Local vaginal bioelectrical impedance can predict preterm delivery in mice.

Preterm birth is a serious pregnancy complication that affects neonatal mortality, morbidity, and long-term neurological prognosis. Predicting spontaneous preterm delivery (PTD) is important for its management. While excluding the risk of PTD is important, identifying women at high risk of PTD is imperative for medical intervention. Currently used PTD prediction parameters in clinical practice have shown high negative predictive values, but low positive predictive values. We focused on sulfated and sialylated glycocalyx changes in the uterus and vagina prior to the onset of parturition and explored the potential of electrophysiological detection of these changes as a PTD prediction parameter with a high positive predictive value. In vivo local vaginal bioelectrical impedance (VZ) was measured using two different mouse PTD models. PTD was induced in ICR mice through the subcutaneous injection of mifepristone or local intrauterine injection of lipopolysaccharide (LPS). The PTD rates were 100% and 60% post-administration of mifepristone (16-20 h, n = 4) and LPS (12-24 h, n = 20), respectively. The local VZ values (15 and 10 h after mifepristone or LPS treatment, respectively) were significantly lower in the PTD group than in the non-PTD group. Receiver operator characteristic (ROC) curve analysis of VZ at 125 kHz as a predictor of PTD showed an area under the ROC curve of 1.00 and 0.77 and positive predictive values of 1.00 and 0.86, for the mifepristone and LPS models, respectively, suggesting that local VZ value can predict PTD. Histological examination of the LPS-treated model 6 h post-treatment revealed increased expression of sulfomucins and/or sulfated proteoglycans and sialomucins in the cervical epithelium, cervical stroma and vaginal stroma. In conclusion, local VZ values can determine sulfated and sialylated glycocalyx alterations within the uterus and vagina and might be a useful PTD prediction parameter.

Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

Differentiating localized autoimmune pancreatitis and pancreatic ductal adenocarcinoma using endoscopic ultrasound images with deep learning.

Objectives: Localized autoimmune pancreatitis is difficult to differentiate from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. In recent years, deep learning methods have improved the diagnosis of diseases. Hence, we developed a special cross-validation framework to search for effective methodologies of deep learning in distinguishing autoimmune pancreatitis from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. Methods: Data from 24 patients diagnosed with localized autoimmune pancreatitis (8751 images) and 61 patients diagnosed with pancreatic ductal adenocarcinoma (20,584 images) were collected from 2016 to 2022. We applied transfer learning to a convolutional neural network called ResNet152, together with our innovative imaging method contributing to data augmentation and temporal data process. We divided patients into five groups according to different factors for 5-fold cross-validation, where the ordered and balanced datasets were created for the performance evaluations. Results: ResNet152 surpassed the endoscopists in all evaluation metrics with almost all datasets. Interestingly, when the dataset is balanced according to the factor of the endoscopists' diagnostic accuracy, the area under the receiver operating characteristic curve and accuracy were highest at 0.85 and 0.80, respectively. Conclusions: It is deduced that image features useful for ResNet152 correlate with those used by endoscopists for their diagnoses. This finding may contribute to sample-efficient dataset preparation to train convolutional neural networks for endoscopic ultrasonography-imaging diagnosis.

Clinical significance of CDT1 mRNA expression in chronic hepatitis C or liver cirrhosis.

We have previously reported that chromatin licensing and DNA replication factor 1 (CDT1) is associated with the postoperative recurrence of hepatocellular carcinoma (HCC). Based on this fact, we verified whether CDT1 mRNA expression is also associated with HCC development from chronic hepatitis C (CHC) and liver cirrhosis (LC). There were 142 cases with CHC or LC who underwent liver biopsy. Detection of CDT1 mRNA in liver was performed by RT-qPCR using frozen liver biopsy tissues. We examined the association between the CDT1 mRNA expression and clinical conditions and long-term outcome. We then examined the association between serum cytokine/chemokine levels and CDT1 mRNA expression in 58 cases. The cumulative incidence rates of HCC development in cases with CDT1 mRNA in the low expression group showed significantly lower than those in the high expression group (p = 0.0391). A significant correlation was found between CDT1 mRNA expression and the extent of proliferation of atypical hepatocytes in hematoxylin and eosin-stained sections (p<0.0001). CDT1 mRNA expression has been associated with cytokines involved in tumorigenesis in experimental and human cancers. We found that cases with high CDT1 mRNA expression were at risk for developing HCC, even if they were CHC or LC.

Stabilization of adalimumab Fab through the introduction of disulfide bonds between the variable and constant domains.

Fab is a promising format for antibody drug. Therefore, efforts have been made to improve its thermal stability for therapeutic and commercial use. So far, we have attempted to introduce a disulfide bond into the Fab fragment to improve its thermal stability and demonstrated that it is possible to do this without sacrificing its biochemical function. In this study, to develop a novel stabilization strategy for Fab, we attempted to introduce a disulfide bond between the variable and constant domains and prepared three variants of Fab; H:G10C + H:P210C, L:P40C + L:E165C, and H:G10C + H:P210C + L:P40C + L:E165C. Differential scanning calorimetry measurements showed that each of these variants had improved thermal stability. In addition, the variants with two disulfide bonds demonstrated a 6.5 °C increase in their denaturation temperatures compared to wild-type Fab. The introduction of disulfide bonds was confirmed by X-ray crystallography, and the variants retained their antigen-binding activity. The variants were also found to be less aggregative than the wild type. Our results demonstrate that the introduction of a disulfide bond between the variable and constant domains significantly improves the thermal stability of Fab.

In Situ TEM/STEM Investigation of Crystallization in Y3Al5O12:Ce at High Temperatures Inside a Transmission Electron Microscope.

Y3Al5O12:Ce (YAG:Ce) phosphors are extensively used in the field of white light-emitting diodes (LEDs) due to their efficient luminescent properties. To optimize the performance of YAG:Ce phosphors, a comprehensive understanding of their synthesis and structural evolution is essential. This paper presents a direct in situ transmission electron microscopy (TEM) /scanning TEM (STEM) investigation on the transformation process of a precursor comprising nanocrystalline CeO2 dispersed in an amorphous Y-Al oxide matrix into crystalline YAG:Ce particles. The study reveals that nanocrystalline CeO2 particles dissolve completely in the Y-Al oxide matrix at a temperature above 900 °C, while YAlO3 (YAP)-type crystalline particles with Al2O3 phase in grain boundaries are observed above 1000 °C. Finally, YAG:Ce-type crystalline particles are formed above 1180 °C. Atomic-resolution energy-dispersive X-ray spectroscopy (EDS) elemental mapping demonstrates that the doped cerium (Ce) atoms occupy the same atomic sites as yttrium (Y). Photoluminescence measurements validate the efficient luminescent properties of the obtained YAG:Ce phosphor.