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Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project is supported by the Wellcome Trust and EPSRC Centre for Medical Engineering. Background QRS duration derived from 12-lead ECGs provides an estimate of the ventricular depolarization time and is an important metric to assess cardiac function. The QRS duration is determined in part by the combination of heart size and conduction velocity (CV). Differences in QRS duration in terms of gender, body mass index (BMI) and age have been well-documented, however, the relative impact of concurrent changes in heart size and CV on QRS duration is poorly understood. Cardiac digital twins, as in-silico replicas, provide a non-invasive physics and physiology-constrained framework to separate the impact of CV and heart anatomy on the QRS duration across populations. Purpose This study aims to identify the impact of CV and heart size on differences in QRS duration and quantify their difference in the general population in different groups of gender, BMI and age. Methods Patient-specific biventricular models (n=400) were constructed using long- and short-axis cardiac magnetic resonance (CMR) images from patients without self-reported cardiovascular diseases in the UK Biobank. Cardiac electrophysiology was simulated using a physiological-detailed model that includes fiber orientation, anisotropic conductivity, the His-Purkinje system activation, and fast endocardial conductivity[1]. 12-lead ECGs were reconstructed from the simulations and the QRS duration was computed based on corresponding vectorcardiogram (VCG) reconstructed from ECG data [2]. We calibrated patient-specific CVs to match the clinically measured QRS duration in ECGs at rest and then compare the heart size, QRS duration and estimated CVs for different patient groups. Results QRS duration was approx. 7% longer in males than females (median: 90ms vs 84ms, P Conclusions QRS duration is shorter in females and individuals with healthy weights. Most of the change in QRS duration can be explained by heart size, with the estimated CV remaining consistent across groups.

Funding Acknowledgements Type of funding sources: None. Background Given the crucial role of obesity as a risk factor for progression of cardiovascular disease (CVD), various guidelines have emphasized the importance of its prevention 1,2. The non-linear relationships of changes in weight, body mass index (BMI), and waist circumference (WC) to all-cause deaths were observed. Evidence on the associations of changes in obesity indices with CVD mortality is scarce. Purposes This study aimed to explore the linear and non-linear relationships of 1- and 3-year changes in obesity indices (i.e., weight, BMI, WC, waist-to-hip ratio (WHR), waist-to-hip ratio (WHRtR)), respectively, to CVD and all-cause mortality. Methods We included adults aged 18 - 65 years from an on-going longitudinal cohort in Taiwan. Multivariable logistics regression models and restricted cubic splines were used to explore the linear and non-linear associations of 1- and 3-year absolute and relative changes in weight, BMI, WC, WHR, and WHtR with CVD and all-cause mortality, respectively. Results A total of 18,024 participants were included in the 1-year change study, and 1,761 and 1,038 cases of all-cause and CVD mortality were reported (follow-up: 6 (range: 2 - 21) years). The 3-year study sample consisted of 12,695 participants, and 1,025 and 931 all-cause and CVD deaths were recorded (follow-up: 6 (range: 2 - 19) years). Results from multivariable logistics regression models showed that the CVD mortality risks were significantly reduced by 1-year absolute and relative increases in weight, BMI, WC, WHR, and WHtR. However, 3-year changes in WC and WHtR did not affect the risk of CVD deaths, while both absolute and relative increases in weight, BMI, and WHR were associated with a lower risk of CVD mortality. For all-cause mortality, any increase in obesity indices was associated with a reduced risk (Table 1). Additionally, restricted cubic splines visually showed U- and L-shaped relationships of changes in obesity indices to CVD and all-cause deaths. Risks of CVD mortality decreased until around 1-year changes of 2.1 cm (2.7%) in WC and 0.01 (2.8%) in WHtR and then increased. Also, below around 3-year change of 2.2 kg (2.5%) in weight, 0.7 kg/m2 (-1.6%) in BMI, 0.03 (3.5%) in WHR, and 0.03 (6.3%) in WHtR, the risks of CVD mortality went down with increases in obesity indices. Above the cut-off points, increased WHR and WHtR were associated with greater risks of CVD mortality. Moreover, an increase was a risk factor for CVD deaths among participants with increased WC of more than approximately 5.5 cm (6.3%) within three years. Similar trends were found among the relationships between changes in obesity indices with all-cause mortality (Figure 1-16). Conclusions We found U- and L-shaped relationships between changes in obesity indices and mortality from CVD and any cause. Risks of CVD and all-cause deaths decreased until a certain value of changes in obesity indices, especially central obesity indices, and then increased.

Background The current CNS WHO classification of brain tumors distinguishes three malignancy grades in meningiomas, with increasing risk of recurrence from CNS WHO grade 1 to 3. Radiotherapy is recommended by current EANO guidelines for patients not safely amenable to surgery or after incomplete resection in higher grades. Despite adequately predicting recurrence probability for the majority of CNS WHO grade 2 meningioma patients, a considerable subset of patients demonstrates an unexpectedly early tumor recurrence following radiotherapy. Methods A retrospective cohort of 44 patients with CNS WHO grade 2 meningiomas was stratified into 3 risk groups (low, intermediate, high) using an integrated morphological, CNV- and methylation family-based classification. Local progression-free survival (lPFS) following radiotherapy (RT) was analyzed and total dose of radiation was correlated with survival outcome. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities were further assessed. Results Risk stratification of CNS WHO grade 2 meningioma into integrated risk groups demonstrated a significant difference in 3-year lPFS following radiotherapy between the molecular low- and high-risk group. Recurrence pattern analysis revealed that 87.5 % of initial relapses occurred within the RT planning target volume or resection cavity. Conclusion Integrated risk scoring can identify CNS WHO grade 2 meningioma patients at risk or relapse and dissemination following radiotherapy. Therapeutic management of CNS WHO grade 2 meningiomas and future clinical trials should be adjusted according to the molecular risk-groups, and not rely on conventional CNS WHO grading alone.

X-ray bursts are among the brightest stellar objects frequently observed in the sky by space-based telescopes. A type-I X-ray burst is understood as a violent thermonuclear explosion on the surface of a neutron star, accreting matter from a companion star in a binary system. The bursts are powered by a nuclear reaction sequence known as the rapid proton capture process (rp process), which involves hundreds of exotic neutron-deficient nuclides. At so-called waiting-point nuclides, the process stalls until a slower β+ decay enables a bypass. One of the handful of rp process waiting-point nuclides is 64Ge, which plays a decisive role in matter flow and therefore the produced X-ray flux. Here we report precision measurements of the masses of 63Ge, 64,65As and 66,67Se—the relevant nuclear masses around the waiting-point 64Ge—and use them as inputs for X-ray burst model calculations. We obtain the X-ray burst light curve to constrain the neutron-star compactness, and suggest that the distance to the X-ray burster GS 1826–24 needs to be increased by about 6.5% to match astronomical observations. The nucleosynthesis results affect the thermal structure of accreting neutron stars, which will subsequently modify the calculations of associated observables.

This study aimed to investigate Chinese physicians' perception and attitudes toward menopausal hormone therapy (MHT).This nationwide online survey was conducted in China. Physicians registered in the WeChat groups of the Gynecological Endocrinology Committee of China's Maternal and Child Health Care Association received a message invitation to complete this anonymous online survey from April 2020 to July 2020. Physicians' knowledge of and attitudes toward MHT were surveyed.In total, 4672 questionnaires were submitted; only completed questionnaires could be submitted. The message was sent to 6021 doctors, so the response rate was 77.6%. Overall, 77.9-92.9% of physicians knew the common indications and contraindications to MHT. Additionally, 90.6%, 85.4%, 80.7% and 37.5% of physicians thought that MHT would increase the risk of venous thrombosis, breast cancer, endometrial cancer and weight gain, respectively. In total, 58.1% of the physicians mistakenly believed that a sex hormone test was one of the necessary examinations to reassess MHT prescription during follow-up visits. We found that 68.5% of physicians would consider using MHT themselves or recommend MHT to their partners in the future, and 11.4% were currently using MHT.Most Chinese physicians have basic knowledge of MHT. Their misunderstandings about MHT mainly centered on the risks of endometrial cancer, weight gain and the necessary examinations during follow-up visits. These misunderstandings need to be clarified in future professional training programs.

The parathyroid and thymus are derived from the common primordia, the third pharyngeal pouch. During their development, endodermal cells actively interact with surrounding mesenchymal cells, mainly derived from neural crest cells (NCCs). However, the mechanism by which NCCs regulate the development of the third pharyngeal pouch remains largely unknown. In this study, we showed that fibronectin 1 ( Fn1), which is synthesized by NCCs, modulates the functions of NCCs in the third pharyngeal pouch patterning and in the morphogenesis of the thymus/parathyroid. Loss of Fn1 in NCCs leads to decreased Foxn1 expression in the presumptive thymus domain at E11.5. In the mutant, we detected upregulation of the Hedgehog signaling activity in the presumptive parathyroid domain and downregulation of Bmp4 in the presumptive thymus domain. Tbx1, a Hedgehog signaling target gene in endoderm development, was ectopically expanded to the presumptive mutant thymus domain at E11.5. Fgf10, an important gene regulating the proliferation of endoderm development, was downregulated in the mutant NCCs. At later organogenesis stages, derivatives of the third pharyngeal pouch endoderm of mutant embryos were abnormal, showing conditions such as hypoparathyroidism, hypoplastic thymus, and ectopic thymus and parathyroid. These data support that Fn1 plays an important role in NCCs by regulating the patterning of the third pharyngeal pouch and morphogenesis of the thymus/parathyroid.

By analyzing 4.48 × 108 ψ(3686) events collected with the BESIII detector, we observe the decays χ cJ → nK S 0 Λ ¯ $$ {nK}_S^0\overline{\Lambda} $$ + c.c. (J = 0, 1, 2) for the first time, via the radiative transition ψ(3686) → γχ cJ . The branching fractions are determined to be (6.65 ± 0.26stat ± 0.41syst) × 10 −4, (1.66 ± 0.12stat ± 0.12syst) × 10 −4, and (3.58 ± 0.16stat ± 0.23syst) × 10 −4 for J = 0, 1, and 2, respectively.

Genetics for blood pressure (BP) in human and animals has been partitioned into two separate specialties. However, this divide is mechanistically-misleading. BP physiology is mechanistically participated by products of quantitative trait loci (QTLs). The key to unlocking its mechanistic mystery lies in the past with mammalian ancestors before humans existed. By pivoting from effects to causes, physiological mechanisms determining BP by six QTLs have been implicated. Our work relies on congenic knock-in genetics in vivo using rat models, and has reproduced the physiological outcome based on a QTL being molecularly equal to one gene. A gene dose for a QTL is irrelevant to physiological BP controls in causation. Together, QTLs join one another as a group in modularized Mendelian fashion to achieve polygenicity. Mechanistically, QTLs in the same module appear to function in a common pathway. Each is involved in a different step in the pathway toward polygenic hypertension. This work has implicated previously-concealed components of these pathways. This emerging concept is a departure from the human-centric precept that the level of QTL expressions, not physiology, would ultimately determine BP. The modularity/pathway paradigm breaks a unique conceptual ground for unravelling the physiological mechanisms of polygenic and quantitative traits like BP.

Lung ischemia-reperfusion injury (LIRI)is a common complication after lung transplantation and cardiopulmonary bypass. It is an important factor affecting the success rate of transplantation. Its specific pathogenesis has not yet been fully elucidated. It is very significant to find the targets and drugs for the prevention and treatment of LIRI in order to improving the utilization rate of "marginal donor lung" and the long-term survival rate of lung transplant patients. Dipeptidyl peptidase 4(DPP4) inhibitors are a class of oral hypoglycemic agents. Previous studies have shown that DPP4 inhibitors have a variety of pharmacological activities, including anti-inflammatory, anti-fibrotic, immunomodulatory and other extrapancreatic functions. Recent studies have shown that DPP4 inhibitors may alleviate LIRI through various mechanisms, including inhibiting inflammatory responses, reducing oxidative stress, regulating blood glucose levels, and activating autophagy. This article reviewed the clinical and preclinical applications and mechanisms of DPP4 inhibitors in LIRI.肺缺血再灌注损伤（LIRI）是肺移植、体外循环术后常见并发症，是影响移植成功率的重要因素，但其具体发病机制目前尚未被完全阐明。寻找防治LIRI的靶点和药物，对提高“边缘性供肺”利用率和肺移植患者的远期生存率具有重要的临床意义。二肽基肽酶4（DPP4）抑制剂是一类口服降糖药，既往研究显示DPP4抑制剂具有多种药理活性，包括抗炎、抗纤维化、免疫调节等多种胰腺外功能。最近的研究显示DPP4抑制剂可能通过抑制炎症反应、减轻氧化应激、调控血糖水平和激活自噬等多种机制减轻LIRI。本文就DPP4抑制剂在LIRI中的临床及临床前应用和作用机制进行综述。.

Henan Province is one of the provinces where taeniasis and cysticercosis were historically highly prevalent, and