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Naomi Matsumoto,1,2 Hirohide Yokokawa,1 Hirotake Mori,1 Makoto Hiki,2,3 Yoko Tabe,4,5 Kazuhisa Takahashi,5,6 Toshio Naito1,5 1Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 2Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 3Department of Cardiovascular Biology and Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 4Department of Clinical Laboratory Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 5Department of Research Support Utilizing Bioresource Bank, Juntendo University Graduate School of Medicine, Tokyo, Japan; 6Department of Respiratory Medicine Juntendo University Faculty of Medicine, Tokyo, JapanCorrespondence: Hirohide Yokokawa, Department of General Medicine, Juntendo University Faculty of Medicine, 2-1-1 hongo, Bunkyo-ku, Tokyo, 113-8421, Japan, Tel/Fax +81-3-5802-1190, Email hyokoka@juntendo.ac.jpBackground: It has been reported that zinc deficiency is related to severe inflammatory conditions especially those of respiratory diseases. However, studies that have examined the association between the serum zinc concentration and the severity of coronavirus disease 2019 (COVID-19) are still limited. The aim of this study was to assess that association in Japanese inpatients with COVID-19.Methods: This cross-sectional study, conducted from April 2020 to August 2021, included 467 eligible adult inpatients with COVID-19 whose serum zinc concentration was measured. Serum zinc concentration categories were defined as deficiency (< 60 μg/dL), marginal deficiency (≥ 60 to < 80 μg/dL), and normal (≥ 80 μg/dL). Multivariate logistic regression was used to assess the association between serum zinc deficiency and severe COVID-19. Serum zinc concentration levels were compared between mild and other severities of COVID-19 by Dunnett’s method. The P for trend was estimated using the Jonckheere-Terpstra test.Results: The proportions of subjects with serum zinc deficiency (< 60 μg/dL) and marginal zinc deficiency (≥ 60 to < 80 μg/dL) were 39.5% and 54.3% in women, and 36.4% and 57.0% in men, respectively. Serum zinc deficiency was significantly associated with severe COVID-19 compared to marginal deficiency and normal (odds ratio = 3.60, 95% confidence interval = 1.60– 8.13, P < 0.01) after adjusting for confounders. An increase in severity of COVID-19 was inversely related to increases in serum zinc concentration levels (P < 0.01 for trend). Each serum zinc concentration of moderate and severe cases was also significantly lower compared with mild cases (P < 0.01).Conclusion: The severity of COVID-19 was significantly related to serum zinc concentration levels. These results suggest the importance of considering the serum zinc concentration when treating patients with COVID-19.Keywords: COVID-19, Zinc, severity, nutrition, epidemiology

Fractures in body-centered-cubic metals and alloys below the ductile-to-brittle transition temperature are brittle. This is theoretically explained by the notion that the critical stress intensity factor of a given crack front for brittle fracture is smaller than that for plastic deformation; hence, brittle fracture is selected over plastic deformation. Although this view is true from a macroscopic perspective, such a fracture is always accompanied by small-scale plastic deformation near the crack tip, that is, crack tip plasticity. This paper investigates the origin of this plasticity using atomistic modeling with the machine learning interatomic potential of α -Fe. Some plastic modes are activated by rapid crack propagation, whereas no plasticity is activated when the crack tips are gradually fractured. The group of activated atoms dynamically caused by brittle crack propagation was identified as the precursor of plasticity. [ABSTRACT FROM AUTHOR]

Background: Novel diamond-embedded catheter enables precise temperature-controlled ablation. However, the effects of contact angle on lesion formation of this catheter are poorly understood., Objective: The purpose of this study was to evaluate lesion formation using the temperature-controlled ablation catheter embedded with diamond at different angles in a porcine experimental model., Methods: Freshly sacrificed porcine hearts were used. Radiofrequency catheter ablation was performed at 50 W for 15 seconds at an upper temperature setting of 60°C. The contact force (5g, 10g, 30g) and catheter contact angles (30°, 45°, 90°) were changed in each set (n = 13 each). Surface width, maximum lesion width, lesion depth, surface area, distance from the distal edge to the widest area, and impedance drop were evaluated., Results: Surface width and maximum lesion width were longer at 30° than at 90° (P <.05). There were no significant differences in the lesion depth by catheter angle except at 30g. Surface area was larger at 30° than at 90° (P <.05). Distance from the distal edge to the widest area was longer at 30° than at 90° (P <.05). There were no significant differences in impedance drop according to catheter angle., Conclusion: With diamond-embedded temperature-controlled ablation catheters, lesion width increased at a shallower contact angle, whereas lesion depth did not. Surface area also increased at a shallower contact angle. This catheter created a large ablation lesion on the proximal side of the catheter, which looked like a "honey pot.", Competing Interests: Disclosures Dr Hidehira Fukaya and Dr Junya Ako received lecture fees from Medtronic Japan. All other authors have no conflicts of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Using the free latissimus dorsi muscle flap for dynamic reconstruction for established facial paralysis helps reconstruct various facial dysfunctions, depending on nerve and muscle arrangements. The authors divided the latissimus dorsi muscle into 3 flaps, 2 placed in the cheek area to reconstruct a "voluntary and spontaneous smile" and 1 fixed to the fascia implanted in the eyelid to treat lagophthalmos in a 1-stage procedure in a 61-year-old woman who underwent tumor resection for a left facial nerve schwannoma and developed complete facial paralysis. Fascia lata and free latissimus dorsi muscle grafting were performed. Spontaneous smile was reconstructed using the contralateral facial nerve as a motor source. Voluntary smile and eyelid closure were reconstructed using the ipsilateral masseter nerve, dividing the latissimus dorsi muscle flap into 3 muscle bodies. This procedure restored her smile and eyelid closure ability, with a nearly normal overall facial impression, making it a valuable technique for 1-term reconstruction of smiles and eyelid closure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM's C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs)., (© 2024. The Author(s).)

Background: Accuracy in diagnoses recorded using International Classification of Diseases (ICD) coding is the most important element ensuring the foundation of research using real-world data analyses., Objective: To evaluate the validity of ICD coding for diagnoses of disseminated intravascular coagulation (DIC) using International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria and Japanese Association for Acute Medicine (JAAM) DIC criteria as reference standards., Methods: This retrospective observational study included adult hospitalized patients diagnosed as having diseases potentially causing DIC extracted from a part of a large-scale database in Japan. The index test was diagnosis of DIC based on the ICD-10 codes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using ISTH overt DIC criteria and JAAM DIC criteria as the reference standards. We also conducted subgroup analyses according to the underlying diseases., Results: We included 84,300 patients in this study. In the overall study population, sensitivity, specificity, PPV, and NPV of the ICD-based diagnosis for ISTH criteria were 26.28%, 98.10%, 35.12%, and 97.14%, respectively. In subgroup analyses according to the underlying disease, sensitivity ranged from 9.48% to 52.08%, and specificity ranged from 96.94% to 99.47%. Accuracy of the ICD-based diagnosis for JAAM criteria were similar to those in ISTH criteria., Conclusion: Identification of DIC patients using ICD-10 codes had relatively low sensitivity but very high specificity for DIC diagnostic criteria, suggesting that the majority of patients identified by ICD coding can be assumed to meet the DIC diagnostic criteria., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry., Methods and Results: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN., Conclusions: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Background: Various methods for closing tracheocutaneous fistulas have been reported; however, there is no established consensus. This study reports the successful closure of a large tracheocutaneous fistula using a Modified Hinge Flap and DP flap., Methods: Between July 2014 and December 2023, four patients underwent a modified hinge flap and DP flap for tracheocutaneous fistula at a single center., Results: The maximum diameter of the fistula was 10-33 mm, the cartilage defect was 1/4-1/2 of the total circumference of the trachea, and no radiation was administered to the neck during the perioperative period. In all cases, postoperative speech and swallowing improved, and none of the patients complained of cosmetic appearance., Conclusions: The method in this study is simple and allows reliable closure of relatively large tracheocutaneous fistula of 10 mm or more, and we believe that it can be a new treatment method for tracheocutaneous fistula closure., (© 2024 Wiley Periodicals LLC.)

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8-11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7-8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield, has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 hours of arrival) or other clinical outcomes of CDB., Methods: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (&lt;30 days) and late (&lt;1 year) rebleeding, length of hospital stay and transfusion requirements., Results: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], -7.9 to 12.3; P=0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, -9.4 to 10.4; P=1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay and transfusion requirements., Conclusion: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN Registry number, UMIN000026865)., (S. Karger AG, Basel.)

The reaction of γ -stannylated propargyl esters in the presence of a cationic gold(I) catalyst affords vinylidenecyclopropane derivatives as a mixture of diastereomers. The cis -geometry of the alkenes is almost entirely retained in the product. DFT calculations suggest the involvement of the gold(I)-stabilized propargyl cation as a resonance form of gold(I)-coordinated allenylidene species.

Kiso A, Maeda H, Otaka Y, Mori H, Kagaya H. A comparative study of changes in H max /M max under spinning permanent magnet stimulation, repetitive peripheral magnetic stimulation, and transcutaneous electrical nerve stimulation in healthy individuals. Jpn J Compr Rehabil Sci 2024; 15: 58-62., Objective: We have developed a compact device using a spinning permanent magnet (SPM) that induces an electrical field by changing the magnetic flux. We hypothesized that SPM stimulation also reduced spasticity, comparable with repetitive peripheral magnetic stimulation (rPMS) and transcutaneous electrical nerve stimulation (TENS). This study evaluated the effect of a single session of SPM stimulation and compared it with those of rPMS and TENS in healthy individuals., Methods: Eleven healthy adult men participated in this study. The active electrode was placed on the soleus muscle, and the reference electrode was placed at 5 cm distal from the active electrode on the medial side of the Achilles tendon. The stimulating electrodes were fixed on the popliteal fossa to stimulate the tibial nerve. The maximum H-reflex (H max ) and the maximum motor response (M max ) were measured, and H max /M max was calculated under the following conditions: a) 15 min SPM stimulation, b) 30 min SPM stimulation, c) 10,000 pulses rPMS, d) 15 min TENS, and e) 15 min rest (control). The devices for SPM, rPMS, and TENS were applied to the belly of the soleus muscle in the prone position., Results: Compared with the control, H max /M max significantly decreased under SPM stimulation for 15 and 30 min, as well as under rPMS and TENS ( p < 0.005). The changes in H max /M max under 15 min SPM stimulation were significantly smaller than those under 30 min SPM stimulation and rPMS ( p < 0.005)., Conclusion: SPM stimulation reduced H max /M max in healthy individuals and is a potential new treatment for spasticity., Competing Interests: Conflict of Interest: IFG Corporation has a pending patent and Drs. Mori and Kagaya are listed as inventors of the spinning permanent magnet (SPM) device. The SPM device was loaned free of charge from IFG Corporation. Dr. Mori is a stockholder with IFG Corporation. The remaining authors have no conflicts of interest., (©2024 Kaifukuki Rehabilitation Ward Association.)

The grey matter of the brain develops and declines in coordinated patterns during the lifespan. Such covariation patterns of grey matter structure can be quantified as grey matter networks, which can be measured with magnetic resonance imaging. In Alzheimer's disease, the global organization of grey matter networks becomes more random, which is captured by a decline in the small-world coefficient. Such decline in the small-world value has been robustly associated with cognitive decline across clinical stages of Alzheimer's disease. The biological mechanisms causing this decline in small-world values remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and small-world coefficient in mutation carriers ( N = 219) and non-carriers ( N = 136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Amyloid beta, Tau, synaptic (Synaptosome associated protein-25, Neurogranin) and neuronal calcium-sensor protein (Visinin-like protein-1) preceded loss of small-world coefficient by several years, while increased levels in CSF markers for inflammation (Chitinase-3-like protein 1) and axonal injury (Neurofilament light) co-occurred with decreasing small-world values. This suggests that axonal loss and inflammation play a role in structural grey matter network changes., Competing Interests: C.C.: receives research support from: Biogen, EISAI, Alector and Parabon. The funders of the study had no role in the collection, analysis, interpretation of data; or in the writing of the report; or in the decision to submit the paper for publication. C.C. is a member of the advisory board of ADx Healthcare and Vivid Genomics Marty Farlow: Grant/Research Support from AbbVie, ADCS Posiphen, AstraZeneca, Biogen, Eisai, Eli Lilly, Genentech, Novartis, Suven Life Sciences, Ltd., vTv Therapeutics; Consultant/Advisory Boards/DSMB Boards for Allergan, Avanir, AZTherapies, Biogen MA Inc., Cerecin (formerly Accera), Chemigen, Cognition Therapeutics, Cortexyme, Danone, Eisai Inc., Eli Lilly, Longeveron, Green Valley, Medavante, Otsuka Pharmaceutical, Proclara, Neurotrope Bioscience, Samumed, Takeda, vTv Therapeutics, Zhejian Hisun Pharmaceuticals; patent Elan Johannes Levin reports speaker’s fees from Bayer Vital, speaker’s fees from Willi Gross Foundation, consulting fees from Axon Neuroscience, consulting fees from Ionis Pharmaceuticals, non-financial support from Abbvie, MODAG compensation for part time CMO, Thieme medical publishers and W. Kohlhammer GmbH medical publishers author fees, outside the submitted work. E.M.: NIA (research Funding); Eli Lilly-DSMB; ESAI—CMS; Alzamend—scientific advisory board. P.S. is partner at LSP Invester fund and has acquired grant support (for the institution) from GE Healthcare, Danone Research, Piramal and Merck. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, GE Healthcare, Novartis, Sanofi, Nutricia, Probiodrug, Biogen, Roche, Avraham and EIP Pharma. Outside of this manuscript, R.J.B. reports grant/research/clinical trial support: NIH, Alzheimer's Association, BrightFocus Foundation, Rainwater Foundation Tau Consortium, Association for Frontotemporal Degeneration, Cure Alzheimer's Fund, the Tau SILK Consortium (AbbVie, Biogen and Eli Lilly), Janssen, and an anonymous foundation. R.J.B. reports consulting fees/honoraria from Janssen, Pfizer, Roche, Eisai, and Merck. R.J.B. reports equity ownership interest/advisory board income from C2N Diagnostics. All other authors report no disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Skin barrier dysfunction initiates or deteriorates various cutaneous problems, such as atopic dermatitis. At high concentrations, the nonreducing disaccharide trehalose (α-d-glucopyranosyl α-d-glucopyranoside) induces a transient senescence-like state in fibroblasts and promotes wound repair. In this study, we investigated the effect of trehalose on normal human keratinocytes and demonstrated its specific role in the skin barrier. RNA-sequencing analysis revealed that trehalose regulates the expression of many skin barrier-associated genes. T helper 2 cytokines IL-4/IL-13 were observed to downregulate several differentiation markers (FLG, loricrin, keratin 1, and keratin 10) and epidermal antimicrobial proteins in monolayer-cultured keratinocytes and living skin equivalents and impaired skin barrier function in living skin equivalents, all of which were significantly upregulated or restored by trehalose. Trehalose inhibited IL-33 expression and reduced nuclear IL-33 levels by activating MAPK/extracellular signal-regulated kinase kinase 5-extracellular signal-regulated kinase 5 and suppressing extracellular signal-regulated kinase kinase 1/2-extracellular signal-regulated kinase pathway. It also increased NRF2 activation to trigger antioxidant enzyme production through JNK, thus neutralizing IL-4/IL-13-mediated oxidative stress. Trehalose prevented IL-4/IL-13-mediated signal transducer and activator of transcription 3/signal transducer and activator of transcription 6 activation and restored IL-4/IL-13-suppressed skin barrier molecules through IL-33 downregulation and NRF2 activation. This study demonstrated that trehalose may play a role in skin barrier repair in atopic dermatitis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Although arteriovenous malformations (AVMs) are typically benign lesions, massive ones can lead to severe complications, including heart failure. Notably, there is no standardized treatment for AVMs. Moreover, management of AVMs can be challenging when these lesions involve vital organ systems, such as the head and neck. In this report, we describe embolization of a massive cervical AVM in a pediatric patient with heart failure., Case Report: A 10-year-old boy presented with severe heart failure secondary to a massive AVM in the neck (right side). Despite 3 unsuccessful arterial embolization procedures, venous embolization of the dominant outflow vein using a coil and n -butyl-2-cyanoacrylate, lipiodol, and ethanol proved effective, and symptoms, cerebral natriuretic peptide level (568-29 pg/mL), and echocardiography were significantly improved. Although residual AVM persisted in the right upper extremity for 6 months after surgery, his cardiac function remained preserved, and his activities of daily living have improved., Conclusion: Venous embolization is a valuable treatment modality for type II AVMs with a dominant outflow vein. However, considering the patient burden associated with large AVMs, multiple therapeutic interventions at appropriate intervals and long-term follow-up are important., Clinical Impact: We present a pediatric patient with a type II massive arteriovenous malformation (AVM) in the neck and severe heart failure. Despite undergoing 3 arterial embolization procedures, his condition remained unchanged. However, venous embolization of the dominant outflow vein resulted in a significant improvement in symptoms. This case emphasizes the importance of considering multiple and appropriately timed therapeutic interventions, particularly for massive AVMs, to optimize patient outcomes while minimizing treatment burden., 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.

Exciton binding energy (E b ) is understood as the energy required to dissociate an exciton in free-charge carriers, and is known to be an important parameter in determining the performance of organic opto-electronic devices. However, the development of a molecular design to achieve a small level of E b in the solid state continues to lag behind. Here, to investigate the relationship between aggregation and E b , star-shaped π-conjugated compounds DBC-RD and TPE-RD were developed using dibenzo[g,p]chrysene (DBC) and tetraphenylethylene (TPE). Theoretical calculations and physical measurements in solution showed no apparent differences between DBC-RD and TPE-RD, indicating that these molecules possess similar properties on a single-molecule level. By contrast, pristine films incorporating these molecules showed significantly different levels of electron affinity, ionization potential, and optical gap. Also, DBC-RD had a smaller E b value of 0.24 eV compared with that of TPE-RD (0.42 eV). However, these molecules showed similar E b values under dispersed conditions, which suggested that the decreased E b of DBC-RD in pristine film is induced by molecular aggregation. By comparison with TPE-RD, DBC-RD showed superior performances in single-component organic solar cells and organic photocatalysts. These results indicate that a molecular design suitable for aggregation is important to decrease the E b in films., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background and Purpose: The rise of large language models such as generative pretrained transformers (GPTs) has sparked considerable interest in radiology, especially in interpreting radiologic reports and image findings. While existing research has focused on GPTs estimating diagnoses from radiologic descriptions, exploring alternative diagnostic information sources is also crucial. This study introduces the use of GPTs (GPT-3.5 Turbo and GPT-4) for information retrieval and summarization, searching relevant case reports via PubMed, and investigates their potential to aid diagnosis., Materials and Methods: From October 2021 to December 2023, we selected 115 cases from the "Case of the Week" series on the American Journal of Neuroradiology website. Their Description and Legend sections were presented to the GPTs for the 2 tasks. For the Direct Diagnosis task, the models provided 3 differential diagnoses that were considered correct if they matched the diagnosis in the diagnosis section. For the Case Report Search task, the models generated 2 keywords per case, creating PubMed search queries to extract up to 3 relevant reports. A response was considered correct if reports containing the disease name stated in the diagnosis section were extracted. The McNemar test was used to evaluate whether adding a Case Report Search to Direct Diagnosis improved overall accuracy., Results: In the Direct Diagnosis task, GPT-3.5 Turbo achieved a correct response rate of 26% (30/115 cases), whereas GPT-4 achieved 41% (47/115). For the Case Report Search task, GPT-3.5 Turbo scored 10% (11/115), and GPT-4 scored 7% (8/115). Correct responses totaled 32% (37/115) with 3 overlapping cases for GPT-3.5 Turbo, whereas GPT-4 had 43% (50/115) of correct responses with 5 overlapping cases. Adding Case Report Search improved GPT-3.5 Turbo's performance ( P  = .023) but not that of GPT-4 ( P  = .248)., Conclusions: The effectiveness of adding Case Report Search to GPT-3.5 Turbo was particularly pronounced, suggesting its potential as an alternative diagnostic approach to GPTs, particularly in scenarios where direct diagnoses from GPTs are not obtainable. Nevertheless, the overall performance of GPT models in both direct diagnosis and case report retrieval tasks remains not optimal, and users should be aware of their limitations., (© 2024 by American Journal of Neuroradiology.)

Background/aim: The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated as a prognostic factor in colorectal cancer after surgical resection of malignancy, but knowledge on their role in pancreatic cancer is lacking. The Immunoscore (IS) assesses TILs at the core of the tumor (CT) and invasive margin (IM) and is being evaluated as a new concept in tumor immunity. The aim of this study was to evaluate the relationship between IS and prognosis in PDAC., Patients and Methods: The IS was analyzed by immunohistochemistry using surgical tissue blocks from 131 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgery to investigate the relationship between immune cell infiltration into the tumor and prognosis in PDAC., Results: A high IS in both CT and IM of the tumor was significantly associated with prolonged overall survival (OS) (p<0.01) and relapse-free survival (RFS) (p<0.01). In multivariate logistic regression models adjusted for clinical pathology data, IS predicted survival and recurrence (p<0.01 and p<0.01, respectively). Moreover, in patients who received preoperative chemotherapy, a high IS was statistically significantly associated with longer OS and RFS (p<0.01 and p<0.01, respectively)., Conclusion: The immunohistochemically assessed IS might be a useful prognostic marker for patients with PDAC who underwent primary tumor resection., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The heterogeneous character of functional gastrointestinal disorders, recently renamed into disorders of gut-brain interaction, makes finding effective treatment options challenging. Compared to synthetic drugs, phytotherapy can have broader pharmacological effects and is often better tolerated. This study aimed to investigate the effect of peppermint oil and caraway oil (POCO) on gastric function and symptom levels in 32 healthy subjects in a single-blinded, placebo-controlled, randomized, parallel design., Methods: Gastric emptying rate was assessed using a 13 C-breath test. Intragastric pressure was measured using high-resolution manometry in fasted state and during intragastric infusion of a nutrient drink (350 mL or until full satiation). GI symptoms were rated on a 100 mm VAS. Data were analyzed using linear mixed models., Key Results: POCO had no effect on intragastric pressure in fasted or fed state (p > 0.08 for all). No significant differences in gastric emptying rate were observed (p = 0.54). In the fasted state, a stronger increase in hunger and decrease in satiety were observed following POCO (p = 0.016 and p = 0.008, respectively). No differences in hunger and satiety were observed in the fed state (p > 0.31 for all). POCO induced less epigastric burning, bloating, and fullness (p < 0.05 for all)., Conclusions: Acute POCO administration did not affect gastric function in healthy subjects, but increased fasted hunger ratings. The effects of POCO on gastric function and hunger sensations in patients with disorders of gut-brain interaction, and the contribution to symptom improvement, needs to be elucidated in future studies., (© 2024 John Wiley & Sons Ltd.)

Background: Caregivers of patients with chronic dysphasia experience stress and guilt regarding their eating behaviors. Dysphagia rehabilitation, including minimal oral intake with tube feeding, may be vital for caregivers. This study investigated the effects of dysphagia rehabilitation on caregiver well-being and attitudes toward eating assistance., Methods: This cross-sectional questionnaire study was conducted at two dental university hospitals on caregivers of homebound patients with dysphagia undergoing rehabilitation. Caregivers' experiences, with an emphasis on guilt and psychological status, were assessed using the Apathy Scale and Patient Health Questionnaire-5 Depression Scale. Patients were evaluated at the time of the survey and rehabilitation commencement using the Barthel Index and Functional Oral Intake Scale (FOIS). Changes in FOIS scores and caregiver guilt were assessed using the Wilcoxon signed rank test and McNemar test, respectively. The impact of oral intake changes on caregiving motivation was assessed using the Fisher exact test., Results: Between August 2019 and January 2021, 55 of 100 targeted caregivers responded (median age=64.5 years). A significant difference in FOIS scores was found (median rehabilitation duration=9.7 months). Despite 25 pneumonia cases, 65% of the caregivers continued to encourage oral intake. Guilt decreased from 48% during peak dysphagia to 22% at survey time (odds ratio=0.2, 95% CI=0.04-0.70; P < 0.01). No association was found between caregiving motivation and improved oral intake., Conclusion: Severe dysphagia impacted caregiver well-being, indicating preferences for patients' oral intake. To support caregivers, healthcare professionals should explore and integrate new multidisciplinary approaches into dysphagia rehabilitation strategies., (© 2024 American Society for Parenteral and Enteral Nutrition.)

We measured the intracellular zinc ion concentration of murine fetal neural stem/progenitor cells (NSPCs) and that in the differentiated cells. The NSPCs cultured with 1.5 μM Zn 2+ proliferated slightly faster than that in the zinc-deficient medium and the intracellular zinc concentration of the NSPCs and that of their differentiated cells (DCs) cultured with 1.5 μM Zn 2+ was 1.34-fold and 2.00-fold higher than those in the zinc-deficient medium, respectively. The zinc transporter genes upregulated over the 3.5-fold change were Zip1, Zip4, Zip12, Zip13, ZnT1, ZnT8, and ZnT10 whereas the only downregulated one was Zip8 during the differentiation of NSPCs to DCs. The cell morphologies of both NSPCs and DCs in the low oxygen culture condition consisting of 2%O 2 and 5%CO 2 , the high carbon dioxide condition consisting of 21%O 2 and 10%CO 2 , and the normal condition consisting of 21%O 2 and 5%CO 2 were essentially the same each other. The expression of Zip4, Zip8, Zip12, and Zip14 was not drastically changed depending on the O 2 and CO 2 concentrations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack., Methods: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy or carotid artery stenting before the ulcer was first discovered, follow-up data of less than 1 month, or carotid endarterectomy or carotid artery stenting performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed., Results: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs 21; P = .028). The median follow-up duration was 3.8 years (interquartile range, 1.5-6.2 years). Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs 59%; P = .005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank P = .021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.13-7.65; P = .03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1: OR, 3.85; 95% CI, 1.26-11.78; P = .03; Model 2: OR, 4.31; 95% CI, 1.49-12.49; P = .009)., Conclusions: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The extent to which maxillary anterior alveolar osteotomy alters the facial profile remains unclear. The present study retrospectively analyzed and evaluated changes in maxillary anterior fragments and soft tissue from the nose to upper lip from pre- to postoperatively in patients who underwent the Wassmund and Wunderer (WW) technique., Methods: Thirty-seven Japanese patients with maxillary prognathism underwent orthognathic surgery with the WW technique were retrospectively included in the present study. Changes in both hard- and soft-tissue landmarks and correlations between both tissues were evaluated using lateral cephalograms taken immediately before and ≥6 months after orthognathic surgery., Results: The maxillary anterior segment showed predominantly posterior movement, with only slight upward movement. Posterior shift and lingual inclination of the maxillary anterior teeth were prominent. As for soft tissues, the change in the nasal tip was small and posterior change was large in the subnasal and upper lip areas. Nasolabial angle, nasal height, and inclination of nasal tip increased, while upper lip protrusion, nasal tip angle, and philtrum length decreased. Correlations were found between posterior changes in hard tissues and posterior changes in soft tissues. Among these, posterior changes and lingual inclination of the maxillary anterior teeth strongly correlate with posterior changes of the upper lip., Conclusion: Posterior shift of the maxillary anterior segment using the WW technique is useful because it can greatly improve the protrusion of the upper lip while minimizing nasal morphological changes, and the positioning of the maxillary anterior teeth may be an important key factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

A 74 year-old woman suffering 1 month persisting lumbago was referred with diagnosis of thoracic aortic aneurysm. Blood examinations indicated slightly or moderately elevated noradrenaline, dopamine, and homovanillic acid with normal-range vanillylmandelic acid. Contrast-enhanced CT scans revealed a tumor, protruding both intra- and extra-luminally, in the wall of the distal descending thoracic aorta without any primary focuses in the whole body. Primary aortic sarcoma or periaortic catecholamine-producing paraganglioma infiltrating the aorta was suspected. The tumor with the normal proximal and distal aorta 2-3 cm apart from it was completely resected under femoro-femoral partial cardiopulmonary bypass. Macroscopically, the tumor was originated from the aortic wall and protruded both intra- and extra-luminally. Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature., 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.

Background: This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect., Methods: We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters., Results: The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (< 10 µg/mL). Serum SA levels during the recovery period were significantly lower in patients who received steroids. There were no significant differences in IVIG responsiveness based on serum SA levels., Conclusions: Serum SA trough levels in KD patients treated with moderate-dose ASA were highly variable and did not reach sufficient levels. Serum SA levels were not associated with IVIG responsiveness., (© 2024. The Author(s).)

We herein report a case of reversible cerebral vasoconstriction syndrome (RCVS) with an unusual presentation of hyperdense blood vessels. A 53-year-old woman developed thunderclap headache. Brain computed tomography (CT) showed hyperdensity of the anterior cerebral artery. Brain magnetic resonance imaging revealed cerebral infarctions in the left anterior cerebral artery (ACA) territory and cerebellum. The left ACA presented with a hyperintense vessel sign, although magnetic resonance angiography (MRA) appeared normal. One week later, stenotic changes were confirmed using MRA. The vasoconstriction disappeared on day 20, and the patient was diagnosed with RCVS. CT-defined hyperdense vessel signs can be observed at an early stage of RCVS, leading to ischemic events.

Herein, we present the case of a 76-year-old man diagnosed with an iliopsoas abscess 3 months prior and consequently administered metronidazole. The patient visited our facility complaining of difficulty in speaking and feeling unsteady when walking. Neurological findings showed dysarthria, nystagmus, and bilateral cerebellar ataxia. Head MRI-FLAIR demonstrated symmetrical hyperintensities in the bilateral cerebellar dentate nuclei, red nucleus, periaqueductal of the midbrain, periventricular third ventricle, and the corpus callosum. Although Wernicke's encephalopathy was among the differential diagnoses based on the imaging findings, the thiamine level was normal and improvement in symptoms and hyperintensity on FLAIR within 5 days of discontinuing metronidazole led to the diagnosis of metronidazole-induced encephalopathy. Although there were many similarities in the imaging findings of metronidazole-induced encephalopathy and Wernicke's encephalopathy, Metronidazole-induced encephalopathy should be initially considered when midbrain red nucleus lesions are observed.

Mucosa-associated lymphoid tissue (MALT) lymphoma commonly arises from chronic inflammation or autoimmune diseases, such as Sjögren syndrome (SjS). Although rare, amyloid deposition in MALT lymphoma has been reported. We present a rare case of parotid gland MALT lymphoma in a 49-year-old woman, in whom preoperative diagnosis was challenging due to atypical imaging findings resulting from amyloid deposits. MRI showed T2-hypointense and T1-iso- to slightly hyperintense masses in the left parotid gland and right sublingual gland, with predominant marginal contrast enhancement and no significant diffusion restriction. Additionally, atrophy and fatty replacement of the parenchyma were noted in bilateral parotid glands, suggesting SjS. Left superficial parotidectomy was performed and pathological findings confirmed MALT lymphoma with extensive amyloid deposition. Histopathological findings of the resected parotid gland parenchyma also suggested SjS. MALT lymphoma should be considered in the differential diagnosis of multiple salivary gland masses in patients with suspected SjS. If MRI reveals atypical imaging findings for malignant lymphoma, particularly T2-hypointensity with no significant diffusion restriction, the possibility of amyloid deposition in MALT lymphoma should be considered., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Purpose: Enlargement of the trigeminal nerve is observed in 20-53% of patients with IgG4-related ophthalmic disease (IgG4-ROD) and is known to be a useful finding for the diagnosis of IgG4-ROD. On the other hand, enlargement of the trigeminal nerve has also been found at a certain frequency in orbital lymphoproliferative diseases other than IgG4-ROD. Therefore, we here re-evaluated the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-ROD., Study Design: Retrospective, comparative study., Methods: A total of 149 consecutive cases of IgG4-ROD diagnosed at the Department of Ophthalmology, Tokyo Medical University Hospital were studied. As controls, 218 cases of orbital lymphoma, 13 cases of reactive lymphoid hyperplasia (RLH), and 117 cases of benign orbital tumors other than lymphoproliferative diseases were included. Enlargement of the trigeminal nerve (infraorbital or supraorbital nerve) in IgG4-ROD and all the control cases was evaluated on MRI or CT coronal images., Results: Enlargement of the trigeminal nerve was observed in 35 of the 149 cases (23.5%) of IgG4-ROD and in 7 of the 218 cases (3.2%) of lymphoma, with a significantly highly frequency in IgG4-ROD (P < .0001). No cases of trigeminal nerve enlargement were observed in the cases of RLH or benign orbital tumors. The sensitivity and the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-ROD were 23.5% and 96.8%, respectively. Additionally, enlargement of the trigeminal nerve was significantly more common in men than in women (P < .028)., Conclusions: The present study indicates that trigeminal nerve enlargement is a characteristic imaging finding and has diagnostic value for IgG4-ROD., (© 2024. Japanese Ophthalmological Society.)

Starch degradation in malted barley produces yeast-fermentable sugars. In this study, we compared the amylolytic enzymes and composition of the malt starch hydrolysates of two barley cultivars, Hokudai 1 (the first cultivar established in Japan) and Kitanohoshi (the currently used cultivar for beer production). Hokudai 1 malt contained lower activity of amylolytic enzymes than Kitanohoshi malt, although these cultivars contained α-amylase AMY2 and β-amylase Bmy1 as the predominant enzymes. Malt starch hydrolysate of Hokudai 1 contained more limit dextrin and less yeast-fermentable sugars than that of Kitanohoshi. In mixed malt saccharification, a high Hokudai 1 malt ratio increased the limit dextrin levels and decreased the maltotriose and maltose levels. Even though Kitanohoshi malt contained more amylolytic enzymes than Hokudai 1 malt, addition of Kitanohoshi extract containing the amylolytic enzymes did not enhance malt starch degradation of Hokudai 1. Hokudai 1 malt starch was less degradable than Kitanohoshi malt starch., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Kimono is being reevaluated for its sustainability aspects, such as having fewer offcuts in the production process due to its structural differences from Western-style clothes and its high reusability due to the adaptability to individuals' body shapes. On the other hand, once a common attire for daily wear in Japan, kimono has transitioned to being worn only on special events and the kimono-related industry has also shrunk. To stimulate demand for kimono, it is essential to familiarize younger generations with its potential as daily wear., Methods: A questionnaire survey on perceptions of kimono was conducted among two groups in Japan: 211 college students and 50 kimono enthusiasts. The questionnaire included demographic questions and psychometric scales, primarily focusing on their kimono experiences, challenges associated with wearing kimono, their perceptions of kimono and Western-style clothes, and their attitudes towards kimono., Results: The results revealed that a majority of students had worn kimono before, though they found it difficult to move while wearing it. In contrast, kimono enthusiasts evaluated it as easier to move, hard to become disheveled, and casual. They also rated the ease of wearing Western-style clothes lower compared to students, and this tendency intensified with the length of enthusiast experience. Furthermore, the findings indicated that enthusiasts regarded the kimono more as daily wear compared to students, while still deriving enjoyment from it as formal attire in special events., Conclusions: These results suggest that the cognition that Western-style clothes are easy to move and kimono is not may change with experiences. Therefore, providing opportunities for people in Japan to acquire how to wear kimono in comfortable ways possibly impacts their perceptions of kimono., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Miyashiro K et al.)

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94-100%) in the Monday-Wednesday group and 83% (95% confidence interval: 71-96%) in the Thursday-Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

A 50-year-old man with a history of nephrectomy for renal cell carcinoma (RCC) 11 years prior was diagnosed with gastric and multiple pancreatic metastases of RCC. He underwent a pyloric gastrectomy and total pancreatic resection. RCC metastases to the pancreas are rare, and gastric metastases are even rarer. This case represents a rare instance of simultaneous RCC metastases to both the stomach and pancreas. Although there is no difference in prognosis between solitary and multiple pancreatic metastases, surgical resection is recommended even for multiple lesions. However, preoperative imaging often fails to identify all pancreatic metastatic lesions, making total pancreatectomy a consideration for ensuring complete resection, especially when preoperative detection is challenging., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mori et al.)

Background: As the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH) has improved, chronic disease burden and polypharmacy have increased in PLWH. Simplification of the antiretroviral therapy (ART) regimen for PLWH has become crucial. The real-world treatment patterns and medication persistence of the 2-drug single-tablet regimen (STR), dolutegravir/lamivudine (DTG/3TC), compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) prescribed were investigated., Methods: This retrospective, database study extracted data from a hospital-based medical claims database in Japan. The changes in ART distributions by year during the identification period between January 1, 2018 and December 31, 2021 were observed. Patients with disease record of HIV-1 infection and prescribed DTG/3TC or BIC/FTC/TAF as the first prescription of STR during the identification period were divided into two cohorts; DTG/3TC cohort and BIC/FTC/TAF cohort, respectively. Patient without medication records more than 3 months and no future data more than 6 months were excluded. Patients' characteristics were compared between the DTG/3TC cohort and the BIC/FTC/TAF cohort by Mantel-Haenszel test to adjust for age. Medication persistence was compared between the two cohorts by evaluating the continuation rates using Kaplan-Meier methods, using the log-rank test to assess the difference between the Kaplan-Meier curves. The median time-to-first prescription was compared between the two cohorts by Kaplan-Meier methods., Results: Prescriptions of DTG/3TC and BIC/FTC/TAF increased steadily from 2019 to 2021 after the release year of each STR. There was no significant difference in the time-to-first prescription ( p  = 0.3). A total of 959 patients were included, with 120 patients and 839 patients on DTG/3TC and BIC/FTC/TAF, respectively. The proportion of dyslipidemia at baseline was significantly higher in the DTG/3TC cohort than in the BIC/FTC/TAF cohort after adjusting for mean age ( p  = 0.002). There was no significant difference in medication persistence between the two cohorts ( p  = 0.91)., Conclusion: This study showed that DTG/3TC was likely to be selected for elderly patients and those with chronic disease in real-world clinical practice, which seems in accordance with the treatment strategy recommended by guidelines. Comparable medication persistence was observed with both regimens, aligning with findings from other countries. The 2-drug single-tablet regimen DTG/3TC may be an important ART regimen for PLWH with multiple morbidities and polypharmacy in an aging society. Due to the limitations of the database, further research to assess viral loads, emergence of resistance and adverse events will be encouraged., 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., (Copyright © 2024 Kanamori, Aoki, Kanazawa, Nakamoto, Yuda, Makino, Ohata, Fukui, Mori, Yokokawa and Naito.)

We compared the computed tomography (CT) numbers from monochromatic images obtained using the first-generation (Discovery CT750 HD: GE Healthcare, Milwaukee, WI) and second-generation (Revolution CT: GE HealthCare) dual-energy CT (first and second DECT) scanners in phantom and clinical studies. In a polypropylene phantom, eight polypropylene tubes containing iodine at various concentrations (0.5, 1, 2, 5, 10, 12, 20, 30 mg I per ml) were arranged in an outer circle. The iodine densities and CT numbers obtained after imaging with different-generation DECT scanners were analyzed. The CT numbers from images obtained from 61 consecutive patients with aortic disease who underwent CT with different-generation DECT scanners were compared during the arterial and delayed phases. The iodine concentration obtained from second DECT was more accurate than that from the first DECT in the phantom study. A significantly higher contrast enhancement was observed with the second DECT compared with the first DECT during the arterial phase in the clinical study. Contrast enhancement was higher with the second DECT than with the first DECT, and the second DECT was effective in minimizing the use of contrast materials., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals., Methods: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes., Results: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer., Conclusions: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

VemP is a secretory protein in the Vibrio species that monitors cellular protein-transport activity through its translation arrest, allowing expression of the downstream secD2-secF2 genes in the same operon, which encode components of the protein translocation machinery. When cellular protein-transport function is fully active, secD2/F2 expression remains repressed as VemP translation arrest is canceled immediately. The VemP arrest cancellation occurs on the SecY/E/G translocon in a late stage in the translocation process and requires both trans factors, SecD/F and PpiD/YfgM, and a cis element, Arg-85 in VemP; however, the detailed molecular mechanism remains elusive. This study aimed to elucidate how VemP passing through SecY specifically monitors SecD/F function. Genetic and biochemical studies showed that SecY is involved in the VemP arrest cancellation and that the arrested VemP is stably associated with a specific site in the protein-conducting pore of SecY. VemP-Bla reporter analyses revealed that a short hydrophobic segment adjacent to Arg-85 plays a critical role in the regulated arrest cancellation with its hydrophobicity correlating with the stability of the VemP arrest. We identified Gln-65 and Pro-67 in VemP as novel elements important for the regulation. We propose a model for the regulation of the VemP arrest cancellation by multiple cis elements and trans factors with different roles., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population., Methods: This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS)., Results: Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3 months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS., Conclusions: Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Purpose: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS., Method: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests., Results: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values., Conclusions: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

SARS-CoV-2 vaccines have been administered in many countries after the COVID-19 pandemic. Lymphadenopathy is a side effect of SARS-CoV-2 vaccine. We report a rare example of Kikuchi disease in the cervical lymph nodes after SARS-CoV-2 vaccination. A 41-year-old man complained of a swollen neck and fever 9 days after the first dose of SARS-CoV-2 mRNA-1273 vaccine. Computed tomography revealed enlarged cervical lymph nodes. Fine needle aspiration and resection were performed, and the clinicopathological diagnosis was consistent with Kikuchi disease. Histologically, the resected lymph nodes lost their polarity, and many histiocytes were aggregated with karyorrhectic nuclear debris and apoptosis. SARS-CoV-2 positive cells were small lymphocytes detected by immunohistochemistry. This is the first report that demonstrated SARS-CoV-2 expression in Kikuchi disease post-SARS-CoV-2 vaccination., 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.

Background: In deep inferior epigastric artery (DIEA) perforator (DIEP) flap breast reconstruction, the network with the superficial inferior epigastric artery (SIEA) is key to achieving stable subcutaneous blood flow to the flap. This study investigated how the diameter and location of the DIEA perforator affect continuity with the SIEA., Methods: A retrospective analysis of 94 specimens from 47 patients who underwent DIEA perforator flap breast reconstruction was performed. Relationships between the diameter and location of the DIEA perforator and its continuity with the SIEA were examined on preoperative multi-slice computed tomography., Results: The largest DIEA perforator on each specimen showed continuity with the SIEA in 94 %, significantly more than the second (80 %; p = 0.027) or third largest perforator (76 %; p = 0.005). Medial perforators from 3 cm above to 3 cm below the umbilicus showed more continuity with the SIEA than lateral perforators (p = 0.008)., Conclusions: Selection of the largest perforator of DIEP flap is advantageous in terms of continuity with the SIEA. Also, near the umbilicus, medial perforators communicate with the SIEA more than lateral perforators., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest associated with this study., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) has quickly risen to become the third leading cause of cancer-related death in the United States. This is in part because of its fibrotic tumor microenvironment (TME) that contributes to poor vascularization and immune infiltration and subsequent chemo- and immunotherapy failure. Here, we investigated an immunotherapy approach combining delivery of stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) innate immune agonists by lipid-based nanoparticle (NP) coencapsulation with senescence-inducing RAS-targeted therapies, which can remodel the immune suppressive PDAC TME through the senescence-associated secretory phenotype. Treatment of transplanted and autochthonous PDAC mouse models with these regimens led to enhanced uptake of NPs by multiple cell types in the PDAC TME, induction of type I interferon and other proinflammatory signaling pathways, increased antigen presentation by tumor cells and antigen-presenting cells, and subsequent activation of both innate and adaptive immune responses. This two-pronged approach produced potent T cell-driven and type I interferon-mediated tumor regression and long-term survival in preclinical PDAC models dependent on both tumor and host STING activation. STING and TLR4-mediated type I interferon signaling was also associated with enhanced natural killer and CD8 + T cell immunity in human PDAC samples. Thus, combining localized immune agonist delivery with systemic tumor-targeted therapy can orchestrate a coordinated type I interferon-driven innate and adaptive immune response with durable antitumor efficacy against PDAC.

NRAS Q61 mutations are driver genetic alterations associated with common melanocytic nevi. Herein, we describe a case of NRAS-mutant melanocytic tumor with a blue nevus-like morphology. A 71-year-old Japanese man presented with a 4.6-mm nodule on his back. Histopathological examination revealed a dense distribution of spindle-shaped melanocytes in the upper dermis and a sparse distribution of dendritic melanocytes in the mid-dermis. The vertical periadnexal extension reached the deep dermis at the center of the tumor. A small junctional component, hyperpigmentation, sclerotic stroma, mild nuclear atypia, and a few mitotic figures were observed. Immunohistochemical examination revealed no PRAME expression and preserved p16 expression. Diffuse RASQ61R immunoreactivity was observed in these tumor cells. Nuclear β-catenin expression was not observed. Targeted RNA sequencing revealed two mutations, NRAS c.182A>G (Q61R) and FGFR2 c.-157A>G, but no other pathogenic alterations such as BRAF, GNAQ, GNA11, CTNNB1, PRKAR1A, or IDH1 mutations or kinase gene fusions. The histopathology fits that of compound-type blue nevus, which is called "Kamino nevus"; however, this tumor was genetically considered to be on the spectrum of conventional acquired melanocytic nevi but not on that of blue nevi. Morphologically, NRAS-driven melanocytic nevi resemble blue nevi without IDH1 R132C coexistence., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Intracranial aneurysm growth is a significant risk factor for rupture; however, a few aneurysms remain unruptured for long periods, even after growth. Here, we identified hemodynamic features associated with aneurysmal rupture after growth., Materials and Methods: We analyzed nine middle cerebral artery aneurysms that grew during the follow-up period using computational fluid dynamics analysis. Growth patterns of the middle cerebral artery aneurysms were divided into homothetic growth (Type 1), de novo bleb formation (Type 2), and bleb enlargement (Type 3). Hemodynamic parameters of the four ruptured aneurysms after growth were compared with those of the five unruptured aneurysms., Results: Among nine aneurysms (78%), seven were Type 1, one was Type 2, and one was Type 3. Three (43%) Type 1 aneurysms ruptured after growth. Maximum oscillatory shear index after aneurysmal growth was significantly higher in ruptured Type 1 cases than in unruptured Type 1 cases (ruptured vs. unruptured: 0.455 ± 0.007 vs. 0.319 ± 0.042, p = 0.003). In Type 1 cases, a newly emerged high-oscillatory shear index area was frequently associated with rupture, indicating a rupture point. Aneurysm growth was observed in the direction of the high-pressure difference area before enlargement. In Types 2 and 3 aneurysms, the maximum oscillatory shear index decreased slightly, however, the pressure difference values remain unchanged. In Type 3 aneruysm, the maximum OSI and PD values remained unchanged., Conclusions: This study suggests that hemodynamic variations and growth pattern changes are crucial in rupture risk determination using computational fluid dynamics analysis. High-pressure difference areas may predict aneurysm enlargement direction. Additionally, high maximum oscillatory shear index values after enlargement in cases with homothetic growth patterns were potential rupture risk factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishiwaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)