Background Activity Research Articles

Subacute parkinsonism induced by immune checkpoint inhibitors

Abstract Immune checkpoint inhibitors can trigger immune-related side effects, and while neurological involvement is rare, it can be serious. A woman with treatment-refractory intestinal T-cell lymphoma was initiated pembrolizumab and developed a daily fever and parkinsonian syndrome 2 weeks later. The investigation revealed only mild slowing of the background activity on electroencephalogram and slightly elevated cell count and protein levels in her cerebrospinal fluid. Immunotherapy was discontinued, and the patient recovered after 5 days of methylprednisolone. Minor neurological symptoms recurred after the rechallenge with pembrolizumab. Subacute parkinsonian syndromes should be considered a potential neurological event related to immune checkpoint inhibitors.

Audiogram Estimation Performance Using Auditory Evoked Potentials and Gaussian Processes.

Auditory evoked potentials (AEPs) play an important role in evaluating hearing in infants and others who are unable to participate reliably in behavioral testing. Discriminating the AEP from the much larger background activity, however, can be challenging and time-consuming, especially when several AEP measurements are needed, as is the case for audiogram estimation. This task is usually entrusted to clinicians, who visually inspect the AEP waveforms to determine if a response is present or absent. The drawback is that this introduces a subjective element to the test, compromising quality control of the examination. Various objective methods have therefore been developed to aid clinicians with response detection. In recent work, the authors introduced Gaussian processes (GPs) with active learning for hearing threshold estimation using auditory brainstem responses (ABRs). The GP is attractive for this task, as it can exploit the correlation structure underlying AEP waveforms across different stimulus levels and frequencies, which is often overlooked by conventional detection methods. GPs with active learning previously proved effective for ABR hearing threshold estimation in simulations, but have not yet been evaluated for audiogram estimation in subject data. The present work evaluates GPs with active learning for ABR audiogram estimation in a sample of normal-hearing and hearing-impaired adults. This involves introducing an additional dimension to the GP (i.e., stimulus frequency) along with real-time implementations and active learning rules for automated stimulus selection. The GP's accuracy was evaluated using the "hearing threshold estimation error," defined as the difference between the GP-estimated hearing threshold and the behavioral hearing threshold to the same stimuli. Test time was evaluated using the number of preprocessed and artifact-free epochs (i.e., the sample size) required for locating hearing threshold at each frequency. Comparisons were drawn with visual inspection by examiners who followed strict guidelines provided by the British Society of Audiology. Twenty-two normal hearing and nine hearing-impaired adults were tested (one ear per subject). For each subject, the audiogram was estimated three times: once using the GP approach, once using visual inspection by examiners, and once using a standard behavioral hearing test. The GP's median estimation error was approximately 0 dB hearing level (dB HL), demonstrating an unbiased test performance relative to the behavioral hearing thresholds. The GP additionally reduced test time by approximately 50% relative to the examiners. The hearing thresholds estimated by the examiners were 5 to 15 dB HL higher than the behavioral thresholds, which was consistent with the literature. Further testing is still needed to determine the extent to which these results generalize to the clinic. GPs with active learning enable automatic, real-time ABR audiogram estimation with relatively low test time and high accuracy. The GP could be used to automate ABR audiogram estimation or to guide clinicians with this task, who may choose to override the GP's decisions if deemed necessary. Results suggest that GPs hold potential for next-generation ABR hearing threshold and audiogram-seeking devices.

Semantic-Constraint Matching for transformer-based weakly supervised object localization

Weakly supervised object localization (WSOL) strives to localize objects with only image-level supervision. WSOL often faces challenges such as incomplete localization due to classifier bias and over-localization in real scenes where objects and backgrounds are strongly associated or structurally similar. While the latest Transformer-based methods effectively enhance localization performance by leveraging long-range feature dependencies, they may inadvertently amplify divergent background activation and remain susceptible to classification bias. To this end, we proposed a novel Semantic-Constraint Matching (SeCM) plug-in module tailored for transformer-based approaches. In detail, a local patch shuffle strategy is first introduced to disentangle partial contextual linkages, thereby creating image pairs. Then a semantic matching module extracts co-object knowledge from the primal-shuffled image pairs, drives the network to identify the association of foreground with semantic label to suppress divergent activation. Moreover, to alleviate incomplete localization and prevent excessive suppression of activation, we propose leveraging multi-modal class-specific textual representations to guide object localization by complementing intra-class priori diverse knowledge. Extensive experimental results conducted on CUB-200-2011 and ILSVRC datasets show that our method can achieve the new state-of-the-art performance.

Head-to-head comparison of 18F-sodium fluoride coronary PET imaging between a silicon photomultiplier with digital photon counting and conventional scanners

BackgroundWe compared silicone photomultipliers with digital photon counting (SiPM) and photomultiplier tubes (PMT) PET in imaging coronary plaque activity with 18F-sodium fluoride (18F-NaF) and evaluated comprehensively SiPM PET reconstruction settings. MethodsIn 25 cardiovascular disease patients (mean age 67±12 years), we conducted 18F-NaF PET on a SiPM (Biograph Vision) and conventional PET (Discovery 710) on the same day as part of a prospective clinical trial (NCT03689946). Following administration of 250 MBq of 18F-NaF, patients underwent a contrast-enhanced CT angiography and a 30-min PET acquisition in list mode on each PET consecutively. Image noise was defined as mean standard deviation of blood pool activity within the left atria. Target-to-background ratio (TBR) and signal-to-noise ratio (SNR) were measured within the whole-vessel tubular 3-dimensional volumes of interest on the cardiac motion and attenuation corrected 18F-NaF PET images using dedicated software. ResultsThere were significant differences in image noise and background activity between the two PETs (Image noise (%), PMT: 7.6±3.7 vs. SiPM: 4.0±2.3, p<0.001; background activity, PMT: 1.4±0.4 vs. SiPM: 1.0±0.3, p<0.001). Similarly, the SNR and TBR were significantly higher in vessels scanned with the SiPM PET (SNR, PMT: 16.3±11.5 vs. SiPM: 32.7±29.8, p<0.001; TBR, PMT: 0.8±0.4 vs. SiPM: 1.1±0.6, p<0.001). SiPM PET image reconstruction with a 256 matrix, 1.4 mm pixel, and 2 mm Gaussian filter provided best tradeoff in terms of maximal SNR, TBR and clinically practical file size. ConclusionsIn 18F-NaF coronary PET imaging, the SiPM PET showed superior image contrast and less image noise compared to PMT PET.

Restricted Cortical Activity Involving Parietal Lobe and Sublobar Region Leads to Generalized Spike-Wave Discharges of Juvenile Myoclonic Epilepsy: Evidence from an EEG Source Localization Study.

Previous studies have localized the origin of "generalized" spike-wave discharges of idiopathic generalized epilepsies to specific brain regions. Although there are studies in juvenile myoclonic epilepsy (JME) which have investigated the origin of spike-wave discharges, reports on the propagation of discharges are sparse. The current study investigated the propagation of spike-wave discharges in JME, which was investigated by statistically comparing the electroencephalography (EEG)-derived cortical source activity during (a) various phases of spike-wave discharge versus background (eyes closed) activity, and (b) various phases of the first spike wave versus the corresponding phase of subsequent spike waves. Fourteen patients with JME who had generalized spike/polyspike and slow wave discharges in interictal EEG were included in the study. A total of 179 spike waves (first discernible spike wave - 55; subsequent spike waves - 124) were selected for source localization. Source analysis was carried out using exact low-resolution electromagnetic tomography (eLORETA). Statistical analyses to estimate the probability distribution of differences in cortical activity between (a) eight phases of epileptic discharge versus background (eyes closed) activity and (b) phases of the first spike wave versus the corresponding phases of subsequent spike waves were performed by paired t-tests and corrected for multiple testing using LORETA-KEY software. Widespread activation of cortical voxels (more than 94%) was observed during all phases of epileptic discharge except the initial phase (pre-first spike) and terminal phase (post-peak of the subsequent wave). The parietal lobe, which was the most activated lobe during the pre-first spike, was found to be the least activated during the post-peak of first and subsequent waves. More than 93% of voxels in the sublobar region were consistently activated during all eight phases of discharge. The study findings suggest that the activity generated from the restricted brain network involving parietal lobe could be propagated through sublobar structures to cause widespread cortical activation during the subsequent phases of the spike-wave cycle.

Aperiodic Activity Indexes Neural Hyperexcitability in Generalized Epilepsy.

Generalized epilepsy (GE) encompasses a heterogeneous group of hyperexcitability disorders that clinically manifest as seizures. At the whole-brain level, distinct seizure patterns as well as interictal epileptic discharges (IEDs) reflect key signatures of hyperexcitability in magneto- and electroencephalographic (M/EEG) recordings. Moreover, it had been suggested that aperiodic activity, specifically the slope of the 1/ƒx decay function of the power spectrum, might index neural excitability. However, it remained unclear if hyperexcitability as encountered at the cellular level directly translates to putative large-scale excitability signatures, amenable to M/EEG. In order to test whether the power spectrum is altered in hyperexcitable states, we recorded resting-state MEG from male and female GE patients (n = 51; 29 females; 28.82 ± 12.18 years; mean ± SD) and age-matched healthy controls (n = 49; 22 females; 32.10 ± 12.09 years). We parametrized the power spectra using FOOOF ("fitting oscillations and one over f") to separate oscillatory from aperiodic activity to directly test whether aperiodic activity is systematically altered in GE patients. We further identified IEDs to quantify the temporal dynamics of aperiodic activity around overt epileptic activity. The results demonstrate that aperiodic activity indexes hyperexcitability in GE at the whole-brain level, especially during epochs when no IEDs were present (p = 0.0130; d = 0.52). Upon IEDs, large-scale circuits transiently shifted to a less excitable network state (p = 0.001; d = 0.68). In sum, these results uncover that MEG background activity might index hyperexcitability based on the current brain state and does not rely on the presence of epileptic waveforms.

Phantom test procedures for a new neuro-oncological amino acid PET tracer: [18F]fluciclovine.

Amino acid positron emission tomography (PET) examinations using anti-1-amino-3-[18F]-fluorocyclobutane-1-carboxylic acid ([18F]FACBC) were allowed for routine clinical use in July 2024. However, phantom test procedures for [18F]FACBC reconstruction parameters have not yet been established. The present study aimed to establish new phantom test procedures for [18F]FACBC brain PET imaging to determine optimal reconstruction parameters. Background (BG) activity as well as hot sphere and target-to-background ratios (TBRs) of [18F]FACBC were estimated based on brain activity and tumor-to-normal tissue ratios (TNR) in a Japanese clinical trial of [18F]FACBC. Phantom experiments proceeded under [18F]FACBC or L-[methyl-11C]-methionine ([11C]MET) conditions. The number of iterations and the Gaussian filter parameters were determined from the reconstruction parameters %contrastmean and coefficients of variation (CVs) in ordered subset expectation maximization (OSEM) and time-of-flight (TOF) with or without point-spread-function (PSF) correction. The amounts of activity in the hot spheres and BG were 1.1 and 5.5kBq/mL, respectively, and the TBR was 5.0 at the start of acquisition. The %contrastmean of all hot spheres was higher with [18F]FACBC than [11C]MET, and %contrastmean converged between 4 and 6 iterations in hot spheres with diameters < 10mm. We used four iterations for OSEM + TOF and five for OSEM + TOF + PSF correction for [18F]FACBC and [11C]MET images. The CV was higher for [18F]FACBC than [11C]MET. The optimal sizes of Gaussian filters for OSEM + TOF and OSEM + TOF + PSF correction of image reconstruction were 5mm for [18F]FACBC, and 4 and 3mm, respectively, for [11C]MET images. We estimated phantom activity and TBR based on brain activity in a Japanese clinical trial and established new phantom test procedures for [18F]FACBC. We recommend that the optimal reconstruction parameters for [18F]FACBC should be set to the same number of iterations as [11C]MET and that the FWHM of Gaussian filter should have a few mm higher than [11C]MET to reduce image noise from brain normal tissue.

Amplitude-integrated electroencephalography monitoring results of hospitalized neonates in plateau areas

To investigate the amplitude-integrated electroencephalography (aEEG) monitoring results of hospitalized neonates in plateau areas. A retrospective analysis was conducted on 5 945 neonates who were admitted to the Department of Neonatology, Kunming Children's Hospital, and received aEEG monitoring from January 2020 to December 2022. According to the aEEG monitoring results, they were divided into a normal aEEG group and an abnormal aEEG group. The incidence rate of aEEG abnormalities was analyzed in neonates with various systemic diseases, as well as the manifestations of aEEG abnormalities and the consistency between aEEG abnormalities and clinical abnormalities. Among the 5 945 neonates, the aEEG abnormality rate was 19.28% (1 146/5 945), with an abnormality rate of 29.58% (906/3 063) in critically ill neonates and 8.33% (240/2 882) in non-critically ill neonates (P<0.05). The children with inherited metabolic diseases showed the highest aEEG abnormality rate of 60.77% (79/130), followed by those with central nervous system disorders [42.22% (76/180)] and preterm infants [35.53% (108/304)]. Compared with the normal aEEG group, the abnormal aEEG group had significantly lower age and gestational age, as well as a significantly lower birth weight of preterm infants (P<0.05). Among the 1 146 neonates with aEEG abnormalities, the main types of aEEG abnormalities were sleep cycle disorders in 597 neonates (52.09%), background activity abnormalities in 294 neonates (25.65%), and epileptiform activity in 255 neonates (22.25%), and there were 902 neonates (78.71%) with abnormal clinical manifestations. The sensitivity and specificity of aEEG monitoring for brain function abnormalities were 33.51% and 92.50%, respectively. In plateau areas, there is a relatively high rate of aEEG abnormalities among hospitalized neonates, particularly in critically ill neonates and those with smaller gestational ages and younger ages, suggesting a high risk of brain injury. Therefore, routine aEEG monitoring for the hospitalized neonates can help with the early detection of brain function abnormalities, the decision-making in treatment, and the formulation of brain protection strategies.

Use of sedation-awakening electroencephalography in dogs with epilepsy.

Electroencephalography (EEG) recording protocols have been standardized for humans. Although the utilization of techniques in veterinary medicine is increasing, a standard protocol has not yet been established. Assessment of a sedation-awakening EEG protocol in dogs. Electroencephalography examination was performed in a research colony of 6 nonepileptic dogs (control [C]) and 12 dogs with epilepsy admitted to the clinic because of the epileptic seizures. It was a prospective study with retrospective control. Dogs with epilepsy were divided into 2 equal groups, wherein EEG acquisition was performed using a "sedation" protocol (IE-S, n = 6) and a "sedation-awakening" protocol (IE-SA, n = 6). All animals were sedated using medetomidine. In IE-SA group, sedation was reversed 5 minutes after commencing the EEG recording by injecting atipamezole IM. Type of background activity (BGA) and presence of EEG-defined epileptiform discharges (EDs) were evaluated blindly. Statistical significance was set at P > 0.05. Epileptiform discharges were found in 1 of 6 of the dogs in group C, 4 of 6 of the dogs in IE-S group, and 5 of 6 of the dogs in IE-SA group. A significantly greater number of EDs (spikes, P = .0109; polyspikes, P = .0109; sharp waves, P = .01) were detected in Phase 2 in animals subjected to the "sedation-awakening" protocol, whereas there was no statistically significant greater number of discharges in sedated animals. A "sedation-awakening" EEG protocol could be of value for ambulatory use if repeated EEG recordings and monitoring of epilepsy in dogs is needed.

General process detection through side channel characterization

ABSTRACT In this study, we demonstrate the feasibility of using physical sensors in System-on-a-Chip (SoC) for real-time security monitoring by detecting and characterizing different process types, such as file I/O, CPU/ALU-intensive tasks, network I/O and virtualization. We present models that use sensor data for binary classification to determine whether a specific process category is active or inactive. Analyzing the detection results, we determine the importance of each sensor in identifying process types and providing insights into process behaviors and sensor impacts. We developed adaptive ensemble classifiers to accommodate varying load conditions, enhancing detection accuracy across diverse operational scenarios, including regular background activities that simulate real-world conditions. Our results show effective detection of file I/O and CPU/ALU-intensive processes under various loads. Virtualization processes are accurately detected under light loads but show a moderate accuracy decline under heavier conditions. Network I/O detection faces challenges due to fewer relevant sensors. Our ability to predict process categories consistently and with high performance allows us to discover behaviors of various malicious activities. This research underlines the efficacy of sensor-based analysis for reliable and adaptable real-time process monitoring, demonstrating the feasibility of using sensor data for security purposes in various environmental conditions.

Genotype and phenotype of WWOX gene related developmental and epileptic encephalopathy

Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

The effect of a remote physical activity intervention on postpartum depressive symptoms and stress among low income women: The healthy mom III randomized trial

Background and aimsPhysical activity interventions have been shown to prevent postpartum depression. However, few studies have targeted low income women who are at high risk for postpartum depression. MethodsThis study examined the efficacy of a novel remote physical activity intervention designed to prevent perinatal depression (assessed at 36 weeks gestation and 12 week postpartum). Participants (n = 111) who were low income and pregnant (less than 20 weeks) were randomly assigned to either a six month intervention focusing on increasing physical activity and decreasing sedentary behavior (remote counseling sessions based on Self-Determination Theory) or usual care. All participants wore a Fitbit throughout the study to monitor their activity levels. The Edinburgh Postnatal Depression Scale and Perceived Stress Scale were administered at baseline, 36 weeks gestation, and 12 weeks postpartum. ResultsThere was no effect of the intervention on depressive symptoms or perceived stress at either of the timepoints. Secondary analysis indicated that lower levels of sedentary behavior, β = 0.256, p < 0.05, and higher levels of light activity at 8–12 weeks postpartum was related to lower perceived stress at 12 weeks postpartum, β = −0.284, p < 0.05. ConclusionEven though there was no effect of the intervention on preventing depression and stress, it continues to be important for clinicians to discuss the importance of activity during the perinatal phase due to the many health benefits. There is some evidence that sedentary and physical activity behavior may be important for reducing stress levels, however, additional research is needed.

Visual Electroencephalography Assessment in the Diagnosis and Prognosis of Cognitive Disorders.

Electroencephalography (EEG) is a noninvasive diagnostic tool that can be of diagnostic value in patients with cognitive disorders. In recent years, increasing emphasis has been on quantitative EEG analysis, which is not easily accessible in clinical practice. The aim of this study was to assess the diagnostic and prognostic value of visual EEG assessment to distinguish different causes of cognitive disorders. Patients with cognitive disorders from a specialized memory clinic cohort underwent routine workup including EEG, neuropsychological testing and brain imaging. Electroencephalography parameters including posterior dominant rhythm, background activity, and response to photic stimulation (intermittent photic stimulation) were visually scored. Final diagnosis was made by an expert panel. A total of 501 patients were included and underwent full diagnostic workup. One hundred eighty-three patients had dementia (111 Alzheimer disease, 30 vascular dementia, 15 frontotemporal dementia, and 9 dementia with Lewy bodies), 66 patients were classified as mild cognitive impairment, and in 176, no neurologic diagnosis was made. Electroencephalography was abnormal in 60% to 90% of patients with mild cognitive impairment and dementia, most profoundly in dementia with Lewy bodies and Alzheimer disease, while frontotemporal dementia had normal EEG relatively often. Only 30% of those without neurologic diagnosis had EEG abnormalities, mainly a diminished intermittent photic stimulation response. Odds ratio of conversion to dementia was 6.1 [1.5-24.7] for patients with mild cognitive impairment with abnormal background activity, compared with those with normal EEG. Visual EEG assessment has diagnostic and prognostic value in clinical practice to distinguish patients with memory complaints without underlying neurologic disorder from patients with mild cognitive impairment or dementia.

Effects of a staff physical activity professional development intervention on preschoolers' mental health and self-regulation: The active learning Norwegian Preschool(er)s (ACTNOW) cluster randomised controlled trial

Background and aimPhysical activity may have positive effects on preschoolers' mental health and self-regulation. The preschool setting provides children with opportunities to meet physical activity guidelines and could improve with staff training in delivering physical activity. This study examined the effect of physical activity professional development for preschool staff on preschoolers' proxy-measured mental health and self-regulation. MethodsIn total, 1265 children from 46 preschools were cluster randomised to either the intervention or the control group. The intervention was nested within two levels implemented concurrently: the preschool level, formed as a professional development where preschools conducted development work, and the child level, with whom the staff implemented physical activity with four core components. Data were analysed using an ANCOVA model through structural equation modelling with latent outcome factors of: emotional problems, peer problems, hyperactivity, and prosocial behaviour from the Strength and Difficulties Questionnaire; and cognitive, emotional, and behavioural self-regulation from the Child Self-regulation and Behaviour Questionnaire. ResultsNo effects of the intervention (standardised effect sizes -0.195–0.145, p-values 0.118–0.893) were observed. Secondary analysis showed that children with initially high prosocial behaviour and behavioural self-regulation positively benefited from the intervention (p = 0.035 and p = 0.047, respectively). ConclusionThe ACTNOW intervention had no effects on preschoolers' mental health or self-regulation after 18 months, besides effects for children with initially the highest prosocial behaviour and behavioural self-regulation. Although the professional development was more extensive than previous studies it may have been insufficient to change the preschools physical activity practices. Clinical trial registrationwww.ClinicalTrials.gov identifier NCT04048967.

A machine learning artefact detection method for single-channel infant event-related potential studies

Objective. Automated detection of artefact in stimulus-evoked electroencephalographic (EEG) data recorded in neonates will improve the reproducibility and speed of analysis in clinical research compared with manual identification of artefact. Some studies use very short, single-channel epochs of EEG data with little recorded EEG per infant—for example because the clinical vulnerability of the infants limits access for recording. Current artefact-detection methods that perform well on adult data and resting-state and multi-channel data in infants are not suitable for this application. The aim of this study was to create and test an automated method of detecting artefact in single-channel 1500 ms epochs of infant EEG. Approach. A total of 410 epochs of EEG were used, collected from 160 infants of 28–43 weeks postmenstrual age. This dataset—which was balanced to include epochs of background activity and responses to visual, auditory, tactile and noxious stimuli—was presented to seven independent raters, who independently labelled the epochs according to whether or not they were able to visually identify artefacts. The data was split into a training set (340 epochs) and an independent test set (70 epochs). A random forest model was trained to identify epochs as either artefact or not artefact. Main results. This model performs well, achieving a balanced accuracy of 0.81, which is as good as manual review of data. Accuracy was not significantly related to the infant age or type of stimulus. Significance. This method provides an objective tool for automated artefact rejection for short epoch, single-channel EEG in neonates and could increase the utility of EEG in neonates in both the clinical and research setting.

Analysis of a child with developmental disorder and epilepsy due to a homozygous variant of SLC25A12 gene

To explore the genetic basis for a child featuring global developmental delay and epilepsy. A child who had presented at Guangzhou Women and Children's Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

Enzyme purification and sustained enzyme activity for pharmaceutical biocatalysis by fusion with phase-separating intrinsically disordered protein.

In recent decades, biocatalysis has emerged as an important alternative to chemical catalysis in pharmaceutical manufacturing. Biocatalysis is attractive because enzymatic cascades can synthesize complex molecules with incredible selectivity, yield, and in an environmentally benign manner. Enzymes for pharmaceutical biocatalysis are typically used in their unpurified state, since it is time-consuming and cost-prohibitive to purify enzymes using conventional chromatographic processes at scale. However, impurities present in crude enzyme preparations can consume substrate, generate unwanted byproducts, as well as make the isolation of desired products more cumbersome. Hence, a facile, nonchromatographic purification method would greatly benefit pharmaceutical biocatalysis. To address this issue, here we have captured enzymes into membraneless compartments by fusing enzymes with an intrinsically disordered protein region, the RGG domain from LAF-1. The RGG domain can undergo liquid-liquid phase separation, forming liquid condensates triggered by changes in temperature or salt concentration. By centrifuging these liquid condensates, we have successfully purified enzyme-RGG fusions, resulting in significantly enhanced purity compared to cell lysate. Furthermore, we performed enzymatic reactions utilizing purified fusion proteins to assay enzyme activity. Results from the enzyme assays indicate that enzyme-RGG fusions purified by the centrifugation method retain enzymatic activity, with greatly reduced background activity compared to crude enzyme preparations. Our work focused on three different enzymes-a kinase, a phosphorylase, and an ATP-dependent ligase. The kinase and phosphorylase are components of the biocatalytic cascade for manufacturing molnupiravir, and we demonstrated facile co-purification of these two enzymes by co-phase separation. To conclude, enzyme capture by RGG tagging promises to overcome difficulties in bioseparations and biocatalysis for pharmaceutical synthesis.

Seizure Outcome and Predicting Factors in Adult Patients with Phenylketonuria: Single-center Experience

ABSTRACT Objective: Phenylketonuria (PKU) is one of the most common metabolic disorders worldwide. If left untreated, it causes neuropsychiatric sequelae, with seizures being a common occurrence. There is little information about the clinical features of epilepsy, electroencephalography (EEG) findings, and factors related to seizure outcomes in adult patients. We aimed to investigate these variables in adult PKU patients. Methods: We conducted a retrospective search in our database using the keywords “PKU and epilepsy” for the period between 2008 and 2022. Demographic, clinical, EEG, and cranial magnetic resonance imaging (MRI) findings of the patients were extracted from the electronic health records. Scalp EEG and MRI findings were reassessed. Phenylalanine (Phe) levels of the cases were retrieved. The potential correlation between seizure outcome and laboratory findings was analyzed. Results: Ten patients (4 females; aged: 19–55 years) were included. Seizure onset was various. The most common seizure type was bilateral tonic-clonic. Nine patients were on antiseizure medications (ASMs); seven were seizure-free. EEG background activity was slow in four patients, with paroxysmal discharges in eight individuals. The most frequent MRI finding was periventricular white matter hyperintensity. No correlation existed between seizure outcome and clinical, EEG, MRI results, or Phe levels. Seizure freedom was more common in patients with good dietary compliance. Conclusion: Bilateral tonic–clonic seizures were the most common type of seizure, accompanied by frequent paroxysmal activity in EEG. MRI scans revealed periventricular white matter hyperintensity. Seizure freedom was commonly achieved with ASMs, irrespective of blood Phe levels. Nevertheless, dietary compliance may play a role in seizure control.

Diagnostic Performances of PET/CT Using Fibroblast Activation Protein Inhibitors in Patients with Primary and Metastatic Liver Tumors: A Comprehensive Literature Review.

PET/CT using radiolabeled fibroblast activation protein inhibitors (FAPIs) is a promising diagnostic tool in oncology, especially when non-increased and/or physiologically high [18F]FDG uptake (as in liver parenchyma) is observed. We aimed to review the role of PET/CT using radiolabeled FAPIs in primary and/or metastatic liver lesions, and to compare their performances with more "conventional" radiopharmaceuticals. A search algorithm based on the terms "FAPI" AND ("hepatic" OR "liver") was applied, with the last update on 1st January 2024. Out of 177 articles retrieved, 76 studies reporting on the diagnostic application of radiolabeled FAPI PET/CT in at least one patient harboring primary or metastatic liver lesion(s) were fully analyzed. Although there was some heterogeneity in clinical conditions and/or study methodology, PET/CT with radiolabeled FAPIs showed an excellent performance in common primary liver malignancies (hepatocarcinoma, intrahepatic cholangiocarcinoma) and liver metastases (mostly from the gastrointestinal tract and lungs). A higher tumor-to-background ratio for FAPIs than for [18F]FDG was found in primary and metastatic liver lesions, due to lower background activity. Despite limited clinical evidence, radiolabeled FAPIs may be used to assess the suitability and effectiveness of FAPI-derived therapeutic agents such as [177Lu]Lu-FAPI. However, future prospective research on a wider population is needed to confirm the excellent performance.

Structural Background of Geda Area in Tibet and Its Influence on Exercise and Training Activities

Tectonic geology is one of the most critical factors affecting geological activities in the regional geological background. By studying the structural geological environment of Geda Township and analyzing its geological units and tectonic stresses, it is concluded that: (1) Six large faults developed in the area in the near-north-south direction control the basic geological and tectonic structure of the working area and affect the spatial structure of the area; The depression of the fault is the Geda fault depression basin, and the flat valley area of the basin is relatively flat, which is conducive to the assembly and cantonment of troops. (2) The extension scale of the fault system extends a large scale, the direction of nearly north-south, in the engineering layout or field mobility, and the fault zone should be avoided as much as possible in engineering layout or field maneuvering; (3) There are many valleys, gullies and other connected landforms in the area, which are conducive to the passage of troops and logistics supplies; (4) The tectonic pattern of Geda sedimentary basin formed by the near-north-south oriented Geda sedimentary basin basin-control rupture system provides a good channel for field maneuvering; (5) The north-south fault system leads to the development of cracks and good penetration in the area, and the groundwater penetrates the surface well due to various effects such as pressure or siphon, and the entire water supply system in the area is guaranteed. Based on the combination of structural geology and military geology, this study preliminarily reviews the relationship between the two, and provides ideas for the integration of the two professional disciplines.