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Background: Although 7T functional MRI (fMRI) provides better signal‐to‐noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface‐based analysis. Purpose: To quantify the effectiveness of distortion corrections of 7T fMRI data. Study Type: Prospective. Subjects: Fifteen healthy individuals aged 19–26 years (mean: 21.9 years). Field Strength/Sequence: Multiband gradient‐echo echo‐planar imaging sequence at 7T; 3D T1/T2‐weighted sequences (magnetization prepared rapid acquisition with gradient echo [MPRAGE] and sampling perfection with application optimized contrast using different flip angle evolution [SPACE]) at 3T. Assessment: fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B0 inhomogeneity and gradient nonlinearity (B0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter). Statistical Tests: Repeated measures analyses of variance with post‐hoc t‐tests with Bonferroni correction. Results: The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion). Data Conclusion: B0 distortion correction is crucial for surface‐based analysis of fine‐resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners. Evidence Level: 1 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.

Myoelectric hands are beneficial tools in the daily activities of people with upper-limb deficiencies. Because traditional myoelectric hands rely on detecting muscle activity in residual limbs, they are not suitable for individuals with short stumps or paralyzed limbs. Therefore, we developed a novel electric prosthetic hand that functions without myoelectricity, utilizing wearable wireless sensor technology for control. As a preliminary evaluation, our prototype hand with wireless button sensors was compared with a conventional myoelectric hand (Ottobock). Ten healthy therapists were enrolled in this study. The hands were fixed to their forearms, myoelectric hand muscle activity sensors were attached to the wrist extensor and flexor muscles, and wireless button sensors for the prostheses were attached to each user’s trunk. Clinical evaluations were performed using the Simple Test for Evaluating Hand Function and the Action Research Arm Test. The fatigue degree was evaluated using the modified Borg scale before and after the tests. While no statistically significant differences were observed between the two hands across the tests, the change in the Borg scale was notably smaller for our prosthetic hand (p = 0.045). Compared with the Ottobock hand, the proposed hand prosthesis has potential for widespread applications in people with upper-limb deficiencies.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Purpose: To assess the usefulness of contrast-enhanced 3D STIR FLAIR imaging for evaluation of pituitary adenomas. Methods: Patients with pituitary adenomas underwent MR examinations including contrast-enhanced 3D STIR FLAIR and 2D T1-weighted (T1W) imaging. We subjectively compared the two techniques in terms of 10 categories. In addition, images were rated by side-by-side comparisons into three outcomes: 3D STIR FLAIR imaging superior, equal, or 2D T1W imaging superior. Additionally, the added value of 3D STIR FLAIR imaging for adenoma detection over conventional MR imaging was assessed. Results: Twenty-one patients were included in this study. 3D STIR FLAIR imaging offered significantly better images than 2D T1W imaging in terms of three categories, including overall visualization of the cranial nerves in the cavernous sinus (mean 4.0 vs. 2.8, p

Background and purposeVarious prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021.MethodsIn 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis.ResultsAmong 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84–0.96; P, 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27–0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22–0.67; 0.005).ConclusionsThis study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021.

Abstract Integration of organic thin‐film transistor (OTFT) devices with a wireless data transmission system such as 2.4‐GHz Bluetooth low energy (BLE) is a significant requirement for activating the Internet of Thing (IoT) ecosystem based on a vast number of sensors, while conventional OTFT circuits have problems with their high output impedance and the need for multiple power supplies. Here, a wireless, real‐time, and flexible sodium ion sensing system composed of a printed Na+ sensor, printed OTFT‐based amplifiers, inorganic passive elements, a BLE module, and a 3‐V sheet‐type battery is demonstrated. The printed organic amplifier circuits based on dual threshold technology and dual‐gate structure are combinable with a BLE module because of their low output impedance of 50 kΩ and operate with 3‐V single supply as well as improving operational stability under illumination. The sensitivity to Na+ concentration is improved from 53.7 to 242.5 mV dec−1 (4.5 times higher) by the OTFT‐based amplifier, and the data is transmitted in real‐time to a tablet via the BLE wireless communication.

A head-mounted display could potentially restrict users’ visual fields and thereby impair their spatial cognitive ability. Spatial cognition can be assisted with immersive visual guidance. However, whether this technique is useful for individuals with autism-spectrum disorder (ASD) remains unclear. Given the recent virtual reality (VR) contents targeting individuals with ASD, the relationship between ASD-related traits and the effectiveness of immersive visual guidance should be clarified. This pilot study evaluated how ASD-related traits (autistic traits and empathizing–systemizing cognitive styles) among typically developing individuals are related to the effectiveness of visual guidance. Participants performed visual search and spatial localization tasks while using immersive visual guidance. In the visual search task, participants searched immersive VR environments for a target object and pushed a button according to the target color as quickly as possible. In the localization task, they viewed immersive visual guidance for a short duration and localized the guided direction via a controller. Results showed that visual search times were hastened with systemizing cognition. However, ASD-related traits were not significantly related to localization accuracy. These findings suggest that immersive visual guidance is generally useful for individuals with higher ASD-related traits.

IntroductionParkinson's disease (PD) leads to various types of swallowing disorders. We investigated the effect of cervical percutaneous interferential current stimulation on dysphagia. By conducting detailed qualitative and quantitative analysis of videofluoroscopic examination, we aimed to understand dysphagia in patients with PD and investigate its effects on swallowing function.MethodsPatients received cervical percutaneous interferential current stimulation for 20 min twice a week for 8 weeks. In this exploratory study, we evaluated aspiration/laryngeal penetration, oral cavity residue, vallecular residue, and pharyngeal residue. In addition, we performed temporal analysis.ResultsTwenty-five patients were completely evaluated. At baseline, the proportions of laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecula residue, and pharyngeal residue were 40.0, 88.0, 72.0, 60.0, and 16.0%, respectively. Conversely, pharyngeal transit time, laryngeal elevation delay time, pharyngeal delay time, and swallowing reflex delay were nearly within the normal ranges. Cervical percutaneous interferential current sensory stimulation improved only oral cavity residue at the end of the intervention, from 88.0 to 56.0%.DiscussionPatients with PD demonstrated remarkably high frequencies of residues in the oral and pharyngeal regions. The usefulness of cervical interferential current stimulation was partially demonstrated for oral cavity residue. Considering that PD exhibits diverse symptoms, further accumulation of cases and knowledge is warranted.Trial registrationjRCTs062220013.

Abstract A 67‐year‐old current smoker Japanese man, with no history of asthma, was diagnosed with lung adenocarcinoma. He received first‐line chemotherapy with carboplatin, pemetrexed, ipilimumab, and nivolumab in July 20XX‐1, and subsequently a maintenance therapy with nivolumab. In October 20XX, he became aware of wheezy dyspnoea, and chest computed tomography demonstrated worsening bronchial wall thickenings. Eosinophilia was noted, and a pulmonary function test showed obstructive dysfunction insufficiently responding to beta‐agonists, with 130 mL increase of forced expiratory volume in one second and high fractional exhaled nitric oxide level (85 ppb). He was clinically diagnosed with asthma and chronic obstructive pulmonary disease overlap, secondary to immune checkpoint inhibitors (ICIs). The inhibition of binding between programmed cell death‐protein‐1 (PD‐1), expressed on T cells, and programmed cell death‐ligand‐2 (PD‐L2), expressed on tumour and dendritic cells, can induce airway hyperresponsiveness. Physicians should be wary of asthmatic symptoms and chest image findings during ICIs therapy.

Key message Physicians should consider a pulmonary artery aneurysm complication in patients presenting with hemoptysis during treatment for a pulmonary abscess. Contrast‐enhanced CT or angiography is recommended for diagnosis, followed by pulmonary embolization for treatment.

Abstract Despite Japan’s high vaccination coverage, daily numbers of new COVID-19 cases have been high. However, studies on the seroprevalence among Japanese people and the causative factors for rapid spread have remained limited. In this study, we aimed to examine the seroprevalence and associated factors in healthcare workers (HCWs) of a medical center in Tokyo using blood samples drawn at annual check-ups from 2020 to 2022. We found that of the 3,788 HCWs in 2022 (by mid-June), 669 were seropositive for N-specific antibodies (tested by Roche Elecsys Anti-SARS-CoV-2 assay); the seroprevalence surged from 0.3% in 2020 and 1.6% in 2021 to 17.7% in 2022. Notably, our study found 325 (48.6%; 325/669) cases were infected without awareness. Among those with a previously PCR-confirmed SARS-CoV-2 infection during the past three years, 79.0% (282/357) were found after January 2022, after the Omicron variant was first detected in Tokyo at the end of 2021. This study indicates the fast spread of the SARS-CoV-2 among HCWs during the Omicron surge in Japan. The high percentage of infection without awareness may be a key driving factor causing rapid person-to-person transmission, as shown in this medical center with high vaccination coverage and strict infection control measures.

Abstract Background Hyperprogressive disease (HPD) is a phenomenon with greatly accelerated tumor growth and clinical deterioration rates compared to pre-therapy, in patients treated with immune checkpoint inhibitors (ICI). The aim of this study is to clarify the reality of HPD in patients with advanced hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atez/Bev) using tumor dynamics. Methods Medical records of consecutive patients with advanced HCC who were treated with Atez/Bev were retrospectively reviewed. HPD was defined as a more than two- or fourfold increase in tumor growth rate (TGR) or tumor growth kinetics rate (TGKR) before and after treatment. Overall survival (OS) and baseline characteristics with or without HPD were analyzed. Results A total of 85 patients were included in the analysis. When HPD was defined as a twofold of TGR or TGKR, 8 patients (8/85, 9.4%) had HPD and 11 had PD without HPD. A total of 5 patients (5/85, 5.9%) were diagnosed with HPD and 14 with PD without HPD when HPD was defined as a fourfold of TGR or TGKR. No significant difference was observed in the baseline characteristics between HPD and non-HPD. Conclusion The prevalence of HPD in patients with advanced HCC treated with Atez/Bev was lower than those treated with nivolumab monotherapy. The HPD mechanism in ICI combined with antibodies targeting vascular endothelial growth factor (VEGF) remains to be elucidated.

In recent years, the environment surrounding companies and consumers has been markedly changed with advancement of technology. In particular, the evolution of AI-related technologies, especially machine learning, has enabled companies to collect and analyze big data, providing opportunities to create and communicate customer value. However, in today’s rapidly changing market, it is very difficult to acquire, analyze, and interpret data and link it appropriately to marketing. This paper introduces the efforts of REVISIO Inc. (REVISIO), a company that has achieved growth by acquiring unique data from households and providing companies with comprehensive services, including analysis and solutions. REVISIO collects TV commercial viewing data using proprietary methods and analyzes these data using proprietary metrics. This approach has gained the support of its clients; that is, advertising companies that place TV commercials. In this paper, we examine why REVISIO’s data were accepted by their clients by evaluating the factors behind the success of REVISIO based on interviews. The findings reveal that REVISIO’s marketing satisfies the 4As of the clients and that REVISIO’s efforts create value for their clients.

Abstract Aim The purpose of this study was to examine how the clinical characteristics, indications for surgery, and postoperative course of ulcerative colitis (UC) surgical patients changed before and after the introduction of biological agents. Methods Patients who underwent surgery for UC at Hyogo Medical University between 2000 and 2019 were included in the study; those who underwent surgery between 2000 and 2009 were included in the early group (n = 864), and those who underwent surgery between 2010 and 2019 were included in the late group (n = 834); each study factor was retrospectively compared. Results The mean ages at surgery (y) were 39.7 ± 15.1 y in the early group and 46.7 ± 17.8 y in the late group (P

Abstract Background Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin–angiotensin–aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. Methods This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal outcomes in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and CCB- treated group over 2 years. Results Antihypertensive treatment effectively reduced blood pressure from 222 ± 28/142 ± 21 to 141 ± 18/87 ± 14 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 23.3 to 40.4 ± 22.5 mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1–5.5]) and even in patients with moderately to severely diminished eGFR (

Abstract Hepatitis C virus (HCV) is characterized by a high number of chronic cases due to an impairment of protective innate and adaptive immune responses. Here, we examined the contribution of the individual ectodomains of E1, E2, or a modified E2 with reduced CD81 binding and an inserted N-linked glycosylation site in combination as vaccine antigen mRNA-lipid nanoparticles (LNPs). The induction of a protective immune response to surrogate recombinant vaccinia virus (VV) expressing homologous HCV glycoprotein(s) challenge infection in a BALB/c mouse model was observed. Vaccination with a mRNA-LNP expressing soluble E1 (sE1) significantly reduced vv/HCV titer in the mouse ovary. However, the addition of sE2 mRNA-LNP for immunization impaired the efficacy of the sE1 construct. Further analysis showed that Th1 related cytokine responses to the sE1 mRNA-LNP were significantly altered in the presence of sE2 following co-immunization. Evaluation of immunogenicity revealed that the use of modified sE2F442NYT nucleoside mRNA-LNP vaccine results in an improved cellular immune response, IgG2a isotype switching, enhanced total IgG, and an increase in the neutralizing antibody response against HCV pseudotype virus. HCV cross genotype specific reactivity to peptides representing conserved E2 specific linear epitopes were enhanced in modified E2 vaccinated animal sera. In the absence of a suitable immunocompetent small animal model for HCV infection, protection from surrogate HCV vaccinia challenge infection model was observed in the immunized mice as compared to sE1 alone or an unmodified sE2 mRNA-LNP vaccine. Inclusion of sE1 with modified sE2F442NYT as mRNA-LNP vaccine candidate appeared to be beneficial for protection.

Soft robotics is a growing field, and requires versatile actuation methodology. Here, the authors report high-speed bending of anisole crystals due to natural vibration, induced and amplified by photothermal effect.

Naturally occurring peptides with high membrane permeability often have backbone ester bonds. Here, the authors investigated the effect of an amide-to-ester substitution on membrane permeability of peptides and found the substitution is useful for improving membrane permeability of cyclic peptides.

Abstract Background Micronodular thymic neoplasm with lymphoid stroma (MNT), a subtype of thymic tumor, is histopathologically characterized by micronodular thymic epithelial cell nests with lymphoid stroma. Despite the distinct histopathology of MNT, its pathogenesis remains unclear. Methods In this study, we aimed to examine a thymic tumor harboring thymic epithelial and lymphoid cells in a nonobese diabetic/severe combined immunodeficiency mouse. Results The excised tumor cells were cultured in vitro and comprised epithelial tumor cells and lymphoid cells. During a three‐dimensional cell culture, the epithelial tumor cells formed micronodular cell nests surrounded by lymphoid stroma. Notably, the lymphoid cells underwent apoptosis when they were separated from the epithelial tumor cells. Cutaneous transplantation of the cultured epithelial cells with splenocytes from BALB/c mice led to tumor formation, and these cells demonstrated a histopathology similar to that of human MNT in a nonobese diabetic/severe combined immunodeficiency mouse. Conclusion Given its overlapping features with human MNT, the transplanted tumor could serve as an experimental model of this disease.

Background and Aims: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity. Methods: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed. Results: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort. Conclusion: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.

Introduction: Primary neurolymphomatosis (NL) is a critical differential diagnosis of asymmetric multiple mononeuropathy and radiculoplexopathy. Its diagnosis is often challenging due to the lack of typical clinical signs of systemic lymphoma. We report a case of primary NL where nerve ultrasound (NUS) played an important role in the diagnosis and follow-up of the disease. Case presentation: A 52-year-old man developed asymmetric painful multiple mononeuropathy in the right upper limb with cranial nerve involvement. After being referred to our department, the patient underwent NUS, which revealed marked enlargement and increased vascularity in the right upper limb nerves, brachial plexus, and cervical nerve roots. Furthermore, an epineural hypoechoic mass, a characteristic finding of NL, was seen in the right median nerve. These NUS findings prompted us to perform 18F-fluorodeoxyglucose positron emission tomography/computed tomography and a subsequent biopsy on the right axillary lymph node, confirming NL. Notably, the NUS abnormalities dramatically subsided, demonstrating the effectiveness of chemotherapy. Discussion: The diagnostic utility of NUS for NL has been documented by many recent reports. Additionally, NUS can work as a quick follow-up tool for NL, as seen in our case.

Abstract Global femoral offset (GFO) and femoral offset (FO) reportedly affect outcomes following total hip arthroplasty (THA). However, FO assessed using plain radiography is affected by internal and external rotations of the hip joint. We investigated the relationship between leg length discrepancy and Harris hip score (HHS), and their influence on acetabular offset (AO), FO, GFO, anterior femoral offset, and outcomes after THA. We retrospectively evaluated 140 patients with hip osteoarthritis who underwent THA. A three-dimensional (3D) pelvis and femur model created from computed tomography (data using ZedHip software was used to investigate these parameters. The modified (m)HHS scores were significantly improved from 49.0 to 88.8 in total mHHS, 20.0–44.5 in pain, and 28.9–44.4 points in function. Significant correlations were found between the differences in AO, FO, GFO, and pain score in binominal, with maximum values of − 1.24, + 1.54, and + 0.90 mm/100 cm body height, respectively. The maximum value of GFO and mHHS in binominal was + 1.17 mm/100 cm body height (BH). The optimal range of difference of GFO was − 1.75 to 4.09 mm/100 cm BH. This is the first report using a 3D method for assessing FO. Preoperative planning using the system could improve postoperative function.

Abstract This study aimed to develop a versatile automatic segmentation model of bladder cancer (BC) on MRI using a convolutional neural network and investigate the robustness of radiomics features automatically extracted from apparent diffusion coefficient (ADC) maps. This two-center retrospective study used multi-vendor MR units and included 170 patients with BC, of whom 140 were assigned to training datasets for the modified U-net model with five-fold cross-validation and 30 to test datasets for assessment of segmentation performance and reproducibility of automatically extracted radiomics features. For model input data, diffusion-weighted images with b = 0 and 1000 s/mm2, ADC maps, and multi-sequence images (b0-b1000-ADC maps) were used. Segmentation accuracy was compared between ours and existing models. The reproducibility of radiomics features on ADC maps was evaluated using intraclass correlation coefficient. The model with multi-sequence images achieved the highest Dice similarity coefficient (DSC) with five-fold cross-validation (mean DSC = 0.83 and 0.79 for the training and validation datasets, respectively). The median (interquartile range) DSC of the test dataset model was 0.81 (0.70–0.88). Radiomics features extracted from manually and automatically segmented BC exhibited good reproducibility. Thus, our U-net model performed highly accurate segmentation of BC, and radiomics features extracted from the automatic segmentation results exhibited high reproducibility.

Hereditary ATTR amyloidosis is caused by the point mutation in serum protein transthyretin (TTR) that destabilizes its tetrameric structure to dissociate into monomer. The monomers form amyloid fibrils, which are deposited in peripheral nerves and organs, resulting in dysfunction. Therefore, a drug that dissolves amyloid after it has formed, termed amyloid disruptor, is needed as a new therapeutic drug. Here, we first established a high throughput screening system to find TTR interactors from the LOPAC1280 compound library. Among the hit compounds, thioflavin T-based post-treatment assay determined lead compounds for TTR amyloid disruptors, NSC95397 and Gossypol, designated as B and R, respectively. Because these compounds have naphthoquinone-naphthalene structures, we tested 100 naphthoquinone derivatives, and found 10 candidate compounds that disrupted TTR amyloid. Furthermore, to determine whether these 10 compounds are selective for TTR amyloid, we evaluated them against beta-amyloid (Aβ1-42). We found two compounds that were selective for TTR and did not disrupt Aβ-derived amyloid. Therefore, we succeeded in identifying TTR-selective amyloid disruptors, and demonstrated that naphthoquinone compounds are useful structures as amyloid disruptors. These findings contribute to the on-going efforts to discover new therapeutic tools for TTR amyloidosis.

Abstract Background Preoperative treatment is performed for locally advanced colon cancer with extensive tumor proximity or suspected invasion of skeletal muscles, major organs, and blood vessels. Oxaliplatin-based regimens are often used in preoperative chemotherapy. However, microsatellite instability (MSI)-high colorectal cancer is often resistant to cytotoxic anticancer agents. Herein, we describe a case of treatment of anticancer drug-resistant MSI-high locally advanced colon cancer and review cases of complete response to immune checkpoint inhibitor therapy for colorectal cancer. Case presentation A 57-year-old woman was referred to our hospital with a large tumor in the descending colon and extensive thoracic and abdominal wall involvement, including the ribs and diaphragm. No distant metastasis was observed. The tumor had perforated the abdominal wall and formed an abscess. Upon visiting our hospital, emergency surgery was performed. An abdominal wall incision was made to drain the abscess and laparoscopic colostomy was performed. Histopathological examination of biopsy specimens revealed an adenocarcinoma with positive immunohistochemical expressions of both CDX2 and CK20. The patient was diagnosed with a descending colon cancer. Genetic examination found MSI-high, Kras mutation (F12G), and wild-type BRAF. After the inflammation improved, chemotherapy with the FOLFIRI regimen was initiated, but the tumor grew rapidly. As a second-line treatment, nivolumab and ipilimumab combination therapy was initiated. After four cycles of these therapies, the patient was administered nivolumab alone for five cycles. Tumor shrinkage was observed and radical surgery was performed. The patient underwent laparoscopic descending colon and partial thoracic and abdominal wall resection. The abdominal wall muscle was dissected from the abdominal cavity, and subcutaneous tissues, diaphragm, ribs were dissected from the body surface. Pathological examination revealed mucus components, fibrous tissues, and no malignant cells, indicating a complete pathological response (pCR). The patient had a good postoperative course and returned to work after being discharged. No recurrence was observed six months postoperatively. Conclusions Herein, we report a case of anticancer drug-resistant MSI-high colon cancer that was resected after treatment with immune checkpoint inhibitors, and a pCR was achieved. This new treatment strategy can be used for the treatment of cases that are not responsive to conventional therapies.

Abstract Background Colorectal carcinoma with enteroblastic differentiation is a rare subtype of colorectal carcinomas expressing at least one characteristic immunohistochemical marker among α-fetoprotein, glypican-3, and spalt-like transcription factor 4. On the other hand, colorectal carcinoma with neuroendocrine differentiation is also a unique subtype of colorectal carcinomas showing expression of at least one distinctive marker among chromogranin A, synaptophysin, and CD56. Case presentation We experienced an extremely rare case of rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features in a 53-year-old male patient with long-standing ulcerative colitis (UC). Most of the tumor cells were positive for enteroblastic differentiation markers and approximately a half of them for neuroendocrine differentiation markers. Some tumor cells showed only enteroblastic differentiation, and some did only neuroendocrine feature, but some showed both enteroblastic and neuroendocrine differentiation. Conclusion Colorectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features has not been reported yet. Neoplastic transformation from pluripotent stem cells in dysplastic epithelium of long-standing UC patients may be associated with such dual differentiation features.

Abstract Airborne ultrasound radiation pressure, a nonlinear effect that appears as a static force in mid-air in the presence of strong ultrasound, has recently been applied in novel scientific and industrial fields. However, the output power of an ultrasound transducer remains low mainly due to the significant mismatch in acoustic impedance between a solid diaphragm and air. To circumvent this fundamental challenge, we propose to emit amplified airborne ultrasound pulses by instantaneously releasing stored acoustic energy into free-space. Specifically, we implement an acoustic cavity with a mechanically rotating shutter covering its open top. Once the acoustic cavity is fully charged, the stored energy is released by opening the shutter. By developing a choke structure that reduces leakage of the stored energy, we generate ultrasound pulses with 2.5 times higher peak power than the input continuous waves at 40 kHz. This preliminary result has a great potential to generate high-power ultrasound pulses using a conventional air-coupled transducer by separating the storage and radiation process, thus circumventing the fundamental limitation brought by impedance mismatch.

Abstract Background Mosquitoes of the Culex pipiens complex are found across the globe and are the focus of many research studies. Among the temperate species C. pipiens sensu stricto (s.s.), two forms are usually described: molestus and pipiens. These two forms are indistinguishable in terms of morphology but show behavioral and physiological differences that may have consequences for their associated epidemiology. The two forms are well defined in the northern part of the species distribution, where autogeny is strictly associated with the molestus form. However, whether the two remain distinct and show the characteristic differences in behavior is less clear in North Africa, at the southern edge of their range. Methods The association between autogeny, as determined by ovarian dissection, and molecular forms, based on the CQ11 microsatellite marker, was studied in six Moroccan populations of C. pipiens. Results An overall low prevalence of autogeny was found at three of the Moroccan regions studied, although it reached 17.5% in the Agadir population. The prevalence of form-specific CQ11 alleles was quite similar across all populations, with the molestus allele being rarer (approx. 15%), except in the Agadir population where it reached 43.3%. We found significant deficits in heterozygotes at the diagnostic CQ11 locus in three populations, but the three other populations showed no significant departure from panmixia, which is in line with the results of a retrospective analysis of the published data. More importantly, we found no association between the autogeny status and CQ11 genotypes, despite the many females analyzed. Conclusions There was limited evidence for two discrete forms in Morocco, where individuals carrying pipiens and molestus alleles breed and mate in the same sites and are equally likely to be capable of autogeny. These observations are discussed in the epidemiological context of Morocco, where C. pipiens is the main vector of several arboviruses. Graphical Abstract

During development, astrocytes are generated from radial glia, and migrate to the cortical plate, but the process of astrocyte migration during development is not fully understood. Here the authors labelled cells derived from the cortical ventricular zone in the late stages of cortical plate development in mice, and identified a migration mode in which cells move rapidly and almost at random within the intermediate zone and the cortical plate.

Abstract We fabricated Fe3O4 nanoparticle (NP)-assembled films on flexible polyimide sheets with Pt or Ta cap layer using a spin coating method and DC sputtering. The films were elaborated for spin Seebeck thermoelectric generator applications, and their spin Seebeck voltages were observed. We showed that the thermoelectric power of [Pt film/Fe3O4 NP] n multilayered films increases with increasing number of stacking n. Additionally, we prepared spin Seebeck thermopile devices in which the Fe3O4 NP-assembled films capped by Pt and Ta are connected alternately in series. We demonstrated that spin Seebeck voltages of the thermopile devices are larger than those of single [Pt or Ta film/Fe3O4 NP] n piece. Our results indicate that the spin Seebeck thermoelectric power of Fe3O4 NPs can be enhanced using a simple fabrication process without lithography technique.

Abstract Background Ligation of CD28 with ligands such as CD80 or CD86 provides a critical second signal alongside antigen presentation by class II major histocompatibility complex expressed on antigen-presenting cells through the T cell antigen receptor for naïve T cell activation. A number of studies suggested that CD28 plays an important role in the pathogenesis of various human diseases. Recent genome-wide association studies (GWASs) identified CD28 as a susceptibility locus for lymphocyte and eosinophil counts, multiple sclerosis, ulcerative colitis, celiac disease, rheumatoid arthritis, asthma, and primary biliary cholangitis. However, the primary functional variant and molecular mechanisms of disease susceptibility in this locus remain to be elucidated. This study aimed to identify the primary functional variant from thousands of genetic variants in the CD28 locus and elucidate its functional effect on the CD28 molecule. Results Among the genetic variants exhibiting stronger linkage disequilibrium (LD) with all GWAS-lead variants in the CD28 locus, rs2013278, located in the Rbfox binding motif related to splicing regulation, was identified as a primary functional variant related to multiple immunological traits. Relative endogenous expression levels of CD28 splicing isoforms (CD28i and CD28Δex2) compared with full-length CD28 in allele knock-in cell lines generated using CRISPR/Cas9 were directly regulated by rs2013278 (P

Abstract The zebrafish is widely used as a model in biological studies. In particular, the heart rate and cortisol levels of zebrafish are commonly measured to elucidate the pharmacological effects of chemical substances. Meanwhile, although ventilation is also an important physiological index reflecting emotion-like states, few studies have evaluated the effects of chemicals on ventilation in adult zebrafish. In this study, we assessed whether it is possible to evaluate the pharmacological effects elicited by caffeine in adult zebrafish under free-swimming conditions. We measured the ventilation in adult zebrafish exposed to multiple concentrations of caffeine under restraint and free-swimming conditions and evaluated the pharmacological effects of caffeine using linear mixed model analysis. In addition, results of electrocardiogram analysis and swimming speeds were compared with those in previous reports to ensure that an appropriate dose of caffeine was administered. Under restraint conditions, caffeine significantly decreased heart rate and increased ventilation in a concentration-dependent manner. Under free-swimming conditions, the ventilation rate significantly increased with increasing caffeine concentration. These results indicate that the pharmacological effects elicited by chemicals on ventilation can be evaluated in free-swimming zebrafish.

Abstract Background Listeria monocytogenes is a causative agent of food poisoning and is also known to cause invasive diseases, such as bacteremia, meningitis, and encephalitis, in neonates, elderly and immunocompromised patients. However, the clinical course of a multi-organ disseminated disease secondary to bacteremia has been rarely reported. Case presentation A 76-year-old woman undergoing immunosuppressive therapy for rheumatoid arthritis presented to our outpatient clinic with a chief complaint of weight loss. Computed tomography showed a left adrenal mass, enlarged lymph nodes, and multiple intrahepatic nodules. Positron emission tomography demonstrated accumulation of fluorodeoxyglucose F18 in the adrenal mass, lymph nodes, hepatic nodules, and bones, leading to the suspicion of systemic metastasis of adrenal cancer. She subsequently developed a fever. Blood culture results led to the diagnosis of Listeria monocytogenes bacteremia. Percutaneous needle biopsy of the adrenal lesion revealed no malignant findings. After extended treatment with antimicrobial agents, the fever resolved, along with the disappearance of the systemic lesions. Conclusions This case shows that listeriosis can lead to lesions in the adrenal gland, which can exhibit clinical presentation that is difficult to differentiate from malignancy on imaging studies.

Application of segment-structured tetrahedral amorphous carbon (ta-C) film on soft metal substrate is proposed to improve wear resistance of mechanical parts. It was generally considered that continuous structure ta-C film was effective when applied to hard materials because it could not follow deformation of substrate material and the film tended to delaminate. In contrast, by applying segment structure on ta-C film, tribological properties of ta-C film coated on soft substrate were further improved, and sliding surface exhibited excellent wear resistance even under high sliding loads. Effectiveness of the use of brass substrate in improving wear resistance was demonstrated through large-scale wear resistant test of valve-plate used in oil pump of construction machine. Segment-structured ta-C coated brass valve-plate reduced maximum wear by approximately 80 % as compared with uncoated brass plate.