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Summary: This study compared the effectiveness and cardiovascular safety of romosozumab and teriparatide. The main finding was that there were no significant differences between the two drugs in fracture prevention and risk of major adverse cardiac events. This suggests that romosozumab and teriparatide are comparable options for treating osteoporosis. Purpose: This study aimed to determine the preventive effects of romosozumab versus teriparatide on fractures and the risk of cardiovascular events in patients initiating these drugs. Methods: We conducted an active comparator, a new user cohort design, with confounding controlled by inverse probability of treatment weighting using a Japanese administrative claims database (March 2019 to October 2022). This cohort study included 49,104 patients aged 50 years or older who initiated romosozumab (n = 16,125) or teriparatide (n = 32,979) for osteoporosis. The study exposure was the initiation of romosozumab or teriparatide. Effectiveness outcomes were nonvertebral fracture and hip fracture. The safety outcome was major adverse cardiac events (MACE). Follow-up period was 365 days. Results: The weighted incidence rate difference (IRD) for nonvertebral fracture between romosozumab versus teriparatide was –0.08 (95% confidence interval [CI], –0.34 to 0.17) events per 100 person-years (weighted hazard ratio [HR], 0.95 [95% CI, 0.81 to 1.12]); weighted IRD for hip fracture was 0.00 (95% CI, –0.16 to 0.16) events per 100 person-years (weighted HR, 0.99 [95% CI, 0.76 to 1.29]); and weighted IRD for MACE was –0.06 (95% CI, –0.20 to 0.09) events per 100 person-years (weighted HR, 0.90 [95% CI, 0.68 to 1.19]). Conclusion: In patients with osteoporosis, there was no significant difference in the prevention of nonvertebral fracture and hip fracture between romosozumab and teriparatide. In addition, the risk of MACE was comparable between the two drugs. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to validate the new international guidelines for IPMN and determine the surgical criteria for patients with IPMN exhibiting high-risk stigmata (HRS). Methods: We enrolled 115 IPMN patients exhibiting HRS who were diagnosed between 2004 and 2021. Of the 115 patients, 79 underwent surgery (surgical group) and 36 did not undergo surgery (non-surgical group). The overall survival (OS) of each group was compared, and multivariate analysis was performed to identify factors associated with OS. Results: There was no significant difference in the estimated 5-year OS in the surgical and non-surgical groups (67% vs. 74%; p = 0.75). The presence of a solid component (SC) (hazard ratio [HR], 6.92; 95% confidence interval [CI], 3.30–14.5) and a high score of age-adjusted Charlson comorbidity index (ACCI) (≥5) (HR, 2.27; 95% CI, 1.11–4.64) were independent predictors of poor OS. In the presence of an SC, the surgical group had a significantly better OS than the non-surgical group (estimated 5-year OS, 38% vs. 18%; p = 0.031). In the absence of an SC, the prognosis of patients with a high ACCI was significantly poorer than those with a low ACCI in the surgical group (estimated 5-year OS, 59% vs. 93%; p = 0.005). Conclusions: An SC and a high ACCI are important prognostic factors in IPMN patients exhibiting HRS. Thus, patients with an SC should undergo surgical resection. However, conservative management may be the optimal treatment in patients without an SC and with a high ACCI. [ABSTRACT FROM AUTHOR]

Introduction: Goblet cell adenocarcinoma (GCA) of the appendix is an uncommon type of cancer that includes both epithelial and neuroendocrine features, with goblet cells present. These tumors have traditionally been viewed as one of the more aggressive forms of appendiceal cancer, frequently being diagnosed at a metastatic stage. For patients with stage III–IV disease, the 5-year overall survival rate ranges from 14% to 22%. Due to limited data, the diagnosis and management of GCA are challenging. Case Presentation: We present the case of a 55-year-old female who presented with elevated serum carcinoembryonic antigen levels and a left ovarian tumor. Preoperative imaging indicated a normal appendix. During surgery for suspected ovarian carcinoma, frozen section analysis revealed mucinous adenocarcinoma of the ovary, but distinguishing between primary and metastatic lesions was challenging. Meticulous exploration revealed a firm and thickened appendix, prompting appendectomy and subsequent diagnosis of appendiceal GCA with ovarian metastasis. Conclusion: Pathologies of the appendix, like GCA, can mimic ovarian tumors despite a normal-looking appendix, complicating diagnosis. Through this case, we underscored the need for careful intraoperative examination of the appendix in patients with mucinous ovarian neoplasms to avoid misdiagnosis and ensure appropriate treatment. [ABSTRACT FROM AUTHOR]

A constant weight asset allocation is a popular investment strategy and is optimal under a suitable continuous model. We study the tracking error for the target continuous rebalancing strategy by a feasible discrete-in-time rebalancing under a general multi-dimensional Brownian semimartingale model of asset prices. In a high-frequency asymptotic framework, we derive an asymptotically efficient sequence of simple predictable strategies. [ABSTRACT FROM AUTHOR]

Although the risk of dental procedures as a cause of bacteremia has been recognized, evidence regarding the association between dental procedures and late periprosthetic joint infection (LPJI) is scarce. We sought to determine whether dental procedures are associated with an increased risk of LPJI. The study was conducted under a case-crossover design using a large claims database in Japan. We identified adult patients who had undergone dental procedures and were hospitalized for LPJI between April 2014 and September 2021. Exposure to dental procedures was assessed during a case period of 1–4 weeks, with two control periods of 9–12 weeks and 17–20 weeks, preceding LPJI hospital admission. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of LPJI associated with dental procedures in the case period compared with the two control periods. In total, 241 patients with LPJI were included in the case-crossover study. At least one dental procedure was performed in 46 patients (19.1%) in the hazard period and in 75 patients (31.1%) in the control periods. The OR for LPJI with dental procedures was 0.96 (95% CI, 0.61–1.53; p = 0.88). Findings were robust in several sensitivity analyses, including stratification by whether the dental procedure included antibiotic prophylaxis. This study suggests that dental procedures are not associated with increased risk of LPJI, and will raise questions about the recommendation for antibiotic prophylaxis before dental procedures. [ABSTRACT FROM AUTHOR]

This study aimed to develop and validate a simple scoring system to determine the high-risk group for pancreatic cancer (PC) in the asymptomatic general population. The scoring system was developed using data from PC cases and randomly selected non-PC cases undergoing annual medical checkups between 2008 and 2013. The performance of this score was validated for participants with medical checkups between 2014 and 2016. In the development set, 45 PC cases were diagnosed and 450 non-PC cases were identified. Multivariate analysis showed three changes in clinical data from 1 year before diagnosis as independent risk factors: ΔHbA1c ≥ 0.3%, ΔBMI ≤ −0.5, and ΔLDL ≤ −20 mg/dL. A simple scoring system, incorporating variables and abdominal ultrasound findings, was developed. In the validation set, 36 PC cases were diagnosed over a 3-year period from 32,877 participants. The AUROC curve of the scoring system was 0.925 (95%CI 0.877–0.973). The positive score of early-stage PC cases, including Stage 0 and I cases, was significantly higher than that of non-PC cases (80% vs. 6%, p = 0.001). The simple scoring system effectively narrows down high-risk PC cases in the general population and provides a reasonable approach for early detection of PC. [ABSTRACT FROM AUTHOR]

Objectives: In patients with unresectable malignant hilar biliary obstruction (UMHBO), drainage of ≥ 50% liver volume correlates with better clinical outcomes. Accurately measuring the liver volume to be drained by biliary stents is required. We aimed to develop a novel method for calculating the drained liver volume (DLV) using a 3D volume analyzer (3D volumetry), and assess the usefulness for drainage in patients with UMHBO. Methods: Three-dimensional volumetry comprises the following steps: (1) manual tracing of bile duct using 3D imaging system; (2) 3D reconstruction of bile duct and liver parenchyma; and (3) calculating DLV according to the 3D distribution of bile ducts. Using 3D volumetry, we reviewed data of patients who underwent biliary drainage for UMHBO, calculated the DLV, and determined the association between DLV and biliary drainage outcome. Results: There were 104 eligible cases. The mean DLV was 708 ± 393 ml (53% ± 21%). and 65 patients (63%) underwent drainage of ≥50% liver volume. The clinical success rate was significantly higher in patients with DLV ≥ 50% than in patients with DLV < 50% (89% vs. 28%, P < 0.001). The median time to recurrence of biliary obstruction (TRBO) and survival time were significantly longer in patients with DLV ≥ 50% than in patients with DLV < 50% (TRBO, 292 vs. 119 days, P = 0.03; survival, 285 vs. 65days, P = 0.004, log-rank test, respectively). Conclusions: Three-dimensional volumetry, a novel method to calculate DLV accurately according to bile duct distribution was useful for drainage in UMHBO patients. [ABSTRACT FROM AUTHOR]

Wood decay fungi alter the abiotic and biotic properties of deadwood, which are important as nurse logs for seedling regeneration. However, the relationship between fungal decay type and seedling performance has not been evaluated experimentally. In this study, we examined the germination, growth, and survival of six arbuscular mycorrhizal (AM) and six ectomycorrhizal (ECM) tree species on three substrates (pine logs with brown and white rot and soil) by conducting seed‐sowing experiments in a mixed forest dominated by Pinus densiflora and Quercus serrata. Analysis using ribosomal DNA internal transcribed spacer 1 (rDNA ITS1) sequencing revealed that the fungal community was significantly different across three substrates. The richness of operational taxonomic units (OTUs) of AM and ECM fungi was the largest on brown rot logs and soil, respectively. The substrate significantly affected the seedling performance when comparing wood decay types, but these were not consistent across the mycorrhizal status of the seedlings. Nevertheless, seedlings of some AM trees showed better growth and enhanced mycorrhizal colonization on brown rot logs than on white rot logs. The wood decay type influenced fungal communities in the logs and the performance of some seedling species partly by different mycorrhizal colonization rates. However, the effect was seedling species dependent and showed no apparent difference between AM and ECM trees. [ABSTRACT FROM AUTHOR]

Wood decay fungi alter the abiotic and biotic properties of deadwood, which are important as nurse logs for seedling regeneration. However, the relationship between fungal decay type and seedling performance has not been evaluated experimentally. In this study, we examined the germination, growth, and survival of six arbuscular mycorrhizal (AM) and six ectomycorrhizal (ECM) tree species on three substrates (pine logs with brown and white rot and soil) by conducting seed‐sowing experiments in a mixed forest dominated by Pinus densiflora and Quercus serrata. Analysis using ribosomal DNA internal transcribed spacer 1 (rDNA ITS1) sequencing revealed that the fungal community was significantly different across three substrates. The richness of operational taxonomic units (OTUs) of AM and ECM fungi was the largest on brown rot logs and soil, respectively. The substrate significantly affected the seedling performance when comparing wood decay types, but these were not consistent across the mycorrhizal status of the seedlings. Nevertheless, seedlings of some AM trees showed better growth and enhanced mycorrhizal colonization on brown rot logs than on white rot logs. The wood decay type influenced fungal communities in the logs and the performance of some seedling species partly by different mycorrhizal colonization rates. However, the effect was seedling species dependent and showed no apparent difference between AM and ECM trees. [ABSTRACT FROM AUTHOR]

Background: Dental procedures can lead to bacteremia and have been considered a potential risk factor for pyogenic vertebral osteomyelitis (PVO). However, data on the association between dental procedures and PVO are limited. Questions/purposes: (1) After controlling for relevant confounding variables, are dental procedures associated with an increased risk of PVO? (2) Does antibiotic prophylaxis before dental procedures effectively decrease the risk of PVO? Methods: A case-crossover study was conducted to investigate the association between dental procedures and PVO using a Japanese claims database. The advantage of this study design is that confounding factors that do not vary over time are automatically adjusted for, because cases act as their own controls. From April 2014 to September 2021, the database included 8414 patients who were hospitalized for PVO. Of these, 50% (4182 of 8414) were excluded because they had not undergone any dental procedures before the index date, a further 0.1% (10 of 8414) were excluded because they were younger than 18 years at the index date, and a further 7% (623 of 8414) were excluded because they did not have at least 20 weeks of continuous enrollment before the index date, leaving 43% (3599 of 8414) eligible for analysis here. The mean age was 77 ± 11 years, and 55% (1985 of 3599) were men. Sixty-five percent (2356 of 3599) of patients had a diagnosis of diabetes mellitus, and 42% (1519 of 3599) of patients had a diagnosis of osteoporosis. We compared the frequency of dental procedures between a 4-week hazard period before the admission date for PVO and two control periods, 9 to 12 weeks and 17 to 20 weeks before the admission date for PVO, within individuals. We calculated odds ratios and 95% confidence intervals using conditional logistic regression analysis. Results: Comparing the hazard and matched control periods within individuals demonstrated that dental procedures were not associated with an increased risk of PVO (OR 0.81 [95% CI 0.72 to 0.92]; p < 0.001). Additional analysis stratified by antibiotic prophylaxis use showed that antibiotic prophylaxis was not associated with a lower OR of developing PVO after dental procedures (with antibiotic prophylaxis: OR 1.11 [95% CI 0.93 to 1.32]; p < 0.26, without antibiotic prophylaxis: OR 0.72 [95% CI 0.63 to 0.83]; p < 0.001). Our sensitivity analyses, in which the exposure assessment interval was extended from 4 to 8 or 12 weeks and exposure was stratified by whether the dental procedure was invasive, demonstrated results that were consistent with our main analysis. Conclusion: Dental procedures were not associated with an increased risk of subsequent PVO in this case-crossover study. The effectiveness of antibiotic prophylaxis was not demonstrated in the additional analysis that categorized exposure according to the use of antibiotic prophylaxis. Our results suggest that the association between dental procedures and PVO may have been overestimated. Maintaining good oral hygiene may be important in preventing the development of PVO. The indications for antibiotic prophylaxis before dental procedures should be reconsidered in view of the potential risk of adverse drug reactions to antibiotic prophylaxis and the emergence of drug-resistant pathogens. Larger randomized controlled trials are needed to confirm these findings and assess the role of antibiotic prophylaxis. Level of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

To obtain both the intensities and phases of electric fields, it is necessary to calibrate the data observed by the sensor by consulting the sensor characteristics. The frequency profile of the sensor impedance obtained from the simulation is roughly consistent with that obtained from the theory. However, some differences are identified in the frequency profile of the sensor impedance obtained from the simulation compared to the theory. We conducted simulations using the particle-in-cell (PIC) simulation tool to analyze the impedance of electric field sensors immersed in magnetized space plasmas. The simulation model comprised a dipole sensor placed in a three-dimensional simulation box filled with electrons and ions. The dipole sensor was represented by perfect conductor rods. We carefully selected simulation parameters and employed an appropriate feeding technique to accurately evaluate the sensor impedance. We observed significant changes in the frequency dependence of the sensor impedance as cyclotron frequency varied. To understand the simulation results, we introduced the linear dispersion relation. By comparing the real part of the sensor impedance with the ω - k diagram, we found that the impedance peaks corresponded to frequencies at which branches of plasma waves were present, with k = k half , representing half the wavelength equal to the tip-to-tip sensor length, i.e., the sensor can be assumed as the half-wavelength dipole antenna. [ABSTRACT FROM AUTHOR]

Few studies have made direct comparisons between treatments for palmoplantar pustulosis (PPP); therefore, it is difficult to select the best treatment for each patient. To determine the best therapy and to compare reported measures of efficacy in clinical trials of systemic treatments for PPP in this systematic review and network meta‐analysis. Six databases were used to perform database search on 10 July 2022. Randomized controlled trials (RCTs) were identified through a systematic literature search. The titles and abstracts of articles were initially screened for inclusion by two authors independently using our predetermined criteria. The full texts of selected articles were then independently assessed for inclusion in a blinded fashion. Disagreement between the authors was resolved by consensus. Data were abstracted in duplicate. Random‐effects model was accepted to perform network meta‐analysis. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to the PRISMA guidelines. The analysis was completed in July 2022. The primary outcome was the change of PPP Area and Severity Index (PPPASI) from baseline and the secondary outcome was the achievement of PPPASI‐50 response. Seven RCTs with 567 patients were included. Guselkumab 100 mg was the one with the highest probability of reaching the proposed outcomes (mean difference [MD], −8.00; 95% confidence interval [CI], 4.88–11.11), while the achievement of PPPASI‐50 response did not show a significant difference (odds ratio [OR], 3.79; 95% CI, 0.51–28.37). Guselkumab 200 mg was next to 100 mg of reaching the proposed outcomes (MD, −4.71; 95% CI, 2.12–7.30), while the achievement of PPPASI‐50 response did not show a significant difference (OR, 2.34; 95% CI, 0.48–11.43). Network meta‐analysis showed guselkumab 100 mg was the treatment with the highest probability of reaching both PPPASI and PPPASI‐50 outcomes. Absolute PPPASI may be more appropriate as an outcome than PPPASI‐50. [ABSTRACT FROM AUTHOR]

Lewy body disease (LBD) is characterized by the appearance of Lewy neurites and Lewy bodies, which are predominantly composed of α‐synuclein. Notably, the cardiac plexus (CP) is one of the main targets of LBD research. Although previous studies have reported obvious differences in the frequency of Lewy body pathology (LBP) in the CP, none of them have confirmed whether LBP preferably appears in any part of the CP. Thus, we aimed to clarify the emergence and/or propagation of LBP in the CP. In this study, 263 consecutive autopsy cases of patients aged ≥50 years were included, with one region per case selected from three myocardial perfusion areas (MPAs) and subjected to proteinase K and then immunohistochemically stained with anti‐α‐synuclein antibodies to assess LBP. We stained all three MPAs in 17 cases with low‐density LBP and observed the actual distribution of LBP. LBP were identified in the CP in 20.2% (53/263) of patients. Moreover, we found that LBP may appear in only one region of MPAs, mainly in the young‐old group (35.3% (6/17) of patients). These findings suggest that it is possible to underestimate LBP in the CP, especially in the young‐old group, by restricting the search to only one of the three MPAs. [ABSTRACT FROM AUTHOR]

Lifestyle interventions have been shown to prevent or delay the onset of diabetes; however, inter-individual variability in responses to such interventions makes lifestyle recommendations challenging. We analyzed the Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) study data using a previously published mechanistic simulation model of type 2 diabetes onset and progression to understand the causes of inter-individual variability and to optimize dietary intervention strategies at an individual level. J-DOIT1, a large-scale lifestyle intervention study, involved 2607 subjects with a 4.2-year median follow-up period. We selected 112 individuals from the J-DOIT1 study and calibrated the mechanistic model to each participant's body weight and HbA1c time courses. We evaluated the relationship of physiological (e.g., insulin sensitivity) and lifestyle (e.g., dietary intake) parameters with variability in outcome. Finally, we used simulation analyses to predict individually optimized diets for weight reduction. The model predicted individual body weight and HbA1c time courses with a mean (±SD) prediction error of 1.0 kg (±1.2) and 0.14% (±0.18), respectively. Individuals with the most and least improved biomarkers showed no significant differences in model-estimated energy balance. A wide range of weight changes was observed for similar model-estimated caloric changes, indicating that caloric balance alone may not be a good predictor of body weight. The model suggests that a set of optimal diets exists to achieve a defined weight reduction, and this set of diets is unique to each individual. Our diabetes model can simulate changes in body weight and glycemic control as a result of lifestyle interventions. Moreover, this model could help dieticians and physicians to optimize personalized nutritional strategies according to their patients' goals. [ABSTRACT FROM AUTHOR]

Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. This is a cohort study. In 2015, 193,246 participants aged 40–74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet–smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity–sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet–smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity–sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity–sleep" pattern showed a significant inverse association in non-overweight men. Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults. [ABSTRACT FROM AUTHOR]

Introduction: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. Materials and methods: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. Results: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. Conclusion: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice. [ABSTRACT FROM AUTHOR]

The article focuses on the successful chemotherapy treatment of an elderly patient with double-hit lymphoma, severe renal impairment, and poor performance status. Topics include the challenges of treating double-hit lymphoma, the effectiveness of chemotherapy despite renal dysfunction, and the importance of considering individual patient factors in treatment decisions for elderly patients with malignant lymphoma.

The article describes three cases of psoriasis vulgaris (PsV) complicated by systemic sclerosis (SSc) with guselkumab, an interleukin (IL)-23 inhibitor that specifically binds to the IL-23 p19 subunit. Topics include the therapeutic effect of guselkumab on both PsV and SSC, immune abnormalities in SSc, and limitation of the study.

Cold atmospheric plasma (CAP) is a novel biomedical tool used for cancer therapy. A device using nitrogen gas (N2CAP) produced CAP that induced cell death through the production of reactive nitrogen species and an increase in intracellular calcium. In this study, we investigated the effect of N2CAP‐irradiation on cell membrane and mitochondrial function in human embryonic kidney cell line 293T. We investigated whether iron is involved in N2CAP‐induced cell death, as deferoxamine methanesulfonate (an iron chelator) inhibits this process. We found that N2CAP induced cell membrane disturbance and loss of mitochondrial membrane potential in an irradiation time‐dependent manner. BAPTA‐AM, a cell‐permeable calcium chelator, inhibited N2CAP‐induced loss of mitochondrial membrane potential. These results suggest that disruption of intracellular metal homeostasis was involved in N2CAP‐induced cell membrane rupture and mitochondrial dysfunction. Moreover, N2CAP irradiation generated a time‐dependent production of peroxynitrite. However, lipid‐derived radicals are unrelated to N2CAP‐induced cell death. Generally, N2CAP‐induced cell death is driven by the complex interaction between metal movement and reactive oxygen and nitrogen species produced by N2CAP. Significance statement: CAPs exhibit various biological activities via complicated pathways, and can effectively induce cell death in cancer cell lines. To understand the mechanism of CAP‐induced cell death, we investigated whether N2CAP affects the cellular function in a cultured cell line. Here, we show that N2CAP induced mitochondrial dysfunction and plasma membrane disruption in 293T cells. Moreover, we demonstrate that intracellular calcium and iron are involved in CAP‐induced cellular dysfunction. Thus, the orchestration of intracellular metal movement is essential for N2CAP‐induced cell death. [ABSTRACT FROM AUTHOR]

Focusing on a lognormal stochastic volatility model, we present an elementary introduction to rough volatility modeling for financial assets with some new findings. [ABSTRACT FROM AUTHOR]

Objectives PsA is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. Methods We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A and IL-23 were analysed. Results Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs 84.5%, P  < 0.0001; 25.4% vs 100%, P  < 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95% CI 2, 77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95% CI 1.38, 5.47 and HR 4.49, 95% CI 2.25, 8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. Conclusions NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity. [ABSTRACT FROM AUTHOR]

Community residents exposed to nuclear power plant (NPP) accidents have long-term worry about the effects of radiation. After the 2011 Fukushima NPP accident, those who experienced traumatic events during the Great East Japan Earthquake (GEJE) tended to have greater worry about radiation. Along with the prolonged worry about radiation, there may also be cognitive changes caused by the traumatic events. We hypothesized that if there were cognitive changes underlying the prolonged worry about radiation, those who experienced the traumatic events would tend to have greater worry about other issues unrelated to radiation. We examined the effects of the traumatic events during the GEJE on community residents' worry about radiation and COVID-19 a decade after the Fukushima NPP accident. Using the data of a longitudinal questionnaire survey following a random sample of 4900 community residents outside the evacuation zone in Fukushima, this study analyzed 774 responses (15.8%). The traumatic events consisted of (1) injury, (2) injury or death of a family member, and (3) the loss of a house or other property. We developed a mediation model drawing paths from the traumatic events to worry about radiation and COVID-19, including posttraumatic stress symptoms (PTSS) as a mediator, using structural equation modeling. The traumatic events directly affected worry about radiation. Although it did not directly affect worry about COVID-19, it did so indirectly through worry about radiation and PTSS. Traumatic events can increase trauma-related worry independently of PTSS and increase trauma-unrelated worry indirectly through trauma-related worry and PTSS. [ABSTRACT FROM AUTHOR]

Study Design.: Retrospective cohort study. Objective.: The objective of this study was to compare the incidence of surgical site infection (SSI) after lateral lumbar interbody fusion (LLIF) and posterior/transforaminal lumbar interbody fusion (P /TLIF). Summary of Background Data.: Previous studies have shown that LLIF can improve neurological symptoms to a comparable degree to P /TLIF. However, data on the risk of SSI after LLIF is lacking compared with P /TLIF. Materials and Methods.: The study was conducted under a retrospective cohort design in patients undergoing LLIF or P /TLIF for lumbar degenerative diseases between 2013 and 2020 using a hospital administrative database. We used propensity score overlap weighting to adjust for confounding factors including age, sex, body mass index, comorbidities, number of fusion levels, hospital size, and surgery year. We estimated weighted odds ratios (ORs) and 95% CIs for SSI within 30 days postoperatively. Results.: We compared the risk of SSI between 2874 patients who underwent LLIF and 24,245 patients who received P/TLIF Patients who had received LLIF were at significantly less risk of experiencing an SSI compared with those receiving P/TLIF (0.7% vs. 1.2%; weighted OR: 0.57; 95% CI: 0.36 –0.92; P=0.02). As a secondary outcome, patients who had received LLIF had less risk of transfusion (7.8% vs. 11.8%; weighted OR: 0.63; 95% CI:0.54 –0.73; P <0.001). Conclusions.: In this large retrospective cohort study of adults undergoing lumbar interbody fusion, LLIF was associated with a significantly lower risk of SSI than P /TLIF. The small, but significantly, decreased risk of SSI associated with LLIF may inform decisions regarding the technical approach for lumbar interbody fusion. [ABSTRACT FROM AUTHOR]

Impermanent Loss in Decentralized Finance can be hedged with weighted variance swaps [ABSTRACT FROM AUTHOR]

Simple Summary: DNA is constantly damaged by internal or external factors. Cells have evolved elaborate damage response mechanisms, namely, DNA damage response (DDR), to preserve genomic integrity. In eukaryotes, kinases play a central role in the DDR. Through a phosphorylation-dependent pathway, these mechanisms quickly transmit a DNA damage signal to the cell cycle checkpoint, cell death, or DNA-repair machinery. Recently, the role of Serine-threonine kinase 38 (STK38) in DNA-damage signaling is emerging. Here, we aim to provide an overview of current topics of STK38 in common mechanisms of regulation, DNA damage signaling, cross-talk between the DDR pathways, cancer, and the potential application for radiotherapy. Protein kinases, found in the nucleus and cytoplasm, play essential roles in a multitude of cellular processes, including cell division, proliferation, apoptosis, and signal transduction. STK38 is a member of the protein kinase A (PKA)/PKG/PKC family implicated in regulating cell division and morphogenesis in yeast and C. elegans. However, its function remained largely unknown in mammals. In recent years, advances in research on STK38 and the identification of its substrates has led to a better understanding of its function and role in mammals. This review discusses the structure, expression, and regulation of activity as a kinase, its role in the DNA damage response, cross-talk with other signaling pathways, and its application for radio-sensitization. [ABSTRACT FROM AUTHOR]

The plantar or dorsal approach has been previously reported for the replantation or revascularization of a completely or incompletely amputated lesser toe. However, no reports exist describing an alternative approach for the replantation or revascularization of an amputated lesser toe, either complete or incomplete. We encountered a rare case of revascularization of an incompletely amputated second toe using a mid‐lateral approach. The purpose of this case report was to describe the mid‐lateral approach, which is novel in its nature for the replantation or revascularization of a completely or incompletely amputated lesser toe. A 43‐year‐old male was involved in a motor vehicle accident and had incomplete crush amputation of a second toe at the base of the nail, along with open dislocation of the distal interphalangeal (DIP) joint in the third toe. We performed artery‐only revascularization of the second toe using a mid‐lateral approach, with the patient in the supine position with his hip in flexion and external rotation. The postoperative course was uneventful, and the second toe was deemed viable. The Japanese Society for Surgery of the Foot (JSSF) standard rating system of the lesser toe was rated 90 and the Self‐Administered Foot Evaluation Questionnaire (SAFE‐Q) scored 100 in all the mentioned categories. The mid‐lateral approach could be an option for the replantation or revascularization of an amputated lesser toe distal to the proximal interphalangeal (PIP) joint. [ABSTRACT FROM AUTHOR]

The trace element zinc is essential for diverse physiological processes in humans. Zinc deficiency can impair growth, skin reproduction, immune function, maintenance of taste, glucose metabolism, and neurological function. Patients with chronic kidney disease (CKD) are susceptible to zinc deficiency, which is associated with erythropoiesis-stimulating agent (ESA) hypo-responsive anemia, nutritional problems, and cardiovascular diseases as well as non-specific symptoms such as dermatitis, prolonged wound healing, taste disturbance, appetite loss, or cognitive decline. Thus, zinc supplementation may be useful for the treatment of its deficiency, although it often causes copper deficiency, which is characterized by several severe disorders including cytopenia and myelopathy. In this review article, we mainly discuss the significant roles of zinc and the association between zinc deficiency and the pathogenesis of complications in patients with CKD. [ABSTRACT FROM AUTHOR]

Introduction: A safety signal concerning parkinsonism and related movement disorders with gabapentinoids (gabapentin and pregabalin) or tramadol was detected by reviewing individual case reports and data mining in spontaneous report databases. Well‐designed pharmacoepidemiological studies are needed to assess the signal. Objective: This study aimed to investigate the association of exposure to gabapentinoids or tramadol with the risk of parkinsonism and related movement disorders. Methods: We conducted a case‐crossover study using a Japanese electronic medical records database. Patients with newly diagnosed parkinsonism or related movement disorders between January 1, 2007, and April 14, 2019, were identified. The diagnosis date of outcomes was defined as the index date. We assessed the exposure of each patient to gabapentinoids or tramadol during a 90‐day hazard period ending 1 day before the index date and in three 90‐day reference periods. Multivariable conditional logistic regression models were employed to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). To confirm the robustness of the primary findings, we also performed sensitivity analyses using a case–case‐time‐control design, a different time window for hazard and reference periods, a different definition of outcome, and different number of reference periods. Results: A total of 28,972 eligible cases were included in the primary analysis. Exposure to gabapentinoids (aOR, 2.12; 95% CI, 1.73–2.61) and tramadol (aOR, 2.04; 95% CI, 1.57–2.64) was associated with increased risk. Results were consistent across sensitivity analyses. Conclusion: Our findings serve as a caution to physicians who prescribe gabapentinoids or tramadol in routine clinical practice. [ABSTRACT FROM AUTHOR]

Hall transport and non-collinear magnetoresistance (NCMR) are studied for a chiral antiferromagnet (AFM) with the filled β-Mn-type structure. Magnetic and transport properties of epitaxial thin films of Co2−xPdxMo3N revealed that, in addition to a canted antiferromagnetic behavior above room temperature, thin films with x = 1.01∼1.38 exhibited a transition to a spin spiral state with a higher magnetic moment below TSR of around 50 K, which was assigned to a spin reorientation transition. The low-temperature phase shows both large anomalous Hall effect (AHE) and topological Hall effect (THE). Upon the transition to the canted AFM phase existing up to room temperature, the large AHE still persists with vanishing THE. The behavior of the Hall transport properties coupled with NCMR signals in the current-perpendicular-to-the plane configuration shows the formation of topological spin textures with locally antiferromagnetic order. The present results open the way for the study of topological antiferromagnetic spin textures, manipulation of their properties, and for future spintronic applications. [ABSTRACT FROM AUTHOR]

Sleep plays an important role in cattle production and welfare. Therefore, this study aimed to investigate the development of sleep‐like posture (SLP) expression in dairy calves from birth to the first calving as an indicator of their sleep behavior. Fifteen female Holstein calves were subjected. Daily SLP was measured eight times (0.5, 1, 2, 4, 8, 12, and 18 months and 23 months or 1 month before the first calving) using an accelerometer. Calves were kept in individual pens until weaning at 2.5 months old and then kept in the group. The daily SLP time decreased rapidly in early life; however, the rate of decrease gradually slowed and eventually reached a stable level of approximately 60 min/day after 12 months old. The daily SLP bout frequency showed the same change as the SLP time. In contrast, the averaged SLP bout duration slowly decreased with age. Longer daily SLP time during early life in female Holstein calves might be related to brain development. The individual expression of daily SLP time differs before and after weaning. Some external and/or internal factors associated with weaning may be involved SLP expression. [ABSTRACT FROM AUTHOR]

One concern associated with pancreatic diseases is the poor prognosis of pancreatic cancer. Even with advances in diagnostic modalities, risk stratification of premalignant lesions and differentiation of pancreatic cysts are challenging. Pancreatic lesions of concern include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystadenomas, pseudocysts, and retention cysts, as well as cystic degeneration of solid tumors such as solid pseudopapillary neoplasms and pancreatic neuroendocrine neoplasms. Pancreatic juice obtained during endoscopic retrograde cholangiopancreatography has previously been used for the detection of KRAS mutation. Recently, duodenal fluid, which can be obtained during the relatively minimally invasive procedures of endoscopic ultrasound (EUS) and esophagogastroduodenoscopy, and cyst fluid collected by EUS‐guided fine‐needle aspiration (FNA) were used for molecular biological analysis. Furthermore, advanced analytic methods with high sensitivity were used for the detection of single and multiple markers. Early detection of malignant pancreatic tumors and risk stratification of premalignant tumors can be performed using duodenal fluid samples with a single marker with high sensitivity. Technological advances in simultaneous detection of multiple markers allow for the differentiation of cystic pancreatic tumors. One thing to note is that the clinical guidelines do not recommend pancreatic cyst fluid and pancreatic juice (PJ) sampling by EUS‐FNA and endoscopic retrograde cholangiopancreatography, respectively, in actual clinical practice, but state that they be performed at experienced facilities, and duodenal fluid sampling is not mentioned in the guidelines. With improved specimen handling and the combination of markers, molecular markers in PJ samples may be used in clinical practice in the near future. [ABSTRACT FROM AUTHOR]

Background: Microendoscopic discectomy for lumbar disc herniation has been shown to be as effective as traditional microdiscectomy or open discectomy in terms of clinical outcomes such as pain relief, and it is less invasive. Nevertheless, the reoperation rate for microendoscopic discectomy compared with microdiscectomy or open discectomy remains unclear, possibly due to difficulties in conducting follow-up of sufficient duration and in obtaining information about reoperation in other facilities. Questions/purposes: (1) What is the rate of reoperation after microendoscopic discectomy for primary lumbar disc herniation on a large scale at a median of 4 years postoperatively? (2) Is there any difference in revision rate at a median of 4 years and within 90 days postoperatively based on surgical method? Methods: We conducted a retrospective, comparative study of adult patients who underwent microendoscopic discectomy or microdiscectomy or open discectomy for lumbar disc herniation from April 2008 to October 2017 and who were followed until October 2020 using a commercially available administrative claims database from JMDC Inc. This claims-based database provided information on individual patients collected across multiple hospitals, which improved the accuracy of postoperative reoperation rates. We included 3961 patients who received microendoscopic discectomy or microdiscectomy or open discectomy between April 2008 and October 2017 in the JMDC claims database. After applying exclusion criteria, 50% (1968 of 3961) of patients were eligible for this study. Propensity score–weighted analyses were conducted in 646 patients in the microendoscopic discectomy group and in 1322 in the microdiscectomy or open discectomy group, with a median (IQR) of 4 years (3 to 6) of follow-up in both groups. Mean patient age was 42 ± 12 years in the microendoscopic discectomy group and 43 ± 12 years in the microdiscectomy or open discectomy group. Males accounted for 78% (505 of 646) of patients in the microendoscopic discectomy group and 79% (1050 of 1322) of patients in microdiscectomy or open discectomy group. The proportion of patients with diabetes mellitus in the microendoscopic discectomy group (10% [64 of 646]) was less than in the microdiscectomy or open discectomy group (15% [195 of 1322]). The primary outcome was Kaplan-Meier survivorship free from any type of additional lumbar spine surgery at a median of 4 years after the index surgery. The secondary outcome was survival probability using the Kaplan-Meier method with endpoints of any type of reoperation within 90 days after the index surgery. To determine which procedure had the higher revision rate, we conducted propensity score overlap weighting analysis, which controlled for potential confounding variables such as age, sex, comorbidities, and type of hospital as well as Cox proportional hazard models to estimate HRs and 95% confidence intervals (CIs). Results: The 5-year cumulative reoperation rate was 12% (95% CI 9% to 15%) in the microendoscopic discectomy group and 7% (95% CI 6% to 9%) in the microdiscectomy or open discectomy group. After controlling for potentially confounding variables like age, sex, and diabetes mellitus, the microendoscopic discectomy group had a higher reoperation risk than the microdiscectomy or open discectomy group (weighted HR 1.57 [95% CI 1.14 to 2.16]; p = 0.004). Within 90 days of the index surgery, after controlling for potentially confounding variables like age, sex, and diabetes mellitus, we found no difference between the microendoscopic discectomy group and microdiscectomy or open discectomy group in terms of risk of reoperation (weighted HR 1.38 [95% CI 0.68 to 2.79]; p = 0.38). Conclusion: Given the higher reoperation risk with microendoscopic discectomy compared with microdiscectomy or open discectomy at a median of 4 years of follow-up, surgeons should select microdiscectomy or open discectomy, despite the current popularity of microendoscopic discectomy. The revision risk of microendoscopic discectomy compared with microdiscectomy or open discectomy in the long term remains unclear. Future large, prospective, multicenter cohort studies with long-term follow-up are needed to confirm the association between microendoscopic discectomy and risk of reoperation. Level of Evidence: Level Ⅲ, therapeutic study. [ABSTRACT FROM AUTHOR]

After the 2011 Fukushima nuclear power plant accident, the prevalence of metabolic syndrome sharply increased in municipalities near the nuclear power plant, where a massive evacuation of community residents occurred (the evacuation area). However, after the initial increase, the rate of increase in metabolic syndrome in the evacuation area was slower than that in the surrounding area (non-evacuation area). In this study, we compared the incidence of and recovery from metabolic syndrome as well as its prevalence between evacuation and non-evacuation areas during the 10 years after the accident to explore whether the slower increase in metabolic syndrome after the initial increase in the evacuation area stemmed from suppressed incidence or from fast recovery. We analyzed specific health check-up data of community residents aged 40–74 in Fukushima Prefecture from fiscal year (FY) 2012 to FY 2021 (N = 710,201). To explore the prevalence of metabolic syndrome, we examined the associations of time, residential area, and their interaction with metabolic syndrome using mixed-model repeated measures. We used data from those without metabolic syndrome in FY 2012 to investigate the incidence. We similarly examined the associations of time, residential area, and their interaction with metabolic syndrome using FY 2013 to FY 2021 data. To explore recovery, we used the data of those with metabolic syndrome in FY 2012 and repeated the same procedure. The rate of increase in the prevalence and incidence of metabolic syndrome was slower in the evacuation area than in the non-evacuation area. On the other hand, as for the recovery, the time trend of metabolic syndrome did not differ between the two areas. The slower increase in metabolic syndrome in the evacuation area was partly explained by the slower incidence in the evacuation area but not by recovery. • Metabolic syndrome continuously increased after the nuclear power plant accident. • Prevalence of metabolic syndrome was continuously higher in the evacuation area. • Increasing rate of metabolic syndrome was slower in the evacuation area. • Incidence rate of metabolic syndrome was slower in the evacuation area. • Recovery of metabolic syndrome was not observed. [ABSTRACT FROM AUTHOR]

This study developed a data-driven model for the prediction of fluid–particle dynamics by coupling a flow surrogate model based on the deep convolutional neural network (CNN) and a Lagrangian particle tracking model based on the discrete phase model. The applicability of the model for the prediction of the single-fiber filtration efficiency (SFFE) for elliptical- and trilobal-shaped fibers was investigated. The ground-truth training data for the CNN flow surrogate model were obtained from a validated computational fluid dynamics (CFD) model for laminar incompressible flow. Details of fluid–particle dynamics parameters, including fluid and particle velocity vectors and contribution of Brownian and hydrodynamic forces, were examined to qualitatively and quantitatively evaluate the developed data-driven model. The CNN model with the U-net architecture provided highly accurate per-pixel predictions of velocity vectors and static pressure around the fibers with a speedup of more than three orders of magnitude compared with CFD simulations. Although SFFE was accurately predicted by the data-driven model, the uncertainties in the velocity predictions by the CNN flow surrogate model in low-velocity regions near the fibers resulted in deviations in the particle dynamics predictions. These flow uncertainties contributed to the random motion of particles due to Brownian diffusion and increased the probability of particles being captured by the fiber. The findings provide guidelines for the development of data science-based models for multiphysics fluid mechanics problems encountered in fibrous systems. [ABSTRACT FROM AUTHOR]

Recently, catalytic enantioselective syntheses of N-C axially chiral compounds have been reported by many groups. Most N-C axially chiral compounds prepared through a catalytic asymmetric reaction possess carboxamide or nitrogen-containing aromatic heterocycle skeletons. On the other hand, although N-C axially chiral sulfonamide derivatives are known, their catalytic enantioselective synthesis is relatively underexplored. We found that the reaction (Tsuji–Trost allylation) of allyl acetate with secondary sulfonamides bearing a 2-arylethynyl-6-methylphenyl group on the nitrogen atom proceeds with good enantioselectivity (up to 92% ee) in the presence of (S,S)-Trost ligand-(allyl-PdCl)2 catalyst, affording rotationally stable N-C axially chiral N-allylated sulfonamides. Furthermore, the absolute stereochemistry of the major enantiomer was determined by X-ray single crystal structural analysis and the origin of the enantioselectivity was considered. [ABSTRACT FROM AUTHOR]

Malignant pericardial mesothelioma (MPM) is a rare tumour that arises from the mesothelial cells of the pericardium. No standard treatment has been established owing to a poor treatment response; therefore, MPM has a poor prognosis. We herein report a rare case of MPM in a 70‐year‐old man that was diagnosed immunohistopathologically using cell block sections of pericardial fluid and in which long‐term survival for more than 3 years was achieved with only periodic pericardial drainage. Immunohistopathological staining investigations, especially BRCA1‐associated protein 1 (BAP1) immunostaining using cell block sections of pericardial effusion, are effective in making a diagnosis of MPM. Well‐differentiated papillary mesothelioma (WDPM) with BAP1 loss progresses to MPM in the long term, showing that BAP1 loss may induce phenotypical evolution of WDPM. BAP1 loss may also progress to malignant mesothelioma in situ and then to invasive mesothelioma. BAP1 immunohistochemistry should be considered for the early diagnosis of MPM. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed that T and B cells are involved in its pathogenesis. In addition, the results of clinical trials have suggested that IL-23 is closely related to the pathogenesis. This review describes PPP and the genetic background, the factors involved in the onset and exacerbation of disease and its relation to the molecular mechanism. In addition, we describe the usefulness of biological therapy and its implications in relation to the importance in pathology, the pathogenesis of PPP, the importance of the role of the IL-23–Th17 axis and IL-36 in PPP. Furthermore, we describe an animal experimental model of PPP, the efficacy and mechanism of action of guselkumab, an anti-IL-23 antibody, the latest research, and finally the possibility for it to be effective for other autoimmune diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Analyzed the classification performance of a louver classifier with a tilted sidewall. • Applied classifier for separating unburned carbon from biomass combustion ash. • Separation performance of louver was improved by tilted sidewall addition by increasing gas flow downward velocity. • The modified louver design improved the RUC of ash from 12.7 to 26.9 %. • A blow-up ratio of 30 vol% increased the RUC in the modified louver to 83.8 %. Separating unburned carbon (UC) from biomass combustion ash is necessary to achieve high-quality ash as recyclable raw material and improve energy efficiency by reburning the UC in the furnace. In this study, a novel louver classifier geometry with tilted sidewall was proposed to separate the UC from biomass ash and its classification performance was analyzed via experiments and simulations. The louver classifier with a tilted sidewall provided a smaller 50% cut size and classification accuracy index indicating that the separation performance is improved. The CFD simulations revealed that tilted sidewall in the louver increased gas flow downward velocity in the classification region, increasing the inertia of the particles, and causing more particles to leave gas flow and deposit into the collection box as coarse ash. The UC of classified combustion ash increased with a decrease in the median mass diameter, indicating that the classification process for combustion ash produced coarse ash with a lower UC. The tilted sidewall in the modified louver classifier increased the reduction of unburned carbon (RUC) in ash up to 83.8%. The RUC increased with a cut size of the classified ash which was achieved when a high inlet flow velocity and high blow-up ratio are applied. [ABSTRACT FROM AUTHOR]

Although comprehensive gene analyses of pancreatic cancer provide new knowledge on molecular mechanisms, the usefulness and possibility of the analyses in routinely available clinical samples remain unclear. We assessed the possibility and utility of target sequencing of endoscopically obtained pancreatic cancer samples. Fifty‐eight pancreatic cancer patients who underwent EUS‐FNA or endoscopic biopsy were enrolled. The extracted DNA quantity was assessed and used for next‐generation sequencing (NGS) of 50 cancer‐related genes from which gene mutations, copy number alterations, and microsatellite instability (MSI) were extracted via secondary analysis. A median of 19.2 ng (3.8–228) of DNA was extracted from formalin‐fixed paraffin‐embedded samples. Gene alterations were detected in 55 of 58 samples (94.8%), including all samples with a DNA concentration below the detection limit (n = 11). Four frequently altered genes were KRAS (83%), TP53 (66%), SMAD4 (26%), and PTEN (17%), and molecular targetable genes were detected in 13 cases (22.4%). Five samples (8.6%) had many mutations and suspected MSI with impaired mismatch repair genes. A Cox regression analysis revealed that metastasis (p < 0.005, hazard ratio [HR] 10.1), serum CEA >5 ng/ml (p = 0.01, HR 2.86), ≤10 detected hotspot mutations (p = 0.03, HR 9.86), and intact Ras signaling (p < 0.005, HR 5.57) were associated with a poor pancreatic cancer prognosis. We performed small, targeted sequencing of pancreatic cancer using available samples from real clinical practice and determined the relationship between gene alterations and prognosis to help determine treatment choices. [ABSTRACT FROM AUTHOR]

Since the 2011 Fukushima nuclear power plant accident, multiple social network disruptions have been reported among the community in Fukushima, while posttraumatic stress symptoms among the residents have persisted. In this study, we aimed to explore the influence of time and social networks on the recovery of posttraumatic stress symptoms based on longitudinal data from community residents in Fukushima, following up five to ten years after the nuclear power plant accident. We conducted five questionnaire surveys quasi-annually, the targets of which were randomly sampled 4900 non-evacuee community residents. In this study, the data of 1809 respondents who participated in at least one survey were used (36.9% of the initial target). Setting posttraumatic stress symptoms as the outcome, we examined the interaction between time and social network size using a mixed model, adjusting for sociodemographic characteristics and disaster-related events. Their interaction was statistically significant, and the posttraumatic stress symptoms of those with small social networks persisted, while those with larger social networks recovered. Maintaining and promoting social networks may contribute to mental health recovery after a nuclear disaster. • Posttraumatic stress symptoms remained 10 years after the Fukushima nuclear disaster. • Posttraumatic stress symptoms persisted among those with small social networks. • Posttraumatic stress symptoms decreased among those with not-small social networks. [ABSTRACT FROM AUTHOR]

We consider the bilevel knapsack problem with interdiction constraints, a fundamental bilevel integer programming problem which generalizes the 0–1 knapsack problem. In this problem, there are two knapsacks and n items. The objective is to select some items to pack into the first knapsack such that the maximum profit attainable from packing some of the remaining items into the second knapsack is minimized. We present a combinatorial branch-and-bound algorithm which outperforms the current state-of-the-art solution method in computational experiments for 99% of the instances reported in the literature. On many of the harder instances, our algorithm is orders of magnitude faster, which enabled it to solve 53 of the 72 previously unsolved instances. Our result relies fundamentally on a new dynamic programming algorithm which computes very strong lower bounds. This dynamic program solves a relaxation of the problem from bilevel to 2n-level where the items are processed in an online fashion. The relaxation is easier to solve but approximates the original problem surprisingly well in practice. We believe that this same technique may be useful for other interdiction problems. [ABSTRACT FROM AUTHOR]

Understanding the different patterns of adherence to istradefylline treatment is essential to identifying Parkinson's disease (PD) patients who might benefit from targeted interventions. This descriptive study aimed to identify longitudinal istradefylline adherence patterns and to characterize factors associated with them. We identified PD patients aged 21–99 years who initiated istradefylline treatment in a Japanese hospital administrative database. Group-based trajectory modeling was used to model the monthly proportion of days covered over time to identify distinct 360-day adherence patterns. Factors associated with each adherence pattern were assessed using univariable multinomial logistic regression models. Of 2088 eligible PD patients, 4 distinct adherence groups were identified: consistently high adherence (56.8%); rapidly declining adherence (25.8%); gradually declining adherence (8.5%); and gradually declining and then recovering adherence (9.0%). Compared to the consistently high adherence group, the other groups had the following characteristics associated with a likelihood of lower adherence: the rapidly declining adherence group received fewer dopamine agonists (63.8% vs. 69.4%), monoamine oxidase B (MAO-B) inhibitors (26.8% vs. 31.6%), and catechol- O -methyl transferase inhibitors (31.6% vs. 37.0%) and had a higher prevalence of anxiety/mood disorders (29.9% vs. 24.6%); the gradually declining adherence group received fewer MAO-B inhibitors (22.5% vs. 31.6%) and amantadine (8.4% vs. 16.1%) and had a higher prevalence of mild cognitive impairment/dementia (27.0% vs. 18.8%); and the declining and then recovering adherence group had a higher prevalence of anxiety/mood disorders (34.2% vs. 24.6%). Clinicians should be aware of the heterogeneous patterns of adherence to istradefylline. • Our longitudinal descriptive study included PD patients starting istradefylline. • Group-based trajectory analysis identified 4 adherence groups of istradefylline. • Patient characteristics differed significantly among adherence groups. • Clinicians need to understand the heterogeneity of istradefylline adherence. [ABSTRACT FROM AUTHOR]

Itching can decrease quality of life and exacerbate skin symptoms due to scratching. Itching not only contributes to disease progression but also triggers complications such as skin infections and eye symptoms. Therefore, controlling itching is very important in therapeutic management. In addition to the well-known histamine, IL-31, IL-4 and IL-13 have recently been reported as factors that induce itching. Itching may also be caused by factors other than these histamines. However, we do not know the extent to which these factors are involved in each disease. In addition, the degree of involvement is likely to vary among individuals. To date, antihistamines have been widely used to treat itching and are often effective, suggesting that histamine is more or less involved in itchy diseases. This review discusses the ligand-receptor perspective and describes the dynamics of G protein-coupled receptors, their role as biased agonists, their role as inverse agonists, proactive antihistamine therapy, and drug selection with consideration of impaired performance and anti-PAF effects. [ABSTRACT FROM AUTHOR]

Wood decomposer basidiomycetes are the major agents of lignocellulose decomposition in dead wood. As their interspecific interaction affects wood decomposition, difference in interaction area may alter the magnitude of the effects. This study examines the effects of wood surface area on decomposition by interacting basidiomycetes using laboratory incubation experiments with pine sapwood as a model. Two types of pine wood blocks with equal volume but identical surface area were prepared for colonization by one of four white rot basidiomycete species. The colonized wood blocks were then placed on agar media already colonized by the same strain or one of the other species, simulating fungal monoculture and interspecific interactions on wood surface. Results demonstrated that the decay rate of wood was greater in wood with larger surface, and wood decay was accelerated by the interaction of two fungal species in wood with larger surface but not in wood with smaller surface. In contrast, lignin decomposition was influenced by the competitor in wood with smaller surface but not in wood with larger surface. These results suggest that the observed promotion of decay by fungal interspecific interaction might not be attributable to the resource partitioning between fungal species but to the accelerated carbon of competition cost compensation in this case. [ABSTRACT FROM AUTHOR]

We described the spatial and temporal dynamics of aquatic macrophytes in a Neotropical coastal estuarine river, and identified the negative effects associated to the presence and dominance of the invasive tanner grass. We compared macrophyte beds along the Guaraguaçu River (South Brazil) over four years, using taxonomic and functional dimensions. Biodiversity descriptors were higher in the driest periods compared to the rainiest, although this difference seems to be decreasing over the studied years. Moreover, the spatial organization of biodiversity and community structure slightly changed over time. Such spatial community stability was highlighted by the dominance of the highly invasive tanner grass. In beds dominated by the invasive species, the biodiversity was reduced. As aquatic macrophytes represent an important group in water bodies, the long-term loss of seasonal differences in community structuring is of concern, mainly regarding its potential to impact other groups and ecosystem functioning. By analysing data from standardized monitoring, we were able to identify a poorly discussed facet of biotic homogenisation—the seasonal homogenisation. We also discussed the impact of massive development of invasive species and its consequences for biodiversity in a Neotropical river of outmost importance for biological conservation. [ABSTRACT FROM AUTHOR]

Land abandonment may decrease biodiversity but also provides an opportunity for rewilding. It is therefore necessary to identify areas that may benefit from traditional land management practices and those that may benefit from a lack of human intervention. In this study, we conducted comparative field surveys of butterfly occurrence in abandoned and inhabited settlements in 18 regions of diverse climatic zones in Japan to test the hypotheses that species-specific responses to land abandonment correlate with climatic niches and habitat preferences. Hierarchical models that unified species occurrence and habitat preferences revealed that negative responses to land abandonment were associated with species that have cold climatic niches and use open habitats, suggesting that species negatively impacted by land abandonment will decline more due to future climate warming. Maps representing species gains and losses due to land abandonment, which were created from the model estimates, showed similar geographical patterns, but some areas exhibited high species losses relative to gains. Our hierarchical modelling approach was useful for scaling up local-scale effects of land abandonment to a macro-scale assessment, which is crucial to developing spatial conservation strategies in the era of depopulation. [ABSTRACT FROM AUTHOR]

The bark of live trees provides an important microhabitat for corticolous myxomycetes. However, the association between the presence of myxomycetes and health of host trees has not been studied in detail. In this study, we aimed to investigate the relationship between tree vitality and myxomycetes on the bark of Cryptomeria japonica trees in a montane forest in western Japan. The vitality of trees was categorized into four grades based on the visual assessment of tree shape and leaf density in the upper branches. Myxomycetes on the bark surface were examined using the moist chamber culture method. A decline in tree vitality increased bark pH and decreased electrical conductivity of the bark exudates. Seventeen myxomycete species were recorded in 74 C. japonica trees. The structure of myxomycete communities varied between healthy and unhealthy trees, and species diversity increased as the vitality declined. The relative abundance of Cribraria confusa decreased as the vitality declined, while that of Paradiacheopsis solitaria increased. The results showed that acidophilic myxomycetes grew on healthy C. japonica bark, but changes in bark pH associated with vitality decline led to the weakening of acidity and shifted the community structure; thus, corticolous myxomycete diversity was enhanced as tree vitality decline. [ABSTRACT FROM AUTHOR]

Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr249 (SMURF2Thr249) activates its E3 ubiquitin ligase activity. Here, we demonstrate that SMURF2Thr249 phosphorylation plays an essential role in maintaining GSC stemness and tumorigenicity. SMURF2 silencing augmented the self-renewal potential and tumorigenicity of patient-derived GSCs. The SMURF2Thr249 phosphorylation level was low in human glioblastoma pathology specimens. Introduction of the SMURF2T249A mutant resulted in increased stemness and tumorigenicity of GSCs, recapitulating the SMURF2 silencing. Moreover, the inactivation of SMURF2Thr249 phosphorylation increases TGF-β receptor (TGFBR) protein stability. Indeed, TGFBR1 knockdown markedly counteracted the GSC phenotypes by SMURF2T249A mutant. These findings highlight the importance of SMURF2Thr249 phosphorylation in maintaining GSC phenotypes, thereby demonstrating a potential target for GSC-directed therapy. Hiraiwa et al. show that phosphorylation of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) at Thr249 mediates ubiquitylation and degradation of the TGF-β receptor TGBR1 leading to loss of glioblastoma stem cell tumorigenic capacity. Their data elucidates a mechanism of regulation of the TGF-β signaling pathway that controls the stem cell status in glioblastoma. [ABSTRACT FROM AUTHOR]

The effects of the surface finish of the bag filter for industrial use on the spatial distributions of the fiber mass, air permeability, and thickness were examined using a nonwoven fabric filter made of polytetrafluoroethylene (PTFE) with no surface finish and two nonwoven fabric filters made of PTFE with different surface finishes, i.e., resin finish and membrane finish. The surface finish had no impact on the non‐uniformity in air permeability distribution. However, the air permeability of the filters was reduced with the use of a surface finish. In addition, the specific filtration resistance of the filter media increased by approximately 1.2 times in the case of the resin finish and 4.2 times for the membrane finish. Hence, the influence of the membrane finish on the filter efficiency is extremely strong. [ABSTRACT FROM AUTHOR]

Purpose: Hyperthermia is a promising anticancer treatment modality. However, the molecular mechanism underlying the thermal sensitivity of tumor cells is largely unknown. The aim of this study was to clarify how biochemical changes triggered by heat stimulate antitumor activity. Methods and materials: The expression levels of various MAPK members in HeLa cells with or without hyperthermia were evaluated by western blotting and RT-PCR. The intracellular Ca2þ concentration [Ca2þ]i was monitored by digital imaging using CaTM-2 AM. An in vitro cleavage assay was used to determine whether calcium-dependent protease calpain cleaves MAPK components. Cell proliferation and clonogenicity were assessed in the absence or presence of siRNAs targeting MAPK members. Results: Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2 but not of the downstream MAP2K and MAPK members. The hyperthermia-induced degradation of TAK1 and MEKK2 was rescued by either the proteasome inhibitor MG132 or the calpain inhibitor ALLN; however, RAF1 was not affected by the inhibitors. Heat induced down regulation of RAF1. Hyperthermia increased [Ca2þ]i and calpain I expression. The calcium ionophore A23187 decreased TAK1 and MEKK2 levels. An in vitro cleavage assay demonstrated that TAK1 and MEKK2 are calpain I substrates. Knockdown of TAK1, RAF1 and MEKK2 suppressed cell proliferation and clonogenicity. Conclusions: Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2, without reduction of the downstream components in the MAP3K-MAP2K-MAPK cascade, by a calpain-dependent degradation pathway or transcriptional regulation. TAK1, RAF1 and/or MEKK2 play crucial roles in cell proliferation and clonogenicity and are potential molecular targets for hyperthermia. [ABSTRACT FROM AUTHOR]