Unravelling the genetic causality of immunoglobulin G N-glycans in ischemic stroke.

BACKGROUND: Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. METHODS: Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. RESULTS: After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. CONCLUSIONS: Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.

Free-Rider Games for Cooperative Spectrum Sensing and Access in CIoT Networks.

With the rapid development of technologies such as wireless communications and the Internet of Things (IoT), the proliferation of IoT devices will intensify the competition for spectrum resources. The introduction of cognitive radio technology in IoT can minimize the shortage of spectrum resources. However, the open environment of cognitive IoT may involve free-riding problems. Due to the selfishness of the participants, there are usually a large number of free-riders in the system who opportunistically gain more rewards by stealing the spectrum sensing results from other participants and accessing the spectrum without spectrum sensing. However, this behavior seriously affects the fault tolerance of the system and the motivation of the participants, resulting in degrading the system's performance. Based on the energy-harvesting cognitive IoT model, this paper considers the free-riding problem of Secondary Users (SUs). Since free-riders can harvest more energy in spectrum sensing time slots, the application of energy harvesting technology will exacerbate the free-riding behavior of selfish SUs in Cooperative Spectrum Sensing (CSS). In order to prevent the low detection performance of the system due to the free-riding behavior of too many SUs, a penalty mechanism is established to stimulate SUs to sense the spectrum normally during the sensing process. In the system model with multiple primary users (PUs) and multiple SUs, each SU considers whether to free-ride and which PU's spectrum to sense and access in order to maximize its own interests. To address this issue, a two-layer game-based cooperative spectrum sensing and access method is proposed to improve spectrum utilization. Simulation results show that compared with traditional methods, the average throughput of the proposed TL-CSAG algorithm increased by 26.3% and the proposed method makes the SUs allocation more fair.

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease.

PURPOSE: Positron emission tomography (PET) with the first and only tau targeting radiotracer of 18F-flortaucipir approved by FDA has been increasingly used in depicting tau pathology deposition and distribution in patients with cognitive impairment. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform 18F-flortaucipir PET imaging. METHOD: A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for 18F-flortaucipir PET imaging in Alzheimer's disease (AD), focusing on clinical scenarios, patient preparation, and administered activities, as well as image acquisition, processing, interpretation, and reporting. CONCLUSION: This international consensus and practice guideline will help to promote the standardized use of 18F-flortaucipir PET in patients with AD. It will become an international standard for this purpose in clinical practice.

Structural basis of a multi-functional deaminase in chlorovirus PBCV-1.

2-Deoxycytidylate deaminase (dCD) is a member of the zinc-dependent cytidine deaminase family features in its allosterically regulated mechanism by dCTP and dTTP. The large double-stranded DNA-containing chlorovirus PBCV-1 encodes a dCD family enzyme PBCV1dCD that was reported to be able to deaminize both dCMP and dCTP, which makes PBCV1dCD unique in the dCD family proteins. In this study, we report the crystal structure of PBCV1dCD in complex with dCTP/dCMP and dTTP/dTMP, respectively. We further proved the ability of PBCV1dCD in the deamination of dCDP, which makes PBCV1dCD a multi-functional deaminase. The structural basis for the versatility of PBCV1dCD is analyzed and discussed, with the finding of a unique Trp121 residue key to the deamination and substrate binding ability. Our findings may broaden the understanding of dCD family proteins and provide novel insights into the multi-functional enzyme.

A deep learning framework for 18F-FDG PET imaging diagnosis in pediatric patients with temporal lobe epilepsy.

PURPOSE: Epilepsy is one of the most disabling neurological disorders, which affects all age groups and often results in severe consequences. Since misdiagnoses are common, many pediatric patients fail to receive the correct treatment. Recently, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging has been used for the evaluation of pediatric epilepsy. However, the epileptic focus is very difficult to be identified by visual assessment since it may present either hypo- or hyper-metabolic abnormality with unclear boundary. This study aimed to develop a novel symmetricity-driven deep learning framework of PET imaging for the identification of epileptic foci in pediatric patients with temporal lobe epilepsy (TLE). METHODS: We retrospectively included 201 pediatric patients with TLE and 24 age-matched controls who underwent 18F-FDG PET-CT studies. 18F-FDG PET images were quantitatively investigated using 386 symmetricity features, and a pair-of-cube (PoC)-based Siamese convolutional neural network (CNN) was proposed for precise localization of epileptic focus, and then metabolic abnormality level of the predicted focus was calculated automatically by asymmetric index (AI). Performances of the proposed framework were compared with visual assessment, statistical parametric mapping (SPM) software, and Jensen-Shannon divergence-based logistic regression (JS-LR) analysis. RESULTS: The proposed deep learning framework could detect the epileptic foci accurately with the dice coefficient of 0.51, which was significantly higher than that of SPM (0.24, P < 0.01) and significantly (or marginally) higher than that of visual assessment (0.31-0.44, P = 0.005-0.27). The area under the curve (AUC) of the PoC classification was higher than that of the JS-LR (0.93 vs. 0.72). The metabolic level detection accuracy of the proposed method was significantly higher than that of visual assessment blinded or unblinded to clinical information (90% vs. 56% or 68%, P < 0.01). CONCLUSION: The proposed deep learning framework for 18F-FDG PET imaging could identify epileptic foci accurately and efficiently, which might be applied as a computer-assisted approach for the future diagnosis of epilepsy patients. TRIAL REGISTRATION: NCT04169581. Registered November 13, 2019 Public site: https://clinicaltrials.gov/ct2/show/NCT04169581.

Structural insight into substrate preference for TET-mediated oxidation.

DNA methylation is an important epigenetic modification. Ten-eleven translocation (TET) proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Here we show that human TET1 and TET2 are more active on 5mC-DNA than 5hmC/5fC-DNA substrates. We determine the crystal structures of TET2-5hmC-DNA and TET2-5fC-DNA complexes at 1.80 Å and 1.97 Å resolution, respectively. The cytosine portion of 5hmC/5fC is specifically recognized by TET2 in a manner similar to that of 5mC in the TET2-5mC-DNA structure, and the pyrimidine base of 5mC/5hmC/5fC adopts an almost identical conformation within the catalytic cavity. However, the hydroxyl group of 5hmC and carbonyl group of 5fC face towards the opposite direction because the hydroxymethyl group of 5hmC and formyl group of 5fC adopt restrained conformations through forming hydrogen bonds with the 1-carboxylate of NOG and N4 exocyclic nitrogen of cytosine, respectively. Biochemical analyses indicate that the substrate preference of TET2 results from the different efficiencies of hydrogen abstraction in TET2-mediated oxidation. The restrained conformation of 5hmC and 5fC within the catalytic cavity may prevent their abstractable hydrogen(s) adopting a favourable orientation for hydrogen abstraction and thus result in low catalytic efficiency. Our studies demonstrate that the substrate preference of TET2 results from the intrinsic value of its substrates at their 5mC derivative groups and suggest that 5hmC is relatively stable and less prone to further oxidation by TET proteins. Therefore, TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate the generation of 5hmC as a potentially stable mark for regulatory functions.

A time-trend ecological study for identifying flood-sensitive infectious diseases in Guangxi, China from 2005 to 2012.

BACKGROUND: Flood-related damage can be very severe and include health effects. Among those health impacts, infectious diseases still represent a significant public health problem in China. However, there have been few studies on the identification of the spectrum of infectious diseases associated with floods in one area. This study aimed to quantitatively identify sensitive infectious diseases associated with floods in Guangxi, China. METHODS: A time-trend ecological design was conducted. A descriptive analysis was first performed to exclude infectious diseases with low incidence from 2005 to 2012 in ten study sites of Guangxi. The Wilcoxon rank-sum test was applied to examine the difference in the ten-day attack rate of infectious diseases between the exposure and control periods with different lagged effects. Negative binomial, zero-inflated Poisson and zero-inflated negative binomial models were used to examine the relationship and odd ratios (ORs) of the risk of floods on infectious diseases of preliminary screening. RESULTS: A total of 417,271 infectious diseases were notified. There were 11 infectious diseases associated with floods in the preliminary screening process for flood-sensitive infectious diseases. The strongest effect was shown with a 0-9 ten-day lag in different infectious diseases. Multivariate analysis showed that floods were significantly associated with an increased the risk of bacillary dysentery (odds ratio (OR) = 1.268, 95% confidence interval (CI): 1.072-1.500), acute haemorrhagic conjunctivitis (AHC, OR = 3.230, 95% CI: 1.976-5.280), influenza A (H1N1) (OR = 1.808, 95% CI: 1.721-1.901), tuberculosis (OR = 1.200, 95% CI: 1.036-1.391), influenza (OR = 2.614, 95% CI: 1.476-4.629), Japanese encephalitis (OR = 2.334, 95% CI: 1.119-4.865), and leptospirosis (OR = 1.138, 95% CI: 1.075-1.205), respectively. CONCLUSION: The spectrum of infectious diseases which are associated with floods are bacillary dysentery, AHC, influenza A (H1N1), tuberculosis, influenza, Japanese encephalitis and leptospirosis in Guangxi. Floods can result in differently increased risk of these diseases, and public health action should be taken to control a potential risk of these diseases after floods.

18F-FDG PET and high-resolution MRI co-registration for pre-surgical evaluation of patients with conventional MRI-negative refractory extra-temporal lobe epilepsy.

PURPOSE: Epilepsy that originates outside of the temporal lobe can present some of the most challenging problems for surgical therapy, especially for patients with conventional magnetic resonance imaging (MRI)-negative refractory extra-temporal lobe epilepsy (ETLE). This study aimed to evaluate the clinical value of pre-surgical 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) and high-resolution MRI (HR-MRI) co-registration in patients with conventional MRI-negative refractory ETLE, and compare their surgical outcomes. METHODS: Sixty-seven patients with conventional MRI-negative refractory ETLE were prospectively included for pre-surgical 18F-FDG PET and HR-MRI examinations. Under the guidance of 18F-FDG PET and HR-MRI co-registration, HR-MRI images were re-read. Based on the image result changes from first reading to re-reading, patients were divided into three groups: Change-1 (lesions of subtle abnormality could be identified in re-read), Change-2 (non-specific abnormalities reported in the first reading were considered as lesions on HR-MRI re-read) and No-change. Post-surgical follow-ups were conducted for up to 59 months. RESULTS: Visual analysis of 18F-FDG PET showed focal or regional abnormality in 46 patients (68.6%), while the abnormal rate increased to 94.0% (P < 0.05) by co-registration. Of the 67 patients, 46.3% of them were identified as Change-1, and 11.9% as Change-2 after co-registration and HR-MRI re-read. Patients with Change-1 and -2 were more likely to be recommended to receive surgical resection (P < 0.001). In the 17 post-surgical patients, 88% had good outcomes, whereas 11.7% had poor outcomes during our study period. CONCLUSION: Pre-surgical evaluation by co-registration of 18F-FDG PET and HR-MRI could improve the identification of the epileptogenic onset zone (EOZ), and may further guide the surgical decision-making and improve the outcome of the refractory ETLE with normal conventional MRI; therefore, it should be recommended as a standard procedure for pre-surgical evaluation of these patients.

Preoperative Computed Tomography (CT) Evaluation of Anatomical Abnormalities in Endonasal Transsphenoidal Approach in Pituitary Adenoma.

BACKGROUND This study aimed to retrospectively analyze patient clinical data to investigate the effects of computed tomography (CT) reconstruction and the measurement of abnormal structures in the endonasal sphenoidal sinus approach on the operative effects in patients undergoing pituitary adenoma resection. MATERIAL AND METHODS The records of 53 patients who underwent pituitary adenoma resection via the endonasal transsphenoidal approach in the Neurosurgery Department of Tai'an City Central Hospital from December 2010 to June 2016 were analyzed retrospectively. All cases showed anatomical abnormalities in the endonasal transsphenoidal approach that were detected by conventional CT scans. The clinical data of the patients were reviewed. After review, 26 patients who underwent preoperative CT reconstruction and measurement of abnormal structures before surgery were included in the observation group (CT reconstruction group), and 27 patients who did not undergo CT reconstruction and measurement of abnormal structures were included in the control group. Data on intraoperative blood loss, surgical time, hospital stay, and postoperative complications were collected to assess the quality of the surgery. RESULTS Compared with the control group, the observation group showed less blood loss (p<0.001), a shorter operation time (p<0.001), fewer postoperative complications (p<0.001), and a shorter hospital stay (p<0.001). CONCLUSIONS Preoperative CT reconstruction and measurement of abnormal structures in patients undergoing pituitary adenoma resection by the endonasal transsphenoidal approach can improve operative quality and reduce complications.

Neural correlates of the popular music phenomenon: evidence from functional MRI and PET imaging.

PURPOSE: Music can induce different emotions. However, its neural mechanism remains unknown. The aim of this study was to use functional magnetic resonance imaging (fMRI) and position emission tomography (PET) imaging for mapping of neural changes under the most popular music in healthy volunteers. METHODS: Blood-oxygen-level-dependent (BOLD) fMRI and monoamine receptor PET imaging with 11C-N-methylspiperone (11C-NMSP) were conducted under the popular music Gangnam Style and light music A Comme Amour in healthy subjects. PET and fMRI images were analyzed by using the Statistical Parametric Mapping software (SPM). RESULTS: Significantly increased fMRI BOLD signals were found in the bilateral superior temporal cortices, left cerebellum, left putamen and right thalamus cortex. Monoamine receptor availability was increased significantly in the left superior temporal gyrus and left putamen, but decreased in the bilateral superior occipital cortices under the Gangnam Style compared with the light music condition. Significant positive correlation was found between 11C-NMSP binding and fMRI BOLD signals in the left temporal cortex. Furthermore, increased 11C-NMSP binding in the left putamen was positively correlated with the mood arousal level score under the Gangnam Style condition. CONCLUSION: Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.

Diffusion Tensor Imaging of White Matter Injury Caused by Prematurity-Induced Hypoxic-Ischemic Brain Damage.

BACKGROUND This investigation aimed to evaluate changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of white matter injury (WMI) in preterm neonates with hypoxic-ischemic encephalopathy (HIE) using diffusion tension imaging (DTI). MATERIAL AND METHODS Thirty-eight neonates less than 37 weeks of gestation with leukoencephalopathy (as observation group) and 38 full-term infants with no leukoencephalopathy (as control group) were selected from the Neonatal Care Center in Taian Central Hospital from January 2012 to December 2013. A DTI scan was obtained within 1 week after birth. RESULTS In the observation group, on both sides the ADC values in regions of interest (ROI) of white matter, lesions were greater and FA values were lower than in the control group. ADC and FA values in genu and splenum of corpus callosum were statistically different between the mild and severe injury groups (p<0.05). CONCLUSIONS This study demonstrates that DTI provides sensitive detection and early diagnosis of WMI in brains of premature infants with HIE.

Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis.

BACKGROUND: Interleukin-6 (IL-6) is an important mediator of atherosclerotic disease and is also associated with coronary artery disease (CAD). The growing evidences suggest that polymorphisms in the IL-6 promoter region influence the progression of CAD. This study was performed to update the systematic results of association of IL-6 gene polymorphisms with CAD. METHODS: PubMed, Embase, and China Biology Medicine were searched systematically for English and Chinese articles published up to October 31, 2014. Data were extracted using standardized forms. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Subgroup analyses were made on ethnicity. RESULTS: A total of 42 studies including 15,145 cases and 21,496 controls were combined in this meta-analysis. IL-6 gene -174G/C polymorphism was associated with an increased risk of CAD (for C allele versus G allele: OR = 1.11, 95 % CI 1.02-1.20; for C/C versus G/G: OR = 1.21, 95 % CI 1.03-1.42; for C/C + C/G versus G/G: OR = 1.14, 95 % CI 1.03-1.27). In the subgroup analyses based on ethnicity, a significant association was found between -174 G/C polymorphism and CAD in Caucasians (for C allele versus G allele: OR = 1.12, 95 % CI 1.03-1.22; for C/C versus G/G: OR = 1.21, 95 % CI 1.02-1.42; for C/C + C/G versus G/G: OR = 1.16, 95 % CI 1.05-1.29). In order to reduce heterogeneity, we removed the outlier studies by a Galbraith plot analysis. As a result, the pooled ORs demonstrated no association of -174G/C polymorphism and CAD (C allele versus G allele: OR = 1.02, 95 % CI 0.97-1.06, p = 0.48; C/C versus G/G: OR = 0.1.03, 95 % CI 0.94-1.13, p = 0.48; C/G + C/C versus G/G: OR = 1.03, 95 % CI 0.96-1.09, p = 0.41; C/C versus C/G + G/G: OR = 1.02, 95 % CI 0.94-1.10, p = 0.70, respectively). The polymorphism of -572 G/C was not associated with CAD significantly (for C allele versus G allele: OR = 0.86, 95 % CI 0.74-1.01; C/C versus G/G: OR = 0.99, 95 % CI 0.43-2.27; C/G + C/C versus G/G: OR = 0.96, 95 % CI 0.80-1.15, respectively). In addition, subgroup analyses showed an association between -572 G/C polymorphism and CAD risk among Chinese (C allele versus G allele: OR = 0.64, 95 % CI 0.48-0.85; C/C versus G/G: OR = 0.38, 95 % CI 0.18-0.81; C/G + C/C versus G/G: OR = 0.47, 95 % CI 0.22-1.00; C/C versus C/G + G/G: OR = 0.58, 95 % CI 0.42-0.81). CONCLUSION: The C allele of -174G/C polymorphism may associate with increased sensibility to CAD among Caucasians in overall analysis. Nevertheless, the effect is interfered by heterogeneity across the included studies. The C allele of -572G/C polymorphism may decrease the risk of CAD in Chinese.

Citreoviridin enhances tumor necrosis factor-α-induced adhesion of human umbilical vein endothelial cells.

Endothelial adhesion plays an important role in the process of atherosclerosis, which is regulated by endothelial adhesion molecules and chemoattractant molecules. In some areas of China, citreoviridin (CIT) is considered a risk factor for the development of atherosclerosis. Here, we investigated the role of CIT in adhesion of human umbilical vein endothelial cells (HUVECs) together with the stimulation of tumor necrosis factor-α (TNF-α). Adhesion of HUVECs to monocytes was analyzed by coculture experiments using U937 cells labeled with 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethylester. The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was determined by Western blot and enzyme-linked immunosorbent assay (ELISA). The expression of monocyte chemoattractant protein-1 (MCP-1) was measured by reverse transcription polymerase chain reaction and ELISA. The activation of nuclear factor-κB (NF-κB) was assessed by Western blot and immunofluorescence staining. CIT markedly increased TNF-α-induced HUVECs adhesion to monocytes and the expression levels of ICAM-1, VCAM-1, E-selectin, and MCP-1. TNF-α-induced nuclear translocation of NF-κB in HUVECs was significantly elevated by CIT. Our study demonstrates that CIT upregulates TNF-α-induced endothelial adhesion via increasing activation of NF-κB, which results in the expression of ICAM-1, VCAM-1, E-selectin, and MCP-1. CIT plays a pivotal role in the process of endothelial cell adhesion and may thereby play an important role in the improvement of atherosclerosis in areas of China that have a high prevalence of CIT contamination and atherosclerosis.

Solution small angle X-ray scattering (SAXS) studies of RecQ from Deinococcus radiodurans and its complexes with junction DNA substrates.

RecQ helicases, essential enzymes for maintaining genome integrity, possess the capability to participate in a wide variety of DNA metabolisms. They can initiate the homologous recombination repair pathway by unwinding damaged dsDNA and suppress hyper-recombination by promoting Holliday junction (HJ) migration. To learn how DrRecQ participates in the homologous recombination repair pathway, solution structures of Deinococcus radiodurans RecQ (DrRecQ) and its complexes with DNA substrates were investigated by small angle x-ray scattering. We found that the catalytic core and the most N-terminal HRDC (helicase and RNase D C-terminal) domain (HRDC1) undergo a conformational change to a compact state upon binding to a junction DNA. Furthermore, models of DrRecQ in complexes with two kinds of junction DNA (fork junction and HJ) were built based on the small angle x-ray scattering data, and together with the EMSA results, possible binding sites were proposed. It is demonstrated that two DrRecQ molecules bind to the opposite arms of HJ. This architecture is similar to the RuvAB complex and is hypothesized to be highly conserved in the other HJ migration proteins. This work provides us new clues to understand the roles DrRecQ plays in the RecFOR pathway.

PET imaging reveals brain functional changes in internet gaming disorder.

BACKGROUND: Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism. METHODS: Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and (11)C-N-methylspiperone ((11)C-NMSP) to assess the availability of D2/5-HT2A receptors and with (18)F-fluoro-D-glucose ((18)F-FDG) to assess regional brain glucose metabolism, a marker of brain function. (11)C-NMSP and (18)F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. RESULTS: In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. CONCLUSIONS: For the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects.

The mediating effect of perceived stress on the relationship between big five personality traits and suboptimal health status in Chinese population: a nationwide survey in the framework of predictive, preventive, and personalized medicine.

Background: The effects of psychological factors on suboptimal health status (SHS) have been widely described; however, mechanisms behind the complex relationships among the Big Five personality traits and SHS are unclear. Identifying people with specific traits who are susceptible to SHS will help improve life quality and reduce the chronic disease burden under the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). This study investigated the relationships among personality traits and SHS. It also explored whether perceived stress plays a mediating role in SHS development. Method: A nationwide cross-sectional survey based on multistage random sampling was conducted in 148 cities in China between June 20 and August 31, 2022. Personality traits, perceived stress, and SHS were evaluated using the Big Five Inventory-10 (BFI-10), the 4-item Perceived Stress Scale (PSS-4), and the Short-Form Suboptimal Health Status Questionnaire (SHSQ-SF), respectively. Pearson's correlation analysis was employed to examine the associations between personality traits, perceived stress, and SHS. Structural equation modeling (SEM) was used to discern the mediating role of perceived stress in the relationships among personality traits and SHS. Result: A total of 22,897 participants were enrolled in this study, among whom the prevalence of SHS was 52.9%. SHS was negatively correlated with three trait dimensions (i.e., extraversion, agreeableness, and conscientiousness) but positively correlated with neuroticism. Meanwhile, stress was negatively correlated with extraversion, agreeableness, conscientiousness, and openness, whereas it was positively correlated with neuroticism. The SEM results showed that, when adjusting for covariates (i.e., gender, age, BMI, educational level, current residence, marital status, and occupational status), higher agreeableness (ß = - 0.049, P < 0.001) and conscientiousness (ß = - 0.103, P < 0.001) led to lower SHS prevalence, higher neuroticism (ß = 0.130, P < 0.001), and openness (ß = 0.026, P < 0.001) caused SHS to be more prevalent. Perceived stress played a partial mediating role in the relationships among personality traits and SHS, respectively, contributing 41.3%, 35.9%, and 32.5% to the total effects of agreeableness, conscientiousness, and neuroticism on SHS. Additionally, the mediating impact of stress was significant even though extraversion had no direct effect on SHS. Conclusion: This study revealed a high prevalence of SHS in Chinese residents. Personality traits significantly influenced SHS rates, which perceived stress tended to mediate. From a PPPM perspective, early screening and targeted intervention for people with neuroticism (as well as stress alleviation) might contribute to health enhancement and chronic disease prevention. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00349-x.

Platelet-to-lymphocyte ratio and absolute monocyte count have prognostic potential in primary myelodysplastic neoplasms.

INTRODUCTION: The platelet-to-lymphocyte ratio (PLR), peripheral blood absolute monocyte count (AMC), and monocyte-to-lymphocyte ratio (MLR) are considered biomarkers of systemic immune and inflammation response. However, their prognostic potential in patients with myelodysplastic neoplasms (MDS) remains unclear. This study aimed to explore the predictive impact of PLR, MLR, and AMC on MDS outcomes. METHODS: In total, 334 patients with primary MDS were included between January 2016 and December 2021 and were retrospectively followed up until December 31, 2022. The prognostic significance of PLR, MLR, and AMC was assessed using univariate and multivariate analyses, and predictive models were generated to estimate MDS outcomes. The area under their receiver operating curves was computed to compare the predictive power of these models. RESULTS: Fifty-one patients had disease progression, and 103 patients died during follow-up. In multivariate analyses, a higher PLR was an adverse independent factor for overall survival (OS) (p = 0.011), whereas a higher AMC indicated shorter progression-free survival (p = 0.003). The prognostic model incorporating PLR, MLR, and AMC with the Revised International Prognostic Scoring System (IPSS-R) risk categorization showed higher performance in predicting OS than the model that only utilized the IPSS-R category. CONCLUSION: Elevated PLR and increased AMC had independent prognostic value for adverse outcomes in patients with MDS. PLR, MLR, and AMC enhanced the IPSS-R risk categorization for OS prediction in MDS.

The association between plasma IgG N-glycosylation and neonatal hypoxic-ischemic encephalopathy: a case-control study.

Introduction: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. Methods: This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used to examine the association between initial glycans and HIE, by which the significant parameters were used to develop a diagnostic model. Though receiver operating characteristic (ROC) curves, area under the curve (AUC) and 95% confidence interval (CI) were calculated to assess the performance of the diagnostic model. Results: There were significant differences in 11 initial glycans between the patient and control groups. The levels of fucosylated and galactosylated glycans were significantly lower in HIE patients than in control individuals, while sialylated glycans were higher in HIE patients (p < 0.05). A prediction model was developed using three initial IgG N-glycans and fetal distress, low birth weight, and globulin. The ROC analysis showed that this model was able to discriminate between HIE patients and healthy individuals [AUC = 0.798, 95% CI: (0.716-0.880)]. Discussion: IgG N-glycosylation may play a role in the pathogenesis of HIE. Plasma IgG N-glycans are potential noninvasive biomarkers for screening individuals at high risk of HIE.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational, randomised, controlled effectiveness-implementation trial.

BACKGROUND: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. METHODS: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed. FINDINGS: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found. INTERPRETATION: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up. FUNDING: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

The crystal structure of human protein α1M reveals a chromophore-binding site and two putative protein-protein interfaces.

Lipocalin α1-microglobulin (α1M) is a conserved glycoprotein present in plasma and in the interstitial fluids of all tissues. α1M is linked to a heterogeneous yellow-brown chromophore of unknown structure, and interacts with several target proteins, including α1-inhibitor-3, fibronectin, prothrombin and albumin. To date, there is little knowledge about the interaction sites between α1M and its partners. Here, we report the crystal structure of the human α1M. Due to the crystallization occurring in a low ionic strength solution, the unidentified chromophore with heavy electron density is observed at a hydrophobic inner tube of α1M. In addition, two conserved surface regions of α1M are proposed as putative protein-protein interface sites. Further study is needed to unravel the detailed information about the interaction between α1M and its partners.