SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression.

Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein ß2-microglobulin (ß2m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells, these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8+ T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that down-regulate MHC-I expression to avoid CD8+ T cell recognition. Here, we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, down-regulate MHC-I expression using distinct mechanisms. First, ORF3a, a viroporin, reduces the global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of ß2m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a specific mechanism that allows immune evasion by SARS-CoV-2.

Comparison of transverse dimensional and incisor changes between wide and narrow orthodontic archwires: a randomized controlled trial.

OBJECTIVES: To clinically compare the effects of broader archwires to standard archwires, using conventional brackets in both cases, on the transverse and incisor changes in maxillary and mandibular arches during leveling and alignment. MATERIALS AND METHODS: Fifty-two patients presenting with crowding were allocated into two groups; one group received the broad Damon archwires while the other received standard 3M OrthoForm III Ovoid archwires. All participants were treated with conventional brackets using similar archwire sequences (0.014, 0.018, 0.016 × 0.022/0.016 × 0.025, 0.019 × 0.025 NiTi/CuNiTi archwires). Digital casts were obtained from alginate impressions before treatment (T0) and six weeks after inserting 0.019 × 0.025 NiTi archwires (T1). Pretreatment (T0) and post-alignment (T1) lateral cephalograms were obtained for each patient. The primary outcomes were the changes in the transverse arch dimensions and incisor inclination. The secondary outcomes were the horizontal and vertical linear changes in incisor position. RESULTS: Complete data were collected for 47 patients. There was a significant increase in arch width during treatment within each group, except for upper inter-molar width in 3M group (P = 0.071). Damon wire induced a statistically significant increase in maxillary inter-second premolar width (P = 0.042), and mandibular inter-first premolar (P = 0.043), inter-second premolar (P = 0.008) and inter-molar widths (P = 0.033) compared to 3M group. The increase in incisor proclination and the linear change in incisor position were significant within each group, with less mandibular incisor proclination (P = 0.004) and horizontal advancement (P = 0.038) in the Damon group. CONCLUSIONS: Damon archwires created a comparatively greater increase in the maxillary inter-second premolar width and the mandibular inter-first premolar, inter-second premolar, and inter-molar widths, and less proclination and horizontal advancement in mandibular incisors. The study provides invaluable evidence that using broad archwires with self-ligating brackets is the reason behind any greater expansion observed in this system rather than the unique mechanical and biological features exerted by the self-ligating system. CLINICAL RELEVANCE: Our results suggest that Damon archwire might be a better alternative compared to the narrower standard archwires that are usually used with conventional brackets, especially in the mandibular arch, in cases where mild to moderate crowding is planned to be resolved with a non-extraction approach. However, as arch expansion in the absence of posterior crossbites raises the question of long-term stability, the reported advantage of the use of wide wires should be interpreted with caution and should be considered in the retention phase, bearing in mind that achieving a good post-treatment occlusion is important for enhancing post-treatment stability.

Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar.

The leptin-melanocortin pathway is pivotal in appetite and energy homeostasis. Pathogenic variants in genes involved in this pathway lead to severe early-onset monogenic obesity (MO). The MC4R gene plays a central role in leptin-melanocortin signaling, and heterozygous variants in this gene are the most common cause of MO. A targeted gene panel consisting of 52 obesity-related genes was used to screen for variants associated with obesity. Variants were analyzed and filtered to identify potential disease-causing activity and validated using Sanger sequencing. We identified two novel heterozygous variants, c.253A>G p.Ser85Gly and c.802T>C p.Tyr268His, in the MC4R gene in two unrelated patients with morbid obesity and evaluated the functional impact of these variants. The impact of the variants on the MC4R gene was assessed using in silico prediction tools and molecular dynamics simulation. To further study the pathogenicity of the identified variants, GT1-7 cells were transfected with plasmid DNA encoding either wild-type or mutant MC4R variants. The effects of allelic variations in the MC4R gene on cAMP synthesis, MC4R protein level, and activation of PKA, ERB, and CREB signaling pathways in both stimulated and unstimulated ɑ-MSH paradigms were determined for their functional implications. In silico analysis suggested that the variants destabilized the MC4R structure and affected the overall dynamics of the MC4R protein, possibly leading to intracellular receptor retention. In vitro analysis of the functional impact of these variants showed a significant reduction in cell surface receptor expression and impaired extracellular ligand binding activity, leading to reduced cAMP production. Our analysis shows that the variants do not affect total protein expression; however, they are predicted to affect the post-translational localization of the MC4R protein to the cell surface and impair downstream signaling cascades such as PKA, ERK, and CREB signaling pathways. This finding might help our patients to benefit from the novel therapeutic advances for monogenic forms of obesity.

Perceptions of Pharmacy Graduate Students Toward Research Ethics Education: A Cross-Sectional Study from a Developing Country.

Despite the potential value of graduate-level research ethics training, most Middle East countries, including Jordan, do not routinely offer formal research ethics training. In students enrolled in Jordanian master's level graduate program in pharmacy, the current study assessed: 1- differences in pre- and post-enrollment exposure to research ethics core themes, 2- whether this exposure was through a formal course or in an informal setting, and 3- student attitudes towards research ethics education and the need for integrating a dedicated research ethics course into pharmacy graduate programs. A 12-item on-line survey was developed by the authors and disseminated to a convenience sample of current and former master-level pharmacy students in Jordan. A total of 61 eligible respondents completed the survey. A minority of respondents (38%) acknowledged receiving research ethics training prior to enrollment into a postgraduate pharmacy program with nearly half (16%) describing this training as informal. In comparison, a larger percentage of the total respondents (56%) had received research ethics training during their postgraduate program enrollment, with nearly half of those (25%) indicating that this training was informal. A majority of respondents reported a strong need for integrating a formal research ethics course into postgraduate pharmacy curriculum (90%) to support their research training and thesis writing (89%). Overall, the study revealed a notable lack of research ethics education for graduate-level pharmacy students in Jordan.

Intracellular Ionic Strength Sensing Using NanoLuc.

Intracellular ionic strength regulates myriad cellular processes that are fundamental to cellular survival and proliferation, including protein activity, aggregation, phase separation, and cell volume. It could be altered by changes in the activity of cellular signaling pathways, such as those that impact the activity of membrane-localized ion channels or by alterations in the microenvironmental osmolarity. Therefore, there is a demand for the development of sensitive tools for real-time monitoring of intracellular ionic strength. Here, we developed a bioluminescence-based intracellular ionic strength sensing strategy using the Nano Luciferase (NanoLuc) protein that has gained tremendous utility due to its high, long-lived bioluminescence output and thermal stability. Biochemical experiments using a recombinantly purified protein showed that NanoLuc bioluminescence is dependent on the ionic strength of the reaction buffer for a wide range of ionic strength conditions. Importantly, the decrease in the NanoLuc activity observed at higher ionic strengths could be reversed by decreasing the ionic strength of the reaction, thus making it suitable for sensing intracellular ionic strength alterations. Finally, we used an mNeonGreen-NanoLuc fusion protein to successfully monitor ionic strength alterations in a ratiometric manner through independent fluorescence and bioluminescence measurements in cell lysates and live cells. We envisage that the biosensing strategy developed here for detecting alterations in intracellular ionic strength will be applicable in a wide range of experiments, including high throughput cellular signaling, ion channel functional genomics, and drug discovery.

PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.

Precise intrathymic cell migration is important for thymocyte maturation and organ architecture. The orchestration of thymocyte trafficking, however, is not well understood at a molecular level. Here, we described highly regulated plexinD1 expression on CD4+CD8+ double positive (DP) thymocytes. PlexinD1 expression was further affected by the engagement of T cell receptor complex. Activation of plexinD1 via the ligand, semaphorin 3E, repressed CCL25 chemokine signaling via its receptor CCR9 in CD69+ thymocytes. In the absence of plexinD1, CD69+ thymocytes remained in the cortex, maturing to form ectopic single positive (SP) thymocyte clusters in Plxnd1-deficient fetal liver cell-transplanted mice. As a consequence, the boundary between DP and SP thymocytes at corticomedullary junctions was disrupted and medullary structures formed under the thymic capsule. These results demonstrate the importance of plexinD1 in directing migration of maturing thymocytes via modulation of biological responses to chemokine gradients.

Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice.

STAT5 proteins are constitutively activated in malignant cells from many patients with leukemia, including the myeloproliferative neoplasms (MPNs) chronic myeloid leukemia (CML) and polycythemia vera (PV), but whether STAT5 is essential for the pathogenesis of these diseases is not known. In the present study, we used mice with a conditional null mutation in the Stat5a/b gene locus to determine the requirement for STAT5 in MPNs induced by BCR-ABL1 and JAK2(V617F) in retroviral transplantation models of CML and PV. Loss of one Stat5a/b allele resulted in a decrease in BCR-ABL1-induced CML-like MPN and the appearance of B-cell acute lymphoblastic leukemia, whereas complete deletion of Stat5a/b prevented the development of leukemia in primary recipients. However, BCR-ABL1 was expressed and active in Stat5-null leukemic stem cells, and Stat5 deletion did not prevent progression to lymphoid blast crisis or abolish established B-cell acute lymphoblastic leukemia. JAK2(V617F) failed to induce polycythemia in recipients after deletion of Stat5a/b, although the loss of STAT5 did not prevent the development of myelofibrosis. These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs.

Enhancing machine learning-based sentiment analysis through feature extraction techniques.

A crucial part of sentiment classification is featuring extraction because it involves extracting valuable information from text data, which affects the model's performance. The goal of this paper is to help in selecting a suitable feature extraction method to enhance the performance of sentiment analysis tasks. In order to provide directions for future machine learning and feature extraction research, it is important to analyze and summarize feature extraction techniques methodically from a machine learning standpoint. There are several methods under consideration, including Bag-of-words (BOW), Word2Vector, N-gram, Term Frequency- Inverse Document Frequency (TF-IDF), Hashing Vectorizer (HV), and Global vector for word representation (GloVe). To prove the ability of each feature extractor, we applied it to the Twitter US airlines and Amazon musical instrument reviews datasets. Finally, we trained a random forest classifier using 70% of the training data and 30% of the testing data, enabling us to evaluate and compare the performance using different metrics. Based on our results, we find that the TD-IDF technique demonstrates superior performance, with an accuracy of 99% in the Amazon reviews dataset and 96% in the Twitter US airlines dataset. This study underscores the paramount significance of feature extraction in sentiment analysis, endowing pragmatic insights to elevate model performance and steer future research pursuits.

Attitudes, motivators, and barriers toward influenza vaccination for children: a study from a conflict-ridden country.

BACKGROUND: Despite the increased recommendations for influenza vaccination, particularly among high-risk groups such as young children, Yemen lacks an influenza vaccination program, and the influenza vaccine is not included in the national immunization regime. This is exacerbated by the country's fragile infrastructure, as well as the devastating consequences of the ongoing conflict, which include child undernutrition and strained healthcare resources. Thus, the objective of the current study is to assess the public attitudes and perceptions toward vaccinating children against influenza in Yemen. METHODS: A cross-sectional study was conducted by distributing a validated survey questionnaire to potential participants using convenience sampling. Descriptive statistics were used to summarize sociodemographic data, knowledge of influenza vaccines, and attitudes and perceptions regarding vaccinating children against influenza. Logistic regression analysis was employed to identify associations between independent variables and the acceptance of vaccines for children. RESULTS: A total of 853 eligible individuals, parents and non-parents, successfully completed the survey. The uptake of the influenza vaccine among the participants was notably low as the majority (69.2%) had not previously received the vaccine, although the majority expressed a willingness to get vaccinated in the future (59.4%). The majority (68.5%) were willing to vaccinate children. The largest percentage of the participants who expressed hesitancy toward children's vaccination cited multiple reasons to reject the vaccine (39.7%), with concerns regarding the safety of the vaccine being the predominant barrier to its acceptance for children (29.6%). On the other hand, motivating factors for vaccinating children included the validation of the vaccine's safety and efficacy, endorsement of the vaccine by the government and physicians, integration of the vaccine into the national immunization program, and the provision of the vaccine free of charge and through schools. Significant predictors for vaccine acceptance in children included male gender, knowledge of the protective effect of the influenza vaccine, previous receipt of the vaccine, and a willingness to receive the vaccine in the future. CONCLUSIONS: The study highlights the need for educational health campaigns to raise awareness and remove misconceptions regarding influenza and the role, benefits, and availability of its vaccine. These findings can serve as a robust foundation for the future design and implementation of an influenza vaccination program for children in Yemen.

A slow but steady nanoLuc: R162A mutation results in a decreased, but stable, nanoLuc activity.

NanoLuc (NLuc) luciferase has found extensive application in designing a range of biological assays, including gene expression analysis, protein-protein interaction, and protein conformational changes due to its enhanced brightness and small size. However, questions related to its mechanism of interaction with the substrate, furimazine, as well as bioluminescence activity remain elusive. Here, we combined molecular dynamics (MD) simulation and mutational analysis to show that the R162A mutation results in a decreased but stable bioluminescence activity of NLuc in living cells and in vitro. Specifically, we performed multiple, all-atom, explicit solvent MD simulations of the apo and furimazine-docked (holo) NLuc structures revealing differential dynamics of the protein in the absence and presence of the ligand. Further, analysis of trajectories for hydrogen bonds (H-bonds) formed between NLuc and furimazine revealed substantial H-bond interaction between R162 and Q32 residues. Mutation of the two residues in NLuc revealed a decreased but stable activity of the R162A, but not Q32A, mutant NLuc in live cell and in vitro assays performed using lysates prepared from cells expressing the proteins and with the furimazine substrate. In addition to highlighting the role of the R162 residue in NLuc activity, we believe that the mutant NLuc will find wide application in designing in vitro assays requiring extended monitoring of NLuc bioluminescence activity. SIGNIFICANCE: Bioluminescence has been extensively utilized in developing a variety of biological and biomedical assays. In this regard, engineering of brighter bioluminescent proteins, i.e. luciferases, has played a significant role. This is acutely exemplified by the engineering of the NLuc luciferase, which is small in size and displays much enhanced bioluminescence and thermal stability compared to previously available luciferases. While enhanced bioluminescent activity is desirable in a multitude of biological and biomedical assays, it would also be useful to develop variants of the protein that display a prolonged bioluminescence activity. This is specifically relevant in designing assays that require bioluminescence for extended periods, such as in the case of biosensors designed for monitoring slow enzymatic or cellular signaling reactions, without necessitating multiple rounds of luciferase substrate addition or any specialized reagents that result in increased assay costs. In the current manuscript, we report a mutant NLuc that possesses a stable and prolonged bioluminescence activity, albeit lower than the wild-type NLuc, and envisage a wider application of the mutant NLuc in designing biosensors for monitoring slower biological and biomedical events.

Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

Reversal of the unique Q493R mutation increases the affinity of Omicron S1-RBD for ACE2.

The SARS-CoV-2 Omicron variant containing 15 mutations, including the unique Q493R, in the spike protein receptor binding domain (S1-RBD) is highly infectious. While comparison with previously reported mutations provide some insights, the mechanism underlying the increased infections and the impact of the reversal of the unique Q493R mutation seen in BA.4, BA.5, BA.2.75, BQ.1 and XBB lineages is not yet completely understood. Here, using structural modelling and molecular dynamics (MD) simulations, we show that the Omicron mutations increases the affinity of S1-RBD for ACE2, and a reversal of the unique Q493R mutation further increases the ACE2-S1-RBD affinity. Specifically, we performed all atom, explicit solvent MD simulations using a modelled structure of the Omicron S1-RBD-ACE2 and compared the trajectories with the WT complex revealing a substantial reduction in the Cα-atom fluctuation in the Omicron S1-RBD and increased hydrogen bond and other interactions. Residue level analysis revealed an alteration in the interaction between several residues including a switch in the interaction of ACE2 D38 from S1-RBD Y449 in the WT complex to the mutated R residue (Q493R) in Omicron complex. Importantly, simulations with Revertant (Omicron without the Q493R mutation) complex revealed further enhancement of the interaction between S1-RBD and ACE2. Thus, results presented here not only provide insights into the increased infectious potential of the Omicron variant but also a mechanistic basis for the reversal of the Q493R mutation seen in some Omicron lineages and will aid in understanding the impact of mutations in SARS-CoV-2 evolution.

Identification of a potential DNA methyltransferase (DNMT) inhibitor.

DNA methyltransferases (DNMTs) play an important role in the epigenetic regulation of gene expression through the methylation of DNA. Since hypermethylation and consequent suppression of tumor suppressor genes are associated with cancer development and progression, DNA hypomethylating agents (HMAs) such as DNMT inhibitors have been proposed for cancer therapy. Two nucleoside analogues approved for the treatment of hematological cancers, decitabine and azacytidine, have poor pharmacokinetic properties, and hence there is a critical need for identifying novel HMAs. Virtual screening of a library of ∼40,000 compounds from the ZINC database, followed by molecular docking of 4,000 compounds having potential druggable properties with DNMT1, DNMT3A and DNMT3B were performed. One unique inhibitor (ZINC167686681) was identified that successfully passed through the Lipinski Rule of 5, geometry constraints as well as ADME/Tox filters and having strong binding energy for DNMTs. Further, molecular dynamics simulations of the docked complexes showed detailed structural features critical for its binding with the DNMTs and the stability of their interaction. Our study identified a compound with potential druggable properties and predicted to bind and inhibit DNMTs. Further investigations involving cellular and animal models of ZINC167686681 will help in potentially taking it into clinical trials for the treatment of cancers.Communicated by Ramaswamy H. Sarma.

Attitudes Toward Providing Open Access for Use of Biospecimens and Health Records: A Cross-Sectional Study from Jordan.

Purpose: Biospecimen repositories and big data generated from clinical research are critically important in advancing patient-centered healthcare. However, ethical considerations arising from reusing clinical samples and health records for subsequent research pose a hurdle for big-data health research. This study aims to assess the public's opinions in Jordan toward providing blanket consent for using biospecimens and health records in research. Participants and Methods: A cross-sectional study utilizing a self-reported questionnaire was carried out in different cities in Jordan, targeting adult participants. Outcome variables included awareness of clinical research, participation in clinical research, and opinions toward providing open access to clinical samples and records for research purposes. Descriptive analysis was utilized for reporting the outcome as frequency (percentages) out of the total responses. Univariate and multivariate logistic regression were used to investigate the association between independent variables and the outcome of interest. Results: A total of 1033 eligible participants completed the questionnaire. Although the majority (90%) were aware of clinical research, only 24% have ever participated in this type of research. About half (51%) agreed on providing blanket consent for the use of clinical samples, while a lower percentage (43%) agreed on providing open access to their health records. Privacy concerns and lack of trust in the researcher were cited as major barriers to providing blanket consent. Participation in clinical research and having health insurance were predictors for providing open access to clinical samples and records. Conclusion: The lack of public trust in Jordan toward data privacy is evident from this study. Therefore, a governance framework is needed to raise and maintain the public's trust in big-data research that warrants the future reuse of clinical samples and records. As such, the current study provides valuable insights that will inform the design of effective consent protocols required in data-intensive health research.

Improving sentiment classification using a RoBERTa-based hybrid model.

Introduction: Several attempts have been made to enhance text-based sentiment analysis's performance. The classifiers and word embedding models have been among the most prominent attempts. This work aims to develop a hybrid deep learning approach that combines the advantages of transformer models and sequence models with the elimination of sequence models' shortcomings. Methods: In this paper, we present a hybrid model based on the transformer model and deep learning models to enhance sentiment classification process. Robustly optimized BERT (RoBERTa) was selected for the representative vectors of the input sentences and the Long Short-Term Memory (LSTM) model in conjunction with the Convolutional Neural Networks (CNN) model was used to improve the suggested model's ability to comprehend the semantics and context of each input sentence. We tested the proposed model with two datasets with different topics. The first dataset is a Twitter review of US airlines and the second is the IMDb movie reviews dataset. We propose using word embeddings in conjunction with the SMOTE technique to overcome the challenge of imbalanced classes of the Twitter dataset. Results: With an accuracy of 96.28% on the IMDb reviews dataset and 94.2% on the Twitter reviews dataset, the hybrid model that has been suggested outperforms the standard methods. Discussion: It is clear from these results that the proposed hybrid RoBERTa-(CNN+ LSTM) method is an effective model in sentiment classification.

Knowledge, attitudes, perceptions, and practice toward seasonal influenza and its vaccine: A cross-sectional study from a country of conflict.

Background: The seasonal influenza vaccine is an important preventive measure against influenza and its associated complications. In Yemen, there is no seasonal influenza vaccination policy, and the influenza vaccine is excluded from the national immunization program. Data on vaccination coverage remain scarce with no previous surveillance programs or awareness campaigns implemented in the country. The current study aims to assess the awareness, knowledge, and attitudes of the public in Yemen toward seasonal influenza and their motivators and perceived barriers to receiving its vaccine. Methods: A cross-sectional survey was carried out using a self-administered questionnaire that was distributed to eligible participants using convenience sampling. Results: A total of 1,396 participants completed the questionnaire. The respondents showed a median knowledge score of influenza of 11.0/15.0, and most of them (70%) were able to recognize its modes of transmission. However, only 11.3% of the participants reported receiving the seasonal influenza vaccine. Physicians were the respondents' most preferred information source for influenza (35.2%), and their recommendation (44.3%) was the most cited reason for taking its vaccine. On the contrary, not knowing about the vaccine's availability (50.1%), concerns regarding the safety of the vaccine (17%), and not considering influenza as a threat (15.9%) were the main reported barriers to getting vaccinated. Conclusion: The current study showed a low uptake of influenza vaccines in Yemen. The physician's role in promoting influenza vaccination seems to be essential. Extensive and sustained awareness campaigns would likely increase the awareness of influenza and remove misconceptions and negative attitudes toward its vaccine. Equitable access to the vaccine can be promoted by providing it free of charge to the public.

New tools and novel approaches in treating locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most aggressive malignant tumors and represents the fourth leading cause of cancer-related death. The median survival of locally advanced pancreatic carcinoma is ten to thirteen months. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. Wild et al. (Abstract #4055) explored a novel tool of selective delivery of TNF-alpha intratumoral injection. This approach limited the systemic toxicity, and suggested survival benefit in only the subgroup of patients with locally advanced pancreatic adenocarcinoma with stage T1-T3. Two studies were presented which were designed to assess the use of two novel agents, targeting signaling pathways, in addition to gemcitabine. Van Laethem et al. (Abstract #4050) are testing the MEK inhibitor, BAY 86-9766 in combination with gemcitabine. However, treatment related toxicity is still of concern. In the other study, Evans et al. (Abstract #TPS4134) are testing the combination of dasatinib and gemcitabine. This is a placebo-controlled, randomized, double blind phase II study. However, results are not available. Stereotactic body radiotherapy (SBRT) is an emerging technology with the comparative efficacy of single fraction radiotherapy (as is used in radiosurgery) vs. fractionated SBRT still unknown. Herman et al. (Abstract #4045) examined the role of fractionated SBRT in locally advanced pancreatic cancer. The phase II results showed a median overall survival of 15.9 months, suggesting that SBRT may be an emerging tool in the multi-modality treatment of locally advanced pancreatic cancer.

Efficacy of intralesional injections of platelet-rich plasma in patients with oral lichen planus: A pilot randomized clinical trial.

OBJECTIVE: To evaluate the clinical efficacy of intralesional platelet-rich plasma (PRP) injections compared to intralesional triamcinolone acetonide (TA) injections in the treatment of erosive oral lichen planus (EOLP). MATERIAL AND METHODS: Twenty patients with EOLP were assigned randomly to either PRP or TA group. Patients received weekly intralesional injections for 4 weeks, and then followed up for 3 months on regular visits every 2 weeks. Pain scores using numerical pain score and clinical score were recorded by a blinded assessor each visit for all patients and remission score at the end of the trial was recorded. RESULTS: Both groups showed significant improvement in the clinical parameters (pain and clinical score) "p = .001." Regarding remission of the lesions, 80% of patients in the PRP group showed complete remission compared to 70% in the TA group. However, there is no statistical significance when comparing the two groups in pain score, clinical score, or remission. CONCLUSIONS: PRP injections could be considered as an effective alternative single treatment modality for EOLP. The protocol for this study registered in Clinicaltrials.gov registry under the identifier number: NCT03293368.

Corrigendum: Decreased interfacial dynamics caused by the N501Y mutation in the SARS-CoV-2 S1 spike:ACE2 complex.

[This corrects the article DOI: 10.3389/fmolb.2022.846996.].