Blue-Detuned Magneto-optical Trap of CaF Molecules.

A key method to produce trapped and laser-cooled molecules is the magneto-optical trap (MOT), which is conventionally created using light red detuned from an optical transition. In this work, we report a MOT for CaF molecules created using blue-detuned light. The blue-detuned MOT (BDM) achieves temperatures well below the Doppler limit and provides the highest densities and phase-space densities reported to date in CaF MOTs. Our results suggest that BDMs are likely achievable in many relatively light molecules including polyatomic ones, but our measurements suggest that BDMs will be challenging to realize in substantially heavier molecules due to sub-mK trap depths. In addition to record temperatures and densities, we find that the BDM substantially simplifies and enhances the loading of molecules into optical tweezer arrays, which are a promising platform for quantum simulation and quantum information processing. Notably, the BDM reduces molecular number requirements ninefold compared to a conventional red-detuned MOT, while not requiring additional hardware. Our work therefore substantially simplifies preparing large-scale molecular tweezer arrays, which are a novel platform for simulation of quantum many-body dynamics and quantum information processing with molecular qubits.

Association between education and disability-free life expectancy among Japanese older people: The Ohsaki Cohort 2006 study.

BACKGROUND: Higher education level is associated with longer disability-free life expectancy (DFLE). However, evidence is scarce regarding factors that can contribute to eliminating inequality in DFLE according to education level. This study aimed to clarify the association between education and DFLE and estimate whether DFLE in people with lower education may increase to the same level as that in people with higher education through social participation. METHODS: We analyzed data from 13,849 Japanese people aged 65 years and older who participated in a 13-year prospective study. At baseline, we collected information on education levels (low, middle, or high) and social participation. DFLE was defined as the average duration people expect to live without disability. To calculate DFLE for each education level group, the multistate life table method was employed using a Markov model. RESULTS: At the age of 65 years, DFLE (95 % confidence interval [CI]) in women with low education was 21.3 years (20.8-21.8) without social participation and 24.3 (23.8-24.9) with social participation. In the middle education group, DFLE was 22.1 (21.6-22.6) without social participation and 25.0 (24.6-25.5) with social participation. In the high education group, DFLE was 22.1 (21.5-22.8) without social participation and 25.5 (25.0-26.0) with social participation. Similar results were found for men. CONCLUSIONS: DFLE in people with low or middle education with social participation was almost the same as that in those with high education with social participation, suggesting the possibility that disparities in DFLE by education level could be offset by promoting social participation in older adults.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

On-demand entanglement of molecules in a reconfigurable optical tweezer array.

Entanglement is crucial to many quantum applications, including quantum information processing, quantum simulation, and quantum-enhanced sensing. Because of their rich internal structure and interactions, molecules have been proposed as a promising platform for quantum science. Deterministic entanglement of individually controlled molecules has nevertheless been a long-standing experimental challenge. We demonstrate on-demand entanglement of individually prepared molecules. Using the electric dipolar interaction between pairs of molecules prepared by using a reconfigurable optical tweezer array, we deterministically created Bell pairs of molecules. Our results demonstrate the key building blocks needed for quantum applications and may advance quantum-enhanced fundamental physics tests that use trapped molecules.

Reproductive Factors and Endometrial Cancer Risk Among Women.

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries. Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk. Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023. Exposures: Reproductive factors were assessed using a questionnaire in each cohort. Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs. Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk. Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

Bichromatic Imaging of Single Molecules in an Optical Tweezer Array.

We report on a novel bichromatic fluorescent imaging scheme for background-free detection of single CaF molecules trapped in an optical tweezer array. By collecting fluorescence on one optical transition while using another for laser cooling, we achieve an imaging fidelity of 97.7(2)% and a nondestructive detection fidelity of 95.5(6)%. Notably, these fidelities are achieved with a modest photon budget, suggesting that the method could be extended to more complex laser-coolable molecules with less favorable optical cycling properties. We also report on a framework and new methods to characterize various loss mechanisms that occur generally during fluorescent detection of trapped molecules, including two-photon decay and admixtures of higher excited states that are induced by the trapping light. In particular, we develop a novel method to dispersively measure transition matrix elements between electronically excited states. The method could also be used to measure arbitrarily small Franck-Condon factors between electronically excited states, which could significantly aid in ongoing efforts to laser cool complex polyatomic molecules.

Sleep duration and the risk of endometrial cancer incidence among Japanese women: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

OBJECTIVE: Endometrial cancer has been increasing worldwide, and is one of the most common female hormone-related cancers. The purpose of this study was to examine the association between sleep duration and risk of endometrial cancer among Japanese women. METHODS: We conducted a pooled analysis of two prospective studies conducted among residents of Miyagi Prefecture in rural northern Japan. A total of 36,537 women aged 40-79 years participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994. The participants responded to a self-administered questionnaire that including sleep duration. Sleep duration was assessed at the baseline using a self-administered questionnaire. The participants entered the mean integer number representing the hours of sleep taken per day during the previous year. We divided the participants into three groups (≤6 h, 7-8 h, or ≥9 h). Cox proportional hazards regression analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for endometrial cancer incidence. RESULTS: During 745,993 person-years of follow-up, we identified 146 incident cases of endometrial cancer. Compared with women who slept 7-8 h per day, the multivariate HR (95%CI) for endometrial cancer incidence was 1.07 (0.72-1.60) for those who slept 6 h or less, and 1.05 (0.57-1.93) for those who slept 9 h or longer (p-trend=0.57). CONCLUSION: In analysis of two population -based prospective cohort studies conducted among Japanese women, we found no significant associations between sleep duration and the incidence of endometrial cancer.

Association between psychological distress and disability-free life expectancy in the older Japanese adults.

BACKGROUND: Our study aimed to investigate the association between psychological distress and disability-free life expectancy (DFLE). METHODS: In 2006, a cohort study was conducted of 12,365 Japanese individuals aged ≥65 years, who were followed-up for 13 years. Psychological distress was measured using the Kessler 6-item psychological distress scale and was categorized into no (0-4), mild (5-9), moderate (10-12), and serious distress (13-24). The number of participants was 1277 (22.4 %) for mild distress, 330 (5.8 %) for moderate, and 208 (3.6 %) for serious in men, and was 1635 (24.6 %), 467 (7.0 %), and 384 (5.8 %) in women. Sex-specific DFLE was defined as the mean years a person could expect to live without disability and calculated by Interpolated Markov Chain (IMaCh) software. RESULTS: Compared to no distress, DFLE loss per person was 1.21, 2.61, and 4.43 years for mild, moderate, and serious distress respectively in men. At population level, DFEL loss (i.e., DFLE loss per person×number of participants) was 1545.17, 861.30, and 921.44 years for mild, moderate, and serious distress respectively in men. Accordingly, 46.4 % of the total DFLE loss was attributable to mild distress, 25.9 % to moderate, and 27.7 % to serious in men. Similarly, the results were 42.2 %, 25.4 %, and 32.4 % in women. LIMITATIONS: Psychological distress was measured only once at baseline, and 2409 participants were excluded from the analysis because of missing data on exposure. CONCLUSIONS: At population level, almost half of the total DFLE loss could be attributable to mild distress, underscoring the importance of population strategy for all levels of distress in promoting healthy aging.

Association between dairy intake and risk of incident dementia: the Ohsaki Cohort 2006 Study.

PURPOSE: To investigate the association between dairy intake and risk of incident dementia in older adults. METHODS: A longitudinal analysis of dairy intake with incident dementia was conducted using a cohort study of 11,637 non-disabled Japanese older adults aged ≥ 65 years followed-up for up to 5.7 years (mean: 5.0 years). Data on milk, yogurt, and cheese intake were collected using a validated food frequency questionnaire. Total dairy intake was calculated as the sum of the daily intake of milk, yogurt, and cheese, which was sex-specifically categorized in quintiles. Dementia cases were retrieved from the public long-term care insurance database. Cox proportional hazards model was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident dementia. RESULTS: During 58,013 person-years of follow-up, 946 persons developed dementia. In the primary analysis, compare to the lowest quintile of total dairy intake, Q2 showed a slightly decreased incident dementia risk (HR for Q2 vs Q1: 0.90, 95% CI: 0.73-1.10) after fully adjusted for demographic, lifestyle, psychological, and nutritional factors, and diseases history. Compared to non-consumers of milk, those consuming for 1-2 times/month showed a lower risk of incident dementia (fully-adjusted HR: 0.76, 95% CI: 0.57-1.02). Daily yogurt consumers also had a reduced risk (fully-adjusted HR: 0.89, 95% CI: 0.74-1.09). But daily cheese consumers showed an increased risk of dementia (fully-adjusted HR: 1.28, 95% CI: 0.91-1.79). In the sensitivity analysis where we excluded dementia cases ascertained in the first 2 years, results were consistent with those from the primary analysis and we further found that yogurt intake might be inversely associated with dementia risk (p for trend = 0.025). CONCLUSION: Low total dairy intake or low milk intake frequency might be associated with lower incident dementia risk, however daily cheese consumers seemed to have an increased risk. Our study also suggested a possible inverse dose-response association between yogurt consumption and dementia risk, but further studies are needed to confirm whether this benefit was from yogurt intake itself or as a part of a healthy dietary pattern.

Psychological distress in later life and incident dementia: The Ohsaki Cohort 2006 Study.

BACKGROUND: The role of reverse causation in the association between psychological distress and incident dementia remains unclear. We investigated whether psychological distress is a risk factor for, or prodromal symptom of, dementia. METHODS: A longitudinal analysis of psychological distress with incident dementia was conducted among 12,076 Japanese individuals (age ≥65 years) followed for 5.7 years. Psychological distress was measured using the Kessler 6-item psychological distress scale (0-24 points) at baseline, with participants categorized into four psychological distress groups: no (0-4), mild (5-9), moderate (10-12), and serious (13-24). Dementia cases were retrieved from the public Long-term Care Insurance database. Cox proportional hazards model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95%CIs) for incident dementia. Stratified analysis was conducted by cognitive function (higher or lower) at baseline. RESULTS: During 60,240 person-years of follow-up, 997 individuals developed dementia. A dose-response association was found between psychological distress and dementia; however, the stratified analysis indicated that this association depended on cognitive function at baseline. Among those with higher cognitive function at baseline, a significantly elevated dementia risk was observed only for serious psychological distress (HR: 2.04, 95%CI: 1.24-3.36). Among those with lower cognitive function, both moderate (HR: 1.30, 95%CI: 1.00-1.68) and serious (HR: 1.79, 95%CI: 1.37-2.34) psychological distress showed an increased dementia risk. CONCLUSION: The association between late-life psychological distress and incident dementia is partly explained by reserve causation, whereby mild and moderate distress could be a prodromal symptom of dementia.

Transcription factor Nkx2-3 maintains the self-renewal of hematopoietic stem cells by regulating mitophagy.

Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy, exhibiting a unique capacity to self-renew and differentiate into all blood cells throughout the lifetime. However, how to prevent HSC exhaustion during long-term hematopoietic output is not fully understood. Here, we show that the homeobox transcription factor Nkx2-3 is required for HSC self-renewal by preserving metabolic fitness. We found that Nkx2-3 is preferentially expressed in HSCs with excessive regenerative potential. Mice with conditional deletion of Nkx2-3 displayed a reduced HSC pool and long-term repopulating capacity as well as increased sensitivity to irradiation and 5-flurouracil treatment due to impaired HSC quiescence. In contrast, overexpression of Nkx2-3 improved HSC function both in vitro and in vivo. Furthermore, mechanistic studies revealed that Nkx2-3 can directly control the transcription of the critical mitophagy regulator ULK1, which is essential for sustaining metabolic homeostasis in HSCs by clearing activated mitochondria. More importantly, a similar regulatory role of NKX2-3 was observed in human cord blood-derived HSCs. In conclusion, our data demonstrate an important role of the Nkx2-3/ULK1/mitophagy axis in regulating the self-renewal of HSCs, therefore providing a promising strategy to improve the function of HSCs in the clinic.

Oxymatrine boosts hematopoietic regeneration by modulating MAPK/ERK phosphorylation after irradiation-induced hematopoietic injury.

Hematopoietic toxicity due to ionizing radiation (IR) is a leading cause of death in nuclear incidents, occupational hazards, and cancer therapy. Oxymatrine (OM), an extract originating from the root of Sophora flavescens (Kushen), possesses extensive pharmacological properties. In this study, we demonstrate that OM treatment accelerates hematological recovery and increases the survival rate of mice subjected to irradiation. This outcome is accompanied by an increase in functional hematopoietic stem cells (HSCs), resulting in enhanced hematopoietic reconstitution abilities. Mechanistically, we observed significant activation of the MAPK signaling pathway, accelerated cellular proliferation, and decreased cell apoptosis. Notably, we identified marked increases in the cell cycle transcriptional regulator Cyclin D1 (Ccnd1) and the anti-apoptotic protein BCL2 in HSCs after OM treatment. Further investigation revealed that the expression of Ccnd1 transcript and BCL2 levels were reversed upon specific inhibition of ERK1/2 phosphorylation, effectively negating the rescuing effect of OM. Moreover, we determined that targeted inhibition of ERK1/2 activation significantly counteracted the regenerative effect of OM on human HSCs. Taken together, our results suggest a crucial role for OM in hematopoietic reconstitution following IR via MAPK signaling pathway-mediated mechanisms, providing theoretical support for innovative therapeutic applications of OM in addressing IR-induced injuries in humans.

Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.

Hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have robust self-renewal potential, which is responsible for sustaining normal and malignant hematopoiesis, respectively. Although considerable efforts have been made to explore the regulation of HSC and LSC maintenance, the underlying molecular mechanism remains obscure. Here, we observe that the expression of thymocyte-expressed, positive selection-associated 1 (Tespa1) is markedly increased in HSCs after stresses exposure. Of note, deletion of Tespa1 results in short-term expansion but long-term exhaustion of HSCs in mice under stress conditions due to impaired quiescence. Mechanistically, Tespa1 can interact with CSN subunit 6 (CSN6), a subunit of COP9 signalosome, to prevent ubiquitination-mediated degradation of c-Myc protein in HSCs. As a consequence, forcing c-Myc expression improves the functional defect of Tespa1-null HSCs. On the other hand, Tespa1 is identified to be highly enriched in human acute myeloid leukemia (AML) cells and is essential for AML cell growth. Furthermore, using MLL-AF9-induced AML model, we find that Tespa1 deficiency suppresses leukemogenesis and LSC maintenance. In summary, our findings reveal the important role of Tespa1 in promoting HSC and LSC maintenance and therefore provide new insights on the feasibility of hematopoietic regeneration and AML treatment.

Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury.

Hematopoietic stem cells (HSCs) possess great self-renewal and multidirectional differentiation abilities, which contribute to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, the precise regulation of hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using an MC5R knockout mouse model, we observed that it is not essential for steady-state hematopoiesis. Interestingly, the levels of α-melanocyte stimulating hormone (α-MSH), an important subtype of melanocortin, were elevated in the serum and bone marrow, and the expression of MC5R was upregulated in HSPCs from mice after irradiation. MC5R deficiency aggravates irradiation-induced myelosuppression because of impaired proliferation and reconstitution of HSCs. Further investigation revealed that the melanocortin/MC5R axis regulates the proliferation of HSCs by activating the PI3K/AKT and MAPK pathways. More importantly, α-MSH treatment can significantly accelerate hematopoietic recovery in irradiated mice. In conclusion, our data demonstrate that the melanocortin/MC5R axis plays a crucial role in regulating HSC proliferation under stress, thus providing a promising strategy to promote hematopoietic regeneration when suffering from injury.

Akt-mediated mitochondrial metabolism regulates proplatelet formation and platelet shedding post vasopressin exposure.

BACKGROUND: Platelet shedding from mature megakaryocytes (MKs) in thrombopoiesis is the critical step for elevating circulating platelets fast and efficiently, however, the underlying mechanism is still not well-illustrated, and the therapeutic targets and candidates are even less. OBJECTIVES: In order to investigate the mechanisms for platelet shedding after vasopressin treatment and find new therapeutic targets for thrombocytopenia. METHODS: Platelet production was evaluated both in vivo and in vitro after arginine vasopressin (AVP) administration. The underlying biological mechanism of AVP-triggered thrombopoiesis were then investigated by a series of molecular and bioinformatics techniques. RESULTS: it is observed that proplatelet formation and platelet shedding in the final stages of thrombopoiesis promoted by AVP, an endogenous hormone, can quickly increases peripheral platelets. This rapid elevation is thus able to speed up platelet recovery after radiation as expected. The mechanism analysis reveal that proplatelet formation and platelet release from mature MKs facilitated by AVP is mainly mediated by Akt-regulated mitochondrial metabolism. In particular, phosphorylated Akt regulates mitochondrial metabolism through driving the association of hexokinase-2 with mitochondrial voltage dependent anion channel-1 in AVP-mediated thrombopoiesis. Further studies suggest that this interaction is stabilized by IκBα, the expression of which is controlled by insulin-regulated membrane aminopeptidase. CONCLUSION: these data demonstrate that phosphorylated Akt-mediated mitochondrial metabolism regulates platelet shedding from MKs in response to AVP, which will provide new therapeutic targets and further drug discovery clues for thrombocytopenia treatment.

How Long Would You Like to Live? A 25-year Prospective Observation of the Association Between Desired Longevity and Mortality.

BACKGROUND: Desired longevity represents how strongly people esteem possible extensions of their own lifetime. The association between desired longevity and mortality risk has been reported in only one prospective study, which examined a small sample of older participants. We aimed to examine the hypothesis that desired longevity at middle-age predicted long-term survival. METHODS: In the prospective cohort study, residents aged 40-64 years were asked how long they would like to live and asked to choose one from three options: longer than, as long as, or shorter than the life expectancy. We used Cox proportional hazards model to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to the three groups for desired longevity, treating the "longer than" group as the reference. We conducted mediation analysis to investigate the mechanism for the association between desired longevity and mortality. RESULTS: We recruited 39,902 residents to the study. Risk of all-cause mortality was significantly higher in the "shorter than" group (HR 1.12; 95% CI, 1.04-1.21). The association was independent of sex, age, marital status, education, medical history, and health status. Regarding cause of death, mortality risk of cancer (HR 1.14; 95% CI, 1.00-1.29) and suicide (HR 2.15; 95% CI, 1.37-3.38) were also higher in the "shorter than" group. The unhealthy lifestyle mediated this association with all-cause mortality by 30.4%. CONCLUSION: Shorter desired longevity was significantly associated with an increased risk of all-cause mortality, and mortality from cancer and suicide. Lifestyle behaviors particularly mediated this association.

Dairy consumption and incident risk of thyroid cancer in Japan: a pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

PURPOSE: The impact of dairy consumption on thyroid cancer is unclear. The purpose of this study was to elucidate the association between dairy consumption and the risk of thyroid cancer in Japanese people. METHODS: The association between dairy consumption and the risk of thyroid cancer in Japanese people was examined by conducting a pooled analysis of two prospective studies of residents in Miyagi Prefecture, Japan. Data from 64,340 men and women aged 40-79 years registered in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994 were analyzed. Dairy consumption was assessed at baseline using a self-administered food frequency questionnaire and was divided into quartiles based on the weight (in grams) of total dairy consumption per day. RESULTS: During 1,075,018 person-years of follow-up, there were 190 incident cases of thyroid cancer (29 men and 161 women). The hazard ratios (HRs) and 95% confidence intervals (CIs) for thyroid cancer incidence in the highest quartile of dairy consumption compared with the lowest quartile were 0.83 (95% CIs 0.28-2.43, P-trend = 0.823) for men and 0.67 (95% CIs 0.42-1.06, P-trend = 0.056) for women. After stratification for BMI, a decreased risk was observed in women with BMI ≥ 25 kg/m2 (HRs: 0.37, 95% CIs 0.18-0.79, P-trend = 0.010). CONCLUSION: Dairy consumption is inversely associated with the risk of thyroid cancer in women with BMI ≥ 25 kg/m2.