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Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality and it is often diagnosed at advanced stages due to non-specific clinical presentation. Disease detection at localized disease stage followed by surgical resection remains the only potentially curative treatment. In this era of precision medicine, a multifaceted approach to early detection of PDAC includes targeted screening in high-risk populations, serum biomarkers and "liquid biopsies", and artificial intelligence augmented tumor detection from radiologic examinations. In this review, we will review these emerging techniques in the early detection of PDAC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis mostly due to the advanced stage at which disease is diagnosed. Early detection of disease at a resectable stage is, therefore, critical for improving outcomes of patients. Prior studies have demonstrated that pancreatic abnormalities may be detected on CT in up to 38% of CT studies 5 years before clinical diagnosis of PDAC. In this review, we highlight commonly missed signs of early PDAC on CT. Broadly, these commonly missed signs consist of small isoattenuating PDAC without contour deformity, isolated pancreatic duct dilatation and cutoff, focal pancreatic enhancement and focal parenchymal atrophy, pancreatitis with underlying PDAC, and vascular encasement. Through providing commentary on demonstrative examples of these signs, we demonstrate how to reduce the risk of missing or misinterpreting radiological features of early PDAC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: For safe drinking water, household water treatments (HWT) is important to reduce the risk of diarrhea in low-and-middle countries including Lao People's Democratic Republic (Lao PDR). However, the measurement of HWT relies chiefly on self-report in most nationwide surveys. Thus, the validity of self-reported measurement is of concern. The objective of this study was to determine the proportion of households with the presence of boiled water among households that report boiling practices in a rural area of the Lao PDR., Methods: This study was conducted with randomly selected 108 households in the four villages in the catchment area of the two health centers, in Xepon district of the Savannakhet province, between September and October 2023. The inclusion criterion of the households was the households that report boiling as HWT. Surveyors conducted interviews with an adult household member and observations on boiled water through household visits, using a questionnaire. Descriptive statistics were conducted to summarize the collected information using the frequency with proportion for categorical variables and the median with interquartile range for continuous variables. Bivariate analyses were conducted to assess an association between each of the factors and the presence of boiled water, using Fisher's exact test., Results: Among the 108 households that reported boiling practice, 91 households were able to show the surveyor self-reported boiled water. Thus, the proportion of households with the presence of boiled water was 90.1% (95% confidence interval: 82.5-95.1%). Households with a fixed schedule of boiling were significantly more likely to present boiled water, compared to households without (94.5% vs. 50.0%). Not all household members do not necessarily drink boiled water: approximately a quarter (25.7%) of the participants reported that some household members drink unboiled water., Conclusions: This study showed that among households that reported boiling drinking water, 90.1% were able to present a container with self-reported boiled water. It suggests that the self-reported measure of boiling practices can be valid in the study villages., (© 2024. The Author(s).)

Purpose: The purpose of this study was to develop a radiomics-based algorithm to identify small pancreatic neuroendocrine tumors (PanNETs) on CT and evaluate its robustness across manual and automated segmentations, exploring the feasibility of automated screening., Materials and Methods: Patients with pathologically confirmed T1 stage PanNETs and healthy controls undergoing dual-phase CT imaging were retrospectively identified. Manual segmentation of pancreas and tumors was performed, then automated pancreatic segmentations were generated using a pretrained neural network. A total of 1223 radiomics features were independently extracted from both segmentation volumes, in the arterial and venous phases separately. Ten final features were selected to train classifiers to identify PanNETs and controls. The cohort was divided into training and testing sets, and performance of classifiers was assessed using area under the receiver operator characteristic curve (AUC), specificity and sensitivity, and compared against two radiologists blinded to the diagnoses., Results: A total of 135 patients with 142 PanNETs, and 135 healthy controls were included. There were 168 women and 102 men, with a mean age of 55.4 ± 11.6 (standard deviation) years (range: 20-85 years). Median PanNET size was 1.3 cm (Q1, 1.0; Q3, 1.5; range: 0.5-1.9). The arterial phase LightGBM model achieved the best performance in the test set, with 90 % sensitivity (95 % confidence interval [CI]: 80-98), 76 % specificity (95 % CI: 62-88) and an AUC of 0.87 (95 % CI: 0.79-0.94). Using features from the automated segmentations, this model achieved an AUC of 0.86 (95 % CI: 0.79-0.93). In comparison, the two radiologists achieved a mean 50 % sensitivity and 100 % specificity using arterial phase CT images., Conclusion: Radiomics features identify small PanNETs, with stable performance when extracted using automated segmentations. These models demonstrate high sensitivity, complementing the high specificity of radiologists, and could serve as opportunistic screeners., Competing Interests: Declaration of competing interest Dr. Elliot K. Fishman discloses the following relationships: Siemens Medical Systems, research grant support, and HIP Graphics, co-founder. The other authors have no competing interests or disclosures to declare., (Copyright © 2024 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide. In this review, based on information from a database of papers related to NBRP bioresources, we present the bioresources that have proved useful for mammalian genome research, including mice, rats, other animal resources; DNA-related materials; and human/animal cells and microbes., (© 2024. The Author(s).)

Background/objectives: Pancreatic cyst management can be distilled into three separate pathways - discharge, monitoring or surgery- based on the risk of malignant transformation. This study compares the performance of artificial intelligence (AI) models to clinical care for this task., Methods: Two explainable boosting machine (EBM) models were developed and evaluated using clinical features only, or clinical features and cyst fluid molecular markers (CFMM) using a publicly available dataset, consisting of 850 cases (median age 64; 65 % female) with independent training (429 cases) and holdout test cohorts (421 cases). There were 137 cysts with no malignant potential, 114 malignant cysts, and 599 IPMNs and MCNs., Results: The EBM and EBM with CFMM models had higher accuracy for identifying patients requiring monitoring (0.88 and 0.82) and surgery (0.66 and 0.82) respectively compared with current clinical care (0.62 and 0.58). For discharge, the EBM with CFMM model had a higher accuracy (0.91) than either the EBM model (0.84) or current clinical care (0.86). In the cohort of patients who underwent surgical resection, use of the EBM-CFMM model would have decreased the number of unnecessary surgeries by 59 % (n = 92), increased correct surgeries by 7.5 % (n = 11), identified patients who require monitoring by 122 % (n = 76), and increased the number of patients correctly classified for discharge by 138 % (n = 18) compared to clinical care., Conclusions: EBM models had greater sensitivity and specificity for identifying the correct management compared with either clinical management or previous AI models. The model predictions are demonstrated to be interpretable by clinicians., Competing Interests: Declaration of competing interest E.K.F. has educational grant support with GE Medical, Siemens Healthineers research grant support, HipGraphics Inc (co-founder and shareholder), Exact Sciences (consultant), Imaging Endpoints (consultant). A.M.L. is a consultant with Exact Sciences. K.W.K. is also a member of the Scientific Advisory Boards of Eisai-Morphotek, Syxmex-Inostics, CAGE, and NeoPhore. These companies, as well as other companies, have licensed technologies from Johns Hopkins University, on which K.W.K. is an inventor. These licenses and relationships are associated with equity or royalty payments to K.W.K. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. D.S.K. is a consultant and equity holder in PAIGE. AI. The terms of all these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies. The following patents are related to this work: Safe Sequencing System US201161476150P, Rapid Aneuploidy Detection US201261615535P, Mutations in pancreatic neoplasms US9976184B2, and Differential identification of pancreatic cysts US9637796B2., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic pancreatitis (CP) is a progressive benign fibroinflammatory condition involving repeated episodes of pancreatic inflammation, which lead to fibrotic tissue replacement and subsequent pancreatic insufficiency. A lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC) in patients with chronic pancreatitis is reported to be 1.5%-4%. However, diagnosis of PDAC in patients with CP can be challenging, in part due to overlapping imaging features. In rare instances, pancreatic parenchymal calcifications that are typically associated with chronic pancreatitis may diminish in the case of a developing PDAC. In this article, we present a patient with chronic pancreatitis in whom calcifications decreased at the time of pancreatic ductal adenocarcinoma diagnosis, as compared to prior CT imaging. The unique imaging features of "diminishing calcifications" associated with a hypoattenuating lesion can potentially be a useful sign of pancreatic ductal adenocarcinoma and may aid in early diagnosis and prompt treatment intervention., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2 cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs)., Patients and Methods: An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally., Results: Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2 cm)., Conclusions: Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible., (© 2024. Society of Surgical Oncology.)

There is a lack of data regarding the safety and effectiveness of implanting the Pipeline Embolization Device with Shield technology (PED-Shield) compared with the previous generation of Pipeline (PED-Flex). This retrospective single-center study aimed to compare treatment outcomes between the PED-Shield and PED-Flex for treating unruptured internal carotid artery aneurysms. The PED-Flex was used in 62 procedures (67 aneurysms, 59 patients) and the PED-Shield in 53 procedures (59 aneurysms, 58 patients). The mean aneurysm diameter was significantly lower in the PED-Shield group than in the PED-Flex group (11.9 ± 7.0 mm vs. 15.2 ± 6.9 mm, p < 0.001). At the 12-month follow-up, the complete angiographic occlusion rate was 72.1% and 72.3% in the PED-Flex and PED-Shield groups, respectively (p = 0.9808). Limited to aneurysms larger than 10 mm, 70.6% and 68.0%, respectively (p = 0.8175). The incidence of more than three high signal intensity areas on diffusion-weighted imaging after treatment was significantly lower in the PED-Shield group than in the PED-Flex group (27.7% vs. 67.7%; p < 0.001). Limited to aneurysms larger than 10 mm, 41.1% and 69.6%, respectively (p < 0.0117). Symptomatic ischemic complications occurred within 30 days of four PED-Flex procedures (6.5%) and one PED-Shield procedure (2.0%) (p = 0.2315). Limited to aneurysms larger than 10 mm, 1.8% and 3.2%, respectively (p = 0.6677). The incidence of mRS score worsening at 6 months was 3.2% and 1.9% in the PED-Flex and PED-Shield groups, respectively (p = 0.6534). The PED-Shield can achieve outcomes equivalent to or better than the PED-Flex. Further large-scale studies are warranted to confirm our findings.

In recent years, there has been increasing attention towards understanding the relationship between age-related alterations in the oral microbiota and age-associated diseases, with reports emphasizing the significance of maintaining a balanced oral microbiota for host health. However, the precise mechanisms underlying age-related changes in the oral microbiota remain elusive. We recently reported that cellular senescence of ileal germinal center (GC) B cells, triggered by the persistent presence of commensal bacteria, results in diminished IgA production with aging and subsequent alterations in the gut microbiota. Consequently, we hypothesize that a similar phenomenon may occur in the oral cavity, potentially contributing to age-related changes in the oral microbiota. Examination of p16-luc mice, wherein the expression of the senescent cell marker p16 INK4a can be visualized, raised under specific pathogen-free (SPF) or germ-free (GF) conditions, indicated that, unlike ileal GC B cells, the accumulation of senescent cells in GC B cells of cervical lymph nodes increases with age regardless of the presence of commensal bacteria. Furthermore, longitudinal studies utilizing the same individual mice throughout their lifespan revealed concurrent age-related alterations in the composition of the oral microbiota and a decline in salivary IgA secretion. Further investigation involving Rag1 -/- mice transplanted with B cells from wild-type or p16 INK4a and p21 Waf1/Cip1 -double knockout mice unveiled that B cell senescence leads to reduced IgA secretion and alteration of the oral microbiota. These findings advance our understanding of the mechanism of age-associated changes in the oral microbiota and open up possibilities of their control., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Two phenomena, the accumulation of senescent cells and changes in the gut microbiota, are thought to contribute to the decline of biological functions and the development of diseases associated with aging. However, the relationship between these two phenomena and their effects on aging remains to be clarified. Recently, we have reported that gut bacteria induce cellular senescence in ileal germinal center (GC) B cells, resulting in decreased IgA production and diversity. This, in turn, leads to an imbalance in the gut microbiota. Thus, the crosstalk between the gut microbiota and cellular senescence via the host immune system may establish a vicious cycle and contribute to the disruption of gut homeostasis associated with aging., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01-2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31-6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner., (© 2024. The Author(s).)

Purpose: Accurate staging of disease is vital in determining appropriate care for patients with pancreatic ductal adenocarcinoma (PDAC). It has been shown that the quality of scans and the experience of a radiologist can impact computed tomography (CT) based assessment of disease. The aim of the current study was to evaluate the impact of the rereading of outside hospital (OH) CT by an expert radiologist and a repeat pancreatic protocol CT (PPCT) on staging of disease., Methods: Patients evaluated at the our institute's pancreatic multidisciplinary clinic (2006 to 2014) with OH scan and repeat PPCT performed within 30 days were included. In-house radiologists staged disease using OH scans and repeat PPCT, and factors associated with misstaging were determined., Results: The study included 100 patients, with a median time between OH scan and PPCT of 19 days (IQR: 13-23 days.) Stage migration was mostly accounted for by upstaging of disease (58.8 % to 83.3 %) in all comparison groups. When OH scans were rereviewed, 21.5 % of the misstaging was due to missed metastases, however, when rereads were compared to the PPCT, occult metastases accounted for the majority of misstaged patients (62.5 %). Potential factors associated with misstaging were primarily related to imaging technique., Conclusion: A repeat PPCT results in increased detection of metastatic disease that rereviews of OH scans may otherwise miss. Accessible insurance coverage for repeat PPCT imaging even within 30 days of an OH scan could help optimize delivery of care and alleviate burdens associated with misstaging., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Effective and feasible educational methods are needed to control salt intake. We performed a single-center, non-randomized controlled study to investigate the effectiveness and feasibility of self-monitoring using a urinary sodium/potassium (Na/K) ratio-measuring device in patients with difficulty in reducing salt intake. This study included 160 patients with hypertension, chronic kidney disease, or heart disease who were followed up in the outpatient clinic of the Dokkyo Medical University Nikko Medical Center. Urinary Na/K ratio measuring Na/K ratio meter were loaned for 2-6 weeks to the treatment (T) group (n = 80) and not to the patients in the control (C) group (n = 80). In the T group, patients were instructed to measure the urinary Na/K ratio at least three times a day and maintain a Na/K ratio below 2.0. Salt reduction education and home blood pressure measurement guidance continued in both groups. The mean device loan period in the T group was 25.1 days, the mean number of measurements was 3.0 times/day, and the proportion of patients achieving three measurements per day was 48.8% (39/80). Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake by -1.9 g/day at the second visit (p < 0.001) in the T group. In contrast, no change was observed over time in the C group. Self-monitoring using the urinary Na/K ratio meter successfully reduced salt intake in patients with difficulty reducing salt intake., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

We herein report a 76-year-old woman with situs inversus and dextrocardia who underwent pacemaker implantation for sick sinus syndrome. Situs inversus with dextrocardia, which is frequently associated with cardiovascular malformation, is a rare congenital malformation wherein the thoracic and abdominal viscera are inverted compared with their normal positions. This renders the implantation of cardiac devices an arduous task. We therefore decided to gather preoperative anatomical information on patients with situs inversus and dextrocardia. We used three-dimensional computed tomography to collect preoperative information in order to facilitate the safe implantation of cardiac devices.

Although left ventricular thrombi (LVTs) are closely related to the prognosis of patients with systolic dysfunction, anticoagulation therapy is not recommended for the primary prevention of LVTs in patients with sinus rhythm heart failure. We report a case of a patient with systolic dysfunction who developed a giant LVT in an extremely short period of time (one month) after an infection. The LVT led to acute limb ischemia, gangrene, and death. Additionally, we incidentally detected pulmonary thrombosis in this patient., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kawamoto et al.)

Introduction: Recent studies have reported the efficacy of the cryoballoon (CB)-guided left atrial roof block line (LARB) creation in patients with persistent atrial fibrillation (AF). However, it can be technically challenging to attach the balloon to the left atrial (LA) roof due to its anatomical variations. We designed a new procedure called the "Raise-up Technique," which may facilitate the firm adhesion of the CB to the LA roof during freezing. This study aimed to evaluate the efficacy of the Raise-up technique in LARB creation., Methods and Results: In total, 100 consecutive patients with persistent AF who underwent CB-LARB creation were enrolled. Fifty-seven patients underwent LARB creation using the Raise-up technique (Raise-up group), and the remaining 43 did not use it (control group). The Raise-up technique was performed as follows: An Achieve catheter was inserted as deeply as possible into the upper branch of the right superior pulmonary vein to anchor the CB. The balloon was placed below the targeted site on the LA roof and frozen. When the temperature of the CB reached approximately -10°C and the CB was easier to attach to the LA tissue, the CB was raised and pressed against the LA roof immediately by sheath advancement. Then the balloon could be in firm contact with the target site on the roof. If necessary, additional sheath advancement after sufficient freezing (-20°C to -30°C) was allowed the CB to have more firm and broad contact with the target site. LARB creation without touch-up ablation was achieved in 54 of 57 patients (94.7%) in the Raise-up group and 33 of 43 patients (76.7%) in the control group (p < .05). The lesion size of the LARB in the Raise-up group was significantly larger than that in the control group (15.2 cm 2 vs. 12.8 cm 2 , p < .05). Moreover, the width of the LARB lesion in the Raise-up group was wider than that in the control group (32.0 mm vs. 26.6 mm, p < .05)., Conclusion: The Raise-up technique enabled the creation of seamless and thick LARB lesions with a single stroke. In addition, the CB-LARB lesions created using the Raise-up technique tended to be large, resulting in extensive debulking of the LA posterior wall arrhythmia substrates. In CB ablation for persistent AF, the Raise-up technique can be considered one of the key strategies for LARB creation., (© 2024 Wiley Periodicals LLC.)

Lipases with high interesterification activity are important enzymes for industrial use. The lipase from Burkholderia stagnalis (BsL) exhibits higher interesterification activity than that from Burkholderia plantarii (BpL) despite their significant sequence similarity. In this study, we determined the crystal structure of BsL at 1.40 Å resolution. Utilizing structural insights, we have successfully augmented the interesterification activity of BpL by over twofold. This enhancement was achieved by substituting threonine with serine at position 289 through forming an expansive space in the substrate-binding site. Additionally, we discuss the activity mechanism based on the kinetic parameters. Our study sheds light on the structural determinants of the interesterification activity of lipase., (© 2024 Federation of European Biochemical Societies.)

Governing dual-use research of concern (DURC) in the life sciences has become difficult owing to the diversification of scientific domains, digitalization of potential threats, and the proliferation of actors. This paper proposes three approaches to realize bottom-up governance of DURC from laboratory operation to institutional decision-making levels. First, a technological approach can predict and monitor the dual-use nature of the research target pathogens and their information. Second, an interactive approach is proposed in which diverse stakeholders proactively discuss and examine dual-use issues through research practice. Third, a personnel approach can identify the right persons involved in DURC. These approaches suggest that, going beyond self-governance by researchers, collaborative and networked governance involving diverse actors should become essential. This mode of governance can also be seen in light of the management of research use. Therefore, program design by funding agencies and publication screening by journal publishers continuously contribute to governance at the meso-level. Bottom-up governance may be realized by using an appropriately integrated design of these three approaches at the micro-level, such as dual-use prediction and monitoring, stakeholder dialogue, and background checks. Given that the term 'open science' has been promoted to the research community as part of top-down governance, paying due attention on site to research subjects, research practices, and persons involved in research will provide an opportunity to develop a more socially conscious open science.

Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign., Competing Interests: K.Yakushijin has received research grants and honoraria from Chugai Pharmaceutical and Pfizer. T.M. is an employee of Maruho Co., Ltd. K.D. and H.S. are employees of Cellspect Co., Ltd. T.S. is an employee of KAICO Ltd. N.K. has received grants from Roche Pharmaceuticals. H.M. has received research grants and honoraria from Chugai Pharmaceutical. The other authors declare no conflicts of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

We report four cases of syphilitic uveitis with diverse clinical presentations. All patients were men who have sex with women, and were aged 19-68 years, and none were HIV-positive. All cases were bilateral. One case presented with anterior uveitis, while three exhibited panuveitis. One patient had acute syphilitic posterior placoid chorioretinitis and two had retinal vasculitis resulting in damage to the outer retinal and retinal pigment epithelium. The rapid plasma reagin (RPR) test and Treponema pallidum (TP) hemagglutination test were both positive in all cases. Six of eight eyes had improved vision and best-corrected visual acuity better than 20/20 after antibiotic treatment. Serological testing is mandatory for the diagnosis of syphilitic uveitis. Additionally, multimodal imaging, including optical coherence tomography (OCT), fundus autofluorescence (FAF), and fluorescein angiography (FA), can provide useful adjunctive information for early diagnosis and assessment of treatment response., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kawamoto et al.)

Background: Respiratory syncytial virus (RSV) affects children, causing serious infections, particularly in high-risk groups. Given the seasonality of RSV and the importance of rapid isolation of infected individuals, there is an urgent need for more efficient diagnostic methods to expedite this process., Objective: This study aimed to investigate the performance of a machine learning model that leverages the temporal diversity of symptom onset for detecting RSV infections and elucidate its discriminatory ability., Methods: The study was conducted in pediatric and emergency outpatient settings in Japan. We developed a detection model that remotely confirms RSV infection based on patient-reported symptom information obtained using a structured electronic template incorporating the differential points of skilled pediatricians. An extreme gradient boosting-based machine learning model was developed using the data of 4174 patients aged ≤24 months who underwent RSV rapid antigen testing. These patients visited either the pediatric or emergency department of Yokohama City Municipal Hospital between January 1, 2009, and December 31, 2015. The primary outcome was the diagnostic accuracy of the machine learning model for RSV infection, as determined by rapid antigen testing, measured using the area under the receiver operating characteristic curve. The clinical efficacy was evaluated by calculating the discriminative performance based on the number of days elapsed since the onset of the first symptom and exclusion rates based on thresholds of reasonable sensitivity and specificity., Results: Our model demonstrated an area under the receiver operating characteristic curve of 0.811 (95% CI 0.784-0.833) with good calibration and 0.746 (95% CI 0.694-0.794) for patients within 3 days of onset. It accurately captured the temporal evolution of symptoms; based on adjusted thresholds equivalent to those of a rapid antigen test, our model predicted that 6.9% (95% CI 5.4%-8.5%) of patients in the entire cohort would be positive and 68.7% (95% CI 65.4%-71.9%) would be negative. Our model could eliminate the need for additional testing in approximately three-quarters of all patients., Conclusions: Our model may facilitate the immediate detection of RSV infection in outpatient settings and, potentially, in home environments. This approach could streamline the diagnostic process, reduce discomfort caused by invasive tests in children, and allow rapid implementation of appropriate treatments and isolation at home. The findings underscore the potential of machine learning in augmenting clinical decision-making in the early detection of RSV infection., (©Shota Kawamoto, Yoshihiko Morikawa, Naohisa Yahagi. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.04.2024.)

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2-13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted., (© 2024. The Author(s).)

Addressing venous bleeding is a frequent complication of vascular and abdominopelvic surgeries. We present a novel sutureless repair technique using Hydrofit Ⓡ  (Terumo, Tokyo, Japan), an elastomeric sealant. In a patient experiencing common iliac vein bleeding during abdominal aortic aneurysm surgery, this technique successfully achieved complete hemostasis. By applying the elastomeric sealant with an autologous arterial patch to the bleeding site, we demonstrate the simplicity and effectiveness of sutureless hemostasis for venous bleeding., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nakahara et al.)

We have previously performed a hierarchical in silico screening of a Mycobacterium tuberculosis shikimic acid kinase [1]. Specifically, 11 compounds were screened from a library of 154,118 compounds provided by ChemBridge [2] using UCSF DOCK [3] and the GOLD [4] program in the first and second steps, respectively. Molecular dynamic simulations were further performed on compound 2 (2-[(5Z)-5-(1-benzyl-5bromo-2-oxoindol-3-(5Z)-5-(1-benzyl-5-bromo-2-oxoindol-3-(5Z)-4-oxo-2 ylidene)-4oxo-2-sulfanylidene-1,3-thiazolidin-3-yl] acetic acid), which showed antimicrobial efficacy. These processes yielded ligand docking scores and trajectories. In this data article, we have added solvent-accessible surface area and PCA analyses, which were calculated from the raw docking scores and trajectories. Data obtained from molecular docking and molecular dynamic simulations are useful in two ways: (1) Further support for previous work (2) Provides a stepping stone for experimental scientists to conduct in silico studies and research ideas for other drug discovery researchers and computational biologists. We believe that this article will provide an opportunity to develop new Mycobacterium tuberculosis therapeutics through searching for analogs and inhibitors against new targets., (© 2024 The Authors.)

Survivors' adaptation to a suicide loss is likely influenced by their attitudes toward suicide and their respective sociocultural contexts. Our study aimed to compare suicide attitudes and their association with depressive symptoms and sense of community safety in Japanese and American suicide loss survivors. A total of 193 Japanese survivors and 232 American survivors completed online surveys. The results show that Japanese survivors tended not to consider suicide as an illness or to recognize that others understood their experience but were more likely than American survivors to consider suicide as justifiable. Regression analyses indicated that taking suicide as a right was associated with depressive symptoms. Further, their sense of being understood by others was positively correlated with perceived community safety in both samples, but justifying suicide and considering it to be an illness was positively related to perceived community safety only among Japanese survivors., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Purpose: Delay in diagnosis can contribute to poor outcomes in pancreatic ductal adenocarcinoma (PDAC), and new tools for early detection are required. Recent application of artificial intelligence to cancer imaging has demonstrated great potential in detecting subtle early lesions. The aim of the study was to evaluate global and local accuracies of deep neural network (DNN) segmentation of normal and abnormal pancreas with pancreatic mass., Methods: Our previously developed and reported residual deep supervision network for segmentation of PDAC was applied to segment pancreas using CT images of potential renal donors (normal pancreas) and patients with suspected PDAC (abnormal pancreas). Accuracy of DNN pancreas segmentation was assessed using DICE simulation coefficient (DSC), average symmetric surface distance (ASSD), and Hausdorff distance 95% percentile (HD95) as compared to manual segmentation. Furthermore, two radiologists semi-quantitatively assessed local accuracies and estimated volume of correctly segmented pancreas., Results: Forty-two normal and 49 abnormal CTs were assessed. Average DSC was 87.4 ± 3.1% and 85.5 ± 3.2%, ASSD 0.97 ± 0.30 and 1.34 ± 0.65, HD95 4.28 ± 2.36 and 6.31 ± 6.31 for normal and abnormal pancreas, respectively. Semi-quantitatively, ≥95% of pancreas volume was correctly segmented in 95.2% and 53.1% of normal and abnormal pancreas by both radiologists, and 97.6% and 75.5% by at least one radiologist. Most common segmentation errors were made on pancreatic and duodenal borders in both groups, and related to pancreatic tumor including duct dilatation, atrophy, tumor infiltration and collateral vessels., Conclusion: Pancreas DNN segmentation is accurate in a majority of cases, however, minor manual editing may be necessary; particularly in abnormal pancreas., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In mammals, females undergo reproductive cessation with age, whereas male fertility gradually declines but persists almost throughout life. However, the detailed effects of ageing on germ cells during and after spermatogenesis, in the testis and epididymis, respectively, remain unclear. Here we comprehensively examined the in vivo male fertility and the overall organization of the testis and epididymis with age, focusing on spermatogenesis, and sperm function and fertility, in mice. We first found that in vivo male fertility decreased with age, which is independent of mating behaviors and testosterone levels. Second, overall sperm production in aged testes was decreased; about 20% of seminiferous tubules showed abnormalities such as germ cell depletion, sperm release failure, and perturbed germ cell associations, and the remaining 80% of tubules contained lower number of germ cells because of decreased proliferation of spermatogonia. Further, the spermatozoa in aged epididymides exhibited decreased total cell numbers, abnormal morphology/structure, decreased motility, and DNA damage, resulting in low fertilizing and developmental rates. We conclude that these multiple ageing effects on germ cells lead to decreased in vivo male fertility. Our present findings are useful to better understand the basic mechanism behind the ageing effect on male fertility in mammals including humans., (© 2024. The Author(s).)

Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies that can be divided into two types-warm and cold-depending on their thermal amplitudes. The pathology differs depending on the type of autoantibody involved; however, the underlying etiology can differ even when the pathology is the same. Therefore, understanding the underlying mechanisms and making an accurate diagnosis is critical, as inappropriate treatment not only results in treatment failure, but can also cause life-threatening complications and reduce patient quality of life. Corticosteroids are the first-line treatment for warm AIHA, but have limited efficacy against cold agglutinin disease (CAD). Moreover, long-term and high-dose administration of corticosteroids increases risk of infection, fracture, and thromboembolism. A novel therapeutic agent for CAD targeting the complement system is effective only against hemolysis, but does not improve symptoms induced by red blood cell aggregation. In addition, elderly patients who present with either warm AIHA or CAD should also be assessed for possible malignancy. This review discusses the etiologies and pathological conditions associated with AIHA and describes the recommendations for diagnosis and treatment according to the Japanese guideline for AIHA revised in 2022.

Objective: Treatment of anterior choroidal artery (AChA) aneurysms is frequently associated with ischemic complications. This study aimed to report the outcomes of treatment of unruptured AChA aneurysms in our hospital., Methods: Between January 2015 and March 2022, 40 patients were treated for an unruptured AChA aneurysm in our hospital. Age, sex, aneurysm size, AChA branching type, treatment, occlusion rate, complications, modified Rankin Scale (mRS) score before surgery and after 90 days, and recurrence were investigated. The branching type was classified as internal carotid artery (ICA), neck, or dome type based on the location of the AChA origin., Results: The mean age was 61.1 ± 1.9 years; 15 patients were men and 25 were women. The mean aneurysm diameter was 4.4 ± 0.3 mm. The branching type was ICA in four patients, neck in 35, and dome in one. Treatment was surgical clipping in 22 patients and endovascular coil embolization in 18 (14 with stent assistance). Motor-evoked potential (MEP) monitoring was used in all patients of the clipping group and 9 cases of the coiling group. Treatment complications occurred in eight patients (20%). mRS score worsened by more than one point 90 days after treatment in four patients (10%); however, the proportion of patients who experienced this did not significantly differ between the clipping and coiling groups. Although the odds of a thrombotic complication were higher with coiling than clipping, the difference was not significant (odds ratio: 10.2; P = 0.08). The rate of complete occlusion was lower in the coiling group (72.2% vs. 95.3%), but the difference was not significant. The median follow-up was 696 days (range: 99-2053). No aneurysm recurrence or rupture occurred., Conclusion: AChA branching type is important for treatment decision-making in patients with AChA aneurysms. Rates of complications and occlusion do not significantly differ between clipping and coiling of AChA aneurysms. MEP monitoring may be useful in preventing thrombotic complications during coil embolization., (©2024 The Japanese Society for Neuroendovascular Therapy.)

Purpose: The purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs)., Materials and Methods: A retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference., Results: A total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3-85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71-0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7-95.3) and 73.3% (95% CI: 62.9-83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001)., Conclusion: Non-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making., Competing Interests: Declaration of Competing Interest The authors do not have any conflict of interest to disclose in relation with this article., (Copyright © 2023. Published by Elsevier Masson SAS.)

Objective: Traumatic middle meningeal artery (MMA)-middle meningeal vein (MMV) fistula (MMA-MMV fistula) and MMA pseudoaneurysm are the 2 main MMA-related vascular diseases occurring after blunt head trauma. These are rare but known causes of delayed intracranial hemorrhage. This study investigated predictors that may aid in the diagnosis of these diseases., Methods: In our department, screening digital subtraction angiography (DSA) is performed for patients with blunt head trauma accompanied by intracranial hemorrhage and skull or facial bone fracture. This study included 87 patients who underwent screening DSA without craniotomy from January 2019 to June 2023. The patients' clinical characteristics were retrospectively collected from the database. Statistical analysis was performed to examine the associations of various evaluation items with MMA-related vascular diseases., Results: The first DSA examination revealed 34 MMA-MMV fistulas and 1 MMA pseudoaneurysm. The second follow-up DSA examination revealed 13 MMA-MMV fistulas and four MMA pseudoaneurysms. Temporal/parietal bone fracture (odds ratio, 5.33; P = 0.0005; 95% confidence interval, 1.95-14.60) was significantly associated with MMA-related vascular diseases. Endovascular treatments were performed in 9 patients. All procedures were successfully completed without complications; no delayed bleeding was observed., Conclusions: Temporal/parietal bone fracture in patients with blunt head trauma is a likely predictor of MMA-related vascular diseases. When initial head computed tomography reveals this pathology, we recommend careful imaging follow-up (e.g., DSA) and treatment as needed, while considering the possibility of MMA-related vascular diseases., (Copyright © 2023 Elsevier Inc. All rights reserved.)