More than the SRY: The Non-Coding Landscape of the Y Chromosome and Its Importance in Human Disease.

Historically, the Y chromosome has presented challenges to classical methodology and philosophy of understanding the differences between males and females. A genetic unsolved puzzle, the Y chromosome was the last chromosome to be fully sequenced. With the advent of the Human Genome Project came a realization that the human genome is more than just genes encoding proteins, and an entire universe of RNA was discovered. This dark matter of biology and the black box surrounding the Y chromosome have collided over the last few years, as increasing numbers of non-coding RNAs have been identified across the length of the Y chromosome, many of which have played significant roles in disease. In this review, we will uncover what is known about the connections between the Y chromosome and the non-coding RNA universe that originates from it, particularly as it relates to long non-coding RNAs, microRNAs and circular RNAs.

Bridging frontiers: The role of a Global Breast Research Working Group.

Breast cancer remains a significant cause of death for women globally, despite advancements in detection and treatment, low- and middle-income countries face unique obstacles. Role of Research Working Group (RWG) can expedite research progress by fostering collaboration between scientists, clinicians, and stakeholders. Benefits of a Global RWG include pooling resources and expertise to develop new research ideas, addressing disparities, and building local research capacity, with the potential to improve breast cancer research and outcomes.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

Global research on centenarians: A historical and comprehensive bibliometric analysis from 1887 to 2023.

Background: Centenarians are considered the most successful human biological aging model. However, the characteristics and patterns of research among centenarians have not been described or analyzed. Thus, this study aimed to disclose the historical landscape of global research on centenarians. Methods: This bibliometric study investigated historical evidence on centenarian research published in the Scopus database. The bibliometrix package in R was used to perform visual and quantitative analyses of research metrics, trends, and patterns. Results: Of the 2061 documents included between 1887 and 2023, 84.2% (n = 1736) were published as articles with primary data. We identified international collaboration and annual growth rates of 21.4% and 3.15%, respectively. The United States published the highest number of papers on centenarians (n = 786), whereas the publications from Italy had the highest impact (h-index = 90). Based on the frequency of keywords, mortality, genetics, dementia, Alzheimer's disease, and immunosenescence are a few of the most studied topics among centenarians, with emerging research related to mitochondrial DNA and comparison of results between nonagenarians and centenarians. Italy, the United States, and China lead the global research collaboration network, collaborating most frequently with Japan and European countries. Conclusions: Global research on centenarians has grown over the last 20 years, primarily led by Italy, the United States, and China. Latin American and African countries have conducted little or no research on centenarians. The most widely studied topics include mortality, cognition, immunosenescence, and genetics.

Autoimmunity in centenarians. A paradox.

Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.

On the Edge of Psychopathology: Strong Relations Between Reversed Self-compassion and Symptoms of Anxiety and Depression in Young People.

Self-compassion is assumed to have a protective role in the etiology of emotional problems in adolescents. This assumption is primarily based on correlational data revealing negative correlations between the total score on the Self-Compassion Scale (SCS) and symptom measures of anxiety and depression. Recently, however, the SCS has been criticized because this scale not only consists of items measuring compassionate self-responding (i.e., self-kindness, common humanity, and mindfulness), but also includes 'reversed' items measuring uncompassionate self-responding (i.e., self-criticism, isolation, and overidentification), which would undermine the validity of the scale as an index of a protective construct. The present article used two methods to demonstrate that compassionate (positive) and uncompassionate (negative) self-responding have differential effects on emotional problems in youths. In the first part, a meta-analysis based on 16 relevant studies demonstrated a modest protective effect of positive self-compassion on anxiety/depression and a large (and significantly stronger) vulnerability effect of negative self-compassion on such emotional symptoms. In the second part, network analyses were conducted on three previously collected data sets and these analyses again showed that negative self-compassion is more closely connected to young people's symptoms of anxiety and depression than positive self-compassion. It is argued that the observed differential effects should not be discarded as a subversive fallacy, but rather offer an opportunity for studying the role of self-compassion in adolescents' emotional psychopathology in a more sophisticated way, taking into account both protection and vulnerability.

Historical evolution of cancer genomics research in Latin America: a comprehensive visual and bibliometric analysis until 2023.

Background: Cancer genomics, as an interdisciplinary research area within the Global Cancer Research agenda, genomics and precision medicine, its important in research and clinical practice in Latin America. To date, there has been no study investigating evolution of this area in this region. The aim of this study was to evaluate for first time, the historical evolution of cancer genomics research in Latin America. Methods: Bibliometric cross-sectional study of documents on cancer genomics published by Latin American authors until 2023 in Scopus was performed. Statistical and visual analysis was performed with R programming language. Results: A total of 1534 documents were obtained. The first document of cancer genomics research was published in 1997, marking the inception of a 26-year evaluation period that extended until 2023. Among the documents, 74.3% (n = 1140) constituted original articles, followed by 22.7% (n = 349) classified as reviews. International collaboration was observed in 6.5% (n = 100) of the articles. Within the compilation of the ten most prolific authors in this region, 90% of them are from Brazil. This observed pattern extends to affiliations as well, wherein the Universidade de São Paulo emerges as the most active institution (n = 255 documents). This arrangement firmly establishes Brazil's prominence as the preeminent country in the region concerning cancer genomics research, showcasing robust collaboration networks both regionally and intercontinentally. An important transition in the studied hot topics over the last 20 years was identified, from the exploration of the human genome and the characterization of genomic and proteomic cancer profiles (1997-2010) to an in-depth investigation of cancer stem cells and personalized medicine (2011-2023). Among the array of cancer types under study, predominant attention has been directed towards breast, lung, prostate, and leukemia. Conclusion: Over the course of the past 26 years, a favorable and notable evolution has characterized cancer genomics research within Latin America, with Brazil leading the way, which possess a robust network of regional and intercontinental collaboration. Furthermore, the lines of research and hot topics have change in harmony with the region's objectives, strategies, and requisites.

Genetic Variants Associated with Suicide Risk in the Mexican Population: A Systematic Literature Review.

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4, SAT-1, TPH-2, ANKK1, GSHR, SCARA50, RGS10, STK33, COMT, and FKBP5. This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.

Knowledge and attitudes of health professionals in Chile towards people living with human immunodeficiency virus: A cross-national survey.

Introduction: People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often experience discrimination from both other individuals and the health personnel who care for them. Chile has experienced a marked increase in the number of new HIV cases.Methods: Prospective cross-sectional study. The HIV/AIDS questionnaire for providers and health personnel was obtained from the International Planned Parenthood Federation, initially carrying out a pilot test and evaluating its validity.Results: A total of 784 health professionals answered the questionnaire correctly. Among them, 68.4% (n = 536) were women, and 36.2% (n = 284) were physicians. The study revealed that more than 90% of respondents had a positive attitude towards caring for people living with HIV, and more than 75% did not mind buying food from them or sharing services with them. Furthermore, more than 99% rejected the religiously endorsed labeling of people living with HIV/AIDS as immoral. Additionally, 95.5% (n = 749) mentioned that they did not feel anxious about knowing whether the next patient on their care list was living with HIV, and 76.9% (n = 603) of the respondents felt safe taking blood samples.Conclusions: Chilean health professionals have good knowledge about HIV infection and its mode transmission. Their attitudes towards people living with HIV are also generally positive.

Descripción de 4 casos: tumor desmoide de la mama, diagnóstico y manejo de un tumor infrecuente / Description of four cases: desmoid tumor of the breast, diagnosis and management of a rare tumor

Introducción: el tumor desmoide (TD) de la mama es una lesión poco frecuente constituida por proliferación de células fibroblásticas. Puede localizarse a nivel intra o extraabdominal y la localización mamaria es excepcional. Aunque es una lesión benigna tiene un comportamiento localmente agresivo sin metástasis ganglionar o a distancia. Su etiología es desconocida y entre el 10 y 20% de los casos están relacionados con la poliposis adenomatosa familiar. Se presenta como un nódulo sólido de nueva aparición e indoloro. El tratamiento clásicamente ha sido la resección quirúrgica, con elevadas tasas de recurrencia a pesar de márgenes libres. Otras terapias están siendo estudiadas. Nuestro objetivo es revisar el manejo del TD de la mama a través del análisis de la casuística en nuestro centro en los últimos 10 años y la revisión de las evidencias disponibles. Métodos: análisis descriptivo retrospectivo. Los casos se identificaron empleando el sistema de explotación de la información del hospital. Se realizó una revisión narrativa de la literatura. Resultados: nuestra serie consta de 4 casos, mujeres de entre 36 y 66 años. Tres de ellas consultaron por nódulo palpable. La BAG presentó hallazgos compatibles con un TD. Los casos fueron presentados en un comité multidisciplinar y se propuso una resección quirúrgica amplia. La AP confirmó el diagnóstico y en uno de los casos informó de márgenes afectos. Durante el seguimiento se evidenció recidiva en dicho caso. Conclusiones: los TD son tumores infrecuentes, de repercusión clínica y respuesta al tratamiento variable. Este debe incluir la opción expectante y, en cualquier caso, individualizarse y consensuarse dentro de una perspectiva multidisciplinar. (AU)

Introduction: The desmoid tumor (DT) of the breast is a rare lesion consisting of proliferation of fibroblastic cells. It can be located intra- or extra-abdominally and the mammary location is exceptional. Although it is a benign lesion, it has a locally aggressive behavior without lymph node or distant metastasis. Its etiology is unknown and 10–20% of cases are related to familial adenomatous polyposis. It presents as a new, painless solid nodule. The treatment has traditionally been surgical resection, with high rates of recurrence despite free margins. Other therapies are being studied. Our objective is to review the management of DT of the breast through the analysis of the casuistry in our center in the last 10 years and the review of the available evidence. Methods: Retrospective descriptive analysis. The cases were identified using the hospital information exploitation system. A narrative review of the literature was performed. Results: Our series consists of 4 cases, women between 36 and 66 years old. Three of them consulted for a palpable nodule. The CNB presented findings compatible with DT. The cases were presented to a multidisciplinary committee and a wide surgical resection was proposed. The AP confirmed the diagnosis and in one of the cases reported affected margins. During follow-up, recurrence was observed in this case. Conclusions: DTs are infrequent tumors, with clinical repercussions and variable response to treatment. This must include the expectant option and, in any case, be individualized and agreed upon within a multidisciplinary perspective. (AU)

Relationship between Duffy Genotype/Phenotype and Prevalence of Plasmodium vivax Infection: A Systematic Review.

The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Plasmodium Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against Plasmodium vivax infection. However, recent studies suggest that this microorganism's evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of P. vivax infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and P. vivax invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with P. vivax. In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of P. vivax infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria.

CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells.

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of ΔOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.

Formulation and optimization of polymeric nanoparticles loaded with riolozatrione: a promising nanoformulation with potential antiherpetic activity.

Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the Jatropha dioica root. This compound has been shown to possess moderate antiherpetic activity in vitro. However, because of the poor solubility of this compound in aqueous vehicles, generating a stable formulation for potential use in the treatment of infection is challenging. The aim of this work was to optimize and physio-chemically characterize Eudragit® L100-55-based polymeric nanoparticles (NPs) loaded with RZ (NPR) for in vitro antiherpetic application. The NPs formulation was initially optimized using the dichloromethane extract of J. dioica, the major component of which was RZ. The optimized NPR formulation was stable, with a size of 263 nm, polydispersity index < 0.2, the zeta potential of -37 mV, and RZ encapsulation efficiency of 89 %. The NPR showed sustained release of RZ for 48 h with release percentages of 95 and 97 % at neutral and slightly acidic pH, respectively. Regarding in vitro antiherpetic activity, the optimized NPR showed a selectivity index for HSV-1 of ≈16 and for HSV-2 of 13.

Evolution of Plasmodium vivax and resistance patterns for infection based on Duffy genotype and phenotype.

The Duffy protein, a transmembrane molecule, acts as a receptor for various chemokines and facilitates binding between reticulocytes and the Plasmodium Duffy antigen binding protein. Duffy expression is associated with the Duffy chemokine receptor antigen genotype on chromosome 1 and exhibits variation across different geographic regions. Traditionally, the Duffy negative genotype and phenotype have been described to confer a certain level of protection against infection and symptom development. However, recent data suggest a shift in this behavior, with significantly higher prevalence observed in individuals with Duffy negative genotype or phenotype. Given that malaria is an endemic vector-borne disease in regions of Asia, Africa, and Latin America, posing a substantial global burden of disease and prioritizing public and global health, identifying evolutionary changes in infection and resistance patterns holds great importance for the design of strategies and reevaluation of conventional interventions. Hence, the aim of this review was to analyze the evolution of Plasmodium vivax and infection resistance patterns based on Duffy genotype and phenotype. The distribution of genotypes, phenotypes, and polymorphisms of P. vivax ligands and erythrocyte receptors varies geographically, notably resistance patterns of this microorganism in individuals with Duffy negative genotype and phenotype have significantly changed compared to studies conducted 30 years ago. The prevalence of vivax malaria in individuals with a Duffy negative status can reach up to 100%. Consequently, prioritizing research on this topic is essential for public health.