Prediction of angiogenesis in extrahepatic cholangiocarcinoma using MRI-based machine learning.

Purpose: Reliable noninvasive method to preoperative prediction of extrahepatic cholangiocarcinoma (eCCA) angiogenesis are needed. This study aims to develop and validate machine learning models based on magnetic resonance imaging (MRI) for predicting vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) of eCCA. Materials and methods: In this retrospective study from August 2011 to May 2020, eCCA patients with pathological confirmation were selected. Features were extracted from T1-weighted, T2-weighted, and diffusion-weighted images using the MaZda software. After reliability testing and feature screening, retained features were used to establish classification models for predicting VEGF expression and regression models for predicting MVD. The performance of both models was evaluated respectively using area under the curve (AUC) and Adjusted R-Squared (Adjusted R2). Results: The machine learning models were developed in 100 patients. A total of 900 features were extracted and 77 features with intraclass correlation coefficient (ICC) < 0.75 were eliminated. Among all the combinations of data preprocessing methods and classification algorithms, Z-score standardization + logistic regression exhibited excellent ability both in the training cohort (average AUC = 0.912) and the testing cohort (average AUC = 0.884). For regression model, Z-score standardization + stochastic gradient descent-based linear regression performed well in the training cohort (average Adjusted R2 = 0.975), and was also better than the mean model in the test cohort (average Adjusted R2 = 0.781). Conclusion: Two machine learning models based on MRI can accurately predict VEGF expression and the MVD of eCCA respectively.

Long-term outcomes of ultrasound guided high intensity focused ultrasound ablation for patients with uterine fibroids classified by T2WI: a multicenter retrospective study.

OBJECTIVE: To evaluate the long-term outcomes of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids classified by T2-weighted magnetic resonance imaging (T2WI-MRI). MATERIALS AND METHODS: The data of 1427 premenopausal women with symptomatic uterine fibroids who underwent USgHIFU at four teaching hospitals in China were analyzed retrospectively. The uterine fibroids were classified based on their T2WI-MRI signal intensities relative to that of skeletal muscle, myometrium and endometrium as: hypointense, isointense, heterogeneous hyperintense fibroids (HHF), slightly HHF (sHHF) and markedly HHF (mHHF), respectively. The rates of symptom relief and reintervention post-USgHIFU ablation were compared between the classified groups. RESULTS: A total of 1303 patients were followed up for 44 (40, 49) months. The symptom relief rate of the hypointense and isointense fibroids was 83.3% and 79.5%, respectively, which were significantly higher (p < .05) compared to that of HHF, sHHF and mHHF (58.3%, 44.2% and 60.4%), respectively. sHHF had the lowest symptom relief rate (p < .05). The cumulative reintervention rate for hypointense, isointense, HHF, sHHF and mHHF types were 8.8%, 10.8%, 21.4%, 39.9% and 19.8%, respectively. The reintervention rate of hypointense/isointense fibroids was significantly lower than that of HHF/mHHF/sHHF (p < .01), while sHHF had the highest re-intervention rate (p < .01). Thus, reintervention rate is inversely correlated to the rate of symptom relief. CONCLUSIONS: USgHIFU ablation is effective for hypointense, isointense, HHF and mHHF with acceptable long-term follow-up outcomes. However, sHHF is associated with a higher reintervention rate.

Causes of epigastric pain and vomiting after laparoscopic-assisted radical right hemicolectomy - superior mesenteric artery syndrome.

BACKGROUND: Superior mesenteric artery syndrome (SMAS) is a rare condition causing functional obstruction of the third portion of the duodenum. Postoperative SMAS following laparoscopic-assisted radical right hemicolectomy is even less prevalent and can often be unrecognized by radiologists and clinicians. AIM: To analyze the clinical features, risk factors, and prevention of SMAS after laparoscopic-assisted radical right hemicolectomy. METHODS: We retrospectively analyzed clinical data of 256 patients undergoing laparoscopic-assisted radical right hemicolectomy in the Affiliated Hospital of Southwest Medical University from January 2019 to May 2022. The occurrence of SMAS and its countermeasures were evaluated. Among the 256 patients, SMAS was confirmed in six patients (2.3%) by postoperative clinical presentation and imaging features. All six patients were examined by enhanced computed tomography (CT) before and after surgery. Patients who developed SMAS after surgery were used as the experimental group. A simple random sampling method was used to select 20 patients who underwent surgery at the same time but did not develop SMAS and received preoperative abdominal enhanced CT as the control group. The angle and distance between the superior mesenteric artery and abdominal aorta were measured before and after surgery in the experimental group and before surgery in the control group. The preoperative body mass index (BMI) of the experimental group and the control group was calculated. The type of lymphadenectomy and surgical approach in the experimental and control groups were recorded. The differences in angle and distance were compared preoperatively and postoperatively in the experimental group compared. The differences in angle, distance, BMI, type of lymphadenectomy and surgical approach between the experimental and control groups were compared, and the diagnostic efficacy of the significant parameters was assessed using receiver operating characteristic curves. RESULTS: In the experimental group, the aortomesenteric angle and distance after surgery were significantly decreased than those before surgery (P < 0.05). The aortomesenteric angle, distance and BMI were significantly higher in the control group than in the experimental (P < 0.05). There was no significant difference in the type of lymphadenectomy and surgical approach between the two groups (P > 0.05). CONCLUSION: The small preoperative aortomesenteric angle and distance and low BMI may be important factors for the complication. Over-cleaning of lymph fatty tissues may also be associated with this complication.

Bifocal computational near eye light field displays and Structure parameters determination scheme for bifocal computational display.

We propose a bifocal computational near eye light field display (bifocal computational display) and structure parameters determination scheme (SPDS) for bifocal computational display that achieves greater depth of field (DOF), high resolution, accommodation and compact form factor. Using a liquid varifocal lens, two single-focal computational light fields are superimposed to reconstruct a virtual object's light field by time multiplex and avoid the limitation on high refresh rate. By minimizing the deviation between reconstructed light field and original light field, we propose a determination framework to determine the structure parameters of bifocal computational light field display. When applied to different objective to SPDS, it can achieve high average resolution or uniform resolution display over scene depth range. To analyze the advantages and limitation of our proposed method, we have conducted simulations and constructed a simple prototype which comprises a liquid varifocal lens, dual-layer LCDs and a uniform backlight. The results of simulation and experiments with our method show that the proposed system can achieve expected performance well. Owing to the excellent performance of our system, we motivate bifocal computational display and SPDS to contribute to a daily-use and commercial virtual reality display.

Near eye light field display based on human visual features.

We introduce a near eye light field display proposal to reconstruct a light field in high synthesis speed by utilizing the multi-layer light field display technology and human visual features. The resolution distribution of the reconstructed light field is set to be identical to human visual acuity which decreases with the increasing visual eccentricity. We compress the light field information by using different sampling rates in different visual eccentricity area. A new optimization method for the compressed light field is proposed, which dramatically reduces the amount of calculation. The results demonstrate that the acceleration of the proposed scheme is obvious and escalates when the spatial resolution increases. The synthesis scheme is verified and its key aspects are analyzed by simulation and an experimental prototype.

Measuring (13)C/(15)N chemical shift anisotropy in [(13)C,(15)N] uniformly enriched proteins using CSA amplification.

Extended chemical shift anisotropy amplification (xCSA) is applied for measuring (13)C/(15)N chemical shift anisotropy (CSA) of uniformly labeled proteins under magic-angle spinning (MAS). The amplification sequence consists of a sequence of π-pulses that repetitively interrupt MAS averaging of the CSA interaction. The timing of the pulses is designed to generate amplified spinning sideband manifolds which can be fitted to extract CSA parameters. The (13)C/(13)C homonuclear dipolar interactions are not affected by the π-pulses due to the bilinear nature of the spin operators and are averaged by MAS in the xCSA experiment. These features make the constant evolution-time experiment suitable for measuring CSA of uniformly labeled samples. The incorporation of xCSA with multi-dimensional (13)C/(15)N correlation is demonstrated with a GB1 protein sample as a model system for measuring (13)C/(15)N CSA of all backbone (15)NH, (13)CA and (13)CO sites.

Systemic treatment with liver X receptor agonists raises apolipoprotein E, cholesterol, and amyloid-ß peptides in the cerebral spinal fluid of rats.

BACKGROUND: Apolipoprotein E (apoE) is a major cholesterol transport protein found in association with brain amyloid from Alzheimer's disease (AD) patients and the ε4 allele of apoE is a genetic risk factor for AD. Previous studies have shown that apoE forms a stable complex with amyloid ß (Aß) peptides in vitro and that the state of apoE lipidation influences the fate of brain Aß, i.e., lipid poor apoE promotes Aß aggregation/deposition while fully lipidated apoE favors Aß degradation/clearance. In the brain, apoE levels and apoE lipidation are regulated by the liver X receptors (LXRs). RESULTS: We investigated the hypothesis that increased apoE levels and lipidation induced by LXR agonists facilitates Aß efflux from the brain to the cerebral spinal fluid (CSF). We also examined if the brain expression of major apoE receptors potentially involved in apoE-mediated Aß clearance was altered by LXR agonists. ApoE, cholesterol, Aß40, and Aß42 levels were all significantly elevated in the CSF of rats after only 3 days of treatment with LXR agonists. A significant reduction in soluble brain Aß40 levels was also detected after 6 days of LXR agonist treatment. CONCLUSIONS: Our novel findings suggest that central Aß lowering caused by LXR agonists appears to involve an apoE/cholesterol-mediated transport of Aß to the CSF and that differences between the apoE isoforms in mediating this clearance pathway may explain why individuals carrying one or two copies of APOE ε4 have increased risk for AD.

PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans. PCSK9 has also been shown to regulate the levels of additional membrane-bound proteins in vitro, including the very low-density lipoprotein receptor (VLDLR), apolipoprotein E receptor 2 (ApoER2) and the beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), which are all highly expressed in the CNS and have been implicated in Alzheimer's disease. To better understand the role of PCSK9 in regulating these additional target proteins in vivo, their steady-state levels were measured in the brain of wild-type, PCSK9-deficient, and human PCSK9 overexpressing transgenic mice. We found that while PCSK9 directly bound to recombinant LDLR, VLDLR, and apoER2 protein in vitro, changes in PCSK9 expression did not alter the level of these receptors in the mouse brain. In addition, we found no evidence that PCSK9 regulates BACE1 levels or APP processing in the mouse brain. In conclusion, our results suggest that while PCSK9 plays an important role in regulating circulating LDL cholesterol levels by reducing the number of hepatic LDLRs, it does not appear to modulate the levels of LDLR and other membrane-bound proteins in the adult mouse brain.

Subunit interactions and requirements for inhibition of the yeast V1-ATPase.

Disassembly of the yeast V-ATPase into cytosolic V(1) and membrane V(0) sectors inactivates MgATPase activity of the V(1)-ATPase. This inactivation requires the V(1) H subunit (Parra, K. J., Keenan, K. L., and Kane, P. M. (2000) J. Biol. Chem. 275, 21761-21767), but its mechanism is not fully understood. The H subunit has two domains. Interactions of each domain with V(1) and V(0) subunits were identified by two-hybrid assay. The B subunit of the V(1) catalytic headgroup interacted with the H subunit N-terminal domain (H-NT), and the C-terminal domain (H-CT) interacted with V(1) subunits B, E (peripheral stalk), and D (central stalk), and the cytosolic N-terminal domain of V(0) subunit Vph1p. V(1)-ATPase complexes from yeast expressing H-NT are partially inhibited, exhibiting 26% the MgATPase activity of complexes with no H subunit. The H-CT domain does not copurify with V(1) when expressed in yeast, but the bacterially expressed and purified H-CT domain inhibits MgATPase activity in V(1) lacking H almost as well as the full-length H subunit. Binding of full-length H subunit to V(1) was more stable than binding of either H-NT or H-CT, suggesting that both domains contribute to binding and inhibition. Intact H and H-CT can bind to the expressed N-terminal domain of Vph1p, but this fragment of Vph1p does not bind to V(1) complexes containing subunit H. We propose that upon disassembly, the H subunit undergoes a conformational change that inhibits V(1)-ATPase activity and precludes V(0) interactions.

Structural and functional separation of the N- and C-terminal domains of the yeast V-ATPase subunit H.

The H subunit of the yeast V-ATPase is an extended structure with two relatively independent domains, an N-terminal domain consisting of amino acids 1-348 and a C-terminal domain consisting of amino acids 352-478. We have expressed these two domains independently and together in a yeast strain lacking the H subunit (vma13Delta mutant). The N-terminal domain partially complements the growth defects of the mutant and supports approximately 25% of the wild-type Mg(2+)-dependent ATPase activity in isolated vacuolar vesicles, but surprisingly, this activity is both largely concanamycin-insensitive and uncoupled from proton transport. The C-terminal domain does not complement the growth defects, and supports no ATP hydrolysis or proton transport, even though it is recruited to the vacuolar membrane. Expression of both domains in a vma13Delta strain gives better complementation than either fragment alone and results in higher concanamycin-sensitive ATPase activity and ATP-driven proton pumping than the N-terminal domain alone. Thus, the two domains make complementary contributions to structural and functional coupling of the peripheral V(1) and membrane V(o) sectors of the V-ATPase, but this coupling does not require that they be joined covalently. The N-terminal domain alone is sufficient for activation of ATP hydrolysis in V(1), but the C-terminal domain is essential for proper communication between the V(1) and V(o) sectors.