Active metamaterials for realizing odd mass density.

Solids built out of active components have exhibited odd elastic stiffness tensors whose active moduli appear in the antisymmetric part and which give rise to non-Hermitian static and dynamic phenomena. Here, we present a class of active metamaterial featured with an odd mass density tensor whose asymmetric part arises from active and nonconservative forces. The odd mass density is realized using metamaterials with inner resonators connected by asymmetric and programmable feed-forward control on acceleration and active forces along the two perpendicular directions. The active forces produce unbalanced off-diagonal mass density coupling terms, leading to non-Hermiticity. The odd mass is then experimentally validated through a one-dimensional nonsymmetric wave coupling where propagating transverse waves are coupled with longitudinal ones whereas the reverse is forbidden. We reveal that the two-dimensional active metamaterials with the odd mass can perform in either energy-unbroken or energy-broken phases separated by exceptional points along principal directions of the mass density. The odd mass density contributes to the wave anisotropy in the energy-unbroken phase and directional wave energy gain in the energy-broken phase. We also numerically illustrate and experimentally demonstrate the two-dimensional wave propagation phenomena that arise from the odd mass in active solids. Finally, the existence of non-Hermitian skin effect is discussed in which boundaries host an extensive number of localized modes. It is our hope that the emergent concept of the odd mass can open up a new research platform for mechanical non-Hermitian system and pave the ways for developing next-generation wave steering devices.

Glutathione-Responsive Organosilica Hybrid Nanosystems for Targeted Dual-Starvation Therapy in Luminal Breast Cancer.

Starvation therapy is an innovative approach in cancer treatment aimed at depriving cancer cells of necessary resources by impeding tumor angiogenesis or blocking the energy supply. In addition to the commonly observed anaerobic glycolysis energy supply mode, adipocyte-rich tumor tissue triggers the fatty acid energy supply pathway, which fuels the proliferation and metastasis of cancer cells. To completely disrupt these dual-energy-supply pathways, we developed an exceptional nanoreactor. This nanoreactor consisted of yolk-shell mesoporous organosilica nanoparticles (YSMONs) loaded with a fatty acid transport inhibitor (Dox), conjugated with a luminal breast-cancer-specific targeting aptamer, and integrated with a glucose oxidation catalyst (GOx). Upon reaching cancer cells with the assistance of the aptamer, the nanoreactor underwent a structural collapse of the shell triggered by the high concentration of glutathione within cancer cells. This collapse led to the release of GOx and Dox, achieving targeted delivery and exhibiting significant efficacy in starving therapy. Additionally, the byproducts of glucose metabolism, gluconic acid and H2O2, enhanced the acidity and reactive oxygen species levels of the intracellular microenvironment, inducing oxidative damage to cancer cells. Simultaneously, released Dox acted as a potent broad-spectrum anticancer drug, inhibiting the activity of carnitine palmitoyltransferase 1A and exerting marked effects. Combining these effects ensures high anticancer efficiency, and the "dual-starvation" nanoreactor has the potential to establish a novel synergistic therapy paradigm with considerable clinical significance. Furthermore, this approach minimizes damage to normal organs, making it highly valuable in the field of cancer treatment.

Determination of trace chelating carboxylic acids in rice by green extraction combined with liquid chromatography-mass spectrometry analysis and its application in the evaluation of old and new rice.

RATIONALE: Accurate identification of old rice samples from new ones benefits their market circulation and consumers. However, the current detection methods are still not satisfactory because of their insufficient accuracy or (and) time-consuming process. METHODS: Chelating carboxylic acids (CCAs) were selectively extracted from rice, by stirring with chelating resin and a dilute Na2CO3 solution. The green analytical chemistry guidelines for sample preparation were investigated by using the green chemistry calculator AGREE prep. The extractant was determined by liquid chromatography-mass spectrometry (LC/MS), and statistical analysis of the analytical data was carried out to evaluate the significance of the difference by ChiPlot. RESULTS: The limit of quantitation for the CCAs is in the range of 1 to 50 ng/mL, with a reasonable reproducibility. The CCAs in 23 rice samples were determined within a wide concentration range from 0.03 to 1174 µg/g. Intriguingly, the content of citric acid, malonic acid, α-ketoglutaric acid and cis-aconite acid in new rice was each found to be distinctively higher than that in old rice by several times. Even mixtures of old and new rice were found to show much difference in the concentration of citric acid and malic acid. CONCLUSION: A green analytical method has been developed for the simultaneous determination of CCAs by LC/MS analysis, and the identification of old rice samples from new ones was easily carried out according to their CCA content for the first time. The results indicated that the described method has powerful potential for the accurate identification of old rice samples from new ones.

Potential Antihuman Epidermal Growth Factor Receptor 2 Target Therapy Beneficiaries: The Role of MRI-Based Radiomics in Distinguishing Human Epidermal Growth Factor Receptor 2-Low Status of Breast Cancer.

BACKGROUND: Multiparametric MRI radiomics could distinguish human epidermal growth factor receptor 2 (HER2)-positive from HER2-negative breast cancers. However, its value for further distinguishing HER2-low from HER2-negative breast cancers has not been investigated. PURPOSE: To investigate whether multiparametric MRI-based radiomics can distinguish HER2-positive from HER2-negative breast cancers (task 1) and HER2-low from HER2-negative breast cancers (task 2). STUDY TYPE: Retrospective. POPULATION: Task 1: 310 operable breast cancer patients from center 1 (97 HER2-positive and 213 HER2-negative); task 2: 213 HER2-negative patients (108 HER2-low and 105 HER2-zero); 59 patients from center 2 (16 HER2-positive, 27 HER2-low and 16 HER2-zero) for external validation. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted contrast-enhanced imaging (T1CE), diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC). ASSESSMENT: Patients in center 1 were assigned to a training and internal validation cohort at a 2:1 ratio. Intratumoral and peritumoral features were extracted from T1CE and ADC. After dimensionality reduction, the radiomics signatures (RS) of two tasks were developed using features from T1CE (RS-T1CE), ADC (RS-ADC) alone and T1CE + ADC combination (RS-Com). STATISTICAL TESTS: Mann-Whitney U tests, the least absolute shrinkage and selection operator, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: For task 1, RS-ADC yielded higher area under the ROC curve (AUC) in the training, internal, and external validation of 0.767/0.725/0.746 than RS-T1CE (AUC = 0.733/0.674/0.641). For task 2, RS-T1CE yielded higher AUC of 0.765/0.755/0.678 than RS-ADC (AUC = 0.706/0.608/0.630). For both of task 1 and task 2, RS-Com achieved the best performance with AUC of 0.793/0.778/0.760 and 0.820/0.776/0.711, respectively, and obtained higher clinical benefit in DCA compared with RS-T1CE and RS-ADC. The calibration curves of all RS demonstrated a good fitness. DATA CONCLUSION: Multiparametric MRI radiomics could noninvasively and robustly distinguish HER2-positive from HER2-negative breast cancers and further distinguish HER2-low from HER2-negative breast cancers. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

A microfluidic-chip-based system with loop-mediated isothermal amplification for rapid and parallel detection of Trichomonas vaginalis and human papillomavirus.

Cervical cancer is a significant global health issue primarily caused by high-risk types of human papillomavirus (HPV). Recent studies have reported an association between Trichomonas vaginalis (T. vaginalis) infections and HPV infections, highlighting the importance of simultaneously detecting these pathogens for effective cervical cancer risk management. However, current methods for detecting both T. vaginalis and HPV are limited. In this study, we present a novel approach using a microfluidic-chip-based system with loop-mediated isothermal amplification (LAMP) for the rapid and parallel detection of T. vaginalis, HPV16, HPV18, and HPV52 in a reagent-efficient and user-friendly manner. Compared to conventional LAMP assays in tubes, our system exhibits enhanced sensitivity with values of 2.43 × 101, 3.00 × 102, 3.57 × 101, and 3.60 × 102 copies per reaction for T. vaginalis, HPV16, HPV18, and HPV52, respectively. Additionally, we validated the performance of our chip by testing 47 clinical samples, yielding results consistent with the diagnostic methods used by the hospital. Therefore, our system not only offers a promising solution for concurrent diagnosis of T. vaginalis and HPV infections, particularly in resource-limited areas, due to its cost-effectiveness, ease of use, and rapid and accurate detection performance, but can also contribute to future research on the co-infection of these two pathogens. Moreover, the system possesses the capability to simultaneously detect up to 22 different types of pathogens, making it applicable across a wide range of domains such as diagnostics, food safety, and water monitoring.

Pencil-paper on-skin electronics.

Pencils and papers are ubiquitous in our society and have been widely used for writing and drawing, because they are easy to use, low-cost, widely accessible, and disposable. However, their applications in emerging skin-interfaced health monitoring and interventions are still not well explored. Herein, we report a variety of pencil-paper-based on-skin electronic devices, including biophysical (temperature, biopotential) sensors, sweat biochemical (pH, uric acid, glucose) sensors, thermal stimulators, and humidity energy harvesters. Among these devices, pencil-drawn graphite patterns (or combined with other compounds) serve as conductive traces and sensing electrodes, and office-copy papers work as flexible supporting substrates. The enabled devices can perform real-time, continuous, and high-fidelity monitoring of a range of vital biophysical and biochemical signals from human bodies, including skin temperatures, electrocardiograms, electromyograms, alpha, beta, and theta rhythms, instantaneous heart rates, respiratory rates, and sweat pH, uric acid, and glucose, as well as deliver programmed thermal stimulations. Notably, the qualities of recorded signals are comparable to those measured with conventional methods. Moreover, humidity energy harvesters are prepared by creating a gradient distribution of oxygen-containing groups on office-copy papers between pencil-drawn electrodes. One single-unit device (0.87 cm2) can generate a sustained voltage of up to 480 mV for over 2 h from ambient humidity. Furthermore, a self-powered on-skin iontophoretic transdermal drug-delivery system is developed as an on-skin chemical intervention example. In addition, pencil-paper-based antennas, two-dimensional (2D) and three-dimensional (3D) circuits with light-emitting diodes (LEDs) and batteries, reconfigurable assembly and biodegradable electronics (based on water-soluble papers) are explored.

Multiscale porous elastomer substrates for multifunctional on-skin electronics with passive-cooling capabilities.

In addition to mechanical compliance, achieving the full potential of on-skin electronics needs the introduction of other features. For example, substantial progress has been achieved in creating biodegradable, self-healing, or breathable, on-skin electronics. However, the research of making on-skin electronics with passive-cooling capabilities, which can reduce energy consumption and improve user comfort, is still rare. Herein, we report the development of multifunctional on-skin electronics, which can passively cool human bodies without needing any energy consumption. This property is inherited from multiscale porous polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS) supporting substrates. The multiscale pores of SEBS substrates, with characteristic sizes ranging from around 0.2 to 7 µm, can effectively backscatter sunlight to minimize heat absorption but are too small to reflect human-body midinfrared radiation to retain heat dissipation, thereby delivering around 6 °C cooling effects under a solar intensity of 840 W⋅m-2 Other desired properties, rooted in multiscale porous SEBS substrates, include high breathability and outstanding waterproofing. The proof-of-concept bioelectronic devices include electrophysiological sensors, temperature sensors, hydration sensors, pressure sensors, and electrical stimulators, which are made via spray printing of silver nanowires on multiscale porous SEBS substrates. The devices show comparable electrical performances with conventional, rigid, nonporous ones. Also, their applications in cuffless blood pressure measurement, interactive virtual reality, and human-machine interface are demonstrated. Notably, the enabled on-skin devices are dissolvable in several organic solvents and can be recycled to reduce electronic waste and manufacturing cost. Such on-skin electronics can serve as the basis for future multifunctional smart textiles with passive-cooling functionalities.

A Photocured Bio-based Shape Memory Thermoplastics for Reversible Wet Adhesion.

Development of reversible wet or underwater adhesives remains a grand challenge. Because weakened intermolecular interactions by water molecules or/and low effective contact area cause poor interface to the wet surfaces, which significantly decreases adhesive strength. Herein, a new photocured, bio-based shape memory polymer (SMP) that shows both chemical and structural wet adhesion to various types of surfaces is developed. The SMP is polymerized from three monomers mainly from bio-sources to form linear polymer chains dangled with hydrophobic side chains. The hydrogen acceptor and donor groups in the chains form hydrogen bonding with the surfaces, which is protected by the hydrophobic chains in the interface. The SMP shows tunable phase transition temperature (Tg) of 17-38 °C. In a rubbery state above Tg, the adhesive forms conformable contact with the targeted surfaces. Below Tg, a transition to a glassy state locks the conformed shapes to largely increase the effective contact area. As a result, the adhesive exhibits long-term underwater adhesion of > 15 days with the best adhesion strength of ~ 0.9 MPa. Its applications in leak repair, underwater on-skin sensors were demonstrated. This new, general strategy would pave avenues to designing bio-based, long-lasting, and reversible adhesives from renewable feedstocks for widespread applications.

Rapid, Highly Sensitive, and Label-Free Pathogen Assay System Using a Solid-Phase Self-Interference Recombinase Polymerase Amplification Chip and Hyperspectral Interferometry.

Recombinase polymerase amplification (RPA) is a useful pathogen identification method. Several label-free detection methods for RPA amplicons have been developed in recent years. However, these methods still lack sensitivity, specificity, efficiency, or simplicity. In this study, we propose a rapid, highly sensitive, and label-free pathogen assay system based on a solid-phase self-interference RPA chip (SiSA-chip) and hyperspectral interferometry. The SiSA-chips amplify and capture RPA amplicons on the chips, rather than irrelevant amplicons such as primer dimers, and the SiSA-chips are then analysed by hyperspectral interferometry. Optical length increases of SiSA-chips are used to demonstrate RPA detection results, with a limit of detection of 1.90 nm. This assay system can detect as few as six copies of the target 18S rRNA gene of Plasmodium falciparum within 20 min, with a good linear relationship between the detection results and the concentration of target genes (R2 = 0.9903). Single nucleotide polymorphism (SNP) genotyping of the dhfr gene of Plasmodium falciparum is also possible using the SiSA-chip, with as little as 1% of mutant gene distinguished from wild-type loci (m/wt). This system offers a high-efficiency (20 min), high-sensitivity (6 copies/reaction), high-specificity (1% m/wt), and low-cost (∼1/50 of fluorescence assays for RPA) diagnosis method for pathogen DNA identification. Therefore, this system is promising for fast identification of pathogens to help diagnose infectious diseases, including SNP genotyping.

Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer.

BACKGROUND: Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). METHODS: Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. RESULTS: High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. CONCLUSION: Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

Independent Flexural Wave Frequency Conversion by a Linear Active Metalayer.

Wave frequency is a critical parameter for applications ranging from structural health monitoring, noise control, and medical imaging to quantum of energy in matter. Frequency conversion is an inevitable wave phenomenon in nonlinear or time-modulated media. However, frequency conversion in linear media holds the promise of breaking limits imposed by the physics laws of wave diffraction such as Snell's law and Rayleigh criterion. In this Letter, we physically introduce a linear active metalayer in a structural beam that can convert the wave frequency of an flexural incidence into arbitrary frequencies of transmitted waves, which is underpinned by time modulation of sensing signals and insensitive to incident amplitude. The active element, involving piezoelectric components and time-modulated transfer function, breaks energy conservation such that the generated harmonics can be fully decoupled, making the frequency conversion linear and independent. By leveraging the time-modulated unit, phase-gradient and frequency-gradient metalayers are proposed for frequency-converted wave steering and dynamic beam steering, respectively. The linear active metalayer proposed herein suggests a promising solution to fully control time-domain signals of flexural waves, in stark contrast with existing elastic metasurfaces, regardless of being passive or active.

Single cell capture, isolation, and long-term in-situ imaging using quantitative self-interference spectroscopy.

Single cell research with microfluidic chip is of vital importance in biomedical studies and clinical medicine. Simultaneous microfluidic cell manipulations and long-term cell monitoring needs further investigations due to the lack of label-free quantitative imaging techniques and systems. In this work, single cell capture, isolation and long-term in-situ monitoring was realized with a microfluidic cell chip, compact cell incubator and quantitative self-interference spectroscopy. The proposed imaging method could obtain quantitative and dynamic refractive index distribution in living cells. And the designed microfluidic chip could capture and isolate single cells. The customized incubator could support cell growth conditions when single cell was captured in microfluidic chip. According to the results, single cells could be trapped, transferred and pushed into the culture chamber with the microfluidic chip. The incubator could culture single cells in the chip for 120 h. The refractive index sensitivity of the proposed quantitative imaging method was 0.0282 and the relative error was merely 0.04%.

Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid loaded onto fluorescent mesoporous silica nanoparticles for the location and therapy of nasopharyngeal carcinoma.

Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is a diterpenoid that is isolated and purified from the Chinese herbal medicine Pteris semipinnata L., and is known to exert antitumour activity in several kinds of malignant cancer cells by leading cancer cells to apoptosis. However, the antitumour effect of 5F in vivo is rarely reported due to the complexity of the physiological environment and limitations of 5F as a small anticancer drug. In the present study, we utilized FITC-doped nanoparticles for the accumulation and delivery of 5F in nasopharyngeal carcinoma CNE2 tumours transplanted in nude mice by the enhanced permeation and retention (EPR) effect. In vivo studies demonstrated that nanoparticles could efficiently deliver 5F in CNE2 transplanted tumours, and the tumour growth was effectively inhibited by the drug-loaded nanoparticles with minimal side effects. The study indicated the benefits of combining well-studied nanoparticles with traditional herbal medicine treatment and establishes a delivery platform for 5F chemotherapy.

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

OBJECTIVE: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target. DESIGN: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases. RESULTS: FLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis. CONCLUSIONS: Based on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

Physical Observation of a Robust Acoustic Pumping in Waveguides with Dynamic Boundary.

Research on breaking time-reversal symmetry to realize one-way wave propagation is a growing area in photonic and phononic crystals and metamaterials. In this Letter, we present physical realization of an acoustic waveguide with spatiotemporally modulated boundary conditions to realize nonreciprocal transport and acoustic topological pumping. The modulated waveguide inspired by a water wheel consists of a helical tube rotating around a slotted tube at a controllable speed. The rotation of the helical tube creates moving boundary conditions for the exposed waveguide sections at a constant speed. We experimentally demonstrate acoustic nonreciprocity and topologically robust bulk-edge correspondences for this system, which is in good agreement with analytical and numerical predictions. The nonreciprocal waveguide is a one-dimensional analog to the two-dimensional quantum Hall effect for acoustic circulators and is characterized by a robust integer-valued Chern number. These findings provide insight into practical implications of topological modes in acoustics and the implementation of higher-dimensional topological acoustics where time serves as a synthetic dimension.

Physical Realization of Elastic Cloaking with a Polar Material.

An elastic cloak is a coating material that can be applied to an arbitrary inclusion to make it indistinguishable from the background medium. Cloaking against elastic disturbances, in particular, has been demonstrated using several designs and gauges. None, however, tolerate the coexistence of normal and shear stresses due to a shortage of physical realization of transformation-invariant elastic materials. Here, we overcome this limitation to design and fabricate a new class of polar materials with a distribution of body torque that exhibits asymmetric stresses. A static cloak for full two-dimensional elasticity is thus constructed based on the transformation method. The proposed cloak is made of a functionally graded multilayered lattice embedded in an isotropic continuum background. While one layer is tailored to produce a target elastic behavior, the other layers impose a set of kinematic constraints equivalent to a distribution of body torque that breaks the stress symmetry. Experimental testing under static compressive and shear loads demonstrates encouraging cloaking performance in good agreement with our theoretical prediction. The work sets a precedent in the field of transformation elasticity and should find applications in mechanical stress shielding and stealth technologies.

A model based on CT radiomic features for predicting RT-PCR becoming negative in coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic. According to the diagnosis and treatment guidelines of China, negative reverse transcription-polymerase chain reaction (RT-PCR) is the key criterion for discharging COVID-19 patients. However, repeated RT-PCR tests lead to medical waste and prolonged hospital stays for COVID-19 patients during the recovery period. Our purpose is to assess a model based on chest computed tomography (CT) radiomic features and clinical characteristics to predict RT-PCR negativity during clinical treatment. METHODS: From February 10 to March 10, 2020, 203 mild COVID-19 patients in Fangcang Shelter Hospital were retrospectively included (training: n = 141; testing: n = 62), and clinical characteristics were collected. Lung abnormalities on chest CT images were segmented with a deep learning algorithm. CT quantitative features and radiomic features were automatically extracted. Clinical characteristics and CT quantitative features were compared between RT-PCR-negative and RT-PCR-positive groups. Univariate logistic regression and Spearman correlation analyses identified the strongest features associated with RT-PCR negativity, and a multivariate logistic regression model was established. The diagnostic performance was evaluated for both cohorts. RESULTS: The RT-PCR-negative group had a longer time interval from symptom onset to CT exams than the RT-PCR-positive group (median 23 vs. 16 days, p < 0.001). There was no significant difference in the other clinical characteristics or CT quantitative features. In addition to the time interval from symptom onset to CT exams, nine CT radiomic features were selected for the model. ROC curve analysis revealed AUCs of 0.811 and 0.812 for differentiating the RT-PCR-negative group, with sensitivity/specificity of 0.765/0.625 and 0.784/0.600 in the training and testing datasets, respectively. CONCLUSION: The model combining CT radiomic features and clinical data helped predict RT-PCR negativity during clinical treatment, indicating the proper time for RT-PCR retesting.

A density-watershed algorithm (DWA) method for robust, accurate and automatic classification of dual-fluorescence and four-cluster droplet digital PCR data.

Droplet digital PCR (ddPCR) is a single-molecule amplification technology with broad applications in precision medicine and clinical diagnosis. Dual-fluorescence and four-cluster ddPCR (two/four-ddPCR) assay is an effective way to quantify copy numbers. Currently, two/four-ddPCR data are usually classified with manual thresholds. For clinical applications, automatic and accurate methods are required to avoid subjectivity in diagnosis. Although there are some automatic classification algorithms, their accuracy and robustness still need to be improved to meet the needs of clinical diagnosis. Therefore, a new method is in high demand to automatically classify two/four-ddPCR data in an accurate and robust way. Here, a novel density-watershed algorithm (DWA) method was developed for the accurate, automatic and unsupervised classification of two/four-ddPCR data. First, data gridding was applied to a scatter plot of the fluorescence signal intensity to calculate data densities. Based on the data densities, the watershed algorithm was used to divide the gridded scatter plot into isolated regions automatically. Next, an optimal cluster pattern was determined based on these isolated regions, and excess regions were merged. Finally, the two/four-ddPCR data were classified based on the merged regions, and DNA template copy numbers were calculated accordingly. Using the DWA method for the quantification of both wild types and mutants of epidermal growth factor receptor (EGFR) L858R and T790M, the classification results were highly consistent with expectations, and significantly better than commonly-used automatic algorithms for now. The computed template copy numbers scaled proportionally to the relative concentration of input templates (r2 > 0.998) in four orders of magnitude with a good reproducibility, and achieved a limit of detection over 40 times lower than the commonly-used automatic algorithms. Furthermore, the DWA method was validated on 254 clinical DNA samples derived from frozen tissues, formalin-fixed paraffin-embedded tissues and peripheral blood. In most cases, the DWA method derived accurate and valid classification results. This highly effective DWA method may be widely used for automatically classifying two/four-ddPCR data, and it will greatly promote the application of ddPCR in clinical diagnosis.

Association between body weight status and suicidal ideation among Chinese adolescents: the moderating role of the child's sex.

PURPOSE: Suicidality (ranging from suicidal ideation to suicidal attempts and completed suicide) is a major and preventable public health concern, and body weight is considered a modifiable factor which might be helpful to the early risk assessment of suicidal ideation. This study aimed to comprehensively evaluate the association of body weight status with suicidal ideation across sex among Chinese adolescents. METHODS: Data were drawn from the 2015 National School-based Chinese Adolescents Health Survey, and 54,640 students' questionnaires were completed and qualified for the survey. Body mass index z scores were calculated and categorized into four levels: underweight (less than the 5th percentile for sex and age), normal weight (between the 5th and 85th percentile), overweight (between the 85th and 95th percentile), and obese (above the 95th percentile). RESULTS: Of the total sample, 47.3% (25,852) were boys. The weighted prevalence of suicidal ideation among Chinese adolescents is 15.7% (14.6% in boys and 17.3% in girls). After adjusting for demographics, smoking, drinking, and depressive symptoms, our final multivariate logistic regression models demonstrated that only boys identified as underweight (Adjusted odds ratio [AOR] = 1.23, 95% CI = 1.06-1.44) or obese (AOR = 1.19, 95% CI = 1.02-1.38) were at a higher risk of suicidal ideation. Additionally, the association between weight status and suicidal ideation among boys might be moderated by academic pressure, smoking, and depressive symptoms. CONCLUSIONS: There was a significant J-shaped association between relative body weight and suicidal ideation in boys. The child's sex should be taken into consideration when developing interventions against unhealthy weight and suicidal ideation.

Association between weekday sleep duration and nonmedical use of prescription drug among adolescents: the role of academic performance.

Nonmedical use of prescription drug (NMUPD) among adolescents has increased substantially over the last 2 decades, and evidence suggests that sleep duration may impact upon drug use and academic performance. This study aimed to estimate the prevalence of sleep duration, NMUPD, and academic performance among Chinese adolescents, to test the independent associations of sleep duration with NMUPD, and to investigate whether these associations vary by academic performance. Data were from the 2015 School-based Chinese Adolescents Health Survey using a multi-stage, stratified-cluster, random-sampling method to collect information from 162,601 high school students [mean age (SD) =15.2 (1.9) years; 47.4% were male] from 42 cities in China. The weighted prevalence of sleeping ≤ 5 h/weekday was 1.1% (95% CI, 1.0-1.1%), and the weighted prevalence of sleeping > 9 h/weekday was 7.6% (95% CI 7.4-7.7%). After adjusting for significant covariates and academic performance, the results showed that compared with those with 7-9 h/weekday sleep duration, students reporting ≤5 h/weekday were more likely to misuse opioids (AOR = 2.12, 95% CI 1.73-2.59), sedatives (AOR = 2.00, 95% CI 1.65-2.42), and any prescription drug use (AOR = 1.89, 95% CI 1.60-2.23); students with>9 h/weekday sleep duration were also at a higher risk of opioids use, sedative use, and any prescription drug misuse; the U-shaped association of sleep duration with NMUPD was found. Moreover, there exist significant associations between weekday sleep duration and NMUPD among Chinese adolescents, and academic performance plays a moderating role in the aforementioned associations. The efforts to prevent NMUPD should be focused on adolescents who report abnormal sleep duration or poor academic performance.