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Vision-based methods have shown great potential in vibration-based structural health monitoring (SHM). However, these methods are not standard practices yet, since their accuracy and robustness may be influenced by extreme environmental conditions. To this end, this paper proposed a method, named dynamic regularized total variation correlation filter (DTVCF). In DTVCF, an effective optimization problem, which contains the space and structural shape information, is defined for dynamically updating the regularization weight map. Then the regularization weight map is smoothed by a total variation (TV) optimization. These are to better track the dramatically changing or almost invisible structural shape, caused by extreme environmental conditions. Moreover, efficient subpixel image registration (ESR) is used in each tracked region of interest (ROI), over time, to achieve subpixel accuracy. The superiority of DTVCF was validated in extreme environmental conditions. DTVCF could achieve subpixel level structural displacement estimation with high accuracy. Furthermore, DTVCF could process approximately 9.00 frame/s, and 3.50 frame/s in two shaking table tests, indicating its high efficiency for SHM applications. [ABSTRACT FROM AUTHOR]

Objectives: To establish and validate a predictive model integrating with clinical and dual-energy CT (DECT) variables for individual recurrence-free survival (RFS) prediction in early-stage glottic laryngeal cancer (EGLC) after larynx-preserving surgery. Methods: This retrospective study included 212 consecutive patients with EGLC who underwent DECT before larynx-preserving surgery between January 2015 and December 2018. Using Cox proportional hazard regression model to determine independent predictors for RFS and presented on a nomogram. The model's performance was assessed using Harrell's concordance index (C-index), time-dependent area under curve (TD-AUC) plot, and calibration curve. A risk stratification system was established using the nomogram with median scores of all cases to divide all patients into two prognostic groups. Results: Recurrence occurred in 39/212 (18.4%) cases. Normalized iodine concentration in arterial (NICAP) and venous phases (NICVP) were verified as significant predictors of RFS in multivariate Cox regression (hazard ratio [HR], 4.2; 95% confidence interval [CI]: 2.3, 7.7, p <.001 and HR, 3.0; 95% CI: 1.5, 5.9, p =.002, respectively). Nomogram based on clinical and DECT variables was better than did only clinical variables. The prediction model proved well-calibrated and had good discriminative ability in the training and validation samples. A risk stratification system was built that could effectively classify EGLC patients into two risk groups. Conclusions: DECT could provide independent RFS indicators in patients with EGLC, and the nomogram based on DECT and clinical variables was useful in predicting RFS at several time points. Key Points: • Dual-energy CT(DECT) variables can predict recurrence-free survival (RFS) after larynx-preserving surgery in patients with early-stage glottic laryngeal cancer (EGLC). • The model that integrates clinical and DECT variables predicted RFS better than did only clinical variables. • A risk stratification system based on the nomogram could effectively classify EGLC patients into two risk groups. [ABSTRACT FROM AUTHOR]

To study the seismic behavior of composite-sectioned high strength concrete filled steel tubular (CSCFT) columns, quasi-static tests on six specimens were conducted. The test variables included the axial force ratio, wall thickness and width-to-thickness ratio of square steel tube, confinement index of circular concrete filled steel tube (CFT). Test results indicate that the failure mode of the CSCKF column specimens is characterized by wall buckling of square steel tube and crushing of partial concrete between the square steel tube and the circular steel tube within a height of 300mm from the column base. The lateral force-displacement hysteretic loops are plump. At the peak lateral force, the drift ratio of one specimen is a little bit less than 1/100 since it has a design value of axial force ratio close to 1.0, and the drift ratios of other 5 specimens are larger than 1/100. As the wall width-to-thickness ratio of square steel tube reduced, or the confinement index of CFT increased, the initial secant stiffness and the ultimate drift ratio are increased. As the wall thickness of square steel tube increased, the bending strength of specimen under axial compressive force is enhanced. The bending strength of the specimens calculated by the superposition method and by the plane section assumption has good agreement with the test results. [ABSTRACT FROM AUTHOR]

Abstract: We have demonstrated that D5 and D2 dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D5 receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D2 receptor two adjacent arginine residues. Any pairing of these three D5 receptor glutamic acids were sufficient for heteromer formation. These identified residues in D5 and D2 receptors are oppositely charged and likely interact by electrostatic interactions. [Copyright &y& Elsevier]

This study proposes a deep neural network-based wind energy assessment method, aiming to systematically evaluate the effects of the spatiotemporal variations in air density on wind energy assessment in China. On this basis, the spatiotemporal patterns of air density are modelled on a high-spatial-resolution scale (1000 m × 1000 m). The influence of the spatiotemporal distribution characteristics of air density on the wind energy production is quantified, and the spatiotemporal variability of the corresponding wind energy production is estimated. The results demonstrate that changes in air density during the year present typical periodic characteristics. The mean air density value in January is 1.079 kg/m3, the highest throughout the year. The difference in mean air density between cold and warm seasons in the study area shows a decreasing law of higher in the northeast and lower in the southwest. When the elevation is less than 3500 m, it reaches 5.06%. The observed spatiotemporal variability in annual energy production exhibits a distinct seasonal cycle, with the highest production appears in spring (2.968 GWh/yr). The total annual energy production in the cold season is 16.08 GWh/yr, whereas the annual energy production decreases by higher than 23.46% when it comes to the warm season. • A new wind energy assessment method based on deep neural network was developed. • High-spatial resolution mapping for the spatiotemporal distribution of air density. • Changes in air density during the year present typical periodic characteristics. • The influence of variations in air density on energy production is quantified. • Assessment of variability in energy production at different spatiotemporal scales. [ABSTRACT FROM AUTHOR]

Vision-based structural motion estimation methods show great potential in structural health monitoring (SHM). However, available methods cannot automatically estimate and eliminate three-dimensional (3D) camera motion effects caused by environmental factors from the video containing structural motions. This limits further applications of vision-based methods in SHM. To this end, this paper proposed a target-free video measurement method, which is formulated as a feature point congealing problem, and its solution includes two steps. First, the links of feature points from stationary backgrounds are assumed to have consistent and smooth motions, and are detected by a maximum a posteriori (MAP) estimation of the Bayesian model. Second, based on the detected links, the joint homography matrix containing only 3D camera motion effects can be updated iteratively, by minimizing transformation differences between the current frame and other frames. The superiority of the proposed method over traditional methods was validated in case studies of Humen bridge motion estimations. It was shown the proposed method has the best performance in video stabilization and camera motion effects estimation. Moreover, combined with the phase-based method, subpixel small structural motions can be well estimated. • The proposed method can estimate 3D camera motion effects from the video containing structural motions. • When using the proposed method, manual selections and trainings can be avoided. • The proposed method was validated in estimaing 3D camera motion effects imposed with earthquake motions. [ABSTRACT FROM AUTHOR]

[Display omitted] • PMS can be photocatalytic activated by multi-phase CdS loaded on biochar. • Adsorption energy of peroxymonosulfate is improved by π-conjugation. • Oiii is the primary location for adsorption and activation of PMS by CdS@BC at 298 K. Mounting evidence highlights the negative impacts of thiamethoxam (THM) on non-target organisms and ecosystem. Herein, multi-phase cadmium sulfide loaded on biochar (CdS@BC) was used to photocatalytic activate peroxymonosulfate (PMS) to remove THM. The obtained CdS@BC significantly improved the photocatalytic performance of PMS on THM degradation with a superior rate constant of 0.165 min−1, 60 times more than that of BC. In addition, the catalyst displayed excellent stability and reusability. The mechanism of free radical formation by adsorption activation of PMS adsorbed on CdS@BC was characterized using active species detection and Density functional theory (DFT) calculations. According to the DFT study, the phase junction and π-conjugated structure contribute to the stable migration of π-electrons, thus effectively activating the PMS to produce active substances for the degradation of THM. The findings provide a theoretical basis for the design and synthesis of effective catalysts for AOPs to remove emerging organic contaminants from wastewater. [ABSTRACT FROM AUTHOR]

Serotonin modulates many motivated behaviours via multiple receptor subtypes. Agonists at 5-HT 2 C receptors have potential for treating behavioural problems associated with obesity and drug use. In this work we examined the impact of the 5-HT 2C receptor agonist lorcaserin on several motivated behaviours related to feeding, reward and waiting impulsivity, and on neuronal activation in key brain areas mediating those behaviours. In male C57BL/6J mice effects of lorcaserin (0.2, 1 and 5 mg/kg) were examined on feeding, and on operant responding for a palatable reward. Feeding was reduced only at 5 mg/kg, whereas operant responding was reduced at 1 mg/kg. At a much lower dose range lorcaserin 0.05–0.2 mg/kg also reduced impulsive behaviour measured as premature responding in the 5-choice serial reaction time (5-CSRT) test, without affecting attention or ability to perform the task. Lorcaserin induced Fos expression in brain regions related to feeding (paraventricular nucleus and arcuate nucleus), reward (ventral tegmental area), and impulsivity (medial prefrontal cortex, VTA) although these effects did not show the same differential sensitivity to lorcaserin as the behavioural measures. These results indicate a broad profile of action of 5-HT 2C receptor stimulation on brain circuitry and on motivated behaviours, but with clear evidence of differential sensitivity across behavioural domains. This is exemplified by the fact that impulsive behaviour was reduced at a much lower dose range than was feeding behaviour. Along with previous work, and some clinical observations, this work supports the idea that 5-HT 2C agonists may be useful for behavioural problems associated with impulsivity. • The 5-HT 2C agonist lorcaserin reduced feeding, operant responding, and impulsivity. • Lorcaserin activated brain regions mediating all three behavioural domains. • Impulsive behaviour was much more sensitive to effects of lorcaserin than was feeding. • 5-HT 2C agonists may be useful for behavioural problems associated with impulsivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A Z-scheme photocatalyst g-C 3 N 4 with N 2C -type defects/MoO 3 was synthesized. • The optimal composite materials could photodegrade 100 % MC-LR within 25 min. • D-CN/MoO 3 exhibits great adaptability and reusability to eutrophic water bodies. • MC-LR has multiple free radical degradation pathways in photodegradation. Algal blooms have resulted in the buildup of microcystin (MC-LR) in water bodies, posing a severe hazard to the safety of the aquatic ecosystem and human health. This study produced a g-C 3 N 4 with N 2C -type defects/MoO 3 Z-scheme photocatalyst (D-CN/MoO 3) for MC-LR degradation in visible light. D-CN/MoO 3 could photodegrade 100 % MC-LR within 25 min, which was substantially more significant than pure g-C 3 N 4 (12.5%). Meanwhile, the kinetic constant was 32.5 times higher than pure g-C 3 N 4 , attributed to the defect engineering and Z-scheme heterojunction cooperative interaction. Based on the LC-MS results, the vital degradation mechanism is the selective assault of 1O 2 on the Adda side chain of MC-LR and the following decarboxylation reaction of h+, which leads to effective mineralization and reduced toxicity of MC-LR. Moreover, the excellent stability and adaptability of D-CN/MoO 3 are verified and have a significant potential for application in the decontamination of MC-LR in eutrophic water. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new joint probability density function of air density and wind speed was developed. • Integration of the air density distribution into statistical wind resource models. • Introduction to Weibull–Gamma distribution for fitting air density distributions. • Modelling of bivariate air density and wind speed distributions with Gumbel copulas. • Mean annual energy production is higher than 7.00 GWh/yr for 4.62% of the study area. This paper proposes a joint probability density function of air density and wind speed, aiming to integrate the air density distribution into statistical wind resource models, thereby helping better understand the correlation between air density and wind speed at different spatiotemporal scales. Hourly air pressure, temperature, and wind speed time series data from 1745 meteorological stations distributed over China for the period 2008–2019 were used to calculate the empirical distributions of air density and wind speed. Four one-component probability density functions and ten two-component mixture probability density functions were fitted to the empirical distributions. It is indicated that the five-parameter Weibull–Gamma distribution is able to achieves more accurate and stable effects in both unimodal and bimodal air density empirical distribution, and the six-parameter Weibull–Burr distribution is the most appropriate distribution for describing wind speed regimes. The parameterised air density and wind speed marginal distributions were linked using five joint copulas. The goodness-of-fit evaluation of the copula models demonstrates that the Gumbel copula most accurately reproduces the bivariate empirical distribution of air density and wind speed. The application of joint distribution has the capability to simplify the evaluation procedures for wind resource assessment while significantly increasing the accuracy of the evaluation results, and also achieve a systematic assessment of available wind resources, considering the temporal patterns of air density. The results of this study will contribute to offering critical information for making better decisions on wind energy projects to realise full development and effective utilisation of wind resources. [ABSTRACT FROM AUTHOR]

• A new GFRP-bamboo shear connection composed of pultruded H-section GFRP profile and engineered bamboo was proposed. • A total of 46 specimens with three types of connections including bolted, glue and hybrid connectors were studied by push-out tests. • The experimental results were compared with the predicted values using Eurocode 5-1995 and GB/T 50005-2017 to evaluate their serviceability. • Theoretical model based on Foschi formula was built to predict the load-slip relationship. Sustainable development has become an important and urgent topic for civil engineering. More and more green and renewable materials, like engineered bamboo, have been designed to work with other traditional building materials to utilize the ecological benefit and mechanical advantages. Nonetheless, few researches investigated the mechanical performance of the composite structure made of fiber-reinforced polymer and engineered bamboo. A new composite connection made of pultruded H-section glass fiber-reinforced polymer (GFRP) profile and engineered bamboo was proposed and studied by push-out tests to assess the shear performance. A total of 46 specimens with bolted, glue or hybrid connectors were tested to investigate the influence of the connection type, bolt diameter and spacing, as well as the bamboo thickness, on the strength and stiffness of GFRP-bamboo connections. The load-carrying capacity and shear stiffness were analyzed, and three types of failure modes were identified. When the bamboo thickness was 17 mm and 20 mm, a single plastic hinge was formed in the shear connectors, and the bamboo panels performed splitting and edge crushing failures. When the bamboo thickness was 34 mm and 40 mm, two plastic hinges formed in the connectors with embedment failure in the bamboo panels. Nonetheless, when using glue connection, brittle and undesirable failure occurred. When increasing the bamboo thickness from 17 mm to 34 mm, the average peak load increased from 67.52 kN to 100.64 kN, and the yield and ultimate loads both increased by about 49%. In addition, the results showed that hybrid connections were more effective than bolted and glue connections. The average peak load of hybrid connections increased by 42.72% and 13.16% compared to that connected with glue and bolts, respectively. The experimental results were compared with those calculated according to Eurocode 5-1995 and GB/T50005-2017, and it could be concluded that the formulas of the codes were not suitable for such shear connections due to the conservative design. To predict the nonlinear behavior of the specimens, the theoretical model based on Foschi formula was built. The analytical predictions showed good agreement with the test results in case of bolted connections. In a word, the shear performance and theoretical model of the proposed composite shear connections make it possible to predict the bending strength and stiffness of GFRP-bamboo composite beams, but the sharp drop of load-carrying capacity induced by the failure of glue connection needs more consideration and research. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to explore the importance of an MRI-based radiomics nomogram in predicting the progression-free survival (PFS) of endometrial cancer. Methods: Based on clinicopathological and radiomic characteristics, we established three models (clinical, radiomics and combined model) and developed a nomogram for the combined model. The Kaplan-Meier method was utilized to evaluate the association between nomogram-based risk scores and PFS. Results: The nomogram had a strong predictive ability in calculating PFS with areas under the curve (ROC) of 0.905 and 0.901 at 1 and 3 years, respectively. The high-risk groups identified by the nomogram-based scores had shorter PFS compared with the low-risk groups. Conclusion: The radiomics nomogram has the potential to serve as a noninvasive imaging biomarker for predicting individual PFS of endometrial cancer.

Background: Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear., Purpose: To evaluate the efficacy and mechanism of Geniposide in treating AS., Study Design and Methods: Geniposide was administered to high-fat diet-fed ApoE -/- mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression., Results: In vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1., Conclusion: Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM., Methods: Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted., Results: Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model., Conclusions: The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Du, Zhu, Lu, Wu, Zhang, Ji and Zheng.)

COVID-19 caused by Omicron BA.1 has resulted in a global humanitarian crisis. In this COVID-19 pandemic era, hypertension has been receiving increased attention. Omicron BA.1 infection combined with hypertension created a serious public health problem and complicated the treatment and prognosis of COVID-19. The aim of our study was to assess the implications of hypertension for the clinical manifestations of adult patients (APs) infected with Omicron BA.1. This single-center retrospective cohort study enrolled consecutive COVID-19 APs, who were admitted to Tianjin First Central Hospital from 01 August 2022 to 30 November 2022. All included APs were divided into two groups: hypertension and non-hypertension group. The APs' baseline demographic, laboratory, clinical, and radiological characteristics were collected and analyzed. Of 512 APs admitted with PCR proven COVID-19, 161 (31.45%) APs had comorbid hypertension. Hypertension APs have older age, higher body mass index, lower Ct-values of the viral target genes at admission, and longer hospital stay than non-hypertension APs. Furthermore, hypertension aggravates the clinical classification, impairs liver, kidney, and myocardium function, and abnormalizes the coagulation system in Omicron BA.1- infected APs. Moreover, hypertension elevates inflammation levels and lung lesion involvement while weakened virus-specific IgM level in APs with Omicron BA.1 infection. Hypertension APs tend to have worse clinical conditions at baseline than those non-hypertension APs. This study indicates that hypertension is a contributor to the poor clinical manifestations of Omicron BA.1-infected APs and supports that steps to control blood pressure should be a vital consideration for reducing the burden of Omicron BA.1 infection in hypertension individuals., Importance: This study provided inclusive insight regarding the relationship between hypertension and Omicron BA.1 infection and supported that hypertension was an adverse factor for COVID-19 APs. In conclusion, this study showed that hypertension was considered to be associated with severe conditions, and a contributor to poor clinical manifestations. Proper medical management of hypertension patients is an imperative step in mitigating the severity of Omicron BA.1 variant infection., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the impact of critical care management on patients diagnosed with acute respiratory distress syndrome (ARDS) during their stay in intensive care units (ICU)., Methods: A total of 62 ARDS patients admitted to the ICU of our hospital between March 2020 and March 2023 were enrolled as research participants. The patients were randomly assigned to either the research group (n=31) receiving critical care management or the control group (n=31) receiving routine care. Key parameters, including the duration of ICU stay, mean hospital length of stay (HLOS), duration of mechanical ventilation, and the incidence of ventilator-associated pneumonia (VAP), were recorded. Additionally, changes in the Self-rating Anxiety/Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI), Acute Physiology and Chronic Health Evaluation II (APACHE), and Clinical Pulmonary Infection Score (CPIS) were assessed before and after the intervention. A self-designed questionnaire was employed to evaluate nursing quality and patient satisfaction., Results: In comparison to the control group, the research group exhibited significantly shorter durations of ICU stay, mean HLOS, and mechanical ventilation, along with a reduced incidence of VAP (P < .05). Moreover, the SAS, SDS, PSQI, APACHE II, and CPIS scores in the research group were lower than those in the control group, while the quality of care and satisfaction scores were notably higher (P < .05)., Conclusions: ICU critical care management demonstrates the potential to enhance the rehabilitation of ARDS patients and decrease the incidence of VAP, suggesting its clinical applicability.

Aim: To assess baseline histogram parameters from apparent diffusion coefficient (ADC) images in predicting early treatment response in newly diagnosed multiple myeloma (NDMM) patients. Methods: The histogram parameters of lesions in 68 NDMM patients were obtained with the Firevoxel software. The presence of deep response after two cycles of induction was recorded. Results: Some parameters were significantly different between the two groups, for example, ADC 75% in lumbar spine (p = 0.026). No significant difference in mean ADC for any anatomic site was found (all p > 0.05). The combination of ADC 75, ADC 90 and ADC 95% in lumbar spine; ADC skewness and ADC kurtosis in rib achieved a sensitivity of 100% in predicting deep response. Conclusion: Histogram analysis of ADC images can describe NDMM heterogeneity and accurately predict treatment response.

BACKGROUND . The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE . The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS . This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS . A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10 -3 mm 2 /s vs 1.08 × 10 -3 mm 2 /s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10 -3 mm 2 /s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION . Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT . WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.

The multiplexed cancer cell line screening platform PRISM demonstrated its utility in testing hundreds of cell lines in a single run, possessing the potential to speed up anti-cancer drug discovery, validation and optimization. Here we described the development and implementation of a next-generation PRISM platform combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated gene editing, cell line DNA barcoding and next-generation sequencing to enable genetic and/or pharmacological assessment of target addiction in hundreds of cell lines simultaneously. Both compound and CRISPR-knockout PRISM screens well recapitulated the results from individual assays and showed high consistency with a public database.

Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

We have demonstrated that D(5) and D(2) dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D(5) receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D(2) receptor two adjacent arginine residues. Any pairing of these three D(5) receptor glutamic acids were sufficient for heteromer formation. These identified residues in D(5) and D(2) receptors are oppositely charged and likely interact by electrostatic interactions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The crystal structure of the mu and kappa opioid receptors has revealed dimeric structural arrangements. Mu-delta receptors heteromers also exist and we have identified discrete cytoplasmic regions in each receptor required for oligomer formation. In the carboxyl tail of the delta receptor we identified three glycine residues (-GGG), substitution of any of these residues prevented heteromer formation. In intracellular loop 3 of both mu and delta receptors we identified three residues (-SVR), substitution of any of these residues prevented heteromer formation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

D(1) and D(2) dopamine receptors exist as heteromers in cells and brain tissue and are dynamically regulated and separated by agonist concentrations at the cell surface. We determined that these receptor pairs interact primarily through discrete amino acids in the cytoplasmic regions of each receptor, with no evidence of any D(1)-D(2) receptor transmembrane interaction found. Specifically involved in heteromer formation we identified, in intracellular loop 3 of the D(2) receptor, two adjacent arginine residues. Substitution of one of the arginine pair prevented heteromer formation. Also involved in heteromer formation we identified, in the carboxyl tail of the D(1) receptor, two adjacent glutamic acid residues. Substitution of one of the glutamic acid pair prevented heteromer formation. These amino acid pairs in D(1) and D(2) receptors are oppositely charged, and presumably interact directly by electrostatic interactions., (Copyright © 2011 Elsevier Inc. All rights reserved.)