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Background: For the accurate positioning of surgical tools, conventional intraoperative navigation systems have been developed to recognize the relationship between target positions and the tools. However, since an internal organ is deformed during the operation, registratin between real-time two-dimensional (2D) ultrasound images and three-dimensional (3D) CT or MRI images is not always effective. Therefore, this study developed image registration between 2D and 3D ultrasound images considering deformation for tracking target vessel movement in the liver. Methods: 3D ultrasound image was obtained in advance with 3D coordinates, including the target vessel. Then real-time 2D images and ultrasound probe position were simultaneously acquired using a 3D position sensor. We applied multiple image resolution registration, where rapid and fine optimizations can be expected in higher and lower levels, respectively. Meanwhile, gradient descent method was adopted for the optimization, which determines the relative arrangements to obtain maximum similarity between 2D and 3D images. We experimentally established resolution level parameters using a phantom before applying it to track liver blood vessel movements in a normal healthy subject. Results: Comparing between the 2D images and the registered images, although the approach has some limitations in tracking large displacement, we confirmed that the cross section of the target blood vessel was clearly visualized. Conclusion: This method has a potential for an ultrasound therapy targeting blood vessels under natural respiration conditions.

To compare the radiation dose and diagnostic ability of the 100-kVp protocol, based on the contrast noise ratio (CNR) index, during coronary artery bypass graft (CABG) vessels with those of the 120-kVp protocol. For the 120-kVp scans (150 patients), the targeted image level was set at 25 Hounsfield units (HU) (CNR120 = iodine contrast/25 HU). For the 100-kVp scans (150 patients), the targeted noise level was set at 30 HU to obtain the same CNR as in the 120-kVp scans (i.e. using 1.2-fold higher iodine contrast, CNR100 = 1.2 × iodine contrast/(1.2 × 25 HU) = CNR120). We compared the CNRs, radiation doses, detection of CABG vessels and visualisation scores of the scans acquired at 120 and 100 kVp, respectively. At the same CNR, the 100-kVp protocol may help reduce the radiation dose by ⁓30% compared with the 120-kVp protocol, without degradation of diagnostic ability during CABG.

Background Previously, we reported the clinical outcomes of the combination of anti-PD-1 Ab, cyclin-dependent kinase 4/6 inhibitors, and endocrine therapy (ET) in patients with ER positive/HER2 negative advanced breast cancer in SABCS2020; biomarker analysis has been performed to provide insight into the hepatotoxicy frequently observed in the study. Methods Subjects received 240 mg nivolumab IV on days 1 and 15, 150 mg abemaciclib PO twice daily, and either 500 mg fulvestrant (FUL) on days 1, 15, 29, and every 4 weeks thereafter (FUL cohort) or 2.5 mg letrozole (LET) once daily (LET cohort). The primary endpoint was objective response rate and secondary endpoints included toxicity evaluated in the CTCAE along with an exploratory endpoint as related to the biomarker analysis. Archival tumor tissues were collected before study entry and blood and stool samples were collected at baseline and on cycle3 day1. Tumor tissues were subjected to IHC analysis and RNA sequencing followed by subtyping using NGS. High throughput cytokine analysis using ELISA-based assay were performed with serum samples and cell sorting analysis of PBMC was performed with FACS. Results From June 2019 to December 2019, 17 subjects were enrolled (FUL cohort [n = 12], LET cohort [n = 5]). The study was prematurely closed due to safety concerns such as hepatotoxicity and interstitial lung disease. AEs ≥ Grade 3 were observed in 91.7% and 100% of patients in the FUL and LET cohorts, respectively. The most frequent AEs ≥ Grade 3 were elevated liver function tests (LFT; FUL cohort: 50.0%, LET cohort: 60.0%). Serum cytokine analysis from the subjects with severe hepatotoxicity indicated cytokine storm with elevations of sCD30/TNFRSF8, IL-11, -34, Pentraxin-3, sTNF-R1, -R2, TSLP, which was supported by the findings of reduction of effector regulatory T cells in PBMC. IHC study in liver biopsy from three subjects with the toxicity revealed infiltration of CD8+ T cells and FOXP3+ T reg into the liver, suggesting the immune related liver injury upon the treatment with nivolumab and abemaciclib. HLA typing was performed in the 17 patients but no association between HLA type and ILD or hepatotoxicity were observed. Conclusions The frequent and severe immune related hepatotoxicity induced by the combination of anti-DD-1 and CDK 4/6 inhibitors might have been an immune-boosting therapy as suggested in the preclinical studies. This study was supported by the Ono Pharmaceutical Co., LTD. The registration number of the study is UMIN000036970. Citation Format: Junji Tsurutani, Jun Masuda, Norikazu Masuda, Yuko Tanabe, Tsutomu Iwasa, Masato Takahashi, Manabu Futamura, Koji Matsumoto, Kenjiro Aogi, Hiroji Iwata, Mari Hosonaga, Toru Mukohara, Kiyoshi Yoshimura, Chiyo K. Imamura, Sakiko Miura, Toshiko Yamochi, Kenichi Yoshimura, Toshimi Takano, Hidetaka Kawabata. Biomarker analysis of hepatotoxicity in a Phase II study of nivolumab, abemaciclib and endocrine therapy in patients with HR-positive, HER2-negative breast cancer: WJOG11418BTR NEWFLAME_TR [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-08.

Background and objectives: There are few details available regarding the prevalence of hepatitis B virus (HBV) infection in the general Bangladeshi population. There is a dearth of data on prevalence of HBV infection in children and adolescents who were born before the hepatitis B vaccine was introduced in the Expanded Program on Immunization (EPI). The objective of the current study was to use archived data to describe the seroepidemiology of HBV infection (HBsAg and anti-HBc Antibody) among school children in a particular rural area of Bangladesh. Also, the study correlated serum vitamin A level with the HBV infection status among a subset of children. Materials and method: The study analyzed the archived data of a study conducted in 2003 and 2004. The samples were collected from 1995 children, aged 5 to 15 years, from a purposively selected rural area located about 100 km north-east of capital Dhaka. HBsAg (HBV surface antigen) and anti-HBc antibody were determined by ELISA method. Vitamin A (retinol) in blood was assayed by HPLC technique. The prevalence rates of HBsAg and anti-HBc antibody was determined by simple percentages. All associations between different characteristics were tested by Chi square test. Results: Of the total 1995 children, 988 (49.5%) and 1007 (50.5%) were male and female respectively. Among them, 23 (1.2%) were HBsAg positive or HBV carriers and 79 (8.1%) were anti-HBc antibody positive. Neither HBsAg nor anti-HBc antibody positivity rate showed any difference in male and female children. There was also no significant difference of HBsAg positivity rate amongst children of different age groups; whereas, anti-HBc antibody positivity rate increased significantly (p

Previous studies have demonstrated that eye-like images promote prosocial behavior and reduce antisocial behavior (watching-eyes effect). However, several recent reports of replication failure have called into question the replicability of the watching-eyes effect. It also remains unclear whether eye-like images promote prosocial tendencies or norm compliance. In this study, we attempted to replicate the watching-eyes effect on the behavioral intention of blood donation and examined the moderation effect of social norms in a high-powered pre-registered experiment. Participants were 1408 Japanese adults. A 2 × 2 (image: eye, control; norm: pro-donation, neutral) between-participants design was used. Participants first read an essay on either the importance of donating blood or a neutral topic. Then they reported their behavioral intention to donate blood while observing an eye-like or control image. The results showed non-significant effects of eye-like images and no interaction between eyes and norms. However, interestingly, our exploratory analysis suggests the possibility that the watching-eyes effect emerges only under specific contexts. We discuss the interpretations of the results and implications for future research.

ExteNET showed that neratinib, an irreversible pan-HER tyrosine ki- nase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved inva- sive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET.

When the etiology of pancreatitis cannot be determined despite sufficient investigation, recurrence and progression to chronic pancreatitis often involve genetic mutations. Herein, we describe a case of recurrent pancreatitis with the IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene that progressed to chronic pancreatitis in only 3 years. A 35-year-old man was referred to our hospital, where he was diagnosed with mild pancreatitis and was treated conservatively. However, the patient experienced recurrent episodes of pancreatitis, which progressed to become chronic pancreatitis with a pancreatic calcification 1 year later. After 3 years, the patient developed pancreatic duct stenosis and required a pancreatic duct stent placement. Regarding the cause of chronic pancreatitis, alcohol abuse was ruled out based on history taking. Considering the course of treatment, autoimmune pancreatitis and obstructive pancreatitis, such as pancreatic divisum, were also ruled out. Finally, a germline genetic test was performed to determine the etiology of pancreatitis, which revealed the IVS3+2T>C mutation in SPINK1. This case shows the importance of genetic testing in patients with idiopathic pancreatitis to determine their etiology and is a rare incident that can report the progression of the disease from acute to chronic pancreatitis.

Noroviruses (NoVs) are one of the major causes of acute viral gastroenteritis in humans. Virus-like particles (VLPs) without genomes that mimic the capsid structure of viruses are promising vaccine candidates for the prevention of NoVs infection. To produce large amounts of recombinant protein, including VLPs, the silkworm-expression vector system (silkworm-BEVS) is an efficient and powerful tool. In this study, we constructed a recombinant baculovirus that expresses VP1 protein, the major structural protein of NoV GII.4. Expression analysis showed that the baculovirus-infected silkworm pupae expressed NoV VP1 protein more efficiently than silkworm larval fat bodies. We obtained about 4.9 mg of purified NoV VP1 protein from only five silkworm pupae. The purified VP1 protein was confirmed by dynamic light scattering and electron microscopy to form VLPs of approximately 40 nm in diameter. Antisera from mice immunized with the antigen blocked NoV VLPs binding to histo-blood group antigens of pig gastric mucin and also blocked NoV infection in intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells. Our findings demonstrated that NoV VLP eliciting protective antibodies could be obtained in milligram quantities from a few silkworm pupae using the silkworm-BEVS.

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Resumen Introduccion y objetivos En la obtencion de imagenes de angiografia por cardiotomografia (ACT) es importante escoger una ubicacion adecuada para inyectar el medio de contraste (p. ej., el brazo o la pierna) a fin de evitar la formacion de artefactos que este provoca. En este estudio se comparan los valores de tomografia computarizada (TC) y las puntuaciones de visualizacion de las imagenes tridimensionales (3 D) de los lumenes de los vasos sanguineos del brazo y la pierna durante la ACT en pacientes neonatos y lactantes. Pacientes o materiales y metodos Entre los meses de enero de 2017 y enero de 2020 se evaluaron 253 pacientes de forma consecutiva para determinar su inclusion en el estudio. Se utilizaron las puntuaciones de propension estimadas en funcion de los datos demograficos, incluidos la edad, el peso corporal y la ubicacion de la inyeccion (lado derecho o izquierdo) en el brazo (n = 58) y la pierna (n = 58) de los pacientes neonatos y lactantes. A continuacion, se compararon los valores medios de TC de la arteria pulmonar, la aorta ascendente y la vena cava superior izquierda; las relaciones contraste-ruido (RCR); y las puntuaciones de visualizacion del brazo y la pierna como lugares de inyeccion. Resultados Los valores medios de TC durante la ACT para el brazo y la pierna fueron de 479,4 y 461,3 UH en la aorta ascendente, de 464,2 y 448,1 UH en la arteria pulmonar y de 232,8 y 220,1 UH en la vena cava superior izquierda, respectivamente. Los valores medios de ruido de la imagen (DE) y de RCR fueron, respectivamente, de 38,9 y 12,1 UH para el brazo y de 39,1 y 12,3 UH para la pierna. Las puntuaciones medias de visualizacion de la representacion del volumen de las imagenes 3 D fueron de 3,0 y 3,0 para los lugares de inyeccion del brazo y la pierna, respectivamente. No se observaron diferencias significativas en los valores medios de TC de la aorta ascendente, la arteria pulmonar y la vena cava superior izquierda; el valor de DE; la RCR; y las puntuaciones de visualizacion del brazo y la pierna. Conclusiones Los valores de TC del lumen de los vasos sanguineos y las puntuaciones de visualizacion de las imagenes 3 D observados durante la realizacion de una ACT en pacientes neonatos y lactantes con cardiopatias congenitas son los mismos, independientemente de si el lugar de inyeccion es el brazo o la pierna.

Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients.Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n = 58) and leg (n = 58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast-noise ratios (CNR); and visualization scores between the arm and leg as the injection locations.The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations.The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.