There are limited therapeutic methods for triple negative breast cancer in the clinic, which is easy to progress into the brain to form metastatic lesions and evolve into the terminal stage. Because ...both the primary cancer and the brain metastasis have high glycolysis, we hypothesize that lactate dehydrogenase (LDH), which catalyzes the final step of glycolysis, may be a predictor, as well as a treatment target, for breast cancer brain metastasis. Therefore, the expression of LDH-A was detected on 119 triple negative breast cancer tissues with immunohistochemistry, and the serum LDH levels were also measured. Our results showed that the LDH-A expression inside the tumor was significantly higher than the matched normal tissues. Tumor LDH-A expression, serum LDH status, and the slope of serum LDH status were closely associated with triple negative breast cancer brain metastasis and brain metastasis free survival. This study indicates that tumor LDH and serum LDH status are two predictors for triple negative breast cancer brain metastasis.
AbstractObjectiveTo investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and ...body weight.DesignProspective cohort study.SettingHealth professionals in the United States.Participants8828 women from the Nurses’ Health Study and 5218 men from the Health Professionals Follow-up Study.ExposureGenetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED).Main outcome measuresFive repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006).ResultsDuring a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses’ Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and −0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus −0.02 (0.05) kg weight change every four years (P<0.001 for interaction). Viewed differently, changes in body mass index per 1 SD increment of AHEI-2010 score were −0.12 (0.01), −0.14 (0.01), and −0.18 (0.01) (weight change: −0.35 (0.03), −0.36 (0.04), and −0.50 (0.04) kg) among participants with low, intermediate, and high genetic risk, respectively. Similar interaction was also found for DASH but not for AMED.ConclusionsThese data indicate that improving adherence to healthy dietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity.
The prevalence of multidrug-resistant highly virulent Klebsiella pneumoniae (MDR-hvKP) requires the development of new therapeutic agents. Herein, a novel lytic phage vB_KpnS_ZX4 against MDR-hvKP was ...discovered in hospital sewage. Phage vB_KpnS_ZX4 had a short latent period (5 min) and a large burst size (230 PFU/cell). It can rapidly reduce the number of bacteria in vitro and improve survival rates of bacteremic mice in vivo from 0 to 80 % with a single injection of 10
PFU. LysZX4, an endolysin derived from vB_KpnS_ZX4, exhibits potent antimicrobial activity in vitro in combination with ethylenediaminetetraacetic acid (EDTA). The antimicrobial activity of LysZX4 was further enhanced by the fusion of KWKLFKI residues from cecropin A (LysZX4-NCA). In vitro antibacterial experiments showed that LysZX4-NCA exerts broad-spectrum antibacterial activity against clinical Gram-negative bacteria, including MDR-hvKP. Moreover, in the mouse model of MDR-hvKP skin infection, treatment with LysZX4-NCA resulted in a three-log reduction in bacterial burden on the skin compared to the control group. Therefore, the novel phages vB_KpnS_ZX4 and LysZX4-NCA are effective reagents for the treatment of systemic and local MDR-hvKP infections.
Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of ...population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.
Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the ...association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported 'always' use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19.
A spacecraft power processing unit (PPU) is utilized to convert power from solar arrays or electric batteries to the payload, including electric propulsion, communication equipment, and scientific ...instruments. Currently, a high-voltage converter is widely applied to the spacecraft PPU to improve power density and save launch weight. However, the high voltage level poses challenges such as high step-down ratios and high power losses. To achieve less conduction loss, a SiC-based T-type three-level (TL) LLC resonant converter is proposed. To further broaden the gain range and achieve high step-down ratios, a variable frequency and adjustable phase-shift (VFAPS) modulation scheme is proposed. Meanwhile, the steady-state time-domain model is established to elaborate the operation principles and boundary conditions for soft switching. Furthermore, the optimal resonant element design considerations have been elaborated to achieve wider gain range and facilitate easier soft switching. Furthermore, the numerical solutions for switching frequency and phase shift (PS) angle under each specific input could be figured out. Finally, the effectiveness of this theoretical analysis is demonstrated via a 500-W experimental prototype with 650∼950-V input and constant output of 48-V/11-A.
Although soil is typically an unsaturated (three‐phase) medium, previous studies on the dynamic impedance of pile groups primarily considered the piles embedded in either the single‐phase or fully ...saturated (two‐phase) soils. In this work, the dynamic impedance of end‐bearing pile groups embedded in homogeneous unsaturated soil subject to a vertical time‐harmonic load is analytically obtained. The soil is modeled as a three‐dimensional axisymmetric continuum, and both the radial and vertical displacements as well as the influence of the saturation degree on the soil's dynamic shear modulus are considered. The governing equations of vibrating unsaturated soil are uncoupled by virtue of the potential function and operator decomposition methods. The attenuation function of soil displacement, surrounding soil resistance factor, and vertical dynamic impedance of a single pile are derived from the pile−soil compatibility conditions. Pile‐to‐pile dynamic interaction factors are then derived and used, along with the superposition principle, to find the vertical dynamic impedance of end‐bearing pile groups in the frequency domain. The proposed analytical solution is verified by comparison with two benchmark solutions. Finally, the influence of various parameters on the dynamic response of end‐bearing pile groups is determined.
Background
Novel interventions are needed to improve lifestyle and prevent noncommunicable diseases, the leading cause of death and disability globally. This study aimed to systematically review, ...synthesize, and grade scientific evidence on effectiveness of novel information and communication technology to reduce noncommunicable disease risk.
Methods and Results
We systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand‐alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. We included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. American Heart Association criteria were used to evaluate and grade the strength of evidence. From 8654 s, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (N=20 studies) (Class IIa A), physical activity (N=33), adiposity (N=35), tobacco (N=22), and excess alcohol (N=47) (Class I A each). Mobile interventions improved physical activity (N=6) and adiposity (N=3) (Class I A each). Evidence limitations included relatively brief durations (generally <6 months, nearly always <1 year), heterogeneity in intervention content and intensity, and limited representation from middle/low‐income countries.
Conclusions
Internet and mobile interventions improve important lifestyle behaviors up to 1 year. This systematic review supports the need for long‐term interventions to evaluate sustainability.
Haiyang-2A (HY-2A), China’s first altimetry satellite mission, was launched more than ten years ago, and its follow-up satellites, HY-2B, HY-2C, and HY-2D, have also been launched. More attention has ...been paid to the evaluation of these satellite observations in marine gravity field inversion. However, this is not the case for bathymetry inversion. This study is aimed at evaluating the performance of HY-2 gravity field products in bathymetry recovery. Not only gravity anomaly, but also deflection of the vertical from the HY-2 series’ observations is also used. The results show that the bathymetry derived from the deflection of the vertical from HY-2A has a precision of around 128~130 m, and the north-south component performs better than the east-west component. Three versions of the gravity anomaly are used in bathymetry inversion, i.e., HY2ONLY_GRA, WHU16_GRA, and NSOASS22_GRA, and three bathymetry models are derived correspondingly, named as HY2ONLY_BAT, NSOASS22_BAT, and WHU16_BAT, respectively. The results show that HY2ONLY_BAT has a precision of 82.93 m, which is a little poorer than WHU16_BAT; NSOAS22_BAT has the best performance in bathymetry inversion among the three versions of the gravity anomaly. It indicates that HY-2 observations can also contribute to bathymetry inversion compared to current altimetry datasets, since the main difference between WHU16_GRA and NSOASS22_GRA is the use of HY-2 observations. According to spatial analysis results, considerable improvements appear in the west of the Pacific and Indian oceans, and most of the improvements are within 20 m. Meanwhile, the improvements are stronger in the regions with depths ranging between 2600~5500 m. Correlation analysis demonstrates that NSOASS22_BAT is very close to SIO V19.1 and DTU21BAT, which once again indicates the excellent performance of NSOASS22_BAT.
Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary ...pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men.
We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we profiled serial stool metagenomes and metatranscriptomes and assessed diet using semiquantitative food frequency questionnaires to identify food groups associated with 43 bacterial species involved in sulfur metabolism. We used these data to develop a sulfur microbial dietary score. We then used Cox proportional hazards modeling to evaluate adherence to this pattern among eligible individuals (n = 48,246) from 1986 through 2012 with risk for incident CRC.
Foods associated with higher sulfur microbial diet scores included increased consumption of processed meats and low-calorie drinks and lower consumption of vegetables and legumes. Increased sulfur microbial diet scores were associated with risk of distal colon and rectal cancers, after adjusting for other risk factors (multivariable relative risk, highest vs lowest quartile, 1.43; 95% confidence interval 1.14–1.81; P-trend = .002). In contrast, sulfur microbial diet scores were not associated with risk of proximal colon cancer (multivariable relative risk 0.86; 95% CI 0.65–1.14; P-trend = .31).
In an analysis of participants in the Health Professionals Follow-up Study, we found that long-term adherence to a dietary pattern associated with sulfur-metabolizing bacteria in stool was associated with an increased risk of distal CRC. Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis.
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