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Background: Precise localization of small pancreatic tumors during laparoscopic distal pancreatectomy (LDP) can be difficult because of decreased tactile ability of laparoscopy and the homogeneous appearance of the pancreas and surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection and preserving healthy pancreatic tissue. EUS-guided fine-needle tattooing (EUS-FNT) of a pancreatic lesion before LDP has been described in single case reports, but no large series have reported its effectiveness in patients undergoing LDP. Objective: To assess the feasibility, safety, and efficacy of EUS-FNT in consecutive patients undergoing LDP. Design: Retrospective cohort study. Setting: Tertiary-care referral hospital. Patients: This study involved 30 consecutive patients who underwent LDP from 2008 to 2010. Thirteen had EUS-FNT followed by LDP, and 17 had LDP alone. Interventions: LDP or EUS-FNT with a sterile carbon-particle tattoo followed by LDP. Main Outcome Measurements: The following features were examined: the technical success and complication rates of EUS-FNT, visibility of the tattoo at the time of laparoscopy, durability of the tattoo, and pathologic absence of tumor at the resection margin. Results: The final pathology of pancreatic lesions of patients who had EUS-FNT was similar to those who had LDP alone. The median resected tumor size was significantly larger for the LDP-alone patients (median 4.0 cm vs 1.3 cm; P = .03). Thirty-one percent (4/13) of lesions in the EUS-FNT group were not visualized by prior preoperative pancreatic protocol CT. EUS-FNT was feasible in all 13 patients at laparoscopy, with R0 resection and negative final pathology margins in all cases. The tattoo was visible in all 13 EUS-FNT cases, with mean time from EUS-FNT to surgery of 20.3 days (range, 3-69 days). There were no significant complications associated with EUS-FNT. Limitations: Small, retrospective, single-center study. Conclusions: Preoperative EUS-FNT of lesions was technically feasible and safe, and it assisted in the localization of lesions in patients before LDP. The carbon particle tattoo was durable and visible in all cases. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the development of fetal surgery, morbidity and mortality are substantial. A natural orifice transluminal endoscopic surgery (NOTES)-guided approach to the gravid uterus may offer a less-invasive technique. Objective: To assess the feasibility of NOTES for diagnostic and therapeutic intrauterine fetal interventions. Setting: Survival and nonsurvival experiments on pregnant sheep. Design and Intervention: Nonsurvival experiments performed in 2 pregnant sheep (80-110 days' gestation). A third ewe underwent NOTES and survived for 4 weeks. Transgastric (nonsurvival ewes) and transvaginal (1 nonsurvival and the survived ewe) peritoneoscopy was performed after standard needle-knife entry into the peritoneal cavity. Endoscopic access to the gravid uterus was assessed. EUS-guided, transuterine injection of saline solution into the fetal cardiac ventricle and vessels was attempted in all. Main Outcome Measurements: Feasibility of NOTES- and EUS-guided intervention in a pregnant animal model, visibility of fetal parts via EUS compared with transabdominal US. Results: Entry into the peritoneal cavity was achieved in each ewe. Access to and complete visualization of the gravid uterus were successful once within the abdominal cavity. Visualization of the fetal parts and the placental cotyledons by EUS was achieved in all animals. EUS-guided amniocenteses and transuterine intracardiac and intravascular injection of saline were successful. There were no complications or preterm delivery after the procedures. Limitations: Animal model. Conclusions: NOTES is technically feasible in the pregnant ewe. Intraperitoneal EUS via a NOTES approach provides excellent access and visualization of the intrauterine cavity and fetal parts. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The utility of the greater omentum has not been assessed in transluminal access closure after natural orifice transluminal endoscopic surgery (NOTES) procedures. OBJECTIVE: Our purpose was to evaluate the feasibility, efficacy, and safety of omentoplasty for gastrotomy closure. METHODS AND PROCEDURES: Survival experiments in 9 female 40-kg pigs were randomly assigned to 3 groups: group A, endoscopic full-thickness resection (EFTR) for transgastric access and peritoneoscopy without closure; group B, ETFR and peritoneoscopy with omentoplasty (flap of omentum is pulled into the stomach and attached to the gastric mucosa with clips but no clips are used for gastrotomy closure itself); group C, balloon dilation for opening and peritoneoscopy followed by omentoplasty for closure. The animals were observed for 2 weeks and then underwent endoscopy and necropsy with histologic evaluation. RESULTS: Transgastric opening and peritoneoscopy were achieved in all pigs. In groups B and C, a flap of omentum was easily placed to seal the gastrotomy and then attached to the gastric mucosa with 2 to 5 clips (median 4) in 7 to 20 minutes (median 15 minutes). In group A, peritonitis developed in all animals. In both groups B and C, all animals survived 15 days with no peritonitis and minimal adhesions outside the gastrotomy site. In addition, all achieved complete healing (transmural, n = 4; mucosal ulceration, n = 2) of the gastrotomy site. One animal in group B had an 18-mm abscess in the omental flap. LIMITATIONS: Animal model, small sample size, lack of appropriate controls for group C. CONCLUSIONS: Omentoplasty of the gastrotomy site is a technically feasible method to seal balloon-created transgastric access to the peritoneal cavity after NOTES procedures. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPSS) is an effective treatment for portal hypertension and its associated complications. EUS-guided creation of an intrahepatic portosystemic shunt (IPSS) may become a useful alternative to conventional TIPSS. OBJECTIVE: To assess the feasibility of EUS-guided IPSS creation in a live porcine model. SETTING: Acute and survival experiments in 50-kg pigs. DESIGN AND INTERVENTIONS: Under linear-array EUS guidance, the hepatic vein (HV) and then the portal vein (PV) were punctured with a 19-gauge FNA needle. A 0.035-inch guidewire was advanced through the needle into the PV lumen. The needle was exchanged over the wire, a metal stent was deployed under EUS and fluoroscopic guidance, and the distal end of the stent was positioned inside the PV and the proximal end within the HV. Eight animals were euthanized after the procedure, and 2 animals were kept alive for 2 weeks. MAIN OUTCOME MEASUREMENTS: Successful EUS-guided IPSS creation. RESULTS: Portosystemic shunt placement was successful in all animals. Intrahepatic vascular puncture and stent deployment were technically easy. Portosystemic flow through the shunt was documented by portal venogram and EUS Doppler. Necropsy performed after acute and survival experiments revealed no evidence of bleeding or damage to any intraperitoneal organs. There were no complications during the follow-up period in the 2 animals that were kept alive. LIMITATION: Experiments were performed in healthy animals with normal PV pressure. CONCLUSION: EUS-guided IPSS creation is technically feasible and may become an alternative to the currently used method of TIPSS placement. [ABSTRACT FROM AUTHOR]

BACKGROUND: Leak-resistant closure of transluminal access is a major challenge facing natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate a hydrogen (H(2))-based leak test for assessment of transluminal-access closure integrity after NOTES procedures. SETTING: Nine acute porcine experiments. DESIGN AND INTERVENTION: After gastric-wall puncture and balloon dilation, peritoneoscopy was performed, followed by transmural closure of the gastric opening. The animals were randomly assigned to complete or incomplete closure groups. The H(2) leak test was performed by using 1000 mL of 4% H(2) gas mixture and the Hydrogen Leak Detector H2000+. The animals were then euthanized for a methylene blue (MB) test of gastric closure integrity. MAIN OUTCOME MEASUREMENT: Intraperitoneal H(2) concentration after gastric insufflation with H(2). RESULTS: The H(2) leak test was quick and easy. Intraperitoneal H(2) concentrations in parts per million in both groups were similar at baseline (mean +/- SD, 0.18 +/- 0.29 parts per million [ppm] vs 0.22 +/- 0.35 ppm, P = .97) and after balloon dilation (414.8 +/- 198.5 ppm vs 601.3 +/- 116.1 ppm, P > .99). Postclosure intraperitoneal H(2) concentrations dropped to 0.01 +/- 0.77 ppm in the complete-closure group, similar (P = .81) to matched-pairs preopening levels and significantly lower than in the incomplete-closure group (162.0 +/- 83.0 ppm, P < .02). On necropsy, the MB test was negative in all 5 animals of the complete-closure group and positive in all 4 animals of the incomplete-closure group. A cutoff of 25 ppm in intraperitoneal H(2) concentration after closure gave 100% sensitivity, specificity, and positive and negative predictive values for MB leakage. LIMITATIONS: Nonsurvival animal experiments. CONCLUSIONS: The H(2) leak test is highly accurate for detection of leakage after NOTES procedures and could become a substitute for currently used MB leak tests. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ventral hernia repair is currently performed via open surgery or laparoscopic approach. OBJECTIVE: To develop an alternative ventral hernia repair technique. SETTING: Acute and survival experiments on twelve 50-kg pigs. DESIGN AND INTERVENTIONS: An endoscope was introduced transgastrically into the peritoneal cavity. An abdominal wall hernia was created through a 5-mm skin incision followed by a 5-cm-long incision of the abdominal wall muscles and aponeurosis. A hernia repair technique was developed in 3 acute experiments. Then animals were randomized into 2 groups. In the experimental group (5 animals) Gore-Tex mesh was transgastrically attached to the abdominal wall, repairing the previously created abdominal wall hernia. In the control group (4 animals), the hernia was not repaired. In both groups, the endoscope was then withdrawn into the stomach, and the gastric wall incision was closed with T-bars. The animals survived for 2 weeks and were then euthanized. MAIN OUTCOME MEASUREMENT: The presence of ventral hernia on necropsy. RESULTS: In the control group, the ventral hernia was present on necropsy in all animals. In the experimental group, the ventral hernia was easily repaired, with no evidence of hernia on necropsy. In the first animal in the experimental group, necropsy revealed infected mesh. After this discovery, we used sterilized cover for mesh delivery and did not find any signs of infection in 4 subsequent study animals. LIMITATION: The study was performed in a porcine model. CONCLUSIONS: Transgastric ventral hernia repair is feasible, technically easy, and effective. It can become a less invasive alternative to the currently used laparoscopic and surgical ventral hernia repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transluminal access site closure remains a major challenge in natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: Our purpose was to develop in vivo leak tests for evaluation of the integrity of transgastric access closure. SETTINGS: Survival experiments on 12 50-kg pigs. DESIGN AND INTERVENTIONS: After a standardized transgastric approach to the peritoneal cavity and peritoneoscopy, the gastric wall incision was closed with T-bars (Wilson-Cook Medical, Winston-Salem, NC) deployed on both sides of the incision and then cinched together. Gastrotomy closure was assessed with air and fluid leak tests. The animals were observed for 1 week and then underwent endoscopic evaluation and necropsy. MAIN OUTCOME MEASUREMENTS: (1) Leak-proof closure of the gastric wall incision. (2) Gastric incision healing 1 week after the procedure. RESULTS: The mean intraperitoneal pressure increased 10.7 +/- 3.7 mm Hg during gastric insufflation when the air leak test was performed before closure compared with 0.9 +/- 0.8 mm Hg after transmural closure of the transgastric access site with T-bars (P < .001). Fluid leak tests demonstrated no leakage of liquid contrast from the stomach into the peritoneal cavity after closure. Necropsy in 1 week confirmed completeness of the gastric closure in all animals with full-thickness healing and no spillage of the gastric contents into the peritoneal cavity. LIMITATIONS: Leak tests were only evaluated on an animal model. CONCLUSIONS: Fluid and air leak tests are simple techniques to evaluate in vivo the adequacy of the transluminal access site closure after NOTES procedures. Leak-proof gastric closure resulted in adequate tissue approximation and full-thickness healing of the gastric wall incision. [ABSTRACT FROM AUTHOR]

Objectives: Replication-competent, vesicular stomatitis virus (VSV) has been demonstrated to be an effective oncolytic agent in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the use of combining these two approaches, an oncolytic VSV vector (rVSV-IL12) was designed to express the murine interleukin 12 (IL12) gene. This cytokine-carrying oncolytic virus was compared with an analogous noncytokine-carrying fusogenic virus (rVSV-F) in the treatment of murine SCC VII squamous cell carcinoma (SCC).Study Design and Setting: The authors performed in vitro testing of recombinant VSV-F and recombinant VSV-IL12 in SCC cell lines. In vivo testing of multiple direct intratumoral injections of rVSV-F or rVSV-IL12 in an orthotopic floor of mouth murine model was performed. Each cell line was tested using rVSV-F or rVSV-IL12 at multiplicity of infection of 0.01. The ability of each virus to replicate was tested by real-time reverse transcriptase-polymerase chain reaction over 48 hours to determine viral copies of RNA. Cell survival was determined by MTT assay over 72 hours. IL12 expression by rVSV-IL12-treated cells was determined by enzyme-linked immunosorbent assay.Results: Both viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. In an SCC VII orthotopic floor of mouth model in immunocompetent C3H/HeJ mice, multiple intratumoral injections with each virus caused a significant reduction in tumor volume when compared with saline injections alone. The rVSV-IL12-treated tumors showed a striking reduction in tumor volume when compared with rVSV-F and saline-treated tumors (P < .005). This striking reduction in tumor volume translated into a substantial survival benefit in rVSV-IL12-treated animals. No treatment-related toxicity was observed in either group.Conclusion/significance: rVSV-IL12 is a novel oncolytic vesicular stomatitis virus that effectively expresses IL12 and significantly enhances the treatment of head and neck murine carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of head and neck cancers. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Pulsatile tinnitus in the face of normal findings on otoscopy is a common otological diagnostic dilemma and can be due to serious vascular malformations such as transverse or sigmoid sinus dural arteriovenous fistula (transverse or sigmoid sinus [TS] DAVF). Left untreated, TS DAVF may result in significant morbidity and mortality. TS DAVF can be suspected or diagnosed with computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA), with the gold standard being angiography. Our objective was to assess the utility of these various diagnostic modalities in the diagnosis of dural arteriovenous fistula. Study Design: Retrospective clinical review. Methods: Between 1986 and 1996, 54 patients were evaluated and treated for TS DAVF. Between 1996 and 1999, an additional 33 patients underwent MRI combined with MRA for the evaluation of pulsatile tinnitus. A retrospective review of the medical records for both groups, with special attention to clinical presentation, diagnostic evaluation, therapy, and outcome, was performed. Results: All patients had pulsatile tinnitus with normal findings on otoscopy. CT scan was relatively insensitive in the detection of TS DAVF. MRI and MR/MRA were significantly more sensitive than CT. In the evaluation of patients with subjective pulsatile tinnitus, MRI/MRA defined anatomical abnormalities that may contribute to pulsatile tinnitus in 63% of patients. Conclusions: In the absence of objective pulsatile tinnitus, MRI/MRA is an appropriate initial diagnostic step. When a patient has an objective bruit, the clinician may choose to proceed directly to angiography to make certain that a TS DAVF is not missed. [ABSTRACT FROM AUTHOR]

The past decade has seen several innovations in the surgical techniques available for treatment of patients with sleep-disordered breathing. Outpatient techniques such as laser-assisted uvulopalatoplasty (LAUP) and more aggressive procedures designed to address hypopharyngeal and base of tongue obstruction (genioglossus advancement and hyoid myotomy) have been developed and proven successful. We describe the efficacy of LAUP for snoring (72.7%), upper airway resistance syndrome (81.8%), and mild (mean [+/-SD] respiratory disturbance index [RDI] = 12 +/- 8.1) obstructive sleep apnea (41.7%) in 56 patients who underwent 132 LAUP procedures in a 26-month period. Thirty-two patients with more significant obstructive sleep apnea (mean RDI = 41.8 +/- 23.1) underwent multilevel pharyngeal surgery consisting of genioglossus advancement and hyoid myotomy combined with uvulopalatopharyngoplasty. The surgical success rate in this group of patients was 85.7% when commonly accepted criteria were applied. We recommend a stratified surgical approach to patients with sleep-disordered breathing. Progressively worse airway obstruction marked by multilevel pharyngeal collapse and more severe sleep-disordered breathing is treated with incrementally more aggressive surgery addressing multiple areas of the upper airway. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-β (TGF-β)-treated LX-2 cells. TGF-β-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-β-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-β facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

L-type voltage-gated calcium channels (L-VGCCs) are thought to be involved in epileptogenesis and acute excitotoxicity. However, little is known about the role of L-VGCCs in neuroinflammation or delayed neuronal death following excitotoxic insult. We examined the effects of repeated treatment with the L-VGCC blocker nimodipine on neuroinflammatory changes and delayed neuronal apoptosis in the dentate gyrus following trimethyltin (TMT)-induced convulsions. Male C57BL/6 N mice were administered TMT (2.6 mg/kg, i.p.), and the expression of the Ca v 1.2 and Ca v 1.3 subunits of L-VGCC were evaluated. The expression of both subunits was significantly decreased; however, the astroglial expression of Ca v 1.3 L-VGCC was significantly induced at 6 and 10 days after TMT treatment. Furthermore, astroglial Ca v 1.3 L-VGCCs colocalized with both the pro-inflammatory phenotype marker C3 and the anti-inflammatory phenotype marker S100A10 of astrocytes. Nimodipine (5 mg/kg, i.p. × 5 at 12-h intervals) did not significantly affect TMT-induced astroglial activation. However, nimodipine significantly attenuated the pro-inflammatory phenotype changes, while enhancing the anti-inflammatory phenotype changes in astrocytes after TMT treatment. Consistently, nimodipine reduced the levels of pro-inflammatory astrocytes-to-microglia mediators, while increasing the levels of anti-inflammatory astrocytes-to-microglia mediators. These effects were accompanied by an increase in the phosphorylation of extracellular signal-regulated kinase (ERK), supporting our previous finding that p-ERK is a signaling factor that regulates astroglial phenotype changes. In addition, nimodipine significantly attenuated TMT-induced microglial activation and delayed apoptosis of dentate granule neurons. Our results suggest that L-VGCC blockade attenuates neuroinflammation and delayed neurotoxicity following TMT-induced convulsions through the regulation of astroglial phenotypic changes by promoting ERK signaling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cellulose nanocrystal is a nanomaterial that has a large specific surface area, high surface energy, and high strength. As well, it is biocompatible, environmentally friendly, nontoxic, and can be extracted from biomass resources. Because of these features, cellulose nanocrystals can be used to improve the mechanical properties of polymer matrices with a shape memory effect and as a shape memory switch. In this study, a polytrimethylene ether glycol-based thermoplastic polyurethane (TPU)/cellulose nanocrystal (CNC) composite was prepared via an in-situ polymerization process to create a self-healing polymer matrix. Also, the effect of CNC doses in low concentrations (≤2 wt%) on the different properties of the resulting bio-nanocomposite was investigated. The results showed that the introduction of CNCs affects the hydrogen bonding within the polymer matrix and provides better thermal stability in the high temperature range than pure TPU. Furthermore, the samples with 0 wt%, 0.75 wt%, 1 wt%, and 2 wt% of CNC exhibited an increasing trend in tensile strength with values of 11.71 MPa, 18.95 MPa, 17.88 MPa, and 26.18 MPa, respectively, which indicates a remarkable improvement in mechanical strength. The shape memory behavior was also notably prominent in this polymer composite, where the composite containing 2 wt% of CNC showed the fastest recovery time (240 s) at 75 °C with the highest shape retention. Moreover, their flow behavior and deformation capacity were examined through rheology tests. Besides, docking simulations were conducted in silico to assess the interaction of the TPU/CNC composite with the DNA gyrase enzyme. The interaction between CNC/TPU composite and DNA gyrase was meticulously analyzed across 10 distinct conformations, yielding docking scores ranging from -6.5 Kcal/mol to -5.3 Kcal/mol. Overall, the physico-mechanical properties of the TPU/CNC composites were substantially enhanced with the incorporation of nanofillers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dermatological lesions are typically located just a few millimeters below the surface of the skin, which constrains the efficacy of optical-based therapeutic methods such as photothermal and photodynamic therapy due to limited therapeutic depth caused by optical scattering. As an alternative, high-intensity focused ultrasound (HIFU) has been explored for its potential to treat a variety of dermatological conditions because it offers greater flexibility in terms of treatment depth. Since dermatological lesions have a small thickness ranging from 1.5 to 2.0 mm, high-frequency ultrasound (3-10 MHz or higher) is preferred as the focal area is proportional to the operating frequency. However, due to the difficulty in fabricating HIFU array transducers at this frequency range, the majority of HIFU treatments for dermatology rely on single element transducers. Despite the advantages of HIFU, single-element-based HIFU systems are limited in prevalent use for dermatology treatment due to their fixed focal length and mechanical movement for treatment, which can be time-consuming and unsuitable for treating multiple lesions. To address this, we present a newly developed HIFU linear array and 128-channel driving electronics specifically designed for dermatology treatment. This array consists of 128 elements, has a center frequency of 3.7 MHz, an elevation focal length of 28 mm, and an F-number of 1.27 in the elevation direction. The array has a footprint of 71.6 mm by 22 mm. Experiments using a tissue-mimicking phantom have demonstrated that the HIFU linear array and system are capable of transmitting sufficient ultrasound energy to create coagulation inside the phantom., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Despite considerable increases in road freight traffic and associated crashes over the past decade, our understanding of their spatial distribution remains limited. This is concerning because freight vehicle crashes often lead to fatal and severe injuries. This study focuses on Seoul, South Korea and contributes to the literature by investigating the patterns and sources of spatial inequity in freight crashes. Specifically, it examines whether socioeconomically disadvantaged neighborhoods experience a higher concentration of freight crashes. Using the Gelbach's decomposition technique, this study also aims to identify the factors contributing to differences in freight crashes between disadvantaged and less-disadvantaged neighborhoods and quantify their relative contributions. The regression results show that severe freight crashes are more prevalent in disadvantaged neighborhoods before adjusting for other factors-a pattern not observed in non-severe crashes. The decomposition analysis reveals that the observed disparities in severe freight crashes between disadvantaged and less-disadvantaged neighborhoods are fully explained by differences in several neighborhood characteristics, including local road density, truck traffic volume density, proximity to logistics terminals, and off-road bicycle lane density, between neighborhood types. Interestingly, differences in built environment characteristics between neighborhood types not only fail to explain but instead counteract the disparities in severe freight crashes. The findings of this study suggest detailed policy implications for mitigating freight crash occurrences and addressing related spatial inequities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Dr Shin is a consultant for Boston Scientific. All other authors have no potential conflicts relevant to the content presented in this manuscript.

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored. Here, we show that both the intrinsic timescale and the timescales of task-related activity follow a similar hierarchical gradient in the cortices of monkeys, rats, and mice. We also found that these timescales covary similarly in both the cortex and basal ganglia, whereas the timescales of thalamic activity are shorter than cortical timescales and do not conform to the hierarchical order predicted by their cortical projections. These results suggest that the hierarchical gradient of cortical timescales might be a universal feature of intra-cortical circuits in the mammalian brain.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven., Objective: To compare the survival of patients with surveillance-detected PDAC with US national data., Design, Setting, and Participants: This comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023., Exposures: Endoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment., Main Outcomes and Measures: Stage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted., Results: A total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P < .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P < .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P < .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%])., Conclusions and Relevance: These findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration., Competing Interests: Conflict of Interest Manoop S. Bhutani: Nanobiotix, Trisalis, Oncosil, Starpax Medical, Augmenix/Boston Scientific. Amol K. Narang: Boston Scientific, Flavocure, Nanocan Therapeutics Corporation. Kai Ding: Boston Scientific. Brenna Casey: no COI to declare. Kumar Krishnan: Boston Scientific, Olympus. Eugene J. Koay: AstraZeneca, RenovoRx, Quantum Aurea Capital, Kallisio, International Cholangiocarcinoma Research Network. Theodore S. Hong: Synthetic Biologics, Novocure, Boston Scientific, Inivata, Merck, GSK, PanTher Therapeutics, Lustgarten, Taiho, AstraZeneca, BMS, IntraOp, Ipsen. Joseph M. Herman: Histosonics, Boston Scientific, Canopy Cancer Collective, 1440 Foundation, BTG. Kristen H. Griffin: Boston Scientific (employee). Eun Ji Shin: Boston Scientific., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum., Methods and Materials: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT., Results: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum., Conclusions: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control., Competing Interests: Disclosures Amol Kumar Narang reports grants or contracts from Boston Scientific, Nanocan, and Flavocure. Theodore S. Hong reports grants or contracts from National Cancer Institute and SU2C. Received consulting fees from Synthetic Biologics, Boston Scientific, Merck, Inviata, GSK, and NextCure. Participated on a Data Safety Monitoring Board or Advisory Board for Novocure and Galera. Has stock or stock options from Panther Therapeutics. Kai Ding reports support for the present manuscript from Augmenix and Boston Scientific. Grants or contracts with NIH. Joseph Herman reports grants or contracts from 1440 Canopy Cancer Collective. Royalties or licenses from Springer Publishing. Consulting fees from Histosonics and Boston Scientific. Support for attending meetings and/or travel from Histosonics and 1440 Canopy Cancer Collective. Patents planned, issued or pending with Oncospace. Has stock or stock options from Histosonics. Jeffrey Meyer reports support for the present manuscript from Boston Scientific. Royalties or licenses from Springer and UpToDate. Manoop S. Bhutani reports support for the manuscript from Boston Scientific. Grants or contracts from Nanobiotix-Research Grant and Trisalis. Consulting fees from Oncosil Inc and Starpax Medical. Kumar Krishnan reports consulting fees from Boston Scientific and Olympus Medical. Euin Ji Shin reports consulting fees from Boston Scientific. Payment for expert testimony from US Dept of Justice. Eugene J, Koay reports support for the present manuscript from Dept of Defense and the NIH. Grants or contracts from Philips Health care, GE Health care, Stand up to Cancer, Project Purple, Elekta, and Dept of Defense. Royalties or licenses from Taylor and Francis LLC. Consulting fees from RenovoRx, AstraZeneca, and Augmenix. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Apollo Cancer Hospitals in Chennai India, Bayer Health care, Philips Health care, and Aptitude Health. Patents planned, issued or pending for the design and fabrication of 3D printed oral stents for head and neck cancer. Leadership of fiduciary role in other board, society, committee or advocacy group, paid or unpaid with International Cholangiocarcinoma Research Network. Has stock or stock options with Quantum Aurea Capital., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Training in interventional endoscopy is offered by nonaccredited advanced endoscopy fellowship programs (AEFPs). The number of these programs has increased dramatically with a concurrent increase in the breadth and complexity of interventional endoscopy procedures. Accreditation is governed by competency-based education, yet what constitutes a "high-quality" nonaccredited AEFP has not been defined. Using an evidence-based consensus process, we aimed to establish standards for AEFPs., Methods: The RAND UCLA appropriateness method, a well-described modified Delphi process to develop quality indicators, was used. A task force established by the American Society for Gastrointestinal Endoscopy drafted potential quality indicators (structure, process, and outcome) in 6 categories: activity preceding training; structure of AEFPs; training in ERCP, EUS, and EMR; and luminal stent placement. Three rounds of iterative feedback from 20 experts were conducted. Round 0 involved discussion of project details. In round 1, experts independently ranked proposed quality indicators on a 9-point interval scale ranging from highly inappropriate (1) to highly appropriate (9). Next, proposed quality indicators were discussed and reworded in a group meeting followed by round 2, in which experts independently reranked proposed quality indicators and provided benchmarks (when applicable). The median score for each quality indicator was calculated. Mean absolute deviation from the median was calculated, and appropriateness of potential quality indicators was assessed using the BIOMED concerted action on appropriateness definition, P value method, and interpercentile range adjusted for symmetry definition. A quality indicator was deemed appropriate if the median score was ≥7 and met criteria for appropriateness using all 3 defined statistical methods., Results: Of 89 proposed quality indicators, 37 statements met criteria as appropriate for a quality indicator (activity preceding training, 2; structure of AEFPs, 10; training in ERCP, 7; training in EUS, 8; training in EMR, 7; luminal stent placement, 3). Minimum thresholds were defined for 19 relevant quality indicators for number of trainers, procedures during fellowship, and procedures before assessment of competence. Among the final appropriate quality indicators were that all trainees should undergo qualitative and quantitative competence assessments using validated tools at least quarterly with documented feedback throughout the training period and that trainees should track outcomes and relevant quality metrics for specific procedures., Conclusions: This consensus process using validated methodology established standards for an AEFP in an effort to ensure adequate training in the most commonly taught interventional endoscopic procedures (ERCP, EUS, EMR, and luminal stent placement) during fellowship. An important component of an AEFP is the use of competency-based assessments that are compliant with the Accreditation Council for Graduate Medical Education's Next Accreditation System, with the goal of ensuring that trainees achieve specific milestones in their progression to achieving cognitive and technical competency., Competing Interests: Disclosure The following authors disclosed financial relationships: G. A. Cote: Consultant for Interpace Diagnostics and Olympus Corporation; research support from Abbvie Pharmaceuticals. R. N. Keswani: Consultant for Medtronic and Boston Scientific. R. H. Yadlapati: Consultant for Medtronic, Phathom Pharmaceuticals, and StatLinkMD; research support from Ironwood Pharmaceuticals; advisory board with stock options in RJS Mediagnostix. T. M. Berzin: Consultant for Medtronic, Boston Scientific, Wision AI, Magentiq Eye, and RSIP Vision. P. Chahal: Consultant for Boston Scientific and Medtronic. J. Cohen: Consultant for Olympus America and Micro-Tech; stock owner in GI Windows, Virtual Health Partners, and Rom-Tech; owner of MD Medical Navigators. W. J. Coyle: Speaker for Abbvie, Pharm and Regeneron, and Pharm D. Early: Scientific advisory board for Guardant Health. N. M. Guda: Consultant for Boston Scientific and Hemostasis Inc LLC; speaker for Lupin Pharmaceuticals, India. S. Inamdar: Consultant for Pentax Medical. E. J. Shin: Consultant for Boston Scientific. U. D. Siddiqui: Consultant and speaker for Olympus, Boston Scientific, ConMed, Medtronic, and Cook Medical; research support from Olympus and Boston Scientific. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 ., (© 2024. The Author(s).)

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca 2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.

Introduction: Despite evidence showing higher fatality rates in freight-related crashes, there has been limited exploration of their spatial distribution and factors associated with such distribution. This gap in the literature primarily stems from the focus of existing studies on micro-level factors predicting the frequency or severity of injuries in freight crashes. The present study delves into the factors contributing to freight crashes at the neighborhood level, particularly focusing on different types of freight crashes: collisions involving a freight vehicle and a passenger vehicle, crashes between freight vehicles, and freight vehicle-non-motorized crashes., Method: This study analyzes traffic crash data from the urbanized region of Seoul, collected between 2016 and 2019. To effectively deal with spatial autocorrelation and model different types of crashes in a unified framework, a Bayesian multivariate conditional autoregressive model was employed., Results: Findings show substantial differences in the factors associated with various types of freight crashes. The predictors for crashes between freight vehicles diverge significantly from those for freight vehicle-non-motorized crashes. Crashes between freight vehicles are relatively more influenced by road network structure, while freight crashes involving non-motorized users are relatively more affected by the built environment and freight facilities than the other crash types examined. Freight vehicle-passenger vehicle crashes fall into an intermediate category, sharing most predictors with either of the other two types of freight crashes., Conclusions and Practical Applications: The findings of this study offer valuable lessons for transportation practitioners and policymakers. They can guide the formulation of effective land use policies and infrastructure planning, specifically designed to address the unique characteristics of different types of freight crashes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Evidence suggests that the neuroprotective effects of melatonin involve both receptor-dependent and -independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post-KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression-like behaviors following KA-induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0.12 μg/μL) in the hippocampus of mice. Ramelteon (3 or 10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) mitigated KA-induced oxidative stress and impairment of glutathione homeostasis and promoted the nuclear translocation and DNA binding activity of Nrf2 in the hippocampus after KA treatment. Ramelteon and melatonin also attenuated microglial activation but did not significantly affect astroglial activation induced by KA, despite the astroglial induction of melatonin receptors after KA treatment. However, ramelteon attenuated KA-induced proinflammatory phenotypic changes in astrocytes. Considering the reciprocal regulation of astroglial and microglial activation, these results suggest ramelteon inhibits microglial activation by regulating astrocyte phenotypic changes. These effects were accompanied by the attenuation of the nuclear translocation and DNA binding activity of nuclear factor κB (NFκB) induced by KA. Consequently, ramelteon attenuated the KA-induced hippocampal neuronal loss, memory impairment, and depression-like behaviors; the effects were comparable to those of melatonin. These results suggest that ramelteon-mediated activation of melatonin receptors provides neuroprotection against KA-induced neurotoxicity in the mouse hippocampus by activating Nrf2 signaling to attenuate oxidative stress and restore glutathione homeostasis and by inhibiting NFκB signaling to attenuate neuroinflammatory changes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood., Methods: We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated., Results: We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM., Conclusion: HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To identify the most suitable size of imaging-visible embolic agents with balanced safety and efficacy for bariatric arterial embolization (BAE) in a preclinical model., Materials and Methods: Twenty-seven pigs were divided into 3 cohorts. In Cohort I, 16 pigs were randomized to receive (n = 4 each) 40-100-μm microspheres in 1 or 2 fundal arteries, 70-340-μm radiopaque microspheres in 2 fundal arteries, or saline. In Cohort II, 3 pigs underwent renal arterial embolization with either custom-made 100-200-μm, 200-250-μm, 200-300-μm, or 300-400-μm radiopaque microspheres or Bead Block 300-500 μm with microsphere distribution assessed histologically. In Cohort III, 8 pigs underwent BAE in 2 fundal arteries with tailored 100-200-μm radiopaque microspheres (n = 5) or saline (n = 3)., Results: In Cohort I, no significant differences in weight or ghrelin expression were observed between BAE and control animals. Moderate-to-severe gastric ulcerations were noted in all BAE animals. In Cohort II, renal embolization with 100-200-μm microspheres occluded vessels with a mean diameter of 139 μm ± 31, which is within the lower range of actual diameters of Bead Block 300-500 μm. In Cohort III, BAE with 100-200-μm microspheres resulted in significantly lower weight gain (42.3% ± 5.7% vs 51.6% ± 2.9% at 8 weeks; P = .04), fundal ghrelin cell density (16.1 ± 6.7 vs 23.6 ± 12.6; P = .045), and plasma ghrelin levels (1,709 pg/mL ± 172 vs 4,343 pg/mL ± 1,555; P < .01) compared with controls and superficial gastric ulcers (5/5)., Conclusions: In this preclinical model, tailored 100-200-μm microspheres were shown to be most suitable for BAE in terms of safety and efficacy., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors., Methods: Thirty-eight patients with well-differentiated, nonfunctioning PanNETs were obtained from two tertiary referral centers. Patient demographic characteristics and tumor, clinicopathologic features were collected. Tissue from both the EUS-FNA specimen and the primary tumor was extracted from archival tissue blocks. NGS using a panel of ten genes was performed on both samples., Results: In our series, the median age was 61.1 years. Tumors were predominantly left-sided (60.5%) and unifocal (94.7%). The median tumor size was 2.2 cm. NGS detected somatic mutations in 29% of primary tumors and 36.8% of EUS-FNA specimens. In primary tumors, DAXX/ATRX mutations were predominantly detected (63.6%). In EUS-FNA specimens, MEN1 mutations were predominantly detected (64.3%). Among non-wild-type specimens, mutational concordance was achieved in 31.6% of cases. In 11 patients with a detectable mutation in the primary tumor, a mutation was detected in the EUS-FNA specimen in 45.5% of cases, with a mutational concordance of 54.5%., Conclusions: NGS can detect somatic mutations in EUS-FNA specimens of well-differentiated PanNETs. Efforts to improve detection sensitivity and mutational concordance are required to overcome current technical limitations., (© 2023. Society of Surgical Oncology.)

In this study, to develop soft pressure sensor applicable to wearable robots using stretchable polymers and conductive fillers, 3.25 wt% carbon nanotubes/thermoplastic polyurethane filament with shore 94 A were manufactured. Three infill densities (20%, 50%, and 80%) and patterns (zigzag (ZG), triangle (TR), honeycomb (HN)) were applied to print cubes via fused filament fabrication 3D printing. Most suitable infill conditions were confirmed based on the slicing images, morphologies, compressive properties, electrical properties, and electrical heating properties. For each infill pattern, ZG and TR divided the layers into lines and figures, and the layers were stacked by rotation. For HN, the same layers were stacked in a hexagonal pattern. Consequently, TR divided layer in various directions, showed the strongest compressive properties with toughness 1.99 J for of infill density 80%. Especially, the HN became tougher with increased infill density. Also, the HN laminated with the same layer showed excellent electrical properties, with results greater than 14.7 mA. The electrical heating properties confirmed that ZG and HN had the high layer density, which exhibited excellent heating characteristics. Therefore, it was confirmed that performance varies depending on the 3D printing direction, and it was confirmed that HN is suitable for manufacturing soft sensors., (© 2023. Springer Nature Limited.)

Objective: Gastrointestinal stromal tumor (GIST) is a rare kind of neoplasm at the gastrointestinal tract. There are few studies regarding the comparison of gastric and small bowel GIST in Korea. We aimed to analyze clinical characteristics and outcomes between gastric and small bowel GIST after curative resection., Methods: Between May 2005 and Dec 2017, 165 patients who underwent curative resection for gastric GIST (n = 115) and small bowel GIST (n = 50) were retrieved from a retrospective database. They were compared with respect to clinical, pathologic and oncological outcomes., Results: The mean age at surgery in both two group was similar (58.8 vs. 58.6, p = 0.772). The rate of emergency admission and surgery was higher in small bowel GIST group (p < 0.005). The mitotic rate and risk category were not significantly different between the two groups. However, the T stage was higher in small bowel GIST compared to the T stage of gastric GIST (22.6% vs. 44.0%, p = 0.025). During the follow-up, 5-year disease free survival rate was worse in small bowel GIST (82.0%) compared gastric GIST (93.7%) (p = 0.032). 5-year survival rate was not significantly different between the two groups (100.0% vs. 97.7%, p = 0.578). The T stage, mitotic count, and risk category were independent prognostic factors for disease free survival of Gastric and small bowel GIST in Cox multivariate analysis., Conclusion: Small bowel GIST has more advanced T stage and higher rate of emergency surgery. Disease free survival rate was worse in small bowel GIST. Larger scaled prospective study of small bowel GIST is needed., Competing Interests: Declaration of competing interest All authors declare no conflict of interest in this work., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

To enhance the effectiveness and safety of focused ultrasound (FUS) therapy, ultrasound image-based guidance and treatment monitoring are crucial. However, the use of FUS transducers for both therapy and imaging is impractical due to their low spatial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To address this issue, we propose a new method that significantly improve the quality of images obtained by a FUS transducer. The proposed method employs coded excitation to enhance SNR and Wiener deconvolution to solve the problem of low axial resolution resulting from the narrow spectral bandwidth of FUS transducers. Specifically, the method eliminates the impulse response of a FUS transducer from received ultrasound signals using Wiener deconvolution, and pulse compression is performed using a mismatched filter. Simulation and commercial phantom experiments confirmed that the proposed method significantly improves the quality of images acquired by the FUS transducer. The -6 dB axial resolution was improved 1.27 mm to 0.37 mm that was similar to the resolution achieved by the imaging transducer, i.e., 0.33 mm. SNR and CNR also increased from 16.5 dB and 0.69 to 29.1 dB and 3.03, respectively, that were also similar to those by the imaging transducer (27.8 dB and 3.16). Based on the results, we believe that the proposed method has great potential to enhance the clinical utility of FUS transducers in ultrasound image-guided therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)