Functional Evaluation of a Novel Homozygous ADCY3 Variant Causing Childhood Obesity.

Adenylate cyclase 3 () is a transmembrane protein predominantly expressed in the primary cilia of neurons. It plays a vital role in converting ATP to cAMP, a secondary messenger that regulates various downstream signaling pathways such as carbohydrates and lipids metabolism. Homozygous loss-of-function variants in the gene lead to severe early-onset obesity and insulin resistance whereas gain-of-function variants protect against obesity.

A potential allosteric inhibitor of SARS-CoV-2 main protease (M) identified through metastable state analysis.

Anti-COVID19 drugs, such as nirmatrelvir, have been developed targeting the SARS-CoV-2 main protease, M, based on the critical requirement of its proteolytic processing of the viral polyproteins into functional proteins essential for viral replication. However, the emergence of SARS-CoV-2 variants with M mutations has raised the possibility of developing resistance against these drugs, likely due to therapeutic targeting of the M catalytic site. An alternative to these drugs is the development of drugs that target an allosteric site distant from the catalytic site in the protein that may reduce the chance of the emergence of resistant mutants.

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.

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.

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.

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.

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.

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.

Functional Characterization of Novel 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 gene plays a central role in leptin-melanocortin signaling, and heterozygous variants in this gene are the most common cause of MO.

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.

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.

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.

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.

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 β-microglobulin (βm), 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.

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.

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 genetically encoded BRET-based SARS-CoV-2 M protease activity sensor.

The main protease, M, is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting M proteolytic activity in live cells as well as in vitro.

Decreased Interfacial Dynamics Caused by the N501Y Mutation in the SARS-CoV-2 S1 Spike:ACE2 Complex.

Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a massive health crisis across the globe, with some genetic variants gaining enhanced infectivity and competitive fitness, and thus significantly aggravating the global health concern. In this regard, the recent SARS-CoV-2 alpha, beta, and gamma variants (B.1.

Motivators and barriers towards clinical research participation: A population-based survey from an Arab MENA country.

Jordan was the first Arab country to enact clinical research regulations. The country has a well-flourished pharmaceutical industry that leans heavily on clinical research (CR) for drug development and post-marketing surveillance. In this cross-sectional study, we sought to assess the public's awareness and attitude towards CR as well as their perceived motivators and barriers to CR participation.

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

Unlabelled: Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β -microglobulin (β m), 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.

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.

Management of Primary Plasma Cell Leukemia Remains Challenging Even in the Era of Novel Agents.

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm distinguishes it from MM.

Assessment of research ethics education offerings of pharmacy master programs in an Arab nation relative to top programs worldwide: A qualitative content analysis.

The importance of research ethics (RE) training has led academic and funding institutions to require that students, trainees, and faculty obtain such training at various stages of their careers. Despite the increasing awareness of the value RE education offers, this training requirement is absent in Jordan. We aimed to assess RE education offerings of pharmacy master programs in Jordan and compare with the top-ranked pharmacy graduate programs globally.

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.