Search

Abstract Background Francisella tularensis, the causative agent of tularemia, is a facultative intracellular bacterium. Although the life cycle of this bacterium inside phagocytic cells (e.g., macrophages, neutrophils) has been well analyzed, the difficulty of gene silencing and editing genes in phagocytic cells makes it difficult to analyze host factors important for the infection. On the other hand, epithelial cell lines, such as HeLa, have been established as cell lines that are easy to perform gene editing. However, the infection efficiency of Francisella into these epithelial cells is extremely low. Methods In order to facilitate the molecular biological analysis of Francisella infection using epithelial cells, we constructed an efficient infection model of F. tularensis subsp. novicida (F. novicida) in HeLa cells expressing mouse FcγRII (HeLa-FcγRII), and the system was applied to evaluate the role of host GLS1 on Francisella infection. Results As a result of colony forming unit count, HeLa-FcγRII cells uptake F. novicida in a serum-dependent manner and demonstrated an approximately 100-fold increase in intracellular bacterial infection compared to parental HeLa cells. Furthermore, taking advantage of the gene silencing capability of HeLa-FcγRII cells, we developed GLS1, a gene encoding glutaminase, knockdown cells using lentiviral sh RNA vector and assessed the impact of GLS1 on F. novicida infection. LDH assay revealed that GLS1-knockdown HeLa-FcγRII cells exhibited increased cytotoxicity during infection with F. novicida compared with control HeLa-FcγRII cells. Furthermore, the cell death was inhibited by the addition of ammonia, the metabolite produced through glutaminase activity. These results suggest that ammonia plays an important role in the proliferation of F. novicida. Conclusions In this report, we proposed a new cell-based infection system for Francisella infection using HeLa-FcγRII cells and demonstrated its effectiveness. This system has the potential to accelerate cell-based infection assays, such as large-scale genetic screening, and to provide new insights into Francisella infection in epithelial cells, which has been difficult to analyze in phagocytic cells.

Abstract Magnetoencephalography (MEG) provides crucial information in diagnosing focal epilepsy. However, dipole estimation, a commonly used analysis method for MEG, can be time-consuming since it necessitates neurophysiologists to manually identify epileptic spikes. To reduce this burden, we developed the automatic detection of spikes using deep learning in single center. In this study, we performed a multi-center study using six MEG centers to improve the performance of the automated detection of neuromagnetically recorded epileptic spikes, which we previously developed using deep learning. Data from four centers were used for training and evaluation (internal data), and the remaining two centers were used for evaluation only (external data). We used a five-fold subject-wise cross-validation technique to train and evaluate the models. A comparison showed that the multi-center model outperformed the single-center model in terms of performance. The multi-center model achieved an average ROC-AUC of 0.9929 and 0.9426 for the internal and external data, respectively. The median distance between the neurophysiologist-analyzed and automatically analyzed dipoles was 4.36 and 7.23 mm for the multi-center model for internal and external data, respectively, indicating accurate detection of epileptic spikes. By training data from multiple centers, automated analysis can improve spike detection and reduce the analysis workload for neurophysiologists. This study suggests that the multi-center model has the potential to detect spikes within 1 cm of a neurophysiologist’s analysis. This multi-center model can significantly reduce the number of hours required by neurophysiologists to detect spikes.

Population growth and limited availability of agricultural land have created immense pressure for accessible food and nutritional supplements in Indonesia. To establish new food sources that will be sustainable in the long term, various government programmes have opened up land for agriculture in the peatlands of Central Kalimantan. However, the establishment of both large-scale plantations and community-based agriculture has required drainage of the peatlands leading to a decline in the habitat along with increased greenhouse gas emissions and incidence of peatland fires. The option of rewetting and adopting wetland agriculture (paludiculture) in these areas could significantly improve the preservation of both terrestrial carbon stocks and the native flora and fauna. Cultivating microalgae as part of paludiculture could provide additional resources including food for both humans and aquatic animals, benefitting agriculture and fisheries in the future. This preliminary study aims to identify microalgae genera in the tropical peat swamp waters of Central Kalimantan, and in particular to determine which of the microalgae present may have potential as sources of human nutrition as well as for other uses. Peat water samples were obtained from three distinct locations in Palangka Raya City. Specimens were identified using techniques based on morphological characteristics observed by photomicrography, and the nutritional potential of each genus was determined by literature review. The analysis revealed paludi-microalgae belonging to a total of 17 genera, two from Class Bacillariophyceae (Pinnularia, Navicula), two from Class Chlorophyceae (Pandorina, Scenedesmus), three from Class Cyanobacteria (Microcystis, Anabaena, Oscillatoria), four from Class Euglenophyceae (Euglena, Trachelomonas, Lepocinclis, Phacus) and six from Class Zygnematophyceae (Closterium, Cosmarium, Euastrum, Micrasterias, Spirogyra, Pleurotaenium). The highest number of microalgae genera was found in peat swamp ponds in Palangka Raya City Forest, which contributed 95 % of all genera obtained. Literature review revealed that several of these genera such as Spirogyra, Navicula and Euglena have high potential as food sources with significant nutritional properties, containing carbohydrates, proteins, lipids, fats, minerals and a range of vitamins. Various other useful properties were also identified.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50 of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.

Abstract Purpose While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r. Methods A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality. Results This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1–3.1]. Conclusions Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.

Abstract This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term “midline” areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4–78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9–11.9, 95% CI) and 16.6 ± 1.4 (13.9–19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Akibat serangkaian bencana alam yang terjadi di Indonesia, diperlukan upaya rehabilitasi dan rekonstruksi yang cepat untuk memperbaiki rumah dan fasilitas dengan bangunan tahan gempa. Menjawab kebutuhan ini, Kementerian Pekerjaan Umum dan Perumahan Rakyat telah mengembangkan konstruksi Rumah Instan Sederhana Sehat (RISHA) yang tidak hanya dapat dibangun dengan cepat tetapi juga diklaim ramah lingkungan. Metode RISHA diharapkan mampu mengurangi emisi karbon yang dihasilkan dari proses pembangunan. Pemilihan bahan bangunan berperan penting dalam konstruksi karena produksi bahan tersebut memerlukan banyak energi dan menghasilkan karbon dioksida (CO2). Pemilihan material yang ramah lingkungan dapat mengurangi konsumsi energi dan emisi karbon sepanjang siklus hidup bangunan. Penelitian ini bertujuan menghitung emisi karbon yang dihasilkan dari pembangunan rumah menggunakan metode RISHA. Metode perhitungan dilakukan dengan menggunakan koefisien dari The Inventory of Carbon and Energy (ICE) Bath University. Hasil penelitian menunjukkan bahwa satu unit rumah RISHA menghasilkan total emisi karbon sebesar 18.392,34 KgCO2, dengan material besi beton, bata ringan, dan semen sebagai kontributor utama. Optimalisasi dilakukan dengan mengganti mengganti material dinding yang semula menggunakan bata ringan menjadi material batako serta material penutup lantai yang semula menggunakan keramik, digantikan dengan parket kayu. Hasilnya terjadi pengurangan emisi karbon sebesar 5,49% menjadi 17.382,15 KgCO2.

Background: Educational environment is one of the most important determinants of an effective curriculum. Students' perceptions of their educational environment have a significant impact on their behavior and academic progress. Objective: 1. To identify students’ perception to the educational environment.2. To identify any gender or class level differences in the students’ perception.Type of the study: This is a descriptive cross-sectional studyMethodology: The study was carried out on convenient sample of 150 students of 2nd and 5th grade. This study was done in Al Kindy Medical College, Baghdad, Iraq and conducted during the period from the 1st of October 2013 till the end of March 2014, by using DREEM questionnaire a validated universal diagnostic inventory for assessing the quality of educational environment through direct interview. Inclusion criteria include any student from the 2nd and 5th class who agree to participate in the study. The data was entered into a Microsoft Excel spreadsheet and were analyzed using SPSS version 16. Student t test was done to find out the difference between the mean scores, P

Abstract Rabies virus (RABV) causes fatal neurological disease. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) using inactivated-virus vaccines are the most effective measures to prevent rabies. In Japan, HEP-Flury, the viral strain, used as a human rabies vaccine, has historically been propagated in primary fibroblast cells derived from chicken embryos. In the present study, to reduce the cost and labor of vaccine production, we sought to adapt the original HEP-Flury (HEP) to Vero cells. HEP was repeatedly passaged in Vero cells to generate ten- (HEP-10V) and thirty-passaged (HEP-30V) strains. Both HEP-10V and HEP-30V grew significantly better than HEP in Vero cells, with virulence and antigenicity similar to HEP. Comparison of the complete genomes with HEP revealed three non-synonymous mutations in HEP-10V and four additional non-synonymous mutations in HEP-30V. Comparison among 18 recombinant HEP strains constructed by reverse genetics and vesicular stomatitis viruses pseudotyped with RABV glycoproteins indicated that the substitution P(L115H) in the phosphoprotein and G(S15R) in the glycoprotein improved viral propagation in HEP-10V, while in HEP-30V, G(V164E), G(L183P), and G(A286V) in the glycoprotein enhanced entry into Vero cells. The obtained recombinant RABV strain, rHEP-PG4 strain, with these five substitutions, is a strong candidate for production of human rabies vaccine.

Abstract Catalytic antibodies possess a dual function that enables both antigen recognition and degradation. However, their time-consuming preparation is a significant drawback. This study developed a new method for quickly converting mice monoclonal antibodies into catalytic antibodies using site-directed mutagenesis. Three mice type monoclonal antibodies targeting hemagglutinin molecule of influenza A virus could be transformed into the catalytic antibodies by deleting Pro95 in CDR-3 of the light chain. No catalytic activity was observed for monoclonal antibodies and light chains. In contrast, the Pro95-deleted light chains exhibited a catalytic activity to cleave the antigenic peptide including the portion of conserved region of hemagglutinin molecule. The affinity of the Pro95-deleted light chains to the antigen increased approximately 100-fold compared to the wild-type light chains. In the mutants, three residues (Asp1, Ser92, and His93) come closer to the appropriate position to create the catalytic site and contributing to the enhancement of both catalytic function and immunoreactivity. Notably, the Pro95-deleted catalytic light chains could suppress influenza virus infection in vitro assay, whereas the parent antibody and the light chain did not. This strategy offers a rapid and efficient way to create catalytic antibodies from existing antibodies, accelerating the development for various applications in diagnostic and therapeutic applications.

Detecting Ganoderma boninense in Indonesia is crucial for effectively controlling and mitigating the spread of basal stem disease in oil palm fields. While there is ongoing development of tolerant plants, no such plant has been successfully created yet. Consequently, researchers are actively studying detection methods for Ganoderma boninense. One established and highly accurate approach is the use of polymerase chain reaction (PCR) techniques for molecular detection. However, this method requires time‐consuming sample preparation, which can pose challenges in plantation settings. To address this problem, a portable lab‐on‐chip device has been introduced. This technology enables easy and automatic DNA retrieval from liquid samples by absorbing lysed DNA using magnetic beads. An efficient mechanism for manipulating the magnetic bead within the semiconductor has been successfully implemented. The extraction process typically takes around 15 minutes using a modified methodology on the chip device approach. The chip facilitates the retrieval of two samples with a capacity of 120 µL for each sample. The PCR method was utilized to validate the equivalence of the lab‐on‐chip device extraction to the standard extraction method. This represents a promising alternative for expedited and simplified detection of Ganoderma boninense in field conditions.

This research discusses the biography of the pure lady Fatimah al-Zahra (peace be upon her) through the book “Tadhkirat al-Khawas min al-Ummah bi Dhikr Khasa’is al-A’immah” by its author Sibṭ ibn al-Jawzi. The study briefly touches upon the life of the author, then delves into the birth of Lady Fatimah (peace be upon her), her names, titles, blessed marriage, pure offspring, inheritance, virtues, illness, and death. The research includes the text of the narrations, their documentation from other sources, and their authenticity. It also examines whether the author’s adherence to the Hanafi school of thought influenced his transmission of narrations that honor her. Additionally, it addresses the narrations that Sibṭ ibn al-Jawzi omitted.

Escherichia coli O157:H7 is a strain of Escherichia coli known for causing foodborne illness through the consumption of contaminated or raw food. To detect this pathogen, a conductometric immunosensor was developed using a conductometric sensing approach. The sensor was constructed on an interdigitated electrode and modified with a monoclonal anti-Escherichia coli O157:H7 aptamer. A total of 200 electrode pairs were fabricated and modified to bind to the target molecule replica. The binding replica, acting as the bio-recognizer, was linked to the electrode surface using 3-Aminopropyl triethoxysilane. The sensor exhibited excellent performance, detecting Escherichia coli O157:H7 in a short time frame and demonstrating a wide detection range of 1 fM to 1 nM. Concentrations of Escherichia coli O157:H7 were detected within this range, with a minimum detection limit of 1 fM. This innovative sensor offers simplicity, speed, high sensitivity, selectivity, and the potential for rapid sample processing. The potential of this proposed biosensor is particularly beneficial in applications such as drug screening, environmental monitoring, and disease diagnosis, where real-time information on biomolecular interactions is crucial for timely decision-making and where cross-reactivity or interference may compromise the accuracy of the analysis.

BackgroundFor addressing antibiotic overuse, Japan designed a health care policy in which eligible medical facilities could claim a financial reward when antibiotics were not prescribed for early-stage respiratory and gastrointestinal infections. The policy was introduced in a pilot manner in paediatric clinics in April 2018.MethodsWe conducted a quasi-experimental, propensity score-matched, difference-in-differences (DID) design to determine whether the nationwide financial incentives for appropriate non-prescribing of antibiotics as antimicrobial stewardship [800 JPY (≈7.3 US D) per case] were associated with changes in prescription patterns, including antibiotics, and health care use in routine paediatric health care settings at a national level. Data consisted of 9 253 261 cases of infectious diseases in 553 138 patients treated at 10 180 eligible or ineligible facilities.ResultsA total of 2959 eligible facilities claimed 316 770 cases for financial incentives and earned 253 million JPY (≈2.29 million USD). Compared with ineligible facilities, the introduction of financial incentives in the eligible facilities was associated with an excess reduction in antibiotic prescriptions [DID estimate, -228.6 days of therapy (DOTs) per 1000 cases (95% CI, -272.4 to -184.9), which corresponded to a relative reduction of 17.8% (95% CI, 14.8 to 20.7)]. The introduction was also associated with excess reductions in drugs for respiratory symptoms [DID estimates, -256.9 DOTs per 1000 cases (95% CI, -379.3 to -134.5)] and antihistamines [DID estimate, -198.5 DOTs per 1000 cases (95% CI, -282.1 to -114.9)]. There was no excess in out-of-hour visits [DID estimate, -4.43 events per 1000 cases (95% CI, -12.8 to 3.97)] or hospitalizations [DID estimate, -0.08 events per 1000 cases (95% CI, -0.48 to 0.31)].ConclusionsOur findings suggest that financial incentives to medical facilities for not prescribing antibiotics were associated with reductions in prescriptions for antibiotics without adverse health care consequences. Japan's new health policy provided us with policy options for immediately reducing inappropriate antibiotic prescriptions by relatively small financial incentives.

Yoko Tanino,1,2,* Keisuke Nishioka,1,* Chie Yamamoto,2,* Yohei Watanabe,1,3 Tomo Daidoji,1,4 Masataka Kawamoto,5 Sayaka Uda,6 Shoko Kirito,1 Yuta Nakagawa,2 Yu Kasamatsu,2 Yoshiyuki Kawahara,7 Yuri Sakai,7 Shuji Nobori,8 Tohru Inaba,2 Bon Ota,9 Naohisa Fujita,7 Atsushi Hoshino,10 Yoko Nukui,2 Takaaki Nakaya1 1Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3JST, MIRAI, Tokyo, Japan; 4School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan; 5Department of Forensics Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 6Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 7Kyoto Prefectural Institute of Public Health and Environment, Kyoto, Japan; 8Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; 9Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 10Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan*These authors contributed equally to this workCorrespondence: Takaaki Nakaya; Yohei Watanabe, Department of Infectious Diseases, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, Tel +81-75-251-5325, Fax +81-75-251-5328, Email tnakaya@koto.kpu-m.ac.jp; nabe@koto.kpu-m.ac.jpIntroduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs.Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro.Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs.Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.Keywords: SARS-CoV-2, sotrovimab, remdesivir, drug resistance, immunosuppression therapy

Abstract Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light chain is an important issue, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism (CD) spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of the antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.

Abstract Background Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs. Case presentation A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone. Conclusions Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Energy storage (ES) units are vital for the reliable and economical operation of the power system with a high penetration of renewable distributed generators (DGs). Due to ES’s high investment costs and long payback period, energy management with shared ESs becomes a suitable choice for the demand side. This work investigates the sharing mechanism of ES units for low-voltage (LV) energy prosumer (EP) communities, in which energy interactions of multiple styles among the EPs are enabled, and the aggregated ES dispatch center (AESDC) is established as a special energy service provider to facilitate the scheduling and marketing mechanism. A shared ES operation framework considering multiple EP communities is established, in which both the energy scheduling and cost allocation methods are studied. Then a shared ES model and energy marketing scheme for multiple communities based on the leader–follower game is proposed. The Karush–Kuhn–Tucker (KKT) condition is used to transform the double-layer model into a single-layer model, and then the large M method and PSO-HS algorithm are used to solve it, which improves convergence features in both speed and performance. On this basis, a cost allocation strategy based on the Owen value method is proposed to resolve the issues of benefit distribution fairness and user privacy under current situations. A case study simulation is carried out, and the results show that, with the ES scheduling strategy shared by multiple renewable communities in the leader–follower game, the energy cost is reduced significantly, and all communities acquire benefits from shared ES operators and aggregated ES dispatch centers, which verifies the advantageous and economical features of the proposed framework and strategy. With the cost allocation strategy based on the Owen value method, the distribution results are rational and equitable both for the groups and individuals among the multiple EP communities. Comparing it with other algorithms, the presented PSO-HS algorithm demonstrates better features in computing speed and convergence. Therefore, the proposed mechanism can be implemented in multiple scenarios on the demand side.

Objective: Awake craniotomy (AWC) allows intraoperative evaluation of functions involving the cortical surface and subcortical fibers. In epilepsy surgery, indications for and the role of AWC have not been established because evaluation with intracranial electrodes is considered the gold standard. We report herein our case series of patients who underwent AWC in epilepsy surgery and propose the scenarios for and roles of AWC. Methods: Patients who underwent AWC in epilepsy surgery at our institutions between 2014 and 2023 were included. Information about age, sex, etiology, location of epileptogenicity, seizure type, use of intracranial electrode placement, surgical complications, neurological deficits, additional surgery, and seizure outcomes was reviewed. Following a diagnostic and treatment flow for epilepsy surgery, we clarified three different scenarios and roles for AWC. Results: Ten patients underwent AWC. Three patients underwent AWC after non-invasive evaluations. Two patients underwent AWC after intracranial evaluation with stereotactic electroencephalography (SEEG). Five patients underwent AWC after intracranial evaluation with subdural grid electrodes (SDG). Among these, two patients were initially evaluated with SEEG and with SDG thereafter. One patient reported slight numbness in the hand, and one patient showed slight cognitive decline. Seizure outcomes according to the Engel outcome scale were class 1A in three patients, IIA in two patients, IIIA in four patients, and IVA in one patient. Conclusions: AWC can be used for purposes of epilepsy surgery in different situations, either immediately after non-invasive studies or as an additional invasive step after invasive monitoring with either SEEG or SDG. The application of AWC should be individualized according to each patient’s specific characteristics.

A comprehensive analysis of cross-country skiing races is a pivotal step in establishing effective training objectives and tactical strategies. This study aimed to develop a method of classifying sub-techniques and analyzing skiing characteristics during cross-country skiing skating style timed races on snow using high-precision kinematic GNSS devices. The study involved attaching GNSS devices to the heads of two athletes during skating style timed races on cross-country ski courses. These devices provided precise positional data and recorded vertical and horizontal head movements and velocity over ground (VOG). Based on these data, sub-techniques were classified by defining waveform patterns for G2, G3, G4, and G6P (G6 with poling action). The validity of the classification was verified by comparing the GNSS data with video analysis, a process that yielded classification accuracies ranging from 95.0% to 98.8% for G2, G3, G4, and G6P. Notably, G4 emerged as the fastest technique, with sub-technique selection varying among skiers and being influenced by skiing velocity and course inclination. The study’s findings have practical implications for athletes and coaches as they demonstrate that high-precision kinematic GNSS devices can accurately classify sub-techniques and detect skiing characteristics during skating style cross-country skiing races, thereby providing valuable insights for training and strategy development.