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Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Some individuals have a normal audiogram but have listening difficulties (LiD). As many studies have investigated the relationship between listening and developmental disorders, the traits of developmental disorders might explain the symptoms of LiD. In this study, we examined the traits of developmental disorders of adults with LiD to help clarify the cause of LiD symptoms. Methods: In total, 60 adults with LiD and 57 adults without LiD were included. Participants completed a questionnaire for the autism spectrum quotient (AQ) test, the Adult Attention-Deficit Hyperactivity Disorder Self-Rating Scale (A-ADHD), the Adolescent/Adult Sensory Profile (SP), and the severity of subjective LiD in daily life. Results: Before analysis, we excluded participants with LiD who were already diagnosed or met the criteria for autism spectrum disorder (ASD) or ADHD, and the results of the remaining 30 participants (50.0%) with LiD were analyzed. Adults with LiD showed higher scores than those without LiD in the AQ. Attention switching in the AQ and attention ability in the A-ADHD scale were correlated with the severity of LiD symptoms in everyday life. The AQ scores were also significantly correlated with subscales of the SP. Conclusions: Adults with LiD showed greater autistic traits than those without LiD; therefore, LiD symptoms are possibly related to autistic symptoms. Furthermore, adults with LiD might have attention disorder traits of both ASD and ADHD and sensory processing problems. These findings suggest that the attention problems in adults with LiD noted in previous studies might be related to these traits of developmental disorders.

Certain mutations can confer neomorphic gain of function (GOF) activities to the p53 protein that affect cancer progression. Yet the concept of mutant p53 GOF has been challenged. Here, using various strategies to alter the status of mutant versions of p53 in different cell lines, we demonstrate that mutant p53 stimulates cancer cell invasion in three-dimensional environments. Mechanistically, mutant p53 enhances RhoA/ROCK-dependent cell contractility and cell-mediated extracellular matrix (ECM) re-organization via increasing mevalonate pathway-dependent RhoA localization to the membrane. In line with this, RhoA-dependent pro-invasive activity is also mediated by IDI-1, a mevalonate pathway product. Further, the invasion-enhancing effect of mutant p53 is dictated by the biomechanical properties of the surrounding ECM, thereby adding a cell-independent layer of regulation to mutant p53 GOF activity that is mediated by dynamic reciprocal cell-ECM interactions. Together our findings link mutant p53 metabolic GOF activity with an invasive cellular phenotype in physiologically relevant and context-dependent settings., Significance: This study addresses the contribution of mutant p53 to the process of cancer cell dissemination in physiologically relevant three-dimensional environments - a key characteristic of metastatic disease. Several mutant p53 proteins display pro-oncogenic activity with respect to cancer cell invasion in 3D environments via mevalonate pathway-dependent Rho/ROCK signaling axis.

Evaluating the Gibbs-Donnan and volume exclusion effects during protein ultrafiltration and diafiltration (UF/DF) is crucial in biopharmaceutical process development to precisely control the concentration of the drug substance in the final formulation. Understanding the interactions between formulation excipients and proteins under these conditions requires a domain-specific knowledge of molecular-level phenomena. This study developed gradient boosted tree models to predict the Gibbs-Donnan and volume exclusion effects for amino acids and therapeutic monoclonal antibodies using simple molecular descriptors. The models' predictions were interpreted by information gain and Shapley additive explanation (SHAP) values to understand the modes of action of the antibodies and excipients and to validate the models. The results translated feature effects in machine learning to real-world molecular interactions, which were cross-referenced with existing scientific literature for verification. The models were validated in pilot-scale manufacturing runs of two antibody products requiring high levels of concentration. By only requiring a molecule's biophysicochemical descriptors and process conditions, the proposed models provide an in silico alternative to conventional UF/DF experiments to accelerate process development and boost process understanding of the underlying molecular mechanisms through rational interpretation of the models., (© 2024 Chugai Pharmaceutical Co., Ltd. Biotechnology Journal published by Wiley‐VCH GmbH.)

Background: Left ventricular outflow tract stenosis and atrioventricular valve regurgitation are often problems encountered in adulthood after complete atrioventricular septal defect repair. The surgical approach and indications for managing long-term outcomes such as left atrioventricular valve regurgitation and left ventricular outflow tract stenosis after complete atrioventricular septal defect repair have been discussed., Case Presentation: A 23-year-old woman with intellectual disability was diagnosed with complete atrioventricular septal defect and underwent two-patch repair without cleft closure in childhood. Follow-up examination in adulthood demonstrated moderate left-sided atrioventricular valve regurgitation and left ventricular outflow tract stenosis with a circumferential ridge (peak velocity, 3.7 m/s; pressure gradient, 54 mmHg). Intraoperative findings showed a circumferential ridge under the aortic valve, and we removed the ridge. In addition, a cleft was present at the anterior leaflet, and we completely closed the cleft. Anticoagulation therapy was not initiated, and no embolic complications occurred. Follow-up echocardiography demonstrated no ridge under the aortic valve and only mild-range left AVVR., Conclusions: We successfully performed surgical treatment without valve replacement or anticoagulation therapy in a patient with poor medical compliance. Delayed reoperation leads to degeneration of the valve structure and makes more difficult to repair. Atrioventricular valve regurgitation should be evaluated in combination with based on the etiology of the regurgitation especially cleft related or not, in addition to the dilatation annulus, cleft size, and depth of the leaflet coaptation depth, and associated other valve diseases., (© 2024. The Author(s).)

Background: Left atrial (LA) plication is a procedure used to correct an LA that expands posteriorly due to remodeling. This study aimed to determine the efficacy of additional LA plication in reducing postoperative cardiovascular events (CVEs) after mitral valve (MV) repair in atrial functional mitral regurgitation (MR) patients., Methods: Between October 2008 and August 2023, MV repair with or without LA plication in 74 patients was studied. This study examined the efficacy of concomitant LA plication during MV repair., Results: All patients underwent mitral annuloplasty. Of these, 26 underwent additional LA plication. In the mid-term periods, protruding posterior LA length in patients with LA plication was shorter than those without LA plication (2.8±0.49 vs . 3.3±0.72 cm, P=0.01). The percentage change in aortomitral angle from preoperative to mid-term periods in patients with LA plication was bigger than those without LA plication (1.04°±0.102° vs . 0.98°±0.084°, P=0.01). Posterior leaflet coaptation angle in patients with LA plication was smaller than those without LA plication (42°±15° vs . 76°±30°, P<0.001). A postoperative posterior leaflet coaptation angle of 101° had the maximum sum of sensitivity and specificity in predicting postoperative CVEs (96.9% and 76.9%, respectively). Patients with a postoperative posterior leaflet coaptation angle of 101° or higher had a poorer prognosis than those with an angle less than 101°, with an event-free rate of 18% vs . 80% at 7 years after surgery (P<0.0001)., Conclusions: Additional LA plication might be useful in reducing postoperative CVEs in atrial functional MR patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Backgrounds: With recent developments in chemotherapy, the prognosis of head and neck cancer patients has been prolonged, and it is expected that totally implantable venous access devices will be developed for use as feasible and safe chemotherapy routes. We investigated the feasibility of implanting totally implantable venous access ports in the upper arms of head and neck cancer patients in this modern era of chemotherapy., Methods: Relevant data of a cohort of 210 patients with head and neck cancer who had had totally implantable venous access devices implanted between January 2013 and December 2022 were investigated retrospectively. The totally implantable venous access ports were used for chemoradiotherapy, chemotherapy, radiotherapy, and palliative treatment. Adverse events related to totally implantable venous access devices were investigated and the associated variables subjected to statistical analysis., Results: There were 22 (10.5%) adverse events, representing 0.201 adverse events per 1000 catheter days. Non-ultrasound-guided puncture ( p  = 0.015) and forearm implantation ( p  = 0.005) were associated with higher risk of adverse events according to univariate analysis. According to multiple logistic analysis, non-ultrasound-guided puncture was significantly associated with age and sex (OR = 2.89; 95% CI, 1.14, 7.36; p  = 0.026)., Conclusion: Peripherally implanted totally implantable venous access devices in the upper arm are feasible and safe for head and neck cancer patients. Ultrasound-guided implantation of totally implantable venous access ports into the upper arms of head and neck cancer patients may reduce the adverse event rate., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To examine the effects of distractor sounds presented to the contralateral ear on speech intelligibility in patients with listening difficulties without apparent peripheral pathology and in control participants., Design: This study examined and analyzed 15 control participants (age range, 22 to 30 years) without any complaints of listening difficulties and 15 patients (age range, 15 to 33 years) diagnosed as having listening difficulties without apparent peripheral pathology in the outpatient clinic of the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital. Speech intelligibility for 50 Japanese monosyllables presented to the right ear was examined under the following three different conditions: "without contralateral sound," "with continuous white noise in the contralateral ear," and "with music stimuli in the contralateral ear.", Results: The results indicated the following: (1) speech intelligibility was significantly worse in the patient group with contralateral music stimuli and noise stimuli; (2) speech intelligibility was significantly worse with contralateral music stimuli than with contralateral noise stimuli in the patient group; (3) there was no significant difference in speech intelligibility among three contralateral masking conditions (without contra-stimuli, with contra-noise, and with contra-music) in the control group, although average and median values of speech intelligibility tended to be worse with contralateral music stimuli than without contralateral stimuli., Conclusions: Significantly larger masking effects due to a contralateral distractor sound observed in patients with listening difficulties without apparent peripheral pathology may suggest the possible involvement of masking mechanisms other than the energetic masking mechanism occurring in the periphery in these patients. In addition, it was also shown that the masking effect is more pronounced with real environmental sounds, that is, music with lyrics, than with continuous steady noise, which is often used as a masker for speech-in-noise testing in clinical trials. In other words, it should be noted that a speech-in-noise test using such steady noise may underestimate the degree of listening problems of patients with listening difficulties in their daily lives, and a speech-in-noise test using a masker such as music and/or speech sounds could make listening problems more obvious in patients with listening difficulties., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This study aimed to evaluate the efficacy of preoperative computed tomography in assessing mitral annulus anatomy and the posterior annular plication rate in mitral valve repair with annuloplasty., Methods: From July 2018 to August 2023, we performed robotic mitral valve repair with ring annuloplasty using a semi-rigid ring in 100 patients. Preoperative anatomical assessment of the mitral annulus was conducted by three-dimensional computed tomography. The ring size was selected based on the perioperative commissure-to-commissure length or the anterior leaflet area., Results: The mean commissure-to-commissure length, posterior mitral annular length, and minimum distance between the left circumflex artery and mitral annulus values were 31, 109, and 3.8 mm, respectively. No postoperative left circumflex artery injury or ring detachment was recorded. The mean plication rate (length of the posterior side of the prosthetic ring/posterior annular length) was 0.68, and it did not differ among each prosthetic ring size. The posterior plication rate (duplicate ring size 19.4) was a factor influencing the postoperative transmitral mean pressure gradient of 5 mmHg or higher. Freedom from moderate or severe mitral regurgitation was not different between the two groups above and below the posterior plication rate × ring size of 19.4 ( p  = 0.73), with an event-free rate of 97% vs. 96% in 3 years, respectively., Conclusions: Preoperative evaluation of the mitral annular anatomy is useful for safe mitral valve repair with ring annuloplasty. Determining ring size by focusing on the posterior annular plication rate may be a new method for ring size selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Takahashi, Morisaki, Sakon, Nishiya, Inno, Kawase, Nishimoto, Nagao, Kishimoto, Noda and Shibata.)

Introduction: Osseointegration, the direct contact between an implant and bone, can be achieved by direct and/or indirect osteogenesis. Platelet-rich plasma accelerates tissue regeneration, wound healing, and osseointegration. This study aimed to analyze the effects of leukocyte and platelet-rich plasma (L-PRP) on direct and indirect osteogenesis after implant placement in a mouse maxilla., Methods: Blood was collected from the tail vein of 4-8-week-old male ICR mice and L-PRP was obtained after double-spin cycle centrifugation. After the right upper first molars of 4-week-old ICR mice were extracted while under deep anesthesia, the alveolar sockets were prepared with a drill, and titanium implants blasted with hydroxyapatite/β-tricalcium phosphate were placed into the cavity filled with 1.5 μL of L-PRP. Samples were collected from the animals 3-28 days after implantation, and immunohistochemistry for osteopontin, Ki67 (cell proliferation marker), cathepsin-K (osteoclast marker), and osteonectin (osteoblast marker) was performed., Results: Cell proliferation was significantly higher in the L-PRP group than in the control group on postoperative days 3 and 5. The activities of osteoclast-lineage cells and osteoblasts increased significantly on day 5 in the L-PRP group, indicating that L-PRP evoked an active cellular response. Indirect osteogenesis was significantly higher on days 7, 14, and 28, and the osseointegration rate was significantly higher on day 28 in the L-PRP group compared with the control group., Conclusions: L-PRP enhances osseointegration by promoting mesenchymal cell proliferation, osteoclastic and osteoblastic activities, and indirect osteogenesis., Competing Interests: The authors declare no conflicts of interest related to this study., (© 2024 The Author(s).)

Background: fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability., Methods: Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction., Result: NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF., Conclusion: At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP., Competing Interests: The authors declare no conflicts of interest. Particularly, the authors have no benefit in writing the innovativeness of the dye (MT-1) used in the present study., (Copyright © 2024 Tsujino, Kasahara, Kawabata, Watanabe, Nishiyama, Kitamura, Watanabe, Okudera, Mochizuki, Ushiki and Kawase.)

Therapeutic oligonucleotides such as antisense oligonucleotide (ASO) and small interfering RNA (siRNA) are among the most remarkable modalities in modern medicine. ASOs and siRNA are composed of single- or double-stranded 15-25 mer synthesized oligonucleotides, which can be used to modulate gene expression. Liquid chromatography-mass spectrometry (LC/MS) is a necessary technique for the quality control of therapeutic oligonucleotides; it is used to evaluate the quantities of target oligonucleotides and their impurities. The widely applied oligonucleotide therapeutic quantitation method uses both ultraviolet (UV) absorbance and the MS signal intensity. Peaks separated from the main peak, which contains full-length product, are generally quantitated by UV. However, coeluting impurities, such as n - 1 shortmers, abasic oligonucleotides, and PS → PO (phosphorothiate to phosphodiester) oligonucleotides, are quantitated by MS. These coeluting impurities can also be comprised of various isomers with the same modification, thus increasing the difficulty in their separation and relative quantitation by LC/MS. It is possible that a specific isomer with a certain structural form induces toxicities. Therefore, characterization of each isomer separation is in high demand. In this study, we separated and characterized oligonucleotide isomers by employing a cyclic ion mobility mass spectrometry (cyclic IMS) system, which allows the separation of ions with the same m / z ratio based on their structural differences. Patisiran antisense and sense strands and their n - 1 and abasic isomers were used as sample sequences, and their ratio characterization was achieved by cyclic IMS. In addition, we evaluated the PS → PO conversion isomers of the antisense strand of givosiran, which originally contained four PS modification sites. The PS → PO isomers exhibited specific and distinguishable mobiligram patterns. We believe that cyclic IMS is a promising method for evaluating therapeutic oligonucleotide isomers.

The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure-function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells., (© 2024. The Author(s).)

Background: We report a case of suspected autoimmune encephalopathy with involuntary movements and concomitant cognitive dysfunction after COVID-19., Case Presentation: The patient is a male in his 20s who presented with fever and generalized involuntary movements and was diagnosed with COVID-19. The involuntary movements improved slightly, and the fever resolved within a week of the diagnosis. However, about a month later, the patient presented with severe recurrence of the involuntary movements. Antiepileptic drugs were ineffective, and the patient was re-hospitalized with suspected autoimmune encephalopathy. The electroencephalogram (EEG) was difficult to assess accurately due to involuntary movements. Neuropsychological testing on re-admission revealed mild memory impairment, executive dysfunction, and decreased processing speed. We treated the patient with methylprednisolone (mPSL) 1000 mg/day for a total of 8 days and intravenous immunoglobulin therapy (IVIG) 27.5 g/day for 5 days. Involuntary movements were mild after 59 days. A repeat neuropsychological assessment conducted 3 weeks later showed improvement of both memory and executive functions. The patient was discharged on Day 75, and he returned to work the following month., Conclusion: In our patient reported herein, early and appropriate treatment was successful. Impaired activities of daily living and cognitive dysfunction rapidly improved. The case serves to underscore the importance of early detection and intervention for the sequelae of COVID-19., Competing Interests: The authors declare no conflict of interest., (© 2024 The author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complete eradication of the virus remains a formidable challenge. Cytotoxic T lymphocytes, specific to viral antigens, either exhibit a numerical deficiency or succumb to an exhausted state in individuals chronically afflicted with HBV. The comprehension of the genesis and dissemination of stem cell memory T cells (TSCMs) targeting HBV remains inadequately elucidated. We identified TSCMs in subjects with chronic HBV infection and scrutinized their efficacy in a murine model with human hepatocyte transplants, specifically the TK-NOG mice. TSCMs were discerned in all subjects under examination. Introduction of TSCMs into the HBV mouse model precipitated a severe necro-inflammatory response, resulting in the elimination of human hepatocytes. TSCMs may constitute a valuable tool in the pursuit of a remedial therapy for HBV infection., (© 2024 Federation of European Biochemical Societies.)

Plasma gel (PG) is a protein matrix prepared from platelet-poor plasma and can be utilized as a drug carrier for controlled release. We previously demonstrated its applicability as a carrier of polyphosphate. Epigallocatechin-3-gallate (EGCG) is the main flavonoid found in green tea and functions as a strong antioxidant. To explore the applicability of PG as an EGCG carrier, we examined the release of EGCG from the PG matrix using an in vitro system. Pooled platelet-poor plasma (PPP) was prepared from four healthy adult male donors, mixed with EGCG, and heated at 75 °C for 10 or 20 min to prepare the PG matrix. The PG-EGCG matrix was incubated in PBS at 37 °C, and the EGCG released into PBS was determined using spectrophotometry. The antioxidant capacity was determined based on the principle of the iodine decolorization reaction. EGCG precipitated and incorporated into the PG matrix during thermal preparation. Trypsin, used to simulate the in vivo degradation of PG, released EGCG from the PG matrix over time. The released EGCG maintained its antioxidant capacity during incubation. These results indicate that thermally prepared PG matrices can be utilized as a promising EGCG carrier in the fields of tissue engineering and regenerative medicine.

Background: Neuroscience research in Drosophila is benefiting from large-scale connectomics efforts using electron microscopy (EM) to reveal all the neurons in a brain and their connections. To exploit this knowledge base, researchers relate a connectome's structure to neuronal function, often by studying individual neuron cell types. Vast libraries of fly driver lines expressing fluorescent reporter genes in sets of neurons have been created and imaged using confocal light microscopy (LM), enabling the targeting of neurons for experimentation. However, creating a fly line for driving gene expression within a single neuron found in an EM connectome remains a challenge, as it typically requires identifying a pair of driver lines where only the neuron of interest is expressed in both. This task and other emerging scientific workflows require finding similar neurons across large data sets imaged using different modalities., Results: Here, we present NeuronBridge, a web application for easily and rapidly finding putative morphological matches between large data sets of neurons imaged using different modalities. We describe the functionality and construction of the NeuronBridge service, including its user-friendly graphical user interface (GUI), extensible data model, serverless cloud architecture, and massively parallel image search engine., Conclusions: NeuronBridge fills a critical gap in the Drosophila research workflow and is used by hundreds of neuroscience researchers around the world. We offer our software code, open APIs, and processed data sets for integration and reuse, and provide the application as a service at http://neuronbridge.janelia.org ., (© 2024. The Author(s).)

Background: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy., Methods: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively., Results: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss., Conclusion: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively., Clinical Trial Registration: UMIN000023455., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear., Methods: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test., Results: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia., Conclusions: Dysgeusia was the most frequent and severe oral trouble.

Background: According to the sixth Gastric Cancer Treatment Guideline, the regimen included nab-paclitaxel(nab-PTX) is a conditional recommendation as second-line treatment for advanced gastric cancer. However, the selection criteria of nab-PTX is not clear., Method: Questionnaire survey as narrative approach on the problems of paclitaxel premedication, the symptoms due to paclitaxel containing alcohol, and infusion time was conducted for patients who had been treated with paclitaxel., Results: Thirty-six patients answered the questionnaire. Nonelderly patients(<65 years)or patients without comorbid medications complained of dissatisfaction with the inconvenience due to premedication significantly more than elderly patients(≥65 years)or patients with comorbid medications. Females or nonelderly patients were significantly more troubled by sleepiness due to premedication than males or elderly patients. Eight out of 11 patients who had visited hospital by driving a car for first-line treatment were troubled by prohibition of driving on the day of treatment. Thirty out of 36 patients answered that they would feel benefits from 30-minutes shortening of infusion time., Conclusion: Questionnaire survey suggests that we may select the patients for nab-PTX properly by clarifying the inconvenience of daily life associated with premedication, the way of transportation for visiting hospital, and the benefits by shortening of infusion time.

Epicardial adipose tissue (EAT) has been reported to promote myocardial fibrosis and to affect intracardiac conduction. The PR interval reflects the conduction from the atria to the Purkinje fibers and may be associated with the EAT volume, especially in persistent atrial fibrillation (AF) patients. We aimed to investigate the relationship between the EAT and PR interval in patients with persistent AF. We enrolled 268 persistent AF patients who underwent catheter ablation (CA) and divided the patients into two groups: the normal PR interval group (PR interval less than 200 ms: Group N) and long PR interval group (PR interval 200 ms or more: Group L). We then analyzed the association between the total EAT volume around the heart and PR interval and calculated the ratio of the duration of the P wave (PWD) to the PR interval (PWD/PR interval). Moreover, we investigated whether a long PR interval was associated with the outcomes after ablation. The total EAT volume was significantly larger in Group L than Group N (Group N: 131.4 ± 51.8 ml vs. Group L: 151.3 ± 63.3 ml, p = 0.039). A positive correlation was also observed between the PWD/PR interval and EAT volume in Group L (r = 0.345, p = 0.039). A multivariate analysis also revealed that a long PR interval was independently associated with AF recurrence after CA (hazard ratio [HR] 2.071, p = 0.032). The total EAT volume was associated with a long PR interval, and a long PR interval was a significant risk factor for recurrence after ablation in persistent AF patients., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

N -2,6-Di(isopropyl)phenyl-2-azaphenalenyl radical cations were obtained as a dark brown air-sensitive crystalline compound. The high HOMA values and the ACID calculation indicate relatively high aromatic character of a 5,8-di- tert -butyl derivative, and clean generation of a derivative without tert -butyl groups indicates that the di(isopropyl)phenyl group is sufficient for hampering the formation of the σ-dimer.

Background: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data., Methods: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m 2 , day 1; S-1: 80 mg/m 2 , days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%., Results: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%)., Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: The "collapse," a highly flexed, dented, or caved membrane between the endo- and peri-lymph of the saccule and utricle in adults, is considered as a morphological aspect of Ménière's syndrome. Likewise, when mesh-like tissues in the perilymphatic space are damaged or lost, the endothelium loses mechanical support and causes nerve irritation. However, these morphologies were not examined in fetuses., Methods: By using histological sections from 25 human fetuses (crown-rump length[CRL] 82-372 mm; approximately 12-40 weeks), morphologies of the perilymphatic-endolymphatic border membrane and the mesh-like tissue around the endothelium were examined., Results: The highly flexed or caved membrane between the endo- and peri-lymphatic spaces was usually seen in the growing saccule and utricle of fetuses, especially at junctions between the utricle and ampulla at midterm. Likewise, the perilymphatic space around the saccule, utricle and semicircular ducts often lost the mesh-like tissues. The residual mesh-like tissue supported the veins, especially in the semicircular canal., Conclusion: Within a cartilaginous or bony room showing a limited growth in size but containing increased perilymph, the growing endothelium appeared to become wavy. Owing to a difference in growth rates between the utricle and semicircular duct, the dentation tended to be more frequently seen at junctions than at free margins of the utricle. The difference in site and gestational age suggested that the deformity was not "pathological" but occurred due to unbalanced growth of the border membrane. Nevertheless, the possibility that the deformed membrane in fetuses was an artifact caused by delayed fixation is not deniable., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The authors report on the anterior transpetrosal approach (ATPA) and the results of surgeries performed over a 33-year period for petroclival tumors, including meningioma, trigeminal schwannoma, chordoma, and epidermoid tumor. They analyze early postoperative neurological changes, surgical complications, and trends over the decades., Methods: A retrospective analysis of 274 surgical cases that had undergone the ATPA from January 1984 to March 2017 was conducted. Data were collected from charts, clinical summaries, operative records, and operative videos. The analyzed parameters included patient diagnosis, tumor size, disease location, operation date, tumor removal rate, pre- and postoperative neurological symptoms (consciousness level, motor and sensory deficits of the limbs, sensory aphasia, and cranial nerve III-VIII injuries), surgical deaths, and radiologically recognized brain injuries after the operation (contusion, infarction, hemorrhage)., Results: Gross-total resection (GTR) was achieved in 53.5% of the 243 tumors with available data. The GTR rate for meningiomas (148 cases) was 54.1%. Trigeminal schwannomas had a high GTR rate of 87.1%, whereas chordomas had a low GTR rate of 14.3%. The rate of early neurological deterioration immediately after the ATPA, referred to as "early neurological change," was as follows: consciousness disturbance in 1.9% of cases (5 cases), improvement of hemiparesis in 45.0% of cases but deterioration in 8.1% of cases, sensory aphasia in 2.3% of cases due to temporal lobe injury, improvement of cerebellar symptoms in 39.3% of cases with rare deterioration (1.9% of cases), worsening of preoperative diplopia in 49.4% of patients and rarely improving, improvement of trigeminal symptoms in 19.1% of cases (mostly trigeminal neuralgia) among the 43.7% of patients who had them preoperatively, and deterioration of facial hypesthesia and/or paresthesia in 27.4% of cases. Early neurological deterioration was monitored in 183 patients for 6 months to determine the surgical complications of ATPA. Consciousness disturbance recovered in half of the cases but persisted in 3 (1.5%). Hemiparesis fully recovered in 63.2% of cases, resulting in a complication rate of 3.0%. The most frequent complication was diplopia (36.4%), with a complete remission rate of 26.4%. The second most frequent complication was facial hypesthesia (24.0%), with a recovery rate of 16.1%. Facial nerve palsy improved in 63.0% of cases and had a complication rate of 4.9%. Cerebellar symptoms showed complete recovery in all cases., Conclusions: The ATPA allows the removal of petroclival tumors extending into Meckel's cave and the middle fossa, making it preferred for dumbbell trigeminal schwannomas and meningiomas. However, the ATPA's aggressive tumor removal can risk a lower recovery of cranial nerve IV-VI deficits. For benign meningiomas, initial observation with regular follow-up is recommended. Surgery is appropriate for high-growth cases aiming for total removal, accompanied by a thorough explanation of the risks. If the risks are not accepted, subtotal removal can be considered, and radiosurgery is suggested for residual tumor.

The Y-incision technique introduced by Dr. Bo Yang in 2021 is a very innovative technique that can enlarge the aortic annulus by two or more sizes without violating the left atrium or mitral valve. However, we encountered a case in which the left coronary artery ostium was located close to the left-non commissure. Therefore, we considered it would be dangerous to expand the incision to the left coronary annulus. We therefore devised a new technique that enlarges only the noncoronary annulus in an "L" fashion instead of a "Y" fashion. In performing this surgery, preoperative three-dimensional images were useful for understanding the anatomy when planning the aortic annular enlargement procedure. The L-incision technique can be a useful alternative method of aortic annulus enlargement.

Background: Vibrio vulnificus NCIMB2137, a Gram-negative, metalloprotease negative estuarine strain was isolated from a diseased eel. A 45 kDa chymotrypsin-like alkaline serine protease known as VvsA has been recently reported as one of the major virulence factor responsible for the pathogenesis of this strain. The vvsA gene along with a downstream gene vvsB, whose function is still unknown constitute an operon designated as vvsAB., Objective: This study examines the contribution of VvsB to the functionality of VvsA., Method: In this study, VvsB was individually expressed using Rapid Translation System (RTS system), followed by an analysis of its role in regulating the serine protease activity of VvsA., Result: The proteolytic activity of VvsA increased upon the addition of purified VvsB to the culture supernatant of V. vulnificus. However, the attempts of protein expression using an E. coli system revealed a noteworthy observation that protein expression from the vvsA gene exhibited higher protease activity compared to that from the vvsAB gene within the cytoplasmic fraction. These findings suggest an intricate interplay between VvsB and VvsA, where VvsB potentially interacts with VvsA inside the bacterium and suppress the proteolytic activity. While outside the bacterial milieu, VvsB appears to stimulate the activation of inactive VvsA., Conclusion: The findings suggest that Vibrio vulnificus regulates VvsA activity through the action of VvsB, both intracellularly and extracellularly, to ensure its survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Methods in which patient-derived T cells are genetically modified in vitro and administered to patients have been demonstrated effective in the area of cancer immunotherapy. However, these methods have some unresolved issues such as cost, time, and unstable quality. Several groups have developed strategies to overcome these barriers by regenerating T cells from iPSCs. We have been developing a method in which specific TCR genes are introduced into iPSCs and T cells are regenerated from these iPSCs (TCR-iPSC method). We are now using starting iPSCs from the iPSC stock lines provided by CiRA-F, as the iPSC stock cells are less likely to be rejected. A study aimed at application to solid tumors demonstrated the therapeutic effect of regenerated T cells in a patient tissue xenograft model of WT1 antigen-positive renal cell carcinoma. This article will also discuss strategies by other groups to regenerate various types of T cells from iPSCs.

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B 12 (VB 12 ) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB 12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB 12 -free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB 12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB 12 had a low concentration of cecal propionate, adding high amounts of VB 12 to HACS diets provided sufficient amounts of VB 12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB 12 doses. To summarize, feeding high HACS decreased and increased cecal VB 12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB 12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.

A 60s female, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N1bM0, Stage Ⅲb, followed by adjuvant therapy with 8 courses CAPOX 2 years ago, had enhanced- computed tomography(CT)for follow-up and a 15-mm nodule near anastomotic site was found. 18F-fluorodeoxyglucose (FDG)-positron emission tomography(PET)CT revealed abnormal accumulation of 18F-FDG only to the lesion and diagnosis of"anastomotic recurrence"was made. We planned and safely performed resection of the anastomotic site and the nodule. The pathological diagnosis was fibromatosis-like tumor without evidence of recurrence, and margin was negative. Postoperative course was smooth and she was discharged on postoperative day 9. When we diagnose local recurrence, we need to keep it in mind that fibromatosis is one of the differential diagnoses, although its incidence rate is low.

A 70s male, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N3M0, Stage Ⅲc(without adjuvant chemotherapy), had enhanced-computed tomography(CT)for 3-month follow-up and a hepatic low-density area, an newly emergent nodule behind inferior vena cava and distal ileal tumor were found. Three months later, enhanced CT showed that the distal ileal tumor got exponentially larger and the diagnosis of"malignant lymphoma"was suspected. The patient became sepsis, so we planned and safely performed partial resection of the tumor. The pathological diagnosis was diffuse large B-cell lymphoma. Postoperative course was smooth except for the Clostridium difficile colitis and he was discharged on postoperative day 19. Although the regrowth of the remnant tumor was observed soon after surgery, partial response was confirmed after introduction of systemic chemotherapy. When we cope with malignant lymphoma of small intestine, we need to keep it in mind that surgery is an option for the prevention of perforation and bacterial translocation.

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

Immunotherapy has attracted considerable attention as a therapeutic strategy for cancers including acute myeloid leukemia (AML). In this study, we found that the development of several aggressive subtypes of AML is slower in Rag2 -/- mice despite the lack of B and T lymphocytes, even compared to the immunologically normal C57BL/6 mice. Furthermore, an orally active p53-activating drug shows stronger antileukemia effect on AML in Rag2 -/- mice than C57BL/6 mice. Intriguingly, Natural Killer (NK) cells in Rag2 -/- mice are increased in number, highly express activation markers, and show increased cytotoxicity to leukemia cells in a coculture assay. B2m depletion that triggers missing-self recognition of NK cells impairs the growth of AML cells in vivo. In contrast, NK cell depletion accelerates AML progression in Rag2 -/- mice. Interestingly, immunogenicity of AML keeps changing during tumor evolution, showing a trend that the aggressive AMLs generate through serial transplantations are susceptible to NK cell-mediated tumor suppression in Rag2 -/- mice. Thus, we show the critical role of NK cells in suppressing the development of certain subtypes of AML using Rag2 -/- mice, which lack functional lymphocytes but have hyperactive NK cells., (© 2023. The Author(s).)

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-β1 (TGFβ1), platelet factor-4 (PF4), interleukin-1β (IL-1β), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFβ1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1β and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter's higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy.

Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL., (© 2023. The Author(s).)

We studied the clinicopathological findings of 5 patients with perforated colorectal cancer. Three patients were male, and the primary cancer site was left side colon in 4 patents. Two patients had endoscopy-related perforation. The chief complaint was abdominal pain in all cases. All patients underwent emergency surgery. Two patients had Stage Ⅱ cancer, 3 had Stage Ⅳ. The mean ICU stay was 2.8 days. The average postoperative hospital stay was 71.8 days. Three patients were discharged home and 2 were transferred to other hospitals. The 3 patients who were discharged home received chemotherapy. Perforation of the cancer site is a risk factor for recurrence, and early recovery and additional treatment should be considered.

The patient was a 78-year-old woman. She presented with anemia and a positive fecal occult blood test. Endoscopic findings revealed type 3 advanced gastric cancer. As it had metastasized to the para-aortic lymph node(PALN: No. 16a2 lat), it was diagnosed as gastric cancer at cardia cT4aN1(No.1)M1(No.16a2 lat), cStage Ⅳ. She was administered S-1, oxaliplatin, and nivolumab(SOX plus Nivo)therapy as a first-line treatment. SOX plus Nivo resulted in a remarkable reduction of the lymph nodes, which were PR. After 3 courses of chemotherapy, a laparoscopic proximal gastrectomy was performed, with D2 plus No. 16a2 int/lat lymph nodes dissection as conversion surgery. Histopathological examination was pT3N0M0, and R0 resection was pStage ⅡA. She was discharged at POD21 and started S-1 from POD69. The patient is alive with no signs of recurrence 10 months postoperatively.

We report our experience with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma., Methods: Fourteen patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab at our department were retrospectively evaluated for antitumor efficacy and adverse events., Results: Age ranged from 66-91 years(median 77.5 years), 11 males and 3 females, number of doses ranged from 2-26(median 13), and observation period ranged from 31-790 days (median 427 days). Antitumor efficacy was CR in 3 patients, PR in 3, SD in 6, and PD in 2. One patient with PD died 650 days after the start of treatment, but the others are still alive. Adverse events included proteinuria in 9 patients who discontinued bevacizumab, hypothyroidism requiring levothyroxine sodium hydrate in 7 patients, dermatitis in 2 patients, and colitis requiring hospitalization in 2 patients., Discussion: Despite the small number of cases, a high antitumor effect was observed with a CR rate of 21%. Although proteinuria and hypothyroidism were observed relatively frequently as adverse events, they were easily controlled and did not pose a major clinical problem.

Background: Although pancreatoduodenectomy is recommended as a radical surgery for duodenal carcinoma, it has been reported that pancreatoduodenectomy in elderly patients has a high risk of surgical complications., Case Presentation: A man in his 80's was diagnosed with advanced duodenal carcinoma, presenting with anemia(Hb 5.4 g/dL). Computed tomography scanning showed wall thickening in the descending leg of the duodenum, pancreatic invasion was suspected, and clinical diagnosis was Stage ⅡB(cT4N0M0). Although radical surgery was possible, the patient refused surgery considering the risks of surgical complications. The gastroduodenal bypass surgery was performed to control bleeding, and the patient was treated with S-1 plus oxaliplatin(SOX; S-1 100 mg/body, days 1-14; oxaliplatin 100 mg/m2, day 1 q21 days). After 6 courses of the SOX regimen, the wall thickening of duodenum disappeared, and SOX was switched to S-1 monotherapy (S-1 100 mg/body, days 1-28, q42 days)according to Grade 2 thrombocytopenia and decreased performance status. After 11 courses of S-1, upper gastrointestinal endoscopy showed that the tumor had disappeared, the biopsy of duodenum showed no evidence of malignancy, and chemotherapy was terminated. The patient has been followed up for 7 months without recurrence., Conclusions: SOX for elderly patient showed efficacy against hemorrhagic duodenal carcinoma.

Introduction: Neoadjuvant chemotherapy with gemcitabine plus S-1(NAC GS)has been reported to prolong the prognosis of resectable pancreatic cancer, and is now being used in daily practice. In this study, we investigated the tolerability and outcome of neoadjuvant GS therapy for resectable pancreatic cancer in our hospital., Patients: Fifty-two patients who underwent NAC GS for resectable pancreatic cancer between November 2019 and March 2023 were included in this study., Results: The mean age of all 52 patients was 75 years, 28 were male and 24 were female. Tumor site was pancreatic head cancer in 32 patients, pancreatic body cancer in 13 patients, and pancreatic tail cancer in 8 patients. Only 2 patients of the 52 patients completed 2 cycles of GS therapy with full dose, and dose reduction and treatment deferral were performed in remaining 50 patients. The dose intensity was 78.4% for gemcitabine and 66.7% for S-1. Grade 3 or higher adverse events included neutropenia in 21 patients(40.4%), biliary tract infection in 6 patients(11.5%), fatigue, anorexia, hepatic dysfunction, and constipation in 1 patient each(1.9%). 47 patients(90.4%)underwent R0 resection. 4 patients had pancreatic fistula, which was classified as Grade Ⅲ by Clavien-Dindo, and one of them died in the hospital due to bleeding from a pseudoaneurysm., Conclusion: NAC GS therapy for resectable pancreatic cancer was considered feasible with appropriate management of adverse events.

The patient was a 70-year-old man. The patient had progressive anemia while taking 10 mg/day of prednisolone and 100 mg/day of mizoribine orally for bullous pemphigoid, a colonoscopy diagnosed ascending colon cancer. Adenocarcinoma, Group 5 was detected on biopsy. Abdominal computed tomography showed no metastases. The tumor was diagnosed as ascending colon cancer, cT4aN0M0, cStage Ⅱb. We performed laparoscopic right hemicolectomy and D3 dissection. Histopathological examination revealed pT3N0M0, pStage Ⅱa. In the present report, we describe a case of the ascending colon cancer with bullous pemphigoid, and discuss the case with a review of the literature.

Bulky N+ gastric cancer has a poor prognosis. The results of JCOG0405 showed the efficacy of neoadjuvant chemotherapy with S-1 plus cisplatin combination therapy for Bulky N+ gastric cancer. JLSSG0901 demonstrated the safety and efficacy of laparoscopic surgery for advanced gastric cancer. But the safety of laparoscopic surgery for locally advanced and extensive nodal metastasis cancer(T4b, para-aortic lymph node metastasis)is not apparent. After DOS therapy, we performed total laparoscopic gastrectomy, DP(distal pancreatectomy), D2+ #16a2/b1 lat, and Roux-en-Y reconstruction, and histopathological results showed that the aortic lymph node metastasis disappeared. We controlled extensive lymph node metastasis using preoperative triplet chemotherapy. Laparoscopic surgery after preoperative chemotherapy for Bulky N+ gastric cancer can be a treatment option because we performed laparoscopic resection and para-aortic lymph node dissection with no complications, including pancreatic complications.

Platelet-rich fibrin (PRF) is a popular autologous blood-derived biomaterial that is used in regenerative therapy. Owing to its simple preparation without additional factors, the PRF quality directly reflects the characteristics of individual blood samples. Antiplatelet or anticoagulant drugs can hamper the successful preparation of PRF. We recently observed similar phenomena in metformin-taking type-2 diabetics (T2DM). Thus, we hypothesized that metformin interferes with platelet function, thereby suppressing coagulation. For practical reasons, leukocyte- and platelet-rich plasma was prepared from healthy male donors (n = 9-15, age: 26-80 years) and treated with metformin (1-10 mM) for 24-72 h. Intrinsic and extrinsic coagulation activities were evaluated using prothrombin time (PT) and activated partial thromboplastin time (ATPP). Platelet adhesion and aggregation assays were performed using ADP stimulation. Among the parameters tested, APTT was the most sensitive and was significantly prolonged in the concentration range of 1-10 mM in a time- and concentration-dependent manner. Although obtained from healthy platelets and relatively higher concentrations of metformin, these findings suggest that metformin may induce further dysfunction of platelets to suppress intrinsic coagulation activity in T2DM patients, leading to failure of PRF preparation. This phenomenon may not have a severe impact on clinical diabetology or hematology. However, clinicians using PRF are recommended to be more sensitive to such information to avoid unexpected events in clinical settings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tomoyuki Kawase reports financial support was provided by Japan Society for the Promotion of Science. Takashi Ushiki reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To evaluate Eustachian tube (ET) function after Kobayashi plug surgery based on the tympanic membrane (TM) findings and active opening (AO) of the ET assessed with sonotubometry., Subjects and Methods: A retrospective survey of medical records identified 74 ears of 66 patients with patulous ET (PET) received transtympanic insertion of the Kobayashi plug. Excluding the six ears (6 patients) with abnormal preoperative TM, sixty-eight ears of 60 patients were found to have normal TM preoperatively. Among these 68 ears, there were 51 ears in which sonotubometry was performed both before and after surgery to evaluate whether the AO of the ET was positive or not., Results: Out of the 68 ears with normal preoperative TM, 52 ears (76.5%) were judged successful (sum of complete relief and significant improvement). The postoperative TM was normal in 41 ears (60.3%), while 27 ears (39.7%) had abnormal TM findings postoperatively. The success rate was 75.6% (31/41) in ears with normal postoperative TM, while it was 77.8% (21/27) in ears with abnormal TM. Success in maintaining normal postoperative TM was found in 45.6% (31/68) of the total ears treated. Out of the 51 ears in which sonotubometry was performed both before and after surgery, AO was preoperatively positive in 88.2% of the ears (45/51), while it was positive in 64.7% (33/51) postoperatively. In thirty-four ears with normal TM postoperatively, AO was positive in 24 ears (70.6%), while it was positive in 9 out of 17 ears (52.9%) with abnormal postoperative TM. The success rate was 70.6% (36/51) for the 51 ears in which AO was assessed both pre- and postoperatively, and it was 66.7% (22/33) in ears with positive AO postoperatively, while it was 77.8% (14/18) in ears without AO postoperatively. The incidence of ears either having normal postoperative TM or positive AO postoperatively was 84.3% (43/51). Abnormal postoperative TM findings without effectiveness were found in 8.8% (6/68)., Conclusion: The obstructive dysfunction of the ET is a calculated risk but did not occur in most ears after plugging with the Kobayashi plug. Therefore, routine insertion of the VT at the same time as the initial surgery is not recommended for PET cases that are adequately followed up., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: In transfemoral transcatheter aortic valve implantation (TF-TAVI), which approach has lower vascular access site complications between the open puncture (OP) and percutaneous puncture (PP) approaches is still controversial. Moreover, few studies have analyzed risk factors for vascular access site complications in TF-TAVI. This study aimed to compare vascular access site complications between the OP and PP approaches in patients undergoing TF-TAVI and access risk factors for vascular access site complications., Methods: Three hundred fifty-one patients who underwent TF-TAVI via the PP (n=251) and OP (n=100) were retrospectively examined., Results: Incidence of vascular access site complications was 7.0% in the OP group and 8.4% in the PP group (P=0.828). Two deaths from vascular access site complications occurred in the PP group. After performing inverse probability weighting (IPW), regression analysis showed that PP was associated with a significantly higher odds of vascular access site complications [odds ratio =2.033; 95% confidence interval (CI): 1.397-2.958; P<0.001]. Common femoral artery (CFA) depth (hazard ratio =1.04; 95% CI: 1.000-1.070; P=0.045) and sheath/CFA diameter ratio (hazard ratio =971; 95% CI: 22.6-41,700; P<0.001) were independent complication risk factors. In patients with CFA depth ≥35 mm, the incidence of vascular access site complications was higher with PP than OP. Sheath/CFA diameter ratio ≥0.9 was associated with increased risk of vascular injury with both approaches., Conclusions: The incidence of vascular access site complications in patients undergoing TF-TAVI was significantly lower with OP than PP after IPW. OP may be preferable when CFA depth is ≥35 mm. When the sheath/CFA diameter ratio is ≥0.9, approaches other than the TF approach should be considered., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-999/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Aim: This study was conducted to investigate the relationship between the hospitalizations and backgrounds of patients with coronavirus disease 2019 to identify specific risk factors., Methods: This retrospective study used health observation records to analyze the relationship between certain risk factors and the subsequent hospitalization of 321 patients who were discharged from a residential care facility between January 16 and February 8, 2021. The usefulness of a hospitalization prediction score, created based on the presence of comorbidities and sex, was examined., Results: Being older, male, and having a history of high blood pressure or vascular disease were all risk factors. A multivariate analysis with age and hospitalization predictive score as independent variables and hospitalization as the dependent variable showed that age (odds ratio: 1.07, 95 percent confidence interval: 1.03-1.11, p < 0.01) significantly increased hospitalization risk by 7 percent for every 1-year age increase. The median time from illness onset to hospitalization for all patients was 9 days (interquartile range: 8-10). Hypoxia was the most common cause of hospitalization. However, hypoxia and other symptoms, such as cough and dyspnea, were not correlated., Conclusion: Given the pandemic, there may come another time when hospitals are not able to accommodate all patients who require care. In such instances, age, sex, the presence of comorbidities, and checking oxygen saturation regularly using a pulse oximeter around 9 days after the onset of the disease should all be considered important, as it may lead to improved and safer operation of overnight care facilities.

Human leukocyte antigen (HLA)-DPB1 antigens are mismatched in approximately 70% of allogeneic hematopoietic stem cell transplantations (allo-HSCT) from HLA 10/10 matched unrelated donors. HLA-DP-mismatched transplantation was shown to be associated with an increase in acute graft-versus-host disease (GVHD) and a decreased risk of leukemia relapse due to the graft-versus-leukemia (GVL) effect. Immunotherapy targeting mismatched HLA-DP is considered reasonable to treat leukemia following allo-HCT if performed under non-inflammatory conditions. Therefore, we isolated CD4 + T cell clones that recognize mismatched HLA-DPB1 from healthy volunteer donors and generated T cell receptor (TCR)-gene-modified T cells for future clinical applications. Detailed analysis of TCR-T cells expressing TCR from candidate clone #17 demonstrated specificity to myeloid and monocytic leukemia cell lines that even expressed low levels of targeted HLA-DP. However, they did not react to non-hematopoietic cell lines with a substantial level of targeted HLA-DP expression, suggesting that the TCR recognized antigenic peptide is only present in some hematopoietic cells. This study demonstrated that induction of T cells specific for HLA-DP, consisting of hematopoietic cell lineage-derived peptide and redirection of T cells with cloned TCR cDNA by gene transfer, is feasible when using careful specificity analysis., Competing Interests: Y.A. received honoraria and research funding from Bristol-Myers Squibb. All other authors declare no competing financial interests.

Plasma gel (PG) is a blood-derived biomaterial that can be prepared by heating or chemical cross-linking without the aid of intrinsic coagulation activity and has gradually been applied in the field of esthetic surgery. To explore the applicability of PG in regenerative therapy or tissue engineering, in this study, we focused on the advantages of the heating method and verified the retention capacity of the resulting PG for polyphosphate (polyP), a polyanion that contributes to hemostasis and bone regeneration. Pooled platelet-poor plasma (PPP) was prepared from four healthy male adult donors, mixed with synthetic polyP, and heated at 75 °C for 10 or 30 min to prepare PG in microtubes. The PG was incubated in PBS at 37 °C, and polyP levels in the extra-matrix PBS were determined by the fluorometric method every 24 h. The microstructure of PG was examined using scanning electron microscopy. In the small PG matrices, almost all of the added polyP (~100%) was released within the initial 24 h. In contrast, in the large PG matrices, approximately 50% of the polyP was released within the initial 24 h and thereafter gradually released over time. Owing to its simple chemical structure, linear polyP cannot be theoretically retained in the gel matrices used in this study. However, these findings suggest that thermally prepared PG matrices can be applied as carriers of polyP in tissue engineering and regenerative medicine.