A screening method for mild cognitive impairment in elderly individuals combining bioimpedance and MMSE

We investigated a screening method for mild cognitive impairment (MCI) that combined bioimpedance features and the Korean Mini-Mental State Examination (K-MMSE) score. Data were collected from 539 subjects aged 60 years or older at the Gwangju Alzheimer’s & Related Dementias (GARD) Cohort Research Center, A total of 470 participants were used for the analysis, including 318 normal controls and 152 MCI participants. We measured bioimpedance, K-MMSE, and the Seoul Neuropsychological Screening Battery (SNSB-II). We developed a multiple linear regression model to predict MCI by combining bioimpedance variables and K-MMSE total score and compared the model’s accuracy with SNSB-II domain scores by the area under the receiver operating characteristic curve (AUROC). We additionally compared the model performance with several machine learning models such as extreme gradient boosting, random forest, support vector machine, and elastic net. To test the model performances, the dataset was divided into a training set (70%) and a test set (30%). The AUROC values of SNSB-II scores were 0.803 in both sexes, 0.840 for males, and 0.770 for females. In the combined model, the AUROC values were 0.790 (0.773) for males (and females), which were significantly higher than those from the model including MMSE scores alone (0.723 for males and 0.622 for females) or bioimpedance variables alone (0.640 for males and 0.615 for females). Furthermore, the accuracies of the combined model were comparable to those of machine learning models. The bioimpedance-MMSE combined model effectively distinguished the MCI participants and suggests a technique for rapid and improved screening of the elderly population at risk of cognitive impairment

Ultraaccurate genome sequencing and haplotyping of single human cells.

Accurate detection of variants and long-range haplotypes in genomes of single human cells remains very challenging. Common approaches require extensive in vitro amplification of genomes of individual cells using DNA polymerases and high-throughput short-read DNA sequencing. These approaches have two notable drawbacks. First, polymerase replication errors could generate tens of thousands of false-positive calls per genome. Second, relatively short sequence reads contain little to no haplotype information. Here we report a method, which is dubbed SISSOR (single-stranded sequencing using microfluidic reactors), for accurate single-cell genome sequencing and haplotyping. A microfluidic processor is used to separate the Watson and Crick strands of the double-stranded chromosomal DNA in a single cell and to randomly partition megabase-size DNA strands into multiple nanoliter compartments for amplification and construction of barcoded libraries for sequencing. The separation and partitioning of large single-stranded DNA fragments of the homologous chromosome pairs allows for the independent sequencing of each of the complementary and homologous strands. This enables the assembly of long haplotypes and reduction of sequence errors by using the redundant sequence information and haplotype-based error removal. We demonstrated the ability to sequence single-cell genomes with error rates as low as 10-8 and average 500-kb-long DNA fragments that can be assembled into haplotype contigs with N50 greater than 7 Mb. The performance could be further improved with more uniform amplification and more accurate sequence alignment. The ability to obtain accurate genome sequences and haplotype information from single cells will enable applications of genome sequencing for diverse clinical needs

The Flynn effect in Korea: large gains

Secular gains in IQ test scores have been reported for many Western countries. This is the first study of secular IQ gains in South Korea, using various datasets. The first question is what the size of the Flynn effect in South Korea is. The gains per decade are 7.7 points for persons born between 1970 and 1990. These gains on broad intelligence batteries are much larger than the gains in Western countries of about 3 IQ points per decade. The second question is whether the Korean IQ gains are comparable to the Japanese IQ gains with a lag of a few decades. The gains in Japan of 7.7 IQ points per decade for those born approximately 1940 1965 are identical to the gains per decade for Koreans born 1970 1990. The third question is whether the Korean gains in height and education lag a few decades behind the Japanese gains. The Koreans reach the educational levels the Japanese reached 25 30 years before, and the gains in height for Koreans born 1970 1990 are very similar to gains in height for Japanese born 1940 1960, so three decades earlier. These findings combined strongly support the hypothesis of similar developmental patterns in the two countries

Effects of 12 Weeks Weight Training and Plyometric Training on Body Composition, Physical Fitness and Electronic Hogu Hitting Ability in Taekwondo Sparring Athletes

OBJECTIVES The purpose of this study is to identify the effects of differences in muscle function training of Taekwondo sparring athletes on body composition, basic physical fitness, isokinetic muscle function, and electronic hogu hitting ability, and to present basic data for a training program for Taekwondo sparring athletes. METHODS This study randomly sampled 25(M: 20, F: 5) Taekwondo sparring athletes. The sampled subjects were divided into a weight training group (n=8), a plyometric training(plyometric) group (n=8), and a control group (n=9) and trained for 60 minutes, 5 times a week, for 12 weeks. Body composition, basic physical fitness, isokinetic muscle function, and electronic hogu hitting ability were evaluated before and after training. Statistical tests of RM Two-way ANOVA were conducted to verify the interaction between groups and times, main effects of times, and main effects between groups according to 12 weeks of training. Post-hoc was conducted using paired-T test(times) and One-way ANOVA test(groups). RESULTS Taekwondo sparring athletes showed positive changes in body composition(weight, BMI, Lean body mass, % body fat, WHR), basic physical fitness(muscle endurance, flexibility), isokinetic muscle function(knee endurance, low back strength), and electronic hogu hitting ability(round house kick, Turning back kick, number of hit) after participating in weight training for 12 weeks (All p<.05). Additionally, positive changes were observed in flexibility and electronic hogu hitting ability(Turning back kick) after participating in plyometric training for 12 weeks (All p<.05). CONCLUSIONS Weight training for 12 weeks in Taekwondo sparring athletes results in positive changes in body composition, increased flexibility and muscular endurance, increases in knee isokinetic muscular endurance and low back isokinetic strength, and improvement in overall electronic hogu hitting ability. Plyometrics for 12 weeks result in increased flexibility and increased electronic hogu hitting ability for back kick. Weight training shows greater improvement in strength and kick endurance than plyometrics

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo IOP monitoring. The ANN converts captured optical spectra into corresponding IOP levels. We achieved an IOP-measurement accuracy of ±0.1 mmHg at a measurement rate of 100 Hz, which represents a ten-fold improvement from previously reported values. This technique allowed real-time tracking of artificially induced sub-1 s transient IOP elevations and minor fluctuations induced by the respiratory motion of the rabbits during in vivo monitoring. All in vivo sensor readings paralleled those obtained concurrently using a commercial tonometer and showed consistency within ±2 mmHg. Real-time processing is highly useful for IOP monitoring in clinical settings and home environments and improves the overall practicality of the optical IOP-monitoring approach

Coactivation of the CLOCK-BMAL1 complex by CBP mediates resetting of the circadian clock

The transcription factor CLOCK-BMAL1 is a core component of the molecular clock machinery that drives circadian gene expression and physiology in mammals. Recently, we reported that this heterodimeric transcription factor functions as a signaling molecule in response to the resetting stimuli via the Ca(2+)-dependent protein kinase C pathway. Here, we demonstrate that the CREB-binding protein (CBP) plays a key role in rapid activation of the CLOCK-BMAL1 heterodimer that leads to phase resetting of the circadian clock. Under physiological conditions, a bimolecular fluorescence complementation (BiFC) assay revealed that CLOCK and BMAL1 dimerize in the cytoplasm and subsequently translocate into the nucleus in response to serum stimuli (mean time duration was 29.2 minutes and mean velocity 0.7 mu m/minute). Concomitantly, BMAL1 rapidly recruited CBP on Per1 promoter E-box, but not p300 (a functional analog of CBP), in the discrete nuclear foci. However, recruitment of CBP by cAMP/Ca(2+) response element-binding (CREB) protein on CRE was not markedly increased upon delivery of the resetting stimuli. Furthermore, overexpression of CBP greatly potentiated the CLOCK-BMAL1-mediated Per1 transcription, and this effect was completely abolished by site-directed mutation of E-box elements, but not by the mutation of CRE in the Per1 promoter. Furthermore, molecular knockdown of CBP severely dampened circadian oscillation of clock gene expression triggered by the resetting stimuli. These findings suggest that CBP recruitment by BMAL1 mediates acute transactivation of CLOCK-BMAL1, thereby inducing immediate-early Per1 transcription and phase resetting of the circadian clock

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged &gt;60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer’s and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer’s disease

Applying Topographic Classification, Based on the Hydrological Process, to Design Habitat Linkages for Climate Change

The use of biodiversity surrogates has been discussed in the context of designing habitat linkages to support the migration of species affected by climate change. Topography has been proposed as a useful surrogate in the coarse-filter approach, as the hydrological process caused by topography such as erosion and accumulation is the basis of ecological processes. However, some studies that have designed topographic linkages as habitat linkages, so far have focused much on the shape of the topography (morphometric topographic classification) with little emphasis on the hydrological processes (generic topographic classification) to find such topographic linkages. We aimed to understand whether generic classification was valid for designing these linkages. First, we evaluated whether topographic classification is more appropriate for describing actual (coniferous and deciduous) and potential (mammals and amphibians) habitat distributions. Second, we analyzed the difference in the linkages between the morphometric and generic topographic classifications. The results showed that the generic classification represented the actual distribution of the trees, but neither the morphometric nor the generic classification could represent the potential animal distributions adequately. Our study demonstrated that the topographic classes, according to the generic classification, were arranged successively according to the flow of water, nutrients, and sediment; therefore, it would be advantageous to secure linkages with a width of 1 km or more. In addition, the edge effect would be smaller than with the morphometric classification. Accordingly, we suggest that topographic characteristics, based on the hydrological process, are required to design topographic linkages for climate change

Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

BackgroundPreviously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.MethodsNeonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.ResultsRe-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).ConclusionFor clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures