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The optimization of open-loop shallow geothermal systems, which includes both design and operational aspects, is an important research area aimed at improving their efficiency and sustainability and the effective management of groundwater as a shallow geothermal resource. This paper investigates various approaches to address optimization problems arising from these research and implementation questions about GWHP systems. The identified optimization approaches are thoroughly analyzed based on criteria such as computational cost and applicability. Moreover, a novel classification scheme is introduced that categorizes the approaches according to the types of groundwater simulation model and the optimization algorithm used. Simulation models are divided into two types: numerical and simplified (analytical or data-driven) models, while optimization algorithms are divided into gradient-based and derivative-free algorithms. Finally, a comprehensive review of existing approaches in the literature is provided, highlighting their strengths and limitations and offering recommendations for both the use of existing approaches and the development of new, improved ones in this field.

Introduction The COVID-19 pandemic has disproportionately affected patients with severe mental illness (SMI), a vulnerable population with high morbidity and mortality. A UK-based study found reduced vaccination rates in patients with SMI; they therefore need to be prioritised for prevention and disease management. Objectives The objectives were to determine risk factors for vaccine hesitancy, and how best to manage those in patients with SMI, as well as whether our intervention of calling patients for their vaccines had a positive outcome. Methods Following approval from the Lambeth Directorate of South London and Maudsley (SLaM) NHS Foundation Trust, we investigated COVID-19 vaccination rates inpatients with SMI from a psychosis community service in South London (n=236). Dates of first and second doses were recorded through audit; reasons for refusal of vaccination were noted. Patients were encouraged to take the vaccine. A re-audit was performed after allowing three months. Chi-squared statistical analysis was performed to determine the value of our intervention. Results Before the intervention, 143 patients (60.6%) received at least one vaccine. 24 patients (10.2%) received one dose, and 77 (32.8%) were yet to receive any. There was no statistical significance (p=0.1509) between the number of patients who received a vaccine before and after intervention, with 33.1% of patients still remaining unvaccinated. Image: Image 2: Image 3: Conclusions There is limited research on perceptions of receiving vaccines in patients with SMI, despite their cost-effectiveness in disease prevention. Even after intervention, 33.1% of patients remained unvaccinated, compared to 6.6% nationally. A lack of knowledge and recommendations from care teams are reasons for hesitancy. Misinformation, conspiracy theories and propaganda can drive people towards refusal. Patients with SMI typically have disadvantages of healthcare inequality, lower levels of education and access to inaccurate information. Patients and their healthcare team should be knowledgeable about vaccine efficacy and side effects. Studies have shown low uptake in the Black/African/Caribbean ethnic group (49.3%, table 3). Reasons include general mistrust in institutions and access barriers. For minority communities, vaccination sites in community centres or places of worship have proven to be effective, providing familiarity. Patients taking clozapine may have a weaker immune system due to myelosuppression. 24.3% of our patients take this, with many unsure of interactions or side effects. Poorer prognosis means a focussed approach is needed. Vaccine hesitancy is complex and requires targeted, tailor-made strategies, with consideration for patients who may lack capacity. It is evident from our results that calling patients alone may not be effective. A future multi-modal approach may be necessary to address poor vaccine uptake and opens up avenues to further explore vaccine hesitancy. Disclosure of Interest None Declared

In avian species, maternal immunoglobulin Y (IgY) is transferred from the blood to the yolks of maturing oocytes; however, the mechanism underlying this transfer is unknown. To gain insight into the mechanisms of maternal IgY transfer into egg yolks, IgY-depleted chickens were generated by removing the bursa of Fabricius (bursectomy) during egg incubation, and their egg production and IgY transport ability into egg yolks were determined. After hatching, blood IgY concentrations of the bursectomized chickens decreased gradually until sexual maturity, whereas those of IgA remained low from an early stage of growth (from at least 2 wk of age). Chickens identified as depleted in IgY through screening of blood IgY and IgA concentrations were raised to sexual maturity. At 20 wk of age, both blood and egg yolk IgY concentrations in the IgY-depleted group were 600-fold lower than those of the control group, whereas egg production did not differ between the groups. Intravenously injected, digoxigenin-labeled IgY uptake into the egg yolk was approximately 2-fold higher in the IgY-depleted chickens than in the controls, suggesting that IgY depletion may enhance IgY uptake in maturing oocytes. DNA microarray analysis of the germinal disc, including the oocyte nucleus, revealed that the expression levels of 73 genes were upregulated more than 1.5-fold in the IgY-depleted group, although we could not identify a convincing candidate gene for the IgY receptor. In conclusion, we successfully raised IgY-depleted chickens presenting a marked reduction in egg yolk IgY. The enhanced uptake of injected IgY into the egg yolks of the IgY-depleted chickens supports the existence of a selective IgY transport mechanism in maturing oocytes and ovarian follicles in avian species.

The present study experimentally demonstrated that solid H2O is formed through the surface reaction OH + H2 at 10 K. This is the first experimental evidence of solid H2O formation using hydrogen in its molecular form at temperatures as low as 10 K. We further found that H2O formation through the reaction OH + H2 is about one order of magnitude more effective than HDO formation through the reaction OH + D2. This significant isotope effect results from differences in the effective mass of each reaction, indicating that the reactions proceed through quantum tunneling. [ABSTRACT FROM AUTHOR]

The European Union set ambitious goals regarding renewable energy and greenhouse gas (GHG) emissions. This study uses two models to analyze the implications of these goals on the European energy system and on the rest of the world, based on several scenarios for the mid and long term. First, using a linear programming optimization model for capacity expansion and unit commitment, we obtain the optimal design of the European power system in 2030 and 2050. Results for Germany are then used as input in a Multi-Regional Input-Output Analysis with the objective of analyzing the environmental and socioeconomic effects derived from the new energy system. The linking of both models in each scenario is at the core of this study. Results show the capabilities of this method in terms of GHG emissions, cumulative energy demand, value added, and job creation. Keywords: Capacity expansion optimization, Input-output analysis, Socioeconomic impacts, Environmental impacts

Background. Previous studies showed that nicorandil can reduce coronary events in patients with coronary artery disease. However, it is unclear whether oral nicorandil treatment may reduce mortality following acute myocardial infarction (AMI). Methods and Results. We examined the impact of oral nicorandil treatment on cardiovascular events in 1846 AMI patients who were hospitalized within 24 h after AMI onset, treated with emergency percutaneous coronary intervention (PCI), and discharged alive. Patients were divided into those with (Group N, n = 535) and without (Group C, n = 1311) oral nicorandil treatment at discharge. No significant differences in age, gender, body mass index, prevalence of coronary risk factors, or history of myocardial infarction existed between the two groups; however, higher incidences of multi-vessel disease, and a lower rate of successful PCI were observed in Group N. During the median follow-up of 709 (340–1088) days, allcause mortality rate was 43% lower in Group N compared with Group C (2.4% vs. 4.2%, stratified log-rank test: p = 0.0358). Multivariate Cox regression analysis revealed that nicorandil treatment was associated with all-cause death after discharge (Hazard ratio 0.495, 95% CI: 0.254–0.966, p = 0.0393), but not for other cardiovascular events such as re-infarction, admission for heart failure, stroke and arrhythmia. Conclusions. The results suggest that oral administration of nicorandil is associated with reduced incidence of death in the setting of secondary prevention after AMI.

Refractory organic compounds formed in molecular clouds are among the building blocks of the solar system objects and could be the precursors of organic matter found in primitive meteorites and cometary materials. However, little is known about the evolutionary pathways of molecular cloud organics from dense molecular clouds to planetary systems. In this study, we focus on the evolution of the morphological and viscoelastic properties of molecular cloud refractory organic matter. We found that the organic residue, experimentally synthesized at ∼10 K from UV-irradiated H2O-CH3OH-NH3 ice, changed significantly in terms of its nanometer- to micrometer-scale morphology and viscoelastic properties after UV irradiation at room temperature. The dose of this irradiation was equivalent to that experienced after short residence in diffuse clouds (≤104 years) or irradiation in outer protoplanetary disks. The irradiated organic residues became highly porous and more rigid and formed amorphous nanospherules. These nanospherules are morphologically similar to organic nanoglobules observed in the least-altered chondrites, chondritic porous interplanetary dust particles, and cometary samples, suggesting that irradiation of refractory organics could be a possible formation pathway for such nanoglobules. The storage modulus (elasticity) of photo-irradiated organic residues is ∼100 MPa irrespective of vibrational frequency, a value that is lower than the storage moduli of minerals and ice. Dust grains coated with such irradiated organics would therefore stick together efficiently, but growth to larger grains might be suppressed due to an increase in aggregate brittleness caused by the strong connections between grains. [ABSTRACT FROM AUTHOR]

Amelioration of neuropathic spinal cord injury (SCI) pain is a clinical challenge. Increasing the endocannabinoid anandamide and other fatty acid amides (FAA) by blocking fatty acid amide hydrolase (FAAH) has been shown to be antinociceptive in a number of animal models of chronic pain. However, an antinociceptive effect of blocking FAAH has yet to be demonstrated in a rat model of neuropathic SCI pain. Four weeks following a SCI, rats developed significantly decreased hind paw withdrawal thresholds, indicative of below-level cutaneous hypersensitivity. A group of SCI rats were systemically treated (i.p.) with either the selective FAAH inhibitor URB597 or vehicle twice daily for seven days. A separate group of SCI rats received a single dose (p.o.) of either the selective FAAH inhibitor PF-3845 or vehicle. Following behavioral testing, levels of the FAA N-arachidonoylethanolamide, N-oleoyl ethanolamide and N-palmitoyl ethanolamide were quantified in brain and spinal cord from SCI rats. Four weeks following SCI, FAA levels were markedly reduced in spinal cord tissue. Although systemic treatment with URB597 significantly increased CNS FAA levels, no antinociceptive effect was observed. A significant elevation of CNS FAA levels was also observed following oral PF-3845 treatment, but only a modest antinociceptive effect was observed. Increasing CNS FAA levels alone does not lead to robust amelioration of below-level neuropathic SCI pain. Perhaps utilizing FAAH inhibition in conjunction with other analgesic mechanisms could be an effective analgesic therapy.

Background: The post-insertion clinical course of esophageal self-expandable metal stents (SEMS) in initially frail patients with esophageal carcinoma (EC) with dysphagia remains unclear. This study aimed to assess dysphagia improvement and evaluate prognosis in initially frail patients with advanced EC following SEMS insertion., Methods: We retrospectively reviewed EC patients with EC who underwent esophageal SEMS insertion at our institution between January 2014 and March 2023. Inclusion criteria comprised Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3 or ECOG PS 2 for individuals aged ≥ 75 years and recommendation for best supportive care by a multidisciplinary team., Results: Forty-six patients met the inclusion criteria. Among them, 37 patients (80.4%) were ≥ 75 years old, and 21 patients (45.7%) exhibited ECOG PS 3 or 4. Dysphagia score (DS) ≥ 3 was observed in 27 patients (58.7%). All esophageal SEMS insertions were successfully completed. Post-procedure, there were two fatal cases of aspiration pneumonia and one perforation incident. DS improved to ≤ 1 in 25 patients (54.3%), with multivariate analysis indicating DS 3-4 and Glasgow Prognostic Score (GPS) 1-2 as negative predictive factors. The median overall survival was 4.1 months (95% confidence interval 1.8-6.5)., Conclusions: Esophageal SEMS insertion effectively alleviated dysphagia in initially frail EC patients, yet prognosis remained poor, with occurrences of some fatal adverse events. Careful selection of candidates for esophageal SEMS insertions is crucial in this demographic, particularly considering the challenges in improving dysphagia for patients with DS 3-4 and GPS 1-2., (© 2024. The Author(s).)

The air-water interface (AWI) is a ubiquitous reaction field different from the bulk phase where unexpected reactions and physical processes often occur. The AWI is a region where air contacts cloud droplets, aerosol particles, the ocean surface, and biological surfaces such as fluids that line human epithelia. In Earth's atmosphere, short-lived intermediates are expected to be generated at the AWI during multiphase reactions. Recent experimental developments have enabled the direct detection of atmospherically relevant, short-lived intermediates at the AWI. For example, spray ionization mass spectrometric analysis of water microjets exposed to a gaseous mixture of ozone and water vapor combined with a 266 nm laser flash photolysis system (LFP-SIMS) has been used to directly probe organic peroxyl radicals (RO 2 ·) produced by interfacial hydroxyl radicals (OH·) + organic compound reactions. OH· emitted immediately after the laser flash photolysis of carboxylic acid at the gas-liquid interface have been directly detected by time-resolved, laser-induced florescence techniques that can be used to study atmospheric multiphase photoreactions. In this Featured Article, we show some recent experimental advances in the detection of atmospherically important intermediates at the AWI and the associated reaction mechanisms. We also discuss current challenges and future prospects for atmospheric multiphase chemistry.

Purpose: Fearful dental patients often cite various dental instruments or procedures as triggers for their dental fear. Thus, visual dental stimuli provoke anxiety. This preliminary study aimed to assess the level of aversion to visual stimuli in dental patients and compare it with that in dentists., Patients and Methods: A total of 43 dental patients (25 women, 18 men; average age, 29.9 ± 13.3 years; patient group) and 13 dentists (4 women, 9 men; average age, 28.2 ± 2.0 years; dentist group) were included. All participants had previously undergone dental treatment. The dental fear level was assessed using the self-reported Dental Fear Survey (DFS). Thirty-two images associated with dental treatment were prepared and classified into three categories: dental instruments, dental procedures, and the dental environment. All participants rated their level of disgust toward each image on a visual analog scale with scores ranging from 0 to 100., Results: In the patient group, the disgust ratings for tooth extraction, dental drilling, and local anesthesia were >60, which were significantly different from those in the dentist group (Mann-Whitney U- test, p <0.001, p =0.001, and p =0.001, respectively). The ranking order of the disgust ratings for the 32 images showed significant correlation between the patient and dentist groups (Spearman correlation coefficient, r=0.80, p <0.001). In the patient group, the disgust ratings for dental impressions and the interdental brush, dental light, and dental chair were significantly correlated with DFS scores (r=0.61, p <0.001; r=0.47, p =0.001; r=0.41, p =0.006; and r=0.40, p =0.008, respectively)., Conclusion: This study revealed that patients have more negative feelings toward invasive procedures than dentists. However, a significant correlation was identified between the ranking of aversion-provoking dental stimuli by patients and dentists. Furthermore, the level of aversion to several dental-related items that do not cause pain was correlated with the dental fear level., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Tanaka et al.)

Introduction: Humans mainly utilize visual and auditory information as a cue to infer others' emotions. Previous neuroimaging studies have shown the neural basis of memory processing based on facial expression, but few studies have examined it based on vocal cues. Thus, we aimed to investigate brain regions associated with emotional judgment based on vocal cues using an N-back task paradigm., Methods: Thirty participants performed N-back tasks requiring them to judge emotion or gender from voices that contained both emotion and gender information. During these tasks, cerebral hemodynamic response was measured using functional near-infrared spectroscopy (fNIRS)., Results: The results revealed that during the Emotion 2-back task there was significant activation in the frontal area, including the right precentral and inferior frontal gyri, possibly reflecting the function of an attentional network with auditory top-down processing. In addition, there was significant activation in the ventrolateral prefrontal cortex, which is known to be a major part of the working memory center., Discussion: These results suggest that, compared to judging the gender of voice stimuli, when judging emotional information, attention is directed more deeply and demands for higher-order cognition, including working memory, are greater. We have revealed for the first time the specific neural basis for emotional judgments based on vocal cues compared to that for gender judgments based on vocal cues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ohshima, Koeda, Kawai, Saito, Niioka, Okuno, Naganawa, Hama, Kyutoku and Dan.)

Experimentally demonstrating the existence of waters with local structures unlike that of common water is critical for understanding both the origin of the mysterious properties of water and liquid polymorphism in single component liquids. At the interfaces between water and ices I h , III, and VI grown/melted under pressure, we previously discovered low- and high-density unknown waters, that are immiscible with the surrounding water. Here, we show, by in-situ optical microscopy, that an unknown water appears at the ice V-water interface via spinodal-like dynamics. The dewetting dynamics of the unknown water indicate that its characteristic velocity is ~ 90 m/s. The time evolution of the characteristic length of the spinodal-like undulation suggests that the dynamics may be described by a common model for spinodal decomposition of an immiscible liquid mixture. Spinodal-like dewetting dynamics of the unknown water transiently showed anisotropy, implying the property of a liquid crystal., (© 2023. Springer Nature Limited.)

Saturated fatty acids are abundant organic compounds in oceans and sea sprays. Their photochemical reactions induced by solar radiation have recently been found as an abiotic source of volatile organic compounds, which serve as precursors of secondary organic aerosols. However, photoabsorption of wavelengths longer than 250 nanometers in liquid saturated fatty acids remains unexplained, despite being first reported in 1931. Here, we demonstrate that the previously reported absorption of wavelengths longer than 250 nanometers by liquid nonanoic acid [CH 3 (CH 2 ) 7 COOH)] originates from traces of impurities (0.1% at most) intrinsically contained in nonanoic acid reagents. Absorption cross sections of nonanoic acid newly obtained here indicate that the upper limit of its photolysis rate is three to five orders of magnitude smaller than those for atmospherically relevant carbonyl compounds.

This paper considers the total synthesis of a cellular differentiation regulator of Clostridium acetobutylicum , clostrienose, which is a unique fatty-acid glycosyl ester consisting of clostrienoic acid, (3 R ,5 E ,8 E ,10 E )-3-hydroxy-tetradeca-5,8,10-trienoic acid and α-d-galactofuranosyl-(1 → 2)-α-l-rhamnose. The key features of our synthesis include stereoselective construction of a skipped-triene system in clostrienoic acid and its esterification with a disaccharide residue. The partially protected clostrienoic acid employed for the coupling also served for the preparation of l-rhamnosyl clostrienoate, thus leading to confirmation of the proposed structure unambiguously., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Emotional cognitive impairment is a core phenotype of the clinical symptoms of psychiatric disorders. The ability to measure emotional cognition is useful for assessing neurodegenerative conditions and treatment responses. However, certain factors such as culture, gender, and generation influence emotional recognition, and these differences require examination. We investigated the characteristics of healthy young Japanese adults with respect to facial expression recognition., Methods: We generated 17 models of facial expressions for each of the six basic emotions (happiness, sadness, anger, fear, disgust, and surprise) at three levels of emotional intensity using the Facial Acting Coding System (FACS). Thirty healthy Japanese young adults evaluated the type of emotion and emotional intensity the models represented to them., Results: Assessment accuracy for all emotions, except fear, exceeded 60% in approximately half of the videos. Most facial expressions of fear were rarely accurately recognized. Gender differences were observed with respect to both faces and participants, indicating that expressions on female faces were more recognizable than those on male faces, and female participants had more accurate perceptions of facial emotions than males., Conclusion: The videos used may constitute a dataset, with the possible exception of those that represent fear. The subject's ability to recognize the type and intensity of emotions was affected by the gender of the portrayed face and the evaluator's gender. These gender differences must be considered when developing a scale of facial expression recognition., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Disease comorbidity is a major challenge in healthcare affecting the patient's quality of life and costs. AI-based prediction of comorbidities can overcome this issue by improving precision medicine and providing holistic care. The objective of this systematic literature review was to identify and summarise existing machine learning (ML) methods for comorbidity prediction and evaluate the interpretability and explainability of the models., Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework was used to identify articles in three databases: Ovid Medline, Web of Science and PubMed. The literature search covered a broad range of terms for the prediction of disease comorbidity and ML, including traditional predictive modelling., Results: Of 829 unique articles, 58 full-text papers were assessed for eligibility. A final set of 22 articles with 61 ML models was included in this review. Of the identified ML models, 33 models achieved relatively high accuracy (80-95%) and AUC (0.80-0.89). Overall, 72% of studies had high or unclear concerns regarding the risk of bias., Discussion: This systematic review is the first to examine the use of ML and explainable artificial intelligence (XAI) methods for comorbidity prediction. The chosen studies focused on a limited scope of comorbidities ranging from 1 to 34 (mean = 6), and no novel comorbidities were found due to limited phenotypic and genetic data. The lack of standard evaluation for XAI hinders fair comparisons., Conclusion: A broad range of ML methods has been used to predict the comorbidities of various disorders. With further development of explainable ML capacity in the field of comorbidity prediction, there is a significant possibility of identifying unmet health needs by highlighting comorbidities in patient groups that were not previously recognised to be at risk for particular comorbidities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Stabilization/solidification (S/S) with ordinary portland cement (OPC)-based binders is a suitable method to remediate heavy metal (HM)-contaminated soil and reuse resources of industrial wastes. In industrial wastes, alkaline wastes such as red mud (RM), soda residue (SR), pulverized fly ash (PFA), and alkalinity granulated blast furnace slag (GGBS) can immobilize HM ions (Pb 2+ , Zn 2+ , Cd 2+ , Cr 3+ , and Cu 2+ ) by precipitation. However, some HM ions (such as AsO 4 3- ) would redissolve within the strong alkali environment. In this case, PFA, GGBS, metakaolin (MK), and incinerated sewage sludge ash (ISSA) which have low pH, can be used to immobilize HM ions or added to the OPC-based binders to adjust the pH in the soil products. Moreover, the calcium silicate hydrate (CSH), calcium aluminum silicate hydrate (CASH), ettringite (AFt), and calcium monosulfoalumiante hydrates (AFm) generated during the pozzolanic reaction can also immobilize HM ions by adsorption on the surface, ion exchange, and encapsulation. SR and GGBS can be used to immobilize the HMs (such as CrO 4 2- and AsO 4 3- ), which are mainly affected by AFt and AFm. For those not affected by AFt and AFm but related to immobilization by precipitating (such as Mn 2+ ), other wastes except SR and GGBS are suitable for treating contaminated soil. Nevertheless, the formation of AFt is also instrumental for soil product strength. There are several factors affecting soil product strength. In the future, the influence of different hydration products on the S/S effects, competitive adsorption of HM ions, effects on long-term HM stabilization, and novel materials are worth being explored by researchers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The safety and effectiveness of pazopanib are related to plasma trough concentrations in renal cell carcinoma (RCC); however, data on pazopanib plasma trough concentrations with soft tissue sarcoma (STS) are limited. This study investigated the relationship between plasma trough concentrations and pazopanib safety in 45 Japanese patients with RCC or STS. Among the 33 patients included, the median pazopanib trough concentration was 37.5 (range, 12.1-67.6) µg/mL, which was not significantly different between Japanese RCC and STS patients. The plasma trough concentrations showed significant and positive correlations with aspartate aminotransferase and alanine aminotransferase values in blood samples taken for pharmacokinetic measurements after the administration. The incidence of pazopanib treatment discontinuation were significantly higher in RCC patients (p = 0.027). The primary reason for treatment discontinuation was hepatic dysfunction (5/6, 83.3%). Furthermore, this study revealed that pazopanib trough concentration was affected significantly by proton pump inhibitors but not by histamine 2-receptor blockers. In conclusion, the observed pazopanib trough levels and their safety in the Japanese RCC and STS populations in this study were similar to those of the global population. This is the first study to correlate the hepatotoxicity and pharmacokinetic property of pazopanib plasma trough levels by comparing Japanese patients with RCC or STS., (© 2023. The Author(s).)

Although cases of secondary membranous nephropathy associated with autoimmune thyroid disease (AITD) have been reported, most of them, if not all, present with symptomatic thyroid disease. Here we report an asymptomatic case of AITD complicated with secondary membranous nephropathy. A 16-year-old girl was referred to our institute because of proteinuria found by an annual medical checkup. Urinalysis showed a urinary protein creatinine ratio (UPCR) of 3.0 g/gCre. Blood examination revealed that she had Graves' disease, although she did not have any symptoms of hyperthyroidism such as weight loss, anxiety, tremor, tachycardia, or eye symptoms. In a kidney biopsy, periodic acid silver-methenamine staining showed spike formation in the basement membrane. Electron microscopy showed electron-dense deposits on the epithelial side of the glomerular basement membrane. Immunofluorescent staining showed co-localization of thyroid peroxidase and IgG deposition along the glomerular capillary walls. A diagnosis of membranous nephropathy secondary to asymptomatic Graves' disease was made on the basis of results of the examinations. Treatment with thiamazole added to enalapril improved proteinuria (reduction of UPCR to 0.83 g/gCr) and hypoalbuminemia. Consideration should be given to the possibility of AITD in differential diagnosis of etiologies of membranous nephropathy even when typical symptoms of AITD are lacking., (© 2021. Japanese Society of Nephrology.)

Background and Aims: This study aimed to examine the safety of fixed-dose nivolumab., Methods: We retrospectively reviewed the medical records of 113 Japanese patients with gastric cancer who were previously treated with cytotoxic chemotherapy and initiated nivolumab. The endpoints were the incidence of Grade 2 or higher immune-related adverse events (irAEs) in the conventional dose (3 mg/kg) and fixed-dose groups (240 mg)., Results: The incidence rates of irAEs in the conventional-dose and fixed-dose groups were 29.9% and 19.4%, respectively, and the rates of Grade 2 or higher irAEs were 23.3% and 19.4%, respectively, with no significant difference between the two groups, suggesting that nivolumab at 240 mg is as safe as the 3 mg/kg dose., Conclusion: This is the first report on the safety of nivolumab at 240 mg in Japanese patients., Competing Interests: Kensei Yamaguchi has received speaking honoraria from Merck Serono, Takeda Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Eli Lilly, Yakult, Sanofi, Bristol‐Myers Squibb, and Bayer, and research grants from Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Sumitomo Dainippon Pharma, Eli Lilly, Daiichi Sankyo, Yakult, and Gilead Sciences. He also plays consulting and advisory roles for Bristol‐Myers Squibb. The other authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The 3' exonucleolytic processing of stable RNAs is conserved throughout biology. Yeast strains lacking the exoribonuclease Rex1 are defective in the 3' processing of stable RNAs, including 5S rRNA and tRNA. The equivalent RNA processing steps in Escherichia coli are carried out by RNase T. Rex1 is larger than RNase T, the catalytic DEDD domain being embedded within uncharacterized amino- and carboxy-terminal regions. Here we report that both amino- and carboxy-terminal regions of Rex1 are essential for its function, as shown by genetic analyses and 5S rRNA profiling. Full-length Rex1, but not mutants lacking amino- or carboxy-terminal regions, accurately processed a 3' extended 5S rRNA substrate. Crosslinking analyses showed that both amino- and carboxy-terminal regions of Rex1 directly contact RNA in vivo. Sequence homology searches identified YFE9 in Schizosaccharomyces pombe and SDN5 in Arabidopsis thaliana as closely related proteins to Rex1. In addition to the DEDD domain, these proteins share a domain, referred to as the RYS ( R ex1, Y FE9 and S DN5) domain, that includes elements of both the amino- and caroxy-terminal flanking regions. We also characterize a nuclear localization signal in the amino-terminal region of Rex1. These studies reveal a novel dual domain structure at the core of Rex1-related ribonucleases, wherein the catalytic DEDD domain and the RYS domain are aligned such that they both contact the bound substrate. The domain organization of Rex1 is distinct from that of other previously characterized DEDD family nucleases and expands the known repertoire of structures for this fundamental family of RNA processing enzymes., (© 2022 Daniels et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

The occurrence of hydrogen atom-ordered form of ice Ih, ice XI, in the outer Solar System has been discussed based on laboratory experiments because its ferroelectricity influences the physical processes in the outer Solar System. However, the formation of ice XI in that region is still unknown due to a lack of formation conditions at temperatures higher than 72 K and the effect of UV-rays on the phase transition from ice I to ice XI. As a result, we observed the UV-irradiation process on ice Ih and ice Ic using a newly developed ultra-high vacuum cryogenic transmission electron microscope. We found that ice Ih transformed to ice XI at temperatures between 75 and 140 K with a relatively small UV dose. Although ice Ic partially transformed to ice XI at 83 K, the rate of transformation was slower than for ice Ih. These findings point to the formation of ice XI at temperatures greater than 72 K via UV irradiation of ice I crystals in the Solar System; icy grains and the surfaces of icy satellites in the Jovian and Saturnian regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kouchi, Kimura, Kitajima, Katsuno, Hidaka, Oba, Tsuge, Yamazaki, Fujita, Hama, Takahashi, Nakatsubo and Watanabe.)