Long-term outcome of ultrasound-guided focused ultrasound ablation for gestational trophoblastic neoplasia in the cesarean scar: a case report.

BACKGROUND: The treatment of gestational trophoblastic neoplasia (GTN) is one of the success stories in medical oncology. GTN in the cesarean scar is a rare entity, but most cases need to be treated with hysterectomy or localized uterine lesion resection because of chemoresistant lesions and/or massive bleeding. We present a patient with post-molar GTN in the cesarean scar who was non-invasively treated with ultrasound-guided high intensity focused ultrasound (HIFU) to preserve the uterus and fertility. CASE PRESENTATION: A 32-year-old woman was diagnosed with low-risk GTN (FIGO Stage I: 2 prognostic score) after partial hydatidiform mole. The 5th cycle of chemotherapy was interrupted because of persistent hepatic toxicity and impaired ovarian reserve function. However, the uterine lesion persisted (diameter of residual uterine lesion in the cesarean scar: 2.0 cm). Therefore, ultrasound-guided HIFU treatment was performed. A significant gray-scale change was observed during the HIFU treatment. Color Doppler ultrasonography and contrast-enhanced ultrasound (CEUS) was performed to evaluate the ablation effectiveness. Color Doppler ultrasonography showed disappearance of the signal of vascularity and CEUS showed no perfusion in the lesion located in the cesarean scar. The uterine lesion was obviously shrunken one month after HIFU treatment. Menstrual cycle resumed 48 days after HIFU. HIFU treatment decreased the number of chemotherapy cycles and there was complete disappearance of the GTN lesion at 4-month follow-up. The patient has shown no signs of recurrence as of 58-month follow-up. CONCLUSION: Ultrasound-guided HIFU may be a useful alternative to lesion resection for GTN in the cesarean scar in patients who show chemoresistance or are not suitable for chemotherapy. It has the potential to ablate the residual uterine lesion noninvasively to preserve the uterus and fertility, avoiding perioperative risks of lesion resection, especially acute bleeding.

A systematic survey of advances in retinal imaging modalities for Alzheimer's disease diagnosis.

Recent advances in retinal imaging pathophysiology have shown a new function for biomarkers in Alzheimer's disease diagnosis and prognosis. The significant improvements in Optical coherence tomography (OCT) retinal imaging have led to significant clinical translation, particularly in Alzheimer's disease detection. This systematic review will provide a comprehensive overview of retinal imaging in clinical applications, with a special focus on biomarker analysis for use in Alzheimer's disease detection. Articles on OCT retinal imaging in Alzheimer's disease diagnosis were identified in PubMed, Google Scholar, IEEE Xplore, and Research Gate databases until March 2021. Those studies using simultaneous retinal imaging acquisition were chosen, while those using sequential techniques were rejected. "Alzheimer's disease" and "Dementia" were searched alone and in combination with "OCT" and "retinal imaging". Approximately 1000 publications were searched, and after deleting duplicate articles, 145 relevant studies focused on the diagnosis of Alzheimer's disease utilizing retinal imaging were chosen for study. OCT has recently been demonstrated to be a valuable technique in clinical practice as according to this survey, 57% of the researchers employed optical coherence tomography, 19% used ocular fundus imaging, 13% used scanning laser ophthalmoscopy, and 11% have used multimodal imaging to diagnose Alzheimer disease. Retinal imaging has become an important diagnostic technique for Alzheimer's disease. Given the scarcity of available literature, it is clear that future prospective trials involving larger and more homogeneous groups are necessary, and the work can be expanded by evaluating its significance utilizing a machine-learning platform rather than simply using statistical methodologies.

Biomarkers for Alzheimer's Disease in the Current State: A Narrative Review.

Alzheimer's disease (AD) has become a problem, owing to its high prevalence in an aging society with no treatment available after onset. However, early diagnosis is essential for preventive intervention to delay disease onset due to its slow progression. The current AD diagnostic methods are typically invasive and expensive, limiting their potential for widespread use. Thus, the development of biomarkers in available biofluids, such as blood, urine, and saliva, which enables low or non-invasive, reasonable, and objective evaluation of AD status, is an urgent task. Here, we reviewed studies that examined biomarker candidates for the early detection of AD. Some of the candidates showed potential biomarkers, but further validation studies are needed. We also reviewed studies for non-invasive biomarkers of AD. Given the complexity of the AD continuum, multiple biomarkers with machine-learning-classification methods have been recently used to enhance diagnostic accuracy and characterize individual AD phenotypes. Artificial intelligence and new body fluid-based biomarkers, in combination with other risk factors, will provide a novel solution that may revolutionize the early diagnosis of AD.

Microarray is an efficient tool for circRNA profiling.

Circular RNAs (circRNAs) are emerging as a new class of endogenous and regulatory noncoding RNAs in latest years. With the widespread application of RNA sequencing (RNA-seq) technology and bioinformatics prediction, large numbers of circRNAs have been identified. However, at present, we lack a comprehensive characterization of all these circRNAs in interested samples. In this study, we integrated 87 935 circRNAs sequences that cover most of circRNAs identified till now represented in circBase to design microarray probes targeting back-splice site of each circRNA to profile expression of those circRNAs. By comparing the circRNA detection efficiency of RNA-seq with this circRNA microarray, we revealed that microarray is more efficient than RNA-seq for circRNA profiling. Then, we found ∼80 000 circRNAs were expressed in cervical tumors and matched normal tissues, and ∼25 000 of them were differently expressed. Notably, many of these circRNAs detected by this microarray can be validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or RNA-seq. Strikingly, as many as ∼18 000 circRNAs could be robustly detected in cell-free plasma samples, and the expression of ∼2700 of them differed after surgery for tumor removal. Our findings provided a comprehensive and genome-wide characterization of circRNAs in paired normal tissues and tumors and plasma samples from multiple individuals. In addition, we also provide a rich resource with 41 microarray data sets and 10 RNA-seq data sets and strong evidences for circRNA expression in cervical cancer. In conclusion, circRNAs could be efficiently profiled by circRNA microarray to target their reported back-splice sites in interested samples.

Ultrasonography to detect cardiovascular damage in children with essential hypertension.

BACKGROUND: Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. METHODS: All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid-femoral pulse wave velocity (cfPWV), intimal-medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. RESULTS: The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E' among three groups. CONCLUSION: Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Analysis of IV Drugs in the Hospital Workflow by Raman Spectroscopy: The Case of Piperacillin and Tazobactam.

Medical errors associated with IV preparation and administration procedures in a hospital workflow can even cost human lives due to the direct effect they have on patients. A large number of such incidents, which have been reported in bibliography up to date, indicate the urgent need for their prevention. This study aims at proposing an analytical methodology for identifying and quantifying IV drugs before their administration, which has the potential to be fully harmonized with clinical practices. More specifically, it reports on the analysis of a piperacillin (PIP) and tazobactam (TAZ) IV formulation, using Raman spectroscopy. The simultaneous analysis of the two APIs in the same formulation was performed in three stages: before reconstitution in the form of powder without removing the substance out of the commercial glass bottle (non-invasively), directly after reconstitution in the same way, and just before administration, either the liquid drug is placed in the infusion set (on-line analysis) or a minimal amount of it is transferred from the IV bag to a Raman optic cell (at-line analysis). Except for the successful identification of the APIs in all cases, their quantification was also achieved through calibration curves with correlation coefficients ranging from 0.953 to 0.999 for PIP and from 0.965 to 0.997 for TAZ. In any case, the whole procedure does not need more than 10 min to be completed. The current methodology, based on Raman spectroscopy, outweighs other spectroscopic (UV/Vis, FT-IR/ATR) or chromatographic (HPLC, UHPLC) protocols, already applied, which are invasive, costly, time-consuming, not environmentally friendly, and require specialized staff and more complex sample preparation procedures, thus exposing the staff to hazardous materials, especially in cases of cytotoxic drugs. Such an approach has the potential to bridge the gap between experimental setup and clinical implementation through exploitation of already developed handheld devices, along with the presence of digital spectral libraries.

Metadata information and fundus image fusion neural network for hyperuricemia classification in diabetes.

OBJECTIVE: In diabetes mellitus patients, hyperuricemia may lead to the development of diabetic complications, including macrovascular and microvascular dysfunction. However, the level of blood uric acid in diabetic patients is obtained by sampling peripheral blood from the patient, which is an invasive procedure and not conducive to routine monitoring. Therefore, we developed deep learning algorithm to detect noninvasively hyperuricemia from retina photographs and metadata of patients with diabetes and evaluated performance in multiethnic populations and different subgroups. MATERIALS AND METHODS: To achieve the task of non-invasive detection of hyperuricemia in diabetic patients, given that blood uric acid metabolism is directly related to estimated glomerular filtration rate(eGFR), we first performed a regression task for eGFR value before the classification task for hyperuricemia and reintroduced the eGFR regression values into the baseline information. We trained 3 deep learning models: (1) metadata model adjusted for sex, age, body mass index, duration of diabetes, HbA1c, systolic blood pressure, diastolic blood pressure; (2) image model based on fundus photographs; (3)hybrid model combining image and metadata model. Data from the Shanghai General Hospital Diabetes Management Center (ShDMC) were used to develop (6091 participants with diabetes) and internally validated (using 5-fold cross-validation) the models. External testing was performed on an independent dataset (UK Biobank dataset) consisting of 9327 participants with diabetes. RESULTS: For the regression task of eGFR, in ShDMC dataset, the coefficient of determination (R2) was 0.684±0.07 (95 % CI) for image model, 0.501±0.04 for metadata model, and 0.727±0.002 for hybrid model. In external UK Biobank dataset, a coefficient of determination (R2) was 0.647±0.06 for image model, 0.627±0.03 for metadata model, and 0.697±0.07 for hybrid model. Our method was demonstrably superior to previous methods. For the classification of hyperuricemia, in ShDMC validation, the area, under the curve (AUC) was 0.86±0.013for image model, 0.86±0.013 for metadata model, and 0.92±0.026 for hybrid model. Estimates with UK biobank were 0.82±0.017 for image model, 0.79±0.024 for metadata model, and 0.89±0.032 for hybrid model. CONCLUSION: There is a potential deep learning algorithm using fundus photographs as a noninvasively screening adjunct for hyperuricemia among individuals with diabetes. Meanwhile, combining patient's metadata enables higher screening accuracy. After applying the visualization tool, it found that the deep learning network for the identification of hyperuricemia mainly focuses on the fundus optic disc region.

Non-invasive evaluation of endometrial microvessels via in vivo intrauterine photoacoustic endoscopy.

The endometrium microvessel system, responsible for supplying oxygen and nutrients to the embryo, holds significant importance in evaluating endometrial receptivity (ER). Visualizing this system directly can significantly enhance ER evaluation. Currently, clinical methods like Narrow-band hysteroscopy and Color Doppler ultrasound are commonly used for uterine blood vessel examination, but they have limitations in depth or resolution. Endoscopic Photoacoustic Imaging (PAE) has proven effective in visualizing microvessels in the digestive tract, while its adaptation to uterine imaging faces challenges due to the uterus's unique physiological characteristics. This paper for the first time that uses high-resolution PAE in vivo to capture a comprehensive network of endometrial microvessels non-invasively. Followed by continuous observation and quantitative analysis in the endometrial injury model, we further corroborated that PAE detection of endometrial microvessels stands as a valuable indicator for evaluating ER. The PAE system showcases its promising potential for integration into reproductive health assessments.

Near-Native Imaging of Label-Free Silver Nanoparticles-Triggered 3D Subcellular Ultrastructural Reorganization in Microalgae.

Understanding the spatial orientation of nanoparticles and the corresponding subcellular architecture events favors uncovering fundamental toxic mechanisms and predicting response pathways of organisms toward environmental stressors. Herein, we map the spatial location of label-free citrate-coated Ag nanoparticles (Cit-AgNPs) and the corresponding subcellular reorganization in microalgae by a noninvasive 3D imaging approach, cryo-soft X-ray tomography (cryo-SXT). Cryo-SXT near-natively displays the 3D maps of Cit-AgNPs presenting in rarely identified sites, namely, extracellular polymeric substances (EPS) and the cytoplasm. By comparative 3D morphological assay, we observe that Cit-AgNPs disrupt the cellular ultrastructural homeostasis, triggering a severe malformation of cytoplasmic organelles with energy-producing and stress-regulating functions. AgNPs exposure causes evident disruption of the chloroplast membrane, significant attenuation of the pyrenoid matrix and starch sheath, extreme swelling of starch granules and lipid droplets, and shrinkage of the nucleolus. In accompaniment, the number and volume occupancy of starch granules are significantly increased. Meanwhile, the spatial topology of starch granules extends from the chloroplast to the cytoplasm with a dispersed distribution. Linking the dynamics of the internal structure and the alteration of physiological properties, we derive a comprehensive cytotoxic and response pathway of microalgae exposed to AgNPs. This work provides a perspective for assessing the toxicity at subcellular scales to achieve label-free nanoparticle-caused ultrastructure remodeling of phytoplankton.

Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases.

AIM: Steatosis is a common histological feature of chronic liver disease, especially alcoholic and non-alcoholic fatty liver disease, as well as chronic hepatitis C. A recent study showed that evaluating the controlled attenuation parameter (CAP) with transient elastography was an efficient way of non-invasively determining the severity of hepatic steatosis. The objective of this study was to prospectively evaluate the utility of CAP for diagnosing steatosis in patients with chronic liver disease. METHODS: One hundred and fifty-five consecutive patients with suspected chronic liver disease underwent steatosis diagnosis using CAP, blood sample analyses, computed tomography for assessing the liver/spleen ratio and liver biopsy. Steatosis was graded according to the percentage of fat-containing hepatocytes: S0, less than 5%; S1, 5-33%; S2, 34-66%; and S3: more than 66%. RESULTS: The CAP was significantly correlated with steatosis grade, and there were significant differences between the CAP value of the S0 patients and those of the patients with other grades of steatosis. S0 and S1-3 hepatic steatosis were considered to represent mild and significant steatosis, respectively. The CAP values of the patients with mild and significant steatosis were significantly different (P < 0.0001). The area under the receiver-operator curve (AUROC) value of the CAP for diagnosing significant steatosis was 0.878 (95% confidence interval, 0.818-0.939), and the optimal CAP cut-off value for detecting significant steatosis was 232.5 db/m. In multivariate analysis, the CAP (P = 0.0002) and the liver to spleen ratio (P = 0.004) were found to be significantly associated with significant steatosis. CONCLUSION: The CAP is a promising tool for rapidly and non-invasively diagnosing steatosis.

The Feasibility of Targeted Magnetic Iron Oxide Nanoagent for Noninvasive IgA Nephropathy Diagnosis.

IgA nephropathy is the most common glomerular disease in the world and has become a serious threat to human health. Accurate and non-invasive molecular imaging to detect and recognize the IgA nephropathy is critical for the subsequent timely treatment; otherwise, it may progress to end-stage renal disease and lead to glomerular dysfunction. In this study, we have developed a sensitive, specific, and biocompatible integrin αvß3-targeted superparamagnetic Fe3O4 nanoparticles (NPs) for the noninvasive magnetic resonance imaging (MRI) of integrin αvß3, which is overexpressed in glomerular mesangial region of IgA nephropathy. The rat model of IgA nephropathy was successfully established and verified by biochemical tests and histological staining. Meanwhile, the clinical 18F-AlF-NOTA-PRGD2 probe molecule was utilized to visualize and further confirmed the IgA nephropathy in vivo via positron emission computed tomography. Subsequently, the Fe3O4 NPs were conjugated with arginine-glycine-aspartic acid (RGD) molecules (Fe3O4-RGD), and their integrin αvß3-targeted T2-weighted imaging (T2WI) potential has been carefully evaluated. The Fe3O4-RGD demonstrated great relaxation in vivo. The T2WI signal of renal layers in the targeted group at 3 h after intravenous injection of Fe3O4-RGD was distinctly lower than baseline, indicating MRI signal decreased in the established IgA nephropathy rat model. Moreover, the TEM characterization and Prussian blue staining confirmed that the Fe3O4-RGD was located at the region of glomerulus and tubular interstitium. Moreover, no obvious signal decreased was detected in the untargeted Fe3O4 treated and normal groups. Collectively, our results establish the possibility of Fe3O4-RGD serving as a feasible MRI agent for the noninvasive diagnosis of IgA nephropathy.

A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by 18F-positron emitting tomography and fluorescence.

PURPOSE: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). METHODS: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [18F]-IR783-AMBF3. [18F]-IR783-AMBF3 was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. RESULTS: IR783-AMBF3 was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF3 (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF3 was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF3 was safe under the tested dosage both in vitro and in vivo. CONCLUSION: The superior imaging properties of IR783-AMBF3 could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.

Synthesis and characterization of fluorescein-grafted polyurethane for potential application in biomedical tracing.

Redesigned multifunctional biopolymers represent a novel building bridge for interdisciplinary collaborations in biomaterials development. We prepared fluorescein-grafted polyurethane scaffolds (PU-C1, PU-C5, and PU-B1) to meet both clinical needs and biological safety evaluations, using different contents of calcein and different synthesis procedures for potential biomedical tracing. X-ray diffraction, infrared, X-ray photoelectron spectroscopy, nuclear magnetic resonance, scanning electron microscopy, and light microscopy were used to analyze the composition and structure of polyurethanes, as well as to observe their morphology with and without biomarkers. Fluorescence spectrophotometer and fluorescence microscopy were used to detect the fluorescence characteristics. The results showed that the grafting of calcein significantly affected the chemical structure and fluorescence sensitivities of copolymers. When compared to calcein, which was added before synthesis (PU-C1), the marker that was added during the extender process (PU-B1) presented higher fluorescence efficiency. Both PU-C5 and PU-B1 exhibited strong fluorescent response and good cytocompatibility in vitro and in vivo, with no interference from the autofluorescence of tissues after 4 weeks of implantation. The fluorescence-marked material can be used to continuously and noninvasively monitor the dynamic changes in polymers, which provides a way to clearly trace the material or to distinguish between the material and tissue in vivo.