Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer.

Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.

Stabilization of liquid instabilities with ionized gas jets.

Impinging gas jets can induce depressions in liquid surfaces, a phenomenon familiar to anyone who has observed the cavity produced by blowing air through a straw directly above a cup of juice. A dimple-like stable cavity on a liquid surface forms owing to the balance of forces among the gas jet impingement, gravity and surface tension1,2. With increasing gas jet speed, the cavity becomes unstable and shows oscillatory motion, bubbling (Rayleigh instability) and splashing (Kelvin-Helmholtz instability)3,4. However, despite its scientific and practical importance-particularly in regard to reducing cavity instability growth in certain gas-blown systems-little attention has been given to the hydrodynamic stability of a cavity in such gas-liquid systems so far. Here we demonstrate the stabilization of such instabilities by weakly ionized gas for the case of a gas jet impinging on water, based on shadowgraph experiments and computational two-phase fluid and plasma modelling. We focus on the interfacial dynamics relevant to electrohydrodynamic (EHD) gas flow, so-called electric wind, which is induced by the momentum transfer from accelerated charged particles to neutral gas under an electric field. A weakly ionized gas jet consisting of periodic pulsed ionization waves5, called plasma bullets, exerts more force via electrohydrodynamic flow on the water surface than a neutral gas jet alone, resulting in cavity expansion without destabilization. Furthermore, both the bidirectional electrohydrodynamic gas flow and electric field parallel to the gas-water interface produced by plasma interacting 'in the cavity' render the surface more stable. This case study demonstrates the dynamics of liquids subjected to a plasma-induced force, offering insights into physical processes and revealing an interdependence between weakly ionized gases and deformable dielectric matter, including plasma-liquid systems.

Association between placental oxygen transport and fetal brain cortical development: a study in monochorionic diamniotic twins.

Normal cortical growth and the resulting folding patterns are crucial for normal brain function. Although cortical development is largely influenced by genetic factors, environmental factors in fetal life can modify the gene expression associated with brain development. As the placenta plays a vital role in shaping the fetal environment, affecting fetal growth through the exchange of oxygen and nutrients, placental oxygen transport might be one of the environmental factors that also affect early human cortical growth. In this study, we aimed to assess the placental oxygen transport during maternal hyperoxia and its impact on fetal brain development using MRI in identical twins to control for genetic and maternal factors. We enrolled 9 pregnant subjects with monochorionic diamniotic twins (30.03 ± 2.39 gestational weeks [mean ± SD]). We observed that the fetuses with slower placental oxygen delivery had reduced volumetric and surface growth of the cerebral cortex. Moreover, when the difference between placenta oxygen delivery increased between the twin pairs, sulcal folding patterns were more divergent. Thus, there is a significant relationship between placental oxygen transport and fetal brain cortical growth and folding in monochorionic twins.

Polygenic risk score model for renal cell carcinoma in the Korean population and relationship with lifestyle-associated factors.

BACKGROUND: The polygenic risk score (PRS) is used to predict the risk of developing common complex diseases or cancers using genetic markers. Although PRS is used in clinical practice to predict breast cancer risk, it is more accurate for Europeans than for non-Europeans because of the sample size of training genome-wide association studies (GWAS). To address this disparity, we constructed a PRS model for predicting the risk of renal cell carcinoma (RCC) in the Korean population. RESULTS: Using GWAS analysis, we identified 43 Korean-specific variants and calculated the PRS. Subsequent to plotting receiver operating characteristic (ROC) curves, we selected the 31 best-performing variants to construct an optimal PRS model. The resultant PRS model with 31 variants demonstrated a prediction rate of 77.4%. The pathway analysis indicated that the identified non-coding variants are involved in regulating the expression of genes related to cancer initiation and progression. Notably, favorable lifestyle habits, such as avoiding tobacco and alcohol, mitigated the risk of RCC across PRS strata expressing genetic risk. CONCLUSION: A Korean-specific PRS model was established to predict the risk of RCC in the underrepresented Korean population. Our findings suggest that lifestyle-associated factors influencing RCC risk are associated with acquired risk factors indirectly through epigenetic modification, even among individuals in the higher PRS category.

Predictive Synthesis of Transition Metal Carbide via Thermochemical Oxocarbon Equilibrium.

Fabricating nanoscale metal carbides is a great challenge due to them having higher Gibbs free energy of formation (ΔG°) values than other metal compounds; additionally, these carbides have harsh calcination conditions, in which metal oxidation is preferred in the atmosphere. Herein, we report oxocarbon-mediated calcination for the predictive synthesis of nanoscale metal carbides. The thermochemical oxocarbon equilibrium of CO-CO2 reactions was utilized to control the selective redox reactions in multiatomic systems of Mo-C-O, contributing to the phase-forming and structuring of Mo compounds. By harnessing the thermodynamically predicted processing window, we controlled a wide range of Mo phases (MoO2, α-MoC1-x, and ß-Mo2C) and nanostructures (nanoparticle, spike, stain, and core/shell) in the Mo compounds/C nanofibers. By inducing simultaneous reactions of C-O (selective C combustion) and Mo-C (Mo carbide formation) in the nanofibers, Mo diffusion was controlled in C nanofibers, acting as a template for the nucleation and growth of Mo carbides and resulting in precise control of the phases and structures of Mo compounds. The formation mechanism of nanostructured Mo carbides was elucidated according to the CO fractions of CO-CO2 calcination. Moreover, tungsten (W) and niobium (Nb) carbides/C nanofibers have been successfully synthesized by CO-CO2 calcination. We constructed the thermodynamic map for the predictive synthesis of transition metal carbides to provide universal guideline via thermochemical oxocarbon equilibrium. We revealed that our thermochemical oxocarbon-mediated gas-solid reaction enabled the structure and phase control of nanoscale transition metal compounds to optimize the material-property relationship accordingly.

The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation.

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.

Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice.

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption.

Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression.

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1-50%, 51-99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82-0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1-50%, 51-99%, and 100% were 0.85 (0.68-1.07), 0.76 (0.60-0.96), and 0.72 (0.55-0.94), and the respective corresponding slopes of eGFR decline were -3.17 (-3.66 to -2.69), -3.02 (-3.35 to -2.68), -2.62 (-2.89 to - 2.36), and -2.33 (-2.62 to -2.04) ml/min/1.73 m2. Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

Association between epidermal growth factor receptor-tyrosine kinase inhibitors and venous thromboembolism among older patients with advanced non-small cell lung cancer.

BACKGROUND: Venous thromboembolism (VTE) risk is higher among patients with non-small cell lung cancer (NSCLC) and specific subgroups, including the elderly, but little is known about the VTE risk of different generations of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and whether the risk differs by demographic characteristics. This study aims to compare the risk of VTE (deep venous thromboembolism [DVT]; pulmonary embolism [PE]) between a third-generation EGFR-TKI and first/second-generation EGFR-TKIs and stratify VTE risk by sex, age, and race/ethnicity in third-generation EGFR-TKI users. METHODS: Via the 2006-2019 Surveillance, Epidemiology, and End Results-Medicare database, this retrospective cohort study included older patients (aged ≥65 years) with advanced NSCLC who initiated on a third-generation EGFR-TKI (n = 493) and first/second-generation EGFR-TKIs (n = 1036). We estimated the hazard ratio (HR) and its 95% confidence interval (95% CI) with the Cox proportional hazards model. RESULTS: A third-generation EGFR-TKI had a significantly higher VTE risk than first/second-generation EGFR-TKIs (HR, 1.26 [95% CI, 1.01-1.57]; p = .037), with an elevated risk in males (HR, 2.16 [95% CI, 1.47-3.19]; p < .001), patients aged ≥75 years (HR, 1.38 [95% CI, 1.04-1.83]; p = .026), and non-Hispanic Whites (HR, 1.46 [95% CI, 1.10-1.95]; p = .010). Males consistently showed a significantly higher risk of DVT (HR, 2.49 [95% CI, 1.29-4.80]; p = .007) and PE (HR, 2.00 [95% CI, 1.29-3.11]; p = .002). A significantly higher risk of DVT (HR, 1.54 [95% CI, 1.00-2.37]; p = .050) and PE (HR, 1.47 [95% CI, 1.06-2.05]; p = .021) was shown in patients aged ≥75 years and non-Hispanic Whites, respectively. Among third-generation EGFR-TKI users, non-Hispanic Whites had a significantly higher risk of VTE (HR, 2.04 [95% CI, 1.03-4.02]; p = .041) and PE (HR, 2.88 [95% CI, 1.24-6.70]; p = .014) than non-Hispanic Asian/Pacific Islanders. CONCLUSIONS: Close monitoring of VTE events in high-risk patients is essential to promote early diagnosis and treatment.

Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets.

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

Donor fat-to-muscle ratio and kidney transplant outcomes: A proposition of metabolic memory.

AIMS: The impact of donor abdominal fat-to-muscle ratio (FMR) on kidney transplant (KT) outcomes was assessed. Given the transient nature of the donor's metabolic environment in transplant recipients, this study investigated the capacity of body composition to induce metabolic memory effects. MATERIALS AND METHODS: KT patients (n = 895) who received allografts from living donors (2003-2013) were included. Donor fat and muscle were quantified using pre-KT abdominal computed tomography scans. Patients were categorised into donor FMR tertiles and followed up for graft outcomes. Additionally, genome-wide DNA methylation analysis was performed on 28 kidney graft samples from KT patients in the low- and high-FMR groups. RESULTS: Mean recipient age was 42.9 ± 11.4 years and 60.9% were males. Donor FMR averaged 1.67 ± 0.79. Over a median of 120.9 ± 42.5 months, graft failure (n = 127) and death-censored graft failure (n = 109) were more frequent in the higher FMR tertiles. Adjusted hazard ratios for the highest versus lowest FMR tertile were 1.71 (95% CI, 1.06-2.75) for overall graft failure and 1.90 (95% CI, 1.13-3.20) for death-censored graft failure. Genome-wide DNA methylation analysis identified 58 differentially methylated regions (p < 0.05, |Δß| > 0.2) and 35 genes showed differential methylation between the high- (FMR >1.91) and low-FMR (FMR <1.27) groups. CONCLUSIONS: Donors with increased fat and reduced muscle composition may negatively impact kidney allograft survival in recipients, possibly through the transmission of epigenetic changes, implying a body-composition-related metabolic memory effect.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Efficacy and safety of MC-003 solution for endoscopic mucosal or submucosal resection: a prospective, multicenter, randomized, triple-blinded, parallel-group, phase III study.

BACKGROUND AND AIMS: The safety and efficacy of solutions for submucosal injection are critical for endoscopic resection of gastric adenomas or early gastric cancers. Although several injectable solutions have been introduced for endoscopic resection, they have some limitations. We aimed to compare the efficacy of the new sodium alginate-based solution MC-003 with that of normal saline (NS; 0.9% sodium chloride). METHODS: In this randomized, triple-blind study, 70 patients were initially enrolled for EMR or endoscopic submucosal dissection (ESD). The main outcomes included the need for additional injections, completion of en bloc resection, and occurrence of adverse events. RESULTS: Each group ultimately included 34 patients. Complete en bloc resections were achieved in all patients (P = 1.000). The MC-003 group had more peri-neoplasm tissue fibrosis (P = .056) and needed fewer additional injections for lesions >15 mm (P = .037), located in the distal portion of the stomach (P = .007), and during ESD procedures (P = .001). The adverse event rate was comparable in both groups. CONCLUSIONS: MC-003 outperformed NS in reducing the need for additional injections during en bloc resection, particularly in larger lesions located in the distal portion of the stomach (where most lesions were found) during ESD procedures, without increasing the incidence of serious adverse events. MC-003 is a promising submucosal injectable solution in real-world clinical settings.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Altered development of structural MRI connectome hubs at near-term age in very and moderately preterm infants.

Preterm infants may exhibit altered developmental patterns of the brain structural network by endogenous and exogenous stimuli, which are quantifiable through hub and modular network topologies that develop in the third trimester. Although preterm brain networks can compensate for white matter microstructural abnormalities of core connections, less is known about how the network developmental characteristics of preterm infants differ from those of full-term infants. We identified 13 hubs and 4 modules and revealed subtle differences in edgewise connectivity and local network properties between 134 preterm and 76 full-term infants, identifying specific developmental patterns of the brain structural network in preterm infants. The modules of preterm infants showed an imbalanced composition. The edgewise connectivity in preterm infants showed significantly decreased long- and short-range connections and local network properties in the dorsal superior frontal gyrus. In contrast, the fusiform gyrus and several nonhub regions showed significantly increased wiring of short-range connections and local network properties. Our results suggested that decreased local network in the frontal lobe and excessive development in the occipital lobe may contribute to the understanding of brain developmental deviances in preterm infants.

Anticoagulants are a risk factor for delayed bleeding after colorectal endoscopic submucosal dissection: A HASID multicenter study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3 %). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Comparative evaluation of endoscopic anti-reflux mucosectomy and stretta radiofrequency ablation in the management of gastroesophageal reflux disease: insights from a retrospective multicenter cohort study.

BACKGROUND: Treatment options for gastroesophageal reflux disease (GERD) that is unresponsive to proton pump inhibitors (PPIs) remain limited. Therefore, we compared the therapeutic effects of anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for intractable GERD in over 400 individuals who underwent either procedure. METHODS: We conducted a retrospective study between 2016 and 2023 to evaluate the effectiveness of SRF and ARMS treatments for refractory GERD. The primary measure of success was the change in the GERD questionnaire (GERDQ) score. The secondary outcomes were various GERD-related indicators, including endoscopic Los Angeles (LA) classification, Hill's type-based flap valve grade (FVG), EndoFLIP™ distensibility index (DI), rate of PPI discontinuation, resolution rate of Barrett's esophagus, and incidence of adverse events. RESULTS: The ARMS group included patients with high GERDQ scores, FVG, LA grade, and Barrett's esophagus. Both groups had similar rates of improvements in GERDQ score (P = 0.884) and PPI withdrawal (P = 0.866); however, the ARMS group had significantly more side effects and improvements in the median change in GERDQ score (P = 0.011), FVG (P < 0.001), LA grade (P < 0.001), EndoFLIP™ DI (P < 0.001), and resolution of Barrett's esophagus (P < 0.001). CONCLUSIONS: The ARMS group had a greater GERDQ score improvement than the SRF group but had symptom relief and PPI discontinuation rates similar to those of the SRF group. However, objective measures, including EndoFLIP™ DI and endoscopic evaluations, were better in the ARMS group than in the SRF group.

Endoscopic resection and laparoscopic lymph node dissection for early gastric cancer beyond conventional endoscopic treatment indications: a 10-year outcome study.

BACKGROUND: Endoscopic full-thickness gastric resection (EFTGR) with laparoscopic regional lymph node dissection (LLND) and endoscopic submucosal dissection (ESD) with LLND have been investigated as treatment options for early gastric cancer beyond the absolute indications for ESD. However, comparative studies on the long-term outcomes of these procedures are lacking. This study aimed to analyze and compare the 10-year outcomes of both procedures in a real clinical setting. METHODS: Between January 2009 and December 2013, 28 and 37 patients diagnosed with EGC beyond the absolute indications for ESD were treated with EFTGR with LLND and ESD with LLND, respectively. In both procedures, the dye was injected into the tumor. However, after injection and LLND, EFTGR was performed immediately in the EFTGR with LLND group, whereas LLND was followed by ESD in the ESD with LLND group. The primary endpoint was the 10-year survival rate. RESULTS: The EFTGR with LLND group had one case of local recurrence (3.6%) and mortality (3.6%) each, while the ESD with LLND group had none (0.0% for both); however, the differences were not statistically significant (P = 0.247 for each). Furthermore, there was no significant difference in complications such as ischemia and anastomosis leakage between the groups (P = 0.247). CONCLUSIONS: When the procedures were properly applied, EFTGR with LLND and ESD with LLND did not increase the 10-year mortality in patients with EGC beyond the absolute ESD indications compared with conventional radical gastrectomy.