Therefore, the identification of biomarkers that differentiate these diseases is of importance for preventing misdiagnosis. In this regard, the present study aimed to identify the disorders at the early stages, based on lung transcriptomics data and drug-target interactions.To this end, the differentially expressed genes were found in each disease. Then, WGCNA was utilized to find specific and consensus gene modules among the three diseases. Finally, the disease-disease similarity was analyzed, followed by determining candidate drug-target interactions.The results confirmed that the asthma lung transcriptome was more similar to COPD than IPF. In addition, the biomarkers were found in each disease and thus were proposed for further clinical validations. These genes included RBM42, STX5, and TRIM41 in asthma, CYP27A1, GM2A, LGALS9, SPI1, and NLRC4 in COPD, ATF3, PPP1R15A, ZFP36, SOCS3, NAMPT, and GADD45B in IPF, LRRC48 and CETN2 in asthma-COPD, COL15A1, GIMAP6, and JAM2 in asthma-IPF and LMO7, TSPAN13, LAMA3, and ANXA3 in COPD-IPF. Finally, analyzing drug-target networks suggested anti-inflammatory candidate drugs for treating the above mentioned diseases.In general, the results revealed the unique and common biomarkers among three chronic lung diseases. Eventually, some drugs were suggested for treatment purposes. Lungs are considered as vital and vulnerable parts of the respiratory system and play critical roles in the body  are struggling with COPD. The incidence rate has indicated an increase of 44.2% from 1990 to 2015  were estimated based on healthy and patient states for the samples . The mean of expression was used for multiple probes mapping to the same gene  . The gene list of shared DEGs between the two diseases (three states) and among the three diseases was used for further investigations Fig. .Fig. 1WAccording to the study by Horvath and Dong  was calculated using the pickSoftThreshold function. Then, disease-specific adjacency matrices were generated utilizing the selected β threshold and were transformed to the Topological Overlap Matrix (TOM) using the TOMsimilarity function : The correlation between gene expression profile in the modules and the disease states, as well as the correlation between the MEs and the gene expression were referred to as Gene Significance (GS) and Module Membership (MM), respectively. Modules with a P < 0.05 were filtered in the MM-GS analysis for each disease.Analysis of determining the genes associated with the disease: The DisGeNET (version 5.0) online database was used to determine the number of genes associated with each disease within the significant modules that were obtained in previous steps (a and b)  is defined as the first principal component of the gene expression in each module. In the present study, the MEs were combined using the mergeCloseModules function based on their similarity in the profile of the gene expression. This function uses a cutHeight parameter to determine the correlation among the MEs. The parameter was set to 0.15 in this study, and modules with a correlation ≥0.85 (1-cutHeight) were merged accordingly. Finally, three subsequent analyses were used to identify the most important modules for each disease as follows   and pathway databases, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Biocarta, and Reactome via the Enrichr  was utilized to identify the candidate drugs in the studied lung diseases  and GSE23611 (GPL6480) were used in this study. After data normalization and quality control, 34 COPD samples  and 32 healthy controls, as well as 118 IPF samples and 86 healthy controls from the GSE47460 dataset were utilized to determine the DEGs. In addition, 26 samples from asthmatic patients and 7 healthy controls were selected from GSE23611. The results of differential analyses are displayed in Fig. The DEGs with a matching up/down-regulated pattern between two or among three diseases were nominated as the DEGs with Identical Pattern (DIPs) to assess disease-disease expression similarity. The results of the three pairwise comparisons revealed 616, 615, 1452, and 304 shared DEGs between asthma-COPD, asthma-IPF, COPD-IPF, and asthma-COPD-IPF, respectively. Table Based on the results, there are more DIPs between asthma and COPD compared to COPD and IPF, as well as asthma and IPF. However, there are more DIPs between COPD and IPF compared to asthma and COPD or asthma and IPF.Disease-specific DEGs  were used to construct three disease-specific co-expression networks. The optimal β parameter for obtaining a scale-free network was computed as 11, 15, and 21 for COPD, IPF, and asthma, respectively  were constructed, including asthma-COPD, COPD-IPF, and asthma-IPF. Each CN was used to extract the Consensus Modules (CMs). The plots of β parameter computation for the constructed CNs are provided in Additional file A CN including 304 shared DEGs was reconstructed to extract the CMs among the three diseases. However, no CM could be extracted using the WGCNA.Enrichment analysis was performed to functionally evaluate the gene sets that were involved in specific modules, CMs, and overlapping DEGs among three diseases as follows.Table Some of the enriched significant biological pathways and GO biological processes of the CMs are reported in Table Table The candidate drug-target interactions were investigated after identifying consensus and specific modules among three diseases. Figure Figure Figure Progressive chronic respiratory diseases are associated with a persistent and progressive decline in lung function and exacerbations, which require smart diagnosis and treatment. Decreasing the rate of progression, staging, and exacerbations in chronic respiratory diseases such as asthma, COPD, and IPF is critically vital in controlling mortality -beta signaling pathways. These pathways are involved in the inflammation of the respiratory tract, immune system, and chronic inflammatory diseases  were investigated after evaluating the disease-specific modules. Also, two modules (Turquoise and Pink) for asthma-COPD, one module (Purple) for asthma-IPF, and three modules  for COPD-IPF pairs were identified after the module-trait analysis. Biological pathways and GO analysis conducted for the genes, are involved in each significant consensus module.Based on the results of the biological process analysis for the asthma-COPD, the genes of the turquoise module were mainly enriched in cilium assembly, cilium organization, cilium movement, and plasma membrane-bounded cell projection assembly. These processes were due to the dysfunction of the bronchial epithelial and the disruption of cilia function as the important features of asthma and COPD diseases  were identified in asthma-IPF among ten hub DEGs. In the purple module, COL15A1 is involved in the smooth muscle cell (SMC) phenotype that is controlled by the epigenetic state, so that the hypomethylation of COL15A1 transpires during SMC proliferation and the consequent increased gene expression may affect the SMC phenotype (Connelly et al. Ca2+-dependent manner. It also plays a vital role as a mediator in cellular growth, signal transduction pathways, cancer proliferation, invasion, and migration (Wang et al. The results of the biological process analysis for COPD-IPF represented that the genes of the blue module are enriched in immune processes, inflammation, and remodeling. Nine novel hub DEGs were specified in COPD-IPF, including GPM6A, ARHGEF26, ANKRD29, LMO7, TSPAN13, LAMA3, ST6GALNAC5, ANXA3, and CLIC5. In the blue module, LMO7 is known as a negative feedback regulator of TGF-β signaling and extracellular matrix deposition (Xie et al. Previous studies have only evaluated the overlap mechanism between two diseases whereas the present study considered three diseases together and could identify the focal biological processes for all three diseases. These results were not observed due to the presence of other genes available in the top rank between two diseases, and the statistical analysis led to these processes that were not shared in the overlap of two diseases. Likewise, the processes observed in COPD and IPF confirmed the irreversibility of these diseases whereas a cure is suggested in asthma.Based on the data in Tables Drug-target identification for consensus and common DEGs in three diseases revealed that based on specific DEGs, tretinoin as a retinoid drug is recommended for all three diseases. Retinoids are involved in many essential functions of the body such as the immune system, cell proliferation, and differentiation, bone growth, the activation of tumor suppressor genes, as well as natural and malignant epithelial cell growth in various tissues (Buckley et al. Bevacizumab is one of the VEGF inhibitors that can be identified as a candidate for COPD (Papaioannou et al. Low-dose paclitaxel is one of the TGF-β1/Smad3 pathways suppressing drugs, and in this study, it was identified as a candidate drug for IPF. TGF-β1 is responsible for creating a cascade of incidents leading to fibrosis, and the abnormal activation of TGF-β1 plays a vital role in the pathogenesis of IPF (Wang et al. Likewise, sirolimus as an immunosuppressant drug is suggested as a candidate for the asthma-COPD therapy. This drug inhibits the activation of T and B-cells by inhibiting mTOR and plays an essential role in the biogenesis of the ribosome, cell cycle progression, lipid synthesis, mitochondrial biogenesis, and autophagy of COPD (Miłkowska-Dymanowska et al. Tacrolimus is one of the candidate medicines in asthma-IPF as well. This drug inhibits the transcription of IL-2 and several other cytokines, especially in T-helper lymphocytes (Horita et al. In addition, cyclophosphamide is regarded as one of the candidate drugs for COPD-IPF. The combination of this drug with corticosteroids is used to reduce the severity of IPF (Emura and Usuda The current study proposed unique and common biomarkers and drugs among the three diseases. Moreover, it was confirmed that asthma lung transcriptome is more similar to COPD than IPF. These findings could help the researchers to differentiate the mentioned diseases. However, this study has some limitations including ignoring the side effects of the drugs. Additionally, novel biomarkers were proposed computationally. Therefore, the clinical studies are recommended to confirm the validity and reliability of the results of this study, as well as those of similar studies in the future.The findings indicated that the proposed biomarkers in chronic lung diseases might serve as predictive targets among the three diseases. They include RBM42, STX5, and TRIM41 in asthma, CYP27A1, GM2A, LGALS9, SPI1, and NLRC4 in COPD, as well as ATF3, PPP1R15A, ZFP36, SOCS3, NAMPT, and GADD45B in IPF. In addition, other identified genes were LRRC48 and CETN2 in asthma-COPD, COL15A1, GIMAP6, and JAM2 in asthma-IPF, along with LMO7, TSPAN13, LAMA3, and ANXA3 in COPD-IPF. Finally, anti-inflammatory drugs such as corticosteroids were proposed for treating the three diseases.Additional file 1. The list of DIPs and shared DEGs among three diseases.Additional file 2 Selecting the optimal β parameter for disease-specific networks.Additional file 3. The list of all gene symbols in candidate disease-specific modules.Additional file 4. The list of selected modules for three diseases.Additional file 5 Selecting the optimal β parameter for consensus networks.Additional file 6. The list of all gene symbols in candidate consensus modules.Additional file 7. Significant biological pathways and GO Biological Processes in disease-specific modules.Additional file 8. Significant biological pathways and GO Biological Processes in consensus modules.Additional file 9. Significant GO biological processes of overlapping DEGs among three diseases.Additional file 10:. The list of candidate disease-specific drug-target interactions.Additional file 11. The list of candidate consensus drug-target interactions.Additional file 12. The list of candidates shared drug-target interactions among three diseases.


The WSx) electrocatalyst for hydrogen evolution reaction (HER), researchers are pursuing inexpensive and highly efficient materials as an electrocatalyst for large scale practical application. Layered transition metal dichalcogenides (TMDCs) are promising candidates for durable HER catalysts due to their cost-effective, highly active edges and Earth-abundant elements to replace Pt electrocatalysts. Herein, we design an active, stable earth-abundant TMDCs based catalyst, WS Davodi and co-workers [2O3/MWCNTs functionalized with nitrogen-rich emeraldine salt for alkaline HER and OER processes. Luo et al. also demonstrated Fe3O4@NiFexOy core−shell nano-heterostructures toward the OER with an overpotential −410 mV@1 mA cm−2 and Tafel slope of 48 mV dec−1 [2/graphene/Ni foam as a catalyst in HER application and observed the low overpotential of −119 mV@10 mA cm−2, the small Tafel slope of ~43 mV dec−1, and the large cathodic current density. Recently, Zhou et al. has reported ternary tungsten sulfoselenide (WSx)2(1−Sex2) particles with a 3D porous metallic NiSe2 foam to have excellent catalytic performance with −88 mV@10 mA cm−2 of overpotential, 46.7 mV dec−1 of Tafel slope, and 214.7 μA cm−2 of exchange current density [2 QDs film using a solution process and WS2/CoSe2 heterostructure for HER applications [x)2(1− Se2x and WSx)2(1−Sex/graphene/NF (51 mV dec−1) as compared to the WS2/NF and WS2/graphene/NF .Recently, many efficient strategies to increase the number of active edge sites with large surface areas, high porosity, and better intrinsic electrical conductivity or the contact between the catalyst and the electrode were adopted to increase the electrocatalytic activity of electrode material. Herein, we utilized a 3D porous structure nickel (Ni) foam (NF) as a highly conductive skeleton, and produced WS2)/argon (Ar) (30/50 sccm) environment at 900 °C for 30 min in a quartz tube furnace to clean the surface of the Ni foam without breaking the vacuum. Then to prepare the graphene on NF, the mixture of H2/Ar/methane (CH4) flow (H2/Ar/CH4 = 50:100:50 sccm) was maintained for 30 min. Subsequently, the H2/CH4 flow gas channel was shut off, and then rapidly cooled to room temperature in Ar environment. Furthermore, prepared graphene/NF was used as substrate for the growth of WS2 and WSx) was cleaned with ultrasonic baths of acetone, ethanol, and deionized water, baked at 120 °C for 5 min, and then annealed with a hydrogen 2WS4)  was used as the main source material. First, a precursor of (NH4)2WS4 (0.2 g) was dissolved in N,N-Dimethylformamide (DMF) (20 mL), and then the solution was sonicated for 30 min. The 3D graphene/Ni foam was immersed into the prepared (NH4)2WS4 solution and then baked at 100 °C for 30 min. Finally, synthesized films were placed in an annealing chamber and heated up to 450 °C for 30 and 45 min in a sulfur or sulfur/selenium environment to form WS2/Graphene/NF and WSx)(1−Sex/Graphene/NF. The gas flow Ar/H2 flux (50/50 sccm) was maintained, and the pressure of chamber was kept at 2 × 10−2 Torr. The same quantity of sulfur/selenium (0.3/0.3 g) powder was used.For WS−1 in 0.5 M H2SO4 electrolyte at room temperature. For the LSV measurement, a saturated calomel reference electrode (SCE) was used as the reference electrode. WS2(30 min)/NF, WS2(45 min)/NF, WS2/graphene/NF, and WSx) scale with the help of the following equation: E(RHE) = E(SCE) + E°(SCE) + 0.059 pH. Electrochemical impedance spectroscopy (EIS) measurements were carried out in a potentiostatic mode with a frequency range from 0.01 Hz to 100 kHz under an amplitude of 10 mV. All the LSV polarizations were recorded after the ohmic drop iR correction. The stability measurement was examined using a chronoamperometric analysis.The electrochemical measurements were conducted in a three-electrode setup with a Biologic SP-300 workstation. The polarization curves were collected using a linear sweep voltammetry (LSV) with a scan rate of 10 mV.s2 was further grown by a hydrothermal process using an (NH4)2WS4 precursor on 3D graphene with NF. To improve the crystalline quality, the film was further annealed at 500 °C in a sulfur environment at 30~45 min to form WS2 nanoparticle-decorated graphene on NF (WS2/graphene/NF). To form WSx)(1−Sex nanoparticles-decorated graphene on NF (WSx)(1−Sex/graphene/NF), a CVD deposited film was annealed at 450 °C in a sulfur and selenium environment at 30 min, respectively, to form WS(1−x)Sex onto graphene. The schematic representation is given in Initially, the graphene was grown on a 3D NF using a chemical vapor deposition (CVD), as reported previously . WS2 was2/NF, WS2/graphene/NF, and WSx) as presented in x). Ni signals are ascribed from the NF substrate. The elemental mapping images of WS2 and WSx)(1−Sex layers are provided in x) and a high-resolution transmission electron microscopy (HRTEM).  bare NF a is comp bare NF b, the ree nature c. The naM images d. In thex)(1−Sex/graphene/NF particles as reported in previous literature [x)(1−Sex/graphene/NF. From the spectrum of graphene/NF (−1), 2D band (2706 cm−1), and D band (1364 cm−1) were exhibited due to defects in the carbon lattice [2/NF, two prominent Raman peaks originated at 350.1 and 420.5 cm−1 correspond to the E12g and A1g modes, respectively [2/graphene/NF, E12g, and A1g modes (351.6 and 420.5 cm−1) for WS2, two sharp peaks for graphene (G band: 1577.8 cm−1 and 2D band: 2699.8 cm−1) are shown [12g mode peak was observed at 250.6 cm−1, corresponding to WSe2 [x)(1−Sex/graphene/NF were further investigated via an X-ray diffraction (XRD) and X-ray photoelectron (XPS), respectively. The XRD patterns of graphene, WS2/NF, WS2/3D graphene, and WSx)(1−Sex/graphene/NF samples are shown in 2/NF (2 (WS2: JCPDS 657515). For WS2/graphene/NF, (004), (100), (101), (102), and (105) peaks were observed for WS2. In the case of WSx), (004), (104), (105), (112), and (200) lattice planes appeared in addition to the WS2/graphene/NF peaks as shown in 2: JCPDS No. 89-5257). From the XPS survey scan of WS2/graphene/NF (x)(1−Sex/graphene/NF (7/2 and W 4f5/2 (36.4 and 34.5 eV) doublets, which were indicative of the oxidation state of W4+, appeared. The S 2p1/2 and 2p3/2 orbital peaks observed at 163.6 and 161.9 eV, respectively, indicating the S2, confirmed the WS2 crystal [5/2 (53.8 eV) and Se 3d3/2 (55.6 eV) corresponding to the −2 oxidation state of selenium [The structural and chemical composition of the graphene, WS in 2/NF b, the pephene/NF , the obsphene/NF a, an add crystal ,35. The −1 in 0.5 M sulfuric acid (H2SO4) electrolyte solution by linear sweep voltammetry (LSV) with iR correction. As expected, the commercial Pt wire exhibited the lowest overpotential, which was close to zero. The WSx) for a geometric current density of 10 mA cm−2. In contrast, WS2(45 min)/NF, and WS2/graphene/NF exhibited inferior HER activity  (2 adsorption onto the Se facets than the S facets [HER activities were investigated via a standard three-electrode setup with a scan rate of 10 mV sctively) a,b. EarlS facets . Graphenx) hybrid catalyst (−97.2 mV@ 10 mA cm−2) [2/reduced graphene oxide hybrid nanosheets (−150 ~ −200 mV@10 mA cm−2) [2-WS2 (−129 mV@10 mA cm−2) [2@hollow nitrogen-doped carbon nanofibers (−185 mV@10 mA cm−2) [2 2D-nanohybrid electrocatalysts (−140 mV@10 mA cm−2) [x)(1−WxS2 hollow nanospheres on an Ni3S2 nanorod (−98 mV@10 mA cm−2) [2  on NF were used as electrocatalysts, and their LSV curves are provided in the The catalytic overpotential (−93 mV) of the WSmA cm−2) , WS2/redmA cm−2) , MoS2-WSmA cm−2) , WS2@holmA cm−2) , graphdimA cm−2) , and Mo(mA cm−2) . For com−1 was extracted for WSx)/graphene/NF and WS2/NF, respectively (−1 of WSx) [2/CC (127~105 mV dec−1) [2 and WS2 nanosheets on bare oxidized carbon fiber (OCF) (149 ~ 99 mV dec−1) [2 @WS2 nanorattles, WS2 nanoflakes and bulk WS2  [2 nanosheet/graphene (73 mV dec−1) [2 and WSx)2(1−Sex2 nanotubes (105 and 99 mV dec−1) [2 and WSx)2(1−Sex2 with a tunable band gap (100 and 85 mV dec−1) [The inherent property of catalytic activity for HER kinetics was probed by extracting the slopes from the linear regions in Tafel plots. A Tafel slope of 51 mV decectively c. The Tad for WS2 min/grapV dec−1) , bulk WSV dec−1) , WS2 @WSV dec−1) , verticaV dec−1) , and monV dec−1) .j0) was found to be ~0.162, ~0.165, and ~0.274 mA cm−2, for WS2/NF, WS2/graphene/NF and WSx)Sex/graphene/NF may be attributed to the large number of exposed active edge sites, good electrical conductivity, or the porous structure. The observed HER parameters for different electrodes are listed in −1, or a combination reaction ) that leads to a Tafel slope of 30 mV dec−1.The exchange current density (−1 for Pt exposes the hydrogen production proceeds with the fast discharge step (Equation (1)) followed by the Tafel (Equation (3)) [−1  suggest that hydrogen production proceeds with the fast discharge step (equation 1) followed by the Tafel (Equation (3)) or Heyrovsky ion-atom reaction (Equation (2)) [x)) ,54. The ion (2)) ,55,56. TRct) of Pt, WS2(45 min)/NF, WS2/graphene/NF, and WSx)/NF, WS2/graphene/NF, and WSx)(1−Sex/graphene/NF catalyst showed good HER catalytic properties in acidic electrolyte with an overpotential of −93 mV to drive 10 mA cm−2, a small Tafel slope of 51 mV dec−1, and a high exchange current density with excellent long-term durability. Our results proved that Se incorporated WS2/graphene/NF exhibits the highest electrocatalytic activity for HER, and it is stable in acidic media over a long period among the other electrodes due to high active edge sites and porous structures.In summary, an effective and efficient strategy was adopted for the synthesis of WS


New Specific Application Domain (SAD) heuristics or design principles are being developed to guide the design and evaluation of mobile applications in a bid to improve on the usability of these applications. This is because the existing heuristics are rather generic and are often unable to reveal a large number of mobile usability issues related to mobile specific interfaces and characteristics. Mobile Electronic Data Capturing Forms (MEDCFs) are one of such applications that are being used to collect health data particularly in hard to reach areas, but with a number of usability challenges especially when used in rural areas by semi literate users. Existing SAD design principles are often not used to evaluate mobile forms because their focus on features specific to data capture is minimal. In addition, some of these lists are extremely long rendering them difficult to use during the design and development of the mobile forms. The main aim of this study therefore was to generate a usability evaluation checklist that can be used to design and evaluate Mobile Electronic Data Capturing Forms in a bid to improve their usability. We also sought to compare the novice and expert developers’ views regarding usability criteria.included utility, clarity, question naming, categorization and measurability, with utility and measurability having a higher weight respectively. We then determined the proportion of participants who agreed (scored 4 or 5), disagreed (scored 1 or 2) and were neutral (scored 3) to a given criteria regarding a particular question for each of the experts and novice developers. Finally, we selected questions that had an average of 85% agreement (scored 4 or 5) across all the 5 criteria by both novice and expert developers. ‘Agreement’ stands for capturing the same views or sentiments about the perceived likeness of an evaluation question.We conducted a literature review in August 2016 using key words on articles and gray literature, and those with a focus on heuristics for mobile applications, user interface designs of mobile devices and web forms were eligible for review. The data bases included the ACM digital library, IEEE-Xplore and Google scholar. We had a total of 242 papers after removing duplicates and a total of 10 articles which met the criteria were finally reviewed. This review resulted in an initial usability evaluation checklist consisting of 125 questions that could be adopted for designing MEDCFs. The questions that handled the five main categories in data capture namely; form content, form layout, input type, error handling and form submission were considered. A validation study was conducted with both novice and expert developers using a validation tool in a bid to refine the checklist which was based on 5 criteria. The criteria for the validation The validation study reduced the initial 125 usability evaluation questions to 30 evaluation questions with the form layout category having the majority questions. Results from the validation showed higher levels of affirmativeness from the expert developers compared to those of the novice developers across the different criteria; however the general trend of agreement on relevance of usability questions was similar across all the criteria for the developers. The evaluation questions that were being validated were found to be useful, clear, properly named and categorized, however the measurability of the questions was found not to be satisfactory by both sets of developers. The developers attached great importance to the use of appropriate language and to the visibility of the help function, but in addition expert developers felt that indication of mandatory and optional fields coupled with the use of device information like the Global Positioning System (GPS) was equally important. And for both sets of developers, utility had the highest scores while measurability scored least.The generated checklist indicated the design features the software developers found necessary to improve the usability of mobile electronic data collection tools. In the future, we thus propose to test the effectiveness of the measure for suitability and performance based on this generated checklist, and test it on the end users (data collectors) with a purpose of picking their design requirements. Continuous testing with the end users will help refine the checklist to include only that which is most important in improving the data collectors’ experience. Over the years, electronic data collection systems are increasingly being used in health care particularly for data collection and management in health surveys, surveillance and patient monitoring . ElectroUsability is considered as one of the top attributes of assessing quality and its major role is to ensure that the interfaces are easy to use and that users are supported in performing their tasks efficiently and effectively . One of Heuristics that are applicable in one context may not work in another, or may sometimes contradict a heuristic used in another context. Secondly, their being broad often leaves room for the individual evaluator’s interpretation of what they mean, and may also be challenging to less experienced evaluators in finding pertinent design problems , 10. TheThe study therefore sought to generate and validate a design checklist for MEDCFs. We proposed a list of sub-heuristics from literature which focus on the data capturing process. We later validated this list in order to transform and refine it, so that it would be more usable to the intended users.To develop a design checklist for mobile electronic data collection forms (MEDCFs), we used different types of techniques and involved different stakeholders. First we conducted a literature review where we generated an initial usability evaluation checklist. The initial checklist was then validated by a team of software developers using a validation instrument.usability’, ‘evaluation’, ‘mobile’ and ‘heuristic’ and were left with 225 articles. We screened the abstracts and removed those papers which were not in English and those which were not about usability evaluation of user interfaces, leaving us with 134 articles. We then omitted those papers which were not focused on generating or validating usability heuristics for mobile devices or interfaces, and we were then left with 10 articles.We used the ACM digital library, Springer, IEEE-Xplore and Google scholar, together with some literature on best practices from other sources like Google. Our key terms in the search included ‘usability’, ‘usability evaluation’, ‘heuristics’, ‘mobile’, ‘tool’, ‘checklist’, ‘user interface’ and ‘design’. The key words were chosen with a focus on improving usability in mobile electronic data collection based on the assumption that usability can be improved through proper designing and evaluation of the user interfaces by developers using heuristics/design principles that are specific to MEDCFs. The inclusion criteria included papers that were focused on computer applications, usability, heuristic evaluation, generation and validation of heuristics.. Our search generated 242 papers for review after removing the duplicates. On screening based on titles, we then removed 17 papers whose titles did not have the words ‘We derived our usability evaluation questions from 10 papers , the majority of which came from a system checklist by Pierotti , 16.form content, form layout, input process, error handling and form submission [visual feedback and list pickers among others. The 125 questions were categorized as follows. Form content had a total of 35 questions, form layout had a total of 43 questions and the input process category comprised of 22 questions. Error handling had 23 questions, while form submission had the least with only 2 questions.We selected those sub-heuristics that fitted in the 5 categories and are representative of the data capturing process as shown in the design of web forms. This included transfer of sub heuristics from their original sub-heuristic category and placed under a new one based on what they are evaluating. The categories comprised of the bmission . We thenbmission , and yetThe form content depends on the data being collected. Some forms may be in form of questionnaires, whereas others may be in tabular form, hence the variation in content. The main content is usually questions and labels or fields of text entry. However, it is very crucial to map the environment which the users are familiar with in order to ease the use of the form. In this case, designing an electronic form that is analogous to the paper forms will quicken the data collectors’ understanding of the form .The form layout shows how the form is presented on the mobile user interface, and this influences the way a user interacts with it. The form layout is still determined by the nature of the content that is being collected. For example long survey questionnaires will have a different layout from a short mostly graphical form used by a clinician in a health facility. In addition, the designs, positions and lengths of the labels and input fields, the date format, number of columns and buttons among others all define the layout of the form .This refers to the way data is captured or entered into the form and therefore which input type is most appropriate for a given case for example check boxes, radio buttons etc. Care should always be taken not to confuse users by using many different input types in one form . In someUsers need to be guided as quickly and as error free as possible during the process of filling forms from the start by explaining restrictions in advance . This inThe form has to be submitted after filling it using a submission button . The subWe chose to use these categories because they represent some of the main activities a user is involved in when filling a data collection form. And therefore were a good basis for the selection and categorization of the questions that we included in the initial usability evaluation checklist.Heuristics for Specific Application Domains (SAD) can be generated in a number of ways, but one of the most important steps is the validation of the heuristics to ensure that they are able to do what they are supposed to do. According to Van Greunen et al.,  the valistrongly disagree, disagree, somewhat agree, agree and strongly agree with a score of 1,2,3,4 and 5 respectively. Furthermore, the developers were free to add a comment explaining their scores in addition to removing or adding to the usability evaluation questions. The developers could also suggest renaming a given question or re-locating a question to a different category.The software developers validated this initial usability evaluation set in order to refine it further and make it more usable using a validation tool. The validation tool was created as an excel file and each of the 125 usability evaluation questions was scored on a scale of 5 where the options were presented in form of a drop down list. These included The validation tool was based on 5 major assessment criteria, namely utility, clarity, question naming, categorization and measurability. The criteria was based on characteristics proposed by Van Greunen et al.  some of This tests the evaluation question’s contribution and relevance to the design of the mobile data collection form.This tests whether the evaluation question is clear and can easily be understood by the evaluator.The test was on whether the evaluation question name was appropriate.Here the test was whether the evaluation question is placed in the right category.This tested the possibility of measuring and attaching a score to the design feature using this evaluation question.Validation can be a continuous and iterative process involving novice, average and expert users. The initial assessment of the initial usability evaluation questions was performed by novice software developers in March 2017. We presented the main study objectives and the relevance of the activity the novice developers were about to undertake, after which they downloaded the checklist and the validation tool from their individual email addresses. We then trained the developers for about 10 min, after which they were given 90 min to assess the checklist and submit the completed assessment thereafter to the researchers’ email address.n = 9), District Health Information Software (DHIS2) (n = 6), Open Medical Records System (OpenMRS) (n = 5). Other applications included mUzima (n = 2), Medic Mobile Toolkit, CSpro, Survey CTO, koBo Toolbox, Survey Monkey and OpenXData. The 20 developers received an email each indicating the main study objective and the relevance of the activity they were about to engage in. On acceptance to be part of the study, the file with the assessment criteria was forwarded to them via email, and they were expected to submit it after one week.The second validation of the same evaluation questions was done by the expert developers in Uganda between October and November 2017. The expert developers had developed mobile forms for collection of health data for varying periods of time, ranging from 1 year to 8 years using software like Open Data Kit (ODK) ((Is the number of colors limited to 3–4?) was unclear and one had to read it twice to understand it. Three of the comments went on to advise on how we could improve on a given question e.g. splitting question 9  into 2 segments. One developer also felt that progress disclosure in question 38  would not be very important in a mobile view. All the 125 questions that were validated are listed in the Out of the 20 copies of validation tools that were sent out, we received 18 copies back, 3 of which were incomplete. So our results were based on the 15 complete submissions. We received a total of 9 comments from 5 developers. Five of the comments mentioned that some of the evaluation questions were not clear and therefore could possibly lead to misinterpretation or confusion. For example two developers felt that question 12 Are all abbreviated words of the same length?). Eight of the expert developers commented that it was not possible to have abbreviated words of the same length. Some questions were also found to be ambiguous e.g. (Does the tool provide informative progress disclosure when filling a form?) and (Has the skip logic been automated?). The relevance of some of the questions was also questionable e.g. . Some expert developers also pointed out that some of the design features’ performance is influenced by other factors e.g. the feedback time during data collection may be influenced by the internet speed. However this activity is rather subjective and very individualistic and therefore the developers were likely to interpret and evaluate the questions differently based on their varied experiences.All the 20 copies that were sent out to the expert developers were filled and received back after periods ranging from 2 to 4 weeks. We received more comments from the expert developers compared to the novice developers, some of which included renaming or re-categorizing the evaluation questions. For example some of the expert developers felt that questions 6, 10, 14, 15, 27, 28 and 29 needed to be put in other categories rather than the ones they were in . In addiTo generate the usability design checklist, we considered questions where 80% and above of the novice and expert developers agreed to each of the utility, clarity, question name, categorization and measurability of the questions. We then selected those questions where more than 80% of the responses indicated ‘agree’ or ‘strongly agree’ across all the 5 criteria. Because utility and measurability have higher weight than the rest of the criteria, we also considered those questions which scored above 80% in both usability and measurability. We then considered those questions where both novice and expert developers affirmed to the utility of the question. And lastly, we considered those questions where only the experts affirmed to the utility of the question. This led to a total of 64 questions. We then calculated the average of responses with ‘agree’ or ‘strongly agree’ for each question across the 5 criteria, and selected those questions with an average of 85% and above. This led to 30 evaluation questions of which 9 were categorized under the form layout, 12 under form content, 2 under the input process, 6 under error handling and 1 under form submission. These 30 usability evaluation questions are all represented in Table There were no questions where both sets of developers selected ‘agree’ to all the 5 criteria for a particular question. However, there were 11 questions in this checklist where both sets of developers selected ‘agree’ to more than one criterion for a given question. But generally expert developers affirmed to the questions based on the given criteria compared to the novice developers.We further analyzed the data based on the criteria to determine the participants’ decision for each usability evaluation question. We determined the number and the respective percentage of participants who agreed, disagreed and were neutral to a given criteria for a particular usability question for each of the experts and the novice developers.utility had 12 questions , clarity had 8 questions , and question naming had 3 questions . In addition, categorization had 6 questions  while measurability had 4 questions . We also had about 12 novice developers (80%) selecting ‘agree’ to the utility of 14 questions, to the clarity of 24 questions, to the question names of 13 questions, to the categorization of 15 questions and to the measurability of 5 questions. These results depict that majority of the questions that the novice developers agreed to were clear to them. In fact all the novice developers agreed to the clarity of question 66 . The number of novice developers who selected ‘disagree’ against questions was relatively low with the highest being 8 developers disagreeing with the question name for question 9 . There were also 40 and 27% of the developers disagreeing with the clarity and the categorization of this question respectively. The biggest percentage of disagreements (above 27%) was made up of measurability (14 questions) followed by utility (11 questions) and clarity (11 questions), and yet these are the criteria with the highest weights.For 25 usability evaluation questions 85% and above of the novice developers selected ‘agree’ i.e. measurability which was below 85%. There were incidences where all the expert developers affirmed to the criteria regarding a particular question for example utility had 5 questions , clarity had 5 questions , question name had 3 questions  while categorization had 4 questions . Question 92  however had all the expert developers agree to the utility, clarity and categorization of that question. In addition we had 7 questions  where 90% and above of the expert developers agreed on the relevance of 3 criteria and 9 questions  where 90% and above of the developers agreed on the relevance of the 4 criteria. This can be compared to questions 58 (Are inactive menu items greyed out or omitted?) and 59  where 87% of the novice developers agreed to the utility, clarity and categorization value of the questions.There were 50 evaluation questions where 85% and above of the expert developers selected ‘agree’ for all the criteria apart from,  had a high level of disagreement across all the 5 criteria, with utility having the highest diagreement of 50%.We also considered those questions where less than 50% of the novice developers selected ‘disagree’ Measurability had 29 questions, followed by utility with 13, clarity with 9, question name with 8 and lastly categorization with 8 questions. Question 24 The number of expert developers who gave high criteria scores for each usability question was higher than the number of novice developers. In addition, the scores across criteria also varied with the highest being utility followed by clarity, question name, categorization and lastly measurability, and for both sets of developers, utility scored highly while measurability scored least Fig. .Fig. 1ToThe literature search generated 125 usability evaluation questions which after validation by the novice and software developers were reduced to 30 questions. The results after the validation indicate that expert developers appeared to value the utility, clarity, question names, categorization and measurability of the questions more homogeneously as a group than the novice developers. According to both groups of developers, the questions were found to be useful, clear, with proper names and correct categorization; however both sets of developers felt that the measurability of the questions was not satisfactory.The results indicate differences in the agreement and disagreement levels with evaluation criteria of the novice and expert developers, but the general trend was the same i.e. there were some questions where both evaluator groups agreed or disagreed. For example there were 20 questions where more than 85% of the developers found 3 or 4 criteria valuable. In addition, novice developers attached great importance to the use of appropriate language, omission of inactive menus, visibility of help function, prompts and messages and lastly to the ability to switch between data collection and their work. On the other hand, expert developers attached great importance to the appropriate language use as well, visual differences between interaction objects and information objects, indication of mandatory and optional fields, visibility of the help function and the use of device information like the Global Positioning System (GPS).The variations in the levels of agreement and preferences may be attributed to differences in experience and context of operation. For example the expert developers had experience ranging from 3 to 10 years, which the novice developers did not have. Secondly the expert developers had been involved in creating MDCEFs for collection of health data in low resource settings, whereas the novice developers were more involved in mobile software development with nothing specific to Mobile data collection tools. However, in evaluation or validation it is important to have a mix of users with different skill levels e.g. the beginners or novice users, the average level users and the power or expert users to test a given product. This prevents skewing of the design requirements towards a particular group because users have varying needs based on their experience .Most of the questions the developers affirmed to were in the form content category followed by the form layout, error handling, input process and the form submission categories respectively. Measurability was hardest to assess, followed by utility and clarity for both groups of software developers. This may be attributed to the fact that it was not clear to the developers what the criterion was meant to achieve. However, we still need to define ways of measuring the achievement of a particular design feature we are testing.Expert developers had different views on more usability questions compared to the novice developers. This may be attributed to the experience they have had working on these applications such that they are able to know what is achievable or not. Secondly, some of the expert developers have had an opportunity of interacting and getting feedback from the end users especially during the training sessions, which placed them in a more advantaged position of knowing what the users may be comfortable with.Utility of a usability question was considered most important among the validation criteria and as such, the evaluation questions with high percentages of disagreement for utility were automatically eliminated from the checklist. We argue that however clear or well categorized a usability question is, it needs to be useful in the evaluation of the MEDCFs.One of the limitations was the difference in the time allocated to the 2 groups of developers; the expert developers had a lot more time to validate the initial checklist compared to the novice developers who only had 90 min. However, to the best of our knowledge, this was the first exercise of its kind where intended users get to validate the tool they will use to assess their interface designs for MEDCFs, besides the user testing of the prototype or finished product that is done with the end users. Having 2 sets of developers with varying experiences and from different contexts enriched the study because software developers only develop software with a focus on particular features which is partly the reason for the weaknesses of using Open Source Software (OSS) .The objective of this study was to compare the novice and expert developers’ views regarding usability criteria. This study generated and validated a design checklist for Mobile Electronic Data Capture Forms (MEDCFs), and was thus a way of creating awareness to what should be expected of a mobile data collection tool from the software developers’ perspective. The different results from the novice and expert developers, where we registered more affirmative results from the expert developers is an indicator of their expectations as developers. This may also be an indication of their level of engagement and knowledge of the people for whom they are creating the tools as well as the experience acquired over the years. We would thus recommend the use of more experienced developers during validation of checklists for mobile data collection tools.The checklist resulting from this study needs to be evaluated by users as software developers are not the end users of the data collection forms. We thus propose to test the effectiveness of the measure for suitability and performance based on this generated checklist, and test it on the end users (data collectors) with a purpose of picking their design requirements. Continuous testing with the end users will help refine the checklist to include only that which is most important in improving the data collectors’ experience. In addition to this first study that summarized the observations, there will be a deeper data analysis based on the collected material to determine the relationships between the criteria scores on the evaluation checklist and the developer groups.


Gas-sieving (H2/CH4 selectivity up to 25) is observed from the intrinsic defects generated during the chemical-vapor deposition of graphene. Despite the ultralow porosity of 0.025%, an attractive H2 permeance (up to 4.1 × 10−7 mol m−2 s−1 Pa−1) is observed. Finally, we report ozone functionalization-based etching and pore-modification chemistry to etch hydrogen-selective pores, and to shrink the pore-size, improving H2 permeance (up to 300%) and H2/CH4 selectivity (up to 150%). Overall, the scalable transfer, etching, and functionalization methods developed herein are expected to bring nanoporous graphene membranes a step closer to reality.The single-layer graphene film, when incorporated with molecular-sized pores, is predicted to be the ultimate membrane. However, the major bottlenecks have been the crack-free transfer of large-area graphene on a porous support, and the incorporation of molecular-sized nanopores. Herein, we report a nanoporous-carbon-assisted transfer technique, yielding a relatively large area (1 mm Graphene shows great promise for gas separation applications, but obtaining large membranes that are free of cracks and tears remains highly challenging. Here, the authors realize monolayer, crack-free, millimeter-scale graphene membranes that exhibit selective gas permeation solely thanks to their intrinsic defects Several molecular simulations have shown that the two-dimensional nanopores in graphene can yield high gas permeance, orders of magnitude higher than that attainable with the conventional membranes11. Such high-flux membranes can considerably reduce the needed membrane area for separating a volume of a molecular mixture, addressing the problem of scale-up, a longstanding issue with the inorganic membranes. The thermal and chemical robustness and the high mechanical strength of the graphene lattice, even with a porosity as high as 5%13, makes it highly attractive for the gas separation. Recently, several etching methods for incorporating sub-nanometer pores in graphene lattice have been developed, leading to promising sieving performances for liquids and dissolved ions17. However, the demonstration of gas mixture separation from single-layer graphene membrane has remained a challenging task19. A proof-of-concept was demonstrated by measuring the deflation rate of a bilayer graphene microballoon, where pores were incorporated by multiple ultraviolet treatment20. In general, the molecular transport studies through single-layer graphene have been primarily carried out on micron-sized domains, attributing to the poor scalability of the micromechanical exfoliation, and the challenging transfer of the chemical-vapor deposition (CVD) derived graphene. Celebi et al. reported a 2500 μmμm2-sized bilayer graphene membrane by masking cracks in a graphene film by another graphene film21. Using focused-ion beam, an array of nanopores (>7.6 nm in diameter) were incorporated leading to an effusive gas transport. Recently, a centimeter-scale single-layer graphene membrane hosting molecular-sized pores was reported, however, the cracks generated during the transfer limited the separation selectivity close to that expected from the Knudsen diffusion 18. Overall, the demonstration of gas mixture separation from sufficiently-scaled single-layer graphene membrane has remained elusive. To develop graphene membranes, one needs to (a) transfer large-area graphene onto porous supports without generating cracks and tears, and (b) generate molecular-sized pores with a narrow pore-size-distribution (PSD). Development of such method would also allow one to study the gas transport mechanism (activated vs. surface vs. Knudsen transport), and effect of the competitive adsorption through the graphene nanopores.Atom-thick graphene film is the thinnest possible molecular barrier and therefore incorporated with molecular-sized pores, it can be regarded as the ultimate membrane2) single-layer CVD graphene onto a macroporous support (pore-opening of 5 µm) without generating cracks or tears, allowing observation of gas-sieving from the intrinsic defects of CVD graphene. An attractive H2 permeance (up to 4.1 × 10−7 mol m−2 s−1 Pa−1) is obtained despite the ultralow-density of the intrinsic defects (porosity of 0.025%). An activated gas transport is observed with an average activation energy for H2 transport across eight membranes being 20.2 ± 2.7 kJ/mole. The molecular-sized intrinsic defects yield an attractive separated selectivity, including those from the mixed gas feed (H2/CH4 separation factor up to 18). The membrane performance remains stable during several heating and cooling cycles (25–150 °C), and at least up to 7 bar of the transmembrane pressure difference. Finally, in the pursuit to increase the density of gas-selective pores, we also report an ozone functionalization-based etching and pore-modification chemistry, increasing the nanopore density and/or reducing the effective pore-size. A combination of higher selectivity, higher permeance, and higher selectivity/higher permeance is observed.Herein, we report a novel nanoporous-carbon-assisted graphene transfer technique that enables transfer of relatively large area  (PMMA) film). Subsequently, the metal foil is removed by etching the metal in an etchant bath leaving the polymer coated graphene floating on the bath. Finally, the floating film is scooped on top of the desired substrate, and the polymer film is dissolved away to expose the surface of graphene. This wet-transfer process has been proven to be quite successful in fabricating graphene-based devices on smooth non-porous substrates24. However, significant cracks and tears develop in the graphene film when a porous support is used, primarily because of a strong capillary force on the suspended graphene film during the solvent drying stage30. This issue can be mitigated if the mechanically reinforcing film is not removed, and yet somehow the graphene surface is exposed. Motivated by this, we developed a nanoporous carbon (NPC) film-assisted transfer method  images of the NPC/graphene film on Cu, and transmission electron microscopy (TEM) images of the transferred NPC/graphene film on a TEM grid revealed that the NPC film was 100 nm thick, and comprised of 20–30 nm sized nanopores , formed by etching of the graphene lattice in the presence of residual oxygen in the CVD chamber, and are promising for the gas separation. In the current study, the density of defects, estimated by the carbon amorphization trajectory34  revealed several sub-1-nm nanopores with a pore-density of 2.8 × 1011 cm−2  directly on the as-synthesized graphene supported on the Cu foil, we recently imaged the low-density of intrinsic defects in the CVD graphenem−2 Fig. . This sm2 permeance in the range of 5.2 × 10−9–7.2 × 10−8 mol m−2 s−1 Pa−1  with H2/CH4, H2/CO2, and He/H2 ideal selectivities ranging between 4.8–13.0, 3.1–7.2, and 0.7–2.0, respectively, at 25 °C 20. The H2/CH4 selectivity was lower than that from Bi-3.4 membrane20, indicating a wider PSD of intrinsic defects in CVD graphene, compared to PSD from pores incorporated in micromechanically exfoliated graphene. Based on the achieved H2/CH4 selectivities, the estimated percentage of larger nanopores yielding non-selective effusive gas transport is less than 25 ppm .Graphene membranes were sealed in a homemade permeation cell using a metal face seal directly on top of the W support, ensuring a leak-proof measurement of the gas transport (details in the Methods). Typically, the feed side (a pure gas feed or a mixture feed) was pressurized to 1.5–7.0 bar, whereas the permeate side connected to a pre-calibrated mass spectrometer (MS) was maintained at 1 bar with an argon sweep , with H2/CH4, and H2/CO2 selectivities increasing to 7.1–23.5 and 3.6–12.2, respectively. We note that this H2/CH4 separation performance from single-layer graphene with 0.025% porosity approaches the 2008 Robeson upper bound for polymers35 3, providing an indication that the average pore in this study is close to that made from missing 10 carbon atoms, which is supported by the HRTEM images  compared to the corresponding ideal selectivities (IS). However, the separation factors were similar (He/H2 and H2/CO2) or higher (H2/CH4) compared to the corresponding ideal selectivities , while the H2 permeance (3.3 × 10−8–2.2 × 10−7 mol m−2 s−1 Pa−1 between 25 and 150 °C) in the mixture case was similar to the single-component case , the H2 permeance and the H2/CH4 selectivity in the mixture case were similar to those in the single-component case. These results indicate that the competitive adsorption of gases on the basal plane of graphene does not play a significant role in overall transport especially when the transport is in the activated regime, and when the feed pressure is moderate (up to 8 bar in this study). We expect the competitive adsorption to play a role at a higher feed pressure , while the H2/CH4 selectivity increased marginally (8.3 to 10.5). Moreover, the graphene membranes were also stable at least up to 8 bar of mixture feed at 100 °C  allowing a high degree of control is highly attractive. In this pursuit, we report a scalable ozone functionalization-based pore-etching and pore-edge-functionalization chemistry, improving the performance of the single-layer graphene membranes. We demonstrate that a controlled temperature-dependent oxidative functionalization of the graphene lattice with ozone-derived epoxy and carbonyl groups can be used to either etch molecular-sized pores in the CVD derived graphene or constrict the existing pores.The porosity of graphene lattice yielding the attractive H3-hybridized sites (epoxy and carbonyl groups) on the basal plane of graphene43. When the functionalization density is high, such as that in graphene oxide, one can introduce nanopores in the lattice by thermal annealing47. Typically, the functional groups migrate and rearrange forming larger groups (such as lactone), and finally desorb as CO or CO2 leading to a vacancy44. Ozone, in the gas phase, can be conveniently used to oxidize graphene lattice. To understand the evolution of functionalization, CVD graphene supported on a Cu foil was exposed to ozone at various temperatures  and time (1 min to 7 min). The evolution of oxidative groups on graphene was probed by micro-Raman and X-ray photoelectron spectroscopy (XPS). The relative intensity of the D peak with respect to the G peak (ID/IG), which marks the extent of disorder in graphene48, increased from 0.07 to 4.0, while the intensity of the 2D peak decreased in intensity with the increasing reaction time and temperature, indicating that the sp3-hybridized sites in graphene increased after ozone treatment  compared to that in as-synthesized graphene  and CoAactAsur decreased after the functionalization (Supplementary Table Eact-app are complex to interpret because of relative changes in Eact (higher activation energy due to the pore-shrinkage) and ΔEsur , a 20-fold decrease in CoAactAsur for CH4  on a Cu foil . Before CVD, the foil was placed in the fused quartz tube and annealed at 1000 °C in a CO2/Ar atmosphere for 1 h, forming the NPC film on top of graphene. The NPC/graphene/Cu was floated on a Na2S2O8 bath (0.2 M in water) to etch the Cu foil. After Cu etching, the floating NPC/graphene film was rinsed in deionized water to remove the residues. Finally, NPC/graphene was scooped on the porous tungsten support.To deposit the nanoporous carbon (NPC) film on graphene, 0.1 g block-copolymer (poly (styrene-b-4-vinyl pyridine), Polymer Source) and 0.2 g turanose (Sigma-Aldrich) were dissolved in DMF (Sigma-Aldrich). After a heat treatment of the solution at 180 °C, the solution was spin-coated onto the as-synthesized CVD graphene supported on the Cu foil. Pyrolysis of the polymer film was conducted at 500 °C in a H2 and O3 (21% in O3) generated by the ozone generator (Absolute Ozone® Atlas 30) was exposed to the permeate side of graphene. After a certain time, argon was used to sweep-out the residual ozone.Ozone functionalization on the suspended graphene film was conducted in-situ in the membrane module. The gas permeation module was leak-proof based on a metal–metal (Swagelok VCR fittings) seal. The membrane was sandwiched as a gasket in the VCR-based module, making a leak-tight fitting. Before, ozone functionalization, the membrane was heated to 150 °C to remove adsorbed atmospheric contaminations and to allow measurement of the gas separation performance. Then, the membrane was cooled to the functionalization temperature. Subsequently, a mixture of OThe single-component and mixture gas permeation tests were carried out in a homemade permeation cell. Permeation tests were conducted in the open-end mode.All equipment used in the permeation setup (the mass flow controllers (MFCs) and MS) were calibrated within 5% error. The gas permeation module based on the metal–metal (Swagelok VCR fittings) seal was leak-proof. The porous tungsten support was sandwiched as a gasket in the VCR-based module, making a leak-tight fitting. To ensure temperature uniformity and accuracy, the feed and the sweep lines were preheated, and the membrane module was heated inside an oven with the temperature accuracy of ±1 °C.2, He, CO2, and CH4 in Ar, similar to those in the permeate stream.A pre-calibrated MFC regulated the flow rate of feed gas, and the feed pressure was controlled by adjusting the back-pressure regulator installed at the downstream. Another pre-calibrated MFC controlled the flow rate of sweep gas (Ar), which carried the permeate gas to the pre-calibrated MS for real-time analysis of the permeate concentration. The MS was capable to read an extremely low concentration in the permeate stream. To reduce errors, MS was calibrated at low concentration of HThe transmembrane pressure difference was varied between 1.5 to 7.0 bar. Before testing, all membranes were heated to 150 °C to remove the contaminations on the graphene surface. For the mixture permeation tests, an equimolar gas mixture was used on the feed side. The gas flux was calculated once the steady-state was established . The measurements were carried out at continuously, in real-time, and only the steady-state data were reported.SEM was carried out by using FEI Teneo SEM at 0.8–2.0 kV and working distances of 2.5–9.0 mm. No conductive coating was applied on the substrates prior to SEM. TEM imaging and electron diffraction of the NPC film and the composite graphene/NPC film were conducted by FEI Tecnai G2 Spirit Twin with 120 keV incident electron beam.28. Briefly, a thin poly(methyl methacrylate) or PMMA film was spin-coated on top of graphene. Following this, Cu was etched in a sodium persulfate bath. After rinsing the floating graphene/PMMA film with deionized water, the composite film was transferred to the TEM grid. Subsequently, PMMA was removed by heating the sample to 400 °C in a reducing atmosphere of H2/Ar.For HRTEM, graphene was transferred on a quantifoil TEM grid by the traditional wet-transfer techniqueAberration-corrected (Cs) HRTEM was performed using a double-corrected Titan Themis 60-300 (FEI) equipped with a Wein-type monochromator. To reduce the electron radiation damage, an 80 keV incident electron beam was used for all experiments. The incident electron beam was monochromated (“rainbow” mode illumination) to reduce the effects of chromatic aberration, and a negative Cs of ~15–20 μm and slight over focus were used to give a “bright atom” contrast in the images. HRTEM images were post-treated using a combination of Bandpass and Gaussian filters to reduce noise and improve contrast.2/Si wafer by the wet-transfer method28. Single-point data collection and mapping were performed using Renishaw micro-Raman spectroscope . Analysis of the Raman data was carried out using MATLAB. For calculation of the D and the G peak height, the background was subtracted from the Raman data using the least-squares curve fitting tool (lsqnonlin).Raman characterization was carried on graphene transferred onto the SiOThe X-ray photoelectron spectroscopy (XPS) analysis was conducted on the graphene mounted on Cu foil using a Mg Kα X-ray source (1253.6 eV) and Phoibos 100 (SPECS) hemispherical electron analyser with multichanneltron detector. The XPS spectra were recorded in fixed analyser transmission (FAT) mode using pass energies of 90 eV for the survey and 20 eV for the narrow scans. The samples did not show electrostatic charging thus the binding energies are presented without any correction . Because carbonyl group (C=O) is part of (O–C=O), O–C=O was counted in C=O in the summation of functional group. The XPS spectra were processed with CasaXPS, with background subtraction by the Shirley method.The authors declare that all the data supporting the findings of this study are available within the article (and its Supplementary Information file), or available from the corresponding author on reasonable request.Supplementary InformationPeer Review File


We analyze the electronic properties of a hybrid graphene-BN nanoribbon system, using a Hubbard model Hamiltonian within a mean field approximation. Due to the different electronegativities of the boron and nitrogen atoms, an electric field is induced across the zigzag graphene strip, breaking the spin degeneracy of the electronic band structure. Optimal tight-binding parameters are found from first-principles calculations. Edge potentials are proposed as corrections for the on-site energies, modeling the BN-graphene nanoribbon interfaces. We show that half-metallic responses in the hybrid systems may be driven with the help of an external electric field. We also study the role of defects across the graphene nanoribbon and at the h-BN/graphene interface regions. Modulations on the spin-dependent gaps may be achieved depending on the nature and position of the defect, constituting a way towards spin-gap engineering by means of spatial doping. In nanoribbons, the opened gap depends on the edge type and the width of the strip4. Alternatively, combining the properties of large band gap semiconductors, such as hexagonal-boron nitride (h-BN), with the conductive properties of graphene, appears as a promising route for gap modulation5. In fact, h-BN has the same honeycomb lattice as graphene, but composed of alternating boron and nitrogen atoms with a lattice constant (2.50 Å) very similar to that of graphene (2.46 Å). The band gap of h-BN is [∼5–6]eV6. Hybrid graphene and h-BN materials have been synthesized using lithography patterning and sequential CVD growth steps7. Actually, efficient epitaxial growth routes of BN onto graphene edges are possible under particular experimental conditions8, allowing a good matching between both lattices.Graphene is a zero-band-gap semiconductor with valence and conduction bands touching at the corners of the Brillouin zone. However, in order to use graphene in semiconductor electronics, such as in field-effect transistors (FETs), it is very important to open a band gap. This can be achieved, for instance, by patterning graphene into quasi-one-dimensional nanoribbons or tuning its properties for its use as a two-dimensional semiconductor11. Insulator-metal transitions in BN nanoribbons have been predicted with the application of transversal electric fields12; the actual critical field depends on the width of the ribbon. Particularly, when an electric field is applied in the transversal direction of zigzag graphene nanoribbons (ZGNRs), the system behaves as a half-metallic material14. Namely, the spin-degeneracy is broken and the energy gap for electrons with spin down (spin up) decreases (increases) until a critical electric field is reached, for which there is a null gap for the spin-down channel, and the electrons in the other channel have a direct band gap. This opens the possibility of exploring spin filtering properties of carbon systems15. Interestingly, such half-metallic behavior can be achieved even in the absence of an external electric field for some systems19 as embedded ZGNRs in zigzag h-BN nanoribbons (ZBNNRs)20.Gap engineering is also possible by means of external electric fields2 -capture devices21, electronic rectifiers22, and spin-filters activated by strain23, or by edge hydrogenation effects24. Induced half-metallic responses due to spin polarization through defective interfaces of h-BN/graphene was reported in the work of Lan et al.25. Also, laterally repeating h-BN/graphene systems present a variety of electronic properties according to the geometry of the h-BN/layers, and can be potentially used in optical devices26. The electronic properties can also be modified by dihydrogenation of the edges of hybrid C/BN nanostructures27, promoting interesting semiconductor-to-half-metal-to-metal transitions.Graphene/h-BN heterostructures have been proposed for engineering applications; for example, COm-ZBNNR/n-ZGNR/m-ZBNNR  model with electronic correlation given by a Hubbard-like term is used to account for spin-dependent solutions. Simple TB calculations can reproduce quite well the electronic bands near the Fermi level for ZGNRs when compared to first-principles results28. For the case of ZBNNRs, more complex descriptions are necessary due to the large ionicity of BN.Our study focuses on hybrid systems of the form see Fig. , with m 29, mainly related to the π-bands. Alternatively, an edge potential approach was successfully proposed by Zheng et al. as an effective correction to on-site energy values in ZBNNRs30. This attempts to explain not only π-band features, but also some σ-band effects appearing in density functional theory (DFT) results. For the hybrid system m BN/n G/m BN, the presence of a ZGNR in the middle of the boron nitride nanoribbons changes the alternating electron polarization of B and N atoms. In fact, a single edge potential is unable to explain the electronic properties of the hybrid system. For this reason, we look for an electronic effective potential across the BN/graphene interfaces deriving it from DFT results31, resulting in on-site energy corrections for our TB calculations. With this parameterization, we study the band gap behavior of hybrid systems as a function of their geometry and structure. We also consider the presence of defects that are usually frequent in such nanostructured systems, mainly at the edges and interfaces, such as edge disorder and atom migration. Spontaneous magnetization in ZBNNRs doped with carbon atoms in substitutional positions in the lattices has been reported32, so understanding the effects of such lattice imperfections on the electronic properties is relevant to improve the controlled electronic responses of these nanostructured materials. Actually, atomically controlled substitutional boron doping of graphene nanoribbons has been reported to provide a route for the design of mobility gaps and novel types of graphene transistors33.Approaches to overcome this difficulty with similar systems include corrections to on-site energies and hopping integrals at the edges of nanoribbonsσ at site i, niσ is the spin-dependent occupation number operator, and εi, Ui, tij are the on-site energy, the intra-atomic Coulomb repulsion, and integral hopping energy, respectively. Using the mean-field approximation, the Coulomb term in  values for carbon  atoms along the length of the nanoribbon. For non-pristine systems, we consider periodic defects by taking a defective supercell, and following the same self-consistent renormalization procedure described above.The hybrid system is described by a TB approach involving a set of optimal parameters that properly reproduce DFT calculations. The intrasite electron-electron interaction is included via a Hubbard term, which reproduces the half-metallic characteristics related to spin polarization. The Hubbard Hamiltonian is written as term in  reduces entclass1pt{minima38. We use the Quantum ESPRESSO (QE)39 code to compute the electronic structure for the hybrid systems, followed by the WanT Package41 to obtain the on-site and hopping parameters. We call them the post-processed DFT parameter sets. Pseudopotentials from the ultrasoft Vanderbilt type, a cutoff energy of 60Ry, and a k-point sampling for the zigzag nanoribbons of 52 points are employed.In order to obtain the Hubbard and TB parameters, we follow a similar procedure used for other h-BN/graphene systems42 from which we obtain the TB parameter values. Although post-processing DFT calculations consider interactions between a large range of neighbor atoms, we are just interested in the on-site energy and first nearest-neighbor hoppings, so parameters obtained from QE and WanT are adjusted to build an optimal set of TB parameters which give the best agreement to the DFT calculations.The codes provide a procedure based on projecting the Kohn-Sham solutions into localized atomic orbitals. The corresponding Hamiltonian in the real space has a Slater-Koster-matrix shape5. For the present hybrid system, we adjust those parameter values to obtain an electronic effective potential31, affected by the presence of ZBNNR’s edges and BN/C interfaces. More detailed description on the optimized tight-binding model used is presented as a Supplementary Material.Optimal on-site energies and hopping parameter values for other BN/graphene systems are reported elsewhereet al. proposed a TB model for a ZBNNR system with on-site energy corrections in the form of effective edge potentials30. Here we follow a similar approach. In addition to the edge corrections, we also consider the effects of the zigzag interfaces (N/C and C/B), on the on-site energies of the hybrid system.Taking into account the important contribution from edge states to the electronic density of zigzag BN nanoribbons and the electronegativity difference between B and N atoms, Zheng εi, for B, N and C atoms are shown as black circles in Fig. i-sites far enough from the edges or interfaces.The results obtained from post-processing DFT calculations for the on-site energy values, V(x) is not directly obtained from post-processing DFT calculations due to the influence of a large number of neighbor interactions. Here, we are interested in an effective TB model only considering first nearest-neighbor interactions. Blue triangles in the left panel of Fig. et al. to correct the on-site energies in ZBNNRs using exponential-type edge potentials30. Furthermore, our procedure incorporates the effects from BN edges and BN/graphene interfaces, i.e., for the BN region we have the following contribution from the edges,π-electron density at xB and xN edges, while in the internal graphene strip the contributions from the interfaces are chosen as decaying exponential functions centered at the left and right interfaces, xL and xR,The envelope function 43. In order to identify the edge-localized states in a band, we compute the analogous of the inverse participation number for the tight-binding coefficients of the wavefunction, which quantifies the localization of a state45. Thus, we estimate the degree of localization in every band according toOn-site energies taken directly from post-processing DFT calculations do not reproduce some features of the band structures due to the contributions of many neighbors and the poor projection of Kohn-Sham solutions over localized atomic orbitalsThe band structures are shown in the right panel of Fig. The resulting parameters for edge and interface potentials are shown in Table It is important to remark that the same TB parameters explain the main band structure features of other hybrid systems. Actually, we have worked with a set of ;2),\; 5;...,46. The work by Zhao et al. provides TB parameters for BN quantum dots embedded in graphene5. Starting from those values, we have modified them  = , but predicts a half-metallic response for wider ribbons, with  =  and , in agreement with Ding et al.4. Similar band structures with half-metallic response are also exhibited by other h-BN/graphene configurations47. Tight-binding band structures are also calculated with our parameterization and compared with the DFT calculations. The TB results are plotted in Fig. An interesting result of the hybrid systems is their spontaneous half-metallicity without the need of an external field, which is explained by the presence of an effective electric potential generated through the graphene strip, as it can be noticed from Eq. et al.34, i.e. the on-site energies are modified by an electrostatic potential:V is an electrostatic potential produced by a transversal electric field, parallel to axis X of the figures shown in this article and perpendicular to the edgesV being antisymmetric respect to the axis of the nanoribbon. We have chosen this model since our system is electrically neutral, and our calculations follow a procedure that ensures charge neutrality for the system as a whole.In order to further explore the half-metallicity features observed in the hybrid graphene/h-BN nanoribbons we consider the case in which an extra electric field is applied in the transversal direction of the nanoribbons. To introduce the electric field into the calculations, we have followed the same procedure as in Wakabayashi 48. Such behavior can be understood due to the absence of electron-hole symmetry.In the presence of a transversal electric field, first-principle calculations on zigzag BNNRs are shown to exhibit asymmetric responses49. After this point, the system becomes a nonmagnetic semiconductor. In other words, in the hybrid system, a first critical field occurs when a nonzero external field is applied , and a second one happens for larger values, marking the occurrence of the half-metallic behavior. This second critical electric field is shifted to higher values compared to pure graphene nanoribbons, due to the intrinsic field produced by the ZBNNR edges.TB calculations show that when adding a positive external electric field on the hybrid system, the original half-metallicity disappears; with increasing electric field, the bandgap for the spin-up channel decreases rapidly, while the bandgap for the spin-down channel widens. The bandgaps for the up and down spin channels are eventually equal at a particular electric field, marked in Fig. U adopted, but the shape of the gap curve as a function of the electric field is completely preserved . TB calculations from Culchac et al. also show a fast evolution of the gap value around the critical electric field value for ZGNRs49. The rate of change is smoother according to DFT calculations on ZGNRs, but strongly depends on the functional employed50. It is important to remark that the TB calculations can reproduce the removal of half-metallicity for large values of the electric field, a common feature for ZGNRs and h-BN/graphene heterostructures. For negative values of the electric field, the different spin-dependent gaps are moved towards a non-magnetic solution, with degenerate up and down solutions. Therefore, the addition of an external electric field breaks the intrinsic half-metallic behavior that happens for certain hybrid system geometries. This response is in agreement with the DFT results by Bohwmick et al.20.According to our TB calculations, the rate of change of the spin-up gap with respect to the electric field is very high around the first critical electric field value (next to zero field for h-BN/graphene heterostructure). We have checked that the exact electric field for which this abrupt transition takes place depends on the Coulomb potential i, given in terms of the Bohr magneton, with ni,up  being the mean number of electrons with spin up (down) at site i. The results plotted in Fig. 51. A positive external field increasing also leads to a magnetization quenching, but with different field-dependence due to the internal electric field induced by the BN edges. Of course, the critical electric field which produces the magnetization suppression depends on the characteristic sizes of the hybrid system, that may be additionally engineered.We also calculate the magnetization of the hybrid system 5BN/6 G/5BN as a function of the applied electric field. We use the expression 52 and vice versa. The presence of defects at the interface has been reported elsewhere53 and could lead to an enhancement of the half-metallic behavior54. A DFT description of these hybrids would require high computational cost. Dieb et al. overcame this difficulty55 proposing a machine learning algorithm to describe B-doped graphene systems and to find the most stable configurations. Alternatively, we model hybrid systems by means of the tight-binding approximation, using our TB parameterization and fitting curves to model the hybrid system bandgaps. We first consider the possibility of boron or nitrogen atoms placed at carbon atom positions inside the graphene strip, mimicking a migration process, as shown schematically in Fig. A more realistic description of the studied hybrid nanoribbons should certainly include roughness in the zigzag interfaces as well as possible diffusion of boron or nitrogen atoms from the h-BN region into the graphene stripn-th site. We should remember that nitrogen electronegativity is higher than those of carbon and boron atoms. Usually, in an B-doped AGNR the Fermi level is shifted downward due to missing π electrons from the B atoms56. As expected, impurity substitutions with boron and nitrogen atoms induce opposite trends for the bandgap behavior as a function of the impurity position along the graphene material: averaged higher/smaller spin-up gap as the B/N atom migrates from the N-C (left) to the C-B (right) interface. N-substitutions along the graphene strip show, on average, a more robust half-metallic response compared with B-substitutions and to the pristine case. Otherwise, notice that the system enhances the half-metallic response when B and N substitutions happens at the first neighbor carbon atom in both interfaces; site 11 for the B and site 22 for the N impurity. When a B occupies the 11-th position, it follows the natural B-N sequence along the h-BN armchair chain, leading to a narrower effective ZGNR width, what makes the gap increase. The same is valid for an N impurity at site 22. Calculations for less diluted systems  reveal similar bandgap trends, but with more variations.We analyze the gap evolution shown in Fig. As we have not directly included the structural distortions in the discussion on the defects, we have explored a possible alternative approach to include effectively the lattice distortion effects, based on the linear strain theory that changes hopping energies within tight-binding descriptions. Details are presented in the Supplementary Material. We have shown that similar results are obtained, validating our approach.Using our TB parameters with edge and interface potentials, we calculate the total energy of the system when a boron (or a nitrogen) atom substitutes a carbon atom in the graphene strip. The results show (not presented here) that a boron replacing a carbon atom at the interface is the most favorable energetic configuration, where the boron is bonded with a nitrogen atom. As expected, an analogous behavior happens for the nitrogen substitution on the other edge. These results have been corroborated by DFT calculations.Na as a parameter that indicates how far the two defects are from the frontal relative position, in terms of the number of armchair chains separating the two defects. Thus, ΔNa = 0 when both impurities belong to the same armchair chain, but located at different interfaces.We also study other defect configurations. Instead of having atomic diffusion across the graphene strip, we analyze the effect of the presence of impurities located at opposite interfaces. Figure Na = 0, while for other neighboring relative positions of the defects, the gap starts decreasing as the impurities get apart from each other. In fact, the configuration with opposite impurities amounts to an effective reduction of the width of the ribbon, which yields an increased gap.Figure Na shown in Fig. N for the particular system et al. reported57 that doping graphene sheets above a certain concentration leads to a half-metallic response. Therefore, the combined effects of interface potentials and a B(N)-doping in h-BN/graphene/h-BN systems may result in an enhancement of the half-metallic behavior depending on the doping concentration.We should also keep in mind that the oscillatory gap behavior as a function of Δn BN/m C/n BN heterostructure that reproduce the main features of DFT predictions including the effect of external electric fields. The TB parameters are not only valid for a specific size of the heterostructure: they are robust enough to explain main trends of the electronic band structures for a wide range of graphene/h-BN system sizes. Due to the ionic edges of ZBNNRs and BN/C interfaces in the hybrid systems described here, we can estimate an effective potential that gives a best fit to DFT predictions. Another advantage of our TB parameters is the study of transport using Green functions in big hybrid systems and the influence of impurities in a scattering region. The coupling regions between electrodes and scattering regions are minimized, reducing the computational cost of the transport calculations. We have enlarged our discussion on the adequateness of our approach and the possibility of validating our approach with other computational methods in the Supplementary Material.In summary, we have found TB parameters for the With respect to the applied electric fields, due to the polarity of the material, boron and nitrogen edges induce an electric field that competes with the external field, that we have successfully modeled. Half-metallicity becomes intrinsic to the BN/5 C/BN even in the absence of an external electric field. Furthermore, the graphene/h-BN heterostructure can not only work as a spin filter, but also as a spin swapping device by just turning on an external electric field.Taking advantage of our approach, we aim to study larger systems that would be computationally expensive by first-principles calculations. We use our TB parameters to analyze more realistic graphene/h-BN heterostructures by considering boron and nitrogen diffusion across the graphene strip, or graphene/h-BN interface with roughness due to substitutional impurities. We have found that in general nitrogen diffusion enhances the half-metallic response. We have also found an oscillatory gap behavior that is maximum for a pair of boron and nitrogen impurities facing each other at each BN/graphene interfaces. We attributed this maximum gap value to an effective reduction of the width of the nanoribbon. Further studies are needed to analyze a possible suppression or enhancement of the half-metallic response by modulating the concentration of boron and nitrogen impurities at the interfaces.Supplementary Material


The aim of this study was to explore whether spectral computed tomography (CT) imaging parameters are associated with PD‐L1 expression of lung adenocarcinoma.Spectral CT imaging parameters  were analyzed in 34 prospectively enrolled lung adenocarcinoma patients with common molecular pathological markers including PD‐L1 expression detected with immunohistochemistry. Patients were divided into two groups: positive PD‐L1 expression and negative PD‐L1 expression groups. Two‐sample Mann‐Whitney U test was used to test the difference of spectral CT imaging parameters between the two groups.. −54.69 ± 262.04), CT40keVv (124.39 ± 34.71 vs. −45.73 ± 238.97), CT70keVa (49.56 ± 11.76 vs. −136.51 ± 237.08) and CT70keVv (46.13 ± 15.81 vs. −133.10 ± 230.72) parameters in the positive PD‐L1 expression group of lung adenocarcinoma were significantly higher than the negative PD‐L1 expression group . There was no difference detected in IC, NIC and λHU of the arterial and venous phases between both groups .The CT40keVa (127.03 ± 37.92 vsCT40keVa, CT40keVv, CT70keVa and CT70keVv were increased in positive PD‐L1 expression. These parameters may be used to distinguish the PD‐L1 expression state of lung adenocarcinoma. Primary lung cancer is the leading cause of morbidity and mortality both in China and worldwide.At present, the detection of lung cancer‐related mutant genes and PD‐L1 expression is mainly through invasive biopsy, some of which are expensive, which limits its wide clinical use.Recently, the correlation between CT signs of lung adenocarcinoma and common gene mutations of EGFR and ALK has been studied.Spectral CT imaging has been applied in several of the studies on pulmonary nodules. Most researchers believe that quantitative parameters of spectral CT imaging have certain advantages in the differential diagnosis of benign and malignant pulmonary nodules.From January 2018 to August 2018, a total of 34 patients detected with immunohistochemistry of 67 lung adenocarcinomas , were prospectively enrolled in the study. This research protocol was approved by the Medical Ethical Committee of Peking University Cancer Hospital & Institute and written informed consent was obtained from all patients in accordance with the guidelines of National Health Commission of the People's Republic of China. Patients were selected for investigation according to the following inclusion criteria: (i) presence of at least one solitary lung adenocarcinoma proved by pathology and (ii) no contraindications to the administration of iodinated contrast material. Patients without PD‐L1 testing were excluded from this study.vol) for GSI acquisition was 4.73 mGy.CT examinations were performed with two‐phase enhanced CT scanning using spectral imaging mode on a Revolution Xtream CT scanner . Patients were injected with 40/50 mL  Iopromide  at a flow rate of 5/6 mL/second , followed by the 30 mL saline solution at the same injection rate. With a scan delay of 30 and 90 seconds after the start of contrast injection, a GSI examination of the entire chest was performed during arterial phase (AP) and portal venous phase (VP), respectively. There were no serious injection complications or issues in this study. Acquisition parameters were helical tube rotation time 0.6 seconds, helical pitch 0.985, tube current of 600 mA, 512 × 512 pixel matrix, SFOV 500 mm and collimation 40 mm, slice thickness of 5 mm, slice gap of 5 mm. Contiguous axial images (2.5 and 1.25 mm thickness) at a default monochromatic energy level of 40 and 70 KeV were then reconstructed with a soft tissue kernel (standard) with GSI data file. CT dose index . Monochromatic and material decomposition images were performed to analyze the quantitative measurements by a chest radiologist with 10 years experience. During data analysis, the radiologist amplified the display field of view to 15 or 20 cm in each lesion imaged. The region of interest (ROI) was selected as large as possible at the maximum section of the lesion carefully avoiding calcification, liquefaction, or necrosis, away from pulmonary vessels and bronchi, and as large as possible to reduce noise (50 pixels). All measurements were repeated three times at three contiguous imaging levels and average values calculated to ensure consistency.Spectral curve image, iodine‐based material decomposition images, and monochromatic images obtained at the energy level of 40 and 70 keV in both arterial phase (a) and venous phase (v) were reconstructed from the spectral CT acquisition for analysis. In the iodine density image derived from the iodine/water based material decomposition image, the iodine concentration of lesions (ICLa/ ICLv) in double‐phase enhanced scan were measured. The iodine concentration in the aorta descendens or subclavian artery (ICA) were also measured in the same slice. The normalized iodine concentration (NICa and NICv), which is the ratio of iodine concentration in lesion and aorta descendens (NIC = ICL/ICA), were calculated. These iodine concentration parameters ICLa, ICLv, ICAa, ICAv, NICa and NICv were calculated in the arterial and venous phase, respectively. The slope of spectral HU curve (λHU) was assessed only 40–70 keV region by the equations λHU = (CT40 keV−CT70 keV) HU/(70–40) based on previous studies. λHUa = (CT40 keVa−CT70 keVa) HU/(70–40) and λHUv = (CT40 keVv−CT70 keVv) HU/(70–40) were calculated.Pathological specimens were routinely fixed in 10% formalin, paraffin‐embedded. Tissue sections were cut at 4 μm thickness including the largest cut surface of the tumor, and stained with hematoxylin and eosin (H&E). Pathological diagnoses were made by two experienced lung pathologists, based on the new WHO histological classification of lung tumors in 2015,Immunostaining was performed using the standard streptavidin‐perosidase (SP142) technique with the antibodies for PD‐L1. A Leica automatic staining machine was used for immunohistochemical staining. Tumor proportion score (TPS) was counted. TPS >1% was positive and TPS >50% indicated a high expression of PD‐L1.Immunohistochemical EnVision two‐step staining was used to detect antibodies P40, TTF‐1, NapsiA and ki‐67.P‐value less than 0.05 indicated significance. SPSS was used to perform the statistical analysis .Data were transformed using a Box‐Cox power transformation by Statistics 12 , to minimize the influence of extreme values or non‐normal distributions. Parameters were expressed as mean ± SD and tested for normal distribution using Kolmogorov‐Smirnov test. The two‐sample Mann‐Whitney test was used to compare the difference of spectral CT quantitative parameters between positive PD‐L1 expression and negative PD‐L1 expression groups. A A total of 34 patients with PD‐L1 test results were enrolled into the study. The results indicated that there was one patient (2.9%) with minimally invasive adenocarcinoma (MIA) (2.9%) and 33 with invasive adenocarcinomas (IACs) (97.1%). Of these, 15 were solid cases and 19 ground‐glass opacities, which presented as predominant lepidic growth in nine cases, predominant acinar growth in nine cases, solid growth in two cases, papillary growth in two cases, micropapillary growth in one case, infiltrating mucinous adenocarcinoma in one case, and mixed of two growth in 10 cases. All cases were confirmed by pathology. PD‐L1 expression was positively detected in eight cases (23.5%), and PD‐L1 expression was negative in 26 cases (76.5%).P = 0.005; CT40keVv: 124.39 ± 34.71 vs. −45.73 ± 238.97, P = 0.004; CT70keVa: 49.56 ± 11.76 vs. −136.51 ± 237.08, P = 0.002; CT70keVv: 46.13 ± 15.81 vs. −133.10 ± 230.72, P = 0.002, as seen in Figures In the positive PD‐L1 expression and negative PD‐L1 expression groups, raw variables for differentiating positive PD‐L1 expression from negative PD‐L1 expression are shown in Table P > 0.05.IC, NIC and λHU in both arterial and venous phases in the positive PD‐L1 expression group had no statistically significant differences compared to the negative PD‐L1 expression group, and all were Currently, the choice of first‐line treatment for advanced non‐small cell lung cancer (NSCLC) depends on the presence of genetic aberrations, such as mutations of epidermal growth factor receptor (EGFR) and translocations of anaplastic lymphoma kinase (ALK). However, only 10% to 20% of patients with NSCLC have these actionable mutations.At present, using immunohistochemistry (IHC) staining in formalin‐fixed paraffin‐embedded tissue samples is the most popular method to assess PD‐L1 expression. However, there is no unified standard to detect PD‐L1 staining because there are different staining techniques and antibodies. Scoring methods and cutoff values to define positive expression are also different in individual studies which make it difficult to reach a compatible consensus.Radiographic assessment as a noninvasive and quantitative method could bring practical clinical benefit in the development of predictive markers before immunotherapy. Similarly, traditional chest CT features have also been extensively studied as radiologic markers for predicting therapeutic effect and survival time of lung adenocarcinomas. In addition, several studies have been conducted on the relationship between traditional chest CT features and gene mutations of EGFR, ALK in lung adenocarcinomas.89Zr, 64Cu, 68Ga or 111InIn this study, and as seen in Table There were several limitations in this study. First, the number of patients was relatively small, and the PD‐L1‐positive cases were proportionally lower, which probably results in selection bias; however, it is epidemiologically consistent with the incidence of lung cancer with PD‐L1 expression. It means that our results should be further validated in a large number of cases. Second, the biological behavior of different subtypes of lung adenocarcinoma varies greatly, and their spectral CT imaging parameters and PD‐L1 expression may be different. Third, the majority of selected cases in this study were elderly people with a mean age of 61.5 years, and younger patients should be included in future studies. Fourth, monochromatic CT number was measured only enhanced monochromatic spectral CT imaging at the energy level 40 and 70 keV based on previous studies,In conclusion, spectral CT imaging parameters, CT40keVa, CT40keVv, CT70keVa and CT70keVv were significantly increased when PD‐L1 expression was positive. These parameters may be used to distinguish the PD‐L1 expression status of lung adenocarcinoma.The author(s) have no relevant conflicts of interest to disclose.