In mobile system due to limited space mutual coupling between nearby antenna elements is an issue that distort MIMO antenna performance. Defected ground structure is used to control coupling. The defected ground structure has advantages like ease of fabrication, compact size and high efficiency as compare to other techniques. Less than 30dB coupling is achieved for adjacent elements. The -10 dB impedance bandwidth of 700 MHz is achieved for all radiating elements ranging from 3.3 GHz to 4.1 GHz. The value is about 900MHz for -6dB. The proposed antenna offers good results in terms of fundamental antenna parameters like reflection coefficient, transmission coefficient, maximum gain, total efficiency. The antenna achieved average gain more than 3.8dBi and average radiation efficiency more than 80% for single dual polarized element. The antenna provides sufficient radiation coverage in all sides. The MIMO antenna characteristics like diversity gain (DG), envelope correlation coefficient (ECC), total active reflection coefficient (TARC) and channel capacity are calculated and found according to standards. Furthermore, effect of user on antenna performance in data-mode and talk-mode are studied. Proposed design is fabricated and tested in real time. The measured results shows that proposed design can be used in future smartphones applications. The design is compared with some of the existing work and found to be the best one in many parameters and can be used for commercial use.This manuscript presents high performance dual polarized eight-element multiple input multiple output (MIMO) fifth generation (5G) smartphone antenna. The design consists of four dual-polarized microstrip diamond-ring slot antennas, positioned at corners of printed circuit board (PCB). Cheap Fr-4 dielectric with permittivity 4.3 and thickness of 1.6mm is used as substrate with overall dimension of 150 × 75 × 1.6  In modern day, the interest in MIMO wireless communication technology is increased due to key features of MIMO technology like highly improve wireless link reliability, transmission capacity and data rates of wireless system through multi-path transmission and reception . For 5G mm3. The optimized value of the proposed MIMO design is listed in below Here, the design of single element dual-polarized antenna and result analysis of simulated and measured results is discussed. In figure below the configuration of dual-polarized antenna is presented. The aim of the research is the design of a small MIMO antenna that can be easily integrated into a smartphone’s PCB with wide band and having dual polarization capabilities and low mutual coupling. This is accomplished by using microstrip patch antenna with slot in ground plane which increase isolation and wide the antenna bandwidth. Slot antenna is used because of its attractive features like compactness, light wight and ease of fabrication and integration with radio frequency circuits. The width of slot determines operating frequency. The circumference of ring needs to match the dielectric wavelength at the operating frequency as The dual polarization of antenna is achieved by placing radiating elements orthogonal to each other so that they orthogonally polarized. Dual polarization also increase isolation between antenna elements as both elements fed differently. Microstrip feed lines are used for feeding the orthogonal antenna elements. Microstrip feeding techniques offers features like simplicity, miniaturization, low cost, planar compatibility, high integration which is focus of this research. The characteristic impedance (Zo) of microstrip feed line can be calculated as εeff is given by Where effective height of the feed line can be calculated as The configuration of various structures studied in the designing process of proposed dual polarized antenna alongside with their S-parameter are displayed in Reflection coefficient (S11) of various antenna design parameters like Lf, Wf, Wx and x are demonstrated in The photograph of fabricated prototype of proposed antenna design (single element) and the measured reflection and transmission coefficient are given in Snn) and transmission coefficient (Snm). The figure shows that the suggested antenna design for smart mobile phone exhibits good return loss, wide bandwidth, high isolation, low mutual coupling and polarization diversity. Each of the four dual polarized radiating elements offers comparable performance.Smart phone 8 by 8 antenna design on 75mm by 150 mm PCB is illustrated in The photograph of fabricated prototype of 8 by 8 smart phone antenna is illustrated in The measured and simulated 2D polar plots (E & H-plane) of radiation pattern are compared and illustrated in ith and jth element of m by n MIMO antenna can be determined from antennas S-Matrix using equations ECC, DG, TARC and channel capacity (CC) are some crucial factors that need be taken into account in MIMO antennas to find that MIMO system function properly. ECC between ECC of antenna described about how much radiation pattern of two elements of a MIMO system are independent of each other. If on element is vertically polarized and a near-by second element is horizontally polarized then these elements would have a zero correlation between them. Correspondingly, if one antenna only radiated energy towards the ground and the other antenna element has a radiation pattern towards the sky totally opposite the ECC between these antennas would also be zero. Polarization of the antenna, shape of radiation pattern and relative phase of fields between two elements of a MIMO antenna or taken into consideration when calculating ECC of MIMO system. Envelope correlation coefficient of MIMO system can be calculated using S-matrix via An important parameter for assessing performance of MIMO antenna is TARC. It can be calculated from The detailed comparison of proposed work with already present work in literature is given in Effect of human (users) body tissues on proposed design performance is studied considering three common scenarios i.e., Data mode in which two modes single hand mode (SHM) and dual hand mode (DHM) and talking mode (TM). The placement of mobile phone MIMO antenna in different scenarios is illustrated in For 5G MIMO communications, a mobile phone antenna with dual-polarization capabilities is suggested. The antenna layout includes two-port microstrip feed lines with ground plane diamond slots placed at each of the PCB’s four corners. The antenna elements have a broad bandwidth with a 3.6 GHz center frequency. Antenna performance parameters i.e., S-parameters, Efficiency, maximum realized gain, radiation patterns, DG, ECC, TARC and channel capacity are simulated and adequate results are obtained. Antenna has more than 700 MHz bandwidth and radiation efficiency more than 85% with more than 6 dB gain for MIMO configuration. The antenna has exhibits more than 30dB isolation due to orthogonal placement of adjacent element. ECC one of main MIMO antenna parameters is less than 0.001. The antenna’s performance in talk-mode and data-mode scenarios is examined. Also, the proposed design of smart-phone antenna is fabricated and tested. The experimental results are in decent agreement with simulated one’s with very little variations due to experimental errors. The results showed that the suggested smartphone antenna satisfies the criteria for use in upcoming smart-phones. 28 Apr 2023
 PONE-D-23-09968

 Dual Polarized 8-port Sub 6 GHz 5G MIMO Antenna for Smart Phone and Portable Wireless Applications

 PLOS ONEDear Dr. Muhammad,

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If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to Questions  Comments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?  The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: YesReviewer #3: Partly**********  2. Has the statistical analysis been performed appropriately and rigorously?   Reviewer #1: YesReviewer #2: N/AReviewer #3: N/A**********  3. 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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: YesReviewer #3: No**********  5. Review Comments to the Author  Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: This research work demonstrated and practically implemented a mobile phone antenna with dual-polarization capabilities which is a potential candidate for 5G MIMO communications. The antenna layout includes two-port microstrip feed lines with ground plane diamond slots placed at each of the PCB’s four corners. From this reviewer’s point of view promising results have been achieved and well discussed in the well-organized manuscript. So, the results have been experimentally validated and highlighted by providing a fair comparison with state-of-the-art. Although the concept and idea of this work were found interesting and they seem attractive for the scientific society, authors are requested to carefully address the following comments to improve the quality of the manuscript prior to final recommendation.1) Please add the applied design method of the proposed MIMO antenna to the title.2) Please explain some information about the advantage of the proposed decoupling method in the abstract section.3) Average radiation gain and efficiency can be added to the abstract section.4) Introduction section can be improved by adding more explanations along with proper references. For example, more discussions on 5g MIMO antennas are requested. Also, to realize MIMO antennas, isolation between the radiation elements are very important which need to be discussed. There are various decoupling methods which can be briefly mentioned. Below are helpful suggestions.(i) 5G MIMO antenna"H-shaped Eight-Element Dual-band MIMO Antenna for Sub-6 GHz 5G Smartphone Applications", IEEE Access, vol. 10, pp. 85619-85629, 2022."An Innovative Antenna Array with High Inter Element Isolation for Sub-6 GHz 5G MIMO Communication Systems", Scientific Reports, 12, 7907, 2022."mmWave Four-Element MIMO Antenna for Future 5G Systems", Applied Sciences, 12(9), 4280, 2022."Uni-Planar MIMO Antenna for Sub-6 GHz 5G Mobile Phone Applications", Applied Sciences, 12(8), 3746, 2022."Multiple Elements MIMO Antenna System with Broadband Operation for 5th Generation Smart Phones", IEEE Access, vol. 10, pp. 38446-38457, 2022.“Novel MIMO Antenna System for Ultra Wideband Applications”, Applied Sciences, 12(7), 3684, 2022.“A high gain multiband offset MIMO antenna based on a planar log-periodic array for Ku/K-band applications”, Scientific Reports, 12, 4044 (2022)."A Compact CPW-Fed Ultra-Wideband Multi-Input-Multi-Output (MIMO) Antenna for Wireless Communication Networks,", IEEE Access, vol. 10, pp. 25278-25289, 2022."Printed Closely Spaced Antennas Loaded by Linear Stubs in a MIMO Style for Portable Wireless Electronic Devices", Electronics, 10(22), 2848, 2021."MIMO Antenna System for Modern 5G Handheld Devices with Healthcare and High Rate Delivery" Sensors, 21(21), 7415, 2021.(ii) Decoupling methods to realize MIMO antennas"A Comprehensive Survey on "Various Decoupling Mechanisms with Focus on Metamaterial and Metasurface Principles Applicable to SAR and MIMO Antenna Systems"", IEEE Access, vol. 8, pp. 192965-193004, 2020.“Study on Isolation and Radiation Behaviours of a 34×34 Array-Antennas Based on SIW and Metasurface Properties for Applications in Terahertz Band Over 125-300 GHz”, Optik, International Journal for Light and Electron Optics, Volume 206, March 2020, 163222."Isolation Enhancement of Densely Packed Array Antennas with Periodic MTM-Photonic Bandgap for SAR and MIMO Systems", IET Microwaves, Antennas & Propagation, Volume 14, Issue 3, February 2020, pp. 183 - 188."Surface Wave Reduction in Antenna Arrays Using Metasurface Inclusion for MIMO and SAR Systems", Radio Science, 54, 1067–1075, 2019."Mutual-Coupling Isolation Using Embedded Metamaterial EM Bandgap Decoupling Slab for Densely Packed Array Antennas", IEEE Access, vol. 7, pp. 5182–51840, April 29, 2019."Mutual Coupling Suppression Between Two Closely Placed Microstrip Patches Using EM-Bandgap Metamaterial Fractal Loading", IEEE Access, vol. 7, Page(s): 23606 – 23614, March 5, 2019."Interaction Between Closely Packed Array Antenna Elements Using Metasurface for Applications Such as MIMO Systems and Synthetic Aperture Radars", Radio Science, Volume53, Issue11, November 2018, Pages 1368-1381.“Antenna Mutual Coupling Suppression Over Wideband Using Embedded Periphery Slot for Antenna Arrays”, Electronics, 2018, 7(9), 198.“Study on Isolation Improvement Between Closely Packed Patch Antenna Arrays Based on Fractal Metamaterial Electromagnetic Bandgap Structures”, IET Microwaves, Antennas & Propagation, Volume 12, Issue 14, 28 November 2018, p. 2241 – 2247.“Meta-surface Wall Suppression of Mutual Coupling between Microstrip Patch Antenna Arrays for THz-band Applications”, Progress in Electromagnetics Research Letters, Vol. 75, page 105-111, 2018.5) Design process of the proposed single antenna should be elaborated in depth. Please explain why authors have realized diagonal rectangular slots on the back? How were its dimensions optimized?6) Quality of the plots are poor, they need to be improved.7) More discussions on the surface current distributions should be added.8) The feeding mechanism of the MIMO antenna should be explained in detail.9) In comparison table 2 please add the terms “applied design method, radiation gain, and design complexity” as well to make it more comprehensive.10) Please extend the conclusion by adding more numerical results and achievements.11) Reference part needs to be improved as per above mentioned suggestions.Reviewer #2: 1. An 8-port MIMO antenna for smartphone application is proposed.2. Author need top carry out a systematic literature review to establish the technical contribution and need for the proposed work.Please refer below paper for the same: Design and Analysis of Wideband Flexible Self-Isolating MIMO Antennas for Sub-6 GHz 5G and WLAN Smartphone Terminals3. Also authors should refer to some latest sub-6 GHz MIMO antennas and do a thorough comparison to establish the novel contribution:a. Compact wideband four element optically transparent MIMO antenna for mm-wave 5G applicationsb. Multiband hybrid MIMO DRA for Sub‐6 GHz 5G and WiFi‐6 applicationsc. Dual-band and dual-polarization CPW Fed MIMO antenna for fifth-generation mobile communications technology at 28 and 38 GHzd. Wideband flexible/transparent connected-ground MIMO antennas for sub-6 GHz 5G and WLAN applications4. Improve the quality of all the figures 5. Show the coordinate axis next to the antenna geometry.6. In Fig 6(a), gain should be in dBi and not dB.7. For such configuration, the number of input ports increases significantly.8. Present selected data in some of the graphs for brevity of data.9. Fig 15 is not at all clear.10. Authors should carry out SAR analysis.Reviewer #3: The article "Dual Polarized 8-port Sub 6 GHz 5G MIMO Antenna for Smart Phone and PortableWireless Applications" need major revision to process to next level1) The design orientation and associated mathematical formulation is missing in the paper2) Figure captions not given with numbers for review3) For eight ports, the transmission coefficient results shown are of low quality and data in zig zag.4) Human phantom model is used in the work for analysis. I have not found any type SAR readings and related matter.5) The CCL and Diversity Gain and TARC parameters for MIMO was not discussed and presented6) 2D plots with several combinations without any analysis is presented**********  6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  20 Jun 2023Original Manuscript ID: PONE-D-23-09968Original Article Title: Dual Polarized 8-port Sub 6 GHz 5G MIMO Antenna for Smart Phone and Portable Wireless ApplicationsTo: PLOS ONE EditorRe: We are very thankful to the PLOS ONE journal team and reviewers for such a comprehensive and profound review. We have revised our manuscript in light of their valuable queries and suggestions. We hope our revision has improved the paper quality to a level of reviewers’ satisfaction. The answers to their specific suggestions/queries/comments are given below in detail.Dear Editor,Thank you for allowing a resubmission of our manuscript, with an opportunity to address the reviewers’ comments.We are uploading (a) our point-by-point response to the comments (below) (response to reviewers), (b) an updated manuscript with yellow highlighting indicating changes (Revised Manuscript with Track Changes), and (c) a clean updated manuscript without highlights (Manuscript) (PDF main document).Best regards,Dr. Fazal MuhammadCorresponding Author Response to Reviewer #1: We would like to thank the reviewer for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Our response follows . General Comments: This research work demonstrated and practically implemented a mobile phone antenna with dual-polarization capabilities which is a potential candidate for 5G MIMO communications. The antenna layout includes two-port microstrip feed lines with ground plane diamond slots placed at each of the PCB’s four corners. From this reviewer’s point of view promising results have been achieved and well discussed in the well-organized manuscript. So, the results have been experimentally validated and highlighted by providing a fair comparison with state-of-the-art. Although the concept and idea of this work were found interesting and they seem attractive for the scientific society, authors are requested to carefully address the following comments to improve the quality of the manuscript prior to final recommendation.Reviewer #1 Concerns:1. Please add the applied design method of the proposed MIMO antenna to the title.2. Please explain some information about the advantage of the proposed decoupling method in the abstract section. 3. Average radiation gain and efficiency can be added to the abstract section4. Introduction section can be improved by adding more explanations along with proper references. 5. Design process of the proposed single antenna should be elaborated in depth. Please explain why authors have realized diagonal rectangular slots on the back? How were its dimensions optimized?6. Quality of the plots are poor; they need to be improved.7. More discussions on the surface current distributions should be added.8. The feeding mechanism of the MIMO antenna should be explained in detail.9. In comparison table 2 please add the terms “applied design method, radiation gain, and design complexity” as well to make it more comprehensive.10. Please extend the conclusion by adding more numerical results and achievements.11. Reference part needs to be improved as per above mentioned suggestions.Additional Questions:1. Is the manuscript technically sound, and do the data support the conclusions? Yes2. Has the statistical analysis been performed appropriately and rigorously? Yes3. Have the authors made all data underlying the findings in their manuscript fully available? Yes4. Is the manuscript presented in an intelligible fashion and written in standard English? Yes Reviewer#1, Concern#1: Please add the applied design method of the proposed MIMO antenna to the title.Author response: Thanks for valuable suggestion, as per respected reviewer we have change the title of our manuscript and added design method to title. Our new title is as under“Dual-polarized 8-port sub 6 GHz 5G MIMO diamond-ring slot antenna for smart phone and portable wireless applications”________________________________________Reviewer#1, Concern#2: Please explain some information about the advantage of the proposed decoupling method in the abstract section.Author response: Thank you very much for the valuable suggestions, as per the honorable reviewer suggestions we have added the information about the advantage of the proposed coupling method in the abstract section, as highlight in the revised version of the manuscript.________________________________________Reviewer#1, Concern#3: Average radiation gain and efficiency can be added to the abstract sectionAuthor response: Thanks for the suggestion , the average gain and efficiency are added to abstract section, and highlighted in marked version of manuscript.________________________________________Reviewer#1, Concern#4: Introduction section can be improved by adding more explanations along with proper references.Author response: Thank you very much, as per the honorable suggestion, the introduction section is improved by adding more explanation with proper references, and the changes are highlighted in marked version.________________________________________Reviewer#1, Concern#5: Design process of the proposed single antenna should be elaborated in depth. Please explain why authors have realized diagonal rectangular slots on the back? How were its dimensions optimized?Author response: Thanks for your comment, the design process is elaborated and some mathematical equations are included as shown in revised version. The diagonal slot in ground plane is used to reduce the mutual coupling between antenna elements and increase bandwidth. The dimensions are optimized by doing some parametric study.________________________________________Reviewer#1, Concern#6: Quality of the plots are poor; they need to be improved.Author response: Thanks for very much for the comments , the quality of plots is improved in the revised version and highlighted the revised manuscript.________________________________________Reviewer#1, Concern#7: More discussions on the surface current distributions should be added.Author response: Thank you very much, As per honorable reviewer directions, more discussion on surface currents is added as shown in highlighted version.________________________________________Reviewer#1, Concern#8: The feeding mechanism of the MIMO antenna should be explained in detail.Author response: The feeding mechanism is explained in detail. As the honorable reviewer suggested. Thank you________________________________________Reviewer#1, Concern#9: In comparison table 2 please add the terms “applied design method, radiation gain, and design complexity” as well to make it more comprehensive.Author response: Table 2 is updated as per respected reviewer comment, design method, gain, coupling techniques, and material used columns are added to the table. ________________________________________Reviewer#1, Concern#10: Please extend the conclusion by adding more numerical results and achievements.Author response: Thank you very much, Conclusion is extended by adding more numerical results as per honorable reviewer.________________________________________Reviewer#1, Concern#11: Reference part needs to be improved as per above mentioned suggestions Author response: Reference part is improved according to honorable reviewer suggestion. As highlighted in the references section in the revised version.________________________________________________________________________________ Response to Reviewer #2: We would like to thank the reviewer for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Our response follows . General Comments: An 8-port MIMO antenna for smartphone application is proposed.Reviewer #2 Concerns:1. Author needs to carry out a systematic literature review to establish the technical contribution and need for the proposed work. Please refer below paper for the same: Design and Analysis of Wideband Flexible Self-Isolating MIMO Antennas for Sub-6 GHz 5G and WLAN Smartphone Terminals2. Also, authors should refer to some latest sub-6 GHz MIMO antennas and do a thorough comparison to establish the novel contribution.3. Improve the quality of all the figures 4. Show the coordinate axis next to the antenna geometry.5. In Fig 6(a), gain should be in dBi and not dB.6. For such configuration, the number of input ports increases significantly.7. Present selected data in some of the graphs for brevity of data.8. Fig 15 is not at all clear.9. Authors should carry out SAR analysis.Additional Questions:1. Is the manuscript technically sound, and do the data support the conclusions? Yes2. Has the statistical analysis been performed appropriately and rigorously? N/A3. Have the authors made all data underlying the findings in their manuscript fully available? Yes4. Is the manuscript presented in an intelligible fashion and written in standard English? Yes Reviewer#2, Concern#1: Author needs to carry out a systematic literature review to establish the technical contribution and need for the proposed work.Author response: Thanks for valuable suggestion, as per respected reviewer, the introduction section is improved and a systematic literature review is made with proper references. The changes are highlighted in revised marked version. ________________________________________Reviewer#2, Concern#2: Also, authors should refer to some latest sub-6 GHz MIMO antennas and do a thorough comparison to establish the novel contribution. Author response: Thanks for valuable suggestion, as per respected reviewer some of latest work is referred and compared with the proposed design. The changes are highlighted in revised marked version.________________________________________Reviewer#2, Concern#3: Improve the quality of all the figures Author response: Thank you very much, as per the honorable reviewer comments, the quality of figures is improved.________________________________________Reviewer#2, Concern#4: Show the coordinate axis next to the antenna geometry.Author response: Thank you very much, as per the honorable reviewer, coordinate axis is added next to antenna geometry. See Figure 1 and 9.________________________________________Reviewer#2, Concern#5: In Fig 6(a), gain should be in dBi and not dB.Author response: Thank you very much, as per respected reviewer valuable suggestion, the gain is plotted in dBi instead of dB. See Figure 6(a).________________________________________Reviewer#2, Concern#6: For such configuration, the number of input ports increases significantly.Author response: Thank you very much for the quaries, yes the number of input ports is increased but for 5G the data rate is directly proportional to the number of antenna elements and number of ports. ________________________________________Reviewer#2, Concern#7: Present selected data in some of the graphs for brevity of data.Author response: Thank you very much, as per the honorable reviewer valuable suggestion, some of the symmetrical data has been removed for clarity and brevity of data.________________________________________Reviewer#2, Concern#8: Fig 15 is not at all clear.Author response: Thank you very much for your valuable comment, as per the honorable reviewer suggestion, we have replaced Fig no 15 with a clear one.________________________________________Reviewer#2, Concern#9: Authors should carry out SAR analysis.Author response: Thank you very much for suggestion, as per the honorable review suggestion a detailed SAR analysis is done and the results are presented in revised version. ________________________________________________________________________________ Response to Reviewer #3: We would like to thank the reviewer for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Our response follows . General Comments: The article "Dual Polarized 8-port Sub 6 GHz 5G MIMO Antenna for Smart Phone and Portable Wireless Applications" need major revision to process to next levelReviewer #3 Concerns:1. The design orientation and associated mathematical formulation is missing in the paper2. Figure captions not given with numbers for review3. For eight ports, the transmission coefficient results shown are of low quality and data in zig zag.4. Human phantom model is used in the work for analysis. I have not found any type SAR readings and related matter.5. The CCL and Diversity Gain and TARC parameters for MIMO was not discussed and presented6. 2D plots with several combinations without any analysis is presentedAdditional Questions:1. Is the manuscript technically sound, and do the data support the conclusions? Partly2. Has the statistical analysis been performed appropriately and rigorously? N/A3. Have the authors made all data underlying the findings in their manuscript fully available? Yes4. Is the manuscript presented in an intelligible fashion and written in standard English? No Reviewer#3, Concern#1: The design orientation and associated mathematical formulation is missing in the paper.Author response: Thank you very much for bringing our attention to this, as per the honorable reviewer, the mathematical equations are added to the paper.________________________________________Reviewer#3, Concern#2: Figure captions not given with numbers for reviewAuthor response: Sorry for missing this, this time figure captions are added with numbers, Thank you for your comment.________________________________________Reviewer#3, Concern#3: For eight ports, the transmission coefficient results shown are of low quality and data in zig zag.Author response: Thank you very much for the valuable suggestion, as per the honorable reviewer, the quality of plot is improved.________________________________________Reviewer#3, Concern#4: Human phantom model is used in the work for analysis. I have not found any type SAR readings and related matter.Author response: Thank you very much for suggesting SAR analysis, SAR analysis is done and the results are presented in revised version.________________________________________Reviewer#3, Concern#5: The CCL and Diversity Gain and TARC parameters for MIMO was not discussed and presentedAuthor response: Thank you very much for suggesting to add some important MIMO parameters like TARC, DG and channel capacity. The results are calculated and are presented in revised version.________________________________________ Reviewer#3, Concern#6: 2D plots with several combinations without any analysis is presentedAuthor response: Thank you very much for valuable suggestion analysis of 2D plots are added to revised version.________________________________________________________________________________Kind RegardsDr. Fazal Muhammad Corresponding Author 4 Jul 2023Dual Polarized 8-port Sub 6 GHz 5G MIMO Antenna for Smart Phone and Portable Wireless ApplicationsPONE-D-23-09968R1Dear Dr. Muhammad,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. 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Non-coding RNAs (ncRNAs) can control the flux of genetic information; affect RNA stability and play crucial roles in mediating epigenetic modifications. A number of studies have highlighted the potential roles of both virus-encoded and host-encoded ncRNAs in viral infections, transmission and therapeutics. However, the role of an emerging type of non-coding transcript, circular RNA (circRNA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been fully elucidated so far. Moreover, the potential pathogenic role of circRNA-miRNA-mRNA regulatory axis has not been fully explored as yet. The current study aimed to holistically map the regulatory networks driven by SARS-CoV-2 related circRNAs, miRNAs and mRNAs to uncover plausible interactions and interplay amongst them in order to explore possible therapeutic options in SARS-CoV-2 infection. Patient datasets were analyzed systematically in a unified approach to explore circRNA, miRNA, and mRNA expression profiles. CircRNA-miRNA-mRNA network was constructed based on cytokine storm related circRNAs forming a total of 165 circRNA-miRNA-mRNA pairs. This study implies the potential regulatory role of the obtained circRNA-miRNA-mRNA network and proposes that two differentially expressed circRNAs hsa_circ_0080942 and hsa_circ_0080135 might serve as a potential theranostic agents for SARS-CoV-2 infection. Collectively, the results shed light on the functional role of circRNAs as ceRNAs to sponge miRNA and regulate mRNA expression during SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an enveloped RNA virus with a genome size of 29,903 bp, is a highly infectious and pathogenic coronavirus . InitialRecent advances in high-throughput sequencing technologies and computational methods have discovered a substantial number of ncRNA ultimately providing new insights into their role in a range of human diseases , 7. VariOn the other hand, circRNAs, a novel class of ncRNAs have been reported to play crucial role in regulating viral infections and their dysregulation has been implicated in the pathogenesis of various diseases , 18. WhiThe circRNA–miRNA–mRNA regulatory axis has been shown to be of high importance in association with several human diseases including cancers, diabetes, Alzheimer’s disease, and cardiovascular diseases –25. ThesThere is an abundance of COVID-19 related transcriptomics studies and data, however, their use is limited by the confounding factors pertaining to each study. In the current study, we have analyzed different datasets in a unified approach which might help in understanding the molecular basis of COVID-19. Moreover, reverse engineering approach was utilized to derive regulatory interactions between circRNAs, miRNAs and mRNAs from gene expression data of SARS-CoV-2 patients. In order to gain better understanding of molecular and immuno-pathological basis, possible regulatory mechanisms of circRNA-miRNA-mRNA axis during SARS-CoV-2 infection were investigated. The circRNA–miRNA–mRNA regulatory network consisting of differentially expressed circRNAs and their downstream miRNAs and target mRNAs have been constructed for SARS CoV-2 related pathogenesis. The circRNAs that may play critical roles in regulating the cytokine storm during SARS-CoV-2 infection were identified. The results from this study revealed some candidate circRNAs that might function as potential theranostic agents in SARS-CoV-2 infection. Moreover, targeting the "cytokine storm" using circRNAs might be a feasible therapeutic approach to combat COVID-19 . Togethehttps://www.ncbi.nlm.nih.gov/geo/), a database supported by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) was used to access the microarray and RNA-sequencing datasets that contains circRNA, miRNA and mRNA expression profiles of SARS-CoV-2 infected patients at various stages (https://ngdc.cncb.ac.cn/). As the present study does not involve human subjects and due to free availability of data in the GEO database, neither ethical approval nor informed consent was required.The Gene Expression Omnibus (GEO)  ..https://The GSE166552 dataset included 06 samples (03 SARS-CoV-2 positive and 03 controls). The PRJCA002617 dataset included 24 samples (12 SARS-CoV-2 positive and 12 controls). McDonald et al., dataset included 45 samples . The GSE19137 dataset included 21 samples (03 negative and 18 positive for SARS-CoV). Chow et al., dataset included 249 samples (147 SARS-CoV-2 infected samples and 102 controls). Dhar et al., dataset included 2157 samples (including 915 severe COVID-19 patients). Liu et al., dataset contained 40 samples in his study (including 13 severe COVID-19 patients). Farr et al., dataset included 20 samples . Li et al., dataset included 14 samples . Huang et al., dataset comprised of 41 samples (including 13 severe COVID-19 patients). Chi et al., dataset included 70 SARS-CoV-2 infected patients, 04 convalescent cases and 04 healthy controls. Lin et al., dataset included 334 samples in their study (including 23 severe COVID-19 patient samples). Chen et al(b)., dataset included 21 samples (including 11 severe COVID-19 patient samples). Chen et al(c)., dataset study contained 29 samples (including 14 severe COVID-19 patient samples). Blenco Melo et al., included 48 samples (24 SARS-CoV-2 positive samples and 24 negative samples). Del Velle et al., dataset included a total of 1484 samples (1097 positive for SARS-CoV-2 infection and 387 controls). Qin et al., dataset comprised of 452 samples in their study (including 286 severe COVID-19 patient samples). Yang et al., dataset included 50 samples (including 36 severe COVID-19 patient samples).http://www.circbank.cn/) is a comprehensive, publicly available, functionally annotated human circRNAs database containing information of about 140,000 circRNAs from many different sources  Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.2. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, AttachmentManuscript Number PONE D 22 34657.docxSubmitted filename: Click here for additional data file. 23 Feb 2023Response to reviewersDear Editor,We wish to express our appreciation for your in-depth comments, suggestions and corrections, and we would like to convey our sincere thanks for allowing us to improve our manuscript entitled “Mapping CircRNA–miRNA–mRNA Regulatory Axis Identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection”. Thank you for your very careful review of our paper. A major revision of the paper has been carried out to take all of weaknesses and limitations identified by the respective reviewers into account. And in the process, we truly hope that the revised manuscript is clear enough to follow.Below is an abridged summary of reviewer’s comments with a detailed response and description of the changes made to the article. Should you find the paper requires further clarification or revision, we most certainly stand ready to do so.Looking forward to your positive responseSincerely,Dr. Faryal Mehwish AwanJournal Requirements:When submitting your revision, we need you to address these additional requirements.Comment # 1Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. ResponseWe have formatted our manuscript according to PLOS ONE’s style. The format has been updated in the revised version of the manuscript as per journal requirements. Comment # 2https://www.ncbi.nlm.nih.gov/gds/) with accession details , , , , , (Demirci and Demirci 2021), , , , , , , , , , , and  datasets).] Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. [All the datasets analyzed during the current study are accessible from the literature as well as from the GEO database  repository archives and freely distributes microarray, next-generation sequencing and other forms of high-throughput functional genomics data. Such datasets hold great value for knowledge discovery, particularly when integrated and can potentially bring novel insights into essential questions. The present study has aimed at prioritizing the potential circRNA candidates for a prospective theranostic evaluation via exploring the existing publically available datasets in COVID-19 setting. Public databases have a lot of high throughput data, which greatly helps in revealing the possible disease pathogenesis and identifying potential targets for drug design. Experimental validation of all the discovered associations, let alone all the possible interactions between them, is time-consuming and expensive. In conventional approaches, large experimental screenings are currently used to identify potential leading compounds, but they require significant time and resources. However, one of the lessons learned during the current pandemic is that innovative approaches are required to speed up drug development while increasing its success rate. Since gene expression data are high-dimensional data, an important research aim in the analysis of transcription profiles is the discovery of small subset of biomarkers containing the most discriminant information. Therefore, current study computationally prioritized the data available in the databases for potential SARS-CoV-2 inhibitors by using an integrated approach.  A number of recently published research studies have utilized publically available datasets for the prioritization of most promising candidates. Some of these studies are We have added this information in the cover letter to clarify this comment. Comment: 3https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/" https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/Please upload a new copy of Figure 7 as the detail is not clear. Please follow the link for more information: ResponseWe agree with your assessment. We have now followed figure graphics requirements for all the figures and have also uploaded a new copy of Figure 7 as “Fig7.tif”. Fig 7: Pathway analysis of COVID-19 pathogenesis (KEGG pathway ID: map05171). Highlighted genes are targets of miRNAs and indirect targets of two prioritized circRNAs Comment: 4Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.ResponseWe have rechecked the whole manuscript for any errors in the references. Corrections have been made and highlighted. Reviewer #1Comments and Suggestions for AuthorsThis is an interesting small study and the authors have collected a unique dataset using cutting edge methodology. The paper is well written and structured.ResponseWe appreciate the positive feedback from the reviewer and would like to thank the respected reviewer for the encouraging assessment and the comments that helped us to improve the manuscript. Comment: 1The following minor issues should be addressed:In introduction section first paragraph author may update number of total people have been infected and death globally with virus SARS-CoV-2 with updated references.ResponseWe agree with your assessment. As per your suggestion, we have updated total number as per World Health Organization report and revised the statement as follows. Currently, >750 million people have been infected globally while >6.8 million people have lost their lives due to COVID-19 .We have updated this information in the revised version of the manuscript.Reviewer #2Comments and Suggestions for AuthorsThe manuscript entitled Mapping CircRNA–miRNA–mRNA Regulatory Axis Identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection can be accepted for publication after few improvementsResponseWe appreciate the positive feedback from the reviewer and would like to thank the respected reviewer for the encouraging assessment and the comments that helped us to improve the manuscript. Comment: 1The author have selected the common circRNAs from circRNA datasets, mRNA datasets, and miRNA datasets. How the author found cicRNAs from mRNAs and miRNAs datasets? The authors are suggested to clearly describe the results in detail rather than superficial writing.Responsehttp://www.circbank.cn/) is a comprehensive, publicly available, functionally annotated human circRNAs database containing information of about 140,000 circRNAs from many different sources . The Users can access information regarding conservation status, miRNA targets as well as protein coding potential of query circRNAs . CircInteractome (https://circinteractome.nia.nih.gov/) is a readily accessible web tool for mapping miRNAs and protein-binding sites on junctions as well as junction-flanking sequences of human circRNAs . RNA Interactome Database, RNAInter v4.0 (http://www.rnainter.org/) is a comprehensive RNA-associated interactome platform containing information of more than 41 million interactions of cellular RNAs in 154 species with evidence from both computational and experimental sources . Selection criteria, threshold and prediction scores for each database were selected on the basis of their previously reported relationship with low false discovery rate and high accuracy in experimental validation studies via PCR and Luciferase assays. The target circRNAs of differentially expressed miRNAs were predicted using different comprehensive databases including CircBank, CircInteractome and RNAInter v4.0 web tools (Table 2). CircBank (http://mirdb.org/), is an integrative, freely accessible, open platform for the prediction of miRNA targets. miRNA-target interactions with scores ≥80.0 were considered relevant, statistically significant and with higher confidence in the interactions whereas miRNA-target interactions with scores ≤80.0 were considered not relevant. By utilizing high-throughput experimental data, miRDB predicts miRNA targets in five species along with integrative analysis of gene ontology (GO) data . miRWalk 2.0  provides information of more than 949 million computationally predicted as well as experimentally validated miRNA-mRNA interactions. In order to ensure reliability and accuracy of forecast results, miRWalk 2.0 incorporates 12 algorithms for prediction including miRWalk, mirbridge, Targetscan, Microt4, PITA, Pictar2, RNAhybrid, RNA22, miRNAMap, miRanda, miRMap and miRDB . Cut-off value with a binding score of > 0.95 was considered as a screening threshold. miRTarBase (https://miRTarBase.cuhk.edu.cn/~miRTarBase/miRTarBase_2022/php/index.php) is a manually curated database containing information of more than 360,000 experimentally validated miRNA-mRNA interactions . miRNA-mRNA interactions have been validated experimentally using microarray, CLIP-seq technology, reporter assays, high through-put sequencing and western blot experiments . All the targets identified via miRTarBase were selected for further analysis. TargetScan v7.0 (http://www.targetscan.org/vert_80/), a flexible web based tool, predicts sequence based effective regulatory targets of miRNAs by incorporating 14 different features . Conservation aggregate score of > 0.80 was considered as selection criteria as this score provides low false discovery rates. An overlap in at least two databases was used as filtering criteria for prioritizing and considering potential candidate targets. Previous comparative studies conducted on miRNA target prediction programs suggested that no program performed consistently superior to all others. Indeed, it has become a common practice for researchers to look at predictions produced by different miRNA-target prediction programs and focus on their intersection which might enhances the performance of analyses as well as improve prediction precision. The differences between algorithms are mostly seen in their respective weaknesses, i.e., the subset of false positives. For that reason, the fundamental motivation to focus selectively on the shared prediction by two algorithms is to eliminate false positives while preserving the vast majority of true positive RNAs. Therefore, conclusively, predictions are much more reliable when two or more prediction algorithms are combined, and the minimal loss of true positives are greatly outweighed by the removal of false positives. Comprehensive analysis of differentially expressed miRNA datasets revealed 38937 target circRNAs. On the other hand, comprehensive analysis of 5109 predicted miRNAs against differentially expressed mRNAs revealed 858423 circRNAs having binding sites for respective miRNAs.For the prediction of potential circRNAs associated with differentially expressed mRNAs, first we predicted miRNAs associated with these mRNA and then circRNAs associated with predicted miRNAs. We used databases including miRDB, miRWalk 2.0, miRTarBase, and TargetScan 7.0 for the prediction of miRNAs associated with respective mRNAs. miRDB . Highlighted genes are targets of miRNAs and indirect targets of two prioritized circRNAs Comment: 3The quality of image needs to be improved as picture is blur and not clearResponseWe agree with your assessment. We have now uploaded a new copy of Figure 7 as “Fig7.tif”. In addition we have also updated “Table 4” in tabular text form previously uploaded as a figure due to complexity of data. Fig 7: Pathway analysis of COVID-19 pathogenesis (KEGG pathway ID: map05171). Highlighted genes are targets of miRNAs and indirect targets of two prioritized circRNAs  Table 4: Datasets used for the analysis of SARS-CoV-2 related cytokines Genes Study 1 Study 2 Study 3 Study 4 Study 5 Study 6 Study 7 Study 8 Study 9 Study 10 Study 11 Study 12 up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulated up-regulated down-regulatedIL-1β _ _ _ _ _ _ _ _ √ _ _ _ √ _ _ _ _ _ _ _ √ _ _ _IL-2 √ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ √ _IL-4 _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ √ _IL-6 _ _ √ _ √ _ _ _ √ _ √ _ √ _ √ _ √ _ √ _ √ _ √ _IL-7 √ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _IL-8 _ _ _ _ _ _ _ _ √ _ √ _ _ _ √ _ _ _ √ _ _ _ _ _IL-10 √ _ _ _ √ _ _ _ √ _ _ _ √ _ _ _ _ _ √ _ _ _ √ _IL-12 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _IL-13 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _IL-17 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _IL-18 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ √ _ _ _IL-23 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _IL-33 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ IL-37 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _IL-38 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _TNF-α √ _ _ _ √ _ _ _ √ _ √ _ √ _ √ _ _ _ _ _ _ _ √ _IFN-γ _ _ _ _ √ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ √ _CCL2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _CXCL6 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _CXCL8 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _CXCL10 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ _ _ IP-10 √ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ _ _ √ _ √ _ _ _MIP-1A √ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ _ _ √ _ √ _ _ _MIP1-B _ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _PDGF _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _MCP1 √ _ _ _ _ _ √ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _ _ _ GM-CSF _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _M-CSF _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ √ _ _ _G-CSF √ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ √ _ _ _FGF _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _HGF _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ √ _ _ _TGF-β _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ We hope that our additions to the manuscript will satisfy the reviewers, and thank both reviewers for their precise and insightful comments, and for the careful attention that they have paid which allowed us to improve the manuscript. We look forward to hearing from you regarding our submission. We would be glad to respond to any further questions and comments that you may have.Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?Reviewer #1: YesReviewer #2: Yes2. Has the statistical analysis been performed appropriately and rigorously?Reviewer #1: YesReviewer #2: Yes3. Have the authors made all data underlying the findings in their manuscript fully available?Reviewer #1: YesReviewer #2: Yes4. Is the manuscript presented in an intelligible fashion and written in standard English?Reviewer #1: YesReviewer #2: YesReferencesAgarwal, V., et al. (2015) Predicting effective microRNA target sites in mammalian mRNAs, elife, 4, e05005.Blanco-Melo, D., et al. (2020) Imbalanced host response to SARS-CoV-2 drives development of COVID-19, Cell, 181, 1036-1045. e1039.Chen, G., et al. (2020) Clinical and immunological features of severe and moderate coronavirus disease 2019, The Journal of clinical investigation, 130, 2620-2629.Chen, L., et al. (2020) Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia, Zhonghua jie he he hu xi za zhi= Zhonghua jiehe he huxi zazhi= Chinese journal of tuberculosis and respiratory diseases, 43, E005-E005.Chi, Y., et al. (2020) Serum cytokine and chemokine profile in relation to the severity of coronavirus disease 2019 in China, The Journal of infectious diseases, 222, 746-754.Dat, V.H.X., et al. (2022) Identification of potential microRNA groups for the diagnosis of hepatocellular carcinoma (HCC) using microarray datasets and bioinformatics tools, Heliyon, 8, e08987.Del Valle, D.M., et al. (2020) An inflammatory cytokine signature predicts COVID-19 severity and survival, Nature medicine, 26, 1636-1643.Dhar, S.K., et al. (2021) IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression, Heliyon, 7, e06155.Dudekula, D.B., et al. (2016) CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs, RNA biology, 13, 34-42.Dweep, H. and Gretz, N. (2015) miRWalk2. 0: a comprehensive atlas of microRNA-target interactions, Nature methods, 12, 697-697.Farr, R., et al. (2021) Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection.Huang, C., et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The lancet, 395, 497-506.Huang, H.-Y., et al. (2020) miRTarBase 2020: updates to the experimentally validated microRNA–target interaction database, Nucleic acids research, 48, D148-D154.Kang, J., et al. (2021) RNAInter v4. 0: RNA interactome repository with redefined confidence scoring system and improved accessibility, Nucleic acids research.Lin, L., et al. (2020) Long-term infection of SARS-CoV-2 changed the body's immune status, Clinical Immunology, 218, 108524.Liu, J., et al. (2020) Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine, 55, 102763.Liu, M., et al. (2019) Circbank: a comprehensive database for circRNA with standard nomenclature, RNA biology, 16, 899-905.Pandya, P.H., et al. (2020) Systems biology approach identifies prognostic signatures of poor overall survival and guides the prioritization of novel bet-chk1 combination therapy for osteosarcoma, Cancers, 12, 2426.Qin, C., et al. (2020) Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China, Clinical infectious diseases, 71, 762-768.Shams, R., et al. (2020) Identification of potential microRNA panels for pancreatic cancer diagnosis using microarray datasets and bioinformatics methods, Scientific Reports, 10, 7559.Venugopal, P., et al. (2022) Prioritization of microRNA biomarkers for a prospective evaluation in a cohort of myocardial infarction patients based on their mechanistic role using public datasets, Frontiers in Cardiovascular Medicine, 9.Wang, X. (2008) miRDB: a microRNA target prediction and functional annotation database with a wiki interface, Rna, 14, 1012-1017.Wu, A.T., et al. (2021) Multiomics identification of potential targets for Alzheimer disease and antrocin as a therapeutic candidate, Pharmaceutics, 13, 1555.Yang, Y., et al. (2020) Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19, Journal of Allergy and Clinical Immunology, 146, 119-127. e114.Zhang, P., et al. (2021) Bioinformatics analysis of candidate genes and pathways related to hepatocellular carcinoma in China: a study based on public databases, Pathology and Oncology Research, 13.AttachmentResponse to reviewers.docxSubmitted filename: Click here for additional data file. 13 Mar 2023Mapping CircRNA–miRNA–mRNA Regulatory Axis Identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infectionPONE-D-22-34657R1Dear Dr. Awan,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. 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Kα radiation to single-crystal X-ray crystallography and evaluates two different detectors, the Bruker Photon III and the Dectris Eiger2 CdTe, for usage in spherical and aspherical structural models.This paper communicates the first application of MetalJet In  Kα radiation wavelengths for use in X-ray diffraction experiments. The purpose of this paper is to demonstrate the application of indium Kα radiation in independent-atom model refinement, as well as approaches using aspherical atomic form factors. The results vary greatly depending on the detector employed, as the energy cut-off of the Eiger2 CdTe provides a solution to a unique energy contamination problem of the MetalJet In radiation, which the Photon III detector cannot provide.The MetalJet source makes available new  Finally, a C11H10O2S YLID crystal, 5, was used to compare the two detectors and the setup with a second machine using aspherical refinements. The YLID crystal is an established benchmark for IAM refinements but can also be used for benchmarks at low temperatures  and Incoatec Helios optics. With the Bruker Photon III detector, gallium contamination was filtered using a palladium foil of 40 µm thickness. For the Eiger2 CdTe 1M detector, a custom solution within the D8 Venture was implemented. Steering using Diffraction data with silver radiation were collected using a Bruker D8 Venture four-circle diffractometer with an Incoatec IμS 3.0 Ag source and a Bruker Photon III detector as is.2.3.SAINT  was performed using structure factors from periodic projector augmented wave (PAW) density functional theory (DFT) calculations. They employ the SCAN functional  is less than half the energy of indium Kα  % for the Eiger2 and 0.44 (4)% for the Photon III detector. The relative percentages are more indicative than the absolute ones, as effects such as scattering cross sections and absorption have been neglected but should be the same for both detectors. Therefore, we could show a very small residual contamination with a slight advantage of the Eiger2 detector. A higher thickness of the palladium attenuator would have solved the problem, but would have led to a lower overall indium intensity.The second, more quantitative, approach used a pseudo-twin refinement of the two sets of reflections to get an impression of the relative strength of the contamination. Cell parameters and orientation and instrument parameters were determined in a first integration with 3.2.Rr.i.m  shows the superior performance of the Eiger2 detector for each of the structures studied in this work for both the overall and multiplicity-equivalent data sets.The redundancy-independent merge factor  and egross follow the I/σ indicator of the data collection. Accordingly, we see the superior performance of the agreement with the data collected by the Eiger2 CdTe on the In MetalJet, separated by a significant margin from the IμS Ag measurement using the Photon III. The In MetalJet measurement on the Photon III shows the highest values and number of undescribed electrons egross for both evaluated methodologies. For the unweighted agreement factor, both Photon III measurements yield the same value for the HAR. However, for the multipole refinement the Photon III In measurement exhibits a higher value than the Photon III measurement using Ag Kα radiation.The crystallographic quality indicators are very similar for both methods Figs. 3 and 4 ▸:wR2 and the goodness of fit (GOF). For the Ag/Photon III and In/Eiger2 data, the performance of these two indicators is basically identical for the HAR, while the multipole refinement shows a slight advantage for the Ag/Photon III. The In/Photon III data show inferior performance for these indicators as well.The conclusion is less clear on the weighted crystallographic agreement factor The Photon III measurements show a higher value in the negative difference electron density for both minima, and also an overall shift in the Henn–Meindl plots. The IμS Ag data also show a slightly lower maximum in the difference electron density, whereas the In/Photon III data set again exhibits the most pronounced maxima and minima in the difference electron density.The In/Photon III measurement shows a significant jump in the quotient of the sum of observed to the sum of fitted intensities (supporting information) closely follow the Henn–Meindl plots. All refinements show a low level of difference electron density. The indium MetalJet data obtained with the Photon III detector show a noisy overall difference electron density at an isolevel ±0.05 e Å−3, with the highest features being located near the heaviest atom, namely the ylid sulfur. At the same time the IμS 3.0 Ag data with the Photon III show a disposition towards a negative difference electron density, which can be explained by the intensity of the inner data matching less accurately, as observed in the DRKPlot-type plot. In comparison, the difference electron density obtained by the indium MetalJet with the Eiger2 CdTe is much flatter. The visible features at the same low isolevel (±0.05 e Å−3) are limited to the vicinity of the sulfur atom and the oxygen atoms, while also being less strongly expressed at these positions. The resulting difference electron densities of the multipolar refinements are comparable for the three investigations . In the IμS 3.0 Ag/Photon III data, the increased number of parameters does counteract the overall negative density near the sulfur atom and part, but not all, of the discrepancy is assigned to the density, as investigated in the next section.The difference electron densities of the Hirshfeld atom refinement Fig. 5 and the 3.4.2.et al.  ScCoC_eiger, ScCoC_photon, ScPtSi_eiger, ScPtSi_photon, NaWO4_eiger, NaWO4_photon, LAla_eiger, LAla_photon, Ylid_HAR_Ag_Photon, Ylid_HAR_In_Eiger, Ylid_HAR_In_Photon, Ylid_MM_Ag_Photon, Ylid_MM_In_Eiger, Ylid_MM_In_Photon. DOI: 10.1107/S1600576723007215/nb5354ScCoC_eigersup2.hklStructure factors: contains datablock(s) ScCoC_eiger. DOI: 10.1107/S1600576723007215/nb5354ScCoC_photonsup3.hklStructure factors: contains datablock(s) ScCoC_photon. DOI: 10.1107/S1600576723007215/nb5354ScPtSi_eigersup4.hklStructure factors: contains datablock(s) ScPtSi_eiger. DOI: 10.1107/S1600576723007215/nb5354ScPtSi_photonsup5.hklStructure factors: contains datablock(s) ScPtSi_photon. DOI: 10.1107/S1600576723007215/nb5354NaWO4_eigersup6.hklStructure factors: contains datablock(s) NaWO4_eiger. DOI: 10.1107/S1600576723007215/nb5354NaWO4_photonsup7.hklStructure factors: contains datablock(s) NaWO4_photon. DOI: 10.1107/S1600576723007215/nb5354LAla_eigersup8.hklStructure factors: contains datablock(s) LAla_eiger. DOI: 10.1107/S1600576723007215/nb5354LAla_photonsup9.hklStructure factors: contains datablock(s) LAla_photon. DOI: 10.1107/S1600576723007215/nb5354Ylid_HAR_Ag_Photonsup10.hklStructure factors: contains datablock(s) Ylid_HAR_Ag_Photon. DOI: 10.1107/S1600576723007215/nb5354Ylid_HAR_In_Eigersup11.hklStructure factors: contains datablock(s) Ylid_HAR_In_Eiger. DOI: 10.1107/S1600576723007215/nb5354Ylid_HAR_In_Photonsup12.hklStructure factors: contains datablock(s) Ylid_HAR_In_Photon. DOI: 10.1107/S1600576723007215/nb5354Ylid_MM_Ag_Photonsup13.hklStructure factors: contains datablock(s) Ylid_MM_Ag_Photon. DOI: 10.1107/S1600576723007215/nb5354Ylid_MM_In_Eigersup14.hklStructure factors: contains datablock(s) Ylid_MM_In_Eiger. DOI: 10.1107/S1600576723007215/nb5354Ylid_MM_In_Photonsup15.hklStructure factors: contains datablock(s) Ylid_MM_In_Photon. DOI: 10.1107/S1600576723007215/nb5354sup16.pdfAdditional refinement details. DOI:


HemaSphere. 2023;7(9):e942), a correction is needed for Table 3 and Table 4. Bullet points and subheaders were misaligned, therefore reducing clarity for readers. This has now been adjusted. The journal office apologizes for any inconvenience.Since the publication of the article entitled “Measurable Residual Disease Testing in Multiple Myeloma Routine Clinical Practice: A Modified Delphi Study” (https://journals.lww.com/hemasphere/fulltext/2023/09000/measurable_residual_disease_testing_in_multiple.12.aspxThe changes have been made online:


Peroral endoscopic myotomy (POEM) is an increasingly adopted strategy for the treatment of Zenker’s diverticulum . The Z-Video 1 Peroral endoscopic myotomy for Zenker’s diverticulum without tunneling.After the initial mucosal incision, both submucosal sides of the septum are lifted, with a mixture of hydroxyethyl starch and indigo carmine. Then we proceed to direct myotomy of the septum . The diEndoscopy_UCTN_Code_TTT_1AO_2AG


Correction to: Journal of Nuclear Cardiologyhttps://doi.org/10.1007/s12350-022-03164-5The original published Supplementary File I was incorrect and is replaced with the following Supplementary File: “12350_2022_3164_MOESM2_ESM”.The original article has been corrected.


The recruitment process for the position of ECDC Director is handled by the European Commission. The deadline for the submission of applications is 26 June 2023, 12:00 noon CEST.For detailed information on the job description, requirements and the application procedure, please visit:https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ%3AJOC_2023_185_A_0001


Bone mineral content (Z_BMC), fat mass (Z_FM), lean mass (Z_LM), and bone mineral density for the total body (Z_TB) and lumbar spine (Z_L1–4) were measured using dual-energy X-ray absorptiometry. Twenty-nine percent of children  were vitamin D deficient (25-hydroxyvitaminD level of <20 ng/mL). In winter, low vitamin D intake (P = 0.019) and fewer daylight hours (P = 0.015) were associated with low 25-hydroxyvitaminD level. The 25-hydroxyvitamin D level correlated positively with Z_BMC (P = 0.023), Z_TB (P = 0.018), and Z_L1–4 (P = 0.043) independently of sex, puberty, Z_FM, Z_LM, physical activity level, and calcium intake. Z_FM correlated independently with Z_BMC (P< 0.001), Z_TB (P = 0.037), and Z_L1–4 (P < 0.001). In conclusion, almost half of peripubertalnonobese children were vitamin D deficient in winter. Considering the beneficial effects of adequate vitamin D status and adiposity on bone health, the current DRI of vitamin D should be upgraded to prevent vitamin D deficiency.The dietary reference intake (DRI) of vitamin D for Korean children wasreduced from 400IU/day in 2005 to 200IU/day in 2010. We evaluated the risk factors for low vitamin D status and itsrelationships with bone health in peripubertalnonobese children living in Seoul or Gyeonggi-do. One hundred children  participated in the winter (


There was an error in the list of accession numbers in Supplementary File S1 in the Supporting Information. Please view the correct version of S1 here: https://dl.dropboxusercontent.com/u/63557304/File_S1_Updated.pdf


The correct sequences of the primers described in this work are HW_MSchX_F-TGGGTGAAGTAAGTCCAACAG and HW_MSchX_R-TGAAGAACGTATCCAGCCTACA. The amplified fragment corresponds to nucleotides 21227–22122 of the human chromosome Xq22.3 (GenBank ID AL390039.10).