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Objectives: Although radiotherapy is an essential component of pediatric cancer treatment, inadequate radiotherapy information for childhood cancer and unusual treatment situations can negatively affect parental perceptions and emotions. This study aims to investigate the effect of two-step audio-visual instruction system effects introduced by our institution on parent satisfaction and anxiety when initiating radiotherapy. Methods: The two-step audio-visual instruction system comprised instructive animation using patient avatars and a live video system. The live video system has a 55-inch-wide monitor, and a no-latency sound module. Parents in the radiotherapy division can view the patient in the treatment room through the live video system. This prospective study compared satisfaction and anxiety about radiotherapy introduction before and after two-step audio-visual instruction. We enrolled 20 parents whose child underwent radiotherapy, and they completed a set of questionnaires—Client Satisfaction Questionnaire, State-Trait Anxiety Inventory, and original questionnaires about radiotherapy. Results: Satisfaction scores improved significantly after two-step audio visual instruction (25.5 ± 3.4) compared with those before the instruction (27.7 ± 3.1) (p =

Abstract Background IgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported. Case presentation We report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs. Conclusions Our case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.

Abstract To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0–19) with RMS at four institutes in Japan. Thirty‐one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36–60 GyE (median: 50.4 GyE). The median follow‐up period was 24.5 months (range: 1.5–320.3). The 1‐ and 2‐year overall survival rates were 91.9% (95% CI: 84.3–99.5%) and 84.8% (95% CI 75.2–94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low‐, intermediate‐, and high‐risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation‐induced toxicities in nine patients (16%). Proton‐specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation‐induced toxicity.

Abstract Background Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Methods Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. Results The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Conclusions Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.

Abstract The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

Abstract Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI's effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI’s impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.

Abstract Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Pten ff /PR cre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Pten ff /PR cre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.

Abstract Background Multiple joint arthritis patterns require a comprehensive understanding to optimize patient management. This study aimed to present a patient cohort that deviated from known definitions of coxitis knee (CK), identifying and characterizing this atypical group. Methods Patients undergoing both total hip arthroplasty and total knee arthroplasty between January 2008 and December 2018 were retrospectively reviewed. The patients were classified into a typical coxitis knee group (classic, long leg arthropathy, and windswept deformity) and an atypical coxitis knee group. Leg-length discrepancy, body mass index (BMI), and radiographic parameters of the groups were compared and analyzed. Results A total of 31 patients were allocated to the typical coxitis knee group (n = 10), and atypical coxitis knee group (n = 21). In the atypical group, 27 hips were involved, of which 21 had acetabular dysplasia, 5 exhibited subchondral insufficiency fracture-like changes, and only 1 had classic osteoarthritis. Among the 27 knees undergoing total knee arthroplasty, 26 showed varus alignment, 1 was within the normal range, and none was valgus. Acetabular dysplasia involved ipsilateral (n = 1), contralateral (n = 14), and bilateral (n = 6) hips, showing atypical coxitis knee. Patients with acetabular dysplasia were more likely to exhibit atypical CK. Conclusion Most patients in the cohort displayed acetabular dysplasia and contralateral varus knees, constituting a pattern referred to as acetabular dysplasia-associated gonarthritis. Identifying this novel subtype may have important clinical implications for regions with high risk factors, where acetabular dysplasia and constitutional genu varum are prevalent. Graphical Abstract

This paper describes the effects of power device characteristics on the harmonics of the inverter output voltage and magnetic field leakage in a wireless power transfer system for electric vehicles with phase shift control and the suppression method of the haemonics. Even when the phase shift angle is theoretically set to minimize harmonics, the experimental results have confirmed the existence of the remaining harmonics, which have dead-time dependence. Harmonics with dead-time dependence include those caused by changes in the pulse width depending on the dead time, which have been conventionally compensated for by dead-time compensation. However, the targeted harmonics have a dead-time dependence even when the pulse widths are matched. Therefore, we focused on the difference between the dead-time period and other periods. Further, as the conduction resistance differs between these two periods, we performed a circuit analysis, also considering the conduction resistance. From the results, it was theoretically clarified that harmonics are generated because of the difference in resistance in the forward and reverse directions of power devices. Furthermore, the theoretically calculated dead time dependence of the device-induced harmonics was confirmed by experimental measurements of the harmonics of the inverter output voltage waveform and the magnetic field leakage. This confirms that one of the factors responsible for the harmonics is the difference in the device conduction resistance before and after the dead-time period. The main contributions of this paper are the revelation of unconventional dead-time-dependent harmonics and the proposal of a method for suppressing them.

Skeletal muscle segmentation of the L3 slice can be used to estimate total body skeletal muscle mass. However, site-specific three-dimensional (3D) segmentation of each region, such as the erector spinae, quadratus lumborum, psoas major, oblique muscle, and rectus abdominis, in the L3 slice has not yet been achieved for the accurate measurement of skeletal muscle mass. Herein, we propose a method for site-specific 3D segmentation of skeletal muscles in the L3 slice from body CT images. We focused on the characteristics of the erector spinae muscle (ESM), which can be simultaneously observed with other skeletal muscles on craniocaudal slices and can be accurately segmented using machine learning. We introduce a segmentation method with ESM (w/ESM) using 2D U-Net for the simultaneous learning of the erector spinae and skeletal muscles, which are recognized as targets. In a three-fold cross-validation using 30 CT image cases, the mean Dice value of the baseline method, without ESM (wo/ESM), was 0.637, whereas that for the segmentation of skeletal muscles by w/ESM was 0.864, an improvement of 0.227. Our method improves the accuracy of site-specific segmentation of skeletal muscles within the L3 slice and helps evaluate the skeletal muscles through 3D imaging. This effect of w/ESM was confirmed for the skeletal muscles within the L3 slice as well as the trapezius and supraspinatus muscles. These results demonstrate the effectiveness of simultaneously learning the erector spinae and skeletal muscles in improving the accuracy of site-specific segmentation of skeletal muscles.

The data presented here aim to show how to analyze crack propagation of a novel metallic matrix composite of Ti-6Al-4V reinforced with 1 wt.% nano-yttria-stabilized zirconia processed by laser powder bed fusion technology. The data was acquired via microstructural observations and electron backscatter diffraction (EBSD) analyses after the quasistatic tensile tests at room temperature. The overall crack path configuration based on the fracture surface observation by scanning electron microscopy (SEM) was first operated, presenting two main regions: (i) local inclined planes (hereafter denoted as “stair-like”), and (ii) region in accordance with the theoretical mode I fracture plane. Thereafter, a series of EBSD data set on a surface obtained after longitudinal cut off operation on one failed piece was conducted at three distinct positions: (i) in the stair-like configuration region, (ii) in the mode I fracture region, and (iii) in the region where the crack path made his transition between these two mechanisms. Since the EBSD data sets were not prone to any post-processing filtering operation, comparison of the observed mechanism with other Ti-6Al-4V alloy processed by additive manufacturing (AM) technology can be easily carried out.

Abstract A 77‐year‐old male patient underwent esophagogastroduodenoscopy at his family doctor, and an easily hemorrhagic depressed lesion was noted near the anterior wall of the gastric antrum. A biopsy revealed moderately differentiated tubular adenocarcinoma > poorly differentiated adenocarcinoma, and the patient was referred to our department for further examination. A 15‐mm 0–IIc lesion is seen near the anterior wall of the gastric antrum and narrow band imaging magnifying endoscopy revealed obscured glandular duct structures and corkscrew pattern vascular structures. We diagnosed the patient with early‐stage gastric cancer [L, Ant, 15mm, cType0‐IIc, cT1(M‐SM1), cN0, cM0, cStage IA] after an esopahogastroduodenoscopy examination at our hospital, and endoscopic submucosal dissection was performed. Histopathological images with hematoxylin and eosin staining showed tumor cells with pale cytoplasm and the immunostaining for alpha‐fetoprotein, sal‐like protein 4, and Glypican3 was positive. The patient was pathologically diagnosed with gastric adenocarcinoma with enteroblastic differentiation, pT1b1 (SM, 0.4 mm), type 0–IIc, 15 mm, UL (‐), Ly0, and V0. Gastric adenocarcinoma with enteroblastic differentiation is one of the representative histological types of alpah‐fetoprotein‐producing gastric cancer. Alpha‐fetoprotein‐producing gastric cancer is infrequent, accounting for at least 3% of all gastric cancers, and is generally highly malignant. Most cases are already advanced upon diagnosis, and finding them in the early stage is rare. Therefore, pathological findings that may indicate the gastric adenocarcinoma with enteroblastic differentiation should be noted even in early gastric cancer.

Purpose: Kneeling is often difficult after a total knee arthroplasty. However, the reasons behind kneeling difficulties are not yet fully understood. According to several studies, a lateral incision reduces perceptual deficits and improves kneeling performance. This study compared two different skin incisions (lateral and midline) as they relate to postoperative perceptual deficits, as well as kneeling on a mat or in daily life following TKA, and demonstrates the advantage of the lateral incision in postoperative kneeling ability. Methods: This study included 99 patients with lateral incisions and 104 patients with midline incisions. Sensory disturbance was evaluated with a brush on the nine subdivisions of the kneeling area. Patients were tested in the outpatient clinic to determine whether they could kneel on a mat. The level of discomfort in the kneeling area was assessed using a visual analog scale. Questionnaires were used to assess kneeling ability. Results: Compared to a midline incision, a lateral incision significantly reduced the perceptual deficits in the center of the kneeling area and the discomfort associated with kneeling on a mat. There was no significant difference between the two groups in kneeling on a mat in the clinic or kneeling in daily activities. However, less than 30% of patients in both groups could kneel in daily living. The reasons for being unable to kneel were mainly anxiety and pain, rather than numbness. Conclusion: Lateral incisions alone did not improve kneeling in patients' daily living following TKA.

Purpose: Femoral component rotation (FCR) is crucial in total knee arthroplasty (TKA). Currently, the optimal method to select FCR is unknown due to patient anatomy variation. Addressing the variability of femoral component rotation is critical to optimizing TKA outcomes and patient satisfaction. In this study, we aimed to identify outlier frequency and evaluate malrotation risk reduction by setting anatomic limits for FCR selection. Methods: One hundred patients with end-stage knee osteoarthritis requiring TKA were included and categorized as normal rotation, internal rotation outlier, and external rotation outlier based on their expected FCR calculated intraoperatively using the modified gap balancing technique with a tensioning device. The computed FCR was then referenced to their Posterior Condylar Angle (PCA) and Condylar Twist Angle (CTA). The postoperative FCR and 1, 2-, and 5-years functional scores were also measured. Results: Seventy-one knees (71%) were within the limits of PCA and CTA. The combined outlier frequency is 29%. The mean computed FCRs are 4.4° (±1.5), −1° (±2.6), and 8.0° (±3.4) for the normal, internal rotation, and external rotation groups, respectively. Whereas after setting the limits, the postoperative FCRs are 3.1° (±1.5), 3.9° (±1.7), and 2.5° (±1.4) for the three groups, respectively. The relative risk reduction against malrotation was 65%. At 1, 2, and 5 years post-TKA, all groups showed significant functional improvement, with no significant differences in functional outcomes between the normal and outlier groups. Conclusion: The use of lower and upper limits for selecting the FCR based on CTA and PCA can be a valuable approach to reducing malrotation risk and achieving satisfactory functional outcomes in TKA. Addressing the individual patient's anatomic limits contributes to improved TKA outcomes and patient-specific component alignment, thus enhancing the overall success of the procedure.

Purpose: We evaluated the medium-term radiological outcomes of the interface bioactive bone cement (IBBC) technique used in the acetabular component in primary cemented total hip arthroplasty (THA). Methods: In total, 79 patients (88 hips) who underwent primary THA at our hospital between January 2004 and April 2009 were divided into the non-IBBC (NIBBC; n ​= ​39 patients, 44 hips) and IBBC (n ​= ​40 patients, 44 hips) groups. A clear zone (CZ) at the cement-bone interface around the cup was evaluated 5 and 10 years postoperatively. The CZ score, which indicates the spread of the CZ, and loosening of the cup (CZ ​> ​2 ​mm on all sides or movement of the cup >4°) were also evaluated. Results: No patient had loosening of the cup. The mean patient age at surgery was 66.5 ​± ​9.2 years in the NIBBC group and 61.9 ​± ​7.7 years in the IBBC group (p ​= ​0.012). At 5 years postoperatively, the incidence of CZ was 36.4 ​% in the NIBBC group and 18.2 ​% in the IBBC group (p ​= ​0.056). At 10 years postoperatively, the incidence of CZ was 36.4 ​% in the NIBBC group and 20.1 ​% in the IBBC group (p ​= ​0.098). Age at surgery (p ​= ​0.045) significantly affected the incidence of CZ at 5 years but not at 10 years. The IBBC technique (p ​= ​0.042) and age at surgery (p ​= ​0.028) significantly affected the CZ score at 5 years. The IBBC technique (p ​= ​0.036) significantly affected the CZ score at 10 years. Conclusions: The IBBC technique resulted in a significantly lower CZ score than the NIBBC technique in patients undergoing THA.

Abstract Background In systemic lupus erythematosus (SLE), autoreactive B cells are thought to develop by-passing immune checkpoints and contribute to its pathogenesis. Toll-like receptor (TLR) 7 and 9 signaling have been implicated in their development and differentiation. Although some B cell subpopulations such as T-bet + double negative 2 (DN2) cells have been identified as autoreactive in the past few years, because the upregulated surface markers of those cells are not exclusive to them, it is still challenging to specifically target autoreactive B cells in SLE patients. Methods Our preliminary expression analysis revealed that phospholipase D4 (PLD4) is exclusively expressed in plasmacytoid dendritic cells (pDCs) and B cells in peripheral blood mononuclear cells (PBMCs) samples. Monoclonal antibodies against human PLD4 were generated, and flow cytometry analyses were conducted for PBMCs from 23 healthy donors (HDs) and 40 patients with SLE. In vitro cell culture was also performed to study the conditions that induce PLD4 in B cells from HDs. Finally, recombinant antibodies were synthesized from subpopulations of PLD4 + B cells from a patient with SLE, and their antinuclear activity was measured through enzyme-linked immunosorbent assay. Results pDCs from both groups showed comparable frequency of surface PLD4 expression. PLD4 + B cells accounted for only a few percent of HD B cells, whereas they were significantly expanded in patients with SLE (2.1% ± 0.4% vs. 10.8% ± 1.2%, P

Abstract Background Fat embolism syndrome (FES) is a rare syndrome that typically occurs 12–72 h after long bone or pelvic fractures with a classic triad of respiratory distress, neurologic changes, and petechial rash. Although Gurd’s criteria for FES include anuria or oliguria, the mechanism of acute kidney injury (AKI) remain unknown. Here, we present a case of FES complicated by AKI that required blood purification. Case presentation A 79-year-old woman was admitted to our hospital because of a right humerus and pelvic fracture caused by a traffic accident. On the second day of hospitalization, she developed impaired consciousness, respiratory failure, and disseminated intravascular coagulation (DIC). Chest radiography revealed bilateral diffuse alveolar infiltration. Brain magnetic resonance imaging revealed diffuse high signal intensity on diffusion-weighted imaging and diffuse low signal intensity on susceptibility-weighted imaging in the cerebral and cerebellar regions. The diagnosis of FES was confirmed and the patient was treated with methylprednisolone (40 mg/day) and ulinastatin. On the third day of hospitalization, she was admitted to our department because of AKI with oliguria. Although echocardiography showed an elevated right ventricular artery systolic pressure suggestive of pulmonary hypertension (PH), pulmonary congestion was initially considered on chest imaging, and hemodialysis and rapid ultrafiltration were initiated. However, she developed hypovolemic shock and treatment was switched to continuous hemodiafiltration and slow ultrafiltration. Thereafter, her consciousness, hypoxemia, DIC and PH completely improved. She was weaned from blood purification therapy on the 29th day of hospitalization. She had hemolytic anemia that might have been caused by thrombotic microangiopathy (TMA), but it resolved without plasmapheresis. On the 51st day of hospitalization, the patient was transferred to another hospital for rehabilitation. Conclusions FES can be complicated by AKI. In this case, DIC, which was difficult to differentiate from TMA, and/or renal congestion were considered to be a cause of AKI. Chest radiographs of FES may be indistinguishable from pulmonary congestion. In our case, chest radiography showed bilateral diffuse alveolar infiltrates which was not indicative of pulmonary congestion but pulmonary involvement of FES. FES is associated with PH, which may lead to right heart failure. Therefore, the patient could have developed hypovolemic shock due to hemodialysis and rapid ultrafiltration. Clinicians should pay attention to the hemodynamics when blood purification for FES is performed.

Mutations in the complement factor H (CFH) gene are associated with complement dysregulation and the development of atypical hemolytic uremic syndrome (aHUS). Several fusion genes that result from genomic structural variation in the CFH and complement factor H-related (CFHR) gene regions have been identified in aHUS. However, one allele has both CFHR gene duplication and CFH::CFHR1 fusion gene have not been reported. An 8-month-old girl (proband) presented with aHUS and was treated with ravulizumab. Her paternal grandfather developed aHUS previously and her paternal great grandmother presented with anti-neutrophil cytoplasmic antibody-associated vasculitis and thrombotic microangiopathy (TMA). However, the proband’s parents have no history of TMA. A genetic analysis revealed the presence of CFH::CFHR1 fusion gene and a CFHR3-1-4-2 gene duplication in the patient, her father, and her paternal grandfather. Although several fusion genes resulting from structural variations of the CFH–CFHR genes region have been identified, this is the first report of the combination of a CFH::CFHR1 fusion gene with CFHR gene duplication. Because the CFH–CFHR region is highly homologous, we hypothesized that CFHR gene duplication occurred. These findings indicate a novel pathogenic genomic structural variation associated with the development of aHUS.

Our previous study showed that nanobubbles (NBs) encapsulating CO2 gas have bactericidal activity due to reactive oxygen species (ROS) (Yamaguchi et al., 2020). Here, we report that bulk NBs encapsulating CO2 can be efficiently generated by ultrasonically irradiating carbonated water using a piezoelectric transducer with a frequency of 1.7 MHz. The generated NBs were less than 100 nm in size and had a lifetime of 500 h. Furthermore, generation of ROS in the NB suspension was investigated using electron spin resonance spectroscopy and fluorescence spectrometry. The main ROS was found to be the hydroxyl radical, which is consistent with our previous observations. The bactericidal activity lasted for at least one week. Furthermore, a mist generated by atomizing the NB suspension with ultrasonic waves was confirmed to have the same bactericidal activity as the suspension itself. We believe that the strong, persistent bactericidal activity and radical generation phenomenon are unique to NBs produced by ultrasonic irradiation of carbonated water. We propose that entrapped CO2 molecules strongly interact with water at the NB interface to weaken the interface, and high-pressure CO2 gas erupts from this weakened interface to generate ROS with bactericidal activity.

BackgroundIn Japan, recently, the number of children with severe motor and intellectual disabilities (SMID) is steadily increasing. Caregivers such as parents and family members are struggling with how to live with their children at home and in the community after discharge.ObjectiveThe current study aimed to explore the social support needs faced by caregivers while rearing children with SMID in order to identify effective means of social support in Japan.MethodsWe conducted a cross-sectional survey of the primary caregivers of children with SMID at home through special-needs elementary, junior high, and senior high schools nationwide, using a self-administered, anonymous questionnaire to investigate the actual social support needs of the caregivers. All statements of social support need were coded using Krippendorff content analysis.ResultsQuestionnaire returns were obtained from 1,176 families, and the descriptions of 1,173 families were included in the analysis. The results of the analysis showed that the needs of the caregivers consisted of seven categories.ConclusionsThe social support needs expressed by the caregivers are necessary findings for Japan today, both for the soft side, such as the development of local systems and regulations to support these families, and for the hard side, such as the increase and improvement of facilities and equipment.

Abstract Adult T‐cell leukaemia/lymphoma (ATL) remains incurable. The NF‐κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF‐β‐activated kinase 1 (TAK1), an IκB kinase‐activating kinase, triggers the activation of NF‐κB. The resorcylic acid lactone LL‐Z1640‐2 is a potent irreversible inhibitor of TAK1/extracellular signal‐regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL‐Z1640‐2 against ATL. LL‐Z1640‐2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of IRF4 strongly induced ATL cell death while downregulating MYC. LL‐Z1640‐2 as well as the NF‐κB inhibitor BAY11‐7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF‐κB‐IRF4‐MYC axis. The treatment with LL‐Z1640‐2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL‐Z1640‐2 against IL‐2‐responsive ATL cells in the presence of IL‐2. Therefore, LL‐Z1640‐2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL‐Z1640‐2.

Abstract The recent use of noble gases in laser devices and semiconductor lithography has greatly increased. However, there is no commercial technology for the storage of noble gases in solid materials owing to their chemical inertness and relative lightness. Here we report the simple synthesis and characteristics of a hydroquinone clathrate that stably captures neon at atmospheric pressure and room temperature. The highly flexible structure enables neon encapsulation in the one-dimensional channels of the clathrate framework despite their inter-cage migration through the hexagonal entrance of the cages. The neon uptake of as-synthesized hydroquinone clathrates is 37.3 g L−1 at 1 bar and 298 K. Increasing the temperature accelerates the release of neon from the flexible hydroquinone clathrate hydrogen-bonded organic framework, leading to guest-free clathrate formation at 1 bar and 400 K. This method represents a technological development for better storage and the controlled release of noble gases in solid structured materials.

Abstract Background In monarchE and Postoperative Therapy with Endocrine and TS‐1 (POTENT) trials, abemaciclib and S‐1 have, respectively, shown to be effective as adjuvant therapies for luminal breast cancer (BC), although whether patients who meet the criteria are at high risk of recurrence compared to non‐eligible patients is still unknown. Here, we investigated recurrence risk according to the criteria of each trial in Japanese patients. Methods We reviewed the records of 992 patients who received surgery at Chiba University Hospital for stage I–III BC from January 2017 to May 2022 and selected 553 analytic cohort patients and retrospectively analyzed the relapse‐free survival of the patients as the primary endpoint. High‐recurrence risk was defined according to monarchE trial and POTENT trial. Results The 5‐year RFS for monarchE cohort 1 and cohort 2 eligible patients were 77.78% and 89.33%, respectively, which were significantly lower than monarchE non‐eligible patients (98.31%; p

Abstract Background Since the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1‐derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression. Methods Since AR expression was negative in W12 cells and HaCaT cells, a human male skin‐derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions. Results DHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR‐transfected W12 cells. Si‐RNA treatments showed that DHT induced the expression of squamous differentiation‐related genes in AR‐transfected W12 cells via an ELF3‐dependent pathway. DHT also reduced FOXP4 expression in AR‐transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN. Conclusion Androgen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone‐induced differentiation therapy against CIN1 and CIN2.

Abstract Background There is pressing needs to find the biomarker in the selection of neoadjuvant therapy in postmenopausal luminal breast cancer patients. We examined the hypothesis that PIK3CA mutations and low phosphatase and tensin homolog (PTEN) expression affect the response to neoadjuvant therapy and prognosis in postmenopausal luminal breast cancer patients. Methods Postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, up to stage II, who underwent neoadjuvant chemotherapy (NAC; n = 60) or neoadjuvant endocrine therapy (NAE; n = 55) were selected. PIK3CA exon 9 and exon 20 mutations were screened by high resolution melting analysis and confirmed by Sanger sequence. PTEN expression was evaluated by immunohistochemistry. The relationships among PIK3CA mutations, PTEN expression, clinicopathological features, the pathological effect of neoadjuvant therapy, recurrence-free survival (RFS) and overall survival were analyzed. Results Among 115 patients, PIK3CA mutations and low PTEN expression before treatment were detected in 35 patients (30.4%) and in 28 patients (24.3%), respectively. In the NAC group, tumor with PIK3CA mutations showed significantly poorer response than tumor with PIK3CA wild-type (p = 0.03). On the other hand, in the NAE group, there was no significant difference in pathological therapeutic effect between tumor with PIK3CA mutations and tumor with PIK3CA wild-type (p = 0.54). In the NAC group, the log-rank test showed no difference in RFS between patients with PIK3CA mutations and PIK3CA wild-type (p = 0.43), but patients with low PTEN expression showed significantly worse RFS compared to patients with high PTEN expression (5 year RFS 0.64 vs. 0.87, p = 0.01). In the Cox proportional hazards model for RFS, PTEN expression, progesterone receptor, and pathological therapeutic effect were predictive factors for time to recurrence (All p