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Abstract The challenges associated with liquid biopsy of colorectal cancer (CRC) are closely linked to the substantial variations observed in gene expression profiles among patients. This variability complicates the selection of an ideal biomarker for accurate diagnosis. In this report, we propose that employing a combination of miRNAs offers a better change for enhancing the accuracy of CRC diagnosis compared to solely relying on single miRNAs. As an illustrative example, we measured 9 miRNAs from 45 patient samples (comprising 31 CRC cases and 14 healthy controls) via RT-qPCR. We then utilized two methods: (1) LASSO regression for marker ranking and (2) linear discriminant analysis (LDA) to identify the optimal weighted combination of multiple markers. Our data indicates that combination of triple markers, selected based on their ranking, exhibited the highest diagnostic performance, including a sensitivity of 93.6% (95% confidence interval, CI 79.3–98.9%), specificity of 100% (CI 78.5–100.0%), positive predictive value (PPV) of 100%, negative predictive value (NPV) of 87.5%, and an overall accuracy of 95.6%. In contrast, the diagnostic performance of each individual miRNA used in the triple marker combination ranged from 53.3 to 80.0% in accuracy. While we acknowledge the need for further extensive studies involving larger patient cohorts and the consideration of additional miRNA candidates, our research undeniably highlights the potential of combining multiple markers as a robust methodology for identifying biomarkers among heterogeneous patient profiles.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery.

Abstract Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing.

Abstract Background Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer. Methods/design Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate. Discussion Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial. Trial registration Clinical Research Information Service KCT0003523. Registered on February 18, 2019

Background The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC). Methods This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

Abstract We aimed to evaluate whether a short distal resection margin (

Abstract To efficiently prolong analgesic effects, we developed osmotically balanced, large unilamellar liposomes (~ 6 μm in diameter) in which highly concentrated bupivacaine (up to 30 mg/mL) was encapsulated, and their sustained bupivacaine release was highly effective in relieving postoperative pain over 24 h in a rat model. Our reverse-phase evaporation method based on non-toxic alcohol, ethanol, enabled simple and cost-effective production of bupivacaine-loaded liposomes, of which osmotic pressure was readily balanced to improve the structural stability of the enlarged unilamellar liposomes along with extension of their shelf life (> a month). The in vitro release profile verified that the release duration of the bupivacaine-loaded liposomes extended up to 6 days. For the in vivo study, male Sprague–Dawley rats were used for the incisional pain model, simulating postoperative pain, and the mechanical withdrawal threshold (MWT) was measured using a von Frey filament. Compared to the control group that received intraplantar administration of normal saline, the group of liposomal bupivacaine showed that the initially increased MWT gradually decreased up to 24 h, and importantly, the analgesic effect of the liposomal bupivacaine was maintained 6 times longer than that of bupivacaine only, proving the potential of effective long-acting anesthetics.

Background/Aims Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their clinical significance in UC. Methods We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC. Results To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval [CI] 2.944–11.339; area under the curve [AUC] 0.774, 95% CI, 0.690–0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821–7.838; AUC 0.654, 95% CI 0.556–0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 µg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio. Conclusions NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions.

Mineral wool is an insulation material commonly used in passive fire protection (PFP) systems on offshore installations. Insulation materials have only been considered functional materials for thermal analysis in the conventional offshore PFP system design method. Hence, the structural performance of insulation has yet to be considered in the design of PFP systems. However, the structural elements of offshore PFP systems are often designed with excessive dimensions to satisfy structural requirements under external loads such as wind, fire and explosive pressure. To verify the structural contribution of insulation material, it was considered a structural material in this study. A series of material tensile tests was undertaken with two types of mineral wool at room temperature and at elevated temperatures for fire conditions. The mechanical properties were then verified with modified methods, and a database was constructed for application in a series of nonlinear structural and thermal finite-element analyses of an offshore bulkhead-type PFP system. Numerical analyses were performed with a conventional model without insulation and with a new suggested model with insulation. These analyses showed the structural contribution of the insulation in the structural behaviour of the PFP panel. The results suggest the need to consider the structural strength of the insulation material in PFP systems during the structural design step for offshore installations.

Abstract Background The introduction of complete mesocolic excision (CME) with central vascular ligation (CVL) for right-sided colon cancer has improved the oncologic outcomes. Recently, we have introduced a modified CME (mCME) procedure that keeps the same principles as the originally described CME but with a more tailored approach. Some retrospective studies have reported the favourable oncologic outcomes of laparoscopic mCME for right-sided colon cancer; however, no prospective multicentre study has yet been conducted. Methods This study is a multi-institutional, prospective, single-arm study evaluating the oncologic outcomes of laparoscopic mCME for adenocarcinoma arising from the right side of the colon. A total of 250 patients will be recruited from five tertiary referral centres in South Korea. The primary outcome of this study is 3-year disease-free survival. Secondary outcome measures include 3-year overall survival, incidence of surgical complications, completeness of mCME, and distribution of metastatic lymph nodes. The quality of laparoscopic mCME will be assessed on the basis of photographs of the surgical specimen and the operation field after the completion of lymph node dissection. Discussion This is a prospective multicentre study to evaluate the oncologic outcomes of laparoscopic mCME for right-sided colon cancer. To the best of our knowledge, this will be the first study to prospectively and objectively assess the quality of laparoscopic mCME. The results will provide more evidence about oncologic outcomes with respect to the quality of laparoscopic mCME in right-sided colon cancer. Trial registration ClinicalTrials.gov ID: NCT03992599 (June 20, 2019). The posted information will be updated as needed to reflect protocol amendments and study progress.

Abstract Background With the increasing incidence of colorectal cancer (CRC), its accurate diagnosis is critical and in high demand. However, conventional methods are not ideal due to invasiveness and low accuracy. Herein, we aimed to identify efficient CRC mRNA markers in a non-invasive manner using CRC-derived extracellular vesicles (EVs). The expression levels of EV mRNAs from cancer cell lines were compared with those of a normal cell line using quantitative polymerase chain reaction. Eight markers were evaluated in plasma EVs from CRC patients and healthy controls. The diagnostic value of each marker, individually or in combination, was then determined using recessive operating characteristics analyses and the Mann-Whitney U test. Results Eight mRNA markers (MYC, VEGF, CDX2, CD133, CEA, CK19, EpCAM, and CD24) were found to be more abundant in EVs derived from cancer cell lines compared to control cell lines. A combination of VEGF and CD133 showed the highest sensitivity (100%), specificity (80%), and accuracy (93%) and an area under the curve of 0.96; hence, these markers were deemed to be the CRC signature. Moreover, this signature was found to be highly expressed in CRC-derived EVs compared to healthy controls. Conclusions VEGF and CD133 mRNAs comprise a unique CRC signature in EVs that has the potential to act as a novel, non-invasive, and accurate biomarker that would improve the current diagnostic platform for CRC, while also serving to strengthen the value of EV mRNA as diagnostic markers for myriad of diseases.

The west coast of South Korea is characterized by a wide macrotidal area with a maximum tidal range of ∼10 m. The sea surface elevation varies with the tidal phase, which leads to significant changes in the vertical structure of the physical, chemical, and biological properties of the water column, especially when the interaction by waves and/or the freshwater and sediment input from the river increases. Under such conditions, it is difficult to carry out continuous and consistent measurements of the vertical structures of the water qualities using a conventional observation system that is fixed to the seabed or sea surface because the thickness of the water column constantly changes. Based on the demand for long-term observations of the vertical structures of the water properties in macrotidal environments, the Intelligent Buoy System (INBUS) was developed by the Korea Institute of Ocean Science and Technology (KIOST). INBUS is a buoy equipped with an instrument frame, which is similar to other buoys that are fixed to the sea surface. During every measurement, INBUS detects the water depth and sends the frame down to the seabed to measure the water quality at every vertical level set up in the system. For example, if N levels are set in INBUS, the water depth of each measurement is divided by N layers and the instruments in the lifting frame measure the water properties of each of the N layers while they are descending to the bottom. Based on this procedure, the vertical structure of the water column is consistently measured in N layers regardless of changes of the water depth due to tides and waves. The lifting and measuring process is automatically controlled by INBUS once it is set up in the system. In addition, because INBUS allows bidirectional communication through code division multiple access (CDMA), the system can be controlled by stations on land. If the CDMA communication becomes inoperable owing to extreme wave conditions or the buoy is lost because of incidents such as a collision with a ship, the location of INBUS can be tracked by low-earth-orbit satellites.

Abstract Background Transversus abdominis plane (TAP) block and wound infiltration (WI) are common locoregional anesthesia techniques for pain management in patients undergoing colorectal laparoscopic surgery. Comparative data between these two practices are conflicting, and a clear benefit of TAP block over WI is still debated. The main purpose of this study is to determine the efficacy in pain control of WI compared with WI plus laparoscopic TAP block (L-TAP) in cases of laparoscopic colorectal resection. Secondary aims are to evaluate other short-term results directly related to pain management: the need for rescue analgesic drugs, the incidence of postoperative nausea and vomiting, the resumption of gut functions, and the length of hospital stay. Methods/design This is a prospective, randomized, controlled, two-arm, multicenter, single-blind study evaluating the efficacy of postoperative analgesic management of WI versus WI plus L-TAP in the context of laparoscopic colorectal surgery. Randomization is at the patient level, and participants are randomized 1:1 to receive either WI alone or WI plus L-TAP. Those eligible for inclusion were patients undergoing laparoscopic resection for colorectal tumor or diverticular disease at the Division of General and Hepatobiliary Surgery, Verona University, Verona, Italy, and at the Colorectal Cancer Center, Kyungpook National University, Daegu, Korea. Fifty-four patients are needed in each group to evidence a difference greater than 1 of 10 according to the numeric rating scale for pain assessment to establish that this difference would matter in practice. Discussion The demonstration of a noninferiority of WI compared with WI plus L-TAP block would call into question TAP block usefulness in the setting of laparoscopic colorectal surgery. Trial registration ClinicalTrials.gov, NCT03376048. Prospectively registered on 15 December 2017.

Localized surface plasmon resonance (LSPR) is a powerful platform for detecting biomolecules including proteins, nucleotides, and vesicles. Here, we report a colloidal gold (Au) nanoparticle-based assay that enhances the LSPR signal of nanoimprinted Au strips. The binding of the colloidal Au nanoparticle on the Au strip causes a red-shift of the LSPR extinction peak, enabling the detection of interleukin-10 (IL-10) cytokine. For LSPR sensor fabrication, we employed a roll-to-roll nanoimprinting process to create nanograting structures on polyethylene terephthalate (PET) film. By the angled deposition of Au on the PET film, we demonstrated a double-bent Au structure with a strong LSPR extinction peak at ~760 nm. Using the Au LSPR sensor, we developed an enzyme-linked immunosorbent assay (ELISA) protocol by forming a sandwich structure of IL-10 capture antibody/IL-10/IL-10 detection antibody. To enhance the LSPR signal, we introduced colloidal Au nanocube (AuNC) to be cross-linked with IL-10 detection antibody for immunogold assay. Using IL-10 as a model protein, we successfully achieved nanomolar sensitivity. We confirmed that the shift of the extinction peak was improved by 450% due to plasmon coupling between AuNC and Au strip. We expect that the AuNC-assisted LSPR sensor platform can be utilized as a diagnostic tool by providing convenient and fast detection of the LSPR signal.

Purpose Redo surgery in patients with a persistent anastomotic failure (PAF) is a rare procedure, and data about this procedure are lacking. This study aimed to evaluate the surgical outcomes of redo surgery in such patients. Methods Patients who underwent a redo anastomosis for PAF from January 2004 to November 2016 were retrospectively evaluated. Data from a prospective colorectal database were analyzed. Success was defined as the combined absence of any anastomosis-related complications and a stoma at the last follow-up. Results A total of 1,964 patients who underwent curative surgery for rectal cancer during this study period were included. Among them, 32 consecutive patients underwent a redo anastomosis for PAF. Thirteen patients of those 32 had major anastomotic dehiscence with a pelvic sinus, 12 had a recto-vaginal fistula, and 7 had anastomosis stenosis. There were no postoperative deaths. The median operation time was 255 minutes (range, 80–480 minutes), and the median blood loss was 80 mL (range, 30–1,000 mL). The overall success rate was 78.1%, and the morbidity rate was 40.6%. Multivariable analyses showed that the primary tumor height at the lower level was the only statistically significant risk factor for redo surgery (P = 0.042; hazard ratio, 2.444). Conclusion In our experience, a redo anastomosis is a feasible surgical option that allows closure of a stoma in nearly 80% of patients. Lower tumor height (

A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity. The patient was treated with a fluid infusion, and serum glucose level was controlled with insulin. The patient gradually recovered consciousness and was alert within 24 hours as serum glucose level normalized. The basal ganglion lesion caused by hyperglycemia was not accompanied by involuntary limb movement. This is the first report of a patient presenting with decreased consciousness and typical neural radiographic changes associated with nonketotic hyperglycemia but without movement abnormalities.

Background and Objective. Vitamin C has antioxidant, neuroprotective, and neuromodulating effects. Recently, it showed antinociceptive effect as a result of the antioxidant properties. Therefore, we designed this study to assess the effect of intravenous vitamin C on opiate consumption and pain in patients undergoing laparoscopic colectomy. Methods. A total of 100 patients were enrolled and allocated to receive 50 mg/kg vitamin C or placebo by intravenous infusion immediately after induction of anesthesia. Morphine consumption and scores of pain were assessed at 2, 6, and 24 h after completion of surgery. Results. There were 97 patients included in the analysis. Patients who received vitamin C had higher plasma concentrations of vitamin C at the end of surgery, significantly lower morphine consumption at the 2 h after end of surgery, and significantly lower pain scores at rest during first 24 h postoperatively. There was no significant difference between groups in side effects, fatigue score, or pain score during cough. Conclusion. This study shows high dose vitamin C infusion decreased postoperative pain during the first 24 h and reduced morphine consumption in the early postoperative period. Additional research needed to examine whether higher doses of vitamin C and longer infusion times can amplify these effects.

Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.

This article presents a novel passive direct binary amplitude modulator (AM) integrated with two frequency multipliers (FMs) and a drive amplifier. Both FMs are composed of a harmonic generator and a modified cascode buffer, along with an additional single-to-differential amplifier added in front of the first FM. The input frequency band (1.5-1.75 GHz) is up-converted to the intermediate frequency band of 4-5 GHz by the first FM, while the second FM up-converts the IF band to the target millimeter wave band of 24-28 GHz. Furthermore, the mm-wave amplitude is directly modulated by a capacitor ladder whose ratio is digitally programmable. This unique capacitor-ladder structure AM is employed to attain uniformly distributed constellation points and improve the output signal-to-noise ratio. The proposed modulator is fabricated on a 65-nm CMOS with a die size of 0.73 mm2. When applying the modulator to I/Q paths, 1.33% error vector magnitude for 256-QAM was measured at 26 GHz. [ABSTRACT FROM AUTHOR]

Systemic inflammatory response (SIR) is a crucial determinant of disease progression and survival in patients with colorectal cancer. This study investigated the prognostic relevance of changes in the platelet count on survival and the predictive value of changes in the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) on the pathological tumor response to preoperative chemoradiotherapy (CRT) in patients with microsatellite instability-high (MSI-H) rectal cancer. From 2011 to 2022, data of 46 consecutive patients with MSI-H rectal cancer who were treated with preoperative CRT followed by curative surgery at Kyungpook National University Chilgok Hospital (Daegu, South Korea) were retrospectively analyzed. A 235 cut-off value was used to define whether PLR was high or low. Any change in the PLR or NLR was calculated on the basis of subtracting the pre-CRT PLR or NLR from the post-CRT values. Both pre-CRT and post-CRT values of the NLR and PLR were not significantly associated with clinical outcomes. Simple logistic regression analysis showed that a change in the PLR following CRT was not significantly associated with survival out-comes; however, patients who maintained a high change in the PLR following CRT showed significantly better pathologic T-stage. No statistically significant association was noted between changes in the platelet count and clinical outcomes of patients. The results suggested that changes in the PLR following CRT are associated with pathologic T-stage of the group. However, the SIR markers showed no prognostic values on the survival outcomes of the patients with MSI-H/mismatch repair-deficient (dMMR) locally advanced rectal cancer (LARC). [ABSTRACT FROM AUTHOR]

Background: The modified complete mesocolic excision (mCME) procedure for right-sided colon cancer is a tailored approach based on the original complete mesocolic excision (CME) methodology. Limited studies evaluated the safety and feasibility of laparoscopic mCME using objective surgical quality assessments in patients with right colon cancer. The objectives of the PIONEER study were to evaluate oncologic outcomes after laparoscopic mCME and to identify optimal clinically relevant endpoints and values for standardizing laparoscopic right colon cancer surgery based on short-term outcomes of procedures performed by expert laparoscopic surgeons. Materials and methods: This is an ongoing prospective, multi-institutional, single-arm study conducted at five tertiary colorectal cancer centers in South Korea. Study registrants included 250 patients scheduled for laparoscopic mCME with right-sided colon adenocarcinoma (from the appendix to the proximal half of the transverse colon). The primary endpoint was 3-year disease-free survival. Secondary outcomes included 3-year overall survival, incidence of morbidity in the first 4 weeks postoperatively, completeness of mCME, central radicality, and distribution of metastatic lymph nodes. Survival data will be available after the final follow-up date (June 2024). Results: The postoperative complication rate was 12.9%, with a major complication rate of 2.7%. In 87% of patients, central radicality was achieved with dissection at or beyond the level of complete exposure of the superior mesenteric vein. Mesocolic plane resection with an intact mesocolon was achieved in 75.9% of patients, as assessed through photographs. Metastatic lymph node distribution varied by tumor location and extent. Seven optimal clinically relevant endpoints and values were identified based on the analysis of complications in low-risk patients. Conclusions: Laparoscopic mCME for right-sided colon cancer produced favorable short-term postoperative outcomes. The identified optimal clinically relevant endpoints and values can serve as a reference for evaluating surgical performance of this procedure. [ABSTRACT FROM AUTHOR]

Background/Aim: The present study compared the prognostic value of the yield pathologic (yp) stage, tumor regression grade (TRG), and neoadjuvant rectal (NAR) score in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT). Patients and Methods: For the assessment of tumor regression, the Dworak grading system was used. The NAR score was calculated using the following equation: (5ypN−3[cT−ypT]+12)2÷9.61. Results: In univariate analysis, the NAR score and ypTNM stage were significantly associated with DFS [hazard ratio (HR)=2.514, p<0.001 and HR=3.200, p<0.001] and OS (HR=2.292, p=0.001 and HR=2.859, p<0.001), whereas the TRG was significantly associated with only DFS (HR=2.008, p=0.017). In multivariate analysis, the ypTNM stage was the only independent prognostic factor for DFS (HR=3.796, p<0.001) and OS (HR=3.591, p=0.0034). Conclusion: Only the ypTNM stage was significantly associated with survival outcomes in multivariate analysis, suggesting that it is the most powerful prognostic factor of nCRT in patients with LARC. [ABSTRACT FROM AUTHOR]

Chronic mitral valve disease (CMVD) is the most common cardiovascular disease in dogs, causing decreased cardiac output that results in poor tissue perfusion and tissue damage to kidneys, pancreas, and other organs. The purpose of this study was to evaluate the relationships between heart disease severity and N-terminal pro B-type natriuretic peptide (NT-proBNP) and lipase in dogs with CMVD, as well as to evaluate longitudinal changes in these values. A total of 84 dogs participated in this 2015 to 2017 study. Serum values of NT-proBNP and lipase were analyzed; radiography was used to measure the vertebral heart score and assess various echocardiographic values. NT-proBNP showed a strong positive correlation with increasing stage of heart disease; lipase showed a mild positive correlation with heart disease stage. When the three values (NT-proBNP, lipase and month) were continuously measured at 6-month intervals, all showed a correlation with the increasing length of the disease. [ABSTRACT FROM AUTHOR]

FoxP3+ T regulatory (Treg) cells are central elements of immunologic tolerance. They are abundant in many tumors, where they restrict potentially favorable antitumor responses. We used a three-pronged strategy to identify genes related to the presence and function of Tregs in the tumor microenvironment. Gene expression profiles were generated from tumor-infiltrating Tregs (TITRs) of both human and mouse tumors and were compared with those of Tregs of lymphoid organs or normal tissues from the same individuals. A computational deconvolution of wholetumor datasets from the Cancer Genome Atlas (TCGA) was performed to identify transcripts specifically associated with Tregs across thousands of tumors from different stages and locations. We identified a set of TITR-differential transcripts with striking reproducibility between tumor types in mice, between mice and humans, and between different human patients spanning tumor stages. Many of the TITR-preferential transcripts were shared with "tissue Tregs" residing in nonlymphoid tissues, but a tumorpreferential segment could be identified. Many of these TITR signature transcripts were confirmed by mining of TCGA datasets, which also brought forth transcript modules likely representing the parenchymal attraction of, or response to, tumor Tregs. Importantly, the TITR signature included several genes encoding effective targets of tumor immunotherapy. A number of other targets were validated by CRISPR-based gene inactivation in mouse Tregs. These results confirm the validity of the signature, generating a wealth of leads for understanding the role of Tregs in tumor progression and identifying potential targets for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In an attempt to protect the earth in the era of climate change, effort has been put forth to restrict carbon emission globally. Although Korea is not one of the countries being obliged to reduce carbon emission specified in Kyoto Protocol, it has voluntarily implemented the emission trading scheme. In the midst of current situation 'low carbon', 'green growth' and paradigm are receiving global attention from the recent issue of climate change. This will provide a direction on understanding the emission trading of Korea in comparison with other developed countries, while determining the future direction of Korea's emission trading. However, studies and data on domestic and international emission trading are currently lacking. Therefore for the purpose of understanding the nature of emission trading of Korea and corresponding guidelines, this paper analyzed the characteristics of domestic and international emission trading through principal component analysis and cluster analysis. The findings will be useful in identifying emission trading of other countries similar to the position of Korea. The significance of this study was to use the findings to provide reliable reference information for improving emission trading. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to evaluate the efficacy of post-operative oral nutrition supplementation after major gastrointestinal surgery.Methods and Study Design: A prospective randomized controlled trial was conducted to evaluate 174 subjects who were discharged within 2 weeks after major gastrointestinal surgery. The subjects in the study group were prescribed 400 ml/day of Encover® from the day of discharge for 8 weeks, but no supplementation was allowed in the control group. The primary endpoint was the weight loss rate at 8 weeks after discharge compared with the pre-operative weight, and the secondary endpoints included changes in body weight, body mass index, Patient-Generated Subjective Global Assessment score/grade, hematological/ biochemical parameters, and adverse events evaluated at 2, 4, and 8 weeks after discharge.Results: The weight loss rate at 8 weeks after discharge did not differ between two groups (4.23±5.49% vs 4.80±4.84%, p=0.481). The total lymphocyte count, the level of total cholesterol, total protein, and albumin were significantly higher in the study group after discharge. Diarrhea was the most frequent adverse event, and the incidence of adverse events with a severity score of >=3 did not differ between groups (2.3% vs 1.2%).Conclusions: The utility of routine oral nutritional support after major gastrointestinal surgery was not proven in terms of weight loss at 8 weeks after discharge. However, it can be beneficial for early recovery of biochemical parameters. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare serum nitrotyrosine concentrations in healthy dogs with those in dogs with myxomatous mitral valve disease (MMVD). Fifty client-owned dogs were included in this study. Based on echocardiographic results, dogs were categorized into healthy (control), mild-, moderate-, and severe-MMVD groups. Serum nitrotyrosine concentrations were determined from enzyme-linked immunosorbent assays. No significant difference between control dogs and dogs with mild MMVD was detected (p = 0.31). However, dogs with moderate MMVD had significantly higher serum concentrations of nitrotyrosine (p = 0.04) than that in controls, and dogs with severe MMVD had significantly lower serum concentrations of nitrotyrosine (p = 0.03) than that in moderate MMVD dogs. There were negative correlations in the association of serum nitrotyrosine with age (n = 30, R2= 0.067, p = 0.27), left atrial-to-aortic root diameter ratio (n = 30, R2= 0.02, p = 0.57), and platelet count (n = 30, R2= 0.39, p = 0.003); however, only the platelet correlation was significant. Among dogs with MMVD, there was no significant difference in serum nitrotyrosine concentration between males and females. The results of this study suggest that tyrosine nitration end-products might be potential biomarkers for the detection of MMVD in dogs. [ABSTRACT FROM AUTHOR]

Here, we investigated the roles of YAL1 (FAA1) and FAT1 encoding acyl-CoA synthetases (ACSs) and three additional orthologs of ACS genes FAT2-FAT4 of the yeast Yarrowia lipolytica in the assimilation or utilization of n-alkanes and fatty acids. ACS deletion mutants were generated to characterize their function. The FAT1 deletion mutant exhibited decreased growth on n-alkanes of 10-18 carbons, whereas the FAA1 mutant showed growth reduction on n-alkane of 16 carbons. However, FAT2-FAT4 deletion mutants did not show any growth defects, suggesting that FAT1 and FAA1 are involved in the activation of fatty acids produced during the metabolism of n-alkanes. In contrast, deletions of FAA1 and FAT1-FAT4 conferred no defect in growth on fatty acids. The wild-type strain grew in the presence of cerulenin, an inhibitor of fatty acid synthesis, by utilizing exogenously added fatty acid or fatty acid derived from n-alkane when oleic acid or n-alkane of 18 carbons was supplemented. However, the FAA1 deletion mutant did not grow, indicating a critical role for FAA1 in the utilization of fatty acids. Fluorescent microscopic observation and biochemical analyses suggested that Fat1p is present in the peroxisome and Faa1p is localized in the cytosol and to membranes. [ABSTRACT FROM AUTHOR]

Background Recently, nonopioid-based treatment modalities have been used to improve analgesia and decrease opioid-related side effects after surgery. Transversus abdominis plane (TAP) block and local infiltration of the surgical wound are commonly used multimodal analgesia techniques after abdominal surgery; however, few studies have compared the effectiveness of a TAP block with that of local infiltration of surgical wounds in patients who have undergone laparoscopic colorectal surgery. Materials and methods Sixty patients undergoing laparoscopic colorectal surgery participated in this prospective comparative study. All patients were allocated to 1 of 2 groups as follows: the TAP group or the infiltration group. Patients in the TAP group received bilateral TAP blocks at the end of the surgery. Patients in the infiltration group received local infiltration of anesthetics in the surgical wounds after closure of the peritoneum. All patients received postoperative analgesia with morphine as a patient-controlled analgesia. Opioid consumption and pain scores were recorded at 2, 6, 24, and 48 h after the operation. Results The characteristics of patients in the TAP group (n = 30) and local infiltration group (n = 29) were comparable. Pain scores while coughing and at rest were not different between the two groups. Postoperative morphine use was significantly reduced in the TAP group compared with that in the local infiltration group at 2-6 h (2.9 ± 1.9 mg versus 4.5 ± 3.2 mg, P = 0.02), 6-24 h (5.5 ± 3.3 mg versus 10.2 ± 8.4 mg, P = 0.00), the first 24 h (16.6 ± 6.6 mg versus 24.0 ± 9.7 mg), and 48 h (23.6 ± 8.2 mg versus 31.8 ± 12.5 mg, P = 0.00). No differences in rescue analgesic use or side effects were noted between the groups. Conclusions Compared with local anesthetic infiltration, bilateral TAP blocks decreased the cumulative morphine use at 24 h and 48 h postoperatively in patients who had undergone laparoscopic colorectal surgery. [ABSTRACT FROM AUTHOR]

Background: Nerve-preserving surgery has been provided for patients with rectal cancer; however, sexual dysfunction remains a common complication of rectal cancer surgery. This study explored the efficacy of udenafil to treat erectile dysfunction in male patients who underwent total mesorectal excision (TME) for rectal cancer. Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial involving 80 male patients who had decreased International Index of Erectile Function-5 (IIEF-5) scores after TME for rectal cancer. Patients received placebo (50 mg) or udenafil (50 mg) for 12 weeks. The primary outcome variable was the change in IIEF-5 scores. The secondary outcome variables were Sexual Encounter Profile (SEP) questions 2 (Q2) and 3 (Q3), and the Global Assessment Question (GAQ). Results: Baseline IIEF-5 scores, SEP Q2 and Q3 responses, and spontaneous erection rates were consistent in both groups. At the end of treatment, the change in IIEF-5 scores from the baseline was significantly higher in the udenafil group than it was in the placebo group (mean IIEF-5 score, 4.8 ± 4.0 vs 2.0 ± 1.7; P < .05). Responses to SEP Q2, SEP Q3, and GAQ were significantly higher in the udenafil group than they were in the placebo group (SEP Q2, P = .025; SEP Q3, P = .044; GAQ, P < .001). Treatment-related adverse events (n = 4) were all mild in severity. Conclusion: Oral udenafil was deemed safe and effective for the treatment of erectile dysfunction in patients who underwent TME for rectal cancer. [ABSTRACT FROM AUTHOR]