Pilot study of the relation between various dynamics of avatar experience and perceptual characteristics.

In recent years, due to the prevalence of virtual reality (VR) and human-computer interaction (HCI) research, along with the expectation that understanding the process of establishing sense of ownership, sense of agency, and limb heaviness (in this study, limb heaviness is replaced with comfort level) will contribute to the development of various medical rehabilitation, various studies have been actively conducted in these fields. Previous studies have indicated that each perceptual characteristics decrease in response to positive delay. However, it is still unclear how each perceptual characteristic changes in response to negative delay. Therefore, the purpose of this study was to deduce how changes occur in the perceptual characteristics when certain settings are manipulated using the avatar developed in this study. This study conducted experiments using an avatar system developed for this research that uses electromyography as the interface. Two separate experiments involved twelve participants: a preliminary experiment and a main experiment. As observed in the previous study, it was confirmed that each perceptual characteristics decreased for positive delay. In addition, the range of the preliminary experiment was insufficient for the purpose of this study, which was to confirm the perceptual characteristics for negative delay, thus confirming the validity of conducting this experiment. Meanwhile, the main experiment showed that the sense of ownership, sense of agency, and comfort level decreased gradually as delay time decreased, (i.e., this event is prior to action with intention, which could not be examined in the previous study). This suggests that control by the brain-machine interface is difficult to use when it is too fast. In addition, the distribution of the most strongly perceived settings in human perceptual characteristics was wider in regions with larger delays, suggesting this may lead to the evaluation of an internal model believed to exist in the human cerebellum. The avatar developed for this study may have the potential to create a new experimental paradigm for perceptual characteristics.

Structural basis for the recognition of α-1,6-branched α-glucan by GH13_47 α-amylase from Rhodothermus marinus.

Glycoside hydrolase (GH) family 13 is among the main families of enzymes acting on starch; recently, subfamily 47 of GH13 (GH13_47) has been established. The crystal structure and function of a GH13_47 enzyme from Bacteroides ovatus has only been reported to date. This enzyme has α-amylase activity, while the GH13_47 enzymes comprise approximately 800-900 amino acid residues which are almost double those of typical α-amylases. It is important to know how different the GH13_47 enzymes are from other α-amylases. Rhodothermus marinus JCM9785, a thermophilic bacterium, possesses a gene for the GH13_47 enzyme, which is designated here as RmGH13_47A. Its structure has been predicted to be composed of seven domains: N1, N2, N3, A, B, C, and D. We constructed a plasmid encoding Gly266-Glu886, which contains the N3, A, B, and C domains and expressed the protein in Escherichia coli. The enzyme hydrolyzed starch and pullulan by a neopullulanase-type action. Additionally, the enzyme acted on maltotetraose, and saccharides with α-1,6-glucosidic linkages were observed in the products. Following the replacement of the catalytic residue Asp563 with Ala, the crystal structure of the variant D563A in complex with the enzymatic products from maltotetraose was determined; as a result, electron density for an α-1,6-branched pentasaccharide was observed in the catalytic pocket, and Ile762 and Asp763 interacted with the branched chain of the pentasaccharide. These findings suggest that RmGH13_47A is an α-amylase that prefers α-1,6-branched parts of starch to produce oligosaccharides.

Characterization and alteration of product specificity of Beijerinckia indica subsp. indica ß-fructosyltransferase.

The trisaccharide 1-kestose, a major constituent of fructooligosaccharide, has strong prebiotic effects. We used high-performance liquid chromatography and 1H nuclear magnetic resonance spectroscopy to show that BiBftA, a ß-fructosyltransferase belonging to glycoside hydrolase family 68, from Beijerinckia indica subsp. indica catalyzes transfructosylation of sucrose to produce mostly 1-kestose and levan polysaccharides. We substituted His395 and Phe473 in BiBftA with Arg and Tyr, respectively, and analyzed the reactions of the mutant enzymes with 180 g/L sucrose. The ratio of the molar concentrations of glucose and 1-kestose in the reaction mixture with wild-type BiBftA was 100:8.1, whereas that in the reaction mixture with the variant H395R/F473Y was 100:45.5, indicating that H395R/F473Y predominantly accumulated 1-kestose from sucrose. The X-ray crystal structure of H395R/F473Y suggests that its catalytic pocket is unfavorable for binding of sucrose while favorable for transfructosylation.

Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS).

BACKGROUND: This study evaluated the efficacy and safety of baricitinib (Janus kinase-1/2 inhibitor), in adult and pediatric Japanese patients with Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (NNS/CANDLE), stimulator of interferon genes-associated vasculopathy with onset during infancy (SAVI), or Aicardi-Goutières syndrome (AGS). METHODS: A Phase 2/3, multicenter, open-label study (NCT04517253) was conducted across 52 weeks. Primary efficacy endpoint assessed the change in mean daily diary score (DDS) from baseline to the end of primary treatment period. Other efficacy endpoints included change in mean DDS to the end of maintenance period, daily corticosteroid use, Physician's Global Assessment of Disease Activity (PGA) scores, and daily symptom-specific score (DSSS) from baseline to primary and maintenance treatment periods. All treatment-emergent adverse events (TEAEs) that occurred postdosing were recorded. RESULTS: Overall, 9 patients (5 with NNS, 3 with SAVI, and 1 with AGS) were enrolled; 55.6% were females, mean age was 26 years, and mean corticosteroid use/weight was 0.2 mg/kg. At the end of primary treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.22) and SAVI (0.21) and increased in the patient with AGS (0.07). At the end of maintenance treatment period, mean DDS decreased from baseline in patients with NNS/CANDLE (0.18) and SAVI (0.27) and increased in the patient with AGS (0.04). Mean percent corticosteroid use decreased by 18.4% in 3 out of 5 patients with NNS/CANDLE and 62.9% in 1 out of 3 patients with SAVI. Mean PGA score decreased from baseline in patients with NNS/CANDLE (1.60), SAVI (1.33), and AGS (1.0), and mean DSSS improved from baseline. All patients reported ≥ 1 TEAE. Frequently reported AEs included BK polyomavirus detection (3; 33.3%), increased blood creatine phosphokinase (2; 22.2%), anemia (2; 22.2%), and upper respiratory tract infection (2; 22.2%). Three (33.3%) patients reported serious adverse events, 1 of which was related to study drug. One patient with SAVI died due to intracranial hemorrhage, which was not related to study drug. CONCLUSION: Baricitinib may offer a potential therapeutic option for patients with NNS/CANDLE, SAVI, and AGS, with a positive benefit/risk profile in a vulnerable patient population with multiple comorbidities. TRIAL REGISTRATION: NLM clinicaltrials.gov, NCT04517253 . Registered 18 August 2020.

Cleavage of the Jaw1 C-terminal region enhances its augmentative effect on the Ca2+ release via IP3 receptors.

Jaw1 (also known as IRAG2), a tail-anchored protein with 39 carboxyl (C)-terminal amino acids, is oriented to the lumen of the endoplasmic reticulum and outer nuclear membrane. We previously reported that Jaw1, as a member of the KASH protein family, plays a role in maintaining nuclear shape via its C-terminal region. Furthermore, we recently reported that Jaw1 functions as an augmentative effector of Ca2+ release from the endoplasmic reticulum by interacting with the inositol 1,4,5-trisphosphate receptors (IP3Rs). Intriguingly, the C-terminal region is partially cleaved, meaning that Jaw1 exists in the cell in at least two forms - uncleaved and cleaved. However, the mechanism of the cleavage event and its physiological significance remain to be determined. In this study, we demonstrate that the C-terminal region of Jaw1 is cleaved after its insertion by the signal peptidase complex (SPC). Particularly, our results indicate that the SPC with the catalytic subunit SEC11A, but not SEC11C, specifically cleaves Jaw1. Furthermore, using a mutant with a defect in the cleavage event, we demonstrate that the cleavage event enhances the augmentative effect of Jaw1 on the Ca2+ release ability of IP3Rs.

Jaw1/LRMP is associated with the maintenance of Golgi ribbon structure.

Jaw1/LRMP is a membrane protein that is localized to the endoplasmic reticulum and outer nuclear membrane. Previously, we revealed that Jaw1 functions to maintain nuclear shape by interacting with microtubules as a Klarsicht/ANC-1/Syne/homology (KASH) protein. The loss of several KASH proteins causes defects in the position and shape of the Golgi apparatus as well as the nucleus, but the effects of Jaw1 depletion on the Golgi apparatus were poorly understood. Here, we found that siRNA-mediated Jaw1 depletion causes Golgi fragmentation with disordered ribbon structure in the melanoma cell, accompanied by the change in the localization of the Golgi-derived microtubule network. Thus, we suggest that Jaw1 is a novel protein to maintain the Golgi ribbon structure, associated with the microtubule network.

Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance.

OBJECTIVES: To assess the safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice. METHODS: This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks. RESULTS: Safety analyses to February 2021 included 4731 patients (initial baricitinib dose: 4 mg/day, n = 3058; 2 mg/day, n = 1661; other, n = 12); 1059 (22.38%) were ≥75 years and 3362 (71.06%) previously received biologic therapy. The overall observational period was 1863.14 patient-years; 1174 (24.82%) patients discontinued baricitinib before Week 24, mostly for lack of effectiveness (n = 478; 10.10%). Adverse events occurred in 1271 (26.87%) patients [serious: 203 (4.29%); death: 18 (0.38%)]. The incidence of herpes zoster, hepatic function disorder, and serious infection was 3.09%, 2.77%, and 1.90%, respectively. Malignancy occurred in 17 patients (0.36%) and major adverse cardiovascular events in seven patients (0.15%). Among patients with effectiveness data, at least 26.57% (Boolean) achieved remission at Week 24. CONCLUSIONS: This large nationwide surveillance study evaluated the safety and effectiveness of 24 weeks of baricitinib for RA in real-world clinical practice. Continued surveillance of long-term safety is ongoing.

Earable Ω (OMEGA): A Novel Clenching Interface Using Ear Canal Sensing for Human Metacarpophalangeal Joint Control by Functional Electrical Stimulation.

(1) Background: A mouth-free interface is required for functional electrical stimulation (FES) in people with spinal cord injuries. We developed a novel system for clenching the human metacarpophalangeal (MP) joint using an earphone-type ear canal movement sensor. Experiments to control joint angle and joint stiffness were performed using the developed system. (2) Methods: The proposed FES used an equilibrium point control signal and stiffness control signal: electrical agonist-antagonist ratio and electrical agonist-antagonist sum. An angle sensor was used to acquire the joint angle, and system identification was utilized to measure joint stiffness using the external force of a robot arm. Each experiment included six and five subjects, respectively. (3) Results: While the joint angle could be controlled well by clenching with some hysteresis and delay in three subjects, it could not be controlled relatively well after hyperextension in the other subjects, which revealed a calibration problem and a change in the characteristics of the human MP joint caused by hyperextension. The joint stiffness increased with the clenching amplitude in five subjects. In addition, the results indicated that viscosity can be controlled. (4) Conclusions: The developed system can control joint angle and stiffness. In future research, we will develop a method to show that this system can control the equilibrium point and stiffness simultaneously.

Pooled Safety Analysis of Baricitinib in Adult Participants with Atopic Dermatitis in the Japanese Subpopulation from Six Randomized Clinical Trials.

INTRODUCTION: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor approved in Japan and the European Union for the treatment of atopic dermatitis (AD). The aim of this study is to report pooled safety data for baricitinib in the Japanese subpopulation of the clinical development program in moderate-to-severe AD. METHODS: This analysis included participant-level safety data from five double-blind, randomized clinical studies and one double-blind, randomized, long-term extension study, reported in three datasets for the Japanese subpopulation: (1) placebo-controlled, (2) baricitinib 2 mg and 4 mg extended ("2-mg-4-mg extended"), and (3) all baricitinib doses ("All-bari-AD"). The data cutoff was 13 December 2019. Safety outcomes included treatment-emergent adverse events, adverse events of special interest, and abnormal laboratory changes. Proportions of participants with events and incidence rates were calculated. RESULTS: Data were collected for 341 participants from Japan who received baricitinib for 371.7 participant-years (median duration 371.0 days). In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. No gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with exposure up to 2 years in the All-bari-AD dataset. There were no deaths in the Japanese subpopulation. CONCLUSIONS: This integrated safety analysis in the subpopulation of Japanese participants is consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe AD. GOV IDENTIFIERS: NCT02576938, NCT03334396, NCT03334422, NCT03428100, NCT03733301, and NCT03334435.

MicroLED neural probe for effective in vivo optogenetic stimulation.

The MicroLED probe enables optogenetic control of neural activity in spatially separated brain regions. Understanding its heat generation characteristics is important. In this study, we investigated the temperature rise (ΔT) characteristics in the brain tissue using a MicroLED probe. The ΔT strongly depended on the surrounding environment of the probe, including the differences between the air and the brain, and the area touching the brain tissue. Through animal experiments, we suggest an in situ temperature monitoring method using temperature dependence on electrical characteristics of the MicroLED. Finally, optical stimulation by MicroLEDs proved effective in controlling optogenetic neural activity in animal models.

Recombinant lectin Gg for brain imaging of glycan structure and formation in the CNS node of Ranvier.

The nodes of Ranvier are unmyelinated gaps in the axon, important for the efficient transmission of action potentials. Despite the identification of several glycoproteins involved in node formation and maintenance, glycans' structure and formation in the node remain unclear. Previously, we developed a recombinant lectin from the Clostridium botulinum neurotoxin complex, specific to the galactose and N-acetylgalactosamine terminal epitopes (Gg). Gg stained Neuro2a cells. Here, we show Gg punctuate staining in mouse brain cryosections. Thus, we hypothesized that Gg could help study glycans in the node of Ranvier. Lectin histochemistry on mouse brain cryosections confirmed that Gg binds specifically to the node of Ranvier in the central nervous system (CNS). Using a combination of lectin blotting, glycosidase treatment on tissue sections, and lectin histochemistry, Gg ligands were identified as α-galactose terminal glycoproteins in the perinodal extracellular matrix. Furthermore, we detected the spatiotemporal distribution of galactosylated glycans in the CNS node of Ranvier in mouse brain tissues at different postnatal times. Finally, we observed impaired clustering of galactosylated glycans in the nodes during demyelination and remyelination in cuprizone-induced demyelination and remyelination mouse model. In conclusion, Gg can serve as a novel brain imaging tool in glycobiology and report glycoprotein formation and alterations in the CNS node of Ranvier. Our findings might serve as a first step to establish the role of glycans in the node of Ranvier.

Jaw1/LRMP increases Ca2+ influx upon GPCR stimulation with heterogeneous effect on the activity of each ITPR subtype.

Ca2+ influx upon G protein-coupled receptor (GPCR) stimulation is observed as a cytosolic Ca2+ concentration oscillation crucial to initiating downstream responses including cell proliferation, differentiation, and cell-cell communication. Although Jaw1 is known to interact with inositol 1,4,5-triphosphate receptor (ITPRs), Ca2+ channels on the endoplasmic reticulum, the function of Jaw1 in the Ca2+ dynamics with physiological stimulation remains unclear. In this study, using inducible Jaw1-expressing HEK293 cells, we showed that Jaw1 increases Ca2+ influx by GPCR stimulation via changing the Ca2+ influx oscillation pattern. Furthermore, we showed that Jaw1 increases the Ca2+ release activity of all ITPR subtypes in a subtly different manner. It is well known that the Ca2+ influx oscillation pattern varies from cell type to cell type, therefore these findings provide an insight into the relationship between the heterogeneous Ca2+ dynamics and the specific ITPR and Jaw1 expression patterns.

Structural basis for proteolytic processing of Aspergillus sojae α-glucosidase L with strong transglucosylation activity.

An α-glucosidase from Aspergillus sojae, AsojAgdL, exhibits strong transglucosylation activity to produce α-1,6-glucosidic linkages. The most remarkable structural feature of AsojAgdL is that residues 457-560 of AsojAgdL (designated the NC sequence) is not conserved in other glycoside hydrolase family 31 enzymes, and part of this NC sequence is proteolytically cleaved during its maturation. In this study, the enzyme was expressed in Pichia pastoris, and electrophoretic analysis indicated that the recombinant enzyme, rAsojAgdL, consisted of two polypeptide chains, as observed in the case of the enzyme produced in an Aspergillus strain. The crystal structure of rAsojAgdL was determined in complex with the substrate analog trehalose. Electron density corresponding to residues 496-515 of the NC sequence was not seen, and there were no α-helices or ß-strands except for a short α-helix in the structures of residues 457-495 and residues 516-560, both of which belong to the NC sequence. The residues 457-495 and the residues 516-560 both formed extra components of the catalytic domain. The residues 457-495 constituted the entrance of the catalytic pocket of rAsojAgdL, and Gly467, Asp468, Pro469, and Pro470 in the NC sequence were located within 4 Å of Trp400, a key residue involved in binding of the substrate. The results suggest that the proteolytic processing of the NC sequence is related to the formation of the catalytic pocket of AsojAgdL.

Enzymatic and structural characterization of ß-fructofuranosidase from the honeybee gut bacterium Frischella perrara.

Fructooligosaccharide is a mixture of mostly the trisaccharide 1-kestose (GF2), tetrasaccharide nystose (GF3), and fructosyl nystose (GF4). Enzymes that hydrolyze GF3 may be useful for preparing GF2 from the fructooligosaccharide mixture. A ß-fructofuranosidase belonging to glycoside hydrolase family 32 (GH32) from the honeybee gut bacterium Frischella perrara (FperFFase) was expressed in Escherichia coli and purified. The time course of the hydrolysis of 60 mM sucrose, GF2, and GF3 by FperFFase was analyzed, showing that the hydrolytic activity of FperFFase for trisaccharide GF2 was lower than those for disaccharide sucrose and tetrasaccharide GF3. The crystal structure of FperFFase and its structure in complex with fructose were determined. FperFFase was found to be structurally homologous to bifidobacterial ß-fructofuranosidases even though bifidobacterial enzymes preferably hydrolyze GF2 and the amino acid residues interacting with fructose at subsite - 1 are mostly conserved between them. A proline residue was inserted between Asp298 and Ser299 using site-directed mutagenesis, and the activity of the variant 298P299 was measured. The ratio of activities for 60 mM GF2/GF3 by wild-type FperFFase was 35.5%, while that of 298P299 was 23.6%, indicating that the structure of the loop comprising Trp297-Asp298-Ser299 correlated with the substrate preference of FperFFase. The crystal structure also shows that a loop consisting of residues 117-127 is likely to contribute to the substrate binding of FperFFase. The results obtained herein suggest that FperFFase is potentially useful for the manufacture of GF2. KEY POINTS: • Frischella ß-fructofuranosidase hydrolyzed nystose more efficiently than 1-kestose. • Trp297-Asp298-Ser299 was shown to be correlated with the substrate preference. • Loop consisting of residues 117-127 appears to contribute to the substrate binding.

Surgical assistant manipulator with diagonal joints and multi-stage telescopic screws for laparoscopic solo surgery.

PURPOSE: A surgeon in a sterilized area can perform robotically assisted laparoscopic solo surgery while controlling a laparoscope-holding robot for view stabilization and a forceps robot for pulling organs. At present, no locally operated surgical assistant manipulator with a mechanical remote center of motion (RCM) is available to operate within a small space while providing a wide range of movement. The present study describes a new locally operated detachable end-effector manipulator (LODEM) with diagonal joints and multi-stage telescopic screws. METHODS: A forceps manipulator attached to commercial surgical forceps was developed. This manipulator uses RCM diagonal joints for the yaw and pitch axes, providing an intuitive pivot point and free rotation, and telescopic nested screws with multiple sliders clamp the commercial forceps for the axis of insertion. The manipulator placed above the abdominal wall using a fixed arm connected to a bed rail is motor controlled by a handheld interface with button switches for precise traction and is controlled manually for easy rough positioning. RESULTS: Positional accuracy at the tip with a load of 5 N was under 0.5 mm. Mechanical deflection was under 2.1 mm. The manually controlled force was under 4.4 N. Successful simulated laparoscopic cholecystectomy using the prototype manipulator to handle the target and maintain stability was performed on a surgically realistic gallbladder model. CONCLUSIONS: A LODEM with diagonal joints and multi-stage telescopic screws was developed to facilitate minimally invasive, robotically assisted laparoscopic solo surgery by a surgeon working near the patient. This electric motor-controlled laparoscopic instrument holder by the surgeon in the surgical field could be used for such applications.

Novel protocol to observe the intestinal tuft cell using transmission electron microscopy.

The tuft cell is a chemosensory cell, a specific cell type sharing the taste transduction system with a taste cell on the tongue, of which the existence has been discovered in various tissues including the gastrointestinal tract, gall bladder, trachea and pancreatic duct. To date, electron microscopic approaches have shown various morphological features of the tuft cell, such as long and thick microvilli, tubulovesicular network at the apical side and prominent skeleton structures. Recently, it has been reported that the small intestinal tuft cell functions to initiate type-2 immunity in response to helminth infection. However, the mechanisms by which such distinguished structures are involved with the physiological functions are poorly understood. To address this question, a combination of physiological study of tuft cells using genetic models and its morphological study using electron microscopy will be required. However, it is a challenge to observe tuft cells by electron microscopy due to their extremely low frequency in the epithelium. Therefore, in this paper, we suggest an advanced protocol to observe the small intestinal tuft cell efficiently by transmission electron microscopy using serial semi-thin sections on Aclar film. This article has an associated First Person interview with the first author of the paper.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Validation Study of Algorithms to Identify Malignant Tumors and Serious Infections in a Japanese Administrative Healthcare Database.

BACKGROUND: This retrospective observational study validated case-finding algorithms for malignant tumors and serious infections in a Japanese administrative healthcare database. METHODS: Random samples of possible cases of each disease (January 2015-January 2018) from two hospitals participating in the Medical Data Vision Co., Ltd. (MDV) database were identified using combinations of ICD-10 diagnostic codes and other procedural/billing codes. For each disease, two physicians identified true cases among the random samples of possible cases by medical record review; a third physician made the final decision in cases where the two physicians disagreed. The accuracy of case-finding algorithms was assessed using positive predictive value (PPV) and sensitivity. RESULTS: There were 2,940 possible cases of malignant tumor; 180 were randomly selected and 108 were identified as true cases after medical record review. One case-finding algorithm gave a high PPV (64.1%) without substantial loss in sensitivity (90.7%) and included ICD-10 codes for malignancy and photographing/imaging. There were 3,559 possible cases of serious infection; 200 were randomly selected and 167 were identified as true cases after medical record review. Two case-finding algorithms gave a high PPV (85.6%) with no loss in sensitivity (100%). Both case-finding algorithms included the relevant diagnostic code and immunological infection test/other related test and, of these, one also included pathological diagnosis within 1 month of hospitalization. CONCLUSIONS: The case-finding algorithms in this study showed good PPV and sensitivity for identification of cases of malignant tumors and serious infections from an administrative healthcare database in Japan.

Inter-limb Asymmetry of Equilibrium Regulation in the Legs of 10-11-Year-Old Boys during Overground Sprinting.

Short-distance running at top speed is important in field sports. Previous studies have analyzed kinematic and kinetic properties of sprinting in adults, but equivalent knowledge in children is underexplored. Quantifying relevant aspects of children's sprinting is useful for classifying their running skills and providing effective coaching based on motor control theory. This study aimed to clarify differences in equilibrium regulation in more- and less-skilled boy sprinters. Five 10-11-year-old boys regularly participating in lessons at the Mizuno running school performed 30-meter and 50-meter field track sprints, and the kinematic and electromyography findings were recorded. Equilibrium-point-based synergy analysis was then applied to estimate their respective virtual trajectories. The virtual trajectory is an equilibrium time sequence that indicates how the central nervous system controls a skeletal system with multiple muscles. The results suggested that: (1) the equilibrium of the right and left legs was regulated differently, although together the legs showed similar kinematics; (2) in the first type of virtual trajectory (type-I) in one leg, the equilibria after foot-strike were regulated intermittently during the early swing phase; (3) in the second type of virtual trajectory (type-II) in the other leg, the equilibria after foot-strike were continuously regulated during the early swing phase; and (4) the less-skilled child runners showed a slow equilibrium action response in both types of virtual trajectory during the early swing phase. These findings provide insights for "tailor-made" coaching based on the type of leg control during sprinting.Clinical relevance-Information on gait asymmetry would be beneficial not only for coaching to improve sprint training but also from clinical and injury perspectives.

Glycan detecting tools developed from the Clostridium botulinum whole hemagglutinin complex.

Lectins are proteins with the ability to recognize and bind to specific glycan structures. These molecules play important roles in many biological systems and are actively being studied because of their ability to detect glycan biomarkers for many diseases. Hemagglutinin (HA) proteins from Clostridium botulinum type C neurotoxin complex; HA1, HA2, and HA3 are lectins that aid in the internalization of the toxin complex by binding to glycoproteins on the cell surface. HA1 mutants have been previously reported, namely HA1 W176A/D271F and HA1 N278A/Q279A which are specific to galactose (Gal)/N-acetylgalactosamine (GalNAc) and N-acetylneuraminic acid (Neu5Ac) sugars, respectively. In this study, we utilized HA1 mutants and expressed them in complex with HA2 WT and HA3 WT to produce glycan detecting tools with high binding affinity. Particularly, two types were made: Gg and Rn. Gg is an Alexa 488 conjugated lectin complex specific to Gal and GalNAc, while Rn is an Alexa 594 conjugated lectin complex specific to Neu5Ac. The specificities of these lectins were identified using a glycan microarray followed by competitive sugar inhibition experiments on cells. In addition, we confirmed that Gg and Rn staining is clearly different depending on cell type, and the staining pattern of these lectins reflects the glycans present on the cell surface as shown in enzyme treatment experiments. The availability of Gg and Rn provide us with new promising tools to study Gal, GalNAc, and Neu5Ac terminal epitopes which can aid in understanding the functional role of glycans in physiological and pathological events.