Automated Laryngeal Invasion Detector of Boluses in Videofluoroscopic Swallowing Study Videos Using Action Recognition-Based Networks.

We aimed to develop an automated detector that determines laryngeal invasion during swallowing. Laryngeal invasion, which causes significant clinical problems, is defined as two or more points on the penetration-aspiration scale (PAS). We applied two three-dimensional (3D) stream networks for action recognition in videofluoroscopic swallowing study (VFSS) videos. To detect laryngeal invasion (PAS 2 or higher scores) in VFSS videos, we employed two 3D stream networks for action recognition. To establish the robustness of our model, we compared its performance with those of various current image classification-based architectures. The proposed model achieved an accuracy of 92.10%. Precision, recall, and F1 scores for detecting laryngeal invasion (≥PAS 2) in VFSS videos were 0.9470 each. The accuracy of our model in identifying laryngeal invasion surpassed that of other updated image classification models (60.58% for ResNet101, 60.19% for Swin-Transformer, 63.33% for EfficientNet-B2, and 31.17% for HRNet-W32). Our model is the first automated detector of laryngeal invasion in VFSS videos based on video action recognition networks. Considering its high and balanced performance, it may serve as an effective screening tool before clinicians review VFSS videos, ultimately reducing the burden on clinicians.

Assessing Adhesiveness Levels in a Dysphagia Diet for Older Adults.

BACKGROUND: Viscosity is a common focus in the diet of patients with dysphagia. However, adhesiveness is an equally significant property that can affect swallowing function, even in semi-solid foods with similar levels of viscosity. The purpose of this study was to classify the adhesiveness of food into stages and determine whether these classifications are relevant to swallowing function. METHODS: This study included 30 healthy elderly adults aged 65 years. After categorizing adhesiveness into three levels based on the results of the sensory test, 30 participants were asked to swallow representative foods at each level. A videofluoroscopic swallowing study (VFSS) was performed to determine the presence or absence of pharyngeal residues based on the level of adhesiveness. The chi-square test was used to verify whether there was a difference in remnants according to the level of adhesiveness, and significance was judged with a p-value of less than 0.05. RESULTS: Adhesiveness was categorized into three distinct levels: level 1 (0-4 mJ), level 2 (4-18 mJ), and level 3 (>18 mJ). Upon examining the subjects presenting with residual material, we observed three cases of level 1 adhesiveness, 16 cases of level 2, and 25 cases of level 3. The chi-square test was used to assess the statistical significance between the levels, revealing a significant difference with a p-value < 0.0001. CONCLUSIONS: We presented the level of adhesiveness by dividing it into three stages and proved that it is meaningful in relation to the swallowing function. Selecting and recommending foods with an appropriate level of adhesiveness will help enhance swallowing safety in older adults.

Carrier frequency and incidence of alpha-mannosidosis: population database-based study-focus on the East Asian and Korean population.

Background: Alpha-mannosidosis caused by mutations in the MAN2B1 gene is a rare genetic disorder characterized by physical abnormalities and intellectual disabilities. The objective of this study was to analyze the carrier frequency and estimated incidence of alpha-mannosidosis in East Asian populations, as limited data exists on its incidence in this group. Methods: In this study, a total of 125,748 exomes from the gnomAD database was analyzed. Additionally, 5,305 data from the KOVA and 1,722 data from the KRGDB, both representing Korean populations, were included. Results: The global carrier frequency of alpha-mannosidosis in gnomAD was 0.23%; the highest carrier frequency was observed in the Finnish at 0.49%, and East Asians had the second highest carrier frequency at 0.30%. Globally, the approximate incidence of alpha-mannosidosis was calculated at 1 in 784,535, l in 166,801 Europeans (Finnish), and l in 431,689 East Asians. By integrating the data from the 8,936 Koreans in gnomAD Korean, KOVA and KRGDB, the carrier frequency of alpha-mannosidosis in the Korean population was 0.04% and estimated incidence was 1 in 19,963,024. Conclusion: This study is the first to investigate the carrier frequencies of alpha-mannosidosis in East Asians and Koreans, including specific subpopulations, utilizing gnomAD and the Korean genomic database. The variant spectrum of MAN2B1 genes in East Asians showed significant differences compared to other ethnic groups. Our data provide valuable reference information for future investigations into alpha-mannosidosis, aiding in understanding the genetic diversity and specific variants associated with the condition in East Asian populations.

Unraveling the rheology of inverse vulcanized polymers.

Multiple relaxation times are used to capture the numerous stress relaxation modes found in bulk polymer melts. Herein, inverse vulcanization is used to synthesize high sulfur content (≥50 wt%) polymers that only need a single relaxation time to describe their stress relaxation. The S-S bonds in these organopolysulfides undergo dissociative bond exchange when exposed to elevated temperatures, making the bond exchange dominate the stress relaxation. Through the introduction of a dimeric norbornadiene crosslinker that improves thermomechanical properties, we show that it is possible for the Maxwell model of viscoelasticity to describe both dissociative covalent adaptable networks and living polymers, which is one of the few experimental realizations of a Maxwellian material. Rheological master curves utilizing time-temperature superposition were constructed using relaxation times as nonarbitrary horizontal shift factors. Despite advances in inverse vulcanization, this is the first complete characterization of the rheological properties of this class of unique polymeric material.

Carrier frequency and incidence of aromatic L-amino acid decarboxylase deficiency: a gnomAD-based study.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive neurotransmitter metabolism disorder and is clinically characterized by infancy hypotonia, ophthalmic crisis, and developmental delay. With the emergence of gene therapy for AADC deficiency, accurate prediction of AADC deficiency is required. This study aimed to analyze the carrier frequency and expected incidence of AADC deficiency using exome data from the Genome Aggregation Database (gnomAD). METHODS: We analyzed 125,748 exomes from gnomAD, including 9197 East Asian exomes, for the DDC gene. All identified variants were classified according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: The worldwide carrier frequency of AADC deficiency was 0.17%; the highest frequency was observed in East Asians at 0.78%, and the lowest was in Latinos at 0.07%. The estimated incidence of AADC deficiency was 1 in 1,374,129 worldwide and 1 in 65,266 in East Asians. CONCLUSION: The results demonstrated that East Asians have a higher carrier frequency of AADC deficiency than other ethnic groups. The variant spectrum of DDC genes in East Asian populations differed greatly from those of other ethnic groups. Our data will serve as a reference for further investigation of AADC deficiency. IMPACT: This study analyzed exome data from the Genome Aggregation Database (gnomAD) to estimate the carrier frequency and expected incidence of aromatic L-amino acid decarboxylase (AADC) deficiency. The article provides updated carrier frequency and incidence estimates for AADC deficiency, particularly in East Asian populations, and emphasizes the significant differences in the variant spectrum of DDC genes in this population compared to other ethnic groups. The study provides important information for accurate prediction and early diagnosis of AADC deficiency, particularly in high-risk populations, and may aid in the development of more effective targeted screening programs and gene therapies for this disorder.

The Diagnostic Yield and Difficulties of Utilizing Soft-clipped Read Clusters Encountered in Clinical Exome Sequencing.

BACKGROUND: Despite the wide use of next generation sequencing, there are still many difficulties in detecting structural variants. A split read is one of the clues of structural variants and is represented as a soft-clipped read in the raw sequencing data. Considering that most of the breakpoints of structural variants reside in non-coding regions, split read information has not been routinely used in exome sequencing or targeted panel sequencing. Recently, SCRAMble, a software capable of detecting mobile element insertion (MEI) and deletion based on soft-clipped read clusters (SCRCs), was shown to provide an additional diagnostic yield of 0.03 - 0.25%. SCRAMble is the only software that can be used for exome sequencing or targeted panel sequencing to detect structural variants based on SCRC information. The aim of present study was to establish a working procedure of utilizing SCRC information using SCRAMble in clinical exome sequencing and to assess its diagnostic yield. METHODS: Raw sequencing data of clinical exome sequencing were retrospectively analyzed using SCRAMble to search MEIs and deletions. SCRAMble software was installed according to the manufacturer's instructions and default parameters except for one, mei-score, which was adjusted for sensitivity, were used. RefSeq gene annotation was performed for both MEI and deletion calls using ANNOVAR. Blacklist-based filtering was used to reduce candidate MEI/deletion calls. Clinical relevance was manually evaluated for the remaining variant calls. RESULTS: One diagnostic MEI, which is a founder variant in East Asia, was detected in two cases (2/266, 0.75%). In addition, two diagnostic deletions, which had been previously detected in depth-of-coverage (DOC)-based copy number variant (CNV) callers, were detected (2/266, 0.75%). Base-level breakpoints that could not be derived by the DOC-based callers were identified for these two deletions using SCRAMble. Most SCRCs were repetitive among cases and blacklist-based filtering reduced candidate MEI/deletion calls by 49.5 - 94.5%, leaving a considerable number of variant calls to be manually validated. CONCLUSIONS: SCRC screening in exome or targeted panel sequencing may provide additional diagnostic yield either by pathogenic MEI detection or reassurance of deletions identified by DOC-based CNV callers. Development of an efficient filtering algorithm is warranted.

Osteoarthritis improvement effect of Chrysanthemum zawadskii var. latilobum extract in relation to genotype.

Objectives: To determine whether SNPs of osteoarthritis (OA)-related genes predict the effect of Chrysanthemum zawadskii var. latilobum (CZ) extract in OA patients with OA. Subjects/methods: To analyze correlations between CZ extract effects in humans and their genotypes, 121 Korean patients with OA were recruited. Patients ingested 600 mg/day of the CZ extract GCWB106 (one tablet daily), including 250-mg CZ, or placebo (one tablet daily) for 12 weeks. Twenty SNPs were genotyped in 11 genes associated with OA pathogenesis, including tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinases (MMPs), and 9 genes involved in OA-related dietary intervention. The Visual Analogue Scale (VAS) and Korean Western Ontario and McMaster Universities (K-WOMAC) were measured as indicators of GCWB106 effect. Statistical comparisons were performed using Kruskal-Wallis tests to identify associations between these scales and genotyped loci in patients with OA. Results: Three SNPs (PPARG rs3856806, MMP13 rs2252070, and ZIP2 rs2234632) were significantly associated with the degree of change in VAS pain score. Homozygous CC genotype carriers of rs3856806, G allele carriers (GA or GG) of rs2252070, and T allele carriers (GT or TT) of rs2234632 showed lower VAS score (i.e., less severe symptoms) in the GCWB106 group (n=53) than the placebo group (n=57) (p=0.026, p=0.009, and p=0.025, respectively). Gene-gene interaction effects on GCWB106-mediated pain relief were then examined, and it was found that the addition of each genotype resulted in a greater decrease in VAS pain score in the GCWB106 group (p=0.0024) but not the placebo group (p=0.7734). Conclusions: These novel predictive markers for the pain-relieving effects of GCWB106 may be used in the personalized treatment of patients with OA.

Sulfenyl Chlorides: An Alternative Monomer Feedstock from Elemental Sulfur for Polymer Synthesis.

A polymerization methodology is reported using sulfur monochloride (S2Cl2) as an alternative feedstock for polymeric materials. S2Cl2 is an inexpensive petrochemical derived from elemental sulfur (S8) but has numerous advantages as a reactive monomer for polymerization vs S8. This new process, termed sulfenyl chloride inverse vulcanization, exploits the high reactivity and miscibility of S2Cl2 with a broad range of allylic monomers to prepare soluble, high molar-mass linear polymers, segmented block copolymers, and crosslinked thermosets with greater synthetic precision than achieved using classical inverse vulcanization. This step-growth addition polymerization also allows for preparation of a new class of thiol-free, inexpensive, highly optically transparent thermosets (α = 0.045 cm-1 at 1310 nm), which exhibit among the best optical transparency and low birefringence relative to commodity optical polymers, while possessing a higher refractive index (n > 1.6) in the visible and near-infrared spectra. The fabrication of large-sized optical components is also demonstrated.

Carrier frequency and incidence estimation of RPE65-associated inherited retinal diseases in East Asian population by population database-based analysis.

BACKGROUND: Inherited retinal diseases (IRDs) are clinically and genetically heterogenous disorders leading to visual impairment and blindness. Because gene therapy for RPE65-associated IRDs was recently approved, it is necessary to predict the carrier frequency and prevalence for RPE65-associated IRDs. This study aimed to analyze the carrier frequency and expected incidence of RPE65-associated IRDs in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) and the Korean Reference Genome Database (KRGDB). METHODS: We analyzed 9,197 exomes for East Asian populations from gnomAD comprising 1,909 Korean and 1,722 Korean genomes from KRGDB. All identified RPE65 variants were classified according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: The total carrier frequencies of East Asians and Koreans from both gnomAD and KRGDB were 0.10% (11/10,919) and 0.06% (2/3,631), respectively. The estimated incidence of RPE65-associated IRDs was 1/3,941,308 in East Asians and 1/13,184,161 in Koreans. CONCLUSION: This study identified carrier frequencies of RPE65-associated IRDs in East Asians and Koreans using gnomAD and KRGDB. We confirmed that the carrier frequency of RPE65-associated IRDs patients was low in Koreans among all East Asian populations, and the incidence was also predicted to be lower than in other East Asian populations. The variant spectrum of RPE65 gene in East Asian and Korean populations differed greatly from those of other ethnic groups.

Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis.

Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterized by a life-threatening condition caused by severe hypercytokinemia. The hereditary forms of HLH, also called familial HLH (fHLH), have 4 different genes (PRF1, UNC13D, STX11, and STXBP2) and have been identified as being causative for fHLH. This study aimed to analyze the carrier frequency and expected incidence of fHLH in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD). Methods: We analyzed 9,197 exomes for East Asian populations from gnomAD with 1,909 Korean for four fHLH genes. All identified variants were classified according to 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline. Results: 19 pathogenic variant/likely pathogenic variants (PV/LPVs) were identified in 30 East Asian individuals (0.33%). Among them, 7 PV/LPVs were identified in 17 Korean individuals (0.63%). The estimated incidence of fHLH was 1 in 1,105,652 for East Asians and l in 235,128 for Koreans. Conclusions: This study is the first to identify carrier frequencies in East Asian and Korean populations for fHLH using gnomAD. It was confirmed that the carrier frequency of fHLH patients was high in Koreans among East Asians and the incidence was also predicted to be higher than that of other East Asians. The variant spectrum of fHLH genes in East Asian and Korean populations differed greatly from those of other ethnic groups.

Potential anticancer effect of sodium caprate on human gastric cancer cells.

The role of sodium caprate (C10) in enhancing drug absorption is well established; however, little information is available on its role as an anticancer drug. This study aimed to evaluate the anticancer effect of C10 in gastric cancer cells. The mechanism of cytotoxicity of C10 was evaluated by western blotting following treatment of the gastric cancer cells with various concentrations of C10. C10 cytotoxicity was measured via MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), lactate dehydrogenase (LDH), cAMP, and ATP assays. Gastric cancer cells were observed by electron microscopy following treatment with C10. Then, xenograft mice that were inoculated with gastric cancer cells were treated with C10 for 4 weeks, after which the changes in tumor size were measured. C10 triggered apoptosis in the gastric cancer cells through the mitochondrial pathway at concentrations of more than 0.2 mM. However, 15 mM of C10 induced necrosis in gastric cancer cells by causing cellular swelling and the formation of holes in the cell membrane. Levels of cAMP and ATP decreased significantly following exposure to 15 mM C10 for 1 h. Additionally, the size of the xenograft tumors was significantly reduced by 24% after 4 weeks of C10 treatment (p < 0.05). This study indicates that C10 induces apoptosis and necrosis in a concentration-dependent manner and has clear anticancer effects on gastric cancer cells.

Highly Sensitive, Stretchable Pressure Sensor Using Blue Laser Annealed CNTs.

A piezoresistive sensor is an essential component of wearable electronics that can detect resistance changes when pressure is applied. In general, microstructures of sensing layers have been adopted as an effective approach to enhance piezoresistive performance. However, the mold-casted microstructures typically have quite a thick layer with dozens of microscales. In this paper, a carbon microstructure is formed by blue laser annealing (BLA) on a carbon nanotube (CNT) layer, which changes the surface morphology of CNTs into carbonaceous protrusions and increases its thickness more than four times compared to the as-deposited layer. Then, the pressure sensor is fabricated using a spin-coating of styrene-ethylene-butylene-styrene (SEBS) elastomer on the BLA CNTs layer. A 1.32 µm-thick pressure sensor exhibits a high sensitivity of 6.87 × 105 kPa-1, a wide sensing range of 278 Pa~40 kPa and a fast response/recovery time of 20 ms, respectively. The stability of the pressure sensor is demonstrated by the repeated loading and unloading of 20 kPa for 4000 cycles. The stretchable pressure sensor was also demonstrated using lateral CNT electrodes on SEBS surface, exhibiting stable pressure performance, with up to 20% stretching.

Pharmacokinetics and Genetic Factors of Atorvastatin in Healthy Korean Subjects.

Background: Statins are the most popular agents for the primary and secondary prevention of cardiovascular disease; however, the pharmacokinetic parameters and associated genetic factors in the Korean population have not been fully elucidated. This study explored the pharmacokinetic properties of atorvastatin and the association between genetic variations and atorvastatin pharmacokinetics in healthy Korean subjects. Methods: Atorvastatin (80 mg) was administered to 35 healthy Korean volunteers. Plasma levels of atorvastatin and its metabolites were measured sequentially using liquid chromatography-tandem mass spectrometry from 0 to 24 h after atorvastatin administration. Customized next-generation sequencing analysis was performed covering all coding exons of 15 genes, as well as 46 single-nucleotide variants in 29 genes related to statin pharmacokinetics. Results: The mean area under the concentration-time (AUC) and Cmax (maximum peak concentration) were 269.0 ng/ml∙h and 84.3 ng/ml, respectively, which were approximately two times higher than those reported in Caucasians. Genetic analysis revealed that eight genetic variants in ABCB1, ABCG2, APOA5, CETP, and CYP7A1 contributed to the AUC of atorvastatin. The atorvastatin AUC0-24 h prediction model was developed based on age and eight genetic variants using multivariate linear regression (adjusted R 2 = 0.878, p < 0.0001). Conclusion: This study shows that the pharmacokinetic properties of atorvastatin in Koreans are different from those in Caucasians and that atorvastatin AUC0-24 h could be predicted based on age and eight genetic variants of ABCB1, ABCG2, APOA5, CETP, and CYP7A1.

Synergy Through Integration of Wearable EEG and Virtual Reality for Mild Cognitive Impairment and Mild Dementia Screening.

Virtual reality (VR) technologies have shown promising potential in the early diagnosis of dementia by enabling accessible and regular assessment. However, previous VR studies were restricted to the analysis of behavioral responses, so information about degenerated brain dynamics could not be directly acquired. To address this issue, we provide a cognitive impairment (CI) screening tool based on a wearable EEG device integrated into a VR platform. Subjects were asked to use a hardware setup consisting of a frontal six-channel EEG device mounted on a VR device and to perform four cognitive tasks in VR. Behavioral response profiles and EEG features were extracted during the tasks, and classifiers were trained on extracted features to differentiate subjects with CI from healthy controls (HCs). Notably, the performance of the patient classification consistently improved when EEG characteristics measured during cognitive tasks were additionally included in feature attributes than when only the task scores or resting-state EEG features were used, suggesting that our protocol provides discriminative information for screening. These results propose that the integration of EEG devices into a VR framework could emerge as a powerful and synergistic strategy for constructing an easily accessible EEG-based CI screening tool.

A Clinical Decision Support System for Sleep Staging Tasks With Explanations From Artificial Intelligence: User-Centered Design and Evaluation Study.

BACKGROUND: Despite the unprecedented performance of deep learning algorithms in clinical domains, full reviews of algorithmic predictions by human experts remain mandatory. Under these circumstances, artificial intelligence (AI) models are primarily designed as clinical decision support systems (CDSSs). However, from the perspective of clinical practitioners, the lack of clinical interpretability and user-centered interfaces hinders the adoption of these AI systems in practice. OBJECTIVE: This study aims to develop an AI-based CDSS for assisting polysomnographic technicians in reviewing AI-predicted sleep staging results. This study proposed and evaluated a CDSS that provides clinically sound explanations for AI predictions in a user-centered manner. METHODS: Our study is based on a user-centered design framework for developing explanations in a CDSS that identifies why explanations are needed, what information should be contained in explanations, and how explanations can be provided in the CDSS. We conducted user interviews, user observation sessions, and an iterative design process to identify three key aspects for designing explanations in the CDSS. After constructing the CDSS, the tool was evaluated to investigate how the CDSS explanations helped technicians. We measured the accuracy of sleep staging and interrater reliability with macro-F1 and Cohen κ scores to assess quantitative improvements after our tool was adopted. We assessed qualitative improvements through participant interviews that established how participants perceived and used the tool. RESULTS: The user study revealed that technicians desire explanations that are relevant to key electroencephalogram (EEG) patterns for sleep staging when assessing the correctness of AI predictions. Here, technicians wanted explanations that could be used to evaluate whether the AI models properly locate and use these patterns during prediction. On the basis of this, information that is closely related to sleep EEG patterns was formulated for the AI models. In the iterative design phase, we developed a different visualization strategy for each pattern based on how technicians interpreted the EEG recordings with these patterns during their workflows. Our evaluation study on 9 polysomnographic technicians quantitatively and qualitatively investigated the helpfulness of the tool. For technicians with <5 years of work experience, their quantitative sleep staging performance improved significantly from 56.75 to 60.59 with a P value of .05. Qualitatively, participants reported that the information provided effectively supported them, and they could develop notable adoption strategies for the tool. CONCLUSIONS: Our findings indicate that formulating clinical explanations for automated predictions using the information in the AI with a user-centered design process is an effective strategy for developing a CDSS for sleep staging.

Polymerizations with Elemental Sulfur: From Petroleum Refining to Polymeric Materials.

The production of elemental sulfur from petroleum refining has created a technological opportunity to increase the valorization of elemental sulfur by the synthesis of high-performance sulfur-based plastics with improved optical, electrochemical, and mechanical properties aimed at applications in thermal imaging, energy storage, self-healable materials, and separation science. In this Perspective, we discuss efforts in the past decade that have revived this area of organosulfur and polymer chemistry to afford a new class of high-sulfur-content polymers prepared from the polymerization of liquid sulfur with unsaturated monomers, termed inverse vulcanization.

Segmented Polyurethanes and Thermoplastic Elastomers from Elemental Sulfur with Enhanced Thermomechanical Properties and Flame Retardancy.

The production of elemental sulfur from petroleum refining has created a technological opportunity to increase the valorization of elemental sulfur by the creation of high-performance sulfur based plastics with improved thermomechanical properties, elasticity and flame retardancy. We report on a synthetic polymerization methodology to prepare the first example of sulfur based segmented multi-block polyurethanes (SPUs) and thermoplastic elastomers that incorporate an appreciable amount of sulfur into the final target material. This approach applied both the inverse vulcanization of S8 with olefinic alcohols and dynamic covalent polymerizations with dienes to prepare sulfur polyols and terpolyols that were used in polymerizations with aromatic diisocyanates and short chain diols. Using these methods, a new class of high molecular weight, soluble block copolymer polyurethanes were prepared as confirmed by Size Exclusion Chromatography, NMR spectroscopy, thermal analysis, and microscopic imaging. These sulfur-based polyurethanes were readily solution processed into large area free standing films where both the tensile strength and elasticity of these materials were controlled by variation of the sulfur polyol composition. SPUs with both high tensile strength (13-24 MPa) and ductility (348 % strain at break) were prepared, along with SPU thermoplastic elastomers (578 % strain at break) which are comparable values to classical thermoplastic polyurethanes (TPUs). The incorporation of sulfur into these polyurethanes enhanced flame retardancy in comparison to classical TPUs, which points to the opportunity to impart new properties to polymeric materials as a consequence of using elemental sulfur.

Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space.

GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. However, modeling of GPCR families has been performed separately for each of the family, subfamily, and sub-subfamily level. Relationships between GPCR proteins are ignored in these approaches as they process the information in the proteins with several disconnected models. In this study, we propose DeepHier, a deep learning model to simultaneously learn representations of GPCR family hierarchy from the protein sequences with a unified single model. Novel loss term based on metric learning is introduced to incorporate hierarchical relations between proteins. We tested our approach using a public GPCR sequence dataset. Metric distances in the deep feature space corresponded to the hierarchical family relation between GPCR proteins. Furthermore, we demonstrated that further downstream tasks, like phylogenetic reconstruction and motif discovery, are feasible in the constructed embedding space. These results show that hierarchical relations between sequences were successfully captured in both of technical and biological aspects.

Relation of exercise capacity to comprehensive physical functions in individuals with ischemic stroke.

BACKGROUND: Impaired motor control, balance, muscle strength, and respiratory function may affect the exercise capacity related to motor performance and activities in individuals with stroke. OBJECTIVE: To identify a physical parameter that the exercise capacity has the most significant relationship among physical parameters related to motor function, trunk control, balance, and motor performance and activities in individuals with ischemic stroke. METHODS: In total, 241 ischemic stroke patients were recruited in this retrospective study. The clinical measurements included the 6-minute walk test (6 MWT), Montreal cognitive assessment (MoCA), Fugl-Meyer assessment-lower extremity motor function (FMA-LE), trunk impairment scale (TIS), Berg balance scale (BBS), timed up and go test (TUG), 10-meter walk test (10 MWT), functional ambulation category (FAC), and functional independence measure (FIM). RESULTS: The 6 MWT was significantly correlated with the FMA-LE, BBS, TUG, 10 MWT, FAC, and FIM, indicating negative or positive moderate correlations. Additionally, the FMA-LE, TIS, BBS, TUG, 10 MWT, FAC, and FIM, excluding the 6 MWT, showed moderate to strong correlations with all of the other outcome measures, whereas the MoCA showed significant correlations only with the BBS and FIM. CONCLUSIONS: In this study, the exercise capacity has the most significant relationship with the TUG parameter in stroke patients. Additionally, we suggest that significant relationships between 6 MWT and other comprehensive physical functions measurements are closely related to walking ability in individuals with stroke.