Search

Bo Young Oh,1,* Jeonghee Cho,2,* Hye Kyung Hong,3 Joon Seol Bae,4 Woong-Yang Park,4–6 Je-Gun Joung,4 Yong Beom Cho3,5 1Department of Surgery, College of Medicine, Ewha Womans University, Seoul, 2Department of Nanobiomedical Science, Dankook University, Cheonan, 3Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 4Samsung Genome Institute, Samsung Medical Center, 5Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, 6Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea *These authors contributed equally to this work Background: Understanding the genomic determinants associated with metastasis in colorectal cancers (CRCs) provides crucial clues for improving patient care. Patients and methods: In this study, we performed whole-exome sequencing as well as RNA sequencing analyses on five pairs of primary and liver metastasized samples from CRC patients together with blood/normal control samples for each pair. Results: We identified genomic deletions in the region of 8p21-23 (q value

Background: The clinical application of natural orifice transluminal endoscopic surgery (NOTES) for sigmoidectomy is associated with several difficulties that need to be overcome before wider clinical application of the procedure. The purpose of this study was to evaluate the technical feasibility and safety of transgastric sigmoidectomy in a survival animal model, as well as to evaluate the safety and usability of a custom paired magnetic intraluminal device, which we developed for the NOTES procedure.Methods: Survival experiments were conducted on 24-33-kg dogs. After anesthesia, a gastrotomy was created using double-channel endoscope, and peritoneoscopy was performed. The sigmoid colon was retracted laterally using paired magnetic intraluminal device, the mesocolon was dissected, and the branch vessel was sealed. The anvil was placed into the descending colon through anus. A proximal and distal colonic transection was then performed. The circular stapler was passed through the anus and performed end-to-end anastomosis. Afterwards the specimen was removed through gastrotomy, and the gastric incision was closed. Postoperatively, all dogs were recovered and monitored for well-being during convalescence. Reexploration was practiced under anesthesia 2 weeks after surgery for evaluation of intra-abdominal complications, and intra-peritoneal cultures for microorganism.Results: The mean operative time was 141 (range, 122-157) min. There were no complications or physical evidence of sepsis or bowel obstruction during the observation period. Only one dog exhibited decreased body weight, decreasing to 20.4 kg from 22.4 kg after surgery; all of the other dogs exhibited increased body weight. We observed no evidence of peritonitis, intra-abdominal abscess, bleeding, or organ injury on reexploration conducted on day 14 after surgery.Conclusions: Transgastric NOTES sigmoidectomy is a safe operation technique as evaluated in a dog model. The paired magnetic intraluminal device that was used in this study was useful to avoid an abdominal incision for retracting the sigmoid colon. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We report our technique and results for endoscopy-aided CO2 laser therapy for the treatment of intractable granular myringitis, as an out-patient office procedure. MATERIALS AND METHODS: A total of 21 patients (14 women and seven men; mean age 32.6 years) were retrospectively reviewed, all of whom suffered from intractable granular myringitis and had undergone endoscopy-aided laser treatment. Granulation tissue was vaporized for one to two seconds with a CO2 laser (spot size 0.5-1 mm with a power setting of 5-10 W in continuous mode). The mean follow-up period was 11 months. RESULTS: Eighteen of the 21 patients (85 per cent) were cured after a single treatment. Three patients with the diffuse form of the disease required repeat laser treatments coupled with self-irrigation with a diluted vinegar solution. We noted no perforations of patients' tympanic membranes after laser vaporization. We also observed no recurrences over follow-up periods ranging from three months to 2.6 years. Our laser procedure produced no adverse effect on hearing thresholds, nor were any other complications observed. CONCLUSION: Our results suggest that endoscopy-aided CO2 laser ablation is a reliable and minimally invasive method associated with low rates of recurrence and a low incidence of complications. It can be conducted as an office procedure. [ABSTRACT FROM AUTHOR]

Background: Despite advancements in total mesorectal excision (TME) and neoadjuvant radiotherapy, locally advanced rectal cancer remains challenging, impacting patient quality of life and mortality. This study aimed to identify the risk factors for local recurrence in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and assess treatment strategies for recurrence., Methods: This retrospective analysis included 682 patients diagnosed with locally advanced rectal cancer who were treated with neoadjuvant CRT and TME at Samsung Medical Center from 2008 to 2017. The exclusion criteria ensured a homogenous cohort. Clinical staging involved colonoscopies, computed tomography, magnetic resonance imaging, and digital rectal exam. Risk factors, treatment modalities, and oncological outcomes for local recurrence were evaluated., Result: During a median 62-month follow-up, 47 patients (6.9 %) experienced local recurrence. The risk factors for local recurrence included a positive circumferential resection margin (CRM), venous invasion, and perineural invasion. Of the 47 patients with local recurrence, 25 (53.2 %) were considered resectable. Out of these, 23 patients underwent curative resections, and 15 (65.2 %) achieved R0 resection. Patients with R0 resections exhibited superior 5-year survival rates compared to R1-2 resection or non-surgical treatment, and there was no survival difference between R1-2 resection and non-surgical treatment., Conclusion: In locally advanced rectal cancer, positive CRM, venous invasion, and perineural invasion were associated with local recurrence. R0 resection showed favorable outcomes, emphasizing the importance of surveillance in high-risk patients. Treatment decisions should consider these factors for improved oncologic outcomes and quality of life., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Viruses have long been recognized as significant pathogens, contributing to multiple global pandemics throughout human history. Recent examples include the 2009 influenza pandemic and the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. Despite ongoing experimental and clinical efforts, the development of effective antiviral treatments and vaccines remains challenging due to the high mutation rates of many human pathogenic viruses including influenza virus and SARS-CoV-2. As an alternative approach, antiviral strategies targeting host factors shared by multiple viruses could provide a more universally applicable solution. Emerging evidence suggests that viruses exploit the host cytoskeletal network to facilitate efficient viral replication and propagation. Therefore, a comprehensive understanding of the interactions between viral components and the cytoskeletal machinery may offer valuable insights for the development of broad-spectrum antiviral therapeutics. This review compiles and discusses current knowledge on the interactions between viruses and cytoskeletal elements, including kinesin, dynein, myosin, and vimentin, and explores their potential as therapeutic targets. The potential for these cytoskeletal components to serve as targets for new antiviral interventions is discussed in the context of diverse human viruses, including influenza virus, SARS-CoV-2, herpes simplex virus, human papillomavirus, and human immunodeficiency virus., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: To prevent local recurrence caused by exfoliated cancer cells caught in the suture line, intraoperative rectal washout during surgery can be performed to eliminate exfoliated cancer cells. However, the impact of neoadjuvant chemoradiotherapy on exfoliated cancer cells is not well known. This study aimed to identify positive rate of malignant cells in rectal washout fluids of neoadjuvant chemoradiotherapy patients and to determine if neoadjuvant chemoradiotherapy could affect exfoliated cancer cells., Methods: A total of 105 patients who underwent rectal washout intraoperatively for distal sigmoid colon and rectal cancer from April 2020 to September 2021 were analyzed. The primary outcome was positive rate of malignant cells in rectal washout fluids of patients who had received neoadjuvant chemoradiotherapy., Results: The positive rate of malignant cells in washout fluids of patients who had received neoadjuvant chemoradiotherapy was 0.0% and those who had not was 32.1%. The overall positive rate was 23.8%. In the positive group, tumor sizes were bigger (4.64 ± 1.68 cm vs. 3.64 ± 2.00 cm, p = 0.026) and more patients had a fungating tumor shown in preoperative colonoscopy (96.0% vs. 71.3%, p = 0.012). Although these factors did not show statistical significance in multivariable logistic regression analysis, fungating tumor showed a trend towards significance (OR: 7.28, 95% CI: 0.90-58.77, p = 0.063)., Conclusions: Our study suggests that neoadjuvant chemoradiotherapy could reduce exfoliated cancer cells, and rectal washout for the purpose of eliminating exfoliated cancer cells might be unnecessary in patients who have received neoadjuvant chemoradiotherapy., (© 2024. The Author(s).)

Walking is a fundamental aspect of daily life and exercise, with clinical benefits for cardiovascular health and muscle strength. However, accurately measuring energy efficiency during walking poses challenges due to equipment and spatial constraints. In this study, we proposed the cadence-based energy expenditure index (cEEI) and analyzed its correlation with the previously proposed index for measuring energy expenditure under various gait conditions. We enrolled 15 healthy participants and conducted an experimental protocol on a treadmill to measure the following energy expenditure-related indices: oxygen cost index (OCI), energy expenditure index (EEI), and cEEI. The participants underwent stages of walking at different speeds and inclinations that comply with the modified Bruce protocol while their heart rate, oxygen uptake, and cadence were recorded. Participants showed significant increases in heart rate, oxygen uptake, and cadence with higher walking speeds and inclinations. Correlation analysis revealed strong associations between cEEI and OCI, especially during walking conditions. Bland-Altman plots and interclass correlation coefficient analysis demonstrated a favorable agreement between cEEI and OCI, outperforming EEI. In conclusion, this study proposes cEEI as a reliable metric for estimating energy expenditure during walking by proving a strong correlation and agreement with OCI across various gait conditions. This suggests the potential for cEEI to provide real-time, individualized feedback on energy expenditure during walking, facilitating more personalized exercise prescriptions.

Purpose: While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to NCCN guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies., Materials and Methods: A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and CT scans., Results: Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectal). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative CEA levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon cancer and 14.9% in rectal cancer)., Conclusion: Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.

Improving photosynthesis, the fundamental process by which plants convert light energy into chemical energy, is a key area of research with great potential for enhancing sustainable agricultural productivity and addressing global food security challenges. This perspective delves into the latest advancements and approaches aimed at optimizing photosynthetic efficiency. Our discussion encompasses the entire process, beginning with light harvesting and its regulation and progressing through the bottleneck of electron transfer. We then delve into the carbon reactions of photosynthesis, focusing on strategies targeting the enzymes of the Calvin-Benson-Bassham (CBB) cycle. Additionally, we explore methods to increase carbon dioxide (CO2) concentration near the Rubisco, the enzyme responsible for the first step of CBB cycle, drawing inspiration from various photosynthetic organisms, and conclude this section by examining ways to enhance CO2 delivery into leaves. Moving beyond individual processes, we discuss two approaches to identifying key targets for photosynthesis improvement: systems modeling and the study of natural variation. Finally, we revisit some of the strategies mentioned above to provide a holistic view of the improvements, analyzing their impact on nitrogen use efficiency and on canopy photosynthesis., Competing Interests: Conflict of interest statement. K.N. is an inventor on a patent “Transgenic plants with increased photosynthesis efficiency and growth” US20230183731A1, and K.N. and D.P.-T. are inventors on a patent application “Methods of screening for plant gain of function mutations and compositions therefor” US20230323480A1. All other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background: Colorectal carcinoma in situ, characterized by cancer limited to the intramucosal layer or known as intraepithelial carcinoma, has conventionally considered to be without any risk of regional lymph node metastasis. However, isolated cases of regional lymph node metastasis, local recurrence, and distant metastasis challenge this assumption. This study aimed to assess the occurrence of regional lymph node metastasis and recurrence of colorectal carcinoma in situ., Methods: A retrospective analysis was conducted in 1069 patients who underwent full-thickness local excision or radical surgery for colorectal carcinoma in situ between January 1994 and December 2020. Histopathological features were assessed by 2 experienced pathologists. In cases of suspected recurrence, evaluation involved abdomen-pelvis and chest computed tomography, or PET-CT., Results: The recurrence rate of colorectal carcinoma in situ patients was 0.46%. Among the patients, 9 were diagnosed with regional lymph node metastasis or cancer recurrence. Of these, 4 patients were diagnosed with lymph node metastasis during primary surgery; 2 exhibited regional lymph node metastasis, and 2 presented with both regional and distant lymph node metastases. Regional lymph node metastasis occurred in additional 2 patients after radical surgery for the primary tumor. Distant metastasis was observed in 3 patients: hepatic metastasis in 1, hepatic and pulmonary metastases in another, and small bowel metastasis in the third patient. Among the 5 patients experiencing cancer recurrence, 1 expired due to cancer progression., Conclusion: Contrary to previous assumptions, colorectal carcinoma in situ can potentially metastasize to lymph nodes and recur. Therefore, careful assessment at the time of diagnosis is crucial, recognizing the possibility of lymph node metastasis or recurrence. This approach is essential for accurately identifying instances of cancer recurrence and ensuring optimal oncological outcomes., Competing Interests: Disclosure There is no financial or material support to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Seven previously undescribed dihydro-β-agarofurans (1-7) together with 28 known compounds were isolated from Celastrus orbiculatus fruits using LC-MS/MS-based molecular networking-guided purification. Their structures were elucidated through 1D and 2D-NMR, HRESIMS analysis, and ECD quantum chemical calculations. The inhibitory effects of all isolated compounds on α-MSH-induced melanin production in B16F0 melanoma cells were tested. Compounds 1, 11, 12, 19-21, 23, 29, 31, 34, and 35 showed significant inhibitory effects on melanin production with IC 50 values ranging from 11.3 to 30.1 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

LC-HRMS/MS-based molecular networking was applied to investigate the bioactive sesquiterpene lactones and their analogs contained in Inula helenium, enabling the isolation of four undescribed eudesmane-eudesmane sesquiterpene dimers (1-4), a sesquiterpene-amino acid adduct (5), and 17 known sesquiterpenes (6-22). The structures were determined based on 1D, 2D NMR, and HRESIMS data analysis, as well as DP4+ probability analyses and ECD calculations. The biosynthetic pathway of the sesquiterpene dimers is postulated to proceed via the Diels-Alder reaction as the key step. The inhibitory activity of all isolates on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages was evaluated. Compounds 4, 17, and 20 exhibited significant inhibitory activity against NO production, with IC 50 values of 8.4, 5.5, and 9.1 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soil sustains human life by nourishing crops, storing food sources, and housing microbes, which may affect the nutrition and biosynthesis of secondary metabolites, some of which are used as drugs. To identify lead compounds for a new class of drugs, we collected soil-derived fungal strains from various environments, including urban areas. As various human pathogens are assumed to influence the biosynthetic pathways of metabolites in soil fungi, leading to the production of novel scaffolds, we focused our work on densely populated urban areas and tourist attractions. A soil-derived fungal extract library was screened against MDA-MB-231 cells to derive their cytotoxic activity. Notably, 10 μg/mL of the extract of Trichoderma guizhouense (DS9-1) was found to exhibit an inhibitory effect of 71%. Fractionation, isolation, and structure elucidation efforts led to the identification of nine new peptaibols, trichoguizaibols A-I ( 1 - 9 ), comprising 14 amino acid residues (14-AA peptaibols), and three new peptaibols, trichoguizaibols J-L ( 10 - 12 ), comprising 18 amino acid residues (18-AA peptaibols). The chemical structures of 1 - 12 were determined based on their 1D and 2D NMR spectra, HRESIMS, electronic circular dichroism data, and results of the advanced Marfey's method. The 18-AA peptaibols were found to exhibit cytotoxicity against MDA-MB-231, SK-Hep1, SKOV3, DU145, and HCT116 cells greater than that of the 14-AA peptaibols. Among these compounds, 10 - 12 exhibited potent sub-micromolar IC 50 values. These results are expected to shed light on a new direction for developing novel scaffolds as anticancer agents.

This study investigates the energy transfer mechanism between the organic polymer poly(2-methoxy-5(2'-ethyl)heroxyphenylenevinylene) (MEH-PPV) and CdSe/ZnS core-shell quantum dots (CdSe/ZnS CSQDs). Additionally, a hybrid ZnO-based photodetector (PD) is fabricated using the composite of MEH-PPV and CdSe/ZnS CSQDs, aiming to gain deeper insights. The combination of MEH-PPV and CdSe/ZnS CSQDs facilitates a broad spectral response in PDs, spanning from the ultraviolet (UV) to the visible range. In particular, PDs with QDs in the composite demonstrate notably excellent photosensitivity to both ultraviolet (UV) light (365 nm) (~5 fold) and visible light (505 nm) (~3 fold).

Purpose: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF., Materials and Methods: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed., Results: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211)., Conclusion: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL -1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories., (© 2024 The Authors. Biotechnology Journal published by Wiley‐VCH GmbH.)

Background: Locally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection., Methods: In this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival., Results: A total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015)., Conclusion: In conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients., Competing Interests: Declaration of competing interest The authors have no related conflicts of interest to declare., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection., Methods: This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups., Results: After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m 2 , and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group., Conclusions: Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer., (© 2024. Society of Surgical Oncology.)

This study presents the vascularized tissue on mesh-assisted platform (VT-MAP), a novel microfluidic in vitro model that uses an open microfluidic principle for cultivating vascularized organoids. Addressing the gap in 3D high-throughput platforms for drug response analysis, the VT-MAP can host tumor clusters of various sizes, allowing for precise, size-dependent drug interaction assessments. Key features include capability for forming versatile co-culture conditions (EC, fibroblasts and colon cancer organoids) that enhance tumor organoid viability and a perfusable vessel network that ensures efficient drug delivery and maintenance of organoid health. The VT-MAP enables the culture and analysis of organoids across a diverse size spectrum, from tens of microns to several millimeters. The VT-MAP addresses the inconsistencies in traditional organoid testing related to organoid size, which significantly impacts drug response and viability. Its ability to handle various organoid sizes leads to results that more accurately reflect patient-derived xenograft (PDX) models and differ markedly from traditional in vitro well plate-based methods. We introduce a novel image analysis algorithm that allows for quantitative analysis of organoid size-dependent drug responses, marking a significant step forward in replicating PDX models. The PDX sample from a positive responder exhibited a significant reduction in cell viability across all organoid sizes when exposed to chemotherapeutic agents (5-FU, oxaliplatin, and irinotecan), as expected for cytotoxic drugs. In sharp contrast, PDX samples of a negative responder showed little to no change in viability in smaller clusters and only a slight reduction in larger clusters. This differential response, accurately replicated in the VT-MAP, underscores its ability to generate data that align with PDX models and in vivo findings. Its capacity to handle various organoid sizes leads to results that more accurately reflect PDX models and differ markedly from traditional in vitro methods. The platform's distinct advantage lies in demonstrating how organoid size can critically influence drug response, revealing insights into cancer biology previously unattainable with conventional techniques.

Background: The lungs are one of the most common sites for colon cancer metastasis. A few studies reported that approximately 2% to 10% of patients with colon cancer developed pulmonary metastasis. However, among these studies, patient characteristics were heterogeneous, and information on pulmonary metastasis incidence by the TNM stage was scarce., Objective: This study evaluated the incidence of pulmonary metastasis in colon cancer without synchronous metastasis treated with radical surgery and identified risk factors for pulmonary metastasis according to the TNM stage., Design and Settings: This retrospective study included all patients with colon cancer without metastasis who underwent radical surgery for primary tumor at Samsung Medical Center between January 2007 and December 2016., Patients: A total of 4889 patients who underwent radical surgery for stage I and III colon cancer were included., Main Outcome Measures: The main outcome measures were the incidence of pulmonary metastasis and overall survival., Results: A total of 156 patients (3.2%) were diagnosed with pulmonary metastasis after a median of 16 months from the time of radical surgery for colon cancer to detection of pulmonary metastasis. The pulmonary metastasis incidence rate by the TNM stage was 0.5% in stage I, 1.6% in stage II, and 6% in stage III. Risk factors for pulmonary metastasis were preoperative CEA >5 ng/mL, cancer obstruction, N stage, vascular invasion, perineural invasion, and adjuvant chemotherapy for primary colon cancer in multivariable analysis., Limitation: This was a retrospective single-center study., Conclusions: Preoperative CEA >5 ng/mL, cancer obstruction, pN stage, vascular invasion, perineural invasion, and receiving adjuvant chemotherapy for primary colon cancer were risk factors for pulmonary metastasis in colon cancer. Therefore, patients with risk factors for pulmonary metastasis should be recommended for intensive follow-up to detect lung metastases. See Video Abstract ., Metstasis Pulmonar En El Primer Sitio Tras Ciruga Curativa Del Cncer De Colon Incidencia Y Factores De Riesgo Segn Estadio Tnm: ANTECEDENTES:Los pulmones son uno de los sitios más comunes de metástasis del cáncer de colon. Algunos estudios informaron que aproximadamente entre el 2% y el 10% de los pacientes con cáncer de colon desarrollaron metástasis pulmonar. Sin embargo, entre estos estudios, las características de los pacientes fueron heterogéneas y la información sobre la incidencia de metástasis pulmonares según el estadio TNM fue escasa.OBJETIVO:Este estudio evaluó la incidencia de metástasis pulmonar en cáncer de colon sin metástasis sincrónica tratada con cirugía radical e identificó factores de riesgo para metástasis pulmonar según el estadio TNM.DISEÑO Y AJUSTES:Este estudio retrospectivo incluyó a todos los pacientes con cáncer de colon sin metástasis que se sometieron a cirugía radical por tumor primario en el Samsung Medical Center entre enero de 2007 y diciembre de 2016.PACIENTES:Se incluyó un total de 4.889 pacientes sometidos a cirugía radical por cáncer de colon en estadio I-III.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la incidencia de metástasis pulmonar y la supervivencia general.RESULTADOS:Un total de 156 pacientes (3,2%) fueron diagnosticados con metástasis pulmonar con una duración media de 16 meses desde el momento de la cirugía radical por cáncer de colon hasta la detección de la metástasis pulmonar. La tasa de incidencia de metástasis pulmonares por estadio TNM fue del 0,5% en el estadio I, del 1,6% en el estadio II y del 6% en el estadio III. Los factores de riesgo de metástasis pulmonar fueron CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio N, invasión vascular, invasión perineural y quimioterapia adyuvante para el cáncer de colon primario en un análisis multivariable.LIMITACIÓN:Este fue un estudio retrospectivo de un solo centro.CONCLUSIÓN:CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio pN, invasión vascular, invasión perineural y recibir quimioterapia adyuvante para el cáncer de colon primario fueron factores de riesgo de metástasis pulmonar en el cáncer de colon. Por lo tanto, se debe recomendar un seguimiento intensivo a los pacientes con factores de riesgo de metástasis pulmonares para detectar metástasis pulmonares. (Traducción-Dr Yolanda Colorado )., (Copyright © The ASCRS 2023.)

Purpose: The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform., Methods: Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status., Results: During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants' age increased. When the participants' overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P<0.001)., Conclusion: Most of the 2022 Gold Ribbon Campaign participants were satisfied with the metaverse platform. Medical society should pay attention to increasing participation in and satisfaction with future public campaigns.

With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS-CoV-2 to host cell membranes and viral fusion. We developed pioneering IgG4-(HR2) 4 bifunctional antibodies by creating immunoglobulin G4-based and phage display-derived human monoclonal antibodies (mAbs) that specifically bind to the SARS-CoV-2 receptor-binding domain, engineered with four heptad repeat 2 (HR2) peptides. Our in vitro experiments demonstrate the superior neutralization efficacy of these engineered antibodies against various SARS-CoV-2 variants, ranging from original SARS-CoV-2 strain to the recently emerged Omicron variants, as well as SARS-CoV, outperforming the parental mAb. Notably, intravenous monotherapy with the bifunctional antibody neutralizes a SARS-CoV-2 variant in a murine model without causing significant toxicity. In summary, this study unveils the significant potential of HR2 peptide-driven bifunctional antibodies as a potent and versatile strategy for mitigating SARS-CoV-2 infections. This approach offers a promising avenue for rapid development and management in the face of the continuously evolving SARS-CoV-2 variants, holding substantial promise for pandemic control., (© 2024 Wiley Periodicals LLC.)

Purpose: Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery., Methods: We reviewed 39 patients who underwent SPR colectomy from April to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time, docking time, and surgeon console time. We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3., Results: The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average operation time was 186.59±51.30 minutes, the average surgeon console time was 95.49±35.33 minutes, and the average docking time (time from skin incision to robot docking) was 14.87±10.38 minutes. The surgeon console time differed significantly among the different phases (P<0.001). Complications occurred in 8 patients: 2 ileus, 2 postoperation hemoglobin changes, 3 urinary retentions, and 1 complicated fluid collection., Conclusion: In our experience, the learning curve for SPR colectomy was achieved after the 18th case.

In our search for bioactive components, various chromatographic separations of the organic fractions from Filipendula glaberrima leaves led to the isolation of a new ellagitannin and a triterpenoid, along with 26 known compounds. The structures of the isolates were determined based on their spectroscopic properties and chemical evidence, which were then evaluated for their antioxidant activities, inhibitory activities on 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and foam cell formation in THP-1 cells to prevent atherosclerosis. Rugosin B methyl ester ( 1 ) showed the best HMG-CoA reductase inhibition and significantly reduced ox-low-density lipoprotein-induced THP-1 macrophage-derived foam cell formation at 25 µM. In addition, no cytotoxicity was observed in THP-1 cells at 50 μg/mL of all extracts in the macrophage foam cell formation assay. Therefore, F. glaberrima extract containing 1 is promising in the development of dietary supplements due to its potential behavior as a novel source of nutrients for preventing and treating atherosclerosis.

Purpose: To compare plan quality among photon volumetric arc therapy (VMAT), Gamma Knife, and three different proton beam modalities., Methods: Fifty-five brain lesions from 20 patients were planned with three different proton spot size ranges of cyclotron-generated proton beams, CPBs (spot size σ: 2.7-7.0 mm), linear accelerator proton beams, LPBs (σ: 2.9-5.5 mm), and linear accelerator proton minibeams, LPMBs (σ: 0.9-3.9 mm), with and without apertures and compared against photon VMAT and Gamma Knife plans. Dose coverage to each lesion for each proton and photon plan was set to 99% of the GTV receiving the prescription (Rx) dose. All proton plans used ±2 mm setup uncertainty and ±2% range uncertainty in robust evaluation to achieve V 100%Rx > 95% of the GTV. Apertures were applied to proton beams irradiating tumors <1 cm 3 volume and located <2.5 cm depth. Conformity index (CI), gradient index (GI), V 12 Gy , V 4.5 Gy , and mean brain dose were compared across all plan types. The Wilcoxon signed rank test was utilized to determine statistical significance of dosimetric results compared between photon and proton plans., Results: When compared to CPB generated plans, average CI and GI were significantly better for the LPB and LPMB plans. Aperture-based IMPT plans showed improvement from Gamma Knife for all dosimetric metrics. Aperture-based IMPT plans also showed improvement in all dosimetric metrics for shallow tumors (d < 2.5 cm) when compared with non-aperture-based plans., Conclusion: The LPB and LPMB stand as excellent alternatives to CPB or photon therapy and significantly increase the preservation of normal tissue., Competing Interests: Authors’ disclosure of potential conflicts of interest Dr Farr reports collaborative research grant with Advanced Oncotherapy (AVO) — IRB number 19-1180, DATA1119: Using proton mini-beams to improve SBRT/SRS plan conformity, Board member at large for the AAPM Journal of Medical Physics, stock in Advanced Oncotherapy, plc and he is the Chief Clinical Officer of A.D.A.M SA Director General. Dr Xia reports collaborative research grant with Advanced Oncotherapy (AVO) — IRB number 19-1180, DATA1119: Using proton mini-beams to improve SBRT/SRS plan conformity. Other authors have nothing to disclose., (© 2024 Old City Publishing, Inc.)

Chlorophyll is the major light-absorbing pigment for plant photosynthesis. While evolution has been selected for high chlorophyll content in leaves, previous work suggests that domesticated crops grown in modern high-density agricultural environments overinvest in chlorophyll production, thereby lowering light use and nitrogen use efficiency. To investigate the potential benefits of reducing chlorophyll levels, we created ethanol-inducible RNAi tobacco mutants that suppress Mg-chelatase subunit I (CHLI) with small RNA within 3 h of induction and reduce chlorophyll within 5 days in field conditions. We initiated chlorophyll reduction later in plant development to avoid the highly sensitive seedling stage and to allow young plants to have full green leaves to maximise light interception before canopy formation. This study demonstrated that leaf chlorophyll reduction >60% during seed-filling stages increased tobacco seed nitrogen concentration by as much as 17% while canopy photosynthesis, biomass and seed yields were maintained. These results indicate that time-specific reduction of chlorophyll could be a novel strategy that decouples the inverse relationship between yield and seed nitrogen by utilising saved nitrogen from the reduction of chlorophyll while maintaining full carbon assimilation capacity., (© 2023 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study's findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.

Background: Mucinous adenocarcinoma is a rare histologic feature of colorectal cancer and is characterized by oncologic features that are different from those of adenocarcinoma. However, there are conflicting views regarding the prognostic impact of mucinous adenocarcinoma on colon cancer., Objective: This study aimed to evaluate the prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer., Design: This was a retrospective cohort study., Settings: This study was conducted between January 2010 and December 2015. Patients were divided into the mucinous adenocarcinoma and nonmucinous adenocarcinoma groups. Disease-free survival and overall survival were assessed using propensity score matching., Patients: Overall, 2532 patients who underwent radical surgery for stage II and III colon cancer were included in the study., Main Outcome Measures: The main outcome measures were disease-free survival and overall survival., Results: The median follow-up duration was 86 months. The disease-free survival and overall survival were significantly lower in the mucinous adenocarcinoma group than in the nonmucinous adenocarcinoma group. In subgroup analysis, there was no significant difference in the disease-free survival and overall survival between patients with and without mucinous adenocarcinoma with stage II colon cancer. In stage III colon cancer, the disease-free survival and overall survival were significantly lower in patients with mucinous adenocarcinoma than in those without mucinous adenocarcinoma. Multivariable analysis showed that mucinous adenocarcinoma was a poor prognostic factor for disease-free survival and overall survival., Limitation: The study's limitations include those that are inherently associated with retrospective single-center studies., Conclusions: Mucinous adenocarcinoma is a poor prognostic factor in stage III but not in stage II colon cancer. Therefore, mucinous adenocarcinoma might not be regarded as an independent risk factor requiring chemotherapy for favorable oncologic outcomes. However, for stage III colon cancer, patients with mucinous adenocarcinoma require close observation., Impacto Pronstico Del Adenocarcinoma Mucinoso En Las Etapas Ii Y Iii De Cncer De Clon: ANTECEDENTES:El adenocarcinoma mucinoso es una característica histológica rara del cáncer colorrectal, se caracteriza por propiedades oncológicas que son diferentes a las del adenocarcinoma. Sin embargo, existen puntos de vista contradictorios con respecto al impacto pronóstico del adenocarcinoma mucinoso en el cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar el impacto pronóstico del adenocarcinoma mucinoso en las etapas II y III de cáncer de cólon.DISEÑO Y CONFIGURACIONES:Este estudio de cohorte retrospectivo se realizó entre enero de 2010 y diciembre de 2015. Los pacientes se dividieron entre grupos de adenocarcinoma mucinoso y adenocarcinoma no mucinoso. La supervivencia libre de enfermedad y la supervivencia global se evaluaron utilizando emparejamiento por puntuación de propensión.PACIENTES:En general, 2,532 pacientes que se sometieron a cirugía radical para etapa II y III de cáncer de colon se incluyeron en el estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana de duración del seguimiento fue de 86 meses. La supervivencia libre de enfermedad y la supervivencia global fueron significativamente menores en el grupo de adenocarcinoma mucinoso que en el grupo de adenocarcinoma no mucinoso. En el análisis de subgrupos, no hubo diferencias significativas en la supervivencia libre de enfermedad y la supervivencia global entre los pacientes con o sin adenocarcinoma mucinoso con cáncer de cólon etapa II. En el cáncer de colon etapa III, la supervivencia libre de enfermedad y la supervivencia global fueron significativamente más bajas en pacientes con adenocarcinoma mucinoso que en aquellos sin adenocarcinoma mucinoso. El análisis multivariable mostró que el adenocarcinoma mucinoso era un factor de mal pronóstico para la supervivencia libre de enfermedad y la supervivencia global.LIMITACIONES:Las limitaciones del estudio incluyen aquellas que están inherentemente asociadas con estudios retrospectivos de un solo centro.CONCLUSIONES:El adenocarcinoma mucinoso es un factor de mal pronóstico en el cáncer de colon etapa III pero no en etapa II. Por lo tanto, el adenocarcinoma mucinoso podría no considerarse un factor de riesgo independiente que requiera quimioterapia para obtener resultados oncológicos favorables. Sin embargo, para el cáncer de colon etapa III, los pacientes con adenocarcinoma mucinoso requieren observación cercana. (Traducción-Dr. Aurian Garcia Gonzalez )., (Copyright © The ASCRS 2023.)

Background: The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer., Objective: We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer., Design: A retrospective comparative cohort study using propensity score matching., Setting: This study was conducted at a single tertiary center., Patients: Patients with primary colon cancer undergoing curative resection from October 2013 to December 2017 were enrolled. Patients were grouped into micropapillary pattern positive or micropapillary pattern negative., Main Outcome Measurements: Disease-free survival and overall survival., Results: Of the eligible 2192 patients, 334 (15.2%) were with micropapillary pattern (+). After 1:2 propensity score matching, 668 patients with micropapillary pattern-negative status were selected. The micropapillary pattern-positive group showed significantly worse 3-year disease-free survival (77.6% vs 85.1%, p = 0.007). Three-year overall survival of micropapillary pattern-positive and micropapillary pattern-negative patients did not show a statistically significant difference (88.9% vs 90.4%, p = 0.480). In multivariable analysis, micropapillary pattern-positive was an independent risk factor for poor disease-free survival (HR 1.547, p = 0.008). In the subgroup analysis for 828 patients with stage II disease, 3-year disease-free survival deteriorated significantly in micropapillary pattern-positive patients (82.6% vs 93.0, p < 0.001). Three-year overall survival was 90.1% and 93.9% in patients positive and negative for micropapillary pattern, respectively ( p = 0.082). In the multivariable analysis for patients with stage II disease, micropapillary pattern-positive status was an independent risk factor for poor disease-free survival (HR 2.003, p = 0.031)., Limitations: Selection bias due to the retrospective nature of the study., Conclusions: Micropapillary pattern-positive status may serve as an independent prognostic factor for colon cancer, especially for patients with stage II disease., Valor Pronstico Del Patrn Micropapilar Y Su Papel Como Caracterstica De Alto Riesgo En Pacientes Con Cncer De Colon En Estado Ii: ANTECEDENTES:La asociación del patrón micropapilar con los resultados oncológicos no ha sido completamente estudiada en pacientes con cáncer de colon.OBJETIVO:Evaluamos el valor pronóstico del patrón micropapilar, especialmente en pacientes con cáncer de colon en estadio II.DISEÑO:Estudio de cohortes comparativo y retrospectivo que utilize el emparejamiento por puntuación de propensiones.AJUSTE:Estudio realizado en un solo centro terciario.PACIENTES:Se incluyeron los pacientes con cáncer de colon primario sometidos a resección curativa desde octubre de 2013 hasta diciembre de 2017. Los pacientes se agruparon en patrón micropapilar positivo ( + ) o patrón micropapilar negativo ( - ).PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida libre de enfermedad y la sobrevida global.RESULTADOS:De los 2192 pacientes elegibles, 334 (15,2%) tenían patrón micropapilar (+). Después de emparejar el puntaje de propensión 1:2, se seleccionaron 668 pacientes con patrón micropapilar (-). El grupo con patrón micropapilar (+) mostró una sobrevida libre de enfermedad significativamente inferior a los tres años (77,6% frente a 85,1%, p = 0,007). La sobrevida global a los tres años del patrón micropapilar (+) y del patrón micropapilar (-) no mostró una diferencia estadísticamente significativa (88,9 % frente a 90,4%, p = 0,480). En el análisis multivariable, el patrón micropapilar (+) fue un factor de riesgo independiente para una deficiente sobrevida libre de enfermedad (índice de riesgo 1,547, p = 0,008). En el análisis de subgrupos de 828 pacientes con enfermedad en estadio II, la sobrevida libre de enfermedad a los tres años se deterioró significativamente en los pacientes con patrón micropapilar (+) (82,6% frente a 93,0, p < 0,001). La sobrevida global a los tres años fué del 90,1% y del 93,9% en el patrón micropapilar (+) y el patrón micropapilar (-), respectivamente ( p = 0,082). En el análisis multivariable de los pacientes con enfermedad en estadio II, el patrón micropapilar (+) fue un factor de riesgo independiente para una sobrevida libre de enfermedad deficiente (índice de riesgo 2,003, p = 0,031).LIMITACIONES:Sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:El patrón micropapilar (+) sirve como factor pronóstico independiente para el cáncer de colon, especialmente para pacientes con enfermedad en estadio II. (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2023.)

Liquid chromatography-mass spectrometry (LC-MS/MS)-based molecular networking analysis was applied to Streptomyces sp. MC16. The automatic classification of the MolNetEnhancer module revealed that its major constituent was an angucycline derivative. By targeted isolation of unique clusters in the molecular network, which showed different patterns from typical angucycline compounds, two new N -acetylcysteine-attached angucycline derivatives ( 1 and 2 ) were isolated. The structures were elucidated based on intensive NMR analysis and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). All isolated compounds ( 1 - 4 ) were tested for their inhibitory effects on the proliferation of A431, A549, and HeLa cell lines. Antibiotics 100-1 ( 3 ) and vineomycinone B 2 ( 4 ) showed moderate inhibitory effects on these three cell lines with IC 50 values ranging from 18.5 to 59.0 μM, while compounds 1 and 2 with an additional N -acetylcysteine residue showed weak inhibitory effects only on the HeLa cell line with IC 50 values of 54.7 and 65.2 μM, respectively., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

To evaluate the dosimetric impact of titanium implants in spine SBRT using four dose calculation algorithms. Twenty patients with titanium implants in the spine treated with SBRT without density override (DO) were selected. The clinical plan for each patient was created in Pinnacle and subsequently imported into Eclipse (AAA and AcurosXB) and Raystation (CC) for dose evaluation with and without DO to the titanium implant. We renormalized all plans such that 90% of the tumor volume received the prescription dose and subsequently evaluated the following dose metrics: (1) the maximum dose to 0.03 cc (Dmax), dose to 99% (D99%) and 90% (D90%) of the tumor volume; (2) Dmax and volumetric metrics of the spinal cord. For the same algorithm, plans with and without DO had similar dose distributions. Differences in Dmax, D99% and D90% of the tumor were on average <2% with slightly larger variations up to 5.58% in Dmax using AcurosXB. Dmax of the spinal cord for plans calculated with DO increased but the differences were clinically insignificant for all algorithms (mean: 0.36% ± 0.7%). Comparing to the clinical plans, the relative differences for all algorithms had an average of 1.73% (-10.36%-13.21%) for the tumor metrics and -0.93% (-9.87%-10.95%) for Dmax of the spinal cord. A few cases with small tumor and spinal cord volumes, dose differences of >10% in both D99% and Dmax of the tumor, and Dmax of the spinal cord were observed. For all algorithms, the presence of titanium implants in the spine for most patients had minimal impact on dose distributions with and without DO. For the same plan calculated with different algorithms, larger differences in volumetric metrics of >10% could be observed, impacted by dose gradient at the plan normalization volume, tumor volumes, plan complexity, and partial voxel volume interpolation., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Anaerobic bacteria often use antiporters DcuB (malate/succinate antiport) or DcuA (l-aspartate/succinate antiport) for the excretion of succinate during fumarate respiration. The rumen bacterium Actinobacillus succinogenes is able to produce large amounts of succinate by fumarate respiration, using the DcuB-type transporter DcuE for l-malate/succinate antiport. Asuc&#95;0142 was annotated as a second DcuB-type transporter. Deletion of Asuc&#95;0142 decreased the uptake rate for l-[ 14 C]aspartate into A. succinogenes cells. Properties of transport by heterologously expressed Asuc&#95;0142 were investigated in an Escherichia coli mutant deficient of anaerobic C4DC transporters. Expression of Asuc&#95;0142 resulted in high uptake activity for l-[ 14 C]fumarate or l-[ 14 C]aspartate, but the former showed a strong competitive inhibition by l-aspartate. In E. coli loaded with l-[ 14 C]aspartate, [ 14 C]succinate or [ 14 C]fumarate, extracellular C4DCs initiated excretion of the intracellular substrates, with a preference for l-aspartate ex /succinate in or l-aspartate ex /fumarate in antiport. These findings indicate that Asuc&#95;0142 represents a DcuA-type transporter for l-aspartate uptake and l-aspartate ex /C4DC in antiport, differentiating it from the DcuB-type transporter DcuE for l-malate ex /succinate in antiport. Sequence analysis and predicted structural characteristics confirm structural similarity of Asuc&#95;0142 to DcuA, and Asuc&#95;0142 was thus re-named as DcuA As . The bovine rumen fluid contains l-aspartate (99.6 µM), whereas fumarate and l-malate are absent. Therefore, bovine rumen colonisers depend on l-aspartate as an exogenous substrate for fumarate respiration. A. succinogenes encodes HemG (protoporphyrinogen oxidase) and PyrD (dihydroorotate dehydrogenase) for haem and pyrimidine biosynthesis. The enzymes require fumarate as an electron acceptor, suggesting an essential role for l-aspartate, DcuA As , and fumarate respiration for A. succinogenes growing in the bovine rumen.

Molecular networking analysis and in silico tools, such as Network Annotation Propagation (NAP) and MolNetEnhancer, were applied to explore bioactive constituents present in the ethyl acetate-soluble fraction of the rhizomes of Curculigo orchioides. Among the molecular networks, the most abundant cluster was classified as a phenolic glycoside using the ClassyFire module of MolNetEnhancer. Further, the major node in this cluster was accurately predicted as curculigine A using the in silico fragment analysis tool, NAP. Six undescribed chlorophenolic glycosides (1-6) and 11 known phenolic glycosides were isolated, using molecular networking-assisted isolation methods, and their structures were elucidated using 1D, 2D-NMR and HRESIMS. In particular, the structures of the isolated chlorophenolic glycosides, which have non-protonated aromatic rings, were determined using various NMR experiments, such as 1D-selective NOE, ROESY, and LR-HMBC, and acid hydrolysis. All isolated compounds were examined to determine their inhibitory effects on α-glucosidase and compounds 3, 8, 10, 11, 13, 14, and 16 revealed the IC 50 values ranging from 19.6 to 35.5 μM. Their structure-activity relationships were also evaluated based on the analysis of their inhibitory effects and performance of molecular docking simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has caused unprecedented health and socioeconomic crises, necessitating the immediate development of highly effective neutralizing antibodies. Despite recent advancements in anti-SARS-CoV-2 receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs) derived from convalescent patient samples, their efficacy against emerging variants has been limited. In this study, we present a novel dual-targeting strategy using bispecific antibodies (bsAbs) that specifically recognize both the SARS-CoV-2 RBD and fusion peptide (FP), crucial domains for viral attachment to the host cell membrane and fusion in SARS-CoV-2 infection., Methods: Using phage display technology, we rapidly isolated FP-specific mAbs from an established human recombinant antibody library, identifying K107.1 with a nanomolar affinity for SARS-CoV-2 FP. Furthermore, we generated K203.A, a new bsAb built in immunoglobulin G4-(single-chain variable fragment) 2 forms and demonstrating a high manufacturing yield and nanomolar affinity to both the RBD and FP, by fusing K102.1, our previously reported RBD-specific mAb, with K107.1., Results: Our comprehensive in vitro functional analyses revealed that the K203.A bsAb significantly outperformed the parental RBD-specific mAb in terms of neutralization efficacy against SARS-CoV-2 variants. Furthermore, intravenous monotherapy with K203.A demonstrated potent in vivo neutralizing activity without significant in vivo toxicity in a mouse model infected with a SARS-CoV-2 variant., Conclusion: These findings present a novel bsAb dual-targeting strategy, directed at SARS-CoV-2 RBD and FP, as an effective approach for rapid development and management against continuously evolving SARS-CoV-2 variants., 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 © 2023 Kim, Kim, Heo, Lee, Jang, Lee, Park, Cho, Lee, Shin, Yang, Choi, Shim and Lee.)

There is a limited understanding of the carbon assimilation capacity of nonfoliar green tissues and its impact on yield and seed quality since most photosynthesis research focuses on leaf photosynthesis. In this study, we investigate the photosynthetic efficiency of soybean (Glycine max) pods and seeds in a field setting and evaluate its effect on mature seed weight and composition. We demonstrate that soybean pod and seed photosynthesis contributes 13% to 14% of the mature seed weight. Carbon assimilation by soybean pod and seed photosynthesis can compensate for 81% of carbon loss through the respiration of the same tissues, and our model predicts that soybean pod and seed photosynthesis contributes up to 9% of the total daily carbon gain of the canopy. Chlorophyll fluorescence (CF) shows that the operating efficiency of photosystem II in immature soybean seeds peaks at the 10 to 100 mg seed weight stage, while that of immature pods peaks at the 75 to 100 mg stage. This study provides quantitative information about the efficiency of soybean pod and seed photosynthesis during tissue development and its impact on yield., Competing Interests: Conflict of interest statement. The authors declare no conflict of interest., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aimed to evaluate the association between distress at initial diagnosis and disease-free survival in patients with resectable colon cancer., Summary Background Data: Considerable research has examined the psychological impact of having a confirmed diagnosis of cancer, but relatively limited research has examined the impact of distress during the diagnostic phase on oncological outcomes., Methods: This is a retrospective cohort study. We included newly diagnosed colon cancer patients who had resectable surgery and underwent distress screening between July 2014 and July 2021 (N=1,362). The Korean versions of the Distress Thermometer were used to assess distress and related problems. Patients were categorized into 3 groups based on distress score: low (<4), moderate (4-7), and severe (≥8). The primary outcome was disease-free survival., Results: The mean distress was 5.1 (SD=2.4) and 61%, and 15% of patients had moderate and severe distress at diagnosis, respectively. The severe distress group was more likely to report fear, sadness, and concerns regarding insurance/finance, work, and childcare than the low distress group. Compared with the low distress group, the severe distress group had worse disease-free survival (Hazard Ratio=1.84, 95% CI=1.03, 3.29). The association was more evident in patients with stage IV disease (Hazard Ratio=2.53, 95% CI=1.02, 6.25)., Conclusions: A substantial number of patients with colon cancer experience distress at diagnosis, and severe distress has a negative impact on oncologic outcomes. Active monitoring and appropriate management of distress at diagnosis should be adopted at clinical settings., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective. Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the bystander effect were not yet made, the immune process presumably plays an important role in many aspects of the radiotherapy including the bystander effect. A mathematical model of immune response during and after radiation therapy is presented. Approach. Immune response of host body and immune suppression of tumor cells are modelled with four compartments in this study; viable tumor cells, T cell lymphocytes, immune triggering cells, and doomed cells. The growth of tumor was analyzed in two distinctive modes of tumor status (immune limited and immune escape) and its bifurcation condition. Main results. Tumors in the immune limited mode can grow only up to a finite size, named as terminal tumor volume analytically calculated from the model. The dynamics of the tumor growth in the immune escape mode is much more complex than the tumors in the immune limited mode especially when the status of tumor is close to the bifurcation condition. Radiation can kill tumor cells not only by radiation damage but also by boosting immune reaction. Significance. The model demonstrated that the highly heterogeneous dose distribution in spatially fractionated radiotherapy (SFRT) can make a drastic difference in tumor cell killing compared to the homogeneous dose distribution. SFRT cannot only enhance but also moderate the cell killing depending on the immune response triggered by many factors such as dose prescription parameters, tumor volume at the time of treatment and tumor characteristics. The model was applied to the lifted data of 67NR tumors on mice and a sarcoma patient treated multiple times over 1200 days for the treatment of tumor recurrence as a demonstration., (Creative Commons Attribution license.)

Background: Risk factors, including lymphatic, vascular, and perineural invasion, are considered indications for adjuvant treatment in stage II colon cancer. However, tumor budding is not included in the above risk factors., Objective: This study aimed to assess the value of tumor budding as a prognostic factor in stage II colon cancer., Design: This is a retrospective cohort study., Settings: This study was conducted in a tertiary referral center., Patients: This study examined 1390 patients with stage II colon cancer who received curative resection from 2007 to 2013 at an institution., Interventions: These patients were classified according to tumor budding status: low-grade tumor budding (less than 10 buds) and high-grade tumor budding (10 buds or more). Differences between the 2 groups were corrected by propensity score matching., Main Outcome Measures: Disease-free survival and overall survival were the primary end points., Results: Among 1390 patients, 146 (10.5%) had high-grade tumor budding. The high-grade tumor budding group showed adverse histological characteristics such as advanced T stage, histological grade of differentiation, and presence of lymphatic/perineural invasion. After matching, the 5-year disease-free survival rate for the high-grade tumor budding group was significantly lower than for the low-grade group. We also compared survival outcomes according to tumor budding grade for patients who did not have risk factors and did not receive adjuvant treatment. The 5-year overall survival was similar between the 2 groups. However, the 5-year disease-free survival decreased significantly in the high-grade tumor budding group than in the low-grade tumor budding group., Limitations: This was a retrospective study with a single-center design., Conclusions: High-grade tumor budding is a poor prognostic factor in stage II colon cancer and is considered one of the risk factors for adjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B962 ., Es La Gemacin Tumoral Un Factor Pronstico Independiente En El Cncer De Colon En Estadio Ii: ANTECEDENTES:Los factores de riesgo, incluida la invasión linfática/vascular/perineural, se consideran indicaciones para el tratamiento adyuvante en el cáncer de colon en estadio II. Sin embargo, la gemación tumoral (desdiferenciación tumoral aislada), no está incluida en los factores de riesgo anteriores.OBJETIVO:El objeto de este estudio fue evaluar el valor de la gemación tumoral como factor pronóstico en el cáncer de colon en estadio II.DISEÑO:Este es un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en un centro de referencia terciario.PACIENTES:Este estudio analizó 1390 pacientes con cáncer de colon en estadio II que recibieron una resección curativa entre 2007 y 2013 en una institución.INTERVENCIONES:Estos pacientes se clasificaron según el estado de gemación tumoral: gemación tumoral de bajo grado (<10 yemas) y gemación tumoral de alto grado (≥10 yemas). Las diferencias entre los dos grupos se corrigieron mediante el emparejamiento por puntaje de propensión.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia libre de enfermedad y la supervivencia global fueron los puntos finales primarios.RESULTADOS:Entre 1.390 pacientes, 146 (10,5%) tenían brotes tumorales de alto grado. El grupo de gemación tumoral de alto grado mostró características histológicas adversas como estadio T avanzado, grado histológico de diferenciación y presencia de invasión linfática/perineural. Después del emparejamiento, la tasa de supervivencia libre de enfermedad a cinco años para el grupo de brotes de tumores de alto grado fue significativamente menor que para el grupo de bajo grado. También comparamos los resultados de supervivencia según el grado de gemación del tumor para pacientes que no tenían factores de riesgo y que no recibieron tratamiento adyuvante. La supervivencia global a cinco años fue similar entre los dos grupos. Sin embargo, la supervivencia libre de enfermedad a cinco años disminuyó significativamente en el grupo de brotes de tumores de alto grado que en el grupo de brotes de tumores de bajo grado.LIMITACIONES:Este fue un estudio retrospectivo con un diseño de centro único.CONCLUSIÓNES:La gemación tumoral de alto grado es un factor de mal pronóstico en el cáncer de colon estadio II y se considera uno de los factores de riesgo para el tratamiento adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B962 . (Traducción-Dr. Ingrid Melo )., (Copyright © The ASCRS 2023.)

Background and Purpose: Brain radiotherapy (cnsRT) requires reproducible positioning and immobilization, attained through redundant dedicated imaging studies and a bespoke moulding session to create a thermoplastic mask (T-mask). Innovative approaches may improve the value of care. We prospectively deployed and assessed the performance of a patient-specific 3D-printed mask (3Dp-mask), generated solely from MR imaging, to replicate a reproducible positioning and tolerable immobilization for patients undergoing cnsRT., Material and Methods: Patients undergoing LINAC-based cnsRT (primary tumors or resected metastases) were enrolled into two arms: control (T-mask) and investigational (3Dp-mask). For the latter, an in-house designed 3Dp-mask was generated from MR images to recreate the head positioning during MR acquisition and allow coupling with the LINAC tabletop. Differences in inter-fraction motion were compared between both arms. Tolerability was assessed using patient-reported questionnaires at various time points., Results: Between January 2020 - July 2022, forty patients were enrolled (20 per arm). All participants completed the prescribed cnsRT and study evaluations. Average 3Dp-mask design and printing completion time was 36 h:50 min (range 12 h:56 min - 42 h:01 min). Inter-fraction motion analyses showed three-axis displacements comparable to the acceptable tolerance for the current standard-of-care. No differences in patient-reported tolerability were seen at baseline. During the last week of cnsRT, 3Dp-mask resulted in significantly lower facial and cervical discomfort and patients subjectively reported less pressure and confinement sensation when compared to the T-mask. No adverse events were observed., Conclusion: The proposed total inverse planning paradigm using a 3D-printed immobilization device is feasible and renders comparable inter-fraction performance while offering a better patient experience, potentially improving cnsRT workflows and its cost-effectiveness., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Antisense RNAs (asRNAs) are closely associated with cancer malignancy. This study aimed to identify the action mechanism of asRNAs in controlling CRC malignancy. Analysis of the RNA sequencing data revealed that AFAP1-AS1 and MLK7-AS1 were upregulated in CRC patients and cell lines. High levels of both asRNAs were associated with poor prognosis in patients with CRC. Both in vitro and in vivo experiments revealed that the knockdown of the two asRNAs decreased the proliferative and metastatic abilities of CRC cells. Mechanistically, AFAP1-AS1 and MLK7-AS1 decreased the levels of miR-149-5p and miR-485-5p by functioning as ceRNAs. Overexpression of miRNAs by introducing miRNA mimics suppressed the expression of SHMT2 and IGFBP5 by directly binding to the 3' UTR of their mRNA. Knockdown of both asRNAs decreased the expression of SHMT2 and IGFBP5, which was reversed by inhibition of both miRNAs by miRNA inhibitors. In vivo pharmacological targeting of both asRNAs by small interfering RNA-loaded nanoparticles showed that knockdown of asRNAs significantly reduced tumor growth and metastasis. Our findings demonstrate that AFAP1-AS1 and MLK7-AS1 promote CRC progression by sponging the tumor-suppressing miRNAs miR-149-5p and miR-485-5p, thus upregulating SHMT2 and IGFBP5., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)