Role of Global Left Ventricle Longitudinal Strain and Cardiac Biomarkers in the Early Detection of Cancer Therapy-Related Dysfunction in Patients Treated With Cardiotoxic Chemotherapeutic Drugs in a Cardio-Oncology Clinic.

Background Breast cancer (BC) affects many women, and with the prevalence of anthracyclines (AC) used in treatment, cardiotoxicity is a commonly encountered problem. Objective The aim is to early detect subclinical cancer therapy-related cardiac dysfunction (CTRCD) using noninvasive imaging techniques and cardiac biomarkers. Methods Eighty-eight patients with cancer who planned to receive AC or trastuzumab (TZB) were enrolled.

Structure of Aquifex aeolicus lumazine synthase by cryo-electron microscopy to 1.42 Å resolution.

Single-particle cryo-electron microscopy (cryo-EM) has become an essential structural determination technique with recent hardware developments making it possible to reach atomic resolution, at which individual atoms, including hydrogen atoms, can be resolved. In this study, we used the enzyme involved in the penultimate step of riboflavin biosynthesis as a test specimen to benchmark a recently installed microscope and determine if other protein complexes could reach a resolution of 1.5 Å or better, which so far has only been achieved for the iron carrier ferritin.

The Atrial FibriLlatiOn (FLOW-AF) Registry in the Middle East and North Africa: Patient Characteristics, Treatment Patterns and Outcomes.

Introduction: Limited data on atrial fibrillation (AF) are available from the Middle East and North Africa region (MENA). The aim of the FLOW-AF registry was to evaluate the characteristics, treatment patterns, and clinical and economic outcomes of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) in MENA.

Methods: This multi-center, prospective, observational study (the FLOW-AF registry) enrolled patients newly diagnosed with NVAF across Egypt, Lebanon, Kingdom of Saudi Arabia, and United Arab Emirates.

Marine Predator Algorithm-Based Optimal PI Controllers for LVRT Capability Enhancement of Grid-Connected PV Systems.

Photovoltaic (PV) systems are becoming essential to our energy landscape as renewable energy sources become more widely integrated into power networks. Preserving grid stability, especially during voltage sags, is one of the significant difficulties confronting the implementation of these technologies. This attribute is referred to as low-voltage ride-through (LVRT).

Development of Multiplex Real-Time RT-qPCR Assays for the Detection of SARS-CoV-2, Influenza A/B, and MERS-CoV.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (COVID-19) is a serious threat to the general public's health. During influenza seasons, the spread of SARS-CoV-2 and other respiratory viruses may cause a population-wide burden of respiratory disease that is difficult to manage. For that, the respiratory viruses SARS-CoV-2, Influenza A, Influenza B, and Middle East respiratory syndrome (MERS-CoV) will need to be carefully watched over in the upcoming fall and winter seasons, particularly in the case of SARS-CoV-2, Influenza A, and Influenza B, which share similar epidemiological factors like susceptible populations, mode of transmission, and clinical syndromes.

Prognostic value of right ventricular diastolic dysfunction in patients with inferior ST-elevated myocardial infarction.

Background: Right ventricle infarction (RVI) is predominantly a complication of inferior wall myocardial infarction; it occurs in approximately one third of these patients. Right ventricular dysfunction in patients with inferior STEMI and RV infarction was under assessed. Nevertheless, studies which targeted RV assessment by echocardiography, did not routinely evaluate RV diastolic dysfunction.

A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair.

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity.

Cryo-electron structures of the extreme thermostable enzymes Sulfur Oxygenase Reductase and Lumazine Synthase.

Thermostable enzymes have the potential for use in a wide variety of biotechnological applications. Cryo-electron microscopy (cryo-EM) enables the imaging of biomolecules in their native aqueous environment. Here, we present high resolution cryo-EM structures of two thermostable enzymes that exhibit multimeric cage-like structures arranged into two different point-group symmetries.

Distal radial approach between theory and clinical practice.. Time to go distal!

Background: Transradial access (TRA), which has a minimal risk of problems such as radial artery occlusion (RAO), hemorrhage, spasm, and so on, is now considered the standard procedure for cardiac catheterization. The aim of the study is to present the distal transradial access (d-TRA) as a possible promising novel technique in the field of cardiac coronary interventions comparing it to the standard conventional TRA using primary and secondary endpoints, exploring its benefits and drawbacks as a new experience in Alexandria University. One hundred cases with variable indications for coronary interventions were randomized to two arms using systematic random sampling method, coronary interventions in the first one were done via d-TRA (50 patients) and in the second arm via conventional TRA group (50 patients).

Cryo-EM structure of human Pol κ bound to DNA and mono-ubiquitylated PCNA.

Y-family DNA polymerase κ (Pol κ) can replicate damaged DNA templates to rescue stalled replication forks. Access of Pol κ to DNA damage sites is facilitated by its interaction with the processivity clamp PCNA and is regulated by PCNA mono-ubiquitylation. Here, we present cryo-EM reconstructions of human Pol κ bound to DNA, an incoming nucleotide, and wild type or mono-ubiquitylated PCNA (Ub-PCNA).

Implementing fluorescence enhancement, quenching, and FRET for investigating flap endonuclease 1 enzymatic reaction at the single-molecule level.

Flap endonuclease 1 (FEN1) is an important component of the intricate molecular machinery for DNA replication and repair. FEN1 is a structure-specific 5' nuclease that cleaves nascent single-stranded 5' flaps during the maturation of Okazaki fragments. Here, we review our research primarily applying single-molecule fluorescence to resolve important mechanistic aspects of human FEN1 enzymatic reaction.

Quick and Easy Assembly of a One-Step qRT-PCR Kit for COVID-19 Diagnostics Using In-House Enzymes.

One-step reverse-transcription quantitative polymerase chain reaction (qRT-PCR) is the most widely applied method for COVID-19 diagnostics. Notwithstanding the facts that one-step qRT-PCR is well suited for the diagnosis of COVID-19 and that there are many commercially available one-step qRT-PCR kits in the market, their high cost and unavailability due to airport closures and shipment restriction became a major bottleneck that had driven the desire to produce the key components of such kits locally. Here, we provide a simple, economical, and powerful one-step qRT-PCR kit based on patent-free, specifically tailored versions of Moloney murine leukemia virus reverse transcriptase and DNA polymerase and termed R3T (Rapid Research Response Team) one-step qRT-PCR.

Impact of preoperative SYNTAX Scores on short-term outcome following coronary artery bypass grafting surgery in the patients with multi-vessels coronary artery disease.

Background: SYNTAX Scores I (SSI) assesses the complexity of CAD; SYNTAX Score II (SSII) uses both SSI and other clinical variables, in estimation of 4 years mortality following both coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention (PCI) and gives recommendations for the best revascularization strategy in a specific patient. Our aim is to investigate the impact of both SYNTAX Scores on short-term outcome following CABG.

Results: Prospectively, we studied 150 patients with multi-vessels coronary artery disease, referred to perform, elective primary isolated CABG.

The atrial FibriLlatiOn real World management registry in the Middle East and Africa: design and rationale.

Background: Atrial fibrillation is the most common cardiac arrhythmia, affecting 33.5 million patients globally. It is associated with increased morbidity, leading to significant clinical and economic burden.

Single-Molecule Förster Resonance Energy Transfer Methods for Real-Time Investigation of the Holliday Junction Resolution by GEN1.

Bulk methods measure the ensemble behavior of molecules, in which individual reaction rates of the underlying steps are averaged throughout the population. Single-molecule Förster resonance energy transfer (smFRET) provides a recording of the conformational changes taking place by individual molecules in real-time. Therefore, smFRET is powerful in measuring structural changes in the enzyme or substrate during binding and catalysis.

Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level.

Human GEN1 is a cytosolic homologous recombination protein that resolves persisting four-way Holliday junctions (HJ) after the dissolution of the nuclear membrane. GEN1 dimerization has been suggested to play key role in the resolution of the HJ, but the kinetic details of its reaction remained elusive. Here, single-molecule FRET shows how human GEN1 binds the HJ and always ensures its resolution within the lifetime of the GEN1-HJ complex.

Long-term prognostic implication of coronary plaque characterization as detected by 64-multidetector computed tomography in Egyptian population.

Objectives: We aimed to determine the role of multi-detector computed tomography (MDCT) in prognosis of patients with known or suspected coronary artery disease (CAD) by applying plaque characterization and whether obstructive versus non-obstructive plaque volume is a predictor of future cardiac events.

Background: Vulnerable plaques may occur across the full spectrum of severity of stenosis, underlining that also non-obstructive lesions may contribute to coronary events.

Methods: We included 1000 consecutive patients with intermediate pretest likelihood of CAD who were evaluated by 64-MDCT.

Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.

RNA-DNA hybrid primers synthesized by low fidelity DNA polymerase α to initiate eukaryotic lagging strand synthesis must be removed efficiently during Okazaki fragment (OF) maturation to complete DNA replication. In this process, each OF primer is displaced and the resulting 5'-single-stranded flap is cleaved by structure-specific 5'-nucleases, mainly Flap Endonuclease 1 (FEN1), to generate a ligatable nick. At least two models have been proposed to describe primer removal, namely short- and long-flap pathways that involve FEN1 or FEN1 along with Replication Protein A (RPA) and Dna2 helicase/nuclease, respectively.

Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.

The deep-sea brines of the Red Sea are remote and unexplored environments characterized by high temperatures, anoxic water, and elevated concentrations of salt and heavy metals. This environment provides a rare system to study the interplay between halophilic and thermophilic adaptation in biologic macromolecules. The present article reports the first DNA polymerase with halophilic and thermophilic features.

Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1.

Human flap endonuclease 1 (FEN1) and related structure-specific 5'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage.

Replisome speed determines the efficiency of the Tus-Ter replication termination barrier.

In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region.

The role of 64/128-slice multidetector computed tomography to assess the progression of coronary atherosclerosis.

Objectives: We studied the progression of coronary atherosclerosis over time as detected by multidetector computed tomography (MDCT) in relation to risk factors and plaque composition.

Background: Studies using MDCT are limited to the assessment of the degree of stenosis without taking into consideration the plaque composition that is seen by MDCT.

Methods: This study included 200 patients, complaining of chest pain and referred to do 64/128-contrast-enhanced MDCT for the second time, and both studies were retrieved and evaluated for the presence of plaque, plaque type, vessel wall remodeling, percent area, and diameter stenosis and compared in both studies.

Sequential and multistep substrate interrogation provides the scaffold for specificity in human flap endonuclease 1.

Human flap endonuclease 1 (FEN1), one of the structure-specific 5' nucleases, is integral in replication, repair, and recombination of cellular DNA. The 5' nucleases share significant unifying features yet cleave diverse substrates at similar positions relative to 5' end junctions. Using single-molecule Förster resonance energy transfer, we find a multistep mechanism that verifies all substrate features before inducing the intermediary-DNA bending step that is believed to unify 5' nuclease mechanisms.