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Abstract Background Concurrent chemoradiotherapy is the standard therapy for locally advanced non‐small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low‐dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population. To establish a simple and feasible carboplatin administration method, we conducted a study of weekly carboplatin and concurrent radiotherapy for older adults with locally advanced NSCLC. Methods This prospective, single‐arm, multicenter, phase II clinical trial included patients aged ≥75 years with unresectable stage III NSCLC and Eastern Cooperative Oncology Group performance status 0–1. Patients received chemoradiotherapy (60 Gy/30 fractions plus concurrent weekly carboplatin at an area under curve of 2 mg mL−1 min−1). The primary endpoint was the overall response rate (ORR). Key secondary endpoints included progression‐free survival (PFS), overall survival (OS), and safety. Results From July 2020 to June 2022, 37 patients were enrolled from 15 institutions, and 36 patients were evaluable for efficacy and safety. The ORR was 63.9% (95% confidence interval [CI] = 47.6–77.5). Median PFS was 14.6 months (95% CI = 9.1–18.1). Median OS was 25.5 months (95% CI = 17.4–not reached). Grade 4 leucopenia, neutropenia, and thrombocytopenia were observed in one patient (2.8%) each. Conclusion Weekly carboplatin and concurrent radiation therapy was safe in older adults with locally advanced NSCLC, and promising activity was observed.

Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non‐invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin‐4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child–Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child–Pugh class B–C (39 without HCC, 26 with HCC)], fibulin‐4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin‐4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin‐4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin‐4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis.

Abstract Aims/Introduction This study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state. Materials and Methods We selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques. Results Compared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis

Abstract Background Age‐related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3‐month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)‐based Finite Element Method (FEM). Methods This open‐labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual‐energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post‐treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P‐vBMD) and vertebral body (V‐vBMD). Results Romosozumab treatment led to significant gains in P‐vBMD, and V‐vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group. Conclusion Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post‐operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.

Abstract Background and Aim Neutrophil gelatinase‐associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. Methods This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Results Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child–Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Conclusion Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

Abstract Diagnosis and treatment of pulmonary hypertension (PH) in patients with lung diseases (PH‐LD) remain unestablished and pose significant challenges. In this report, we present a case of a 77‐year‐old patient with an indeterminate for usual interstitial pneumonia pattern along with chronic obstructive pulmonary disease, who developed groups 1 and 3 PH. Following diagnosis, upfront triple oral combination therapy (UTOCT) with macitentan, sildenafil, and selexipag was initiated. Stability in disease progression was achieved over 4 years with the addition of pirfenidone to address interstitial lung disease progression. To the best of our knowledge, this represents the first reported case of PH‐LD, where disease control was maintained with the addition of pirfenidone to UTOCT. This case suggests that some patients with PH‐LD, presenting with groups 1 and 3 PH, may benefit from combined UTOCT and antifibrotic agents, potentially improving symptoms and extending their prognosis.

Abstract The electromagnetic interaction between Europa and the plasma sheet in the Jovian magnetosphere generates Alfvén waves, ultimately generating auroral footprints in Jupiter's atmosphere. The position of Europa's auroral footprint is a proxy for travel time of the Alfvén waves. We measured Europa's footprint position using the far‐ultraviolet images of Jupiter obtained by the Hubble Space Telescope in two observing campaigns in 2014 and 2022. The measured footprint position indicates a longer Alfvén travel time in the 2022 campaign. We retrieved the plasma sheet parameters at Europa's orbit from the footprint position by tracing the Alfvén waves launched at Europa and found an increase of both mass density and temperature in the plasma sheet in 2022. The Poynting flux generated at Europa is calculated with the retrieved plasma sheet parameters, which suggests the total energy transfer from Europa to its auroral footprint is similar to the case of Io.

Abstract Lymphoid follicular hyperplasia (LFH) is a benign lymphoproliferative disease. Although it can occur within the thoracic cavity, LFH originating from the chest wall has not been reported. A 79‐year‐old woman was incidentally found to have a well‐defined mass on the left posterior chest wall during a preoperative examination for aortic valve replacement. The mass had slowly grown over 6 years. Thoracoscopic surgical resection was performed without complications. Pathological examination ruled out lymphoproliferative diseases, such as Castleman disease or malignant lymphoma, and a diagnosis of LFH was made. Although LFH generally has a good prognosis, surgical resection is recommended for diagnostic and therapeutic purposes owing to the possibility of malignancy masquerading as a reactive lesion. This is the first report of an LFH arising from the chest wall with imaging findings similar to other benign tumours. Its potential as a differential diagnosis for tumours with similar imaging findings is highlighted.

Abstract Metastatic inflammatory myofibroblastic tumor (IMT) is very rare and detailed reports on diagnosis and treatment are limited. Here, we report a case of metastatic IMT with ALK rearrangement. A 73‐year‐old woman was diagnosed with IMT involving a brain metastasis. Next generation sequencing (NGS) panel testing with Oncomine dx target test revealed that her tumor was positive for EML4‐ALK. Treatment with alectinib was initiated, resulting in remarkable shrinkage of both the primary tumor and the brain metastasis. This report is the first to identify ALK rearrangement in IMT using a commercially available NGS panel testing, followed by treatment with alectinib. This case suggests that NGS panel testing may be useful in the diagnosis and treatment of patients with metastatic IMT.

Abstract IgG4‐related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4‐related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80‐year‐old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography‐guided biopsy of the retroperitoneum showed B cell‐dominant lymphocyte infiltration consistent with IgG4‐related retroperitoneal fibrosis and characteristic CD8‐positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4‐related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4‐related retroperitoneal fibrosis can occur as an immune‐related adverse event when administering anti‐PD‐1 and anti‐CTLA‐4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune‐related adverse event.

Abstract North America is recognized for the exceptional richness of rabies virus (RV) wildlife reservoir species. Management of RV is accomplished through vaccination targeting mesocarnivore reservoir populations, such as the raccoon (Procyon lotor) in Eastern North America. Raccoons are a common generalist species, and populations may reach high densities in developed areas, which can result in contact with humans and pets with potential exposures to the raccoon variant of RV throughout the eastern United States. Understanding the spatial movement of RV by raccoon populations is important for monitoring and refining strategies supporting the landscape‐level control and local elimination of this lethal zoonosis. We developed a high‐throughput genotyping panel for raccoons based on hundreds of microhaplotypes to identify population structure and genetic diversity relevant to rabies management programs. Throughout the eastern United States, we identified hierarchical population genetic structure with clusters that were connected through isolation‐by‐distance. We also illustrate that this genotyping approach can be used to support real‐time management priorities by identifying the geographic origin of a rabid raccoon that was collected in an area of the United States that had been raccoon RV‐free for 8 years. The results from this study and the utility of the microhaplotype panel and genotyping method will provide managers with information on raccoon ecology that can be incorporated into future management decisions.

Abstract We present the first direct evidence of an in situ excitation of drift‐compressional waves driven by drift resonance with ring current protons in the magnetosphere. Compressional Pc4–5 waves with frequencies of 4–12 mHz were observed by the Arase satellite near the magnetic equator at L ∼ 6 in the evening sector on 19 November 2018. Estimated azimuthal wave numbers (m) ranged from −100 to −130. The observed frequency was consistent with that calculated using the drift‐compressional mode theory, whereas the plasma anisotropy was too small to excite the drift‐mirror mode. We discovered that the energy source of the wave was a drift resonance instability, which was generated by the negative radial gradient in a proton phase space density at 20–25 keV. This proton distribution is attributed to a temporal variation of the electric field, which formed the observed multiple‐nose structures of ring current protons.

Abstract Background and Aim Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE‐based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B. Methods A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The primary endpoint was the association between MRE‐based liver stiffness and HCC. Results In a cross‐sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89–4.96) and 2.60 (2.22–3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (P

Abstract Several cases of esophageal stenosis caused by cervical vertebral osteophytes have been reported; however, few reports of esophageal stenosis caused by thoracic osteophytes are available. We describe the case of an 86‐year‐old man with esophageal stenosis caused by a thoracic osteophyte near the tracheal bifurcation. An endoscopic ultrasonography examination was scheduled to determine the cause of acute pancreatitis; however, lacerations observed at the bifurcation following endoscope removal during prior esophagogastroduodenoscopy led us to cancel the ultrasonography to avoid potential esophageal perforation. A review of the present case and six similar previous cases of thoracic osteophyte‐associated esophageal stenosis (identified via a systematic search of the PubMed database) demonstrated the clinical importance of a thoracic osteophyte near physiological esophageal stenosis. Esophagogastroduodenoscopy and computed tomography should be performed to screen for vertebral osteophytes before endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, and transesophageal echocardiography to avoid iatrogenic accidents.

Abstract Objectives Endoscopic transpapillary gallbladder drainage (ETGBD) is a highly technical procedure, but few studies have evaluated factors that predict its technical success. Therefore, in this study, we sought to identify predictors of technically successful ETGBD. Methods One hundred and eighty‐two patients who underwent ETGBD for acute cholecystitis at our hospital were retrospectively investigated. Factors associated with technical failure were identified by focusing on clinical characteristics, anatomical features (direction of the cystic duct branch and course of the cystic duct), and procedural factors (cystic duct and gallbladder with or without contrast and cystic duct injury). Results The technical success rate was 84.6% (154/182) and the clinical success rate was 96.1% (148/154). The adverse event rate was 11.0% (20/182; cystic duct injury in 13 patients, pancreatitis in six, and liver abscess in one. Univariate and multivariate analyses identified the right cranial direction and spiral‐type course of the cystic duct to be significant anatomical features and cystic duct injury to be a significant procedural feature contributing to the technical failure of ETGBD. Conclusions ETGBD is a highly practical procedure for patients with acute cholecystitis. However, difficulty is encountered in some cases because of anatomical and procedural factors. Our results suggest that ETGBD may be difficult and thus should not be performed in cases with the right cranial direction or spiral‐type course of the cystic duct or those with cystic duct injury.

Abstract Objective Few reports have explored the application of urinary trypsinogen‐2 measurement in the early diagnosis of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, and none have demonstrated the benefits of noninvasive testing. This study aimed to evaluate the clinical application of the rapid urinary trypsinogen‐2 dipstick test (Nipro, Japan) compared with serum amylase and lipase levels for the early diagnosis of post‐ERCP pancreatitis (PEP). Methods A total of 100 consecutive patients (54 men and 46 women) who were admitted and underwent ERCP at Tokyo Medical University Hospital from August 2021 to December 2021 were recruited. All patients underwent rapid urinary trypsinogen‐2 measurement using the dipstick test before and after ERCP. Measurements were taken 24 h before ERCP for pre‐ERCP and 1–4 h after ERCP for post‐ERCP. Additionally, serum amylase and lipase levels were measured at 8:00 a.m. of the day after ERCP (at least 8 h after ERCP), and their diagnostic abilities for PEP were compared and evaluated. Results PEP occurred in 5/100 patients (5%). The sensitivity, specificity, positive predictive value, and negative predictive value of the dipstick test for diagnosing PEP were 100%, 83.2%, 23.8%, and 100%, respectively. These results were comparable to the diagnostic performance of serum amylase and lipase levels at 8:00 a.m. on the day after ERCP (at least 8 h after ERCP). However, false positives must be considered. Conclusion The dipstick test may be useful in clinical practice as a noninvasive screening test for the early prediction of PEP.

Abstract Previous studies have shown that auroral kilometric radiation (AKR) can play an important role in the magnetosphere‐atmosphere coupling and has the right‐handed extraordinary (R‐X), left‐handed ordinary (L‐O) and left‐handed extraordinary (L‐X) modes. However, the L‐X mode has not been directly observed in the lower latitude magnetosphere yet, probably because of its very limited frequency range. Here, using observations of the Arase satellite on 6 September 2018, we present an AKR event with two distinct bands (8–20 and 300–1000 kHz) around the location: L = 8 and latitude = −37°. The low (high) band is identified as the L‐X (R‐X) mode based on the polarization and frequency ranges. Simulations of 3‐D ray tracing show that most of ray paths with 14 (11 and 18) kHz pass (miss) the location of Arase, basically consistent with observations. Our study provides direct evidence that the L‐X mode can propagate from high latitudes downward to lower latitudes.

Abstract In summer, the survival zones of cold‐water species are predicted to narrow by both increasing water temperatures from the surface and by expanding hypoxic zones from the lake bottom. To examine how the abundance of cold‐water fishes changes along environmental gradients, we assessed the vertical environmental DNA (eDNA) distributions of three salmonid species which may have different water temperature tolerances during both stratification and turnover periods using quantitative PCR (qPCR). In addition, we examined on the vertical distribution of diverse fish fauna using an eDNA metabarcoding assay. The results suggested that the kokanee salmon (Oncorhynchus nerka) eDNA were abundant in deep, cold waters. On the other hand, rainbow trout (O. mykiss) eDNA were distributed uniformly throughout the water column, suggesting that they may have high water‐temperature tolerance compared with kokanee salmon. The eDNA concentrations of masu salmon (O. masou) were below the detection limit (i.e.,

Abstract Objectives To investigate the efficacy of pharmacotherapy for metastatic non‐clear cell renal cell carcinoma (nccRCC) in Japanese population. Methods In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular‐targeted agents as first‐line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. Results In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian‐target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first‐line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75‐212 days) and mTORIs (21 days, 95% CI: 9‐31 days) didn’t differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174‐243 days and 33 days, 95% CI: 8‐113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p

Abstract Plasmaspheric hiss waves are important to shape the Earth’s electron radiation belt. These waves are commonly envisioned to have a long lifetime which allows them to permeate the global plasmasphere from a spatially restricted source. However, this hypothesis has not been experimentally confirmed yet, because of the challenging observational requirements in terms of location and timing. With wave and particle measurements from five magnetospheric satellites and detailed modeling, we present the first report of long lifetime (∼42 s) hiss rays in the substorm‐disturbed plasmasphere. The low‐frequency hiss waves are found to originate from the middle piece of the plasmaspheric plume, bounce between two hemispheres, and eventually drift into the plasmaspheric core. These hiss rays can travel through ∼3 hr magnetic local time and ∼4 magnetic shell. Such a long‐time and large‐scale permeation of hiss rays could benefit from the ducting process by plasmaspheric field‐aligned density irregularities.

Physical reservoir computing, which is a promising method for the implementation of highly efficient artificial intelligence devices, requires a physical system with nonlinearity, fading memory, and the ability to map in high dimensions. Although it is expected that spin wave interference can perform as highly efficient reservoir computing in some micromagnetic simulations, there has been no experimental verification to date. Herein, reservoir computing is demonstrated that utilizes multidetected nonlinear spin wave interference in an yttrium‐iron‐garnet single crystal. The subject computing system achieves excellent performance when used for hand‐written digit recognition, second‐order nonlinear dynamical tasks, and nonlinear autoregressive moving average (NARMA). It is of particular note that normalized mean square errors for NARMA2 and second‐order nonlinear dynamical tasks are 1.81 × 10−2 and 8.37 × 10−5, respectively, which are the lowest figures for any experimental physical reservoir so far reported. Said high performance is achieved with higher nonlinearity and the large memory capacity of interfered spin wave multidetection.

Abstract Gamma‐ray glows are observational evidence of relativistic electron acceleration due to the electric field in thunderclouds. However, it is yet to be understood whether such relativistic electrons contribute to the initiation of lightning discharges. To tackle this question, we started the citizen science “Thundercloud Project,” where we map radiation measurements of glows from winter thunderclouds along Japan's sea coast area. We developed and deployed 58 compact gamma‐ray monitors at the end of 2021. On 30 December 2021, five monitors simultaneously detected a glow with its radiation distribution horizontally extending for 2 km. The glow terminated coinciding with a lightning flash at 04:08:34 JST, which was recorded by the two radio‐band lightning mapping systems, FALMA and DALMA. The initial discharges during the preliminary breakdown started above the glow, that is, in vicinity of the electron acceleration site. This result provides one example of possible connections between electron acceleration and lightning initiation.

Abstract This study focuses on samples that underwent rapid hydration (∼10 hr) and evolved in permeability (∼10−9 to 10−8 m2) as a result of crustal fracturing. A coupled reactive transport model and thermodynamic analyses, focusing on Si alteration processes within reaction zones, are used to estimate the fluid volume required to induce fluid‐driven seismic activity. Estimated fluid volumes (101–104 m3) are used to approximate the moment magnitudes of potential seismic events. The resulting moment magnitudes (−0.6 to 3.8) and short timescales of fluid infiltration (∼10 hr) are comparable to some slow‐slip events, such as tremors and low‐frequency earthquakes. This indicates that the voluminous fluid flow in a single fracture could be a key control on the generation of crustal fracturing and the induction of seismic activity above the tremor and slow slip events source regions in the lower–middle crust.

Abstract Aims/Introduction Fat mass and fat‐free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat‐free mass index with HbA1c. Materials and Methods We carried out a cross‐sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat‐free mass index were calculated as fat mass and fat‐free mass divided by the height squared, respectively. The indices were classified into sex‐specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat‐free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat‐free mass index, entering the number as a continuous term in the regression model. Results In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat‐free mass index subgroups (P

Abstract Background Dacomitinib is the second‐generation epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) for mutant non–small cell lung cancer (NSCLC). EGFR‐TKIs are often re‐administered in Japan after the disease progression prior EGFR‐TKI. There is little evidence of dacomitinib in rechallenge setting. This study evaluated clinical outcomes of dacomitinib in rechallenge setting. Methods Patients who received dacomitinib for advanced EGFR‐mutant NSCLC who had progressed after EGFR‐TKI in nine institutions in Japan were included in the analyses. Results In total, 43 patients were analyzed. The median progression‐free survival (PFS) was 4.3 months (95% confidence interval [CI], 2.5–5.6). The overall survival (OS) was 10.5 months (95% CI, 7.4–not reached). The overall response rate was 25.5% (95% CI, 13.1–33.7). Subset analysis indicated that patients with EGFR exon 21 L858R showed longer PFS than those with EGFR exon 19 deletion (5.8 vs. 4.1 months) (p = 0.018). The most common adverse events leading to dose modification were diarrhea, paronychia, rash, and oral mucositis. Conclusion In the real practice in Japan, dacomitinib showed a worthwhile treatment option for NSCLC patients with EGFR mutation after failure of previous EGFR‐TKI. The benefit was especially pronounced in patients with the exon 21 mutation.

Abstract Background and Aim Conversion surgery (CS), which aims to cure after systematic therapy, is only scarcely reported in the field of hepatocellular carcinoma (HCC). However, advancements in systemic therapy for HCC are expected to increase the candidates eligible for CS because of the higher response rate. The aim of this study was to clarify the characteristics of patients who underwent CS after tyrosine kinase inhibitor (TKI) therapy. Methods In all, 364 patients who were treated with first‐line sorafenib (SOR; n = 292) and lenvatinib (LEN; n = 72) from July 2009 to October 2020 were retrospectively enrolled. The endpoint of this analysis was overall survival (OS), and factors associated with CS are revealed. Results Six patients underwent CS after TKI therapy, and of these four (1.4%) and two (2.7%) patients received SOR and LEN, respectively. At baseline, patients who underwent CS were significantly younger (median 52 [range, 46–83] years of age, P = 0.019), and their etiology included viral hepatitis, especially hepatitis B virus (HBV) (P = 0.049). Improvements or maintenance of preoperative modified albumin–bilirubin grade from baseline were observed in five (83.3%) patients, and partial radiologic response was observed in four (66.7%) patients. The median OS and 3‐year survival rate of patients treated with CS were “not reached” and 80.0%, respectively. Conclusion The patients who underwent CS after TKI therapy for HCC experienced long survival, were relatively young, and exhibited radiologic response to TKIs, and their liver function was either maintained or improved. Therefore, CS may lead to a better prognosis in patients with advanced HCC.

Abstract Purpose This study aimed to explore whether umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) could be used as a therapeutic resource for endometriosis. Methods Of seven cynomolgus monkeys with endometriosis, five were administered UC‐MSCs (intervention group) and two were administered saline (control group). First, intravenous US‐MSC treatment was administered for three months. Second, weekly intravenous US‐MSC administration combined with monthly intraperitoneal US‐MSC administration was conducted for 3 months. Finally, weekly intraperitoneal US‐MSC administration was conducted for 3 months. The dose of UC‐MSCs was set to 2 × 106 cells/kg for all administration routes. Laparoscopic findings and serum cancer antigen 125 (CA125) levels were also evaluated. The Revised American Society for Reproductive Medicine classification was used for laparoscopic evaluation. Results Laparoscopic findings showed exacerbation of endometriosis after intraperitoneal UC‐MSC administration, although no changes were observed in the control group. Intravenous UC‐MSC administration decreased the level of CA125 in all monkeys; however, the difference was not significant. Intraperitoneal UC‐MSC administration significantly exacerbated endometriosis compared with intravenous administration (p = 0.02). Conclusions This study revealed that intraperitoneal UC‐MSC administration exacerbates endometriosis in a nonhuman primate model of the disease.

Abstract Background We determined the prevalence of current cigarette smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer in Japan and compared the findings with nationally representative studies in other countries. Methods We conducted a cross‐sectional study of baseline data from a prospective cohort study. A self‐administered questionnaire was surveyed during 2013–2015 with residents aged ≥20 years attending a community‐based cardiometabolic screening program in Miyagi prefecture in north‐eastern Japan. Subjects with past cancer histories were classified as cancer survivors. Sex‐specific, age‐standardized prevalence of current smokers, and drinkers were calculated. Age‐adjusted prevalence ratios (PRs: the cancer survivors’ rate divided by the rate of subjects with no history of cancer) and 95% confidence intervals (CIs) were estimated with log‐binomial regressions. Results 36,786 subjects, including 2760 cancer survivors, responded and provided usable information (58.9% of recruited subjects). For men, the age‐standardized prevalence of current smokers and drinkers among survivors was 18.8% and 74.4%, respectively, with an age‐adjusted PR (95%CI) of 0.76 (0.66–0.86, p

Abstract Here, a gated‐anode diode (GAD) is proposed where an anode electrode is formed by connecting a gate electrode and an ohmic electrode of a normally‐off GaN HEMT for a 5.8 GHz rectenna. A wide recessed gate GaN GADs were prepared and the recess length dependence of their electrical characteristics was investigated. Typical DC characteristics of the HEMTs are a threshold voltage (Vth) of +0.3 V and a maximum drain current (Imax) of 300 mA/mm. The GADs showed the characteristics of maximum forward current (If) of 350 mA/mm, reverse breakdown voltage (BVr) of 40 V, and off‐state capacitance (Coff) of 0.28 pF/mm by using optimized recess length. We constructed SPICE model of the GADs. The SPICE simulation predicted a rectifier efficiency of 81% and a DC output power of 10 W for bridge type 5.8 GHz rectifier using four GADs with each gate width of 0.8 mm.

Abstract Objectives Recently, a novel clip device, SureClip® (Micro‐Tech Co. Ltd., Nanjing, China), has been developed, which improved rotation and reopening performance. We aimed to assess the efficacy of the SureClip® in prophylactic closure of the mucosal break after endoscopic papillectomy (EP) for ampullary neoplasm. Methods We retrospectively reviewed the medical records of 40 patients who underwent EP for ampullary neoplasms between October 2009 and March 2020. Prophylactic closure after resection was performed using the conventional clip between 2014 and 2018, and with the SureClip® after 2019. The baseline characteristics, techniques, outcomes, and complications of EP were analyzed. Results The median age of the patients (25 males and 15 females) was 70 years. The en block resection rate was 82.5% and the curative resection rate was 80.0%. Histologically, 11 (27.5%) patients had malignancy. Prophylactic closure was performed in 29 (72.5%) patients (17 conventional clips, 12 SureClip®). Complications occurred in 18 (45.0%) patients, including postprocedure bleeding in 9 (22.5%) patients. However, no postprocedure bleeding was observed in the patients who received prophylactic closure using the SureClip® (p = 0.038). All other factors were not significantly correlated with postprocedure bleeding. The duration of hospital stay after EP was significantly shorter in patients treated with the SureClip® compared to those treated with a conventional clip or without clips (p < 0.05). Conclusions In the present study, prophylactic clipping of the mucosal break using the SureClip® was effective in preventing bleeding after EP.

Abstract Objectives Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double‐ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2–3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α‐diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.