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Abstract Polyploidy is frequently enhanced under pathological conditions, such as tissue injury and cancer in humans. Polyploidization is critically involved in cancer evolution, including cancer initiation and the acquisition of drug resistance. However, the effect of polyploidy on cell fate remains unclear. In this study, we explored the effects of polyploidization on cellular responses to DNA damage and cell cycle progression. Through various comparisons based on ploidy stratifications of cultured cells, we found that polyploidization and the accumulation of genomic DNA damage mutually induce each other, resulting in polyploid cells consistently containing more genomic DNA damage than diploid cells under both physiological and stress conditions. Notably, despite substantial DNA damage, polyploid cells demonstrated a higher tolerance to its impact, exhibiting delayed cell cycle arrest and reduced secretion of inflammatory cytokines associated with DNA damage-induced senescence. Consistently, in mice with ploidy tracing, hepatocytes with high ploidy appeared to potentially persist in the damaged liver, while being susceptible to DNA damage. Polyploidy acts as a reservoir of genomic damage by mitigating the impact of DNA damage, while simultaneously enhancing its accumulation.

Abstract Background In chronic kidney disease (CKD), the durability of patient adherence to fluid and dietary restrictions may depend on the degree to which they have hope that they will enjoy life. Previous cross-sectional studies have shown that higher hope was associated with lower distress from fluid and dietary restrictions and better adherence in the short term. In this study, we aimed to examine the long-term relationship of hope with distress from fluid and dietary restrictions. Methods This prospective observational cohort study included 444 patients with CKD undergoing dialysis in one of five Japanese nephrology centers. Hope as a predictor was measured using an 18-item health-related hope scale. Outcomes were two-item measures of distress from fluid and dietary intake restrictions using the Japanese version of the Kidney Disease Quality of Life Short Form, Version 1.3 (higher scores indicate lower levels of distress). Multivariate linear mixed models were used to estimate the association of baseline health-related hope with distress from fluid and dietary restrictions at baseline and follow-up. Results The mean age of the participants was 67 years, and 31.1% of them were females. In total, 124, 98, and 222 had non-dialysis CKD, peritoneal dialysis, and hemodialysis, respectively. Higher levels of baseline health-related hope were associated with lower levels of distress from fluid restriction after one year (per 10-point increase, 2.6 points (95% confidence interval, 1.0 to 4.1)); whereas the baseline score was not associated with the distress from fluid restriction at 2 years. Similarly, higher levels of baseline health-related hope were associated with lower levels of distress from dietary restriction after one year (per 10-point increase, 2.0 points (95% confidence interval, 0.3 to 3.6)); whereas the baseline score was not associated with the distress from dietary restriction at 2 years. Conclusions Health-related hope, regardless of depression, can potentially mitigate long-term distress from fluid and dietary restrictions in patients with a wide range of CKD severities. Trial registration UMIN000054710.

Abstract Background Local anaesthesia in dental procedures is generally safe, although the occurrence of transient bradycardia (TB) has occasionally been reported. TB is often associated with two reflexes, the trigeminal cardiac reflex (TCR) and the vasovagal reflex (VVR) and is characterised by a rapid decrease in heart rate (HR) and blood pressure (BP). The prevalence of TCR is considered low, and its predictors have not been thoroughly investigated, although an association with the gag reflex has been suggested in recent years. Methods This prospective study assessed TB occurrence during local anaesthesia and its potential associated factors. A comprehensive questionnaire was used to categorise discomforts during dental treatment, and various anxiety scales were used to measure patients’ anxiety levels. We investigated HR variability during local anaesthesia administration under sedation and the association between the incidence of TB and gag reflex. Subsequently, logistic regression analysis was performed to assess factors associated with TB occurrence. Results The prospective analysis included 188 patients of 234 initial patients. The analysis revealed a high TB incidence rate of 41% during local anaesthesia administration under sedation. No severe hypotensive events occurred, indicating a relatively benign nature of TB during local anaesthesia. TB occurrence was significantly higher in the group of patients with the gag reflex. Further analysis revealed that both gag reflex and trait anxiety were significantly associated with TB occurrence, whereas dental phobia did not directly correlate with TB. Conclusion This study highlights the prominent occurrence of TB during local anaesthesia in dental treatment, which is primarily attributed to TCR activation. The identification of gag reflex and trait anxiety as independent factors associated with TB development may pave the way for TB prevention measures. Further research is required to clarify the mechanisms of TCR and perform safer dental procedures under sedation. Future studies should also aim to elucidate the precise mechanisms underlying TB during local anaesthesia through direct measurements of neural activity. A better understanding of TB in dentistry is crucial for improving patient safety and optimising dental practice protocols.

Abstract Silent manipulation is a procedure for frozen shoulders that involves manipulating the shoulder while the patient is awake by performing C5, C6, and C7 cervical nerve root block under ultrasound guidance. This retrospective study, conducted at Yokohama City University Hospital, aimed to evaluate the clinical outcomes of silent manipulation and assess whether the experience level of the practitioner influenced treatment efficacy. Between October 2020 and January 2022, 53 patients who met the inclusion criteria underwent silent manipulation for frozen shoulder. The procedure was performed by either an experienced or a less experienced practitioner, and the patients were followed-up for up to 1 year post-treatment. Silent manipulation resulted in significant improvements in shoulder range of motion, as measured by forward flexion, abduction, external rotation, and hand-behind-back, as well as in patient-reported outcomes, including disabilities of the arm, shoulder, and hand and Shoulder 36 scores. These improvements were observed 1 week, 3 months, and 1 year after silent manipulation, indicating the short-term efficacy of the procedure. Furthermore, this study revealed that the practitioners’ level of experience played a significant role in the outcomes. The experienced doctor achieved better 1st external rotation and belt tying outcomes, as well as Shoulder 36 pain, muscle strength, and activities of daily living domain scores. This suggests that technical expertise in silent manipulation is crucial to achieve optimal outcomes. Silent manipulation offers an effective therapeutic approach for frozen shoulder, leading to significant improvements in range of motion and patient satisfaction. Practitioner expertise is a vital factor in treatment success, emphasizing the importance of skilled professionals in the performance of this procedure.

Abstract Mixed‐phenotype acute leukemia (MPAL) with FLT3‐TKD mutations is a rare and challenging subtype of leukemia. Effective management strategies are crucial for improving patient outcomes. A 31‐year‐old man with FLT3‐TKD‐mutated MPAL achieved hematological remission through the JALSG ALL202‐O protocol and gilteritinib, followed by cord blood transplantation (CBT). Post‐transplant complications included adenovirus‐induced hemorrhagic cystitis, managed with bladder irrigation and ribavirin, and engraftment failure, necessitating a second CBT on Day 35. Subsequent adenoviral conjunctivitis resolved with vidarabine. The patient achieved neutrophil engraftment by Day 76 and was discharged on Day 173 without relapse. This case highlights the importance of vigilant supportive care and tailored therapy in managing MPAL with FLT3 mutations, especially in the context of post‐transplant complications.

Abstract Background Accurate clinical staging is crucial for selection of optimal oncological treatment strategies in non-small cell lung cancer (NSCLC). Although brain MRI, bone scintigraphy and whole-body PET/CT play important roles in detecting distant metastases, there is a lack of evidence regarding the indication for metastatic staging in early NSCLCs, especially ground-grass nodules (GGNs). Our aim was to determine whether checking for distant metastasis is required in cases of clinical T1N0 GGN. Methods This was a retrospective study of initial staging using imaging tests in patients who had undergone complete surgical R0 resection for clinical T1N0 Stage IA NSCLC. Results A total of 273 patients with cT1N0 GGNs (n = 183) or cT1N0 solid tumors (STs, n = 90) were deemed eligible. No cases of distant metastasis were detected on initial routine imaging evaluations. Among all cT1N0M0 cases, there were 191 incidental findings on various modalities (128 in the GGN). Most frequently detected on brain MRI was cerebral leukoaraiosis, which was found in 98/273 (35.9%) patients, while cerebral infarction was detected in 12/273 (4.4%) patients. Treatable neoplasms, including brain meningioma and thyroid, gastric, renal and colon cancers were also detected on PET/CT (and/or MRI). Among those, 19 patients were diagnosed with a treatable disease, including other-site cancers curable with surgery. Conclusions Extensive staging (MRI, scintigraphy, PET/CT etc.) for distant metastasis is not required for patients diagnosed with clinical T1N0 GGNs, though various imaging modalities revealed the presence of adventitious diseases with the potential to increase surgical risks, lead to separate management, and worsen patient outcomes, especially in elderly patients. If clinically feasible, it could be considered to complement staging with whole-body procedures including PET/CT.

Abstract Recent studies have observed high methane concentrations in runoff water and the ambient air at various glacier sites, including the Greenland Ice Sheet, the glacier forefield in Svalbard, and the ice cap in Iceland. This study extends these findings to smaller mountain glaciers in Alaska. Methane and carbon dioxide concentrations in the ambient air near the meltwater outlet, fluxes of these gases at the surface of runoff water and riverbank sediments, and dissolved methane content in the runoff water were measured at four glaciers. Three of the four glaciers showed conspicuous signals of methane emissions from runoff water, with the Castner Glacier terminus exhibiting a methane concentration three times higher than background levels, along with elevated dissolved methane levels in the runoff water. This study marks the detection of significant methane emissions from small mountain glacier runoff, contributing to the understanding that mountain glaciers also release methane into the atmosphere.

Abstract We studied chromophoric (CDOM) and fluorescent (FDOM) dissolved organic matter (DOM) and dissolved organic carbon in surface waters to determine the factors controlling the geographical distribution of DOM along two meridional transects in the Indian Ocean. For CDOM, we calculated the absorption coefficients, spectral slope, and absorption coefficient ratio from the observed absorption spectra. For FDOM, we calculated the biological (BIX) and humification (HIX) indices from the excitation emission matrices (EEMs); parallel factor analysis of the EEMs identified three fluorescent components, i.e., two humic-like and one protein-like. Using these DOM parameters, a factor analysis extracted fewer latent variables than the observed variables to account for the geographical distributions. We obtained three factors (F1, F2, and F3), which explained ~ 84% of the variance in the observed data. From the factor loadings, F1, F2, and F3 were interpreted as the effects of net primary production-derived DOM and its horizontal transport, photodegradation, and vertical transport by physical processes. We characterized seven marine biogeochemical provinces by factor scores. F1 scores gradually decreased from the northernmost to the Antarctic province, with a small maximum around the subtropical front. F2 scores were highest in the subtropical province and decreased in both the northward and southward directions. F3 scores were high in the Antarctic and northernmost provinces, and lowest in the subtropical province. Only BIX was insufficiently explained by these factors. BIX was highest in the northern part of the subtropical province, where photodegradation of DOM was the most intense. This suggests that the possible interaction between photodegradation, autochthonous production, and reworking by heterotrophic bacteria of DOM occurs in the subtropical province.

The presented pilot for the Synthesis Product for Ocean Time Series (SPOTS) includes data from 12 fixed ship-based time-series programs. The related stations represent unique open-ocean and coastal marine environments within the Atlantic Ocean, Pacific Ocean, Mediterranean Sea, Nordic Seas, and Caribbean Sea. The focus of the pilot has been placed on biogeochemical essential ocean variables: dissolved oxygen, dissolved inorganic nutrients, inorganic carbon (pH, total alkalinity, dissolved inorganic carbon, and partial pressure of CO2), particulate matter, and dissolved organic carbon. The time series used include a variety of temporal resolutions (monthly, seasonal, or irregular), time ranges (10–36 years), and bottom depths (80–6000 m), with the oldest samples dating back to 1983 and the most recent one corresponding to 2021. Besides having been harmonized into the same format (semantics, ancillary data, units), the data were subjected to a qualitative assessment in which the applied methods were evaluated and categorized. The most recently applied methods of the time-series programs usually follow the recommendations outlined by the Bermuda Time Series Workshop report (Lorenzoni and Benway, 2013), which is used as the main reference for “method recommendations by prevalent initiatives in the field”. However, measurements of dissolved oxygen and pH, in particular, still show room for improvement. Additional data quality descriptors include precision and accuracy estimates, indicators for data variability, and offsets compared to a reference and widely recognized data product for the global ocean: the GLobal Ocean Data Analysis Project (GLODAP). Generally, these descriptors indicate a high level of continuity in measurement quality within time-series programs and a good consistency with the GLODAP data product, even though robust comparisons to the latter are limited. The data are available as (i) a merged comma-separated file that is compliant with the World Ocean Circulation Experiment (WOCE) exchange format and (ii) a format dependent on user queries via the Environmental Research Division's Data Access Program (ERDDAP) server of the Global Ocean Observing System (GOOS). The pilot increases the data utility, findability, accessibility, interoperability, and reusability following the FAIR philosophy, enhancing the readiness of biogeochemical time series. It facilitates a variety of applications that benefit from the collective value of biogeochemical time-series observations and forms the basis for a sustained time-series living data product, SPOTS, complementing relevant products for the global interior ocean carbon data (GLobal Ocean Data Analysis Project), global surface ocean carbon data (Surface Ocean CO2 Atlas; SOCAT), and global interior and surface methane and nitrous oxide data (MarinE MethanE and NiTrous Oxide product). Aside from the actual data compilation, the pilot project produced suggestions for reporting metadata, implementing quality control measures, and making estimations about uncertainty. These recommendations aim to encourage the community to adopt more consistent and uniform practices for analysis and reporting and to update these practices regularly. The detailed recommendations, links to the original time-series programs, the original data, their documentation, and related efforts are available on the SPOTS website. This site also provides access to the data product (DOI: https://doi.org/10.26008/1912/bco-dmo.896862.2, Lange et al., 2024) and ancillary data.

Background/purpose: The possibility of triggering the trigeminocardiac reflex (TCR) during oral surgery is considerably lower than that during other surgeries. A reduced heart rate (HR) of ≥20% from baseline is usually considered a diagnostical criterion for the TCR. Our automated anesthesia charting system often revealed cases of slight transient HR decrease during sedation. We aimed to explore its incidence and associated factors during local anesthesia administration under intravenous sedation. Materials and methods: This study analyzed the data of 2636 cases that received infiltration anesthesia under intravenous sedation from 2008 to 2010 and had vital signs recorded using an automated anesthesia charting system. Especially, data concerning the average HR before anesthesia and the minimum HR between the initiation and end of anesthesia from anesthetic records were extracted. Moreover, data regarding patients' medical history and unusual reactions during dental treatment were collected. Multivariate logistic regression analysis was performed to identify factors associated with transient bradycardia (TB). Results: TB occurred in 472 patients (17.9%); no patient developed hypotension or any associated symptoms, suggesting that intravenous sedation was effective in stabilizing vital signs. The factors associated with TB were younger age, gag reflex, and allergy to local anesthetics. There were no differences in sex, patient history, or dose of sedatives between patients with TB and those without TB. Conclusion: The incidence of TB during infiltration anesthesia under sedation was found to be higher than that previously reported. Additionally, young age and gag reflex were identified as factors associated with bradycardia development.

Abstract The association between serum tumor necrosis factor receptor (TNFRs: TNFR1, TNFR2) levels and estimated glomerular filtration rate (eGFR) observed in patients with diabetes has not been comprehensively tested in healthy subjects with normal kidney function. It also remains unclear whether TNFR levels differ by age and sex, and between healthy subjects and diabetics. We measured serum TNFR levels in 413 healthy subjects and 292 patients with type 2 diabetes. In healthy subjects, TNFR levels did not differ between men and women. Additionally, TNFR2, but not TNFR1, levels increased with age. In multivariate analysis, TNFR1 was associated only with cystatin C-based eGFR (eGFR-CysC), whereas TNFR2 was associated with systolic blood pressure in addition to eGFR-CysC. Both TNFRs were associated with lower eGFR (eGFR-Cys

Introduction Establishing a scale that can easily be used to appropriately measure the impact of constipation on the quality of life in Japan is a first step toward addressing this important health issue. We developed a Japanese language version of the Constipation-Related Quality of Life scale, which has 18 items and four subscales, and then subjected it to validation testing. Methods After translation according to a standardized and commonly used procedure, the Japanese version of the Constipation-Related Quality of Life scale was administered to people in an internet-based panel, in March 2023. The participants included 1,276 adults who had constipation (median age: 60 years, 690 {54.1%} males). The outcome measures included the Constipation-Related Quality of Life scale, the Constipation Scoring System (an index of constipation severity), and the Medical Outcomes Study (MOS) eight-item short form (a measure of generic health-related quality of life). Results Confirmatory factor analysis (four-factor model) indicated that all 18 Constipation-Related Quality of Life items had sufficiently high factor loadings (0.686-0.926). Internal consistency reliability was high (Cronbach's alpha: 0.86-0.94). Scores on the social impairment subscale and on the distress subscale of the Constipation-Related Quality of Life scale were significantly worse in the participants who had worse scores on the social functioning and mental health domains, respectively, of the MOS eight-item short form, which indicates good concurrent validity. Regarding criterion-based validity, the four subscale scores differed significantly among the four constipation-severity groups. The four subscale scores were also 1.16-4.53 times more sensitive than the MOS eight-item short form's mental component score to differences among the four constipation-severity groups (relative validity: 1.16-4.53), which indicates good discriminant validity. Conclusion The Japanese version of the Constipation-Related Quality of Life scale can be used with confidence in its factor structure, its concurrent, criterion-based, and discriminant validity, and its internal consistency reliability.