Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

The Impact of Multidrug-Resistant Acinetobacter baumannii Infection in Critically Ill Patients with or without COVID-19 Infection.

This is a single-center, retrospective, cohort study aimed to evaluate the clinical outcomes of multi-drug resistance in Acinetobacter baumannii infections (MDR-AB) in intensive care unit (ICU) patients with or without a COVID-19 infection and risk factors for blood stream infection. A total of 170 patients with MDR-AB were enrolled in the study. Of these, 118 (70%) patients were admitted to the ICU due to a COVID-19 infection. Comparing the COVID-19 and non-COVID-19 groups, the use of mechanical ventilation (98.31% vs. 76.92%, p = 0.000), the presence of septic shock (96.61% vs. 82.69%, p = 0.002), and the use of steroid (99.15% vs. 71.15%, p = 0.000) and tocilizumab therapies (33.05% vs. 0%, p = 0.000) were more prevalent and statistically more significant in patients with COVID-19 infections. The average length of the ICU stay (21.2 vs. 28.33, p = 0.0042) was significantly lower in patients with COVID-19 infections. Survival rate was 21.19% for the COVID-19 group and 28.85% for non-COVID-19 group with a p-value = 0.0361. COVID-19 status was associated with significantly higher hazards of death (HR 1.79, CI 95% 1.02-3.15, p = 0.043). Higher SOFAB (15.07 vs. 12.07, p = 0.0032) and the placement of an intravascular device (97.06% vs. 89.71%, p = 0.046) were significantly associated with the development of a bloodstream infection. Our study has shown that critically ill patients with an MDR-AB infection, who were admitted due to a COVID-19 infection, had a higher hazard for death compared to non-COVID-19 infected patients.

An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight.

The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2.

A Review of the Potential of Artificial Intelligence Approaches to Forecasting COVID-19 Spreading

The spread of SARS-CoV-2 can be considered one of the most complicated patterns with a large number of uncertainties and nonlinearities. Therefore, analysis and prediction of the distribution of this virus are one of the most challenging problems, affecting the planning and managing of its impacts. Although different vaccines and drugs have been proved, produced, and distributed one after another, several new fast-spreading SARS-CoV-2 variants have been detected. This is why numerous techniques based on artificial intelligence (AI) have been recently designed or redeveloped to forecast these variants more effectively. The focus of such methods is on deep learning (DL) and machine learning (ML), and they can forecast nonlinear trends in epidemiological issues appropriately. This short review aims to summarize and evaluate the trustworthiness and performance of some important AI-empowered approaches used for the prediction of the spread of COVID-19. Sixty-five preprints, peer-reviewed papers, conference proceedings, and book chapters published in 2020 were reviewed. Our criteria to include or exclude references were the performance of these methods reported in the documents. The results revealed that although methods under discussion in this review have suitable potential to predict the spread of COVID-19, there are still weaknesses and drawbacks that fall in the domain of future research and scientific endeavors.

Multidisciplinary teaching and learning biophotonics: Assessing the effectiveness of fully online outreach events

The demand for biophotonics technologies has rapidly increased over the years and supply of professionals capable of working in multi- and inter-disciplinary topics associated with tissue optics and translating optical technologies to the clinic are still scarce. Despite the number of programs to created to increase the number of high-quality biophotonics professionals, most of these programs are focused on post-graduate audiences and involve in-person activities. Particularly on the education side, online teaching and learning (OTL) have exponentially grown over the years as universities adopted online courses. During the COVID-19 pandemic, social distancing restrictions required courses to be offered fully online. Educators have adopted combinations of resources including online apps, simulations, virtual labs, and massive open online courses (MOOCs) to complement recorded or video-conferenced classes. However, most of these resources were not designed to be integrated into virtual courses, compromising the quality of instruction/education especially in events relying on in-person activities to convey information quicker than online activities. These events include short-term courses and outreach events, where fostering students' engagement and interest with fully online activities can be challenging. The quality of instruction is further compromised when events involve multidisciplinary/interdisciplinary OTL, which includes biophotonics and biomedical optics courses. To overcome the aforementioned challenges, we have developed and tested a variety of activities and resources for a short-term virtual biophotonics workshop (BW) including webinars, at-home experiments, and computer simulations. Our BW targeted undergraduate students and secondary-school teachers with diverse backgrounds and offered activities to meet needs of learners with diverse backgrounds, learning styles and education levels. Resources provided self-paced learning over the duration of the workshop. Our participants' feedback for 2020 and 2021 BWs showed >78.6% of participating respondents considered every activity of the BW important for their learning process. Also, every BW activity received >69.2% "Very good"and ""Good"responses for overall learning, >91.7% for quality of teaching, >90% for quality of subject matter. Similarly, >75% of participants were "Very interested"or "Interested"in every activity. © COPYRIGHT SPIE.

Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach† † Electronic supplementary information (ESI) available: Docking energies of ILs with Mpro, the average values of RMSD, RMSF, Rg and hydrogen bonding interactions, RMSF plots and binding free energies of Mpro with cholinium-based ILs and natural compounds. See DOI: 10.1039/d1ra08604a

The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and control COVID-19 infections. The main protease (Mpro) is a salient enzyme in coronaviruses that plays a vital role in viral replication, making it a fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against the Mpro of SARS-CoV-2 using the Universal Natural Product Database (UNPD). As well, we studied the role of ionic liquids (ILs) on the structural stabilization of Mpro. Cholinium-based ILs are biocompatible and used for a variety of biomedical applications. Molecular docking was employed for the initial screening of natural products and ILs against Mpro. To predict the drug-likeness features of lead compounds, we calculated the ADMET properties. We performed MD simulations for the selected complexes based on the docking outcomes. Using MM/PBSA approaches, we conclude that compounds NP-Hit2 (−25.6 kcal mol−1) and NP-Hit3 (−25.3 kcal mol−1) show stronger binding affinity with Mpro. The hotspot residues of Thr25, Leu27, His41, Met49, Cys145, Met165, and Gln189 strongly interacted with the natural compounds. Furthermore, naproxenate, ketoprofenate, and geranate, cholinium-based ILs strongly interact with Mpro and these ILs have antimicrobial properties. Our findings will aid in the development of effective Mpro inhibitors. The selected natural compounds NP-Hit2, NP-Hit3 and cholinium-based ILs exhibit potential antiviral activity against Mpro of SARS-CoV-2.

An experimental in silico study on COVID-19: Response of neutrophil-related genes to antibiotics.

Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.

Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach.

The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and control COVID-19 infections. The main protease (Mpro) is a salient enzyme in coronaviruses that plays a vital role in viral replication, making it a fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against the Mpro of SARS-CoV-2 using the Universal Natural Product Database (UNPD). As well, we studied the role of ionic liquids (ILs) on the structural stabilization of Mpro. Cholinium-based ILs are biocompatible and used for a variety of biomedical applications. Molecular docking was employed for the initial screening of natural products and ILs against Mpro. To predict the drug-likeness features of lead compounds, we calculated the ADMET properties. We performed MD simulations for the selected complexes based on the docking outcomes. Using MM/PBSA approaches, we conclude that compounds NP-Hit2 (-25.6 kcal mol-1) and NP-Hit3 (-25.3 kcal mol-1) show stronger binding affinity with Mpro. The hotspot residues of Thr25, Leu27, His41, Met49, Cys145, Met165, and Gln189 strongly interacted with the natural compounds. Furthermore, naproxenate, ketoprofenate, and geranate, cholinium-based ILs strongly interact with Mpro and these ILs have antimicrobial properties. Our findings will aid in the development of effective Mpro inhibitors.

Simulation and evaluation of the protective barrier enclosure for cardiopulmonary resuscitation.

INTRODUCTION: The COVID-19 pandemic has presented a significant challenge for infection prevention and control during airway management in anaesthesia and critical care. The protective barrier enclosure has been described and studied particularly for perioperative anaesthesia use. The potential use of the protective barrier enclosure during cardiopulmonary resuscitation has been poorly explored in the current literature. This work aims to demonstrate the potential of protective barrier enclosure in limiting aerosol dispersion during cardiopulmonary resuscitation delivery. METHODS: A proof-of-concept simulation study was conducted to evaluate the protective properties of the protective barrier enclosure during cardiopulmonary resuscitation. Aerosol was simulated using a fluorescent dye trapped within the manikin. Three different methods of cardiopulmonary resuscitation delivery with a protective barrier enclosure applied over the manikin's head were conducted. The first method simulated a chest compression only cardiopulmonary resuscitation, the second method also used chest compressions only, with a face mask fitted on the victim, while the third method, the victim was given chest compression and bag-valve-mask ventilation by two rescuers. RESULTS: In the first method, release of aerosol from the manikin's mouth was observed during chest compression, while in second method, most of the aerosol was trapped within the face mask, with only minor leaking. However, when bag-valve-mask ventilation was delivered, the aerosol leaked out at high speed around the bag-valve-mask seal. No aerosol condensation was found outside of the protective barrier enclosure in all scenes. CONCLUSION: Protective barrier enclosure may reduce aerosol exposure to the rescuers during out-of-hospital cardiac arrest.

Interplay between SARS-CoV-2 and human long non-coding RNAs.

The long non-coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS-CoV-2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID-19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs-PCGs of BALF samples established by three trans-acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS-CoV-2 genome, suggesting the major regulatory role of these lncRNAs during the SARS-CoV-2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS-CoV-2 infected cells. (c) In contrast to the 3' part of the SARS-CoV-2 genome, the 5' part can interact with many human lncRNAs. Therefore, the mRNA-based vaccines will not show any side effects because of the off-label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non-coding RNA-based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.

Developing worksheet assisted guided inquiry learning video

This research and development (R&D) aimed to 1) create worksheet assisted inquiry learning video, 2) describe the specifications of the product, and 3) confirm the feasibility of the product. The intended feasible product will be fruitful either as online and face-to-face scientific learning and overcome its obstacles caused by limited resources in scientific learning. The scientific approach involves the main phases of observing, questioning, data collecting, data associating, and communicating. Basic inductive reasoning could naturally grow. If it has not developed well along cognitive development stages, the inductive reasoning tends to diminish as disruptive information continues to bombard human life in the online era. This intended product will empower the development of inductive inquiry learning to boost scientific skills and bring to have a strong understanding of basic science topics such periodic table of elements. The scientific learning approach would be conducive for developing inquiry learning which needs guidance when the students have not adequately had scientific skills. The limitation of learning video in empowering authentic data such as facilitating the last communicating learning phase at the scientific steps will be overcome by well worksheet design. R&D adapted Luther's development model which involves concept, design, material collecting, assembly, testing, and distribution stages have realized the product. The adequate validity of the product given by learning and media experts and secondary school chemistry teacher and alpha and beta testing to the product has supported to the feasibility of the created product to be implemented as scientific learning either via online, face-to-face, or blended learning. The similar product with this model can be developed further on other learning topics with some adjustment considering the topic characteristics. The learning video model which is also a learning medium is very helpful in inquiry learning in social distance limitations such the Covid-19 pandemic. © 2021 Author(s).

SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.

Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity-Opportunity for Repurposed Chemotherapy of COVID-19 Infection.

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG - residues with predicted or expected low pKa by neighboring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-CoV and MERS. Finally, we identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.

Targeting severe acute respiratory syndrome-coronavirus (SARS-CoV-1) with structurally diverse inhibitors: a comprehensive review.

Coronaviruses, which were discovered in 1968, can lead to some human viral disorders, like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome-related (MERS), and, recently, coronavirus disease 2019 (COVID-19). The coronavirus that leads to COVID-19 is rapidly spreading all over the world and is the reason for the deaths of thousands of people. Recent research has revealed that there is about 80% sequence homology between the coronaviruses that cause SARS and COVID-19. Considering this fact, we decided to collect the maximum available information on targets, structures, and inhibitors reported so far for SARS-CoV-1 that could be useful for researchers who work on closely related COVID-19. There are vital proteases, like papain-like protease 2 (PL2pro) and 3C-like protease (3CLpro), or main protease (Mpro), that are involved in and are essential for the replication of SARS coronavirus and so are valuable targets for the treatment of patients affected by this type of virus. SARS-CoV-1 NTPase/helicase plays an important role in the release of several non-structural proteins (nsps), so it is another essential target relating to the viral life cycle. In this paper, we provide extensive information about diverse molecules with anti-SARS activity. In addition to traditional medicinal chemistry outcomes, HTS, virtual screening efforts, and structural insights for better understanding inhibitors and SARS-CoV-1 target complexes are also discussed. This study covers a wide range of anti-SARS agents, particularly SARS-CoV-1 inhibitors, and provides new insights into drug design for the deadly SARS-CoV-2 virus.