The association between HIV-related stigma, HIV knowledge and HIV late presenters among people living with HIV (PLHIV) attending public primary care clinic settings in Selangor.

INTRODUCTION: HIV late presenters were defined as individuals presenting with a CD4 count below 350 cells/µL or with an AIDS-defining event, according to the European Late Presenter Consensus working group. Early diagnosis and treatment of HIV have proven beneficial for people living with HIV (PLHIV), reducing the burden on healthcare systems, and contributing to ending the HIV/AIDS epidemic. However, in Malaysia, over 50% of newly diagnosed HIV patients present late, leading to increased morbidity and premature mortality. This study aims to determine the prevalence of late HIV presenters and its association with HIV-related stigma and HIV knowledge among PLHIV attending public primary care clinics in Selangor. METHODS: A cross-sectional study was conducted at selected public health clinics in Selangor, involving PLHIV aged 18 years and older, who were diagnosed since 2019. HIV-related stigma was measured using the Malay version of Berger's HIV Stigma Scale, and HIV knowledge was assessed using the Malay version of Brief HIV-KQ-18. Univariate and multivariate logistic regression analyses were performed to identify factors associated with late HIV presentation. RESULTS: A total of 400 participants were included in the study, with 60.0% (n = 240, 95% CI: 55.0-65.0) classified as late presenters. The participants had a mean age of 30.29 (±7.77) years. The risk factors for late presenters were high levels of HIV-related stigma (aOR = 1.049, 95% CI: 1.034-1.063, p-value <0.001), low levels of HIV knowledge (aOR = 0.709, 95% CI: 0.646-0.778, p-value <0.001), tertiary education background (aOR = 15.962, 95% CI: 1.898-134.235, p-value = 0.011), and being single (aOR = 3.582, 95% CI: 1.393-9.208, p-value = 0.008). CONCLUSION: This study highlights the association between high levels of HIV-related stigma, low levels of HIV knowledge, and late HIV presentation. Interventions targeting stigma reduction and HIV education can promote early testing and prompt access to care, improving health outcomes for PLHIV.

Exosomes in Osteoarthritis: A Review on Their Isolation Techniques and Therapeutic Potential.

Background: Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA) involves exosomes carrying complex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords "Exosomes" and "Osteoarthritis". Relevant articles in the last 15 years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded. Results: Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures across various body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation. Conclusion: The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain a balance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.

A novel deep learning framework for accurate melanoma diagnosis integrating imaging and genomic data for improved patient outcomes.

BACKGROUND: Melanoma is one of the most malignant forms of skin cancer, with a high mortality rate in the advanced stages. Therefore, early and accurate detection of melanoma plays an important role in improving patients' prognosis. Biopsy is the traditional method for melanoma diagnosis, but this method lacks reliability. Therefore, it is important to apply new methods to diagnose melanoma effectively. AIM: This study presents a new approach to classify melanoma using deep neural networks (DNNs) with combined multiple modal imaging and genomic data, which could potentially provide more reliable diagnosis than current medical methods for melanoma. METHOD: We built a dataset of dermoscopic images, histopathological slides and genomic profiles. We developed a custom framework composed of two widely established types of neural networks for analysing image data Convolutional Neural Networks (CNNs) and networks that can learn graph structure for analysing genomic data-Graph Neural Networks. We trained and evaluated the proposed framework on this dataset. RESULTS: The developed multi-modal DNN achieved higher accuracy than traditional medical approaches. The mean accuracy of the proposed model was 92.5% with an area under the receiver operating characteristic curve of 0.96, suggesting that the multi-modal DNN approach can detect critical morphologic and molecular features of melanoma beyond the limitations of traditional AI and traditional machine learning approaches. The combination of cutting-edge AI may allow access to a broader range of diagnostic data, which can allow dermatologists to make more accurate decisions and refine treatment strategies. However, the application of the framework will have to be validated at a larger scale and more clinical trials need to be conducted to establish whether this novel diagnostic approach will be more effective and feasible.

Stringent criteria needed for germline genome editing of human IVF embryos.

Germline genome editing of IVF embryos is controversial because it is not directly health or lifesaving but is intended to prevent genetic diseases in yet-unborn future offspring. The following criteria are thus proposed for future clinical trials: (i) Due to medical risks, there should be cautious and judicious application while avoiding any non-essential usage, with rigorous patient counseling. (ii) Genome editing should only be performed on the entire batch of IVF embryos without initial PGT screening if all of them are expected to be affected by genetic disease. (iii) When there is a fair chance that some IVF embryos will not be affected by genetic diseases, initial PGT screening must be performed to identify unaffected embryos for transfer. (iv) IVF embryos with carrier status should not undergo germline genome editing. (v) If patients fail to conceive after the transfer of unaffected embryos, they should undergo another fresh IVF cycle rather than opt for genome editing of their remaining affected embryos. (vi) Only if the patient is unable to produce any more unaffected embryos in a fresh IVF cycle due to advanced maternal age or diminished ovarian reserves, can the genome editing of remaining affected embryos be permitted as a last resort.

The Relationship Between Self-Efficacy and Functional Capacity Among Discharged Heart Failure Patients in Jordan.

BACKGROUND: Self-efficacy is an important factor associated with healthy lifestyle changes in heart failure treatment. Functional capacity testing of heart failure patients (HFPs) can stratify prognosis. Reduced functional capacities in HFPs are linked to a poor heart failure prognosis. Limited research has examined the potential relationship between self-efficacy and functional capacity. AIM: The aims of this study were to assess self-efficacy level and functional capacity among HFPs after hospitalization, and examine whether there is a relationship between them. METHODS: A descriptive correlational design was used. A convenience sample of 220 HFPs was recruited from 2 hospitals in Jordan. The Arabic version of Cardiac Self-Efficacy Questionnaire was used to assess self-efficacy, the 6-Minute Walking Test (6-MWT) was used to assess functional capacity, and the Borg rating of perceived exertion scale (Borg Scale) was used to assess exertion during 6-MWT. RESULT: The sample included 46.8% male (n = 103) and 53.2% female (n = 117). The mean age was 52.66 ± 8.91 years. Most of the HFPs were categorized based on New York Heart Association classification as class I, 35.9% (n = 79), and class II, 41.4% (n = 91). The mean ejection fraction was 41.46 ± 9.44. The global self-efficacy was moderate (32.98 ± 9.92), and the mean score for the 6-MWT was 494.35 ± 143.37. The Borg Scale mean was 10.94 ± 3.34. In addition, there was a positive relationship between self-efficacy and 6-MWT (r = 0.63, n = 220, P = .01). CONCLUSION: This study provides baseline data for further research on treatment of HFPs, and the development of evidence-based tailored health interventions to maintain and improve self-efficacy and functional capacity among these service users. Moreover, replicated researches can test the study results considering different methodologies, such as using objective functional capacity tool and longer follow-up periods.

Are we eating plastic? Science mapping of microplastic pollution in the aquatic food chain.

This study evaluates the knowledge structure of microplastic pollution and its effects on the aquatic food chain. The presence of microplastics has seriously harmed the ecosystem. Through bibliometric analysis, 216 journal publications were retrieved from the Web of Science (WoS) from 2008 to 2023 (April), with no restriction in the time frame. Applying bibliographic coupling and co-word analysis, the emerging, current, and future themes of microplastic pollution are presented. Three research streams are derived from bibliographic coupling, centralized on the source of microplastic pollution and its impact. At the same time, research streams from co-word analysis are associated with overcoming the issue of microplastics in the ecosystem. This study's implications suggest three main principles to mitigate microplastic issues: (1) educating the public on the impact of microplastic pollution, (2) implementing holistic regulations and policies, and (3) developing treatment strategies through conventional, innovative, and hybrid approaches. Microplastic pollution is a global concern, requiring a holistic and comprehensive approach to overcome it. This review is the first to present a scientific mapping of the microplastics literature, which is a fundamental basis for future research on microplastic pollution and its impact on the ecosystem. Integr Environ Assess Manag 2024;00:1-12. © 2024 SETAC.

Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach.

The impact of H. pylori resistance on patient's treatment failure is a major concern. Therefore, the development of novel or alternative therapies for H. pylori is urgently needed. The purpose of this study was to investigate the molecular interactions of various antimicrobial peptides (AMPs) to H. pylori proteins. We performed the peptide-protein molecular docking using HADDOCK 2.4 webserver. Fourteen AMPs were tested for their binding efficacy against four H. pylori proteins. Simulation of the peptide-protein complex was performed using molecular dynamic software package AMBER20. From molecular docking analysis, five peptides (LL-37, Tilapia piscidin 4, napin, snakin-1 and EcAMP1) showed strong binding interactions against H. pylori proteins. The strongest binding affinity was observed in the interactions between Snakin-1 and PBP2, TP4 and type I HopQ and EcAMP1 and type I HopQ with -11.1, -13.6 and -13.8 kcal/mol, respectively. The dynamic simulation was performed for two complexes (snakin1-PBP2 and EcAMP1-HopQ). Results of the dynamics simulation showed that EcAMP1 had stable interaction and binding to type I HopQ protein without significant structural changes. In conclusion, both results of docking and simulation showed that EcAMP1 might be useful as a potential therapeutic agent for H. pylori treatment. This molecular approach provides deep understanding of the interaction insights between AMPs and H. pylori proteins. It paves the way for the development of novel anti-H. pylori using antimicrobial peptides.

Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.

The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.

ZBP1 activation triggers hematopoietic stem and progenitor cell death resulting in bone marrow failure in mice.

Human bone marrow failure (BMF) syndromes result from the loss of hematopoietic stem and progenitor cells (HSPC), and this loss has been attributed to cell death; however, the cell death triggers, and mechanisms remain unknown. During BMF, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) increase. These ligands are known to induce necroptosis, an inflammatory form of cell death mediated by RIPK1, RIPK3, and MLKL. We previously discovered that mice with a hematopoietic RIPK1 deficiency (Ripk1HEM KO) exhibit inflammation, HSPC loss, and BMF, which is partially ameliorated by a RIPK3 deficiency; however, whether RIPK3 exerts its effects through its function in mediating necroptosis or other forms of cell death remains unclear. Here, we demonstrate that similar to a RIPK3 deficiency, an MLKL deficiency significantly extends survival and like Ripk3 deficiency partially restores hematopoiesis in Ripk1HEM KO mice revealing that both necroptosis and apoptosis contribute to BMF in these mice. Using mouse models, we show that the nucleic acid sensor Z-DNA binding protein 1 (ZBP1) is up-regulated in mouse RIPK1-deficient bone marrow cells and that ZBP1's function in endogenous nucleic acid sensing is necessary for HSPC death and contributes to BMF. We also provide evidence that IFNγ mediates HSPC death in Ripk1HEM KO mice, as ablation of IFNγ but not TNFα receptor signaling significantly extends survival of these mice. Together, these data suggest that RIPK1 maintains hematopoietic homeostasis by preventing ZBP1 activation and induction of HSPC death.

Identification of common candidate genes and pathways for Spina Bifida and Wilm's Tumor using an integrative bioinformatics analysis.

Spina Bifida (SB) and Wilm's Tumor (WT) are conditions, both associated with children. Several studies have shown that WT later develops in SB patients, which led us to elucidate common key genes and linked pathways of both conditions, aimed at their concurrent therapeutic management. For this, integrated bioinformatics analysis was employed. A comprehensive manual curation of genes identified 133 and 139 genes associated with SB and WT, respectively, which were used to construct a single protein-protein interaction (PPI) network. Topological parameters analysis of the network showed its scale-free and hierarchical nature. Centrality-based analysis of the network identified 116 hubs, of which, 6 were called the key genes attributed to being common between SB and WT besides being the hubs. Gene enrichment analysis of the 5 most essential modules, identified important biological processes and pathways possibly linking SB to WT. Additionally, miRNA-key gene-transcription factor (TF) regulatory network elucidated a few important miRNAs and TFs that regulate our key genes. In closing, we put forward TP53, DICER1, NCAM1, PAX3, PTCH1, MTHFR; hsa-mir-107, hsa-mir-137, hsa-mir-122, hsa-let-7d; and YY1, SOX4, MYC, STAT3; key genes, miRNAs and TFs, respectively, as the key regulators. Further, MD simulation studies of wild and Glu429Ala forms of MTHFR proteins showed that there is a slight change in MTHFR protein structure due to Glu429Ala polymorphism. We anticipate that the interplay of these three entities will be an interesting area of research to explore the regulatory mechanism of SB and WT and may serve as candidate target molecules to diagnose, monitor, and treat SB and WT, parallelly.Communicated by Ramaswamy H. Sarma.

Role of MicroRNAs in Inflammatory Joint Diseases: A Review.

Inflammatory arthritis commonly initiates in the soft tissues lining the joint. This lining swells, as do the cells in it and inside the joint fluid, producing chemicals that induce inflammation signs such as heat, redness, and swelling. MicroRNA (miRNA), a subset of non-coding small RNA molecules, post-transcriptionally controls gene expression by targeting their messenger RNA. MiRNAs modulate approximately 1/3 of the human genome with their multiple targets. Recently, they have been extensively studied as key modulators of the innate and adaptive immune systems in diseases such as allergic disorders, types of cancer, and cardiovascular diseases. However, research on the different inflammatory joint diseases, such as rheumatoid arthritis, gout, Lyme disease, ankylosing spondylitis, and psoriatic arthritis, remains in its infancy. This review presents a deeper understanding of miRNA biogenesis and the functions of miRNAs in modulating the immune and inflammatory responses in the above-mentioned inflammatory joint diseases. According to the literature, it has been demonstrated that the development of inflammatory joint disorders is closely related to different miRNAs and their specific regulatory mechanisms. Furthermore, they may present as possible prognostic and diagnostic biomarkers for all diseases and may help in developing a therapeutic response. However, further studies are needed to determine whether manipulating miRNAs can influence the development and progression of inflammatory joint disorders.

The Global Landscape of Domestic Violence against Women during the COVID-19 Pandemic: A Narrative Review.

The coronavirus disease (COVID-19) pandemic has led to an alarming increase in domestic violence against women owing to lockdown measures and limited access to support services. This article provides insights into the global prevalence of domestic violence, barriers to seeking help, its impact on women and children, and the best practices implemented worldwide. Domestic violence encompasses various forms of abuse; many young women experience partner violence. Barriers to seeking help include fear, financial constraints, lack of awareness of available services, and distrust among stakeholders. The consequences of domestic violence affect the mental health of both mothers and children. Countries have increased shelter funding and developed innovative protocols to reach survivors and address this issue. However, the healthcare sector's involvement in addressing domestic violence has been limited. This review advocates collaboration among healthcare institutions and government bodies. Key recommendations include utilizing telehealth services, implementing comprehensive training programs, establishing effective referral systems, enhancing health education, developing a domestic violence registry, improving the responses of law enforcement and justice systems through healthcare integration, promoting data sharing, and conducting further research. Healthcare systems should recognize domestic violence as a public health concern and detect, prevent, and intervene in cases to support survivors.

ASPAD dynamic simulation and artificial neural network for atenolol adsorption in GGSWAC packed bed column.

This study aimed to assess the dynamic simulation models provided by Aspen adsorption (ASPAD) and artificial neural network (ANN) in understanding the adsorption behavior of atenolol (ATN) on gasified Glyricidia sepium woodchips activated carbon (GGSWAC) within fixed bed columns for wastewater treatment. The findings demonstrated that increasing the bed height from 1 to 3 cm extended breakthrough and exhaustion times while enhancing adsorption capacity. Conversely, higher initial ATN concentrations resulted in shorter breakthrough and exhaustion times but increased adsorption capacity. Elevated influent flow rates reduced breakthrough and exhaustion times while maintaining constant adsorption capacity. The ASPAD software demonstrated competence in accurately modeling the crucial exhaustion points. However, there is room for enhancement in forecasting breakthrough times, as it exhibited deviations ranging from 6.52 to 239.53% when compared to the actual experimental data. ANN models in both MATLAB and Python demonstrated precise predictive abilities, with the Python model (R2 = 0.985) outperforming the MATLAB model (R2 = 0.9691). The Python ANN also exhibited superior fitting performance with lower MSE and MAE. The most influential factor was the initial ATN concentration (28.96%), followed by bed height (26.39%), influent flow rate (22.43%), and total effluent time (22.22%). The findings of this study offer an extensive comprehension of breakthrough patterns and enable accurate forecasts of column performance.

Unexplained subfertility: active or conservative management?

OBJECTIVES: Unexplained subfertility (UEI) describes a couple whose standard subfertility workout consider acceptable but unable to conceived. METHODS: This retrospective study was conducted in the Advanced Reproductive Centre, UKM Hospital, Kuala Lumpur, from January 2016 to December 2019. The data of 268 UEI couples were obtained from the clinical database. Women aged 21-45 years old was included and further divided into four groups according to the female partner's age and subfertility duration: group A (age <35 years and subfertility <2 years), group B (age <35 years and subfertility >2 years), group C (age >35 years and subfertility <2 years), and group D (age >35 years and subfertility <2 years). All statistical analyses were performed using SPSS 22.0 for Windows. RESULTS: A total of 255 cases were included in this study. The mean age of the women was 32.9 ± 4.04 years, and the mean subfertility duration was 5.04 ± 2.9 years. A total of 51 (20 %) cases underwent timed sexual intercourse, 147 (57.6 %) cases had intrauterine insemination (IUI), whereas 57 (22.4 %) cases opted for in vitro fertilization (IVF). A total of 204 cases underwent active management (IUI/IVF), which showed a significant difference (p<0.05). Out of eight clinical pregnancies, half of them were from group B. CONCLUSIONS: Active management in younger women with a shorter subfertility duration revealed a better pregnancy outcome. Otherwise, individualized treatment should be considered in selecting a suitable treatment plan.

Methotrexate-conjugated zinc oxide nanoparticles exert a substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

In the current study, we report the synthesis of methotrexate-conjugated zinc oxide nanoparticles (MTX-ZnONPs) and their high efficacy against lung cancer cells. Conjugation of MTX with ZnONPs was authenticated by UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). This drug-nanoconjugate also showed high drug-loading efficiency. The therapeutic efficacy of MTX-ZnONPs was further tested in vitro against A549 cells, and the results of MTT and LDH release assays showed that MTX-ZnONPs, in addition to free MTX, were efficient in exerting cytotoxic effect on A549 cells; however, the effectiveness of MTX-ZnONPs was found to be considerably enhanced at very low doses compared to that of free MTX. Moreover, ZnONPs alone significantly inhibited the cell viability of A549 cells at a much higher concentration compared to MTX-ZnONPs and MTX. Furthermore, the cytomorphology of A549 cells was characterized by cellular shrinkage and detachment from the surface in all the treatment groups. Similarly, A549 cells, in all the treatment groups, showed fragmented and condensed nuclei, indicating the initiation of apoptosis. Mitochondrial membrane potential (ψm) in A549 cells showed a gradual loss in all the treatment groups. Results of the qualitative and quantitative analyses depicted increased reactive oxygen species (ROS) levels in A549 cells. The results of the caspase activity assay showed that MTX-ZnONPs andfree MTX caused significant activation of caspase-9, -8, and -3 in A549 cells; however, the effect of MTX-ZnONPs was more profound at very low doses compared to that of free MTX. Thus, our results showed high efficacy of MTX-ZnONPs, suggesting efficient intracellular delivery of the drug by ZnONPs as nanocarriers.

The influence of hazard control and prevention toward safety behaviors and safety outcomes in coal-fired power plants using PLS-SEM.

INTRODUCTION: The electrical utility industry, which plays a vital role in sustaining other sectors, contributes to high occupational accident rates in the utility industries. The high accident rate shows that there has been insufficient effort made to control unsafe actions and conditions in the workplace. This study aims to examine the influence of hazard control and prevention as leading indicators of safety behaviors and outcomes in coal-fired power plants in Malaysia. METHODS: This quantitative research was conducted by distributing survey questionnaires randomly to five coal-fired power plants in Peninsular Malaysia. A total of 340 respondents were involved in this research. Partial least squares structural equation modeling (PLS-SEM) analysis was performed using SmartPLS to validate and examine the relationship of the proposed model. RESULTS: The results validate the construct of hazard control and prevention consisting of planning, action, managing, and verifying, while the safety outcomes construct consists of occupational accidents, fatal accidents, near misses, and lost time injuries. The results indicate that hazard control and prevention significantly relate to safety compliance, safety participation, safety motivation, and safety knowledge. Moreover, safety outcomes were influenced negatively by hazard control and prevention through safety compliance. CONCLUSION: The model provides a better understanding of the influence of hazard control and prevention on safety behavior and outcomes. PRACTICAL APPLICATIONS: The model can be used as guidance for practitioners and researchers in planning and implementing hazard control and prevention to improve health and safety in the workplace.

Runx1-R188Q germ line mutation induces inflammation and predisposition to hematologic malignancies in mice.

Germ line mutations in the RUNX1 gene cause familial platelet disorder (FPD), an inherited disease associated with lifetime risk to hematopoietic malignancies (HM). Patients with FPD frequently show clonal expansion of premalignant cells preceding HM onset. Despite the extensive studies on the role of RUNX1 in hematopoiesis, its function in the premalignant bone marrow (BM) is not well-understood. Here, we characterized the hematopoietic progenitor compartments using a mouse strain carrying an FPD-associated mutation, Runx1R188Q. Immunophenotypic analysis showed an increase in the number of hematopoietic stem and progenitor cells (HSPCs) in the Runx1R188Q/+ mice. However, the comparison of Sca-1 and CD86 markers suggested that Sca-1 expression may result from systemic inflammation. Cytokine profiling confirmed the dysregulation of interferon-response cytokines in the BM. Furthermore, the expression of CD48, another inflammation-response protein, was also increased in Runx1R188Q/+ HSPCs. The DNA-damage response activity of Runx1R188Q/+ hematopoietic progenitor cells was defective in vitro, suggesting that Runx1R188Q may promote genomic instability. The differentiation of long-term repopulating HSCs was reduced in Runx1R188Q/+ recipient mice. Furthermore, we found that Runx1R188Q/+ HSPCs outcompete their wild-type counterparts in bidirectional repopulation assays, and that the genetic makeup of recipient mice did not significantly affect the clonal dynamics under this setting. Finally, we demonstrate that Runx1R188Q predisposes to HM in cooperation with somatic mutations found in FPDHM, using 3 mouse models. These studies establish a novel murine FPDHM model and demonstrate that germ line Runx1 mutations induce a premalignant phenotype marked by BM inflammation, selective expansion capacity, defective DNA-damage response, and predisposition to HM.

Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review.

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.