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Long-term monitoring of viruses and Varroa destructor within the same honey bee colonies is rare in Japan. Thus, we conducted a 4-year fixed-point survey of three Apis mellifera colonies in Tokyo with monthly screening for seven viruses (using polymerase chain reaction) and Varroa infestation. Deformed wing virus was detected year-round, whereas sacbrood virus and black queen cell virus peaked in spring and summer. Israeli acute paralysis virus appeared sporadically, without seasonal trends. Varroa infestation rates (monitored during the latter 2.5 years) did not correlate with the number of detected virus types and showed no seasonality. Although viral load was not quantified, this long-term dataset provides valuable baseline data on local virus dynamics, providing baseline information on seasonal virus dynamics in managed honey bee colonies in Tokyo.
Tuberculosis (TB) remains a major global health challenge, with delayed diagnosis perpetuating transmission in resource-limited settings. Although the sensitivity of molecular diagnostic methods is high, their dependence on the laboratory infrastructure limits accessibility in many regions. Serological approaches that detect host antibody responses represent a technically simple diagnostic strategy; however, the performance of currently available TB serodiagnostic tests is inconsistent, largely due to suboptimal antigen selection and heterogeneity in host immune responses. Therefore, the identification of conserved antigens naturally recognized during human infection is essential for improving serological diagnostics. A cDNA expression library derived from Mycobacterium bovis BCG Tokyo was constructed and screened by colony immunoblotting using pooled sera from patients with active TB. Immunoreactive clones were sequenced and analyzed bioinformatically. The full-length coding sequence of the identified antigen was expressed recombinantly using a cold-shock expression system in Escherichia coli. The recombinant protein was purified and evaluated for immunoreactivity using a Western blot analysis. Serological reactivity was further assessed using a dot-blot assay with individual serum samples from microbiologically confirmed TB patients (n = 40) and healthy controls (n = 40) from the Lao People's Democratic Republic. Diagnostic performance was evaluated by a receiver operating characteristic (ROC) curve analysis. Immunoscreening identified a conserved hypothetical protein corresponding to Rv1073 of M. tuberculosis, designated MtbAg1073, for which no antigenicity had been previously reported. The protein was highly conserved among members of the M. tuberculosis complex. Recombinant expression using a cold-shock system produced soluble His-tagged MtbAg1073, which was specifically recognized by sera from TB patients in the Western blot analysis. Dot-blot assays showed significantly higher antibody responses in TB patients than in controls (median intensity: 761.2 vs. 471.9; the Mann-Whitney U test, P = 0.0002). The ROC analysis demonstrated moderate discriminatory performance (AUC = 0.734; 95% CI: 0.624-0.844), with a sensitivity of 70.0% and specificity of 67.5% at the optimal cut-off value. MtbAg1073 is a conserved and immunoreactive antigen that elicits detectable antibody responses in active TB. These findings provide preliminary evidence of its immunoreactivity and warrant further investigation into its potential utility in serological approaches.
Long-term medical needs after definitive surgery for esophageal atresia (EA) are incompletely understood. The real-world patterns of home medical care and medication use after hospital discharge remain underexplored. Using the Japanese national inpatient Diagnosis Procedure Combination database, we identified infants who underwent definitive surgery for EA between July 2010 and March 2023. We described patients' background characteristics, perioperative information, long-term home medical care (home tracheostomy care, home mechanical ventilation, home oxygen therapy, and home enteral nutrition), and medication use (antacids, prokinetic agents, and anti-asthmatics) at 1, 3, 5, and 7 years post-definitive surgery. Subgroup analysis based on congenital heart disease (CHD) was conducted. Overall, 806 patients met the eligibility criteria. Home enteral nutrition was the most frequently performed home medical care (22.0% of patients at 1 year post-surgery), whose proportion decreased gradually over time. Antacid and prokinetic agent use also declined over time. Subgroup analysis revealed that patients with CHD required home oxygen therapy and home enteral nutrition more frequently than those without CHD. A substantial proportion of patients required home longitudinal nutritional and respiratory support post-definitive surgery for EA. Our findings provide important information for long-term healthcare needs of patients receiving definitive surgery for EA. III (retrospective comparative study).
Metal halide perovskites exhibit exceptional optoelectronic properties arising from their defect tolerance, high absorption coefficient, tunable bandgap, and long-range charge transport. The soft crystal structure and interaction with light lead to a number of interesting observations over the years. Here, we investigate carrier migration in anti-solvent-assisted grown methylammonium lead bromide (MAPbBr3) micro-disks (MDs) using spatially resolved photoluminescence (PL) lifetime microscopy. Confocal excitation reveals rapid outward carrier migration accompanied by pronounced non-linear PL spatial broadening, indicative of super-diffusive carrier migration. Under deep conduction band excitation at 375 nm, carriers exhibit accelerated diffusion over hundreds of nanometers on an ultra-stable nanosecond timescale, with diffusivity increasing from initial average values of ∼0.44 cm2/s to equilibrium values exceeding 0.88 cm2/s. The degree of non-linearity, represented by an average non-linearity coefficient of 1.5, signifies strong deviation from classical diffusion. Comparative measurements with 485 nm excitation, temperature-dependent studies, and analysis of diffusivity gain and non-linearity demonstrate that these dynamics originate from stabilized hot carriers interacting with low-energy LO phonon modes through large-polaron formation. The observation of nanosecond-scale super-diffusion in perovskite microstructures highlights efficient hot-carrier transport, with implications for designing high-performance optoelectronic and hot-carrier energy-harvesting devices.
Objective Infectious mononucleosis (IM) is most commonly caused by Epstein-Barr virus (EBV). However, recent epidemiological shifts have increased the proportion of adult cases attributable to cytomegalovirus (CMV). Early distinction of EBV-related IM (EBV-IM) using routine laboratory parameters may reduce unnecessary testing and facilitate timely counseling regarding activity restriction. This study aimed to identify the laboratory features that distinguish EBV-IM from non-EBV IM and to develop a simple diagnostic scoring system. Methods We retrospectively analyzed 39 consecutive patients with IM (EBV-IM, n = 22; non-EBV IM, n = 17, including CMV-IM, n =8). The laboratory parameters and inflammatory indices were compared between the groups, and receiver operating characteristic curve analyses were used to determine the optimal cutoff values for score development. Results EBV-IM patients had higher alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels than non-EBV IM patients, whereas the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were lower in EBV-IM patients. Four variables were used for scoring: ALT ≥ 120 U/L, ALP ≥ 200 U/L, NLR ≤ 0.6, and CRP ≤ 2.0 mg/dL, collectively termed the EBV-IM Laboratory Score (EL-Score). A score ≥ 2 predicted EBV-IM with an area under the curve of 0.95 (95% confidence interval: 0.88-1.00), a sensitivity of 0.91, and a specificity of 0.94. Conclusions The EL-Score, based on routinely available laboratory parameters, may enable the early distinction between EBV-IM and non-EBV IM in internal medicine practice.
To evaluate segmentation-free three-dimensional convolutional neural networks (3DCNNs) that derive visual field (VF)-shaped representations from macular optical coherence tomography (OCT) volumes (OCT-based estimated VF; OCT-VF) and to assess their performance in forecasting future Humphrey field analyzer (HFA) measurements and characterizing longitudinal variability in clinical datasets. The 3DCNN models were trained on 129,007 heterogeneous real-world paired OCT-HFA datasets from 13,366 patients (24,313 eyes) across five institutions using 10-fold cross-validation. Forecasting accuracy for the last HFA visit was evaluated using HFA-only forecasts and hybrid models that combined HFA-anchored intercept with longitudinal slopes derived from both OCT-VF and HFA (AOS-AVG). Longitudinal variability was assessed as residual deviations from linear trends using jackknife resampling. The AOS-AVG yielded the lowest forecasting errors across endpoints and significantly reduced mean absolute error compared with HFA-only forecasts (pointwise thresholds: 24-2, 2.45 vs. 2.68 dB; 10-2, 2.44 vs. 2.65 dB; both P < 0.001). OCT-VF showed significantly lower residual variability than HFA (MD: 24-2, 0.79 vs. 1.13 dB; 10-2, 0.87 vs. 1.07 dB; both P < 0.001). Eyes classified as progression-positive by OCT-VF but negative by HFA exhibited greater perimetric variability and steeper HFA MD decline than true-negative eyes. Hybrid forecasting approaches that incorporate OCT-VF-derived slope information can improve prediction of future visual-field outcomes. The lower variability of OCT-VF representations may also enable detection of progression-related signals that remain obscured by perimetric noise in routine longitudinal monitoring. OCT-VF may serve as a complementary tool for precision disease monitoring alongside current automated perimetry.
Subacute sclerosing panencephalitis (SSPE) is a rare, fatal, late complication of measles that develops years after infection, particularly following measles in early childhood. In Japan, measles incidence has declined markedly after improved vaccination coverage and verification elimination; however, recent SSPE epidemiology remains poorly characterized. SSPE cases were identified from the Intractable Disease Treatment Research Project, the Research Project on the Treatment of Children with Specified Chronic Diseases, and Okinawa-specific publications. Measles-related outpatient visits (1986-2007) were estimated by public health center jurisdiction using annual pediatric sentinel surveillance reports and outpatient visit volumes from the Static Survey of Medical Institutions. Ratio estimation with finite population correction was applied. Seventeen SSPE cases were identified, 71% in males. SSPE onset occurred during 1994-2009, at a mean age of 8.1 years. The year of measles infection was known for 14 cases, most frequently 1990. For risk estimation, 16 infections occurring during 1986-2007 were included. SSPE risk was estimated as one per 3944 estimated measles-related outpatient visits (95% CI: 1054-6995). In 1990, SSPE risk was one per 1828 outpatient visits (95% CI: 836-2820). Among infants aged < 1 year, SSPE risk was one per 910 outpatient visits (95% CI: 416-1403). Estimating denominators for medically attended measles cases from sentinel surveillance enabled quantification of SSPE risk during historical outbreaks in Okinawa. The higher risk during infancy emphasizes the long-term consequences of measles transmission and the need to maintain high measles vaccination coverage.
Metastatic castration-resistant prostate cancer (mCRPC) is bone-predominant, requiring objective imaging biomarkers to guide Ra-223 therapy. We evaluated overall metabolic bone volume (OMBV) and overall total bone uptake (OTBU) from bone SPECT/CT as prognostic markers in mCRPC patients treated with Ra-223. Thirty mCRPC patients underwent pre-treatment planar and SPECT/CT bone scintigraphy, with OMBV and OTBU derived using GI-BONE software. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and time to symptomatic skeletal event (TTSE) were secondary. Receiver operating characteristic analysis (Youden index) defined cut-offs for OS and TTSE independently. Treatment response was classified by composite changes in OMBV, OTBU, and bone scan index. OS, OMBV, and OTBU were analyzed by univariate Cox regression as continuous and dichotomized variables. Baseline skeletal burden was substantial (median OMBV 1,191.21 cm3 [IQR 93.80-1,948.01]; median OTBU 9,746.18 [1,280.01- 17,587.11]); 87% had extent of disease grade 3-4. Post-treatment imaging in 24 patients yielded 10 responders (42%) and 14 non-responders (58%), with responder mean OMBV and OTBU reductions of 57% and 68%. Dichotomized baseline OMBV (hazard ratio [HR] 6.0320, 95% confidence interval [CI] 1.6880-21.5546; p < 0.001) and OTBU (HR 9.4492, 95% CI 2.0968-42.5826; p < 0.001) were significant predictors of OS. OMBV and OTBU were not significantly associated with PFS or TTSE. OMBV and OTBU from bone SPECT/CT may provide useful prognostic information in mCRPC patients undergoing Ra-223 therapy, offering objective quantification of skeletal tumor burden using widely available technology. Further validation in larger cohorts is warranted.
Although concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may increase the risk of bowel obstruction or ileus, evidence remains inconclusive. In this context of uncertainty, we examined the frequency and determinants of GLP-1RA discontinuation after hospitalization for bowel obstruction/ileus. We conducted a retrospective cohort study using a nationwide Japanese health insurance claims database (DeSC). We identified individuals aged ≥18 years with type 2 diabetes who were hospitalized for bowel obstruction/ileus between 2016 and 2023 while receiving GLP-1RA therapy. The primary outcome was GLP-1RA discontinuation, defined as no prescription at discharge or within 6 months of discharge. Factors potentially associated with discontinuation were grouped into (1) general factors, (2) severity of bowel obstruction/ileus, and (3) potential therapeutic benefit of GLP-1RA therapy. Risk differences (RDs) for discontinuation were estimated using multivariable linear regression with robust standard errors. GLP-1RAs were discontinued in 86 (43.9%) of the 196 patients analyzed. Multivariable analysis revealed that surgery for bowel obstruction during hospitalization (RD = 32.1%; 95% confidence interval [CI] 11.2% to 53.0%, p = 0.003), longer length of stay (≥15 days vs. ≤7 days; RD = 32.4%; 95% CI 11.2% to 53.5%, p = 0.003), and heart failure (RD = 17.6%; 95% CI 2.1% to 33.2%, p = 0.027) were associated with GLP-1RA discontinuation. Nearly half of the patients discontinued GLP-1RAs after a bowel obstruction/ileus event. While GLP-1RAs were more likely to be discontinued after severe events, their potential therapeutic benefits appeared less frequently considered in continuation decisions.
Deep reinforcement learning (DRL) remains constrained by high computational costs, hindering its practical deployment. While neural network pruning offers a solution for model compression, most existing DRL approaches rely on unstructured pruning. This results in irregular sparse matrices that lack compatibility with standard hardware, offering no tangible real-time acceleration. Furthermore, pruning in DRL is notoriously challenging due to inherent training instability, which often leads to catastrophic performance degradation. To overcome these limitations, we propose a novel framework that integrates dynamic structured pruning with model merging. By periodically merging parallel network instances, our method effectively counteracts the instability triggered by aggressive structural changes, enabling the use of structured pruning directly compatible with general-purpose hardware. Experimental results on continuous control tasks demonstrate that our approach reduces cumulative training FLOPs by up to 72% while maintaining performance competitive with dense baselines across the majority of environments. Additionally, inference profiling confirms an average latency reduction of 16.2%, highlighting the framework's potential for accelerating both the training and deployment of DRL agents. Our code is available at https://github.com/hail-mary/neuron-pruning.
The fabrication of maxillary prostheses in patients with flap-reconstructed maxillary defects continues to present both clinical and technical challenges. Conventional impression techniques can be hazardous and often require multiple adjustments. This report presents a simplified digital approach using 3D scan data of an existing, well-adjusted prosthesis. The previously relined and adjusted prosthesis was scanned with an intraoral scanner, and the 3D surface data were used to print an occlusal record base. After recording the jaw relation, the teeth were arranged, and a functional impression was made at the try-in stage. Finally, the definitive prosthesis was fabricated using heat-cured acrylic resin. The printed record base provided accurate adaptation and minimized the clinical risks associated with conventional impression making. Incorporating the functional impression during the try-in stage further improved the fit and reduced the need for postdelivery adjustments. This technique offers a practical and simplified method for maxillary prosthesis fabrication. Reusing the morphology of a clinically adapted prosthesis eliminates complex digital processing and reduces clinical burden, making it especially useful in settings with limited access to advanced technical support.
Periprosthetic joint infection (PJI) remains a challenging complication after arthroplasty. Intraoperative direct sonication (sonicating explanted components or periprosthetic tissue in the operating room and inoculating processed fluid into blood culture bottles) may improve pathogen detection by disrupting biofilm. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of this test for suspected PJI. We searched CENTRAL, MEDLINE (PubMed), and Embase (ProQuest) on June 10, 2025, without language restrictions, and screened trial registries (ICTRP, ClinicalTrials.gov), organizational websites/guidelines, citations, and conference abstracts. Eligible studies evaluated intraoperative direct sonication against a predefined reference standard and reported or allowed reconstruction of 2×2 data. Two reviewers independently performed study selection, data extraction, and QUADAS-2 risk-of-bias assessment. We synthesized sensitivity and specificity using hierarchical models. We also generated forest plots and an SROC (summary receiver operating characteristic) curve. The search yielded 1,910 records plus 124 from other sources; six studies met the inclusion criteria. After confirming cohort overlap, four unique datasets remained; two studies (n=479) used the MSIS 2011 criteria and were pooled. Risk of bias was generally low; one study had unclear patient selection. Summary sensitivity and specificity were 88.7% (95% CI, 82.9-92.7) and 83.1% (95% CI, 73.5-89.7), respectively. Intraoperative direct sonication showed promising diagnostic performance for suspected PJI, but the current pooled evidence is based on only two studies using the Musculoskeletal Infection Society (MSIS) reference standard. Larger, multicenter studies using consistent reference standards are needed to refine accuracy estimates and define its role in diagnostic pathways.
Singular value decomposition (SVD) of spectroscopic datasets generates multiple components whose physical roles are frequently left uninterpreted. The present study establishes that, in non-centered FTIR spectral matrices dominated by positive intensity contributions, the first singular vector component (λ1) functions empirically as a global intensity-scaling axis, and that the ratio λ2/λ1 provides a scale-independent index of qualitative spectral change arising from solid-state intermolecular interactions. Transmission FTIR spectra of KBr tablets containing indomethacin (INM), cimetidine (CIM), and their mixtures were collected across the full molar composition range at ambient temperature and after pre-heating at 333-453 K. Non-centered SVD was applied to baseline-corrected differential spectra, and λ2/λ1 was monitored as the primary analytical index. Benzamide-aspirin (BAM-ASP) binary mixtures, chemically unrelated to INM and CIM, were analyzed in parallel as a non-interacting reference system to establish the generality of the interpretive principle. In BAM-ASP mixtures, λ2/λ1 varied linearly with molar composition, confirming the scaling-factor role of λ1 in the absence of intermolecular interaction. In INM-CIM mixtures at ambient temperature, λ2/λ1 showed pronounced nonlinearity at CIM-predominant compositions, indicating composition-dependent solid-state interactions already present at room temperature. Thermal SVD analysis of pre-heated equimolar INM-CIM mixtures yielded an inflection temperature of Tp = 395 K, consistent with the DSC eutectic point (384.5 K). The second basis function ψ2 identified bathochromic shifts at 2171 cm-1 (CIM C≡N), 1685 cm-1 (INM carboxyl C=O), and 1586 cm-1 (INM amide C=O), implicating these moieties in the solid-state interaction. Cross-system validation across a non-interacting pair (BAM-ASP) and a co-amorphous-forming pair (INM-CIM) demonstrates that the partitioning of spectral information between λ1 (intensity scaling) and λ2/λ1 (qualitative compositional and interaction information) is an intrinsic property of non-centered SVD applied to positive-dominant spectral matrices. This framework provides a rigorous and broadly applicable basis for detecting and characterizing solid-state intermolecular interactions in pharmaceutical binary systems by FTIR spectroscopy.
Only a limited number of disinfectants are capable of inactivating coccidia oocysts, and in Japan, ortho-phenylphenol-based disinfectants (a combination of cresol and 1,2-dichlorobenzene) are mainly used. However, resistance of oocysts to ortho disinfectants has been reported. Previously, we demonstrated a synergistic enhancement of microbicidal activity by adding food-additive-grade calcium hydroxide with a mean particle size of 10 µm to a quaternary ammonium compound. In the present study, we found that the addition of calcium hydroxide and a quaternary ammonium compound to the ortho disinfectant synergistically and significantly enhanced its oocysticidal effect. Nota de investigación- Efecto sinérgico de la adición de hidróxido de calcio y un compuesto de amonio cuaternario en la degradación de ooquistes de coccidias mediante un desinfectante a base de ortofenilfenol. Solo un número limitado de desinfectantes es capaz de inactivar ooquistes de coccidias; en Japón, se utilizan principalmente desinfectantes a base de ortofenilfenol (una combinación de cresol y 1,2-diclorobenceno). Sin embargo, se ha reportado resistencia de los ooquistes a los ortodesinfectantes. Previamente, se demostró una mejora sinérgica de la actividad microbicida mediante la adición de hidróxido de calcio de grado aditivo alimentario con un tamaño medio de partícula de 10 µm a un compuesto de amonio cuaternario. En el presente estudio, observamos que la adición de hidróxido de calcio y un compuesto de amonio cuaternario al ortodesinfectante mejoró sinérgica y significativamente su efecto oocisticida.
We report a crown-ether-assisted topotactic ion-exchange reaction in the β-pyrochlore oxide KOs2O6, enabling complete extraction of K+ ions under mild aqueous conditions without degradation of the rigid Os-O cage framework. Treatment with 18-crown-6 yields a hydrated protonated phase formally described as (H3O)Os2O6, which is inaccessible by conventional acid-mediated ion-exchange routes. Combined synchrotron X-ray and neutron diffraction analyses show that the cubic Fd3̄m symmetry is preserved after ion exchange. The exchanged phase is characterized by protons bonded to cage oxygen atoms and neutral H2O molecules confined within the Os-O cages with orientational disorder, rather than isolated hydronium ions. Partial dehydration induces a large lattice contraction while maintaining the integrity of the Os-O framework. Heat-capacity analysis reveals the complete suppression of low-energy rattling modes associated with K+ ions, accompanied by a marked reduction of the electronic specific heat coefficient. These results demonstrate crown-ether-assisted ion exchange as an effective soft-chemical strategy for selectively modifying guest species in acid-sensitive inorganic cage oxides.
Cell-free protein synthesis (CFPS) offers rapid protein production, yet yield variability from volume constraints and batch-to-batch differences remains a challenge. Bayesian optimization (BO) identifies optimal points under fixed constraints but does not address constraint variability. Here we use Gaussian process (GP) predictive uncertainty in two complementary directions, lower and upper confidence bounds for exploitation and exploration, to design condition spaces under variable constraints. Closed-loop optimization of two CFPS systems improved green fluorescent protein (GFP) yield beyond the standard condition within a few rounds. For exploitation, we defined a yield assurance space (YAS), a low-uncertainty set of conditions selected to exceed a conservative yield threshold. For exploration, we proposed Pareto front expansion under tightened volume constraints via uncertainty-driven sampling. This approach illustrates how GP predictive uncertainty can support both assured condition design and targeted exploration under altered constraints.
Traumatic uterine rupture is a rare and easily overlooked condition. Most cases of traumatic uterine rupture have been reported to occur in pregnancy. Here, we reported the case of a 14-year-old nonpregnant girl who presented to the emergency department with hemorrhagic shock due to multiple traumatic injuries after falling from a height during a suicide attempt. Initial resuscitation stabilized the patient's vital signs. A whole-body computed tomography (CT) scan revealed bilateral pneumothorax, multiple rib fractures, a grade III renal injury, a liver injury, and an unstable pelvic fracture. Although a poorly enhancing area was identified in the anterior wall of the uterine body on the initial CT scan, uterine rupture was not included in the active differential diagnosis at that time, as clinical priorities were directed toward other life-threatening injuries. Persistent unexplained hemoperitoneum led to a repeat CT scan performed on hospital day 4 and prompted magnetic resonance imaging on hospital day 7, which confirmed complete full-thickness rupture of the anterior uterine wall. Laparoscopic uterine repair was performed on hospital day 14. This case highlighted the importance of not dismissing uterine CT scan findings as incidental in female patients with unstable pelvic fractures, even when pregnancy has been excluded, and of considering pelvic magnetic resonance imaging scans when hemoperitoneum persists without a fully identified source. We also discussed the cognitive processes-including anchoring bias, confirmation bias, and task fixation (search satisficing)-that contributed to the delayed recognition of this diagnosis.
Addition of the long-acting muscarinic antagonist umeclidinium (UMEC) to the inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination fluticasone furoate/vilanterol (FF/VI) improved lung function in adults with uncontrolled moderate to severe asthma in the CAPTAIN (Clinical study of Asthma Patients receiving Triple therapy through A single INhaler) study; however, the impact on symptoms requires further investigation. We sought to evaluate the effect of adding UMEC to FF/VI on asthma symptoms. The CAPTAIN study was a phase IIIA, randomized, controlled, 24- to 52-week study of patients with uncontrolled moderate to severe asthma despite ICS/LABA receiving once-daily single-inhaler FF/VI (100/25 or 200/25 μg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, or 200/62.5/25 μg). Here, we compare the effect of pooled FF/UMEC 62.5/VI (100/62.5/25 and 200/62.5/25 μg) versus FF/VI (100/25 and 200/25 μg) on symptom control using prespecified analyses of change from baseline in Evaluating Respiratory Symptoms in Asthma (E-RS: Asthma) total and domain scores, and proportion of patients meeting an E-RS: Asthma total score responder threshold. We also performed post hoc analyses assessing the impact of baseline type 2 inflammation status on treatment response. Least-squares mean (95% CI) reductions from baseline in E-RS: Asthma total score exceeded the minimum clinically important difference (-2.0 units) and were numerically greater with FF/UMEC 62.5/VI (-2.89 [-3.15 to -2.64]; n = 814) versus FF/VI (-2.47 [-2.73 to -2.22]; n = 813). The proportion of responders (45% [n = 360] vs 41% [n = 327]) and odds of response (odds ratio, 1.18 [95% CI, 0.96 to 1.45]) were numerically greater with FF/UMEC 62.5/VI versus FF/VI. Similar trends were observed irrespective of type 2 status. Patients with symptomatic asthma may benefit from optimized treatment interventions, such as adding a long-acting muscarinic antagonist to ICS/LABA.
Gender equity has become an important issue in academic medicine, but data on gender distribution in subspecialty medical societies remain limited. We analyzed gender distribution in membership, leadership positions, and conference participation in the Japanese Society for Hypothalamic and Pituitary Tumors (JSHPT). Membership data as of March 2025 (n = 860) were examined, and gender distribution among speakers and session chairs at the 36th Annual Meeting of the JSHPT was evaluated using the publicly available abstract book. Among all members, 128 (14.9%) were women. Women accounted for 6.6% of councilors and 5.6% of board members and auditors, and only one woman has served as Annual Meeting president among the first 36 annual meetings. At the 36th Annual Meeting, women represented 18.6% of presenters in general oral sessions, but only 5.0% of session chairs in general oral sessions and 3.7% of chairs in other sessions. Women also accounted for 36.4% of members with less than 1 year of membership. These findings suggest that, although women remain underrepresented in leadership positions within the society, female participation may be increasing among newer members, and women are actively participating as conference presenters. Continued efforts to increase opportunities for women to serve as session chairs and to encourage qualified women to apply for councilor positions may contribute not only to a more equitable academic environment, but also to the vitality and future leadership of the field.
Although positive associations between fewer remaining teeth and an increased risk of various systemic diseases have been reported, the precise dose-response relationship has not been fully clarified. This study aimed to evaluate the non-linearity of the dose-response association between the number of lost teeth and the risk of cardiovascular diseases among middle-aged adults. This retrospective cohort study, with over 5 years of follow-up, was based on medical claims and health check-up data. Participants were adults aged 40-64 in Japan. The outcome was the incidence of cardiovascular diseases. Exposure variables were the number of lost teeth, which was modeled using a restricted cubic spline. A Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals. Among the 551,386 participants (mean age = 50.0 years [SD = 6.7], male = 52.0%), the incidence rate of cardiovascular diseases was 0.70 per 100 person-years. A significant non-linear dose-response association was observed between the number of lost teeth and cardiovascular disease risk (p = 0.004). Although the risk increased with greater tooth loss, the dose-response curve bent at around four lost teeth, with an HR of 1.09 (1.05-1.14) at four teeth lost and 1.21 (1.08-1.37) at 27 teeth lost (reference: "no tooth loss"). These findings suggest no clear threshold exists in the non-linear dose-response association between tooth loss and cardiovascular disease risk. Comprehensive public health strategies to prevent periodontal diseases and dental caries are essential throughout life to minimize tooth loss and its systemic consequences. This retrospective cohort study of 551,386 middle-aged adults found a significant non-linear dose-response association between tooth loss and the risk of cardiovascular diseases. Cardiovascular disease risk increased as the number of lost teeth increased; however, the dose-response curve showed an inflection at around four lost teeth, with no clear threshold observed in the association between tooth loss and cardiovascular disease risk.