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We studied the use of the INNO-LIA syphilis score assay in the resolution of discordant positive screening results of the Murex ICE Syphilis enzyme immunoassay (EIA) with the confirmatory results of both the Serodia Treponema pallidum particle agglutination (TPPA) and the fluorescent treponemal antibody-absorption (FTA-Abs) assays, for the serological diagnosis of syphilis. This was an observational study on the serum samples received by the Syphilis Laboratory, Hong Kong, during the period from January 2006 to December 2012. A total of 801 serum samples with discordant positive screening EIA results were used. Consensus results of such serum samples were derived from results of the EIA, TPPA and FTA-abs assays. The age range of the individuals was 14 to 104 years (median of 52). There were 369 males and 432 females. Of 378 serum samples, 139 showed agreement among positive results, 23 of 310 showed agreement among indeterminate results and 277 of 465 showed agreement among negative results. The proportions of agreement among positive, indeterminate and negative results were 0.37 (95% CI 0.32–0.42), 0.07 (95% CI 0.05–0.11) and 0.60 (95% CI 0.55–0.64), respectively; kappa 0.55 (95% CI 0.49–0.60). There were 60 serum samples with positive consensus results but negative INNO-LIA syphilis score results and 10 with negative consensus results but positive INNO-LIA syphilis score results. Although the INNO-LIA syphilis score assay can be considered a valid alternative confirmatory test for the serological diagnosis of syphilis, the present study showed that its use in the resolution of discordant positive screening EIA results was moderate. A more extensive characterization of serum samples with discordant reactive screening treponemal test results is necessary. [ABSTRACT FROM PUBLISHER]

Objective: Metabolism of long-chain fatty acids within the duodenum leads to the activation of duodenal mucosal protein kinase C (PKC)-δ and the cholecystokinin (CCK)-A receptor to lower glucose production through a neuronal network. However, the interfunctional relationship between duodenal PKC-δ and CCK remains elusive. Although long-chain fatty acids activate PKC to stimulate the release of CCK in CCK-secreting cells, CCK has also been found to activate PKC-δ in pancreatic acinar cells. We here evaluate whether activation of duodenal mucosal PKC-δ lies upstream (and/or downstream) of CCK signaling to lower glucose production.Research Design and Methods: We first determined with immunofluorescence whether PKC-δ and CCK were colocalized within the duodenal mucosa. We then performed gain- and loss-of-function experiments targeting duodenal PKC-δ and the CCK-A receptor and evaluated the impact on changes in glucose kinetics during pancreatic (basal insulin) clamps in rats in vivo.Results: Immunostaining of PKC-δ was found to colocalize with CCK in the duodenal mucosa. Intraduodenal coinfusion of either the CCK-A receptor antagonist MK-329 or CR-1409 with the PKC activator negated the ability of duodenal mucosal PKC-δ activation to lower glucose production during the pancreatic clamps in normal rats. Conversely, molecular and pharmacological inhibition of duodenal PKC-δ did not negate the ability of the duodenal CCK-A receptor agonist CCK-8 to lower glucose production, indicating that activation of duodenal PKC-δ lies upstream (and not downstream) of CCK signaling. Finally, intraduodenal PKC activator infusion failed to lower glucose production in rats with high-fat diet-induced duodenal CCK resistance.Conclusions: In summary, activation of duodenal PKC-δ leads to the stimulation of CCK release and activation of the CCK-A receptor signaling axis to lower glucose production in normal rats, but fails to bypass duodenal CCK-resistance in high fat-fed rats. [ABSTRACT FROM AUTHOR]

The shortage of food and freshwater sources threatens human health and environmental sustainability. Spirulina grown in seawater-based media as a healthy food is promising and environmentally friendly. This study used three machine learning techniques to identify important cultivation parameters and their hidden interrelationships and optimize the biomass yield of Spirulina grown in seawater-based media. Through optimization of hyperparameters and features, eXtreme Gradient Boosting, along with the recursive feature elimination (RFE) model demonstrated optimal performance and identified 28 important features. Among them, illumination intensity and initial pH value were critical determinants of biomass, which impacted other features. Specifically, high initial pH values (>9.0) mainly increased biomass but also increased nutrient sedimentation and ammonia (NH 3 ) losses. Both batch and continuous additions could decrease nutrient losses by increasing their availability in the seawater-based media. When illumination intensity exceeded 200 μmol photons/m 2 /s, it amplified the growth of Spirulina by mitigating the light attenuation caused by a high initial inoculum level and counteracted the negative effect of low temperature (<25 °C). In large-scale cultivation, production efficiency would be reduced if illumination was not maintained at a high level. High salinity and sodium bicarbonate (NaHCO 3 ) addition promoted carbohydrate accumulation, but suitable dilution could keep the required protein content in Spirulina with relatively low media and production costs. These findings reveal the interactive influence of cultivation parameters on biomass yield and help us determine the optimal cultivation conditions for large-scale cultivation of Spirulina-based seawater system based on a developed graphical user interface website., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Using current water treatment systems, significant amounts of microplastics (MPs) are passing through and being released into the aquatic environment. However, we do not clearly know what effects disinfection processes have had on these particles. In this study, we applied inductively coupled plasma-mass spectrometry (ICP-MS) operating in time-resolved analysis (TRA) mode for quantifying changes in the chlorine (Cl) content of MPs under a variety of water treatment scenarios. Our results illustrated that time-resolved ICP-MS offers a potential method for sensitive and direct analysis of Cl content, including Cl mass and chlorine association (%Cl/C), of discrete particles in the MP suspension by the fast sequential measurements of signals from 35 Cl 1 H 2 and 12 C 1 H. Our research, across various water treatment scenarios, also showed that polystyrene (PS) MPs exhibited greater reactivity to Cl disinfectant after being pre-disinfected with UV light and in mildly acidic to neutral pH environments. It is noteworthy that about half of the particles in MP suspension exposed to 10 mg Cl 2 /L, a typical Cl dose applied in water treatment, were chlorinated, and had a Cl content comparable to that of particles subjected to extreme conditions. Of even greater concern is the fact that our cell viability tests revealed that chlorinated MPs induced considerably higher rates of cell death in both human A549 and Caco-2 cells, and that the effects were Cl dose- and polymer type-dependent. Overall, this study demonstrates the potential of time-resolved ICP-MS as a valuable technique for quantifying the Cl content of MP particles, which is crucial to assessing the fate and transformation of MPs in our water supply and treatment systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Several studies have shown developmental changes in EEG oscillations during working memory tasks. Although the load-modulated theta and alpha activities in adults are well-documented, the findings are inconsistent if children possess the adult-like brain oscillations that are similarly modulated by memory load. The present study compares children's and adults' true theta and alpha EEG oscillations, separated from aperiodic components, in the maintenance stage of working memory. The EEG was recorded in 25 Chinese-speaking children (14 male, M age = 9.4 yrs) and 31 adults (19 male, M age = 20.8 yrs) in Hong Kong while they performed an n-back task that included four conditions differing in load (1- vs. 2-back) and stimulus type (Chinese character vs. visual pattern). The results show that aperiodic activities (i.e., broadband power and slope) during the maintenance stage in the n-back task were significantly higher in children than adults. The periodic theta and alpha oscillations also changed with age. More importantly, adults showed significant periodic theta increase with memory load, whereas such an effect was absent in children. Regardless of age, there was a significant alpha power decrease with load increase, and a significant theta power enhancement when maintaining visual patterns than Chinese characters. In adults, load-modulated alpha peak shift (towards higher frequency) was linked to higher behavioral efficiency in the n-back task. In children, higher load-modulated theta enhancement was linked to better behavioral efficiency. The findings suggest that the load-modulated theta power during working memory maintenance matures from childhood to adulthood., Competing Interests: Declaration of Competing Interest The authors declare that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Manganese oxide (MnO 2 ) is one of the most abundant metal oxides, and it is renowned for its ability to degrade various phenolic micropollutants. However, under MnO 2 -mediated transformation, BP-3 transforms into 12 different radical-coupled transformation products (TPs) out of 15 identified TPs. These radical-coupled TPs are reported with adverse environmental impacts. This study explored the effects of MnO 2 on organic UV filter mixtures and different water constituents (i.e., bicarbonate ion (HCO 3 - ), humic acid (HA) and halide ions) in terms of degradation efficiency and transformation chemistry. When a mixture of benzophenone-3 (BP-3) and avobenzone (AVO) underwent transformation by MnO 2 , hybrid radical-coupled TPs derived from both organic UV filters were generated. These hybrid radical-coupled TPs were evaluated by an in silico prediction tool and Vibrio fischeri bioluminescence inhibition assay (VFBIA). Results showed that these TPs were potentially toxic to aquatic organisms, even more so than their parent compounds. The higher the concentration of HCO 3 - , HA, chloride ion (Cl - ) and bromide ion (Br - ), the greater the reduction in the efficiencies of degrading BP-3 and AVO. Contrastingly, in the presence of iodide ion (I - ), degradation efficiencies of BP-3 and AVO were enhanced; however, iodinated TPs and iodinated radical-coupled TPs were formed, with questionable toxicity. This study has revealed the environmental risks of hybrid radical-coupled TPs, iodinated TPs and iodinated radical-coupled TPs when the organic UV filters BP-3 and AVO are transformed by MnO 2 ., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Radical-coupled transformation products (TPs) have been identified as the byproducts of various transformation processes, including both natural attenuation and artificial treatments, of phenolic micropollutants. Benzophenone-3 (BP-3), an organic UV filter of emerging concern, has been previously reported with ubiquitous occurrence in the natural environment and water bodies. Current research has demonstrated how TPs are formed from BP-3 when it is treated with manganese oxide (MnO 2 ). The ecological and toxicological risks of these TPs have also been assessed. Polymerization of BP-3 through radical coupling was observed as the major pathway by which BP-3 is transformed when treated with MnO 2 . These radical-coupled TPs haven't shown further degradation after formation, suggesting their potential persistence once occurred in the environment. In silico experiments predict the radical-coupled TPs will increase in mobility, persistence and ecotoxicity. If true, they also represent an ever-increasing threat to the environment, ecosystems and, most immediately, aquatic living organisms. In addition, radical-coupled TPs produced by MnO 2 transformation of BP-3 have shown escalated estrogenic activity compared to the parent compound. This suggests that radical coupling amplifies the toxicological impacts of parent compound. These results provide strong evidence that radical-coupled TPs with larger molecular sizes are having potential adverse impacts on the ecosystem and biota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Otitis media (OM) is a common inflammatory disease spectrum in children and a leading cause of pediatric physician visits, antibiotic prescriptions and surgery. Tobacco exposure is associated with increased risk of OM recurrence, chronicity and surgeries. Tobacco products have changed dramatically in recent years with the advent of electronic cigarettes (e-cigarettes). While users frequently perceive vape as less harmful than traditional cigarettes, burgeoning evidence supports its contribution to respiratory pathologies. The consequences of secondhand exposure, particularly among children, are understudied. The aim of this study was to examine the association of e-cigarette emissions (EE) with OM recurrence and surgeries in the US., Methods: Questionnaire data regarding ear infections and tobacco exposure was gathered for all pediatric respondents of the National Health and Nutrition Examination Survey (NHANES) 2017 to 2018. Weighted analyzes and logistic regression models were used to assess associations., Results: Data was available for 2022 participants (aged 6-17); all were included for analyzes. Tobacco exposure was observed in 42%; 9% were exposed to EE. EE contributed to risk of ≥3 ear infections (OR = 1.61, 95% CI 1.01-2.58, P  = .047). After adjustment for significant covariates (race and asthma), the association fell below significance ( P  = .081). No other significant associations were observed between ear infections, or tympanostomy tube insertion and exposure variables (EE, gestational or other household exposure)., Conclusions: Exposure to EE may confer greater risk of pediatric OM than previously identified factors such as household smoke, or gestational exposure. Further investigation of EE and its health implications in children is warranted., Level of Evidence: IV.

Epidemiological and experimental data have associated exposure to fine particulate matter (PM2.5) with various metabolic dysfunctions and diseases, including overweight and type 2 diabetes. Adipose tissue is an energy pool for storing lipids, a necessary regulator of glucose homeostasis, and an active endocrine organ, playing an essential role in developing various related diseases such as diabetes and obesity. However, the molecular mechanisms underlying PM2.5-impaired functions in adipose tissue have rarely been explored. In this work, metabolomics based on liquid chromatography-mass spectrometry was performed to study the adverse impacts of PM2.5 exposure on brown adipose tissue (BAT) and white adipose tissue (WAT) in the diabetic mouse model. We found the effects of PM2.5 exposure by comparing the different metabolites in both adipose tissues of male db/db mice using real-ambient PM2.5 exposure. The results showed that PM2.5 exposure changed the purine metabolism in mice, especially the dramatic increase of xanthine content in both WAT and BAT. These changes led to significant oxidative stress. Then the results from real-time quantitative polymerase chain reaction showed that PM2.5 exposure could cause the production of inflammatory factors in both adipose tissues. Moreover, the increased reactive oxygen species (ROS) promoted triglyceride accumulation in WAT and inhibited its decomposition, causing increased WAT content in db/db mice. In addition, PM2.5 exposure significantly suppressed thermogenesis and affected energy metabolism in the BAT of male db/db mice, which may deteriorate insulin sensitivity and blood glucose regulation. This research demonstrated the impact of PM2.5 on the adipose tissue of male db/db mice, which may be necessary for public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: More than 62 million people self-identified as Hispanic/Latino (H/L) in the 2020 United States census. The U.S. H/L population has higher burden of certain cancers compared with their non-Hispanic White counterparts., Methods: Key term search using the NIH Query/View/Report (QVR) system, along with Research, Condition, and Disease Categorization codes identified cancer epidemiology research grants in H/L populations funded by the NCI as a primary or secondary funder from fiscal years 2016 through 2021. Three reviewers identified eligible grants based on specified inclusion/exclusion criteria and a codebook for consistency extracting key characteristics., Results: A total of 450 grants were identified through the QVR system using key words related to H/Ls; 41 cancer epidemiology grants remained after applying exclusion criteria. These grants contained specific aims focused on H/Ls (32%) or included H/Ls as part of a racial/ethnic comparison (68%). NCI was the primary funder of the majority of the grants (85%), and most of the research grants focused on cancer etiology (44%) and/or survivorship (49%). Few grants (10%) investigated environmental exposures., Conclusions: This article provides an overview of NCI-funded cancer epidemiology research in H/L populations from 2016 to 2021. Future cancer epidemiology research should reflect the changing dynamics of the U.S. demography with diverse, representative populations and well-characterized ethnicity., Impact: Research that carefully measures the relevant biological, environmental, behavioral, psychologic, sociocultural, and clinical risk factors will be critical to better understanding the nuanced patterns influencing cancer-related outcomes in the heterogenous H/L population., (©2023 American Association for Cancer Research.)

In this Letter, we present a method aiming at background noise removal in the 3D reconstruction of light field microscopy (LFM). Sparsity and Hessian regularization are taken as two prior knowledges to process the original light field image before 3D deconvolution. Due to the noise suppression function of total variation (TV) regularization, we add the TV regularization term to the 3D Richardson-Lucy (RL) deconvolution. By comparing the light field reconstruction results of our method with another state-of-the-art method that is also based on RL deconvolution, the proposed method shows improved performance in terms of removing background noise and detail enhancement. This method will be beneficial to the application of LFM in biological high-quality imaging.

Educational Objective: At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus., Objective: Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H + /K + ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H + /K + ATPase proton pumps., Study Design: In vitro translational., Methods: BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing., Results: Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer., Conclusions: These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE., Level of Evidence: NA Laryngoscope, 133:59-69, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Previous research has shown greater risk aversion when people make choices about lives than cash. We tested the hypothesis that compared to placebo, exogenous testosterone administration would lead to riskier choices about cash than lives, given testosterone's association with financial risk-taking and reward sensitivity. A double-blind, placebo-controlled, randomized trial was conducted to test this hypothesis (Clinical Trials Registry: NCT02734238, www.clinicaltrials.gov). We collected functional magnetic resonance imaging (fMRI) data from 50 non-obese males before and shortly after 28 days of severe exercise-and-diet-induced energy deficit, during which testosterone (200 mg testosterone enanthate per week in sesame oil) or placebo (sesame seed oil only) was administered. Because we expected circulating testosterone levels to be reduced due to severe energy deficit, testosterone administration served a restorative function to mitigate the impact of energy deficit on testosterone levels. The fMRI task involved making choices under uncertainty for lives and cash. We also manipulated whether the outcomes were presented as gains or losses. Consistent with prospect theory, we observed the reflection effect such that participants were more risk averse when outcomes were presented as gains than losses. Brain activation in the thalamus covaried with individual differences in exhibiting the reflection effect. Testosterone did not impact choice, but it increased sensitivity to negative feedback following risky choices. These results suggest that exogenous testosterone administration in the context of energy deficit can impact some aspects of risky choice, and that individual differences in the reflection effect engage a brain structure involved in processing emotion, reward and risk., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: Several measures of upper limb (UL) motor tasks have been developed to characterize recovery. However, UL performance and movement quality measures in isolation may not provide a true profile of functional recovery., Objective: To investigate the measurement properties of a new trunk-based Index of Performance (IPt) of the UL combining endpoint performance (accuracy and speed) and movement quality (trunk displacement) in stroke., Methods: Participants with stroke (n = 25, mean time since stroke: 18.7 ± 17.2 months) performed a reaching task over 3 evaluation sessions. The IPt was computed based on Fitts' Law that incorporated endpoint accuracy and speed corrected by the amount of trunk displacement. Test-retest reliability was analyzed using intraclass correlation coefficient (ICC) and Bland-Altman plots. Standard error of measurement (SEM) and Minimal Detectable Change (MDC) were determined. Validity was investigated through the relationship between IPt, Fugl-Meyer Assessment (FMA-UE), and Action Research Arm Test (ARAT), as well as the ability of IPt to distinguish between levels of UL motor impairment severity., Results: Test-retest reliability was excellent (ICC = .908, 95% CI: 0.807-0.96). Bland-Altman did not show systematic differences. SEM and MDC 95 were 14% and 39%, respectively. Construct validity was satisfactory. The IPt showed low-to-moderate relationships with FMA-UE ( R 2 ranged from .236 to .428) and ARAT ( R 2 ranged from .277 to .306). IPt scores distinguished between different levels of UL severity., Conclusions: The IPt showed evidence of good reliability, and initial validity. The IPt may be a promising tool for research and clinical settings. Further research is warranted to investigate its validity with additional comparator instruments.

Acute leukemia is a type of blood cancer with a high mortality rate. Current therapeutic methods include bone marrow transplantation, supportive therapy, and chemotherapy. Although a satisfactory remission of the disease can be achieved, the risk of recurrence is still high. Therefore, novel treatments are demanding. Chimeric antigen receptor-T (CAR-T) therapy has emerged as a promising approach to treating and curing acute leukemia. To harness the therapeutic potential of CAR-T cell therapy for blood diseases, reliable cell morphological identification is crucial. Nevertheless, the identification of CAR-T cells is a big challenge posed by their phenotypic similarity with other blood cells. To address this substantial clinical challenge, herein we first construct a CAR-T dataset with 500 original microscopy images after staining. Following that, we create a novel integrated model called RCMNet (ResNet18 with Convolutional Block Attention Module and Multi-Head Self-Attention) that combines the convolutional neural network (CNN) and Transformer. The model shows 99.63% top-1 accuracy on the public dataset. Compared with previous reports, our model obtains satisfactory results for image classification. Although testing on the CAR-T cell dataset, a decent performance is observed, which is attributed to the limited size of the dataset. Transfer learning is adapted for RCMNet and a maximum of 83.36% accuracy is achieved, which is higher than that of other state-of-the-art models. This study evaluates the effectiveness of RCMNet on a big public dataset and translates it to a clinical dataset for diagnostic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Chronic hepatitis C virus (HCV) infection can affect immune response and inflammatory pathways, leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: In a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed HCC. Unconditional odds ratios (ORs) from polytomous logistic regression models and canonical discriminant analyses (CDAs) were used to compare categorical (C) baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to produce receiver operating characteristic curves to assess predictive ability of markers. Lastly, biological pathways were assessed in association with cirrhotic development compared to controls. Results: After multivariable adjustment, DEFA-1 (OR: C2v.C1 = 7.73; p < 0.0001), ITGAM (OR: C2v.C1 = 4.03; p = 0.0002), SCF (OR: C4v.C1 = 0.19; p-trend = 0.0001), and CCL11 (OR: C4v.C1 = 0.31; p-trend= 0.002) were all associated with development of cirrhosis compared to controls; these markers, together with clinical/demographics variables, improved prediction of cirrhosis from 55.7% (in clinical/demographic-only model) to 74.9% accuracy. A twelve-marker model based on CDA results further increased prediction of cirrhosis to 88.0%. While six biological pathways were found to be associated with cirrhosis, cell adhesion was the only pathway associated with cirrhosis after Bonferroni correction. In contrast to cirrhosis, DEFA-1 and ITGAM levels were inversely associated with HCC risk. Conclusions: Pending validation, these findings highlight the important role of immunological markers in predicting HCV-related cirrhosis even 11 years post-enrollment.

Multitasking is a common requirement in many occupations. Considerable research has demonstrated that performance declines as a result of multitasking, and that it engages multiple brain regions. Despite growing evidence suggesting that brain regions operate as networks, minimal research has investigated the cognitive brain networks implicated in multitasking. The Multi-Attribute Task Battery II (MATB) is a common method for assessing multitasking ability that simulates a pilot's operational environment inside an aircraft cockpit. The aim of the present study was to examine multitasking performance on the MATB, and the associated neural patterns underlying performance with functional magnetic resonance imaging (fMRI). Twenty-four participants completed the MATB in the fMRI scanner. Participants completed four runs of the MATB in a 2 (Task: multitasking vs. single tasking) × 2 (Difficulty: hard vs. easy) design. MATB performance was measured as a function of accuracy. We analyzed the fMRI brain scans using both static and dynamic functional connectivity to determine whether there were differences in the connectivity patterns associated with each of the four conditions. A significant interaction between Task and Difficulty was observed such that multitasking performance accuracy, which was derived from the average across tasks, was lower than single tasking in the hard, but not easy, condition. The fMRI data revealed that static and dynamic functional connectivity between the default mode and dorsal attention networks was stronger during multitasking relative to single tasking. The static functional connectivity between the default mode and left frontoparietal networks, along with the dynamic functional connectivity between the dorsal attention and left frontoparietal networks, were both more anti-correlated during multitasking relative to single tasking. Taken together, the static and dynamic functional connectivity analyses provide complementary information to reveal the interactions among cognitive networks that support multitasking performance. Targeting these networks may offer a path to enhance multitasking ability through the application of neurostimulation and neuroenhancement techniques., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis., (© 2021. The Author(s).)

Transformation products (TPs) of micropollutants contaminating our water resources have become an emerging issue due to the potential threats they pose to environmental and human health. This study investigated the transformation chemistry, toxicity, physicochemical properties and environmental behavior resulting from photocatalytic transformation of organic UV filters as model micropollutants. 3-Benzylidene camphor (3-BC), 4-hydroxybenzophenone (4-HB) and octocrylene (OC) were effectively degraded by UV-A/TiO 2 treatment, with TPs identified and characterized with high resolution mass spectrometry. Nitrated-TPs were observed to be formed in the presence of nitrite and nitrate for 3-BC and 4-HB, suggesting that the transformation process could be altered by components in the water matrix. Vibrio fischeri bioluminescence inhibition assay revealed an increase in toxicity of TPs derived from photocatalytic treatment, with quantitative structure-activity relationship model (ECOSAR) predicted an enhanced toxicity of individual TPs' after transformation. Assessment of physicochemical properties and environmental behavior suggested that TPs as compared to parent organic UV filters, may represent even greater hazards due to their increased water solubility, persistence and mobility - in addition to retaining the parent organic UV filter's toxicity. The results provide important information relevant to the potential risks for the selected organic UV filters, and their corresponding transformation products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The goals of this project were to assess the status of NCI's rare cancer-focused population science research managed by the Division of Cancer Control and Population Sciences (DCCPS), to develop a framework for evaluation of rare cancer research activities, and to review available resources to study rare cancers., Methods: Cancer types with an overall age-adjusted incidence rate of less than 20 cases per 100,000 individuals were identified using NCI Surveillance, Epidemiology and End Results (SEER) Program data. SEER data were utilized to develop a framework based on statistical commonalities. A portfolio analysis of DCCPS-supported active grants and a review of three genomic databases were conducted., Results: For the 45 rare cancer types included in the analysis, 123 active DCCPS-supported rare cancer-focused grants were identified, of which the highest percentage (18.7%) focused on ovarian cancer. The developed framework revealed five clusters of rare cancer types. The cluster with the highest number of grants ( n = 43) and grants per cancer type (10.8) was the cluster that included cancer types of higher incidence, average to better survival, and high prevalence (in comparison with other rare cancers). Resource review revealed rare cancers are represented in available genomic resources, but to a lesser extent compared with more common cancers., Conclusions: This article provides an overview of the rare cancer-focused population sciences research landscape as well as information on gaps and opportunities., Impact: The findings of this article can be used to develop efficient and comprehensive strategies to accelerate rare cancer research. See related commentary by James V. Lacey Jr, p. 1300 ., (©2021 American Association for Cancer Research.)

Traditionally, it has been assumed that logical thinking requires deliberation. However, people can also make logical responses quickly, exhibiting logical intuitions . We examined the neural correlates of logical intuitions by administering base rate problems during fMRI scanning using a two-response paradigm where participants first responded quickly and then reflectively to problems that did or did not pit a normative response against an intuitively-cued stereotypical response (i.e., conflict vs. non-conflict problems). As predicted, participants were less likely to make judgments in accordance with base rates on conflict problems. Critically, in only 4% of cases did longer deliberation change an initially biased response to a normatively correct response. The fMRI data revealed that intuitively-made initial biased judgments nevertheless activate regions typically involved in cognitive control, executive functions and attention, including anterior, inferior, middle and superior frontal cortex, suggesting that even when errors are made, there might be very early awareness of conflict.

Objective: To describe the technique of sonographic ulnar nerve mapping in the postoperative elbow for surgical planning., Materials and Methods: A retrospective review of a surgical databank identified 24 patients, all aged 18 years and older with a history of orthopedic elbow surgery, who were referred for preoperative sonographic mapping of the ulnar nerve prior to subsequent surgery. All cases were reviewed for patient demographics, clinical presentation, prior surgical interventions, and ultrasound technique. Charts were reviewed for intraoperative and postoperative outcomes, including nerve injury., Results: The cohort included 12 males and 12 females with a mean age of 51 years (range 22-68 years) and a mean BMI of 29 (range 20-48). Preoperative sonographic ulnar nerve mapping occurred following various elbow surgeries including ulnar nerve transposition to assess nerve location prior to subsequent elbow surgery. Of the 24 patients with preoperative sonographic ulnar nerve mapping, subsequent surgery was performed arthroscopically in 14 and open in 10 cases. In 11 of the 24 cases, there was specific mention of a modified approach to joint access which was guided by the ulnar nerve map. There were no perioperative ulnar nerve-related complications, such as nerve transection., Conclusion: Preoperative mapping can facilitate planning of surgical access and ulnar nerve dissection. Sonographic mapping of the ulnar nerve reduces the potential uncertainty of nerve palpation in a complex postoperative elbow following ulnar nerve transposition. This technique may mitigate the risk of ulnar nerve injury.

Organic UV filters are compounds that absorb UV irradiation by their highly conjugated structure. With the developing consciousness over the last century of the skin damage UV radiation can cause, the demand for organic UV filters has risen, for use not only in sunscreens, but also in other personal care products. The massive production and usage of these organic UV filters has resulted in extensive release into the aquatic environment, and thereby making an important group of emerging contaminants. Considering the widespread occurrence of organic UV filters in not only ambient water, but also sediment, soil and even indoor dust, their threats towards the health of living organisms have been a subject of active investigation. In this review article, we present an overall review of existing knowledge on the risks of organic UV filters from the aspects of both environmental and human health impacts. As for the environment, some organic UV filters are proven to bioaccumulate in various kinds of aquatic organisms, and further to have adverse effects on different kinds of animal models. Toxicological studies including in vivo and in vitro studies are important and effective means to ascertain the effects and mechanisms of organic UV filters on both the ecosystem and humans. Subsequent concerns arise that these compounds will affect human health in the long term. This review concludes by suggesting future lines of research based on the remaining knowledge gaps., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Divergent thinking tests have been used extensively in neuroscientific studies of creativity. However, output from tests of divergent thinking can be scored in different ways, and those scores can influence assessments of divergent thinking performance and its relationship with brain activation. Here we sought to investigate the relationship between various methods of scoring the Alternate Uses Task (AUT)-a well-known test of divergent thinking-and regional grey matter volume (GMV) using voxel-based morphometry (VBM). We assessed AUT performance based on (a) traditional approaches that involve scoring participants' output on fluency, flexibility, originality, and elaboration, (b) a subjective approach that involves scoring output directly on "snapshot" creativity, and (c) the definitional approach that involves scoring output separately on novelty and usefulness-the two criteria deemed necessary and jointly sufficient to categorize an idea as creative. Correcting for age, sex, intracranial volume, verbal IQ and working memory capacity, we found negative correlations between regional GMV in the left inferior temporal gyrus (ITG) and novelty and usefulness scores, but no correlation involving other scoring approaches. As part of the brain's core semantic system, this region is involved in concept retrieval and integration. We discuss the implications of these findings for our understanding of the neural bases of divergent thinking, and how ITG could be related to the generation of novel and useful responses., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Primary dermal melanoma (PDM) is a subtype of cutaneous melanoma, confined to the dermis, which poses a challenging clinical dilemma. It may represent a true primary melanoma or a dermal cutaneous metastasis. This study aimed to delineate the histopathological characteristics and prognosis of PDM in a large patient cohort to guide appropriate treatment strategies., Methods: A search of the Melanoma Research Database at Melanoma Institute Australia was conducted to identify all possible PDM patients at our institution diagnosed from 1978 to 2013. Overall, melanoma-specific and disease-free survival outcomes of the PDM group were compared to those of similar cohorts of Stage I-II and Stage IV M1a melanoma patients based on propensity score matching., Results: Sixty-two PDM patients were identified from the MRD with a median follow-up of 6.3 years. Five-year survival was 87.1% and overall survival was 74.2%. PDMs had a significantly improved overall survival (p = 0.0002) and melanoma-specific survival (p = 0.001) compared to Stage I-II controls, however there was no difference in disease-free survival (p = 0.08). PDMs also demonstrated improved overall survival (p < 0.0001), melanoma-specific survival (p < 0.0001) and disease-free survival (p < 0.0001) compared to Stage IV M1a controls., Conclusion: These findings demonstrate that PDMs have a more favorable prognosis compared to stage I-II cutaneous melanomas and suggest that these are in fact true primary lesions. This study thus provides evidence to justify a treatment approach, by way of a wide local excision and possibly sentinel lymph node biopsy, as for early stage primary cutaneous melanomas., Competing Interests: Declaration of competing interest There were no sources of funding for this study. RAS has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia Pty Ltd, Myriad, NeraCare and Amgen. PMF was supported by the Debra and John McMurtrie Pathology Fellowship through MIA. JFT has received honoraria for advisory board participation from BMS Australia, MSD Australia, GSK and Provectus Inc, and travel support from GSK and Provectus Inc. RPMS has received honoraria for advisory board participation from MSD, Novartis, speaking honoraria from BMS and is supported by MIA., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Intervertebral disc degeneration (IDD), a major cause of low back pain, occurs with ageing. The core of the intervertebral disc, the nucleus pulposus (NP), embedded in a proteoglycan-rich and gelatinous matrix, is derived from the embryonic notochord. With IDD, the NP becomes fibrous, containing fewer cells, which are fibroblastic and of unknown origin. Here, we used a lineage tracing strategy to investigate the origin of cells in the NP in injury-induced mouse IDD. We established a Foxa2 notochord-specific enhancer-driven Cre transgenic mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). When this mouse is crossed to one carrying a Cre recombinase reporter, Z/EG, EGFP-labelled NP cells are present even at 2 years of age, consistent with their notochordal origin. We induced tail IDD in Foxa2mNE-Cre; Z/EG mice by annulus puncture and observed the degenerative changes for 12 weeks. Soon after puncture, EGFP-labelled NP cells showed strong Col2a1+ expression unlike uninjured control NP. Later, accompanying fibrotic changes, EGFP-positive NP cells expressed fibroblastic and myofibroblastic markers such as Col1a1, ASMA, FAPA and FSP-1. The number of EGFP+ cells co-expressing the fibroblastic markers increased with time after puncture. Our findings suggest resident NP cells initially upregulate Col2a1+ and later transform into fibroblast-like cells during injury-mediated disc degeneration and remodelling. This important discovery concerning the cellular origin of fibrotic pathology in injury-induced IDD has implications for management in disease and ageing., (© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Damage to the corticospinal tract (CST) from stroke leads to motor deficits. The damage can be quantified as the amount of overlap between the stroke lesion and CST (CST Injury). Previous literature has shown that the degree of motor deficits post-stroke is related to the amount of CST Injury. These studies delineate the stroke lesion from structural T1-weighted magnetic resonance imaging (MRI) scans, often acquired for research. In Canada, computed tomography (CT) is the most common imaging modality used in routine acute stroke care. In this proof-of-principle study, we determine whether CST Injury, using lesions delineated from CT scans, significantly explains the variability in motor impairment in individuals with stroke., Methods: Thirty-seven participants with stroke were included in this study. These individuals had a CT scan within the acute stage (7 days) of their stroke and underwent motor assessments. Brain images from CT scans were registered to MRI space. We performed a stepwise regression analysis to determine the contribution of CST injury and demographic variables in explaining motor impairment variability., Results: Using clinically available CT scans, we found modest evidence that CST Injury explains variability in motor impairment (R2adj = 0.12, p = 0.02). None of the participant demographic variables entered the model., Conclusion: We show for the first time a relationship between CST Injury and motor impairment using CT scans. Further work is required to evaluate the utility of data derived from clinical CT scans as a biomarker of stroke motor recovery.

Hispanics/Latinos are expected to constitute 25% of the U.S. population by 2060. Differences in the prevalence of health risk factors, chronic diseases, and access to and utilization of health-care services between Hispanics/Latinos and other populations in the U.S. have been documented. This study aimed to describe and analyze the landscape of Research Program Grants (RPGs) funded by the National Institutes of Health (NIH) between 2008 and 2015 involving Hispanic/Latino health research in six health condition areas-asthma, cancer, dementia, diabetes, liver/gallbladder disease, and obesity-and to identify opportunities for continued research in these areas. Using an NIH internal search engine, we identified new and renewal Hispanic/Latino health RPGs searching for specific Hispanic/Latino identifiers in the Title, Abstract, and Specific Aims. We used descriptive statistics to examine the distribution of funded RPGs by NIH disease-based classification codes for the six health condition areas of interest, and other selected characteristics. The most prominent clusters of research subtopics were identified within each health condition area, and performance sites were mapped at the city level. Within the selected time frame, 3,221 Hispanic/Latino health-related unique RPGs were funded (constituting 4.4% of all funded RPGs), and of those 625 RPGs were eligible for review and coding in the present study. Cancer and obesity were the most commonly studied health condition areas (72%), while studies on mechanisms of disease-biological and non-biological-(72.6%), behavioral research (42.1%) and epidemiological studies (38.1%) were the most common types of research. Most of the primary performance sites were in California, Texas, the northeastern U.S., and Illinois. The predominance of mechanistic, behavioral, and epidemiological studies in our analysis poses opportunities to evaluate knowledge gained and their clinical application, explore new research questions, or to update some methods or instruments. The findings of the present study suggest opportunities to expand research in understudied mechanisms of disease that could explain differences in prevalence of conditions like diabetes and cancer among different heritage groups. In addition, our findings suggest that the impact of interventions or policies designed to reduce health disparities, innovative multi-level interventions, implementation and dissemination studies, the role of health information technology on health outcomes, and the intersectionality of individual, sociocultural, geographic, and other factors on health outcomes, among others, are understudied approaches, which could potentially advance research in Hispanic/Latino health and contribute to the achievement of better health outcomes in this diverse population., (Copyright © 2020 Avilés-Santa, Hsu, Lam, Arteaga, Artiles, Coady, Cooper, Curry, Desvigne-Nickens, Nicastro and Rosario.)

The application of next-generation sequencing (NGS) technologies in cancer research has accelerated the discovery of somatic mutations; however, progress in the identification of germline variation associated with cancer risk is less clear. We conducted a systematic literature review of cancer genetic susceptibility studies that used NGS technologies at an exome/genome-wide scale to obtain a fuller understanding of the research landscape to date and to inform future studies. The variability across studies on methodologies and reporting was considerable. Most studies sequenced few high-risk (mainly European) families, used a candidate analysis approach, and identified potential cancer-related germline variants or genes in a small fraction of the sequenced cancer cases. This review highlights the importance of establishing consensus on standards for the application and reporting of variants filtering strategies. It also describes the progress in the identification of cancer-related germline variation to date. These findings point to the untapped potential in conducting studies with appropriately sized and racially diverse families and populations, combining results across studies and expanding beyond a candidate analysis approach to advance the discovery of genetic variation that accounts for the unexplained cancer heritability., (©2020 American Association for Cancer Research.)

To assess and advance training of twenty-first century cancer epidemiologists, the National Cancer Institute (NCI) sought to obtain a snapshot of the cancer epidemiology training landscape by conducting a survey across academic institutions and cancer centers, focusing on four key training areas driving current cancer epidemiology research ("drivers"): (1) collaboration, (2) novel methods/technologies, (3) multilevel analysis, and (4) knowledge integration. Complementary to the survey, we conducted a portfolio analysis of active NCI-funded training grants. In the present report, we provide our findings from this effort and contribute to the on-going conversation regarding the training of next-generation cancer epidemiologists. Analyses and insights gained from conversations with leaders/educators across 24 academic institutions/cancer centers and the portfolio analysis of training grants echoed contemporaneous conversation that cancer epidemiology training must adapt to meet the needs of the changing research environment. Currently, with the exception of novel methods/technologies, cancer epidemiology trainees receive the majority of their training in collaboration, multilevel approaches, and knowledge integration/translation either informally, ad hoc, or not at all; exposure to these identified drivers varied considerably by institution, mentor, and other external as well as internal factors.

Unfractionated heparin (UFH) is frequently used in the treatment of venous thromboembolism and acute coronary syndrome. There are many common cutaneous adverse reactions to this medication. We present a unique case of hemorrhagic bullae limited to the oral mucosa that developed within 6 hours of a patient receiving UFH.

Bullous systemic lupus erythematosus (BSLE) is a rare complication of systemic lupus erythematosus (SLE) characterized by cutaneous vesicles and bullae with a primarily neutrophilic infiltrate on histopathology. Bullous SLE is a heterogeneous disease without pathognomonic clinical features, making the diagnosis and differentiation from other blistering diseases challenging. We present the case of a single patient with SLE in whom 3 different clinical appearances of BSLE manifested over 5 years. The cutaneous eruption dramatically improved with rituximab at the initial presentation and continued to respond to rituximab during subsequent flares over the subsequent 5 years.

Background: Vitamin C insufficiency occurs across many countries and has been hypothesised to increase risk of various diseases. Few prospective studies with measured circulating vitamin C have related deficiency to disease mortality, particularly in low-income and middle-income countries., Methods: We randomly selected 948 subjects (473 males and 475 females) aged 53-84 years from a Chinese cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in plasma samples collected in 1999-2000. A total of 551 deaths were accrued from sample collection through 2016, including 141 from cancer, 170 from stroke and 174 from heart diseases. Vitamin C was analysed using season-specific quartiles, as a continuous variable and as a dichotomous variable based on sufficiency status (normal >28 µmol/L vs low ≤28 µmol/L). HRs and 95% CIs were estimated using Cox proportional hazards models., Results: We found significant inverse associations between higher plasma vitamin C concentrations and total mortality in quartile (HR Q4 vs Q1 0.75, 95% CI 0.59 to 0.95), continuous (HR q20umol/L 0.90, 95% CI 0.82 to 0.99) and dichotomous analyses (HR normal-vs-low 0.77, 95% CI 0.63 to 0.95). We observed significant lower risks of heart disease (p trend-by-quantile =0.03) and cancer deaths (p global-across-quantile =0.04) for higher vitamin C, whereas the association was attenuated for stroke in adjusted models. Similar inverse associations were found when comparing normal versus low vitamin C for heart disease (HR normal-vs-low 0.62, 95% CI 0.42 to 0.89)., Conclusion: In this long-term prospective Chinese cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Biomarkers that represent the structural and functional integrity of the motor system enable us to better assess motor outcome post-stroke. The degree of overlap between the stroke lesion and corticospinal tract (CST Injury) is a measure of the structural integrity of the motor system, whereas the left-to-right motor cortex resting state connectivity (LM1-RM1 rs-connectivity) is a measure of its functional integrity. CST Injury and LM1-RM1 rs-connectivity each individually correlate with motor outcome post-stroke, but less is understood about the relationship between these biomarkers. Thus, this study investigates the relationship between CST Injury and LM1-RM1 rs-connectivity, individually and together, with motor outcome. Twenty-seven participants with upper limb motor deficits post-stroke completed motor assessments and underwent MRI at one time point. CST Injury and LM1-RM1 rs-connectivity were derived from T1-weighted and resting state functional MRI scans, respectively. We performed hierarchical multiple regression analyses to determine the contribution of each biomarker in explaining motor outcome. The interaction between CST Injury and LM1-RM1 rs-connectivity does not significantly contribute to the variability in motor outcome. However, inclusion of both CST Injury and LM1-RM1 rs-connectivity explains more variability in motor outcome, than either alone. We suggest both biomarkers provide distinct information about an individual's motor outcome.

Movement is traditionally viewed as a process that involves motor brain regions. However, movement also implicates non-motor regions such as prefrontal and parietal cortex, regions whose integrity may thus be important for motor recovery after stroke. Importantly, focal brain damage can affect neural functioning within and between distinct brain networks implicated in the damage. The aim of this study is to investigate how resting state connectivity (rs-connectivity) within and between motor and frontoparietal networks are affected post-stroke in correlation with motor outcome. Twenty-seven participants with chronic stroke with unilateral upper limb deficits underwent motor assessments and magnetic resonance imaging. Participants completed the Chedoke-McMaster Stroke Assessment as a measure of arm (CMSA-Arm) and hand (CMSA-Hand) impairment and the Action Research Arm Test (ARAT) as a measure of motor function. We used a seed-based rs-connectivity approach defining the motor (seed=contralesional primary motor cortex (M1)) and frontoparietal (seed=contralesional dorsolateral prefrontal cortex (DLPFC)) networks. We analyzed the rs-connectivity within each network (intra-network connectivity) and between both networks (inter-network connectivity), and performed correlations between: a) intra-network connectivity and motor assessment scores; b) inter-network connectivity and motor assessment scores. We found: a) Participants with high rs-connectivity within the motor network (between M1 and supplementary motor area) have higher CMSA-Hand stage (z=3.62, p=0.003) and higher ARAT score (z=3.41, p=0.02). Rs-connectivity within the motor network was not significantly correlated with CMSA-Arm stage (z=1.83, p>0.05); b) Participants with high rs-connectivity within the frontoparietal network (between DLPFC and mid-ventrolateral prefrontal cortex) have higher CMSA-Hand stage (z=3.64, p=0.01). Rs-connectivity within the frontoparietal network was not significantly correlated with CMSA-Arm stage (z=0.93, p=0.03) or ARAT score (z=2.53, p=0.05); and c) Participants with high rs-connectivity between motor and frontoparietal networks have higher CMSA-Hand stage (r s =0.54, p=0.01) and higher ARAT score (r s =0.54, p=0.009). Rs-connectivity between the motor and frontoparietal networks was not significantly correlated with CMSA-Arm stage (r s =0.34, p=0.13). Taken together, the connectivity within and between the motor and frontoparietal networks correlate with motor outcome post-stroke. The integrity of these regions may be important for an individual's motor outcome. Motor-frontoparietal connectivity may be a potential biomarker of motor recovery post-stroke., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism., Methods: Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry., Results: In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression., Conclusions: Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.

Background: Epidemiologic evidence on the association between nut consumption and lung cancer risk is limited. Methods: We investigated this relationship in the Environment and Genetics in Lung Cancer Etiology (EAGLE) study, a population-based case-control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2,098 lung cases for EAGLE and 18,533 incident cases in AARP. Diet was assessed by food frequency questionnaire for both studies. Multivariable ORs and HRs and respective 95% confidence intervals (CI) were calculated using unconditional logistic regression and Cox proportional hazards regression for EAGLE and AARP, respectively. Results: Higher frequency of intake of nut consumption was inversely associated with overall lung cancer risk (highest vs. lowest quintile, OR EAGLE = 0.74; 95% CI, 0.57-0.95; HR AARP = 0.86; 95% CI, 0.81-0.91), regardless of smoking status. Results from the prospective cohort showed similar associations across histologic subtypes and a more pronounced benefits from nut consumption for those who smoked 1 to 20 cigarettes/day (OR EAGLE = 0.61; 95% CI, 0.39-0.95; HR AARP = 0.83; 95% CI, 0.74-0.94). Conclusions: Nut consumption was inversely associated with lung cancer in two large population-based studies, and associations were independent of cigarette smoking and other known risk factors. Impact: To our knowledge, this is the first study that examined the association between nut consumption and lung cancer risk by histologic subtypes and smoking intensity. Cancer Epidemiol Biomarkers Prev; 26(6); 826-36. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Obesity and diabetes are associated with increased chronic low-grade inflammation and elevated plasma glucose levels. Although inflammation in the fat and liver are established features of obesity-associated insulin resistance, the intestine is emerging as a new site for immunologic changes that affect whole-body metabolism. Specifically, microbial and dietary factors incurred by diet-induced obesity influence underlying innate and adaptive responses of the intestinal immune system. These responses affect the maintenance of the intestinal barrier, systemic inflammation, and glucose metabolism. In this Review we propose that an understanding of the changes to the intestinal immune system, and how these changes influence systemic immunity and glucose metabolism in a whole-body integrative and a neuronal-dependent network, will unveil novel intestinal pathologic and therapeutic targets for diabetes and obesity., Competing Interests: The authors have declared that no conflict of interest exists.

In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials., Competing Interests: Authors have no conflict of interests to disclose.

Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes.