We investigated the differential spatial covariance pattern of blood oxygen level-dependent (BOLD) responses to single-task and multitask functional magnetic resonance imaging (fMRI) between patients ...with psychophysiological insomnia (PI) and healthy controls (HCs), and evaluated features generated by principal component analysis (PCA) for discrimination of PI from HC, compared to features generated from BOLD responses to single-task fMRI using machine learning methods. In 19 patients with PI and 21 HCs, the mean beta value for each region of interest (ROIbval) was calculated with three contrast images (i.e., sleep-related picture, sleep-related sound, and Stroop stimuli). We performed discrimination analysis and compared with features generated from BOLD responses to single-task fMRI. We applied support vector machine analysis with a least absolute shrinkage and selection operator to evaluate five performance metrics: accuracy, recall, precision, specificity, and F2. Principal component features showed the best classification performance in all aspects of metrics compared to BOLD response to single-task fMRI. Bilateral inferior frontal gyrus (orbital), right calcarine cortex, right lingual gyrus, left inferior occipital gyrus, and left inferior temporal gyrus were identified as the most salient areas by feature selection. Our approach showed better performance in discriminating patients with PI from HCs, compared to single-task fMRI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and ...caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system X
(xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.
Sn-doped NiO multiroom spheres with unique microreactor morphology were prepared by facile ultrasonic spray pyrolysis of a solution containing tin oxalate, nickel nitrate, and dextrin and subsequent ...heat treatment. The multiroom structure was formed by phase segregation between the molten metal source and liquidlike dextrin and sequent decomposition of dextrin during spray pyrolysis, which played the dual roles of enhancing gas response and selectivity. The response (resistance ratio) of the Sn-doped NiO multiroom spheres to 1 ppm p-xylene was as high as 65.4 at 300 °C, which was 50.3 and 9.0 times higher than those of pure NiO multiroom spheres and Sn-doped NiO dense spheres, respectively. In addition, the Sn-doped NiO multiroom sensors showed a high selectivity to xylene. The unprecedented high response that enables the sensing of sub-ppm xylene was explained by the high gas accessibility of the multiroom structures and the Sn-doping-induced change in oxygen adsorption as well as the charge carrier concentration, whereas the high xylene selectivity was attributed to the decomposition/re-forming of xylene into smaller or more active species within the unique multiroom structure of Sn-doped NiO microreactors characterized by high catalytic activities. The multiroom oxide spheres can be used as a new and generalized platform to design high-performance gas sensors.
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IJS, KILJ, NUK, PNG, UL, UM
The extrastriate cortex in the human visual cortex is divided into two distinct clusters: the “what-information” processing area and the “where-information” processing area. It is widely accepted ...that the “what-information” cluster is processed through the ventral stream to the temporal cortex, and the “where-information” cluster through the dorsal stream to the parietal cortex. In human neuroanatomy, fiber bundles for the ventral stream (such as the inferior longitudinal fasciculus) are well defined, whereas fibers for the dorsal stream are poorly understood. In this study, we attempted to trace the dorsal stream fibers using a fiber tracking method using 7.0T diffusion-weighted MRI. We used data from a healthy male subject as well as from an unbiasedly selected nine-subject dataset in the Human Connectome Project. The surface of the visual area, including V1, V2, V3, V4, MT, was determined from the Brainnetome atlas (Fan et al., 2016), which is the connectivity-based parcellation framework of the human brain. The resulting visual pathway indicated that the putative pathway for the classical dorsal stream is unlikely to exist. Instead, we demonstrated that fiber connections exist between the angular gyrus with MT in the visual cortex, and between the angular gyrus and IT in the temporal cortex. Through that, we composed a two-pathway model for where-information processing that passes through the angular gyrus. Finally, we proposed a modified human visual pathway model based on our fiber tracking results in this report. The modified where-information pathway will provide a new aspect for the study of human visual processing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Monogononta is the most speciose class of rotifers, with more than 2,000 species. The monogonont genus Brachionus is widely distributed at a global scale, and a few of its species are commonly used ...as ecological and evolutionary models to address questions related to aquatic ecology, cryptic speciation, evolutionary ecology, the evolution of sex and ecotoxicology. With the importance of Brachionus species in many areas of research, it is remarkable that the genome has not been characterized. This study aims to address this lacuna by presenting, for the first time, the whole‐genome assembly of the freshwater species Brachionus calyciflorus. The total length of the assembled genome was 129.6 Mb, with 1,041 scaffolds. The N50 value was 786.6 kb, and the GC content was 24%. A total of 16,114 genes were annotated with repeat sequences, accounting for 21% of the assembled genome. This assembled genome may form a basis for future studies addressing key questions on the evolution of monogonont rotifers. It will also provide the necessary molecular resources to mechanistically investigate ecophysiological and ecotoxicological responses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Given the multifactorial nature of obesity, there is current interest on Korean medicine (KM) for weight loss. This survey aimed to investigate current practice patterns of KM treatment for obesity ...among doctors.
A questionnaire on clinical practice patterns of KM treatment for obesity was constructed and distributed to 21,788 KM doctors (KMDs). The questionnaire was consisted of respondent characteristics, state of treated patient, diagnosis, treatment, and usage pattern of herbal medicine for obesity.
A total of 4.9% of KMDs (n = 1,084/21,788) validly completed the survey. Patients with Obesity Class I (25 ≤ Body mass index (BMI) ≤ 29.9) are the most common in KM clinics. Bioelectric impedance and KM Obesity Pattern Identification Questionnaire were routinely used for diagnosis. The average treatment duration was 4.16 weeks, and patients visited on an average 4.25 times per month for treatment. Herbal medicine is the most commonly used for obesity treatment by KMDs, and Taeeumjowui-tang was the most frequently prescribed. Ephedrae Herba, which is identified as the most used herbs for weight loss, was prescribed 5.18 ± 2.7 g/day at minimum and 10.06 ± 4.23 g/day at maximum. A total of 62.9% of responded KMDs had ever a patient with uncomfortable symptoms due to Ephedrae Herba use, neuropsychiatric events were the most common symptoms, followed by gastrointestinal events.
Taken together, this study provides information on real clinical practice patterns of KM including patients, diagnosis, treatments, and herbal medicine for obesity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic ...single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay.
This study reports a successful continuous biohydrogen production from rice straw hydrolysate in both 3-L and 20-L dynamic membrane bioreactor (DMBR). In the 3-L DMBR (DMBR I), the maximum average ...bio-H2 production performance was 32.13 ± 0.71 L H2/L-d, 1.27 ± 0.03 mol H2/mol hexose-equivconsumed, and 96.39 ± 2.12 L H2/d, respectively. The H2 production performance of 20-L DMBR (DMBR II) was comparable to DMBR I, which were 33.15 ± 0.42 L H2/L-d, 1.46 ± 0.03 mol H2/mol hexose-equivconsumed, and 663 ± 8 L H2/d, respectively. Rapid decline of hydraulic retention time (HRT) in the early stages of operation led to the metabolic flux of the mixed culture from the lactic acid pathway to the H2-producing pathway. Genus Clostridium was the dominant microbial population in DMBR I and DMBR II. This study provides operational criteria and insights in the scale-up design and operation of biohydrogen production from lignocellulosic biomass.
•Rice straw was converted to H2 in 3-L and 20-L dynamic membrane bioreactor.•663 ± 8 L H2/d was recovered continuously from a 20-L bioreactor.•Maximum H2 production was 33.8 L H2/L-d and 1.3 mol H2/mol hexose in 20-L bioreactor.•Rapid decrease of HRT in early-stage shifted HLa pathway to H2-producing pathway.•Feeding of rice straw hydrolysate shifted H2-producing pathway from HBu to HAc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand ...the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective:
To investigate anatomical changes in the substantia nigra (SN) of Parkinson disease (PD) patients with age‐matched controls by using ultra‐high field magnetic resonance imaging (MRI).
...Methods:
We performed 7T MRI in 10 PD and 10 age‐matched control subjects. Magnetic resonance images of the SN were obtained from a 3‐dimensional (3D) T2*‐weighted gradient echo sequence. Region of interest‐based 3D shape analysis was performed to quantitatively compare images from the 2 groups.
Results:
The boundary between the SN and crus cerebri was not smooth in PD subjects. Undulation in the lateral surface of the SN appeared more intense in the side contralateral to that with the more severe symptoms, and more prominent at the rostral level of the SN than at the intermediate or caudal levels. In addition to the lateral surface, there was a striking difference in the dorsomedial aspects of the SN between PD and control subjects. In control subjects, a brighter signal region was observed along the dorsomedial surface of the lateral portion of SN, whereas in PD subjects, this region was observed as a dark region containing a hypointense signal in T2*‐weighted images. The measurement of SN volumes, normalized to the intracranial volumes, showed higher values in PD subjects than in control subjects.
Interpretation:
This study demonstrates that 3D 7T MRI can definitively visualize anatomical alterations occurring in the SN of PD subjects. Further pathological studies are required to elucidate the nature of these anatomical alterations. Ann Neurol 2012;71:267–277
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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