Influence of doctors' perception on the diagnostic status of chronic kidney disease: results from 976 409 individuals with electronic health records in China.

BACKGROUND: The diagnostic status of chronic kidney disease (CKD) and its underlying reasons provide evidence that can improve CKD management. However, the situation in developing countries remains under-investigated. METHODS: Adults with electronic health records (EHRs; 2008-19) in Yinzhou, China were included. The gold standard for CKD was defined as having persistently reduced estimated glomerular filtration rate (eGFR), albuminuria/proteinuria, haematuria or a history of CKD. CKD stages (G1-G5) were defined by eGFR. Clinical diagnosis of CKD in the real world setting was evaluated using International Classification of Diseases (ICD)-10 codes related to primary cause or stages of CKD. The specialty of doctors who administered the serum creatinine (SCr) tests and who made the primary-cause/CKD-staging diagnoses was analysed. The accuracy of CKD-staging codes was assessed. RESULTS: Altogether, 85 519 CKD patients were identified from 976 409 individuals with EHRs. Of them, 10 287 (12.0%) having persistent urinary abnormalities or labelled with CKD-related ICD codes did not receive SCr tests within 12 months before or after the urine tests. Among 75 147 patients who received SCr tests, 46 150 (61.4%) missed any CKD-related codes, 6857 (35.7%) were merely labelled with primary-cause codes, and only 2140 (2.9%) were labelled with CKD-staging codes. The majority of CKD patients (51.6-91.1%) received SCr tests from non-nephrologists, whereas CKD-staging diagnoses were mainly from nephrologists (52.3-64.8%). Only 3 of 42 general hospitals had nephrologists. The CKD-staging codes had high specificity (>99.0%) but low sensitivity (G3-G4: <10.0%). CONCLUSIONS: Under-perception of CKD among doctors, rather than unsatisfactory health-seeking behaviour or low detection rates, was the main cause of under-diagnosis of CKD in China. Intensification of CKD education among doctors with different specialties might bring about immediate effective improvement in the diagnosis and awareness of CKD.

Thermoelectric effect in a single molecular junction with a vibrational mode.

We investigate thermoelectric properties of single molecular junctions with electron-phonon interaction (EPI) based on a two-level model, and explore the possibility to obtain a thermoelectric device with high efficiency by engineering the energy level splitting in the molecular junction. We derive analytical expressions for electric conductance, thermopower and electronic thermal conductance in the linear response region within the dressed tunneling approximation of EPI. The effects of EPI and the level splitting in the molecule on thermoelectric properties are discussed. We show large value of thermoelectric figure of meritZTcan be achieved for molecular junctions with strong EPI and relatively small energy level splitting between the bonding and antibonding states of the molecule.

Establishment of a hepatocellular carcinoma patient-derived xenograft platform and its application in biomarker identification.

Using a method optimized in hepatocellular carcinoma (HCC), we established patient-derived xenograft (PDX) models with an increased take rate (42.2%) and demonstrated that FBS +10% dimethyl sulfoxide exhibited the highest tumor take rate efficacy. Among 254 HCC patients, 103 stably transplantable xenograft lines that could be serially passaged, cryopreserved and revived were established. These lines maintained the diversity of HCC and the essential features of the original specimens at the histological, transcriptome, proteomic and genomic levels. Tumor engraftment was associated with lack of encapsulation, poor tumor differentiation, large size and overexpression of cancer stem cell biomarkers, and was an independent predictor for overall survival and tumor recurrence after resection. To confirm the preclinical value of the PDX model in HCC treatment, several antitumor agents were tested in 16 selected PDX models. The results revealed a high degree of pharmacologic heterogeneity in the cohort, as well as heterogeneity to different agents in the same individual. The sorafenib responses observed between HCC patients and the corresponding PDXs were also consistent. After molecular characterization of the PDX models, we explored the predictive markers for sorafenib response and found that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) might play an important role in sorafenib resistance and sorafenib response is impaired in patients with MAP3K1 downexpression. Our results indicated that PDX models could accurately reproduce patient tumors biology and could aid in the discovery of new treatments to advance in precision medicine.

On the competition between the Kondo effect and the exchange interaction in a parallel double quantum dot system.

We study the competition between the Kondo effect and the exchange interaction in the parallel double quantum dot (DQD) system within an effective action field theory. The strong on-site Coulomb interactions in DQDs are treated by using the Hubbard-Stratonovich transformation and the introduction of scalar potential fields. We show that a self-consistent perturbation approach, which takes into account the statistical properties of the potential fields acting on electrons in DQDs, describes well the crossover from the Kondo regime to the spin-singlet state in this system. The linear conductance and the intradot/interdot spin excitation spectra of this system are obtained.

Transient currents of a single molecular junction with a vibrational mode.

By using a propagation scheme for current matrices and an auxiliary mode expansion method, we investigate the transient dynamics of a single molecular junction coupled with a vibrational mode. Our approach is based on the spinless Anderson-Holstein model and the dressed tunnelling approximation for the electronic self-energy in the polaronic regime. The time-dependent currents after a sudden switching on the tunnelling to leads, an abrupt upward step bias pulse and a step potential on the quantum dot are calculated. We show that the strong electron-phonon interaction greatly influences the nonlinear response properties of the system, and gives rise to interesting characteristics on the time traces of transient currents.

Charge transport and ac response under light illumination in gate-modulated DNA molecular junctions.

Using a two-strand tight-binding model and within nonequilibrium Green's function approach, we study charge transport through DNA sequences (GC)NGC and (GC)1(TA)NTA (GC)3 sandwiched between two Pt electrodes. We show that at low temperature DNA sequence (GC)NGC exhibits coherent charge carrier transport at very small bias, since the highest occupied molecular orbital in the GC base pair can be aligned with the Fermi energy of the metallic electrodes by a gate voltage. A weak distance dependent conductance is found in DNA sequence (GC)1(TA)NTA (GC)3 with large NTA. Different from the mechanism of thermally induced hopping of charges proposed by the previous experiments, we find that this phenomenon is dominated by quantum tunnelling through discrete quantum well states in the TA base pairs. In addition, ac response of this DNA junction under light illumination is also investigated. The suppression of ac conductances of the left and right lead of DNA sequences at some particular frequencies is attributed to the excitation of electrons in the DNA to the lead Fermi surface by ac potential, or the excitation of electrons in deep DNA energy levels to partially occupied energy levels in the transport window. Therefore, measuring ac response of DNA junctions can reveal a wealth of information about the intrinsic dynamics of DNA molecules.

Negative differential conductance and hysteretic current switching of benzene molecular junction in a transverse electric field.

We study charge transport through single benzene molecular junction (BMJ) directly sandwiched between two platinum electrodes by using a tight-binding model and the non-equilibrium Green's function approach. Pronounced negative differential conductance is observed at finite bias voltage, resulting from charge redistribution in BMJ and a Coulomb blockade effect at the interface of molecule-electrode contacts. In the presence of a transverse electric field, hysteretic switching behavior and large spin-polarization of current are obtained, indicating the potential application of BMJ for acting as a nanoscale current modulator or spintronic molecular device.

Phonon effects on the current noise spectra and the ac conductance of a single molecular junction.

By using nonequilibrium Green's functions and the equation of motion method, we formulate a self-consistent field theory for the electron transport through a single-molecule junction (SMJ) coupled with a vibrational mode. We show that the nonequilibrium dynamics of the phonons in a strong electron-phonon coupling regime can be taken into account appropriately in this self-consistent perturbation theory, and the self-energy of the phonons is connected with the current fluctuations in the molecular junction. We calculate the finite-frequency nonsymmetrized noise spectra and the ac conductance, which reveal a wealth of inelastic electron tunneling characteristics on the absorption and emission properties of this SMJ. In the presence of a finite bias voltage and the electron tunneling current, the vibration mode of the molecular junction is heated and driven to an unequilibrated state. The influences of unequilibrated phonons on the current and the noise spectra are investigated.

A 41-gene signature derived from breast cancer stem cells as a predictor of survival.

PURPOSE: The aim of this study was to evaluate the ability of a 41-gene signature derived from breast cancer stem cells (BCSCs) to estimate the risk of metastasis and survival in breast cancer patients. METHODS: The centroid expression of the 41-gene signature derived from BCSCs was applied as the threshold to classify patients into two separate groups--patients with high expression (high-EL) of the prognostic signature and patients with low expression (low-EL). The predictive ability of the 41-gene signature was evaluated by Cox regression model and was compared against other popular tests, such as Oncotype and MammaPrint. RESULTS: Our results showed that the 41-gene prognostic signature was significantly associated with age (P = .0351) and ER status (P = .0095). The analysis indicated that patients in the high-EL group had a worse prognosis than those in the low-EL group in terms of both overall survival (OS: HR, 2.05, P = .009) and distant metastasis-free survival (DMFS: HR, 2.24, P = .002). Additionally, the 41-gene signature was an independent risk factor and separates patients based on estrogen receptor status. While comparable to Oncotype, the analysis demonstrated that the 41-gene signature had a better prognostic value in predicting DMFS and OS than AOL, NPI, St. Gallen, Veridex, and MammaPrint. CONCLUSIONS: This study confirms the utility of the 41-gene signature and adds to the growing evidence that gene expression signatures of BCSCs have clinical potential to predict patient outcome and aid in treatment choice.

MicroRNA mediated network and DNA methylation in colorectal cancer.

Colorectal cancer (CRC) is one of the most malignant cancers. A growing number of studies have shown that both genetic and epigenetic play important roles in the etiology of CRC. Both microRNA (miRNA) and DNA methylation belong to the scope of epigenetic and there are complex regulatory mechanisms within miRNA and DNA methylation. We compiled 71 CRC related genes and 134 CRC related miRNAs. Then we identified 417 feed forward loops (FFLs) and 37 feedback loops (FBLs) among these genes, miRNAs and transcription factors (TFs). We constructed a network of miRNAs and TFs mediation for CRC utilizing these FFLs and FBLs. Statistical tests proved that these FFLs were significantly enriched in the CRC comparing to the esophageal cancer, breast cancer and randomly selected CRCmiRNA-gene pairs. Analysis of the network singled out 3 core genes, 2 core miRNAs and 5 core TFs. The KEGG enrichment and GO enrichment for the 2 core miRNA target genes indicated that they were significantly enriched in CRC related pathways. (Ex. MARK pathway, TGFß pathway and cell cycle) Through the investigation on methylation, we found that most of the CRC related genes and miRNAs were prone to be regulated by methylation. This study sheds lights on the regulatory mechanisms in CRC and we provide some insights on the epigenetic of CRC.

The optical conductivity of bilayer zigzag-edge graphene nanoribbons with external transverse electric fields.

The optical absorption properties of bilayer zigzag-edge graphene nanoribbons (BL-ZGNRs) with external transverse electric fields are investigated by taking into account the Coulomb interaction effect in the Hartree-Fock approximation. We study the phase transitions of BL-ZGNRs induced by external electric fields and also the optical selection rules for the incident light polarized along the longitudinal and transverse directions. We find that the excitations from the edge states are crucial for the optical properties of BL-ZGNRs in the antiferromagnetic phase. We show that the low energy part of the optical absorption can be modulated by the external transverse electric field, and there is a broad band low frequency absorption enhancement for the transverse-polarized incident light in the charge-polarized state of BL-ZGNRs.

Spin-polarized electron transport through graphene nanoribbon with zigzag edges.

We investigate the electron transport through a graphene nanoribbon (GNR) junction with zigzag edges. It is shown that the edge state and the magnetization properties of a GNR greatly influence its electron transport properties. By applying sufficient back-gate voltages to the lead parts of a zigzag GNR, the magnetization of the edges is quenched in the leadings parts, but is preserved in the center part of the junction. Without applying external transverse electric field, we show that, by preparing the junction in a ferromagnetic state, a strongly spin-polarized electron current can be obtained even though the incident electron current has no spin polarization.

Spin interference and the Fano effect in electron transport through a mesoscopic ring side-coupled with a quantum dot.

We investigate the electron transport through a mesoscopic ring side-coupled with a quantum dot (QD) in the presence of Rashba spin-orbit (SO) interaction. It is shown that both the Fano resonance and the spin interference effects play important roles in the electron transport properties. As the QD level is around the Fermi energy, the total conductance shows a typical Fano resonance line shape. By applying an electrical gate voltage to the QD, the total transmission through the system can be strongly modulated. By threading the mesoscopic ring with a magnetic flux, the time-reversal symmetry of the system is broken, and a spin polarized current can be obtained even though the incident current is unpolarized.

Quantum phase transition and underscreened Kondo effect in electron transport through parallel double quantum dots.

We investigate electronic transport through a parallel double quantum dot (DQD) system with strong on-site Coulomb interaction and capacitive interdot coupling. By applying the numerical renormalization group (NRG) method, the ground state of the system and the transmission probability at zero temperature have been obtained. For a system of quantum dots with degenerate energy levels and small interdot tunnel coupling, the spin correlations between the DQDs is ferromagnetic and the ground state of the system is a spin-1 triplet state. The linear conductance will reach the unitary limit (2e(2)/h) due to the underscreened Kondo effect at low temperature. As the interdot tunnel coupling increases, there is a quantum phase transition from ferromagnetic to antiferromagnetic spin correlation in DQDs and the linear conductance is strongly suppressed.

Gene expression profiling-based in silico approach to identify potential vaccine candidates and drug targets against B. pertussis and B. parapertussis.

Whooping cough (pertussis) caused by B. pertussis (B.p) is still serious public health threat. B. parapertussis (B.pp), closely related to B.p, also causes whooping cough. The incidence of B.pp infections has been increasing over the last decades, partly because pertussis vaccines have low efficiency against B.pp infections. Moreover, because the majority of pertussis patients are infants, common antimicrobial agents producing serious adverse reactions in infants are not fully satisfactory. Therefore, we try to identify potential vaccine candidates and alternative drug targets against both B.p and B.pp. This preliminary work integrates several different kinds of data from in silico analysis, comparative genomic hybridization, global transcriptional profiling, and protein-protein interaction (PPI) network to screen potential vaccine candidates and drug targets against the two species. Finally, 191 potential crossprotective vaccine candidates are identified. They have high transcriptional levels in both species, or are associated with virulence and pathogenesis. Moreover, these proteins are not only potentially surface-exposed in the bacteria, but also well conserved among the 165 B.p and B.pp strains. Among them, 22 candidates with high essentiality in the two PPI networks of B.p and B.pp are regarded as suitable drug targets against the two species. We just selected Bordetella as an example to develop a rapid and reliable approach for screening alternative drug targets that associated with novel protein pathways, complexes, and cellular functions against these antibiotic-resistant pathogens. Further researches focusing on the 191 vaccine candidates could accelerate the development of more effective vaccines and drug therapy against B.p and B.pp infection.

hBolA, novel non-classical secreted proteins, belonging to different BolA family with functional divergence.

This study reported that all three human BolA proteins (hBolA1, hBolA2, and hBolA3) are novel non-classical secreted proteins identified with bioinformatics and molecular biology experiments. The three BolA fusion proteins with c-Myc tag could be secreted into the culture medium of the transfected Cos-7 cells, although they could not be colocalized with Golgi apparatus. And the secretion of three BolA proteins could not be inhibited after BFA treatment. Furthermore, the secretion was not dependent on its predicted signal peptide. All the experiment results suggested that the secretion was a non-classical export. Phylogenetic analysis showed that the human BolAs belong to three different groups with functional divergence of BolA subfamily, where the different helix-turn-helix motif among hBolA1, hBolA2, and hBolA3 could be responsible for their functional divergence. Our data provided a basis for functional studies of BolA protein family.

Modular co-evolution of metabolic networks.

BACKGROUND: The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. RESULTS: In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. CONCLUSION: The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.