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The protoclusters in the epoch of reionization, traced by galaxy overdensity regions, are ideal laboratories for studying the process of stellar assembly and cosmic reionization. We present the spectroscopic confirmation of the core of the most distant protocluster at z = 7.88, A2744-z7p9OD, with the James Webb Space Telescope NIRSpec integral field unit spectroscopy. The core region includes as many as four galaxies detected in [O iii ] 4960 and 5008 Å in a small area of ∼3″ × 3″, corresponding to ∼11 × 11 kpc, after the lensing magnification correction. Three member galaxies are also tentatively detected in dust continuum in Atacama Large Millimeter/submillimeter Array Band 6, which is consistent with their red ultraviolet continuum slopes, β ∼ −1.3. The member galaxies have stellar masses in the range of log( M _* / M _⊙ ) ∼7.6–9.2 and star formation rates of ∼3–50 M _⊙ yr ^−1 , showing a diversity in their properties. FirstLight cosmological simulations reproduce the physical properties of the member galaxies including the stellar mass, [O iii ] luminosity, and dust-to-stellar mass ratio, and predict that the member galaxies are on the verge of merging in a few to several tens of Myr to become a large galaxy with M _* ∼ 6 × 10 ^9 M _⊙ . The presence of a multiple merger and evolved galaxies in the core region of A2744-z7p9OD indicates that environmental effects are already at work 650 Myr after the Big Bang.

Objectives This research aims to identify genes which are dysregulated in premalignant cells during the development of Adult T-cell Leukaemia/lymphoma (ATL). Monoclonal expansion of HTLV-1infected T cells is observed in > 90% of ATL patients. Our group has previously shown that premalignant 'ATL-like' clones circulate in the blood of HTLV-1 carriers before the development of ATL. In this study, we aimed to identify intracorrelated gene networks which are associated with ATL-like monoclonal expansion, by comparing gene expression of ATL-like clonal with polyclonal HTLV-1 infected and uninfected T cells from within the same individuals. Methods Peripheral blood mononuclear cells (PBMCs) from 17 HTLV-1-infected individuals, who had not been diagnosed with ATL at the time of sample collection, were flow-sorted based on cell surface markers associated with HTLV-1 infection (CD4+CCR4+CD26-) and clonal expansion (T cell receptor Vbeta subunits) to obtain ATL-like clones (n = 9), polyclonal HTLV-1-infected T cells (n = 17), and uninfected T cells (n = 16). RNA was extracted and subjected to RNA-Seq. Here we analysed the RNA-Seq data using a weighted gene co-expression network analysis (WGCNA) program, followed by multiple, complementary gene annotation tools (CytoHubba, DAVID, and GSEA) to identify important networks as well as specific hub genes. Results WGCNA analysis identified 40 modules of correlated genes, two of which showed strong correlations with clonality and infection respectively. GO terms enriched from each module are associated with 'infection' and 'immune response'. The top 30 hub genes, which are the most intra-connected within each module, were identified and ranked using 12 different topological calculations using CytoHubba. Conclusion This research identified the important hub genes which are strongly correlated with HTLV-1 infection and clonal expansion, to be further explored as potential mechanisms for oligoclonal expansion or as biomarkers and/or therapeutic targets. [ABSTRACT FROM AUTHOR]

Understanding the current situation and risk of environmental contamination by anti-influenza drugs in aquatic environments is key to prevent the unexpected emergence and spread of drug-resistant viruses. However, few reports have been focused on newer drugs that have recently been introduced in clinical settings. In this study, the behaviour of the prodrug baloxavir marboxil (BALM)-the active ingredient of Xofluza, an increasingly popular anti-influenza drug-and its pharmacologically active metabolite baloxavir (BAL) in the aquatic environment was evaluated. Additionally, their presence in urban rivers and a wastewater treatment plant (WWTP) in the Yodo River basin was investigated and compared with those of the major anti-influenza drugs used to date (favipiravir (FAV), peramivir (PER), laninamivir (LAN), and its active metabolite, laninamivir octanoate (LANO), oseltamivir (OSE), and its active metabolite, oseltamivir carboxylate (OSEC), and zanamivir (ZAN)) to comprehensively assess their environmental fate in the aquatic environment. The results clearly showed that BALM, FAV, and BAL were rapidly degraded through photolysis (2-h, 0.6-h, and 0.4-h half-lives, respectively), followed by LAN, which was gradually biodegraded (7-h half-life). In addition, BALM and BAL decreased by up to 47 % after 4 days and 34 % after 2 days of biodegradation in river water. However, the remaining conventional drugs, except for LANO (<1 % after 10 days), were persistent, being transported from the upstream to downstream sites. The LogK d values for the rates of sorption of BALM (0.5-1.6) and BAL (1.8-3.1) on river sediment were higher than those of conventional drugs (-0.5 to 1.7). Notably, all anti-influenza drugs were effectively removed by ozonation (>90-99.9 % removal) after biological treatment at a WWTP. Thus, these findings suggest the importance of introducing ozonation to reduce pollution loads in rivers and the environmental risks associated with drug-resistant viruses in aquatic environments, thereby promoting safe river environments., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tigecycline is a last-resort antimicrobial in humans. Tetracyclines are the most widely used antimicrobials in livestock. Mobile tigecycline resistance genes [ tet(X) ] are disseminated worldwide, and tetracycline use may have promoted the selection of tet(X) genes. Thus, the selective pressure on tet(X) genes and their plasmids in livestock must be elucidated. We performed a retrospective study to clarify the prevalence of tigecycline-resistant Escherichia coli from pigs in Thailand. Screening for tigecycline resistance was performed on 107 E. coli strains from 25 samples, and tet(X) -carrying plasmids were characterized. tet(X) genes were cloned and expressed in E. coli . Bacterial growth rate in the presence of tetracycline as a result of the presence of tet(X) genes was also evaluated. Thirty-two tet(X4) -harboring tigecycline-resistant E. coli strains were detected in 10/25 samples (40%). The tet(X4) genes were carried on various Inc-type plasmids and flanked by IS CR2 . The tet(X) -carrying plasmids were transferred to E. coli and Klebsiella pneumoniae . Acquisition of tet(X) genes and their plasmids improved bacterial growth in the presence of tetracycline. In summary, tetracycline use exerts selective pressure on tet(X) genes and their various backbone plasmids; therefore, a reduced amount of tetracycline use is important to limit the spreading of tet(X) genes.

Objectives: Patients with terminal cancer tend to have an increased frequency of a variety of clinical symptoms, including anorexia, at 1 month of life expectancy. This study examined clinical symptoms affecting anorexia in patients with terminal cancer., Methods: Of 1068 patients with terminal cancer who died and were discharged from our hospital between April 2014 and March 2016, we included 471 patients whose clinical symptoms could be subjectively assessed within 4 weeks before death.Patients were evaluated subjectively on a scale of 0 to 10 (11-point scale) using the Numerical Rating Scale (NRS) once a week for nine major clinical symptoms: (1) pain, (2) general fatigue, (3) dyspnea, (4) depressed mood, (5) anorexia, (6) insomnia, (7) nausea, (8) constipation, and (9) dry mouth. Primary data within 4 weeks prior to death were used for analysis, and Spearman's rank correlation was used to examine clinical symptoms affecting anorexia., Results: Spearman's rank correlation coefficients between anorexia and the following clinical symptoms were: pain, 0.186; general fatigue, 0.414; dyspnea, 0.15; depressed mood, 0.287; insomnia, 0.327; nausea, 0.297; constipation, 0.215; and dry mouth, 0.204. General fatigue was positively correlated with anorexia., Conclusions: General fatigue may influence anorexia in patients with terminal cancer., Competing Interests: There are no conflicts of interest related to this study.

Background/aim: Catheter-related bloodstream infections (CRBSI) are frequently life-threatening. Several factors have been reported to be related to CRBSI development; however, the factors associated with CRBSI mortality are unclear as they have rarely been studied. This study investigated the factors associated with mortality in patients with CRBSI, specifically focusing on nutritional factors., Patients and Methods: This retrospective, multicenter study included in-patients with acute conditions and convalescent patients diagnosed with a CRBSI between January 2019 and December 2021 at 33 hospitals (23 general hospitals, two mixed-care hospitals, and eight convalescent hospitals). The primary outcome was death. Unadjusted and multivariable logistic regression analysis was performed to identify factors associated with mortality., Results: A total of 453 patients with CRBSI were enrolled. The causes of death were analyzed for 382 (84.3%) who survived CRBSI and 71 (15.7%) who died. Multivariable analysis revealed that Candida detected in blood culture [adjusted odds ratio (aOR)=2.72, 95% confidence interval (CI)=1.15-6.41; p=0.025)], CRBSI onset within 30 days of catheter insertion (aOR=2.28, 95% CI=1.27-4.09; p=0.005), concurrent infection (aOR=2.07, 95% CI=1.19-3.60; p=0.009), low serum albumin level (aOR=1.64, 95% CI=1.02-2.63; p=0.044), and elevated C-reactive protein level (aOR=1.05, 95% CI=1.01-1.10; p=0.028) were risk factors for mortality, whereas the use of a peripherally inserted central catheter was associated with a reduced risk of CRBSI mortality (aOR=0.30, 95% CI=0.13-0.69; p=0.004)., Conclusion: Enhanced monitoring of factors, such as candida detected in blood culture, CRBSI onset within 30 days of catheter insertion, concurrent infection, low serum albumin level, elevated C-reactive protein (CRP) level and the use of a peripherally inserted central catheter (PICC), is crucial for mitigating CRBSI severity and risk of death., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This study aimed to clarify the effectiveness of nutrition support team (NST) facilities for preventing central line-associated bloodstream infection (CLABSI)., Methods: We retrospectively analyzed the incidence of CLABSI as well as the presence or absence of additional medical fees for NST activity between 2019 and 2021, including the period before and after the COVID-19 pandemic. Subsequently, we performed between-group comparisons of the CLABSI incidence. CLABSI rates were compared based on cumulative per 1000 catheter uses during the relevant period., Results: Among 47 facilities that were registered for participation, there were 34 and 13 facilities with and without additional medical fees for NST activity (NST and non-NST groups, respectively). The CLABSI incidence rate was significantly lower in the NST group 0.96 [0.28-1.73] than in the non-NST group 1.25 [075-6.10] (p < 0.05). Before the pandemic, the NST group had a lower CLABSI rate per 1000 catheter uses than the non-NST group 2019: 0.70 [0.12-1.26] vs 2.10 [0.62-5.97]. During the pandemic, the CLABSI incidence showed no significant between-group difference 2020: 0.99 [0.51-1.61] vs 1.01 [0.80-4.16]; 2021: 1.24 [0.44-2.35] vs 1.96 [1.23-5.31]; however, the CLABSI rates in the NST group remained low., Conclusion: During the COVID-19 pandemic, the incidence of CLABSI was lower in the NST group than in the non-NST group, indicating the effectiveness of NST in preventing the occurrence of CLABSI., (© 2024. The Author(s).)

A submucosal heterotopic gastric gland (SHGG) is characterized by benign ectopic gastric tissue within the submucosa. Neoplasms arising from SHGGs are rare, and their definitive diagnosis via endoscopic biopsy is often challenging. We report the case of a 74-year-old man undergoing screening esophagogastroduodenoscopy, which revealed a subepithelial lesion with a central orifice in the upper body of the stomach. Endoscopic submucosal dissection (ESD) was performed because the endoscopic biopsy revealed a suspected pyloric gland adenoma. Pathological examination of the resected specimen confirmed SHGG with focal dysplasia. The patient recovered uneventfully and remained free of recurrence over a 5-year follow-up period. This case highlights the utility of ESD in both the treatment and accurate pathological diagnosis of neoplasms arising from SHGGs., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: This study determined whether the GENECUBE rapid nucleic acid amplification test could directly detect nuc and mecA genes in clinical blood culture samples of Staphylococcus and various other pathogens., Methods: Between September 2020 and December 2021, 537 blood culture samples from 192 patients with suspected bacteremia were tested using conventional assays (MicroScan WalkAway96 or VITEK 2 systems) and GENECUBE nuc and mecA assays. Isolates from samples with discrepant results between the conventional and GENECUBE assays were further evaluated using MALDI-TOF mass spectrometry, disk diffusion testing using cefoxitin, broth microdilution testing using oxacillin, and sequencing for mecA. Bacterial solutions containing a mixture of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) were prepared to evaluate the limit of detection (LOD) of mecA., Results: Using conventional assays as the reference, the sensitivity, specificity, and positive and negative predictive values (95 % confidence interval) of GENECUBE were 100 % (96.8-100 %), 100 % (99.1-100 %), 100 % (96.8-100 %), and 100 % (99.1-100 %), respectively, for nuc detection and 100 % (96.1-100 %), 98.9 % (97.4-99.6 %), 94.9 % (88.5-98.3 %), and 100 % (99.2-100 %), respectively, for mecA detection. Sequencing analysis of five samples identified as methicillin-sensitive staphylococci using conventional assays and methicillin-resistant staphylococci using GENECUBE revealed the presence of methicillin-resistant isolates in all samples. The estimated LOD of mecA was 10 4 colony-forming units (CFU)/mL of MRSE with GENECUBE, compared with 10 5  CFU/mL with conventional assays., Conclusion: The GENECUBE assay accurately detected mecA in positive blood culture samples and had higher sensitivity than conventional assays., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshihiro Soya is an employee of TOYOBO Co., Ltd., a private company that manufactures the GENECUBE analyzer and related reagents., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Malaria control and elimination efforts would benefit from the identification and validation of new malaria chemotherapeutics. Recently, a transgenic Plasmodium berghei line was used to perform a series of high-throughput in vitro screens for new antimalarials acting against the parasite sexual stages. The screens identified pyrimidine azepine chemotypes with potent activity. Here, we validate the activity of PyAz90 , the most potent pyrimidine azepine chemotype identified, against P. falciparum and P. vivax in the asexual and sexual stages. PyAz90 blocked parasite transmission to the mosquito vector at nanomolar concentrations and inhibited in vitro asexual parasite multiplication with a fast-action profile. Through the generation of P. falciparum PyAz90- resistant parasites and in vitro assays of mitochondrial activity, we identified cytochrome b as a molecular target of PyAz90 . This work characterizes a promising chemotype that can be explored for the future development of new antimalarials targeting the Plasmodium cytochrome bc 1 complex., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Quinolone-resistant Campylobacter jejuni have been increasing worldwide. Quinolones exert their antibacterial activity by inhibiting DNA gyrase, but most of the isolates acquire quinolone resistance via an amino acid substitution in the A subunit of DNA gyrase. WQ-3810 is a quinolone antibiotic that has been reported to have high potency even to DNA gyrase with amino acid substitutions in several bacterial species; however, there was no information on C. jejuni . Hence, this study aimed to evaluate the activity of WQ-3810 to inhibit wild-type/mutant DNA gyrases of C. jejuni and the bacterial growth for accessing the potency for the treatment of quinolone-resistant C. jejuni infection. The inhibitory activity of WQ-3810 was assessed and compared with ciprofloxacin and nalidixic acid by calculating the half maximal inhibitory concentration (IC 50 ) against wild-type/mutant DNA gyrases. Next, the minimum inhibitory concentration (MIC) of WQ-3810 and five other quinolones was determined for C. jejuni including quinolone-resistant strains with amino acid substitutions in GyrA. Furthermore, the interaction between WQ-3810 and wild-type/mutant DNA gyrase was speculated using docking simulations. The IC 50 of WQ-3810 against wild-type DNA gyrase was 1.03 µg/mL and not different from that of ciprofloxacin. However, those of WQ-3810 against mutant DNA gyrases were much lower than ciprofloxacin. The MICs of WQ-3810 ranged <0.016-0.031 µg/mL and were the lowest against both quinolone-susceptible and quinolone-resistant strains among the examined quinolones. The results obtained by the docking simulation agreed well with this observation. WQ-3810 seems to be a promising antimicrobial agent for the infections caused by quinolone-resistant C. jejuni ., Importance: WQ-3810, a relatively new quinolone antibiotic, demonstrates exceptional antibacterial properties against certain pathogens in previous studies. However, its efficacy against quinolone-resistant Campylobacter jejuni was not previously reported. The prevalence of quinolone-resistant C. jejuni as a cause of foodborne illnesses is increasing, prompting this investigation into the effectiveness of WQ-3810 as a countermeasure. This study revealed high inhibitory activity of WQ-3810 against both wild-type and mutant DNA gyrases of C. jejuni . WQ-3810 was equally efficacious as ciprofloxacin against wild-type DNA gyrases but showed superior effectiveness against mutant DNA gyrases. WQ-3810 also demonstrated the lowest minimum inhibitory concentrations, highlighting its enhanced potency against both susceptible and resistant strains of C. jejuni . This observation was well supported by the results of the in silico analysis. Consequently, WQ-3810 exhibits a higher level of bactericidal activity compared to existing quinolones in combating both susceptible and resistant C. jejuni isolates., Competing Interests: The authors declare no conflict of interest.

Background: Angiosarcoma, a very rare malignant tumor constituting 2%-4% of soft tissue sarcomas, manifest in diverse organs including skin, soft tissues, and bones. Histologically, angiosarcoma presents a wide range of morphologies, with epithelioid angiosarcoma (EAS) resemblance to carcinoma. The difficulty arises from the shared epithelial-like morphology and expression of epithelial markers in immunohistochemistry., Case: This study reports a case where EAS diagnosis was achieved through a combination of gross findings in a lung resection sample, imprint cytology, and immunocytochemistry. Imprint cytology revealed clusters of epithelioid cells, while immunocytochemistry showed positive results for CD31, ERG, Fli-1, and AE1/AE3, proving instrumental in diagnosing EAS. The described immunocytochemical protocol facilitates prompt diagnosis exclusively through cytology samples., Conclusion: This report emphasizes the potential for diagnosing EAS using cytological specimens, which is especially useful in cases where obtaining tissue samples proves challenging., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Antimicrobial-resistant bacteria, selected by antimicrobial agent use in livestock, are emerging and their spread to crops from feces via composting represents a public health concern as they are ultimately transmitted to humans. In this study, we investigated Escherichia coli and other ampicillin (AMP)-resistant coliform spread conditions in field soil and dent corn, an agricultural crop, on a livestock-derived compost-applying farm. No AMP-resistant E. coli was detected in any samples of field soil and dent corn. In contrast, AMP-resistant and extended-spectrum β-lactam (ESBL) producing coliforms were consistently present in field soil and dent corn during the entire study period. In particular, extremely high AMP-resistant coliform levels were detected in dent corn stems and roots. AMP-resistant coliform detection in crops is pivotal and raises significant concerns regarding antimicrobial-resistant bacterial spread. Furthermore, AMP-resistant coliform isolate identification defined Enterobacter bugandensis and Enterobacter asburiae as the dominant species among AMP-resistant coliforms, both tested positive for ESBL production. This means that high concentrations of AMP-resistant coliforms are to be present on farms where crops are grown. However, we identified no common species among the AMP-resistant coliforms in the compost, field soil, and dent corn samples. Therefore, the initial hypothesis of the compost being the source of antimicrobial-resistant bacteria was not confirmed. Although their source remains unknown, a certain antimicrobial-resistant bacterial concentration could nonetheless be detected in the field., 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 © 2024. Published by Elsevier B.V.)

Background: Epidemiological data on ruptured aortic aneurysms from large-scale studies are scarce. The aims of this study were to: clarify the clinical course of ruptured aortic aneurysms; identify aneurysm site-specific therapies and outcomes; and determine the clinical course of patients receiving conservative therapy., Methods and Results: Using the Tokyo Acute Aortic Super Network database, we retrospectively analyzed 544 patients (mean [±SD] age 78±10 years; 70% male) with ruptured non-dissecting aortic aneurysms (AAs) after excluding those with impending rupture. Patient characteristics, status on admission, therapeutic strategy, and outcomes were evaluated. Shock or pulselessness on admission were observed in 45% of all patients. Conservative therapy, endovascular therapy (EVT), and open surgery (OS) accounted for 32%, 23%, and 42% of cases, respectively, with corresponding mortality rates of 93%, 30%, and 29%. The overall in-hospital mortality rate was 50%. The prevalence of pulselessness was highest (48%) in the ruptured ascending AA group, and in-hospital mortality was the highest (70%) in the ruptured thoracoabdominal AA group. Multivariable logistic regression analysis indicated in-hospital mortality was positively associated with pulselessness (odds ratio [OR] 10.12; 95% confidence interval [CI] 4.09-25.07), and negatively associated with invasive therapy (EVT and OS; OR 0.11; 95% CI 0.06-0.20)., Conclusions: The outcomes of ruptured AAs remain poor; emergency invasive therapy is essential to save lives, although it remains challenging to reduce the risk of death.

Introduction: Rheocarna's therapeutic effect is associated with fibrinogen (Fib) and low-density lipoprotein cholesterol (LDL-C) adsorptive removal. This study aimed to retrospectively investigate the association between treatment volume (TV) and circulating blood volume (CBV) and the Fib removal rate (Fib-RR) and LDL-C-RR., Methods: CBV and TV/CBV, cut-off value (CO value), and area under the receiver operating characteristic (ROC) curve (AUC) were calculated. The Fib-RR and LDL-C-RR at the midterm and end of treatment were compared. The groups were further categorized into three groups with TV/CBV lower than or higher than the CO value at the midterm and end (midterm/end; Group L: lower than/lower than CO; Group L/H: lower than/higher than CO; Group H: higher than/higher than CO), and the Fib-RR and LDL-RR of each group at the midterm and end were compared., Results: ROC analysis revealed a TV of 1.480 times the BV as CO value, which showed a maximum Youden index predicting a Fib-RR of 20% (AUC: 0.828). Among the three groups, Group L and Group L/H demonstrated significantly higher Fib-RR and LDL-C-RR at the end of the study than in the midterm, while Group H exhibited no difference., Conclusion: The results reveal that a treatment volume of 1.5 times the circulating blood volume is a sufficient solute removal capacity in the Rheocarna-enabled cases., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

The problem of antimicrobial resistance (AMR) is not limited to the medical field but is also becoming prevalent on a global scale in the environmental field. Environmental water pollution caused by the discharge of wastewater into aquatic environments has caused concern in the context of the sustainable development of modern society. However, there have been few studies focused on the treatment of hospital wastewater, and the potential consequences of this remain unknown. This study evaluated the efficacy of the inactivation of antimicrobial-resistant bacteria (AMRB) and antimicrobial resistance genes (AMRGs) in model wastewater treatment plant (WWTP) wastewater and hospital effluent based on direct ultraviolet (UV) light irradiation provided by a conventional mercury lamp with a peak wavelength of 254 nm and an ultraviolet light-emitting diode (UV-LED) with a peak emission of 280 nm under test conditions in which the irradiance of both was adjusted to the same intensity. The overall results indicated that both UV- and UV-LED-mediated disinfection effectively inactivated the AMRB in both wastewater types (>99.9% after 1-3 min of UV and 3 min of UV-LED treatment). Additionally, AMRGs were also removed (0.2-1.4 log 10 for UV 254 nm and 0.1-1.3 log 10 for UV 280 nm), and notably, there was no statistically significant decrease ( p < 0.05) in the AMRGs between the UV and UV-LED treatments. The results of this study highlight the importance of utilizing a local inactivation treatment directly for wastewater generated by a hospital prior to its flow into a WWTP as sewage. Although additional disinfection treatment at the WWTP is likely necessary to remove the entire quantity of AMRB and AMRGs, the present study contributes to a significant reduction in the loads of WWTP and urgent prevention of the spread of infectious diseases, thus alleviating the potential threat to the environment and human health risks associated with AMR problems.

Purpose: Several reports have shown the importance of margins in pancreatoduodenectomy (PD) specimens; however, whether anterior surfaces are included as margins varies among reports. In this study, we aimed to examine the impact of the anterior surface on disease-free survival (DFS) and overall survival (OS)., Method: In total, 98 patients who underwent PD after chemoradiotherapy for pancreatic ductal adenocarcinoma at Mie University Hospital between January 1, 2012, and December 31, 2019, were included. We investigated the prognostic impact of the distance from the anterior surface to tumor cells on DFS and OS using a log-rank test. Multivariate analysis was performed using Cox proportional hazards analysis., Results: A significant difference in DFS and OS was observed up to a distance of 5 mm from the anterior surface of tumor cells. The multivariate analysis revealed that the distance from the anterior surface to tumor cells (≤5 mm) was an independent poor prognostic factor for DFS and OS., Conclusion: In patients with PD treated with neoadjuvant therapy, the distance from the anterior surface to tumor cells is an important assessment and should be included in the pathology report., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Usui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Porphyromonas gingivalis is the most pathogenic periodontal bacterium in the world. Recently, P. gingivalis has been considered responsible for dysbiosis during the development of periodontitis. This study aimed to evaluate a novel immunochromatographic device using monoclonal antibodies against P. gingivalis in subgingival plaques. A total of 72 patients with chronic periodontitis and 53 periodontally healthy volunteers underwent clinical and microbiological examinations. Subgingival plaque samples were analyzed for the presence of P. gingivalis and compared using real-time polymerase chain reaction (PCR). In the periodontitis group, a significant positive correlation was observed between the test device scores and the real-time PCR results. The specificity, positive predictive value, negative predictive value, and accuracy of the test device for P. gingivalis , as determined by real-time PCR, were 98%, 94%, 89%, and 90%, respectively. There were significant differences in bacterial counts by real-time PCR among the groups with different ranges of device scores. Additionally, there was a significant positive correlation between the device scores for P. gingivalis and periodontal parameters. These results suggest that this novel immunochromatographic device can be effectively used for rapid detection and semi-quantification of P. gingivalis in subgingival plaques.

The pathogenicity of Clostridioides difficile in piglets remains controversial. It is unknown whether C. difficile control helps protect piglet health. To clarify the association between C. difficile presence and piglet diarrhea, isolates were obtained from piglets with and without diarrhea. In addition, to determine the genetic relationship of C. difficile from pigs and humans, we performed whole-genome sequencing (WGS) of C. difficile isolates. Diarrheal and non-diarrheal stool samples were collected from neonatal piglets from five farms in Japan in 2021. To clarify the relationship between C. difficile derived from pigs and those from human clinical cases, WGS of C. difficile isolates was performed. Toxin-positive C. difficile were significantly more prevalent in piglets with diarrhea, although the overall frequency of C. difficile did not differ between piglets with and without diarrhea. This observation indicates an association between toxin-positive C. difficile and diarrhea in piglets. However, further studies are needed to establish a direct causal relationship and to explore other contributing factors to diarrhea in piglets. WGS results showed that C. difficile sequence type (ST) 11 including the hypervirulent PCR ribotype 078 isolates derived from Japanese pigs were closely related to ST11 of overseas strains (human clinical and animal-derived) and a Japanese human clinical strain. Toxin-positive C. difficile may cause diarrhea in piglets and hypervirulent C. difficile are spreading among pigs and human populations worldwide.

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants' second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Recent studies have reported the efficacy of the cryoballoon (CB)-guided left atrial roof block line (LARB) creation in patients with persistent atrial fibrillation (AF). However, it can be technically challenging to attach the balloon to the left atrial (LA) roof due to its anatomical variations. We designed a new procedure called the "Raise-up Technique," which may facilitate the firm adhesion of the CB to the LA roof during freezing. This study aimed to evaluate the efficacy of the Raise-up technique in LARB creation., Methods and Results: In total, 100 consecutive patients with persistent AF who underwent CB-LARB creation were enrolled. Fifty-seven patients underwent LARB creation using the Raise-up technique (Raise-up group), and the remaining 43 did not use it (control group). The Raise-up technique was performed as follows: An Achieve catheter was inserted as deeply as possible into the upper branch of the right superior pulmonary vein to anchor the CB. The balloon was placed below the targeted site on the LA roof and frozen. When the temperature of the CB reached approximately -10°C and the CB was easier to attach to the LA tissue, the CB was raised and pressed against the LA roof immediately by sheath advancement. Then the balloon could be in firm contact with the target site on the roof. If necessary, additional sheath advancement after sufficient freezing (-20°C to -30°C) was allowed the CB to have more firm and broad contact with the target site. LARB creation without touch-up ablation was achieved in 54 of 57 patients (94.7%) in the Raise-up group and 33 of 43 patients (76.7%) in the control group (p < .05). The lesion size of the LARB in the Raise-up group was significantly larger than that in the control group (15.2 cm 2 vs. 12.8 cm 2 , p < .05). Moreover, the width of the LARB lesion in the Raise-up group was wider than that in the control group (32.0 mm vs. 26.6 mm, p < .05)., Conclusion: The Raise-up technique enabled the creation of seamless and thick LARB lesions with a single stroke. In addition, the CB-LARB lesions created using the Raise-up technique tended to be large, resulting in extensive debulking of the LA posterior wall arrhythmia substrates. In CB ablation for persistent AF, the Raise-up technique can be considered one of the key strategies for LARB creation., (© 2024 Wiley Periodicals LLC.)

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great public health problem and is associated with many disease outbreaks and high mortality rates. Alarmingly, K. pneumoniae has been isolated from food in several recent studies. This study aimed to investigate the prevalence and characteristics of CRKP in food samples from Egypt., Methods: A total of 311 food samples (including 116 minced meat, 92 chicken meat, 75 diced meat, and 28 mutton) were collected from local markets in Egypt and were screened for CRKP with the determination of their antimicrobial resistance profiles. The whole genome sequence was done for 23 CRKP isolates to clarify the relationship between CRKP from food and human cases in Egypt using the SNP core genome. The conjugation probability of the bla NDM-5 harboring plasmid was identified using oriTfinder RESULTS: CRKP was isolated from 11% (35/311) of the samples, with 45.71% (16/35) of them showing resistance to colistin, one of the last-resort options for treating CRKP-mediated infections. In addition to the carbapenem and colistin resistance, the CRKP isolates frequently exhibited resistance to multiple antimicrobials including β-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and chloramphenicol. In addition, most of the CRKP were potentially hypervirulent K. pneumoniae (HvKP) identified as phylogroup Kp1 and of high-risk groups as detected in STs reported in many human outbreaks globally, such as ST383 and ST147. The core-genome phylogeny showed similarities between the isolates from this study and those previously isolated from clinical human samples in Egypt. In addition, analysis of the plasmid on which bla NDM is encoded revealed that several antimicrobial resistance genes such as bla OXA-9 , bla CTX-M-15 , aac(6')-Ib, qnrS1, and several virulence genes are encoded on the same plasmid., Conclusions: This study is significant for food safety and public health and is important to further identify the change in the epidemiology of CRKP infections, especially the consumption of contaminated food products., Competing Interests: Declaration of Competing Interest There are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Alkali metal alkoxides play a pivotal role in nucleophilic alkoxylation reactions, offering pathways for the synthesis of ethers, including the increasingly sought-after trifluoromethyl ethers. However, the synthesis of long-chain perfluoroalkyl ethers remains a substantial challenge in this field. Through the innovative use of triglyme to encapsulate potassium ions, we enhanced the stability of short-lived, longer-chain perfluoroalkoxy anions, thereby facilitating efficient nucleophilic perfluoroalkoxylation reactions. This method provides a new precedent for the halo-perfluoroalkoxylation of gem -difluoroalkenes and offers a versatile tool for the design of perfluoroalkyl ethers, including those containing complex moieties of heterocycles and drug molecules. We also demonstrated the utility of the resulting halo-perfluoroalkoxyl adducts through various chemical transformations to valuable diverse perfluoroalkyl ethers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Livestock excrement is composted and applied to agricultural soils. If composts contain antimicrobial-resistant bacteria (ARB), they may spread to the soil and contaminate cultivated crops. Therefore, we investigated the degree of transmission of ARB and related antimicrobial resistance genes (ARGs) and, as well as clonal transmission of ARB from livestock to soil and crops through composting. This study was conducted at Rakuno Gakuen University farm in Hokkaido, Japan. Samples of cattle feces, solid and liquid composts, agricultural soil, and crops were collected. The abundance of Escherichia coli, coliforms, β-lactam-resistant E. coli, and β-lactam-resistant coliforms, as well as the copy numbers of ARG (specifically the bla gene related to β-lactam-resistant bacteria), were assessed using qPCR through colony counts on CHROMagar ECC with or without ampicillin, respectively, 160 days after compost application. After the application of the compost to the soil, there was an initial increase in E. coli and coliform numbers, followed by a subsequent decrease over time. This trend was also observed in the copy numbers of the bla gene. In the soil, 5.0 CFU g-1 E. coli was detected on day 0 (the day post-compost application), and then, E. coli was not quantified on 60 days post-application. Through phylogenetic analysis involving single nucleotide polymorphisms (SNPs) and using whole-genome sequencing, it was discovered that clonal blaCTX-M-positive E. coli and blaTEM-positive Escherichia fergusonii were present in cattle feces, liquid compost, and soil on day 0 as well as 7 days post-application. This showed that livestock-derived ARB were transmitted from compost to soil and persisted for at least 7 days in soil. These findings indicate a potential low-level transmission of livestock-associated bacteria to agricultural soil through composts was observed at low frequency, dissemination was detected. Therefore, decreasing ARB abundance during composting is important for public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fukuda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anamorelin (ANAM) is a novel ghrelin receptor agonist for the treatment of cancer cachexia. In clinical trials of ANAM, glucose metabolism disorders as adverse effects were relatively frequent, however, when and how they occur remains unclear. Moreover, the safety in patients with pancreatic cancer and/or diabetes has not been clarified because most previous studies focused on patients with non-small cell lung cancer and had excluded patients with poorly controlled diabetes. Herein, a 66-year-old man with advanced pancreatic cancer and diabetes was administered ANAM, and acute hyperglycemia was developed and could be monitored by the self-monitoring of blood glucose (SMBG). Increasing the insulin dose failed to control hyperglycemia adequately, but the hyperglycemia ameliorated quickly after ANAM discontinuation. The continuous glucose monitoring (CGM) revealed that the sensor glucose levels had remained in the high range throughout the day during ANAM administration despite using 1.5 times more insulin. Our report is one of the few that describe the details of ANAM-induced hyperglycemia and provides important information for the safe and effective use of ANAM.

While it is commonly understood that air temperature can greatly affect the process of photosynthesis and the growth of higher plants, the impact of root zone temperature (RZT) on plant growth, metabolism, essential elements, as well as key metabolites like chlorophyll and carotenoids, remains an area that necessitates extensive research. Therefore, this study aimed to investigate the impact of raising the RZT on the growth, metabolites, elements, and proteins of red leaf lettuce. Lettuce was hydroponically grown in a plant factory with artificial light at four different air temperatures (17, 22, 27, and 30°C) and two treatments with different RZTs. The RZT was raised 3°C above the air temperature in one group, while it was not in the other group. Increasing the RZT 3°C above the air temperature improved plant growth and metabolites, including carotenoids, ascorbic acids, and chlorophyll, in all four air temperature treatments. Moreover, raising the RZT increased Mg, K, Fe, Cu, Se, Rb, amino acids, and total soluble proteins in the leaf tissue at all four air temperatures. These results showed that raising the RZT by 3°C improved plant productivity and the metabolites of the hydroponic lettuce by enhancing nutrient uptake and activating the metabolism in the roots at all four air temperatures. Overall, this research demonstrates that plant growth and metabolites can be improved simultaneously with an increased RZT relative to air temperature. This study serves as a foundation for future research on optimizing RZT in relation to air temperature. Further recommended studies include investigating the differential effects of multiple RZT variations relative to air temperature for increased optimization, examining the effects of RZT during nighttime versus daytime, and exploring the impact of stem heating. This research has the potential to make a valuable contribution to the ongoing growth and progress of the plant factory industry and fundamental advancements in root zone physiology. Overall, this research demonstrates that plant growth and metabolites can be improved simultaneously with an increased RZT relative to air temperature. This study serves as a foundation for future research on optimizing RZT in relation to air temperature. Further recommended studies include investigating the differential effects of multiple RZT variations relative to air temperature for increased optimization, examining the effects of RZT during nighttime versus daytime, and exploring the impact of stem heating. This research has the potential to make a valuable contribution to the ongoing growth and progress of the plant factory industry and fundamental advancements in root zone physiology., Competing Interests: Authors MU and AY were employed by the company Plants Laboratory Inc. The remaining 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 © 2024 Hayashi, Levine, Yu, Usui, Yukawa, Ohmori, Kusano, Kobayashi, Nishizawa, Kurimoto, Kawabata and Yamori.)

It has been reported that patients with moyamoya disease have a high prevalence of coronary artery disease. On the other hand, the pathology of coronary artery disease is not fully understood. We were able to evaluate vascular properties using optical coherence tomography in a case of acute myocardial infarction that occurred in a relatively young woman with moyamoya disease. Previous reports using intravascular ultrasound have shown that coronary artery lesions in patients with moyamoya disease are caused by fibrous cell proliferation. Optical coherence tomography of our case showed a fibrous plaque rich in macrophages and a lipidic plaque. We believe that our case may lead to elucidation of the etiology of coronary artery disease in patients with moyamoya disease., Learning Objective: It is known that patients with moyamoya disease develop coronary artery disease at a young age, but the etiology has not been clarified. We used optical coherence tomography to evaluate the intravascular conditions of coronary artery disease patients with moyamoya disease. The lesions of coronary artery disease associated with moyamoya disease were mainly arteriosclerotic lesions rich in inflammation., Competing Interests: None., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: To evaluate the association between trypsin-like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers., Materials and Methods: This cross-sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue-swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60-89 and <60 mL/min/1.73 m 2 ., Results: The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60-89 (63.8%) and <60 mL/min/1.73 m 2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable-adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02-1.22) per unit increase in the a* value., Conclusions: Higher TLP activity was associated with reduced kidney function in Japanese workers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Linezolid is a last-resort antimicrobial in human clinical settings to treat multidrug-resistant Gram-positive bacterial infections. Mobile linezolid resistance genes (optrA, poxtA, and cfr) have been detected in various sources worldwide. However, the presence of linezolid-not-susceptible bacteria and mobile linezolid resistance genes in Japan remains uncertain. Therefore, we clarified the existence of linezolid-not-susceptible bacteria and mobile linezolid resistance genes in farm environments in Japan., Methods: Enterococci isolates from faeces compost collected from 10 pig and 11 cattle farms in Japan in 2021 were tested for antimicrobial susceptibility and possession of mobile linezolid resistance genes. Whole-genome sequencing of optrA and/or poxtA genes positive-enterococci was performed., Results: Of 103 enterococci isolates, 12 from pig farm compost were not-susceptible (2 resistant and 10 intermediate) to linezolid. These 12 isolates carried mobile linezolid resistance genes on plasmids or chromosomes (5 optrA-positive Enterococcus faecalis, 6 poxtA-positive E. hirae or E. thailandicus, and 1 optrA- and poxtA-positive E. faecium). The genetic structures of optrA- and poxA-carrying plasmids were almost identical to those reported in other countries. These plasmids were capable of transferring among E. faecium and E. faecalis strains. The optrA- and poxtA-positive E. faecium belonged to ST324 (clade A2), a high-risk multidrug-resistant clone. The E. faecalis carrying optrA gene on its chromosome was identified as ST593., Conclusions: Although linezolid is not used in livestock, linezolid-not-susceptible enterococci could be indirectly selected by frequently used antimicrobials, such as phenicols. Moreover, various enterococci species derived from livestock compost may serve as reservoirs of linezolid resistance genes carried on globally disseminated plasmids and multidrug-resistant high-risk clones., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Several studies have reported a negative impact on survival associated with splenic vessel involvement, especially splenic artery (SpA) involvement, in patients diagnosed with pancreatic body or tail cancer. However, there is limited research on splenic vein (SpV) involvement. Therefore, we aimed to elucidate the significance of splenic vessel involvement, especially SpV involvement, in patients with resectable pancreatic body or tail cancer., Methods: Between January 2007 and December 2021, 116 consecutive patients underwent distal pancreatectomies for pancreatic body or tail cancer. Among them, this study specifically examined 88 patients with resectable pancreatic body or tail cancer to elucidate prognostic factors using a multivariable Cox proportional analysis. The Kaplan-Meier method evaluated the impact of SpV involvement in terms of both radiological and pathological aspects and the efficacy of neoadjuvant therapy., Results: Higher pre-operative carcinoembryonic antigen levels, larger tumour size, pathological SpV invasion, and non-completion of adjuvant therapy were identified as independent poor prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Additionally, patients with radiological SpV encasement had significantly worse prognoses in terms of OS (p = 0.039) and RFS (p < 0.001). The sensitivity and specificity of multidetector-row computed tomography for detecting pathological SpV invasion were 81.0% and 61.2%, respectively. However, the prognostic impact of neoadjuvant therapy could not be determined, regardless of radiological SpV involvement., Conclusion: Radiological and pathological SpV involvement is a poor prognostic factor for patients with resectable pancreatic body or tail cancer. New innovative treatments and effective neoadjuvant therapy regimens are required for patients with SpV involvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To determine the status of type A acute aortic dissection using the Tokyo Acute Aortic Super Network., Methods: Data of 6283 patients with acute aortic dissection between 2015 and 2019 were collected. Data of 3303 patients with type A acute aortic dissection were extracted for analysis., Results: Overall, 51.0% of patients were nondirect admissions. On arrival, 23.1% of patients were in shock, 10.0% in cardiopulmonary arrest, and 11.8% in deep coma or coma. Overall, 9.8% of patients were assessed as untreatable. Of 2979 treatable patients, 18.3% underwent medical treatment, whereas 80.7% underwent surgery (open [78.8%], endovascular [1.9%], and peripheral [1.1%] repair). The early mortality rate was 20.5%, including untreatable cases. Among treatable patients, in-hospital mortality rates were 8.6% for open repair, 10.7% for endovascular repair, and 25.3% for medical treatment. Advanced age, preoperative comorbidities, classical dissection, and medical treatment were risk factors for in-hospital mortality. Nondirect admission did not cause increased deaths. The mortality rates were high during the superacute phase following symptom onset., Conclusions: This study demonstrated current practices in the emergency care of type A acute aortic dissection via the Tokyo Acute Aortic Super Network system, specifically a high rate of untreatable or inoperable cases and favorable outcomes in patients undergoing surgical treatment. High mortality rates were observed during the super acute phase after symptom onset or hospital arrival., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires that editors and reviewers disclose conflicts of interest and decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The emergence and spread of antimicrobial resistance (AMR) continue on a global scale. The impacts of wastewater on the environment and human health have been identified, and understanding the environmental impacts of hospital wastewater and exploring appropriate forms of treatment are major societal challenges. In the present research, we evaluated the efficacy of ozone (O 3 )-based advanced wastewater treatment systems (O 3 , O 3 /H 2 O 2 , O 3 /UV, and O 3 /UV/H 2 O 2 ) for the treatment of antimicrobials, antimicrobial-resistant bacteria (AMRB), and antimicrobial resistance genes (AMRGs) in wastewater from medical facilities. Our results indicated that the O 3 -based advanced wastewater treatment inactivated multiple antimicrobials (>99.9%) and AMRB after 10-30 min of treatment. Additionally, AMRGs were effectively removed (1.4-6.6 log 10 ) during hospital wastewater treatment. The inactivation and/or removal performances of these pollutants through the O 3 /UV and O 3 /UV/H 2 O 2 treatments were significantly (P < 0.05) better than those in the O 3 and O 3 /H 2 O 2 treatments. Altered taxonomic diversity of microorganisms based on 16S rRNA gene sequencing following the O 3 -based treatment showed that advanced wastewater treatments not only removed viable bacteria but also removed genes constituting microorganisms in the wastewater. Consequently, the objective of this study was to apply advanced wastewater treatments to treat wastewater, mitigate environmental pollution, and alleviate potential threats to environmental and human health associated with AMR. Our findings will contribute to enhancing the effectiveness of advanced wastewater treatment systems through on-site application, not only in wastewater treatment plants (WWTPs) but also in medical facilities. Moreover, our results will help reduce the discharge of AMRB and AMRGs into rivers and maintain the safety of aquatic environments., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Many studies have shown deterioration of the oral health environment in palliative care patients; however, most of these studies are cross-sectional. In this longitudinal observational study, we aimed to determine the oral symptoms and how they change in palliative care patients., Methods: The participants were 82 patients (37 men, 45 women) admitted to two palliative care units in Japan between January 2018 and December 2021. The oral condition was evaluated once a week from the time of admission using the Oral Health Assessment Tool (OHAT) and performance status (PS). Friedman tests were performed on the OHAT and PS scores at 1, 2, and 3 weeks before the week of death. In addition, the Bonferroni method was used to determine how many weeks before death the changes occurred., Results: PS continuously deteriorated from three weeks before death. The total OHAT score 2 weeks before death (3.44±2.10) was significantly different compared to that in the week of death (4.37±2.45). In terms of oral conditions, the properties of the saliva changed, and dry mouth became obvious., Conclusions: The results of this study revealed that the oral environment of palliative care patients became significantly dry 2 weeks before death, suggesting that it may be useful for predicting the stage of death.

Introduction: Chronic limb-threatening ischemia (CLTI) is a clinical syndrome defined by peripheral arterial disease (PAD) combined with rest pain, gangrene, or leg ulceration for longer than two weeks resulting in lower extremity amputation. In recent years, low-density lipoprotein apheresis (LDL-A) has been implemented for PAD treatment. However, it has not been possible to ensure insurance coverage for patients with lower LDL levels than 140 mg/dL under cholesterol-lowering drugs. Rheocarna is a novel adsorption-type blood purification device for the treatment of CLTI by adsorbing LDL and fibrinogen (Fib) that is not constrained by hypercholesterolemia and is not amenable to or nonresponsive to revascularization surgery. The only requirements for use are that the blood flow rate increases up to 200 mL/min gradually., Methods: To evaluate the applicability of this treatment procedure, we compared the removal rates of Fib and LDL following Rheocarna therapy using various blood treatment volumes (6, 10.5, and 19.5 L)., Results: Fib and LDL removal rates were about 20% and 15%-25% per treatment, with no significant differences between treatment volumes. Following treatment with Rheocarna, blood pressure tends to decrease at first, which later increases, and the higher the treatment volume, the longer the time of low blood pressure tended to be., Conclusion: Although no significant difference was found in the removal rate of Fib and LDL in response to increase volume to 6 L or beyond in this study, the 6 L volume is considered effective enough for the removal of Fib and LDL., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Objectives: Antiemetics have been widely recommended for treating opioid-induced nausea and vomiting (OINV). According to a previous study, the use of prophylactic prochlorperazine at the initiation of treatment with oral oxycodone was ineffective in preventing OINV. This study examined whether prochlorperazine injection prevents OINV and induces drowsiness in patients with end-stage cancer (a different patient population from the previous study)., Methods: Patients with end-stage cancer who received opioid injections for more than 5 days between April 2017 and March 2020 were classified into two groups: the opioid and prochlorperazine injection group and opioid alone group. Their systemic conditions were evaluated on the basis of the performance status and the palliative performance scale, a prognostic indicator., Results: Of 325 patients who received opioid treatment during the study period, 156 patients met the inclusion criteria. Of these, 103 patients and 53 patients were classified into the opioid and prochlorperazine injection group (prochlorperazine) and opioid alone groups (placebo) , respectively. There was no significant difference in characteristics, age, gender, performance status, or palliative performance scale results between the 2 groups. OINV developed in 4 patients in the opioid and prochlorperazine injection groups and in 1 patient in the opioid alone group. Given that sleep disturbance develops in many patients with end-stage cancer who had a specific condition, it is difficult to conclude regarding the relationship between prochlorperazine injection and drowsiness, although this study examined this relationship., Conclusions: As with the previous study, prophylactic prochlorperazine injection was ineffective in preventing OINV in patients who received opioid injections., Competing Interests: There are no conflicts of interest to declare for this article.

Background: Sex differences in the clinical presentation and outcomes of DeBakey type I/II (Stanford type A) acute aortic dissection (AAD) remain unclear., Objectives: The authors aimed to determine the impact of sex on the clinical presentation and in-hospital outcomes of surgically or medically treated patients with type I/II AAD., Methods: We studied 3,089 patients with type I/II AAD enrolled in multicenter Japanese registry between 2013 and 2018. The patients were divided into 2 treatment groups: surgical and medical. Multivariable logistic regression was used to examine the association between sex and in-hospital mortality., Results: In the entire cohort, women were older and more likely to have hyperlipidemia, previous stroke, altered consciousness, and shock/hypotension at presentation than men. Women had higher proportions of intramural hematomas and type II dissections than men. In the surgical group (n = 2,543), men had higher rates of preoperative end-organ malperfusion ( P  = 0.003) and in-hospital mortality ( P  = 0.002) than women. Multivariable analysis revealed that male sex was associated with higher in-hospital mortality after surgery (OR: 1.71; 95% CI: 1.24-2.35; P  < 0.001). In the medical group (n = 546), women were older and had higher rates of cardiac tamponade ( P  = 0.004) and in-hospital mortality ( P  = 0.039) than men; no significant association between sex and in-hospital mortality was found after multivariable adjustment (OR: 0.95; 95% CI: 0.56-1.59; P  = 0.832)., Conclusions: Male sex was associated with higher in-hospital mortality for type I/II AAD in the surgical group but not in the medical group. Further research is needed to understand the mechanisms responsible for worse surgical outcomes in men., Competing Interests: Data collection and maintenance for the Tokyo CCU Network registry is financially supported by the 10.13039/100019702Tokyo Metropolitan Government, which played no role in the execution of this study or the interpretation of the results. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Cancer stem cells (CSCs) are considered to be responsible for recurrence, metastasis, and resistance to treatment in many types of cancers; therefore, new treatment strategies targeting CSCs are attracting attention. In this study, we fabricated a polyethylene glycol-tagged microwell device that enabled spheroid formation from human oral squamous carcinoma cells. HSC-3 and Ca9-22 cells cultured in the microwell device aggregated and generated a single spheroid per well within 24-48 h. The circular shape and smooth surface of spheroids were maintained for up to five days, and most cells comprising the spheroids were Calcein AM-positive viable cells. Interestingly, the mRNA expression of CSC markers ( Cd44 , Oct4 , Nanog , and Sox2 ) were significantly higher in the spheroids than in the monolayer cultures. CSC marker-positive cells were observed throughout the spheroids. Moreover, resistance to cisplatin was enhanced in spheroid-cultured cells compared to that in the monolayer-cultured cells. Furthermore, some CSC marker genes were upregulated in HSC-3 and Ca9-22 cells that were outgrown from spheroids. In xenograft model, the tumor growth in the spheroid implantation group was comparable to that in the monolayer culture group. These results suggest that our spheroid culture system may be a high-throughput tool for producing uniform CSCs in large numbers from oral cancer cells.

In aquaculture, bacterial infections in sea animals are treated using antimicrobials. As seafood is frequently consumed in its raw form, seafood contaminated with water-borne antimicrobial-resistant bacteria presents a potential transmission route to humans and can influence food safety. In this study, we aimed to determine the abundance of water-borne bacteria in retail raw seafood and to characterize their antimicrobial resistance profiles. In total, 85 retail raw seafood samples (32 fish, 26 shellfish, 25 mollusks, and two crustaceans) were purchased from supermarkets in Japan, and water-borne bacteria were isolated. The isolated bacterial species predominantly included Vibrio spp. (54.1%) and Aeromonas spp. (34.1%). Vibrio or Aeromonas spp. were isolated from more than 70% of the seafood samples. Tetracycline-, sulfamethoxazole-, and/or trimethoprim/sulfamethoxazole-resistant Vibrio or Aeromonas spp. isolates were detected in seven (21.9%) fish samples (two wild-caught and five farm-raised) harboring tet , sul , and/or dfr genes. Sulfamethoxazole- and trimethoprim/sulfamethoxazole-resistant isolates were only detected in farm-raised fish. Tetracycline and sulfamethoxazole are commonly used in aquaculture. These results suggest that water-borne bacteria like Vibrio and Aeromonas spp. should be the primary focus of antimicrobial-resistant bacteria monitoring to effectively elucidate their spread of bacteria via seafood., Competing Interests: Conflict of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (©2023 Food Safety Commission, Cabinet Office, Government of Japan.)

Lenalidomide, an immunomodulatory drug (IMiD), is commonly used as a first-line therapy in many haematological cancers, such as multiple myeloma (MM) and 5q myelodysplastic syndromes (5q MDS), and it functions as a molecular glue for the protein degradation of neosubstrates by CRL4 CRBN . Proteolysis-targeting chimeras (PROTACs) using IMiDs with a target protein binder also induce the degradation of target proteins. The targeted protein degradation (TPD) of neosubstrates is crucial for IMiD therapy. However, current IMiDs and IMiD-based PROTACs also break down neosubstrates involved in embryonic development and disease progression. Here, we show that 6-position modifications of lenalidomide are essential for controlling neosubstrate selectivity; 6-fluoro lenalidomide induced the selective degradation of IKZF1, IKZF3, and CK1α, which are involved in anti-haematological cancer activity, and showed stronger anti-proliferative effects on MM and 5q MDS cell lines than lenalidomide. PROTACs using these lenalidomide derivatives for BET proteins induce the selective degradation of BET proteins with the same neosubstrate selectivity. PROTACs also exert anti-proliferative effects in all examined cell lines. Thus, 6-position-modified lenalidomide is a key molecule for selective TPD using thalidomide derivatives and PROTACs., (© 2023. Springer Nature Limited.)

The rapid identification of specific bacterial pathogens in bovine mastitis is crucial for appropriate antimicrobial treatment. Sequencing of 16S rRNA gene amplicons is a proven, useful strategy for diagnosing bacterial infections. In this study, the use of 16S rRNA analysis with nanopore sequencer for the rapid identification of causative bacteria in bovine mastitis, was evaluated. DNA was extracted from 122 milk samples from cattle with suspected mastitis based on clinical symptoms. 16S rRNA gene amplicon sequencing was conducted using a nanopore sequencer. The efficacy of bacterial identification was verified by comparison with conventional culture methods. Nanopore sequencing identified the causative bacteria with high accuracy within approximately 6 h from the time of sample collection. When the major causative bacteria of bovine mastitis (Escherichia coli, Streptcoccus uberis, Klebsiella pneumoniae, and Staphylococcus aureus) were detected by nanopore sequencing, 98.3% of the results were consistent with identification through conventional culturing methods. 16S rRNA gene analysis using a nanopore sequencer enabled the rapid and accurate identification of bacterial species in bovine mastitis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial., Methods: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6-8 months of follow-up., Results: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (-6.14% vs. -1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression., Conclusions: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

This study clarified the effect of adding thermoresponsive xyloglucan on the bread-making properties and preservation of gluten-free rice-flour bread. The thickening polysaccharides used for preparing gluten-free rice-flour bread were modified tamarind gum (MTG; thermoresponsive xyloglucan), tamarind gum (TG), and xanthan gum (XT). The mechanical properties of the added polysaccharide thickener solutions and bread dough, the mechanical properties and sensory characteristics of rice-flour bread, and the aging properties of rice-flour bread were measured. The results showed that the MTG solution exhibited solification at 40 °C and gelation below 40 °C, which affected the dynamic viscoelasticity of the dough. The addition of MTG to gluten-free rice-flour bread reduced the specific volume, increased the moisture content, and reduced the stress at 70% compression. Therefore, the bread with MTG added was soft, moist, and preferred over other those with other additives. In terms of preservation, the addition of 0.5-0.75% of polysaccharides inhibited the hardening and aging of beard with MTG added. This indicates that the addition of MTG at low concentrations is effective in preserving gluten-free rice-flour breads. We found that the thickening polysaccharides had to be added in appropriate concentrations to improve the bread-making properties and achieve the preferred effect.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects ( n = 207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with "cholesterol absorption". Statin usage also had a positive correlation with "cholesterol synthesis". Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

Background: Recent revisions of clinical guidelines by the Japanese Circulation Society, American Heart Association/American College of Cardiology, and European Society of Cardiology updated the management of antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, the extent to which these guidelines have been implemented in real-world daily clinical practice is unclear. Methods and Results: We conducted surveys on the status of antithrombotic therapy for patients with AF undergoing PCI every 2 years from 2014 to 2022 in 14 cardiovascular centers in Japan. The primary use of drug-eluting stents increased from 10% in 2014 to 95-100% in 2018, and the use of direct oral anticoagulants increased from 15% in 2014 to 100% in 2018, in accordance with the revised practice guidelines. In patients with acute coronary syndrome, the duration of triple therapy within 1 month was approximately 10% until 2018, and increased to >70% from 2020. In patients with chronic coronary syndrome, the duration of triple therapy within 1 month was approximately 10% until 2016, and >75% from 2018. Since 2020, the most common timing of discontinuation of dual antiplatelet therapy to transition to anticoagulation monotherapy during the chronic phase of PCI has been 1 year after PCI. Conclusions: Japanese interventional cardiologists have updated their treatment strategies for patients with AF undergoing PCI according to revisions of clinical practice guidelines., Competing Interests: T.M. has received personal fees from Abbott, Bayer Yakuhin, and MSD; research funding from Amgen, Bayer Yakuhin, and Kowa outside the submitted work; and is a member of Circulation Reports’ Editorial Team. H. Tsutsui has received lecture fees (Kowa, Teijin Pharma, Nippon Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Pfizer Japan, Ono Pharmaceutical, Daiichi Sankyo, Novartis Pharma, Bayer Yakuhin, Otsuka Pharmaceuticalm, and AstraZeneca); manuscript fees (Nippon Rinsho); research funding (Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, IQVIA Services Japan, MEDINET, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, and NEC Corporation); and scholarship funds (Abbott Medical Japan, Otsuka Pharmaceutical, Boston Scientific Japan, Ono Pharmaceutical, Bayer Yakuhin, Nippon Boehringer Ingelheim, St. Mary’s Hospital, Teijin Pharma, Daiichi Sankyo, and Mitsubishi Tanabe Pharma) outside the submitted work. The other authors declare no conflicts of interest with regard to this article., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

Acquisition of novel functions caused by gene duplication may be important for termite social evolution. To clarify this possibility, additional evidence is needed. An important example is takeout, encoding juvenile hormone binding protein. We identified 25 takeouts in the termite Reticulitermes speratus genome. RNA-seq revealed that many genes were highly expressed in specific castes. Two novel paralogs (RsTO1, RsTO2) were tandemly aligned in the same scaffold. Real-time qPCR indicated that RsTO1 and RsTO2 were highly expressed in queens and soldiers, respectively. Moreover, the highest RsTO1 expression was observed in alates during queen formation. These patterns were different from vitellogenins, encoding egg-yolk precursors, which were highly expressed in queens than alates. In situ hybridization showed that RsTO1 mRNA was localized in the alate-frontal gland, indicating that RsTO1 binds with secretions probably used for the defence during swarming flight. In contrast, increased RsTO2 expression was observed approximately 1 week after soldier differentiation. Expression patterns of geranylgeranyl diphosphate synthase, whose product functions in the terpenoid synthesis, were similar to RsTO2 expression. In situ hybridization indicated RsTO2-specific mRNA signals in the soldier-frontal gland. RsTO2 may interact with terpenoids, with a soldier-specific defensive function. It may provide additional evidence for functionalization after gene duplication in termites., (© 2023. The Author(s).)