Degree Of Abnormality Research Articles

Concealed cardiomyopathy as an emerging cause of sudden cardiac arrest and sudden cardiac death.

The inherited cardiomyopathies exhibit a broad spectrum of disease, with some patients remaining asymptomatic throughout life, while, for others, the first symptom of disease is sudden cardiac death at a young age. The risk of malignant ventricular arrhythmia in these conditions has traditionally been linked to the degree of structural myocardial abnormalities and functional impairment. However, recent advances in genetic testing and knowledge of the genetic basis of the diseases have led to the identification of concealed cardiomyopathy, in which sudden cardiac arrest or sudden cardiac death occurs in the absence of observable clinical features of cardiomyopathy, with a diagnosis being made only after the identification of a causative genetic variant. Increased awareness of concealed cardiomyopathy, a better understanding of mechanisms of arrhythmia and identification of risk modulators will be vital to improve care for families with concealed cardiomyopathy.

Normal ranges of left atrial phasic strains and strain rates by 2D speckle-tracking echocardiography in pediatrics: a systematic review and meta-analysis

Establishing normal values of left atrial (LA) phasic strains and strain rates is essential for distinguishing between normal and abnormal functions, determining the degree of abnormality, and understanding the clinical significance of reported values in pediatrics. This meta-analysis aimed to establish normal values of two-dimensional speckle-tracking echocardiography (2DSTE)-derived LA phasic strains and strain rates in the pediatric population and identify the sources of inter-study heterogeneity for these values. A comprehensive search of PubMed, Scopus, and Embase databases was conducted using keywords such as “left atrial/left atrium,” “strain/speckle/deformation,” and “echocardiography” combined with pediatric age categories. Inclusion criteria comprised English-language human studies involving healthy subjects under 18 years of age. Subjects were categorized as neonates (up to 1 month), infants (1–12 months), and children (1–18 years). A random-effects model was applied to determine 2DSTE-derived LA strains and strain rates, and a meta-regression analysis was performed to investigate inter-study heterogeneity. Our analysis included 17 studies involving 1448 healthy subjects. For children, the mean values of LA strains during the reservoir, conduit, and contraction phases were 47.3% (95% CI 42.5–52.1%), 32.8% (95% CI 27.8–37.8%), and 12% (95% CI 10.0–14.1%), respectively. The mean values for LA strain rates were 2.4 s−1 (95% CI 1.1–3.8 s−1), 4.3 s−1 (95% CI 0.6–8.0 s−1), and 2.4 s−1 (95% CI 0.4–4.5 s−1), respectively. Inter-study heterogeneity for 2DSTE-derived LA phasic strains and strain rates was attributed to factors such as the number of study participants, publication year, software utilized, gating methods, the number of analyzed segments, the geographical region of the study, and heart rate. This study established the normal range of 2DSTE-derived LA phasic strains and strain rates. Additionally, inter-study heterogeneity was found to be influenced by various demographic, physiologic, and methodological factors.

Anemia in patients with chronic kidney disease and its association with cardiac abnormalities

Abstract Introduction Chronic kidney disease (CKD) is a pathology characterized by multisystemic comorbidities, predominantly associated with cardiovascular disease and anemia. However, the precise association between the degree of anemia and the development of cardiac abnormalities in patients with CKD undergoing hemodialysis remains unclear. Purpose To determine the association between the degree of anemia and cardiac abnormalities in patients with CKD receiving hemodialysis treatment. Methods A cross-sectional multicenter study that included individuals with CKD undergoing hemodialysis was conducted. Electronic medical records containing information regarding medical conditions and pertinent laboratory parameters was collected, and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the associated between the degree of anemia and echocardiographic parameters, with significant set at p <0.05. Results Ninety-nine individuals were included, with a median age of 48 years. The population was categorized based on hemoglobin (Hb) levels into non/mild anemia (Hb >10 mg/dL) and moderate/severe anemia (Hb <9.9 mg/dL) groups (table). Significant differences were observed in left ventricle (LV) posterior wall thickness (10mm in non/mild vs. 11mm in moderate/severe, p<0.015), left atrial (LA) volume (34 mL/m2 in non/mild vs. 39 mL/m2 in moderate/severe, p<0.007) and left ventricular ejection fraction (LVEF) (59% in non/mild vs. 55% in moderate/severe, p<0.025). Negative correlations (figure) were observed between Hb levels and LV mass index (r= -0.21, p= 0.03) and pulmonary artery systolic pressure (PASP)(r= -0.27, p= 0.006). Conclusion The degree of anemia demonstrated an association with cardiac abnormalities, as evidenced by alterations in echocardiographic parameters such as LVEF, LA volume and PSAP. This study underscores the importance of further prospective investigations to enhance early identification and stratification of anemia in patients with CKD aiming to mitigate further cardiac complications.Clinical demographics tableScatter plots with correlation graphs

A longitudinal study on the development trajectory of auditory processing and its relationship with language development in Chinese preschool children with autism spectrum disorder: study protocol

BackgroundIt was reported that more than 96% of autism spectrum disorder (ASD) children are accompanied with different degrees of sensory processing abnormalities, and up to 50% of ASD children exhibit abnormal auditory response. Studies have confirmed that some ASD children’s abnormal auditory response may be related to their abnormal auditory processing. Prior research demonstrated that ASD children’s auditory processing has high heterogeneity, thus, ASD children’s auditory processing may have different developmental trajectories. However, no study has concentrated on the developmental trajectories of ASD children’s auditory processing. In addition, auditory processing plays a crucial role in ASD children’s language development, thus, ASD children’s different language development outcomes may be related to different auditory processing development tracks. Therefore, this study aims to explore the developmental trajectory of auditory processing in ASD children and analyze the relationship between different developmental trajectories of auditory processing and language impairment.Methods/DesignIn this study, 220 ASD children aging 3 years and 0 months to 4 years and 11 months are recruited as the research objects, and their demographic characteristics are collected. The subjects are tested for peripheral hearing, intelligence, and autism symptoms. Furthermore, ASD children’s auditory processing and language development are evaluated at baseline, 1 year, and 2 years later. In addition, ASD children’s auditory processing is evaluated by electrophysiological test and the Preschool Auditory Processing Assessment Scale. Moreover, ASD children’s language skills are assessed using the Language Development Assessment Scale for Children Aged 1–6. The various categories of the developmental trajectory of ASD children’s auditory processing are examined through the latent category growth model. Additionally, a hierarchical regression model is developed to analyze the predictive impact of different auditory processing development trajectories on language impairment in ASD children.DiscussionThis longitudinal study will explore the categories of auditory processing developmental trajectories in ASD children, and analyze the relationship between different categories of auditory processing developmental trajectories and language development, providing new ideas and targeted targets for the rehabilitation training of language impairment in ASD children, as well as promoting early and accurate interventions for ASD children.

Learning to rank anomalies: scalar performance criteria and maximization of rank statistics

AbstractThe ability to collect and store ever more massive data, unlabeled in many cases, has been accompanied by the need to process them efficiently in order to extract relevant information and possibly design solutions based on the latter. In various situations, the vast majority of the observations exhibit the same behavior, while a small proportion deviates from it. Detecting these outlier observations (or equivalently defined as anomalies) is now one of the major challenges for machine learning applications (e.g. fraud detection or predictive maintenance). We propose here a novel methodology for outlier/anomaly detection, by learning a scoring function defined on the feature space allowing for ranking the observations by degree of abnormality. The scoring function is built through maximization of an empirical performance criterion taking the form of a (two-sample) linear rank statistic. We show that bipartite ranking algorithms can thus be used to learn nearly optimal scoring function with provable theoretical guarantees. We illustrate our methodology with numerical experiments based on open access online code.

Pre- and post-therapy functional MRI connectivity in severe acute brain injury with suppression of consciousness: a comparative analysis to epilepsy features.

Severe acute brain injury (SABI) with suppressed consciousness is a major societal burden, with early prognosis being crucial for life-and-death treatment decisions. Resting-state functional MRI (rs-fMRI) is promising for prognosis and identifying epileptogenic activity in SABI. While established for SABI prognosis and seizure networks (SzNET) identification in epilepsy, the rs-fMRI use for SzNET detection in SABI is limited. This study compared evolution of SzNET and resting-state networks (RSN) pre-to-post treatment in SABI and epilepsy, hypothesizing that changes would align with clinical evolution. Therapies included epilepsy surgery for the epilepsy group and antiseizure medication for the SABI group. Independent component analysis (ICA) was used to identify SzNET and RSNs in all rs-fMRI. High-frequency BOLD (HF-BOLD), an ICA power spectrum-based index, quantified RSN and SzNET changes by the patient. Confidence intervals measured HF-BOLD changes pre-to-post-therapy. Baseline HF-BOLD and HF-BOLD changes were compared using linear-mixed models and interaction tests. Five SABI and ten epilepsy patients were included. SzNET were identified in all SABI's pre-therapy rs-fMRI. The clinical changes in SABI and epilepsy were consistent with rs-fMRI findings across groups. HF-BOLD reduced in the epilepsy group RSN post-therapy (-0.78, 95% CI -3.42 to -0.33), but the evidence was insufficient to determine an HF-BOLD reduction in SABI patients or SzNET. The HF-BOLD change trend in pre-to-post epilepsy surgery scans paralleled the clinical improvement, suggesting that the power spectrum may quantify the degree of abnormality on ICA-derived networks. Despite limitations such as small sample sizes, this exploratory study provides valuable insights into network dysfunction in SABI and epilepsy.

Correlation of serum Krebs von den Lungen-6 levels with fibrosis score on high resolution chest tomography and pulmonary function parameters in treatment naïve Idiopathic Pulmonary Fibrosis.

While serum Krebs von den Lungen-6 (KL-6) has been found to be a helpful biomarker in interstitial lung diseases for evaluating disease severity and progression, especially in connective tissue disease-associated interstitial lung disease (CTD ILD) and idiopathic non-specific interstitial pneumonia (NSIP), data on correlation of serum KL-6 levels with radiological fibrosis and pulmonary function parameters is lacking in treatment naïve Idiopathic Pulmonary Fibrosis (IPF) patients. Serum KL-6 levels were measured in thirty-nine treatment naïve newly detected IPF patients using automated immunofluorescence enzyme assay (AIA) by Tosoh Corporation, bioscience division, Tokyo, Japan. Fibrosis score was calculated by independent visual assessment of the pattern and severity of abnormalities on high resolution computed tomography (HRCT) thorax. HRCT fibrosis scores were correlated with serum KL-6 levels and pulmonary function parameters like forced vital capacity (FVC), diffusion capacity of lung for carbon monoxide (DLco). Median value of serum KL-6 levels was 1519 U/ml (range 199.41-6055 U/ml). There was positive correlation of serum KL-6 with HRCT fibrosis score (r=0.692, p<0.001) and negative correlation with FVC (r=-0.511, p=0.001) and DLco (r=-0.354, p=0.043). In the HRCT fibrosis score pattern subset analysis, the presence of reticulation revealed weak negative and statistically insignificant correlation (r=-0.116, p=0.481) while traction bronchiectasis and honeycombing exhibited statistically significant positive correlation (r=0.425, p=0.007; r=0.584, p<0.001 respectively) with serum KL-6 levels. Serum KL-6 levels showed a positive correlation with the degree of fibrotic abnormalities on HRCT thorax and pulmonary function parameters, indicating a potential use of serum KL-6 in monitoring of parenchymal fibrosis in Idiopathic Pulmonary fibrosis.

Clinical, biochemical, molecular characteristics and clinical outcome of hyperhomocysteinemia in Malaysian children

BackgroundHyperhomocysteinemia can be due to various abnormalities of the complex interaction of methionine, folate and vitamin B12. It has been known to be a cardiovascular risk factor. This study aims to review the clinical presentation, underlying causes and clinical outcome in paediatric patients diagnosed with significant hyperhomocysteinemia in Malaysia. Design and methodsData were obtained from the medical records and the laboratory information system. Paediatric patients with significant hyperhomocysteinemia were identified from a selective high-risk screening of 96,721 patients, performed between 2010 and 2022. Inclusion criteria for the study were paediatric patients with significant hyperhomocysteinemia (>40 µmol/L). ResultsSixteen patients were identified. The average total homocysteine (tHcy) and methionine were 269 µmol/L and 499 µmol/L in cystathionine β-synthase deficiency (CBS), 127 µmol/L and 29 µmol/L in patients with remethylation defects and 390 µmol/L and 4 µmol/L in congenital B12 deficiency. We found c.609G>A as the most prevalent mutation in MMACHC gene and possible novel mutations for CBS (c.402del, c.1333C>T and c.1031T>G) and MTHFR genes (c.266T>A and c.1249del). Further subclassification revealed CBS was 5/16 patients (31 %), remethylation defects was 9/16 (56 %) and congenital B12 deficiency was 2/16 (13 %). All patients received standard treatment and regular monitoring of the main biomarkers. The average age at the time of diagnosis were 9.2 years (CBS) and 1.2 years (remethylation defects). Congenital B12 deficiency had slight delay in milestones, remethylation defects had mild to moderate learning disabilities, CBS had variable degree of intellectual disability, delayed milestones, ophthalmological abnormalities, and thrombosis at an early adolescent/adulthood. ConclusionsThe majority of significant hyperhomocysteinemia in Malaysian children was due to remethylation defects. Screening for hyperhomocysteinemia in Malaysian children is recommended for earlier treatment and improved clinical outcome.

Unsupervised anomaly detection of multivariate time series based on multi-standard fusion

With the wide application of the Internet of Things, industrial systems generate a large amount of multivariate time series data every day. Industrial data often contains a wide variety of anomalies. The existing anomaly detection methods have some shortcomings in dealing with large-scale, high-dimensional, and real-time industrial data. Particularly in the absence of prior knowledge, unsupervised learning methods are easily influenced by noise. Therefore, we propose a new unsupervised anomaly detection algorithm of multivariate time series based on multi-standard fusion (MSAD). Specifically, MSAD first classifies the data by analyzing the data density and sample spacing, thereby converting unsupervised anomaly detection into weakly supervised anomaly detection. Then, based on the characteristics of the data and deep learning technology, the degree of abnormality in the sample is comprehensively measured from four perspectives: holistic, local, time, and deep feature learning. At this stage, MSAD 's ability to learn edge features of data has been improved. Finally, based on MSAD, we design an anomaly detection method for industrial data streams in combination with data filtering techniques. The experimental results show that MSAD can detect anomalies more accurately and show stronger robustness to the influence of noise.

Lipodystrophic Laminopathies: From Dunnigan Disease to Progeroid Syndromes.

Lipodystrophic laminopathies are a group of ultra-rare disorders characterised by the presence of pathogenic variants in the same gene (LMNA) and other related genes, along with an impaired adipose tissue pattern and other features that are specific of each of these disorders. The most fascinating traits include their complex genotype-phenotype associations and clinical heterogeneity, ranging from Dunnigan disease, in which the most relevant feature is precisely adipose tissue dysfunction and lipodystrophy, to the other laminopathies affecting adipose tissue, which are also characterised by the presence of signs of premature ageing (Hutchinson Gilford-progeria syndrome, LMNA-atypical progeroid syndrome, mandibuloacral dysplasia types A and B, Nestor-Guillermo progeria syndrome, LMNA-associated cardiocutaneous progeria). This raises several questions when it comes to understanding how variants in the same gene can lead to similar adipose tissue disturbances and, at the same time, to such heterogeneous phenotypes and variable degrees of metabolic abnormalities. The present review aims to gather the molecular basis of adipose tissue impairment in lipodystrophic laminopathies, their main clinical aspects and recent therapeutic strategies. In addition, it also summarises the key aspects for their differential diagnosis.

Phenotypic and molecular characterizations of 46,XY disorders of sex development due to variants of NR5A1 gene

The clinical and molecular genetic characteristics of 46,XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. The clinical data of children with NR5A1 gene variants diagnosed at the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1 ~ 9), including micropenis (100.0%), hypospadias (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~ Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomal karyotypes were 46,XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. The clinical phenotype of 46,XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.

Association between lymphatic abnormalities in the neck and thorax in primary chylopericardium and surgical outcomes evaluated by non-enhanced magnetic resonance (MR) lymphangiography.

Chylopericardium refers to the accumulation of chylous fluid in the pericardial cavity. Non-enhanced magnetic resonance lymphangiography (MRL) can show neck and thoracic lymphatic abnormalities in the primary chylopericardium. It is not clear whether there is a relationship between neck and thoracic lymphatic abnormalities in primary chylopericardium and thoracic duct terminal release surgery. This study aimed to explore the correlation between the severity of neck and thoracic lymphatic abnormalities observed in non-enhanced MRL and the surgical outcomes in primary chylopericardium. This is a retrospective cohort study. A retrospective analysis was conducted on fifty-six patients diagnosed with primary chylopericardium between January 2016 and December 2021, all of whom underwent thoracic duct terminal release surgery. Ultrasonography, chest computed tomography (CT) and non-enhanced MRL were performed prior to the surgical intervention. Patients were categorized into four types based on the severity of neck and thoracic lymphatic abnormalities observed in the non-enhanced MRL. Clinical and laboratory examinations and surgical outcomes were compared across different types using χ 2-test or Fisher's exact test, t-test, and Kruskal-Wallis H-test. Additionally, independent factors influencing surgical outcomes were analyzed. Among primary chylopericardium cases (n=56), 22 (39.2%) were classified as type I or II, 17 (30.4%) as type III, and 17 (30.4%) as type IV. Surgical outcomes were more favorable for type I or II patients than those with type III or IV, accompanied by a reduction in postoperative primary chylopericardium volume (P=0.002). Postoperative chest CT scans indicated that type I or II patients had fewer instances of large grid shadows, small grid shadows, and bronchovascular bundle thickening compared to preoperative scans (P=0.001, P=0.02, P=0.03). Age and bronchomediastinal trunk dilation emerged as independent factors influencing surgical outcomes [odds ratio (OR) 0.03, 95% confidence interval (CI): 0.003-0.220, P=0.001; OR 11.10, 95% CI: 1.70-72.39, P=0.01, respectively]. A more severe degree of neck and thoracic lymphatic abnormalities is associated with worse surgical outcomes. Moreover, age and bronchomediastinal trunk dilatation are independent predictors of surgical outcomes. Preoperative utilization of non-enhanced MRL for severity of lymphatic abnormalities classification in primary chylopericardium patients offers a noninvasive means of assessing surgical risk.

Abnormal Degree Centrality in Zoster-Associated Pain with or Without Psychiatric Comorbidities: A Resting-State Functional MRI Study.

Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood. Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed. One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively. This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.

Masseteric Vestibular Evoked Myogenic Potentials in Wallenberg Syndrome: A Case Report.

We report the clinical findings of mVEMP responses in conjunction with cVEMPs and oVEMPs in an individual with Wallenberg syndrome. The results indicated that the degree of abnormality in mVEMP was comparatively higher than in cVEMPs and oVEMPs. mVEMPs can offer valuable insights into the Wallenberg syndrome's brainstem pathophysiology.

The impact of illness duration on brain activity in goal-directed and habit-learning systems in obsessive-compulsive disorder progression: A resting-state functional imaging study

It is increasingly evident that structural and functional changes in brain regions associated with obsessive–compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.

Pre-mating exposure with hesperidin protects N-ethyl-N-nitrosourea-induced neurotoxicity and congenital abnormalities in next generation of mice as a model of glioma.

Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents.

FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review.

FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

NERO: NEural algorithmic reasoning for zeRO-day attack detection in the IoT: A hybrid approach

Anomaly detection approaches for network intrusion detection learn to identify deviations from normal behavior on a data-driven basis. However, current approaches strive to infer the degree of abnormality of out-of-distribution samples when these appertain to different zero-day attacks. Inspired by the successes of the neural algorithmic reasoning paradigm to leverage the generalization of rule-based behavior, this paper presents a deep learning strategy for solving zero-day network attack detection and categorization. Moreover, focusing on the particular scenario of the Internet of Things (IoT), the privacy preservation requirement may imply a low training data regime for any learning algorithm. To this respect, the presented framework uses metric-based meta-learning to achieve few-shot learning capabilities. The presented pipeline is called NERO, as it imports the encode-process-decode architecture from the NEural algorithmic reasoning blueprint to converge zeRO-day attack detection policies within constrained training data.

Quantitative comparison of binocular suppression of patients with anisometropic amblyopia and ametropic amblyopia

Objective: To explore the differences in clinical characteristics and interocular interactions between patients with anisometropic amblyopia and ametropic amblyopia. Methods: Cross-sectional study. The newly diagnosed anisometropic (the binocular difference in spherical equivalent≥1.00 D) amblyopia patients and ametropic amblyopia patients (aged 4 to 6 years) in Beijing Tongren Hospital from January 2020 to December 2022 were involved. Patients were further categorized by the refractive status after cycloplegia, including hyperopia, myopia, astigmatism, hyperopia with astigmatism, myopia with astigmatism, mild anisometropia and severe anisometropia. Quantitative measurements of best-corrected visual acuity (logMAR), stereoacuity (transformed to log units), perceptual eye position and interocular suppression were performed, and the differences between groups were analyzed. The rank sum test was used for statistical evaluation. Results: The average age of 45 ametropic amblyopia patients (21 males and 24 females) and 84 anisometropic amblyopia patients (48 males and 36 females) was 5.0 (4.0, 5.0) years and 5.0 (4.0, 6.0) years, respectively. The interocular differences in spherical equivalent [2.56 (1.50, 4.19) D vs. 0.25 (0.13, 0.56) D] and best-corrected visual acuity [0.40 (0.18, 0.70) logMAR vs. 0.07 (0.00, 0.12) logMAR] were larger in patients with anisometropic amblyopia than those with ametropic amblyopia. The anisometropic amblyopia patients had worse stereoacuity [2.60 (2.00, 2.90) log arcsec vs. 2.00 (2.00, 2.30) log arcsec] and deeper suppression [20.0% (13.3%, 40.0%) vs. 10.0% (0, 23.3%)], compared with the ametropic amblyopia patients. The differences were all statistically significant (P<0.05). The suppression and stereoacuity between patients with hyperopic anisometropic amblyopia [suppression, 30.0% (17.5%, 50.0%); stereoacuity, 2.90 (2.30, 2.90) log arcsec] and astigmatic anisometropic amblyopia [suppression, 10.0% (0, 20.0%); stereoacuity, 2.00 (2.00, 2.30) log arcsec] were significantly different (P<0.05). The differences of suppression and stereoacuity between patients with severe (binocular difference in spherical equivalent>2.50 D) [suppression, 30.0% (20.0%, 53.3%); stereoacuity, 2.90 (2.57, 2.90) log arcsec] and mild anisometropia [suppression, 20.0% (0, 30.0%); stereoacuity, 2.00 (2.00, 2.90) log arcsec] were also statistically significant (P<0.05). Conclusions: Patients with anisometropic amblyopia have deeper binocular suppression, worse stereoacuity and more severe binocular interaction abnormality than those with ametropic amblyopia. The severity of anisometropia affects the degree of the interaction abnormality.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. ClinicalTrials.gov: NCT02485808.