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Abstract The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.

IntroductionSweetpotato faces breeding challenges due to physiological and genomic issues. Gamma radiation is a novel approach for inducing genetic variation in crops. We analyzed the transcriptomic changes in gamma ray-induced sweetpotato mutants with altered stem development compared with those in the wild-type 'Tongchaeru’ cultivar.MethodsRNA sequencing analyses were performed to identify changes in the expression of genes related to stem development.ResultsTranscriptomic analysis identified 8,931 upregulated and 6,901 downregulated genes, including the upregulation of the auxin-responsive SMALL AUXIN UP RNA (SAUR) and three PHYTOCHROME INTERACTING FACTOR 4 (PIF4) genes. PIF4 is crucial for regulating the expression of early auxin-responsive SAUR genes and stem growth in Arabidopsis thaliana. In the mutant, several genes related to stem elongation, including PIF4 and those involved in various signaling pathways such as auxin and gibberellin, were upregulated.DiscussionOur results suggest that gamma ray-induced mutations influence auxin-dependent stem development by modulating a complex regulatory network involving the expression of PIF4 and SAUR genes, and other signaling pathways such as gibberellin and ethylene signaling genes. This study enhances our understanding of the regulatory mechanisms underlying stem growth in sweetpotato, providing valuable insights for genomics-assisted breeding efforts.

Abstract To present rectal endoscopic findings and toxicity after definitive moderately hypofractionated, intensity-modulated radiotherapy (IMRT) for prostate cancer. We retrospectively reviewed patients who underwent IMRT for prostate cancer and underwent post-radiotherapy endoscopies between 2008 and 2018. Endoscopic findings were reviewed and graded using Vienna Rectoscopy Score (VRS). We have analyzed the association between endoscopic findings and rectal bleeding, and investigated risk factors for rectal bleeding. Total 162 patients met the inclusion criteria of this study. There was a trend of VRS worsening during the initial 3 years after radiotherapy followed by recovery. Rectal bleeding was highest at 1 year after radiotherapy and improved thereafter. The 5-year cumulative incidence of grade ≥ 2 rectal bleeding was 14.8%. In the multivariable Cox regression analysis, cardiovascular disease (hazard ratio [HR] 2.732, P = 0.037), rectal wall V65 (HR 1.158, P = 0.027), and VRS ≥ 3 in first post-radiotherapy endoscopy (HR 2.573, P = 0.031) were significant risk factors for rectal bleeding. After IMRT for prostate cancer, VRS and rectal bleeding worsened over 1–3 years after radiotherapy and recovered. Cardiovascular disease, rectal wall V65, and VRS ≥ 3 in first post-radiotherapy endoscopy were significant risk factors for rectal bleeding.

Background/Aims We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). Methods Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. Results In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the group with the second cycle but remained stable in the group with one cycle. Conclusions Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

Abstract Aim Patients with locoregionally uncontrolled breast tumors are frequently referred for breast palliative radiotherapy (PRT) to mitigate symptoms. We analyzed the outcomes following breast PRT to optimize PRT according to risk groups. Methods We reviewed 133 patients who underwent breast PRT. A median total dose of 45 Gy was prescribed with an equivalent dose in 2 Gy fractions (EQD2, α/β = 3.5) of 53 Gy. The Cox proportional hazards model was used to analyze the prognostic factors of local control (LC). Results Most (90.2%) had polymetastatic disease (> 5 lesions), and 48.9% had bone metastasis. With a median follow-up of 17.2 months, the 2-year LC and overall survival (OS) rates were 49.4%, and 48.3%, respectively. Multivariable analyses demonstrated progressive or mixed responses outside the breast and > 2 lines of previous therapy as adverse features for clinical outcomes. Group 1 (0 risk factors) showed favorable 2-year LC and OS of 63.9%, and 72.8%, respectively, whereas group 3 (2 risk factors) showed the worst outcomes of 0%, and 6.8%, respectively. Breast PRT with EQD2 ≥ 63 Gy showed a significant benefit in LC for group 1 and marginal benefit (p = 0.055) for group 2, but no improvement for group 3 (p = 0.300). Conclusion Breast PRT showed favorable LC outcomes in patients with stable disease outside the breast and treated with ≤ 2 lines of systemic treatment. Our findings warrant future clinical trials investigating the role of higher than palliative dose and early intervention of PRT in stage IV patients.

Background: This study aimed to evaluate the treatment outcomes and define the prostate-specific antigen (PSA) kinetics as potential prognostic factors in patients with intermediate- or high-risk localized prostate cancer (PCa) who underwent moderately hypofractionated radiation therapy. Methods: The study retrospectively reviewed the medical records of 149 patients with intermediate- or high-risk localized PCa who underwent definitive radiation therapy (70 Gy in 28 fractions) without androgen deprivation therapy. Clinical outcomes were analyzed based on risk stratification (favorable-intermediate, unfavorable-intermediate, and high-risk). The biochemical failure rate (BFR) and clinical failure rate (CFR) were stratified based on the PSA nadir and the time to the PSA nadir to identify the prognostic effect of PSA kinetics. Acute and late genitourinary and gastrointestinal adverse events were analyzed. Results: Significant differences were observed in the BFR and CFR according to risk stratification. No recurrence was observed in the favorable intermediate-risk group. The 7-year BFR and CFR for the unfavorable intermediate-risk and high-risk groups were 19.2% and 9.8%, and 31.1% and 25.3%, respectively. Patients with a PSA nadir >0.33 ng/mL or a time to the PSA nadir

PurposeOrgan-at-risk segmentation is essential in adaptive radiotherapy (ART). Learning-based automatic segmentation can reduce committed labor and accelerate the ART process. In this study, an auto-segmentation model was developed by employing individual patient datasets and a deep-learning-based augmentation method for tailoring radiation therapy according to the changes in the target and organ of interest in patients with prostate cancer.MethodsTwo computed tomography (CT) datasets with well-defined labels, including contoured prostate, bladder, and rectum, were obtained from 18 patients. The labels of the CT images captured during radiation therapy (CT2nd) were predicted using CT images scanned before radiation therapy (CT1st). From the deformable vector fields (DVFs) created by using the VoxelMorph method, 10 DVFs were extracted when each of the modified CT and CT2nd images were deformed and registered to the fixed CT1st image. Augmented images were acquired by utilizing 110 extracted DVFs and spatially transforming the CT1st images and labels. An nnU-net autosegmentation network was trained by using the augmented images, and the CT2nd label was predicted. A patient-specific model was created for 18 patients, and the performances of the individual models were evaluated. The results were evaluated by employing the Dice similarity coefficient (DSC), average Hausdorff distance, and mean surface distance. The accuracy of the proposed model was compared with those of models trained with large datasets.ResultsPatient-specific models were developed successfully. For the proposed method, the DSC values of the actual and predicted labels for the bladder, prostate, and rectum were 0.94 ± 0.03, 0.84 ± 0.07, and 0.83 ± 0.04, respectively.ConclusionWe demonstrated the feasibility of automatic segmentation by employing individual patient datasets and image augmentation techniques. The proposed method has potential for clinical application in automatic prostate segmentation for ART.

Aim: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. Methods: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. Results: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. Conclusion: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Abstract Background Cancer‐associated fibroblasts (CAFs) play an important role in the induction of chemo‐resistance. This study aimed to clarify the mechanism underlying CAF‐mediated resistance to two tyrosine kinase inhibitors (TKIs), sorafenib and lenvatinib, and to identify a novel therapeutic target for overcoming TKI resistance in hepatocellular carcinoma (HCC). Methods We performed a systematic integrative analysis of publicly available gene expression datasets and whole‐transcriptome sequencing data from 9 pairs of CAFs and para‐cancer fibroblasts isolated from human HCC and para‐tumor tissues, respectively, to identify key molecules that might induce resistance to TKIs. We then performed in vitro and in vivo experiments to validate selected targets and related mechanisms. The associations of plasma secreted phosphoprotein 1 (SPP1) expression levels before sorafenib/lenvatinib treatment with progression‐free survival (PFS) and overall survival (OS) of 54 patients with advanced HCC were evaluated using Kaplan‐Meier and Cox regression analysis. Results Bioinformatic analysis identified CAF‐derived SPP1 as a candidate molecule driving TKI resistance. SPP1 inhibitors reversed CAF‐induced TKI resistance in vitro and in vivo. CAF‐derived SPP1 activated rapidly accelerated fibrosarcoma (RAF)/mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) through the integrin‐protein kinase C‐alpha (PKCα) signaling pathway and promoted epithelial‐to‐mesenchymal transition (EMT). A high plasma SPP1 level before TKI treatment was identified as an independent predictor of poor PFS (P = 0.026) and OS (P = 0.047) in patients with advanced HCC after TKI treatment. Conclusions CAF‐derived SPP1 enhances TKI resistance in HCC via bypass activation of oncogenic signals and EMT promotion. Its inhibition represents a promising therapeutic strategy against TKI resistance in HCC. Moreover, plasma SPP1 level before TKI treatment represents a potential biomarker for treatment response prediction.

Manganese porphyrins reportedly exhibit synergic effects when combined with irradiation. However, an in-depth understanding of intratumoral heterogeneity and immune pathways, as affected by Mn porphyrins, remains limited. Here, we explored the mechanisms underlying immunomodulation of a clinical candidate, MnTnBuOE-2-PyP5+ (BMX-001, MnBuOE), using single-cell analysis in a murine carcinoma model. Mice bearing 4T1 tumors were divided into four groups: control, MnBuOE, radiotherapy (RT), and combined MnBuOE and radiotherapy (MnBuOE/RT). In epithelial cells, the epithelial–mesenchymal transition, TNF-α signaling via NF-кB, angiogenesis, and hypoxia-related genes were significantly downregulated in the MnBuOE/RT group compared with the RT group. All subtypes of cancer-associated fibroblasts (CAFs) were clearly reduced in MnBuOE and MnBuOE/RT. Inhibitory receptor–ligand interactions, in which epithelial cells and CAFs interacted with CD8+ T cells, were significantly lower in the MnBuOE/RT group than in the RT group. Trajectory analysis showed that dendritic cells maturation-associated markers were increased in MnBuOE/RT. M1 macrophages were significantly increased in the MnBuOE/RT group compared with the RT group, whereas myeloid-derived suppressor cells were decreased. CellChat analysis showed that the number of cell–cell communications was the lowest in the MnBuOE/RT group. Our study is the first to provide evidence for the combined radiotherapy with a novel Mn porphyrin clinical candidate, BMX-001, from the perspective of each cell type within the tumor microenvironment.

The initial electrical characteristics and bias stabilities of thin-film transistors (TFTs) are vital factors regarding the practical use of electronic devices. In this study, the dependence of positive bias stress (PBS) instability on an initial threshold voltage (VTH) and its origin were analyzed by understanding the roles of slow and fast traps in solution-processed oxide TFTs. To control the initial VTH of oxide TFTs, the indium oxide (InOx) semiconductor was doped with aluminum (Al), which functioned as a carrier suppressor. The concentration of oxygen vacancies decreased as the Al doping concentration increased, causing a positive VTH shift in the InOx TFTs. The VTH shift (∆VTH) caused by PBS increased exponentially when VTH was increased, and a distinct tendency was observed as the gate bias stress increased due to a high vertical electric field in the oxide dielectric. In addition, the recovery behavior was analyzed to reveal the influence of fast and slow traps on ∆VTH by PBS. Results revealed that the effect of the slow trap increased as the VTH moved in the positive direction; this occured because the main electron trap location moved away from the interface as the Fermi level approached the conduction band minimum. Understanding the correlation between VTH and PBS instability can contribute to optimizing the fabrication of oxide TFT-based circuits for electronic applications.

Fusarium root rot, caused by Fusarium solani, is a major post-harvest disease in sweet potatoes (Ipomoea batatas (L.) Lam.). An effective strategy for controlling this disease is the development of resistant varieties. In this study, a genome-wide association study (GWAS) was conducted on 96 sweet potato genotypes to identify novel candidate loci and dissect the genetic basis of Fusarium root rot resistance. Genotyping was performed using genotyping-by-sequencing (GBS), and 44,255 SNPs were identified after filtering. The genotypes (n = 96) were evaluated through resistance tests in 2021 and 2022, separately and combined. The GWAS identified two significant SNP markers (LG3_22903756 and LG4_2449919) on chromosomes 3 and 4 associated with Fusarium root rot resistance, respectively. Lesion length showed significant differences between homozygous A and G alleles of LG3_22903756, which can potentially be used to develop molecular markers for selecting accessions resistant to Fusarium root rot. Expression analysis of 11 putative genes flanking the significant SNPs revealed the alteration in the expression of nine genes, indicating their possible involvement in Fusarium root rot resistance. The results of this study will aid in the marker-assisted selection and functional analysis of candidate genes for Fusarium root rot resistance in sweet potatoes.

Aim: Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease. Methods: We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR. Results: With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001). Conclusion: We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.

Abstract Background Postoperative radiotherapy (PORT) could be useful for pN1 breast cancer patients who have undergone breast-conserving surgery (BCS) or mastectomy. However, the value of regional nodal irradiation (RNI) for BCS patients, and the indications for post-mastectomy radiotherapy (PMRT) for pN1 breast cancer mastectomy patients, have recently been challenged due to the absence of relevant trials in the era of modern systemic therapy. “PORT de-escalation” should be assessed in patients with pN1 breast cancer. Methods The PORT-N1 trial is a multicenter, randomized, phase 3 clinical trial for patients with pN1 breast cancer that compares the outcomes of control [whole-breast irradiation (WBI) and RNI/PMRT] and experimental (WBI alone/no PMRT) groups. PORT-N1 aims to demonstrate non-inferiority of the experimental group by comparing 7-year disease-free survival rates with the control group. Female breast cancer patients with pT1-3 N1 status after BCS or mastectomy are eligible. Participants will be randomly assigned to the two groups in a 1:1 ratio. Randomization will be stratified by surgery type (BCS vs. mastectomy) and histologic subtype (triple-negative vs. non-triple-negative). In patients who receive mastectomy, dissection of ≥5 nodes is required when there is one positive node, and axillary lymph node dissection when there are two or three positive nodes. Patients receiving neoadjuvant chemotherapy are not eligible. RNI includes a “high-tangent” or wider irradiation field. This study will aim to recruit 1106 patients. Discussion The PORT-N1 trial aims to verify that PORT de-escalation after BCS or mastectomy is safe for pN1 breast cancer patients in terms of oncologic outcomes and capable of reducing toxicity rates. This trial will provide information crucial for designing PORT de-escalation strategies for patients with pN1 breast cancer. Trial registration This trial was registered at ClinicalTrials.gov (NCT05440149) on June 30, 2022.

Abstract Background The Korean Radiation Oncology Group (KROG) 19 − 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. Methods Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. Results We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss’s kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. Conclusion We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 − 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 − 09 study results.

Background/Aims The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusions Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.

Purpose: Sacroiliitis refers to the inflammatory condition of the sacroiliac joints, frequently causing lower back pain. It is often associated with systemic conditions. However, its signs on radiographic images can be subtle, which may result in it being overlooked or underdiagnosed. This study aims to utilize artificial intelligence (AI) to create a diagnostic tool for more accurate sacroiliitis detection in radiological images, with the goal of optimizing treatment plans and improving patient outcomes. Materials and Method: The study included 492 patients who visited our hospital. Right sacroiliac joint films were independently evaluated by two musculoskeletal radiologists using the Modified New York criteria (Normal, Grades 1–4). A consensus reading resolved disagreements. The images were preprocessed with Z-score standardization and histogram equalization. The DenseNet121 algorithm, a convolutional neural network with 201 layers, was used for learning and classification. All steps were performed on the DEEP:PHI platform. Result: The AI model exhibited high accuracy across different grades: 94.53% (Grade 1), 95.83% (Grade 2), 98.44% (Grade 3), 96.88% (Grade 4), and 96.09% (Normal cases). Sensitivity peaked at Grade 3 and Normal cases (100%), while Grade 4 achieved perfect specificity (100%). PPVs ranged from 82.61% (Grade 1) to 100% (Grade 4), and NPVs peaked at 100% for Grade 3 and Normal cases. The F1 scores ranged from 64.41% (Grade 1) to 95.38% (Grade 3). Conclusions: The AI diagnostic model showcased a robust performance in detecting and grading sacroiliitis, reflecting its potential to enhance diagnostic accuracy in clinical settings. By facilitating earlier and more accurate diagnoses, this model could substantially impact treatment strategies and patient outcomes.

Purpose: To assess the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive bladder cancer (MIBC). Materials and Methods: Patients with clinical T2-T4aN0M0 MIBC eligible for radical cystectomy and cisplatin-based chemotherapy were treated with gemcitabine 1,000 mg/m2 on days 1, 8 and 15, and cisplatin 70 mg/m2 on day 1 every 28 days for 3 cycles. After clinical re-staging with computed tomography scans and cystoscopy, patients with clinical complete response (CR) were eligible to proceed without cystectomy and receive bladder preservation chemoradiotherapy involving weekly cisplatin 10 mg/m2 and up to 70.2 Gy of radiation. The primary endpoint of the present prospective phase II study was metastasis-free survival (MFS). Results: Between Oct 2017 and Nov 2019, a total of 138 MIBC patients were enrolled and treated with neoadjuvant gemcitabine/cisplatin. Neoadjuvant chemotherapy was well-tolerated, with fatigue, nausea, and pruritus being the most commonly observed adverse events. After completion of planned neoadjuvant chemotherapy, 54 patients with a clinical CR and 10 patients who did not have CR but refused surgery received bladder preservation chemoradiotherapy. With a median follow-up duration of 34 months (95% confidence interval [CI], 32%–36%), the 3-year MFS rate in 64 chemoradiotherapy patients was calculated to be 70% (95% CI, 58%–82%). Conclusions: Neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy based on the clinical CR was feasible and efficacious in the treatment of MIBC.

High-performance oxide transistors have recently attracted significant attention for use in various electronic applications, such as displays, sensors, and back-end-of-line transistors. In this study, we demonstrate atomically thin indium–oxide (InOx) semiconductors using a solution process for high-performance thin-film transistors (TFTs). To achieve superior field-effect mobility and switching characteristics in TFTs, the bandgap and thickness of the InOx were tuned by controlling the InOx solution molarity. As a result, a high field-effect mobility and on/off-current ratio of 13.95 cm2 V−1 s−1 and 1.42 × 1010, respectively, were achieved using 3.12-nanometer-thick InOx. Our results showed that the charge transport of optimized InOx with a thickness of 3.12 nm is dominated by percolation conduction due to its low surface roughness and appropriate carrier concentration. Furthermore, the atomically thin InOx TFTs showed superior positive and negative gate bias stress stabilities, which are important in electronic applications. The proposed oxide TFTs could provide an effective means of the fabrication of scalable, high-throughput, and high-performance transistors for next-generation electronic applications.

Introduction Low-dose radiation therapy (LDRT) for osteoarthritis (OA) has been performed for several decades. However, supporting evidence from randomised studies using modern methodologies is lacking, and a recently published randomised study failed to show the significant benefit of LDRT. The presented trial aims to evaluate the efficacy and safety of LDRT for patients with knee OA.Methods and analysis This prospective, multicentre, randomised trial will be conducted in the Republic of Korea. A total of 114 participants will be randomly assigned (1:1:1) to receive sham irradiation, 0.3 Gy/6 fractions of LDRT or 3 Gy/6 fractions of LDRT. Key inclusion criteria are primary knee OA with Kellgren-Lawrence grade 2–3 and visual analogue scale 50–90 when walking at the baseline. The primary endpoint is the rate of responders at 4 months after LDRT according to the OARSI-OMERACT criteria. Concomitant use of analgesics is prohibited until the primary efficacy evaluation is scheduled.Ethics and dissemination Currently, approval from the Ministry of Food and Drug Safety of the Republic of Korea and the institutional review board of each participating hospital has been obtained. Patient enrolment began in October 2022 and is ongoing at three participating sites. The results will be disseminated to academic audiences and the public via publication in an international peer-reviewed journal and presentation at conferences. This trial will provide valuable information on the safety and efficacy of LDRT for patients with knee OA.Trial registration number NCT05562271.

The interest in low processing temperature for printable transistors is rapidly increasing with the introduction of a new form factor in electronics and the growing importance of high throughput. This paper reports the fabrication of low-temperature-processable enhancement-mode amorphous oxide thin-film transistors (TFTs) using the solution process. A facile low-pressure annealing (LPA) method is proposed for the activation of indium oxide (InOx) semiconductors at a significantly low processing temperature of 200 °C. Thermal annealing at a pressure of about ~10 Torr induces effective condensation in InOx even at a low temperature. As a result, the fabricated LPA InOx TFTs not only functioned in enhancement mode but also exhibited outstanding switching characteristics with a high on/off current ratio of 4.91 × 109. Furthermore, the LPA InOx TFTs exhibit stable operation under bias stress compared to the control device due to the low concentration of hydroxyl defects.

Sweetpotatoes require a storage period for year-round use and improved sweetness by starch degradation. However, long-term storage can cause root rot, and a large amount of sweetpotatoes can be discarded. Root rot is typically caused by pathogenic soil-borne Fusarium spp., and the development of root rot induced by the characteristics of cultivating soil in stored sweetpotato has not yet been identified. In this study, the effect of Fusarium spp. and microbial community in the cultivated soil on the root rot of sweetpotatoes was to be elucidated. Wounded sweetpotato were treated in soil cultures inoculated with F. solani or F. oxysporum for 2 days, and showed symptoms of root rot after 2 months of storage. The three study fields (Naju, Yeongam A, and B) were subjected to the same curing and storage treatments after harvest, and the incidence of root rot was 1.7- to 1.8-fold different after 3 months of storage. Across the three fields, concentrations of Fusarium spp. and of microbial communities differed according to the cultivation soil and period. In particular, Naju, which had the lowest incidence of root rot, had the lowest concentration of Fusarium spp. before harvest, and the smallest change in diversity of the microbial community during the cultivation period. However, tuberous roots harvested from the fields showed no significant differences in antioxidant activity or lesion size with the treatment of 106 conidia/ml F. solani. By solidifying the importance of cultivating soil and related microorganisms in the advancement of root rot of sweetpotato, our results may aid in preventing the decrease in the yield of cultivated sweetpotatoes through root rot control.

Tumor migration and invasion induced by the epithelial-to-mesenchymal transition (EMT) are prerequisites for metastasis. Here, we investigated the inhibitory effect of a mimic of superoxide dismutase (SOD), cationic Mn(III) ortho-substituted N-n-hexylpyridylporphyrin (MnTnHex-2-PyP5+, MnHex) on the metastasis of breast cancer in cellular and animal models, focusing on the migration of tumor cells and the factors that modulate this behavior. Wound healing and Transwell migration assays revealed that the migration of mouse mammary carcinoma 4T1 cells was markedly reduced during the concurrent treatment of MnHex and radiation therapy (RT) compared with that of the control and RT alone. Bioluminescence imaging showed that MnHex/RT co-treatment dramatically reduced lung metastasis of 4T1 cells in mice, compared with the sham control and both single treatments. Western blotting and immunofluorescence showed that MnHex treatment of 4T1 cells reversed the RT-induced EMT via inhibiting AKT/GSK-3β/Snail pathway in vitro, thereby decreasing cell migration and invasion. Consistently, histopathological analyses of 4T1 tumors showed that MnHex/RT reduced Snail expression, blocked EMT, and in turn suppressed metastases. Again, in the human metastatic breast cancer MDA-MB-231 cell line, MnHex inhibited metastatic potential in vitro and in vivo and suppressed the RT-induced Snail expression. In addition to our previous studies showing tumor growth inhibition, this study demonstrated that MnHex carries the ability to minimize the metastatic potential of RT-treated cancers, thus overcoming their radioresistance.

Although one of the challenges in college remedial mathematics courses involves dealing with negative emotions adversely impacting student achievement, little empirical research has been conducted to examine the factors contributing to the formation of such emotions in these settings. The purpose of this study was to examine whether background variables, motivation, and self-regulation predicted students' negative emotions, measured with boredom, frustration, and test anxiety. A total of 201 students taking a remedial mathematics course using an adaptive system - Assessment Learning in Knowledge Space (ALEKS) - participated in the study at a small public university in the midwestern United States. Hierarchical regression was used for the data analysis. Results indicate that students' age (a background variable) and motivation as shown in extrinsic goal orientation, task value, and self-efficacy were significantly associated with boredom, frustration, and test anxiety. In addition, students' self-regulation, specifically effort regulation and metacognitive regulation, was related to negative emotions. Discussion of the results and educational implications are included.