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We report on the quantitative nondestructive analysis of the natural isotopic abundances of hafnium and tungsten elements using nuclear resonance fluorescence. Metallic samples of hafnium and tungsten were irradiated to six quasi-monochromatic γ -ray beams generated by laser Compton scattering in the energy range of 2.4–3.2 MeV. Multiple nuclei were simultaneously excited at each of the six γ -ray beam energies. A high-purity germanium detector array detected deexcitations of the nuclei. In total, 51 transitions were unprecedentedly employed to estimate the isotopic abundances of heavy elements nondestructively. The estimated abundances of three hafnium isotopes and three tungsten isotopes are consistent with standard known natural abundances within the experimental uncertainties. The deviation from the standard values ranges from 0.18 % to 1.36 %. [ABSTRACT FROM AUTHOR]

Limb reduction has occurred multiple times in tetrapod history. Among ratites, wing reductions range from mild vestigialization to complete loss, with emus (Dromaius novaehollandiae) serving as a model for studying the genetic mechanisms behind limb reduction. Here, we explore the developmental mechanisms underlying wing reduction in emu. Our analyses reveal that immobilization resulting from the absence of distal muscles contributes to skeletal shortening, fusion and left-right intraindividual variation. Expression analysis and single cell-RNA sequencing identify muscle progenitors displaying a dual lateral plate mesodermal and myogenic signature. These cells aggregate at the proximal region of wing buds and undergo cell death. We propose that this cell death, linked to the lack of distal muscle masses, underlines the morphological features and variability in skeletal elements due to reduced mechanical loading. Our results demonstrate that differential mobility during embryonic development may drive morphological diversification in vestigial structures., (© 2024. The Author(s).)

Laser-driven neutron sources (LDNSs) can generate strong short-pulse neutron beams, which are valuable for scientific studies and engineering applications. Neutron resonance transmission analysis (NRTA) is a nondestructive technique used for determining the areal density of each nuclide in a material sample using pulsed thermal and epithermal neutrons. Herein, we report the first successful NRTA performed using an LDNS driven by the Laser for Fast Ignition Experiment at the Institute of Laser Engineering, Osaka University. The key challenge was achieving a well-resolved resonance transmission spectrum for material analysis using an LDNS with a limited number of laser shots in the presence of strong background noise. We addressed this by employing a time-gated 6 Li -glass scintillation neutron detector to measure the transmission spectra, reducing the impact of electromagnetic noise and neutron and gamma-ray flashes. Output waveforms were recorded for each laser shot and analyzed offline using a counting method. This approach yielded a spectrum with distinct resonances, which were attributed to 115 In and 109 Ag , as confirmed through neutron transmission simulation. The spectrum was analyzed using the least-square nuclear-resonance fitting program, REFIT, demonstrating the possibility of using an LDNS for nondestructive areal-density material characterization., (© 2024. The Author(s).)

Objective: To investigate the accurate volume changes in the paranasal sinus and nasal cavity with age development, using three-dimensional (3D) imaging software METHODS: Paranasal sinus and nasal cavity volumes from computed tomography (CT) images in patients aged 0-24 years were measured using a 3D model to examine age-related changes. Paranasal sinus and nasal cavity growth were compared between age groups. Additionally, the correlation between body height and paranasal sinus growth was examined., Results: A total of 139 CT scans from 137 patients were analyzed. Volume growth of maxillary, ethmoidal, sphenoid, frontal sinuses, and nasal cavity was observed until 18, 16, 20, 20, and 22 years, respectively. Maxillary sinus rapidly grew at 2-8 and 9-12 years, ethmoid sinus 2-8 and 13-16 years, sphenoid sinus 5-8 years, frontal sinus 2-10 years, and nasal cavity 7-12 years. The median volume after growth completion for maxillary, ethmoidal, sphenoid, frontal sinuses, and nasal cavities was 21,937 mm³, 4868 mm³, 5870 mm³, 3172 mm³, and 15,555 mm³, respectively. The left-right difference in the nasal cavity volume increased with age. Sinus and nasal cavity growth completion was delayed by 2-4 years compared to general height growth., Conclusion: Growth of the ethmoid, maxillary, sphenoid, frontal sinus, and nasal cavity was completed in approximately 20 years. Compared to the results shown in reports based primarily on 2D measurements, the ethmoid and sphenoid sinuses and nasal cavity were found to continue to grow until older age than previously thought., (Copyright © 2024. Published by Elsevier B.V.)

Estimated glomerular filtration rate (eGFR) variation is associated with end-stage kidney disease (ESKD) development in patients with chronic kidney disease; whether annual variations in eGFR at health check-ups is associated with ESKD risk in the general population is unclear. We conducted a retrospective cohort study using Japanese national medical insurance claims from 2013 to 2020. Individuals who had their eGFR levels measured three times in annual health check-ups were included (N = 115,191), and the coefficient of variation of eGFR (CVeGFR) was calculated from 3-point eGFR. The end-point was ESKD as reported in the claims data. We analyzed the association between CVeGFR and ESKD incidence after adjusting for conventional ESKD risk factors. The CVeGFR median distribution was 5.7% (interquartile range: 3.5-8.5%). During a median follow-up period of 3.74 years, 164 patients progressed to ESKD. ESKD incidence was significantly higher in the highest quartile group (CVeGFR ≥ 8.5%) than in the other groups (P < 0.0001). After adjusting for risk factors, individuals with CVeGFR ≥ 8.5% had a significantly high ESKD incidence (adjusted hazard ratio: 3.01; 95% CI 2.14-4.30). High CVeGFR in annual health check-ups was associated with high ESKD incidence, independent of its other conventional risk factors, in the general population., (© 2024. The Author(s).)

Background/aim: There are only a few studies on dosimetry with ultrahigh-dose-rate (uHDR) scanned carbon-ion beams. This study investigated the characteristics of four types of ionization chambers for the uHDR beam., Materials and Methods: We employed a newly developed large-plane parallel chamber to monitor a 208.3-MeV/u uHDR scanned carbon-ion beam with a 110-Gy/s average dose rate. The ionization chambers used were the Advanced Markus chamber (AMC), PinPoint 3D chamber (PPC), Farmer chamber (FC), and large-plane parallel chamber (StingRay). The AMC and StingRay surfaces and the PPC and FC geometric centers were aligned to the radiation isocenter using treatment room lasers. Using the voltage range stated in the instruction manuals, we obtained the saturation curves of the chambers. From these curves, we obtained the ion recombination correction factors using the two-voltage and three-voltage linear methods. The dose linearity was evaluated using five measurement points, and the chamber repeatability was verified by conducting repeated measurements for different dose values., Results: Although all chambers, except for AMC, reached saturation when specified voltages were applied, they exhibited excellent linearity for different dose values. The ion recombination correction factors of the AMC obtained using the aforementioned linear methods were nearly 1. Additionally, all chambers exhibited excellent repeatability. Although the standard deviation of the PPC for the lowest dose was ~1.5%, those of all the other chambers were <1.0%., Conclusion: All ionization chambers can be used for measuring the relative dose, and absolute dose can be conveniently measured using the AMC with an uHDR carbon-ion scanned beam., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: This study assessed the feasibility of using three-dimensional (3D) models of intrapelvic vascular patterns constructed using computed tomography (CT) and magnetic resonance imaging (MRI) fusion data for preoperative planning in patients with locally recurrent rectal cancer., Methods: Eleven patients scheduled for pelvic exenteration were included. The 3D fusion data of the intrapelvic vessels constructed using CT and MRI with true fast imaging with steady-state precession sequence (True FISP) were evaluated preoperatively. Contrast ratios (CR) between the piriformis muscle and the intrapelvic vessels were calculated to identify a valid modality for 3D modeling and creating CT/MRI fusion-reconstructed volume-rendered images., Results: The CR values of the internal and external iliac arteries were significantly higher on CT images than MR images (CT vs. MRI; 0.63 vs. 0.45, p < 0.01). However, the CR value of the internal iliac vein was significantly higher on MR than CT images (CT vs. MRI; 0.23 vs. 0.55, p < 0.01)., Conclusions: MRI with True FISP yielded high signal-to-noise ratios and aided in delineating the internal iliac vein around the piriformis muscle. More precise 3D models can be constructed using this technique in the future to aid in the resection of locally recurrent rectal cancer., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease (CVD), is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear., Objective: We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD., Design: Cross-sectional single-center observational study., Methods: We assessed 222 patients (94 men and 128 women; age 20-80) who were diagnosed with MASLD via liver biopsy with available medical history, physical examination, and biochemical measurement data. Serum ester-type cholesterol and free cholesterol contents in the remnant lipoproteins were measured using an enzymatic method., Results: Serum Rem-C levels were significantly higher in patients with NAFLD activity score (NAS) 5-8, ＞66% steatosis grade, lobular inflammation with ≥5 foci, and many cells/prominent ballooning cells (a contiguous patch of hepatocytes showing prominent ballooning injury) than in patients with NAS 1-4, <33% steatosis grade, lobular inflammation with <2 foci, and few ballooning cells (several scattered balloon cells), respectively. While univariate analysis revealed no significant association between Rem-C levels and advanced fibrosis, a significant association between Rem-C levels and NAS was evident. This relationship remained significant in multivariate analysis adjusted for confounders. Furthermore, in the analysis by sex, these relationships were significant for men but not for women., Conclusion: High serum Rem-C levels were associated with high NAS, but not with fibrosis stage, particularly in men. Controlling serum Rem-C level may improve MASLD activity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. 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. See the journal About page for additional terms.)

Pauci-immune crescentic glomerulonephritis (PICGN) is one of the pathologies causing rapidly progressive glomerulonephritis, often associated with anti-neutrophil cytoplasmic antibody (ANCA); however, in 10-30% of cases, ANCAs are negative. While a relatively large number of cases of ANCA-positive PICGN complicated with malignancy have been previously reported, the number of cases of ANCA-negative PICGN with malignancy is limited. The prognosis for such cases was poor, and many patients died within a relatively short period. Here, we report the case of ANCA-negative PICGN complicated with malignancy successfully treated by corticosteroid and radiation therapy. A 63-year-old Japanese man was admitted to our hospital due to spiking fevers in the previous 3 months. Based on the findings of imaging and pathological tests, he was diagnosed with locally advanced lung adenocarcinoma with mediastinal involvement. After admission, his renal function rapidly deteriorated, and urinalysis showed heavy proteinuria. In serological tests, serology for autoantibodies, including ANCAs, was negative. The kidney biopsy revealed PICGN with prominent endocapillary proliferation. We administered corticosteroid therapy for glomerulonephritis and subsequent radiation therapy for lung carcinoma, both of which were effective. He has been alive without progression of malignancy or kidney disease for 5 years after discharge. In patients with malignancy presenting with acute deterioration of kidney function, although infrequent, one of the conceivable pathological conditions to consider is ANCA-negative PICGN associated with malignancy. In such cases, even with negative antibodies such as ANCA, pathological examination is warranted, and a combination of anti-tumor therapy and immunosuppressive therapy is expected to be effective., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The pharmacokinetics and tissue distribution of renadirsen sodium, a dystrophin exon-skipping phosphorothioate-modified antisense oligonucleotide with 2'- O ,4'- C -ethylene-bridged nucleic acid (ENA), after subcutaneous or intravenous administration to cynomolgus monkeys were investigated. The plasma concentration of renadirsen after subcutaneous administration at 1, 3, and 10 mg/kg increased with the dose. The absolute bioavailability at 3 mg/kg after subcutaneous administration was calculated as 88.6%, and the time to reach maximum plasma concentration of renadirsen was within 4 h, indicating the efficient and rapid absorption following subcutaneous administration. The exposure of muscle tissues to renadirsen was found to increase with repeated dosing at 6 mg/kg, and higher exposure was observed in the diaphragm and heart than in the quadriceps femoris and anterior tibialis muscles. Renadirsen achieved more exon 45-skipped dystrophin mRNA in the diaphragm and heart than in the quadriceps femoris and anterior tibialis muscles. Renadirsen also showed a cumulative skipping effect in a repeated-dose study. The findings on exon 45-skipped dystrophin mRNA in these muscle tissues were consistent with the concentration of renadirsen in these tissues. Because it is not feasible to directly evaluate drug concentration and exon skipping in the heart and diaphragm in humans, the pharmacokinetics and pharmacodynamics of renadirsen in these tissues in monkeys are crucial for the design and interpretation of clinical settings.

The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis., (© 2024. The Author(s).)

Background/aim: Caudal-type homeobox transcription factor 2 (CDX2) is a master regulator of intestinal development and maintenance of the intestinal epithelium. We previously revealed that CDX2 Low colorectal cancers (CRCs) were associated with poor survival and differential response to adjuvant chemotherapy. MicroRNAs (miRNAs), a class of non-coding RNAs typically composed of fewer than 25 nucleotides, are known to regulate gene expression and signaling pathways. This study aimed to identify oncogenic miRNAs induced by CDX2 in CRC., Materials and Methods: HCT116 cells were cultured and transfected with CDX2 siRNA. The expression levels of four oncogenic miRNAs (miR-9, miR-25, miR-106b and miR-221) were quantified by RT-qPCR. To understand whether CDX2 represented a key regulator of miR-221 expression in vivo, we analyzed the relationship between CDX2 and miR-221expression levels in the TCGA COAD database (n=454)., Results: The expression level of miR-221 was significantly up-regulated in CDX2 knockdown cells (n=2, p<0.05). In the TCGA database, we observed an inverse correlation between CDX2 and miR-221 expression levels, consistent with our in vitro data (r=-0.114, p=0.0149). Furthermore, the expression level of miR-221 was significantly elevated in patients with CDX2 Low CRC (p<0.05)., Conclusion: Knockdown of CDX2 induces microRNA-221 up-regulation in human CRC. Further research is warranted to elucidate the molecular mechanisms underlying miR-221 up-regulation in CDX2 Low CRCs., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Despite the established antitumor effectiveness and synergistic interactions of melatonin with photon irradiation, its role in carbon-ion radiotherapy remains uncertain. This study aimed to elucidate the mechanisms and potential clinical advantages of combining exogenous melatonin therapy with carbon-ion radiotherapy., Materials and Methods: The investigation assessed the impact of combining exogenous melatonin with photon or carbon-ion irradiation on cell-cycle modulation and DNA-repair capability using the melanoma cell line B16F10. RNA sequencing and bioinformatics analysis were conducted to explore mechanisms and evaluate potential clinical benefits, with validation performed on the osteosarcoma cell line LM8., Results: Pre-treatment with melatonin reduced the survival fraction of B16F10 and LM8 cells upon exposure to photon and carbon-ion radiation. Mechanistically, melatonin was found to inhibit G 2 /M arrest, preserve DNA damage, and suppress key genes involved in DNA double-strand break repair after 8 Gy carbon-ion radiation. Furthermore, RNA sequencing and bioinformatics analysis revealed favorable changes in genes associated with survival and metastasis, highlighting potential clinical significance. LM8 cells treated with melatonin exhibited increased radiosensitivity and suppression of DNA-repair proteins., Conclusion: The combination of exogenous melatonin not only heightened radiosensitivity and modulated hallmark tumor gene sets in vitro but also markedly suppressed the efficiency of DNA double-strand break-repair pathway, thus enhancing the cytotoxicity of carbon-ion radiotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Doege-Potter syndrome, characterized by solitary fibrous tumors and non-islet cell tumor hypoglycemia, is rare. Here, we report a case of Doege-Potter syndrome in which retroperitoneal tumor resection was performed with continuous intraoperative blood glucose monitoring., Case Presentation: A 37-year-old man presented with hypoglycemia-related symptoms, and a 10 × 12 × 9 cm tumor was found in his right kidney. Following tumor resection, insulin secretory abnormalities improved, and intraoperative blood glucose monitoring showed no hypoglycemic events. High levels of insulin-like growth factor-II confirmed the diagnosis of an insulin-like growth factor-II-producing tumor with non-islet cell tumor hypoglycemia. Postoperative serum insulin-like growth factor-II levels normalized, with no recurrence observed over 3 years., Conclusions: This case highlights the rarity of primary retroperitoneal Doege-Potter syndrome, emphasizes the safety of intraoperative blood glucose levels during surgery, and suggests rapid recovery of insulin secretion postoperatively., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Purpose: Non-invasive reduction in patients with incarcerated obturator hernias is an emergency surgery alternative. There are two non-invasive reduction types: manual and ultrasonographic (ultrasound-guided and ultrasound-assisted reduction). However, the impact of ultrasound guidance on manual reduction has not been adequately evaluated. We aimed to compare non-invasive ultrasound reduction with manual reduction in patients with incarcerated obturator hernias., Methods: We searched MEDLINE, Cochrane Central Library, Embase, Ichushi Web, ClinicalTrial.gov, and ICTRP for relevant studies. The primary outcomes were success and bowel resection rates. We performed a subgroup analysis between ultrasound-guided and ultrasound-assisted reductions. This study was registered in PROSPERO (CRD 42,024,498,295)., Results: We included six studies (112 patients, including 12 from our cohort). The success rate was 78% (69 of 88 cases) with ultrasonographic reduction and 33% (8 of 24 cases) with manual reduction. The success rate was higher with ultrasonographic than with manual reduction. Subgroup analysis revealed no significant difference between ultrasonography-assisted (76%) and ultrasonography-guided (80%) reductions (p = 0.60). Non-invasive reductions were predominantly successful within 72 h of onset, although durations extended up to 216 h in one case. Among the successful reduction cases, emergency surgery and bowel resection were necessary in two cases after 72 h from onset. Bowel resection was required in 48% (12 of 25), where the non-invasive reduction was unsuccessful within 72 h of confirmed onset., Conclusions: Ultrasonographic reduction can be a primary treatment option for patients with obturator hernias within 72 h of onset by emergency physicians and surgeons on call. Future prospective studies are needed to evaluate ultrasonographic reduction's impact., (© 2024. The Author(s).)

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The temperature measurement of material inside of an object is one of the key technologies for control of dynamical processes. For this purpose, various techniques such as laser-based thermography and phase-contrast imaging thermography have been studied. However, it is, in principle, impossible to measure the temperature of an element inside of an object using these techniques. One of the possible solutions is measurements of Doppler brooding effect in neutron resonance absorption (NRA). Here we present a method to measure the temperature of an element or an isotope inside of an object using NRA with a single neutron pulse of approximately 100 ns width provided from a high-power laser. We demonstrate temperature measurements of a tantalum (Ta) metallic foil heated from the room temperature up to 617 K. Although the neutron energy resolution is fluctuated from shot to shot, we obtain the temperature dependence of resonance Doppler broadening using a reference of a silver (Ag) foil kept to the room temperature. A free gas model well reproduces the results. This method enables element(isotope)-sensitive thermometry to detect the instantaneous temperature rise in dynamical processes., (© 2024. The Author(s).)

A 66-year-old man presented to our institution with a positive fecal occult blood test and lower abdominal pain. Although a tumor was found in the sigmoid colon, biopsy and imaging studies failed to enable the diagnosis of the cancer, and the patient underwent surgery for treatment and diagnosis. The tumor had two distinct areas with differing features shown both histopathologically and on imaging; it was thus diagnosed as a leiomyosarcoma of the sigmoid colon with a pleomorphic component. Here, we describe a rare case of leiomyosarcoma of the sigmoid colon with a pleomorphic component. There are no reports of leiomyosarcoma with pleomorphic components arising in the colon in the literature; thus, the recurrence and metastatic characteristics are unknown. Therefore, accumulating cases in the literature may provide valuable insights into diagnosing and treating these rare tumors., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Thanatophoric dysplasia (TD) is a rare and severe type of skeletal dysplasia. Typical clinical findings include macrocephaly, shortening of the four limbs, underdeveloped lungs, and thoracic hypoplasia. Neonates with TD develop severe respiratory problems due to thoracic hypoplasia and require respiratory management for survival. Despite the resolution of respiratory problems, long-term survival cases are rare. Previous studies have reported that surgical procedures in patients with TD are limited to those necessary for survival, including tracheostomy, laminectomy, and ventricular shunt. A 1-year-old boy with TD was treated with laparoscopic herniorrhaphy. To the best of our knowledge, this is the first report of TD treated with laparoscopic procedure., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Resistance to potassium tellurite (PT) is an important indicator in isolating Shiga toxin-producing Escherichia coli (STEC) O157:H7 and other major STEC serogroups. Common resistance determinant genes are encoded in the ter gene cluster. We found an O157:H7 isolate that does not harbor ter but is resistant to PT. One nonsynonymous mutation was found in another PT resistance gene, tehA , through whole-genome sequence analyses. To elucidate the contribution of this mutation to PT resistance, complementation of tehA and the related gene tehB in isogenic strains and quantitative RT‒PCR were performed. The results indicated that the point mutation not only changed an amino acid of tehA , but also was positioned on a putative internal promoter of tehB and increased PT resistance by elevating tehB mRNA expression. Meanwhile, the amino acid change in tehA had negligible impact on the PT resistance. Comprehensive screening revealed that 2.3% of O157:H7 isolates in Japan did not harbor the ter gene cluster, but the same mutation in tehA was not found. These results suggested that PT resistance in E. coli can be enhanced through one mutational event even in ter -negative strains., Importance: Selective agents are important for isolating Shiga toxin-producing Escherichia coli (STEC) because the undesirable growth of microflora should be inhibited. Potassium tellurite (PT) is a common selective agent for major STEC serotypes. In this study, we found a novel variant of PT resistance genes, tehAB , in STEC O157:H7. Molecular experiments clearly showed that one point mutation in a predicted internal promoter region of tehB upregulated the expression of the gene and consequently led to increased resistance to PT. Because tehAB genes are ubiquitous across E. coli , these results provide universal insight into PT resistance in this species., Competing Interests: The authors declare no conflict of interest.

In linear accelerator-based stereotactic irradiation (STI) for brain metastasis, cone-beam computed tomography (CBCT) image quality is essential for ensuring precise patient setup and tumor localization. However, CBCT images may be degraded by the deviation of the CBCT isocenter from the brain center. This study aims to investigate the effects of the distance from the brain center to the CBCT isocenter (DBI) on the image quality in STI. An anthropomorphic phantom was scanned with varying DBI in right, anterior, superior, and inferior directions. Thirty patients undergoing STI were prospectively recruited. Objective metrics, utilizing regions of interest included contrast-to-noise ratio (CNR) at the centrum semiovale, lateral ventricle, and basal ganglia levels, gray and white matter noise at the basal ganglia level, artifact index (AI), and nonuniformity (NU). Two radiation oncologists assessed subjective metrics. In this phantom study, objective measures indicated a degradation in image quality for non-zero DBI. In this patient study, there were significant correlations between the CNR at the centrum semiovale and lateral ventricle levels (r s = - 0.79 and - 0.77, respectively), gray matter noise (r s = 0.52), AI (r s = 0.72), and NU (r s = 0.91) and DBI. However, no significant correlations were observed between the CNR at the basal ganglia level, white matter noise, and subjective metrics and DBI (r s  < ± 0.3). Our results demonstrate the effects of DBI on contrast, noise, artifacts in the posterior fossa, and uniformity of CBCT images in STI. Aligning the CBCT isocenter with the brain center can aid in improving image quality., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Objective: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223., Methods: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed., Results: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15)., Conclusions: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Pancreas divisum (PD) represents a prevalent congenital pancreatic variant, typically arising from the failure of fusion between the ventral and dorsal pancreatic ducts. This condition is frequently associated with recurrent pancreatitis. We herein present a case involving an incomplete PD diagnosis following the identification of a refractory postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (DP) for pancreatic cancer. A 74-year-old female patient, who had undergone laparoscopic DP for pancreatic cancer, developed a POPF accompanied by intraabdominal bleeding, necessitating urgent intervention radiology to avert life-threatening complications. Following this, intraabdominal drainage was performed through an intraoperative drainage root. Subsequent fistulography and endoscopic retrograde pancreatography unveiled the presence of an incomplete PD for the first time. Consequently, a stent was placed in the Santorini duct. However, the volume of pancreatic juice from the intraabdominal drainage tube exhibited no reduction. Despite repeated attempts to access the pancreatic duct via a guidewire through the drainage tube, these endeavors proved futile. Paradoxically, the removal of the external drainage tube led to a recurrence of intraabdominal abscess formation. Consequently, reinsertion of the drainage tube became imperative. Consideration was given to draining the abscess under endoscopic ultrasonography and performing pancreatic duct drainage. However, due to the diminution of the abscess cavity through the external fistula drainage procedure, coupled with the absence of pancreatic duct dilation and its tortuous course, it was deemed a formidable challenge. the patient necessitated a lifestyle adaptation with a permanently placed percutaneous drainage tube., (© 2024. Japanese Society of Gastroenterology.)

Objective: Previous studies show that the COVID-19 pandemic affected the number of surgeries performed. However, data on the association between the COVID-19 pandemic and otolaryngologic surgeries according to subspecialties are lacking. This study was performed to evaluate the impact of the COVID-19 pandemic on various types of otolaryngologic surgeries., Methods: We retrospectively identified patients who underwent otolaryngologic surgeries from April 2018 to February 2021 using a Japanese national inpatient database. We performed interrupted time-series analyses before and after April 2020 to evaluate the number of otolaryngologic surgeries performed. The Japanese government declared its first state of emergency during the COVID-19 pandemic in April 2020., Results: We obtained data on 348,351 otolaryngologic surgeries. Interrupted time-series analysis showed a significant decrease in the number of overall otolaryngologic surgeries in April 2020 (-3619 surgeries per month; 95% confidence interval, -5555 to -1683; p < 0.001). Removal of foreign bodies and head and neck cancer surgery were not affected by the COVID-19 pandemic. In the post-COVID-19 period, the number of otolaryngologic surgeries, except for ear and upper airway surgeries, increased significantly. The number of tracheostomies and peritonsillar abscess incisions did not significantly decrease during the COVID-19 pandemic., Conclusion: The COVID-19 pandemic was associated with a decrease in the overall number of otolaryngologic surgeries, but the trend differed among subspecialties., Competing Interests: Declaration of competing interest The authors have no financial relationship to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer., Methods: Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45 Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated., Results: Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D 99% in group 1 (n = 29) was significantly higher than that in group 2 (n = 26), and D max , D 0.03cc , D 1cc , and D 10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5 ± 12.2%) in group 1 was significantly higher (p < 0.05) than that in group 2 (74.7 ± 10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%., Conclusions: The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer., (© 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.)

Background: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test., Methods: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation., Results: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation., Conclusion: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

To investigate the geometric accuracy of the radiation focal point (RFP) and cone-beam computed tomography (CBCT) over long-term periods for the ICON Leksell Gamma Knife radiosurgery system. This phantom study utilized the ICON quality assurance tool plus, and the phantom was manually set on the patient position system before the implementation of treatment for patients. The deviation of the RFP position from the unit center point (UCP) and the positions of the four ball bearings (BBs) in the CBCT from the reference position were automatically analyzed. During 544 days, a total of 269 analyses were performed on different days. The mean ± standard deviation (SD) of the deviation between measured RFP and UCP was 0.01 ± 0.03, 0.01 ± 0.03, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively. The deviations with offset values after the cobalt-60 source replacement (0.00 ± 0.03, -0.01 ± 0.01, and -0.01 ± 0.01 mm in the X, Y, and Z directions, respectively) were significantly (p = 0.001) smaller than those before the replacement (0.02 ± 0.03, 0.02 ± 0.01, and -0.02 ± 0.01 mm in the X, Y, and Z directions, respectively). The overall mean ± SD of four BBs was -0.03 ± 0.03, -0.01 ± 0.05, and 0.01 ± 0.03 mm in the X, Y, and Z directions, respectively. Geometric positional accuracy was ensured to be within 0.1 mm on most days over a long-term period of more than 500 days., (© 2024. The Author(s).)

The purpose of the study is to investigate the variation in Hounsfield unit (HU) values calculated using dual-energy computed tomography (DECT) scanners. A tissue characterization phantom inserting 16 reference materials were scanned three times using DECT scanners [dual-layer CT (DLCT), dual-source CT (DSCT), and fast kilovoltage switching CT (FKSCT)] changing scanning conditions. The single-energy CT images (120 or 140 kVp), and virtual monochromatic images at 70 keV (VMI 70 ) and 140 keV (VMI 140 ) were reconstructed, and the HU values of each reference material were measured. The difference in HU values was larger when the phantom was scanned using the half dose with wrapping with rubber (strong beam-hardening effect) compared with the full dose without the rubber (reference condition), and the difference was larger as the electron density increased. For SECT, the difference in HU values against the reference condition measured by the DSCT (3.2 ± 5.0 HU) was significantly smaller (p < 0.05) than that using DLCT with 120 kVp (22.4 ± 23.8 HU), DLCT with 140 kVp (11.4 ± 12.8 HU), and FKSCT (13.4 ± 14.3 HU). The respective difference in HU values in the VMI 70 and VMI 140 measured using the DSCT (10.8 ± 17.1 and 3.5 ± 4.1 HU) and FKSCT (11.5 ± 21.8 and 5.5 ± 10.4 HU) were significantly smaller than those measured using the DLCT 120 (23.1 ± 27.5 and 12.4 ± 9.4 HU) and DLCT 140 (22.3 ± 28.6 and 13.1 ± 11.4 HU). The HU values and the susceptibility to beam-hardening effects varied widely depending on the DECT scanners., (© 2024. The Author(s).)

Background: Few studies have reported reliable prognostic factors for immune checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC). Therefore, we investigated prognostic factors in patients treated with ICIs for unresectable or metastatic RCC., Methods: We included 43 patients who received ICI treatment for RCC between January 2018 and October 2021. Blood samples were drawn before treatment, and 73 soluble factors in the plasma were analyzed using a bead-based multiplex assay. We examined factors associated with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAE) using the Chi-squared test, Kaplan-Meier method, and the COX proportional hazards model., Results: Patients exhibited a median PFS and OS of 212 and 783 days, respectively. Significant differences in both PFS and OS were observed for MMP1 (PFS, p < 0.001; OS, p = 0.003), IL-1β (PFS, p = 0.021; OS, p = 0.008), sTNFR-1 (PFS, p = 0.017; OS, p = 0.005), and IL-6 (PFS, p = 0.004; OS, p < 0.001). Multivariate analysis revealed significant differences in PFS for MMP1 (hazard ratio [HR] 5.305, 95% confidence interval [CI], 1.648-17.082; p = 0.005) and OS for IL-6 (HR 23.876, 95% CI, 3.426-166.386; p = 0.001). Moreover, 26 patients experienced irAE, leading to ICI discontinuation or withdrawal. MMP1 was significantly associated with irAE (p = 0.039)., Conclusion: MMP1 may be associated with severe irAE, and MMP1, IL-1β, sTNFR-1, and IL-6 could serve as prognostic factors in unresectable or metastatic RCC treated with ICIs. MMP1 and IL-6 were independent predictors of PFS and OS, respectively. Thus, inhibiting these soluble factors may be promising for enhancing antitumor responses in patients with RCC treated with ICIs., (© 2024. The Author(s).)

The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DR spot )) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DR spot ). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode., (© 2024. The Author(s).)

Objective: We devised a split-bolus injection and imaging protocol for pulmonary artery and vein separation computed tomography (CT) angiography based on time enhancement curve characterization. Furthermore, we aimed to evaluate the contrast enhancement effect and success rate of blood vessel separation between the pulmonary artery and vein of this proposed protocol., Methods: In this study, 102 patients (45 patients with the standard protocol and 57 patients with the proposed protocol) who underwent pulmonary arteriovenous computed tomography angiography were included. The CT values of various vessels, CT value difference between the pulmonary trunk and left atrium, and coefficient of variation in pulmonary arteries and veins were obtained from images of the standard and proposed protocols., Results: The CT values in the proposed protocol for the pulmonary trunk were significantly higher than those in the standard protocol (487.3 [415.5-546.9] HU vs. 293.0 [259.0-350.0] HU, P < 0.01). The CT value difference between the pulmonary trunk and left atrium in the proposed protocol was significantly higher than that in the conventional protocol (211.3 [158.0-265.7] HU vs. 32 [-30.0-55.0] HU, P < 0.01). The coefficient of variation in the proposed protocol was 0.08 (0.06-0.10) and 0.09 (0.08-0.11) in pulmonary arteries and 0.08 (0.06-0.09) and 0.09 (0.07-0.12) in pulmonary veins, respectively., Conclusions: The proposed protocol achieved separation between the pulmonary artery and vein in many patients, making it useful for the preoperative assessment of individual thoracic anatomy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Backgruound: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD., Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%., Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses., Conclusion: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

This study explored sentence processing in two typologically distinct languages: Korean, a verb-final language, and Tongan, a verb-initial language. The first experiment revealed that in Korean, sentences arranged in the scrambled OSV (Object, Subject, Verb) order were processed more slowly than those in the canonical SOV order, highlighting a scrambling effect. It also found that sentences with subject topicalization in the SOV order were processed as swiftly as those in the canonical form, whereas sentences with object topicalization in the OSV order were processed with speeds and accuracy comparable to scrambled sentences. However, since topicalization and scrambling in Korean use the same OSV order, independently distinguishing the effects of topicalization is challenging. In contrast, Tongan allows for a clear separation of word orders for topicalization and scrambling, facilitating an independent evaluation of topicalization effects. The second experiment, employing a maze task, confirmed that Tongan's canonical VSO order was processed more efficiently than the VOS scrambled order, thereby verifying a scrambling effect. The third experiment investigated the effects of both scrambling and topicalization in Tongan, finding that the canonical VSO order was processed most efficiently in terms of speed and accuracy, unlike the VOS scrambled and SVO topicalized orders. Notably, the OVS object-topicalized order was processed as efficiently as the VSO canonical order, while the SVO subject-topicalized order was slower than VSO but faster than VOS. By independently assessing the effects of topicalization apart from scrambling, this study demonstrates that both subject and object topicalization in Tongan facilitate sentence processing, contradicting the predictions based on movement-based anticipation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tamaoka, Yu, Zhang, Otsuka, Lim, Koizumi and Verdonschot.)