Critical Time Window Research Articles

Time-Varying Associations Between Device-Based and Ecological Momentary Assessment-Reported Sedentary Behaviors and the Concurrent Affective States Among Adolescents: Proof-of-Concept Study.

BackgroundPrevious studies on affective state–sedentary behavior (SB) associations have not accounted for their potentially time-varying nature and have used inconsistent SB measurement modalities. We investigated whether the strength of the associations between affective states and SB varied as a function of the time of day and by SB measurement modality (device-measured SB vs ecological momentary assessment–reported screen-based SB) in youth.ObjectiveThis study aimed to establish a proof of concept that SB–affective state associations may not be static during the day. In addition, we aimed to inform the methodology of future work, which may need to model associations as functions of the time of day and carefully consider how SB is operationalized or measured.MethodsA total of 15 adolescents (age: mean 13.07, SD 1.03 years; 10/15, 67% female; 6/15, 40% Hispanic; 10/15, 67% healthy weight) wore thigh-mounted activPAL accelerometers and simultaneously reported their screen-based SBs and concurrent positive and negative affective states via ecological momentary assessment for 7 to 14 days (N=636 occasions). Time-varying effect models (varying slopes) examined how each measure of SB was associated with concurrent affective states from 7 AM to 8 PM.ResultsTime-varying effect model plots revealed that these associations varied in strength throughout the day. Specifically, device-based SB was related to greater concurrent negative affect only after approximately 5 PM and was unrelated to concurrent positive affect. Screen-based SB was related to greater concurrent negative affect only from 7 AM to approximately 9 AM. This was also related to greater concurrent positive affect from 7 AM to approximately 9:30 AM and from approximately 3 PM to approximately 7 PM.ConclusionsWe provide preliminary evidence to suggest that future confirmatory studies investigating the SB–affective state relationship should consider the time-varying nature of these associations and SB measurement modality. There may be critical time windows when specific types of SBs co-occur with affect, suggesting that interventions may need tailoring to the time of day and type of SB if future studies using similar methodologies can replicate our findings.

Environmental inequality: Air pollution and asthma in children.

Whether you benefit from high-quality urban environments, such as those rich in green and blue spaces, that may offer benefits to allergic and respiratory health depends on where you live and work. Environmental inequality, therefore, results from the unequal distribution of the risks and benefits that stem from interactions with our environment. Within this perspective, this article reviews the evidence for an association between air pollution caused by industrial activities, traffic, disinfection-by-products, and tobacco/e-cigarettes, and asthma in children. We also discuss the proposed mechanisms by which air pollution increases asthma risk, including environmental epigenetic regulations, oxidative stress, and damage, disrupted barrier integrity, inflammatory pathways, and enhancement of respiratory sensitization to aeroallergens. Environmental air pollution is a major determinant of childhood asthma, but the magnitude of effect is not shared equally across the population, regions, and settings where people live, work, and spend their time. Improvement of the exposure assessment, a better understanding of critical exposure time windows, underlying mechanisms, and drivers of heterogeneity may improve the risk estimates. Urban conditions and air quality are not only important features for national and local authorities to shape healthy cities and protect their citizens from environmental and health risks, but they also provide opportunities to mitigate inequalities in the most deprived areas where the environmental burden is highest. Actions to avoid exposure to indoor and outdoor air pollutants should be complementary at different levels-individual, local, and national levels-to take effective measures to protect children who have little or no control over the air they breathe.

The GluN2A Subunit of the NMDA Receptor Modulates the Rate of Functional Maturation in Parvalbumin‐positive Interneurons

N‐methyl‐D‐aspartate receptors are glutamate‐gated, calcium‐permeable ion channels involved in a host of normal brain functions, including neuronal development. Traditionally, the GluN2A subunit, encoded by the GRIN2A gene, is thought to signal brain and circuit maturation, given its unique expression pattern where transcripts are low embryonically and then significantly increase during preadolescence in mice. Advances in whole exome sequencing have identified mutations in the GRIN2A gene to be causal to several neuropathological diseases, including epilepsy and intellectual delay. More specifically, 56% of GRIN2A mutations are loss‐of‐function, displaying diminished receptor function and/or surface expression, with Grin2a­‐/‐ mice have been reported as having signatures of epileptiform activity. However, little is understood regarding GluN2A’s impact on neurodevelopmental and how its absence may the GABAergic interneuron network. Our data show that Grin2a ‐/‐ mice contain 33% more parvalbumin+ interneurons in the CA1 region of the hippocampus during preadolescence and adulthood. This increase in GABAergic interneuron cell density appears to be unique to parvalbumin+ cells, as cholecystokinin+ and somatostatin+ interneurons are unchanged across Grin2a‐/‐ and wildtype mice. Despite an increased cell count, colocalization staining for parvalbumin+ synaptic densities and measures of parvalbumin cell‐specific tonic inhibition remains unchanged in preadolescence and increases as the animal ages, suggesting delayed maturation. In addition, parvalbumin+ cells from preadolescent Grin2a‐/‐ mice exhibit immature intrinsic and firing properties, such as an increased membrane time constant and input resistance, lower threshold for depolarization‐induced block, and longer action potential half‐widths than age‐matched WT controls, all of which become corrected in adulthood. The sum of these data suggest that the GluN2A subunit is involved in promoting cues for interneuron apoptosis during development, as well as influencing the rate of parvalbumin+ cell functional maturation. The ramifications of these abnormalities are still underexplored, but likely generate a vulnerability time window during preadolescence in which an epileptiform network can manifest. Viral strategies aimed at reintroduction of the GRIN2A gene during this critical time window could represent a viable gene therapy option for loss‐of‐function GRIN2A EE patients.

New Insights in Pathogenesis of Endometriosis.

Endometriosis is a gynecological disease characterized by the growth of endometrial glands and stroma outside the uterine cavity. The incidence of the disease is very high, there are currently no reliable early diagnostic tests, the therapies are only symptomatic and, consequently, the social impact of endometriosis is very important, also considering the related fertility problems. Despite this, the pathogenesis of endometriosis is still not fully defined. Retrograde menstruation and coelomic metaplasia are currently the most recognized pathogenetic hypotheses. Recent experimental evidences generated by our research group and by others have indicated an alteration of the fine-tuning of the female genital system developmental program during a critical window of time in the fetal life as the pathogenetic event prompting to the development of endometriosis later in life. Goal of this article is to present a revision of the recent literature about the different pathogenetic mechanisms proposed for endometriosis with particular emphasis on the embryologic theory. The possible clinical and pathological implications of these findings will be discussed.

Depression screening using a non-verbal self-association task: A machine-learning based pilot study

BackgroundEffective screening is important to combat the raising burden of depression and opens a critical time window for early intervention. Clinical use of non-verbal depression screening is nascent, yet a promising and viable candidate to supplement verbal screening. Differential self- and emotion-processing in depression patients were previously reported by non-verbal behavioural assessments, corroborated by neuroimaging findings of distinct neuroanatomical markers. Thus non-verbal validated brain-behaviour based self-emotion-related assessment data reflect physiological differences and may support individual level screening of depression. MethodsIn this pilot study (n = 84) we collected two longitudinal sessions of behavioural assessment data in a laboratory setting. Depression was assessed using Beck Depression Inventory II (BDI-II), to explore optimal screening methods with machine-learning, and to establish the validity of adapting a novel behavioural assessment focusing on self and emotions for depression screening. ResultsThe best machine-learning model achieved high performance in depression screening, 10-Fold cross-validation (CV) Area Under the receiver operating characteristic Curve (AUC) of 0.90 and balanced accuracy of 0.81, using a Gradient Boosting algorithm. Prospective prediction using a model trained with session 1 data to predict session 2 depression status achieved a 10-Fold CV AUC of 0.77 and balanced accuracy of 0.66. We also identified interpretable behavioural signatures for depression patients based on the best model. ConclusionThe study supports the utility of using behavioural data as a viable and cost-effective solution for depression screening, with a potential wide range of applications in clinical settings.

A novel prognostic time window based on conditional survival and outcomes analyses of primary liver cancer patients.

BackgroundLiver cancer is one of the most deadly and prevalent cancers. A routine follow‐up plan for liver cancer is crucial but limited. In the present study, we aimed to disclose possible risk factors and critical survival time windows for primary liver cancer.MethodsWe enrolled 692 liver cancer patients from Sun Yat‐sen University Cancer Center (SYSUCC). Univariate and multivariate logistic regression analyses of cirrhosis and recurrence were conducted. A meta‐analysis was utilized to validate an indication of creatinine (CRE) in recurrence. Conditional survival analysis was performed using the Kaplan–Meier method. The results were further verified by the SYSUCC validation cohort and Surveillance, Epidemiology, and End Results (SEER) validation cohort.ResultsOur results indicated that A/G, history of hepatitis, history of alcohol consumption and platelet (PLT) might be potential prognostic factors for cirrhosis in liver cancer patients. CRE was significantly correlated with recurrence due to various therapies, especially after transarterial embolization. Moreover, 1.5 years to 2 years may be a critical time window for deterioration in survival rate based on the conditional survival analysis.ConclusionA/G, history of hepatitis, alcohol consumption and PLT may be potential prognostic factors for cirrhosis in liver cancer patients. More attention should be focused on the renal function when treating the patients due to the significant role of CRE. 1.5 years to 2 years is a critical time window for deterioration in survival rate for liver cancer patients that contributes to determining the optimal follow‐up plan in the future.

Complex Perinatal Syndromes Affecting Early Human Growth and Development: Issues to Consider to Understand Their Aetiology and Postnatal Effects.

Complex perinatal syndromes (CPS) affecting pregnancy and childhood, such as preterm birth, and intra- and extra-uterine growth restriction, have multiple, diverse contexts of complexity and interaction that determine the short- and long-term growth, health and development of all human beings. Early in life, genetically-guided somatic and cerebral development occurs alongside a psychism “in statu nascendi,” with the neural structures subjected to the effects of the intra- and extra-uterine environments in preparation for optimal postnatal functioning. Different trajectories of fetal cranial and abdominal growth have been identified before 25 weeks’ gestation, tracking differential growth and neurodevelopment at 2 years of age. Similarly, critical time-windows exist in the first 5–8 months of postnatal life because of interactions between the newborn and their environment, mother/care-givers and feeding practices. Understanding these complex relational processes requires abandoning classical, linear and mechanistic interpretations that are placed in rigid, artificial biological silos. Instead, we need to conduct longitudinal, interdisciplinary research and integrate the resulting new knowledge into clinical practice. An ecological-systemic approach is required to understand early human growth and development, based on a dynamic multidimensional process from the molecular or genomic level to the socio-economic-environmental context. For this, we need theoretical and methodological tools that permit a global understanding of CPS, delineating temporal trajectories and their conditioning factors, updated by the incorporation of new scientific discoveries. The potential to optimize human growth and development across chronological age and geographical locations – by implementing interventions or “treatments” during periods of greatest instability or vulnerability – should be recognized. Hence, it is imperative to take a holistic view of reproductive and perinatal issues, acknowledging at all levels the complexity and interactions of CPS and their sensitive periods, laying the foundations for further improvements in growth and development of populations, to maximize global human potential. We discuss here conceptual issues that should be considered for the development and implementation of such a strategy aimed at addressing the perinatal health problems of the new millenium.

Behavioral Tagging: Role of Neurotransmitter Receptor Systems in Novel Object Recognition Long-Term Memory.

Strong training is known to form long-term memory (LTM) as it is an inducer for both a learning tag (just like a synaptic tag/molecular tag) and plasticity-related proteins (PRPs), while weak training is an inducer of only a learning tag. However, weak training can also lead to LTM if paired with another behavioral task (open field in our study—a representative of a novel environment) around the time of PRP arrival. Weak behavioral training is a learning tag inducer, while the open field is a PRP inducer. The learning tag then captures these PRPs to form LTM. This is the basis of behavioral tagging (BT). BT is a well-known model for the evaluation of a few learning and memory forms. In this work, we examined the role of glutamate and D1/D5 (dopamine) receptors in the synthesis of a novel object recognition (NOR) tag (learning) as well as in PRP arrival, which come together to form NOR-LTM. Employing antagonists and/or agonists preceding or proceeding the open field and/or NOR training, it was revealed that the activation/stimulation of D1/D5 (dopamine) receptors and glutamatergic NMDA receptors plays a critical part in PRP arrival. We found that the activation/stimulation of NMDA receptors also contributes to the setting of the learning tag. Moreover, changes in glutamate, dopamine, and GABA neurotransmitter levels were also analyzed. These findings thus demonstrate the critical time window required for NOR-LTM formation based on the process of BT along with the role of activation/stimulation of D1/D5 (dopamine) receptors and NMDA receptors in the arrival of PRPs and learning tags for NOR-LTM formation.

Dextromethorphan reduces prenatal lipopolysaccharide exposure-induced dopaminergic neuronal loss and cytokine changes in offspring.

Maternal infection during pregnancy may affect fetal brain development and increase the risk of developing neurological and mental disorders later in life in offspring. In this study, we used low-dose lipopolysaccharide (LPS) injection to mimic mild maternal infection at a critical time window for fetal dopamine (DA) and serotonin (5-HT) neuron development. The affected offspring exhibited reduction of dopaminergic and serotonergic neurons and anxiety- and depression-related behaviors in adulthood. In the current study, we evaluated whether dextromethorphan (DM, 30 mg/kg), an over-the-counter antitussive drug with anti-inflammatory and neuroprotective properties, could reduce the adverse effects of maternal infection mimicked by LPS exposure. We discovered that DM application did not change the baseline serum interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) levels in the LPS-exposed offspring. However, DM treatment could reduce the heightened immune responses induced by a postnatal LPS challenge test in prenatal LPS-exposed offspring. The neuroprotective effect of DM was only seen in DA neurons but not in 5-HT neurons. We concluded that DM treatment can partially protect the offspring against the adverse effects of LPS-induced maternal immune activation. The reduction in heightened immune responses and dopaminergic neuronal loss in LPS-exposed offspring could potentially reduce the risk of DA-related neurological and psychiatric disorders later in life.

152. Factors Impacting HPV Vaccination Rates Among Minority Adolescents and Young Adults (AYA)

In 2018, there were 43 million Human papillomavirus (HPV) infections, majority were among adolescent and young adults (AYA). To decrease risk of HPV, individuals aged 9-26 years old should get vaccinated. However, vaccination rates have remained stagnant in the last several years. There are racial/ethnic and gender disparities in knowledge, awareness, and overall vaccine uptake. Cost of the vaccine is a barrier to vaccine uptake among uninsured AYA. The purpose of this is to examine factors impacting HPV vaccination uptake and completion rates among AYA utilizing a clinic-system located in Southeast Texas. The setting was a nine-clinic system that, through state funds, provides free preventive primary and reproductive health services to >10,000 Medicaid, low-income, and uninsured AYA ages 13 – 24 years old annually. Services include free immunizations including the HPV vaccine. Majority (97.9%) of patients fall below the 250% Federal Poverty Level threshold and 96% belong to racial/ethnic minority groups. We retrospectively collected demographic information, immunization status, and billed services data among clinic AYAs from March 2018 to December 2020. We set statistical significance at p < 0.05. A total of 19,045 AYAs were seen between March 2018 and December 2020 with 2,258 HPV vaccines administered and 3,119 having completed their HPV vaccination series. There were statistically significant differences in HPV vaccine uptake between females and males (6.7% vs. 3.2%, respectively), minors and adults (6.9% vs. 3.1%, respectively), and between school-based and community-based clinic locations (7.8% vs. 2.1%, respectively). Around 49% of AYAs who received an HPV vaccine also received additional vaccines during their visit versus 51% who only got the HPV vaccine. Additionally, those who had any sexually transmitted infection screening during the visit had a lower HPV administration rate than those who did not have an STI screening (2.3% vs. 5.6%, respectively). A logistical regression model found age, income, sex, clinic location type and having additional vaccines given during the visit were significantly correlated with receiving an HPV vaccine (R2=0.28). There were statistically significant differences in series completion between females and males (17.7% vs. 12.7%, respectively), minors and adults (19.3% vs. 15.3%), and clinic location type (27.0% vs. 10.9%). A logistical regression model found age, income, sex, and clinic location type were significantly correlated with series completion (R2=0.06). However, both logistical regression models had negligible to weak correlation meaning there are additional factors impacting HPV vaccination uptake and series completion. Clinic HPV completion rates were lower than state and national averages. Some barriers may be the lack of vaccine records for AYAs that access primary care elsewhere, and health seeking behavior specifically for sexual health. The findings support policies such as removing cost barriers, and creative strategies including gender-neutral and school-based sexual health messaging that includes HPV vaccine promotion as it may provide a critical time window for AYA to get vaccinated earlier. Targeting AYA who only utilize reproductive health care may be another tactic to reach unvaccinated AYA. Future studies should explore other factors such as systems-related factors impacting HPV vaccination uptake and series completion.

Pre-Weaning Exposure to Maternal High-Fat Diet Is a Critical Developmental Window for Programming the Metabolic System of Offspring in Mice.

BackgroundMaternal high-fat diet (HFD) during pregnancy and lactation exerts long-term effects on the health of offspring. However, the critical developmental window for metabolic programming of maternal exposure to HFD on pathogenesis of obesity in offspring needs further clarification.Materials & MethodsFemale ICR mice were fed low-fat diet (LFD) or HFD for 8 weeks until delivery. During lactation, half of LFD dams received HFD while the other half of LFD dams and HFD dams maintained the previous diet. Male offspring were weaned at postnatal day 21 (P21) and fed LFD or HFD for 7 weeks. Metabolic parameters, biochemical, and histological indicators of thermogenesis, rectal temperature, and sympathetic nerve tone were detected at P21 and 10 weeks old.ResultsAt P21, LH (maternal LFD before delivery but HFD during lactation) and HH (maternal HFD before delivery and during lactation) offspring gained more body weight and showed higher serum glucose and triglyceride levels as compared with LL (maternal LFD before delivery and during lactation), and the metabolic characters were maintained until 10 weeks age when fed with LFD after weaning. However, LH offspring exhibited a greater degree of metabolic abnormalities compared to HH offspring, with increased body weight, as well as lower norepinephrine (NE)-stimulated rectal temperature rise when fed with HFD after weaning. The lower UCP1 levels and HSL phosphorylation in LH offspring further suggested that brown adipose tissue (BAT) thermogenic function was impaired.ConclusionExposure to maternal HFD feeding during pre-weaning period alone showed similar detrimental effects on programming metabolic system of offspring as those of both prenatal and early postnatal HFD feeding. Early postnatal stage is a critical time window for metabolic programming and has profound and long-lasting effects on BAT development and function through sympathetic nerve-mediated thermogenesis.

Cognate facilitation effect during auditory comprehension of a second language: A visual world eye-tracking study

Aims and Objectives: The cognate facilitation effect (CFE) is a robust effect in language production and visual word comprehension, but evidence for CFE during auditory comprehension is still scarce. This study aimed to explore the CFE during auditory comprehension of a second language (L2) while manipulating proficiency in the L2 and cognate type. These two variables are known to influence the CFE. Methodology: Low and highly proficient Spanish–English bilinguals listened to individual words in their L2, English, that shared high, low, and no phonological overlap (PO) with their native language Spanish. We designed a visual world paradigm task that consisted of selecting an image shown as a spoken word unfolded in time while eye movements were recorded. Data and Analysis: Response times revealed a clear CFE in low proficiency bilinguals, while this effect was absent in highly proficient bilinguals. The eye-tracking (ET) data showed late coactivation of low-PO words and, surprisingly, no coactivation of high-PO words in low proficiency bilinguals. Highly proficient bilinguals showed no clear pattern of language coactivation in the ET data. The English monolingual control group showed no effects during the critical time window. Conclusions: These results are interpreted within the framework of L2 processing models. At low levels of proficiency, the PO between translations facilitates access to meaning. On the other hand, highly proficient bilinguals no longer benefit from the PO between translations, at least for concrete and simple nouns. Originality: The findings demonstrate a clear CFE in auditory comprehension. Proficiency in L2 and PO modulated the effect, as shown in both the response time and in the ET data, respectively. Implications: These findings suggest that at low levels of L2 proficiency, learners more easily access the conceptual information if the auditory input is similar to their native language. Nevertheless, as proficiency increases, this facilitation disappears.

A method for identifying critical time windows of maternal air pollution exposures associated with low birth weight in offspring using massive geographic data.

Associations between maternal exposures to air pollutants and low birth weight (LBW) in offspring varied when different exposure windows were considered. Methods used in previous studies lacked flexibility in delineating exposure windows and did not consider time periods before conception, which may restrict the discoveries of critical exposure windows. This study introduces a novel method to identify critical windows of maternal air pollution exposures associated with LBW in offspring using massive georeferenced data. Through a case-control study based on birth data (94,106 LBW cases and 376,424 controls) and air quality monitoring data (367 chemicals) in Texas during 1996-2008, this study used the average ambient concentration measured by the monitoring site closest to the residence location of a mother during a time window as the maternal exposure to a specific chemical during that exposure window. Binary logistic regression was utilized to estimate air pollutant-LBW associations in different exposure windows. The odds ratios (ORs) were adjusted for child's sex, gestational weeks, maternal age, race/ethnicity, and education. The adjusted ORs were plotted against the exposure window series of different sizes for each chemical, aiming at interactively visualizing and exploring the critical exposure windows across multiple temporal scales. This study identifies ten chemicals and seventeen corresponding critical exposure windows where strong air pollutant-LBW associations are detected. The ten identified chemicals are benzaldehyde, sum of Photochemical Assessment Monitoring Stations (PAMS) target compounds, n-undecane, m-tolualdehyde, organic carbon fraction 2 (OC2), ethylene dibromide, valeraldehyde, propionaldehyde, 4-methyl-1-pentene, and zirconium. Nine critical exposure windows involving six chemicals start more than fivemonths prior to conception, seven windows involving five chemicals commence in the second and/or third trimester of pregnancy, and the remaining one window is located in other time periods. The novel method reveals a number of critical time windows of maternal exposure to ten chemicals that are positively associated with LBW in offspring. These ten chemicals were identified as LBW risk factors for the first time. Additional studies with more data are needed to validate the results in the future.

Immunogenicity and waning immunity from the oral cholera vaccine (Shanchol™) in adults residing in Lukanga Swamps of Zambia.

IntroductionIn cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps.MethodsWe enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres.ResultsOverall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points.ConclusionWe found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.

Error-based structure prediction in language comprehension: Evidence from verb bias effects in a visual-world structural priming paradigm for Mandarin Chinese.

Structural priming studies in production have demonstrated stronger priming effects for unexpected sentence structures (inverse preference effect). This is consistent with error-based implicit learning accounts that assume learning depends on prediction error. Such prediction error can be verb-specific, leading to strong priming when a verb that is for instance biased toward the prepositional object (PO) structure occurs with an unexpected double object (DO) structure. However, it is unclear whether this mechanism also holds for language comprehension, especially for languages like Mandarin Chinese, which arguably depends strongly on semantics to predict syntax in comprehension. Experiment 1 was a norming study (N = 367) that measured the biases (DO vs. PO) of 48 Mandarin Chinese dative verbs. Experiment 2 (N = 72) crossed verb bias (DO-bias or PO-bias) and structure (DO or PO) of prime sentences in a visual-world paradigm, to examine whether Mandarin comprehenders show an inverse preference effect. The priming effect is expressed as the proportion of looks to the predicted referent (i.e., the recipient after a DO-prime, the theme after a PO-prime), for two critical time windows during target sentence processing: the verb and the first syllable of the first postverbal noun (which was identical in theme and recipient). There was priming in both time windows, even though the verb differed between prime and target. Importantly, there was an inverse preference effect (i.e., stronger priming after a DO prime with a PO-biased verb than with a DO-biased verb) in the second time window. These results provide evidence for an error-based structure prediction system in comprehension. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Emerging early diagnostic methods for acute kidney injury.

Many factors such as trauma and COVID-19 cause acute kidney injury (AKI). Late AKI have a very high incidence and mortality rate. Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure. However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI. In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine. These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers. Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI. Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI. In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios. In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI. Finally, we discuss current challenges and prospects of machine learning and biomarker detection. The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.

History-dependent dopamine release increases cAMP levels in most basal amygdala glutamatergic neurons to control learning.

Dopaminergic inputs to basal amygdala (BA) instruct learning of motivational salience. This learning depends on intracellular plasticity signals such as cyclic adenosine monophosphate (cAMP), which is regulated by activation of dopamine receptors. We examine the dynamics of dopamine release and downstream signaling during multiple salient events occurring within tens of seconds. We perform real-time tracking and manipulation of cAMP in BA neurons invitro and invivo. Optogenetically evoked release of dopamine drives proportional increases in cAMP in almost all BA glutamatergic neurons, suggesting widespread actions of dopamine across neurons preferring positive or negative valence. This cAMP response decreases across trials with short intertrial intervals owing to depression of dopamine release. No such depression is evident when photostimulating cAMP production directly. cAMP and protein kinase A responses to repeated appetitive or aversive stimuli also exhibit pronounced depression. Thus, history-dependent dynamics of dopamine and cAMP may regulate learning of temporally clustered, salient stimuli.

Heterostructure carbon-packed MoSSe nanospheres for flexible ReRAM and synapse devices

This paper reports on the synthesis of vacancy-assisted carbon-packed MoSSe (C@MoSSe) nanospheres and their use in memristor and neuromorphic devices. The heterostructure C@MoSSe nanospheres were fabricated using simple hydrothermal and sonication methods to synthesize large-scale, uniform C@MoSSe films on flexible substrates. The carbon skeleton, tightly adhered to the heterostructure MoSSe nanospheres, helped assign low sp2 characteristics to the vacancies on the defective surfaces of the MoSSe nanospheres, thereby facilitating the realization of highly stable memristor and neuromorphic performance. In addition, the defects in the crystal lattice of the pure phase of MoSSe increased the band gap (around 4.39 eV) to be larger than the bulk and Janus structure of MoSSe (1.2 and 1.9 eV, respectively), resulting in carrier transport owing to trap filling. The C@MoSSe-based memristor successfully mimicked the basic and complex properties of synaptic plasticity, with a critical time window of around 460 μs, lower than that of the human brain. Bipolar memory performance, such as a high on/off current ratio, a reasonably low operating voltage, and stability, depended on the thickness of the C@MoSSe layers. The findings demonstrate the application potential of C@MoSSe-based memristors and can promote the realization of large-scale neuromorphic circuits.

Intelligent Early Warning Method Based on Drone Inspection

Commonly used UAV emergency inspection methods are executed by the instructions of the ground command center. The response rate depends on the stability of the communication network and the rapid response ability of the commander. The critical time window is fleeting, which is likely to cause unnecessary loss. Crisis rapid response capability has become the key to measuring system capabilities. In order to improve the system’s rapid response capability, a method of deploying decision-making agents on airborne computers and ground early warning systems is proposed. This early warning method uses key technologies such as multi-network integration, situation assessment, neural network architecture, deep learning, reinforcement learning, and intelligent cognitive reasoning to effectively ensure the effectiveness of crisis warning. The early warning method of the early warning system is as follows: the mission computer uniformly collects the flight control status parameters, the load status parameters and the load real-time data form a composite information flow. The task computer adopts the methods of protocol conversion, data classification, and danger recognition to the compound information flow to identify the crisis information and make a preliminary analysis and judgment of the crisis state. If it is determined that it is necessary to track the target in real time, the initial task assignment and parameter adjustment of the load are carried out, and the continuous tracking of the task target is carried out to realize the rapid response to the crisis on the edge side. At the same time, the composite data are downloaded to the command center. The command center performs the secondary crisis analysis and risk level determination and outputs the crisis plan deduced by the agent to realize the strategy assistance. The accuser refers to the plan strategy and issues instructions to the task computer, and the task computer receives it. Instruction and secondary adjustment and optimization of the load parameters. If there is a flight route adjustment instruction, the adjustment route will be sent to the flight controller, which greatly improves the flexibility and efficiency of handling the crisis in the UAV inspection process. By adopting this set of early warning methods, it can provide users with an updated, faster and more efficient way to realize the early warning requirements in drone inspections, which is a new breakthrough in the field of drone command methods.

Prenatal and postnatal exposures to four metals mixture and IQ in 6-year-old children: A prospective cohort study in South Korea.

Humans are exposed to a mixture of metals during their lifetime; however, evidence of neurotoxicity of such mixtures in critical time windows is still insufficient. We aimed to elucidate the associations of four metals mixture across multiple time points with children's intelligence quotient (IQ) in a prospective cohort study. Prenatal exposure and exposure at age 4 and 6years to four types of blood metals, namely lead, mercury, cadmium, and manganese were quantified in 502 pregnant women and their children who participated in the Environment and Development Cohort study. Children' s IQ scores were assessed using the Wechsler Intelligence Scale at age 6. Bayesian kernel machine regression (BKMR), quantile g-computation models, and elastic net (ENET) models were used to assess the associations of their blood metals mixture with IQ scores. Multivariate linear regression models indicated that postnatal blood manganese exposure at the age of 4years was significantly negatively associated with children's IQ [β=-5.99, 95% confidence interval (CI): -11.37 to-0.61]. In the multi-chemical BKMR and quantile g-computation model, statistically significant inverse associations were found between the mixture of prenatal and postnatal metals and children's IQ score (Difference in children' IQ per quartile increase: -2.83; 95% CI: -5.28, -0.38). Interestingly, we found that manganese levels at both age of 4 and 6years were contributing factors to children's IQ in the mixture models, namely, BKMR, quantile g-computation, and ENET models. Multi-pollutant mixtures of prenatal and postnatal exposures to four metals affected child IQ at 6years of age. We found a relationship between manganese exposure at both age 4, and 6years and children's IQ. Additional studies are warranted to confirm these associations and to control the exposure to different metals during pregnancy and preschool childhood.