Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

Computed tomography-based COVID-19 triage through a deep neural network using mask-weighted global average pooling.

Background: There is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases. Methods: A total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases. Results: The results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists. Conclusions: This study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.

Two transporters mobilize magnesium from vacuolar stores to enable plant acclimation to magnesium deficiency.

Magnesium (Mg) is an essential metal for chlorophyll biosynthesis and other metabolic processes in plant cells. Mg is largely stored in the vacuole of various cell types and remobilized to meet cytoplasmic demand. However, the transport proteins responsible for mobilizing vacuolar Mg2+ remain unknown. Here, we identified two Arabidopsis (Arabidopsis thaliana) Mg2+ transporters (MAGNESIUM TRANSPORTER 1 and 2; MGT1 and MGT2) that facilitate Mg2+ mobilization from the vacuole, especially when external Mg supply is limited. In addition to a high degree of sequence similarity, MGT1 and MGT2 exhibited overlapping expression patterns in Arabidopsis tissues, implying functional redundancy. Indeed, the mgt1 mgt2 double mutant, but not mgt1 and mgt2 single mutants, showed exaggerated growth defects as compared to the wild type under low-Mg conditions, in accord with higher expression levels of Mg-starvation gene markers in the double mutant. However, overall Mg level was also higher in mgt1 mgt2, suggesting a defect in Mg2+ remobilization in response to Mg deficiency. Consistently, MGT1 and MGT2 localized to the tonoplast and rescued the yeast (Saccharomyces cerevisiae) mnr2Δ (manganese resistance 2) mutant strain lacking the vacuolar Mg2+ efflux transporter. In addition, disruption of MGT1 and MGT2 suppressed high-Mg sensitivity of calcineurin B-like 2 and 3 (cbl2 cbl3), a mutant defective in vacuolar Mg2+ sequestration, suggesting that vacuolar Mg2+ influx and efflux processes are antagonistic in a physiological context. We further crossed mgt1 mgt2 with mgt6, which lacks a plasma membrane MGT member involved in Mg2+ uptake, and found that the triple mutant was more sensitive to low-Mg conditions than either mgt1 mgt2 or mgt6. Hence, Mg2+ uptake (via MGT6) and vacuolar remobilization (through MGT1 and MGT2) work synergistically to achieve Mg2+ homeostasis in plants, especially under low-Mg supply in the environment.

Correction: Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

[This corrects the article DOI: 10.2196/33995.].

Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

BACKGROUND: Many countries and organizations recommended people living with HIV/AIDS (PLWHA) receive the COVID-19 vaccine. However, vaccine hesitancy still exists and becomes a barrier for promoting COVID-19 vaccination among PLWHA. OBJECTIVE: This study aims to investigate factors that contributed to COVID-19 vaccine hesitancy among PLWHA. METHODS: The study used a multicenter cross-sectional design and an online survey mode. We recruited PLWHA aged 18-65 years from 5 metropolitan cities in China between January 2021 and February 2021. Participants completed an online survey through Golden Data, a widely used encrypted web-based survey platform. Multiple linear regression models were used to assess the background characteristics in relation to COVID-19 vaccine hesitancy, and structural equation modeling was performed to assess the relationships among perceived benefits, perceived risks, self-efficacy, subjective norms, and COVID-19 vaccine hesitancy. RESULTS: Among 1735 participants, 41.61% (722/1735) reported COVID-19 vaccine hesitancy. Older age, no other vaccinations in the past 3 years, and having chronic disease history were positively associated with COVID-19 vaccine hesitancy. Structural equation modeling revealed a direct relationship of perceived benefits, perceived risks, and subjective norms with self-efficacy and vaccine hesitancy and an indirect relationship of perceived benefits, perceived risks, and subjective norms with vaccine hesitancy. Moreover, self-efficacy toward COVID-19 vaccination was low. PLWHA had concerns of HIV disclosure during COVID-19 vaccination. Family member support could have an impact on COVID-19 vaccination decision-making. CONCLUSIONS: COVID-19 vaccine hesitancy was high among PLWHA in China. To reduce COVID-19 vaccine hesitancy, programs and strategies should be adopted to eliminate the concerns for COVID-19 vaccination, disseminate accurate information on the safety and efficacy of the COVID-19 vaccine, encourage family member support for COVID-19 vaccination, and improve PLWHA's trust of medical professionals.

Four plasma membrane-localized MGR transporters mediate xylem Mg2+ loading for root-to-shoot Mg2+ translocation in Arabidopsis.

Magnesium (Mg2+), an essential structural component of chlorophyll, is absorbed from the soil by roots and transported to shoots to support photosynthesis in plants. However, the molecular mechanisms underlying root-to-shoot Mg2+ translocation remain largely unknown. We describe here the identification of four plasma membrane (PM)-localized transporters, named Mg2+ release transporters (MGRs), that are critical for root-to-shoot Mg transport in Arabidopsis. Functional complementation assays in a Mg2+-uptake-deficient bacterial strain confirmed that these MGRs conduct Mg2+ transport. PM-localized MGRs (MGR4, MGR5, MGR6, and MGR7) were expressed primarily in root stellar cells and participated in the xylem loading step of the long-distance Mg2+ transport process. In particular, MGR4 and MGR6 played a major role in shoot Mg homeostasis, as their loss-of-function mutants were hypersensitive to low Mg2+ but tolerant to high Mg2+ conditions. Reciprocal grafting analysis further demonstrated that MGR4 functions in the root to determine shoot Mg2+ accumulation and physiological phenotypes caused by both low- and high-Mg2+ stress. Taken together, our study has identified the long-sought transporters responsible for root-to-shoot Mg2+ translocation in plants.

Conserved mechanism for vacuolar magnesium sequestration in yeast and plant cells.

Magnesium (Mg2+) is an essential nutrient for all life forms. In fungal and plant cells, the majority of Mg2+ is stored in the vacuole but mechanisms for Mg2+ transport into the vacuolar store are not fully understood. Here we demonstrate that members of ancient conserved domain proteins (ACDPs) from Saccharomyces cerevisiae and Arabidopsis thaliana function in vacuolar Mg2+ sequestration that enables plant and yeast cells to cope with high levels of external Mg2+. We show that the yeast genome (as well as other fungal genomes) harbour a single ACDP homologue, referred to as MAM3, that functions specifically in vacuolar Mg2+ accumulation and is essential for tolerance to high Mg. In parallel, vacuolar ACDP homologues were identified from Arabidopsis and shown to complement the yeast mutant mam3Δ. An Arabidopsis mutant lacking one of the vacuolar ACDP homologues displayed hypersensitivity to high-Mg conditions and accumulated less Mg in the vacuole compared with the wild type. Taken together, our results suggest that conserved transporters mediate vacuolar Mg2+ sequestration in fungal and plant cells to maintain cellular Mg2+ homeostasis in response to fluctuating Mg2+ levels in the environment.

A Sandwich Metal-Insulation-Metal Composite for Magnetoelectric Memory: Experiment and Modeling.

Driven by the development of internet technology, higher requirements on information materials and data storage devices were demanded. To improve the work efficiency and performance of the new generation of information materials and data storage devices, the magnetoelectric (ME) coupling and storage mechanism of magnetoelectric composites deserve more attention. Here, we explored the influence of applied magnetic fields on the output voltage on a metal-insulation-metal (MIM) sandwich composite for realizing the magnetoelectric memory by experiments and modeling. It is found that the DC magnetic field (H dc) and the output voltage of the polyvinylidene fluoride film are linearly correlated. At a frequency of 1 kHz, the magnetoelectric voltage coefficient is 60.71 mV cm-1 Oe-1, which is evidently larger than that of other film materials. From this work, we can conclude that the MIM sandwich composite could generate higher magnetoelectric voltage under the AC magnetic field (H ac) with higher frequency, which could be used as the magnetoelectric memory device, and provides significant support for improving the performance of magnetoelectric memory devices and the whole internet system.

Changes in NK Cell Subsets and Receptor Expressions in HIV-1 Infected Chronic Patients and HIV Controllers.

Natural killer (NK) cells are major effectors of the innate immune response and purported to play an influential role in the spontaneous control of HIV infection. In the present study, we compared the phenotypes of NK cells in the peripheral blood of three groups of subjects with chronic HIV-1 infection, HIV controllers, and healthy donors. The results showed that CD56+/CD16- NK cell subsets decreased in chronic patients and remained unchanged in controllers. Notably, we found that people living with chronic HIV-1 infection had suppressed NKp80, NKp46, and NKG2D expressions on NK cells compared to healthy donors, while HIV controllers remained unchanged. In contrast, NKG2D expression was substantially higher in controllers than in chronic patients (M=97.67, p<0.001). There were no significant differences in inhibitory receptors KIR3DL1 and KIR2DL1 expressions. In addition, plasma cytokine IFN-γ, TNF-α and IL-12showed higher levels in HIV controllers compared to chronic patients. Overall, our study revealed that, as compared to chronic patients, HIV controllers show an increased activating receptors expression and higher number ofCD56+/CD16-NK cell subset, with increased expression levels of plasma cytokines, suggesting that higher immune activation in controllers may have a key role in killing and suppressing HIV.

Spatio-temporal dynamics of arbuscular mycorrhizal fungi and soil organic carbon in coastal saline soil of China.

A comprehensive understanding of the relationship between arbuscular mycorrhizal (AM) fungi and coastal saline soil organic carbon (SOC) is crucial for analysis of the function of coastal wetlands in soil carbon sequestration. In a field experiment, the temporal and spatial dynamics of AM fungi, glomalin-related soil protein (GRSP) - which is described as a N-linked glycoprotein and the putative gene product of AM fungi, SOC, and soil aggregates were investigated in halophyte Kosteletzkya virginica rhizosphere soil of coastal saline areas of North Jiangsu, China. Soil samples were collected from a depth of up to 30 cm in two plantation regions from August 2012 to May 2013. Results showed K. virginica formed a strong symbiotic relationship to AM fungi. AM colonization and spore density were the highest in the 10-20 cm soil layer of Jinhai farm in August 2012, because of the presence of numerous fibrous roots in this soil layer. The total GRSP and SOC were the highest in the 0-10 cm soil layer in May 2013 and November 2012, respectively. Correlation coefficient analysis revealed that AM colonization and spore density were positively correlated with total GRSP. Meanwhile, total GRSP was significantly positively correlated with large macroaggregates (>3 mm), SOC, total P, Olsen P, and soil microbial biomass carbon (SMBC), but negatively correlated with microaggregates (<0.25 mm), soil EC, total N, and pH. SOC was positively correlated with spore density, large macroaggregates, small macroaggregates (2-0.25 mm), alkaline N, and SMBC and negatively correlated with microaggregates, EC, pH, and total K. Although it may be a statistical artifact, we found an interesting phenomenon that there was no significant correlation between soil aggregates and AM colonization or spore density. Hence, total GRSP is a vital source of saline soil C pool and an important biological indicator for evaluating coastal saline SOC pool and soil fertility, while AM colonization or spore density may not be.

Author Correction: A calcium signalling network activates vacuolar K+ remobilization to enable plant adaptation to low-K environments.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A calcium signalling network activates vacuolar K+ remobilization to enable plant adaptation to low-K environments.

Potassium (K) is an essential nutrient, but levels of the free K ions (K+) in soil are often limiting, imposing a constant stress on plants. We have discovered a calcium (Ca2+)-dependent signalling network, consisting of two calcineurin B-like (CBL) Ca2+ sensors and a quartet of CBL-interacting protein kinases (CIPKs), which plays a key role in plant response to K+ starvation. The mutant plants lacking two CBLs (CBL2 and CBL3) were severely stunted under low-K conditions. Interestingly, the cbl2 cbl3 mutant was normal in K+ uptake but impaired in K+ remobilization from vacuoles. Four CIPKs-CIPK3, 9, 23 and 26-were identified as partners of CBL2 and CBL3 that together regulate K+ homeostasis through activating vacuolar K+ efflux to the cytoplasm. The vacuolar two-pore K+ (TPK) channels were directly activated by the vacuolar CBL-CIPK modules in a Ca2+-dependent manner, presenting a mechanism for the activation of vacuolar K+ remobilization that plays an important role in plant adaptation to K+ deficiency.

Plant Membrane Transport Research in the Post-genomic Era.

Membrane transport processes are indispensable for many aspects of plant physiology including mineral nutrition, solute storage, cell metabolism, cell signaling, osmoregulation, cell growth, and stress responses. Completion of genome sequencing in diverse plant species and the development of multiple genomic tools have marked a new era in understanding plant membrane transport at the mechanistic level. Genes coding for a galaxy of pumps, channels, and carriers that facilitate various membrane transport processes have been identified while multiple approaches are developed to dissect the physiological roles as well as to define the transport capacities of these transport systems. Furthermore, signaling networks dictating the membrane transport processes are established to fully understand the regulatory mechanisms. Here, we review recent research progress in the discovery and characterization of the components in plant membrane transport that take advantage of plant genomic resources and other experimental tools. We also provide our perspectives for future studies in the field.

The current status of syphilis prevention and control in Jiangsu province, China: A cross-sectional study.

OBJECTIVE: To analyze the midterm evaluation data from the National Syphilis Prevention and Control Plan (2010-2020) and evaluate the current status of syphilis prevention and control in Jiangsu province, China. METHODS: We collected data via (1) field surveys conducted in 2015 and (2) data recorded in existing syphilis surveillance systems. We conducted descriptive statistical analysis to evaluate the current landscape of syphilis control initiatives and their potential effect in syphilis control. RESULTS: The incidence of all cases of syphilis decreased from 2010 (32.3 per 100,000) to 2015 (30.1 per 100,000), with an annual growth of -1.17% (x2trend = -7.52, P<0.001) in Jiangsu province. The incidence of primary and secondary syphilis and congenital syphilis both decreased significantly from 2010 to 2015. The average awareness rate of syphilis knowledge among professional personnel was 95.4% (3781/3963). Rural residents had the lowest awareness rate (83.5%, 1875/2245) and commercial sex workers had the highest awareness rate (92.1%, 7804/8474) in 2015. Only 47.8% (33908/70894) of patients received provider-initiated syphilis counseling and testing (PISTC) services in sexually transmitted disease (STD) clinics, but 94.5% (87927/93020) of all syphilis patients received free testing for syphilis. Overall, 97.2% (9378/9648) of syphilis reported cases of syphilis at medical institutions were confirmed to be accurate, and 92.2% (5850/6345) of patients diagnosed with syphilis at medical institutions received treatment with penicillin. CONCLUSION: The syphilis incidence rate in Jiangsu has decreased in recent years, but remains at a high level. It is essential to promote PISTC services to improve knowledge of syphilis and rates of testing and treatment in Jiangsu province.

Two tonoplast MATE proteins function as turgor-regulating chloride channels in Arabidopsis.

The central vacuole in a plant cell occupies the majority of the cellular volume and plays a key role in turgor regulation. The vacuolar membrane (tonoplast) contains a large number of transporters that mediate fluxes of solutes and water, thereby adjusting cell turgor in response to developmental and environmental signals. We report that two tonoplast Detoxification efflux carrier (DTX)/Multidrug and Toxic Compound Extrusion (MATE) transporters, DTX33 and DTX35, function as chloride channels essential for turgor regulation in Arabidopsis Ectopic expression of each transporter in Nicotiana benthamiana mesophyll cells elicited a large voltage-dependent inward chloride current across the tonoplast, showing that DTX33 and DTX35 each constitute a functional channel. Both channels are highly expressed in Arabidopsis tissues, including root hairs and guard cells that experience rapid turgor changes during root-hair elongation and stomatal movements. Disruption of these two genes, either in single or double mutants, resulted in shorter root hairs and smaller stomatal aperture, with double mutants showing more severe defects, suggesting that these two channels function additively to facilitate anion influx into the vacuole during cell expansion. In addition, dtx35 single mutant showed lower fertility as a result of a defect in pollen-tube growth. Indeed, patch-clamp recording of isolated vacuoles indicated that the inward chloride channel activity across the tonoplast was impaired in the double mutant. Because MATE proteins are widely known transporters of organic compounds, finding MATE members as chloride channels expands the functional definition of this large family of transporters.

High HIV incidence epidemic among men who have sex with men in china: results from a multi-site cross-sectional study.

BACKGROUND: Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, timely and comprehensive investigation. METHODS: Mixed methods were used to recruit MSM from seven cities in China between 2012 and 2013. Recent and established HIV infections were estimated by Western Blot and BED HIV-1 capture enzyme immunoassay. Syphilis and herpes simplex virus-2 (HSV-2) were also tested. RESULTS: A total of 4496 eligible MSM were recruited. The majority was aged ≤35 years (77.5 %), migrants (60.3 %), never married (69.8 %), and played receptive role in anal sex (70.5 %). The HIV prevalence was 9.9 %, and 41.9 % were recently infected, with sensitivity/specificity adjusted HIV incidence of 8.9 (95 % CI: 7.6-10.2)/100 Person-Years. The prevalence of history HSV-2 and syphilis were 12.5 % and 8.5 %, respectively. Recent HIV infection was associated with having multiple male partners (aOR = 1.4, 95 % CI 1.1-1.9), recreational drug use (aOR = 2.2, 95 % CI 1.6-3.0), anal bleeding (aOR = 2.1, 95 % CI 1.4-3.0), syphilis infection (aOR = 2.8, 95 % CI 1.9-4.3) and history HSV-2 infection (aOR = 2.3, 95 % CI 1.5-3.3). CONCLUSION: High rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having multiple partners, history of recreational drug use and syphilis or HSV-2 infection seemed to be the need of the hour.

PdCo/Pd-Hexacyanocobaltate Hybrid Nanoflowers: Cyanogel-Bridged One-Pot Synthesis and Their Enhanced Catalytic Performance.

Elaborate architectural manipulation of nanohybrids with multi-components into controllable 3D hierarchical structures is of great significance for both fundamental scientific interest and realization of various functionalities, yet remains a great challenge because different materials with distinct physical/chemical properties could hardly be incorporated simultaneously into the synthesis process. Here, we develop a novel one-pot cyanogel-bridged synthetic approach for the generation of 3D flower-like metal/Prussian blue analogue nanohybrids, namely PdCo/Pd-hexacyanocobaltate for the first time. The judicious introduction of polyethylene glycol (PEG) and the formation of cyanogel are prerequisite for the successful fabrication of such fascinating hierarchical nanostructures. Due to the unique 3D hierarchical structure and the synergistic effect between hybrid components, the as-prepared hybrid nanoflowers exhibit a remarkable catalytic activity and durability toward the reduction of Rhodamine B (RhB) by NaBH4. We expect that the obtained hybrid nanoflowers may hold great promises in water remediation field and beyond. Furthermore, the facile synthetic strategy presented here for synthesizing functional hybrid materials can be extendable for the synthesis of various functional hybrid nanomaterials owing to its versatility and feasibility.