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Abstract Thermoelectric textile devices represent an intriguing avenue for powering wearable electronics. The lack of air‐stable n‐type polymers has, until now, prevented the development of n‐type multifilament yarns, which are needed for textile manufacturing. Here, the thermomechanical properties of the recently reported n‐type polymer poly(benzodifurandione) (PBFDO) are explored and its suitability as a yarn coating material is assessed. The outstanding robustness of the polymer facilitates the coating of silk yarn that, as a result, displays an effective bulk conductivity of 13 S cm−1, with a projected half‐life of 3.2 ± 0.7 years at ambient conditions. Moreover, the n‐type PBFDO coated silk yarn with a Young's modulus of E = 0.6 GPa and a strain at break of εbreak = 14% can be machine washed, with only a threefold decrease in conductivity after seven washing cycles. PBFDO and poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) coated silk yarns are used to fabricate two out‐of‐plane thermoelectric textile devices: a thermoelectric button and a larger thermopile with 16 legs. Excellent air stability is paired with an open‐circuit voltage of 17 mV and a maximum output power of 0.67 µW for a temperature difference of 70 K. Evidently, PBFDO coated multifilament silk yarn is a promising component for the realization of air stable thermoelectric textile devices.

Key Clinical Message The sheath‐in‐sheath technique, utilizing a 15Fr cryoballoon delivery sheath inserted into a 25 cm 16Fr sheath, effectively navigates tortuous iliac veins during cryoballoon ablation for atrial fibrillation, ensuring safe delivery and maintaining essential device performance without complications.

Key Clinical Message The newly‐proposed tandem approach, Wire ThRoUgh Snare Twice (Wire TRUST) is effective for grasping a lead with inaccessible ends. This case report shows that Wire TRUST can also enable successful extraction of a left ventricular lead by iteratively grasping and repositioning to the distal portion of the lead.

Abstract Aim After pancreaticoduodenectomy, 20–40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin‐like phospholipase domain‐containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results Forty‐three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real‐time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver‐to‐spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis‐4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Abstract Aim This study focuses on the fathers of children with chronic illnesses in an effort to clarify how the stressor and the father’s sense of coherence (SOC) influence their mental health and how the father’s SOC is associated with the social support. Design Cross‐sectional study. Methods We conducted a self‐reported questionnaire survey of 137 respondents (51 fathers of children with chronic illnesses, 86 fathers of healthy children) were statistically using ANOVA. Results The fathers’ stressor was significantly related to their SOC. Furthermore, the SOC of the fathers majorly influenced their mental health, while having a buffering effect on the stressor with respect to depression. And their SOC was significantly positively associated with the social support. Our findings underscore that father's SOC has a buffering effect on self‐mental health and is important for maintaining mental health and enhancing SOC to reduce the stressors of these fathers with respect to depression.

Abstract Objective The prognosis of patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) is poor. Although patients who fail first‐line salvage chemotherapy are candidates for second‐line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. Methods The present, single‐center, retrospective study included transplant‐eligible patients with R/R DLBCL who received second‐line salvage chemotherapy with curative intent. Results Seventy‐six patients with R/R DLBCL received second‐line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first‐line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second‐line salvage chemotherapy than those who did not. Forty‐one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T‐cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second‐line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second‐line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T‐cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T‐cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T‐cell therapy after the response to second‐line salvage chemotherapy. Discussion In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T‐cell therapy irrespective of the administration timing, and that both ASCT and CAR T‐cell therapy were acceptable after the response to second‐line salvage chemotherapy.

Abstract We report a case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a 31‐year‐old man. He had been diagnosed with mild COVID‐19 3 days earlier and presented to the emergency department with altered mental status. Brain magnetic resonance imaging (MRI) showed a high‐intensity area confined to the splenium of the corpus callosum on diffusion‐weighted imaging, which is consistent with MERS. MERS is characterized by a reversible change in the splenium of the corpus callosum. MERS secondary to COVID‐19 has been reported recently. It is important to consider MERS in COVID‐19 patients with impaired consciousness.

Abstract Aim Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune‐related adverse events (irAEs). Given that severe irAEs can be life‐threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts. Methods Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival. Results Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p

ABSTRACT Aims/Introduction This study was designed and carried out to investigate the association of dipeptidyl peptidase‐4 inhibitor (DPP‐4i) use with pancreatic cancer (PC) in individuals with diabetes in Japan. Materials and Methods The JMDC Claims Database, which contains the medical and prescription information of Japanese employment‐based health insurance programs, was used. The primary outcome was duration to the first occurrence of PC (International Classification of Diseases 10th Revision code C25), both all and hospitalized, from prescription of DPP‐4is or other oral glucose‐lowering agents (GLAs). Results Individuals with diabetes who received DPP‐4is (n = 61,430) or other oral GLAs (n = 83,304) were analyzed. Follow‐up periods (median [interquartile range]) were 17 months (8–33) for DPP‐4is and 14 months (7–28) for other oral GLAs. Kaplan–Meier curve analysis to determine the duration of first use of DPP4i or other oral GLA to diagnosis of PC disclosed no differences between the two groups in duration to all or hospitalized PC (log‐rank test: all, P = 0.7140; hospitalized, P = 0.3446). Cox proportional hazards models showed that use of DPP‐4is did not affect the PC risk adjusted for medications, age, sex and risk comorbidities (all, hazard ratio 1.1, 95% confidence interval 0.8–1.3, P = 0.6518; hospitalized, hazard ratio 1.1, 95% confidence interval 0.8–1.4, P = 0.6662). Similar results were obtained when individuals with ≥2 years oral GLA treatment and those with medical checkup data (e.g., smoking or drinking habit) available were analyzed. Conclusion This database study shows that there is not a significant PC risk due to DPP‐4i treatment in individuals with diabetes in Japan, but larger studies with longer follow up are required to confirm these findings.

Abstract Aims/Introduction The aim of this study was to develop a scale to evaluate disease stigma in patients with lifestyle‐related chronic non‐communicable diseases (LCNCDs), which we named the Kanden Institute Stigma Scale (KISS), and to consider its possible clinical application for patients with diabetes. Materials and methods An initial 90 questions were drafted and categorized into six subscales according to the manifestations of stigma. The final version of the KISS was developed as a 24‐item questionnaire comprising four items for each subscale. Results A total of 539 outpatients including 452 patients with diabetes and 87 patients without diabetes were recruited. Construct validity was confirmed by assessing the correlation with previously established measures. Confirmatory factor analysis showed the KISS to have good model fitness (adjusted goodness‐of‐fit index = 0.856). Test–retest reproducibility analysis showed that the intraclass coefficient of the first and a second KISS was 0.843 (P

Transmembrane protein 160 (TMEM160) was recently reported to be localized to the mitochondrial inner membrane, but mitochondrial function was noted to be unaffected by loss of TMEM160. In contrast to these previously published findings, we report here that the absence of TMEM160 influences intracellular responses. After confirming that TMEM160 is localized in the inner mitochondrial membrane, we knocked down TMEM160 in human cultured cells and analyzed the changes in cellular responses. TMEM160 depletion led to an upregulation of the mitochondrial chaperone HSPD1, suggesting that depletion induced the mitochondrial unfolded protein response (UPRmt). Indeed, the expression of key transcription factors that induce the UPRmt (ATF4, ATF5, and DDIT3) was increased following TMEM160 depletion. Expression of the mitochondrial protein import‐receptors TOMM22 and TOMM20 was also enhanced. In addition, we observed a significant increase in reactive oxygen species (ROS) generation following TMEM160 depletion. Glutathione S‐transferases, which detoxify the products of oxidative stress, were also upregulated in TMEM160‐depleted cells. Immunoblot analysis was performed to detect proteins modified by 4‐hydroxynonenal (which is released after the peroxidation of lipids by ROS): the expression patterns of 4‐hydroxynonenal‐modified proteins were altered after TMEM160 depletion, suggesting that depletion enhanced degradation of these proteins. HSPD1, TOMM22, ATF4, ATF5, and DDIT3 remained upregulated after ROS was scavenged by N‐acetylcysteine, suggesting that once the UPRmt is induced by TMEM160 depletion, it is not suppressed by the subsequent detoxification of ROS. These findings suggest that TMEM160 may suppress ROS generation and stabilize mitochondrial protein(s).

Cell migration plays an important role in multicellular organism development. The cellular slime mold Dictyostelium discoideum is a useful model organism for the study of cell migration during development. Although cellular ATP levels are known to determine cell fate during development, the underlying mechanism remains unclear. Here, we report that ATP‐rich cells efficiently move to the central tip region of the mound against rotational movement during the mound phase. A simulation analysis based on an agent‐based model reproduces the movement of ATP‐rich cells observed in the experiments. These findings indicate that ATP‐rich cells have the ability to move against the bulk flow of cells, suggesting a mechanism by which high ATP levels determine the cell fate of differentiation.

Abstract Aim Early detection of surgical site infection (SSI) allows for appropriate management after Crohn's disease (CD) surgery. The aim of this study was to evaluate the usefulness of bacterial culture of postoperative drainage fluid after CD surgery. Methods This study included 110 patients with CD who underwent surgery with bowel resection between January 2010 and March 2020 at Osaka University Hospital. Patients with only perianal surgery or incomplete records were excluded. Risk factors for SSI were evaluated in the context of clinical findings, including bacterial culture of postoperative drainage fluid, and bacterial species related to SSI were also examined. Results Of 110 patients, 18 (16.4%) developed SSI. Organ/space SSI developed in six, and a positive bacterial culture of drainage fluid (D‐Posi) was found in five (83.3%). Of 104 patients without organ/space SSI, 31 (29.8%) were D‐Posi (P = .027). Similarly, 68.8% with incisional SSI were D‐Posi, whereas 26.6% without incisional SSI were D‐Posi (P = .0021). Multivariate analysis revealed that D‐Posi was an independent risk factor in both organ/space and incisional SSI. Bacterial examination showed that Pseudomonas aeruginosa and Enterococcus faecalis were significantly detected in patients with SSI. Conclusion This study suggests the usefulness of postoperative drainage fluid bacterial culture for early diagnosis of SSI after CD surgery.

Abstract Sit‐to‐stand (STS) movement is a frequently performed activity of daily living. The analysis of STS movement can lead to the early detection of a decline in physical functioning. There is thus interest in home‐based STS monitoring systems. The present study (1) extracted universal differences by age group in common STS movements of daily life and (2) clarified where the differences between age groups lie in the sequence of movements. We experimented to measure the three patterns of STS movement assumed to be performed in living spaces. Ten young adults and seventeen elderly people participated. Data were acquired by an Azure Kinect DK, an RGB‐D camera, and converted into angles and angular velocities of the major body segments. Principal component analysis was applied to the overall time series data. From the synthesized principal component space, principal components with significant differences between the elderly and young‐adult groups were extracted, and the movements of the elderly participants were evaluated. We found parameters and movement strategies that show the characteristics of each age group for each movement pattern. The results of this study can contribute to the design of home‐based STS monitoring systems.

Abstract Aims/Introduction Differences in the glucose‐lowering mechanisms of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. Materials and Methods A single‐arm, prospective, observational study was conducted to evaluate the effects of various GLP‐1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP‐1RA initiation. Effects on postprandial secretions of glucose‐dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. Results Eighteen subjects with type 2 diabetes received one of three GLP‐1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12‐week administration of all of the GLP‐1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP‐1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP‐1RAs. Conclusions All of the GLP‐1RAs were found to improve HbA1c in a 12‐week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose‐lowering effects and body weight reduction were observed.

Abstract A 58‐year‐old male was diagnosed with splenic B‐cell lymphoma/leukemia, unclassifiable (SPLL‐U). The lymphoma transformed into diffuse large B‐cell lymphoma (DLBCL), and multidrug chemotherapy and autologous stem cell transplantation achieved complete remission. Two years later, the lymphoma relapsed as SPLL‐U. Serial whole‐exome sequencing indicated that the mutation profiles were similar between the onset and relapsed samples while those in DLBCL were partially distinctive, which was in line with the clinical course. Hierarchical clustering revealed that an IGLL5 mutation was the founder mutation proceeding the development of the diseases and suggested that KRAS and other mutations might contribute to the transformation.

Abstract To clarify the association between lifestyle changes as a result of coronavirus disease 2019 containment measures and changes in metabolic and glycemic status in patients with diabetes, a cross‐sectional, single‐center, observation study was carried out. A self‐reported questionnaire was provided to ascertain the frequency of various lifestyle activities before and after the coronavirus disease 2019 containment measures in Japan. Among 463 patients, change in glycated hemoglobin was significantly associated with change in bodyweight. After stratification by age 65 years, binary logistic regression analysis showed that increased frequency of snack eating increased bodyweight (odds ratio 1.709, P = 0.007) and glycated hemoglobin (odds ratio 1.420, P = 0.025) in the younger group, whereas in the older patients, reduced walking activities resulted in weight gain (odds ratio 0.726, P = 0.010). In conclusion, changes in eating behavior and physical activity increased bodyweight and reduced glycemic control among diabetes patients, but by different processes depending on age under the coronavirus disease 2019 containment measures in Japan.

Abstract ROS1 rearrangements are found in 1–2% of patients with non‐small‐cell lung cancer. The detection of the rearrangements is crucial since clinically effective molecular targeted drugs are available for them. We present a case of lung adenocarcinoma with a previously unknown ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based test for ROS1 fusion gene detection but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant.

Abstract Aims/Introduction Controlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes. Materials and Methods We enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C‐peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two‐thirds of the necessary dose of the premeal bolus insulin. Results The levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (

Abstract Background Wolff‐Parkinson‐White (WPW) syndrome is characterized by an anomalous accessory pathway (AP) that connects the atrium and ventricles, which can cause abnormal myocardial excitation and cardiac arrhythmias. The morphological and electrophysiological details of the AP remain unclear. The size and conductivity of the AP may affect conduction and WPW syndrome symptoms. Methods To clarify this issue, we performed computer simulations of antegrade AP conduction using a simplified wall model. We focused on the bundle size of the AP and myocardial electrical conductivity during antegrade conduction (from the atrium to the ventricle). Results We found that a thick AP and high ventricular conductivity promoted antegrade conduction, whereas a thin AP is unable to deliver the transmembrane current required for electric conduction. High ventricular conductivity amplifies transmembrane current. These findings suggest the involvement of a source‐sink mechanism. Furthermore, we found that high AP conductivity blocked antegrade conduction. As AP conductivity increased, sustained outward transmembrane currents were observed. This finding suggests the involvement of an electrotonic effect. Conclusions The findings of our theoretical simulation suggest that AP size, ventricular conductivity, and AP conductivity affect antegrade conduction through different mechanisms. Our findings provide new insights into the morphological and electrophysiological details of the AP.

Abstract Sarcopenia is an adverse prognostic factor for diffuse large B‐cell lymphoma. A case of diffuse large B‐cell lymphoma whose diagnosis, severity, and therapeutic effect of sarcopenia were difficult to determine owing to lymphoma cell infiltration into the psoas major and femoral bone marrow is reported. At presentation, the cross‐sectional area of left psoas major at L3 was enlarged owing to lymphoma cell infiltration; thus, sarcopenia evaluation was impossible by L3 skeletal muscle index. The patient was bedridden; thus, sarcopenia evaluation was impossible by the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria at presentation. At the terminal stage, she could not walk due to bilateral anterior thigh pain caused by lymphoma infiltration into femoral marrow; thus, sarcopenia evaluation was impossible by the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria. Although the L3 skeletal muscle index and the Asian Working Group for Sarcopenia 2019 consensus diagnostic criteria are representative sarcopenia evaluation systems, they cannot be used to evaluate sarcopenia in some diffuse large B‐cell lymphoma patients.

Abstract Objectives Since carbonized clots and tissue (debris) tend to adhere firmly to the tip of the endoscopic submucosal dissection (ESD) knife as the procedure proceeds, manual removing the firm debris is often challenging and time‐consuming. Recently, effective ultrasonic cleaning for other medical devices has been reported. The aim of the present study was to clarify whether ultrasonic cleaning is effective in removing the debris on the insulation‐tipped diathermic (IT) knife‐2. Methods This study was an ex‐vivo experimental randomized study. A total of 40 IT knife‐2 knives with debris on their tip surfaces were prepared and randomly assigned to two groups (Group A and Group B). The knives in Group A were cleaned using the conventional scrubbing method for 30 s (conventional cleaning method), while those in Group B were cleaned using a combined method of scrubbing for 20 s and ultrasonic cleaning for 10 s (combined ultrasonic cleaning method). The tip electrode of the knife after cleaning was photographed under a microscope (40x). The 40 images of the knives were evaluated by independent three endoscopists and two clinical engineers using the five‐step evaluation criteria ranging from cleaning score 1 (dirty) to 5 (clean). Results The mean cleaning score of 3.78 (range: 2.33–4.67) in Group B was significantly higher than that of 1.68 (range: 1.00–2.83) in Group A. Conclusions The combined ultrasonic cleaning method could remove debris adhering to the IT knife‐2 more effectively than the conventional cleaning method. Ultrasonic cleaning may be applied for real‐world ESD.

Abstract The brain produces steroids de novo from cholesterol, so‐called “neurosteroids.” The Purkinje cell, a cerebellar neuron, was discovered as a major site of the biosynthesis of neurosteroids including sex steroids, such as progesterone, from cholesterol in the brain. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on the Purkinje cell to prevent cell death of this neuron. Recently, the pineal gland was discovered as an important site of the biosynthesis of neurosteroids. Allopregnanolone, a major pineal neurosteroid, acts on the Purkinje cell for the survival of this neuron by suppressing the expression of caspase‐3, a crucial mediator of apoptosis. This review summarizes the discovery of cerebellar and pineal allopregnanolone and its neuroprotective action on Purkinje cells.

Abstract Aims/Introduction The role of glucagon abnormality has recently been reported in type 2 diabetes; however, its role in gestational diabetes mellitus (GDM) is still unknown. The glucose intolerance in GDM is heterogeneous, and not all patients require insulin treatment during pregnancy. Here, we investigated whether glucagon abnormality is associated with the requirement for insulin treatment during pregnancy. Materials and Methods A total of 49 pregnant women diagnosed with GDM were enrolled. They underwent a 75‐g oral glucose tolerance test during mid‐gestation, and we measured their plasma glucagon levels (by a new sandwich enzyme‐linked immunosorbent assay) at fasting (0 min), and at 30, 60 and 120 min after glucose load in addition to the levels of plasma glucose and serum insulin. All participants underwent another oral glucose tolerance test at postpartum. Results Of the 49 patients, 15 required insulin treatment (Insulin group) and 34 were treated with diet therapy alone until delivery (Diet group). The early‐phase glucagon secretion after glucose load, as determined by the changes in glucagon from the baseline to 30 min, was paradoxically augmented during mid‐gestation in the Insulin group, but not in the Diet group. The impaired glucagon suppression during mid‐gestation in the Insulin group was not associated with insulin secretory/sensitivity indexes studied, and was ameliorated postpartum, although the plasma glucose levels remained higher in the Insulin group versus the Diet group. Conclusions Impaired early‐phase suppression of glucagon could be associated with the requirement for insulin treatment during pregnancy in patients with GDM.

Abstract Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2, has become a global pandemic. Many survivors of serious COVID‐19 pneumonia have long‐term residual pulmonary disease. However, there is little documentation of the histopathological characteristics of lung sequelae post‐COVID‐19 and effective treatments. We present two Japanese cases of lung sequelae post‐COVID‐19. The patients were histopathologically diagnosed with organizing pneumonia (OP) or OP with fibrosis and no diffuse alveolar damage on video‐assisted thoracoscopic surgery. Case 1, who had been diagnosed with OP, was successfully treated with corticosteroid and other immunosuppressive agents over a 6‐month period. Although case 2, who had been diagnosed with OP with fibrosis, had a partial and unsatisfactory response to immunosuppressive agents, the patient responded to antifibrotic treatment including nintedanib.

Objective There is increasing evidence that the high-sensitivity modified Glasgow prognostic scores are inflammatory indices that can predict survival for many cancer types. However, there is limited information regarding their prognostic values in cases of head and neck cancer. This study aimed to evaluate whether the high-sensitivity modified Glasgow prognostic scores could predict outcomes among patients with oropharyngeal squamous cell carcinoma (OPC). Study Design Retrospective study. Setting University hospital. Methods We reviewed the records of 106 patients with histologically confirmed OPC between March 2009 and June 2020. The high-sensitivity modified Glasgow prognostic scores were calculated as 0 (C-reactive protein [CRP] concentration: ≤0.3 mg/dL), 1 (CRP concentration >0.3 mg/dL and albumin concentration ≥3.5 mg/dL), or 2 (CRP concentration >0.3 mg/dL and albumin concentration

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J‐SSCG 2020), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created as revised from J‐SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high‐quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J‐SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU‐acquired weakness [ICU‐AW], post‐intensive care syndrome [PICS], and body temperature management). The J‐SSCG 2020 covered a total of 22 areas with four additional new areas (patient‐ and family‐centered care, sepsis treatment system, neuro‐intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large‐scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE‐based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J‐SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Abstract IODP Site U1437 is located in the Izu rear‐arc region, approximately 330 km west of the Izu‐Bonin trench axis. The oldest four units (Units IV through Unit VII) include volcaniclastic sediment and in situ hyaloclastites. They have ages of about 6–15 Ma, shortly after cessation of Shikoku backarc basin opening. Three magma types are identified by their distinct geochemistry; they are similar types to those found in the modern Izu arc (Rear Arc Seamount Chain [RASC]‐type, Rift‐type, and volcanic front [VF]‐type). RASC‐type has the most enriched Nd and Hf isotope and fluid‐immobile trace element ratios and dominates from 9 to 6 Ma. Rift‐type, dominant from 15 to 9 Ma, is similar to VF‐type in Nd‐Hf isotopes but has the least radiogenic Sr and Pb, and intermediate La/Yb and Nb/Yb, indicating a more fertile mantle source and less hydrous slab component than VF‐type. Less common and randomly distributed VF‐type sediments have the most radiogenic Sr and Pb, and the highest Ba/(Th, LREE [light rare earth element]) ratios, and are interpreted to be distally derived. The genesis of mafic Unit VII samples (~15 Ma) was modeled using the Arc Basalt Simulator. Results are most similar to those for basalts in the modern rift environment indicating the addition of ~1% of a melt‐rich slab component generated at ~125 km, to a Philippine Sea Plate ambient mantle that was more depleted than DMM (depleted MORB mantle). The initial post‐Shikoku basin magmatism in the Izu rear‐arc generated Rift‐type magmas for about 6 million years before the distinctive RASC‐type magmatism began, which then became increasingly enriched.

Background Detection of the fiber orientation pattern of the myocardium using diffusion tensor magnetic resonance imaging lags ≈12 weeks of gestational age (WGA) behind fetal myocardial remodeling with invasion by the developing coronary vasculature (8 WGA). We aimed to use diffusion tensor magnetic resonance imaging tractography to characterize the evolution of fiber architecture in the developing human heart from the later embryonic period. Methods and Results Twenty human specimens (8–24 WGA) from the Kyoto Collection of Human Embryos and Fetuses, including specimens from the embryonic period (Carnegie stages 20–23), were used. Diffusion tensor magnetic resonance imaging data were acquired with a 7T magnetic resonance system. Fractional anisotropy and helix angle were calculated using standard definitions. In all samples, the fibers ran helically in an organized pattern in both the left and right ventricles. A smooth transmural change in helix angle values (from positive to negative) was detected in all 16 directions of the ventricles. This feature was observed in almost all small (Carnegie stage 23) and large samples. A higher fractional anisotropy value was detected at the outer side of the anterior wall and septum at Carnegie stage 20 to 22, which spread around the ventricular wall at Carnegie stage 23 and in the early fetal samples (11–12 WGA). The fractional anisotropy value of the left ventricular walls decreased in samples with ≥13 WGA, which remained low (≈0.09) in larger samples. Conclusions From the human late embryonic period (from 8 WGA), the helix angle arrangement of the myocardium is comparable to that of the adult, indicating that the myocardial structure blueprint, organization, and integrity are already formed.

Abstract Volcanoes in the East Asian/Pacific region have been the source of some of the largest magnitude eruptions during the Late Quaternary, and accurately evaluating their eruptive histories is essential for hazard assessments. To overcome difficulties in resolving and precisely dating eruptions in the near‐source realm, the high‐resolution (varved) sediments of Lake Suigetsu (central Honshu, Japan) were examined for the presence of non‐visible (cryptotephra) layers from 50 ka up until the 30 ka Aira‐Tanzawa (AT) caldera‐forming event of Aira volcano. Cryptotephra layers are four times more frequently preserved than visible markers in the Suigetsu sediments, meaning that this archive provides a unique and unprecedented record of eruptions that were dispersed over the densely populated regions of central Honshu. Major and trace element volcanic glass chemistry is used to fingerprint the ash layers and pinpoint their volcanic origin. Tephras are found throughout the investigated sediments, but the highest abundance of ash fall events are recorded between 39 and 30 ka, capturing a period of intense volcanism at calderas on Kyushu Island (Japan). The augmented Suigetsu tephrostratigraphy records at least seven eruptions from Aso caldera (southern Kyushu) that post‐date the widespread ACP‐4 Plinian eruption (ca. 50 ka) and four explosive events from Aira (central Kyushu) that occurred leading up to the catastrophic caldera‐forming AT eruption (ca. 30 ka).

Abstract Background Effects of nonparoxysmal atrial fibrillation (non‐PAF) ablation targeting complex fractionated atrial electrogram (CFAE) areas and/or low voltage areas (LVAs) are still controversial. Methods and Results A recently developed online real‐time phase mapping system (ExTRa Mapping) was used to conduct LVA mapping and simultaneous ExTRa and CFAE mapping in 28 non‐PAF patients after pulmonary vein isolation (PVI). Nonpassively activated areas, in the form of meandering rotors and/or multiple wavelets assumed to contain non‐PAF drivers, partly overlapped with CFAE/LVAs but not always coincided with them. Conclusion Real‐time rotor imaging, rather than conventional indirect indicators only, might be very useful for detecting non‐PAF drivers.

Abstract Aim This prospective, randomized, controlled, rater‐blinded study investigated the effect of G protein‐activated inwardly rectifying potassium (GIRK) channel inhibitor ifenprodil on alcohol use in patients with alcohol dependence. Methods The participants were 68 outpatients with alcohol dependence who were assigned to an ifenprodil group (administered 60 mg ifenprodil per day for 3 months) or control group (administered 600 mg ascorbic acid and calcium pantothenate per day for 3 months). The participants completed a questionnaire that included the frequency of alcohol drinking and presence of heavy drinking before the study period (time 1) and 3 months after the start of the study period (time 2). The alcohol use score was calculated using these two items. Results Valid data were obtained from 46 participants (25 in the ifenprodil group and 21 in the control group). The alcohol use score at time 2 in the ifenprodil group was significantly lower than that in the control group after adjusting for the score at time 1 and some covariates. The intention‐to‐treat analysis of multiply imputed datasets indicated similar results. Group differences in the frequency of alcohol drinking were significant in the multiply imputed datasets but not in 46 participants. The ifenprodil group had a significantly lower rate of heavy drinking at time 2 than the control group. Conclusions This study found an inhibitory effect of ifenprodil on alcohol use in patients with alcohol dependence. The results support the hypothesis that GIRK channel inhibitors ameliorate alcohol dependence. Trial registry This trial was registered in the UMIN clinical trial registry (UMIN000006347).