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Background/Aims Helicobacter pylori infection-negative gastric cancer (HPNGC) has not been systematically investigated in consecutive patients. Hence, this study aimed to investigate the clinicopathological and endoscopic features of HPNGC. Methods This single-center retrospective study selected participants from patients with gastric cancer who were treated at the Fukuoka University Chikushi Hospital between January 2013 and December 2021. Only patients diagnosed with HPNGC were enrolled, and their clinicopathological and endoscopic features were analyzed in detail. Results The prevalence of HPNGC in the present study was 2.6% (54/2,112). The types of HPNGC observed in each gastric region were as follows: advanced gastric cancer was observed in the cardia; gastric adenocarcinoma of fundic-gland differentiation, gastric adenocarcinoma of foveolar-type presenting with whitish elevation and raspberry-like foveolar-type gastric adenocarcinoma, gastric adenocarcinoma arising in polyposis, and gastric adenocarcinoma with autoimmune gastritis were observed in the fundic gland region ranging from the gastric fornix to the gastric body; signet-ring cell carcinoma was observed in the gastric-pyloric transition region ranging from the lower gastric body to the gastric angle; and well-differentiated tubular adenocarcinoma with low-grade atypia was observed in the antrum. Conclusions This study revealed that tumors from each gastric region exhibited distinct macroscopic and histological types in HPNGC.

Abstract The meniscal position within the knee is critical to maintain normal knee function. The joint capsule might dynamically coordinate the medial meniscus (MM) by transmitting a semimembranosus action. However, their interrelationships in vivo are unclear. We aimed to determine relationships among the MM, joint capsule, and semimembranosus during passive tibial external-internal and isometric tibial internal rotation at the medial and posteromedial knees of 10 healthy individuals in vivo using ultrasound. We analyzed images of the MM and joint capsule locations at the medial and posteromedial knee and the velocity waveform similarity of each structure during rotational tasks. Both isometric internal rotation with semimembranosus action and passive tibial external rotation displaced the MM inward at the medial knee. The MM and joint capsule during these MM displacements coordinately moved with more than moderate cross-correlation coefficients (passive external and isometric internal rotations, ≥ 0.54 and ≥ 0.90, respectively). The movements of the MM and joint capsule to the semimembranosus during isometric internal rotation also coordinated with moderate cross-correlation coefficients (≥ 0.62). Therefore, the joint capsule might dynamically coordinate the MM by transmitting semimembranosus action. Whether increased tibial internal rotation or semimembranosus shortening causes MM extrusion awaits further investigation.

We developed three e-learning systems for endoscopists to acquire the necessary skills to improve the diagnosis of early gastric cancer (EGC) and demonstrated their usefulness using randomized controlled trials. The subjects of the three e-learning systems were “detec­tion”, “characterization”, and “preoperative assessment”. The contents of each e-learning system included “technique”, “knowledge”, and “obtaining experience”. All e-learning systems proved useful for endoscopists to learn how to diagnose EGC. Lecture videos describing “the technique” and “the knowledge” can be beneficial. In addition, repeating 100 self-study cases allows learners to gain “experience” and improve their diagnostic skills further. Web-based e-learning systems have more advantages than other teaching methods because the number of participants is unlimited. Histopathological diagnosis is the gold standard for the diagnosis of gastric cancer. Therefore, we developed a comprehensive diagnostic algorithm to standardize the histopathological diagnosis of gastric cancer. Once we have successfully shown that this algorithm is helpful for the accurate histopathological diagnosis of cancer, we will complete a series of e-learning systems designed to assess EGC accurately.

Background: Cardiac amyloidosis is a fatal disease of severe heart failure caused by the accumulation of amyloid in the myocardium. This disease is often advanced by the time cardiac symptoms appear; therefore, early detection and treatment are critical for a good prognosis. Recently, it has been suggested that cardiac amyloidosis is implicated in several orthopedic diseases, including carpal tunnel syndrome (CTS), which is often reported to precede cardiac dysfunction. Shoulder disease has also been suggested to be associated with cardiac amyloidosis; however, there have been no reports investigating the rate of amyloid deposition in shoulder specimens and the simultaneous prevalence of cardiac amyloidosis. Herein, we investigated the prevalence of intraoperative specimen amyloid deposition and cardiac amyloidosis in shoulder disease and CTS to determine the usefulness of shoulder specimen screening as a predictor of cardiac amyloidosis development. Methods: A total of 41 patients undergoing arthroscopic shoulder surgery and 33 patients undergoing CTS surgery were enrolled in this study. The shoulder group included rotator cuff tears, contracture of the shoulder, synovitis, and calcific tendonitis. In the shoulder group, a small sample of synovium and the long head of the biceps brachii tendon were harvested, while the transverse carpal ligament was harvested from the CTS group. The intraoperative specimens were pathologically examined for amyloid deposition, and patients with amyloid deposition were examined for the presence of cardiac amyloidosis by cardiac evaluation. Results: In the shoulder group, three cases (7.3%) of transthyretin amyloid deposition were found, all of which involved rotator cuff tears. None of these three cases with amyloid deposition were associated with cardiac amyloidosis. When examining the specimens, the amyloid deposition rate in the long head of the biceps brachii tendon was higher than that in the synovium. In the CTS group, 12 cases (36.4%) of transthyretin amyloid deposition were observed. Of these cases, seven underwent cardiac evaluation and two were identified with cardiac amyloidosis. Conclusion: While the prevalence of amyloid deposition and cardiac amyloidosis in the CTS group was consistent with previous reports, the shoulder group showed a lower deposition rate and no concomitant cardiac amyloidosis. Therefore, it remains debatable whether investigating amyloid deposition in samples obtained from shoulder surgery is beneficial for the early detection of cardiac amyloidosis.

The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines. Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands. Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects.

A multiobjective high-degree-of-freedom design optimization algorithm that enables topological changes in design is proposed for multiobjective aerodynamic design optimization. In this method, a design is encoded using a regional quadtree, which is often used in computer graphics to increase the speed and save memory in image processing. The optimization problem is solved using multiobjective genetic programming with new crossover, mutation, regularization, and decoding operators designed to handle the evolution of the quadtree structure efficiently and properly. The proposed algorithm is evaluated by solving two multiobjective airfoil shape reproduction problems. The results show that the proposed method can represent typical airfoil shapes with different topologies more efficiently than the conventional evolutionary algorithm.

Background/Aims Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. Methods The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. Results In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p

Abstract Background The flexion adduction internal rotation (FADIR) test is performed by the combined motions of hip flexion (with knee flexion), adduction, and internal rotation, and can often reproduce anterior hip pain consistent with an individual’s presenting pain. Since it has high sensitivity for intraarticular pathology diagnosis but low specificity, understanding the extraarticular pathology that can induce anterior hip pain in the FADIR test may also be essential. This study hypothesized that the interrelationships between the joint capsule and gluteus minimus differ in individuals with and without FADIR-positive pain and aimed to elucidate the in vivo interrelationships at hip internal rotation in 90°-flexion, which is also often restricted in individuals with FADIR-positive pain. Methods Ten hips were included in the FADIR-positive group, and ten hips without hip pain in the FADIR test were included in a control group. Based on the ultrasound images at the four hip rotation conditions (20° and 10° external rotations, 0° external/internal rotation, and 10° internal rotation), orientation measurements of the gluteus minimus (muscle belly portion) and joint capsule were performed and quantitatively compared between the FADIR-positive and control groups. Additionally, 3 hips of 3 participants were randomly selected from each of the control and FADIR-positive groups for magnetic resonance imaging analysis. Results At 0°-external/internal and 10°-internal rotation, on ultrasound images, fibers of the gluteus minimus and joint capsule in the FADIR-positive group were significantly more oriented in the same direction than those in the control group. Magnetic resonance imaging showed that the loose connective tissue between the gluteus minimus and joint capsule was prominent at 10°-internal rotation in the control group, although this was not apparent in the FADIR-positive group. Conclusions At hip internal rotation in 90° flexion, the muscular belly portion of the gluteus minimus and joint capsule were oriented in the same direction to a greater extent in the FADIR-positive group than in the control group owing to a morphological change in the loose connective tissue between them. The pathological changes in the loose connective tissue may inhibit smooth movement of the gluteus minimus relative to the joint capsule in individuals with FADIR-positive pain.

Abstract Medial meniscal extrusion (MME) is a structural abnormality that leads to early knee osteoarthritis; however, its formation remains debated. For anatomical consideration of the mechanism underlying MME formation, we examined the capsular attachment on the posteromedial tibia and its layered association with the semimembranosus. Fourteen knees of eight body donors were analyzed in this study; six knees were grouped for macroscopic analysis, whereas four knees each were grouped for histological and phosphotungstic acid-enhanced micro-computed tomography analyses. The capsular attachment varied in width according to location and was not distant from the articular cartilage and posterior root. A portion of the posteromedial joint capsule formed the semimembranosus tendinous sheath. The dense fibrous membrane superficial to the semimembranosus, which was continuous from its tendinous sheath, existed as one of the layers of the joint capsule. The aforementioned findings were confirmed in all specimens. Based on the capsular attachment and its layered association with the semimembranosus, the conventional posteromedial knee ligaments may be only a part of the joint capsule divided into two layers by the semimembranosus. If the coordinated action of the joint capsule and semimembranosus partially contributes to the medial meniscus stability, such a structural problem may affect MME formation.

Abstract Early detection of cervical myelopathy (CM) is important for a favorable outcome, as its prognosis is poor when left untreated. We developed a screening method for CM using machine learning-based analysis of the drawing behavior of 38 patients with CM and 66 healthy volunteers. Using a stylus pen, the participants traced three different shapes displayed on a tablet device. During the tasks, writing behaviors, such as the coordinates, velocity, and pressure of the stylus tip, along with the drawing time, were recorded. From these data, features related to the drawing pressure, and time to trace each shape and combination of shapes were used as training data for the support vector machine, a machine learning algorithm. To evaluate the accuracy, a receiver operating characteristic curve was generated, and the area under the curve (AUC) was calculated. Models with triangular waveforms tended to be the most accurate. The best triangular wave model identified patients with and without CM with 76% sensitivity and 76% specificity, yielding an AUC of 0.80. Our model was able to classify CM with high accuracy and could be applied to the development of disease screening systems useful outside the hospital setting.

Numerous cyanobacteria capable of oxygenic photosynthesis possess multiple large plasmids exceeding 100 kbp in size. These plasmids are believed to have distinct replication and distribution mechanisms, as they coexist within cells without causing incompatibilities between plasmids. However, information on plasmid replication proteins (Rep) in cyanobacteria is limited. Synechocystis sp. PCC 6803 hosts four large plasmids, pSYSM, pSYSX, pSYSA, and pSYSG, but Rep proteins for these plasmids, except for CyRepA1 on pSYSA, are unknown. Using Autonomous Replication sequencing (AR-seq), we identified two potential Rep genes in Synechocystis 6803, slr6031 and slr6090, both located on pSYSX. The corresponding Rep candidates, Slr6031 and Slr6090, share structural similarities with Rep-associated proteins of other bacteria and homologs were also identified in various cyanobacteria. We observed autonomous replication activity for Slr6031 and Slr6090 in Synechococcus elongatus PCC 7942 by fusing their genes with a construct expressing GFP and introducing them via transformation. The slr6031/slr6090-containing plasmids exhibited lower copy numbers and instability in Synechococcus 7942 cells compared to the expression vector pYS. While recombination occurred in the case of slr6090, the engineered plasmid with slr6031 coexisted with plasmids encoding CyRepA1 or Slr6090 in Synechococcus 7942 cells, indicating the compatibility of Slr6031 and Slr6090 with CyRepA1. Based on these results, we designated Slr6031 and Slr6090 as CyRepX1 (Cyanobacterial Rep-related protein encoded on pSYSX) and CyRepX2, respectively, demonstrating that pSYSX is a plasmid with “two Reps in one plasmid.” Furthermore, we determined the copy number and stability of plasmids with cyanobacterial Reps in Synechococcus 7942 and Synechocystis 6803 to elucidate their potential applications. The novel properties of CyRepX1 and 2, as revealed by this study, hold promise for the development of innovative genetic engineering tools in cyanobacteria.

An 80-year-old non-smoking woman was admitted to hospital due to persistent sputum production and dyspnea. She developed respiratory failure, and chest imaging revealed multifocal consolidation and cavities. Her respiratory status did not respond to antimicrobial treatment and progressively worsened, with massive sputum production of approximately 1 L per day, and she died 19 days after admission. The patient was diagnosed with invasive mucinous adenocarcinoma based on a postmortem needle biopsy of the lung. Clinicians should consider invasive mucinous adenocarcinoma in the differential diagnosis of patients who present with massive bronchorrhea and diffuse pulmonary cavity abnormalities.

Sulfatides are a type of sulfated glycosphingolipid that are secreted with lipoproteins into the serum. These molecules are involved in the inflammatory pathway of vessels in addition to coagulation and platelet aggregation. Previous studies have proposed that sulfatides play a pivotal role in regulating inflammation-related disorders. Systemic vasculitis (SV) diseases are generally caused by autoimmune diseases and often involve kidney vasculitis, which may lead to rapidly progressive kidney dysfunction and end-stage kidney disease. Our earlier pilot study revealed that the level of serum sulfatides (SSs) was significantly decreased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), a representative disease-causing SV with kidney involvement (SVKI), especially in patients exhibiting active crescentic findings on kidney biopsy. To further explore the clinical significance of an association between SS and SVKI, we analyzed and compared the SS level of patients with various SVKI diseases in this retrospective cohort study. Among patients admitted to our hospital between 2008 and 2021, we ultimately enrolled 26 patients with IgA vasculitis (IgAV), 62 patients with AAV, and 10 patients with anti-glomerular basement membrane disease (GBM) as examples of SVKI diseases, as well as 50 patients with IgA nephropathy (IgAN) and 23 donors for living kidney transplantation as controls. The mean ± standard deviation SS level in the donor, IgAN, IgAV, AAV, and GBM groups was 8.26 ± 1.72, 8.01 ± 2.21, 6.01 ± 1.73, 5.37 ± 1.97, and 2.73 ± 0.99 nmol/mL, respectively. Analysis of patients in the SVKI disease group showed that those with the crescentic class kidney biopsy finding exhibited a significantly lower SS level than did those with other class biopsy features. Additionally, the SS level had a higher detection ability for SVKI patients with crescentic class kidney biopsy findings (area under the receiver operating characteristic curve 0.90, 95% confidence interval 0.82–0.99) than did several other predictor candidates. Our results indicate that the SS level is decreased in more severe SVKI diseases and may be associated with active glomerular lesions in SVKI kidney biopsy samples.

Abstract Olecranon fractures are a common injury in fractures. The tension band technique for olecranon fractures yields good clinical outcomes; however, it is associated with significant complications. In many patients, implants irritate overlying soft tissues and cause pain. This is mostly due to protrusion of the proximal ends of the K-wires or by the twisted knots of the metal wire tension band. Below we described 2 cases of olecranon fractures treated with a unique technique using FiberWire without any metallic implants. Technically, the fragment was reduced, and two K-wires were inserted from the dorsal cortex of the distal segment to the tip of the olecranon. K-wire was exchanged for a suture retriever, and 2 strands of FiberWire were retrieved twice. Each of the two FiberWires was manually tensioned and knotted on the posterior surface of the olecranon. Bony unions could be achieved, and patients had no complaint of pain and skin irritation. There was only a small loss of flexion and extension in comparison with that of the contralateral side, and the patient did not feel inconvenienced in his daily life. Using the method described, difficulty due to K-wire or other metallic implants was avoided.

Abstract Background Though sera are essential for Mesenchymal stem cells (MSCs), the effect of heat-inactivation remains unknown. Autologous human serum is recommended for clinical use; however, it is unclear whether differentiation potentials are maintained. To examine whether heat-inactivation of serum affected the proliferation and whether autologous human serum influenced their multipotentiality. Methods After whole blood collection, human synovium and bone marrow were harvested. Nucleated cells were expanded with autologous human serum and FBS. Results Heat-inactivation of autologous human serum enhanced proliferation of synovial MSCs. Heat-inactivation of each types of serum didn't affect calcification of synovial MSCs. The induction of calcification increased ALP activity, with the exception of bone marrow MSCs with autologous human serum. For adipogenesis of synovial MSCs, the Oil Red-O positive colony forming efficiency with autologous human serum was similar to or less than that with FBS. Conclusion These clarified the processing of human autologous serum and the influence of different sera for differentiation of synovial and bone marrow MSCs.

Background/Aims Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. Methods This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. Results Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p