Brain and Systemic Inflammation in De Novo Parkinson's Disease.

OBJECTIVE: To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD). BACKGROUND: Evidence for a pathophysiologic role of inflammation in PD is growing. However, several key gaps remain as to the role of inflammation in PD, including the extent of immune activation at early stages, potential effects of PD treatments on inflammation and whether pro-inflammatory signals are associated with clinical features and/or predict more rapid progression. METHODS: We enrolled subjects with de novo PD (n = 58) and age-matched controls (n = 62). Subjects underwent clinical assessments, including the Movement Disorder Society-United Parkinson's Disease rating scale (MDS-UPDRS). Comprehensive cognitive assessment meeting MDS Level II criteria for mild cognitive impairment testing was performed. Blood was obtained for flow cytometry and cytokine/chemokine analyses. Subjects underwent imaging with 18 F-DPA-714, a translocator protein 18kd ligand, and lumbar puncture if eligible and consented. RESULTS: Baseline demographics and medical history were comparable between groups. PD subjects showed significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, Scales for Outcomes in PD autonomic dysfunction, and MDS-UPDRS scores. Cognitive testing demonstrated significant differences in cognitive composite, executive function, and visuospatial domain scores at baseline. Positron emission tomography imaging showed increased 18 F-DPA-714 signal in PD subjects. 18 F-DPA-714 signal correlated with several cognitive measures and some chemokines. CONCLUSIONS: 18 F-DPA-714 imaging demonstrated increased central inflammation in de novo PD subjects compared to controls. Longitudinal follow-up will be important to determine whether the presence of inflammation predicts cognitive decline. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Magnetic Resonance Elastography in the Assessment of Acute Effects of Kinesio Taping on Lumbar Paraspinal Muscles.

BACKGROUND: Kinesio tape (KT) is an elastic therapeutic tape used for treating sports-related injuries and a number of other disorders. To date, the objective evidence to link pathophysiological effects and actual reactions triggered by KT is limited. PURPOSE: To explore the effect of KT on the lumbar paraspinal muscles by magnetic resonance (MR) elastography. STUDY TYPE: Prospective observational study. POPULATION: Sixty-six asymptomatic volunteers with 31 women and 35 men. FIELD STRENGTH/SEQUENCE: 3.0T MRI and elastography with vibration frequency of 120 Hz. ASSESSMENT: The 5-cm-width KT with full tension was placed on a single side of the lumbar paraspinal muscle. The taping side and adhering direction were randomly decided. Two rectangular regions of interest (ROIs) of 5- and 2.5-cm-width were positioned at the bilateral paraspinal regions from the L2 to L4 level on the confidence map of MR elastography before and after KT taping. The mean shear stiffness values of the ROIs at the superficial, middle, and deep depths were recorded; then the differences between the taping and reference sides were calculated. STATISTICAL TESTS: Paired t-test and Pearson correlations were used to evaluate the stiffness changes after KT application and intraoperator errors of the stiffness measures on the reference side, respectively. RESULTS: A significant decrease in the muscle stiffness value between taping and reference sides (-0.71 kPa ± 0.60 with KT and -0.25 kPa ± 0.78 without KT, P < 0.0001 for 5-cm ROI; -0.67 kPa ± 1.12 with KT and -0.16 kPa ± 1.17 without KT, P = 0.0004 for 2.5-cm ROI) was found in the superficial depth, but no significant differences in the middle and deep depths (P = 0.25 and P = 0.79 for 5-cm ROI; P = 0.09 and P = 0.67 for 2.5-cm ROI, respectively). There were no significant differences of muscle stiffness differences between gender (P = 0.11 for superficial, P = 0.37 for middle, P = 0.78 for deep) and taping direction (P = 0.18 for superficial, P = 0.13 for middle, P = 0.15 for deep). DATA CONCLUSION: Our results demonstrate that KT can reduce the MR elastography-derived shear stiffness in the superficial depth of paraspinal muscles. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1039-1045.

Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies.

OBJECTIVE: Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD. METHODS: We retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner-specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET-MAP+ abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated to identify the optimal threshold for QPET-MAP analysis. RESULTS: A total of 104 patients were included. When QPET thresholds of SD = -1, -2, and -3 were used, complete resection of the QPET-MAP+ region was significantly associated with seizure-free outcome when compared with the partial resection group (P = 0.023, P < 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001). The SD threshold of -2 showed the best combination of positive rate (55%), sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and negative predictive value (0.69). Surgical pathology of the resected QPET-MAP+ areas revealed mainly FCD type I. Multiple QPET-MAP+ regions were present in 12% of the patients at SD = -2. SIGNIFICANCE: Our study demonstrates a practical and effective approach to combine quantitative analyses of functional (QPET) and structural (MAP) imaging data to improve identification of subtle epileptic abnormalities. This approach can be readily adopted by epilepsy centers to improve postresective seizure outcomes for patients without apparent lesions on MRI.

Heterogeneity of (18)F-FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma.

The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC.

TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib.

PURPOSE: In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. METHODS: We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015). CONCLUSIONS: TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib.

Quantity of lymph nodes correlates with improvement in lymphatic drainage in treatment of hind limb lymphedema with lymph node flap transfer in rats.

PURPOSE: This study was conducted to investigate the correlation between the number of vascularized lymph nodes (LN) transferred and resolution of hind limb lymphedema in a rat model. METHODS: Unilateral hind limb lymphedema was created in 18 male Sprague-Dawley rats following inguinal and popliteal LN resection and radiation. A para-aortic LN flap based on the celiac artery was subsequently transferred to the affected groin. The three study groups consisted of Group A (no LN transfer), Group B (transfer of a single vascularized LN), and Group C (transfer of three vascularized LNs). Volumetric analysis of bilateral hind limbs was performed using micro-CT imaging at 1, 2, and 3 months postoperatively. Lymphatic drainage was assessed with Tc(99) lymphoscintigraphy preoperatively and at 3 months postoperatively. RESULTS: A statistically significant volume reduction was seen in Groups B and C compared to Group A at all time points. Volume reduction of Group A vs.Group B at 1 month (8.6% ± 2.0% vs. 2.7% ± 2.6%, P < 0.05), 2 months (9.3% ± 2.2% vs. -4.3% ± 2.7%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -8.9% ± 5.2%, P < 0.05). Volume reduction of Group A vs. Group C at 1 month (8.6% ± 2.0% vs. -6.6% ± 3.1%, P < 0.05), 2 months (9.3% ± 2.2% vs. -10.2% ± 4.6%, P < 0.05), and 3 months (7.6% ± 3.3% vs. -9.1% ± 3.1%, P < 0.05). Of note, comparison of Groups B and C demonstrated greater volume reduction in Group C at 1 (P < 0.02) and 2 (P = 0.07) months postoperatively. CONCLUSIONS: LN flap transfer is an effective procedure for the treatment of lymphedema. The number of vascularized LNs transferred correlates positively with the degree of volume reduction.

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PURPOSE: The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. METHODS: We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. RESULTS: Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. CONCLUSION: ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Regenerating cartilages by engineered ASCs: prolonged TGF-ß3/BMP-6 expression improved articular cartilage formation and restored zonal structure.

Adipose-derived stem cells (ASCs) hold promise for cartilage regeneration but their chondrogenesis potential is inferior. Here, we used a baculovirus (BV) system that exploited FLPo/Frt-mediated transgene recombination and episomal minicircle formation to genetically engineer rabbit ASCs (rASCs). The BV system conferred prolonged and robust TGF-ß3/BMP-6 expression in rASCs cultured in porous scaffolds, which critically augmented rASCs chondrogenesis and suppressed osteogenesis/hypertrophy, leading to the formation of cartilaginous constructs with improved maturity and mechanical properties in 2-week culture. Twelve weeks after implantation into full-thickness articular cartilage defects in rabbits, these engineered constructs regenerated neocartilages that resembled native hyaline cartilages in cell morphology, matrix composition and mechanical properties. The neocartilages also displayed cartilage-specific zonal structures without signs of hypertrophy and degeneration, and eventually integrated with host cartilages. In contrast, rASCs that transiently expressed TGF-ß3/BMP-6 underwent osteogenesis/hypertrophy and resulted in the formation of inferior cartilaginous constructs, which after implantation regenerated fibrocartilages. These data underscored the crucial role of TGF-ß3/BMP-6 expression level and duration in rASCs in the cell differentiation, constructs properties and in vivo repair. The BV-engineered rASCs that persistently express TGF-ß3/BMP-6 improved the chondrogenesis, in vitro cartilaginous constructs production and in vivo hyaline cartilage regeneration, thus representing a remarkable advance in cartilage engineering.

Employing a PhI(OAc)2-mediated domino reaction to assemble nitrogen-containing heterocyclic derivatives and assessing their anti-inflammatory activity.

Metal-free radical cascade synthesis of substituted pyrazole derivatives was initiated by PhI(OAc)2 at 23 °C. This protocol features wide functional group tolerance, a simple purification process without column chromatography, and an oxygen migration. Compound 5 demonstrated significant anti-inflammatory activity, indicating potential for therapy.

Associations between femoral 3D curvature and sagittal imbalance of spine.

Background: The sagittal imbalance (SI) of spine triggers compensatory mechanisms (CMs) of lower extremity (LE) to restore trunk balance. These CMs can cause long-period stress on the femur and may possibly alter the femoral morphology. This cross-sectional observational study aimed to answer the following questions: (a) Do SI subjects exhibit greater femoral bowing compared to subjects with sagittal balance? (b) Are there associations between femoral bowing and CMs of LE in SI subjects? Methods: Subjects who underwent biplanar full body radiographs with the EOS imaging system between January 2016 and September 2021 were recruited. Sagittal parameters included T1-pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope, lumbar lordosis (LL), PI-LL, and PT/PI ratio. LE parameters were femoral obliquity angle (FOA), knee flexion angle (KA), and ankle dorsiflexion angle. Femoral bowing was quantified as 3D radius of femoral curvature (RFC). Associations between 3D RFC and the radiographic parameters were analyzed. Results: A total of 105 subjects were included, classified into balance group (TPA < 14°, n = 40), SI group (TPA ≥ 14° and KA <5°, n = 30), and SI with knee flexion group (TPA ≥ 14° and KA ≥ 5°, n = 35). 3D RFC was significantly lower in SI with knee flexion group compared to the other two groups (both p < 0.001). Stepwise linear regression showed that age, SI and knee flexion, femoral length (FL), FOA, and KA were independent predictors for 3D RFC. Conclusion: Greater femoral bowing is observed in subjects with SI and knee flexion compared to the balanced population. CM parameters, including KA and FOA, are associated with 3D RFC. Further longitudinal study is needed to investigate the cause-and-effect relationship between SI, CMs of LE, and femoral bowing.

ADT-1004: A First-in-Class, Orally Bioavailable Selective pan-RAS Inhibitor for Pancreatic Ductal Adenocarcinoma.

Here, we evaluated in vivo antitumor activity, target engagement, selectivity, and tumor specificity of ADT-1004, an orally bioavailable prodrug of ADT-007 having highly potent and selective pan-RAS inhibitory activity. ADT-1004 strongly blocked tumor growth and RAS activation in mouse PDAC models without discernable toxicity. As evidence of target engagement and tumor specificity, ADT-1004 inhibited activated RAS and ERK phosphorylation in PDAC tumors at dosages approximately 10-fold below the maximum tolerated dose and without discernable toxicity. ADT-1004 inhibited ERK phosphorylation in PDAC tumors. In addition, ADT-1004 blocked tumor growth and ERK phosphorylation in PDX PDAC models with KRAS G12D , KRAS G12V , KRAS G12C , or KRAS G13Q mutations. ADT-1004 treatment increased CD4 + and CD8 + T cells in the TME consistent with exhaustion and increased MHCII + M1 macrophage and dendritic cells. ADT-1004 demonstrated superior efficacy over sotorasib and adagrasib in tumor models involving human PDAC cells resistant to these KRAS G12C inhibitors. As evidence of selectivity for tumors from PDAC cells with mutant KRAS, ADT-1004 did not impact the growth of tumors from RAS WT PDAC cells. Displaying broad antitumor activity in multiple mouse models of PDAC, along with target engagement and selectivity at dosages that were well tolerated, ADT-1004 warrants further development. Significance: ADT-1004 displayed robust antitumor activity in aggressive and clinically relevant PDAC models with unique tumor specificity to block RAS activation and MAPK signaling in RAS mutant cells. As a pan-RAS inhibitor, ADT-1004 has broad activity and potential efficacy advantages over allele-specific KRAS inhibitors by averting resistance. These findings support clinical trials of ADT-1004 for KRAS mutant PDAC.

Prediction of MCI-to-AD progression with atrophy-weighted standard uptake value ratios of 18 F-Florbetapir PET.

Accurate prediction of MCI-to-AD progression is an important yet challenging task. We introduce a new quantitative parameter: the atrophy-weighted standard uptake value ratio (awSUVR), defined as the PET SUVR divided by the hippocampal volume measured with MR, and evaluate whether it may provide better prediction of the MCI-to-AD progression. MATERIALS AND METHODS: We used ADNI data to evaluate the prediction performances of the awSUVR against SUVR. 571, 363 and 252 18-F-Florbetaipir scans were selected based on criteria of conversion at the third, fifth and seventh year after the PET scans, respectively. Corresponding MR scans were segmented with Freesurfer and applied on PET for SUVR and awSUVR computation. We also searched for the optimal combination of target and reference regions. In addition to evaluating the overall prediction performances, we also evaluated the prediction for APOE4 carriers and non-carriers. For the scans with false predictions, we used 18-F-Flortaucipir scans to investigate the potential source of error. RESULTS: awSUVR provides more accurate prediction than the SUVR in all three progression criteria. The 5-year prediction accuracy/sensitivity/specificity is 90/81/93% for awSUVR and 86/81/88% for SUV. awSUVR also yields good 3- and 7-year prediction accuracy/sensitivity/specificity of 91/57/96 and 92/89/93, respectively. APOE4 carriers generally are slightly more difficult to predict for the progression. False negative prediction is found to either due to a near-cutoff mis-classification or potentially non-AD dementia pathology. False positive prediction is mainly due to the slightly delayed progression than the expected progression time. CONCLUSION: We demonstrated with ADNI data that 18-F-Florbetapir SUVR weighted with hippocampus volume may provide good prediction power with over 90% accuracy in MCI-to-AD progression.

Understanding post-surgical decline in left ventricular function in primary mitral regurgitation using regression and machine learning models.

Background: Class I echocardiographic guidelines in primary mitral regurgitation (PMR) risks left ventricular ejection fraction (LVEF) < 50% after mitral valve surgery even with pre-surgical LVEF > 60%. There are no models predicting LVEF < 50% after surgery in the complex interplay of increased preload and facilitated ejection in PMR using cardiac magnetic resonance (CMR). Objective: Use regression and machine learning models to identify a combination of CMR LV remodeling and function parameters that predict LVEF < 50% after mitral valve surgery. Methods: CMR with tissue tagging was performed in 51 pre-surgery PMR patients (median CMR LVEF 64%), 49 asymptomatic (median CMR LVEF 63%), and age-matched controls (median CMR LVEF 64%). To predict post-surgery LVEF < 50%, least absolute shrinkage and selection operator (LASSO), random forest (RF), extreme gradient boosting (XGBoost), and support vector machine (SVM) were developed and validated in pre-surgery PMR patients. Recursive feature elimination and LASSO reduced the number of features and model complexity. Data was split and tested 100 times and models were evaluated via stratified cross validation to avoid overfitting. The final RF model was tested in asymptomatic PMR patients to predict post-surgical LVEF < 50% if they had gone to mitral valve surgery. Results: Thirteen pre-surgery PMR had LVEF < 50% after mitral valve surgery. In addition to LVEF (P = 0.005) and LVESD (P = 0.13), LV sphericity index (P = 0.047) and LV mid systolic circumferential strain rate (P = 0.024) were predictors of post-surgery LVEF < 50%. Using these four parameters, logistic regression achieved 77.92% classification accuracy while RF improved the accuracy to 86.17%. This final RF model was applied to asymptomatic PMR and predicted 14 (28.57%) out of 49 would have post-surgery LVEF < 50% if they had mitral valve surgery. Conclusions: These preliminary findings call for a longitudinal study to determine whether LV sphericity index and circumferential strain rate, or other combination of parameters, accurately predict post-surgical LVEF in PMR.

Evidence of neuroinflammation in fibromyalgia syndrome: a [ 18 F]DPA-714 positron emission tomography study.

ABSTRACT: This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs), as measured with positron emission tomography using [ 18 F]DPA-714, a second-generation radioligand for the translocator protein (TSPO). Fifteen women with FM and 10 HCs underwent neuroimaging. Distribution volume (V T ) was calculated for in 28 regions of interest (ROIs) using Logan graphical analysis and compared between groups using multiple linear regressions. Group (FM vs HC) was the main predictor of interest and TSPO binding status (high- vs mixed-affinity) was added as a covariate. The FM group had higher V T in the right postcentral gyrus ( b = 0.477, P = 0.033), right occipital gray matter (GM; b = 0.438, P = 0.039), and the right temporal GM ( b = 0.466, P = 0.042). The FM group also had lower V T than HCs in the left isthmus of the cingulate gyrus ( b = -0.553, P = 0.014). In the subgroup of high-affinity binders, the FM group had higher V T in the bilateral precuneus, postcentral gyrus, parietal GM, occipital GM, and supramarginal gyrus. Group differences in the right parietal GM were associated with decreased quality of life, higher pain severity and interference, and cognitive problems. In support of our hypothesis, we found increased radioligand binding (V T ) in the FM group compared with HCs in several brain regions regardless of participants' TSPO binding status. The ROIs overlapped with prior reports of increased TSPO binding in FM. Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain.

A universal programmable Gaussian boson sampler for drug discovery.

Gaussian boson sampling (GBS) has the potential to solve complex graph problems, such as clique finding, which is relevant to drug discovery tasks. However, realizing the full benefits of quantum enhancements requires large-scale quantum hardware with universal programmability. Here we have developed a time-bin-encoded GBS photonic quantum processor that is universal, programmable and software-scalable. Our processor features freely adjustable squeezing parameters and can implement arbitrary unitary operations with a programmable interferometer. Leveraging our processor, we successfully executed clique finding on a 32-node graph, achieving approximately twice the success probability compared to classical sampling. As proof of concept, we implemented a versatile quantum drug discovery platform using this GBS processor, enabling molecular docking and RNA-folding prediction tasks. Our work achieves GBS circuitry with its universal and programmable architecture, advancing GBS toward use in real-world applications.

Parametric imaging with Bayesian priors: a validation study with (11)C-Altropane PET.

It has been suggested that Bayesian estimation methods may be used to improve the signal-to-noise ratio of parametric images. However, there is little experience with the method and some of the underlying assumptions and performance properties of Bayesian estimation remain to be investigated. We used a sample population of 54 subjects, studied previously with (11)C-Altropane, to empirically evaluate the assumptions, performance and some practical issues in forming parametric images. By using normality tests, we showed that the underpinning normality assumptions of data and parametric distribution apply to more than 80% of voxels. The standard deviation of the binding potential can be reduced 30-50% using Bayesian estimation, without introducing substantial bias. The sample size required to form the a priori information was found to be modest; as little as ten subjects may be sufficient and the choice of specific subjects has little effect on Bayesian estimation. A realistic simulation study showed that detection of localized differences in parametric images, e.g. by statistical parametric mapping (SPM), could be made more reliable and/or conducted with smaller sample size using Bayesian estimation. In conclusion, Bayesian estimation can improve the SNR of parametric images and better detect localized changes in cohorts of subjects.

Single-scan rest∕stress imaging (18)F-labeled flow tracers.

PURPOSE: The authors report a novel measurement strategy to obtain both rest and stress blood flow during a single, relatively short, scan session. METHODS: Measurement of rest-stress myocardial blood flow with long-lived tracers usually requires separate scan sessions to remove the confounding effects of residual radioactivity concentration in the blood and tissue. The innovation of this method is to treat the rest-stress scan as a single entity in which the flow parameters change due to pharmacological challenge. With this approach the fate of a tracer molecule is naturally accounted for, no matter if it was introduced during the rest or stress phase of the study. Two new dual-injection kinetic models are considered that represent the response to pharmacological stress as a transitional or transient increase of myocardial blood flow. The authors present the theory of the method followed by the specific application of the theory to (18)F-Flurpiridaz, a new myocardial flow-imaging agent. RESULTS: Myocardial blood flow was accurately and precisely estimated from a single-scan rest∕stress study for the long half-lived tracer (18)F-Flurpiridaz. By accounting for the time-dependence of the kinetic parameters, the proposed models achieved good accuracy and precision (5%) under different vasodilators and different ischemic states. CONCLUSIONS: Detailed simulations predict that accurate and precise rest-stress blood flow measurements can be obtained in 20-30 min.

[Clinical observation of treating 62 patients with severe aplastic anemia failing in immunosuppressive therapy by integrative medicine].

OBJECTIVE: To explore treatment methods for patients with severe aplastic anemia (SAA) failing in immunosuppressive therapy (IST). METHODS: Totally 62 SAA patients failing in IST were treated by integrative medicine (IM). The treatment course was divided into three stages: the critical emergency stage, the improvement stage, and the recovery stage. In the critical emergency stage, patients were treated with Lingyang Yigui Decoction (LYD, consisting of 1.2 g antelope horn, 6 g coptis chinensis, 12 g stir-baked Fructus Gardeniae, 30 g rehmannia rhizoma, 50 g lalang grass rhizome, 9 g amur corktree bark, 12 g Cortex Moutan, 9 g ass-hide gelatin, 30 g red date, 6 g prepared licorice root, etc.) and Erzhi Busui Decoction (EBD, consisting of 120 g glossy privet fruit, 100 g eclipta prostrata, 24 g prepared Gold Theragran, 12 g fructus lycii, 90 g rehmannia rhizoma, 60 g astragalus, 9 g Angelica sinensis, 9 g ass-hide gelatin, 30 g honeysuckle flower, 12 g lotus plumule, and so on) alternatively, one dose daily, decocted twice, taken in two portions. Meanwhile, 50 mg Testosterone Propionate was intramuscularly injected every other day to the improvement stage. Those with fever were treated with LYD by adding 60 g gypsum, 60 g common anemarrhena, 30 g dandelion, 30 g bittersweet herb, 30 g blackend swallowwort root and rhizome, 15 g hemsley rockvine root tuber, and so on. In the improvement stage patients were treated with Jixueteng Compound (Jixueteng Zhengyang Decoction was administered to those of Shen-yang deficiency syndrome: consisting of 100 g spatholobus suberectus, 60 g astragalus, 3 g red ginseng, 12 g psoralea corylifolia, 18 g dodder seed, 12 g angelica, 18 g Herba Epimedii, 6 g common fenugreek seed, 24 g Gold Theragran, 30 g glossy privet fruit, 30 g eclipta prostrata, 6 g dried human placenta, and so on). Meanwhile, 50 mg Testosterone Propionate was intramuscularly injected every other day. Jixueteng Yijing Decoction was administered to those of Shen-yin deficiency syndrome: consisting of 100 g glossy privet fruit, 100 g eclipta prostrata, 90 g rehmannia rhizoma, 30 g spatholobus suberectus, 12 g dodder seed, 6 g psoralea corylifolia, 30 g prepared Gold Theragran, 9 g ass-hide gelatin, 9 g fructus lycii, 24 g Salvia miltiorrhiza, 30 g astragalus, 6 g angelica, and so on), one dose daily, decocted twice, taken in two portions. The treatment lasted to the recovery stage. The medication was gradually reduced to the follow-ups of drug discontinuance. Results After 6 -57 months of treatment, 12 patients (accounting for 19.4%) were basically cured, 14 (22.6%) relieved, 8 (12. 9%) markedly improved, 28 (45.2%) ineffectively, with the total effective rate of 54. 8%. Totally 23 patients had the body temperature ranging 37.6-38.5 degrees C at the first visit to our hospital. They took 2 h- 6 days to have pyretolysis ( <37.5 degrees C) after treatment. Twenty patients with body temperature higher than 38.5 degrees C took 4 h - 5 days to have pyretolysis after treatment. Totally 26 patients suffering from IST induced abnormalities of liver and renal functions (ALT, AST, BUN, and Cr) at the first visit were treated by IM for 2 months. They were restored to the normal levels in 25 cases. CONCLUSIONS: The treatment of SAA failing in IST had its specificity. The staging targeted treatment is in line with its pathophysiology. The key points for its treatment might be lie in the improvement and protection of hematopoietic microenvironment of bone marrows. The antisepsis and anti-inflammation of Chinese herbs hindered its aggravating tendency.

Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method.

There is a growing interest in using 18F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of 18F-DPA-714 binding can be achieved through kinetic modeling analysis with an arterial input function (AIF) measured with blood sampling procedures, the invasiveness of such procedures has been an obstacle for wide application. To address these challenges, we developed an image-derived input function (IDIF) that noninvasively estimates the arterial input function from the images acquired for 18F-DPA-714 quantification. Methods: The method entails three fully automatic steps to extract the IDIF, including a segmentation of voxels with highest likelihood of being the arterial blood over the carotid artery, a model-based matrix factorization to extract the arterial blood signal, and a scaling optimization procedure to scale the extracted arterial blood signal into the activity concentration unit. Two cohorts of human subjects were used to evaluate the extracted IDIF. In the first cohort of five subjects, arterial blood sampling was performed, and the calculated IDIF was validated against the measured AIF through the comparison of distribution volumes from AIF (VT,AIF) and IDIF (VT,IDIF). In the second cohort, PET studies from twenty-eight healthy controls without arterial blood sampling were used to compare VT,IDIF with VT,REF measured using a reference region-based analysis to evaluate whether it can distinguish high-affinity (HAB) and mixed-affinity (MAB) binders. Results: In the arterial blood-sampling cohort, VT derived from IDIF was found to be an accurate surrogate of the VT from AIF. The bias of VT, IDIF was −5.8 ± 7.8% when compared to VT,AIF, and the linear mixed effect model showed a high correlation between VT,AIF and VT, IDIF (p < 0.001). In the nonblood-sampling cohort, VT, IDIF showed a significance difference between the HAB and MAB healthy controls. VT, IDIF and standard uptake values (SUV) showed superior results in distinguishing HAB from MAB subjects than VT,REF. Conclusions: A novel IDIF method for 18F-DPA-714 PET quantification was developed and evaluated in this study. This IDIF provides a noninvasive alternative measurement of VT to quantify the TSPO binding of 18F-DPA-714 in the human brain through dynamic PET scans.

Generative Adversarial Network (GAN) for Automatic Reconstruction of the 3D Spine Structure by Using Simulated Bi-Planar X-ray Images.

In this study, we modified the previously proposed X2CT-GAN to build a 2Dto3D-GAN of the spine. This study also incorporated the radiologist's perspective in the adjustment of input signals to prove the feasibility of the automatic production of three-dimensional (3D) structures of the spine from simulated bi-planar two-dimensional (2D) X-ray images. Data from 1012 computed tomography (CT) studies of 984 patients were retrospectively collected. We tested this model under different dataset sizes (333, 666, and 1012) with different bone signal conditions to observe the training performance. A 10-fold cross-validation and five metrics-Dice similarity coefficient (DSC) value, Jaccard similarity coefficient (JSC), overlap volume (OV), and structural similarity index (SSIM)-were applied for model evaluation. The optimal mean values for DSC, JSC, OV, SSIM_anteroposterior (AP), and SSIM_Lateral (Lat) were 0.8192, 0.6984, 0.8624, 0.9261, and 0.9242, respectively. There was a significant improvement in the training performance under empirically enhanced bone signal conditions and with increasing training dataset sizes. These results demonstrate the potential of the clinical implantation of GAN for automatic production of 3D spine images from 2D images. This prototype model can serve as a foundation in future studies applying transfer learning for the development of advanced medical diagnostic techniques.