Overview: Cellular plasticity,cancer stem cells and metastasis

Recently, a number of hypotheses have converged into a unified theoretical framework which addresses the most vexing aspects of cancer: metastasis, relapse and therapeutic resistance. The central component of this framework is the new paradigm of cellular differentiation, once viewed as a unidirectional process, but now recognized as a plastic process in which cancer cells can dedifferentiate into more primitive, stem-like phenotypes. This plasticity is controlled by both intrinsic biochemical processes and bi-directional environmental cues involving cancer-associated non-cancerous cells. Such plastic phenotypic shifts may influence the discontinuous behavior of cancers, in which some cancers remain dormant for months or years after therapy, only to relapse and wreak havoc. This Special Issue of Cancer Letters assembles a collection of mini-reviews describing the current knowledge of cellular plasticity and its relationship to cancer “stemness” and progression, illuminating how progress in this field may yield major benefits in overcoming resistance and thwarting metastasis.     

SARS-CoV-2 Genetic Diversity and Lineage Dynamics in Egypt during the First 18 Months of the Pandemic

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.     

Structural,Thermal and Magnetic Analysis of Two Fe-X-B (X = Nb,NiZr) Nanocrystalline Alloy

High-energy ball milling was used to produce two Fe-X-B (X = Nb, NiZr) nanocrystalline alloys. X-ray diffraction (XRD), differential scanning calorimetry (DSC), and vibrating sample magnetometry (VSM) were used to analyze the microstructure, thermal, and magnetic characteristics of the milled powders, the agglomerated particles (also generated during the milling process), and the compacted specimens of both alloys. The main crystallographic phase is always a bcc Fe-rich solid solution; whereas a minor Nb(B) phase is detected on powders and agglomerated particles in the Fe₈₀Nb₈B₁₂ alloy. The crystalline size of the Fe₈₀(NiZr)₈B₁₂ alloy is between 11 and 14 nm, whereas in the Fe₈₀Nb₈B₁₂ alloy, it ranges between 8 and 12 nm. Microstrain and dislocation density are higher in agglomerated samples for both alloys than in milled powders. Thermal analysis detects structural relaxation and crystal growth exothermic processes with high dispersion in the temperature intervals and in the calculated apparent activation energy of the main crystallization process. Regarding magnetic behavior, the coercivity values of all powdered-agglomerated specimens were around 800 A/m. The coercivity is higher in compacted sample, but controlled annealing favors enhanced soft behavior.     

Assessment of family physicians' knowledge about fibromyalgia in Egypt

Aim of the workTo assess knowledge of Egyptian family physicians about the diagnostic criteria and treatment modalities of fibromyalgia.Subjects and methodsA questionnaire and an informed consent were sent by email to family physicians working in primary health care centers in Egypt. The questionnaire assessed 3 areas: sociodemographic and professional data; knowledge about diagnosis; and knowledge about treatment modalities. Scoring system was used to categorize levels of knowledge into very low, low, moderate, high and very high.ResultsA total of 108 family physicians responded, with a response rate of 60%.The respondents were 27 consultants, 54 specialists and 27 residents, with a median age of 33 years and a median experience of 12 years. Very low, low and moderate levels of familiarity with fibromyalgia were perceived by 28.7%, 30.6% and 28% respectively. Close to half of participants (46.2%) gained their knowledge about fibromyalgia through self-study. According to the scoring system, 39.8% had low level of knowledge about clinical presentation and 37% had the same level of knowledge about treatment modalities. About three quarters (76%) of participants agreed that patients with fibromyalgia should be referred to rheumatologists. The most common selected clinical presentations were widespread pain (94.4%) and excessive fatigue (91.7%), while the most selected treatment modalities were non-steroidal anti-inflammatory drugs (89.8%) and selective serotonin reuptake inhibitors (47.2%).ConclusionKnowledge about clinical presentation and treatment modalities of fibromyalgia among Egyptian family physicians is low. Continuing medical education about fibromyalgia is needed to improve quality of health care.     

The immunological axis in heart failure: importance of the leukocyte differential

The important role of the immune system and inflammation in the pathophysiology of heart failure (HF) is becoming increasingly appreciated. We have reviewed the prognostic significance of under-recognized aspects of the leukocyte differential in HF, including lymphocytes, monocytes, eosinophils and mast cells. Studies to date evaluating lymphocyte counts in both chronic and hospitalized HF patients have consistently shown worse prognosis associated with low lymphocyte counts, despite widely heterogeneous study designs. Limited data suggest elevations in monocyte-derived cytokines and serum monocyte count may be predictive of poor outcomes in HF. Further data are required to better define the relationship between eosinophils, mast cells and HF. Leukocyte differentials are widely available, simple, inexpensive and appear to have independent prognostic significance, beyond traditional risk factors. Enhanced sympathetic activation and increased circulating cytokine levels (particularly tumor necrosis factor) have been implicated in the variability of leukocyte subpopulations. To date, immune-modulators targeting these mediators have been largely unsuccessful in improving cardiovascular outcomes in HF. Given the potential role of the immunological axis in HF, there may be an unmet need for novel therapeutic agents that can safely and effectively ameliorate these leukocyte derangements and perhaps improve the unacceptably high event rate in this population. Variations in leukocyte differentials may identify a high-risk subset of patients that may benefit from tailored immune therapies.     

Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C

Hereditary hemorrhagic telangiectasia is a group of autosomal dominant disorders, characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Currently, there is no satisfactory treatment of hereditary hemorrhagic telangiectasia. Interferon has never been used for the treatment of hereditary hemorrhagic telangiectasia. In this case, we report disappearance of hereditary hemorrhagic telangiectasia lesions after 12 months of treatment with interferon-alpha for chronic hepatitis C. Further studies are warranted to evaluate its role and potential use in the treatment of hereditary hemorrhagic telangiectasia.