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The Jikei Academic Nursing Practice Center for the Community developed a community nursing practice that matched community health problems and concerns in Chofu and Komae cities, suburban areas of the Tokyo Metropolis. This study aimed to identify health problems and high‐risk populations via an understanding of the practice of health behaviors, health literacy, and quality of life. This was an online, cross‐sectional study conducted in September 2023. In total, 1520 (Chofu: n = 1170; Komae: n = 350) participants were enrolled. Participants' demographic characteristics, health literacy, health behaviors, and quality of life scores were obtained. Sleep quality was poor compared with national data. Younger participants had higher poor health literacy, did not practice health behaviors, and had a lower quality of life. In addition, parenting and informal nursing care for family members were associated with unhealthy eating, smoking, drinking, and poor quality of life. This study found that health problems and concerns before planning were significant in increasing the salience of interventions for community residents. Based on the findings of this study, an action plan for community‐wide nursing practice was created. [ABSTRACT FROM AUTHOR]

We present two cases of middle‐aged men who developed Fanconi syndrome and renal dysfunction after consuming "foods with functional claims (FFC)" containing red yeast rice. In the first case, the patient had consumed an FFC for 1 year and another FFC suspected to have contained nephrotoxin for 3 weeks; kidney biopsy performed during the acute phase of renal injury showed severe acute tubular necrosis and tubular cell regeneration. He achieved near‐complete recovery 40 days after the FFC was discontinued. In the second case, the patient had consumed FFC for 4 years and stopped 70 days prior to presentation; kidney biopsy revealed significant tubular recovery, persistent tubular injuries, and interstitial fibrosis. Although the manifestations of Fanconi syndrome subsided, mild renal dysfunction persisted. These cases suggest that FFC with nephrotoxins may induce Fanconi syndrome owing to acute tubular necrosis. Recovery is possible after discontinuing the FFC; while short‐term ingestion of FFC allows for tubular regeneration, its long‐term ingestion may cause irreversible damage and lead to chronic kidney disease. Long‐term follow‐up is crucial for preventing further renal deterioration. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Aerobic exercise may be an effective treatment for knee osteoarthritis and central sensitization, but no interventional studies have examined its effects. In this study, the patient showed improvement in central sensitization, pain, and autonomic nervous system activity after aerobic exercise using an arm ergometer. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate real‐world epidemiologic trends and treatment patterns in newly diagnosed patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in Japan. Methods: This retrospective analysis included adults with newly diagnosed la/mUC in Japan (January 2015–December 2019) from a nationwide‐linked electronic medical record Diagnostic Procedure Combination claims dataset. Outcomes included epidemiologic trends (incidence and prevalence), baseline demographics, clinical characteristics, and treatment patterns in newly diagnosed patients with la/mUC before (2015–2017) and after (2018–2019) approval of pembrolizumab in Japan. Results: Of 975 patients included, 76.4% were men; 71.6% were aged 70 years or older. Most cases (70.5%) were of the bladder. Between 2015 and 2019, the annual age‐adjusted incidence increased from 6.8 to 12.4 per 100 000; the annual age‐adjusted period prevalence increased from 13.0 to 25.2 per 100 000; and 307 (31.5%) and 668 (68.5%) patients were diagnosed from 2015 to 2017 and 2018 to 2019, respectively. Overall, 731 (75%) patients received systemic anticancer therapy; all received 1 line and 50.2% received 2 lines of therapy; 78.3% of patients received gemcitabine plus platinum‐based therapy and 2.2% received pembrolizumab as first‐line treatment. First‐line treatment rates increased from 69.4% to 77.5% after pembrolizumab approval. Of 367 patients who received second‐line treatment, 22.3% received gemcitabine plus platinum‐based therapy; 14.7% received pembrolizumab. Conclusions: In the Japanese regions considered, incidence and prevalence of newly diagnosed la/mUC increased over time and first‐line treatment with pembrolizumab increased after approval. [ABSTRACT FROM AUTHOR]

We conducted an autopsy on a 3‐month‐old boy in whom Kawasaki disease (KD) was strongly suspected based on the autopsy findings. The infant had a fever and was brought to a nearby clinic, where he was prescribed antipyretics and kept under observation. However, 15 days after onset of the fever, he suddenly died in bed. He exhibited no obvious redness of the lips, tongue, or conjunctiva. Membranous desquamation was present on his distal fingers. Vasculitis was observed in the coronary arteries, renal artery, splenic artery, and pulmonary vein. In addition, coronary artery aneurysms were present in the right coronary artery and left anterior descending artery. Thrombotic occlusion was observed in one aneurysm in the right coronary artery, resulting in acute myocardial infarction. The coronary artery wall showed infiltration of numerous macrophages and neutrophils. This case was classified as incomplete KD because the coronary artery aneurysm could not be demonstrated before death and was only recognized at autopsy. Pathologists and forensic scientists need to be aware that there are cases in which KD goes undiagnosed and untreated, leading to coronary artery aneurysm formation and sudden death. [ABSTRACT FROM AUTHOR]

The reactivity of an isolable 2‐germapropadiene with acids, ketones, and amines was investigated. The reactions of 2‐germapropagiene 1 with hydrogen chloride and acetic acid afforded the corresponding dichlorogermane (2) and diacetoxygermane (3), respectively, indicating that the central germanium atom of 1 is electrophilic. The reaction of 1 with benzaldehyde proceeds via a formal [2+2] cycloaddition to afford the corresponding spiro compound (4). Moreover, 1 reacts smoothly with acetone to furnish germane 5, which contains a six‐membered ring involving two acetone molecules. Furthermore, 1 undergoes N−H bond insertion with methylamine or aniline to afford diamino germanes 7 and 8, respectively. The reaction of 1 with urea selectively afforded the corresponding N−H−insertion product (8). [ABSTRACT FROM AUTHOR]

A 12-year-old spayed female Dalmatian presented with acute vomiting and anorexia. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and multiple diffuse splenic hypoechogenic nodules. Cholecystectomy was performed to remove the obstruction, followed by liver biopsy and splenectomy. Histopathological and immunohistology evaluation of the spleen, liver, and gallbladder revealed splenic marginal zone lymphoma (MZL) with gallbladder and hepatic infiltration of neoplastic CD20/CD79α-positive cells. Moreover, we observed clonal rearrangements of the immunoglobulin heavy-chain (IgH) gene in all three tissues. The dog was in good condition without chemotherapy. However, there was progressive elevation of liver enzymes, which could be attributed to neoplastic hepatic infiltration. Chlorambucil and prednisolone were administered until day 108, when the liver enzyme levels normalized. On day 156, the dog developed diffuse large B-cell lymphoma (DLBCL) of the peripheral lymph nodes. Sequence analysis of the clonally rearranged IgH gene revealed that all neoplastic cells in the spleen, gallbladder, and liver at initial presentation, as well as lymph nodes on day 156, possessed the same sequence identity of the amplified IgH fragments. This demonstrated that all neoplastic cells were derived from the same B-lymphocyte clone. The DLBCL was considered to have transformed from the splenic MZL, with gallbladder involvement. In cases of splenic MZL, it is important to consider gallbladder involvement and transformation to DLBCL. Moreover, gallbladder lymphoma should be included in the differential diagnosis of dogs with gallbladder abnormalities. Further studies are warranted to investigate the prognosis of splenic MZL. [ABSTRACT FROM AUTHOR]

Aim: C‐reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC). Methods: A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C‐reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score. Results: Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin–bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313–5.107; log‐rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin–bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1‐year survival prediction after first‐line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively. Conclusions: CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy. [ABSTRACT FROM AUTHOR]

To further our understanding of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E17 guideline and promote effective implementation, a public workshop was held in Japan by regulatory agency and industry representatives. In this workshop, important concepts explained in the ICH E17 guideline, such as intrinsic/extrinsic ethnic factors that influence treatment effects ("effect modifiers") and the holistic evaluation of consistency of treatment effect were actively discussed through case studies. The importance of holistic evaluation of consistency was recognized, and it was concluded that the evaluation and relevant discussion should be shared with regulatory authorities, sponsors, and broader stakeholders. [ABSTRACT FROM AUTHOR]

Luciferase is a popular enzyme used for biological analyses, such as reporter assays. In addition to a conventional reporter assay using a pair of firefly and Renilla luciferases, a simple multicolor reporter assay using multiple firefly or beetle luciferases emitting different color luminescence with a single substrate has been reported. Secretory luciferases have also been used for convenient sample preparation in reporter assays; however, reporter assay using secretory luciferase mutants that emit spectrum‐shifted luminescence have not yet been reported. In this study, we generated blue‐ and red‐shifted (−16 and 12 nm) luminescence‐emitting Cypridina secretory luciferase (CLuc) mutants using multiple cycles of random and site‐directed mutagenesis. Even for red‐shifted CLuc mutant, which exhibited relatively low activity and stability, its enzymatic activity was sufficiently high for a luciferase assay (3.26 × 106 relative light unit/s), light emission was sufficiently prolonged (half‐life is 3 min), and stability at 37°C was high. We independently determined the luminescence of these CLuc mutants using a luminometer with an optical filter. Finally, we replaced the commonly used reporters, firefly and Renilla luciferases used in a conventional nuclear receptor–reporter assay with these CLuc mutants and established a secretory luciferase‐based single‐substrate dual‐color nuclear receptor–reporter assay. [ABSTRACT FROM AUTHOR]

Introduction: Dual atrioventricular nodal non‐reentrant tachycardia (DAVNNT) is a rare and challenging‐to‐diagnose arrhythmia, without previous reports associating it with a leftward inferior extension (LIE). Methods: Diagnosis was made using adenosine triphosphate (ATP) injection during atrial pacing in a suspected DAVNNT patient. Results: Ablation of the rightward inferior extension was unsuccessful in eliminating DAVNNT; however, subsequent ablation of the LIE successfully eradicated the arrhythmia. Conclusion: This unique case, marked by the first instance of DAVNNT caused by LIE, diagnosed through ATP injection, underscores the utility of this diagnostic approach and broadens the spectrum of our understanding and management of this condition. [ABSTRACT FROM AUTHOR]

Aim: To compare the effects of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) versus dipeptidyl peptidase‐4 inhibitors (DPP4is) on liver function in patients with type 2 diabetes (T2D) in Japan. Materials and Methods: This was a Japanese retrospective cohort study using the RWD Database (1 January 2015 to 24 September 2021). Patients newly treated with an SGLT2i or a DPP4i were matched 1:4 (SGLT2i:DPP4i) using propensity score. The primary endpoint was the change from baseline to 1 year after the index date in alanine aminotransferase (ALT). Secondary endpoints included change from baseline in various laboratory test results, including the Fibrosis‐4 (FIB‐4) index, aspartate aminotransferase, gamma‐glutamyl transpeptidase (GGT), albumin and HbA1c. Endpoints were compared between treatment groups using Welch's t‐test in the full population and in subgroups stratified by baseline characteristics. Results: Baseline characteristics of 955 and 3063 matched patients newly treated with an SGLT2i and a DPP4i, respectively, were well balanced. Patients receiving an SGLT2i had significantly greater reductions in ALT, FIB‐4 index and GGT and a significantly greater increase in albumin than patients receiving a DPP4i. A significantly greater change from baseline in ALT was observed in the SGLT2i group than in the DPP4i group among subgroups with lower baseline FIB‐4 index and HbA1c. Conclusions: In this study, improvements in various measures, including ALT, the FIB‐4 index, GGT and albumin, were observed with SGLT2is compared with DPP4is, suggesting that SGLT2is may provide hepatoprotective benefits, including the prevention of liver fibrosis, in patients with T2D in Japan. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hip fractures are associated with a reduction in activities of daily living (ADL) and require long‐term care. The physical activity of patients with hip fractures is temporarily impaired immediately after surgery, causing difficulty in the measurement of physical activities at the time of rehabilitation admission. This study examined the relationship between ADL at discharge and light‐ and moderate‐intensity physical activity at the time of rehabilitation admission by determining a cut‐off value predicting ADL independence. Methods: This retrospective case control study analyzed 43 postoperative hip fracture patients aged ≥65 years admitting into inpatient rehabilitation. ADL at discharge was assessed using the Functional Independent Measure motor items (FIM‐m). The duration of physical activity at the time of rehabilitation admission was measured using an activity tracker equipped with an accelerometer. Prehospital frailty was evaluated using Clinical Frailty Scale. The relationship between these variables was examined using Spearman's product‐moment correlation coefficient. Differences in physical activity between patients requiring and not requiring assistance with ADLs were examined using the analysis of covariance. A receiver operating characteristic curve of the need for ADL assistance at discharge was constructed from the duration of physical activity. Results: The duration of physical activity at the time of rehabilitation admission was related to FIM‐m at discharge. The cut‐off value of the duration of physical activity for predicting the need for ADL assistance at discharge was 135 s, with a sensitivity of 83.3% and specificity of 68.4% (area under the curve: 0.76). Discussion: The duration of physical activity at the time of rehabilitation admission may be a factor that can quantitatively predict the risk of requiring assistance with ADLs at discharge in older hip fracture patients. The duration of light‐and‐moderate intensity physical activity may be a component of multidisciplinary inpatient rehabilitation to improve patients' ADL. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to conduct a meta‐analysis to evaluate the methods and effects of interventions to increase life‐space mobility among community‐dwelling older adults. Methods: Records were identified through nine databases. Eligible study designs for inclusion in the review were randomized controlled trials of interventions on life‐space mobility for community‐dwelling older adults. The risk of bias was assessed using the Risk of Bias 2 tool. We followed the Grading of Recommendations, Assessment, Development, and Evaluation approach to summarize the evidence. Results: Four studies (558 participants) identified via search strategies were included. Two studies involved individualized exercise and lifestyle interventions. In three out of the four studies, individual interventions were applied. Overall, when compared with a control group, the intervention group was more likely to positively affect increasing life‐space mobility (standardized mean difference 0.47, 95% confidence interval [0.020 to 0.92]). The heterogeneity statistic indicated considerable heterogeneity (I2 = 84%). The evidence was downgraded one step owing to imprecision. Conclusions: Interventions on increasing life‐space mobility for community‐dwelling older adults have a positive effect. Combination interventions may be more effective than single interventions, and individual interventions may be more effective than group interventions. However, owing to the limited number of studies, conducting further research to enhance the generalizability of results is crucial. Additionally, subgroup analysis should be conducted to clarify differences in intervention methods and effects. Geriatr Gerontol Int 2023; 23: 842–848. [ABSTRACT FROM AUTHOR]

Spinal motor neurons (SMNs) are the primary target of degeneration in amyotrophic lateral sclerosis (ALS). Degenerating motor neurons accumulate cytoplasmic TAR DNA‐binding protein 43 (TDP‐43) aggregates in most ALS cases. This SMN pathology can occur without mutation in the coding sequence of the TDP‐43‐encoding gene, TARDBP. Whether and how wild‐type TDP‐43 drives pathological changes in SMNs in vivo remains largely unexplored. In this study, we develop a two‐photon calcium imaging setup in which tactile‐evoked neural responses of motor neurons in the brainstem and spinal cord can be monitored using the calcium indicator GCaMP. We devise a piezo‐assisted tactile stimulator that reproducibly evokes a brainstem descending neuron upon tactile stimulation of the head. A direct comparison between caudal primary motor neurons (CaPs) with or without TDP‐43 overexpression in contiguous spinal segments demonstrates that CaPs overexpressing TDP‐43 display attenuated Ca2+ transients during fictive escape locomotion evoked by the tactile stimulation. These results show that excessive amounts of TDP‐43 protein reduce the neuronal excitability of SMNs and potentially contribute to asymptomatic pathological lesions of SMNs and movement disorders in patients with ALS. [ABSTRACT FROM AUTHOR]

Aerobic methane‐oxidizing bacteria (MOB) play an important role in mitigating methane emissions from paddy fields. In this study, we developed a differential quantification method for the copy number of pmoA genes of type Ia, Ib, and IIa MOB in paddy field soil using chip‐based digital PCR. Three probes specific to the pmoA of type Ia, Ib, and IIa MOB worked well in digital PCR quantification when genomic DNA of MOB isolates and PCR‐amplified DNA fragments of pmoA were examined as templates. When pmoA genes in the surface soil layer of a flooded paddy were quantified by digital PCR, the copy numbers of type Ia, Ib, and IIa MOB were 105–106, 105–106, and 107 copies g−1 dry soil, respectively, with the highest values in the top 0–2‐mm soil layer. Especially, the copy numbers of type Ia and Ib MOB increased by 240% and 380% at the top layer after soil flooding, suggesting that the soil circumstances at the oxic–anoxic interfaces were more preferential for growth of type I MOB than type II MOB. Thus, type I MOB likely play an important role in the methane consumption at the surface paddy soil. [ABSTRACT FROM AUTHOR]

Previously, cytotoxic drugs were the only option for patients with non‐small cell lung cancer (NSCLC) and the prognosis was poor. However, molecularly targeted therapies and immune checkpoint inhibitors represent a breakthrough in the treatment of advanced NSCLC and have improved survival rates. In addition, advances in next‐generation sequencing (NGS) have revealed the landscape of genomic alterations in patients with different cancers, aiding in the development of new molecularly targeted drugs. The patient reported here was a 54‐year‐old woman with left lower lung adenocarcinoma. The lung cancer was staged as T2aN3M1a stageIVA 11 years ago. She had received seven regimens of chemotherapy for 11 years. Among these, pemetrexed (PEM) regimens particularly showed long‐term effects totaling more than 5 years. We performed NGS after disease progression of the seventh treatment. NGS revealed CD74‐ROS1 fusion and she was treated with entrectinib. She has been taking entrectinib for over 20 months now. Herein, we report a rare case of CD74‐ROS1‐positive lung adenocarcinoma diagnosed by NGS that achieved long‐term survival with cytotoxic drugs, especially PEM regimens. In patients showing favorable clinical response to PEM regimens, physicians should consider testing for ROS1/ALK rearrangement. [ABSTRACT FROM AUTHOR]

Aim: To test a modified team‐based learning approach on undergraduate learning outcomes in an acute‐care nursing course in Japan. Design: Mixed‐methods. Methods: Students worked on three simulated cases, engaged in pre‐class preparation, completed a quiz and engaged in group work. We collected data on team approach, critical‐thinking disposition and time spent in self‐learning at four time‐points: before the intervention and after each simulated case. Data were analysed using a linear mixed model, a Kruskal–Wallis test and a content analysis. Data sources: We recruited nursing students attending a mandatory course in acute‐care nursing at University A. Data were collected at four time‐points between April and July 2018. Data from 73 of 93 respondents were analysed. Results: Team approach, critical thinking and self‐learning all increased significantly across the time‐points. Four categories emerged from students' comments: 'achievement of teamwork', 'sense of learning efficacy', 'satisfaction with course approach' and 'issues related to course approach'. The modified team‐based learning approach led to improvements in team approach and critical‐thinking disposition across the course. Conclusion: Incorporating team‐based learning into the curriculum not only contributes to team building but is also effective as a teaching method to improve student learning. Implications for the profession and/or patient care: The intervention led to improvements in team approach and critical‐thinking disposition across the course. The educational intervention also led to more time for self‐learning. Future studies should include participants from various universities and evaluate the outcomes over a longer period. [ABSTRACT FROM AUTHOR]

Allenes (>C=C=C<) are classified as cumulated dienes with a linear structure and an sp‐hybridized central carbon atom. We have synthesized and isolated a stable 2‐germapropadiene with bulky silyl substituents. The 2‐germapropadiene allene moiety adopts a linear structure both in the solid state and in solution. An X‐ray diffraction electron‐density‐distribution (EDD) analysis of this 2‐germapropadiene confirmed the linear C=Ge=C geometry with a formally sp‐hybridized germanium atom that bears two orthogonal C=Ge π‐bonds. Based on detailed structural and computational studies, we concluded that the linear geometry of the isolated 2‐germapropadiene most likely arises from the negative hyperconjugation of the silyl substituents at the terminal carbon atoms. The 2‐germapropadiene reacts rapidly with nucleophiles, indicating that the linearly oriented germanium atom is highly electrophilic. [ABSTRACT FROM AUTHOR]

The synthesis and isolation of the first examples of a tetraselenolane and a hexaselenepane, obtained from the reaction of a bissilylcarbenoid (RSi2CBrLi; RSi=SiMePh2) with elemental selenium, is reported. The molecular structures of these cyclic polyselenides were determined using single‐crystal X‐ray diffraction analysis. The selective synthesis of these polyselenides was achieved by controlling the reaction temperature. Stoichiometric deselenation of the hexaselenepane with triphenylphosphine afforded the corresponding tetraselenolane in quantitative yield. Further deselenation of the tetraselenolane with excess triphenylphosphine did not furnish the expected selenoketone but the diselenirane, as confirmed by spectroscopic analysis. [ABSTRACT FROM AUTHOR]

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene‐deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin‐like modifier (SUMO)‐specific ubiquitin‐like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1‐related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene‐deleted meiotic cells. The Top2‐12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin‐binding proteins is regulated by the NPC‐bound SUMO‐specific protease and is important for the progression of meiosis. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have shown beneficial effects on cardiometabolic risk factors (hemoglobin A1c, body mass index, systolic blood pressure) in patients with type 2 diabetes mellitus. We compared combined cardiometabolic effects of SGLT2i on hemoglobin A1c, body mass index and systolic blood pressure versus dipeptidyl peptidase‐4 inhibitors (DPP4i) in Japanese patients with type 2 diabetes mellitus. Materials and Methods: This Japanese retrospective cohort study used the JMDC claims database. Patients newly treated with an SGLT2i (n = 18,936) or DPP4i (n = 55,484) were enrolled (January 2015–March 2020) and matched 1:1 using the propensity score. The primary end‐point was the proportion of patients achieving a composite outcome (i.e., simultaneous absolute/percent reduction in hemoglobin A1c ≥0.5%, body mass index ≥3% and systolic blood pressure ≥2 mmHg) 1 year after first SGLT2i or DPP4i prescription; Mantel–Haenszel common risk difference and its 95% confidence interval were estimated. Other end‐points included treatment persistence, with the associated hazard ratio calculated using the Cox proportional hazards model. Results: After matching, patient characteristics were balanced (7,302 patients each). The proportion of patients achieving the composite outcome was significantly greater in patients receiving an SGLT2i than those receiving a DPP4i (31.0% [1,279/4,120] vs 12.9% [524/4,070], risk difference 18.6%, 95% confidence interval 16.3, 20.9, P < 0.001). Risk of treatment discontinuation was significantly lower in the SGLT2i group than in the DPP4i group (hazard ratio 0.85, 95% confidence interval 0.81, 0.90, P < 0.001). Conclusions: In the present study, SGLT2i showed favorable cardiometabolic risk reduction and longer treatment persistence than DPP4i in Japanese patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

The most common treatment option for patients with bullous pemphigoid is systemic corticosteroids. CYP3A4, a drug‐metabolizing enzyme in the liver, metabolizes synthetic steroids to a varying degree. Although there are many CYP3A4‐inducing drugs, several antiepileptic drugs, such as phenytoin and phenobarbital, strongly induce CYP3A4, thereby reducing the effects of corticosteroids. Here, we report a case of refractory bullous pemphigoid that rapidly improved after the discontinuation of phenytoin and phenobarbital. To achieve adequate pharmacological effects of corticosteroids, we must always ensure that patients who require corticosteroids for treatment are not medicated with CYP3A4‐inducing agents. [ABSTRACT FROM AUTHOR]

New antiviral drugs for COVID-19 have been launched with special approval. Successful treatment of an older patient with COVID-19 pneumonia using herbal medicine - especially saikanto Herein, we describe our experience of successfully treating COVID-19 pneumonia in an older patient using a Japanese herbal medicine without new antiviral drugs. [Extracted from the article]

Coronavirus disease 2019 (COVID‐19) has become a worldwide outbreak, and it can cause various symptoms and complications. However, pneumothorax secondary to COVID‐19 is relatively uncommon. We herein report a 60‐year‐old man with bilateral refractory pneumothorax with severe COVID‐19. In patients with poor general health and who are difficult to undergo surgery for pneumothorax post‐COVID‐19, internal treatments such as chest drainage, bronchial occlusion, and pleurodesis are essential to relieving refractory pneumothorax. It also indicates that autologous blood patch pleurodesis is a useful method in terms of efficacy and side effects. Bilateral pneumothorax secondary to COVID‐19 is a very rare complication and can be refractory. In patients with poor general condition and who are unfit for surgery, combining internal treatments (chest drainage, pleurodesis, and bronchial occlusion) is essential for relieving refractory pneumothorax. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate prognostic factors of biochemical recurrence (BCR) in each risk group of prostate cancer patients who underwent low‐dose‐rate brachytherapy (LDR‐BT). Methods: A total of 944 patients with clinically confirmed prostate cancer (cT1c‐3aN0M0) who had underwent LDR‐BT were enrolled. The low‐, intermediate‐, and high‐risk groups included 278, 498, and 168 patients, respectively. The median age, PSA value at diagnosis, and the follow‐up period were 70 years (range: 48–84), 7.2 ng/ml (range: 1.2–113), and 91 months (range: 2–192), respectively. We evaluated the BCR‐free rate, BCR‐free survival, clinical recurrence‐free rate, overall survival (OS), and cancer‐specific survival (CSS). We conducted multivariate analysis to elucidate prognostic factors of BCR for all patients and for each risk group. Results: The 5‐ and 10‐year OS rates were 96.0% and 89.5% and the 5‐ and 10‐year CSS rates were 99.8% and 99.1%, respectively, while the 5‐ and 10‐year BCR‐free rates were 96.6% and 92.5% in low‐risk patients, 95.7% and 90.7% in intermediate‐risk patients and 93.8% and 89.0% in high‐risk patients, respectively. There were no significant differences between the risk groups. Age‐adjusted multivariate analysis indicated biologically effective dose (BED) <180 Gy2 as an independent prognostic factor of BCR in all patients (p = 0.005). There were no independent factors in the low‐ and high‐risk groups, but neoadjuvant androgen deprivation therapy (ADT) (p = 0.022) and BED <180Gy2 (p = 0.042) were independent prognostic factors in the intermediate‐risk group. Conclusions: LDR‐BT can achieve a higher recurrence‐free survival with an adequate local radiation dose (BED ≥ 180 Gy2). [ABSTRACT FROM AUTHOR]

The nuclear envelope (NE) provides a permeable barrier that separates the eukaryotic genome from the cytoplasm. NE is a double membrane composed of inner and outer nuclear membranes. Ish1 is a stress‐responsive NE protein in the fission yeast, Schizosaccharomyces pombe. Les1 is another NE protein that shares several similar domains with Ish1, but the relationship between them remains unknown. In this study, using fluorescence and electron microscopy, we found that most regions of these proteins were localized within the NE lumen. We also found that Ish1 interacted with Les1 via its C‐terminal region in the NE lumen and that the NE localization of Ish1 depended on the C‐terminal region of Les1. Ish1 and Les1 were co‐localized at the NE in interphase cells, but when the nucleus divided at the end of mitosis (closed mitosis), they showed distinguishable localization at the midzone membrane domain. These results suggest the regulated interaction between Ish1 and Les1 in the NE lumen, although this interaction does not appear to be essential for cell survival. [ABSTRACT FROM AUTHOR]

Background: Idiopathic cutaneous telangiectasia has been rarely described in the dog. Objectives: We present the first case of idiopathic focal cutaneous telangiectasia in a young dog of probable congenital origin. Methods: An 18‐month‐old spayed female Maltese dog presented with demarcated erythema of the skin on the right thorax. The lesion consisted of scattered, florid, ramified macules with mild dermatrophia and desquamation. The lesion was examined with histopathology and immunohistochemistry using antibodies for alfa‐SMA. Results: Diascopy revealed a blanchable lesion. Tortuous capillary expansion was observed by dermoscopy. The histopathological examination revealed dilated but otherwise unremarkable capillaries in the superficial dermis compatible with cutaneous telangiectasia. The lesion was followed up over a 3‐year period and had essentially remained stable. Other vascular anomalies displaying similarities with telangiectasia are discussed. Conclusions: In human vascular anomalies, this case would be presumably classified as 'telangiectasia' by the International Society for the Study of Vascular Anomalies. We propose that primary cutaneous telangiectasia should be included in the list of differential diagnoses for this type of lesions in dogs. We also suggest that dermoscopy would be a valuable tool for the identification of vascular anomalies in dogs. [ABSTRACT FROM AUTHOR]

An 11‐year‐old spayed female American Cocker Spaniel was presented with a 4‐week history of anorexia and a 1‐week history of abdominal distension. Clinicopathologic and imaging abnormalities included intra‐abdominal hemorrhage, granular lymphocytes (GLs) in abdominal fluid smears, a splenic mass, and hepatomegaly with diffuse multiple hypoechogenic nodules. Based on the cytologic, histologic, and immunohistochemical evaluation of the spleen and liver, the diagnosis was hepatosplenic T‐cell lymphoma (HSTCL) of GLs. Postoperatively, the dog was maintained in good condition with chemotherapy (ACNU [nimustine], L‐asparaginase, and prednisolone). However, on day 85, ultrasound‐guided fine‐needle aspiration of the liver revealed a proliferation in neoplastic mast cells not associated with the GLs. The dog was diagnosed with a visceral mast cell tumor (MCT) originating from the liver. The chemotherapy was switched to vinblastine and toceranib. The dog remained in good condition until day 141 but died due to the progression of MCT on day 158. Liver cytology on day 155 showed no GLs, although HSTCL is thought to be resistant to chemotherapy. After the definitive diagnosis of HSTCL, we monitored this patient's response to chemotherapy with blood tests, including complete blood counts, ultrasound imaging, and cytologic aspirates of liver. Although canine HSTCL has a poor prognosis, the possibility of a new neoplasm, including visceral MCT, should be considered. Periodic liver cytology might be worthwhile in dogs receiving chemotherapy for HSTCL. [ABSTRACT FROM AUTHOR]

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However, computed tomography (CT) revealed acute appendicitis with fecaliths (Figure 1a). CONFLICT OF INTEREST N/A. APPROVAL OF THE RESEARCH PROTOCOL BY AN INSTITUTIONAL REVIEWER BOARD AND THE APPROVAL NUMBER N/A. INFORMED CONSENT Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Acute appendicitis with fecaliths requiring surgery in a patient with COVID-19 successfully treated with daiobotanpito and antibiotics. [Extracted from the article]

Natural hybridization between the native species Rumex madaio endemic to Japan and the congeneric invasive species R. obtusifolius, which frequently co‐occurs with R. madaio, was examined by molecular identification. At low frequencies, interspecific hybrids between the two species were confirmed using restriction fragment length polymorphism analyses of the internal transcribed spacer region of ribosomal DNA. Whereas these two species can hybridize because their flowering periods overlapped to some extent, the extremely low fertility of R. madaio caused by unknown genetic factors seemed to prevent extensive hybridization between these species. Population genetic analyses based on single nucleotide polymorphisms showed that there was a distinct population genetic structure in R. madaio, suggesting that local populations should be treated separately for genetic conservation of the species. [ABSTRACT FROM AUTHOR]

Background: The incidence of postoperative delirium after anatomical lung resection ranges from 5 to 16%. This study aimed to analyze the risk factors and prognosis of postoperative delirium in anatomical lung resection for lung cancer. Methods: This study included 1351 patients undergoing anatomical lung resection between April 2010 and October 2020. We analyzed the perioperative risk factors of postoperative delirium. We also compared postoperative complications and survival between the delirium and non-delirium groups. Results: Postoperative delirium was identified in 44 (3.3%) of 1351 patients who underwent anatomical lung resection for lung cancer. Age, peripheral vascular disease, depression, and current smoking status were independent risk factors for postoperative delirium in the multivariate analysis. The percentage of postoperative delirium was 0.6% in never smokers and 6.0% in current smokers. The delirium and non-delirium groups showed significant differences in overall survival (p = 0.0144) and non-disease-specific survival (p = 0.0080). After propensity score matching, the two groups did not significantly differ in overall survival (p = 0.9136), non-disease-specific survival (p = 0.8146), or disease-specific survival (p = 0.6804). Conclusions: Age, peripheral vascular disease, depression, and current smoking status were considered independent risk factors for postoperative delirium in anatomical lung resection for lung cancer. Smoking cessation for at least four weeks before surgery is recommended for reducing incidence of post-operative delirium. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine whether modifiable risk factors can predict tooth loss over 10 years and estimate population attributable risk (PAR) for a combination of modifiable factors.Methods: This longitudinal study included 1466 participants who underwent dental examinations in 2007 and 2017 and were aged 40 to 79 years at baseline. Periodontal conditions were assessed using the 2018 periodontal classification. Incident tooth loss was defined as ≥4 teeth lost over a 10-year period. We calculated the partial PAR (pPAR%) for tooth loss to estimate the combined effect of modifiable risk factors.Results: Incidence of tooth loss was 17.5%. Directed acyclic graphs were used to identify risk factors for tooth loss. A logistic regression model showed that baseline periodontitis, dental caries experience, no regular dental visit, periodontal treatment, smoking, and obesity were associated with tooth loss after adjusting for covariates; pPAR% was 55.5% (95% confidence interval: 31.1% to 73.0%) in periodontitis Stage III to IV and 87.6% (50.4% to 97.4%) in the combination of all factors, respectively. The sex-stratified analysis showed that smoking and no regular dental visit in men and obesity in women were identified as potential risk factors for tooth loss.Conclusions: Modifiable factors accounted for most cases of incident tooth loss. Risk factors for tooth loss might differ by sex, suggesting that the appropriate approach for preventing tooth loss base on sex. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the longitudinal association between yogurt product intake and oral health in a population‐based study. Materials and Methods: This study included 1967 Japanese residents aged 40–79 years who underwent dental examinations in 2012. Among them, 1469 participants were followed up in 2017 for the incidence of tooth loss, which was defined as two or more teeth lost over 5 years. The intake of yogurt products, defined as yogurt and lactic acid beverages, was estimated using a semi‐quantitative food frequency questionnaire. The composition of the salivary microbiota was evaluated. Results: The Poisson regression model showed that a higher intake of yogurt products was negatively associated with the incidence of tooth loss (p for trend =.020), adjusted for potential confounding factors. Mediation analysis confirmed that periodontal condition partly mediated the effect of yogurt product intake on tooth loss, while dental caries experience did not. Additionally, we confirmed the association of a high intake of yogurt products with a low percentage of the salivary microbiota pattern, which was associated with poor oral health. Conclusion: These findings suggest that the intake of yogurt products is associated with a lower risk of tooth loss resulting from periodontal disease, probably via modulation of the oral microbiome composition. [ABSTRACT FROM AUTHOR]

Cysteine and methionine, two sulfur‐containing amino acids (AA), were introduced in their surfactant forms as potential antioxidants. The antioxidative (AOX) properties of lauroyl methionine (C12‐Met) and lauroyl cysteine (C12‐Cys) was investigated by means of the oxygen radical absorbance capacity assay. Both the surfactants exhibited excellent AOX behavior at the premicellar state and micellar medium. The AOX behavior was found to be comparable for both the surfactants at their premicellar states. However, in micellar medium, C12‐Met showed better AOX property than C12‐Cys. The AOX power of the surfactants was compared with other previously developed AA‐type surfactants. The order of the AOX power was found to be: C12‐tryptophan > C12‐tyrosine ≈ C12‐methionine ≈ C12‐cysteine > C12‐histidine at the premicellar state and C12‐tryptophan > C12‐tyrosine > C12‐methionine > C12‐cysteine > C12‐histidine at the micellar state. C12‐Cys displayed lower AOX property in micellar medium due to its dimer formation tendency. Based on the HPLC and UPLC‐Q‐TOF‐MS analysis, the dimer formation of C12‐Cys was found to be accelerated due to the micellar environment and results into negative synergistic effect on other aromatic AA‐type surfactants. However, the presence of C12‐His in the micellar solution of C12‐Cys resulted no synergistic effect due to stronger H‐bonding between the surfactants and resulting less dimer formation. [ABSTRACT FROM AUTHOR]

Objective: Higher quality of postimplant dosimetric evaluation is associated with higher biochemical recurrence‐free survival rates after low‐dose‐rate brachytherapy for localized prostate cancer. Postimplant prostate D90 is a key dosimetric parameter showing the quality of low‐dose‐rate brachytherapy. In this study, to improve the quality of low‐dose‐rate brachytherapy for localized prostate cancer, we investigated pre‐implant factors affecting the reduction of postimplant prostate D90. Methods: A total of 441 patients underwent low‐dose‐rate brachytherapy monotherapy and 474 patients underwent low‐dose‐rate brachytherapy with external beam radiation therapy. Logistic regression analysis was carried out to identify predictive factors for postimplant D90 decline. The cut‐off value of the D90 decline was set at 170 Gy and 130 Gy in the low‐dose‐rate brachytherapy monotherapy group and low‐dose‐rate brachytherapy with external beam radiation therapy group, respectively. Results: On multivariate analysis, neoadjuvant androgen deprivation therapy was identified as an independent predictive factor for the decline of postimplant D90 in both the low‐dose‐rate brachytherapy monotherapy group (P < 0.001) and low‐dose‐rate brachytherapy with external beam radiation therapy group (P = 0.003). Prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly and negatively correlated with the postimplant D90. The prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly higher in patients with neoadjuvant androgen deprivation therapy than those without neoadjuvant androgen deprivation therapy (P < 0.001). Conclusions: Neoadjuvant androgen deprivation therapy decreased postimplant D90 with substantial prostate gland swelling after low‐dose‐rate brachytherapy. When neoadjuvant androgen deprivation therapy is required to reduce prostate volume for patients with large prostate glands and offer adequate local control for patients with high‐risk prostate cancer before low‐dose‐rate brachytherapy, intraoperative D90 adjustment might be necessary. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low‐dose‐rate brachytherapy (LDR‐BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR‐BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post‐implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR‐BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR‐BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self‐monitoring fetal heart rate (FHR) in low‐risk singleton pregnant women. Methods: This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self‐monitoring FHR using the mobile CTG device. Results: A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4–100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self‐monitoring using the iCTG. Conclusion: The mobile CTG device is a feasible tool for self‐monitoring FHR, with a high participant satisfaction level. [ABSTRACT FROM AUTHOR]

Small molecules with polar functional groups, including substituted phenethylamines, are commonly analyzed by liquid chromatography‐mass spectrometry (LC‐MS) with electrospray ionization (ESI). Analyte molecules are mostly detected in protonated and cation‐adducted forms through positive‐ion electrospray ionization‐mass spectrometry (ESI‐MS). However, the ESI of substituted phenethylamines commonly provides an intense signal of fragment ions by ESI in‐source collision‐induced dissociation (IS‐CID), which hinders the unambiguous identification of phenethylamines. This phenomenon was approximated as a unimolecular dissociation model, and the dissociation efficiency was evaluated by various quantum chemistry calculations to determine the ESI IS‐CID efficiency. The calculated results were consistent with the experimental data, when the dissociation threshold energy of phenethylamines was calculated using the post‐Hartree‐Fock (post‐HF) method, CCSD(t)/cc‐pVTZ//MP2(full)/6‐311++G(d,p). In contrast to post‐HF methods, the utilization of density functional theory calculations with a suitable functional is recognized as an accurate and competitive low‐cost approach. In particular, ωB97‐XD, M06‐2X‐D3, and recently developed Minnesota functionals, such as M11, MN12‐SX, and MN15, provided reliable results, as in the case of the post‐HF method. The results obtained by the recently developed double hybrid functionals, DSD‐PEBP86‐D3(BJ), PBE0‐DH, and PBE‐QIDH, were also reliable. The consideration of ESI IS‐CID can facilitate the identification of analyte molecules because most phenethylamines, except for N‐methylated analogs, provide an intense signal in the ESI mass spectrum. [ABSTRACT FROM AUTHOR]

Objectives: Lower urinary tract symptoms are transiently exacerbated by low‐dose‐rate brachytherapy (LDR‐BT) for prostate cancer and recover to pretreatment levels 1 year thereafter. Generally, these symptoms are influenced by temperature. We aimed to search for factors affecting the lower urinary tract symptoms after seed implant including seasons. Methods: We retrospectively enrolled 812 patients who underwent LDR‐BT at Nara Medical University Hospital from January 2010 to December 2018 and for whom the International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency volume charts were available. We investigated the relationships between lower urinary tract symptoms, 24‐hours urinary frequency, 24‐hours urinary volume before and after seed implant, radiation dose, and season of seed implant. Results: The mean age was 69.5 years. The mean prostate volume was 24.2 mL. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and 24‐hours urinary frequency increased until 3 months and gradually decreased over 6 months after seed implant. Multiple linear regression analysis revealed that 24‐hours urinary frequency at 3 months after seed implant was significantly influenced by external beam radiotherapy, larger prostate volume before implant, higher 24‐hours urinary frequency at baseline, larger 24‐hours urinary volume at 3 months after implant, and performance of implant in summer. Conclusions: Lower urinary tract symptoms worsened 3 months after seed implant of LDR‐BT regardless of the season of implant. The urinary frequency 3 months after seed implant was slightly lower when seed implant was performed in the summer. [ABSTRACT FROM AUTHOR]