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Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies. [ABSTRACT FROM AUTHOR]

Hematopoiesis is maintained throughout life from the hematopoietic stem cell niche in which hematopoietic stem cells and lineage-specific hematopoietic progenitors (HSPCs) reside and regulate hematopoiesis. Meanwhile, HSPCs behavior is modulated by both cell intrinsic (e.g., transcriptional factors) and cell extrinsic (e.g., cytokines) factors. Dysregulation of these factors can alter HSPCs function, leading to disrupted hematopoiesis, cellular changes, and subsequent hematological diseases and malignancies. Moreover, it has been reported that chromosomal aberration (CA) in HSPCs following exposure to carcinogenic or genotoxic agents can initiate leukemia stem cells (LSCs) formation which lays a fundamental mechanism in leukemogenesis. Despite reported studies concerning the chromosomal integrity in HSPCs, CA analysis in lineage-specific HSPCs remains scarce. This indicates a need for a laboratory technique that allows the study of CA in specific HSPCs subpopulations comprising differential hematopoietic lineages. Thus, this chapter focuses on the structural (clastogenicity) and numerical (aneugenicity) form of CA analysis in lineage-specific HSPCs comprised of myeloid, erythroid and lymphoid lineages.In this protocol, we describe how to perform CA analysis in lineage-specific HSPCs derived from freshly isolated mouse bone marrow cells (MBMCs) using the combined techniques of colony-forming unit (CFU) and karyotyping. Prior to CA analysis, lineage-specific HSPCs for myeloid, erythroid, and lymphoid were enriched through colony-forming unit (CFU) assay. CFU assay assesses the proliferative ability and differentiation potential of an individual HSPC within a sample. About 6 to 14 days of cultures are required depending on the type of HSPCs lineage. The optimal duration is crucial to achieve sufficient colony growth that is needed for accurate CFU analysis via morphological identification and colony counting. Then, the CA focusing on clastogenicity and aneugenicity anomalies in respective HSPCs lineage for myeloid, erythroid and Pre-B lymphoid were investigated. The resulted karyotypes were classified according to the types of CA known as Robertsonian (Rb) translocation, hyperploidy or complex. We believe our protocol offers a significant contribution to be utilized as a reference method for chromosomal analysis in lineage-specific HSPCs subpopulations., (© 2023. Springer Science+Business Media, LLC.)

The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies' immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively ( p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal.

The key enzymes of lipid biosynthesis in oleaginous filamentous fungi exist as metabolons. However, the existence of a similar organization in other groups of oleaginous microorganisms is still unknown. In this study, we confirmed the occurrence of two separate and distinct lipogenic metabolons in a thraustochytrid, Aurantiochytrium SW1. These involve the Type I Fatty Acid Synthase (FAS) pathway, consisting of six enzymes: fatty acid synthase, malic enzyme (ME), ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), malate dehydrogenase (MD) and pyruvate carboxylase (PC), and the Polyketide Synthase-like (PKS) pathway, consisting of PKS subunits a, b, c, glucose-6-phosphate dehydrogenase (G6PDH) 6-phosphogluconate dehydrogenase (6PGDH), ACL and ACC. This suggests that the NADPH requirement for the FAS pathway is primarily generated and channelled by ME whereas G6PDH and 6PGDH fulfil this role for the PKS pathway. Diminished biosynthesis of palmitic acid (16:0), docosahexaenoic acid (22:6 n-3, DHA) and docosapentaenoic acid (22:5 n-6, DPA) correlated with the dissociation of their respective metabolons thereby suggesting that regulation of the pathways is achieved through the formation and dissociation of the metabolons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Modern radiation therapy has become an effective method to treat and monitor tumour growth in cancer patients. It has proved to be a successful way to minimise mortality rates. However, the adverse effects of radiation have been historical evidence in the clinical environment involving diminishing the quality and density of bone and causing fragility fracture to the bone in the long run. This systematic review was aimed at identifying and evaluating the effects of irradiation on morphology and mechanical properties of murine model bone in previous publications., Methods: A systematic literature review was undertaken following the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was performed using Scopus, Web of Science, and Science Direct databases (English only studies published between 2015 and 2020). The selected studies were evaluated according to three criteria: (1) criteria for study sample selection; (2) criteria for methodological procedures; and (3) criteria for detection and evaluation., Results: The initial search strategy identified 1408 related studies, 8 of were included based on inclusion and exclusion criteria. This review revealed an association between bone destruction and the magnitude of time and dose postirradiation. We agreed that the effect of radiation on bone morphology and strength primarily is a later stage event but noticeable in both low (1 Gy) and high dose (30 Gy) radiation. Trabecular and cortical bone microstructures were significantly altered at irradiation and contralateral sites. Besides, the mechanical strength was significantly impacted in both shorter and longer periods., Conclusion: Overall, the radiotherapy altered bone microstructures and substantially decreases bone mechanical properties. The alteration was related to quantity and the activity of the osteoblast and osteoclast. Early detection of those most at risk for radiation-induced bone alterations could lead to better prophylactic intervention decisions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Ayuni Amalina Abu Bakar et al.)

Introduction: Hydatidiform moles (HMs) include complete and partial moles, are the result of abnormal fertilisation. The accurate classification of HMs and its distinction from non-molar specimens is utmost important for clinical management and risk assessment. It is diagnostically challenging if the distinction is based solely on histomorphology with poor interobserver reproducibility, especially in early gestations. This study aimed to investigate the diagnostic ability of combined p57 immunohistochemistry and DNA ploidy analysis to distinguish between complete moles, partial moles and non-molar abortus., Materials and Methods: We included all HMs cases diagnosed in our centre over a six-year period. p57 immunohistochemistry stain was performed. Only nuclear immunoreactivity in >50% of cytotrophoblasts and villous stromal cells was regarded as positive for p57. DNA ploidy status was determined by fluorescence in situ hybridisation. A total of 250 cells from five chorionic villi were counted and were scored as diploid or triploid if more than 10% of nuclei demonstrated two or three signals, respectively., Results: A total of 51 cases originally diagnosed by histomorphology as complete mole (n = 18), partial mole (n = 24) and non-molar abortus (n = 9) were recruited. The cases were reclassified based on the p57 immunostaining pattern and DNA ploidy status, into 27 complete moles (p57-/diploid), 9 partial moles (p57+/triploid) and 15 non-molar abortus (p57+/diploid). The diagnostic accuracy by histomorphological features alone in each category: complete moles, partial moles and non-molar abortus was 78.4%, 70.6% and 88.2% respectively., Conclusion: This study highlighted the importance of the utility of combined p57 immunostain and DNA ploidy analysis in arriving at an accurate diagnosis in HMs. An algorithmic approach utilising these ancillary techniques is advocated in routine diagnostic workup for a more refined diagnostic approach to HMs.

The high dimensionality of software metric features has long been noted as a data quality problem that affects the performance of software defect prediction (SDP) models. This drawback makes it necessary to apply feature selection (FS) algorithm(s) in SDP processes. FS approaches can be categorized into three types, namely, filter FS (FFS), wrapper FS (WFS), and hybrid FS (HFS). HFS has been established as superior because it combines the strength of both FFS and WFS methods. However, selecting the most appropriate FFS (filter rank selection problem) for HFS is a challenge because the performance of FFS methods depends on the choice of datasets and classifiers. In addition, the local optima stagnation and high computational costs of WFS due to large search spaces are inherited by the HFS method. Therefore, as a solution, this study proposes a novel rank aggregation-based hybrid multifilter wrapper feature selection (RAHMFWFS) method for the selection of relevant and irredundant features from software defect datasets. The proposed RAHMFWFS is divided into two stepwise stages. The first stage involves a rank aggregation-based multifilter feature selection (RMFFS) method that addresses the filter rank selection problem by aggregating individual rank lists from multiple filter methods, using a novel rank aggregation method to generate a single, robust, and non-disjoint rank list. In the second stage, the aggregated ranked features are further preprocessed by an enhanced wrapper feature selection (EWFS) method based on a dynamic reranking strategy that is used to guide the feature subset selection process of the HFS method. This, in turn, reduces the number of evaluation cycles while amplifying or maintaining its prediction performance. The feasibility of the proposed RAHMFWFS was demonstrated on benchmarked software defect datasets with Naïve Bayes and Decision Tree classifiers, based on accuracy, the area under the curve (AUC), and F-measure values. The experimental results showed the effectiveness of RAHMFWFS in addressing filter rank selection and local optima stagnation problems in HFS, as well as the ability to select optimal features from SDP datasets while maintaining or enhancing the performance of SDP models. To conclude, the proposed RAHMFWFS achieved good performance by improving the prediction performances of SDP models across the selected datasets, compared to existing state-of-the-arts HFS methods., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Abdullateef O. Balogun et al.)

Introduction: Multiparous labor inductions are typically successful, and the process can be rapid, starting from a ripened cervix with a predictable response to amniotomy and oxytocin infusion. Outpatient Foley catheter labor induction in multiparas with unripe cervixes is a feasible option as the mechanical process of ripening is usually without significant uterine contractions and well tolerated. Labor contractions can be initiated by amniotomy and titrated oxytocin infusion in the hospital for well-timed births during working hours as night birth are associated with adverse events. We sought to evaluate outpatient compared with inpatient Foley catheter induction of labor in multiparas for births during working hours and maternal satisfaction., Material and Methods: A randomized trial was conducted in the University of Malaya Medical Center. A total of 163 term multiparas (no dropouts) with unripe cervixes (Bishop score ≤5) scheduled for labor induction were randomized to outpatient or inpatient Foley catheter. Primary outcomes were delivery during "working hours" 08:00-18:00 h and maternal satisfaction on allocated care (assessed by 11-point visual numerical rating score 0-10, with higher score indicating more satisfied)., Clinical Trial Registration: ISRCTN13534944., Results: Comparing outpatient and inpatient arms, delivery during working hours were 54/82 (65.9%) vs. 48/81 (59.3%) (relative risk 1.1, 95% CI 0.9-1.4, p = 0.421) and median maternal satisfaction visual numerical rating score was 9 (interquartile range 9-9) vs. 9 (interquartile range 8-9, p = 0.134), repectively. Duration of hospital stay and membrane rupture to delivery interval were significantly shorter in the outpatient arm: 35.8 ± 20.2 vs. 45.2 ± 16.2 h (p = 0.001) and 4.1 ± 2.9 vs. 5.3 ± 3.6 h (p = 0.020), respectively. Other maternal and neonatal secondary outcomes were not significantly different., Conclusions: The trial failed to demonstrate the anticipated increase in births during working hours with outpatient compared with inpatient induction of labor with Foley catheter in parous women with an unripe cervix. Hospital stay and membrane rupture to delivery interval were significantly shortened in the outpatient group. The rate of maternal satisfaction was high in both groups and no significant differences were found., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Feature selection is known to be an applicable solution to address the problem of high dimensionality in software defect prediction (SDP). However, choosing an appropriate filter feature selection (FFS) method that will generate and guarantee optimal features in SDP is an open research issue, known as the filter rank selection problem. As a solution, the combination of multiple filter methods can alleviate the filter rank selection problem. In this study, a novel adaptive rank aggregation-based ensemble multi-filter feature selection (AREMFFS) method is proposed to resolve high dimensionality and filter rank selection problems in SDP. Specifically, the proposed AREMFFS method is based on assessing and combining the strengths of individual FFS methods by aggregating multiple rank lists in the generation and subsequent selection of top-ranked features to be used in the SDP process. The efficacy of the proposed AREMFFS method is evaluated with decision tree (DT) and naïve Bayes (NB) models on defect datasets from different repositories with diverse defect granularities. Findings from the experimental results indicated the superiority of AREMFFS over other baseline FFS methods that were evaluated, existing rank aggregation based multi-filter FS methods, and variants of AREMFFS as developed in this study. That is, the proposed AREMFFS method not only had a superior effect on prediction performances of SDP models but also outperformed baseline FS methods and existing rank aggregation based multi-filter FS methods. Therefore, this study recommends the combination of multiple FFS methods to utilize the strength of respective FFS methods and take advantage of filter-filter relationships in selecting optimal features for SDP processes.

Previous reports on hematotoxicity and leukemogenicity related to benzene exposure highlighted its adverse effects on hematopoiesis. Despite the reported findings, studies concerning the mechanism of benzene affecting chromosomal integrity in lineage-committed hematopoietic stem/progenitor cells (HSPCs) remain unclear. Here, we studied the clastogenicity and aneugenicity of benzene in lineage-committed HSPCs via karyotyping. Isolated mouse bone marrow cells (MBMCs) were exposed to the benzene metabolite 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, 5, 7, and 12 μM for 24 h, followed by karyotyping. Then, the chromosomal aberration (CA) in 1,4-BQ-exposed hematopoietic progenitor cells (HPCs) comprising myeloid, Pre-B lymphoid, and erythroid lineages were evaluated following colony-forming cell (CFC) assay. Percentage of CA, predominantly via Robertsonian translocation (Rb), was increased significantly ( p < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA ( p < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage ( p < 0.05) than myeloid progenitor at 7 μM of 1,4-BQ. In conclusion, 1,4-BQ induced CA, particularly via Rb in both MBMCs and HPCs, notably via a lineage-dependent response. The role of lineage specificity in governing the clastogenicity and aneugenicity of 1,4-BQ deserves further investigation.

Introduction: The advent of BCR-ABL1-targeted therapy with the tyrosine kinase inhibitor (TKI), for example, imatinib and nilotinib, marked a turning point in the therapy of chronic myeloid leukaemia (CML). However, a substantial proportion of patients experience primary or secondary disease resistance to TKI. There are multifactorial causes contributing to the treatment failure of which BCR-ABL1 kinase domain mutation being the most common. Here, we describe a case of a CML patient with H396P mutation following treatment with nilotinib., Case: A 60-year-old woman presented with abdominal discomfort and hyperleukocytosis. She was diagnosed as CML in the chronic phase with positive BCR-ABL1 transcripts. Due to the failure to obtain an optimal response with imatinib treatment, it was switched to nilotinib. She responded well to nilotinib initially and achieved complete haematological and cytogenetic responses, with undetectable BCR-ABL1 transcripts. However, in 4 years she developed molecular relapse. Mutation analysis which was done 70 months after commencement of nilotinib showed the presence of BCRABL1 kinase domain mutation with nucleotide substitution at position 1187 from Histidine(H) to Proline(P) (H396P). Currently, she is on nilotinib 400mg twice daily. Her latest molecular analysis showed the presence of residual BCR-ABL1 transcripts at 0.22%., Discussion/conclusion: This case illustrates the importance of BCR-ABL1 mutation analysis in CML patients with persistent BCR-ABL1 positivity in spite of treatment. Early detection and identification of the type of BCRABL1 mutation are important to guide appropriate treatment options as different mutation will have different sensitivity to TKI.

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chia, Cheah, Abdul Aziz, Kampan, Shuib, Khong, Tan and Wong.)

Magnetoactive (MA) foam, with its tunable mechanical properties and magnetostriction, has the potential to be used for the development of soft sensor technology. However, researchers have found that its mechanical properties and magnetostriction are morphologically dependent, thereby limiting its capabilities for dexterous manipulation. Thus, in this work, MA foam was developed with additional capabilities for controlling its magnetostriction, normal force, storage modulus, shear stress and torque by manipulating the concentration of carbonyl iron particles (CIPs) and the magnetic field with regard to morphological changes. MA foams were prepared with three weight percentages of CIPs, namely, 35 wt.%, 55 wt.% and 75 wt.%, and three different modes, namely, zero shear, constant shear and various shears. The results showed that the MA foam with 75 wt.% of CIPs enhanced the normal force sensitivity and positive magnetostriction sensitivity by up to 97% and 85%, respectively. Moreover, the sensitivities of the storage modulus, torque and shear stress were 8.97 Pa/mT, 0.021 µN/mT, and 0.0096 Pa/mT, respectively. Meanwhile, the magnetic dipolar interaction between the CIPs was capable of changing the property of MA foam from a positive to a negative magnetostriction under various shear strains with a low loss of energy. Therefore, it is believed that this kind of highly sensitive MA foam can potentially be implemented in future soft sensor systems.

Introduction: Mixed phenotype acute leukaemia (MPAL) is a rare entity of acute leukaemia., Case Report: Here we report a case of a 39-year-old lady, with an incidental finding of hyperleukocytosis (white blood cells count: 139.2 x 109/L). Her peripheral blood film revealed 36% of blasts and a bone marrow aspiration showed 53% of blasts. Immunophenotyping showed a population of blasts exhibiting positivity of two lineages, myeloid lineage and B-lymphoid lineage with strong positivity of CD34 and terminal deoxynucleotidyl transferase (Tdt). A conventional karyotyping revealed the presence of Philadelphia chromosome. She was diagnosed with MPAL with t(9,22), BCR ABL1, which carried a poor prognosis. She was treated with acute lymphoblastic leukaemia (ALL) chemotherapy protocol coupled with a tyrosine kinase inhibitor and was planned for an allogeneic stem cells transplant., Conclusion: This MPAL case was diagnosed incidentally in an asymptomatic patient during medical check-up. We highlight this rare case report to raise the awareness about this rare disease. Understanding the pathogenesis of the disease with the underlying genes responsible for triggering the disease, uniform protocols for diagnosis and targeted treatment will help for proper management of these patients.

Hematopoietic stem/progenitor cells (HSPCs) are susceptible to benzene-induced genotoxicity. However, little is known about the mechanism of DNA damage response affecting lineage-committed progenitors for myeloid, erythroid, and lymphoid. Here, we investigated the genotoxicity of a benzene metabolite, 1,4-benzoquinone (1,4-BQ), in HSPCs using oxidative stress and lineage-directed approaches. Mouse bone marrow cells (BMCs) were exposed to 1,4-BQ (1.25-12 μM) for 24 h, followed by oxidative stress and genotoxicity assessments. Then, the genotoxicity of 1,4-BQ in lineage-committed progenitors was evaluated using colony forming cell assay following 7-14 days of culture. 1,4-BQ exposure causes significant decreases ( p < 0.05) in glutathione level and superoxide dismutase activity, along with significant increases ( p < 0.05) in levels of malondialdehyde and protein carbonyls. 1,4-BQ exposure induces DNA damage in BMCs by significantly ( p < 0.05) increased percentages of DNA in tail at 7 and 12 μM and tail moment at 12 μM. We found crucial differences in genotoxic susceptibility based on percentages of DNA in tail between lineage-committed progenitors. Myeloid and pre-B lymphoid progenitors appeared to acquire significant DNA damage as compared with the control starting from a low concentration of 1,4-BQ exposure (2.5 µM). In contrast, the erythroid progenitor showed significant damage as compared with the control starting at 5 µM 1,4-BQ. Meanwhile, a significant ( p < 0.05) increase in tail moment was only notable at 7 µM and 12 µM 1,4-BQ exposure for all progenitors. Benzene could mediate hematological disorders by promoting bone marrow oxidative stress and lineage-specific genotoxicity targeting HSPCs.

Background: Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58 , with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia., Methods: Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR., Results: The majority of multiple sclerosis patients were female (85.2%). The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct., Conclusions: The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution., Competing Interests: Competing interestThe authors declare that they have no competing interest., (© The Author(s) 2019.)

Introduction: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars., Materials and Methods: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)]., Results: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts., Conclusion: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

Introduction: BCR-ABL fusion gene, the oncogenic driver of CML, results from a translocation between short arms of chromosome 9 and 22. Monitoring of CML patients during treatment is essential, not only for tailoring the treatment but also to detect early relapse to enable timely intervention. Commonly used methods for detection of residual disease are conventional karyotyping, FISH and molecular methods. In this study, we compared FISH with QRT-PCR for detection of residual disease in CML., Materials and Methods: CML patients on tyrosine kinase inhibitor (TKI) therapy and on regular follow up at University Kebangsaan Malaysia Medical Center (UKMMC) were selected. A comparative study was conducted between FISH and QRT-PCR for BCR-ABL transcripts at diagnosis and during follow-up., Results: There was good correlation between FISH and QRT-PCR for BCR-ABL. At 6th month of follow-up post diagnosis, FISH had a sensitivity of 83.3% and specificity of 65.2% (k >0.339, p<0.033). At 12th month, the sensitivity of FISH was 83% and the specificity was 59.1% (k >0.286, p <0.065). Similarly, at the 24th month, FISH had a sensitivity of 100% and specificity of 68.8% (k >0.642, p<0.000)., Discussion: Early achievement of major molecular response (MMR) and complete cytogenetic remission (CCyR) were reliable predictors of long-term maintenance of molecular remission.

Purpose: To relate the principal stress, strain, and total deformation in the premaxilla region beneath a complete denture to the pattern of premaxilla bone resorption when opposed by a conventional complete denture (CD) or by a two-implant-retained overdenture (IOD) using finite element analysis (FEA)., Materials and Methods: Three-dimensional solid models of the maxilla, mucosa, and denture of a selected edentulous patient were created using Mimics and CATIA software. The FEA model was created and duplicated in ANSYS 16.0 to perform two simulations for the IOD and the CD models. The values of maximum stress and strain and total deformation were obtained and compared to the outcomes of premaxilla resorption from a parallel clinical study., Results: The maximum principal stress in the premaxilla in the IOD model ranged from 0.019 to 0.336 MPa, while it ranged from 0.011 to 0.193 MPa in the CD model. The maximum principal strain in the IOD model was 1.75 times greater than that in the CD model. Total deformation was 1.8 times higher in the IOD model. Greater bone resorption was observed in regions of higher stress, which were on the occlusal and buccal sides of the premaxilla residual ridge., Conclusion: Stress, strain, and total deformation values present in the premaxilla area beneath a CD were approximately two times greater in a comparison between an opposing mandibular two-IOD and an opposing mandibular CD. The results were consistent with a parallel clinical study in which the rate of premaxilla bone resorption was almost three times greater in the IOD group., (© 2018 by the American College of Prosthodontists.)

The aim of this study is to investigate the estimation of density from the Hounsfield unit of cone beam computed tomography data in dental imaging, especially for dental implant application. A jaw phantom with various known densities of anatomical parts (e.g. soft tissue, cortical bone, trabecular bone, tooth enamel, tooth dentin, sinus cavity, spinal cord and spinal disc) has been used to test the accuracy of the Hounsfield unit of cone beam computed tomography in estimating the mechanical density (true density). The Hounsfield unit of cone beam computed tomography data was evaluated via the MIMICS software using both two-dimensional and three-dimensional methods, and the results showed correlation with the true density of the object. In addition, the results revealed that the Hounsfield unit of cone beam computed tomography and bone density had a logarithmic relation, rather than a linear one. To this end, the correlation coefficient of logarithmic correlation (R 2  = 0.95) is higher than the linear one (R 2  = 0.77).

Introduction: Essential thrombocythaemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterised by persistent thombocytosis. It is an indolent disorder but transformation to myelofibrosis (MF), acute myeloid leukaemia (AML) or myelodyplastic syndrome (MDS) has been reported., Case Report: We described a patient with ET whose disease evolved into MDS with fibrosis and complex karyotype after 15 years of stable disease. She was asymptomatic and was on hydroxyurea (HU) treatment until recently when she presented with worsening anaemia. Physical examination showed mild splenomegaly. Full blood picture showed leukoerythroblastic picture with presence of 3% circulating blasts and background of dysplastic features such as hypogranular cytoplasm and nuclear hyposegmentation of neutrophils. The bone marrow aspiration was haemodiluted but revealed presence of 6% blast cells, trilineage dysplasia and predominant erythroid precursors (60%). Trephine biopsy showed no excess of blast cells and normal quantity of erythroid precursors, but there was increased in fibrosis (WHO grade 2) and presence of dysmegakaryopoeisis such as nuclear hypolobation, multinucleation and micromegakaryocytes. Cytogenetic study showed complex karyotype; monosomy of chromosome 2, chromosome 5, chromosome 18 and presence of a marker chromosome (42~44, XX,-2,-5,-18,+mar). Fluorescence in situ hybridisation (FISH) showed 5q deletion (CSF1R and EGR1)., Conclusion: The findings were consistent with transformation of ET to MDS with fibrosis and complex karyotype. ET progression to MDS is considered rare. The presence of complex karyotype and fibrosis in MDS are associated with unfavourable outcome.

In this study, optimization of growth, lipid and DHA production of Aurantiochytrium SW1 was carried out using response surface methodology (RSM) in optimizing initial fructose concentration, agitation speed and monosodium glutamate (MSG) concentration. Central composite design was applied as the experimental design and analysis of variance (ANOVA) was used to analyze the data. ANOVA analysis revealed that the process which adequately represented by quadratic model was significant (p < 0.0001) for all the response. All the three factors were significant (p < 0.005) in influencing the biomass and lipid data while only two factors (agitation speed and MSG) gave significant effect on DHA production (p < 0.005). The estimated optimal conditions for enhanced growth, lipid and DHA production were 70 g/L fructose, 250 rpm agitation speed and 10 g/L MSG. Consequently, the quadratic model was validated by applying the estimated optimum conditions, which confirmed the model validity where 19.0 g/L biomass, 9.13 g/L lipid and 4.75 g/L of DHA were produced. The growth, lipid and DHA were 28, 36 and 35% respectively higher than that produced in the original medium prior to optimization.

Malic enzyme (ME) plays a vital role in determining the extent of lipid accumulation in oleaginous fungi being the major provider of NADPH for the activity of fatty acid synthase (FAS). We report here the first direct evidence of the existence of a lipogenic multienzyme complex (the lipid metabolon) involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and lipid accumulation phases were prepared by protoplasting and subjected to Blue Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A high molecular mass complex (approx. 3.2 MDa) consisting of the above enzymes was detected during lipid accumulation phase indicating positive evidence of multienzyme complex formation. The complex was not detected in cells during the balanced phase of growth or when lipid accumulation ceased, suggesting that it was transiently formed only during lipogenesis.

Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome, trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key features of such patients are autism spectrum disorder, learning disabilities, developmental delay, attention-deficit disorder, infantile hypotonia and cardiovascular abnormalities. Previous studies using microarray identified variations in the size and extent of the duplicated region of chromosome 17p11.2. However, there are a few genes which are considered as candidates for PTLS which include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In this report, we investigated a case of a 3-year-old girl who has developmental delay. Her chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH (4X44 K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome 17p11.2. The result was confirmed by fluorescence in situ hybridization (FISH) using probes in the critical PTLS region. This report demonstrates the importance of microarray and FISH in the diagnosis of PTLS.

Background: The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL., Methods: "nCounter® Leukemia fusion gene expression assay" by NanoString was employed to detect various fusion transcripts in a large set samples (n = 94) utilizing RNA from formalin fixed paraffin embedded (FFPE) diagnostic bone marrow biopsy specimens. This series included AL patients with various recurrent translocations (n = 49), normal karyotype (n = 19), or complex karyotype (n = 21), as well as normal bone marrow samples (n = 5). Fusion gene expression data were compared with results obtained by conventional karyotype and FISH technology to determine sensitivity/specificity, as well as positive /negative predictive values., Results: Junction probes for PML/RARA; RUNX1-RUNX1T1; BCR/ABL1 showed 100 % sensitivity/specificity. A high degree of correlation was noted for MLL/AF4 (85 sensitivity/100 specificity) and TCF3-PBX1 (75 % sensitivity/100 % specificity) probes. CBFB-MYH11 fusion probes showed moderate sensitivity (57 %) but high specificity (100 %). ETV6/RUNX1 displayed discordance between fusion transcript assay and FISH results as well as rare non-specific binding in AL samples with normal or complex cytogenetics., Conclusions: Our study presents preliminary data with high correlation between fusion transcript detection by a throughput automated multiplexed platform, compared to conventional karyotype/FISH technique for detection of chromosomal translocations in AL patients. Our preliminary observations, mandates further vast validation studies to explore automated molecular platforms in diagnostic pathology.

A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.