Association between oral frailty and Prevotella percentage in the oral microbiota of community-dwelling older adults who participated in the CHEER Iwamizawa project, Japan.

BACKGROUND: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified. OBJECTIVE: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults. METHODS: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis. RESULTS: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576). CONCLUSION: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline.

First molecular characterization of Burkholderia mallei strains isolated from horses in Mongolia.

Glanders, a highly contagious and often fatal disease affecting equids, is caused by Burkholderia mallei. Although sporadic cases of equine glanders have recently been documented in Mongolia, genome sequencing and molecular studies of the bacteria within this region are lacking. This study provided the first molecular characterization of B. mallei isolated from four native Mongolian horses from two different provinces in 2019 and 2022 by applying whole-genome sequencing with two SNP types (previously developed genotyping with 15 SNP markers that provide global coverage of the B. mallei population and the core genome coding SNP typing developed in this study). The Mongolian isolates were located within the L3B1 cluster, which was previously associated with the V-120 strain from Russia. Within the L3B1 cluster shared by neighboring countries, they were in a unique subbranch. In this study, specific SNP markers unique to the Mongolian strains were identified to track these strains using a high-resolution melting analysis (HRMA). This study revealed the unique phylogenetic background of Mongolian strains isolated from the eastern part of Mongolia. HRMA specific to the Mongolian subbranch may contribute to the molecular epidemiological monitoring of glanders in Mongolia and surrounding countries.

Sub-photon accuracy noise reduction of a single shot coherent diffraction pattern with an atomic model trained autoencoder.

Single-shot imaging with femtosecond X-ray lasers is a powerful measurement technique that can achieve both high spatial and temporal resolution. However, its accuracy has been severely limited by the difficulty of applying conventional noise-reduction processing. This study uses deep learning to validate noise reduction techniques, with autoencoders serving as the learning model. Focusing on the diffraction patterns of nanoparticles, we simulated a large dataset treating the nanoparticles as composed of many independent atoms. Three neural network architectures are investigated: neural network, convolutional neural network and U-net, with U-net showing superior performance in noise reduction and subphoton reproduction. We also extended our models to apply to diffraction patterns of particle shapes different from those in the simulated data. We then applied the U-net model to a coherent diffractive imaging study, wherein a nanoparticle in a microfluidic device is exposed to a single X-ray free-electron laser pulse. After noise reduction, the reconstructed nanoparticle image improved significantly even though the nanoparticle shape was different from the training data, highlighting the importance of transfer learning.

The ratio of intratumoral CD15+ neutrophils to CD8+ lymphocytes predicts recurrence in patients with gastric cancer after curative resection.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is an independent prognostic indicator of various cancers. AIMS: In this study, we aimed to investigate the prognostic relevance of the intratumoral immune cell balance in gastric cancer. METHODS AND RESULTS: The study included 82 patients who underwent curative resection for gastric cancer. The intratumoral cluster of differentiation (CD) 15- and CD8-positive cells were evaluated using immunohistochemical staining. Additionally, clinicopathological factors and prognoses were analyzed. Patients with high intratumoral CD15/CD8 ratios had significantly lower overall survival (OS) and relapse-free survival (RFS) compared to those with low CD15/CD8 ratios (p = .0026 and p < .0001, respectively). Additionally, a high CD15/CD8 ratio was associated with lymph node metastasis (p = .019). Patients with high NLR had a significantly lower RFS than those with low NLR (p = .0050). Multivariate analysis revealed that the intratumoral CD15/CD8 ratio, NLR, and venous invasion were independent prognostic indicators of RFS (CD15/CD8 ratio: p < .001, hazard ratio (HR) = 14.7, 95% confidence interval (CI) = 3.8-56.8; NLR: p = .010, HR = 5.4, 95% CI = 1.5-19.6; venous invasion: p = .005, HR = 7.4, 95% CI = 1.8-29.7). CONCLUSION: In summary, we found that the intratumoral CD15/CD8 ratio is an independent prognostic factor following gastric cancer resection and its increase is associated with lymph node metastasis and microscopic lymph vessel invasion. Immunological evaluation with additional aspects of innate immunity may be useful in predicting cancer prognosis.

Synthesis of Few-Layer Hexagonal Boron Nitride for Magnetic Tunnel Junction Application.

Hexagonal boron nitride (hBN), a wide-gap two-dimensional (2D) insulator, is an ideal tunneling barrier for many applications because of the atomically flat surface, high crystalline quality, and high stability. Few-layer hBN with a thickness of 1-2 nm is an effective barrier for electron tunneling, but the preparation of few-layer hBN relies on mechanical exfoliation from bulk hBN crystals. Here, we report the large-area growth of few-layer hBN by chemical vapor deposition on ferromagnetic Ni-Fe thin films and its application to tunnel barriers of magnetic tunnel junction (MTJ) devices. Few-layer hBN sheets mainly consisting of two to three layers have been successfully synthesized on a Ni-Fe catalyst at a high growth temperature of 1200 °C. The MTJ devices were fabricated on as-grown hBN by using the Ni-Fe film as the bottom ferromagnetic electrode to avoid contamination and surface oxidation. We found that trilayer hBN gives a higher tunneling magnetoresistance (TMR) ratio than bilayer hBN, resulting in a high TMR ratio up to 10% at ∼10 K.

Ultrastrong magnon-magnon coupling and chiral spin-texture control in a dipolar 3D multilayered artificial spin-vortex ice.

Strongly-interacting nanomagnetic arrays are ideal systems for exploring reconfigurable magnonics. They provide huge microstate spaces and integrated solutions for storage and neuromorphic computing alongside GHz functionality. These systems may be broadly assessed by their range of reliably accessible states and the strength of magnon coupling phenomena and nonlinearities. Increasingly, nanomagnetic systems are expanding into three-dimensional architectures. This has enhanced the range of available magnetic microstates and functional behaviours, but engineering control over 3D states and dynamics remains challenging. Here, we introduce a 3D magnonic metamaterial composed from multilayered artificial spin ice nanoarrays. Comprising two magnetic layers separated by a non-magnetic spacer, each nanoisland may assume four macrospin or vortex states per magnetic layer. This creates a system with a rich 16N microstate space and intense static and dynamic dipolar magnetic coupling. The system exhibits a broad range of emergent phenomena driven by the strong inter-layer dipolar interaction, including ultrastrong magnon-magnon coupling with normalised coupling rates of Δ f ν = 0.57 , GHz mode shifts in zero applied field and chirality-control of magnetic vortex microstates with corresponding magnonic spectra.

The Association between COVID-19-Related Discrimination and Probable Post-Traumatic Stress Disorder among Patients with COVID-19 in Sapporo, Japan.

BackgroundDisasters such as earthquakes, terrorism, and pandemics have triggered post-traumatic stress disorder (PTSD), and discrimination against the affected individuals has been linked to the development of PTSD. However, there is limited evidence regarding the association between discrimination against coronavirus disease 2019 (COVID-19) patients and probable PTSD in Japan.MethodsWe conducted a cross-sectional study utilizing a web-based questionnaire targeting individuals who had contracted the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sapporo City. A total of 4247 individuals with laboratory-confirmed SARS-CoV-2 infection spanning from February 2020 to February 2022 completed the questionnaire (response rate: 15.9%). Probable PTSD was measured using the three-item Posttraumatic Diagnostic Scale. The stratified exact logistic regression was applied to calculate the odds ratios (OR) of probable PTSD for COVID-19-related discrimination with adjusted factors.ResultsThis study included 3626 patients who had a history of SARS-CoV-2 infection. Among them, 321 patients (8.9%) experienced COVID-19-related discrimination. The prevalence of probable PTSD was 19.6% (63/321) among the patients who experienced COVID-19-related discrimination, and 4.6% (152/3305) among those who had not encountered such discrimination. The adjusted OR of COVID-19-related discrimination for probable PTSD was 4.68 (95% confidence interval [95% CI], 3.36-6.53). The population attributable fraction of probable PTSD attributable to COVID-19-related discrimination among COVID-19 patients was estimated to be 23.4% (95% CI, 21.5-25.3).ConclusionThe comprehensive epidemiological survey of COVID-19 patients in Japan showed that COVID-19-related discrimination was associated with a higher prevalence of probable PTSD. Mitigating discrimination could be helpful to attenuate PTSD in future pandemics.

Microbial Detoxification of Sediments Underpins Persistence of Zostera marina Meadows.

Eelgrass meadows have attracted much attention not only for their ability to maintain marine ecosystems as feeding grounds for marine organisms but also for their potential to store atmospheric and dissolved CO2 as blue carbon. This study comprehensively evaluated the bacterial and chemical data obtained from eelgrass sediments of different scales along the Japanese coast to investigate the effect on the acclimatization of eelgrass. Regardless of the eelgrass habitat, approximately 1% Anaerolineales, Babeliales, Cytophagales, and Phycisphaerales was present in the bottom sediment. Sulfate-reducing bacteria (SRB) were present at 3.69% in eelgrass sediment compared to 1.70% in bare sediment. Sulfur-oxidizing bacteria (SOB) were present at 2.81% and 1.10% in the eelgrass and bare sediment, respectively. Bacterial composition analysis and linear discriminant analysis revealed that SOB detoxified H2S in the eelgrass meadows and that the larger-scale eelgrass meadows had a higher diversity of SOB. Our result indicated that there were regional differences in the system that detoxifies H2S in eelgrass meadows, either microbial oxidation mediated by SOB or O2 permeation via the physical diffusion of benthos. However, since bacterial flora and phylogenetic analyses cannot show bias and/or causality due to PCR, future kinetic studies on microbial metabolism are expected.

Exchange Bias Induced by the Spin-Glass-Like State in a Te-Rich FeGeTe van der Waals Ferromagnet.

We have experimentally investigated the mechanism of the exchange bias in 2D van der Waals (vdW) ferromagnets by means of the anomalous Hall effect (AHE) together with the dynamical magnetization property. The temperature dependence of the AC susceptibility with its frequency response indicates a glassy transition of the magnetic property for the Te-rich FeGeTe vdW ferromagnet. We also found that the irreversible temperature dependence in the anomalous Hall voltage follows the de Almeida-Thouless line. Moreover, the freezing temperature of the spin-glass-like phase is found to correlate with the disappearance temperature of the exchange bias. These important signatures suggest that the emergence of magnetic exchange bias in the 2D van der Waals ferromagnets is induced by the presence of the spin-glass-like state in FeGeTe. The unprecedented insights gained from these findings shed light on the underlying principles governing exchange bias in vdW ferromagnets, contributing to the advancement of our understanding.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Real-world experience with eculizumab and switching to ravulizumab for generalized myasthenia gravis.

OBJECTIVE: Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real-world experience. METHODS: Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG-ADL. We performed a questionnaire of preference between eculizumab and ravulizumab. RESULTS: Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG-ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab. INTERPRETATION: Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings.

New-onset egg allergy in an adult: A case report.

Most adult cases of hen's egg allergy are carried over from childhood, and new-onset adult cases are rare. Such cases may result from cross-reactivity or sensitization by inhalation. Here we present a rare case of adult-onset egg allergy due to monosensitization to ovalbumin (Gal d 2) with an unclear sensitization pathway. A 27-year-old woman developed recurrent gastrointestinal symptoms after ingestion of raw and under-cooked eggs. She had never suffered from atopic dermatitis or food allergies. She had never kept birds as pets and had no history of exposure to egg allergens. Prick to prick testing was positive only with raw egg white. Specific IgE testing revealed monosensitization to Gal d 2. She was advised to avoid raw and undercooked eggs and her symptoms resolved. In the management of adult-onset egg allergy, evaluation of allergen components will lead to appropriate elimination guidelines, and investigation of sensitization pathways may help identify the cause of this disease.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

BACKGROUND: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. METHODS: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. RESULTS: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. CONCLUSION: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Relationship between the Tortuosity of the Extracranial Internal Carotid and Vertebral Arteries on Magnetic Resonance Imaging/Angiography and Vascular Risk Factors in a Japanese Population.

Objective We aimed to investigate the relationship between tortuosity of the extracranial internal carotid artery (ICA) or vertebral artery (VA) and vascular risk factors among residents of Asahikawa, northeast Japan. Methods We retrospectively surveyed participants of "brain dock" medical brain checkups, which involved magnetic resonance imaging and angiography. We measured the tortuosity of the ICA and VA, and evaluated vascular risk factors based on medical interviews, questionnaires, and medical records. Results A total of 218 participants were enrolled in the study. ICA tortuosity (right and left) was significantly correlated with age [odds ratio (OR): 2.452, 95% confidence interval (CI): 1.695-3.548, p<0.001]. A more pronounced correlation was observed in females than in males (OR: 1.678, 95% CI: 1.004-2.807, p=0.048). VA tortuosity (right and left) was significantly correlated with age (OR: 1.786, 95% CI: 1.250-2.550, p=0.001) and smoking history (OR: 2.140, 95% CI: 1.235-3.707, p=0.007), and was more pronounced in females than in males (OR: 1.864, 95% CI: 1.107-3.137, p=0.019). Conclusion ICA tortuosity was correlated with age, while VA tortuosity was correlated with age and smoking history. ICA and VA tortuosity were more pronounced in females than in males.

Traditional and Social Media Usage Associated With COVID-19 Vaccine Uptake in Sapporo, Japan.

This study aimed to determine the relationship between specific information source usage and uptake of the coronavirus disease 2019 (COVID-19) vaccine. We analyzed 3348 participants aged 20 to 65 years who were not diagnosed with COVID-19 in a case-control study in Sapporo, Japan. The most prevalent information source on COVID-19 was television (TV; 87.8%), followed by online news sites (74.3%), newspapers (38.7%), websites of public institutions (30.9%), and families (29.7%). Multivariate logistic regression showed that the adjusted odds ratios of incompletion of second vaccinations for users of TV and newspaper to gather COVID-19 information were 0.31 and 0.32, respectively, whereas those for users of books, commercial video sites, Facebook, and "personal blog or bulletin board system" were 3.34, 2.22, 2.36, and 4.81, respectively. Social media use among older or male participants was associated with lower vaccine uptake.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.