Atypical Integration of Sensory-to-Transmodal Functional Systems Mediates Symptom Severity in Autism.

A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology

Geriatric Nutritional Risk Index and First-Year Mortality in Incident Hemodialysis Patients

Objective. The Geriatric Nutritional Risk Index is a simple nutritional screening method, and this study aimed to investigate the association between the initial Geriatric Nutritional Risk Index and all-cause mortality in incident patients in the first year after the initiation of hemodialysis. Materials and Methods. This study is a retrospective cohort study and used the Korean Renal Data System database. Patients who were eligible for Geriatric Nutritional Risk Index assessment and underwent hemodialysis from January 2016 to December 2019 were included. The primary outcome was all-cause mortality, and outcome evaluation was performed in December 2020. A Cox proportional hazard model was used to analyze the association between the Geriatric Nutritional Risk Index and mortality. Results. A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. The patients were divided into four groups by the quartile of the Geriatric Nutritional Risk Index with a mean value of 96.2 ± 8.2. During the study period, 545 (5.2%) deaths occurred. The surviving patients had higher Geriatric Nutritional Risk Index values than ones who died in the first year of hemodialysis initiation (96.6 ± 7.5 vs. 88.2 ± 9.3, p p p p < 0.001). Conclusions. These findings suggest that a low Geriatric Nutritional Risk Index (<91.8) is associated with first-year all-cause and cardiovascular mortality in patients who start hemodialysis and may be a useful and reproducible tool for assessing prognoses in this population

A Survey on Perceptions of the Direction of Korean Medicine Education and National Licensing Examination

Recent changes in medical education and assessment led to a focus on occupational competency, and this study investigated the perceptions of Korean medicine doctors (KMDs) on the national licensing examination for KMDs (NLE-KMD). The survey aimed to understand KMDs’ recognition of the current situation, items to improve, and items to emphasize in the future. We conducted the web-based survey from 22 February to 4 March 2022, and 1244 among 23,338 KMDs answered voluntarily. Through this study, we found the importance of competency-related clinical practice and Korean standard classification of disease (KCD), and the presence of a generation gap. KMDs considered clinical practice (clinical tasks and clinical work performance) and the item related to the KCD important. They valued (1) the focus on KCD diseases that are frequently seen in clinical practice and (2) the readjustment and introduction of the clinical skills test. They also emphasized KCD-related knowledge and skills for the assessment and diagnosis of KCD diseases, especially those frequently treated at primary healthcare institutes. We confirmed the generation gap in the subgroup analysis according to the license acquisition period, and the ≤5-year group emphasized clinical practice and the KCD, while the >5-year group stressed traditional KM theory and clinical practice guidelines. These findings could be used to develop the NLE-KMD by setting the direction of Korean medicine education and guiding further research from other perspectives

Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84), and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy

Superresolution TOA Estimation With Computational Load Reduction

Although the superresolution multipath delay profile (MDP) estimation technique enhances the time resolution of a low-resolution MDP by using matrix computations, the computational load for the matrix computations is a problem, because it drastically increases with the length of the MDP. Because positioning systems require the time of arrival (TOA) of the first path only, it is possible to reduce the computational load by applying the matrix computations only to the part of the MDP that is narrowed but still includes the TOA of the first path. This paper proposes a scheme for determining the observation window of MDP from the low-resolution TOA estimates, which are obtained from the MDPs produced by the pseudonoise correlation method. The proposed scheme makes use of the random nature of the low-resolution TOA estimates to further reduce the observation window. The computational efficiency and estimation accuracy of the proposed scheme are examined by channel simulations based on the Saleh–Valenzuela indoor channel model and are also compared with the computational efficiency and estimation accuracy of the conventional superresolution technique without the observation window reduction

Development of 3D Cell Printed Patch-Type Stem Cell Therapy for Treatment of Liver Cirrhosis

Liver cirrhosis is an irreversible end-stage liver disease which has no effective therapy except for liver transplantation, but donor shortage has been a critical limitation. Stem cell injection has been regarded as an alternative to the liver transplantation; yet, there is no optimal condition for such therapy. Moreover, the efficiency of delivery is below 10%, and the efficacy is reported to be minimal or even none. Therefore, we developed a liver patch, which is a 3D cell printed patch-type stem cell therapy with liver decellularized extracellular matrix (LdECM) bioink and human bone marrow derived mesenchymal stem cell to enhance the efficacy and delivery efficiency. The liver patch showed in vitro efficacy in the inactivation of the activated hepatic stellate cell (aHSC) by paracrine effect in transwell coculture condition. For in vivo efficacy assessment, the liver patch was implanted to the pathological liver tissue of irreversible cirrhosis mouse models. The deposited endogenous collagen was significantly decreased, and aHSCs were inactivated in the liver patch delivered cirrhosis model. Consequently, the results demonstrated that the liver patch with functional LdECM bioink and stem cell would be an effective therapy for liver cirrhosis treatment.1

Neurocognitive Changes and Their Neural Correlates in Patients with Type 2 Diabetes Mellitus

As the prevalence and life expectancy of type 2 diabetes mellitus (T2DM) continue to increase, the importance of effective detection and intervention for the complications of T2DM, especially neurocognitive complications including cognitive dysfunction and dementia, is receiving greater attention. T2DM is thought to influence cognitive function through an as yet unclear mechanism that involves multiple factors such as hyperglycemia, hypoglycemia, and vascular disease. Recent developments in neuroimaging methods have led to the identification of potential neural correlates of T2DM-related neurocognitive changes, which extend from structural to functional and metabolite alterations in the brain. The evidence indicates various changes in the T2DM brain, including global and regional atrophy, white matter hyperintensity, altered functional connectivity, and changes in neurometabolite levels. Continued neuroimaging research is expected to further elucidate the underpinnings of cognitive decline in T2DM and allow better diagnosis and treatment of the condition

Negative Mood States Correlate with Laterobasal Amygdala in Collegiate Football Players

A number of studies have suggested that sports-related concussion (SRC) may place individuals at increased risk for depression and negative outcomes including suicide. However, the mechanisms underlying a potential relationship between brain integrity and mood remain unclear. The current study is aimed at examining the association between amygdala shape, mood state, and postconcussion symptoms in collegiate football players. Thirty members of 1 football team completed the Profile of Mood States (POMS), the postconcussion symptom scale (PCSS), and an MRI protocol during preseason camp. T1-weighted images were acquired and three-dimensional amygdala and probabilistic maps were created for shape analysis. Correlation analyses between POMS and PCSS and the relationship between POMS and amygdala shape were completed. In the amygdala, the left laterobasal subregion showed a positive relationship with the POMS total score and subscales scores. No significant relationship between PCSS and amygdala shape was found. Significant positive correlations were found between POMS subscales and PCSS. These results indicate that amygdala structure may be more closely associated with negative mood states than postconcussion symptoms. These findings suggest that premorbid individual differences in effect may provide critical insight into the relationship between negative mood and outcomes in collegiate football players with SRC

Use of 3D Human Liver Organoids to Predict Drug-Induced Phospholipidosis

Drug-induced phospholipidosis (PL) is a storage disorder caused by the formation of phospholipid-drug complexes in lysosomes. Because of the diversity of PL between species, human cell-based assays have been used to predict drug-induced PL in humans. We established three-dimensional (3D) human liver organoids as described previously and investigated their liver characteristics through multiple analyses. Drug-induced PL was initiated in these organoids and in monolayer HepG2 cultures, and cellular changes were systemically examined. Organoids that underwent differentiation showed characteristics of hepatocytes rather than HepG2 cells. The organoids also survived under PL-inducing drug conditions for 48 h and maintained a more stable albumin secretion level than the HepG2 cells. More cytoplasmic vacuoles were observed in organoids and HepG2 cells treated with more potent PL-induced drugs, but to a greater extent in organoids than in HepG2 cells. Lysosome-associated membrane protein 2, a marker of lysosome membranes, showed a stronger immunohistochemical signal in the organoids. PL-distinctive lamellar bodies were observed only in amiodarone-treated organoids by transmission electron microscopy. Human liver organoids are thus more sensitive to drug-induced PL and less affected by cytotoxicity than HepG2 cells. Since PL is a chronic condition, these results indicate that organoids better reflect metabolite-mediated hepatotoxicity in vivo and could be a valuable system for evaluating the phospholipidogenic effects of different compounds during drug development