GlyComb: A novel glycoconjugate data repository that bridges glycomics and proteomics.

The glycosylation of proteins and lipids is known to be closely related to the mechanisms of various diseases such as influenza, cancer, and muscular dystrophy. Therefore, it has become clear that the analysis of post-translational modifications of proteins, including glycosylation, is important to accurately understand the functions of each protein molecule and the interactions among them. In order to conduct large-scale analyses more efficiently, it is essential to promote the accumulation, sharing, and reuse of experimental and analytical data in accordance with the FAIR (Findability, Accessibility, Interoperability, and Re-usability) data principles. However, a FAIR data repository for storing and sharing glycoconjugate information, including glycopeptides and glycoproteins, in a standardized format did not exist. Therefore, we have developed GlyComb (https://glycomb.glycosmos.org) as a new standardized data repository for glycoconjugate data. Currently, GlyComb can assign a unique identifier to a set of glycosylation information associated with a specific peptide sequence or UniProt ID. By standardizing glycoconjugate data via GlyComb identifiers and coordinating with existing web resources such as GlyTouCan and GlycoPOST, a comprehensive system for data submission and data sharing among researchers can be established. Here we introduce how GlyComb is able to integrate the variety of glycoconjugate data already registered in existing data repositories to obtain a better understanding of the available glycopeptides and glycoproteins, and their glycosylation patterns. We also explain how this system can serve as a foundation for a better understanding of glycan function.

Effective hemostasis by preperitoneal pelvic packing for common iliac vein injury without pelvic fracture in severe blunt trauma: a case report.

Background: A common iliac vein injury in the absence of pelvic fractures due to blunt trauma is rare, with no treatment strategy established. Case Presentation: A 48-year-old man, who was injured in a dumbwaiter accident, presented to the hospital with hemorrhagic shock. Computed tomography (CT) revealed active bleeding from the intercostal and hepatic arteries as well as the left common iliac vein. No pelvic fracture was noted. Preperitoneal pelvic packing was performed for the left common iliac vein injury as a damage control surgery. After the operation, endovascular embolization was performed to address the arterial bleeding. The patient became hemodynamically stable, and follow-up CT showed no signs of bleeding. The packing gauze was removed 3 days after the admission. The patient was discharged without complications. Conclusion: Preperitoneal pelvic packing provided temporary hemostasis in a hemodynamically unstable patient with common iliac vein injury but with no pelvic fractures.

[Resection of Left Upper Division by Uniportal Video-assisted Thoracoscopic Surgery for Congenital Bronchial Atresia:Report of a Case].

We report a case of congenital bronchial atresia resected by the uniportal thoracoscopic approach. A man in his 20s with congenital bronchial atresia diagnosed at 16 years of age visited our hospital with gradually worsening shortness of breath. Chest computed tomography revealed a localized emphysematous area that progressively increased in size, in the left upper lobe and the absence of a left upper division bronchus with mucoid impaction. Surgical treatment was deemed necessary in view of dyspnea and progressively worsening emphysema, and the resection of left upper division was performed by uniportal video-assisted thoracoscopic surgery.

Development of a novel monosaccharide substitution matrix for improved comparison of glycan structures.

Unlike DNA and proteins, there is a limit to inferring the structure and function of glycans only by analyzing their sequence. Due to their structural flexibility, it can be said that an understanding of the 3D structural conformations of glycans is important to better understand their functions. While there are several tools now available that aid in analyzing the 3D structures of glycans, they are very computationally intensive and not easily useable by non-experts. Thus, as a first step, we decided to investigate the monosaccharides that make up the building blocks of glycans and their similarities. We developed a method and software that takes the three-dimensional structures of monosaccharides and finds their commonalities through an efficient algorithm, which we call TouCom (tou = "sugar" in Japanese). We then created a similarity matrix to represent the degree of similarity of pairs of monosaccharides based on this information and the properties of their functional groups. We performed an analysis of pairwise glycan alignment using this similarity matrix, confirming that the scores of pairwise-alignments obtained were improved compared to alignments without using this matrix. As a result, we propose the first monosaccharide substitution matrix that has been developed based on 3D atomic structure. In the future, we will apply this matrix to other glycan alignment tools so that glycan sequence analysis can better utilize this information. We expect that this monosaccharide substitution matrix can improve the analysis of glycan function based on glycan structural information.

A Model of Predictive Postural Control Against Floor Tilting in Rats.

Humans and animals learn the internal model of bodies and environments from their experience and stabilize posture against disturbances based on the predicted future states according to the internal model. We evaluated the mechanism of predictive control during standing, by using rats to construct a novel experimental system and comparing their behaviors with a mathematical model. In the experiments, rats (n = 6) that were standing upright using their hindlimbs were given a sensory input of light, after a certain period, the floor under them tilted backward. Initially, this disturbance induced a large postural response, including backward rotation of the center-of-mass angle and hindlimb segments. However, the rats gradually adjusted to the disturbance after experiencing 70 sequential trials, and a reduction in the amplitude of postural response was noted. We simulated the postural control of the rats under disturbance using an inverted pendulum model and model predictive control (MPC). MPC is a control method for predicting the future state using an internal model of the control target. It provides control inputs that optimize the predicted future states. Identification of the predictive and physiological parameters so that the simulation corresponds to the experiment, resulted in a value of predictive horizon (0.96 s) close to the interval time in the experiment (0.9-1.15 s). These results suggest that the rats predict posture dynamics under disturbance based on the timing of the sensory input and that the central nervous system provides plasticity mechanisms to acquire the internal model for MPC.

Perihepatic Abscess due to a Liver Suture with Pledgets Used to Treat a Penetrating Liver Injury.

BACKGROUND: Selective nonoperative management has become the standard for liver injuries. Accordingly, we cannot perform surgery for liver injuries as frequently as in the past. This report is aimed at sharing a valuable experience of postoperative complications after surgery for a liver injury. Case Presentation. A 40-year-old man was stabbed in his abdomen and underwent an emergency laparotomy for a severe liver injury. Five months after the operation, he developed fever, and purulent discharge was observed from an abdominal fistula. He was diagnosed with a perihepatic abscess and duodenal perforation due to the pledgets used for the operation. He underwent a second surgery to remove the pledgets and the abscess cavity for infection control and was discharged in good condition. CONCLUSION: The intra-abdominal environment should be considered contaminated due to bile leakage in surgeries following liver injury. Furthermore, nonabsorbable agents should not be used in these contaminated areas.

Cloning of the cycloisomaltotetraose-forming enzymes using whole genome sequence analyses of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006.

We performed whole genome sequence analyses of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006 that secrete enzymes to produce cyclo-{→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→} (CI4) from dextran. Full-length amino acid sequences of CI4-forming enzymes were identified by matching known N-terminal amino acid sequences with products of the draft genome. Domain searches revealed that the CI4-forming enzymes are composed of Glycoside Hydrolase family 66 (GH66) domain, Carbohydrate Binding Module family 35 (CBM35) domain, and CBM13 domain, categorizing the CI4-forming enzymes in the GH66. Furthermore, the amino acid sequences of the two CI4-forming enzymes were 71% similar to each other and up to 51% similar to cycloisomaltooligosaccharide glucanotransferases (CITases) categorized in GH66. Differences in sequence between the CI4-forming enzymes and the CITases suggest mechanisms to produce specific cycloisomaltooligosaccharides, and whole genome sequence analyses identified a gene cluster whose gene products likely work in concert with the CI4-forming enzymes.

[A Case of Intrahepatic Cholangiocarcinoma Confused with a Recurrent Hepatocellular Carcinoma Treated by RFA at Diagnosis].

Intrahepatic cholangiocarcinoma(ICC)is the second most common malignant liver tumor after hepatocellular carcinoma (HCC). ICC is usually ischemic; however, it has variable findings and may be difficult to differentiate from HCC. We report about a case of ICC that was difficult to distinguish from HCC treated by radiofrequency ablation(RFA). A 79‒year‒old woman underwent RFA for HCC of the caudate lobe. Two years after RFA, a spindle‒shaped tumor was identified near the previous treatment site using contrast‒enhanced MRI. Images showed posterior segment bile duct dilation, posterior segment atrophy of the liver parenchyma, and posterior segmental portal vein disruption. We performed surgery because of the suspicion of a recurrent HCC invading into the bile duct. Intraoperative findings showed posterior segment atrophy. Intraoperative echocardiography could not identify the tumor but revealed a tumor plug and portal vein disruption in the posterior segment. The patient underwent post‒enlargement segmentectomy, caudate lobectomy of the liver, and biliary neoplastic resection. Histopathological findings showed no malignant findings in the hepatocytes. A moderately differentiated adenocarcinoma was found in the expanded bile duct, which was diagnosed as an intrahepatic cholangiocarcinoma. Here, we report about the case along with a discussion and a bibliographical consideration.

Purification and characterization of cycloisomaltotetraose-forming glucanotransferases from Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006.

Glucanotransferases that can synthesize cyclo-{→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→} (CI4) from dextran were purified to homogeneity from the culture supernatant of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006. The molecular mass of both enzymes was estimated to be 86 kDa by SDS-PAGE. The glucanotransferase, named CI4-forming enzyme, from Agreia sp. exhibited the highest activity at pH 6.0 and 40 °C. The enzyme was stable on the pH range of 4.6-9.9 and up to 40 °C. On the other hand, the enzyme from M. trichothecenolyticum exhibited the highest activity at pH 5.7 and 40 °C. The enzyme was stable on the pH range of 5.0-6.9 and up to 35 °C. Both enzymes catalyzed 4 reactions, namely, intramolecular α-1,6-transglycosylation (cyclization), intermolecular α-1,6-transglycosylation, hydrolysis of CI4, and coupling reaction. Furthermore, the CI4-forming enzyme produced CI4 from α-1,6-linked glucan synthesized from starch by 6-α-glucosyltransferase. These findings will enable the production of CI4 from starch.

[A Case of Internal Hernia into a Reconstructed Pelvic Floor and Torsion of Jejunum near the Treitz Ligament after Laparoscopic Abdominoperineal Resection].

A 50s women underwent laparoscopic abdominoperineal resection(APR)for rectal cancer. Laparotomy was performed on the 8th postoperative day because of intestinal obstruction. An internal hernia was observed at the pelvic floor and the hernia orifice was found at the retroperitoneum that was sutured in the initial operation. On the other hand, the jejunum near the Treitz ligament was twisted, resulting in ischemic necrosis. The reason of the internal hernia is considered that a suction drain placed during the initial operation may have caused the rupture of the fragile part of the sutured peritoneum. Furthermore, increase of intra-abdominal pressure due to the internal hernia may have exacerbated the torsion of the jejunum near the Treitz ligament. This is probably due to the failure to the adequate reposition of the small intestine at the end of the initial operation. There is no consensus of the need for retroperitoneal sutures for APR. Currently, we only spray anti-adhesion agents on the pelvic floor without retroperitoneal reconstruction. Although the mobilization of small intestine is important to provide a good operative view in laparoscopic colorectal surgery, it is also important to confirm the reposition of the small intestine at the end of surgery.

The international glycan repository GlyTouCan version 3.0.

Glycans serve important roles in signaling events and cell-cell communication, and they are recognized by lectins, viruses and bacteria, playing a variety of roles in many biological processes. However, there was no system to organize the plethora of glycan-related data in the literature. Thus GlyTouCan (https://glytoucan.org) was developed as the international glycan repository, allowing researchers to assign accession numbers to glycans. This also aided in the integration of glycan data across various databases. GlyTouCan assigns accession numbers to glycans which are defined as sets of monosaccharides, which may or may not be characterized with linkage information. GlyTouCan was developed to be able to recognize any level of ambiguity in glycans and uniquely assign accession numbers to each of them, regardless of the input text format. In this manuscript, we describe the latest update to GlyTouCan in version 3.0, its usage, and plans for future development.

[Transmitral Septal Myectomy and Mitral Valve Plasty for Hypertrophic Obstructive Cardiomyopathy Combined with Organic Mitral Regurgitation;Report of a Case].

A 60-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) combined with organic mitral regurgitation underwent transmitral septal myectomy and mitral valve plasty. Although a transaortic septal myectomy (Morrow's procedure) is generally accepted as the standard surgical treatment for HOCM, it may be difficult to perform sufficient septal myectomy for mid-ventricular obstructive hypertrophic cardiomyopathy and apical hypertrophic cardiomyopathy (HCM). The transmitral approach with temporary detachment of the anterior mitral leaflet provides a good surgical view in the left ventricle, which allows sufficient septal myectomy from the outflow tract to the apex.

A cyclic tetrasaccharide, cycloisomaltotetraose, was enzymatically produced from dextran and its crystal structure was determined.

Two bacterial strains isolated from soil, namely Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006, were found to produce a novel oligosaccharide. The oligosaccharide was enzymatically produced from dextran using the culture supernatant of Agreia sp. D1110 or M. trichothecenolyticum D2006. LC-MS and NMR analysis identified the novel oligosaccharide as cyclo-{→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→}, which was named cycloisomaltotetraose, and abbreviated as CI4. CI4 was subsequently crystalized and its X-ray crystallographic structure was determined. CI4 crystals were shown to be pentahydrate, with the CI4 molecules in the crystal structure displaying a unique 3D structure, in which two glucosyl residues in the molecule were facing each other. This unique 3D structure was quite different from the 3D structure of known cyclic tetrasaccharides. This is the first report of CI4 molecules and their unique crystal structure.

[Gastric Complications in Stomach-Preserving Procedures on Total Pancreatectomy].

Whether the stomach should be preserved during total pancreatectomy(TP)is controversial. Therefore, we examined the correlation between stomach-preserving procedures on TP and postoperative gastric complications. Seven consecutive cases underwent TP(standard TP: 1 case, SSPTP: 3 cases, PPTP: 3 cases)for pancreatic cancer during the time period 2011-2019 at our hospital. There was no clinical case of postoperative gastric ulcer nor bleeding. Delayed gastric emptying(DGE)was observed in 4 cases of Grade A and 2 cases of Grade C. One of the Grade C cases was considered to be secondary DGE due to postoperative intestinal necrosis. The other was SSPTP case whose left gastric artery(LGA)was ligated. The patient had difficulty of food intake after the surgery and gastrointestinal endoscopy showed widespread hemorrhage and erosion of the gastric mucosa, considered to be ischemic gastropathy. Regarding primary DGE, most of cases were within Grade A even in stomach-preserving cases. Whereas, stomach-preserving procedure should be avoided when the LGA is ligated, because ischemic gastropathy may occur.

Pharmacokinetics and lung distribution of macrolide antibiotics in sepsis model rats.

Recent studies have shown azithromycin-specific clinical efficacy against macrolide-resistant strains of Streptococcus pneumoniae, despite the low susceptibility of the bacteria in vitro. This discrepancy complicates dosing and selection for treatment of macrolide-resistant strains. Although phagocyte delivery of azithromycin to inflamed tissues is considered a possible factor for clinical efficacy, there is a lack of sufficient evidence, and other pharmacokinetic factors under systemic inflammation may contribute.The concentrations of azithromycin, clarithromycin and erythromycin in the plasma and buffy coat were determined in normal and sepsis model rats. Furthermore, we compared the transport of the drug into the lung.The levels of all three macrolides in the buffy coat were higher than the levels in the plasma, and lower leukocyte counts in plasma were observed in septic rats, suggesting accumulation of the drugs per leukocyte was increased. The concentrations in the lung tissue of septic rats at each sampling time were the same as those in normal rats, and azithromycin-specific long-term stasis in the lung was evident.These results suggest that both the phagocyte delivery and the stasis of azithromycin in the lung could contribute to its clinical efficacy in treating infections caused by macrolide-resistant strains.

Traffic flow in a crowd of pedestrians walking at different speeds.

This study investigates motion in a crowd of pedestrians walking at different speeds. Three pedestrian groups are considered (slow walkers, normal walkers, and fast walkers), and we design the experimental condition by mixing the normal walkers with either the slow or the fast walkers to create flows with different speed compositions. All the walkers in this experiment were instructed to walk along a circular course unidirectionally. Fundamental diagrams and multiple regression analysis show that the speed at which a particular pedestrian walks is determined by both the local density and the speed at which the surrounding pedestrians are walking. We also find that the spontaneous lane formation, that occurs in bidirectional flow, does not occur in flow in which the speed is heterogeneous, thereby resulting in a spatial density distribution with large variance. This corresponds to pedestrian clustering, which reduces both the mean speed and the flow rate.

[Adenosquamous Carcinoma in the Remnant Pancreas after Pancreatoduodenectomy for Invasive Pancreas Cancer-A Resected Case with Five-Year Relapse-Free Survival].

A 52-year-old man underwent pancreatoduodenectomy(PD)for invasive cancer of the pancreatic head, with a histopathological diagnosis of moderately to poorly differentiated invasive ductal carcinoma. One year and 2 months after PD, follow- up CT revealed a mass 3 cm in diameter in the remnant pancreas without distant metastasis. Therefore, total remnant pancreatectomy was performed with a histopathological diagnosis of adenosquamous carcinoma. Five years after re-excision, the patient remains alive without recurrence. Although no tumor component was found at the anastomotic site of the pancreatojejunostomy, squamous metaplasia with chronic inflammation with carcinogenic potential was diffusely observed in the main pancreatic duct. Clinical cases of remnant pancreatic resection after PD for invasive cancer are relatively rare. Furthermore, this case of adenosquamous carcinoma with long-term recurrence-free survival is extremely rare.

[A Rare Case of Gastric Metastasis from Cholangio Carcinoma].

An 80-year-old man was referred to our hospital because of jaundice and fatigue. Abdominal computed tomography(CT) scan revealed an extrahepatic bile duct tumor, and biliary cytology detected adenocarcinoma; therefore, subtotal stomachpreserving pancreaticoduodenectomy was performed. Histological analysis showed that the tumor was a well-differentiated adenocarcinoma without lymph node metastasis. Two years after the initial surgery, blood examination detected an elevated serum CA19-9 level and submucosal tumor which is 2.5 cm diameter with an ulcer at the gastrojejunostomy anastomosis. Tumor biopsy was performed, and histological analysis revealed a recurrent cholangiocarcinoma. The tumor directly invaded the transverse colon mesentery; therefore, distal gastrectomy and right hemicolectomy were performed. The patient survived 12 months postoperatively without recurrence. Gastric metastasis from cholangiocarcinoma rarely occurs. Intraoperative exposure of bile juice may have caused gastric metastasis in this case.

[A Case of Pancreatic Mixed Acinar-Neuroendocrine Carcinoma with Main Pancreatic Duct Development].

A 78-year-old man was referred to our hospital owing to a pancreatic tumor detected on ultrasonography. He showed weight loss, and his diabetes mellitus had worsened over 3 months. Abdominal contrast-enhanced computed tomography revealed a 3 cm diameter pancreatic head tumor with peripheral enhancement and a dilated pancreatic duct. He underwent subtotal stomach-preserving pancreaticoduodenectomy. Examination of intraoperative frozen sections did not indicate cancer involvement at the edge of the resected pancreatic duct. The tumor was histologically diagnosed as mixed acinar-neuroendocrine carcinoma(MANEC). It was mainly detected in the pancreatic head and was accompanied by intra-ductal growth in the pancreatic duct. The patient has survived for 21 months without recurrence. MANEC is a rare disease associated with intraductal growth. Intraoperative diagnosis of tumor involvement at the edge of the pancreatic duct may be useful for R0 resection in surgery for MANEC.