. To do so, defects mainly observed on the surface were classified into four types by form: pore, minor, critical, and error, and the effect of each defect on the printed structure was tested. In order to improve the classification efficiency and accuracy of normal and defective states, preprocessing of images obtained based on cropping, dimensionality reduction, and RGB pixel standardization was performed. After training and testing the preprocessed images based on the DenseNet algorithm, a high classification accuracy of 98% was obtained. Additionally, for pore and minor defects, experiments confirmed that the defect surfaces can be improved through the reblading process. Therefore, this study presented a defect detection system as well as a feedback system for process modifications based on classified defects.

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as 'gaps' in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss., Competing Interests: EW, JI, SS, MN, TI, SL, DC, KN, YN, DA, WX, GH, KA, PO, JS No competing interests declared, (© 2023, Wagner et al.)

In this paper, a method for optimizing the mixing ratio of filler coke and binder for high-strength carbon-carbon composites is proposed. Particle size distribution, specific surface area, and true density were analyzed to characterize the filler properties. The optimum binder mixing ratio was experimentally determined based on the filler properties. As the filler particle size was decreased, a higher binder mixing ratio was required to enhance the mechanical strength of the composite. When the d 50 particle size of the filler was 62.13 and 27.10 µm, the required binder mixing ratios were 25 and 30 vol.%, respectively. From this result, the interaction index, which quantifies the interaction between the coke and binder during carbonization, was deduced. The interaction index had a higher correlation coefficient with the compressive strength than that of the porosity. Therefore, the interaction index can be used in predicting the mechanical strength of carbon blocks and optimizing their binder mixing ratios. Furthermore, as it is calculated from the carbonization of blocks without additional analysis, the interaction index can be easily used in industrial applications.

Activated carbon supports for Si deposition with different porosities were prepared, and the effect of porosity on the electrochemical characteristics was investigated. The porosity of the support is a key parameter affecting the Si deposition mechanism and the stability of the electrode. In the Si deposition mechanism, as the porosity of activated carbon increases, the effect of particle size reduction due to the uniform dispersion of Si was confirmed. This implies that the porosity of activated carbon can affect the rate performance. However, excessively high porosity reduced the contact area between Si and activated carbon, resulting in poor electrode stability. Therefore, controlling the porosity of activated carbon is essential to improving the electrochemical characteristics., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA)., Experimental Design: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment., Results: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and emergence of novel clones after the initial treatment, and a higher mutation burden pretreatment with subsequent reduction posttreatment. Autophagy, TGFβ, and Th1 differentiation pathways were the most downregulated in nonresponders after treatment, while upregulated in responders. Finally, CTLA-4 but not PD-1 blockade attributed to favorable changes in immune landscape., Conclusions: Analysis of tumor-immune landscape in MDS during immunotherapy provides clinical response biomarkers., (©2023 American Association for Cancer Research.)

Objective: To evaluate a regional anesthetic technique for blocking the abdominal midline in horses., Study Design: Anatomical description and prospective, crossover, placebo-controlled, blinded study., Animals: Adult horses; two cadavers, six healthy animals., Methods: In stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg -1 ) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg -1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded., Results: The cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9-L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed., Conclusions and Clinical Relevance: Antinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision of "A Healthy Country with No Concerns about Cancer Anywhere at Any Time," which aims to build and disseminate high-quality cancer data, reduce preventable cancer cases, and reduce gaps in cancer control. Its main strategies include (1) activation of cancer big data, (2) advancement of cancer prevention and screening, (3) improvement in cancer treatment and response, and (4) establishment of a foundation for balanced cancer control. The fourth NCCP has many positive expectations, similar to the last 3 plans; however, cross-domain support and participation are required to achieve positive results in cancer control. Notably, cancer remains the leading cause of death despite decades of management efforts and should continue to be managed carefully from a national perspective.

Purpose: This study aimed to report the projected cancer incidence and mortality for the year 2023 to estimate Korea's current cancer burden., Materials and Methods: Cancer incidence data from 1999 to 2020 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2021 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2023. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend., Results: In total, 273,076 new cancer cases and 81,818 cancer deaths are expected to occur in Korea in 2023. The most common cancer site is expected to be the lung, followed by the thyroid, breast, colon and rectum, and stomach. These five cancers are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and gallbladder cancers., Conclusion: The incidence rates for all types of cancer in Korea are estimated to gradually decrease. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2020., Materials and Methods: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2020, with survival follow-up until December 31, 2021. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea., Results: The number of new cancer diagnoses in 2020 decreased by 9,218 cases (3.6%) compared to 2019. In 2020, newly diagnosed cancer cases and deaths from cancer were reported as 247,952 (age-standardized rate [ASR], 262.2 per 100,000) and 82,204 (ASR, 69.9 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.0% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years. The 5-year relative survival between 2016 and 2020 was 71.5%, which contributed to prevalent cases reaching over 2.2 million in 2020., Conclusion: In 2020, the number of newly diagnosed cancer patients decreased due to the coronavirus disease 2019 pandemic, but the overall trend is on the rise. Cancer survival rates have improved over the past decades. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics. The long-term impact of the coronavirus disease 2019 pandemic on cancer statistics needs to be investigated in the future.

Objectives: This study investigated regional disparities in the incidence of 8 major cancers at the municipal level in Korea during 1999-2018 and evaluated the presence or absence of hot spots of cancer clusters during 2014-2018., Methods: The Korea National Cancer Incidence Database was used. Age-standardized incidence rates were calculated by gender and region at the municipal level for 4 periods of 5 years and 8 cancer types. Regional disparities were calculated as both absolute and relative measures. The possibility of clusters was examined using global Moran's I with a spatial weight matrix based on adjacency or distance., Results: Regional disparities varied depending on cancer type and gender during the 20-year study period. For men, the regional disparities of stomach, colon and rectum, lung, and liver cancer declined, and those of thyroid and prostate cancer recently decreased, despite an overall increasing incidence. For women, regional disparities in stomach, colon and rectum, lung, liver, and cervical cancer declined, that of thyroid cancer recently decreased, despite an overall increasing incidence, and that of breast cancer steadily increased. In 2014-2018, breast cancer (I, 0.61; 95% confidence interval [CI], 0.53 to 0.70) showed a high probability of cancer clusters in women, and liver cancer (I, 0.48; 95% CI, 0.40 to 0.56) showed a high probability of cancer clusters in men., Conclusions: Disparities in cancer incidence that were not seen at the national level were discovered at the municipal level. These results could provide important directions for planning and implementing local cancer policies.

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity., Competing Interests: The technology was advanced through research conducted at MD Anderson by LC. In January 2015, the technology was licensed by The University of Texas MD Anderson Cancer Center for commercial application to Alaunos Therapeutics formerly Ziopharm Oncology, Inc., and Precigen formerly Intrexon Corporation, in exchange for equity interests in each of these companies. LC and some co-authors received equity because of the licensing of this technology. From 2015 to 2021 LC was Chief Executive Officer at ZIOPHARM. The information being reported in this publication is research in which The University of Texas MD Anderson Cancer Center has an institutional financial conflict of interest. Because The University of Texas MD Anderson Cancer Center is committed to the protection of human subjects and the effective management of its financial conflicts of interest in relation to its research activities, The University of Texas MD Anderson Cancer Center has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to The University of Texas MD Anderson Cancer Center’s conduct of this research. EG and LC were formerly employed by Alaunos Therapeutics and have equity ownership in the company. KR and The University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical and Affimed GmbH. KR participates on the Scientific Advisory Board for GemoAb, AvengeBio, Virogin Biotech, GSK, Bayer, Navan Technologies, and Caribou Biosciences. ES participates on Scientific Advisory Boards for Adaptimmune, Axio, Navan, Fibroblasts and Fibrobiologics, and the NY Blood Center; has licensing or patents with Takeda and Affimed; and honorarium from Bayer Healthcare Pharmaceuticals. PK has served on advisory boards for Kite and Pfizer; received research support from Amgen and Alaunos; and has been a consultant for Jazz. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Singh, Srour, Milton, McCarty, Dai, Gaballa, Ammari, Olivares, Huls, De Groot, Marin, Petropoulos, Olson, Anderlini, Im, Khouri, Hosing, Rezvani, Champlin, Shpall, Cooper and Kebriaei.)

Potato late blight caused by Phytophthora infestans is a destructive disease in Korea. To elucidate the genomic variation of the mitochondrial (mt) genome, we assembled its complete mt genome and compared its sequence among different haplotypes. The mt genome sequences of four Korean P. infestans isolates were revealed by Illumina HiSeq. The size of the circular mt genome of the four major genotypes, KR&#95;1&#95;A1, KR&#95;2&#95;A2, SIB-1, and US-11, was 39,872, 39,836, 39,872, and 39,840 bp, respectively. All genotypes contained the same 61 genes in the same order, comprising two RNA-encoding genes, 16 ribosomal genes, 25 transfer RNA, 17 genes encoding electron transport and ATP synthesis, 11 open reading frames of unknown function, and one protein import-related gene, tatC. The coding region comprised 91% of the genome, and GC content was 22.3%. The haplotypes were further analyzed based on sequence polymorphism at two hypervariable regions (HVRi), carrying a 2 kb insertion/deletion sequence, and HVRii, carrying 36 bp variable number tandem repeats (VNTRs). All four genotypes carried the 2 kb insertion/deletion sequence in HVRi, whereas HVRii had two VNTRs in KR&#95;1&#95;A1 and SIB-1 but three VNTRs in US-11 and KR&#95;2&#95;A2. Minimal spanning network and phylogenetic analysis based on 5,814 bp of mtDNA sequences from five loci, KR&#95;1&#95;A1 and SIB-1 were classified as IIa-6 haplotype, and isolates KR&#95;1&#95;A2 and US-11 as haplotypes IIa-5 and IIb-2, respectively. mtDNA sequences of KR&#95;1&#95;A1 and SIB-1 shared 100% sequence identity, and both were 99.9% similar to those of KR&#95;2&#95;A2 and US-11.

This study evaluated the effect of pitch coating on graphite anode materials used in lithium-ion batteries and investigated the mechanism whereby pitch coating improves the electrochemical properties. The FG (flake graphite) and pitch were mixed in weight ratios of 95:5-80:20. The mixture was pressed and prepared into a block form. Additionally, heat treatment was performed at 900 °C for 1 h and pulverized in the size range of 10-25 μm. The results showed that the particles of uniform pitch-coated graphite became more spherical. However, when the pitch is added excessively, pitch aggregation occurs rather than a thicker coating, indicating a nonuniform particle shape. Pitch has a randomly oriented structure and a small crystal size. Therefore, pitch serves as a lithium-ion diffusion pathway, resulting in an improved rate of performance. Notably, the uniform pitch-coated graphite exhibited an outstanding rate of performance owing to the relieving of particle orientation in the electrode rolling process. During the rolling process, the particles are oriented perpendicular to the lithium-ion diffusion pathway, making it difficult for the lithium ions to diffuse. Adding an excessive amount of pitch was found to deteriorate the rate of performance. Pitch aggregation increased the interfacial resistance by forming a heterogeneous surface.

With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% confidence interval [CI], 2 to 4.9; P < .001) and inferior progression-free survival (HR, 1.8; 95% CI, 1.4 to 2.4; P < .001) and overall survival (OS; HR, 2.2; 95% CI, 1.6 to 3; P < .001) compared with the MUD group. Relapse was the most common cause of death in all groups. Among causes of NRM, the haploidentical group had more infection-related deaths and fewer GVHD-related deaths than the other groups. The haploidentical group also had a higher risk of viral and fungal infections, grade ≥3 hemorrhagic cystitis, and cardiovascular toxicities and slower reconstitution of CD4, CD8, and regulatory T cells but faster reconstitution of natural killer cells. In an exploratory analysis, older patients with older donors (>50 years for both) appeared to have particularly high NRM and lower OS in the haploidentical group compared with the other groups. Our data suggest that even with the use of PTCy, the outcomes of haploidentical HCT are inferior to those of HLA-matched donor HCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic stem cell transplantation is a curative immunotherapy where patients receive myeloablative chemotherapy and/or radiotherapy, followed by donor stem cell transplantation. Graft versus host disease (GVHD) is a major complication caused by dysregulated donor immune system, thus a novel strategy to modulate donor immunity is needed to mitigate GVHD. Tissue damage by conditioning regimen is thought to initiate the inflammatory milieu that recruits various donor immune cells for cross-priming of donor T cells against alloantigen and eventually promote strong Th1 cytokine storm escalating further tissue damage. Bilirubin nanoparticles (BRNP) are water-soluble conjugated of bilirubin and polyethylene glycol (PEG) with potent anti-inflammatory properties through its ability to scavenge reactive oxygen species generated at the site of inflammation. Here, we evaluated whether BRNP treatment post-transplantation can reduce initial inflammation and subsequently prevent GVHD in a major histocompatibility (MHC) mismatched murine GVHD model. After myeloablative irradiation, BALB/c mice received bone marrow and splenocytes isolated from C57BL/6 mice, with or without BRNP (10 mg/kg) daily on days 0 through 4 post-transplantation, and clinical GVHD and survival was monitored for 90 days. First, BRNP treatment significantly improved clinical GVHD score compared to untreated mice (3.4 vs 0.3, p=0.0003), and this translated into better overall survival (HR 0.0638, p=0.0003). Further, BRNPs showed a preferential accumulation in GVHD target organs leading to a reduced systemic and local inflammation evidenced by lower pathologic GVHD severity as well as circulating inflammatory cytokines such as IFN-γ. Lastly, BRNP treatment post-transplantation facilitated the reconstitution of CD4 + iNK T cells and reduced expansion of proinflammatory CD8α + iNK T cells and neutrophils especially in GVHD organs. Lastly, BRNP treatment decreased ICOS + or CTLA-4 + T cells but not PD-1 + T cells suggesting a decreased level of T cell activation but maintaining T cell tolerance. In conclusion, we demonstrated that BRNP treatment post-transplantation ameliorates murine GVHD via diminishing the initial tissue damage and subsequent inflammatory responses from immune subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pareek, Flegle, Boagni, Kim, Yoo, Trujillo-Ocampo, Lee, Zhang, Jon and Im.)

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: This study aimed to report the projected cancer incidence and mortality for the year 2022 to estimate Korea's current cancer burden., Materials and Methods: Cancer incidence data from 1999 to 2019 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2020 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2022. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend., Results: In total, 274,488 new cancer cases and 81,277 cancer deaths are expected to occur in Korea in 2022. The most common cancer site is expected to be the thyroid, followed by the lung, colon and rectum, breast, and stomach. These five cancers are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and gallbladder cancers., Conclusion: The incidence rates for all types of cancer in Korea are estimated to gradually decrease. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2019., Materials and Methods: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2019, with survival follow-up until December 31, 2020. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea., Results: In 2019, newly diagnosed cancer cases and deaths from cancer were reported as 254,718 (ASR, 275.4 per 100,000) and 81,203 (ASR, 72.2 per 100,000), respectively. For the first time, lung cancer (n=29,960) became the most frequent cancer in Korea, excluding thyroid cancer. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. The incidence of thyroid cancer increased again from 2016 (annual percentage change, 6.2%). Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.7% from 2002 to 2013; 3.3% from 2013 to 2019). The 5-year relative survival between 2015 and 2019 was 70.7%, which contributed to prevalent cases reaching over 2 million in 2019., Conclusion: Cancer survival rates have improved over the past decades, but the number of newly diagnosed cancers is still increasing, with some cancers showing only marginal improvement in survival outcomes. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics.

To increase the energy density of today's batteries, studies on adding Si-based materials to graphite have been widely conducted. However, adding a Si-based material in the slurry mixing step suffers from low distribution due to the self-aggregation property of the Si-based material. Herein, a hierarchical structure is proposed to increase the integrity by using APS to provide a bonding effect between graphite and SiO x . Additionally, to endow a protection layer, carbon is coated on the surface using the CVD method. The designed structure demonstrates enhanced integrity based on electrochemical performance. The MSG (methane decomposed SiO x @G) electrode demonstrates a high ICE of 85.6% with 429.8 mA h g -1 initial discharge capacity. In addition, the MSG anode has superior capacity retention (89.3%) after 100 cycles, with enhanced volumetric expansion (12.7%) after 50 cycles. We believe that the excellent electrochemical performance of MSG is attributed to increased integrity by using APS (3-aminopropyltrimethoxysilane) with a CVD carbon coating., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The present study focused on the development of a binder pitch to allow for low-temperature forming processes when fabricating coke-based artificial graphite blocks while increasing the density of the resultant blocks. To this end, high-softening-point (200 °C) pitches were fabricated. The pitch and byproducts obtained from the pitch synthesis were then used as binders to fabricate blocks with high mechanical strength and low porosity. Pitches were fabricated using pyrolyzed fuel oil (PFO), a petroleum residue. A high-softening-point (200 °C) pitch synthesized at 420 °C for 3 h was used as a binder pitch, and conventional pitch (124 °C) was synthesized at 400 °C for 1 h and then used. Pitch byproducts were extracted according to the boiling point of naphthalene (two rings) and anthracene (three rings) with varying numbers of aromatic rings by distillation. The largest amount of pitch byproduct was obtained in the temperature range from 220 to 340 °C, and the content of naphthalene in the byproduct was the highest over the entire temperature range. The fabricated pitches at 420 °C and byproducts were mixed to form modified pitches. It was found that their softening point and coking value (CV) decreased with the increasing content of the pitch byproduct. Low-boiling point components of the byproducts were removed from the modified pitches at the kneading process temperature (200 °C), and the mass-loss rate observed in the carbonization process temperature range (200-900 °C) was comparable to that of the high-softening-point pitch. The kneading rate of the pitch and byproduct was determined and selected based on the mass-loss rate described above, and blocks were then fabricated using a hot press. Subsequently, the fabricated blocks were subjected to heat treatment for carbonization (900 °C) and graphitization (2700 °C). After the heat treatment, the true density and apparent density of the blocks were measured, and the porosity of the blocks was calculated based on these values. The porosity of the graphite block fabricated using the pitch with a softening point of 120 °C was 21.84%, while the porosity of the graphite block fabricated using the modified pitch was 14.9%. For mechanical strength analysis, their compressive strength was measured. The compressive strength of the graphite block made of the conventional pitch (CP) was measured to be 47.59 MPa, while the compressive strength of the graphite block made of pitch mixed with a byproduct distilled at 220-340 °C was 58.79 MPa. This result suggested that a decrease in the porosity resulted in increased mechanical strength. The application of the modified pitches developed in the present study temporarily decreased the softening point of the high-softening-point pitch due to the effect of the added byproducts, allowing for a low-temperature forming process. It was also possible to fabricate artificial graphite blocks with low porosity due to the high CV of the high-softening-point pitch. As a result, blocks with high mechanical strength could be obtained., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: This study reports data regarding the awareness and practice of cancer prevention among Koreans in 2021 and behavioral changes during the coronavirus disease 2019 (COVID-19) pandemic., Methods: We collected Cancer Prevention Awareness and Practice Survey data through face-to-face interview surveys using a structured questionnaire completed by 4,000 randomly selected men and women aged between 20 years and 74 years in 17 provinces. We examined the awareness and practice of 10 cancer prevention recommendations and evaluated their associations with potential risk factors through multiple logistic regression analysis adjusted for age, gender, residence, marital status, education, and income., Results: Eighty percent of participants knew that cancer is preventable, while 45% practiced cancer prevention. Cancer prevention practice tended to be more common among older participants (adjusted odds ratio [aOR], 1.39 per 10-year increment; 95% confidence interval [CI], 1.29 to 1.49) and less common among rural inhabitants (aOR, 0.66; 95% CI, 0.51 to 0.86) than among urban residents and among single people (aOR, 0.55; 95% CI, 0.45 to 0.66) than among married people. Practices were the highest for avoiding burned or charred foods (87.6%) and lowest for vaccination against human papillomavirus (14.5%). Refusal to follow recommendations was most common for avoiding alcohol consumption (7.9%). The most difficult recommendations to follow were (1) regular exercise (57.7%); (2) maintaining a healthy body weight (46.1%); and (3) avoiding alcohol (40.1%). The most significant COVID-19-related changes were less exercise (32.5%) and increased body weight (25.6%)., Conclusions: The awareness of cancer prevention was high, but the practice was low. Recommendations targeting awareness and practice need to be further promoted.

Cigarette smoking is a major cause of lung cancer. Although tobacco smoking-induced genotoxicity has been well established, there is apparent lack of abundance functional epigenetic effects reported On cigarette smoke-induced lung carcinogenesis. The aim of this study was to determine effects of intratracheal administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) utilizing target gene expression DNA methylation patterns in lung tissues of mice following twice weekly for 8 weeks treatment. An unbiased approach where genomic regions was undertaken to assess early methylation changes within mouse pulmonary tissues. A methylated-CpG island recovery assay (MIRA) was performed to map the DNA methylome in lung tissues, with the position of methylated DNA determined using a Genome Analyzer (MIRA-SEQ). Alterations in epigenetic-regulated target genes were confirmed with quantitative reverse transcription-PCR, which revealed 35 differentially hypermethylated genes including Cdkn1C, Hsf4, Hnf1a, Cdx1 , and Hoxa5 and 30 differentially hypomethylated genes including Ddx4, Piwi1, Mdm2 , and Pce1 in NNK-exposed lung tissue compared with controls. The main pathway of these genes for mediating biological information was analyzed using the Kyoto Encyclopedia of Genes and Genomes database. Among them, Rssf1 and Mdm2 were closely associated with NNK-induced lung carcinogenesis. Taken together, our data provide valuable resources for detecting cigarette smoke-induced lung carcinogenesis.

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: The crab spider genus Bassaniana Strand, 1928 consists of six species mainly distributed in North America and Far East Asia. Two species of them, Bassanianadecorata (Karsch, 1879) and Bassanianaora Seo, 1992, are known in Korea so far., New Information: A new crab spider, Bassanianabirudis sp. nov. is described, based on a male collected from Gumi-si, Gyeongsangbuk-do, South Korea. Distribution records are provided, as well as photos of habitus and illustrations of the male copulatory organ. The type specimens of this study are deposited in the collection of the Nakdonggang National Institute of Biological Resources (NNIBR) and Konkuk University (KKU), South Korea., (Jae Seong Im, Seung Tae Kim, Sue Yeon Lee.)

Compared to reduced-intensity conditioning regimen, myeloablative conditioning (MAC) for hematopoietic stem cell transplantation (HCT) reduces relapse but is avoided in older patients because of higher non-relapse mortality (NRM). To meet the need for a myeloablative regimen for older patients, we developed a novel fludarabine and busulfan MAC regimen. We fractionated the dose of busulfan and gave it for 6 days over a 2-week period and demonstrated the feasibility and safety of this approach. However, the disease-specific efficacy of this regimen is not known. The purpose of this study was to estimate the efficacy of fractionated busulfan regimen by estimating diseases specific survival outcomes. The conditioning regimen consisted of busulfan and fludarabine. On days -13 and -12 before HCT, patients received 80 mg/m 2 busulfan intravenously (IV) daily in an outpatient clinic. Additional chemotherapy was administered during inpatient treatment from day -6 through day -3, including fludarabine 40 mg/m 2 and busulfan IV once daily. The dosing of busulfan was determined from pharmacokinetic analyses to achieve for the course a target area under the curve of 20,000 ± 12% μmol/min, which is close to the average exposure of myeloablative dose of busulfan. One hundred fifty patients with high-risk hematological malignancies up to 75 years were enrolled in this prospective phase II study. The objective was to evaluate NRM, relapse, survival, the rates of graft-versus-host disease (GVHD), and long-term complications. The median age of the patient population was 61 years (interquartile range, 55-67). The most common diagnoses were acute myeloid leukemia (AML; N = 59 [39.3%]), myelodysplastic syndrome (MDS; n = 29 [19.3%]), and myelofibrosis (MF; N = 22 [14.7%]). Most had an unrelated donor (n = 93 [62%]) and received peripheral blood graft (n = 110 [73.3%]). Over half had an HCT-specific comorbidity index of ≥3 (n = 79 [52.7%]). The median follow-up among survivors was 43.4 months (interquartile range, 38.9-50.4). In patients with AML in complete remission, MDS, and myelofibrosis, 3-year overall survival was 66.7% (95% confidence interval [CI], 50.2-88.5%), 43.6% (95% CI, 28.6-66.4%), and 59.1% (95% CI, 41.7-83.7%) respectively. The cumulative incidence of NRM was 22% (15.3%-28.7%), extensive chronic GVHD was 27% (95% CI, 20-34%), bronchiolitis obliterans was 4.7% (95% CI, 1.3-8.1%), and secondary malignancy was 8.7% (95% CI, 4.1-13.2%) at 3 years. Lengthening the duration of busulfan (fractionation) permits safe delivery of myeloablative conditioning in older patients, leading to prolonged survival. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT)., Patients and Methods: We evaluated 194 patients with follicular lymphoma who received an alloSCT ( n = 98) or autoSCT ( n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan)., Results: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT ( P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively ( P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27)., Conclusions: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma., (©2021 American Association for Cancer Research.)

In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8 + cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy - resistant patients. Trajectory analysis reveals a continuum of CD8 + T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8 + T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia., (© 2021. The Author(s).)

The proper cellular response to DNA double-strand breaks (DSBs) is critical for maintaining the integrity of the genome. RecQL4, a DNA helicase of which mutations are associated with Rothmund-Thomson syndrome (RTS), is required for the DNA DSB response. However, the mechanism by which RecQL4 performs these essential roles in the DSB response remains unknown. Here, we show that RecQL4 and its helicase activity are required for maintaining the stability of the Mre11-Rad50-Nbs1 (MRN) complex on DSB sites during a DSB response. We found using immunocytochemistry and live-cell imaging that the MRN complex is prematurely disassembled from DSB sites in a manner dependent upon Skp2-mediated ubiquitination of Nbs1 in RecQL4-defective cells. This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS, and RecQL4-depleted cells. These results suggest that the essential role of RecQL4 in the DSB response is to maintain the stability of the MRN complex on DSB sites and that defects in the DSB response in cells of patients with RTS can be recovered by controlling the stability of the MRN complex., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option., Methods: We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed., Results: Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement., Conclusion: Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT., Competing Interests: David MarinHonoraria: TakedaResearch Funding: TakedaPatents, Royalties, Other Intellectual Property: Licensing of cell therapy product to Takeda Hind RafeiPatents, Royalties, Other Intellectual Property: Pending patent: United States Provisional Appl. No. 62/963,121, Ref.: UTSC.P1172US.P1-1001106067 Rafet BasarResearch Funding: TakedaPatents, Royalties, Other Intellectual Property: Institutional financial conflict of interest with Takeda Pharmaceutical for the licensing of the technology related to CAR NK cells research. MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to MDACC's conduct of any other ongoing or future research related to this relationship. MD declares no competing financial interest Pinaki BanerjeePatents, Royalties, Other Intellectual Property: Pinaki Banerjee and The University of Texas MD Anderson Cancer Center (MDACC) have an institutional financial conflict of interest with Takeda Pharmaceutical for the licensing of the technology related to CAR-NK cell research. MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to MDACC's conduct of any other ongoing or future research related to this relationship Fleur M. AungHonoraria: ALX Oncology Roy ChemalyHonoraria: Merck Sharp & Dohme, Oxford Immunotec, GenentechConsulting or Advisory Role: Partner Therapeutics, Merck, Ansun Biopharma, Shiniogi, Pulmotect, Paratek, ADMA Biologics, Cidara Therapeutics, Xenex, Kyorin, Janssen, Wockhardt Pharmaceuticals, ReViral, AdagioResearch Funding: Merck, Chimerix, Viracor Eurofins, Ansun Biopharma, Karius, Gilead Sciences, XenexTravel, Accommodations, Expenses: Merck, Oxford Immunotec Victor MulanovichConsulting or Advisory Role: Legend Biotech, Swedish Orphan Biovitrum Amin M. AlousiHonoraria: Generon, Genentech, Kadmon, Prolacta Bioscience Qaiser BashirConsulting or Advisory Role: Takeda, Spectrum Pharmaceuticals, Kite Pharma, Amgen, Purdue PharmaResearch Funding: Takeda, Celgene, Acrotech Biopharma, Stemline Therapeutics May DaherResearch Funding: TakedaPatents, Royalties, Other Intellectual Property: Institutional financial conflict of interest with Takeda Pharmaceutical for the licensing of the technology related to CAR-NK cell research. MD Anderson has implemented an Institutional Conflict of Interest Management and Monitoring Plan to manage and monitor the conflict of interest with respect to MDACC's conduct of any other ongoing or future research related to this relationship Chitra HosingHonoraria: SanofiConsulting or Advisory Role: Sanofi, Alexion Pharmaceuticals, NKARTAResearch Funding: CelgeneTravel, Accommodations, Expenses: Celgene Roy B. JonesEmployment: Stafa, Bayer, NovartisTravel, Accommodations, Expenses: Velos Partow KebriaeiHonoraria: Kite Pharma, Novartis, PfizerConsulting or Advisory Role: Jazz PharmaceuticalsResearch Funding: ZIOPHARM Oncology, AmgenTravel, Accommodations, Expenses: Kite Pharma, Novartis, Pfizer Issa KhouriResearch Funding: Pfizer, Bristol Myers Squibb Rohtesh MehtaResearch Funding: Kadmon, CSL Behring, Incyte Yago NietoResearch Funding: Affimed Therapeutics, AstraZeneca, Secura Bio Betul OranResearch Funding: Arog Phamarceuticals, Astex Pharmaceuticals Uday PopatResearch Funding: Abbvie, Novartis, Bayer Muzaffar QazilbashSpeakers' Bureau: Merck, SanofiResearch Funding: Amgen, BiolineRx, Angiocrine Bioscience, Janssen Samer SrourConsulting or Advisory Role: Celgene Richard E. ChamplinConsulting or Advisory Role: Johnson & Johnson/Janssen, Omeros, Actinium Pharmaceuticals, Kadmon, ArogPatents, Royalties, Other Intellectual Property: Royalty from Takeda Corporation Elizabeth J. ShpallHonoraria: Magenta Therapeutics, Novartis, Partner Therapeutics, BayerConsulting or Advisory Role: Novartis, Magenta Therapeutics, Adaptimmune, Partner Therapeutics, Mesoblast, AXIO Research, Bayer HealthCare PharmaceuticalsPatents, Royalties, Other Intellectual Property: TakedaTravel, Accommodations, Expenses: Magenta Therapeutics, Novartis Katayoun RezvaniConsulting or Advisory Role: Adicet Bio, ViroGen, GemoAb, TakedaResearch Funding: Affimed Therapeutics, Pharmacyclics, TakedaPatents, Royalties, Other Intellectual Property: Patent on generation of BKV CTLs for the treatment of HC or PML, Patent on generation of CAR NK cells, License agreement and research agreement with Takeda to develop CB-CAR NK cells for the treatment of B-cell malignancies and other cancers, which creates an institutional conflict of interest under MD Anderson policyNo other potential conflicts of interest were reported.

Aberrant T-cell function is implicated in the pathogenesis of myelodysplastic syndrome (MDS). Monitoring the T-cell receptor (TCR) repertoire can provide insights into T-cell adaptive immunity. Previous studies found skewed TCR repertoires in MDS compared to healthy patients; however these studies that leverage mRNA-based spectratyping have limitations. Furthermore, evaluating the TCR repertoire in context of hypomethylating agents (HMAs) treatment can provide insights into the dynamics of T-cell mediated responses in MDS. We conducted immunosequencing of the CDR3 regions of TCRβ chains in bone marrows of 11 MDS patients prior to treatment (n=11 bone marrows prior to treatment), and in at least 2 timepoints for each patient following treatment (n=26 bone marrow aspirates post-treatment) with (HMA), alongside analyzing bone marrows from 4 healthy donors as controls. TCR repertoires in MDS patients were more clonal and less diverse than healthy donors. However, unlike previous reports, we did not observe significant skewness in CDR3 length or spectratyping. The global metrics of TCR profiling including richness, clonality, overlaps were not significantly changed in responders or non-responders following treatment with HMAs. However, we found an emergence of novel clonotypes in MDS patients who responded to treatment, while non-responders had a higher frequency of contracted clonotypes following treatment. By applying GLIPH2 for antigen prediction, we found rare TCR specificity clusters shared by TCR clonotypes from different patients at pre- or following treatment. Our data show clear differences in TCR repertoires of MDS compared with healthy patients and that novel TCR clonotype emergence in response to HMA therapy was correlated with response. This suggests that response to HMA therapy may be partially driven by T-cell mediated immunity and that the immune-based therapies, which target the adaptive immune system, may play a significant role in select patients with MDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abbas, Reville, Jiang, Yang, Reuben, Im, Little, Sinson, Chen, Futreal and Garcia-Manero.)

The present study aimed to identify the required characteristics of binder pitches in the filler-binder mixing process to effectively manufacture graphite blocks. To this end, a binder pitch was separated into pitch fractions of varying molecular-weight segments. The role and effectiveness of each pitch fraction were then analyzed with respect to their molecular-weight distribution. As a result, the optimal molecular-weight distribution was determined. More specifically, a coal-tar pitch was separated into solvent-soluble and solvent-insoluble fractions. The molecular-weight distribution was determined according to this classification, and the characteristics of each pitch fraction were examined. The pitch separation process was conducted using three solvents: hexane, toluene, and quinoline. The resulting pitch was separated into the following pitch fractions: hexane-soluble (HS), hexane-insoluble-toluene-soluble (HI-TS), toluene-insoluble-quinoline-soluble (TI-QS), and quinoline-insoluble (QI). Fourier transform infrared (FT-IR) spectrum, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF), and softening point of each pitch fraction were measured. Also, pitch samples were refabricated while varying the mixing ratio of these pitch fractions, and carbon blocks were then prepared using them. The compressive strength and porosity of these blocks were measured and compared. The P154&#95;B pitch with a high content of TI-QS was used to fabricate a green block. Due to the high viscosity of the binder used, the fluidity was not sufficiently high, and thus, the green block made of this pitch had relatively low strength. The other blocks had similar levels of strength. After the carbonization process, the carbon block with a high content of HS (P352&#95;B-C) and the carbon block with the HS content removed (P073&#95;B-C) showed lower compressive strength than their respective green-block counterparts (P352&#95;B and P073&#95;B). However, their strength was higher compared to those of the other carbon blocks. In the case of carbon block P073&#95;B-C, the HS content was completely removed, and thus, the content of TI-QS (β-resin) was relatively high. Accordingly, this carbon block ended up with large amounts of components that had high coking values (CVs), and this contributed to limiting the formation of pores. Therefore, the compressive strength of this carbon block was high. In the case of the carbon block with a high content of HS (P352&#95;B-C), a suitable level of viscosity was achieved because the HS components ensured high fluidity. As a result, blocks with higher density and compressive strength could be fabricated. The major findings of the present study confirm that producing carbon blocks with high mechanical properties requires binder pitches with a balanced combination of suitable viscosity to ensure sufficiently high fluidity and a proper level of CV to effectively suppress the formation of pores in the mixing and molding process., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)