Tsukuba Medical Center Hospital

This cross-sectional study explored outcomes in patients with cancer following opioid initiation (maximum observation period: 6 months), based on an analysis of laxative prescription patterns for opioid-induced constipation (OIC) using the Medical Data Vision Co., Ltd., a nationwide acute care hospital claims database in Japan. Of 26,939 patients included, 16,214 (60.2%) developed OIC, defined as the prescription of a laxative on or after the fourth day following the initiation of opioid therapy. At baseline, the average age was 69.3 years, with 58.0% being male patients. Overall, 42.7% of patients were hospitalized at the time of opioid initiation (OIC subgroup: 51.1%; non-OIC subgroup: 30.1%). The majority of patients (53.9%) had observation data for less than 6 months (OIC subgroup: 61.8%; non-OIC subgroup: 42.0%). Although there were disparities in patient backgrounds and observation periods, the total healthcare costs incurred were approximately ¥2,400,000, with ¥2,800,000 in the OIC subgroup and ¥1,800,000 in the non-OIC subgroup. Overall, these results highlight the importance of implementing appropriate OIC management strategies in Japan. However, it is noteworthy that the sequence of events between OIC onset and clinical outcomes remains unclear.

The role of transcatheter aortic valve replacement (TAVR) in nonagenarians remains uncertain, especially regarding long-term outcomes and prognostic factors. This study aimed to evaluate long-term outcomes of TAVR in nonagenarians, focusing on cause-specific mortality and the prognostic influence of frailty and malnutrition. We analyzed 4,623 patients who underwent transfemoral TAVR in a multicenter Japanese registry, including 700 aged ≥90 years. Outcomes were followed for 5 years. We analyzed all-cause mortality, cause-specific mortality, and the prognostic impact of the Clinical Frailty Scale and Geriatric Nutritional Risk Index. At 5 years, all-cause mortality was higher in patients aged ≥90 years than in those <90 years (53.2% vs37.0%, P < 0.001), primarily due to noncardiovascular deaths such as senility and infections (32.5% vs 19.9%; P < 0.001). Cardiovascular mortality was similar (20.3% vs 17.0%; P = 0.198). Multivariable analysis showed that age ≥90 years was not an independent predictor; frailty and malnutrition were the strongest prognostic factors. A Clinical Frailty Scale-Geriatric Nutritional Risk Index heatmap revealed marked heterogeneity, identifying subgroups of nonagenarians with preserved nutrition and low frailty who achieved favorable long-term survival. In this large multicenter registry, excess mortality in nonagenarians after TAVR was driven mainly by noncardiovascular causes. Frailty and malnutrition, rather than chronological age, were central determinants of long-term outcomes. These findings emphasize that TAVR candidacy in nonagenarians should be guided on geriatric assessment of frailty and nutrition to identify patients most likely to achieve meaningful survival while avoiding futile interventions.

Sodium taurocholate cotransporting polypeptide (NTCP) is a hepatic transmembrane (TM) protein that functions both as a bile acid transporter and as a host receptor for hepatitis B and D viruses via the viral preS1 binding. The structural and mechanistical determinants for NTCP’s dual functions remain largely undefined. In this study, using comprehensive structure-guided alanine-scanning mutagenesis based on the cryo-electron microscopy structure of the preS1/NTCP complex, we identified 13, 8 and 9 NTCP amino acid residues critical for viral infection, preS1 binding, and bile acid transport, respectively. Key residues overlappingly regulating viral receptor and transporter functions were located primarily at TM1 and TM8, whereas TM5 and outer-surface NTCP loops mediated viral receptor-specific activity. In addition to 8 amino acids key to preS1 binding, 5 residues likely acted at a post-preS1 binding step of infection. We further found naturally-occurring single nucleotide polymorphism-associated F274C/S NTCP variants abolished viral receptor function, via the potential conformational changes in bile acid tunnel and outer-surface hollow, as analyzed by molecular dynamics simulations. Our domain-specific structural-functional map of NTCP defines the mechanism how NTCP’s dual functionality is separately regulated, and provides a framework for designing selective antiviral agents that preserve bile acid transport.

Multicenter retrospective cohort study. To evaluate the impact of abscess presence and type on treatment duration and clinical outcomes in patients undergoing minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis. Surgical management is increasingly favored for pyogenic spondylitis. Abscesses, particularly epidural and iliopsoas, have been linked to poorer prognoses, and empyema, though uncommon, tends to be particularly severe. However, the effect of specific abscess types on surgical outcomes remains unclear. This study included 92 patients who underwent minimally invasive posterior fixation across 10 centers between 2014 and 2024. Patients were classified into an abscess group (epidural, iliopsoas, empyema, or other) and a non-abscess group. Clinical outcomes, including total duration of intravenous antibiotics and unplanned additional surgeries, were compared. Subgroup and regression analyses were conducted to assess the impact of specific abscess type. Abscesses were present in 65 patients (71%): epidural (n=51), iliopsoas (n=38), and empyema (n=3), with some overlap. Compared with the non-abscess group (n=27; 29%), there were no significant differences in antibiotic duration or rates of unplanned additional surgery. However, iliopsoas abscess was associated with longer antibiotic duration (8.1 weeks vs. 6.6 weeks, p =0.044), while all empyema cases required additional surgery for poor infection control (p =0.000). Regression analysis identified iliopsoas abscess and age ≥65 years as independent predictors of prolonged antibiotic use, whereas epidural abscess was associated with shorter antibiotic duration. Iliopsoas abscesses were associated with longer antibiotic courses, while empyema was linked to poor infection control and a higher likelihood of additional surgery.

ABSTRACTSulf1 and Sulf2 are extracellular sulfatases that remove 6‐O‐sulfate from heparan sulfate and thereby regulate cell signaling. Previous studies have revealed that Sulf1/Sulf2 double knockout (KO) mice had defects in differentiation and axon guidance during development, but their functional roles in the adult brain remain largely unknown. We recently found that Sulf1 mRNA is highly expressed in the nucleus accumbens (NAc) shell and that Sulf1 expression is detected in both types of medium spiny neurons expressing dopamine D1 or D2 receptors. Moreover, we found that Sulf1 KO led to changes in membrane excitability and excitatory synaptic transmission in medium spiny neurons of the NAc in adult mice. These findings suggest possible roles of Sulf1 in the functions of NAc circuitry. To address this question, we performed behavioral tests using Sulf1 KO mice. We found that constitutive Sulf1 KO mice showed impairment in both the cocaine‐induced conditioned place preference (CPP) test and inhibitory avoidance (IA) test. Next, to examine which cell types the Sulf1 gene is required for, we generated Sulf1 floxed mice by means of CRISPR‐Cas9‐mediated genome editing and mated them with mice expressing Cre recombinase under a promoter for either the dopamine D1 or D2 receptor‐encoding genes. Sulf1 conditional knockout (cKO) in cells expressing dopamine D1 receptors led to impairment only in the CPP test, whereas Sulf1 cKO in D2 receptor‐expressing cells resulted in impairment only in the IA test. These results demonstrate that Sulf1 is required for both reward and aversion learning, and that the D1‐ and D2‐pathways distinctly regulate these functions. The present study suggests that Sulf1 is essential for neuronal functions and behavioral control in the adult brain.

The management of very low-gradient (LG) severe aortic stenosis (AS) remains challenging. Moreover, limited evidence exists regarding the outcomes of patients with very LG severe AS following transcatheter aortic valve implantation (TAVI). Weaimedto elucidate the prognosis of patients with very LG severe AS after TAVI and the influence of flow status. Data were retrospectively collected from the OCEAN-TAVI multicenter registry in Japan, including patients with severe AS who underwent TAVI. In total, 7103 patients were classified into three groups based on their baseline mean pressure gradient (MPG): very LG (MPG ≤ 20 mmHg), LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). The primary endpoint was a composite of all-cause mortality and hospitalization for heart failure. During a median follow-up period of 741 days, the composite endpoint was reached in 2081 patients. Patients with very LG severe AS had a higher prevalence of comorbidities. Kaplan-Meier analysis showed that very LG severe AS was associated with significantly lower event-free survival compared to that with LG and HG severe AS. Multivariable Cox regression analysis identified very LG severe AS as an independent poor prognostic indicator, regardless of the flow state. Moreover, within the very LG severe AS group, a low body mass index and myocardial infarction history were associated with worse outcomes. This study indicates that patients with very LG severe AS have worse prognoses compared to those with LG or HG severe AS following TAVI, regardless of the flow state.

Headaches are common in youth and can impact school and daily life. Data on headaches and care-seeking in Japanese schoolchildren are scarce. We investigated prevalence, impact, and consultation patterns. A school-based online survey was conducted between February and March 2025 among 3,766 students in seven elementary and three junior high schools in Ami-town, Ibaraki-prefecture, Japan. Two questionnaire versions were distributed: one for lower-grade students (grades 1-3) and one for upper-grade students (grades 4-9). The survey included items on headache frequency, triggers, associated symptoms, medication use, and consultation experiences. The prevalence of headaches was 29.1% in lower-grade and 37.6% in upper-grade students. The most common age of onset was 10 years. Students with Headaches that meet most of the diagnostic criteria for episodic migraine experienced more headache days and more school absences compared to students with other headache characteristics. Although nearly half of the students had taken medication, fewer than one-third had consulted a physician. Despite experiencing headaches, only a small number of children sought medical care, which may raise concerns about the potential overuse of over-the-counter medications. Therefore, collaboration between educational and medical institutions is essential to improve early recognition and intervention.

Rhizospheric microbiomes differ between active and dormant plants due to changes in root activity and exudate production, especially under environmental stress. In arid regions, native plants such as Potaninia mongolica Maxim enter dormancy to survive harsh conditions. However, rhizospheric microbial and chemical differences between active and dormant states of plants remain poorly described. This study investigated rhizospheric microbial communities and soil chemical changes in the case of active and dormant P.mongolica plants. Rhizospheric soil samples were collected, and soil texture and chemical variables were analyzed. High-throughput sequencing targeting the 16S rRNA and ITS regions was conducted to profile bacterial and fungal communities, respectively. Results showed that the dominant fungal phyla were Ascomycota and Basidiomycota, while Proteobacteria and Actinobacteria were the dominant bacterial phyla in both plant states. Although bacterial diversity did not differ significantly between active and dormant plants (p > 0.05, Welch’s t-test), fungal diversity was significantly different. Among soil chemical variables, total nitrogen was notably elevated in the rhizosphere of dormant plants (mean = 7.93; SD = 5.91). These findings reveal differences in fungal community structure and nitrogen levels in the rhizosphere between active and dormant plant states. Understanding these interactions contributes to our knowledge of desert plant microbiome dynamics and may inform the use of microbial indicators or amendments to support vegetation restoration in arid environments.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22696-7.

This study aimed to investigate the incidence and risk factors of thoracolumbar noncontiguous spinal fractures (NSF) in surgically treated older patients with cervical spine injuries and to evaluate their association with functional outcomes. We retrospectively reviewed 115 patients aged ≥ 65 years who underwent surgery for traumatic cervical spine injuries between 2015 and 2025. Thoracolumbar NSF were defined as fractures located at least two vertebral levels away from the cervical injury. Patient background, comorbidities, laboratory data, and imaging findings were collected. Functional outcome was assessed using the Barthel Index (BI) at discharge, with BI ≥ 60 indicating functional independence. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of NSF and BI ≥ 60. Thoracolumbar NSF were observed in 39.1% of patients. High-energy trauma (odds ratio [OR]: 70.7) and pre-existing vertebral fractures (OR: 12.8) were identified as independent positive predictors, whereas the presence of ossification of the posterior longitudinal ligament was negatively associated with NSF (OR: 0.12). In multivariate analysis for BI ≥ 60, higher serum albumin (OR: 10.7) and lower Charlson Comorbidity Index (OR: 0.46) were associated with better functional outcomes, while spinal cord injury was a negative predictor (OR: 0.17). The presence of thoracolumbar NSF was not associated with functional outcome. Thoracolumbar NSF are relatively common in surgically treated older patients with cervical spine injuries. Although they were not linked to worse functional outcomes, their strong association with high-energy trauma and skeletal fragility highlights the need for comprehensive spinal imaging and early risk assessment.

BackgroundSecondary‐radiation background (BG) generated in kilovoltage X‐ray flat‐panel detectors (FPDs) under scanning proton beam irradiation has not been thoroughly analyzed.PurposeThis study aimed to determine and mathematically model the characteristics of secondary‐radiation BG in FPDs under scanning proton beam irradiation.MethodsUsing a synchrotron‐based proton system and two FPDs mounted on a gantry tilted at 135° to the proton beam axis, we acquired images of two phantoms (block and thorax). The FPD images were captured during three conditions: only X‐ray exposure, proton irradiation, and pauses between proton irradiations. Because the FPD readout rate (30 fps) was twice the X‐ray exposure rate (15 pps), the images were further categorized into two types: those corresponding to with and without X‐ray exposure. These FPD images were analyzed to determine the characteristics of the secondary‐radiation BG. In addition, a Monte Carlo simulation was conducted to complement the performed measurements.ResultsAnalysis of the FPD images without X‐ray exposure revealed that the pure secondary‐radiation BG appeared as sparse spike patterns without a noticeable spatial bias across the FPD area in most images. The BG affected only 1.25% of the FPD pixels and could be modeled as an exponentially decreasing function with increasing pixel intensity. When considering typical X‐ray image brightness for the block and thorax phantoms, the impact of the BG on mean‐pixel‐intensity variation was < 1%. Monte Carlo simulations suggested that prompt photons were the primary source reaching the FPD.ConclusionsThis study demonstrates that the secondary‐radiation BG characteristics observed in the X‐ray FPD images during scanning proton beam irradiation can be quantitatively modeled. The impact of the secondary‐radiation BG on mean‐pixel‐intensity of FPD images was minimal.