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    The identification of individuals at high risk of developing hypertension can be of great value to improve the efficiency of primary prevention strategies for hypertension. The objective of this study was to develop a risk prediction model for incident hypertension based on prospective longitudinal data from a general Japanese population. A total of 982 subjects aged 40-59 years without hypertension at baseline were followed up for 10 years (2002-12) for the incidence of hypertension. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive agents. The risk prediction model was developed using a Cox proportional hazards model. A simple risk scoring system was also established based on the developed model. During the follow-up period (median 10 years, interquartile range 5-10 years), 302 subjects (120 men and 182 women) developed new-onset hypertension. The risk prediction model for hypertension consisted of age, sex, SBP, DBP, use of glucose-lowering agents, body mass index (BMI), parental history of hypertension, moderate-to-high alcohol intake, and the interaction between age and BMI. The developed model demonstrated good discrimination (Harrell’s C statistic=0.812 [95% confidence interval, 0.791-0.834]; optimism-corrected C statistic based on 200 bootstrap samples=0.804) and calibration (Greenwood-Nam-D’Agostino χ2 statistic=12.2). This risk prediction model is a useful guide for estimating an individual’s absolute risk for hypertension and could facilitate the management of Japanese individuals at high risk of developing hypertension in the future.Seeds are a key life cycle stage for many plants. Seeds are also the basis of agriculture and the primary source of calories consumed by humans1. Here, we employ single-nucleus RNA-sequencing to generate a transcriptional atlas of developing Arabidopsis thaliana seeds, with a focus on endosperm. Endosperm, the primary site of gene imprinting in flowering plants, mediates the relationship between the maternal parent and the embryo2. We identify transcriptionally uncharacterized nuclei types in the chalazal endosperm, which interfaces with maternal tissue for nutrient unloading3,4. selleck products We demonstrate that the extent of parental bias of maternally expressed imprinted genes varies with cell-cycle phase, and that imprinting of paternally expressed imprinted genes is strongest in chalazal endosperm. Thus, imprinting is spatially and temporally heterogeneous. Increased paternal expression in the chalazal region suggests that parental conflict, which is proposed to drive imprinting evolution, is fiercest at the boundary between filial and maternal tissues.

    Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study.

    In 350,512 UK Biobank participants aged 38-73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression.

    During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95-1.07) and 1.04 (95% CI 0.97-1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08-1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96-1.26).

    Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.

    Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1-30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted.Severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT). This multinational, prospective, observational study (NCT03032016), performed by the EBMT, enrolled patients treated with defibrotide from April 2015 to July 2018. This analysis focused on defibrotide-treated patients with VOD/SOS post-HCT. The primary endpoint was incidence of serious adverse events (SAEs) of interest up to 12 months post-HCT in patients with severe VOD/SOS. Overall, 104 defibrotide-treated patients with VOD/SOS post-HCT were enrolled 62 had severe VOD/SOS and comprised the primary study population, including 36 with multi-organ dysfunction/failure (MOD/MOF). SAEs of interest occurred in 20 of 62 (32%) severe VOD/SOS patients; the most common by category were infection (24%) and bleeding (13%). In patients with severe VOD/SOS, the Kaplan-Meier-estimated Day 100 survival rate was 73% (95% CI 60%, 82%) with VOD/SOS resolution by Day 100 in 45 of 62 (73%) patients.

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