Evolving brain network dynamics in early childhood: Insights from modular graph metrics.

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics-temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity-and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.

Eating Frequency, Timing, and Duration in Relation to Cognitive Performance and Alzheimer Disease Biomarkers in Adults.

BACKGROUND: The potential association between temporal dimensions of eating and cognition/cognitive declines has been poorly investigated so far. OBJECTIVES: The aim of this study was to examine relationships among eating frequency, timing and time window, and cognitive performance and novel Alzheimer disease (AD) biomarkers in cognitively healthy and mildly cognitively impaired middle-aged and older adults. METHODS: Cross-sectional data were derived from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) cohort study, including people aged 40 y or older who have a positive family history of cognitive disorder or cognition-related concerns. Cognitive performance was assessed by a battery of neuropsychological tests. Amyloid ß (Αß42), a biomarker of AD-related pathology, was measured in cerebrospinal fluid. Eating frequency, timing, and the eating time window between the first and the last meal were estimated using time-related information recorded in four 24-h recalls. RESULTS: Study participants had, on average, 5.3 ± 1.2 eating episodes per day, consumed at 8:20 ± 1.3 and 21:14 ± 1.3 h their first and their last eating episode, respectively, while their eating time window was 12.9 ± 1.6 h. Eating frequency, but not eating time window, was positively associated with global cognition, executive and language performance even after controlling for age, sex, education, BMI, and Mediterranean diet. Increasing eating frequency by 1 eating episode per day was associated with 0.169 higher global z-score. Furthermore, compared with ≤4, having 5-6 or >6 eating episodes per day was associated with better global and memory z-scores. Time of last eating episode was also positively associated with language performance. No associations were detected among eating frequency, timing and window, and AD pathology. CONCLUSIONS: An eating pattern characterized by less frequent eating and/or by earlier times is present in individuals with worse cognitive performance. Our results shed light on the relevance of temporal eating patterns as potential early markers of behavioral or metabolic changes related to AD pathology.

Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT.

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Brain Evoked Response Qualification Using Multi-Set Consensus Clustering: Toward Single-Trial EEG Analysis.

In event-related potential (ERP) analysis, it is commonly assumed that individual trials from a subject share similar properties and originate from comparable neural sources, allowing reliable interpretation of group-averages. Nevertheless, traditional group-level ERP analysis methods, including cluster analysis, often overlook critical information about individual subjects' neural processes due to using fixed measurement intervals derived from averaging. We developed a multi-set consensus clustering pipeline to examine cognitive processes at the individual subject level. Initially, consensus clustering from diverse methods was applied to single-trial EEG epochs of individual subjects. Subsequently, a second level of consensus clustering was performed across the trials of each subject. A newly modified time window determination method was then employed to identify individual subjects' ERP(s) of interest. We validated our method with simulated data for ERP components N2 and P3, and real data from a visual oddball task to confirm the P3 component. Our findings revealed that estimated time windows for individual subjects provide precise ERP identification compared to fixed time windows across all subjects. Additionally, Monte Carlo simulations with synthetic single-trial data demonstrated stable scores for the N2 and P3 components, confirming the reliability of our method. The proposed method enhances the examination of brain-evoked responses at the individual subject level by considering single-trial EEG data, thereby extracting mutual information relevant to the neural process. This approach offers a significant improvement over conventional ERP analysis, which relies on the averaging mechanism and fixed measurement interval.

Individualized time windows enhance TMS-EEG signal characterization and improve assessment of cortical function in schizophrenia.

Transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings are crucial to directly assess cortical excitability and inhibition in a non-invasive and task-free manner. TMS-EEG signals are characterized by TMS-evoked potentials (TEPs), which are employed to evaluate cortical function. Nonetheless, different time windows (TW) have been used to compute them over the years. Moreover, these TWs tend to be the same for all participants omitting the intersubject variability. Therefore, the objective of this study is to assess the effect of using different TWs to compute the TEPs, moving from a common fixed TW to more adaptive individualized TWs. Twenty-nine healthy (HC) controls and twenty schizophrenia patients (SCZ) underwent single-pulse (SP) TMS-EEG protocol. Firstly, only the HC were considered to evaluate the TEPs for three different TWs in terms of amplitude and topographical distribution. Secondly, the SCZ patients were included to determine which TW is better to characterize the brain alterations of SCZ. The results indicate that a more individualized TW provides a better characterization of the SP TMS-EEG signals, although all of them show the same tendency. Regarding the comparison between groups, the individualized TW is the one that provides a better differentiation between populations. They also provide further support to the possible imbalance of cortical excitability/inhibition in the SCZ population due to its reduced activity in the N45 TEP and greater amplitude values in the N100. Results also suggest that the SCZ brain has a baseline hyperactive state since the TEPs of the SCZ appear earlier than those of the HC.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

To be and not to be: wide-field Ca2+ imaging reveals neocortical functional segmentation combines stability and flexibility.

The stability and flexibility of the functional parcellation of the cerebral cortex is fundamental to how familiar and novel information is both represented and stored. We leveraged new advances in Ca2+ sensors and microscopy to understand the dynamics of functional segmentation in the dorsal cerebral cortex. We performed wide-field Ca2+ imaging in head-fixed mice and used spatial independent component analysis (ICA) to identify independent spatial sources of Ca2+ fluorescence. The imaging data were evaluated over multiple timescales and discrete behaviors including resting, walking, and grooming. When evaluated over the entire dataset, a set of template independent components (ICs) were identified that were common across behaviors. Template ICs were present across a range of timescales, from days to 30 seconds, although with lower occurrence probability at shorter timescales, highlighting the stability of the functional segmentation. Importantly, unique ICs emerged at the shorter duration timescales that could act to transiently refine the cortical network. When data were evaluated by behavior, both common and behavior-specific ICs emerged. Each behavior is composed of unique combinations of common and behavior-specific ICs. These observations suggest that cerebral cortical functional segmentation exhibits considerable spatial stability over time and behaviors while retaining the flexibility for task-dependent reorganization.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Improved visual outcomes of central retinal artery occlusion with local intra-arterial fibrinolysis beyond the conventional time window.

Local intra-arterial fibrinolysis (LIF) is a promising therapeutic option for CRAO. However, the narrow time window of 6 h has greatly limited the application of LIF. In this study, we explored the efficacy of LIF beyond the conventional time windows and compared the result with conservative therapy. This prospective study included 179 CRAO patients with baseline visual acuity (VA) ≤ 20/400 treated at Renmin Hospital of Wuhan University. The mean time from vision loss to presentation was 5.5 days. 58 patients received conventional standard therapy (CST) alone.121 patients underwent LIF. Main outcome was VA improvement ≥ 0.3 logMAR. Secondary outcome was a favorable VA outcome of 20/200 or better. Logistic regressions were performed to identify predictors of visual improvement. 43% patients in the LIF group experienced VA improvement versus 19% with CST (P = 0.002). LIF was associated with 4.0-fold higher likelihood of visual improvement compared to CST (P = 0.001). Poor baseline VA (light perception or no light perception) and shortened prothrombin time (PT) were associated with greater chance of visual improvement with LIF. However, LIF showed no significant advantage over CST for favorable VA outcomes. No major complications occurred. LIF beyond the therapeutic time window improved vision in functionally blind CRAO patients and showed better efficacy when compared with CST. PT may be a potential predictor of visual outcome after LIF. Our findings could complement existing time-based treatment guidelines and potentially allow for personalized decisions on the use of LIF beyond time windows.

Defining the Treatment Window: Early Versus Late Pulsed Dye Laser Therapy for Posttraumatic and Surgical Scars in Asian Patients.

OBJECTIVES: This retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes. METHODS: The medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re-visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow-up visits where photographs of their current skin condition were captured. The pretreatment and latest follow-up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale. RESULTS: Among the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week-to-treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04). CONCLUSIONS: Early intervention using a PDL within 10 weeks post-injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions.

Impact of temperature and relative humidity variability on children's allergic diseases and critical time window identification.

BACKGROUND: The effects of temperature and relative humidity on different types of children's allergic diseases have not been comprehensively evaluated so far. This study aims to assess the impact of temperature and relative humidity variability on children's allergic diseases and to identify the critical time window. METHODS: We collected outpatient data on allergen testing in children between July 2020 and January 2022 from the Affiliated Children's Hospital of Nanjing Medical University. We defined the 1st, 10th, 90th, and 99th percentiles as extreme cold, moderate cold, moderate hot, and extreme hot for temperature, and as low, moderate high, and extreme high for relative humidity, respectively. A distributed lag nonlinear model (DLNM) combined with a binomial regression model was used to assess the possible nonlinear relationship at different periods. Subgroup analysis by gender and age was conducted. RESULTS: We found that extreme and moderate cold temperatures were positively associated with skin allergies and total allergies (28 days: OR = 4.69, 95% CI: 2.88, 7.63; OR = 3.36, 95% CI: 2.39, 4.73) and (28 days: OR = 3.76, CI: 2.43, 5.81; OR = 2.71, 95% CI: 2.00, 3.68), respectively. Moderate and extreme hot temperatures were negatively associated with food allergies (28 days: OR = 0.13, 95% CI: 0.04, 0.41 and OR = 0.04; 95% CI: 0.01, 0.27). Low relative humidity was negatively associated with respiratory allergies, skin allergies, and total allergic diseases (28 days: OR = 0.26, 95% CI: 0.10, 0.71; OR = 0.29, 95% CI: 0.15, 0.55; and OR = 0.42, 95% CI: 0.26, 0.68). Meanwhile, extreme high relative humidity was negatively associated with respiratory allergies, and positively associated with skin allergies, food allergies, and total allergies (28 days: OR = 0.16, 95%CI: 0.07, 0.37; OR = 3.60, 95% CI: 2.52, 5.14; OR = 15.61, 95% CI: 3.23, 75.56; and OR = 2.33, 95% CI: 1.73, 3.15). A stronger relationship between temperature, relative humidity, and allergic diseases was observed in children under 5 years, specifically girls. CONCLUSIONS: Our study provides evidence that temperature and relative humidity variability may be associated with allergic diseases, however, the directionality of the relationship differs by allergic type.

Spindle Detection Based on Elastic Time Window and Spatial Pyramid Pooling.

BACKGROUND: Sleep spindles have emerged as valuable biomarkers for assessing cognitive abilities and related disorders, underscoring the importance of their detection in clinical research. However, template matching-based algorithms using fixed templates may not be able to fully adapt to spindles of different durations. Moreover, inspired by the multiscale feature extraction of images, the use of multiscale feature extraction methods can be used to better adapt to spindles of different frequencies and durations. METHODS: Therefore, this study proposes a novel automatic spindle detection algorithm based on elastic time windows and spatial pyramid pooling (SPP) for extracting multiscale features. The algorithm utilizes elastic time windows to segment electroencephalogram (EEG) signals, enabling the extraction of features across multiple scales. This approach accommodates significant variations in spindle duration and polarization positioning during different EEG epochs. Additionally, spatial pyramid pooling is integrated into a depthwise separable convolutional (DSC) network to perform multiscale pooling on the segmented spindle signal features at different scales. RESULTS: Compared with existing template matching algorithms, this algorithm's spindle wave polarization positioning is more consistent with the real situation. Experimental results conducted on the public dataset DREAMS show that the average accuracy of this algorithm reaches 95.75%, with an average negative predictive value (NPV) of 96.55%, indicating its advanced performance. CONCLUSIONS: The effectiveness of each module was verified through thorough ablation experiments. More importantly, the algorithm shows strong robustness when faced with changes in different experimental subjects. This feature makes the algorithm more accurate at identifying sleep spindles and is expected to help experts automatically detect spindles in sleep EEG signals, reduce the workload and time of manual detection, and improve efficiency.

Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury.

PURPOSE: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. METHODS: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. RESULTS: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. CONCLUSION: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Early Response to Endovascular Thrombectomy after Stroke: Early, Late, and Very Late Time Windows.

BACKGROUND AND PURPOSE: Endovascular thrombectomy (EVT) has benefits in selected patients 6-24 h after stroke onset. However, the response to EVT >24 h after stroke onset is still unclear. We compared the early response to EVT in patients with different time windows. METHODS: Patients who underwent EVT in an emergency setting were enrolled and categorized according to when EVT was performed: within 6 (early), 6-24 (late), and >24 h (very late) after stroke onset. Early neurological improvement (ENI) and deterioration (END) were defined as improvement and worsening, respectively, of National Institutes of Health Stroke Scale (NIHSS) score by ≥4 points after EVT. The three groups' clinical characteristics and response to EVT were compared. We also investigated factors associated with ENI and END. RESULTS: During study period, 274 patients underwent EVT (109 early, 104 late, and 61 very late). Patients who underwent EVT very late were younger (p = 0.007), had smaller ischemic cores, and had lower initial NIHSS scores (8 ± 5) than those who underwent EVT early (14 ± 6) and late (13 ± 7; p < 0.001). Stroke mechanisms also differed according to the time window (p < 0.001): cardioembolism was more common after early EVT, whereas large-artery atherosclerosis was more prevalent among patients who underwent EVT very late. ENI was significantly more common after early (60.6%) and late EVT (51.0%) than after very late EVT (29.5%; p = 0.001); however, rates of END did not differ (11.0%, 13.5%, and 4.9%, respectively). ENI was independently associated with male, higher NIHSS score, and early and late EVT. END was associated with failure of recanalization. CONCLUSIONS: ENI was more observed and associated with early and late EVT. Highly selected patients receiving very late EVT may not benefit from ENI but may still have a chance to prevent END. The occurrence of END was associated not with time window but with failure of recanalization.

The Representation of Time Windows in Primate Auditory Cortex.

Whether human and nonhuman primates process the temporal dimension of sound similarly remains an open question. We examined the brain basis for the processing of acoustic time windows in rhesus macaques using stimuli simulating the spectrotemporal complexity of vocalizations. We conducted functional magnetic resonance imaging in awake macaques to identify the functional anatomy of response patterns to different time windows. We then contrasted it against the responses to identical stimuli used previously in humans. Despite a similar overall pattern, ranging from the processing of shorter time windows in core areas to longer time windows in lateral belt and parabelt areas, monkeys exhibited lower sensitivity to longer time windows than humans. This difference in neuronal sensitivity might be explained by a specialization of the human brain for processing longer time windows in speech.

Maternal exposure to fine particulate matter and congenital heart defects during preconception and pregnancy period: A cohort-based case-control study in the Taiwan maternal and child health database.

BACKGROUND: Few studies have explored the association between maternal exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and congenital heart defects occurring before and during pregnancy. We aimed to investigate the association and the critical time windows between the maternal exposure to PM2.5 and congenital heart defects. METHOD: We conducted a cohort-based case-control study of 507,960 participants obtained from the Taiwan Maternal and Child Health Database between 2004 and 2015. We applied satellite-based spatiotemporal models with 1-km resolution to calculate the average PM2.5 concentration during preconception and the specific periods of pregnancy. We also performed conditional logistic regression with distributed lag non-linear models (DLNMs) to assess the effects of weekly average PM2.5 on both congenital heart defects and their isolated subtypes, as well as the concentration-response relationships. RESULTS: In DLNMs, exposure to PM2.5 (per 10 µg/m3) during weeks 7-12 before conception and weeks 3-9 after conception was associated with congenital heart defects. The strongest association at 12 weeks before conception (odds ratio [OR] = 1.026, 95% confidence intervals [CI]: 1.012-1.040) and 7 weeks after conception (OR = 1.024, 95% CI: 1.012-1.036) for every 10 µg/m3 increase in PM2.5 concentration. In modification analysis, strongest associations were observed for low SES. CONCLUSIONS: Our study revealed that exposure to ambient PM2.5 raises the risk of congenital heart defects, particularly among individuals with lower socioeconomic status. Moreover, our findings suggest that preconception exposure to PM2.5 may be a crucial period for the development of congenital heart defects.

Optimal time window for minimally invasive surgery in treating spontaneous intracerebral hemorrhage in the basal ganglia region: a multicenter and retrospective study.

BACKGROUND: The current treatment spontaneous intracerebral hemorrhage (sICH) is limited. AIM: To determine the optimal time window for minimally invasive surgery in patients with sICH. MATERIALS AND METHODS: sICH patients with a hematoma volume of 30-80 mL in the basal ganglia region were included in our study. A total of 357 patients were divided into groups according to different operative times from ICH onset (group 1: 0-6 h, group 2: 6-12 h, group 3: >12 h) and hematoma volumes (30-50 mL and >50 mL). All patients were followed-up for three months' post-operation, and their clinical outcomes were compared. RESULTS: In the three groups of patients with hematoma volumes of 30-50 mL, the rebleeding and mortality rate were higher in group 1 than groups 2 and 3 (p < .05). The activities of daily living evaluated by Barthel Index (BI) three months' post-operation was significantly lower in group 3 than other groups (p < .05) and group 2 had the highest proportion of good outcomes. Among the patients with the hematoma volumes of 50-80 mL, the rebleeding risk was higher in group 1 than groups 2 and 3 (p < .05). However, there were no significant differences in mortality rates among these three groups. Moreover, group 1 had significantly higher BI than groups 2 and 3 (p < .05). CONCLUSIONS: Minimally invasive surgery is safe and effective in patients with sICH. 6-12 h after sICH onset is the optimal surgical window for patients with hematoma volumes of 30-50 mL, while ultra-early (≤6 h) may achieve better results in patients with hematoma volumes of >50 mL.

Air-GR: An Over-the-Air Handwritten Character Recognition System Based on Coordinate Correction YOLOv5 Algorithm and LGR-CNN.

Traditional human-computer interaction technology relies heavily on input devices such as mice and keyboards, which limit the speed and naturalness of interaction and can no longer meet the more advanced interaction needs of users. With the development of computer vision (CV) technology, research on contactless gesture recognition has become a new research hotspot. However, current CV-based gesture recognition technology has the limitation of a limited number of gesture recognition and cannot achieve fast and accurate text input operations. To solve this problem, this paper proposes an over-the-air handwritten character recognition system based on the coordinate correction YOLOv5 algorithm and a lightweight convolutional neural network (LGR-CNN), referred to as Air-GR. Unlike the direct recognition of captured gesture pictures, the system uses the trajectory points of gesture actions to generate images for gesture recognition. Firstly, by combining YOLOv5 with the gesture coordinate correction algorithm proposed in this paper, the system can effectively improve gesture detection accuracy. Secondly, considering that the captured gesture coordinates may contain multiple gestures, this paper proposes a time-window-based algorithm for segmenting the gesture coordinates. Finally, the system recognizes user gestures by plotting the segmented gesture coordinates in a two-dimensional coordinate system and feeding them into the constructed lightweight convolutional neural network, LGR-CNN. For the gesture trajectory image classification task, the accuracy of LGR-CNN is 13.2%, 12.2%, and 4.5% higher than that of the mainstream networks VGG16, ResNet, and GoogLeNet, respectively. The experimental results show that Air-GR can quickly and effectively recognize any combination of 26 English letters and numbers, and its recognition accuracy reaches 95.24%.

[Intravenous thrombolysis of ischemic stroke-Current status]. / Intravenöse Thrombolyse des ischämischen Schlaganfalls ­ aktueller Stand.

Intravenous thrombolysis (IVT) treatment with alteplase (rtPA) is an essential part of the routine treatment of patients with ischemic stroke since its introduction in the late 1990s. Rapid treatment is of essential importance. For patients with an unclear time window, various mismatch concepts have been established to identify salvageable brain tissue prior to IVT. Numerous official contraindications for rtPA are not evidence-based; for example, current data from observational studies show that systemic thrombolytic treatment is possible even in patients receiving direct oral anticoagulant (DOAC) treatment. Tenecteplase (TNK) is an alternative thrombolytic agent with some pharmacologic advantages. The most recent guidelines indicate that TNK is particularly advantageous over rtPA in patients treated in combination with endovascular stroke therapy (EST). The combination of IVT and EST should primarily be performed in the 4.5­h time window in patients without contraindications; in the later time window EST alone is conceivable if it can be performed without delay.

Network Delay and Cache Overflow: A Parameter Estimation Method for Time Window Based Hopping Network.

A basic understanding of delayed packet loss is key to successfully applying it to multi-node hopping networks. Given the problem of delayed data loss due to network delay in a hop network environment, we review early time windowing approaches, for which most contributions focus on end-to-end hopping networks. However, they do not apply to the general hopping network environment, where data transmission from the sending host to the receiving host usually requires forwarding at multiple intermediate nodes due to network latency and network cache overflow, which may result in delayed packet loss. To overcome this challenge, we propose a delay time window and a method for estimating the delay time window. By examining the network delays of different data tasks, we obtain network delay estimates for these data tasks, use them as estimates of the delay time window, and validate the estimated results to verify that the results satisfy the delay distribution law. In addition, simulation tests and a discussion of the results were conducted to demonstrate how to maximize the reception of delay groupings. The analysis shows that the method is more general and applicable to multi-node hopping networks than existing time windowing methods.