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Background: This study compares the perioperative outcomes of robotic rectal cancer surgery between da Vinci single-port (SP) system, the most recent system allowing minimally invasive surgery with reduced ports, and the da Vinci Xi system. Methods: Patients who underwent robotic surgery for rectal adenocarcinoma from January 2016 to September 2023 at two tertiary referral centers were included. A retrospective analysis was conducted to compare key parameters between patient cohorts before and after propensity score matching. Results: A total of 378 patients (SP, 65 vs. Xi, 313) were analyzed. The SP group comprised a higher proportion of females (44.6% vs. 28.4%; p = 0.016) and a higher tumor location (8.25 cm vs. 6.71 cm from the anal verge; p < 0.001) than did the Xi group. SP surgery promoted a shorter total incision length (4.9 cm vs. 9.2 cm; p < 0.001), lower maximum pain scores (5 vs. 7; p < 0.001), and shorter hospital stay (6 vs. 7 days; p < 0.001) than did Xi surgery. Operation time (175 vs. 182 min; p = 0.829) and postoperative complications (9.2% vs. 12.1%; p = 0.650) did not significantly differ between the groups. Lower lying rectal tumors were more frequently treated using the Xi system than the SP system, promoting a higher diverting stoma rate (13.8% vs. 45.4%; p < 0.001) and a lower anastomosis level (4.6 cm vs. 3.3 cm; p < 0.001). After 1:1 matching, SP maintained its advantages over Xi in terms of incision length (p < 0.001), maximum pain scores (p = 0.001), and hospital stay (p < 0.001). Overall postoperative complication rates were similar between both groups (10.8% vs. 12.3%; p = 0.777). Conclusions: The da Vinci SP system continues to offer minimal invasive benefits in rectal cancer surgery. However, the Xi system's instrument diversity provides a certain advantage, particularly in cases involving low-lying rectal tumors. Tailoring robotic approaches based on individual patient characteristics remains pivotal for optimizing outcomes of rectal cancer surgery. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions. However, gut microbiome biomarkers for ICB response have been inconsistent across different studies. Here, we identify TANB77, an uncultured and distinct bacterial clade, as the most consistent responder-enriched taxon through meta-analysis of ten independent ICB recipient cohorts. Traditional taxonomy fails to distinguish TANB77 from unrelated taxa, leading to its oversight. Mice with higher gut TANB77 abundance, either naturally or through transplantation, show improved response to anti-PD-1 therapy. Additionally, mice injected with TANB77-derived pilin-like protein exhibit improved anti-PD-1 therapy response, providing in vivo evidence for the beneficial role of the pilin-like protein. These findings suggest that pilins from the TANB77 order may enhance responses to ICB therapy across diverse cohorts of cancer patients. Here, the authors show that higher levels of the gut bacterial clade TANB77 associate with better response to cancer immunotherapy, and further demonstrate in mice that a conserved pilin from TANB77 plays a role in enhancing immunotherapy efficacy, suggesting a potential therapeutic avenue. [ABSTRACT FROM AUTHOR]

mRNA therapeutics are set to revolutionize disease prevention and treatment, inspiring the development of platforms for safe and effective mRNA delivery. However, current mRNA delivery platforms face some challenges, including limited organ tropism for nonvaccine applications and inflammation induced by cationic nanoparticle components. Herein, we address these challenges through a versatile, noncationic nanoparticle platform whereby mRNA is assembled into a poly(ethylene glycol)-polyphenol network stabilized by metal ions. Screening a range of components and relative compositional ratios affords a library of stable, noncationic, and highly biocompatible metal–organic nanoparticles with robust mRNA transfection in vitro and in mice. Intravenous administration of the lead mRNA-containing metal–organic nanoparticles enables predominant protein expression and gene editing in the brain, liver, and kidney, while organ tropism is tuned by varying nanoparticle composition. This study opens an avenue for realizing metal–organic nanoparticle-enabled mRNA delivery, offering a modular approach to assembling mRNA therapeutics for health applications. Potential toxicity from cationic moieties and limited organ tropism are two challenges faced by current mRNA delivery vehicles. Here, authors develop non-cationic, highly biocompatible metal–organic nanoparticles that enable robust mRNA expression in vivo with tunable organ tropism. [ABSTRACT FROM AUTHOR]

Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC. [ABSTRACT FROM AUTHOR]

Oxide/Nitride/Oxide/Nitride (ONON; SiO2/SiNx/SiO2/SiNx) stacked structure is widely used in the 3D vertical structure of semiconductor cells. Previously, to form a 3D cells, photoresist (PR) was patterned and repeatedly trimmed on the top of ONON after the etching of one ON layer. Due to the time-consuming process of etching layer-by-layer of ON layer, two-step etch processing using C4F8-based or C4F6-based gases composed of maskless ONON stack feature etching and followed one ON layer-by layer etching by PR trimming in the ONON stack feature are employed these days. However, the two-step etching method resulted in poor etch profiles of maskless ONON stack feature in addition to high global warming potential of C4F8 and C4F6. In this study, we investigated the etching of maskless ONON stack feature using C4H2F6-based gas having a low global warming potential and the effects of C4H2F6-based gas on the etch characteristics of maskless ONON stack feature such as etch rate, etch profile, change in critical dimensional (CD), and etch selectivity between SiO2 and SiNx have been investigated. C4H2F6-based gas showed the highest etch rates compared to C4F6 and C4F8-based gases in addition to the etch selectivity of ~ 1:1 between SiO2 and SiNx due to hydrogen included in the gas structure. In addition, the change in horizontal CD was lower in the order of C4H2F6, C4F6, and C4F8-based gases due to the more effective sidewall passivation in the order of C4F8, C4F6, and C4H2F6-based gases. The thicker carbon-based polymer layer on the sidewall also played an important role in maintaining the shape of the top edge shape of maskless ONON stack feature when etching a line feature in an environment without a mask. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). Methods: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. Results: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). Conclusion: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia. [ABSTRACT FROM AUTHOR]

Printed-circuit type multi-stream heat exchanger was designed and fabricated to produce high-temperature steam and air simultaneously from high-temperature helium heated using the helium loop, which is simulating VHTR (Very-High Temperature gas-cooled Reactor). This study describes the design methodology and the heat transfer performance evaluation results of the multi-stream heat exchanger for stable supply of high temperature steam and air to a 30 kWe SOEC (solid-oxide electrolyzer cell) system to produce hydrogen with high-temperature nuclear reactor systems. In order to control the steam supply above 700 ℃, the steam supply control methodology was established with a pressure control valve between the multi-stream heat exchanger and a steam generator. In this study, 20 kg/hr of steam over 800 ℃ and 110 SLPM of air over 750 ℃ were supplied stably with the multi-stream heat exchanger using helium loop. The heat transfer performance evaluation for steam is 1.1% below the design condition, which meets the design value within the error range. However, for air, the heat transfer was found to be 50.6% less than the design value due to a decrease in flow rate and reduced heat transfer performance caused by the formation of a deposition layer along the flow path. This high-temperature steam and air supply system will be connected with a high-temperature steam electrolysis system to perform the integral hydrogen production test using helium loop. [ABSTRACT FROM AUTHOR]

Background: Since the introduction of powered circular staplers in colorectal surgery, there has been growing interest in their impact on reducing complications, particularly anastomotic leakage. This study compared short-term postoperative outcomes between powered and manual circular staplers. Methods: This retrospective study included colorectal cancer patients at the tertiary referral center from April to October 2023 who underwent anterior or low anterior resection (LAR) using a circular stapler. According to energy source, patients were divided into powered and manual groups, which used two powered and four types of manual staplers, respectively. All open, laparoscopic, and robotic approaches were included. Propensity score matching (PSM) analysis was used to reduce selection bias. Postoperative complications within 30 days, especially for anastomosis-related complications, were compared between the groups. Results: Among 511 patients, the powered group was 161 (32%). After PSM, 143 pairs of 286 patients were analyzed. The proportions of LAR were 53.8% and 51.0%, and initial diverting stoma rates were 23.1% and 22.4% for the Powered and Manual groups, respectively. Comprehensive complication rates were similar between the Powered group and the Manual group, without statistical significance (13.3% vs. 21.0%, P = 0.063). Anastomotic leakage was not different between the Powered and Manual groups (4.2% vs. 4.9%, P = 0.782). There was no significant difference in other complications, including anastomotic bleeding, ileus, surgical site infection, and intra-abdominal hematoma. Conclusions: The study implies that powered circular staplers may not significantly reduce postoperative complications, including anastomotic leakages, compared to manual staplers in colorectal surgery of high-volume centers. [ABSTRACT FROM AUTHOR]

Forging dies, which are crucial for manufacturing automobile tripod housings, are frequently replaced owing to their extensive use under challenging conditions, leading to the disposal of many components and increasing manufacturing costs. The development of repair and remanufacturing technologies for high-hardness forging dies is a challenging. This study explores the on-site repair of tripod forging dies using wire arc directed energy deposition (arc-DED), assesses the hardness and tensile properties of remanufactured components, and compares them with the specified forging die requirements for on-site usability. A validated novel slicer is employed in remanufacturing experiments on a 9.8 % Cr die steel tripod-forging die. Results show the effectiveness of arc-DED in remanufacturing, surpassing the specified requirements by at least 111 HV and 61 MPa in hardness and tensile strength, respectively. Thus, this study presents a promising approach to reduce the manufacturing costs and environmental impact associated with the forging-die-component disposal. [ABSTRACT FROM AUTHOR]

Activities and structures of metal oxide catalysts significantly rely on the synthesis procedures and conditions. In this study, a novel solvent-free mechanochemical method was employed to prepare catalysts for the ammoxidation of propylene. Multicomponent oxide catalysts containing bismuth, iron, cobalt, and molybdenum were successfully synthesized using a ball mill mixer and zirconia jars without the use of nitric acid. The mechanochemically synthesized catalysts exhibited higher catalytic performance than traditional catalysts prepared by coprecipitation (CP) and rotary evaporation (RE) methods in propylene ammoxidation. The synergistic effect of the mechanochemical method was investigated using various analyses, such as inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray diffraction (XRD), scanning electron microscopy, energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). ICP-AES analysis revealed that the ball-mill-based catalysts contained metal elements in designated amounts more accurately than those prepared by the CP or RE methods. Propylene ammoxidation reactions with ball-milled catalysts showed a synergistic effect and improved acrylonitrile yield, especially at a 50:50 wt% ratio of Bi2Mo3O12 to Fe0.36Co0.64MoO4. Comprehensive analyses, including XRD, SEM–EDS, Raman spectroscopy, and XPS, support the conclusion that the improved performance of the mechanochemically synthesized catalysts can be attributed to the increased interaction between different phases prepared under mechanical forces, leading to a favorable change in the oxidation state of iron. [ABSTRACT FROM AUTHOR]

Cyclic imines (CIs) produced by microalgal species that accumulate in the food chains of marine organisms are novel biotoxins that do not belong to the classic group of marine biotoxins. In the past, CIs were found only in limited areas; however, in recent years, rapid changes in marine ecosystems have led to widespread CIs and increased exposure to toxic risks. In this study, we analyzed seven CI toxins, GYM-A, SPX (13-desmethyl spirolide C, 13, 19-dideMe spirolide C, 20-methyl spirolide G), and PnTX-E, F, and G, using LC/MRM-MS. Shellfish samples were purchased from a domestic Korean fish market (67 samples in 2021 and 216 samples in 2022). The entire body of the shellfish was ground and extracted with 50% methanol, followed by lipophilic-specific SPE. Only GYM-A, PnTX-G, and 13-desmethyl spirolide C were detected in all analyzed samples. The maximum concentrations of GYM-A is maximum 179 ppt (ng/kg) in Crassostrea nippona (March 2022), PnTX-G is maximum 7 ppt in Anadara broughtonii (April 2022), 13-desmethyl SPX C is maximum 58 ppt in Crassostrea nippona (April 2022). The southern coast exhibited the highest frequency of detection of these toxins, which was attributed to elevated sea-surface temperatures, aligned with conducive conditions for toxin-producing phytoplankton. According to the monitoring results, there were no significant CI toxins in the shellfish; however, it is important to monitor CI toxin accumulation in shellfish because of their high risk of toxicity. [ABSTRACT FROM AUTHOR]

This study investigated the predictive factors for perinatal bacterial transmission in very-low-birth-weight infants (VLBWIs) born to mothers with a history of intrapartum colonization. We retrospectively reviewed the medical records of 173 VLBWIs, wherein pathogens were confirmed in maternal cultures obtained from the blood, urine, and vagina during the intrapartum period from 2013 to 2020. Newborns were categorized based on microbiological tests, including gastric aspirates, endotracheal aspirates, blood, and skin/nasal swab cultures collected immediately after birth. Infants whose cultures matched their maternal pathogens were categorized into the "transmission group" (n = 45), while those who tested negative were assigned to the "control group" (n = 128). The predominant maternal-colonizing pathogen observed was Escherichia coli (30.6%), which also emerged as the primary colonizing pathogen in neonates (35.6%). Transmission group had higher incidences of maternal leukocytosis, chorioamnionitis, and cervical cerclage. Regarding neonatal characteristics, the transmission group demonstrated lower initial base excesses (− 6.3 ± 3.9 vs. − 9.2 ± 4.9, P < 0.05) and higher C-reactive protein levels (0.1 ± 0.3 vs. 0.4 ± 0.8, P < 0.05). Notably, regarding major neonatal outcomes, transmission group had higher mortality rates and incidences of severe intraventricular hemorrhage. These findings may be useful for making decisions when considering antibiotic treatment for infants with a history of maternal colonization. [ABSTRACT FROM AUTHOR]

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system. The role of olfactory pathways in the development of neurodegeneration in Alzheimer's disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system. [ABSTRACT FROM AUTHOR]

Peritoneal metastases (PM) in colorectal cancer (CRC) is associated with a dismal prognosis. Identifying and exploiting new biomarkers, signatures, and molecular targets for personalised interventions in the treatment of PM in CRC is imperative. We conducted transcriptomic profiling using RNA-seq data generated from the primary tissues of 19 CRC patients with PM. Using our dataset established in a previous study, we identified 1422 differentially expressed genes compared to non-metastatic CRC. The profiling demonstrated no differential expression in liver and lung metastatic CRC. We selected 12 genes based on stringent criteria and evaluated their expression patterns in a validation cohort of 32 PM patients and 84 without PM using real-time reverse transcription-polymerase chain reaction. We selected cartilage intermediate layer protein 2 (CILP2) because of high mRNA expression in PM patients in our validation cohort and its association with a poor prognosis in The Cancer Genome Atlas. Kaplan–Meier survival analysis in our validation cohort demonstrated that CRC patients with high CILP2 expression had significantly poor survival outcomes. Knockdown of CILP2 significantly reduced the proliferation, colony-forming ability, invasiveness, and migratory capacity and downregulated the expression of molecules related to epithelial-mesenchymal transition in HCT116 cells. In an in vivo peritoneal dissemination mouse knockdown of CILP2 also inhibited CRC growth. Therefore, CILP2 is a promising biomarker for the prediction and treatment of PM in CRC. [ABSTRACT FROM AUTHOR]

Although mice are social, multiple animals’ neural activities are rarely explored. To characterise the neural activities during multi-brain interaction, we simultaneously recorded local field potentials (LFP) in the prefrontal cortex of four mice. The social context and locomotive states predominately modulated the entire LFP structure. The power of lower frequency bands—delta to alpha—were correlated with each other and anti-correlated with gamma power. The high-to-low-power ratio (HLR) provided a useful measure to understand LFP changes along the change of behavioural and locomotive states. The HLR during huddled conditions was lower than that during non-huddled conditions, dividing the social context into two. Multi-brain analyses of HLR indicated that the mice in the group displayed high cross-correlation. The mice in the group often showed unilateral precedence of HLR by Granger causality analysis, possibly comprising a hierarchical social structure. Overall, this study shows the importance of the social environment in brain dynamics and emphasises the simultaneous multi-brain recordings in social neuroscience. [ABSTRACT FROM AUTHOR]

Purpose: Although adrenal computed tomography (CT) percentage washout is a potentially powerful imaging technique for differentiating adrenal adenomas from non-adenomas, its application to non-adenomas can be problematic. Recently, modified criteria for diagnosing pheochromocytomas using adrenal CT were developed based on data from 199 patients with surgically proven pheochromocytomas and adenomas. However, these criteria have not been thoroughly validated. The purpose of this study was to validate the performance of the modified criteria for diagnosing non-adenomas including pheochromocytomas. Methods: The conventional and modified criteria were applied to 266 patients from two cohorts who had surgically proven lipid-poor adenomas (155/266, 58.3%) and non-adenomas (111/266, 41.7%) and underwent adrenal CT. Two radiologists calculated the attenuation on each dynamic phase and percentage washout of adrenal masses. The final assessments based on the conventional and modified criteria were categorized into adenomas or non-adenomas. The diagnostic performance of each criterion for diagnosing non-adenomas was evaluated using the area under the receiver operating characteristic curve (AUC). False negatives and positives were also compared. Results: The AUC for the diagnosis of non-adenomas was 0.806 for conventional criteria and 0.858 for modified criteria (p = 0.047). The false-negative rate of conventional criteria for the diagnosis of non-adenomas was 29.7%. Use of modified criteria could have reduced the false-negative rate by to 7.2%. The false-positive rate increased from 9% to 21.3% when using the modified criteria. Conclusion: The utilization of modified criteria has the potential to identify additional non-adenomas that would otherwise be misdiagnosed as adenomas using conventional criteria alone. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the baseline intraocular pressure (IOP)-related risk of severe steroid-induced ocular hypertension (SIOH). We hypothesized that the incidence and severity of SIOH may differ according to baseline IOP in patients who received intravitreal dexamethasone implants. Methods: A total of 889 eyes treated with intravitreal dexamethasone implants and a baseline IOP of ≤ 23 mmHg were enrolled. Enrolled patients were divided into two groups: the steroid-responders (127 eyes) and the non-steroid-responders (762 eyes). The steroid-responders group was subdivided into post-injection IOP of ≥ 25, > 30, or > 35 mmHg or IOP elevation of ≥ 10 mmHg over the baseline value. The odds ratio of SIOH was calculated using univariable logistic regression analysis, and significant variables were analyzed with a multivariable model. IOP was measured before (baseline IOP) and after dexamethasone implant injection at 1 week and 1, 2, 3, 6, and 12 months. Results: Although baseline IOP was significantly associated with the development of SIOH in logistic regression analysis, the results from the subgroup analysis differed. In the group with IOP elevation of ≥ 10 mmHg over the baseline, SIOH was not significantly associated with baseline IOP, but it was significantly related to higher baseline IOP in the severe SIOH group (IOP > 30 and > 35 mmHg). Conclusions: Higher baseline IOP is a risk factor for severe SIOH. Clinicians should be aware of the risk of SIOH when administering steroids intravitreally to patients with high baseline IOP (IOP > 19 mmHg). [ABSTRACT FROM AUTHOR]

Background: An anastomotic stricture after colorectal surgery is principally managed by endoscopic balloon dilation (EBD). Although this intervention is effective, however, subsequent procedures or surgical interventions are often required. This study aimed to assess the long-term outcomes of EBD for anastomotic stricture arising from colorectal cancer surgery. Materials and methods: We analyzed 173 patients who received curative surgery for colorectal cancer at our hospital between January 2000 and December 2022 and had undergone EBD to manage anastomotic stricture. The medical records of these cases were retrospectively reviewed to assess the outcomes and risk factors for restenosis and permanent stoma. Results: Of the 173 study patients, 41 (23.7%) presented with restenosis with a median time to recurrence of 49 [37–150] days. The restenosis group was significantly younger (55.6 years versus 60.8 years), with a more prominent rectal location (80.5% versus 57.6%), a higher incidence of hand-sewn anastomosis (24.4% versus 5.3%), and a higher percentage of neoadjuvant radiotherapy (34.1% versus 5.3%, P < 0.001). Multivariable analysis indicated neoadjuvant radiotherapy (adjusted HR 2.48; 95% CI 1.03–5.95) and cerebral vascular disease (adjusted HR 6.97; 95% CI 2.15–22.54) as independent prognostic factors for restenosis. Fourteen patients (8.1%) required a permanent stoma due to treatment failure. All cases needing a permanent stoma were male (14 patients, 100%, P = 0.007) and this group had a higher rate of neoadjuvant radiotherapy, adjuvant chemotherapy, and hand-sewn anastomosis. Conclusion: Patients receiving neoadjuvant radiotherapy are most prone to restenosis after an EBD intervention to manage an anastomotic stricture. Neoadjuvant radiotherapy is also a strong risk factor for requiring a permanent stomas due to treatment failure. [ABSTRACT FROM AUTHOR]

To determine the sources and pathways of lead (Pb) and zinc (Zn) in river sediments contaminated with metals from mining and smelting activities, metal concentrations and Pb and Zn isotope ratios were measured in river water and sediment, and potential metal contaminant samples (imported Zn concentrates, smelting wastes, soils around the smelter, mine ores, and riverside tailings). Zn and cadmium (Cd) concentrations in river water and sediment samples were 30- and 11–25-fold higher, respectively, near the smelter than upstream, while a 6-fold increase in sediment Pb concentrations was detected over the same region. Sediment samples near the smelter (207Pb/206Pb = 0.8638 and 208Pb/206Pb = 2.0960) were observed to have a different Pb isotopic composition from upstream of the smelter (207Pb/206Pb = 0.8322 and 208Pb/206Pb = 2.0502), with δ66Zn values increasing from –0.01 to 0.82‰. Analysis of Pb and Zn isotopes and concentrations revealed that dust-contaminated soils were a major Pb source, and baseline sediments were found to be contaminated by regional mining tailings. For Zn in sediments, the main Zn sources were groundwater-derived Zn (δ66Zn = 1.02 ± 0.43‰, n = 4), dust-contaminated soils (δ66Zn = –0.18 ± 0.08‰, n = 3), and tailings-contaminated sediments (δ66Zn = 0.01 ± 0.07‰, n = 10). Endmember mixing model results showed that dust-contaminated soils contributed 78% and 64% of sediment Pb and Zn, respectively, within 2 km of the Zn smelter, decreasing to negligible levels after 47.1 km downstream. Downstream of the smelter, groundwater-derived Zn contributed 54% of sediment Zn, whereas tailings contaminated sediments contributed 70% and 25% of Pb and Zn, respectively. [ABSTRACT FROM AUTHOR]

The CRISPR-Cas nickase system for genome editing has attracted considerable attention owing to its safety, efficiency, and versatility. Although alternative effectors to Cas9 have the potential to expand the scope of genome editing, their application has not been optimized. Herein, we used an enhanced CRISPR-Cas12a nickase system to induce mutations by targeting genes in a human-derived cell line. The optimized CRISPR-Cas12a nickase system effectively introduced mutations into target genes under a specific directionality and distance between nickases. In particular, the single-mode Cas12a nickase system can induce the target-specific mutations with less DNA double-strand breaks. By inducing mutations in the Thymine-rich target genes in single- or dual-mode, Cas12a nickase compensates the limitations of Cas9 nickase and is expected to contribute to the development of future genome editing technologies. [ABSTRACT FROM AUTHOR]

In this work, we study the jetting dynamics of individual cavitation bubbles using x-ray holographic imaging and high-speed optical shadowgraphy. The bubbles are induced by a focused infrared laser pulse in water near the surface of a flat, circular glass plate, and later probed with ultrashort x-ray pulses produced by an x-ray free-electron laser (XFEL). The holographic imaging can reveal essential information of the bubble interior that would otherwise not be accessible in the optical regime due to obscuration or diffraction. The influence of asymmetric boundary conditions on the jet's characteristics is analysed for cases where the axial symmetry is perturbed and curved liquid filaments can form inside the cavity. The x-ray images demonstrate that when oblique jets impact the rigid boundary, they produce a non-axisymmetric splash which grows from a moving stagnation point. Additionally, the images reveal the formation of complex gas/liquid structures inside the jetting bubbles that are invisible to standard optical microscopy. The experimental results are analysed with the assistance of full three-dimensional numerical simulations of the Navier–Stokes equations in their compressible formulation, which allow a deeper understanding of the distinctive features observed in the x-ray holographic images. In particular, the effects of varying the dimensionless stand-off distances measured from the initial bubble location to the surface of the solid plate and also to its nearest edge are addressed using both experiments and simulations. A relation between the jet tilting angle and the dimensionless bubble position asymmetry is derived. The present study provides new insights into bubble jetting and demonstrates the potential of x-ray holography for future investigations in this field. [ABSTRACT FROM AUTHOR]

X-ray Free Electron Lasers (XFEL) are cutting-edge pulsed x-ray sources, whose extraordinary pulse parameters promise to unlock unique applications. Several new methods have been developed at XFELs; however, no methods are known, which allow ab initio atomic level structure determination using only a single XFEL pulse. Here, we present experimental results, demonstrating the determination of the 3D atomic structure from data obtained during a single 25 fs XFEL pulse. Parallel measurement of hundreds of Bragg reflections was done by collecting Kossel line patterns of GaAs and GaP. To the best of our knowledge with these measurements, we reached the ultimate temporal limit of the x-ray structure solution possible today. These measurements open the way for obtaining crystalline structures during non-repeatable fast processes, such as structural transformations. For example, the atomic structure of matter at extremely non-ambient conditions or transient structures formed in irreversible physical, chemical, or biological processes may be captured in a single shot measurement during the transformation. It would also facilitate time resolved pump-probe structural studies making them significantly shorter than traditional serial crystallography. X-ray Free Electron Lasers allow fast structure determination. Here, the authors push the temporal limit of atomic level structure determination to 25 fs, the length of a single pulse, paving the way to the study of fast, non-repeatable processes. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111–0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198–0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT. [ABSTRACT FROM AUTHOR]

Purpose: To investigate computed tomography (CT)-based prediction model for identifying patients with high probability of non-muscle-invasive bladder cancer (NMIBC). Methods: This retrospective study evaluated 147 consecutive patients who underwent contrast-enhanced CT and surgery for bladder cancer. Using corticomedullary-to-portal venous phase images, two independent readers analyzed bladder muscle invasion, tumor stalk, and tumor size, respectively. Three-point scale (i.e., from 0 to 2) was applied for assessing the suspicion degree of muscle invasion or tumor stalk. A multivariate prediction model using the CT parameters for achieving high positive predictive value (PPV) for NMIBC was investigated. The PPVs from raw data or 1000 bootstrap resampling and inter-reader agreement using Gwet's AC1 were analyzed, respectively. Results: Proportion of patients with NMIBC was 81.0% (119/147). The CT criteria of the prediction model were as follows: (a) muscle invasion score < 2; (b) tumor stalk score > 0; and (c) tumor size < 3 cm. From the raw data, PPV of the model for NMIBC was 92.7% (51/55; 95% confidence interval [CI] 82.4–98.0) in reader 1 and 93.3% (42/45; 95% CI 81.7–98.6) in reader 2. From the bootstrap data, PPV was 92.8% (95% CI 85.2–98.3) in reader 1 and 93.4% (95% CI 84.9–99.9) in reader 2. The model's AC1 was 0.753 (95% CI 0.647–0.859). Conclusion: The current CT-derived prediction model demonstrated high PPV for identifying patients with NMIBC. Depending on CT findings, approximately 30% of patients with bladder cancer may have a low need for additional MRI for interpreting vesical imaging-reporting and data system. [ABSTRACT FROM AUTHOR]

We give a proof of a soft version of the p-converse to a theorem of Gross–Zagier and Kolyvagin for non-CM elliptic curves with good ordinary reduction at p > 3 under the irreducibility assumption on the residual representation. In particular, no condition on the conductor is imposed. Combining with the known results, we obtain the equivalence for every elliptic curve E over Q . [ABSTRACT FROM AUTHOR]

This multi-phase study designed a program evaluation rubric which used a qualitative rating system to help teachers identify key learning goals, dimensions, and principles related to the socio-scientific issues (SSI)-based science, technology, engineering, arts and mathematics (STEAM) approach for science education. This rubric contains 37 criteria that address one or more key principles of the SSI-based STEAM approach embedded in a 6E inquiry-based instructional model. It is organised into seven evaluation categories: (1) learning outcomes, (2) engage, (3) explain, (4) explore, (5) elaborate, (6) evaluate, and (7) enact. The newly developed rubric was used to evaluate six different climate change programs to determine whether it could measure the intended dimensions and principles and to assess its applicability across varying contexts. This research has implications for providing a tool for teachers to plan and design SSI-based STEAM programs. [ABSTRACT FROM AUTHOR]

Recent advancements in robotic systems have led to the introduction of the da Vinci SP system, which allows surgeons to perform colon cancer surgery through fewer ports. This study aimed to evaluate the perioperative outcomes of colon cancer surgeries conducted using the da Vinci SP and Xi systems. Patients who underwent robotic colon cancer surgeries between November 2020 and December 2022 at two tertiary referral centers were considered for inclusion. Following propensity-score matching, short-term outcomes between the two systems were retrospectively analyzed. Out of 189 patients included in the study, 106 from 53 propensity-score matched pairs were analyzed. Patients operated on with the SP system exhibited smaller incision lengths (5.0 cm vs. 9.4 cm, p < 0.001) experienced less pain at 8 h (3.0 vs. 3.5, p < 0.001) and at 24 h post-operation (2.9 vs. 3.3, p = 0.001) and had a shorter duration of hospital stay (5 days vs. 6 days, p = 0.002). The overall rate of postoperative complications was 10.4%, with no significant difference between the SP and Xi groups (7.5% vs. 13.2%). Robotic-assisted colon cancer surgery using the da Vinci SP system is feasible and demonstrates favorable short-term outcomes. Compared to the Xi system, the SP system offers advantages in terms of cosmesis, postoperative pain, and recovery duration for colon cancer patients. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophage (TAM) imaging is critical to provide greater insight into cancer diagnosis and treatment, but current strategies to accomplish this are often inadequate. In this study, we prepared a TAM imaging probe by conjugating self-assembled dextran-sulfate nanoparticles (DSNPs) with a near-infrared (NIR) dye, Flamma® 675 (FPR675). The FPR675-labeled DSNPs showed a spherical shape with a hydrodynamic size of 188 nm in the aqueous condition. Interestingly, exhibiting selective cellular uptake behavior mediated by macrophage scavenger receptor class A (SR-A), the FPR675-labeled DSNPs were shown to discriminate between cancer cells and macrophages and were preferentially taken up by TAMs. Furthermore, biocompatible FPR675-labeled DSNPs are favorable for whole-body NIR imaging. When systemically administered into tumor-bearing mice, these nanoprobes effectively accumulated in the tumor site. In immunohistochemistry, we also found that the SR-A-mediated targeting mechanism of the nanoprobes allowed for a robust visualization of TAMs present in the tumor microenvironment. Overall, these findings suggest that DS-based nanoprobes hold the potential for significant breakthroughs in the context of cancer theragnostics for TAM targeting. We developed biocompatible dextran-sulfate nanoparticles to evaluate the presence of tumor-associated macrophages (TAMs) in the tumor microenvironment. TAMs are known to play a critical role in the prognosis of cancer patients. To create the TAMs probe, we incorporated a fluorophore and 5β-cholanic acid into the dextran-sulfate polymer, resulting in the formation of spherical nanoparticles. These nanoparticles can serve as an effective tool for detecting TAMs in vivo. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293–1.1942); 1.0694 (1.0077–1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349–1.1466)) and CCB (1.0548 (1.0122–1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG. [ABSTRACT FROM AUTHOR]

Background: Radical cystectomy is a major urological procedure with high morbidity and mortality. The chart-derived frailty index (CFI), a measure of preoperative frailty, can be calculated by using demographic and routine laboratory variables. We assessed the impact of CFI on 1-year mortality after radical cystectomy. Methods: This retrospective study included patients with bladder cancer who underwent radical cystectomy between 2007 and 2021. The CFI was calculated as the sum of the presence of the following parameters: age > 70 years, body mass index < 18.5 kg/m2, hematocrit < 35%, albumin < 3.4 g/dL, and creatinine > 2.0 mg/dL. Patients were divided into those with low (0–2) and high (3–5) CFI. The 1-year, all-cause and cancer-specific mortalities after radical cystectomy were evaluated. Results: Of the 1004 patients, 914 (91.0%) had a low CFI and 90 (9.0%) had a high CFI. The 1-year, all-cause mortality in the low and high CFI groups was 12.0% and 27.8%, respectively (P < 0.001). Multivariate Cox regression analysis revealed that high CFI (P < 0.001), tumor stage (P = 0.003), and red blood cell transfusion amount (P < 0.001) were significantly associated with 1-year, all-cause mortality after radical cystectomy. Kaplan–Meier survival analysis demonstrated significantly different 1-year, all-cause and cancer-specific mortalities after radical cystectomy between patients with a high CFI and those with a low CFI (log-rank test, both P < 0.001). Conclusions: High CFI is associated with higher 1-year mortality after radical cystectomy, suggesting that the CFI can effectively predict mortality after radical cystectomy. [ABSTRACT FROM AUTHOR]

The treatment of lateral pelvic lymph node (LPLN) metastasis of rectal cancer has evolved because of technical difficulties from open surgery to laparoscopy and, recently, robot-assisted surgery. This study aimed to evaluate the technical feasibility and short- and long-term outcomes of robot-assisted LPLN dissection (LPND) following total mesorectal excision (TME) in advanced rectal cancer. Clinical data of 65 patients who underwent robotic-assisted TME with LPND from April 2014 to July 2022 were reviewed. Data regarding operative details, postoperative morbidity (within 90 postoperative days) for short-term outcomes and lateral recurrence as long-term outcomes were analyzed. Among the 65 patients with LPND, preoperative chemoradiotherapy was performed in 49 (75.4%). The mean operative time was 306.8 (range 191–477) min, and the mean time of unilateral LPND was 38.6 (range 16–66) min. LPND was bilaterally performed in 19 (29.2%) patients. The mean number of each side of harvested LPLNs was 6.8. Lymph node metastasis was observed in 15 (23.0%) patients, and 10 (15.4%) patients had postoperative complications. Lymphocele (n = 3) and pelvic abscess (n = 3) were the most common, followed by voiding difficulty, erectile dysfunction, obturator neuropathy, and sciatic neuropathy (all n = 1). During the 25 months of median follow-up, no lateral recurrence of the LPND site was noted. Robot-assisted LPND following TME is safe and feasible and showed acceptable short- and long-term outcomes. Despite some study limitations, we may be able to apply this strategy more widely through subsequent prospective controlled studies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate change in prostate biopsy accuracy regarding tumor grade before and after the release of Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) in a single tertiary institution. Methods: We retrospectively evaluated 1191 patients with biopsy-proven prostate cancer (PCa) who had undergone prostate magnetic resonance imaging (MRI) and surgery before (2013 cohort, n = 394) and 5 years after PI-RADSv2 release (2020 cohort, n = 797). The highest tumor grade of each biopsy and surgical specimen was recorded, respectively. We compared concordant, underestimated, and overestimated biopsy rates regarding tumor grade to surgery between two cohorts, respectively. For patients who underwent both prostate MRI and biopsy at our institution, we investigated proportion of pre-biopsy MRI, age, and prostate-specific antigen of patients, and performed logistic regression to analyze which parameters are associated with concordant biopsy. Results: Concordant and underestimated biopsy rates were significantly different between two cohorts: Concordance and underestimation rates were 47.2% and 46.3% in 2013 and 54.5% and 36.4% in 2020 (p =.019; p =.003), respectively. Overestimated biopsy rates were similar (p =.993). Proportion of pre-biopsy MRI was significantly higher in 2020 than in 2013 (80.9% versus 4.9%; p <.001), and was independently associated with concordant biopsy results in multivariate analysis (odds ratio = 1.486; 95% confidence interval, 1.057–2.089; p =.022). Conclusions: There was a significant change in proportion of pre-biopsy MRI before and after the release of PI-RADSv2 in patients who underwent surgery for PCa. This change appears to have improved biopsy accuracy regarding tumor grade by reducing underestimation. [ABSTRACT FROM AUTHOR]

It is important to identify at-risk patients prior to administering steroid injections to prevent avoidable irreversible blindness inducted by steroid-induced ocular hypertension (SIOH). We aimed to investigate the association of SIOH following intravitreal dexamethasone implantation (OZURDEX) using anterior segment optical coherence tomography (AS-OCT). We conducted a retrospective case control study to assess the association between trabecular meshwork and SIOH. A total of 102 eyes that underwent both AS-OCT and intravitreal dexamethasone implant injection were divided into the post-steroid ocular hypertension and normal intraocular pressure groups. Ocular parameters that can contribute to intraocular pressure were measured using AS-OCT. Univariable logistic regression analysis was used to calculate the odds ratio of the SIOH and significant variables were further analyzed using a multivariable model. Trabecular meshwork (TM) height was significantly shorter in the ocular hypertension group (716.13 ± 80.55 μm) than that in the normal intraocular pressure group (784.27 ± 82.33 μm) (p < 0.001). The receiver operating characteristic curve technique analysis showed that the optimal cut-off of ≥ 802.13 μm for TM height specificity was 96.2%, and TM height with < 646.75 μm had a sensitivity of 94.70%. The odds ratio of the association was 0.990 (p = 0.001). TM height was identified as a newly observed association with SIOH. TM height can be assessed using AS-OCT, with acceptable sensitivity and specificity. Caution must be exercised while injecting steroids in patients with short TM height (especially < 646.75 μm) as it may cause SIOH and irreversible blindness. [ABSTRACT FROM AUTHOR]

We prove the conjecture of Pollack and Weston on the quantitative analysis of the level lowering congruence à la Ribet for modular forms of higher weight. It was formulated and studied in the context of the integral Jacquet–Langlands correspondence and anticyclotomic Iwasawa theory for modular forms of weight two and square-free level for the first time. We use a completely different method based on the R = T theorem established by Diamond–Flach–Guo and Dimitrov and an explicit comparison of adjoint L-values. We briefly discuss arithmetic applications of our main result at the end. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection. [ABSTRACT FROM AUTHOR]

Purpose: Duodenal fistula in Crohn's disease (CDF) is a rare condition with an unclear optimal surgical management approach. We reviewed a Korean multicenter cohort of CDF surgery cases and assessed their perioperative outcomes to evaluate the effectiveness of the surgical interventions. Methods: The medical records of patients who underwent CD surgery between January 2006 and December 2021 from three tertiary medical centers were retrospectively reviewed. Only CDF cases were included in this study. The demographic and preoperative characteristics, perioperative details, and postoperative outcomes were analyzed. Results: Among the initial population of 2149 patients who underwent surgery for CD, 23 cases (1.1%) had a CDF operation. Fourteen of these patients (60.9%) had a history of previous abdominal surgery, and 7 had duodenal fistula at the previous anastomosis site. All duodenal fistulas were excised and primarily repaired via a resection of the originating adjacent bowel. Additional procedures such as gastrojejunostomy, pyloric exclusion, or T-tube insertion were performed in 8 patients (34.8%). Eleven patients (47.8%) experienced postoperative complications including for anastomosis leakages. Fistula recurrence was noted in 3 patients (13%) of which one patient required a re-operation. Biologics administration was associated with fewer adverse events by multivariable analysis (P = 0.026, odds ratio = 0.081). Conclusion: Optimal perioperative conditioning of patients receiving a primary repair of a fistula and resection of the original diseased bowel can successfully cure CDF. Along with primary repair of the duodenum, other complementary additional procedures should be considered for better postoperative outcomes. [ABSTRACT FROM AUTHOR]

Optimal preparation is recommended for patients with advanced chronic kidney disease to minimize complications during dialysis initiation. This study evaluated the effects of planned dialysis initiation on survival in patients undergoing incident hemodialysis and peritoneal dialysis. Patients newly diagnosed with end-stage kidney disease who started dialysis were enrolled in a multicenter prospective cohort study in Korea. Planned dialysis was defined as dialysis therapy initiated with permanent access and maintenance of the initial dialysis modality. A total of 2892 patients were followed up for a mean duration of 71.9 ± 36.7 months and 1280 (44.3%) patients initiated planned dialysis. The planned dialysis group showed lower mortality than the unplanned dialysis group during the 1st and 2nd years after dialysis initiation (1st year: adjusted hazard ratio [aHR] 0.51; 95% confidence interval [CI] 0.37–0.72; P < 0.001; 2nd year: aHR 0.71; 95% CI 0.52–0.98, P = 0.037). However, 2 years after dialysis initiation, mortality did not differ between the groups. Planned dialysis showed a better early survival rate in hemodialysis patients, but not in peritoneal dialysis patients. Particularly, infection-related mortality was reduced only in patients undergoing hemodialysis with planned dialysis initiation. Planned dialysis has survival benefits over unplanned dialysis in the first 2 years after dialysis initiation, especially in patients undergoing hemodialysis. It improved infection-related mortality during the early dialysis period. [ABSTRACT FROM AUTHOR]

Top loader washing machines are composed of an outer tub, inner drum, actuator and suspension with spring and dampers. When the drum rotates at a high speed, clothes are attached to the inner wall of the inner drum and the centrifugal force due to the unbalance mass makes a vibrating motion. In this study, the dynamic model of top loader washing machine was established to analyze the vibrating characteristics of the washing machine due to the unbalance mass effect and the mass effect of the fluid balancer. An integrated model of RecurDyn and Particleworks was made and used to analyze the dynamic behavior of the washing machine. The vibrating amount of the washing machine according to the position of the unbalance mass and its magnitude was analyzed. The accuracy of the dynamic model was verified by comparisons of the analysis results with experiments. By using the modal coordinates for the flexible multibody model, it was noted that the vibration of the top-loader washing machine was due to the deformation of the drum by unbalance masses. [ABSTRACT FROM AUTHOR]

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target. Glioblastoma stem-like cells (GSCs) contribute to therapeutic resistance and recurrence of glioblastomas. Here the authors show that Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) promotes GSCs invasion. [ABSTRACT FROM AUTHOR]

Objectives: To investigate inter-method agreement between wash-out and wash-in computed tomography (CT) to determine whether hyperattenuating adrenal lesions are characterized as adenomas or non-adenomas. Methods: We evaluated 243 patients who underwent wash-out CT for a solid enhancing hyperattenuating (i.e., > 10 Hounsfield unit [HU]) adrenal mass of ≥ 1 to < 4 cm. Wash-out (absolute percentage wash-out [APW]; relative percentage wash-out [RPW]) and wash-in values (enhancement ratio [ER]; relative enhancement ratio [RER]) were analyzed by two independent readers. Diagnostic criteria of wash-out CT for adenoma were APW ≥ 60% or RPW ≥ 40% (conventional method). Three different criteria for wash-in CT were set: ER ≥ 3.0; RER ≥ 200%; and RER ≥ 210%. Concordance rate and inter-method agreement between wash-out and wash-in CT were investigated using Gwet's AC1. Results: For all lesions, concordance rates between wash-out and wash-in CT were > 83%. AC1 between conventional method and ER ≥ 3.0 or between conventional method and RER ≥ 200% were identically 0.843 for reader 1 and 0.776 for reader 2. AC1 between conventional method and RER ≥ 210% were 0.780 for reader 1 and 0.737 for reader 2. For lesions of > 10 to ≤ 30 HU, concordance rates between wash-out and wash-in CT were > 89%. AC1 between conventional method and ER ≥ 3.0 or between conventional method and RER ≥ 200% were identically 0.914 for reader 1 and 0.866 for reader 2. AC1 between conventional method and RER ≥ 210% were 0.888 for reader 1 and 0.874 for reader 2. Conclusion: In approximately 90% of patients with a hyperattenuating adrenal lesion of ≥ 1 to < 4 cm and >10 to ≤ 30 HU, wash-out CT with 15-min contrast-enhanced images may be replaced by wash-in CT. Key Points: • An enhancement ratio of ≥ 3.0 or a relative enhancement ratio of ≥ 200% appears to be appropriate as the threshold of wash-in computed tomography (CT) comprising unenhanced and 1-min contrast-enhanced CT. • Measurement of enhancement ratio or relative enhancement ratio was reproducible. • We found good agreement between wash-in and wash-out CT for determining whether hyperattenuating adrenal lesions of ≥ 1 to < 4 cm and >10 to ≤ 30 Hounsfield unit would be characterized as adenomas. [ABSTRACT FROM AUTHOR]

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00–2.77) and 1.20 (0.60–2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT. [ABSTRACT FROM AUTHOR]

Females are known to have a better survival rate than males in the general population, but previous studies have shown that this superior survival is diminished in patients on dialysis. This study aimed to investigate the risk of mortality in relation to sex among Korean patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). A total of 4994 patients with kidney failure who were receiving dialysis were included for a prospective nationwide cohort study. Cox multivariate proportional hazard models were used to determine the association between sex and the risk of cause-specific mortality according to dialysis modality. During a median follow-up of 5.8 years, the death rate per 100 person-years was 6.4 and 8.3 in females and males, respectively. The female-to-male mortality rate in patients on dialysis was 0.77, compared to 0.85 in the general population. In adjusted analyses, the risk of all-cause mortality was significantly lower for females than males in the entire population (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71–0.87, P < 0.001). No significant differences in the risk of cardiovascular and infection-related deaths were observed according to sex. The risk of mortality due to sudden death, cancer, other, or unknown causes was significantly lower for females than males in the entire population (HR 0.66, 95% CI 0.56–0.78, P < 0.001), in patients on HD (HR 0.75, 95% CI 0.62–0.90, P = 0.003), and in patients on PD (HR 0.49, 95% CI 0.34–0.70, P < 0.001). The survival advantage of females in the general population was maintained in Korean dialysis patients, which was attributed to a lower risk of noncardiovascular and noninfectious death. Trial registration: ClinicalTrials.gov Identifier: NCT00931970. [ABSTRACT FROM AUTHOR]