Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Practical targeting errors during optically tracked transcranial focused ultrasound using MR-ARFI and array-based steering.

OBJECTIVE: Transcranial focused ultrasound (tFUS) is being explored for neuroscience research and clinical applications due to its ability to affect precise brain regions noninvasively. The ability to target specific brain regions and localize the beam during these procedures is important for these applications to avoid damage and minimize off-target effects. Here, we present a method to combine optical tracking with magnetic resonance (MR) acoustic radiation force imaging to achieve targeting and localizing of the tFUS beam. This combined method provides steering coordinates to target brain regions within a clinically practical time frame. METHODS: Using an optically tracked hydrophone and bias correction with MR imaging we transformed the FUS focus coordinates into the MR space for targeting and error correction. We validated this method in vivo in 18 macaque FUS studies. RESULTS: Across these in vivo studies a single localization scan allowed for the average targeting error to be reduced from 4.8 mm to 1.4 mm and for multiple brain regions to be targeted with one transducer position. CONCLUSIONS: By reducing targeting error and providing the means to target multiple brain regions within a single session with high accuracy this method will allow further study of the effects of tFUS neuromodulation with more advanced approaches such as simultaneous dual or multi-site brain stimulation.

Association between serum creatinine to albumin ratio and short- and long-term all-cause mortality in patients with acute pancreatitis admitted to the intensive care unit: a retrospective analysis based on the MIMIC-IV database.

Background: Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP. Methods: We conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted. Results: A total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups. Conclusion: The CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.

Directed evolution of the fluorescent protein CGP with in situ biosynthesized noncanonical amino acids.

The incorporation of noncanonical amino acids (ncAAs) into proteins can enhance their function beyond the abilities of canonical amino acids and even generate new functions. However, the ncAAs used for such research are usually chemically synthesized, which is expensive and hinders their application on large industrial scales. We believe that the biosynthesis of ncAAs using metabolic engineering and their employment in situ in target protein engineering with genetic code expansion could overcome these limitations. As a proof of principle, we biosynthesized four ncAAs, O-L-methyltyrosine, 3,4-dihydroxy-L-phenylalanine, 5-hydroxytryptophan, and 5-chloro-L-tryptophan using metabolic engineering and directly evolved the fluorescent consensus green protein (CGP) by combination with nine other exogenous ncAAs in Escherichia coli. After screening a TAG scanning library expressing 13 ncAAs, several variants with enhanced fluorescence and stability were identified. The variants CGPV3pMeoF/K190pMeoF and CGPG20pMeoF/K190pMeoF expressed with biosynthetic O-L-methyltyrosine showed an approximately 1.4-fold improvement in fluorescence compared to the original level, and a 2.5-fold improvement in residual fluorescence after heat treatment. Our results demonstrated the feasibility of integrating metabolic engineering, genetic code expansion, and directed evolution in engineered cells to employ biosynthetic ncAAs in protein engineering. These results could further promote the application of ncAAs in protein engineering and enzyme evolution. IMPORTANCE: Noncanonical amino acids (ncAAs) have shown great potential in protein engineering and enzyme evolution through genetic code expansion. However, in most cases, ncAAs must be provided exogenously during protein expression, which hinders their application, especially when they are expensive or have poor cell membrane penetration. Engineering cells with artificial metabolic pathways to biosynthesize ncAAs and employing them in situ for protein engineering and enzyme evolution could facilitate their application and reduce costs. Here, we attempted to evolve the fluorescent consensus green protein (CGP) with biosynthesized ncAAs. Our results demonstrated the feasibility of using biosynthesized ncAAs in protein engineering, which could further stimulate the application of ncAAs in bioengineering and biomedicine.

Evaluating the efficacy and timing of blood purification modalities in early-stage hyperlipidemic acute pancreatitis treatment.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is characterized by a violent cytokine storm-driven inflammation and is associated with a predisposition to severe disease. The treatment strategy for HTG-AP consists mainly of conventional symptomatic and lipid-lowering treatments. For early-stage HTG-AP, blood purification (BP) can rapidly and effectively reduce serum triglyceride and inflammatory cytokine levels, block the development of systemic inflammatory response syndrome, and improve patient outcomes. Currently, the primary modalities for BP in patients with HTG-AP include plasma exchange, hemoperfusion, and hemofiltration. When using BP to treat patients with HTG-AP, a comprehensive analysis incorporating the elevated lipid levels and severity of the patient's condition contributes to the selection of different treatment modes. Moreover, the timing of the treatment is also imperative. Early intervention is associated with a better prognosis for patients with HTG-AP requiring lipid-lowering treatment.

Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array.

The use of focused ultrasound to open the blood-brain barrier (BBB) has the potential to deliver drugs to specific regions of the brain. The size of the BBB opening and ability to localize the opening determines the spatial extent and is a limiting factor in many applications of BBB opening where targeting a small brain region is desired. Here we evaluate the performance of a system designed for small opening volumes and highlight the unique challenges associated with pushing the spatial precision of this technique. To achieve small volume openings in cortical regions of the macaque brain, we tested a custom 1 MHz array transducer integrated into a magnetic resonance image-guided focused ultrasound system. Using real-time cavitation monitoring, we demonstrated twelve instances of single sonication, small volume BBB opening with average volumes of 59 ± 37 mm3 and 184 ± 2 mm3 in cortical and subcortical targets, respectively. We found high correlation between subject-specific acoustic simulations and observed openings when incorporating grey matter segmentation (R2 = 0.8577), and the threshold for BBB opening based on simulations was 0.53 MPa. Analysis of MRI-based safety assessment and cavitation signals indicate a safe pressure range for 1 MHz BBB opening and suggest that our system can be used to deliver drugs and gene therapy to small brain regions.

Fabrication of a micro/nanocomposite structure on the surface of high oxygen concentration titanium to promote bone formation.

This study investigated the properties of the micro/nano composite structure on the surface of high oxygen concentration titanium (HOC-Ti) after anodic oxidation modification (HOC-NT) and evaluated its biocompatibility as a dental implant material in vitro and in vivo. HOC-Ti was produced by titanium powders and rutile powders using the powder metallurgy method. Its surface was modified by anodic oxidation. After detecting the electrochemical characteristics, the surface properties of HOC-NT were investigated. MC3T3 and MLO-Y4 cells were employed to evaluate the biocompatibility of HOC-NT and cocultured to study the effects of the changes in osteocytes induced by HOC-NT on osteoblasts. While, its possible mechanism was investigated. In addition, osseointegration around the HOC-NT implant was investigated through in vivo experiments. The results showed that a unique micronano composite structure on the HOC-Ti surface with excellent hydrophilicity and suitable surface roughness was created after anodic oxidation promoted by its electrochemical characteristics. The YAP protein may play an important role in regulating bone remodeling by ß-catenin and Rankl/OPG Signaling Pathways. An in vivo study also revealed an accelerated formation rate of new bone and more stable osseointegration around the HOC-NT implant. In view of all experimental results, it could be concluded that the unique morphology of HOC-NT has enhanced physicochemical and biological properties. The promotion of bone formation around implants indicated the feasibility of HOC-NT for applications in oral implants.

Disrupting nociceptive information processing flow through transcranial focused ultrasound neuromodulation of thalamic nuclei.

BACKGROUND: MRI-guided transcranial focused ultrasound (MRgFUS) as a next-generation neuromodulation tool can precisely target and stimulate deep brain regions with high spatial selectivity. Combined with MR-ARFI (acoustic radiation force imaging) and using fMRI BOLD signal as functional readouts, our previous studies have shown that low-intensity FUS can excite or suppress neural activity in the somatosensory cortex. OBJECTIVE: To investigate whether low-intensity FUS can suppress nociceptive heat stimulation-induced responses in thalamic nuclei during hand stimulation, and to determine how this suppression influences the information processing flow within nociception networks. FINDINGS: BOLD fMRI activations evoked by 47.5 °C heat stimulation of hand were detected in 24 cortical regions, which belong to sensory, affective, and cognitive nociceptive networks. Concurrent delivery of low-intensity FUS pulses (650 kHz, 550 kPa) to the predefined heat nociceptive stimulus-responsive thalamic centromedial_parafascicular (CM_para), mediodorsal (MD), ventral_lateral (VL_ and ventral_lateral_posteroventral (VLpv) nuclei suppressed their heat responses. Off-target cortical areas exhibited reduced, enhanced, or no significant fMRI signal changes, depending on the specific areas. Differentiable thalamocortical information flow during the processing of nociceptive heat input was observed, as indicated by the time to reach 10% or 30% of the heat-evoked BOLD signal peak. Suppression of thalamic heat responses significantly altered nociceptive processing flow and direction between the thalamus and cortical areas. Modulation of contralateral versus ipsilateral areas by unilateral thalamic activity differed. Signals detected in high-order cortical areas, such as dorsal frontal (DFC) and ventrolateral prefrontal (vlPFC) cortices, exhibited faster response latencies than sensory areas. CONCLUSIONS: The concurrent delivery of FUS suppressed nociceptive heat response in thalamic nuclei and disrupted the nociceptive network. This study offers new insights into the causal functional connections within the thalamocortical networks and demonstrates the modulatory effects of low-intensity FUS on nociceptive information processing.

Individually tailored spatial-spectral pulsed CEST MRI for ratiometric mapping of myocardial energetic species at 3T.

PURPOSE: CEST MRI has been used to probe changes in cardiac metabolism via assessment of CEST contrast from Cr. However, B1 variation across the myocardium leads to spatially variable Cr CEST contrast in healthy myocardium. METHODS: We developed a spatial-spectral (SPSP) saturation pulsed CEST protocol to compensate for B1 variation. Flip angle maps were used to individually tailor SPSP pulses comprised of a train of one-dimensional spatially selective subpulses selective along the principal B1 gradient dimension. Complete Z-spectra in the hearts of (n = 10) healthy individuals were acquired using conventional Gaussian saturation and SPSP schemes and supported by phantom studies. RESULTS: In simulations, the use of SPSP pulses reduced the average SD of the effective saturation B1 values within the myocardium (n = 10) from 0.12 ± 0.02 µT to 0.05 ± 0.01 µT (p < 0.01) and reduced the average SD of Cr CEST contrast in vivo from 10.0 ± 4.3% to 6.1 ± 3.5% (p < 0.05). Results from the hearts of human subjects showed a significant reduction of CEST contrast distribution at 2 ppm, as well as amplitude, when using SPSP saturation. Corresponding phantom experiments revealed PCr-specific contrast generation at body temperature when SPSP saturation was used but combined PCr and Cr contrast generation when Gaussian saturation was used. CONCLUSION: The use of SPSP saturation pulsed CEST resulted in PCr-specific contrast generation and enabled ratiometric mapping of PCr to total Cr CEST contrast in the human heart at 3T.

Chitosan Oligosaccharides Alleviate Heat-Stress-Induced Lipid Metabolism Disorders by Suppressing the Oxidative Stress and Inflammatory Response in the Liver of Broilers.

Heat stress has been reported to induce hepatic oxidative stress and alter lipid metabolism and fat deposition in broilers. Chitosan oligosaccharides (COSs), a natural oligosaccharide, has anti-oxidant, anti-inflammatory, and lipid-lowering effects. This study is conducted to evaluate dietary COS supplementation on hepatic anti-oxidant capacity, inflammatory response, and lipid metabolism in heat-stressed broilers. The results indicate that heat-stress-induced poor (p < 0.05) growth performance and higher (p < 0.05) abdominal adiposity are alleviated by COS supplementation. Heat stress increases (p < 0.05) serum AST and ATL activity, serum and liver MDA, TG, TC, and LDL-C levels, and the expression of hepatic IL-1ß, IL-6, SREBP-1c, ACC, and FAS, while it decreases (p < 0.05) serum SOD and CAT activity, liver GSH-Px and SOD activity, and the expression of hepatic Nrf2, GPX1, IL-10, MTTP, PPARα, and CPT1. Nevertheless, COS supplementation decreases (p < 0.05) serum AST and ATL activity, serum and liver MDA, TG, TC, and LDL-C levels, and the expression of hepatic IL-1ß, IL-6, SREBP-1c, ACC, and FAS, while it increases (p < 0.05) serum SOD and CAT activity, liver GSH-Px activity, and the expression of hepatic Nrf2, CAT, IL-10, LPL, MTTP, PPARα, and CPT1. In conclusion, COS could alleviate heat-stress-induced lipid metabolism disorders by enhancing hepatic anti-oxidant and anti-inflammatory capacity.

Semiconductor Optical Amplifier (SOA)-Driven Reservoir Computing for Dense Wavelength-Division Multiplexing (DWDM) Signal Compensation.

Optical signal processing (OSP) technology is a crucial part of the optical switching node in the modern optical-fiber communication system, especially when advanced modulation formats, e.g., quadrature amplitude modulation (QAM), are applied. However, the conventional on-off keying (OOK) signal is still widely used in access or metro transmission systems, which leads to the compatibility requirement of OSP for incoherent and coherent signals. In this paper, we propose a reservoir computing (RC)-OSP scheme based on nonlinear mapping behavior through a semiconductor optical amplifier (SOA) to deal with the non-return-to-zero (NRZ) signals and the differential quadrature phase-shift keying (DQPSK) signals in the nonlinear dense wavelength-division multiplexing (DWDM) channel. We optimized the key parameters of SOA-based RC to improve compensation performance. Based on the simulation investigation, we observed a significant improvement in signal quality over 10 dB compared to the distorted signals on each DWDM channel for both the NRZ and DQPSK transmission cases. The compatible OSP achieved by the proposed SOA-based RC could be a potential application of the optical switching node in the complex optical fiber communication system, where incoherent and coherent signals meet.

TSLP/TSLPR promotes renal fibrosis by activating STAT3 in renal fibroblasts.

Previous studies have demonstrated the importance of TSLP-TSLPR in inflammatory, allergic, and fibrotic diseases. However, their exact molecular mechanism in regulating renal fibrosis has not been fully explored yet. The current study identified the high expression levels of TSLP and TSLPR in human and mouse hydronephrotic tissues. In addition, immunofluorescence staining showed that TSLP was highly expressed in renal tubular cells, while TSLPR was mainly co-localized with α-SMA, a marker of fibroblasts. Knocking out TSLPR in the UUO model could alleviate the severity of renal fibrosis. Most importantly, the application of antibody blockade of TSLP reduced the fibrotic level in the UUO model. The functional analysis revealed that the hypoxic exposure could induce the overexpression of TSLP in renal tubular cells via HIF-1α. The tubular cell-derived TSLP could bind to the TSLPR of fibroblasts in a paracrine manner to activate them. Specifically, the HIF-1α/TSLP/TSLPR-axis could activate fibroblasts through the STAT3 signaling pathway. This study revealed a mechanistic interaction of HIF-1α/TSLP/TSLPR and STAT3 signaling pathways in the activation and proliferation of human and murine kidney fibroblasts; these pathways might be exploited as a therapeutic target in renal fibrosis.

Small volume blood-brain barrier opening in macaques with a 1 MHz ultrasound phased array.

Focused ultrasound blood-brain barrier (BBB) opening is a promising tool for targeted delivery of therapeutic agents into the brain. The volume of opening determines the extent of therapeutic administration and sets a lower bound on the size of targets which can be selectively treated. We tested a custom 1 MHz array transducer optimized for cortical regions in the macaque brain with the goal of achieving small volume openings. We integrated this device into a magnetic resonance image guided focused ultrasound system and demonstrated twelve instances of small volume BBB opening with average opening volumes of 59 ± 37 mm 3 and 184 ± 2 mm 3 in cortical and subcortical targets, respectively. We developed real-time cavitation monitoring using a passive cavitation detector embedded in the array and characterized its performance on a bench-top flow phantom mimicking transcranial BBB opening procedures. We monitored cavitation during in-vivo procedures and compared cavitation metrics against opening volumes and safety outcomes measured with FLAIR and susceptibility weighted MR imaging. Our findings show small BBB opening at cortical targets in macaques and characterize the safe pressure range for 1 MHz BBB opening. Additionally, we used subject-specific simulations to investigate variance in measured opening volumes and found high correlation (R 2 = 0.8577) between simulation predictions and observed measurements. Simulations suggest the threshold for 1 MHz BBB opening was 0.53 MPa. This system enables BBB opening for drug delivery and gene therapy to be targeted to more specific brain regions.

Detection of laser-associated heating in the brain during simultaneous fMRI and optogenetic stimulation.

PURPOSE: To calculate temperatures from T2 *-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. METHODS: fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T2 *-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. RESULTS: The temperature SD was 0.05°C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13°C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. CONCLUSION: The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.

Transcatheter arterial embolization followed by laparoscopic anatomic hepatectomy for spontaneous rupture of a giant hepatic angiomyolipoma: a case report.

Hepatic angiomyolipoma is a rare and possibly cancerous mesenchymal tumor that consists of three components: blood vessels, smooth muscle cells, and adipose tissue. In this paper, we reported a case of a 36-year-old man who had a giant hepatic angiomyolipoma with spontaneous rupture and hemorrhage. The patient was admitted to our hospital with sudden upper abdominal pain for 3 h. A giant tumor was found in the left and caudate lobes of the liver, as well as significant blood collection around the liver and in the pelvis. Hemoglobin, liver function test results, and serum tumor maker levels were all within normal ranges. To prevent bleeding, emergency angiography and embolization were performed. During angiography, it was discovered that the tumor was supplied by the left hepatic artery and had a very rich internal blood supply. A massive left hepatic mass of about 11 cm in diameter was found bulging from the surface of the liver and rupturing there during laparoscopic exploration a week later. The rupture was strongly adhered to the smaller curvature of the stomach. The patient underwent laparoscopic left hemihepatectomy and caudate lobectomy, and the tumor specimen was brown, with clear boundaries with the surrounding normal liver parenchyma, and there were a large number of necrotic lesions inside the tumor. Histopathological results confirmed the mass as hepatic angiomyolipoma with negative resection margins. Immunohistochemical staining indicated that the tumor had positive homatropine methylbromide-45. After 13 months of follow-up, no tumor recurrence or metastasis occurred in the patient.

Safety and feasibility of laparoscopic radical resection for bismuth types III and IV hilar cholangiocarcinoma: a single-center experience from China.

Background: Surgery represents the only cure for hilar cholangiocarcinoma (HC). However, laparoscopic radical resection remains technically challenging owing to the complex anatomy and reconstruction required during surgery. Therefore, reports on laparoscopic surgery (LS) for HC, especially for types III and IV, are limited. This study aimed to evaluate the safety and feasibility of laparoscopic radical surgery for Bismuth types III and IV HC. Methods: The data of 16 patients who underwent LS and 9 who underwent open surgery (OS) for Bismuth types III and IV HC at Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, between December 2017 and January 2022 were analyzed. Basic patient information, Bismuth-Corlette type, AJCC staging, postoperative complications, pathological findings, and follow-up results were evaluated. Results: Sixteen patients underwent LS and 9 underwent OS for HC. According to the preoperative imaging data, there were four cases of Bismuth type IIIa, eight of type IIIb, and four of type IV in the LS group and two of type IIIa, four of type IIIb, and three of type IV in the OS group (P>0.05). There were no significant differences in age, sex, ASA score, comorbidity, preoperative percutaneous transhepatic biliary drainage rate, history of abdominal surgery, or preoperative laboratory tests between the two groups (P>0.05). Although the mean operative time and mean intraoperative blood loss were higher in the LS group than in OS group, the differences were not statistically significant (P=0.121 and P=0.115, respectively). Four patients (25%) in the LS group and two (22.2%) in the OS group experienced postoperative complications (P>0.05). No significant differences were observed in other surgical outcomes and pathologic findings between the two groups. Regarding the tumor recurrence rate, there was no difference between the groups (P>0.05) during the follow-up period (23.9 ± 13.3 months vs. 17.8 ± 12.3 months, P=0.240). Conclusion: Laparoscopic radical resection of Bismuth types III and IV HC remains challenging, and extremely delicate surgical skills are required when performing extended hemihepatectomy followed by complex bilioenteric reconstructions. However, this procedure is generally safe and feasible for hepatobiliary surgeons with extensive laparoscopy experience.

Reduced-field of view three-dimensional MR acoustic radiation force imaging with a low-rank reconstruction for targeting transcranial focused ultrasound.

PURPOSE: To rapidly image and localize the focus in MR-guided focused ultrasound (FUS) while maintaining a low ultrasound duty cycle to minimize tissue effects. METHODS: MR-acoustic radiation force imaging (ARFI) is key to targeting FUS procedures such as neuromodulation, and works by encoding ultrasound-induced displacements into the phase of MR images. However, it can require long scan times to cover a volume of tissue, especially when minimizing the FUS dose during targeting is paramount. To simultaneously minimize scan time and the FUS duty cycle, a 2-min three-dimensional (3D) reduced-FOV spin echo ARFI scan with two-dimensional undersampling was implemented at 3T with a FUS duty cycle of 0.85%. The 3D k-space sampling scheme incorporated uniform undersampling in one phase-encoded axis and partial Fourier (PF) sampling in the other. The scan interleaved FUS-on and FUS-off data collection to improve displacement map quality via a joint low-rank image reconstruction. Experiments in agarose and graphite phantoms and living macaque brains for neuromodulation and blood-brain barrier opening studied the effects of the sampling and reconstruction strategy on the acquisition, and evaluated its repeatability and accuracy. RESULTS: In the phantom, the distances between displacement centroids of 10 prospective reconstructions and a fully sampled reference were below 1 mm. In in vivo brain, the distances between centroids ranged from 1.3 to 2.1 mm. Results in phantom and in vivo brain both showed that the proposed method can recover the FUS focus compared to slower fully sampled scans. CONCLUSION: The proposed 3D MR-ARFI reduced-FOV method enables rapid imaging of the FUS focus while maintaining a low FUS duty cycle.

Exploring Long Non-Coding RNAs Associated with IP3/DAG Signaling Pathway as Potential Biomarkers Involved in Mast Cell Degranulation in Chronic Spontaneous Urticaria with 2-Year Follow-Up.

PURPOSE: Chronic spontaneous urticaria (CSU) pathogenesis involves mast cell degranulation induced by the inositol 1,4,5-trisphosphate/diacylglycerol (IP3/DAG) pathway, but the condition lacks specific biomarkers. This study was performed to investigate long non-coding RNA (lncRNA) expression profiles, identify those associated with IP3/DAG pathway, and assess their diagnostic and prognostic value for CSU. METHODS: Ten samples were selected from CSU and control groups, and microarray was performed to screen differentially expressed (DE) lncRNAs and mRNAs. Bioinformatic and co-expression network analyses were used to identify lncRNAs associated with IP3/DAG pathway. Quantitative real-time polymerase chain reaction was used to validate lncRNA expression levels. Combined with disease characteristics and serum indices detected with enzyme-linked immunosorbent assays, Spearman analysis and logistic regression were applied to analyze lncRNA-associated disease risk. Receiver operating characteristic (ROC) curves and 2-year follow-up data were applied to evaluate lncRNA diagnostic and prognostic value. RESULTS: A total of 678 up- and 573 downregulated DE lncRNAs and 609 up- and 176 downregulated DE mRNAs were identified. Seven lncRNAs (upregulated T264761, T280622, ENST00000587970, T224062, ENST00000562459, and his-1_RNA_dna; downregulated ENST00000417930) were associated with the IP3/DAG pathway. D-dimer and histamine levels were significantly different between the two groups. Correlation analysis showed that his-1_RNA_dna positively correlated with the frequency of symptom appearance, while his-1_RNA_dna, ENST00000417930, T264761, and T280622 negatively correlated with the maximum wheal diameter. Regression analysis showed T264761 was associated with CSU risk. ROC analysis showed that the specificity of T264761 was 90%, with an area under the curve of 0.666. In follow-up, the rate of well-controlled disease in the low T264761 expression group was 82.61%. CONCLUSION: This study established lncRNA and mRNA expression profiles in CSU and identified lncRNAs associated with IP3/DAG pathway, which is mechanistically involved in this disease. T264761 may be a novel biomarker for CSU, but further study is needed to confirm its specific mechanism.

A novel methodology concentrating on risk propagation to conduct a risk analysis based on a directed complex network.

A novel methodology is proposed in the present study to describe the risk propagation process by quantitatively evaluating the criticality and sensitivity of risk events according to complex network theory, based on which risk matrices are developed to interrupt the risk propagation process by setting up safety barriers. The applicability and accuracy of the improved k-shell decomposition algorithm and risk flow model for calculating the criticality proposed in this study are verified by the susceptible-infected-recovered (SIR) simulation, which is widely regarded as a benchmark for complex networks (CN) issues. The results confirm the advantages of the proposed methodologies considering comprehensively various comparison indicators. The sensitivity of the nodes is quantified by running an SIR simulation with a variable infection rate and recovery rate. Finally, the criticality and sensitivity of risk events contribute to the development of risk matrices with three different risk scenarios, based on which the applicability and effectiveness of safety barriers are qualitatively analyzed to interrupt the risk propagation process. The framework and methodologies proposed in this study could well present the risk propagation process within CNs and are proven to have a great potential for studies on safety barriers.

Association of shared decision making with inpatient satisfaction: a cross-sectional study.

BACKGROUND: We assessed inpatient perceived shared decision making (SDM) and tested the association of SDM with inpatient satisfaction in public tertiary hospitals in Shanghai, China. METHODS: A cross-sectional survey of 2585 inpatients in 47 public tertiary hospitals in Shanghai in July and August 2018 was conducted. We assessed overall SDM and 4 aspects of SDM and tested the factors influencing SDM and the association of SDM with patient satisfaction (patient satisfaction with physician services, medical expenses, outcomes and overall inpatient care), by adopting linear or two-level regression models. RESULTS: The positive response rate (PRR) and high positive response rate (HPRR) to overall SDM among the inpatients of public tertiary hospitals in Shanghai were relatively high (95.30% and 87.86%, respectively), while the HPRR to "My physician informed me of different treatment alternatives" was relatively low (80.09%). In addition, the inpatients who underwent surgery during admission had higher HPRRs and adjusted HPRRs to overall SDM than those who did not undergo surgery. The study showed that the adjusted high satisfaction rates (HSRs) with physician services, medical expenses, outcomes and overall inpatient care among the inpatients with high level of overall SDM were higher (96.50%, 68.44%, 89.50% and 92.60%) than those among the inpatients without a high level of overall SDM (71.77%, 35.19%, 57.30% and 67.49%). The greatest differences in the adjusted HSRs between the inpatients with and without a high level of SDM were found in inpatient satisfaction with medical expenses and informed consent in SDM. Moreover, 46.22% of the variances in the HSRs with overall inpatient care across the hospitals were attributed to the hospital type (general hospitals vs. specialty hospitals). CONCLUSIONS: Inpatient PRRs and HPRRs to SDM in public tertiary hospitals in Shanghai are relatively high overall but lower to information regarding alternatives. SDM can be affected by the SDM preference of both the patients and physicians and medical condition. Patient satisfaction can be improved through better SDM and should be committed at the hospital level.