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Presbycusis is a major public issue that affecting elderly adults. However, the neural substrates between normal cognition and cognitive deficits in these patients need to be illustrated. 47 patients with presbycusis and 33 well-matched healthy controls were recruited in present study. Each subject underwent pure-tone audiometry (PTA), MRI scanning and cognition evaluations, then we found 22 patients with cognitive deficits and 25 patients with common cognition. We analyzed the Degree centrality (DC) characteristics among three groups, and try to recognize key nodes which contribute significantly. Subsequent functional connectivity analysis was applied using the key nodes as seeds. Compared with controls, presbycusis without cognitive impairments showed deceased DC in superior temporal gyrus (STG), inferior frontal gyrus (IFG) and supramarginal gyrus (SMG). Additionally, presbycusis with cognitive impairments showed enhanced DC in fusiform gurus (FFG), cerebellum and para-hippocampal gyrus (PHG), while weakened DC in SMG, middle frontal gyrus (IFG) and inferior Parietal lobule (IPL). Compared with normal cognition, increased DC value of cerebellum and STG, as well as decreased DC value of IPL in presbycusis with cognitive impairments were observed. We noticed that SMG may play an important role. Then the left and right SMG were used as seeds in functional connections analysis. With the seed set at left SMG, presbycusis without cognitive impairments showed decreases connections with cerebellum, temporal pole (TP), superior temporal gyrus (STG) and median cingulate cortex (MCC). Presbycusis with cognitive impairments showed weakened connectivity with cerebellum, IFG, IPL and superior frontal gyrus (SFG). The right SMG showed decrease connections with cerebellum, middle temporal gyrus (MTG), STG and increase connection with middle frontal gyrus (MFG) in presbycusis without cognitive impairments. While the right SMG showed enhanced connections with left TP, caudate, anterior cingulate cortex (ACC), angular, SFG and weakened connectivity with right SFG presbycusis with cognitive impairments. In comparison with normal cognition and impaired cognition, MFG, IFG, PHG, rolandic operculum and cerebellum were involved. These findings enriched our understanding of the neural mechanisms underlying cognitive impairments associated with presbycusis and may serve as a potential imaging biomarker for investigating and predicting cognitive difficulties.

Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.

The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD).A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association.High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk.Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD.

Atherosclerosis (AS) is the most common cardiovascular disease (CVD). Currently, it is widely believed that R-TFA and I-TFA may cause different biological effects. In the present study, we aim to elucidate the effect of mixed R-TFA derived from butter on the development of AS in high-fat diet-fed ApoE

We aimed to validate the Children's Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) in Mainland China, which can reflect the profiles of empathizing and systemizing, and describing specific characteristics of autism spectrum disorder (ASD) and gender-typical behaviors in general population. A total of 800 typically developing (TD) children, aged 4–12 years was recruited initially with whose parents/guardians complete the measurements, and 782 TD children who met inclusion criteria were finally included. A 23-item three-factor EQ-C and a 22-item four-factor SQ-C was developed with good internal consistency (Omega total values of 0.87 and 0.86) and test–retest reliability (Pearson correlation coefficients of 0.82 and 0.69). In TD children, girls scored significantly higher on EQ-C (31.4 ± 7.8 vs. 28.2 ± 7.7) but there were no gender differences in SQ-C scores. TD children showed different cognitive styles (empathizing-dominant for girls with 42.6% identified as Type E; systemizing-dominant for boys with 40.7% identified as Type S). A further sample of 222 children with ASD indicated that they scored lower on EQ/SQ-C compared to TD children (13.2 ± 5.1 vs. 29.7 ± 7.9, 12.4 ± 5.8 vs. 23.5 ± 8.3) and were generally systemizing-dominant (Type S: 50.8% for boys and 64.0% for girls). Autistic children scored higher on the SQ-C in those without intellectual disability and with higher paternal education level and family income (14.2 ± 6.1 vs. 10.9 ± 5.0, 13.3 ± 6.2 vs. 11.5 ± 5.1, 13.7 ± 5.6 vs. 11.9 ± 5.8), while there were no differences in the EQ-C. This study indicated good reliability and validity of the Chinese version of EQ/SQ-C, which can be used in Chinese children with and without ASD. Lay Summary: We developed the Chinese version of the Children's Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) in 782 typically developing (TD) children aged 4–12 years in Mainland China, yielding a 23-item, 3-factor EQ-C and a 22-item, 4-factor SQ-C with good psychometric properties. In TD children, we found gender difference only in scores of EQ-C. Further analyses of 222 autistic children indicated that differences were found in scores of SQ-C when considering their gender, intelligence and socio-economic status.

Targeting the virulence factors of phytopathogenic bacteria is an innovative strategy for alleviating or eliminating the pathogenicity and rapid outbreak of plant microbial diseases. Therefore, several types of 1,2,4-triazole thioethers bearing an amide linkage were prepared and screened to develop virulence factor inhibitors. Besides, the 1,2,4-triazole scaffold was exchanged by a versatile 1,3,4-oxadiazole core to expand molecular diversity. Bioassay results revealed that a 1,2,4-triazole thioether

Background To examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline. Methods Data were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2–7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline. Results Both passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job. Limitations Information on working conditions was based on self-reported recollections. Conclusions Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.

Objective Electroencephalography (EEG) is an important tool for neurological outcome prediction after cardiac arrest. However, the complexity of continuous EEG data limits timely and accurate interpretation by clinicians. We develop a deep neural network (DNN) model to leverage complex EEG trends for early and accurate assessment of cardiac arrest coma recovery likelihood. Methods We developed a multiscale DNN combining convolutional neural networks (CNN) and recurrent neural networks (long short-term memory [LSTM]) using EEG and demographic information (age, gender, shockable rhythm) from a multicenter cohort of 1,038 cardiac arrest patients. The CNN learns EEG feature representations while the multiscale LSTM captures short-term and long-term EEG dynamics on multiple time scales. Poor outcome is defined as a Cerebral Performance Category (CPC) score of 3-5 and good outcome as CPC score 1-2 at 3-6 months after cardiac arrest. Performance is evaluated using area under the receiver operating characteristic curve (AUC) and calibration error. Results Model performance increased with EEG duration, with AUC increasing from 0.83 (95% Confidence Interval [CI] 0.79-0.87 at 12h to 0.91 (95%CI 0.88-0.93) at 66h. Sensitivity of good and poor outcome prediction was 77% and 75% at a specificity of 90%, respectively. Sensitivity of poor outcome was 50% at a specificity of 99%. Predicted probability was well matched to the observation frequency of poor outcomes, with a calibration error of 0.11 [0.09-0.14]. Conclusions These results demonstrate that incorporating EEG evolution over time improves the accuracy of neurologic outcome prediction for patients with coma after cardiac arrest.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47–0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

BackgroundThe evidence for associations of emotional/behavioral status with sedentary behavior (SB), physical activity (PA) and step counts is scarce in children with autism spectrum disorder (ASD). Also, ASD-related deficiencies may affect actual levels of PA. We aimed to describe accelerometer-measured SB, PA and step counts in children with ASD, and to examine the associations of emotional/behavioral problems with SB, PA and step counts after assessing associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies.MethodsA total of 93 ASD children, aged 6–9 years, were recruited from the Center for Child and Adolescent Psychology and Behavioral Development of Sun Yat-sen University in Guangzhou, China. Participants wore an accelerometer for seven consecutive days. Of the original 93, 78 participants' accelerometer-measured valid PA were obtained, and the data were shown as time spent in SB, light, moderate, moderate-to-vigorous and vigorous PA, and step counts. Participants' emotional/behavioral problems were assessed via the Strengths and Difficulties Questionnaire (SDQ), and anxiety symptoms were evaluated by the Screen for Child Anxiety Related Emotional Disorders (SCARED). ASD-associated deficiencies include restricted repetitive behaviors (Repetitive Behavior Scale-Revised), poor social competence (Social Responsiveness Scale Second Edition) and motor development restrictions (Developmental Coordination Disorder Questionnaire).ResultsOf the 78 participants, daily vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) averaged 15.62 and 51.95 min, respectively. After adjustment for covariates, SDQ emotional symptoms (β = −0.060, p = 0.028) were inversely associated with the average daily minutes in VPA. Meanwhile, SDQ emotional symptoms (β = −0.033, p = 0.016) were inversely associated with the average daily MVPA minutes in the crude model. After adjustment for covariates, SCARED somatic/panic (β = −0.007, p = 0.040) and generalized anxiety (β = −0.025, p = 0.014) were negatively associated with the average daily VPA minutes; SCARED total anxiety (β = −0.006, p = 0.029) was conversely associated with daily MVPA duration. After adjustment for covariates, no significant associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies were found (p > 0.05).ConclusionsAccelerometer-measured SB, PA and step counts showed no associations with ASD-related deficiencies. On this basis, we further found that the emotional symptoms were inversely associated with VPA and MVPA. These results emphasize the importance of VPA and MVPA in children with ASD. The longitudinally investigations on the directionality of these associations between emotional symptoms with VPA and MVPA are needed in the future.

Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19-related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%-15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; inoculation of permissive cell lines produced less than 0.7-7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients.A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6).Peak epileptiform burden was independently associated with poor outcomes (p 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) 5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290);10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%.Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Purpose Migraine is often accompanied with chronic tinnitus that will affect the cerebral blood flow (CBF) and exacerbate the tinnitus distress. However, the potential relationship between migraine and tinnitus remains unclear. This study will investigate whether aberrant CBF patterns exist in migraine patients with tinnitus and examine the influence of migraine on CBF alterations in chronic tinnitus. Materials and methods Participants included chronic tinnitus patients (n = 45) and non-tinnitus controls (n = 50), matched for age, sex, education, and hearing thresholds. CBF images were collected and analyzed using arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI). Regions with major CBF differences between tinnitus patients and non-tinnitus controls were first detected. The effects of migraine on tinnitus for CBF alterations were further examined. Correlation analyses illustrated the association between CBF values and tinnitus severity as well as between CBF and severity of migraine. Results Compared with non-tinnitus controls, chronic tinnitus patients without migraine exhibited decreased CBF, primarily in right superior temporal gyrus (STG), bilateral middle frontal gyrus (MFG), and left superior frontal gyrus (SFG); decreased CBF in these regions was correlated with tinnitus distress. There was a significant effect of migraine on tinnitus for CBF in right STG and MFG. Moreover, the severity of migraine correlated negatively with CBF in tinnitus patients. Conclusions Chronic tinnitus patients exhibited reduced CBF in the auditory and prefrontal cortex. Migraine may facilitate a CBF decrease in the setting of tinnitus, which may underlie the neuropathological mechanisms of chronic tinnitus comorbid with migraine.

To study the association between paternal age at childbirth and the risk of autism spectrum disorder (ASD) in offspring.In this cross-sectional study, 71 children with ASD who were diagnosed in the Department of Child Healthcare in six hospitals in Guangzhou, Foshan, Beijing, Wuhan, Hangzhou, and Chongqing of China from August 2016 to March 2017 were enrolled as subjects, and 284 typically developing children matched for age, sex, and maternal age at childbirth with the ASD children served as controls. A self-design questionnaire was used to collect the data on social demography, maternal pregnancy, and delivery. The association between paternal age at childbirth and the development of ASD in offspring was evaluated by the logistic regression analysis.After control for demographic factors and pregnancy- and delivery-related factors, the logistic regression analysis showed that a relatively high paternal age at childbirth was significantly associated with the increased risk of ASD in offspring (High paternal age at childbirth is significantly associated with the increased risk of ASD in offspring, and paternal age at childbirth ≥40 years may be the high-risk age group for ASD in offspring.

Objective The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. Methods Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. Results A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. Discussion Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. Clinical trial registration ClinicalTrials.gov number: NCT02430259

Aims/Introduction The association between plasma irisin and glucose levels in the general population is controversial, and few studies have longitudinally detected this correlation. We aimed to examine whether irisin in pregnancy was associated with postpartum glucose levels among Chinese women and explore the modifiable factors. Materials and Methods We carried out a prospective cohort study in Guangzhou, China, during 2017 and 2018, and 453 pregnant women (20–28 weeks) were enrolled. Plasma irisin levels in pregnancy were tested. At 6–8 weeks after delivery, 93 women with gestational diabetes mellitus (GDM) underwent a 75‐g oral glucose tolerance test, and the other 360 women had a fasting blood glucose (FBG) test. Multivariable linear, quantile and logistic regressions were carried out. Results The mean plasma irisin in mid‐pregnancy was 13.73 ng/mL. We observed a significantly negative association between mid‐pregnancy irisin and postpartum FBG (β: −0.056 ± 0.024). However, quantile regression showed the association was only significant in high percentiles of FBG levels (P 50 to P 95), and the magnitude showed an increasing trend. Higher baseline irisin was also associated with a lower risk of postpartum impaired fasting glucose (relative risk 0.563, 95% confidence interval 0.384–0.825). Furthermore, we found significant interactions between irisin and predominant breast‐feeding on FBG and impaired fasting glucose (both P interaction, The present study suggested that plasma irisin levels in mid‐pregnancy were negatively associated with FBG and IFG at 6‐8 weeks postpartum among Chinese women, and stronger associations were observed in women with higher FBG values. Moreover, breast‐feeding may modify this relationship. The results implied that irisin may play a protective role on glucose levels in postpartum women, especially in women with impaired glucose levels.

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.

Aim To determine the effects of glycine powder air-polishing (GPAP) as an adjunct to full-mouth scaling and root planing (SRP) on clinical, inflammatory and microbiological outcomes in patients with untreated periodontitis. Materials and methods Forty-one patients were randomly assigned to the control group A (SRP) and test groups B1 (subgingival GPAP right after SRP) and B2 (subgingival GPAP right before SRP). Clinical examinations and sample collections (saliva, subgingival plaque, serum and gingival crevicular fluid) were performed at assessment visits and before therapies at clinical visits of baseline, 6-week and 3-month. C-reactive protein, IL-6 and TNF-α were assessed in serum and gingival crevicular fluid, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum were measured in saliva and subgingival plaque. Results Patients in control and test groups did not significantly differ by age, sex and disease severity at baseline. Participants in control and intervention groups had similar improvements in clinical parameters (PD, BOP, PLI and BI). All groups had a similar percentage of sites showing PD reduction of ≥2 mm between baseline and follow-up visits, with a few exceptions. Reduced C-reactive protein, IL-6 and TNF-α in serum were found after treatments. Conclusion Full-mouth SRP with and without GPAP resulted in largely similar clinical, inflammatory and microbiological outcomes in the care of untreated periodontitis.

This study aimed to examine individual and combined associations between after-school sedentary time (ST) and daily physical activity (PA) with executive function development in children.The study included 4304 children aged 6 to 12 years. ST and PA were assessed using the International Physical Activity Questionnaire Short Form, and executive function was assessed using the Behavior Rating Inventory of Executive Function (Parent Version). Participants were classified as low (2 h per day) or high (≥2 h per day) ST and low (not meeting guidelines) or high (meeting guidelines) PA. Resulting groups were defined as 1) low ST/high PA, 2) low ST/low PA, 3) high ST/high PA, and 4) high ST/low PA.Children in group 4 had the highest mean T-scores for BRIEF indices (48.23 ± 8.44, indicating increased symptoms of executive function dysfunction), followed by those in group 3 (47.10 ± 8.05), group 2 (45.81 ± 7.78), and group 1 (44.41 ± 7.31). ST was positively related to the T-score of all indices, independent of moderate-to-vigorous physical activity (MVPA). Significantly negative associations were observed between MVPA and Metacognition Index only in the high ST subgroup.Low ST and high PA were positively associated with executive function development in children. Notably, children with high ST and high PA demonstrated more significant deficits in executive function than those with low ST and low PA, suggesting that intervention efforts should focus on ST reduction in addition to promoting PA.

Objective: To evaluate the diagnostic performance of artificial intelligence (AI)–based algorithms for identifying the presence of interictal epileptiform discharges (IEDs) in routine (20-min) electroencephalography (EEG) recordings. Methods: We evaluated two approaches: a fully automated one and a hybrid approach, where three human raters applied an operational IED definition to assess the automated detections grouped into clusters by the algorithms. We used three previously developed AI algorithms: Encevis, SpikeNet, and Persyst. The diagnostic gold standard (epilepsy or not) was derived from video-EEG recordings of patients' habitual clinical episodes. We compared the algorithms with the gold standard at the recording level (epileptic or not). The independent validation data set (not used for training) consisted of 20-min EEG recordings containing sharp transients (epileptiform or not) from 60 patients: 30 with epilepsy (with a total of 340 IEDs) and 30 with nonepileptic paroxysmal events. We compared sensitivity, specificity, overall accuracy, and the review time-burden of the fully automated and hybrid approaches, with the conventional visual assessment of the whole recordings, based solely on unrestricted expert opinion. Results: For all three AI algorithms, the specificity of the fully automated approach was too low for clinical implementation (16.67%; 63.33%; 3.33%), despite the high sensitivity (96.67%; 66.67%; 100.00%). Using the hybrid approach significantly increased the specificity (93.33%; 96.67%; 96.67%) with good sensitivity (93.33%; 56.67%; 76.67%). The overall accuracy of the hybrid methods (93.33%; 76.67%; 86.67%) was similar to the conventional visual assessment of the whole recordings (83.33%; 95% confidence interval [CI]: 71.48–91.70%; p >.5), yet the time-burden of review was significantly lower (p

We sought to investigate electroencephalographers’ real-world behaviors and opinions concerning reading routine EEG (rEEG) with or without clinical information. An eight-question, anonymous, online survey targeted at electroencephalographers was disseminated on social media from the authors’ personal accounts and emailed to authors’ select colleagues. A total of 389 responses were included. Most respondents reported examining clinical information before describing rEEG findings. Nonetheless, only a minority of respondents believe that EEG analysis/description should be influenced by clinical information. We recommend reviewing clinical data only after an unbiased EEG read to prevent history bias and ensure generation of reliable electrodiagnostic information.

Few studies have suggested that long-term adherence to low-carbohydrate diets (LCD) may affect maternal glucose metabolism in Western countries. We aimed to investigate the association between LCD during pregnancy and glucose metabolism in a Chinese population. A total of 1018 women in mid-pregnancy were recruited in 2017–2018. Participants underwent a 75 g oral glucose tolerance test (OGTT). Daily dietary intakes over the past month were accessed using a validated FFQ. The overall, animal and vegetable LCD scores which represent adherence to different low-carbohydrate dietary patterns were calculated. Mixed linear regression and generalised linear mixed regression were conducted to evaluate the associations between LCD scores and maternal glucose metabolism. Of the 1018 subjects, 194 (19·1 %) were diagnosed with gestational diabetes mellitus (GDM). The overall LCD score (β: 0·024, se 0·008, PFDR = 0·02) and animal LCD score (β: 0·023, se 0·008, PFDR = 0·02) were positively associated with OGTT 1-h glucose. No significant associations were found between the three different LCD scores with fasting plasma glucose, OGTT 2-h glucose, or insulin resistance, respectively. Compared with the lowest quartile, the crude OR of GDM for the highest quartile were 1·84 (95 % CI 1·14, 2·95) for overall LCD score (Pfor trend = 0·02) and 1·56 (95 % CI 1·00, 2·45) for animal LCD score (Pfor trend = 0·02). However, these associations became non-significant after adjustment for covariates. In conclusion, a low-carbohydrate dietary pattern with high animal protein and fat is associated with higher postprandial 1-h glucose levels in Chinese pregnant women.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that usually persists into adulthood. However, limited evidence is available regarding its influence on adult health outcomes beyond neuropsychiatric comorbidities. This study aimed to examine the association of ADHD with diabetes in US adults.We analyzed data from the National Health Interview Survey (NHIS), a leading health survey of a nationally representative sample in the United States. We included adults aged 20-79 years who participated in the NHIS 2007 and 2012. Physician-diagnosed ADHD and diabetes were reported during an in-person household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of diabetes.This analysis included 52 821 adults (weighted mean age 45.5 years; 48.6% males). Among them, 1642 participants reported a diagnosis of ADHD and 4631 reported a diagnosis of diabetes. In the multivariable analysis adjusting for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of diabetes among adults with ADHD vs those without ADHD was 1.54 (95% CI, 1.16-2.04). In the stratified analyses, the significant association of ADHD with diabetes remained in most strata, and the associations were not significantly modified by age, sex, race/ethnicity, or obesity status.In a nationally representative sample of US adults, we found a significant association between a history of ADHD diagnosis and diabetes.背景: 注意缺陷力/多动症(ADHD)是一种儿童期出现并通常持续到成年的一种神经发育障碍。除外神经精神病合并症以外, ADHD对患者长期健康结局影响的研究证据非常有限。本项研究旨在了解美国成人ADHD与糖尿病的关系。 方法: 美国国家健康访谈调查(NHIS)是一项针对美国全国代表性样本的健康调查。我们纳入了2007年和2012参加这项调查的20-79岁成年人。在面对面的家庭访谈中收集了ADHD和糖尿病的诊断信息。用纳入了调查样本权重的逻辑回归分析来估计糖尿病的优势比(OR)和95%置信区间(CI)。 结果: 这项分析包括52821名成年人(加权平均年龄45.5岁；48.6%为男性)。其中, 有1642名受试者报告了ADHD的诊断, 4631名受试者报告了糖尿病的诊断。在对年龄, 性别, 种族/族裔, 教育程度, 家庭收入水平, 吸烟, 饮酒, 体育锻炼和体重指数进行校正的多变量分析中, 患有ADHD的成年人与未患ADHD的成年人相比, 其糖尿病OR为1.54(95 % CI:1.16-2.04)。在分层分析中, ADHD与糖尿病之间的显著关联存在于大多数层级中, 并且该关联并未因年龄, 性别, 种族/民族或肥胖状况有明显改变。 结论: 在美国成年人的全国代表性样本中, 我们发现了ADHD的诊断历史与糖尿病之间存在显著关联。.

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is a common, focal, transient, developmental epilepsy syndrome characterized by unilateral or bilateral, independent epileptiform spikes in the Rolandic regions of unknown etiology. Given that CECTS presents during a period of dramatic white matter maturation and thatspikes in CECTS are activated during non–rapid eye movement (REM) sleep, we hypothesized that children with CECTS would have aberrant development of white matter connectivity between the thalamus and the Rolandic cortex. We further tested whether Rolandic thalamocortical structural connectivity correlates with spike rate during non-REM sleep. METHODS: Twenty-three children with CECTS (age = 8-15 years) and 19 controls (age = 7-15 years) underwent 3-T structural and diffusion-weighted magnetic resonance imaging and 72-electrode electroencephalographic recordings. Thalamocortical structural connectivity to Rolandic and non-Rolandic cortices was quantified using probabilistic tractography. Developmental changes in connectivity were compared between groups using bootstrap analyses. Longitudinal analysis was performed in four subjects with 1-year follow-up data. Spike rate was quantified during non-REM sleep using manual and automated techniques and compared to Rolandic connectivity using regression analyses. RESULTS: Children with CECTS had aberrant development of thalamocortical connectivity to the Rolandic cortex compared to controls (P = .01), where the expected increase in connectivity with age was not observed in CECTS. There was no difference in the development of thalamocortical connectivity to non-Rolandic regions between CECTS subjects and controls (P = .19). Subjects with CECTS observed longitudinally had reductions in thalamocortical connectivity to the Rolandic cortex over time. No definite relationship was found between Rolandic connectivity and non-REM spike rate (P > .05). SIGNIFICANCE: These data provide evidence that abnormal maturation of thalamocortical white matter circuits to the Rolandic cortex is a feature of CECTS. Our data further suggest that the abnormalities in these tracts do not recover, but are increasingly dysmature over time, implicating a permanent but potentially compensatory process contributing to disease resolution.

What is known and objective Drug consultation is an important part of pharmaceutical care offered by clinical pharmacists. We explored the characteristics of telephone drug consultations in an obstetrics and gynaecology speciality hospital to provide a reference as to how to improve drug consultation and pharmaceutical care. Methods We retrospectively analysed records of telephone consultations regarding medication use between 2014 and 2019 in our hospital. Any consultation cases with incomplete records were excluded from our analysis. Of the 1353 consultation cases included in our study, we further classified them into different categories based on the content of the consultations, the type of medications being inquired about, and the groups of people who sought medication guidance. Pareto analysis was performed to separate the main issues the callers were concerned about from the more minor concerns. Results and discussion The medication issues that prompted the caller to consult with our clinical pharmacists could be divided into 12 categories, among which the main issues concerned usage and dosage, choice of drug variety, drug incompatibility (drug mixture in infusion bag or tube), adjustment of the treatment plan, and skin tests (cumulative percentage 76.3%). The minor issues involved medication use during pregnancy and lactation and adverse reactions. The top three types of drugs that callers asked about were antimicrobials (600 cases, 44.4%), anti‐tumour drugs (151 cases, 11.2%) and reproductive system drugs (111 cases, 8.2%). The callers could be divided into four groups as follows: doctors (865 cases, 63.9%), nurses (280 cases, 20.7%), patients (116 cases, 8.6%) and other medical professionals (92 cases, 6.8%). What is new and conclusion Usage and dosage, choice of drug variety, drug incompatibility, adjustment of treatment plan and skin tests represented the main issues for telephone drug consultations in our hospital. Doctors and nurses were most likely to consult clinical pharmacists regarding these issues. Improved drug consultation services are needed to allow more patients to have access to advice from pharmacists. Such access would better enable pharmacists to fulfil their roles in advising the appropriate use of drugs to ensure better patient care and medication compliance.

Background Depression is the most common mental health problem and often co-occurs with dementia in old age. This study investigates the influence of late-life depression on risk of dementia. Methods A total of 16210 dementia-free participants aged 60+ from the Survey of Health, Aging, and Retirement in Europe were followed up for 10 years to detect incident dementia. Depression was assessed by a 12-item Europe-depression scale, dementia was determined by physician diagnosis reported by the participants and their informants. Fine and Gray model was performed to explore the association between depression and incident dementia taking into account competing risk of death. Results During an average of 8 years follow-up, 1030 (6.35%) incident dementia were identified. Late-life depression was related to higher subdistribution hazard ratio (sHR) of dementia (sHR=1.52, 95%CI: 1.32-1.75) after adjusting for age, gender, country, education, smoking, drinking, living arrangement, BMI, chronic disease, and physical activity. Further, the risk was only existed in those below age of 80 (sHR=1.75, 95%CI: 1.47-2.07). In addition, a dose-response association was observed between the severity of depression and dementia risk (p for trend Limitation The ascertainment of depression and dementia was based on information reported by the participants and/or their informants, which might result in information bias. The causal relationship could not be determined because limited follow-up time. Conclusions Late-life depression is associated with higher incidence of dementia in a dose-response fashion. Interventions targeting depression patients aged 60-79 years and those with severe depression may be effective strategies to prevent dementia.

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

Objectives Our goal was to explore the pharmaceutical service and teaching methods of obstetric clinical pharmacists to establish standardised pharmaceutical care procedures for obstetric diseases. Methods According to the evidence-based medicine method, the “Standard of Pharmaceutical Care” was established to standardise the procedure and content of the pharmaceutical care procedure including preface, purpose, scope of application, responsibilities, procedures, references, and appendix, with seven parts in total. The object of the pharmaceutical care procedure was selected by the harmfulness of the disease and the drugs used. The clinical pharmacists in obstetrics formulated the pharmaceutical care procedure for each disease according to the standard and carried out clinical practice and teaching. A retrospective study was conducted to investigate the impact of the pharmaceutical care procedure before and after its implementation on both clinical practice and training. Obstetric pharmaceutical consultation and adverse reaction were the key indicators for clinical practice. The graduation assessment for students was strictly carried out in accordance with the regulations of the Chinese Hospital Association Pharmaceutical Affairs Professional Committee including communication and consultation capacity interview, case assessment, and training procedure assessment. Results We established the standards for the pharmaceutical care procedures for three diseases: pregnancy with diabetes; pregnancy with thyroid disease; and pregnancy with hypertensive disorder. The clinical pharmacist conducted the pharmaceutical care procedure, participated in drug treatment management, and improved the recognition of the role of clinical pharmacists by the obstetric clinicians, often inviting the clinical pharmacists to participate in the consultations. The clinical pharmacists discovered and addressed any adverse reactions in a timely manner through patient drug education, subsequently reducing the underreporting of adverse reactions and improving the patient9s medication compliance, which aimed to improve the medical quality of patients in our hospital. Second, the use of the pharmaceutical care procedure as a teaching tool helped to train students to grasp the key points of drug treatment and care of the disease and improve the students9 scores in the graduation assessment (P Conclusions As a pharmacy service and teaching method that can be promoted and implemented, the pharmaceutical care procedure is beneficial for clinical pharmacists to carry out in-depth pharmaceutical services and can also be used as a teaching tool for clinical pharmacist training.

Aims/Introduction The role of irisin in maternal glucose metabolism and how it would respond to dietary n‐3 polyunsaturated fatty acid (n‐3 PUFA) intake remains unclear. This study aimed to explore whether maternal plasma irisin is associated with glucose metabolism and whether this association is modified by dietary n‐3 PUFA. Materials and Methods A total of 932 pregnant women (20–28 weeks’ gestation) aged 20–45 years were recruited. Dietary n‐3 PUFA was estimated using a validated quantitative food frequency questionnaire. Plasma irisin and insulin were tested by enzyme‐linked immunosorbent assay, and insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA). Gestational diabetes mellitus was diagnosed with a 75‐g oral glucose tolerance test. Adjusted multivariable linear regression and logistic regression were carried out to examine the associations between plasma irisin and glucose metabolism. The moderating effect of dietary n‐3 PUFA intake was determined by fully multiplicative models by including the interaction term. Results Maternal plasma irisin was negatively associated with HOMA‐IR and oral glucose tolerance test 0 h glucose level (β −0.250, −0.067; corrected P‐value for false discovery rate = 0.012, 0.018, respectively), positively associated with HOMA of insulin sensitivity (β 0.028; corrected P‐value for false discovery rate = 0.012), but not associated with postprandial glucose or the risk of gestational diabetes mellitus. Furthermore, we found a moderating effect of dietary n‐3 PUFA on the relationships of plasma irisin with HOMA‐IR and HOMA of insulin sensitivity; these associations were strengthened with increased n‐3 PUFA intake (β −0.037, 0.004; P = 0.014, 0.041, respectively). Conclusions Plasma irisin was negatively associated with HOMA‐IR and fasting glucose, whereas it was positively associated with HOMA of insulin sensitivity in pregnant women. We first showed that these associations were modified by dietary n‐3 PUFA intake., Plasma irisin was negatively associated with HOMA‐IR while positively associated with HOMA‐IS in pregnant women, and we first demonstrated these associations were modified by dietary n‐3 PUFA intake.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Background As the most common biliary malignancy, gallbladder cancer (GC) is an elderly-biased disease. Although extensive studies have elucidated the molecular mechanism of microRNA 182 (miR-182) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) in various cancers, the specific role of exosomal miR-182 and RECK in GC remains poorly understood. Aim To explore the relationship between exosomal miR-182/RECK and metastasis of GC. Methods Paired GC and adjacent normal tissues were collected from 78 patients. Quantitative polymerase chain reaction was employed to detect miR-182 and exosomal miR-182 expression, and Western blotting was conducted to determine RECK expression. In addition, the effects of exosomal miR-182/RECK on the biological function of human GC cells were observed. Moreover, the double luciferase reporter gene assay was applied to validate the targeting relationship between miR-182 and RECK. Results Compared with normal gallbladder epithelial cells, miR-182 was highly expressed in GC cells, while RECK had low expression. Exosomal miR-182 could be absorbed and transferred by cells. Exosomal miR-182 inhibited RECK expression and promoted the migration and invasion of GC cells. Conclusion Exosomal miR-182 can significantly promote the migration and invasion of GC cells by inhibiting RECK; thus miR-182 can be used as a therapeutic target for GC.

The X-linked recessive degenerative disease dystrophinopathy results from variants in the DMD gene. Given the large size and complexity of the DMD gene, molecular diagnosis for all dystrophinopathies remains challenging. Here we identified two cryptic exon retention variants caused by intronic single nucleotide variants in dystrophinopathy patients using combined RNA- and DNA-based methods. As one variant was previously unreported, we explored its likely pathogenic mechanism, via bioinformatic prediction for in silico verification of splicing. Then we constructed a minigene system harboring the variant and used morpholino modified antisense oligonucleotides (ASOs) to induce cryptic exon skipping. ASOs treatment corrected the mis-splicing in the mutant minigene system. Our study defines a novel intronic variant that can cause dystrophinopathy, and illustrates a strategy to overcome the aberrant splicing.

Background MicroRNA 34c (miR-34c) has been reported to be associated with malignant types of cancer, however, it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer (GC). Aim To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells. Methods Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients. miR-34c and E2F1 were detected by real-time quantitative PCR (qPCR) and Western blot. In addition, the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods, and changes in miR-34c and E2F1 during this process were measured. Furthermore, E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells. MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin, qPCR was adopted to detect the expression of miR-34c, Western blot was applied to detect the expression levels of E2F1, drug resistance-related proteins and apoptosis-related proteins, and flow cytometry was used for the determination of cell apoptosis and cell cycle status. Results E2F1 was overexpressed while miR-34c was underexpressed in GC. After inducing GC cells to be resistant to paclitaxel and cisplatin, E2F1 expression increased while miR-34c expression decreased. Both silencing E2F1 and over-expressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin, promote cell apoptosis and inhibit cell proliferation. Among which, silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins, while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1, MRP and other drug resistance-related proteins. Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells, and Si E2F1 to paclitaxel combined with cisplatin. Conclusion E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin, and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.

Alzheimer’s disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.

Background The efficacy of the recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) against virologically-confirmed dengue (VCD) has been documented in a phase 3 trial in Latin America (CYD15, NCT01374516). This is a descriptive secondary analysis of the efficacy and safety of CYD-TDV in participants from Colombia. Methods Data from 9740 Colombian participants 9-16 years of age who were randomized 2:1 to receive CYD-TDV or placebo were assessed to describe the vaccine efficacy of CYD-TDV against VCD and severe VCD. Estimation was made of the relative risk (RR) for hospitalized VCD cases and severe hospitalized VCD cases after the first dose of CYD-TDV, as well as a description of the incidence of hospitalized dengue from the start of the study and per year of the study until study completion. Results During the active phase of the trial in Colombia, the efficacy of CYD-TDV was 67.5% [95% confidence interval (CI): 58.3-74.7] against symptomatic VCD due to any serotype from injection 1 (month 0) to 25 months postinjection 1. Over 6 years, the RR across all 4 serotypes was 0.166 (95% CI: 0.09-0.29) in hospitalized VCD patients and 0.154 (95% CI: 0.04-0.50) in patients with severe hospitalized VCD. Conclusions Analysis of the data from Colombia mimics the efficacy observed in CYD15 during the active surveillance follow-up (25 months), but with a sustained beneficial RR for dengue hospitalizations on the subsequent years of follow-up. In Colombia, where seroprevalence has been demonstrated to be high in several regions of the country, CYD-TDV is a useful tool to consider as part of an integrated control strategy against endemic dengue, a disease with a high economic impact on the health system.

Objective Develop a high-performing algorithm to detect mesial temporal lobe (mTL) epileptiform discharges on intracranial electrode recordings. Methods An epileptologist annotated 13,959 epileptiform discharges from a dataset of intracranial EEG recordings from 46 epilepsy patients. Using this dataset, we trained a convolutional neural network (CNN) to recognize mTL epileptiform discharges from a single intracranial bipolar channel. The CNN outputs from multiple bipolar channel inputs were averaged to generate the final detector output. Algorithm performance was estimated using a nested 5-fold cross-validation. Results On the receiver-operating characteristic curve, our algorithm achieved an area under the curve (AUC) of 0.996 and a partial AUC (for specificity > 0.9) of 0.981. AUC on a precision-recall curve was 0.807. A sensitivity of 84% was attained at a false positive rate of 1 per minute. 35.9% of the false positive detections corresponded to epileptiform discharges that were missed during expert annotation. Conclusions Using deep learning, we developed a high-performing, patient non-specific algorithm for detection of mTL epileptiform discharges on intracranial electrodes. Significance Our algorithm has many potential applications for understanding the impact of mTL epileptiform discharges in epilepsy and on cognition, and for developing therapies to specifically reduce mTL epileptiform activity.

This study aims to validate the simplified Chinese version of the Social Communication Questionnaire (SCQ) in children aged 2-12 years from both general and clinical populations. We recruited 819 Chinese children in this study, including 505 typically developing (TD) children, 202 children with autism spectrum disorder (ASD) and 112 children with non-ASD neurodevelopmental disorders. All the children's parents completed the simplified Chinese version of the SCQ and all children with ASD were additionally assessed for intelligence and the Childhood Autism Rating Scale to confirm their diagnosis. We have developed a 40-item, 4-factor structure of SCQ with two domains (social communication and social interaction; and restricted, repetitive, and stereotyped patterns of behavior), which showed adequate goodness of fit (comparative fit index [CFI] = 0.96, Tucker-Lewis index [TLI] = 0.95, standardized root mean squared residual [SRMR] = 0.07, root mean square error of approximation [RMSEA] = 0.05), with good internal consistency (Cronbach's alpha = 0.92). We have provided different cut-offs to distinguish ASD cases from TD children (11 for children under 4 years [sensitivity: 0.96, specificity: 0.95], 12 for children 4 years and above [sensitivity: 0.93, specificity: 0.98]) or children with other neurodevelopmental disorders (14 [sensitivity: 0.85, specificity: 0.88]). Through this large sample validation, we confirmed that the simplified Chinese version of the SCQ could be used for children aged 2-12 years with relatively good psychometric properties. LAY SUMMARY: We aimed to develop the simplified Chinese version of the Social Communication Questionnaire (SCQ) for Chinese children aged 2-12 years as a screening tool to identified potential risk of autism spectrum disorder (ASD). We have developed a 40-item, 4-factor structure of SCQ with two domains, which showed adequate goodness of fit and good psychometric properties. We also provided different cut-offs to identify ASD cases in general or clinical populations.

Tinea capitis is the most common pediatric dermatophytosis of the scalp and hair follicles that require oral antifungals therapy. It usually occurs in children between 3 and 7 years old, whereas it is rarely reported in children under 2 years old. Although oral terbinafine has been broadly used to treat tinea capitis, it is not approved for pediatric patients under 2 years old. Previous studies reported that a doubled oral terbinafine dose could improve the cure rates of tinea capitis due to Microsporum canis. However, the doses are all not strictly weight-based. Here, we report four pediatric tinea capitis patients under 2 years of age who were treated with a high, strictly weight-based dose of oral terbinafine therapy (10 mg/kg/day). We determine the efficacy and safety of this novel oral terbinafine therapy schedule. It may be a promising therapy to treat pediatric tinea capitis under 2 years old.

The bidirectional associations between parenting styles and conduct problems in Chinese children attending preschools were rarely discussed. A study covering 171 preschools in Longhua District of Shenzhen, China was conducted among children when they first attended preschools. Parents of children reported the self-perceived parenting styles and their children's conduct problems using validated questionnaires. The bidirectional associations between parenting styles and conduct problems in children were assessed using multivariate linear or logistic regressions in both cross-sectional and cohort settings. In cross-sectional settings, the bidirectional associations were present in all dimensions of parenting styles with children's conduct problems. After 1.01 years of follow-up, increases in parenting dimensions of rejection, control attempts, and favoring subject were significantly associated with children's conduct problems at follow-up, while increases in emotional warmth of parents significantly reduced such risk. In addition, parents of children who had conduct problems at baseline but regressed to normal at follow-up showed decreased scores in negative parenting dimensions. In contrast, among children who developed conduct problems during the study period, the scores of rejection and favoring subject in their parents have increased significantly, while the scores of emotional warmth have decreased. Parent-to-child effect was similar between fathers and mothers, while child-to-parent effect was stronger in fathers than that in mothers. In order to stop the negative feedback loop between poor parenting styles and children's conduct problems, our study underscored the importance of intervention not only in parents but also in their children.

Empathizing, systemizing, and empathizing-systemizing difference can be linked to autistic traits in the general adult population and those with autism spectrum disorder (ASD), but these profiles and associations remain unclear in children with ASD, with and without intellectual disability (ASD + ID; ASD-noID). We recruited three groups including 160 boys with ASD (73 ASD + ID; 87 ASD-noID) and 99 typically developing (TD) boys (6-12 years). We measured empathizing, systemizing, and empathizing-systemizing difference using the parent-reported child Empathy and Systemizing Quotient (EQ-C/SQ-C). We measured autistic traits using the Social Responsiveness Scale (SRS). Among the three groups, children with ASD + ID and ASD-noID scored lower on the EQ-C and SQ-C than TD children (all p 0.001). There was no difference in the EQ-C between children with ASD + ID and ASD-noID (16.59 ± 5.53 vs. 16.23 ± 5.85, p = 0.973), and the difference in the SQ-C attenuated to null when adjusting for intelligence between children with ASD-noID and TD children (18.89 ± 7.80 vs. 24.15 ± 6.73, p = 0.089). Children with ASD + ID scored higher on empathizing-systemizing difference than TD children but lower than children with ASD-noID (all p 0.05). Negative associations between EQ-C and all autistic traits, null associations between SQ-C and all autistic traits, and positive associations between empathizing-systemizing difference and all autistic traits were found in all groups. We observed differences in empathizing, systemizing, and empathizing-systemizing difference and the consistency of their associations with autistic traits among the three groups. Our findings provide implication that behavioral interventions of ASD should consider the balance of empathizing and systemizing. LAY SUMMARY: We examined the profiles of empathizing, systemizing, and empathizing-systemizing difference in children with autism spectrum disorder, with and without intellectual disability (ASD + ID; ASD-noID), and typically developing (TD) children aged 6-12 years. We observed differences in these profiles and the consistency of their associations with autistic traits among the three groups. Empathizing and empathizing-systemizing difference, rather than systemizing, were associated with autistic traits within the three groups. Our findings provide implication that behavioral interventions of ASD should consider these imbalance profiles.

Key Points Question Can adding oxaliplatin to postoperative capecitabine-based chemoradiotherapy (CRT) and contemporary adjuvant chemotherapy regimens in locally advanced rectal cancer improve the efficacy of treatment? Findings In this randomized clinical trial of 602 adults, the addition of oxaliplatin to capecitabine-based postoperative CRT did not significantly improve disease-free survival. Meaning These findings suggest that capecitabine-based postoperative CRT could be considered to be an alternative type of multidisciplinary management of locally advanced rectal cancer for patients who did not receive neoadjuvant CRT., This randomized clinical trial examines the efficacy and toxic effects of postoperative capecitabine vs oxaliplatin plus capecitabine with radiotherapy for stage II and III rectal cancer., Importance Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)– or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures The primary end point was 3-year disease-free survival (DFS). Results A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration ClinicalTrials.gov Identifier: NCT00714077

Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke inWe conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carriedA total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively.Among Chinese patients with minor ischemic stroke or TIA who were carriers of

Summary: Background: The aberrant brain network that gives rise to the phantom sound of tinnitus is believed to determine the effectiveness of tinnitus therapies involving neuromodulation with repetitive transcranial magnetic stimulation (rTMS) and sound therapy utilizing tailor-made notch music training (TMNMT). To test this hypothesis, we determined how effective rTMS or TMNMT were in ameliorating tinnitus in patients with different functional brain networks. Methods: Resting-state functional MRI was used to construct brain functional networks in patients with tinnitus (41 males/45 females, mean age 49.53±11.19 years) and gender-matched healthy controls (22 males/35 females, mean age 46.23±10.23 years) with independent component analysis (ICA). A 2 × 2 analysis of variance with treatment outcomes (Effective group, EG/Ineffective group, IG) and treatment types (rTMS/TMNMT) was used to test the interaction between outcomes and treatment types associated with functional network connections (FNCs). Findings: The optimal neuroimaging indicator for responding to rTMS (AUC 0.804, sensitivity 0.700, specificity 0.913) was FNCs in the salience network-right frontoparietal network (SN-RFPN) while for responding to TMNMT (AUC 0.764, sensitivity 0.864, specificity 0.667) was the combination of FNCs in the auditory network- salience network (AUN-SN) and auditory network-cerebellar network (AUN-CN). Interpretation: Tinnitus patients with higher FNCs in the SN-RFPN is associated with a recommendation for rTMS whereas patients with lower FNCs in the AUN-SN and AUN-CN would suggest TMNMT as the better choice. These results indicate that brain network-based measures aid in the selection of the optimal form of treatment for a patient contributing to advances in precision medicine. Funding: Yuexin Cai is supported by Key R&D Program of Guangdong Province, China (Grant No. 2018B030339001), National Natural Science Foundation of China (82071062), Natural Science Foundation of Guangdong province (2021A1515012038), the Fundamental Research Funds for the Central Universities (20ykpy91), and Sun Yat-Sen Clinical Research Cultivating Program (SYS-Q-201903). Yu-Chen Chen is supported by Medical Science and Technology Development Foundation of Nanjing Department of Health (No. ZKX20037), and Natural Science Foundation of Jiangsu Province (No. BK20211008).

Background: Evidence concerning the effects of greenness on childhood visual impairment is scarce. Objectives: We aimed to assess whether greenness surrounding schools was associated with visual impairment prevalence and visual acuity levels in Chinese schoolchildren and whether the associations might be explained by reduced air pollution. Methods: In September 2013, we recruited 61,995 children and adolescents 6–18 years of age from 94 schools in seven provinces/municipalities in China. Greenness exposure was assessed using the normalized difference vegetation index (NDVI) and the soil-adjusted vegetation index (SAVI) from July to August 2013. Visual impairment was defined as at least one visual acuity level (dimensionless) lower than 4.9 (Snellen 5/6 equivalent). Three-year annual averages of particulate matter (PM) with an aerodynamic diameter of ≤1μm (PM1) and nitrogen dioxide (NO2) at each school were assessed using machine learning methods. We used generalized linear mixed models to estimate the associations between greenness and prevalent visual impairment and visual acuity levels and used mediation analyses to explore the potential mediating role of air pollution. Results: In the adjusted model, an interquartile range increase in NDVI500m was associated with lower odds of prevalent visual impairment [odds ratio (OR)=0.95; 95% confidence interval (CI): 0.93, 0.97]. The same increase in NDVI500m was also associated with 0.012 (95% CI: 0.008, 0.015) and 0.011 (95% CI: 0.007, 0.015) increases in visual acuity levels for left- and right-eye, respectively. Our results also suggested that PM1 and NO2 significantly mediated the association between NDVI500m and visual impairment. Similar effect estimates were observed for SAVI500m, and our estimates were generally robust in several sensitivity analyses. Discussion: These findings suggest higher greenness surrounding schools might reduce the risk of visual impairment, possibly owing in part to lower PM1 and NO2 in vegetated areas. Further longitudinal studies with more precise greenness assessment are warranted to confirm these findings. https://doi.org/10.1289/EHP8429