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In Japan, influenza activity was low throughout the COVID-19 pandemic until the 2022-23 season, when the first influenza outbreak occurred since the 2020-21 season. In our influenza surveillance during the COVID-19 pandemic, co-infection with SARS-CoV-2 and influenza virus had not been detected; however, in January 2024, we identified three pediatric outpatients co-infected with these viruses: one with SARS-CoV-2 Omicron EG.5 sublineage HK.3 and influenza A(H3N2) and two with SARS-CoV-2 Omicron BA.2.86 sublineage JN.1.5 and influenza A(H1N1)pdm09. We evaluated the susceptibility of SARS-CoV-2 against RNA-dependent RNA polymerase inhibitors (remdesivir and molnupiravir) and 3C-like protease inhibitors (nirmatrelvir and ensitrelvir), and that of influenza viruses against neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and the cap-dependent endonuclease inhibitor baloxavir. All viruses tested were susceptible to these antiviral drugs and did not possess amino acid substitutions associated with reduced antiviral susceptibility. The patients were treated with anti-influenza drugs and did not develop severe symptoms despite the co-infection. Since SARS-CoV-2 and influenza viruses continue to evolve, continuous monitoring of their circulation remains essential to assess public health measures and support clinical management., Competing Interests: Declarations of competing interest Yoshihiro Kawaoka has received collaborative research funds from FUJIFILM Toyama Chemical Co. LTD, Shionogi & Co. LTD, and Daiichi Sankyo Pharmaceutical and is a founder of FluGen. Other 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to develop a user-friendly prediction formula for dose rate adjustment after initial 177 Lu-Dotatate therapy from a prospective observational study of patients., Materials and Methods: This study included consenting patients in a prospective observational study who underwent their first treatment in four cycles of 177 Lu-Dotatate treatment at our hospital between January 2022 and February 2024. All patients received 7.4 GBq of 177 Lu-Dotatate. The prediction formula was derived from the regression analysis of tumor-related factors and renal function. Creatinine clearance was estimated using the Cockcroft-Gault equation in this study for renal function., Results: Among the 13 patients (seven males, six females, median age: 59 years), logarithmically transformed total tumor volume (cc) and maximum tumor diameter (mm) of primary tumors or metastases showed strong correlations (p < 0.001, R 2  = 0.897). As such, the maximum tumor diameter was used as the tumor parameter in the prediction formula. Additionally, maximum tumor diameter and creatinine clearance showed strong (p < 0.001, R 2  = 0.768) and moderate (p = 0.013, R 2  = 445) correlations, respectively, with the ratio of the dose rate 5.5-h post-administration to the dose rate immediately post-administration (%) at 1 m from the body surface. The resulting formula, 51.4 + 0.360 × maximum tumor diameter (mm) - 0.212 × creatinine clearance (ml/min), demonstrated an extremely strong correlation (p < 0.001, R 2  = 0.937)., Conclusion: The present study showed that the maximum tumor diameter and renal function affected the declining the dose rate of patients surface after 177 Lu-Dotatate, which can inform post-administration dose rate management and potentially facilitate outpatient treatment in Japan., (© 2024. The Author(s).)

Background: Road safety for older adults should receive more attention in low-income and middle-income countries with rapidly ageing populations., Methods: Using injury surveillance data from Khon Kaen Regional Hospital in northeastern Thailand, we calculated the proportion of older adults in the total number of patients who were fatally and non-fatally injured in road traffic crashes in each year from 2001 to 2020 and the proportion of road user type in the fatal and non-fatal patients by age groups for the entire study period to examine the extent to which older adults were involved in the crashes and with what mode of transportation., Results: During the 20-year period, there were 5046 fatal and 180 353 non-fatal patients of whom 509 (10%) and 6087 (3%) were aged 65 years or older, respectively. From 2001 to 2020, this proportion increased from 3% to 20% among the fatal patients and from 1% to 6% among the non-fatal patients. Of the fatal and non-fatal patients aged 65 years or older, 50% and 54% were involved in road traffic crashes while driving motorcycles and 28% and 22% while riding bicycles or walking, respectively. Compared with patients aged 65-74 years, those aged 75 years or older tended to be bicyclists or pedestrians in the crashes, though as high as 40% of them were motorcycle drivers., Conclusion: Older adults are increasingly injured in road traffic crashes as vulnerable road users in Thailand. Therefore, road safety efforts should consider their presence on the road., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent studies have suggested that gastric cancer does not occur in patients with Helicobacter pylori- negative autoimmune gastritis (AIG); however, this notion is controversial. We encountered a case of gastric cancer associated with AIG in which H. pylori infection was excluded. A woman in her 70s was referred to our hospital for endoscopic resection of an antral adenoma. An H. pylori antibodies test, stool antigens test, H. pylori culture, and histological analysis using Giemsa staining yielded negative results. AIG was suspected because the antrum was endoscopically normal but the body was severely atrophic, which are typical findings of AIG. Anti-parietal cell antibodies were 40-fold positive, the gastrin level was 2950 pg/ml, and the pepsinogen I level, pepsinogen II level, and pepsinogen I/II ratio were 6.3 ng/ml, 5.7 ng/ml, and 1.1, respectively. A pathological examination of the gastric body revealed severe oxyntic atrophy with hyperplasia of enterochromaffin-like cells, whereas the antrum showed no pyloric gland atrophy or inflammation. These findings indicated that the patient had H. pylori -negative AIG. Four years later, a depressed lesion in the lower body and a flat lesion at the angle were observed; the former was a poorly cohesive carcinoma, and the latter was a differentiated adenocarcinoma. Surgical resection revealed that the lesion in the lower body was a poorly cohesive carcinoma invading the submucosa with vascular involvement, whereas the lesion in the angle was an intramucosal differentiated adenocarcinoma. A review of previous studies of gastric cancer with H. pylori -negative AIG suggested that patients with histologically and serologically advanced gastritis are at high risk for carcinogenesis. Even in H. pylori -negative cases, severe gastric mucosal atrophy in AIG cases may indicate a carcinogenic risk; therefore, surveillance for gastric cancer is especially recommended for these cases. Large cohort studies on the association between H. pylori -negative AIG and gastric cancer are warranted., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Tokyo Dental College Ichikawa General Hospital issued approval I-21-43R. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kishikawa et al.)

Objective This study assessed the efficacy of machine learning in predicting thyrotoxicosis and hypothyroidism [thyroid-stimulating hormone >10.0 mIU/L] by leveraging age and sex as variables and integrating biochemical test parameters used by the Japan Society of Health Evaluation and Promotion (JHEP) and the Japan Society of Ningen Dock (JND). Methods Our study included 20,653 untreated patients with Graves' disease, 3,435 untreated patients with painless thyroiditis, 4,266 healthy individuals, and 18,937 untreated patients with Hashimoto's thyroiditis. Machine learning was conducted using Prediction One on three distinct datasets: the Ito dataset (age, sex, and 30 blood tests and biochemical test data), the JHEP dataset (age, sex, and total protein,total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γGTP), alkaline phosphatase, creatinine (CRE), uric acid (UA), and T-Cho test data), and the JND dataset (age, sex, and AST, ALT, γGTP, CRE, and UA test data). Results The results for distinguishing thyrotoxicosis patients from the healthy control group showed that the JHEP dataset yielded substantial discriminative capacity with an area under the curve (AUC) of 0.966, sensitivity of 92.2%, specificity of 89.1%, and accuracy of 91.7%. The JND dataset displayed similar robustness, with an AUC of 0.948, sensitivity of 92.0%, specificity of 81.3%, and accuracy of 90.4%. Differentiating hypothyroid patients from the healthy control group yielded similarly robust performances, with the JHEP dataset yielding AUC, sensitivity, specificity, and accuracy values of 0.864, 84.2%, 72.1%, and 77.4%, respectively, and the JND dataset yielding values of 0.840, 83.2%, 67.2%, and 74.3%, respectively. Conclusion Machine learning is a potent screening tool for thyrotoxicosis and hypothyroidism.

Objective: There are few reports of subacute thyroiditis (SAT) during pregnancy. This study aimed to clarify the clinical characteristics of SAT in pregnant patients., Methods and Results: Seven patients diagnosed with SAT during pregnancy at our institution from January 2004 to December 2021 were identified, and their clinical findings were retrospectively examined. At SAT diagnosis, the median age was 34 [range 31-42] years, the median duration of pregnancy was 5 [4-24] weeks, and all patients had neck pain but no fever. On laboratory examination, median (range) free thyroxine, free triiodothyronine, and C-reactive protein levels were 2.66 (1.14-7.77) ng/dL, 7.1 (3.3-16.1) pg/mL, and 2.22 (0.42-5.79) mg/dL, respectively, and all patients had a hypoechoic lesion of the thyroid gland. Three patients (43%) were treated with steroids, and 3 patients (43%) received replacement therapy with levothyroxine for hypothyroidism following destructive thyroiditis. There were no pregnancy complications in any of the cases. These 7 patients (pregnancy group) were compared with 217 non-pregnant female patients (non-pregnancy group) aged 31 to 42 years who were diagnosed with SAT at our institution from 2016 to 2019. The frequency of body temperatures above 37°C was lower in the pregnancy group than in the non-pregnancy group (0% vs. 65%)., Conclusion: Patients who develop SAT during pregnancy may have less fever than non-pregnant patients with SAT. There were no pregnancy complications in the pregnancy group in this study. This suggests that adverse pregnancy outcomes may be avoided by appropriate management of SAT, including hypothyroidism after destructive thyroiditis.

A 10-year-old neutered male cross-bred cat was referred to our clinic for a solid mass tightly fixed to the right side of the thoracic wall from the 2nd to 4th ribs. Computed tomography revealed the mass had remarkable calcifications and arose from the 3rd costal cartilage. After removal, it was diagnosed histopathologically as a multilobular osteochondrosarcoma (MLO). For tumor resection, extremely wide surgical margins included 6 costal cartilages and 3 sternal segments were required; however, the tumor was successfully resected, followed by reconstruction of the thoracic wall using artificial materials. The cat recovered uneventfully and was good in health for ~4 y. This is apparently the first report of surgical resection of MLO from the costal cartilage of a cat. Key clinical message: To our knowledge, this is the first report of MLO from the costal cartilage in a cat, demonstrating aggressive surgical resection despite extremely wide surgical margins., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Introduction: The underlying risks of asymptomatic embolization during high-power short-duration (HPSD) ablation for atrial fibrillation remain unclear. We aimed to evaluate microembolic signals (MESs) during HPSD ablation with power settings of 50 and 90 W in comparison with those during cryoballoon (CB) ablation using a novel carotid ultrasound-Doppler system that classifies solid and air bubble signals using real-time monitoring., Methods and Results: Forty-seven patients underwent HPSD ablation using radiofrequency (RF), and 13 underwent CB ablation. MESs were evaluated using a novel pastable soft ultrasound probe equipped with a carotid ultrasound during pulmonary vein isolation. We compared the detailed MESs and their timing between RF and CB ablations. The number of MESs and solid signals were significantly higher in the RF group than in CB group (209 ± 229 vs. 79 ± 32, p = .047, and 83 ± 89 vs. 28 ± 17, p = .032, respectively). In RF ablation, the number of MESs, solid, and bubble signals per ablation point, or per second, was significantly higher at 90 W than at 50 W ablation. The MESs, solid, and bubble signals were detected more frequently in the bottom and anterior walls of the left pulmonary vein (LPV) ablation. In contrast, many MESs were observed before the first CB application and decreased chronologically as the procedure progressed. Signals were more prevalent during the CB interval rather than during the freezing time. Among the 28 patients, 4 exhibited a high-intensity area on postbrain magnetic resonance imaging (MRI). The MRI-positive group showed a trend of larger signal sizes than did the MRI-negative group., Conclusion: The number of MESs was higher in the HPSD RF group than in the CB group, with this risk being more pronounced in the 90 W ablation group. The primary detection site was the anterior wall of the LPV in RF and the first interval in CB ablation., (© 2024 Wiley Periodicals LLC.)

Background: Carbon ion radiotherapy (CIRT) is currently used to treat prostate cancer. Rectal bleeding is a major cause of toxicity even with CIRT. However, to date, a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been shown. Similarly, the clinical risk factors for rectal bleeding were absent after 12 fractions of CIRT., Aim: To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate cancer., Methods: Among 259 patients who received 51.6 Gy [relative biological effectiveness (RBE)], in 12 fractions of CIRT, 15 had grade 1 (5.8%) and nine had grade 2 rectal bleeding (3.5%). The dose-volume parameters included the volume (cc) of the rectum irradiated with at least x Gy (RBE) (Vx) and the minimum dose in the most irradiated x cc normal rectal volume (Dx)., Results: The mean values of D6cc, D2cc, V10 Gy (RBE), V20 Gy (RBE), V30 Gy (RBE), and V40 Gy (RBE) were significantly higher in the patients with rectal bleeding than in those without. The cutoff values were D6cc = 34.34 Gy (RBE), D2cc = 46.46 Gy (RBE), V10 Gy (RBE) = 9.85 cc, V20 Gy (RBE) = 7.00 cc, V30 Gy (RBE) = 6.91 cc, and V40 Gy (RBE) = 4.26 cc. The D2cc, V10 Gy (RBE), and V20 Gy (RBE) cutoff values were significant predictors of grade 2 rectal bleeding., Conclusion: The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Takotsubo syndrome (TTS) is characterized by transient regional left ventricular (LV) dysfunction occurring in individuals exposed to physical or emotional stress. Various stressors are triggers for TTS in cancer patients, and anti-cancer drugs have recently been proposed as a trigger. Therefore, further studies are needed to clarify these triggers and avoid the unnecessary interruption of anti-cancer treatment., Case Summary: A 66-year-old woman presented with dyspnoea 10 days after the initiation of atezolizumab in combination with bevacizumab. She had previously received osimertinib as first-line therapy for recurrent lung cancer after primary resection and atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin as second-line therapy. She was admitted due to electrocardiography abnormalities and elevated troponin I and brain natriuretic peptide levels. Echocardiography revealed circumferential severe LV hypokinesis at the mid-ventricular level, with preserved wall motion at the base and apex. Cardiac catheterization performed after the attenuation of symptoms with 20 mg of intravenous furosemide showed normal coronary arteries. Cardiac magnetic resonance imaging on Day 4 revealed increases in T 1 and T 2 values and extracellular volume fraction; however, neither myocardial infiltration of inflammatory cells or myocardial necrosis was observed in endomyocardial samples obtained on the day of her arrival. Atypical TTS was suspected, and she was treated with perindopril, bisoprolol, and spironolactone. Magnetic resonance imaging 1.5 months after the onset of TTS showed improvements in LV contractility, T 1 and T 2 values, and the extracellular volume fraction., Discussion: A more detailed understanding of the relationship between anti-cancer drugs and TTS is crucial for preventing interruptions to anti-cancer therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized to re-populate the tumor milieu due to selection following conventional therapies. Here, we show that 5-aminolevulinic acid (ALA) treatment-a pro-fluorophore used for fluorescence-guided cancer surgery-leads to elevated levels of fluorophore conversion in patient-derived GSC cultures, and subsequent red light-activation induces apoptosis in both intrinsically temozolomide chemotherapy-sensitive and -resistant GSC phenotypes. Red light irradiation of ALA-treated cultures also exhibits the ability to target mesenchymal GSCs (Mes-GSCs) with induced temozolomide resistance. Furthermore, sub-lethal light doses restore Mes-GSC sensitivity to temozolomide, abrogating GSC-acquired chemoresistance. These results suggest that ALA is not only useful for fluorescence-guided glioblastoma tumor resection, but that it also facilitates a GSC drug-resistance agnostic, red light-activated modality to mop up the surgical margins and prime subsequent chemotherapy., (© 2024 American Society for Photobiology.)

Maca ( Lepidium meyenii ), mainly grown in Peru, is a traditional herbal medicine that is mostly used to improve sperm motility and serum hormone levels. Maca phenotypes are represented by purple, black, yellow, white, and mixed colors. Recently, a method for Maca cultivation has been established in Japan. Therefore, we determined the effects of different phenotypes and portions on the antioxidant activities and total polyphenols, anthocyanins, and benzyl-glucosinolate contents in Japanese Maca. Purple Maca skin possessed the highest contents of both total polyphenols, antioxidant activity and anthocyanin content in all Macas. Regarding the benzyl-glucosinolate content, white maca had the highest content and was not correlated with antioxidant activity. In the present study, we revealed that purple Maca skin is recommended for high polyphenol content, antioxidant activity, and anthocyanin content. The results of this study will be useful for selecting phenotypes for the improvement of antioxidant activity or hormone balance., Competing Interests: 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., (© 2024 The Authors.)

Background: Endometriosis is a multifaceted gynecological condition that poses diagnostic challenges and affects a significant number of women worldwide, leading to pain, infertility, and a reduction in patient quality of life (QoL). Traditional diagnostic methods, such as the revised American Society for Reproductive Medicine (r-ASRM) classification, have limitations, particularly in preoperative settings. The Numerical Multi-Scoring System of Endometriosis (NMS-E) has been proposed to address these shortcomings by providing a comprehensive preoperative diagnostic tool that integrates findings from pelvic examinations and transvaginal ultrasonography., Methods: This retrospective study aims to validate the effectiveness of the NMS-E in predicting surgical outcomes and correlating with the severity of endometriosis. Data from 111 patients at Nippon Medical School Hospital were analyzed to determine the correlation between NMS-E scores, including E-score-a severity indicator-traditional scoring systems, surgical duration, blood loss, and clinical symptoms. This study also examined the need to refine parameters for deep endometriosis within the NMS-E to enhance its predictive accuracy for disease severity., Results: The mean age of the patient cohort was 35.1 years, with the majority experiencing symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. A statistically significant positive correlation was observed between the NMS-E's E-score and the severity of endometriosis, particularly in predicting surgical duration (Spearman correlation coefficient: 0.724, p < 0.01) and blood loss (coefficient: 0.400, p < 0.01). The NMS-E E-score also correlated strongly with the r-ASRM scores (coefficient: 0.758, p < 0.01), exhibiting a slightly more excellent predictive value for surgical duration than the r-ASRM scores alone. Refinements in the methodology for scoring endometriotic nodules in uterine conditions improved the predictive accuracy for surgical duration (coefficient: 0.752, p < 0.01)., Conclusions: Our findings suggest that the NMS-E represents a valuable preoperative diagnostic tool for endometriosis, effectively correlating with the disease's severity and surgical outcomes. Incorporating the NMS-E into clinical practice could significantly enhance the management of endometriosis by addressing current diagnostic limitations and guiding surgical planning.

Background: In Japan, older drivers have been encouraged to surrender their driving licenses for traffic safety, despite the potential adverse social and health outcomes of driving cessation. We reconsidered such policies and social pressure by comparing the risk of at-fault motor vehicle collisions (MVCs) across the age groups of drivers., Methods: Using the national data of police-reported MVCs that occurred between 2016 and 2020, we examined the number of at-fault MVCs per licensed driver (MVC rate) and the number of fatally and non-fatally injured persons per at-fault MVC by the sex and age groups of at-fault drivers., Results: The MVC rate of older drivers was higher than that of middle-aged drivers but lower than that of young drivers. The number of injured persons among the collided counterparts (collided car occupants, motorcyclists, bicyclists, and pedestrians) per MVC caused by older drivers was not greater than that by drivers in other age groups. In fatal MVCs caused by older drivers, drivers themselves or their passengers tend to be killed rather than their collided counterparts. Overall, the results were mostly consistent between male and female drivers., Conclusion: The risk of at-fault MVCs increased with the advancing age of drivers after middle age; however, this risk among older drivers did not exceed that among young drivers, without posing a high risk of injuries to their collided counterparts.

The use of a drug-coated balloon (DCB) to treat dysfunctional arteriovenous fistula (AVF) has shown promising results. After percutaneous coronary intervention with DCB, late lumen enlargement (LLE) often develops in the early follow-up phase, but questions regarding the natural history of changes in lesions after DCB angioplasty have not been clearly elucidated. Here, we reported on a patient in whom angiography and angioscopy were performed immediately and 4 months after DCB angioplasty to treat cephalic vein stenosis of the dysfunctional AVF. Immediately after DCB application, angiography showed good dilatation and blood flow and mild vascular dissection that did not affect blood flow. Angioscopy showed that although the balloon had damaged the intima and the paclitaxel particles had adhered to the vessel wall. Four months after DCB treatment, follow-up angiography and angioscopy were performed. Angiography showed LLE in the cephalic vein of the AVF that had been treated by DCB angioplasty. Angioscopy showed that the intima of the vessel had almost completely healed, and the paclitaxel particles had disappeared. LLE might occur when DCB is used for AVF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Postoperative intracranial complications are rare in spine surgery not including cranial procedures. We describe an uncommon case of pseudohypoxic brain swelling (PHBS) and secondary hydrocephalus after transforaminal lumbar interbody fusion (TLIF) presenting as impaired consciousness and repeated seizures., Case Presentation: A 65-year-old man underwent L4-5 TLIF for lumbar spondylolisthesis and began experiencing generalized seizures immediately postoperatively. Computed tomography (CT) revealed diffuse cerebral edema-like hypoxic ischemic encephalopathy. He was transported to our hospital, at which time epidural drainage was halted and anti-edema therapy was commenced. His impaired consciousness improved. However, he suffered secondary hydrocephalus due to continuous bleeding from a dural defect and spinal epidural fluid collection 3 months later. Following the completion of dural repair and insertion of a ventriculoperitoneal shunt, his neurologic symptoms and neuroimaging findings improved significantly., Conclusions: PHBS can be considered in patients with unexpected neurological deterioration following lumbar spine surgery even with the absence of documented durotomy. This might be due to postoperative intracranial hypotension-associated venous congestion, and to be distinguished from the more common postoperative cerebral ischemic events-caused by arterial or venous occlusions-or anesthetics complications.

Background: This study aimed to evaluate the clinical acceptability of rotational gantry-based single-position carbon-ion radiotherapy (CIRT) to reduce the gastrointestinal (GI) dose in pancreatic cancer. We also evaluated the usefulness of the deformable image registration (DIR)-based dosimetry method for CIRT., Material and Methods: Fifteen patients with pancreatic cancer were analyzed. The treatment plans were developed for four beam angles in the supine (SP plan) and prone (PR plan) positions. In the case of using multiple positions, the treatment plan was created with two angles for each of the supine and prone position (SP + PR plan). Dose evaluation for multiple positions was performed in two ways: by directly adding the values of the DVH parameters for each position treatment plan (DVH sum), and by calculating the DVH parameters from the accumulative dose distribution created using DIR (DIR sum). The D 2cc and D 6cc of the stomach and duodenum were recorded for each treatment plan and dosimetry method and compared., Results: There were no significant differences among any of the treatment planning and dosimetry methods (p > 0.05). The DVH parameters for the stomach and duodenum were higher in the PR plan and SP plan, respectively, and DVH sum tended to be between the SP and PR plans. DVH sum and DIR sum, DVH sum tended to be higher for D 2cc and DIR sum tended to be higher for D 6cc ., Conclusion: There were no significant differences in the GI dose, which suggests that treatment with a simple workflow performed in one position should be clinically acceptable. In CIRT, DIR-based dosimetry should be carefully considered because of the potential for increased uncertainty due to the steep dose distributions., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Solution nuclear magnetic resonance (NMR) analysis of polysaccharides can provide valuable information not only on their primary structures but also on their conformation, dynamics, and interactions under physiological conditions. One of the main problems is that non-anomeric 1 H signals typically overlap, and this often hinders detailed NMR analysis. Isotope enrichment, such as with 13 C and 15 N, will add a new dimension to the NMR spectra of polysaccharides, and spectral analysis can be performed with enhanced sensitivity using isolated peaks. For this purpose, here we have prepared uniformly 13 C- and/or 15 N-labeled chondroitin polysaccharides -4)-β-D-glucuronopyranosyl-(1-3)-2-acetamido-2-deoxy-β-D-galactopyranosyl-(1- with molecular weights in the range from 310 to 460 k by bacterial fermentation. The enrichment ratios for 13 C and 15 N were 98.9 and 99.8%, respectively, based on the mass spectrometric analysis of the constituent chondroitin disaccharides. 1 H and 13 C NMR signals were assigned mainly based on HSQC and 13 C-detection experiments including INADEQUATE, HETCOR, and HETCOR-TOCSY. The carbonyl carbon signal of the N-acetyl-β-D-galactosamine residue was unambiguously distinguished from the C6 carbon of the β-D-glucuronic acid residue by the observation of 13 C peak splitting due to 1 J CN coupling in 13 C- and 15 N-labeled chondroitin. The T 2 * and T 1 were measured and indicate that both rigid and mobile sites are present in the long sequence of chondroitin. The conformation, dynamics, and interactions of chondroitin and its derivatives will be further analyzed based on the results obtained in this study., (© 2024 John Wiley & Sons Ltd.)

In recent years, there has been a growing interest in engineering dynamic and autonomous systems with robotic functionalities using biomolecules. Specifically, the ability of molecular motors to convert chemical energy to mechanical forces and the programmability of DNA are regarded as promising components for these systems. However, current systems rely on the manual addition of external stimuli, limiting the potential for autonomous molecular systems. Here, we show that DNA-based cascade reactions can act as a molecular controller that drives the autonomous assembly and disassembly of DNA-functionalized microtubules propelled by kinesins. The DNA controller is designed to produce two different DNA strands that program the interaction between the microtubules. The gliding microtubules integrated with the controller autonomously assemble to bundle-like structures and disassemble into discrete filaments without external stimuli, which is observable by fluorescence microscopy. We believe this approach to be a starting point toward more autonomous behavior of motor protein-based multicomponent systems with robotic functionalities.

Genome-editing tools such as the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system have become essential tools for increasing the efficiency and accuracy of plant breeding. Using such genome-editing tools on maize, one of the most important cereal crops of the world, will greatly benefit the agriculture and the mankind. Conventional genome-editing methods typically used for maize involve insertion of a Cas9-guide RNA expression cassette and a selectable marker in the genome DNA; however, using such methods, it is essential to eliminate the inserted DNA cassettes to avoid legislative concerns on gene-modified organisms. Another major hurdle for establishing an efficient and broadly applicable DNA-free genome-editing system for maize is presented by recalcitrant genotypes/cultivars, since cell/tissue culture and its subsequent regeneration into plantlets are crucial for producing transgenic and/or genome-edited maize. In this study, to establish a DNA-free genome-editing system for recalcitrant maize genotypes/cultivars, Cas9-gRNA ribonucleoproteins were directly delivered into zygotes isolated from the pollinated flowers of the maize-B73 cultivar. The zygotes successfully developed and were regenerated into genome-edited plantlets by co-culture with phytosulfokine, a peptide phytohormone. The method developed herein made it possible to obtain DNA- and selectable-marker-free genome-edited recalcitrant maize genotypes/cultivars with high efficiency. This method can advance the molecular breeding of maize and other important cereals, regardless of their recalcitrant characteristics., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: Down syndrome is the most common chromosomal abnormality associated with intellectual impairments. Unexpected deaths are common with this disease. There are certain difficulties in clarifying the cause of death because the manifestations may be quite diverse and involve many organ systems. Atlantoaxial subluxation is a dangerous complication of Down syndrome, as it may lead to cervical cord-medullary compression., Case Presentation: Herein, we present a case of Down syndrome in a patient who completely recovered from cardiac arrest due to atlantoaxial subluxation. The neck was immobilized during post-cardiac arrest care, and the patient underwent surgery after 14 days. The patient could walk independently and was discharged 3 months later. At the last follow-up 5 years after surgery, the patient's general condition was good., Discussion: Physicians should be aware that atlantoaxial instability can cause cardiac arrest in patients with genetic syndromes., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC., Methods: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13)., Results: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups., Conclusions: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Tubulin C-terminal tail (CTT) is a disordered segment extended from each tubulin monomer of αβ tubulin heterodimers, the building blocks of microtubules. The tubulin CTT contributes to the cellular function of microtubules such as intracellular transportation by regulating their interaction with other proteins and cell shape regulation by controlling microtubule polymerization dynamics. Although the mechanical integrity of microtubules is crucial for their functions, the role of tubulin CTT on microtubule mechanical properties has remained elusive. In this work, we investigate the role of tubulin CTTs in regulating the mechanical properties of microtubules by estimating the persistence lengths and investigating the buckling behavior of microtubules with and without CTT. We find that microtubules with intact CTTs exhibit twice the rigidity of microtubules lacking tubulin CTTs. Our study will widen the scope of altering microtubule mechanical properties for its application in nano bio-devices and lead to novel therapeutic approaches for neurodegenerative diseases with altered microtubule properties., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ikei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. We determined the cryogenic electron microscopy (cryo-EM) structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5'-phosphate derivatives, pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) and pyridoxal phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS), and performed structure-based mutational analysis by patch-clamp recording as well as molecular dynamics (MD) simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo- and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes., Competing Interests: DS, CY, FJ, YW, MI, YY, CG, MH No competing interests declared, (© 2023, Sheng, Yue et al.)

Objective: To examine the association between home safety hazards and unintentional poisoning in children in Mongolia., Methods: We conducted a case-control study using structured questionnaires to investigate safety behaviours, safety equipment use, and home hazards in households with or without children aged 0-5 years who had suffered from poisoning at home (i.e., cases and controls). We recruited 190 cases (105 medicinal and 84 non-medicinal poisonings, and one each) at the National Center for Maternal and Child Health and 379 controls in the communities between 1 March and 30 October 2021., Results: There were large differences between cases' and controls' households in safety behaviours and home hazards: the failure to store all medicines out of reach of children (68% of cases vs. 25% of controls), the failure to store all medicines safely (out of reach, locked or non-existent) (61% vs. 22%), the failure to put all medicines away immediately after use (77% vs. 43%), the presence of things that a child could climb on to reach high surfaces (82% vs. 67%), the presence of medicines transferred into different containers (28% vs. 9%) and the presence of household products transferred into different containers (28% vs. 16%). These home safety hazards were strongly associated with poisoning after controlling for confounders., Conclusion: Children's risk of unintentional poisoning was strongly associated with the unsafe storage of potentially poisonous agents by caregivers and home hazards. Since unsafe storage is widespread, a fail-safe approach such as child-resistant closure of medicines and household products should be considered., (© 2024 John Wiley & Sons Ltd.)

Background: Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho-MLC (p-MLC). A recent study demonstrated mineralocorticoid receptor-related hypertension is associated with RhoA/Rho-associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor-related hypertension., Methods and Results: HL-1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24-hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p-MLC in a dose-dependent manner. MYPT2 knockdown decreased CTGF. Cardiac-specific MYPT2-knockout (c-MYPT2 -/- ) mice exhibited decreased type 1 phosphatase catalytic subunit β and increased p-MLC. A disease model of mouse was induced by subcutaneous aldosterone and 8% NaCl food for 4 weeks after uninephrectomy. Blood pressure elevation and left ventricular hypertrophy were observed in both c-MYPT2 -/- and MYPT2 +/+ mice, with no difference in heart weights or nuclear localization of mineralocorticoid receptor in cardiomyocytes. However, c-MYPT2 -/- mice had higher ejection fraction and fractional shortening on echocardiography after aldosterone treatment. Histopathology revealed less fibrosis, reduced CTGF, and increased p-MLC in c-MYPT2 -/- mice. Basal global radial strain and global longitudinal strain were higher in c-MYPT2 -/- than in MYPT2 +/+ mice. After aldosterone treatment, both global radial strain and global longitudinal strain remained higher in c-MYPT2 -/- mice compared with MYPT2 +/+ mice., Conclusions: Cardiac-specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p-MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor-associated hypertension.

Introduction: Seniors are vulnerable to frailty, a condition linked to falls, fractures, hospitalizations, and sarcopenia. Even with regular meals, senior daycare users are at risk for malnutrition., Methods: This study assessed malnutrition risk in daycare users, using the web-based Mini Nutritional Assessment Form (MNA®-SF). Individuals identified as malnourished or at risk were examined for changes in nutritional status with and without oral nutritional supplementation (ONS)., Results: Of 507 subjects, 138 (27.2%) were malnourished or at risk. Discontinuation rates were 20.0% (7/35) for the ONS group and 40.0% (10/25) for the regular care (RC) group. Among 29 patients with measurable weight change after six months, 19 (ONS group) and 10 (RC group) participated. The ONS group exhibited significant increases in body weight (+1.4 ± 2.9 kg, p  < 0.01), body mass index (BMI) (+0.6 ± 0.9 kg/m 2 , p  < 0.01), calf circumference (+3.2 ± 0.2 cm, p  < 0.01), and grip strength (+1.2 ± 1.9 kg, p  = 0.069). Conversely, the RC group showed no significant increases in body weight (+1.0 ± 1.9 kg, p  = 0.146), BMI (+0.4 ± 0.8 kg/m 2 , p  = 0.176), or grip strength (-0.7 ± 1.7 kg, p  = 0.327), with decreased grip strength and calf circumference (-0.8 ± 0.9 cm, p  < 0.05). In the ONS group, 52.6% (10/19) consumed over 400 kcal/day of ONS, and 84.2% maintained this intake for three months. Malnutrition is prevalent among daycare users., Conclusion: ONS influences weight, BMI, and calf circumference, potentially reducing discontinuation rates., Clinical Trial Registration: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000049767, UMIN000043580., Competing Interests: HT, YK, and MI are employed by Nestlé Health Science Company, Nestlé Japan Ltd., Tokyo, Japan. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Nestlé Japan Ltd., Tokyo, Japan. The funder had the following involvement in the study: the funders were involved in research protocol planning and creation, data collection, statistical analysis, and interpretation of results, but were not directly involved in study data entry. SY has received advisory fees from Nestlé Japan Ltd., for consultation services., (Copyright © 2024 Takano, Kamada, Ichikawa and Yoshida.)

Dry gene powder is a novel non-viral gene-delivery system, which is inhalable with high gene expression. Previously, we showed that the transfection of p16 INK4a or TP53 by dry gene powder resulted in growth inhibitions of lung cancer and malignant pleural mesothelioma (MPM) in vitro and in vivo. Here, we report that dry gene powder containing p53- expression-plasmid DNA enhanced the therapeutic effects of cisplatin (CDDP) against MPM even in the presence of endogenous p53. Furthermore, our results indicated that the safe transfection with a higher plasmid DNA (pDNA) concentration suppressed MPM growth independently of chemotherapeutic agents. To develop a new therapeutic alternative for MPM patients without safety concerns over "vector doses", our in vitro data provide basic understandings for dry gene powder., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims/introduction: This study evaluated the effects of the Medtronic MiniMed 770G hybrid closed-loop system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus., Materials and Methods: This 3-month prospective observational study included 22 participants with type 1 diabetes mellitus who used the Medtronic MiniMed 640G predictive low-glucose suspend system and were switched to the 770G system. Time in the range of 70-180 mg/dL and glycated hemoglobin levels were evaluated; satisfaction, emotional distress and quality of life were assessed using self-reported questionnaires, including the Diabetes Treatment Satisfaction Questionnaire Status, Problem Area in Diabetes and Diabetes Therapy-Related Quality of Life., Results: Time in the range of 70-180 mg/dL increased (63.5 ± 13.4 to 73.0 ± 10.9% [mean ± standard deviation], P = 0.0010), and time above the range of 181-250 mg/dL decreased (26.9 ± 8.9 to 19.6 ± 7.1%, P < 0.0005). Glycated hemoglobin levels decreased (7.7 ± 1.0 to 7.2 ± 0.8%, P = 0.0021). The percentage of participants with time below the range of 54-69 mg/dL <4% of readings increased from 91% to 100% (P < 0.0005). No significant changes were detected in the satisfaction, emotional distress and quality of life levels, but increased sensor calibration might be related to worsened emotional distress and quality of life., Conclusions: The hybrid closed-loop system decreased hyperglycemia and minimized hypoglycemia, but did not improve psychological aspects compared with the predictive low-glucose suspend system, probably because sensor calibration was increased., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Miyazawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis., (© 2023. The Author(s).)

Ischemic stroke in patients with abnormal glucose tolerance results in poor outcomes. Nicotinamide phosphoribosyltransferase (NAMPT), an adipocytokine, exerts neuroprotective effects. However, the pathophysiological role of NAMPT after ischemic stroke with diabetes and the relationship of NAMPT with cerebrovascular lesions are unclear. The purpose of this study was to clarify the pathophysiological role of NAMPT in cerebral ischemia with diabetes, using db/db mice as a type 2 diabetes animal model. The number of degenerating neurons increased after middle cerebral artery occlusion and reperfusion (MCAO/R) in db/db mice compared with the degenerating neurons in db/+ mice. Extracellular NAMPT (eNAMPT) levels, especially monomeric eNAMPT, increased significantly in db/db MCAO/R mice but not db/+ mice in isolated brain microvessels. The increased eNAMPT levels were associated with increased expression of inflammatory cytokine mRNA. Immunohistochemical analysis demonstrated that NAMPT colocalized with GFAP-positive cells after MCAO/R. In addition, both dimeric and monomeric eNAMPT levels increased in the conditioned medium of primary cortical astrocytes under high glucose conditions subsequent oxygen/glucose deprivation. Our findings are the first to demonstrate the ability of increased monomeric eNAMPT to induce inflammatory responses in brain microvessels, which may be located near astrocyte foot processes., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No potential conflicts of interest relevant to this article were reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Irreversible electroporation (IRE) is a tissue ablation technology that kills cells with short electrical pulses that do not induce thermal damage, thereby preserving the extracellular matrix. Preclinical research suggests that IRE may be developed as a tool for regenerative surgery by clearing existing host cells within a solid organ and creating a supportive niche for new cell engraftment. We hypothesized that hepatocytes transplanted by injection into the portal circulation would preferentially engraft within liver parenchyma pretreated with IRE., Methods: Transgene-positive β-galactosidase-expressing hepatocytes were isolated from B6.129S7-Gt(ROSA)26Sor/J (ROSA26) mice and transplanted by intrasplenic injection into wild-type littermates that received liver IRE pretreatment or control sham treatment. Engraftment of donor hepatocytes in recipient livers was determined by X-gal staining., Results: Significantly higher numbers of X-gal + donor hepatocytes engrafted in the livers of IRE-treated mice as compared to sham-treated mice. X-gal + hepatocytes persisted in IRE-treated recipients for at least 11 d post-transplant and formed clusters. Immunostaining demonstrated the presence of HNF4A/Ki67/β-galactosidase triple-positive cells within IRE-ablation zones, indicating that transplanted hepatocytes preferentially engrafted in IRE-treated liver parenchyma and proliferated., Conclusions: IRE pretreatment of the liver increased engraftment of transplanted hepatocytes within the IRE-ablation zone. IRE treatment of the host liver may be developed clinically as a strategy to increase engraftment efficiency of primary hepatocytes and/or hepatocytes derived from stem cells in cell transplant therapies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)