Estimation of the rupture point of the craniovertebral junction intradural arteriovenous fistula with vessel wall magnetic resonance image and its pathological findings: A case report.

Background: Arteriovenous fistulas (AVFs) of the craniocervical junction (CCJ) and intradural AVFs are often associated with aneurysms and varics, and it is sometimes difficult to identify the ruptured point on radiological images. We report a case in which vessel wall magnetic resonance image (VW-MRI) was useful for identifying the ruptured point at the CCJ AVF. Case Description: A 70-year-old man presented with a sudden onset of headache. He had Glasgow Coma Scale E4V5M6, world federation of neurosurgical societies (WFNS) Grade I. Fisher group 3 subarachnoid hemorrhage and hydrocephalus were found on head computed tomography. Cerebral angiography showed a spinal AVF at the C1 level of the cervical spine. Magnetic resonance image-enhanced motion sensitized driven equilibrium (MSDE-method showed an enhancing effect in part of the AVF draining vein, but the vascular architecture of this lesion was indeterminate. We performed continuous ventricular drainage for acute hydrocephalus and antihypertensive treatment. Cerebral angiography was performed 30days after the onset of the disease, and was revealed an aneurysmal structure in a portion of the AVF draining vein, which VW-MRI initially enhanced. On the 38th day after onset, he underwent direct surgery to occlude the AV fistula and dissect the aneurysmal structure. Histopathology showed that the aneurysmal structure was varices with lymphocytic infiltration, and hemosiderin deposition was observed near the varices. Conclusion: Recently, VW-MRI has been reported to show an association between the enhancement of varices in dural AVF and rupture cases. VW-MRI, especially the enhanced MSDE method, may be useful in estimating the ruptured point in arteriovenous shunt disease.

Evaluation of co-speech gestures grounded in word-distributed representation.

The condition for artificial agents to possess perceivable intentions can be considered that they have resolved a form of the symbol grounding problem. Here, the symbol grounding is considered an achievement of the state where the language used by the agent is endowed with some quantitative meaning extracted from the physical world. To achieve this type of symbol grounding, we adopt a method for characterizing robot gestures with quantitative meaning calculated from word-distributed representations constructed from a large corpus of text. In this method, a "size image" of a word is generated by defining an axis (index) that discriminates the "size" of the word in the word-distributed vector space. The generated size images are converted into gestures generated by a physical artificial agent (robot). The robot's gesture can be set to reflect either the size of the word in terms of the amount of movement or in terms of its posture. To examine the perception of communicative intention in the robot that performs the gestures generated as described above, the authors examine human ratings on "the naturalness" obtained through an online survey, yielding results that partially validate our proposed method. Based on the results, the authors argue for the possibility of developing advanced artifacts that achieve human-like symbolic grounding.

A Japanese Boy With Spotted Fever and Overlapping Symptoms of Kawasaki Disease: A Case Report.

Japanese spotted fever (JSF) is a tick-transmitted infection caused by Rickettsia japonica (R. japonica), which is indigenous to Japan. Patients with JSF typically present with fever and spotted erythema on the palms and/or soles, and most of them have site(s) of tick bites. The prognosis is good, but some cases have a fatal course. Kawasaki disease (KD) is a systemic vasculitis with an unknown cause that is characterized by symptoms such as fever, conjunctival injection, oral findings, amorphous rash, rigid edema, and nonsuppurative cervical lymphadenopathy. Although the symptoms of JSF are partially similar to those of KD, case reports of JSF overlapping KD have never been internationally published. Herein, we report a boy with JSF and KD symptoms. A five-year-old boy presented with fever and rash after he had been on a mountain inhabited by R. japonica. On the fifth day, erythema was spotted mainly on his bilateral palms, bilateral cervical lymphadenopathy, rigid edema of his lower feet, and mild conjunctival injection appeared. Intravenous immunoglobulin (IVIG) therapy was performed because these symptoms satisfied five out of the six diagnostic criteria for KD. However, on the sixth day, the fever persisted, and then we readministered IVIG in addition to tosufloxacin and azithromycin since we found a tick-bite eschar, which suggested a complication of JSF. His symptoms resolved soon after this treatment. Coronary artery lesions were never observed. This case indicates that the R. japonica infection overlaps clinically with KD. Tosufloxacin and azithromycin should be considered to avoid the use of minocycline in younger patients with JSF.

Intracranial parenchymal capillary hemangioma: A case report.

Background: Capillary hemangioma is a rare benign hemangioma that occurs in the soft tissues of the skin, orbit, head, and neck. Intracranial cases, especially intraparenchymal cases, are extremely rare. In this study, we report the course of an intracranial parenchymal capillary hemangioma with left mild motor paresis and involuntary movements of the left upper extremity and was successfully treated by surgical resection, including radiological and pathological examinations. Case Description: This is a case of a 60-year-old woman who presented with motor weakness and involuntary movement of the left upper extremity. Computed tomography and magnetic resonance imaging revealed the right frontal hemorrhagic mass lesion without enhancement of contrast medium. Cerebral digital subtraction angiography showed no vascular stain and abnormal arteriovenous shunt. Preoperatively, we diagnosed cavernous hemangioma with a hemorrhagic component located in the right motor cortex. Because this case was symptomatic, we performed a craniotomy and gross total resection of the right frontal lesion. The diagnosis of capillary hemangioma was made by histological examination, including immunohistological study. Conclusion: Because intraparenchymal capillary hemangiomas are difficult to diagnose with preoperative imaging, surgical treatment, and histopathological examination are important.

Prealbumin level is a predictor of activities of daily living at discharge in older patients with heart failure who became ADL-independent after hospitalization: - Acute and early recovery cardiac rehabilitation trials.

Chiba T, Yokota J, Takahashi R, Sasaki K, Suzuki H. Prealbumin level is a predictor of activities of daily living at discharge in older patients with heart failure who became ADL-independent after hospitalization - Acute and early recovery cardiac rehabilitation trials. Jpn J Compr Rehabil Sci 2023; 14: 69-77. Objective: To determine the relationship between prealbumin level and activities of daily living (ADL) at discharge in patients with heart failure (HF) and assess the usefulness of prealbumin measurement in predicting discharge Barthel Index (BI) in older patients with HF who become non-independent in ADL after hospital admission. Methods: Patients with HF, aged ≥75 years, who were admitted to an acute hospital and underwent acute and early recovery cardiac rehabilitation (CR) were studied retrospectively. The exclusion criteria were non-independent ADL before admission (BI < 85 points) and independent ADL at the start of CR (BI ≥ 85 points). The usefulness of prealbumin level in predicting discharge BI was compared between four models. Albumin and Controlling Nutritional Status (CONUT) were used as comparison variables. The models and independent variables were model 1 (covariates only), model 2 (prealbumin + covariates), model 3 (albumin + covariates), and model 4 (CONUT score + covariates). Adjusted R2, a measure of model fit, was used to compare predictive ability. Results: A total of 152 patients were included in the analysis. Prealbumin level was a significant variable for BI at discharge but not albumin or CONUT. The adjusted R2 was higher in model 2 with the addition of prealbumin than that in model 1 (0.362 vs. 0.347). Conclusion: Prealbumin levels are useful in predicting discharge BI in older patients with HF who become non-independent in ADL after hospitalization.

Survival and medical costs of non-small cell lung cancer patients according to the first-line treatment: An observational study using the Kyoto City Integrated Database.

BACKGROUND: Lung cancer is the primary cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases. New drug treatments have been developed since 2010 but there are concerns about the increase in medical costs. This study aimed to compare survival and medical costs among patients with NSCLC according to their initial treatment to estimate the impact of early NSCLC detection. METHODS: Patients with primary NSCLC who filed insurance claims between April 2013 and March 2019 were identified using the Kyoto City Integrated Database. Patients were divided into two groups depending on their initial treatment: the resection group and drug or radiation group. The survival and medical costs were calculated. RESULTS: A total of 2609 patients with primary NSCLC were identified. Among them, 1035 patients underwent resection. The 5-year survival was 75% for the resection group while below 25% for the drug or radiation group. At 6 months of survival, the median cumulative total cost was 2409 thousand yen (interquartile range [IQR] 1947-4012 thousand yen) in the resection group and 2951 thousand yen (IQR 1600-4706 thousand yen) in the drug or radiation group. At 4 years of survival, the cumulative median total cost was 5257 thousand yen (IQR 3808-8243 thousand yen) in the resection group and 10 202 thousand yen (IQR 4845-20 450 thousand yen) in the drug or radiation group. CONCLUSIONS: As a first-line therapy in newly diagnosed patients with NSCLC, surgical resection is associated with longer survival and lower medical costs than pharmacotherapy or radiotherapy.

Remote cognitive behavioral therapy for older adults with anxiety symptoms: A systematic review and meta-analysis.

INTRODUCTION: In-person cognitive behavioral therapy (CBT) can reduce self-reported anxiety in older adults. However, studies are limited for remote CBT. We assessed the effectiveness of remote CBT in mitigating self-reported anxiety in older adults. METHODS: We conducted a systematic review and meta-analysis based on a literature search of PubMed, Embase, PsycInfo, and Cochrane databases up to March 31, 2021, for randomized controlled clinical trials comparing the effectiveness of remote CBT versus non-CBT controls on mitigating self-reported anxiety in older adults. We calculated within-group pre-to-post-treatment standardized mean difference using Cohen's d, obtained the difference between a remote CBT group and a non-CBT control group as our effect size for cross-study comparison, and conducted a random-effects meta-analysis. Changes in scores on self-reported anxiety symptoms (Generalized Anxiety Disorder-7 item Scale, Penn State Worry Questionnaire, or Penn State Worry Questionnaire - Abbreviated), and self-reported depressive symptoms (Patient Health Questionnaire-9 item Scale or Beck Depression Inventory) were primary and secondary outcomes, respectively. RESULTS: Six eligible studies, containing 633 participants with a pooled mean age of 66.6 years, were included in the systematic review and meta-analysis. There was a significant mitigating effect of intervention on self-reported anxiety, favoring remote CBT over non-CBT controls (between-group effect size: -0.63; 95% CI: -0.99 to -0.28). We also found a significant mitigating effect of intervention on self-reported depressive symptoms (between-group effect size: -0.74; 95% CI: -1.24 to -0.25). DISCUSSION: Remote CBT is more effective in reducing self-reported anxiety and depressive symptoms than non-CBT control in older adults.

Dysphagia is an independent predictor of hospital-acquired disability in older patients with heart failure: a propensity score-matched analysis : Predictors of HAD in older HF patients.

This study aims to identify the relationship between dysphagia and developing hospital-acquired disability (HAD) in older patients with heart failure (HF). This single-center retrospective cohort study included 360 patients (median age, 84 years: 58.1% female, 41.9% male) who had undergone rehabilitation and were aged 65 years and older. Patients were divided into dysphagia and non-dysphagia groups and compared based on the Functional Oral Intake Scale score. HAD was defined as a decline in the Barthel Index score (indication of daily activity levels) at discharge relative to that before admission. The relationship between dysphagia and HAD was analyzed using bivariate analysis after adjusting for age, sex, body mass index, medical history, clinical and laboratory data, short physical performance battery (SPPB), and cognitive function at the start of rehabilitation, using propensity score matching. HAD was observed in 38.1% of the patients. Patients with dysphagia were significantly older, and had lower body mass index and physical and cognitive function than those without. After propensity score matching, the prevalence of HAD was significantly higher in the dysphagia group than in the non-dysphagia group (61.9% vs. 42.9%, P = 0.032). Dysphagia at the start of rehabilitation was an independent predictor of HAD. The results of this study may contribute to risk stratification of HAD.

Physical performance and maximum tongue pressure associated with oral intake independence: a retrospective study on hospitalized patients with heart failure.

Dysphagia in patients with heart failure leads to poorer outcomes during hospitalization and after discharge. Therefore, addressing dysphagia is critical for improving patient prognosis. This retrospective observational study aimed to evaluate associations between improvements in swallowing dysfunction at the time of hospital discharge and the physical function, cognitive function, nutritional status, and maximum tongue pressure (MTP). Overall, 111 patients who underwent cardiac rehabilitation and were deemed to have oral intake impairment were included. The exclusion criteria comprised the following: pre-admission diagnosis of dysphagia, in-hospital death, and missing data. Patients were categorized based on whether they did (n = 65) or did not (n = 46) exhibit improvements in oral intake impairment, which were determined from the functional oral intake scale (FOIS) score at discharge. Associations between potential explanatory variables and the FOIS score at discharge were assessed using a linear regression model. After adjusting for covariates, such as age, sex, heart failure severity, short physical performance battery score, Mini-Mental State Examination score, transthyretin level, and provision of swallowing therapy, the FOIS score at discharge was significantly associated with the MTP (P = 0.024, confidence interval: 0.006-0.046). In conclusion, the MTP was independently associated with improvements in FOIS in patients with heart failure.

mRNA-Loaded Lipid Nanoparticles Targeting Dendritic Cells for Cancer Immunotherapy.

Dendritic cells (DCs) are attractive antigen-presenting cells to be targeted for vaccinations. However, the systemic delivery of mRNA to DCs is hampered by technical challenges. We recently reported that it is possible to regulate the size of RNA-loaded lipid nanoparticles (LNPs) to over 200 nm with the addition of salt during their formation when a microfluidic device is used and that larger LNPs delivered RNA more efficiently and in greater numbers to splenic DCs compared to the smaller counterparts. In this study, we report on the in vivo optimization of mRNA-loaded LNPs for use in vaccines. The screening included a wide range of methods for controlling particle size in addition to the selection of an appropriate lipid type and its composition. The results showed a clear correlation between particle size, uptake and gene expression activity in splenic DCs and indicated that a size range from 200 to 500 nm is appropriate for use in targeting splenic DCs. It was also found that it was difficult to predict the transgene expression activity and the potency of mRNA vaccines in splenic DCs using the whole spleen. A-11-LNP, which was found to be the optimal formulation, induced better transgene expression activity and maturation in DCs and induced clear therapeutic antitumor effects in an E.G7-OVA tumor model compared to two clinically relevant LNP formulations.

Temporal Trend in an Initial Treatment, Survival, and Medical Costs Among Patients With Lung Cancer Between 2013 and 2018 in Kyoto City, Japan.

OBJECTIVES: This study aimed to identify the variation of treatment contents and outcomes and economic burden of lung cancer among the elderly population in Japan. METHODS: New-onset primary lung cancer from April 2013 to March 2019 were identified by using the Kyoto City administrative database for National Health Insurance and Advanced Elderly Medical Service System. Patient characteristics, initial treatment, medical costs, and deaths were analyzed. Continuous variables were calculated using standard descriptive statistical methods. RESULTS: A total of 4845 people who were diagnosed as having lung cancer and received any treatment between 2013 and 2018 were included in the study. The average age of patients was 73 to 74 years for a 6-year study period. The proportion of patients who received surgery, drug therapy, and radiation therapy as initial treatment was 31% to 42%, 36% to 44%, and 21% to 24%, respectively. Healthcare costs increased between fiscal year (FY) 2014 and FY 2018, with a particularly significant increase of 340 million for drug therapy, whereas the mortality rate in <2-year follow-up decreased from 42.7% in FY 2013 to 368% in FY 2016. CONCLUSIONS: This cross-sectional study demonstrated that the improvement in the survival rate and proportion of surgery as an initial treatment was increased whereas drug therapy decreased and medical costs increased among patients with lung cancer over time. Based on these results, it is necessary to implement sustainable healthcare measures with a consideration of cost-effectiveness.

On the size-regulation of RNA-loaded lipid nanoparticles synthesized by microfluidic device.

The use of lipid nanoparticles (LNPs) for nucleic acid delivery is now becoming a promising strategy with a number of clinical trials as vaccines or as novel therapies against a variety of genetic and infectious diseases. The use of microfluidics for the synthesis of the LNPs has attracted interest because of its considerable advantages over other conventional synthetic methods including scalability, reproducibility, and speed. However, despite the potential usefulness of large particles for nucleic acid delivery to dendritic cells (DCs) as a vaccine, the particle size of the LNPs prepared using microfluidics is typically limited to approximately from 30 to 100 nm. In this study, focusing on Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, the effect of some synthetic parameters, including total flow rate, flow rate ratio, buffer pH, lipid concentration, molar ratio of PEG-lipid as well as salt concentration, on particle size was systematically examined by means of the design of experiment approaches. The findings indicated that the simple addition of salt (e.g. NaCl) to a buffer containing nucleic acids contributed greatly to the synthesis of large LNPs over 200 nm and this effect was concentration-dependent with respect to the salt. The effect of salt on particle size was consistent with a Hofmeister series. The systemic injection of larger mRNA-loaded LNPs resulted in a higher transgene expression in mouse splenic DCs, a higher activation of various splenic immune cells, and had a superior effect as a therapeutic cancer vaccine in a syngeneic mouse model compared to the smaller-sized counterpart with constant lipid composition prepared with lower NaCl concentration. Collectively, size-regulation by the simple addition of salt is a promising strategy for developing potent LNPs.

Outcomes of Rerouting the Palmaris Longus to Extensor Pollicis Longus Tendon Transfer through the Second Extensor Compartment for Radial Nerve Palsy.

Background: A palmaris longus (PL) to extensor pollicis longus (EPL) is a standard tendon transfer used to restore thumb extension in patients with radial nerve palsy. This transfer is done by withdrawing the EPL from the third compartment and passing it subcutaneously to reach the PL. We modified this transfer by rerouting the EPL through the second extensor compartment to improve the retropulsion of the thumb. The aim of this study is to report the outcomes of this modified transfer. Methods: Four patients with traumatic radial nerve palsy underwent the modified PL to EPL transfer. They also underwent transfer of the pronator teres (PT) to extensor carpi radialis brevis (ECRB) and flexor carpi radialis (FCR) to extensor digitorum communis (EDC). Patients were followed up for at least 1 year after surgery. The data with regard to age, gender, cause of radial nerve palsy, duration between injury and surgery, and duration of follow-up was recorded. At final follow-up, the arc of motion at the interphalangeal joint (IPJ), metacarpophalangeal joint (MCPJ), palmar and radial abduction and retropulsion were measured for the reconstructed thumb and contralateral normal thumb. Results: All patients were male, with a mean age of 34.3 (range, 19-46) years. The mean duration between the injury and surgery was 15.9 (7-27) months, and the mean post-operative follow-up period was 16.8 (12-25) months. All patients recovered good thumb function. The mean arc of motion of the affected and contralateral thumb were IPJ flexion: 52°/80°; IPJ extension: 21°/14°; MCPJ flexion: 30°/33°; MCPJ extension:24°/31°; radial abduction: 70°/74°; palmar abduction: 68°/75° and retropulsion: 4.8cm/5.0cm. Conclusion: Rerouting the PL to EPL tendon transfer through the second extensor compartment in radial nerve palsy can restore good thumb function especially retropulsion. Level of Evidence: Level IV (Therapeutic).

High Median Nerve Entrapment by Fracture Callus in Surgically Treated Pediatric Supracondylar Humeral Fracture: A Case Report.

CASE: We describe a patient with incomplete high median nerve palsy after surgical treatment of pediatric supracondylar humeral fracture (SCHF). Preoperative images after 11 months after the surgical treatment of the SCHF showed rotational deformity and an isolated median nerve entrapped between the proximal humerus anteriorly and callus posteriorly in the bony tunnel of the distal humerus. Two years after neurolysis, he showed clinical recovery. Four cases similar to our case were reported previously. CONCLUSION: Common pediatric fractures may cause unusual neuropathy. Rotational deformity of fracture might be an important factor for isolated median nerve entrapment after SCHF.

C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer.

BACKGROUND: Recent studies indicate that complement plays pivotal roles in promoting or suppressing cancer progression. We have previously identified C4b-binding protein α-chain (C4BPA) as a serum biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). However, its mechanism of action remains unclear. Here, we elucidated the functional roles of C4BPA in PDAC cells and the tumor microenvironment. METHODS: We assessed stromal C4BPA, the C4BPA binding partner CD40, and the number of CD8+ tumor-infiltrating lymphocytes in resected human PDAC tissues via immunohistochemical staining. The biological functions of C4BPA were investigated in peripheral blood mononuclear cells (PBMCs) and human PDAC cell lines. Mouse C4BPA (mC4BPA) peptide, which is composed of 30 amino acids from the C-terminus and binds to CD40, was designed for further in vitro and in vivo experiments. In a preclinical experiment, we assessed the efficacy of gemcitabine plus nab-paclitaxel (GnP), dual immune checkpoint blockades (ICBs), and mC4BPA peptide in a mouse orthotopic transplantation model. RESULTS: Immunohistochemical analysis revealed that high stromal C4BPA and CD40 was associated with favorable PDAC prognosis (P=0.0005). Stromal C4BPA strongly correlated with the number of CD8+ tumor-infiltrating lymphocytes (P=0.001). In in vitro experiments, flow cytometry revealed that recombinant human C4BPA (rhC4BPA) stimulation increased CD4+ and CD8+ T cell numbers in PBMCs. rhC4BPA also promoted the proliferation of CD40-expressing PDAC cells. By contrast, combined treatment with gemcitabine and rhC4BPA increased PDAC cell apoptosis rate. mC4BPA peptide increased the number of murine T lymphocytes in vitro and the number of CD8+ tumor-infiltrating lymphocytes surrounding PDAC tumors in vivo. In a preclinical study, GnP/ICBs/mC4BPA peptide treatment, but not GnP treatment, led to the accumulation of a greater number of CD8+ T cells in the periphery of PDAC tumors and to greater tumor regression than did control treatment. CONCLUSIONS: These findings demonstrate that the combination of GnP therapy with C4BPA inhibits PDAC progression by promoting antitumor T cell accumulation in the tumor microenvironment.

Complement factor B regulates cellular senescence and is associated with poor prognosis in pancreatic cancer.

BACKGROUND: The interplay between cancer cells and stromal components, including soluble mediators released from cancer cells, contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). Here, we set out to identify key secreted proteins involved in PDAC progression. METHODS: We performed secretome analyses of culture media of mouse pancreatic intraepithelial neoplasia (PanIN) and PDAC cells using Stable Isotope Labeling by Amino acid in Cell culture (SILAC) with click chemistry and liquid chromatography-mass spectrometry (LC-MS/MS). The results obtained were verified in primary PDAC tissue samples and cell line models. RESULTS: Complement factor B (CFB) was identified as one of the robustly upregulated proteins, and found to exhibit elevated expression in PDAC cells compared to PanIN cells. Endogenous CFB knockdown by a specific siRNA dramatically decreased the proliferation of PDAC cells, PANC-1 and MIA PaCa-II. CFB knockdown induced increases in the number of senescence-associated-ß-galactosidase (SA-ß-gal) positive cells exhibiting p21 expression upregulation, which promotes cellular senescence with cyclinD1 accumulation. Furthermore, CFB knockdown facilitated downregulation of proliferating cell nuclear antigen and led to cell cycle arrest in the G1 phase in PDAC cells. Using immunohistochemistry, we found that high stromal CFB expression was associated with unfavorable clinical outcomes with hematogenous dissemination after surgery in human PDAC patients. Despite the presence of enriched CD8+ tumor infiltrating lymphocytes in the PDAC tumor microenvironments, patients with a high stromal CFB expression exhibited a significantly poorer prognosis compared to those with a low stromal CFB expression. Immunofluorescence staining revealed a correlation between stromal CFB expression in the tumor microenvironment and an enrichment of immunosuppressive regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We also found that high stromal CFB expression showed a positive correlation with high CD8+/Foxp3+ Tregs populations in PDAC tissues. CONCLUSIONS: Our data indicate that CFB, a key secreted protein, promotes proliferation by preventing cellular senescence and is associated with immunological tumor promotion in PDAC. These findings suggest that CFB may be a potential target for the treatment of PDAC.

Multimaterial decomposition algorithm for quantification of fat in hepatocellular carcinoma using rapid kilovoltage-switching dual-energy CT: A comparison with chemical-shift MR imaging.

ABSTRACT: Understanding intratumoral fat in hepatocellular carcinoma (HCC) is clinically important to elucidate prognosis. We sought to quantify HCC and liver fat with a multimaterial decomposition (MMD) algorithm with rapid kilovoltage-switching dual-energy computed tomography (DECT) relative to chemical-shift magnetic resonance imaging (CSI).In this retrospective study, 40 consecutive patients with HCC underwent non-contrast-enhanced (non-CE) and four-phases contrast-enhanced (four-CE) DECT (80 and 140 kVp) and abdominal MR imaging (including CSI) between April 2011 and December 2012. Fat volume fraction (FVFDECT) maps were generated by MMD algorithm to quantify HCC and liver fat. Fat fraction measured by CSI (FFCSI) was determined for HCC and liver on dual-echo sequence using 1.5- or 3-Tesla MR systems. The correlation between FVFDECT and FFCSI was evaluated using Pearson correlation test, while non-CE FVFDECT and four-CE FVFDECT were compared by one-way ANOVA and Bland-Altman analysis.Forty patients (mean age, 70.1 years ± 7.8; 25 males) were evaluated. FVFDECT and FFCSI exhibited weak to moderate correlations for HCC in non-CE and four-CE except in equilibrium phase (r = 0.42, 0.44, 0.35, and 0.33; all P < .05), and very strong correlations for liver in all phases (r = 0.86, 0.83, 0.85, 0.87, and 0.84; all P < .05). Those correlation coefficients were significantly higher for liver for each phase (all P < .05). FVFDECT did not differ significantly across scan phases regarding HCC or liver (P = .076 and 0.56). Bland-Altman analysis showed fixed bias in all phases between non- and four-CE FVFDECT in HCC and liver.As compared with liver, correlations between FVF measured by DECT-based MMD and FF measured by CSI were weak in HCC in all phases. FVF is reproducible across all scan phases in HCC and liver. The MMD algorithm requires modification for HCC fat quantification given the heterogeneous components of HCC.

Fucosylated C4b-binding protein α-chain, a novel serum biomarker that predicts lymph node metastasis in pancreatic ductal adenocarcinoma.

C4b-binding protein α-chain (C4BPA) was previously identified as a novel serum biomarker for pancreatic ductal adenocarcinoma (PDAC). To apply this biomarker for clinical diagnosis, a lectin ELISA was established to measure serum fucosylated (Fuc)-C4BPA levels in 45 patients with PDAC, 20 patients with chronic pancreatitis (CP) and 50 healthy volunteers (HVs) in one training and three validation sets. The lecithin ELISA developed in the current study exhibited satisfactory within-run (2.6-6.7%) and between-day (1.8-3.6%) coefficient of variations. Serum Fuc-C4BPA levels in patients with PDAC (0.54±0.27 AU/ml) was significantly higher than that in HVs (0.21±0.06 AU/ml; P<0.0001) and patients with CP (0.25±0.03 AU/ml; P<0.0001). Additionally, serum Fuc-C4BPA levels in preoperative patients were significantly decreased compared with postoperative patient sera (P<0.0003). The receiver operating characteristic (ROC) curve analyses revealed that the area under the curve (AUC) of Fuc-C4BPA (0.985) was higher than that of carbohydrate antigen (CA)19-9 (0.843), carcinoembryonic antigen (0.548) and total C4BPA (0.875) (P<0.001). To analyze the clinical significance of Fuc-C4BPA, the ability of Fuc-C4BPA to predict lymph node metastasis was compared with that of CA19-9. The AUC of serum Fuc-C4BPA levels (0.703) was significantly higher than that of serum CA19-9 levels (0.500) in patients with PDAC (P<0.001). The current study established a novel lectin ELISA for measuring serum Fuc-C4BPA levels. Thus, Fuc-C4BPA has potential clinical applications owing to its high diagnostic value in PDAC.

Dual-Energy Computed Tomography of the Liver: Uses in Clinical Practices and Applications.

Dual-energy computed tomography (DECT) is an imaging technique based on data acquisition at two different energy settings. Recent advances in CT have allowed data acquisitions and simultaneous analyses of X-rays at two energy levels, and have resulted in novel developments in the field of abdominal imaging. The use of low and high X-ray tube voltages in DECT provide fused images that improve the detection of liver tumors owing to the higher contrast-to-noise ratio (CNR) of the tumor compared with the liver. The use of contrast agents in CT scanning improves image quality by enhancing the CNR and signal-to-noise ratio while reducing beam-hardening artifacts. DECT can improve detection and characterization of hepatic abnormalities, including mass lesions. The technique can also be used for the diagnosis of steatosis and iron overload. This article reviews and illustrates the different applications of DECT in liver imaging.

Three-dimensional, symmetrically assembled microfluidic device for lipid nanoparticle production.

Sub 100 nm-sized lipid nanoparticles (LNPs) have been widely used in drug delivery systems (DDSs). The size of the LNPs is an important parameter for the DDS performance, such as biodistribution and gene silencing using siRNAs. However, the LNPs prepared by the conventional preparation method show a wide size distribution. To improve the LNP size distribution, we developed a microfluidic device, named the iLiNP™ device, in a previous study. This device could produce LNPs in the size range of 20 to 150 nm, but the size distribution of the large-sized LNPs needs to be further improved. From the viewpoint of the LNP formation process, a homogeneous and slow rate dilution of ethanol plays an important role in improving the large-size LNP size distribution. In this study, we developed a three-dimensional, symmetrically assembled microfluidic device named the 3D-iLiNP device with the aim of precise size control of large-sized LNPs. We designed the 3D-iLiNP device using a computational fluid dynamics simulation and demonstrated that the 3D-iLiNP device can improve the LNP size distribution. The gene silencing activity of four kinds of siRNA-loaded LNPs was investigated via in vitro and in vivo experiments to elucidate the effect of the LNP size distribution. The results revealed that the LNPs with a size between 90 and 120 nm showed higher gene silencing activity than those with other sizes. The 3D-iLiNP device is expected to improve DDS performance by precisely controlling the size of LNPs.