Sequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that—when mutated, deficient or improperly functioning—associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the “negative selection” of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies.

Comparing mammalian proteomes for molecular mimicry with infectious pathogens highlights the highest levels of heptapeptide sharing between pathogens and human, murine, and rat proteomes, while the peptide sharing level is minimal (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque. From the medical point of view, the data might be useful to clinicians and vaccinologists to develop and evaluate immunomodulatory and immunotherapeutic approaches. As a matter of fact, primates seem to be unreliable animal models for revealing potential autoimmune events in preclinical testing of immunotherapies. In terms of genomics, the scarce or absent peptide sharing between pathogens and primates versus the massive peptide sharing existing between pathogens and humans lets foresee mechanisms of pathogen sequence insertion/deletion/alteration that have differently operated in mammals over evolutionary timescales. Why and how the human genome has been colonized by pathogen sequences and why and how primates escaped such a colonization appears to be the new scientific challenge in our efforts to understand not only the origin of Homo sapiens but also his autoimmune diseasome.

By examining the issue of the thromboses and hemostasis disorders associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through the lens of cross-reactivity, it was found that 60 pentapeptides are shared by SARS-CoV-2 spike glycoprotein (gp) and human proteins that— when altered, mutated, deficient or, however, improperly functioning— cause vascular diseases, thromboembolic complications, venous thrombosis, thrombocytopenia, coagulopathies, and bleeding, inter alia. The peptide commonality has a relevant immunological potential as almost all of the shared sequences are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes, thus supporting the possibility of cross-reactions between the viral gp and the thromboses-related human proteins. Moreover, many of the shared peptide sequences are also present in pathogens to which individuals have previously been exposed following natural infection or vaccinal routes, and of which the immune system has stored imprint. Such an immunological memory might rapidly trigger anamnestic secondary cross-reactive responses of extreme affinity and avidity, in this way explaining the thromboembolic adverse events that can associate with SARS-CoV-2 infection or active immunization.

Orofacial clefts (OFCs) are the most common congenital birth defects in humans and immediately recognized at birth. The etiology remains complex and poorly understood and seems to result from multiple genetic and environmental factors along with gene-environment interactions. It can be classified into syndromic (30%) and nonsyndromic (70%) clefts. Nonsyndromic OFCs include clefts without any additional physical or cognitive deficits. Recently, various genetic approaches, such as genome-wide association studies (GWAS), candidate gene association studies, and linkage analysis, have identified multiple genes involved in the etiology of OFCs.
This article provides an insight into the multiple genes involved in the etiology of OFCs. Identification of specific genetic causes of clefts helps in a better understanding of the molecular pathogenesis of OFC. In the near future, it helps to provide a more accurate diagnosis, genetic counseling, personalized medicine for better clinical care, and prevention of OFCs.

Infectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present study (1) analyzed the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) described how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) framed human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it was shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics.

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case-control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case-parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case-parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

Recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. To acquire more data on the issue, analyses here have been expanded to Ebola virus, Francisella tularensis, human immunodeficiency virus-1 (HIV-1), Toxoplasma gondii, Variola virus, and Yersinia pestis. Results confirm that heptapeptide overlap is high between pathogens and Homo sapiens, but not between pathogens and primates. Data are discussed in light of the possible genetic bases that differently model primate phenomes, thus possibly underlying the zero/low level of molecular mimicry between infectious agents and primates. Notably, this study might help address preclinical vaccine tests that currently utilize primates as animal models, since autoimmune cross-reactions and the consequent adverse events cannot occur in absentia of shared sequences.

Objectives While DNA profiling has become the principal technique for individualization of biological evidences, ABO blood grouping is still a useful test method in the initial stages of crime investigation. Objectives of the study were blood group determination using slide agglutination method, blood group determination from saliva using absorption inhibition method, and comparison of slide agglutination method with that of absorption inhibition method from saliva sample.
Materials and Methods A total of 60 subjects were taken randomly with their age ranging from 20 to 60 years. Sixty subjects were divided in to two groups, study group and control group. 5 to 10 mL of unstimulated saliva was collected from 60 patients and Wieners agglutination test was performed to detect the secretor status of blood using absorption inhibition method and compared with that of slide agglutination method
Results Out of 60 subjects, 52 subjects showed secretors of antigen in saliva with percentage value of 86.66% and eight subjects were nonsecretors (13.33%). Slightly higher percentage of secretor status was seen in males 84.6 and 88.2% in females.
Conclusion Evaluation of secretor status of blood group antigen from saliva using absorption inhibition method can be useful method in identification of medicolegal cases.

Bone is a specialized form of connective tissue, which is mineralized and made up of approximately 28% type I collagen and 5% noncollagenous matrix proteins. The properties of bone are very remarkable, because it is a dynamic tissue, undergoing constant renewal in response to mechanical, nutritional, and hormonal influences. In 1978, “The International Nomenclature of Constitutional Diseases of Bone” divided bone disorders into two broad groups: osteochondrodysplasias and dysostoses. The osteochondrodysplasia group is further subdivided into two categories: dysplasias (abnormalities of bone and/or cartilage growth) and osteodystrophies (abnormalities of bone and/or cartilage texture). The dysplasias form the largest group of bone disorders, hence the loose term “skeletal dysplasia” that is often incorrectly used when referring to a condition that is in reality an osteodystrophy or dysostosis. The word “dystrophy” implies any condition of abnormal development. “Osteodystrophies,” as their name implies, are disturbances in the growth of bone. It is also known as osteodystrophia. It includes bone diseases that are neither inflammatory nor neoplastic but may be genetic, metabolic, or of unknown origin. Recent studies have shown that bone influences the activity of other organs, and the bone is also influenced by other organs and systems of the body, providing new insights and evidencing the complexity and dynamic nature of bone tissue. The 1,25-dihydroxyvitamin D3, or simply vitamin D, in association with other hormones and minerals, is responsible for mediating the intestinal absorption of calcium, which influences plasma calcium levels and bone metabolism. Diagnosis of the specific osteodystrophy type is a rather complex process and various biochemical markers and radiographic findings are used, so as to facilitate this condition. For diagnosis, we must consider the possibility of lesions related to bone metabolism altered by chronic renal failure (CRI), such as the different types of osteodystrophies, and differentiate from other possible neoplastic and/or inflammatory pathologies. It is important that the dentist must be aware of patients medical history, suffering from any systemic diseases, and identify the interference of the drugs and treatments to control them, so that we can able to perform the correct diagnosis and propose the most adequate treatment and outcomes of the individuals with bone lesions.

Acinetobacter baumannii is a bacterium found in most places, especially in clinics and hospitals, and an important agent of nosocomial infections. The presence of class D enzymes such as OXA-type carbapenemases in A. baumannii is proven to have a key function in resistance to carbapenem. The aim of the current study is to determine the blaOXA_-type carbapenemase genes and antimicrobial resistance among clinically isolated samples of A. baumannii. We assessed 100 clinically isolated specimens of A. baumannii from patients in intensive care units of educational hospitals of Hamadan, West of Iran. The A. baumannii isolates' susceptibility to antibiotics was performed employing disk diffusion method. Multiplex polymerase chain reaction was used to identify the bla_OXA-24-like , bla_OXA-23-like , bla_OXA-58-like , and bla_OXA-51-like genes. The bla_OXA-23-like , bla_{OXA-24-like ,} and bla_OXA-58-like genes' prevalence were found to be 84, 58, and 3%, respectively. The highest coexistence of the genes was for bla_OXA-51/23 (84%) followed by bla_{OXA-51/24-like} (58%). The bla_{OXA-51/23- like} pattern of genes is a sort of dominant gene in resistance in A. baumannii from Hamadan hospitals. The highest resistance to piperacillin (83%) and ciprofloxacin (81%) has been observed in positive isolates of bla_OXA-23-like . The A. baumannii isolates with bla_OXA-58-like genes did not show much resistance to antibiotics. Based on the results of the phylogenetic tree analysis, all isolates have shown a high degree of similarity. This study showed the high frequency of OXA-type carbapenemase genes among A. baumannii isolates from Hamadan hospitals, Iran. Thus, applying an appropriate strategy to limit the spreading of these strains and also performing new treatment regimens are necessary.

The development of craniofacial complex and dental structures is a complex and delicate process guided by specific genetic mechanisms. Genetic and environmental factors can influence the execution of these mechanisms and result in abnormalities. An insight into the mechanisms and genes involved in the development of orofacial and dental structures has gradually gained by pedigree analysis of families and twin studies as well as experimental studies on vertebrate models. The development of novel treatment techniques depends on in-depth knowledge of the various molecular or cellular processes and genes involved in the development of the orofacial complex. This review article focuses on the role of genes in the development of nonsyndromic orofacial, dentofacial variations, malocclusions, excluding cleft lip palate, and the advancements in the field of molecular genetics and its application to obtain better treatment outcomes.

One of the significant consequences of alcohol consumption is cancer formation via several contributing factors such as action of alcohol metabolites, vitamin deficiencies, and oxidative stress. All these factors have been shown to cause epigenetic modifications via DNA hypomethylation, thus forming a basis for cancer development. Several published reviews and studies were systematically reviewed. Omnivores and vegetarians differ in terms of nutritional intake and deficiencies. As folate deficiency was found to be common among the omnivores, chronic alcoholism could possibly cause damage and eventually cancer in an omnivorous individual via DNA hypomethylation due to folate deficiency. Furthermore, as niacin was found to be deficient among vegetarians, damage in vegetarian chronic alcoholics could be due to increased NADH/NAD⁺ ratio, thus slowing alcohol metabolism in liver leading to increased alcohol and acetaldehyde which inhibit methyltransferase enzymes, eventually leading to DNA hypomethylation. Hence correcting the concerned deficiency and supplementation with S-adenosyl methionine could prove to be protective in chronic alcohol use.

Objectives Age estimation in forensic odontology is having a great importance in recent times because of the request by court or other government authorities so that immigrants whose real age is unknown should not suffer unfair disadvantages because of their supposed age, and so that all legal procedures to which an individual's age is relevant can be properly followed.
Purpose The present study was planned to be conducted on pulp tissue and dental hard tissues derived from individuals for DNA isolation and age determination .
Materials and Methods The present study was an experimental single-blinded study consisting of 30 extracted teeth categorized into three groups as follows: Group A: 10 to 20 years, Group B: 21 to 30 years, Group C: 31 to 40 years. DNA was isolated from the pulp of each tooth and quantitative polymerase chain reaction (qPCR) for calculating telomere length was performed.
Results With increase in age, the length of telomere gets shortened which will be helpful in analyzing the age of the person when morphological and biological remnants are not available except the tooth.
Conclusion The present study found that estimation of human age based on the relative TL measured by the real-time quantitative PCR may be a useful method for age prediction, especially when there is no morphologic information in the biological sample. This is the first study to accesses the age of a person by telomere length using dental pulp.

Background and Aim Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can—via molecular mimicry and the consequent cross-reactivity—also hit human proteins involved in infantile diseases.
Methods Human proteins that—if altered—associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena.
Results Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible.
Conclusion Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela.

Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis.
Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies.
Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories.
Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants.
Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

The prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.
In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

Background Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died following SARS-CoV-2 infection. This raises the question of the causes of the virus-induced immune immunosuppression. Searching for molecular link(s) between SARS-CoV-2 immunization and the decay of the adaptive immune responses, SARS-CoV-2 proteome was analyzed for molecular mimicry with human proteins related to immunodeficiency. The aim was to verify the possibility of cross-reactions capable of destroying the adaptive immune response triggered by SARS-CoV-2.
Materials and Methods Human immunodeficiency-related proteins were collected from UniProt database and analyzed for sharing of minimal immune determinants with the SARS-CoV-2 proteome.
Results Molecular mimicry and consequent potential cross-reactivity exist between SARS-CoV-2 proteome and human immunoregulatory proteins such as nuclear factor kappa B (NFKB), and variable diversity joining V(D)J recombination-activating gene (RAG).
Conclusion The data (1) support molecular mimicry and the associated potential cross-reactivity as a mechanism that can underlie self-reactivity against proteins involved in B- and T-cells activation/development, and (2) suggest that the extent of the immunosuppression is dictated by the extent of the immune responses themselves. The higher the titer of the immune responses triggered by SARS-CoV-2 immunization, the more severe can be the cross-reactions against the human immunodeficiency-related proteins, the more severe the immunosuppression. Hence, SARS-CoV-2-induced immunosuppression can be defined as a molecular mimicry syndrome. Clinically, the data imply that booster doses of SARS-CoV-2 vaccines may have opposite results to those expected.

This study shows that oligonucleotide sequences are shared between the human genome and primers that have been proposed/used for SARS-CoV-2 detection by polymerase chain reaction (PCR). The high level of sharing (namely, up to 19mer with a maximum number of gaps equal to 2) might bear implications for the diagnostic validity of SARS-CoV-2 detection by PCR.

Background Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm with features of the myelodysplastic syndromes (MDSs) and myeloproliferative neoplasm presenting with peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia, while the abnormal DNA methylation plays a critical role in the pathogenesis of MDS, which is a disease of disordered differentiation. Recently, with the rapid development of molecular biology, hypomethylating agents (HMAs) for the treatment of MDS has gradually become a research focus. The objective of this study was to evaluate the benefits and risks of HMAs for patients with CMML.
Materials and Methods PubMed, Embase, the Cochrane Library, and three Chinese databases were searched for studies published before November 2020 that used HMAs in CMML.
Results The pooled objective response rate (ORR), complete response (CR), and partial response (PR) were 50.0, 21.0, and 2.0%, respectively. The proportion of patients with minor response (MR) was significantly higher for decitabine (DAC) than for azacitidine (AZA). There was no significant difference in hematologic improvement, ORR, CR, and PR rates between the DAC and AZA groups. Hematological toxicity included neutropenia grade 3/4 (14.0%), anemia grade 3/4 (17.0%), and thrombocytopenia grade 3/4 (22.0%).
Conclusion This study showed that HMAs were effective and safe in the treatment of CMML, but large multicenter study would be needed to confirm the efficacy of HMAs for the treatment of CMML with different risk level and genetic abnormality, to support individualization treatment theoretically.

Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells against reactive species. The most common PON1 Q192R and L55M polymorphisms are responsible for a wide variation of PON1 activity, which showed an up to 13-fold interindividual variation among the same genotype. PON1 genotypes were evaluated with the development of pancreatitis, colorectal cancer, and hypothyroidism in a hospital-based, case-control study. Individuals with rs662 G allele had a two-fold risk of developing hypothyroidism. A weak association was found between rs854560 T allele and pancreatitis. The results were preliminary. Further studies with a larger number and detailed biochemical parameters are needed.