Treatment with Sacubitril/Valsartan Effectively Manages Hypertension and Ameliorates Left Ventricular Hypertrophy in Hemodialysis Patients.

INTRODUCTION: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. METHODS: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. RESULTS: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = -4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. CONCLUSION: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load.

Development of a sensitive droplet digital PCR according to the HPV infection specificity in Chinese population.

HPV16 and 18 are positively correlated with cervical carcinogenesis. However, HPV prevalence tends to vary according to region, nationality, and environment. The most prevalent high-risk (HR) HPV genotypes are HPV16, 52, 58, 56, 18, 33, and 45), while the low-risk (LR) genotypes are HPV6 and 11 in the Chinese population. Importantly, undetectable low-copy HPV DNA could be an important indicator of integration into the human genome and may be a precursor to cancer progression. The HPV viral load changes dramatically, either increasing or decreasing rapidly during carcinogenesis, and traditional quantitative real-time PCR (qPCR) cannot accurately capture this subtle change. Therefore, in this study, a reliable droplet digital PCR (ddPCR) method was developed to simultaneously detect and quantify HPV genotypes. The ddPCR quantitative results showed high accuracy, sensitivity, and specificity compared to qPCR results employing the same clinical specimens and supplemented the ddPCR assay for HPV52/56/58/6 genotypes according to the infection specificity of the Chinese population. In summary, this procedure is valuable for quantifying HPV DNA, especially under conditions of low template copy number in cervical intraepithelial neoplasia (CIN) and/or cervical cancer. Additionally, this method can dynamically observe the prognosis and outcome of HPV infection and thus be used as an effective means for real-time monitoring of tumor load.

Association of Changes in Neural Targets and Dietary Outcomes among Patients with Comorbid Obesity and Depression: Post hoc Analysis of ENGAGE-2 Mechanistic Clinical Trial.

BACKGROUND: Disruptions in brain circuits that regulate cognition and emotion can hinder dietary change and weight loss among individuals with obesity and depression. OBJECTIVE: The study aimed to investigate whether changes in brain targets in the cognitive control, negative affect, and positive affect circuits after 2-mo problem-solving therapy (PST) predict changes in dietary outcomes at 2 and 6 mo. METHODS: Adults with obesity and depression from an academic health system were randomly assigned to receive PST (7-step problem-solving and behavioral activation strategies) over 2 mo or usual care. Seventy participants (mean age = 45.9 ± 11.6 y; 75.7% women, 55.7% Black, 17.1% Hispanic, 20.0% White; mean BMI = 36.5 ± 5.3 kg/m2; mean Patient Health Questionnaire-9 depression score = 12.7 ± 2.8) completed functional MRI and 24-h food recalls. Ordinary least square regression analyses were performed. RESULTS: Among intervention participants, increased left dorsal lateral prefrontal cortex (dLPFC) activity of the cognitive control circuit at 2 mo was associated with increased diet quality (ß: 0.20; 95% CI: -0.02, 0.42) and decreased calories (ß: -0.19; 95% CI: -0.33, -0.04), fat levels (ß: -0.22; 95% CI: -0.39, -0.06), and high-sugar food intake (ß: -0.18; 95% CI: -0.37, 0.01) at 6 mo. For the negative affect circuit, increased right dLPFC-amygdala connectivity at 2 mo was associated with increased diet quality (ß: 0.32; 95% CI: -0.93, 1.57) and fruit and vegetable intake (ß: 0.38; 95% CI: -0.75, 1.50) and decreased calories (ß: -0.37; 95% CI: -1.29, 0.54), fat levels (ß: -0.37; 95% CI: -1.50, 0.76), sodium concentrations (ß: -0.36; 95% CI: -1.32, 0.60), and alcohol intake (ß: -0.71; 95% CI: -2.10, 0.68) at 2 but not at 6 mo. The usual care group showed opposing associations. The 95% CIs of all between-group differences did not overlap the null, suggesting a significant treatment effect. CONCLUSIONS: Among adults with obesity and depression who underwent PST compared with those under usual care, improved dLPFC-amygdala regulation of negative affective brain states predicted dietary improvements at 2 mo, whereas improvements in dLPFC-based cognitive control predicted dietary improvements at 6 mo. These findings warrant confirmatory studies. This trial was at clinicaltrials.gov as NCT03841682.

Investigating the potential anti-inflammatory mechanism of benzophenone compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on network pharmacology and molecular docking strategies.

BACKGROUND: Aquilaria sinensis (Lour.) Gilg (ASG) has been used as traditional medicine for centuries. However, the active ingredients from leaves and their anti-inflammatory mechanism are rarely reported. The network pharmacology and molecular docking strategies were applied to explore the potential mechanisms of Benzophenone compounds from the leaves of ASG (BLASG) against inflammation. METHODS: BLASG-related targets were obtained from the SwissTargetPrediction and PharmMapper databases. Inflammation-associated targets were retrieved from GeneGards, DisGeNET, and CTD databases. Cytoscape software was used to draw a network diagram of BLASG and its corresponding targets. DAVID database was applied for enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify the hub targets of BLASG. Molecular docking analyses were performed by AutoDockTools 1.5.6. Moreover, we used ELISA and qRT-PCR assays to validate the anti-inflammatory effects of BLASG by cell experiments. RESULTS: Four BLASG were extracted from ASG, and corresponding 225 potential targets were identified. PPI network analysis indicated that SRC, PIK3R1, AKT1, and other targets were the core therapeutic targets. Enrichment analyses revealed that the effects of BLASG are regulated by targets associated with apoptosis and inflammation-related pathways. In addition, molecular docking revealed that BLASG combined well with PI3K and AKT1. Furthermore, BLASG significantly decreased the inflammatory cytokines levels and down-regulated PIK3R1 and AKT1 gene expression in RAW264.7 cells. CONCLUSION: Our study predicted the potential targets and pathways of BLASG against inflammation, which offered a promising strategy to reveal the therapeutic mechanism of natural active components in the treatment of diseases.

New Analysis Protocol for Stable Isotopes by a Standard Doping Method─An Example of Antimony.

The current analytical methods of stable antimony isotopes are cumbersome and not suitable for rock samples with low antimony content (<1 µg/g). In this study, we propose a new protocol for antimony isotopic analysis with a single column of AG50W-X8 resin and antimony standard doping. This method separates antimony effectively from matrices and then mixes it with the Sb standard. As Te does not affect the accuracy of antimony measurement when the Te/Sb ratio is low, we can obtain an accurate Sb isotope composition of the mixture. Then, we can calculate the antimony isotope composition of natural samples. The error propagation of the mixing and calculation processes was evaluated by the Monte Carlo method, and no significant error was found. The antimony isotope compositions were measured using a Thermo Fisher Scientific Neptune Plus multicollector-inductively coupled-mass spectrometry instrument. The instrumental mass bias of Sb isotopes was corrected with a standard-sample bracketing combined with a Sn internal normalization technique. Using the standard doping method, the measured δ123Sb values of standard solutions (Alfa, SPEX, GSB, and SCP) relative to NIST SRM 3102a were 0.02 ± 0.03‰ (2SD, N = 50), 0.29 ± 0.03‰ (2SD, N = 15), 0.24 ± 0.03‰ (2SD, N = 56), and 0.30 ± 0.03‰ (2SD, N = 15), respectively. The reproducibility for δ123Sb was better than 0.03‰ (2SD) throughout one year. This methodology has been testified by geological samples, yielding δ123Sb identical to the previously reported values. The actual Sb consumption for each sample test is as low as 5 ng. This standard doping method provides new insights into the analytical strategy of stable isotopes.

Unlocking the High Capacity Ammonium-Ion Storage in Defective Vanadium Dioxide.

Aqueous ammonium-ion storage has been considered a promising energy storage competitor to meet the requirements of safety, affordability, and sustainability. However, ammonium-ion storage is still in its infancy in the absence of reliable electrode materials. Here, defective VO2 (d-VO) is employed as an anode material for ammonium-ion batteries with a moderate transport pathway and high reversible capacity of ≈200 mAh g-1 . Notably, an anisotropic or anisotropic behavior of structural change of d-VO between c-axis and ab planes depends on the state of charge (SOC). Compared with potassium-ion storage, ammonium-ion storage delivers a higher diffusion coefficient and better electrochemical performance. A full cell is further fabricated by d-VO anode and MnO2 cathode, which delivers a high energy density of 96 Wh kg-1 (based on the mass of VO2 ), and a peak energy density of 3254 W kg-1 . In addition, capacity retention of 70% can be obtained after 10 000 cycles at a current density of 1 A g-1 . What's more, the resultant quasi-solid-state MnO2 //d-VO full cell based on hydrogel electrolyte also delivers high safety and decent electrochemical performance. This work will broaden the potential applications of the ammonium-ion battery for sustainable energy storage.

Integrated Behavioral Interventions for Adults with Comorbid Obesity and Depression: a Systematic Review.

PURPOSE OF REVIEW: To synthesize evidence from randomized controlled trials on the effects of integrated behavioral interventions for comorbid obesity and depression in adults. RECENT FINDINGS: Seven trials (n = 33 to 409) were included. The quality of evidence was mixed. In 2 trials, integrated interventions led to greater improvements in both obesity and depression over 12 months, compared with usual care. Of 4 trials comparing integrated interventions with a standalone obesity intervention, 2 showed incremental effects on depression only, and 2 did not detect a significant effect for either outcome. One 3-arm trial compared an integrated intervention with standalone obesity and depression interventions and only detected incremental effects on obesity when compared with a standalone depression intervention. The effects of integrated interventions for comorbid obesity and depression are varied but promising. Implications for future research to guide intervention optimization and implement integrated interventions in clinical practice are provided.

RBD spatial orientation of the spike protein and its binding to ACE2: insight into the high infectivity of the SARS-CoV-2 Delta variant from MD simulations.

The spike glycoprotein on the surface of the SARS-CoV-2 envelope plays an important role in its invasion into host cells. The binding of the spike glycoprotein RBD to the angiotensin-converting enzyme 2 (ACE2) receptor as a critical step in the spread of the virus has been explored intensively since the outbreak of COVID-19, but the high transmissibility of the virus such as the Delta variant is still not fully understood. Here, molecular simulations on the binding interactions of the wild-type spike protein and its four variants (Beta, Kappa, Delta, and Mu) with ACE2 and the antibody were performed, and the present results reveal that the residue mutations will not strengthen the binding affinity of the variant for ACE2, but remarkably influences the spatial orientation of the spike protein. Only the up-right conformational receptor binding domain (RBD) can bind ACE2, which is stabilized by the nearby RBDs in the down state, revealing that the RBD bears dual functional characteristics. The present results provide new insights into plausible mechanisms for high infectivity of the virus variants and their immune escape.

Integrated collaborative care intervention for depression and obesity in primary care: translation from research to practice.

The objective of this study was to present lessons learned about engagement, delivery modality and pandemic impact while delivering a collaborative care intervention with a socioeconomically, racially and ethnically diverse sample. Participants completed a post-intervention survey (n = 41) on experiences and preferred intervention delivery modality, coronavirus 2019 (COVID-19) Impact Survey (n = 50) and provided open-ended feedback about the intervention (n = 27). Intervention process data included attendance, modality, and withdrawals. Data were analyzed using descriptive statistics and inductive content analyses. Of 71 intervention participants, 6 (8%) withdrew before session 1. Completers adhered to intervention timeline better than withdrawals. Participants liked the in-person interaction, efficient coach support, accountability of in-person and Zoom vs. phone sessions and the flexibility and convenience of phone and Zoom vs. in-person sessions. A majority of participants reported experiencing pandemic impacts such as heightened emotional distress, decreased activity engagement, poorer eating behaviors and being unable to meet basic needs. Participants deviating from intervention timelines may be re-engaged by targeted outreach attempts. Videoconference has the potential for providing as-needed coaching. Future interventions may be optimized to account for and address areas impacted by the pandemic. Findings revealed specific strategies that can be implemented in future interventions to improve emotional and physical health among diverse populations.

Inoculating indoleacetic acid bacteria promotes the enrichment of halotolerant bacteria during secondary fermentation of composting.

The secondary fermentation stage is critical for stabilizing composting products and producing various secondary metabolites. However, the low metabolic rate of mesophilic bacteria is regarded as the rate-limiting stage in composting process. In present study, two indoleacetic acid (IAA)-producing bacteria (Bacillus safensis 33C and Corynebacterium stationis subsp. safensis 29B) were inoculated to strengthen the secondary fermentation stage to improve the plant-growth promoting potential of composting products. The results showed that the addition of IAA-producing bacteria promoted the assimilation of soluble salt, the condensation and aromatization of humus, and the accumulation of dissolved organic nitrogen (DON) and dissolved organic carbon (DOC). The bioaugmentation strategy also enabled faster microbial community succession during the medium-late phase of secondary fermentation. However, the colonization of Bacillus and Corynebacterium could not explain the disproportionate increase of IAA yield, which reached up to 5.6 times compared to the control group. Deeper analysis combined with physicochemical properties and microbial community structure suggested that IAA-producing bacteria might induce the increase of salinity, which enriched halotolerant bacteria capable of producing IAA, such as Halomonas, Brachybacterium and Flavobacterium. In addition, the results also proved that it was necessary to shorten secondary fermentation time to avoid IAA degradation without affecting composting maturity. In summary, enhancing secondary fermentation of composting via adding proper IAA-producing bacteria is an efficient strategy for upgrading the quality of organic fertilizer.

Accelerated increase in vegetation carbon sequestration in China after 2010: A turning point resulting from climate and human interaction.

China has increased its vegetation coverage and enhanced its terrestrial carbon sink through ecological restoration since the end of the 20th century. However, the temporal variation in vegetation carbon sequestration remains unclear, and the relative effects of climate change and ecological restoration efforts are under debate. By integrating remote sensing and machine learning with a modelling approach, we explored the biological and physical pathways by which both climate change and human activities (e.g., ecological restoration, cropland expansion, and urbanization) have altered Chinese terrestrial ecosystem structures and functions, including vegetation cover, surface heat fluxes, water flux, and vegetation carbon sequestration (defined by gross and net primary production, GPP and NPP). Our study indicated that during 2001-2018, GPP in China increased significantly at a rate of 49.1-53.1 TgC/yr2 , and the climatic and anthropogenic contributions to GPP gains were comparable (48%-56% and 44%-52%, respectively). Spatially, afforestation was the dominant mechanism behind forest cover expansions in the farming-pastoral ecotone in northern China, on the Loess Plateau and in the southwest karst region, whereas climate change promoted vegetation cover in most parts of southeastern China. At the same time, the increasing trend in NPP (22.4-24.9 TgC/yr2 ) during 2001-2018 was highly attributed to human activities (71%-81%), particularly in southern, eastern, and northeastern China. Both GPP and NPP showed accelerated increases after 2010 because the anthropogenic NPP gains during 2001-2010 were generally offset by the climate-induced NPP losses in southern China. However, after 2010, the climatic influence reversed, thus highlighting the vegetation carbon sequestration that occurs with ecological restoration.

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylation-mediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described. METHODS: Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions. RESULTS: The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH. CONCLUSION: Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

Resistance of osteosarcoma cells to the proapoptotic effects of carfilzomib involves activation of mitogen activated protein kinase pathways.

NEW FINDINGS: What is the central question of this study? Carfilzomib, a second-generation proteasome inhibitor approved for the treatment of multiple myeloma, shows efficacy against osteosarcoma. However, drug resistance remains a major challenge. What is the role of carfilzomib-induced changes in mitogen-activated protein kinase (MAPK) pathways in the sensitivity of osteosarcoma cells to the proapoptotic effects of the drug? What is the main finding and its importance? The dose-dependent antiapoptotic effects in osteosarcoma are associated with activation of MAPK signalling. Combinational targeting of MAPK signalling pathways can synergistically enhance carfilzomib-induced cell apoptosis, suggesting that MAPK inhibitors in combination with proteasome inhibitors can serve as a novel therapeutic tool for osteosarcoma. ABSTRACT: Osteosarcoma is the most common primary bone malignancy. Despite efforts to improve outcomes, the overall survival rates for osteosarcoma have remained unchanged over the past three decades. In this study, we assessed the proapoptotic effects of the second-generation proteasome inhibitor carfilzomib on osteosarcoma and investigated the potential mechanisms underlying the synergistic proapoptotic action when combined with mitogen-activated protein kinase (MAPK) inhibitors. We found that carfilzomib alone significantly inhibited cell proliferation and induced apoptosis in a dose-dependent manner, characterized by the induction of cleaved caspase 3 and poly (ADP-ribose) polymerase. More importantly, focusing on the changes of antiapoptotic B-cell lymphoma 2 (Bcl-2) family members and signalling pathways, we found a striking induction of myeloid cell leukaemia 1 (Mcl-1) and the activation of MAPK pathways. Furthermore, we observed that combinational targeting of the MAPK pathways using the specific inhibitors U0126, SP600125 or SB203580 synergistically enhanced carfilzomib-induced cell apoptosis. Notably, we found that the combinational inhibition of extracellular signal-regulated kinase or c-Jun N-terminal kinase MAPK pathways significantly decreased the expression of the three antiapoptotic Bcl-2 family proteins, and in particular this reversed induction of Mcl-1 by carfilzomib. Collectively, our findings show that activation of the MAPK pathways contributes to the mechanisms of drug resistance to carfilzomib. In addition, the synergistic proapoptotic action of MAPK and proteasome inhibitors in osteosarcoma cells suggests that combinational therapy with both drug types may serve as a novel strategy for the clinical management of osteosarcoma.

Sex Moderates Treatment Effects of Integrated Collaborative Care for Comorbid Obesity and Depression: The RAINBOW RCT.

BACKGROUND: Sex influences health and related behaviors due to biological and psychosocial/socioeconomic factors. Assessing sex-specific responses to integrated treatment for comorbid obesity and depression could inform intervention targeting. PURPOSE: To test (a) whether sex moderates the effects of integrated collaborative care on weight and depression outcomes through 24 months and (b) whether treatment response at 6 months predicts 12 and 24 month outcomes by sex. METHODS: Secondary data analyses on weight and depression severity (SCL-20) measured over 24 months among 409 adults with obesity and depression in the Research Aimed at Improving Both Mood and Weight trial. RESULTS: Men achieved significantly greater weight reductions in intervention versus usual care than women, whereas women achieved significantly greater percentage reductions in SCL-20 than men at both 12 and 24 months. In logistic models, at 80% specificity for correctly identifying participants not achieving clinically significant long-term outcomes, women who lost <3.0% weight and men who lost <4.1% weight at 6 months had ≥84% probability of not meeting 5% weight loss at 24 months. Similarly, at 80% specificity, women who reduced SCL-20 by <39.5% and men who reduced by <53.0% at 6 months had ≥82% probability of not meeting 50% decrease in SCL-20 at 24 months. CONCLUSIONS: Sex modified the integrated treatment effects for obesity and depression. Sex-specific responses at 6 months predicted clinically significant weight loss and depression outcomes through 24 months. Based on early responses, interventions may need to be tailored to address sex-specific barriers and facilitators to achieving healthy weight and depression outcomes at later time points. CLINICAL TRIAL REGISTRATION: NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Cell cycle exit during bortezomib-induced osteogenic differentiation of mesenchymal stem cells was mediated by Xbp1s-upregulated p21Cip1 and p27Kip1.

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into a variety of cell types. Bortezomib, the first approved proteasome inhibitor used for the treatment of multiple myeloma (MM), has been shown to induce osteoblast differentiation, making it beneficial for myeloma bone disease. In the present study, we aimed to investigate the effects and underlying mechanisms of bortezomib on the cell cycle during osteogenic differentiation. We confirmed that low doses of bortezomib can induce MSCs towards osteogenic differentiation, but high doses are toxic. In the course of bortezomib-induced osteogenic differentiation, we observed cell cycle exit characterized by G0 /G1 phase cell cycle arrest with a significant reduction in cell proliferation. Additionally, we found that the cell cycle exit was tightly related to the induction of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 . Notably, we further demonstrated that the up-regulation of p21Cip1 and p27Kip1 is transcriptionally dependent on the bortezomib-activated ER stress signalling branch Ire1α/Xbp1s. Taken together, these findings reveal an intracellular pathway that integrates proteasome inhibition, osteogenic differentiation and the cell cycle through activation of the ER stress signalling branch Ire1α/Xbp1s.

Correction to: Cone-beam breast CT features associated with HER2/neu overexpression in patients with primary breast cancer.

The original version of this article, published on 03 January 2020, unfortunately contained two mistakes.

Cone-beam breast CT features associated with HER2/neu overexpression in patients with primary breast cancer.

OBJECTIVES: To identify the relationship between human epidermal growth factor receptor 2 (HER2) status and cone-beam breast CT (CBBCT) characteristics in surgically resected breast cancer. METHODS: Preoperative CBBCT of patients with BI-RADS 4 or 5 lesions identified on mammography or ultrasound and dense or very dense breast tissue were retrospectively evaluated in 181 surgically resected breast cancer (triple-negative excluded) between May 2012 and November 2014. A set of CBBCT descriptors was semiquantitatively assessed by consensus double reading. Reader reproducibility was analyzed. Multivariable logistic regression analysis using backward elimination (BEA) with the Wald criterion was performed to identify independent predictive factors of harboring HER2/neu. Principle component analysis (PCA) was used to determine characteristics that might differentiate HER2 status. Receiver operating characteristic (ROC) curve analyses were conducted to determine the predictive capability. RESULTS: HER2 positive was found in 101 (55.8%) of 181 patients. Inter-observer agreement was high for characteristics' assessment. Based on BEA, pathologic grade, maximum dimension, lobulation, ΔCT, and calcification morphology were confirmed as independent predictive factors of HER2/neu overexpression. PCA showed that calcification- and border-related characteristics were the most important for differentiation. ROC curve analyses showed that CBBCT features (AUC = 0.853) were superior to clinicopathologic features (AUC = 0.613, p < 0.001) and comparable with combination (AUC = 0.856, p = 0.866). CONCLUSIONS: CBBCT features could be used to prognosticate HER2 status independently, which are potentially complementary to histopathologic result and helpful in guiding biopsy. KEY POINTS: • Dmax, lobulation, ΔCT, and calcification morphology are independent predictors of HER2 status. • CBBCT features are superior to clinicopathologic features in HER2+/- discrimination. • CBBCT features are comparable with combination with clinicopathologic features in HER2+/- discrimination.

TeroKit: A Database-Driven Web Server for Terpenome Research.

Natural products are the major resource of drug discovery, and terpenoids represent the largest family of natural products. Terpenome is defined as all terpenoid-like and terpenoid-derived natural compounds, including the terpenoids, steroids, and their derivatives. Herein, aiming to navigate the chemical and biological space of terpenome, the first comprehensive database dedicated to terpenome research has been developed by collecting over 110 000 terpenome molecules from various resources, distributed in 14 351 species, belonging to 1109 families, and showing activity against 1366 biological targets. Much of the publically available information or computationally predicted properties for each terpenome molecule is annotated and integrated into TeroKit (http://terokit.qmclab.com/), serving as free Web server for academic use. Moreover, several practical toolkits, such as target profiling and conformer generation modules, are also implemented to facilitate the drug discovery of terpenome.

Comparing enhanced versus standard Diabetes Prevention Program among indigenous adults in an urban setting: a randomized controlled trial.

BACKGROUND: Indigenous people in the United States are at high risk for diabetes. Psychosocial stressors like historical trauma may impede success in diabetes prevention programs. METHODS: A comparative effectiveness trial compared a culturally tailored diabetes prevention program (standard group) with an enhanced one that addressed psychosocial stressors (enhanced group) in 2015 to 2017. Participants were 207 Indigenous adults with a body mass index (BMI) of ≥30 and one additional criterion of metabolic syndrome, and were randomized to the standard or enhanced group. Both groups received a culturally tailored behavioral diabetes prevention program. Strategies to address psychosocial stressors were provided to the enhanced group only. Change in BMI over 12 months was the primary outcome. Secondary outcomes included change in quality of life, and clinical, behavioral, and psychosocial measures at 6 and 12 months. RESULTS: The two groups did not significantly differ in BMI change at 12 months. The two groups also did not differ in any secondary outcomes at 6 or 12 months, with the exception of unhealthy food consumption; the standard group reported a larger mean decrease (95% CI) in consumption of unhealthy food compared with the enhanced group (- 4.6 [- 6.8, - 2.5] vs. -0.7 [- 2.9, 1.4], p = 0.01). At 6 months, significant improvements in weight and the physical component of the quality of life measure were observed for both groups compared with their baseline level. Compared with baseline, at 12 months, the standard group showed significant improvement in BMI (mean [95% CI], - 0.5 [- 1.0, - 0.1]) and the enhanced group showed significant improvement in the physical component of the quality of life (2.9 [0.7, 5.2]). CONCLUSIONS: Adding strategies to address psychosocial barriers to a culturally tailored diabetes prevention program was not successful for improving weight loss among urban Indigenous adults. TRIAL REGISTRATION: (if applicable): NCT02266576. Registered October 17, 2014 on clinicaltrials.gov. The trial was prospectively registered.

Differing views regarding diet and physical activity: adolescents versus parents' perspectives.

BACKGROUND: Today, approximately one in five United States adolescents age 12 to 19 years is obese and just over a third are either overweight or obese. This study examines how parents and peers influence diet and physical activity behaviors of older adolescents (14-18 years) with overweight or obesity to inform weight management interventions. METHODS: Adolescent participants included 14 to 18-year-olds with a Body Mass Index (BMI) greater than the 85th percentile for their age and sex who were receiving care in a large healthcare system in Northern California. Adolescents and their parents participated in separate focus groups and interviews (if not able to attend focus groups) that were held at the same time in the same location. We used qualitative thematic analysis to identify common themes discussed in the adolescent and parent focus groups as well as paired analysis of adolescent-parent dyads. RESULTS: Participants included 26 adolescents and 27 parents. Adolescent participants were 14 to 18 years old. Half were female and the participants were almost evenly distributed across year in school. The majority self-identified as White (56%) and Asian (36%).Three themes were identified which included 1) parents overestimated how supportive they were compared to adolescents' perception 2) parents and adolescents had different views regarding parental influence on adolescent diet and physical activity behaviors 3) parents and adolescents held similar views on peers' influential role on lifestyle behaviors. CONCLUSION: Parents' and adolescents' differing views suggest that alignment of parent and adolescent expectations and behaviors for supporting effective weight management could be incorporated into interventions.