Dynamics of antibody binding and neutralization during viral infection.

In vivo in infection, virions are constantly produced and die rapidly. In contrast, most antibody binding assays do not include such features. Motivated by this, we considered virions with n=100 binding sites in simple mathematical models with and without the production of virions. In the absence of viral production, at steady state, the distribution of virions by the number of sites bound is given by a binomial distribution, with the proportion being a simple function of antibody affinity (Kon/Koff) and concentration; this generalizes to a multinomial distribution in the case of two or more kinds of antibodies. In the presence of viral production, the role of affinity is replaced by an infection analog of affinity (IAA), with IAA=Kon/(Koff+dv+r), where dv is the virus decaying rate and r is the infection growth rate. Because in vivo dv can be large, the amount of binding as well as the effect of Koff on binding are substantially reduced. When neutralization is added, the effect of Koff is similarly small which may help explain the relatively high Koff reported for many antibodies. We next show that the n+2-dimensional model used for neutralization can be simplified to a 2-dimensional model. This provides some justification for the simple models that have been used in practice. A corollary of our results is that an unexpectedly large effect of Koff in vivo may point to mechanisms of neutralization beyond stoichiometry. Our results suggest reporting Kon and Koff separately, rather than focusing on affinity, until the situation is better resolved both experimentally and theoretically.

[68Ga]Pentixafor PET/CT for staging and prognostic assessment of newly diagnosed multiple myeloma: comparison to [18F]FDG PET/CT.

PURPOSE: To evaluate the prognostic performance of [68Ga]Pentixafor PET/CT at baseline for staging of patients with newly diagnosed multiple myeloma (MM) and to compare it with [18F]FDG PET/CT and the Revised-International Staging System (R-ISS). METHODS: Patients who underwent [68Ga]Pentixafor and [18F]FDG PET/CT imaging were retrospectively included. Patient staging was performed according to the Durie-Salmon PLUS staging system based on [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT images, and the R-ISS. Progression-free survival (PFS) at patient follow-up was estimated using the Kaplan-Meier estimator and compared using the log-rank test. Area under the receiver operating characteristic curve (AUC) was calculated to assess predictive performance. RESULTS: Fifty-five MM patients were evaluated. Compared with [18F]FDG PET, [68Ga]Pentixafor PET detected 25 patients as the same stage, while 26 patients were upstaged and 4 patients were downstaged (P = 0.001). After considering the low-dose CT data, there was no statistically significant difference in the number of patients classified in each stage using [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT (P = 0.091). [68Ga]Pentixafor PET/CT-based staging discriminated PFS outcomes in patients with different disease stages (stage I vs. stage II, stage I vs. stage III, and stage II vs. stage III; all P < 0.05), whereas for [18F]FDG PET/CT, there was only a difference in median PFS between stage I and III (P = 0.021). When staged by R-ISS, the median PFS for stage III was significantly lower than that for stage I and II (P = 0.008 and 0.035, respectively). When predicting 2-year PFS based on staging, the AUC of [68Ga]Pentixafor PET/CT was significantly higher than that of [68Ga]Pentixafor PET (0.923 vs. 0.821, P = 0.002), [18F]FDG PET (0.923 vs. 0.752 P = 0.002), and R-ISS (0.923 vs. 0.776, P = 0.005). CONCLUSIONS: [68Ga]Pentixafor PET/CT-based staging possesses substantial potential to predict disease progression in newly diagnosed MM patients.

Double-single-atom MoCu-embedded porous carbons boost the electrocatalytic N2 reduction reaction.

NH3 is an essential ingredient of chemical, fertilizer, and energy storage products. Industrial nitrogen fixation consumes an enormous amount of energy, which is counter to the concept of carbon neutrality, hence eNRR ought to be implemented as a clean alternative. Herein, we propose a double-single-atom MoCu-embedded porous carbon material derived from uio-66 (MoCu@C) by plasma-enhanced chemical vapor deposition (PECVD) to boost eNRR capabilities, with an NH3 yield rate of 52.4 µg h-1 gcat.-1 and a faradaic efficiency (FE) of 27.4%. Advanced XANES shows that the Mo active site receives electrons from Cu, modifies the electronic structure of the Mo active site and enhances N2 adsorption activation. The invention of rational MoCu double-single-atom materials and the utilization of effective eNRR approaches furnish the necessary building blocks for the fundamental study and practical application of Mo-based materials.

Nuclear Medicine Application of Pentixafor/Pentixather Targeting CXCR4 for Imaging and Therapy in Related Disease.

C-X-C-motif chemokine receptor 4 (CXCR4) is a novel predictive biomarker for metastasis and poor prognosis in individuals with malignancies. CXCL12 is the only cognate ligand of CXCR4. CXCL12/CXCR4 signaling pathways are involved in the cross-talk among cancer cells, T cells, stromal cells, and their microenvironments, including the regulation and direction of T cell migration (chemotaxis), proliferation, and differentiation of immature progenitor stem cells. As CXCR4 overexpression is related to tumor prognosis, it is essential to quantitatively evaluate CXCR4 expression levels in vivo. 68Ga-Pentixafor, as a radiolabeled tracer, shows high specificity and affinity for CXCR4 in tumors. Thus, CXCR4-directed imaging with 68Ga-Pentixafor has been investigated to evaluate CXCR4 expression in patients non-invasively. In recent years, many small cohorts, including those of individuals with hematologic malignancies, solid tumors, and cardiovascular and infectious diseases, have been reported. So far, 68Ga-Pentixafor has been used successfully in individuals with hematologic malignancies. In addition, Lutetium-177 (177Lu) or Yttrium-90 (90Y)-labeled Pentixather (an analog of Pentixafor) suggested high potential applicability in tumor endoradiotherapy (ERT) with CXCR4 overexpression. Patients with advanced-stage multiple myeloma, refractory acute leukemia, and diffuse large B-cell lymphoma received a certain amount of 177Lu-Pentixather or 90Y-Pentixather. This review aimed to overview the current CXCR4-directed positron emission computed tomography (PET) molecular imaging based on Pentixafor in several diseases and ERT.

Utility of an In-Vitro Micro-Neutralizing Test in Comparison to a Plaque Reduction Neutralization Test for Dengue Virus, Japanese Encephalitis Virus, and Zika Virus Serology and Drug Screening.

Flavivirus infections, including dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), present significant global public health challenges. For successful vaccine design, the assessment of neutralizing antibody activity requires reliable and robust methodologies for determining antibody titers. Although the plaque reduction neutralization test (PRNT) is commonly acknowledged as the gold standard, it has limitations in terms of time and cost, and its usage may be limited in resource-limited settings. To address these challenges, we introduced the micro-neutralization test (MNT) as a simplified alternative to the PRNT. The MNT employs a 96-well plate format, conducts microscale neutralization assays, and assesses cell viability by dissolving cells to create a uniform color solution, which is measured with a spectrometer. In this study, we evaluated the utility of the MNT by contrasting the end-point titers of the MNT and PRNT using 4 monoclonal antibodies, 15 non-human primate serum samples, and 2 therapeutic drug candidates across flaviviruses. The results demonstrated a strong correlation between the MNT and PRNT titers, affirming the robustness and reproducibility of the MNT for evaluating control measures against flaviviruses. This research contributes valuable insights toward the development of a cost-effective antibody titer testing approach that is particularly suitable for resource-limited settings.

68Ga-FAPI and 18F-FDG PET/CT Images of a Patient With Rosai-Dorfman Disease With Liver Involvement.

ABSTRACT: Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis that is histopathologically characterized by the accumulation of CD68-positive and S100-positive histiocytes. The pathological changes are mostly discovered in lymph nodes. We report a case of Rosai-Dorfman disease with liver and bone marrow involvement. In this case, 18F-FDG PET/CT revealed FDG avidity in multiple lymph nodes, liver, and bone marrow. 68Ga-FAPI PET/CT showed higher uptake of 68Ga-FAPI than that of 18F-FDG in the same lesions. The findings of 68Ga-FAPI PET/CT in this patient highlighted the potential value of 68Ga-FAPI for staging in Rosai-Dorfman disease.

[68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of gastric cancer: comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to compare the performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the evaluation of primary and metastatic lesions of gastric cancer. METHODS: Fifty-six patients with histologically proven gastric carcinomas were enrolled in this study, including 45 patients for staging and 11 patients for restaging after surgery. Each patient underwent both [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. The activity of tracer accumulation in lesions was assessed by maximum standardized uptake value (SUVmax) and TBR (lesions SUVmax/ascending aorta SUVmean). Histological workup served as a standard of reference. If tissue diagnosis was not applicable, the follow-up data including the results of laboratory tests and medical imaging could also serve as a reference. RESULTS: [68Ga]Ga-DOTA-FAPI-04 PET/CT was comparable to [18F]FDG on detecting primary tumors and lymph node (LN) metastases, whereas [68Ga]Ga-DOTA-FAPI-04 outperformed [18F]FDG in detecting peritoneal (159 vs. 47, P < 0.001) and bone metastases (64 vs. 55, P = 0.003) by the lesion-based analysis. [68Ga]Ga-DOTA-FAPI-04 showed higher SUVmax (10.3 vs. 8.1, P = 0.004) and TBR (11.6 vs. 5.8, P < 0.001) in primary tumor, and higher TBR in LN involvement (8.0 vs. 3.7, P < 0.001) and peritoneal metastases (8.1 vs. 3.2, P < 0.001), compared with [18F]FDG PET/CT. The specificity and positive predictive value of [68 Ga]Ga-DOTA-FAPI-04 were significantly higher than that of [18F]FDG (100.0% vs. 97.7%, P < 0.001; 100.0% vs. 57.1%, P = 0.001) in determining the LN status. [68Ga]Ga-DOTA-FAPI-04 was comparable to [18F]FDG in evaluating N-staging (47.1% vs. 23.5%, P = 0.282). [68Ga]Ga-DOTA-FAPI-04 PET/CT detected more positive recurrent lesions in all restaging patients and showed clearer tumor delineation. Two patients underwent follow-up [68Ga]Ga-DOTA-FAPI-04 PET/CT scans after chemotherapy, which both showed remission. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/CT can better evaluate primary gastric cancer and metastatic lesions in the peritoneum, abdominal LNs, and bone. Furthermore, [68Ga]Ga-DOTA-FAPI-04 PET/CT provided more information for patients with recurrent disease and had the potential in monitoring response to treatment.

Synergistic effects of mechanical stimulation and crimped topography to stimulate natural collagen development for tendon engineering.

Suitable scaffold structures and mechanical loading are essential for functional tendon engineering. However, the bipolar fibril structure of native tendon collagen is yet to be recaptured in engineered tendons. This study compared the development of Achilles tendons of postnatal rats with and without (via surgical section) mechanical loading to define the mechanism of mechanical stimulation-mediated tendon development. The results demonstrated that the severed tendons weakened mechanically and exhibited disorganization without a bipolar fibril superstructure. Proteomic analysis revealed differentially expressed key regulatory molecules related to the collagen assembly process, including decreased fibromodulin, keratocan, fibroblast growth factor-1, and increased lumican and collagen5a1 in the severed tendons with immunohistochemical verification. Additionally, a complex regulatory network of mechanical stimulation-mediated collagen assembly in a spatiotemporal manner was also revealed using bioinformatics analysis, wherein PI3K-Akt and HDAC4 may be the predominant signaling pathways. A wavy microgrooved surface (Y = 5.47sin(0.015x)) that biomimics tendon topography was observed to enhance the expression of collagen assembly molecules under mechanical loading, and the aforementioned pathways are particularly involved and verified with their respective inhibitors of LY-294002 and LMK-235. Furthermore, an electrospun crimped nanofiber scaffold (approximately 2 µm fiber diameter and 0.12 crimpness) was fabricated to biomimic the tenogenic niche environment; this was observed to be more effective on enhancing collagen production and assembly under mechanical stimulation. In conclusion, the synergistic effect between topographical niche and mechanical stimulation was observed to be essential for collagen assembly and maturation and should be applied to functional tendon engineering in the future. STATEMENT OF SIGNIFICANCE: In biomaterial-mediated tendon regeneration, mechanical stimulation is essential for tendon collagen assembly. However, the underlying mechanisms remain not fully defined, leading to the failure of the native-like collagen regeneration. In this study, a mechanical stimulation deprivation model of rat tendon was established to reveal the mechanisms in tendon development and define the key regulatory molecules including small leucine-rich proteoglycans, lysyl oxidase and collagen V. After ensuring the importance of biomimetic structure in tendon remodeling, crimped nanofibers were developed to verify these regulatory molecules, and demonstrated that mechanical stimulation significantly enhanced collagen assembly via PIK3 and HDAC4 pathways in biomaterial-regulated tendon regeneration. This study provides more insightful perspectives in the physiologically remodeling progression of tendon collagen and design of tendon scaffolds.

Accurate preoperative staging with [68Ga]Ga-FAPI PET/CT for patients with oral squamous cell carcinoma: a comparison to 2-[18F]FDG PET/CT.

OBJECTIVE: To evaluate the potential value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in preoperative staging for patients with oral squamous cell carcinoma (OSCC) as compared to 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT. METHODS: Thirty-six treatment-naïve patients with OSCC who underwent 2-[18F]FDG and [68Ga]Ga-FAPI PET/CT for preoperative staging were enrolled. The maximum standardised uptake value (SUVmax) of the primary tumour and suspected cervical metastatic lymph nodes, and the tumour-to-background ratio (TBR) of the primary tumour, were measured. The accuracy of two imaging modalities for preoperative diagnosis of metastatic lymph nodes was analysed. Histopathology served as the standard of reference. RESULTS: Thirty-seven primary lesions of 36 patients were accurately detected by both [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT. Regarding primary tumours, the SUVmax and TBR of the two imaging modalities in stage T3-T4 were significantly higher than those of stage T1-T2 (all p < 0.05). On the patient analysis, the accuracy for the evaluation of N1-N3 neck status was 52.6% (10/19) for [68Ga]Ga-FAPI PET/CT and 57.9% (11/19) for 2-[18F]FDG PET/CT. Notably, the accuracy for the evaluation of the N0 neck status between [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT was 100% (17/17) and 29% (5/17), respectively. Based on the patient, neck side and neck level, [68Ga]Ga-FAPI PET/CT resulted in higher specificity and accuracy in diagnosing metastatic neck lymph nodes than 2-[18F]FDG PET/CT (all p < 0.05). CONCLUSION: [68Ga]Ga-FAPI PET/CT is a promising tool for preoperative staging of OSCC, and appears to reduce the false positivity seen with 2-[18F]FDG PET/CT for the detection of neck lymph node metastases. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising tool targeting cancer-associated fibroblasts with comparable diagnostic performance to 2-[18F]FDG PET/CT for identifying the primary lesions of OSCC. • [68Ga]Ga-FAPI PET/CT showed higher specificity and accuracy for the evaluation of neck lymph node metastases of OSCC than 2-[18F]FDG PET/CT, especially for N0 neck status.

Burkitt Lymphoma/Leukemia Presented on 68Ga-Pentixafor and 18F-FDG PET/CT.

ABSTRACT: An 18-year-old man with newly diagnosed Burkitt lymphoma/leukemia was referred for 18F-FDG and 68Ga-Pentixafor PET/CT. 68Ga-Pentixafor PET/CT revealed similar radioactivity uptake pattern to the 18F-FDG PET/CT in superior phrenic lymph node, ascending colon, ileocecum, peritoneal, marrow, and spleen. This case highlighted that it might be interesting to further investigate the role of 68Ga-Pentixafor PET/CT imaging in staging, treatment evaluation, and especially the feasibility of CXCR4-directed radioligand therapy in Burkitt lymphoma with positive expression of CXCR4.

CXCR4-Directed PET/CT with [68Ga]Pentixafor in Central Nervous System Lymphoma: A Comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to evaluate the value of [68 Ga]Pentixafor PET/CT for the detection of lesions in central nervous system lymphoma (CNSL) patients before chemotherapy, during treatment and suspected CSNL recurrence, compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). PROCEDURES: Twenty-six patients with newly or previously diagnosed CNSL who underwent [68 Ga]Pentixafor PET/CT were included retrospectively. Histopathological results, magnetic resonance imaging (MRI), and follow-up were used as the standard reference. The accuracy of lesion detection, maximum standardized uptake value (SUVmax) of tumors, and ratio of tumor-to-normal brain (T/N) with [68 Ga]Pentixafor PET/CT were calculated and compared to those obtained with [18F]FDG PET/CT. CXCR4 expression was analyzed through immunohistochemistry. RESULTS: Of 26 patients, 18 were newly diagnosed with a total of 23 lesions, 4 had recurrent with 4 lesions, and 4 underwent a mid-term treatment assessment after 4 cycles of chemotherapy (3 achieved complete response (CR), 1 experienced progressive disease (PD) with a total of 8 lesions). Thirty-five lesions were all clearly detected with favorable contrast by [68 Ga]Pentixafor PET/CT (accuracy, 100%), consistent with the results of contrast-enhanced magnetic resonance imaging (CE-MRI). The SUVmax of positive lesions in [68 Ga]Pentixafor PET/CT was correlated with tumor size (r = 0.555, P = 0.001). In 21 patients, compared with [18F]FDG PET/CT, [68 Ga]Pentixafor PET/CT showed a remarkably higher T/N ratio (21.93 ± 10.77 vs 4.29 ± 2.16, P = 0.000) and detected 5 more lesions in the mid-term treatment assessment of patients (P = 0.026). The CXCR4 expression of CNSL lesions was correlated with SUVmax of [68 Ga]Pentixafor PET/CT (r = 0.772, P = 0.000). CONCLUSIONS: CXCR4-directed PET/CT using [68 Ga]Pentixafor, with excellent tumor-to-background contrast, might be a more promising agent for the detection of lesions in CNSL patients than [18F]FDG PET/CT.

Quinone-Enriched Conjugated Microporous Polymer as an Organic Cathode for Li-Ion Batteries.

Among various organic cathode materials, C═O group-enriched structures have attracted wide attention worldwide. However, small organic molecules have long suffered from dissolving in electrolytes during charge-discharge cycles. π-Conjugated microporous polymers (CMPs) become one solution to address this issue. However, the synthesis strategy for CMPs with rich C═O groups and stable backbones remains a challenge. In this study, a novel CMP enriched with C═O units was synthesized through a highly efficient Diels-Alder reaction. The as-prepared CMP exhibited a fused carbon backbone and a semiconductive characteristic with a band gap of 1.4 eV. When used as an organic electrode material in LIBs, the insoluble and robust fused structure caused such CMPs to exhibit remarkable cycling stability (a 96.1% capacity retention at 0.2 A g-1 after 200 cycles and a 94.8% capacity retention at 1 A g-1 after 1500 cycles), superior lithium-ion diffusion coefficient (5.30 × 10-11 cm2 s-1), and excellent rate capability (95.8 mAh g-1 at 1 A g-1). This study provided a novel synthetic method for fabricating quinone-enriched fused CMPs, which can be used as LIB cathode materials.

B/N-Enriched Semi-Conductive Polymer Film for Micro-Supercapacitors with AC Line-Filtering Performance.

Microsupercapacitors (MSCs) have drawn great attention for use as miniaturized electrochemical energy storage devices in portable, wearable, as well as implantable electronics. Many materials have been developed as electrodes for MSCs. However, the thin-film fabrication for most of these materials involves multistep operations, including filtration, spray coating, and sputtering. Most importantly, these methods present challenges for the preparation of thin films at the atomic or molecular scale. Therefore, the understanding of performance of ultrathin-film-based MSCs remains challenge. Herein, a B/N-enriched polymer film is successfully prepared using the photoassisted interfacial approach. The as-synthesized polymer film exhibits typical semiconductive characteristics and can be easily scaled up to a large area of up to tens of square centimeters. This ultrathin polymer film can be directly transferred to silicon wafers to fabricate MSC through laser scribing. The prepared MSC exhibits specific volumetric capacitance as high as 20.9 F cm-3, corresponding to volumetric energy density of 2.9 mWh cm-3 (at 0.1 V s-1). Moreover, the volumetric power density can reach 1461 W cm-3, surpassing most existing semiconductive polymer film-based MSC devices. In addition, the prepared MSC exhibits typical AC line-filtering ability (-67° at 120 Hz). This study offers a facile interfacial approach to preparing semiconductive polymer films with aromatic moieties for microsized energy storage devices.

A Novel Heterostructure Based on RuMo Nanoalloys and N-doped Carbon as an Efficient Electrocatalyst for the Hydrogen Evolution Reaction.

Heterostructures exhibit considerable potential in the field of energy conversion due to their excellent interfacial charge states in tuning the electronic properties of different components to promote catalytic activity. However, the rational preparation of heterostructures with highly active heterosurfaces remains a challenge because of the difficulty in component tuning, morphology control, and active site determination. Herein, a novel heterostructure based on a combination of RuMo nanoalloys and hexagonal N-doped carbon nanosheets is designed and synthesized. In this protocol, metal-containing anions and layered double hydroxides are employed to control the components and morphology of heterostructures, respectively. Accordingly, the as-made RuMo-nanoalloys-embedded hexagonal porous carbon nanosheets are promising for the hydrogen evolution reaction (HER), resulting in an extremely small overpotential (18 mV), an ultralow Tafel slope (25 mV dec-1 ), and a high turnover frequency (3.57 H2 s-1 ) in alkaline media, outperforming current Ru-based electrocatalysts. First-principle calculations based on typical 2D N-doped carbon/RuMo nanoalloys heterostructures demonstrate that introducing N and Mo atoms into C and Ru lattices, respectively, triggers electron accumulation/depletion regions at the heterosurface and consequently reduces the energy barrier for the HER. This work presents a convenient method for rational fabrication of carbon-metal heterostructures for highly efficient electrocatalysis.

A Comparison of the Development of Medical Informatics in China and That in Western Countries from 2008 to 2018: A Bibliometric Analysis of Official Journal Publications.

Objective: We focused on medical informatics journal publications rather than on conference proceedings by comparing and analyzing the data from journals and conferences from a broader perspective. The aim is to summarize the unique contributions of China to medical digitization and foster more multilevel international cooperation. Method: In February 2019, publications from 2008 to 2018 in three major English-language medical informatics journals were retrieved through Scopus, including the journals, namely, International Journal of Medical Informatics (IJMI, international community), JAMIA (United States), and Methods of Information in Medicine (MIM, Europe). Three major Chinese-language journals, namely, China Digital Medicine (CDM), Chinese Journal of Health Informatics and Management (CJHIM), and Chinese Journal of Medical Library and Information Science (CJMLIS), were searched within the major three Chinese literature databases. The datasets were preprocessed using the NLP package on Python, and a smart local moving algorithm was used as a clustering method for identifying the aforementioned journals. Result: Between 2008 and 2018, the total number of published papers and H-index of the three English-language journals was 1371 and 67 (IJMI), 1752 and 86 (JAMIA), and 637 and 35 (MIM), respectively. In the same period, the total number of published papers and H-index in the three Chinese-language journals was 6668 and 23 (CDM), 1668 and 22 (CJHIM), and 2557 and 25 (CJMLIS), respectively. IJMI, JAMIA, and MIM received submissions from 82, 59, and 62 countries/regions, respectively. By contrast, the three Chinese journals only received submissions from seven foreign countries. The proportions of authors from institutional affiliations were similar between the three English-language journals (IJMI, JAMIA, and MIM) and CJMLIS because the majority of the authors were from universities (81%, 74%, 73%, and 65.2%), followed by medical institutions (12%, 10%, 9%, and 23.4%) or research institutes (2%, 4%, 10%, and 4.3%). Furthermore, the proportions of the authors from enterprises were low (2%, 6%, 4%, and 0.3%) for all journals. However, the authors in CDM and CJHIM were mainly from medical institutions (50% and 40%), followed by universities (33% and 32%) and research institutes (3% and 4%). In addition, the proportions of enterprises were only 3% and 2%, respectively. Among the top five authors in three English-language journals (ranked in terms of the number of published papers), 100% had doctoral or master's degrees, compared with only 60% in the Chinese journals. Additionally, 28204 different keywords were extracted from the aforementioned papers, covering 275 specific high-frequency key terms. Based on these key terms, four clusters were found in the English literature-"Health and Clinical Information Systems," "Internet and Telemedicine," "Medical Data Statistical Analysis," and "EHRs and Information Management"-and three clusters were found in the Chinese literature: "Hospital Information Systems and EMR," "Library Science and Bibliometrics Analysis," and "Medical Reform Policy and Health Digitization." Only two clusters are similar, and Chinese-language journals focus more on health information in technology and industrial applications than in medical informatics basic research. Conclusion: This study provides important insights into the development of medical informatics (MI) in China and Western countries showing that the medical informatics journals of China, the United States, and Europe have distinct characteristics. Specifically, first, compared with the Western journals, the number of papers published in the journals of professional associations in the field of MI in China is large and the application value is high, but the academic influence and academic value are relatively low; second, most of the authors of the Chinese papers are from hospitals, and most of the counterparts in the Western countries are from universities. The proportion of master's or doctoral degrees in the former is also lower than that of the latter; furthermore, regarding paper themes, on the one hand, China MI has no theoretical and basic research on medical data statistics and consumer health based on the Internet and telemedicine; on the other hand, after nearly 10 years of hospital digital development, China has fully used the latecomer and application advantages in hospitals and, through extensive international cooperation, has made significant advancements in and contributions to the development of medical information.

The experience and challenges of healthcare-reform-driven medical consortia and Regional Health Information Technologies in China: A longitudinal study.

OBJECTIVE: To achieve universal access to medical resources-a partial goal of the second ambitious health reform since 2010-the Chinese government aimed to build a regional medical consortium and enhance the efficiency of health information exchange (HIE). We analyzed the experience of constructing a medical consortium in Chinese hospitals, which was based on regional health information technology (RHIT) promoted by HIE. METHOD: In this longitudinal study, we analyzed the results of the annual surveys that were conducted by the China Hospital Information Management Association from 2006 to 2015. The survey results mainly concerned whether hospitals should join the regional medical consortium, the methods used for sharing inter-hospital medical data, and the out-of-hospital information interaction system. The Bass diffusion model was adopted to fit and predict the proportion of Chinese hospitals joining the consortium from 2006 to 2025. RESULT: As of 2015, the survey results of 7272 hospitals were obtained. The proportion of hospitals in partnership systems increased from 3.0% in 2007 to 57.2% in 2015. There has been a rapid development in the electronic sharing of medical data between hospitals. The proportion of hospitals that relied solely on paper documents for data interaction decreased from 43.3% in 2011 to 8.0% in 2015. There was a strong positive linear correlation between hospitals joining the consortium and the accessibility of electronic medical data exchange within hospitals (r = 0.925). The proportions of hospitals that supported dual referral systems and appointments, data browsing between hospitals and regional information systems, and remote consultation services increased to 65.0%, 61.6%, and 81.9% in 2015, as compared to 18.8%, 16.8%, and 10.9% in 2011, respectively. The Bass prediction model showed that the goal of recruiting 90% of the hospitals to the consortium by 2020 will likely be achieved (adjusted R2 = 0.93). CONCLUSION: The Chinese government has applied a top-down, high-level design model to promote the rapid development of a medical consortium, in which the RHIT technologies are crucial technical enabler.

Sulfur-anchored azulene as a cathode material for Li-S batteries.

A benzene-free and vinyl-free molecule, azulene, is used to polymerize with sulfur through inverse vulcanization. The sulfur radical promoted reaction mechanism has been studied through solid-state NMR experiments combined with DFT calculations. The as produced polymer has high sulfur content and can serve as a cathode material for Li-S batteries with longer lifetime stability compared to pure sulfur, providing a new protocol to develop new cathode materials for Li-S batteries.

Effects of chronic lead exposure on the sympathoexcitatory response associated with the P2X7 receptor in rat superior cervical ganglia.

Chronic lead exposure frequently brings about increased blood pressure and other cardiovascular diseases associated with autonomic nervous dysfunction. Purinergic signaling is involved in the development of abnormal sympathoexcitatory response due to myocardial ischemic injury. However, the potential implication of P2X7 receptor in altered sympathoexcitatory response caused by chronic lead exposure and the underlying mechanisms remain unclear. In this study, a rat model of chronic lead exposure was used to explore the changes in sympathoexcitatory response and possible involvement of P2X7 receptor in the superior cervical ganglion (SCG). Rats were divided into three groups called control, low lead and high lead groups according to daily lead exposure levels, i.e. 0, 0.5 and 2 g/L respectively. One year later, changes in P2X7 receptor expression in SCG, sympathetic nerve activity and myocardial function were measured for these rats. Our results showed that increased blood pressure and heart rate, decreased heart rate variability, enhanced cervical sympathetic nerve discharge, higher phosphorylation of ERK1/2, and up-regulated protein and mRNA levels of P2X7 expression in SCG occurred after lead exposure. In addition, double-label immunofluorescence staining of P2X7 receptor and glutamine synthetase (GS) revealed activation of the satellite glial cells of SCG by lead exposure. Moreover, knockdown of P2X7 could effectively relief the effect of lead exposure on enhanced expression of P2X7 receptor and GS. Thus our data suggest that the up-regulation of P2X7 receptor activity in satellite glial cells of SCG may contribute to the raised sympathoexcitatory response due to chronic lead exposure.

A room-temperature interfacial approach towards iron/nitrogen co-doped fibrous porous carbons as electrocatalysts for the oxygen reduction reaction and Zn-Air batteries.

The development of nonprecious and efficient catalysts to boost the oxygen reduction reaction (ORR) is imperative. However, the majority of previously reported approaches suffered from a complicated fabrication procedure, both time consuming and difficult to scale up. Herein, large-scale iron ion embedded polyaniline fibers were successfully fabricated as precursors for preparing iron/nitrogen co-doped fibrous porous carbons (Fe/NPCFs) through an interfacial engineering strategy at room temperature. As ORR electrocatalysts in an alkaline medium (0.1 M KOH), Fe/NPCFs display a positive half-wave potential of 0.827 V (vs. RHE), and high limited current density (up to 5.76 mA cm-2), which are better than those of commercial Pt/C (E1/2 = 0.815 V, JL = 5.47 mA cm-2). Also, Fe/NPCFs exhibit a high ORR catalysis activity (E1/2 = 0.632 V, JL = 5.07 mA cm-2) in acidic medium (0.5 M H2SO4). When used as an air cathode in a primary Zn-air battery, high power density (158.5 mW cm-2) and specific capacity (717.8 mA h g-1) can be easily achieved, outperforming the commercial Pt/C.

[99mTc]3PRGD2 for integrin receptor imaging of esophageal cancer: a comparative study with [18F]FDG PET/CT.

OBJECTIVES: This study was designed to investigate the efficacy of 99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([99mTc]3PRGD2) in the evaluation of patients with esophageal cancer. METHODS: Twenty-nine patients with a suspected esophageal lesion and for whom definite pathological diagnosis was finally obtained were recruited. Whole-body planar scanning and chest single-photon-emission computed tomography/computed tomography (SPECT/CT) were performed at 30 and 40 min, respectively, after intravenous injection of 11.1 MBq/kg of [99mTc]3PRGD2. 2-Deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) was performed in 1 week. The tumor-to-background ratio (T/B) and the maximum standard uptake value (SUVmax) were calculated for semi-quantitative and quantitative analyses. Integrin αvß3 was analyzed through immunohistochemistry. RESULTS: The T/B, SUVmax and expression of integrin αvß3 in malignant lesions were higher than those in benign lesions (t = 3.691, P = 0.001; t = 8.271, P = 0.000; t = 3.632, P = 0.001, respectively). There was a significant correlation between T/B and SUVmax in esophageal lesions (r = 0.660, P = 0.000). The expression of integrin αvß3 was correlated with [99mTc]3PRGD2 uptake (r = 0.782, P = 0.000). In visual analysis, the sensitivity and accuracy of the whole-body planar RGD scan were lower than those of the chest SPECT/CT RGD scan and the [18F]FDG PET/CT scan (x2 = 6.769, P = 0.022). The sensitivity, specificity and accuracy of the chest SPECT/CT RGD scan were similar to those of the [18F] FDG PET/CT scan. In semi-quantitative analysis, the sensitivity, specificity and accuracy of chest SPECT/CT RGD from the receiver operating characteristic (ROC) analysis were 87%, 100% and 94%, respectively [cutoff = 3.1 of T/B, area under the curve (AUC) = 0.957]. Thirteen patients (30 lymph nodes) and 16 patients (105 lymph nodes) were suspected to have lymph node metastases based on the RGD and FDG scans, respectively. CONCLUSION: This prospective study demonstrated that [99mTc]3PRGD2 imaging is valuable for the diagnosis and staging of esophageal cancer. It may be less sensitive than [18F]FDG imaging for detecting metastatic lesions in small lymph nodes. The T/B value was correlated with the expression of integrin αvß3. NIH CLINICALTRIALS.GOV: NCT 02744729.