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Introduction Cisplatin is currently the key drug in the chemotherapy regimen for metastatic penile cancer. There are few reports of alternative medicines for patients who cannot tolerate cisplatin. This report describes a case in which carboplatin was used instead. Case presentation The patient presented with a chief complaint of edema in the groin area. On close examination, penile cancer (cT2‐3N3M0 stage IV) with pelvic lymph node metastasis was diagnosed. He was started on chemotherapy with cisplatin (50 mg/m2 on days 1 and 2), paclitaxel (120 mg/m2 on day 1), and 5‐fluorouracil (1000 mg/m2 on days 2–5), but he developed acute kidney failure on the 12th day, thought to be caused by cisplatin. Cisplatin was changed to carboplatin, and chemotherapy was continued. He has received nine courses of chemotherapy and is doing well. Conclusion A case of penile cancer safely and effectively treated with chemotherapy using carboplatin was reported.

Abstract Background Poor patient accrual can delay reporting of clinical trials and, consequently, the development of new treatments. For reducing the risk of additional resource requirements, a method for setting planned accrual periods with minimal deviation from the actual accrual periods is desirable. Risk factors for poor patient accrual and the appropriate method of estimating the required accrual period for timely completion of clinical trials were evaluated using the data of trials conducted by the Japan Clinical Oncology Group. Methods The study included 199 trials that started patient accrual between January 1, 1990, and June 30, 2021. The explanatory variables included factors that could be evaluated prior to trial commencement. We also evaluated whether the estimation methods for accrual pace could lead to completion within the planned accrual period. Results Approximately 23.6% of trials were completed within the planned accrual period. The risk factors for trial extension included planned accrual periods > 3 years (reference group: ≤ 3 years, odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.15–0.92, P = 0.033) and stratified trial design (reference group: nonrandomized phase II trials, nonrandomized phase III trial [OR: 3.28, 95% CI: 0.99–10.9, P = 0.051], randomized phase II trial [OR: 3.91, 95% CI: 0.75–20.30, P = 0.105], and randomized phase III trial [OR: 9.29, 95% CI: 3.39–25.40, P

Background: Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. Methods: This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. Results: The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p

Abstract Background Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. Methods The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p

Purpose: To evaluate the utility of model-based deep learning reconstruction in prostate diffusion-weighted imaging (DWI). Methods: This retrospective study evaluated two prostate diffusion-weighted imaging (DWI) methods: deep learning reconstruction (DL-DWI) and traditional parallel imaging (PI-DWI). We examined 32 patients with radiologically diagnosed and histologically confirmed prostate cancer (PCa) lesions ≥10 mm. Image quality was evaluated both qualitatively (for overall quality, prostate conspicuity, and lesion conspicuity) and quantitatively, using the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) for prostate tissue. Results: In the qualitative evaluation, DL-DWI scored significantly higher than PI-DWI for all three parameters (p

Lignocellulosic materials have inherent complexities and natural nanoarchitectures, such as various chemical constituents in wood cell walls, structural factors such as fillers, surface properties, and variations in production. Recently, the development of lignocellulosic filler-reinforced polymer composites has attracted increasing attention due to their potential in various industries, which are recognized for environmental sustainability and impressive mechanical properties. The growing demand for these composites comes with increased complexity regarding their specifications. Conventional trial-and-error methods to achieve desired properties are time-intensive and costly, posing challenges to efficient production. Addressing these issues, our research employs a data-driven approach to streamline the development of lignocellulosic composites. In this study, we developed a machine learning (ML)-assisted prediction model for the impact energy of the lignocellulosic filler-reinforced polypropylene (PP) composites. Firstly, we focused on the influence of natural supramolecular structures in biomass fillers, where the Fourier transform infrared spectra and the specific surface area are used, on the mechanical properties of the PP composites. Subsequently, the effectiveness of the ML model was verified by selecting and preparing promising composites. This model demonstrated sufficient accuracy for predicting the impact energy of the PP composites. In essence, this approach streamlines selecting wood species, saving valuable time.

Background Retrohepatic inferior vena cava (IVC) injuries remain among the most lethal and serious liver injuries. Gauze packing is currently the first choice for IVC injuries; however, laparotomy itself poses the risk of circulatory collapse. Thus, less invasive treatment strategies are needed.Methods In this study, we conducted an animal experiment to replicate and validate successful treatments for an actual case of retrohepatic IVC injury that we had encountered.Results A woman in her 80s presented to our hospital due to cardiac arrest caused by a pulmonary artery embolism. Venoarterial extracorporeal membrane oxygenation (ECMO) was introduced, and the patient was resuscitated. After resuscitation, contrast-enhanced CT revealed liver and retrohepatic IVC injuries, possibly caused by chest compressions. Liver injury was treated using transarterial embolization of the left hepatic artery. To treat the retrohepatic IVC injury, ECMO flow was increased to enhance the negative drainage pressure. The extravasation of the contrast medium had resolved in IVC angiography, and we opted for nonoperative management. The patient’s hemodynamic status gradually stabilized, and ECMO was withdrawn on day 6. We confirmed these findings in a dog model of retrohepatic IVC injury.Conclusions Our findings from the patient and the animal model suggest that the flow diversion effect of ECMO can effectively manage active bleeding from the IVC by inserting a drainage cannula across the injured lesion. We think this procedure represents a novel treatment option for retrohepatic IVC injuries.

Abstract Physical reservoir computing is a promising solution for accelerating artificial intelligence (AI) computations. Various physical systems that exhibit nonlinear and fading-memory properties have been proposed as physical reservoirs. Highly-integrable physical reservoirs, particularly for edge AI computing, has a strong demand. However, realizing a practical physical reservoir with high performance and integrability remains challenging. Herein, we present an analogue circuit reservoir with a simple cycle architecture suitable for complementary metal-oxide-semiconductor (CMOS) chip integration. In several benchmarks and demonstrations using synthetic and real-world data, our developed hardware prototype and its simulator exhibit a high prediction performance and sufficient memory capacity for practical applications, showing promise for future applications in highly integrated AI accelerators.

Abstract Background In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m2) was non‐inferior to 3‐weekly cisplatin (100 mg/m2) for postoperative high‐risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose‐limiting toxicity effect of cisplatin, affects overall survival (OS). Methods We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5‐fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log‐rank test. Results The total incidence of AKI was lower in the weekly arm than in the 3‐weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3‐weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m2 vs. 239.2 mg/m2; p = 0.94), but lower in the 3‐weekly arm for those who developed AKI (median, 276.3 mg/m2 vs. 297.4 mg/m2; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3‐weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). Conclusions In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3‐weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m2 in this setting.

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is an effective treatment for out-of-hospital cardiac arrest and refractory ventricular fibrillation. Despite the success of this intervention, trauma is a potential complication that may adversely impact patient outcomes. This study assessed the incidence and impact of trauma in patients who underwent ECPR. We hypothesized that all trauma incurred until the conclusion of ECPR would have a significant negative effect on survival and neurological outcomes. Methods: This retrospective observational study examined all ECPR patients admitted to a tertiary emergency medical center between January 2015 and December 2021. All patients underwent pan-scan computed tomography (CT) before admission to the intensive care unit. The head and body trauma were assessed from CT images taken after ECPR. Trauma was defined as all trauma affecting post-ECPR management. In other words, all trauma caused by collapse, trauma caused by resuscitative actions such as chest compressions, and vascular injuries associated with ECPR were included. Univariate analysis of neurological prognosis and 30-day survival due to complicated trauma was performed. Results: A total of 189 patients (mean age 55.2 ± 13.4 years; 85.2% male) were included in this study. Four patients (2.1%) had head trauma, and 31 patients (16.4%) had torso trauma. All patients with head trauma died during extracorporeal membrane oxygenation management. In patients with torso trauma, 30-day survival was not significantly different compared with that in those without trauma (31.5% vs. 41.9%, P = 0.60); good neurological outcomes were almost the same (26.0% vs. 25.8%, P = 1.00). Approximately half of the patients with torso trauma (48%) underwent transarterial embolization. Conclusion: Patients treated with ECPR can suffer a variety of traumatic injuries from the time of collapse to the establishment of ECMO. Head trauma may be lethal and warrants caution. With appropriate treatment, patients with torso trauma may have an equivalent prognosis to those without traumatic complications.

Abstract Background Congenital esophageal stenosis (CES) is a rare condition. We encountered a case of esophageal cancer that developed in an adult with persistent CES. Although many studies have investigated the therapeutic outcomes and performed surveillance for symptoms after treatment for CES, few have performed long-term surveillance or reported on the development of esophageal cancer. We report this case because it is extremely rare and has important implications. Case presentation A 45-year-old woman with worsening dysphagia was transferred to our hospital. The patient was diagnosed with CES at 5 years of age and underwent surgery at another hospital. The patient underwent esophageal dilatation for stenosis at 36 years of age. Esophagoscopy performed at our hospital revealed a circumferential ulcerated lesion and stenosis 15–29 cm from the incisors. Histological examination of the biopsy specimen revealed squamous cell carcinoma. Computed tomography (CT) revealed abnormal circumferential wall thickening in parts of the cervical and almost the entire thoracic esophagus. 18F-fluorodeoxyglucose-positron emission tomography-CT revealed increased uptake in the cervical and upper esophagus. No uptake was observed in the muscular layers of the middle or lower esophagus. Based on these findings, the patient was diagnosed with clinical stage IVB cervical and upper esophageal cancer (T3N1M1 [supraclavicular lymph nodes]). The patient underwent a total esophagectomy after neoadjuvant chemotherapy. The esophagus was markedly thickened and tightly adhered to the adjacent organs. Severe fibrosis was observed around the trachea. Marked thickening of the muscular layer was observed throughout the esophagus; histopathological examination revealed that this thickening was due to increased smooth muscle mass. No cartilage, bronchial epithelium, or glands were observed. The carcinoma extended from the cervical to the middle esophagus, oral to the stenotic region. Finally, we diagnosed the patient with esophageal cancer developing on CES of the fibromuscular thickening type. Conclusions Chronic mechanical and chemical irritations are believed to cause cancer of the upper esophagus oral to a persistent CES, suggesting the need for long-term surveillance that focuses on residual stenosis and cancer development in patients with CES.

Abstract Background There is urgent clinical need to identify reliable prognostic biomarkers that predict the progression of dementia symptoms in individuals with early-phase Alzheimer’s disease (AD) especially given the research on and predicted applications of amyloid-beta (Aβ)-directed immunotherapies to remove Aβ from the brain. Cross-sectional studies have reported higher levels of cerebrospinal fluid and blood glial fibrillary acidic protein (GFAP) in individuals with AD-associated dementia than in cognitively unimpaired individuals. Further, recent longitudinal studies have assessed the prognostic potential of baseline blood GFAP levels as a predictor of future cognitive decline in cognitively unimpaired individuals and in those with mild cognitive impairment (MCI) due to AD. In this systematic review and meta-analysis, we propose analyzing longitudinal studies on blood GFAP levels to predict future cognitive decline. Methods This study will include prospective and retrospective cohort studies that assessed blood GFAP levels as a prognostic factor and any prediction models that incorporated blood GFAP levels in cognitively unimpaired individuals or those with MCI. The primary outcome will be conversion to MCI or AD in cognitively unimpaired individuals or conversion to AD in individuals with MCI. Articles from PubMed and Embase will be extracted up to December 31, 2023, without language restrictions. An independent dual screening of abstracts and potentially eligible full-text reports will be conducted. Data will be dual-extracted using the CHeck list for critical appraisal, data extraction for systematic Reviews of prediction Modeling Studies (CHARMS)-prognostic factor, and CHARMS checklists, and we will dual-rate the risk of bias and applicability using the Quality In Prognosis Studies and Prediction Study Risk-of-Bias Assessment tools. We will qualitatively synthesize the study data, participants, index biomarkers, predictive model characteristics, and clinical outcomes. If appropriate, random-effects meta-analyses will be performed to obtain summary estimates. Finally, we will assess the body of evidence using the Grading of Recommendation, Assessment, Development, and Evaluation Approach. Discussion This systematic review and meta-analysis will comprehensively evaluate and synthesize existing evidence on blood GFAP levels for prognosticating presymptomatic individuals and those with MCI to help advance risk-stratified treatment strategies for early-phase AD. Trial registration PROSPERO CRD42023481200.

Abstract Background ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation. Methods and results Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels. Results In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions. Conclusions The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions.

Abstract Recent advancements on electrohydrodynamic (EHD) soft pumps demonstrate their applicability to various fluid-driven systems such as soft robots, wearable devices, and stretchable electronics. In particular, fiber type EHD pumps reported more recently is a promising pumping element thanks to their versatile fibrous structure. Yet existing EHD fiber pumps are less stretchable and require sophisticated, complex fabrication equipment, implying opportunity for technology advancement. This paper presents a simplified method to create highly stretchable multifunctional fiber EHD pumps. The method employs highly compliant silicone elastomers for the fiber structure that is formed by simple dipping fabrication process. The fabricated pumps (length of 100 mm, inner diameter 4 mm, and mass 5.3 g) exhibit a high stretchability (up to 40% strain) and flow rate and pressure of 167.4 ± 7.6 mL/min (31.6 mL/min/g) and 4.1 ± 0.6 kPa (0.8 kPa/g), respectively. These performances are comparable or even higher than those of previously reported EHD pumps including fiber types. The output performance of the fabricated pumps remain constant for repeated strain cycles (0–25%, up to 2000 cycles) and bending angle up to 180° (corresponding to curvature of 0–30/m). Moreover, the pumps demonstrate unprecedented functionality as a sensor to distinguish the type of fluid inside the tube and to detect strains by reading the capacitance between the electrodes. The characterization result reveals the sensing ability of the pumps as high repeatability up to 30% strain with negligible hysteresis, which is consistent for 5000 cycles.

Abstract Background Predicting the periovulatory period is very important for conception. Current approaches to predicting the periovulatory period include monitoring of basal body temperature and urine luteinizing hormone (LH) concentration; however, these methods are time-consuming. Here, we examined the potential of using vaginal discharge (VD) as a non-invasive means of sample collection for determining the LH surge that indicates ovulation. Methods Urine and VD samples were collected from 35 healthy women aged 20–39 years. VD samples were collected with panty liners to reduce the burden on participants. Daily first urine samples and used panty liners were collected from the 10th through 19th days of the menstrual cycle. Urine and VD LH (uLH and vLH) levels in the samples were measured by enzyme-linked immunosorbent assay. Measured vLH baseline and first surge values were analyzed using Student's t-test and ROC curves. Results Samples for a total of 55 menstrual cycles were collected. We used uLH surge to establish the date of ovulation. uLH surges were observed in 49 cycles, 34 of which had corresponding VD samples that qualified for measurement. Five cycles were excluded due to a lack of vLH data. In the remaining 29 cycles, the vLH surge appeared within the fertile window 90% of the time, and the sensitivity and specificity of the test were 86% and 83%, respectively. Conclusions VD has potential for use as a sample for predicting the periovulatory period by measuring LH content.

Abstract The Osaka Bay is situated at a seismically active region north of the Median Tectonic Line and east of Awaji Island in western Japan, known as part of the Kinki Triangle and the Niigata–Kobe Tectonic Zone. Dense distribution of active faults and high geodetic strain rates characterize the region, posing a major seismic hazard potential to the coastal and metropolitan areas of the Kansai region. To investigate the shallow structure and recent deformation history of active faults in the Osaka Bay, we acquired 15 high-resolution seismic profiles using a Mini-GI airgun and a Boomer as active sources, together with multi-beam bathymetry data across the Osaka Bay Fault. Our seismic sections image a ~ 0.1 to 3.7 km-wide asymmetric anticline forelimb above the Osaka Bay Fault at shallow depths, coupled with a ~ 2.6 km-wide syncline to the west, and a broad, ~ 11 km-wide syncline in the footwall to the east. The synclinal axial surface at shallow depths measured in this study ranges 75°–89°. We observe the vertical displacement of the Osaka Bay Fault increasing northwards along strike. The sediment thickness on the hanging wall, however, is variable, modified by non-tectonic processes such as by tidal currents, affecting the geometry of growth strata. The most recent deformation by the Osaka Bay Fault reaches to near the seafloor by active folding, with large vertical offsets of 8–14 m over the last ~ 11 ka, and 5–11 m over the last ~ 5 ka. By combining with previously reported borehole age data, the average uplift rate on the Osaka Bay Fault is estimated to be ~ 1.0 to 1.7 m/ka during the Latest Pleistocene to Holocene. The inferred slip of the Osaka Bay Fault during the Holocene is likely to account for > 5% of the regional geodetic strain accumulation within the Kinki Triangle. Further studies to evaluate the Holocene slip rates of regional faults are necessary to assess the seismic hazards and the internal strain budgets within the Kinki Triangle and the Niigata–Kobe Tectonic Zone. Graphical abstract

Urine sediment analysis plays a vital role in the evaluation of kidney health. Traditional machine learning techniques approach the task of urine sediment particle detection as an image classification problem, wherein the particles are segmented based on features like edges or thresholds. However, the segmentation process for sediment particles in urine images is complex due to the inherent limitations of low contrast and weak edge characteristics. To mitigate the background noise on detection, that is, to focus more on the important part (i.e., cells), there have appeared several works that employ attention-based urinary sediment detector; however, their works did not consider the best location attention modules. This paper YOLOv7-based urinary sediment detection with attention modules. YOLOv7 is one of state-of-the-art models, and we additionally implement attention modules in the backbone of YOLOv7 so that they empower its network to enhance the feature extraction with mitigating the background noises. In experiments, we perform the proposed models on urinary sediment dataset and the results demonstrate that our proposed models outperform original YOLOv7 and a state-of-the-art urinary sediment detector in terms of recall score by 12.4% and 4.3% as well as mAP score by 7.4% and 1.6%. Our source is provided in the following link: https://github.com/Info-Sys-OU/Multi-class-Urinary-Sediment-Particles-Detection-based-on-YOLOv7-with-Attention-Modules.

Abstract Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

Abstract Background The worldwide vaccination response to COVID-19 has been associated with rare thrombotic complications, including the case of postvaccination splanchnic venous thrombosis we report here. Case presentation An 80-year-old Japanese male with abdominal pain presented to our hospital six days after receiving a dose of the COVID-19 messenger ribonucleic acid vaccine. Abdominal computed tomography showed localized edema of the small intestine, increased density of the surrounding adipose tissue, and a thrombus in the superior mesenteric vein. Conservative inpatient treatment with unfractionated heparin relieved the thrombosis, and the patient is currently receiving oral apixaban as an outpatient. Conclusion Reported cases of thrombosis after COVID-19 vaccination typically have been associated with viral vector vaccines, with few reports of thrombosis induced by mRNA vaccines. The potential for venous thrombosis should be explored when patients present with abdominal pain soon after COVID-19 vaccination.

IntroductionIntra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system.MethodsNE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane.ResultsIn the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5–1.5)% to 4 (4–4)% without activating the system, the MAP was lowered from 95 (91–99) to 41 (37–42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0–1.5)% to 4 (4–4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89–95) to 47 (43–49) mmHg but recovered to 58 (57–58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89–100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were − 2.9 (−4.7 to 1.9)%, 2.9 (2.0–4.7)%, 1.3 (0.8–1.8)%, and − 0.24 (−0.34 to −0.11)%·min−1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully.ConclusionThis system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs.

Abstract Cardiogenic shock is a complex and diverse pathological condition characterized by reduced myocardial contractility. The goal of treatment of cardiogenic shock is to improve abnormal hemodynamics and maintain adequate tissue perfusion in organs. If hypotension and insufficient tissue perfusion persist despite initial therapy, temporary mechanical circulatory support (t-MCS) should be initiated. This decade sees the beginning of a new era of cardiogenic shock management using t-MCS through the accumulated experience with use of intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO), as well as new revolutionary devices or systems such as transvalvular axial flow pump (Impella) and a combination of VA-ECMO and Impella (ECPELLA) based on the knowledge of circulatory physiology. In this transitional period, we outline the approach to the management of cardiogenic shock by t-MCS. The management strategy involves carefully selecting one or a combination of the t-MCS devices, taking into account the characteristics of each device and the specific pathological condition. This selection is guided by monitoring of hemodynamics, classification of shock stage, risk stratification, and coordinated management by the multidisciplinary shock team.

Background: The principle of hepatoblastoma (HB) treatment is complete resection. The removal of tumor-bearing section(s) or hemiliver is widely accepted. However, neither the standardized anterior approach for right hepatectomy nor parenchymal sparing anatomical liver resection has been described for HB. Methods: We retrospectively reviewed the clinical course of two pediatric HB patients who underwent extended right hepatectomy using the anterior approach with the liver hanging maneuver and one who underwent parenchymal sparing anatomical liver resection of S4 apical+S8 ventral/dorsal+S7. The critical aspects of surgical techniques are described in detail. Results: In all three patients, R0 resection was achieved without complications and are currently alive without recurrence after an average follow-up of 28 months. Intraoperative cardiac hemodynamics were stable, even in a trisomy 18 patient with cardiac disease. Conclusions: Our findings suggest that these innovative techniques established in adults are safe and feasible for HB in children. These techniques also allow optimal anatomical liver resection to accomplish curative surgery while maintaining the functional reserve of the remnant liver.

Abstract Background Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN. Methods This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score. Discussion If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT. Trial registration This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 ( https://jrct.niph.go.jp/latest-detail/jRCTs031210100 ). Date of Registration: May 2021.

Abstract The evolutionary transition to self-compatibility facilitates polyploid speciation. In Arabidopsis relatives, the self-incompatibility system is characterized by epigenetic dominance modifiers, among which small RNAs suppress the expression of a recessive SCR/SP11 haplogroup. Although the contribution of dominance to polyploid self-compatibility is speculated, little functional evidence has been reported. Here we employ transgenic techniques to the allotetraploid plant A. kamchatica. We find that when the dominant SCR-B is repaired by removing a transposable element insertion, self-incompatibility is restored. This suggests that SCR was responsible for the evolution of self-compatibility. By contrast, the reconstruction of recessive SCR-D cannot restore self-incompatibility. These data indicate that the insertion in SCR-B conferred dominant self-compatibility to A. kamchatica. Dominant self-compatibility supports the prediction that dominant mutations increasing selfing rate can pass through Haldane’s sieve against recessive mutations. The dominance regulation between subgenomes inherited from progenitors contrasts with previous studies on novel epigenetic mutations at polyploidization termed genome shock.

Abstract Background Anastomotic recurrence of colorectal cancer is rare, but reoperation improves prognosis. However, there is no clear evidence regarding the extent of dissection, and there are few reports on the details of surgery. We used intraoperative lymphatic flow imaging with indocyanine green (ICG) fluorescence as a reference to determine the range of additional resection. Case presentation The patient was a 75-year-old man who underwent laparoscopic right hemicolectomy and extracorporeal functional terminal anastomosis for ascending colon cancer 4 years ago. Histopathological examination revealed a well-differentiated tubular adenocarcinoma, T4aN0M0, pathological stageIIB. During follow-up, anemia was observed, and colonoscopy indicated anastomotic recurrence, so additional laparoscopic resection was performed. Intraoperatively, ICG was injected into the anastomotic site, and the operation proceeded under near-infrared light observation. Lymphatic vessels along the middle colonic artery were visualized down to the root of the vessel. Using this as an indicator, the vessel was ligated from the root. Using the fact that the lymphatic vessels were also depicted in the small intestinal mesentery on the oral side of the anastomosis as an indicator, the small intestine and mesentery were resected about 7 cm from the anastomosis. Conclusions The optimal surgical approach for anastomotic recurrence of colorectal cancer has not been defined. Intraoperative ICG fluorescence imaging can provide images of lymphatic flow from the site of recurrence and may be an indicator of lymph node dissection in the case of anastomotic recurrence.

Despite advancements in the sensitivity and performance of analytical instruments, sample preparation remains a bottleneck in the analytical process. Currently, solid-phase extraction is more widely used than traditional organic solvent extraction due to its ease of use and lower solvent requirements. Moreover, various microextraction techniques such as micro solid-phase extraction, dispersive micro solid-phase extraction, solid-phase microextraction, stir bar sorptive extraction, liquid-phase microextraction, and magnetic bead extraction have been developed to minimize sample size, reduce solvent usage, and enable automation. Among these, in-tube solid-phase microextraction (IT-SPME) using capillaries as extraction devices has gained attention as an advanced “green extraction technique” that combines miniaturization, on-line automation, and reduced solvent consumption. Capillary tubes in IT-SPME are categorized into configurations: inner-wall-coated, particle-packed, fiber-packed, and rod monolith, operating either in a draw/eject system or a flow-through system. Additionally, the developments of novel adsorbents such as monoliths, ionic liquids, restricted-access materials, molecularly imprinted polymers (MIPs), graphene, carbon nanotubes, inorganic nanoparticles, and organometallic frameworks have improved extraction efficiency and selectivity. MIPs, in particular, are stable, custom-made polymers with molecular recognition capabilities formed during synthesis, making them exceptional “smart adsorbents” for selective sample preparation. The MIP fabrication process involves three main stages: pre-arrangement for recognition capability, polymerization, and template removal. After forming the template-monomer complex, polymerization creates a polymer network where the template molecules are anchored, and the final step involves removing the template to produce an MIP with cavities complementary to the template molecules. This review is the first paper to focus on advanced MIP-based IT-SPME, which integrates the selectivity of MIPs into efficient IT-SPME, and summarizes its recent developments and applications.

Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors have exerted cardioprotective effects in clinical trials, but underlying mechanisms are not fully understood. As mitigating sympathetic overactivity is of major clinical concern in the mechanisms of heart failure treatments, we examined the effects of modulation of glucose handling on baroreflex-mediated sympathetic nerve activity and arterial pressure regulations in rats with chronic myocardial infarction (n = 9). Repeated 11-min step input sequences were used for an open-loop analysis of the carotid sinus baroreflex. An SGLT2 inhibitor, empagliflozin, was intravenously administered (10 mg/kg) after the second sequence. Neither the baroreflex neural nor peripheral arc significantly changed during the last observation period (seventh and eighth sequences) compared with the baseline period although urinary glucose excretion increased from near 0 (0.0089 ± 0.0011 mg min−1 kg−1) to 1.91 ± 0.25 mg min−1 kg−1. Hence, empagliflozin does not acutely modulate the baroreflex regulations of sympathetic nerve activity and arterial pressure in this rat model of chronic myocardial infarction.

Abstract In vivo deuterated water (2H2O) labeling leads to deuterium (2H) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with 2H and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a brief period of in vivo systemic 2H2O administration. We initiated systemic 2H2O administration in two xenograft mouse models harboring either human colorectal, HT-29, or pancreatic, MiaPaCa-2, tumors and 2H2O level of ~ 8% in total body water (TBW). Three schemas of 2H2O administration were tested: (1) starting at tumor seeding and continuing for 7 days of in vivo growth with imaging on day 7, (2) starting at tumor seeding and continuing for 14 days of in vivo growth with imaging on day 14, and (3) initiation of labeling following a week of in vivo tumor growth and continuing until imaging was performed on day 14. Deuterium chemical shift imaging of the tumor bearing limb and contralateral control was performed on either day 7 of 14 after tumor seeding, as described. After 14 days of in vivo tumor growth and 7 days of systemic labeling with 2H2O, a clear deuterium contrast was demonstrated between the xenografts and normal tissue. Labeling in the second week after tumor implantation afforded the highest contrast between neoplastic and healthy tissue in both models. Systemic labeling with 2H2O can be used to create imaging contrast between tumor and healthy issue, providing a non-radioactive method for in vivo cancer imaging.