Yamamoto Hospital

Metalloproteins represent a major fraction of the protein kingdom and often exploit the redox chemistry of transition metals to drive key biological events involving proton and electron transfer. Copper is one of the most widely used transition metals whose redox properties are utilised in both electron transfer and catalysis of chemical substrates. Copper nitrite reductases (CuNiRs) utilise two types of copper centres and have become a model system for studying complex biological events that underpin the reaction mechanisms of redox enzymes, including proton-coupled electron transfer and substrate gating. We utilised the higher X-ray energy (13 keV) available at the SACLA X-ray Free Electron Laser (XFEL) and SHELXL refinement to obtain accurate atomic resolution structures of CuNiRs at ~1 Å from three organisms - in the oxidised (low and high pH), reduced and substrate-bound states. A consistent picture now emerges with the observation of a pentacoordinated oxidised catalytic type-2 Cu (T2Cu2+) centre in all cases. A tetracoordinated reduced T2Cu+ site with a single solvent ligand has also been captured, giving structural support to the random-sequential schemewith ordered pathway being dominant.

The street food sector, which is very significant for urban nutrition, tends to operate informally with poor hygiene standards. This, therefore, poses grave health hazards, especially to consumers in developing countries. This study therefore assessed food hygiene behaviours among food vendors in Yamfo, Ghana, exploring compliance with safety protocols and the impact on consumer health. A descriptive cross-sectional study design using quantitative methods was employed to examine hygiene practices among 251 food vendors in Yamfo, Ahafo Region. Data were analysed using SPSS Version 26. Chi-square tests and linear regression analysis were performed to assess the impact of food hygiene practices on consumer health. Among vendors, 74.5% were females and 60.3% were under 34 years of age. While 79.4% reported always washing hands after visiting the lavatory, only 18.3% did so after handling money. The availability of clean water (p = 0.021), gender (p = 0.007), educational qualification (p = 0.004), and years of experience (p = 0.001) were significant predictors of hygiene practices. Additionally, practices such as utensil sanitisation (p = 0.022), food covering (p = 0.018), and temperature control (p = 0.008) significantly impacted consumer health. Notably, 91.7% of vendors agreed that good hygiene reduces foodborne illnesses. Food safety and hygiene practices among Yamfo food vendors are moderately observed, but significantly influenced by infrastructural, educational, and behavioural factors. Consumer health is directly impacted by food hygiene practices, reinforcing the need for policy reforms, training programs, and infrastructure improvement to safeguard public health and well-being of consumers.

Multiple myeloma remains a therapeutic challenge despite recent advances with proteasome inhibitors, immunomodulatory drugs (IMiDs), and monoclonal antibodies. Among new approaches, the combination of IMiDs and histone deacetylase inhibitors has shown promise in relapsed or refractory multiple myeloma. Here, we elucidate the molecular basis of their synergy and its role in overcoming drug resistance in myeloma cells. We demonstrate that these agents converge to downregulate the master oncogene MYC, resulting in synergistic cytotoxicity. Importantly, this effect persists even in models intrinsically resistant to IMiDs, where the canonical IKZF1/3-IRF4/MYC axis is functionally uncoupled. In this context, the combination engages an alternative ARID2-MYC axis, mediated by the synergistic downregulation of the IMiD neosubstrate ARID2. This finding highlights the functional relevance of IMiD's inherent polypharmacology in circumventing primary resistance mechanisms at the cellular level. Together, our results identify the ARID2-containing PBAF complex as a critical vulnerability in resistant myeloma cells and provide a mechanistic rationale for designing combination strategies that co-target this complex, with the potential to enhance therapeutic efficacy by overcoming drug resistance.

Standard treatment for metastatic biliary tract cancer is systemic chemotherapy, not local therapy, such as surgery or radiation therapy. This is because long-term survival is not expected with local therapy. We present the case of a 49-year-old man who underwent extended right hepatectomy with extrahepatic bile duct resection for hilar cholangiocarcinoma. Postoperative adjuvant chemotherapy with oral S-1 for six months was completed. At 20months post-operation, para-aortic lymphadenopathy was detected, and endoscopic ultrasound-guided biopsy confirmed lymph node recurrence. Gemcitabine and cisplatin were administered for six months, resulting in partial tumor regression. As no other lesions were identified, radiotherapy with a total dose of 55Gy in 22 fractions was performed. At 37months following the completion of radiotherapy, the patient remained disease-free based on imaging. This case suggests that the addition of local radiotherapy to systemic chemotherapy may be beneficial for patients with oligometastatic recurrence of hilar cholangiocarcinoma.

側枝静脈瘤に対するレーザー焼灼術の治療手技を比較し，術後有害事象の発生状況を調査するために，多施設共同研究を実施した．直径1.27 mmのRadial 2ring slim fiberを，波長1470 nmのレーザー発生装置に接続し，不全伏在静脈本幹を焼灼した．側枝静脈瘤は，16 G静脈留置針でエコーガイド下に内腔を穿刺し，slim fiberを挿入後，出力5–8 W，LEED 20–40 J/cmで血管内焼灼を行った．4施設から集めた計400例を検討した結果，瘤焼灼に伴う皮膚熱傷や重篤な神経損傷は認められず，1カ月後のエコー検査で焼灼部位は100%閉塞しており，良好な治療成績が得られた．

Background: Improving the anaerobic threshold (AT) provides benefits by avoiding overload, especially for patients with advanced COPD. However, the variables related to improving AT are poorly known. The aim of this study was to investigate which variables are related to improved AT after pulmonary rehabilitation (PR) using cardiopulmonary exercise testing (CPET). Methods: Stable patients with severe and very severe COPD who performed 4-week PR and whose ATs were identified both before and after PR were selected; they were divided into two groups based on whether the AT increased after PR, and their responses were compared. Results: In the 26 eligible subjects, there was no correlation between the mean change from baseline after PR in the inspired minus expired mean O2 concentrations (ΔFO2) and minute ventilation (V˙E) at peak exercise. Compared with the AT no-increase group, the AT increase group, at peak exercise, showed significant increases in peak oxygen uptake (V˙O2) and ΔFO2 but not in V˙E, after PR. The increase in V˙O2 at the AT after PR was well correlated with the mean change after PR in ΔFO2 at peak exercise (r = 0.66, P < .001), rather than V˙E. Of all the peaks and throughout exercise variables, ΔFO2 at peak exercise was identified as one of the variables more closely correlated with improved AT after PR. Conclusions: Improvement of ΔFO2 at peak exercise, rather than V˙E, correlated with an increased AT in subjects with advanced COPD, which suggests that improving ΔFO2 independent of V˙E may be a useful strategy to individualize PR.

The tourism industry is a critical sector in Türkiye’s economy and plays a significant role in reducing the country's trade deficit. This research paper presents a comprehensive overview of the tourism industry and international tourism in Türkiye. The research paper conducts an empirical analysis of pertinent variables and investigates the association between international trade and tourism revenues. Utilizing the VAR model with data spanning from 2000 to 2021, the study scrutinizes the linkage between the two variables. Firstly, the study checks the stationarity of the variables, then uses the Johansen cointegration test to detect whether there exists a long-term relationship between the variables. Next, the direction of the relationship is determined through the Toda Yamamoto causality analysis. The results show that there is a long-run relationship between the variables. The results obtained from the causality analysis also show that there is a reciprocal causality relationship between the rate of openness to trade, which is used as an indicator of international trade, and tourism revenues. Finally, the variance decomposition shows that tourism revenues are an important factor in international trade and this effect gradually increases over time.

Saccharomyces cerevisiae, a widely studied yeast known for its industrial applications, is increasingly recognized for its potential in immunomodulation. This study aimed to systematically analyze and compare the immune-modulating properties of various S. cerevisiae strains under controlled experimental conditions. Three essential signals crucial for immune response activation were evaluated to elucidate the immunological responses elicited by these strains, i.e., dendritic cells (DC) cytokine secretion profiles, maturation status, and T cell polarization. Analysis of DC cytokine secretion profiles and maturation status revealed that all tested yeast strains induced DC activation, characterized by significant IL-6 secretion and modest IL-10 induction, as well as upregulation of MHC II molecules. Additionally, strain-specific effects were observed, particularly, strain AJM109 and Y1383 uniquely enhanced CD86 and PD-L1 expression, respectively, suggesting differential impacts on DC co-stimulatory signaling. Furthermore, strain Y1383 showed a unique capacity to support Treg-mediated immune suppression, demonstrating its potential in immune tolerance induction. These findings underscore the complexity of S. cerevisiae-based immune modulation and emphasize the importance of standardized evaluation methods to distinguish their specific immunological effects.

Studies have shown that duration perception depends on several visual processes. However, the stages of visual processes that contribute to duration perception remain unclear. This study examined the effects of categorical differences in face adaptation on perceived duration. In all the experiments, we compared the perceived durations of human, monkey, and cat faces (comparison stimuli) after adapting to a human face. Results revealed that the human comparison stimuli were perceived shorter than the monkey and cat comparison stimuli (categorical face adaptation on duration perception [CFAD]). The difference between the face categories disappeared when the adapting stimulus was rendered unrecognizable by phase scrambling, indicating that adaptation to low-level visual properties cannot fully account for the CFAD effect. Furthermore, CFAD was preserved but attenuated when the adapting stimulus was inverted or a 1,000-ms interval was inserted before the comparison stimuli, which implied that CFAD occurred as long as the adapting stimulus was perceived as a face and not simply based on conceptual category processes. These findings indicate that face adaptation affects perceived duration in a category-specific manner (the CFAD effect) and highlights the involvement of visual categorical processes in duration perception.