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Laboratory-based nucleic acid amplification tests (NAATs) are highly sensitive and specific, but they require the transportation of samples to centralized testing facilities and have long turnaround times. During the Coronavirus Disease 2019 (COVID-19) pandemic, substantial advancement has been achieved with the development of paper-based point-of-care (POC) NAATs, offering features such as low cost, being easy to use, and providing rapid sample-to-answer times. Although most of the POC NAATs innovations are towards clinical settings, we have developed a portable, paper-based loop-mediated isothermal amplification (LAMP) testing platform for on-farm applications, capable of detecting Bacteroidales as a fecal contamination biomarker. Our integrated platform includes a drop generator, a heating and imaging unit, and paper-based biosensors, providing sensitive results (limit of detection 3 copies of Bacteroidales per cm 2 ) within an hour of sample collection. We evaluated this integrated platform on a commercial lettuce farm with a concordance of 100% when compared to lab-based tests. Our integrated paper-based LAMP testing platform holds great promise as a reliable and convenient tool for on-site NAATs. We expect that this innovation will encourage the fresh produce industry to adopt NAATs as a complementary tool for decision-making in growing and harvesting. We also hope that our work can stimulate further research in the development of on-farm diagnostic tools for other agricultural applications, leading to improved food safety and technology innovation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohit S. Verma reports financial support was provided by Center For Produce Safety. Mohit S. Verma reports financial support was provided by California Department of Food and Agriculture. Mohit S. Verma reports financial support was provided by Agricultural Marketing Service. Mohit S. Verma reports a relationship with Krishi, Inc. that includes: board membership, equity or stocks, and funding grants. Mohit S. Verma has patent pending to Purdue Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Exhaled breath electrochemical sensing is a promising biomedical technology owing to its portability, painlessness, cost-effectiveness, and user-friendliness. Here, we present a novel approach for target analysis in exhaled breath by integrating a comfortable paper-based collector into an N95 face mask, providing a universal solution for analyzing several biomarkers. As a model analyte, we detected SARS-CoV-2 spike protein from the exhaled breath by sampling the target analyte into the collector, followed by its detection out of the N95 face mask using a magnetic bead-based electrochemical immunosensor. This approach was designed to avoid any contact between humans and the chemicals. To simulate human exhaled breath, untreated saliva samples were nebulized on the paper collector, revealing a detection limit of 1 ng/mL and a wide linear range of 3.7-10,000 ng/mL. Additionally, the developed immunosensor exhibited high selectivity toward the SARS-CoV-2 spike protein, compared to other airborne microorganisms, and the SARS-CoV-2 nucleocapsid protein. Accuracy assessments were conducted by analyzing the simulated breath samples spiked with varying concentrations of SARS-CoV-2 spike protein, resulting in satisfactory recovery values (ranging from 97 ± 4 to 118 ± 1%). Finally, the paper-based hybrid immunosensor was successfully applied for the detection of SARS-CoV-2 in real human exhaled breath samples. The position of the collector in the N95 mask was evaluated as well as the ability of this paper-based analytical tool to identify the positive patient.

We report the development and initial validation of a paper-based nucleic acid testing platform that integrates Loop-mediated isothermal amplification (LAMP) with clustered regularly interspaced short palindromic repeats (CRISPR) technology, referred to as PLACID (Paper-based LAMP-CRISPR Integrated Diagnostics). LAMP eliminates the need for thermal cycling, resulting in simplified instrumentation, and the CRISPR-associated protein (Cas 12a) system eliminates false positive signals from LAMP products, resulting in highly selective and sensitive assays. We optimized the assay to perform both amplification and detection entirely on paper, eliminating the need for complex fluid handling steps and lateral flow assay transfers. Additionally, we engineered a smartphone-operated system that includes a low-powered, non-contact IR heating chamber to actuate paper-based LAMP and CRISPR reactions and enable the detection of fluorescent signals from the paper. The platform demonstrates high specificity and sensitivity in detecting nucleic acid targets with a limit of detection of 50 copies/μL. We integrate an equipment-free sample preparation separation technology designed to streamline the preparation of crude samples prior to nucleic acid testing. The practical utility of our platform is demonstrated by the successful detection of spiked SARS-CoV-2 RNA fragments in saliva, E. Coli in soil, and pathogenic E. Coli in clinically fecal samples of infected patients. Furthermore, we demonstrate that the paper-based LAMP CRISPR chips employed in our assays possess a shelf life of several weeks, establishing them as viable candidates for on-site diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Paper-based rapid diagnostic tests (RDTs) are an essential component of modern healthcare, particularly for the management of infectious diseases. Despite their utility, these capillary-driven RDTs are compromised by high failure rates, primarily caused by user error. This limits their utility in complex assays that require multiple user operations. Here, we demonstrate how this issue can be directly addressed through continuous electrochemical monitoring of reagent flow inside an RDT using embedded graphenized electrodes. Our method relies on applying short voltage pulses and measuring variations in capacitive discharge currents to precisely determine the flow times of injected samples and reagents. This information is reported to the user, guiding them through the testing process, highlighting failure cases and ultimately decreasing errors. Significantly, the same electrodes can be used to quantify electrochemical signals from immunoassays, providing an integrated solution for both monitoring assays and reporting results. We demonstrate the applicability of this approach in a serology test for the detection of anti-SARS-CoV-2 IgG in clinical serum samples. This method paves the way towards "smart" RDTs able to continuously monitor the testing process and improve the robustness of point-of-care diagnostics.

Neutralizing antibodies (nAbs) produced from infection or vaccination play an important role in acquired immunity. Determining virus-specific nAb titers is a useful tool for measuring aquired immunity in an individual. The standard methods to do so rely on titrating serum samples against live virus and monitoring viral infection in cultured cells which requires high biosafety level containment. The surrogate virus neutralization test (sVNT) reduces the biohazards and it is suitable for designing rapid test device in a lateral flow assay (LFA) format. Here, we introduce the fabrication and development of a unique paper-based LFA device for determining the level of SARS-CoV-2 nAb in a sample with a semiquantitative direct colorimetric readout. A LFA-based gradient assay design was used to facilitate the sVNT, where the spike glycoprotein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) stand in as proxies for viruses and cells, respectively. The gradient assay employed multiple test dots of ACE2 spotted in increasing concentration along the sample flow path and gold nanoparticle-conjugated RBD for readout. In this way, the number of developed spots is inversely proportional to the concentration of nAbs present in the sample. The assay was tested with both standard solutions of nAb as well as human serum samples. We have demonstrated that the device can effectively provide semiquantitative test results of nAbs by direct instrument-free colorimetric detection.

The rapid spread of SARS-CoV-2 caused the COVID-19 pandemic and accelerated vaccine development to prevent the spread of the virus and control the disease. Given the sustained high infectivity and evolution of SARS-CoV-2, there is an ongoing interest in developing COVID-19 serology tests to monitor population-level immunity. To address this critical need, we designed a paper-based multiplexed vertical flow assay (xVFA) using five structural proteins of SARS-CoV-2, detecting IgG and IgM antibodies to monitor changes in COVID-19 immunity levels. Our platform not only tracked longitudinal immunity levels but also categorized COVID-19 immunity into three groups: protected, unprotected, and infected, based on the levels of IgG and IgM antibodies. We operated two xVFAs in parallel to detect IgG and IgM antibodies using a total of 40 μL of human serum sample in <20 min per test. After the assay, images of the paper-based sensor panel were captured using a mobile phone-based custom-designed optical reader and then processed by a neural network-based serodiagnostic algorithm. The serodiagnostic algorithm was trained with 120 measurements/tests and 30 serum samples from 7 randomly selected individuals and was blindly tested with 31 serum samples from 8 different individuals, collected before vaccination as well as after vaccination or infection, achieving an accuracy of 89.5%. The competitive performance of the xVFA, along with its portability, cost-effectiveness, and rapid operation, makes it a promising computational point-of-care (POC) serology test for monitoring COVID-19 immunity, aiding in timely decisions on the administration of booster vaccines and general public health policies to protect vulnerable populations.

Respect for the scientific process and a diversity of views; open discourse and debate based on principles of ethics, best available evidence, and scientific inquiry and integrity; and an understanding of evidence gaps and uncertainty and how to communicate about them are important values in the advancement of science and the practice of medicine. Physicians often must make decisions about their recommendations to patients in the face of scarce or conflicting data. Are these characteristics of medicine and science widely understood and effectively communicated among members of the profession and to patients and the public? Issues of scientific integrity are longstanding, but COVID-19 brought them to the forefront, in an environment that was sometimes characterized by communication missteps as guidance came and went-or changed-quickly. Today, is open debate flourishing? Have some debates shed more heat than light? Are people losing confidence in science and medicine? In health care institutions? The American College of Physicians explores these issues and offers guidance in this position paper., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0648.

Background Since the outbreak of COVID-19, how to reduce the risk of spreading viruses and other microorganisms while performing aerosol generating procedures (AGPs) has become a challenging question within the dental and dental hygiene communities. The purpose of this position paper is to summarize the existing evidence about the effectiveness of various mitigation methods used to reduce the risk of infection transmission during AGPs in dentistry. Methods The authors searched six databases, MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, and Google Scholar, for relevant scientific evidence published in the last ten years (January 2012 to December 2022) to answer six research questions about the the aspects of risk of transmission, methods, devices, and personal protective equipment (PPE) used to reduce contact with microbial pathogens and limit the spread of aerosols. Results A total of 78 studies fulfilled the eligibility criteria. There was limited literature to indicate the risk of infection transmission of SARS-CoV-2 between dental hygienists and their patients. A number of mouthrinses are effective in reducing bacterial contaminations in aerosols; however, their effectiveness against SARS-CoV-2 was limited. The combined use of eyewear, masks, and face shields are effective for the prevention of contamination of the facial and nasal region, while performing AGPs. High volume evacuation with or without an intraoral suction, low volume evacuation, saliva ejector, and rubber dam (when appropriate) have shown effectiveness in reducing aerosol transmission beyond the generation site. Finally, the appropriate combination of ventilation and filtration in dental operatories are effective in limiting the spread of aerosols. Conclusion Aerosols produced during clinical procedures can potentially pose a risk of infection transmission between dental hygienists and their patients. The implementation of practices supported by available evidence are best practices to ensure patient and provider safety in oral health settings. More studies in dental clinical environment would shape future practices and protocols, ultimately to ensure safe clinical care delivery., (Copyright © 2024 The American Dental Hygienists’ Association.)

Background: Since the outbreak of COVID-19, how to reduce the risk of spreading viruses and other microorganisms while performing aerosolgenerating procedures (AGPs) has become a challenging question within the dental and dental hygiene communities. The purpose of this position paper is to summarize the evidence of the effectiveness of various mitigation methods used to reduce the risk of infection transmission during AGPs in dentistry., Methods: The authors searched 6 databases-MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, and Google Scholar-for relevant scientific evidence published between January 2012 and December 2022 to answer 6 research questions about the risk of transmission, methods, devices, and personal protective equipment (PPE) used to reduce contact with microbial pathogens and limit the spread of aerosols., Results: A total of 78 studies fulfilled the eligibility criteria. The literature on the risk of infection transmission including SARS-CoV-2 between dental hygienists and their patients is limited. Although several mouthrinses are effective in reducing bacterial contaminations in aerosols, their effectiveness against SARS-CoV-2 is also limited. The combined use of eyewear, masks, and face shields is effective in preventing contamination of the facial and nasal region while performing AGPs. High-volume evacuation with or without an intraoral suction, low-volume evacuation, saliva ejector, and rubber dam (when appropriate) have shown effectiveness in reducing aerosol transmission beyond the generation site. Finally, the appropriate combination of ventilation and filtration in dental operatories is effective in limiting the spread of aerosols., Discussion and Conclusion: Aerosols produced during clinical procedures can pose a risk of infection transmission between dental hygienists and their patients. The implementation of practices supported by available evidence will ensure greater patient and provider safety in oral health settings. More studies in oral health clinical environments would shape future practices and protocols, ultimately to ensure the delivery of safe clinical care., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 American Dental Hygienists' Association and the Canadian Dental Hygienists Association.)

Polymerase chain reaction (PCR)-based diagnostic kits for point-of-care (POC) testing are highly desirable to prevent the spread of infectious diseases. Here, we demonstrate a rapid PCR testing kit that involves integrating a lateral flow paper strip with a nichrome-based thin film heater. The use of a paper membrane as a PCR-solution container results in fast thermocycling without a cooler because the membrane can contain the solution with a high specific surface area where Joule heating is applied. After PCR, amplified products are simultaneously detected at the lateral flow paper strip with the naked eye. Severe acute respiratory syndrome β-coronavirus RNA can be detected within 30 min after PCR solution injection. This work reveals that the paper membrane can act as not only a capillary flow channel but also as a promising platform for fast PCR and detection.

SARS-CoV-2 has mutated many times since the onset of the COVID-19 pandemic, and the omicron is currently the most dominant variant. Determining the specific strain of the virus is beneficial in providing proper care and containment of the disease. We have previously reported a novel method of counting the number of particle immunoagglutination on a paper microfluidic chip using a smartphone-based fluorescence microscope. A single-copy-level detection was demonstrated from clinical saline gargle samples. In this work, we further evaluated two different SARS-CoV-2 monoclonal antibodies to spike vs. nucleocapsid antigens for detecting omicron vs. delta and spike vs. nucleocapsid proteins. The SARS-CoV-2 monoclonal antibody to nucleocapsid proteins could distinguish omicron from delta variants and nucleocapsid from spike proteins. However, such distinction could not be found with the monoclonal antibody to spike proteins, despite the numerous mutations found in spike proteins among variants. This result may suggest a clue to the role of nucleocapsid proteins in recognizing different variants., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

We tested the use of nasal swabs spotted onto filter paper (Whatman 3M) for the molecular diagnosis of SARS-CoV-2 infection. Spots of a positive nasal swab in conservation medium (B.1.177 strain, 21Ct) were still positive (duo E-gene/IP4) after 10, 20, and 30 days of conservation at room temperature, with Ct values of 28, 27, and 26, respectively. Direct spotting of the swab at bedside (omicron strain) still gave a positive result after 10 days in two RT-qPCR systems: 33.7 Ct using duo E-gene/IP4, and 34.8 using a specific Omicron system. Spotting of a dilution range of media spiked with the Delta (strain 2021/FR/0610, lineage B 1.617.2) and Omicron strains (strain UVE/SARS-CoV-2/2021/FR/1514) showed a threshold of 0.04 TCID 50 after 10 days of conservation. We show, for the first time, that this simple and low-cost conservation method can be used to store samples for RT-qPCR against SARS-CoV-2 for up to at least 1 month., (© 2022 Wiley Periodicals LLC.)

Background: Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection., Methods: A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection., Results: A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%-78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%)., Conclusion: Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects., Trial Registration: NCT06170320 (retrospectively registered on December 21, 2023)., (© 2024. The Author(s).)

Enzyme-linked immunosorbent assay (ELISA) is widely employed for detecting target molecules in bioassays including the serological assays that measure specific antibody titers. However, ELISA tests are inherently limited to centralized laboratories staffed with trained personnel as the assay workflow requires multiple steps to be performed in a specific sequence. Here, we report a dipstick ELISA test that automates this otherwise laborious process and reports the titer of a target molecule in a digital manner without the need for an external instrument or operator. Our assay measures titer by gradually immuno-depleting the target analyte from a flowing sample effectively diluting the residual target - a process conventionally achieved through serially diluting the whole sample in numerous, time-consuming pipetting steps performed manually. Furthermore, the execution of the depletion ELISA process is automated by a built-in flow controller which sequentially delivers different reagents with preset delays. We apply the technology to develop assays measuring (1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers (IgM/IgG antibodies to nucleocapsid and spike protein) and (2) troponin I, a cardiac biomarker.

We leverage electroosmotic-flow generation in porous media in combination with a hydrophobic air gap to create a controllable valve capable of operating in either finite dosing or continuous flow mode, enabling the implementation of multi-step assays on paper-based devices. The hydrophobic air gap between two paper pads creates a barrier keeping the valve nominally closed. Electroosmotic actuation, implemented using a pair of electrodes under the upstream pad, generates sufficient pressure to overcome the barrier and connect the two pads. We present a model describing the flow and governing parameters, including the electric potentials required to open and close the valve and the threshold potential for switching between the modes of operation. We construct the air gap using a hierarchical superhydrophobic surface and study the stability of the closed valve under strenuous conditions and find good agreement between our model and experimental results, as well as stable working conditions for practical applications. We present a straightforward design for a compact and automated device based on paper pads placed on top of printed circuit boards (PCB), equipped with heating and actuation electrodes and additional power and logic capabilities. Finally, we demonstrate the use of the device for amplification of SARS-CoV-2 sequences directly from raw saliva samples, using a loop-mediated isothermal amplification (LAMP) protocol requiring sample lysis followed by enzymatic deactivation and delivery to multiple amplification sites. Since PCB costs scale favorably with mass-production, we believe that this approach could lead to a low-cost diagnostic device that offers the sensitivity of amplification methods.

Purpose: To evaluate filter paper as a means to transport oro/nasopharyngeal samples from laboratories with few resources for SARS-CoV-2 detection by RT-qPCR in a central laboratory that usually performs this technique as routine., Methods: A total of 40 specimens were evaluated in parallel by RT-qPCR carried out after RNA extraction using two different protocols: direct RNA extraction (Protocol A - reference method) and RNA extraction after impregnation in filter paper (Protocol B)., Results: The RT-qPCR for SARS-CoV-2 using Protocol B presented 97.22% (35/36) of agreement for SARS-CoV-2-positive samples when compared to the reference method (Protocol A), even for specimens with low viral load (increased Ct values). Noteworthy, three clinical specimens which were categorized as inconclusive by Protocol A presented amplification of both N1 and N2 targets using Protocol B, presenting positive results for SARS-CoV-2., Conclusion: The use of filter paper to transport oro/nasopharyngeal clinical samples presented very satisfactory results to detect SARS-CoV-2 by RT-qPCR. In addition, it proved to be a feasible and sensitive approach, being able to generate the detection of SARS-CoV-2 even at low concentrations, without presenting false-negative results., (Copyright © 2022. Published by Elsevier B.V.)

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for versatile diagnostic assays that can discriminate among emerging variants of the virus. Here we report the development and performance benchmarking of an inexpensive (approximately US$0.30 per test) assay for the rapid (sample-to-answer time within 30 min) colorimetric detection of SARS-CoV-2 variants. The assay, which we integrated into foldable paper strips, leverages nucleic acid strand-displacement reactions, the thermodynamic energy penalty associated with single-base-pair mismatches and the metal-ion-controlled enzymatic cleavage of urea to amplify the recognition of viral RNAs for the colorimetric readout of changes in pH via a smartphone. For 50 throat swab samples, the assay simultaneously detected the presence of SARS-CoV-2 and mutations specific to the SARS-CoV-2 variants Alpha, Beta and Gamma, with 100% concordance with real-time quantitative polymerase chain reaction and RNA sequencing. Customizable and inexpensive paper-based assays for the detection of viruses and their variants may facilitate viral surveillance., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, we developed a rotatable paper device integrating loop-mediated isothermal amplification (RT-LAMP) and a novel naked-eye readout of the RT-LAMP results using a food additive, carmoisine, for infectious pathogen detection. Hydroxyl radicals created from the reaction between CuSO 4 and H 2 O 2 were used to decolor carmoisine, which is originally red. The decolorization of carmoisine can be interrupted in the presence of DNA amplicons produced by the RT-LAMP reaction due to how DNA competitively reacts with the hydroxyl radicals to maintain the red color of the solution. In the absence of the target DNA, carmoisine is decolored, owing to its reaction with hydroxyl radicals; thus, positive and negative samples can be easily differentiated based on the color change of the solution. A rotatable paper device was fabricated to integrate the RT-LAMP reaction with carmoisine-based colorimetric detection. The rotatable paper device was successfully used to detect SARS-CoV-2 and SARS-CoV within 70 min using the naked eye. Enterococcus faecium spiked in milk was detected using the rotatable paper device. The detection limits for the SARS-CoV-2 and SARS-CoV targets were both 10 3 copies/µL. The rotatable paper device provides a portable and low-cost tool for detecting infectious pathogens in a resource-limited environment.

Surveillance of SARS-CoV-2 infection is critical for controlling the current pandemic. Antigen rapid tests (ARTs) provide a means for surveillance. Available lateral flow assay format ARTs rely heavily on nitrocellulose paper, raising challenges in supply shortage. Vertical flow assay (VFA) with cellulose paper as test material attracts much attention as a complementary test approach. However, current reported VFAs are facing challenges in reading the test signal from the bottom face of the test cassette, complicating the test workflow and hindering translation into rapid test application. Here, we address this gap with an enhanced VFA against SARS-CoV-2 N protein that adapts a cellulose pull-down test format allowing (1) one-step sample application at the top of the test cassette and (2) readout of the test signal from the top. We also demonstrate the feasibility of translating the enhanced VFA into a point-of-care application that can help in SARS-CoV-2 surveillance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants., Competing Interests: SE: Research support from GSK, Sanofi and Vifor. Speaker’s fees from GSK, Pfizer, Novartis, Sanofi Pasteur and MSD in the past three years. BA is supported by Michael Smith Health Research BC. MO’R: Received research funding for Phase III Covid-19 vaccine trial from Janssen; Received research funding for Phase II Pneumococcal conjugate vaccine trial from Pfizer. VD-B: no conflict of interest to declare. SM: Institution received funding on COVID-19 from BMGF, South African Medical Research Council and Novavax. Also, participating in clinical trials of Pfizer/Biontech and JJ Covid-19 vaccines in pregnant women. MS is a member of the data safety and monitoring board for Janssen and CEPI and received research grants and/or consultancy fees from Astra Zeneca, Janssen, Pfizer, Sanofi, Seqirus, Takeda, MSD and GSK. KF is a member of the Australian Technical Advisory Group on Immunisation noting that this paper represents her own personal view; received honoraria as a member of the vaccine advisory boards for Seqiris and Sanofi Pasteur in the last 5 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abu-Raya, Madhi, Omer, Amirthalingam, Giles, Flanagan, Zimmermann, O’Ryan, Safadi, Papaevangelou, Maertens, Wanlapakorn, Diaz-Brito, Tommelein and Esposito.)

The 2019 outbreak of coronavirus disease (COVID-19) in Wuhan (Hubei province of China) has given rise to a pandemic spread of virus, more than 240 million incidences and a death toll larger than 5 million people. COVID-19 has set off large efforts in research, therapy and patient care, as well as public and private debates in every imaginable form. A number of scientists used the publication platforms provided by the Federation of the European Biochemical Societies (FEBS) to present their research data, reviews, opinions and other contributions relating to COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, I highlight the recent COVID-19 papers which have been published and collected in a Virtual Issue in FEBS Letters, and discuss their implications towards understanding the molecular, biochemical and cellular mechanisms of SARS-CoV-2 infections, vaccine development and antiviral discovery strategies., (© 2021 The Author. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Detection methods for monitoring infectious pathogens has never been more important given the need to contain the spread of the COVID-19 pandemic. Herein we propose a highly sensitive magnetic-focus-enhanced lateral flow assay (mLFA) for the detection of SARS-CoV-2. The proposed mLFA is simple and requires only lateral flow strips and a reusable magnet to detect very low concentrations of the virus particles. The magnetic focus enhancement is achieved by focusing the SARS-CoV-2 conjugated magnetic probes in the sample placed in the lateral flow (LF) strips for improved capture efficiency, while horseradish peroxidase (HRP) was used to catalyze the colorimetric reaction for the amplification of the colorimetric signal. With the magnetic focus enhancement and HRP-based amplification, the mLFA could yield a highly sensitive technology for the recognition of SARS-CoV-2. The developed methods could detect as low as 400 PFU/mL of SARS-CoV-2 in PBS buffer based on the visible blue dots on the LF strips. The mLFA could recognize 1200 PFU/mL of SARS-CoV-2 in saliva samples. With clinical nasal swab samples, the proposed mLFA could achieve 66.7% sensitivity and 100% specificity.

Background: Introducing new liver transplantation (LT) practices, like unconventional donor use, incurs higher costs, making evaluation of their prognostic justification crucial. This study reexamines the spread pattern of new LT practices and its prognosis across the United States., Methods: The study investigated the spread pattern of new practices using the UNOS database (2014-2023). Practices included LT for hepatitis B/C (HBV/HCV) nonviremic recipients with viremic donors, LT for COVID-19-positive recipients, and LT using onsite machine perfusion (OMP). One year post-LT patient and graft survival were also evaluated., Results: LTs using HBV/HCV donors were common in the East, while LTs for COVID-19 recipients and those using OMP started predominantly in California, Arizona, Texas, and the Northeast. K-means cluster analysis identified three adoption groups: facilities with rapid, slow, and minimal adoption rates. Rapid adoption occurred mainly in high-volume centers, followed by a gradual increase in middle-volume centers, with little increase in low-volume centers. The current spread patterns did not significantly affect patient survival. Specifically, for LTs with HCV donors or COVID-19 recipients, patient and graft survivals in the rapid-increasing group was comparable to others. In LTs involving OMP, the rapid- or slow-increasing groups tended to have better patient survival (p = 0.05) and significantly improved graft survival rates (p = 0.02). Facilities adopting new practices often overlap across different practices., Discussion: Our analysis revealed three distinct adoption groups across all practices, correlating the adoption aggressiveness with LT volume in centers. Aggressive adoption of new practices did not compromise patient and graft survivals, supporting the current strategy. Understanding historical trends could predict the rise in future LT cases with new practices, aiding in resource distribution., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The "future of work" refers to workplace modifications projected to occur following large scale events impacting workforce health and safety such as pandemics, technological advancements, or economic shifts. This paper examines the influence of the COVID-19 pandemic on the future of work., Methods: The electronic databases PubMed, Google Scholar, and Scopus were explored using search terms such as "post-pandemic," "working force," and "future of work" to retrieve papers published between 2000 and 2023., Results: The main characteristics of the future of work modification revealed are blurring of work-home boundaries, increase in telework and the gig economy, demand for artificial intelligence, smart working, quiet hiring, diversity and inclusion, and algocratic governance. Needed skills include virtual collaboration capability, cross-cultural competency, computational thinking, news media literacy, transdisciplinarity, sense making, and focusing on mental health and well-being., Conclusions: Organizations are remodeling workforces to meet employee, employer, regulatory, and market expectations to adapt to future workplace needs., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Loop-mediated isothermal amplification (LAMP) is a molecular diagnosis technology with the advantages of isothermal reaction conditions and high sensitivity. However, the LAMP reactions are prone to producing false-positive results and thus are usually less reliable. This study demonstrates a gold nanoparticle (AuNP)-assisted colorimetric LAMP technique for diagnosing SARS-CoV-2, which aims to overcome the false-positive results. The AuNPs were functionalized with E gene probes, specifically tailored to bind to the amplified E-gene LAMP product, using the freezing method. Varied salt concentration and AuNP/probe combinations were tested for the highest visual performance. The experiments were conducted on synthetic SARS-CoV-2 RNA (Omicron variant), as well as on clinical samples. The assay showed an exceptional sensitivity of 8.05 fg of LAMP amplicon mixture (0.537 fg/µL). The average reaction time was ~ 30 min. In conclusion, AuNP-assisted LAMP detection will not identify any potential unspecific amplification, which helps to improve the efficiency and reliability of LAMP assays in point-of-care applications. The freezing method to functionalize the AuNPs with probes simplifies the assay, which can be utilized in further diagnostic studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Molecular diagnostics involving nucleic acids (DNA and RNA) are regarded as extremely functional tools. During the 2020 global health crisis, efforts intensified to optimize the production and delivery of molecular diagnostic kits for detecting SARS-CoV-2. During this period, RT-LAMP emerged as a significant focus. However, the thermolability of the reagents used in this technique necessitates special low-temperature infrastructure for transport, storage, and conservation. These requirements limit distribution capacity and necessitate cost-increasing adaptations. Consequently, this report details the development of a lyophilization protocol for reagents in a colorimetric RT-LAMP diagnostic kit to detect SARS-CoV-2, facilitating room-temperature transport and storage. We conducted tests to identify the ideal excipients that maintain the molecular integrity of the reagents and ensure their stability during room-temperature storage and transport. The optimal condition identified involved adding 5% PEG 8000 and 75 mM trehalose to the RT-LAMP reaction, which enabled stability at room temperature for up to 28 days and yielded an analytical and diagnostic sensitivity and specificity of 83.33% and 90%, respectively, for detecting SARS-CoV-2. This study presents the results of a lyophilized colorimetric RT-LAMP COVID-19 detection assay with diagnostic sensitivity and specificity comparable to RT-qPCR, particularly in samples with high viral load., (© 2024. The Author(s).)

The highly contagious nature of SARS-CoV-2 has led to several studies on the transmission of the virus. A little studied potential fomite of great concern in the community is currency, which has been shown to harbor microbial pathogens in several studies. Since the onset of the COVID-19 pandemic, many businesses in the United States have limited the use of banknotes in favor of credit cards. However, SARS-CoV-2 has shown greater stability on plastic in several studies. Herein, the stability of SARS-CoV-2 at room temperature on banknotes, money cards and coins was investigated. In vitro studies with live virus suggested SARS-CoV-2 was highly unstable on banknotes, showing an initial rapid reduction in viable virus and no viral detection by 24 hours. In contrast, SARS-CoV-2 displayed increased stability on money cards with live virus detected after 48 hours. Environmental swabbing of currency and money cards on and near the campus of Brigham Young University supported these results, with no detection of SARS-CoV-2 RNA on banknotes, and a low level on money cards. However, no viable virus was detected on either. These preliminary results suggest that the use of money cards over banknotes in order to slow the spread of this virus may be ill-advised. These findings should be investigated further through larger environmental studies involving more locations., Competing Interests: The authors have declared that no competing interests exist.

The zoonotic emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing coronavirus disease 2019 (COVID-19) pandemic have profoundly affected our society. The rapid spread and continuous evolution of new SARS-CoV-2 variants continue to threaten global public health. Recent scientific advances have dissected many of the molecular and cellular mechanisms involved in coronavirus infections, and large-scale screens have uncovered novel host-cell factors that are vitally important for the virus life cycle. In this Review, we provide an updated summary of the SARS-CoV-2 life cycle, gene function and virus-host interactions, including recent landmark findings on general aspects of coronavirus biology and newly discovered host factors necessary for virus replication., (© 2024. Springer Nature Limited.)

The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not only the core structural protein required for viral packaging, but also participates in the regulation of viral replication, and its post-translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP ubiquitination is currently unknown. In this study, we first pinpointed TRIM6 as the E3 ubiquitin ligase responsible for NP ubiquitination, binding to NP's CTD via its RING and B-box-CCD domains. TRIM6 promotes the K29-typed polyubiquitination of NP at K102, K347, and K361 residues, increasing its binding to viral genomic RNA. Consistently, functional experiments such as the use of the reverse genetic tool trVLP model and gene knockout of TRIM6 further confirmed that blocking the ubiquitination of NP by TRIM6 significantly inhibited the proliferation of SARS-CoV-2. Notably, the NP of coronavirus is relatively conserved, and the NP of SARS-CoV can also be ubiquitinated by TRIM6, indicating that NP could be a broad-spectrum anti-coronavirus target. These findings shed light on the intricate interaction between SARS-CoV-2 and the host, potentially opening new opportunities for COVID-19 therapeutic development., (© 2024 Wiley Periodicals LLC.)

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population., (© 2024 UICC.)

Background: COVID-19 is a highly contagious virus that causes pneumonia, which quickly progresses to acute respiratory distress. In the case of COVID-19, physiotherapy is critical in non-invasive support management, postural changes, chest physiotherapy (CPT), and bed mobility. This study aims to look into the effects of physiotherapy intervention on functional outcome levels in COVID-19 patients in the acute stage., Methods: A total of 60 severe COVID-19 patients (54 males and 6 females) with a mean age of 50 years were studied. The intervention group (n = 30) had two daily physiotherapy sessions that included positioning, CPT, cardio exercises, breathing exercises, and early mobility, whereas the control group (n = 30) received only standard medical care. Patients were tested twice at the baseline and discharge using peripheral oxygen saturation, respiratory rate (RR) test, dyspnea rate, two-min walk test, and spirometer scores, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1)., Results: The two groups improved significantly between the baseline and discharge ratings. The intervention group, on the other hand, significantly improved all outcome indicators at discharge (p-value = 0.00). This study found that physiotherapy management improved oxygen saturation, RR, dyspnea, and lung function tests in COVID-19 patients except in FVC (p-value = 0.402) and FEV1(p-value = 0.114)., Conclusion: Physiotherapist interventions with COVID-19 patients increase respiratory function and treatment time., (© 2024 John Wiley & Sons Ltd.)

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The global crisis of the COVID-19 pandemic has highlighted the need for mathematical models to inform public health strategies. The present study introduces a novel six-compartment epidemiological model that uniquely incorporates a higher isolation rate for unreported symptomatic cases of COVID-19 compared to reported cases, aiming to enhance prediction accuracy and address the challenge of initial underreporting. Additionally, we employ optimal control theory to assess the cost-effectiveness of interventions and adapt these strategies to specific epidemiological scenarios, such as varying transmission rates and the presence of asymptomatic carriers. By applying this model to COVID-19 data from India (30 January 2020 to 24 November 2020), chosen to capture the initial outbreak and subsequent waves, we calculate a basic reproduction number of 2.147, indicating the high transmissibility of the virus during this period in India. A sensitivity analysis reveals the critical impact of detection rates and isolation measures on disease progression, showing the robustness of our model in estimating the basic reproduction number. Through optimal control simulations, we demonstrate that increasing isolation rates for unreported cases and enhancing detection reduces the spread of COVID-19. Furthermore, our cost-effectiveness analysis establishes that a combined strategy of isolation and treatment is both more effective and economically viable. This research offers novel insights into the efficacy of non-pharmaceutical interventions, providing a tool for strategizing public health interventions and advancing our understanding of infectious disease dynamics., (© 2024. The Author(s).)

Goal: This research aimed to evaluate variations in perceived organizational support among physicians during the first year of the COVID-19 pandemic and the associations between perceived organizational support, physician burnout, and professional fulfillment., Methods: Between November 20, 2020, and March 23, 2021, 1,162 of 3,671 physicians (31.7%) responded to the study survey by mail, and 6,348 of 90,000 (7.1%) responded to an online version. Burnout was assessed using the Maslach Burnout Inventory, and perceived organizational support was assessed by questions developed and previously tested by the Stanford Medicine WellMD Center. Professional fulfillment was measured using the Stanford Professional Fulfillment Index., Principal Findings: Responses to organizational support questions were received from 5,933 physicians. The mean organizational support score (OSS) for male physicians was higher than the mean OSS for female physicians (5.99 vs. 5.41, respectively, on a 0-10 scale, higher score favorable; p < .001). On multivariable analysis controlling for demographic and professional factors, female physicians (odds ratio [OR] 0.66; 95% CI: 0.55-0.78) and physicians with children under 18 years of age (OR 0.72; 95% CI: 0.56-0.91) had lower odds of an OSS in the top quartile (i.e., a high OSS score). Specialty was also associated with perceived OSS in mean-variance analysis, with some specialties (e.g., pathology and dermatology) more likely to perceive significant organizational support relative to the reference specialty (i.e., internal medicine subspecialty) and others (e.g., anesthesiology and emergency medicine) less likely to perceive support. Physicians who worked more hours per week (OR for each additional hour/week 0.99; 95% CI: 0.99-1.00) were less likely to have an OSS in the top quartile. On multivariable analysis, adjusting for personal and professional factors, each one-point increase in OSS was associated with 21% lower odds of burnout (OR 0.79; 95% CI: 0.77-0.81) and 32% higher odds of professional fulfillment (OR 1.32; 95% CI: 1.28-1.36)., Practical Applications: Perceived organizational support of physicians during the COVID-19 pandemic was associated with a lower risk of burnout and a higher likelihood of professional fulfillment. Women physicians, physicians with children under 18 years of age, physicians in certain specialties, and physicians working more hours reported lower perceived organizational support. These gaps must be addressed in conjunction with broad efforts to improve organizational support., Competing Interests: The authors declare no conflicts of interest. The opinions offered in this article are those of the authors and do not necessarily reflect American Medical Association policy., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Foundation of the American College of Healthcare Executives.)

Purpose of Review: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV., Recent Findings: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Understanding how COVID-19 impacts the expression of clinically relevant drug metabolizing enzymes and membrane transporters (DMETs) is vital for addressing potential safety and efficacy concerns related to systemic and peripheral drug concentrations. This study investigates the impact of COVID-19 severity on DMETs expression and the underlying mechanisms to inform the design of precise clinical dosing regimens for affected patients., Methods: Transcriptomics analysis of 102 DMETs, 10 inflammatory markers, and 12 xenosensing regulatory genes was conducted on nasopharyngeal swabs from 50 SARS-CoV-2 positive (17 outpatients, 16 non-ICU, and 17 ICU) and 13 SARS-CoV-2 negative individuals, clinically tested through qPCR, in the Greater Toronto area from October 2020 to October 2021., Results: We observed a significant differential gene expression for 42 DMETs, 6 inflammatory markers, and 9 xenosensing regulatory genes. COVID-19 severity was associated with the upregulation of AKR1C1, MGST1, and SULT1E1, and downregulation of ABCC10, CYP3A43, and SLC29A4 expressions. Altogether, SARS-CoV-2-positive patients showed an upregulation in CYP2C9, CYP2C19, AKR1C1, SULT1B1, SULT2B1, and SLCO4A1 and downregulation in FMO5, MGST3, ABCC5, and SLCO4C1 compared with SARS-CoV-2 negative individuals. These dysregulations were associated with significant changes in the expression of inflammatory and xenosensing regulatory genes driven by the disease. GSTM3, PPARA, and AKR1C1 are potential biomarkers of the observed DMETs dysregulation pattern in nasopharyngeal swabs of outpatients, non-ICU, and ICU patients, respectively., Conclusion: The severity of COVID-19 is associated with the dysregulation of DMETs involved in processing commonly prescribed drugs, suggesting potential disease-drug interactions, especially for narrow therapeutic index drugs., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19, may lead to multiple organ dysfunctions and long-term complications. The induction of microvascular dysfunction is regarded as a main player in these pathological processes. To investigate the possible impact of SARS-CoV-2-induced endothelial-to-mesenchymal transition (EndMT) on fibrosis in "long-COVID" syndrome, we used primary cultures of human microvascular cells derived from the lungs, as the main infection target, compared to cells derived from different organs (dermis, heart, kidney, liver, brain) and to the HUVEC cell line. To mimic the virus action, we used mixed SARS-CoV-2 peptide fragments (PepTivator ® ) of spike (S), nucleocapsid (N), and membrane (M) proteins. TGFβ2 and cytokine mix (IL-1β, IL-6, TNFα) were used as positive controls. The percentage of cells positive to mesenchymal and endothelial markers was quantified by high content screening. We demonstrated that S+N+M mix induces irreversible EndMT in all analyzed endothelial cells via the TGFβ pathway, as demonstrated by ApoA1 treatment. We then tested the contribution of single peptides in lung and brain cells, demonstrating that EndMT is triggered by M peptide. This was confirmed by transfection experiment, inducing the endogenous expression of the glycoprotein M in lung-derived cells. In conclusion, we demonstrated that SARS-CoV-2 peptides induce EndMT in microvascular endothelial cells from multiple body districts. The different peptides play different roles in the induction and maintenance of the virus-mediated effects, which are organ-specific. These results corroborate the hypothesis of the SARS-CoV-2-mediated microvascular damage underlying the multiple organ dysfunctions and the long-COVID syndrome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129 Xe ventilation MRI in human., Methods: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129 Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129 Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129 Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis., Results: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129 Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm 3 . Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129 Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm 3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R 2  = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%])., Conclusion: Zigzag sampling combined with GRE sequence provides a way for rapid 129 Xe ventilation imaging., (© 2024 International Society for Magnetic Resonance in Medicine.)

COVID-19 has resulted in a significant global impact on health, the economy, education, and daily life. The disease can range from mild to severe, with individuals over 65 or those with underlying medical conditions being more susceptible to severe illness. Early testing and isolation are vital due to the virus's variable incubation period. Chest radiographs (CXR) have gained importance as a diagnostic tool due to their efficiency and reduced radiation exposure compared to CT scans. However, the sensitivity of CXR in detecting COVID-19 may be lower. This paper introduces a deep learning framework for accurate COVID-19 classification and severity prediction using CXR images. U-Net is used for lung segmentation, achieving a precision of 0.9924. Classification is performed using a Convulation-capsule network, with high true positive rates of 86% for COVID-19, 93% for pneumonia, and 85% for normal cases. Severity assessment employs ResNet50, VGG-16, and DenseNet201, with DenseNet201 showing superior accuracy. Empirical results, validated with 95% confidence intervals, confirm the framework's reliability and robustness. This integration of advanced deep learning techniques with radiological imaging enhances early detection and severity assessment, improving patient management and resource allocation in clinical settings., (© 2024. The Author(s).)

The COVID-19 pandemic has profoundly reshaped postgraduate medical education, driving immediate and significant adaptations in teaching methodologies and educational frameworks. This review examines the multifaceted transformations within medical education environments, particularly in response to the pandemic. Through a structured narrative review of recent literature, we identify key lessons learned and the subsequent shifts in educational practices. Our analysis underscores the critical importance of flexibility in educational delivery, the integration of technology, and the emphasis on mental health and resilience among medical trainees. We also explore the challenges and successes associated with maintaining equality and diversity in a rapidly evolving educational landscape. The findings highlight the necessity for continuous professional development and robust support systems to navigate future challenges effectively. Recommendations are provided for educational institutions to enhance adaptability, foster inclusive learning environments, and prepare for unforeseen global health emergencies. This study aims to contribute to the ongoing discourse on optimizing postgraduate medical education to better prepare health professionals for a dynamic and uncertain future.