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Fulltext Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Dadaev T, Saunders EJ, Newcombe PJ, Anokian E, Leongamornlert DA, Brook MN, et al.

Nat Commun, 2018 06 11;9(1):2256.
PMID: 29892050 DOI: 10.1038/s41467-018-04109-8

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
Gender differences in the associations between knee pain and urinary incontinence in older adults: Cross-sectional analysis from the Malaysian Elders Longitudinal Research Study (MELoR)

Mat S, Jaafar MH, Razack AHA, Lim J, Ong TA, Khong SY, et al.

Neurourol Urodyn, 2023 Mar;42(3):641-649.
PMID: 36728321 DOI: 10.1002/nau.25136

INTRODUCTION: The common assumption that urinary incontinence occurs in osteoarthritis (OA) due to poor mobility is supported by limited evidence. The influence of gender in such associations is also yet to be elucidated.
OBJECTIVE: This study, therefore, identified any potential associations between knee OA symptoms and urinary incontinence and further explore sex differences in the associations.
DESIGN: Cross-sectional study.
SETTING: University Hospital.
PARTICIPANTS: This was a cross-sectional study from a longitudinal research study comprising 1221 community-dwelling older persons (57% women), mean age (SD) 68.95 (7.49) years.
MAIN OUTCOME MEASURE(S): Presence of urinary incontinence: mixed, stress and urge symptoms. Physical performance and C-reactive protein levels were also assessed.
RESULTS: Two hundred and seventy-seven (22.83%) individuals reported the presence of urinary incontinence: mixed (41.5%), stress (30%), and urge (28.5%) symptoms. In an unadjusted analysis, stratified by gender, the association between knee pain and urinary incontinence was only present in women with mixed symptoms. After further adjustment of demographics differences and body mass index, the association between knee pain with any urinary incontinence and mixed symptoms remained significant with the odds ratios (95% confidence interval): 1.48 (1.02-2.15) and 1.73 (1.06-2.83), respectively. This relationship was attenuated after further adjustment for waist circumference and impaired lower limb mobility.
CONCLUSION: Our study refutes previous assumptions that urinary incontinence in individuals with OA is attributed to impaired mobility alone, but introduces the role of abdominal obesity in this relationship, particularly in women. Future studies should assess the temporal relationship between body fat distribution and OA with urinary incontinence.
Fulltext Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting

Mohd-Zahid MH, Zulkifli SN, Che Abdullah CA, Lim J, Fakurazi S, Wong KK, et al.

RSC Adv, 2021 Apr 26;11(26):16131-16141.
PMID: 35481195 DOI: 10.1039/d1ra01093j

The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and complement the deficiencies of the passive targeting approach. Here we report on the design of the carboxyl-terminated PEGylated gold nanoparticles (AuNPs), their functionalization with anti-CD133 monoclonal antibody (mAb) via a crosslinking reaction, and subsequent 5-fluorouracil (5-FU) drug loading. The synthesized products in the form of stable colloids were characterised using a range of physicochemical techniques, including X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Conjugation of anti-CD133 mAb onto PEGylated AuNPs was confirmed with the use of UV-Vis, BCA protein assay and fluorescence microscopy. HCT116 colorectal cancer cells abundantly expressed CD133: 92.4 ± 1.3%, as measured by flow cytometry. Whereas PEGylated AuNPs not conjugated with anti-CD133 mAb accumulated mainly at the cellular membrane, nanoparticles conjugated with anti-CD133 mAb were contained within the nuclear region of the cells. Anti-CD133 mAb conjugation facilitated the specific intracellular uptake due to specific antigen-antibody binding interaction. In vitro cytotoxicity studies on HCT116 cells showed that PEGylated AuNPs and PEGylated AuNPs-CD133 did not elicit any toxicity at any of the tested concentrations. Meanwhile, 5-FU-PEGylated AuNPs-CD133 significantly reduced the cell viability relative to the treatment with 5-FU-PEGylated AuNPs without anti-CD133 mAb conjugates (p < 0.0001). This study shows that the conjugation of nanocarriers with the anti-CD133 antibody improves the specific targeting of 5-FU against colorectal cancer cells. These results demonstrate that simultaneous functionalisation of PEGylated AuNPs with antibodies and chemotherapeutic drugs is a viable strategy to combat cancer through targeted drug delivery.
Gut microbiome: Microflora association with obesity and obesity-related comorbidities

Lone JB, Koh WY, Parray HA, Paek WK, Lim J, Rather IA, et al.

Microb Pathog, 2018 Nov;124:266-271.
PMID: 30138755 DOI: 10.1016/j.micpath.2018.08.036

Obesity and obesity-related comorbidities have transformed into a global epidemic. The number of people suffering from obesity has increased dramatically within the past few decades. This rise in obesity cannot alone be explained by genetic factors; however, diet, environment, lifestyle, and presence of other diseases undoubtedly contribute towards obesity etiology. Nevertheless, evidence suggests that alterations in the gut microbial diversity and composition have a role to play in energy assimilation, storage, and expenditure. In this review, the impact of gut microbiota composition on metabolic functionalities, and potential therapeutics such as gut microbial modulation to manage obesity and its associated comorbidities are highlighted. Optimistically, an understanding of the gut microbiome could facilitate the innovative clinical strategies to restore the normal gut flora and improve lifestyle-related diseases in the future.
Fulltext Health-Related Quality of Life Assessment in Prostate Cancer Patient Undergoing Androgen Deprivation Therapy: Real-World Experience in the READT Study

Lim J, Ng CF, Wei Y, Ong TA, Chu PS, Chan WKW, et al.

World J Mens Health, 2024 Apr;42(2):449-459.
PMID: 37853536 DOI: 10.5534/wjmh.230042

PURPOSE: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer.
MATERIALS AND METHODS: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multi-center, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12.
RESULTS: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876-1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment time-points. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I-III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70-90), indicating good overall health on average during ADT initiation.
CONCLUSIONS: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.
Health-care providers' perceptions, attitudes towards and recommendation practice of cervical cancer screening

Hweissa NA, Lim JN, Su TT

Eur J Cancer Care (Engl), 2016 Sep;25(5):864-70.
PMID: 27350095 DOI: 10.1111/ecc.12537

In Libya, cervical cancer is ranked third as the most frequent cancer among women with early diagnosis being shown to reduce morbidity and mortality. Health-care providers can influence women's screening behaviours, and their lack of recommendations for screening can be one of the barriers that affect women's participation in screening programmes. This study aims to assess the health-care provider's perception around cervical cancer screening. In-depth, face-to-face interviews were conducted with 16 health-care providers, from both public and private sectors in Az-Zawiya city, Libya, between February and July of 2014. The interviews were recorded and transcribed, then analysed using thematic analysis. Our findings suggest that health-care providers did not provide sufficient information regarding cervical cancer screening for women who attend health-care facilities. The results highlight the role played by health-care professionals in motivating women to attend cervical cancer screening programs, and the need for health education of health-care providers to offer a precious advice regarding the screening. On the other hand, health-care providers highlighted that implementation of reminding system of cervical cancer screening will support them to improve screening attendance. In addition, health-care providers stressed the necessity for educational and awareness campaigns of cervical cancer screening among Libyan women.
Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate

Tan JSJ, Ong KC, Ong DBL, Razack A, Lim J, Yunus R, et al.

Malays J Pathol, 2018 Aug;40(2):103-110.
PMID: 30173226 MyJurnal

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer.
METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade.
RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01).
CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.
Fulltext Hyponatraemia in hospitalised elderly patients

Lim JKH, Yap KB

Med J Malaysia, 2001 Jun;56(2):232-5.
PMID: 11771085

This study aims to investigate the incidence and causes of hyponatraemia in hospitalised elderly patients. There was a total of 407 new patients. 55 (13.5%) patients were found to have at least one episode of hyponatraemia during their hospitalization. There were 58 deaths. Fifteen out of 55 (27.3%) patients who had hyponatraemia died compared to 43 out of 352 (12.2%) normonatraemic patients (chi-square significant, p < 0.01). The three most common causes of hyponatraemia were syndrome of inappropriate antidiuretic hormone secretion (SIADH), poor oral intake and diuretics. The two most common causes of SIADH were lower respiratory tract infection and stroke.
Identification and selection of immunodominant B and T cell epitopes for dengue multi-epitope-based vaccine

Lim HX, Lim J, Poh CL

Med Microbiol Immunol, 2021 Feb;210(1):1-11.
PMID: 33515283 DOI: 10.1007/s00430-021-00700-x

Dengue virus (DENV) comprises four serotypes (DENV1-4) which cause 390 million global infections with 500,000 hospitalizations and 25,000 fatalities annually. Currently, the only FDA approved DENV vaccine is the chimeric live-attenuated vaccine, Dengvaxia®, which is based on the yellow fever virus (YFV) genome that carries the prM and E genes of the respective DENV 1, 2, 3, and 4 serotypes. However, it has lower efficacies against serotypes DENV1 (51%) and DENV2 (34%) when compared with DENV3 (75%) and DENV4 (77%). The absence of T cell epitopes from non-structural (NS) and capsid (C) proteins of the yellow fever vaccine strain might have prevented Dengvaxia® to elicit robust cellular immune responses, as CD8+ T cell epitopes are mainly localized in the NS3 and NS5 regions. Multi-epitope-based peptide vaccines carrying CD4+, CD8+ T cell and B cell epitopes represent a novel approach to generate specific immune responses. Therefore, assessing and selecting epitopes that can induce robust B and T cell responses is a prerequisite for constructing an efficient multi-epitope peptide vaccine. Potent B and T cell epitopes can be identified by utilizing immunoinformatic analysis, but the immunogenicity of the epitopes have to be experimentally validated. In this review, we presented T cell epitopes that have been predicted by bioinformatic approaches as well as recent experimental validations of CD4+ and CD8+ T cell epitopes by ex-vivo stimulation of PBMCs with specific peptides. Immunoproteomic analysis could be utilized to uncover HLA-specific epitopes presented by DENV-infected cells. Based on various approaches, immunodominant epitopes capable of inducing strong immune responses could be selected and incorporated to form a universally applicable multi-epitope-based peptide dengue vaccine.
Inclusive Search for a Highly Boosted Higgs Boson Decaying to a Bottom Quark-Antiquark Pair

Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.

Phys Rev Lett, 2018 Feb 16;120(7):071802.
PMID: 29542941 DOI: 10.1103/PhysRevLett.120.071802

An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (p_{T}) and decaying to a bottom quark-antiquark pair (bb[over ¯]) is performed using a data set of pp collisions at sqrt[s]=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1}. A highly Lorentz-boosted Higgs boson decaying to bb[over ¯] is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Z→bb[over ¯] decays. The Z→bb[over ¯] process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of H→bb[over ¯] with reconstructed p_{T}>450 GeV and in the pseudorapidity range -2.5
Fulltext Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.

J Med Genet, 2018 02;55(2):97-103.
PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947

BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.
METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.
RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.
CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.
Intravaginal misoprostol for termination of midtrimester pregnancy

Lim JM, Soh EB, Raman S

Aust N Z J Obstet Gynaecol, 1995 Feb;35(1):54-5.
PMID: 7772001

Misoprostol seems to be a drug with many potential uses apart from the treatment of gastric and duodenal ulcers. The oral tablet appears to be effective for termination of midtrimester pregnancy when administered intravaginally. Further research should be carried out to determine its full range of action in order that the drug can be utilized to its maximum potential.
Fulltext JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

Nairismägi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al.

Leukemia, 2016 06;30(6):1311-9.
PMID: 26854024 DOI: 10.1038/leu.2016.13

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Jet Shapes of Isolated Photon-Tagged Jets in Pb-Pb and pp Collisions at sqrt[s_{NN}]=5.02 TeV

Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.

Phys Rev Lett, 2019 Apr 19;122(15):152001.
PMID: 31050516 DOI: 10.1103/PhysRevLett.122.152001

The modification of jet shapes in Pb-Pb collisions, relative to those in pp collisions, is studied for jets associated with an isolated photon. The data were collected with the CMS detector at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Jet shapes are constructed from charged particles with track transverse momenta (p_{T}) above 1 GeV/c in annuli around the axes of jets with p_{T}^{jet}>30 GeV/c associated with an isolated photon with p_{T}^{γ}>60 GeV/c. The jet shape distributions are consistent between peripheral Pb-Pb and pp collisions, but are modified for more central Pb-Pb collisions. In these central Pb-Pb events, a larger fraction of the jet momentum is observed at larger distances from the jet axis compared to pp, reflecting the interaction between the partonic medium created in heavy ion collisions and the traversing partons.
Fulltext Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, et al.

Hum Mutat, 2019 Sep;40(9):1557-1578.
PMID: 31131967 DOI: 10.1002/humu.23818

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.
Life cycle assessment: Sustainability of biodiesel production from black soldier fly larvae feeding on thermally pre-treated sewage sludge under a tropical country setting

Seng Liew C, Ren Mong G, Wei Lim J, Raksasat R, Rawindran H, Hong Leong W, et al.

Waste Manag, 2023 Apr 20;164:238-249.
PMID: 37086606 DOI: 10.1016/j.wasman.2023.04.013

More energy is needed nowadays due to global population growth. Concurrently, sewage sludge generation has also increased steadily stemming from the inevitable urbanization. As such, black soldier fly larvae (BSFL) can be potentially deployed to solve both issues. This paper investigates the environmental sustainability of biodiesel production derived from sludge-fed BSFL feedstock. A cradle-to-gate life cycle assessment (LCA) was performed through SimaPro software utilizing the ReCiPe 2016 Midpoint (H) and Endpoint (H) methods. The entire LCA covered 3 main stages, including the thermal pre-treatment of sludge, BSFL rearing and processing, and lastly lipid extraction and biodiesel production. LCA showed that the sludge pre-treatment stage had the highest environmental impact, while BSFL rearing and processing had the least due to the suitable geographical climate. Electricity usage during the pre-treatment stage was the main contributing component, followed by chemical usage during biodiesel production. After normalizing, it was observed that land occupation, marine ecotoxicity, freshwater ecotoxicity and freshwater eutrophication were more impactful than the commonly studied global warming potential (GWP). Lipid content and biodiesel conversion efficiency were determined as the sensitive factors which could influence the LCA outcome. In comparison with other types of biodiesel, BSFL biodiesel had a milder impact in terms of climate change, land occupation, terrestrial acidification, marine and freshwater eutrophication. Furthermore, this biological reduction of sludge through BSFL valorization avoided sludge landfilling, which reduced up to 100 times GWP. Therefore, sludge-fed BSFL biodiesel production is an environmentally-sound and highly potential solution that should be investigated comprehensively.
Low-Gradient Magnetophoresis of Nanospheres and Nanorods through a Single Layer of Paper

Law JKC, Ng WM, Chong WH, Li Q, Zhang L, Khoerunnisa F, et al.

Langmuir, 2023 Apr 11;39(14):4904-4916.
PMID: 36992604 DOI: 10.1021/acs.langmuir.2c03164

The possible magnetophoretic migration of iron oxide nanoparticles through the cellulosic matrix within a single layer of paper is challenging with its underlying mechanism remained unclear. Even with the recent advancements of theoretical understanding on magnetophoresis, mainly driven by cooperative and hydrodynamics phenomena, the contributions of these two mechanisms on possible penetration of magnetic nanoparticles through cellulosic matrix of paper have yet been proven. Here, by using iron oxide nanoparticles (IONPs), both nanospheres and nanorods, we have investigated the migration kinetics of these nanoparticles through grade 4 Whatman filter paper with a particle retention of 20-25 μm. By performing droplet tracking experiments, the real-time stained area growth of the particle droplet on the filter paper, under the influences of a grade N40 NdFeB magnet, were recorded. Our results show that the spatial and temporal expansion of the IONP stain is biased toward the magnet and such an effect is dependent on (i) particle concentration and (ii) particle shape. The kinetics data were first analyzed by treating it as a radial wicking fluid, and later the IONP distribution within the cellulosic matrix was investigated by optical microscopy. The macroscopic flow front velocities of the stained area ranged from 259 μm/s to 16 040 μm/s. Moreover, the microscopic magnetophoretic velocity of nanorod cluster was also successfully measured as ∼214 μm/s. Findings in this work have indirectly revealed the strong influence of cooperative magnetophoresis and the engineering feasibility of paper-based magnetophoretic technology by taking advantage of magnetoshape anisotropy effect of the particles.
Low-gradient magnetic separation of magnetic nanoparticles under continuous flow: Experimental study, transport mechanism and mathematical modelling

Tan YW, Leong SS, Lim J, Yeoh WM, Toh PY

Electrophoresis, 2022 Nov;43(21-22):2234-2249.
PMID: 35921231 DOI: 10.1002/elps.202200078

Low-gradient magnetic separation (LGMS) of magnetic nanoparticles (MNPs) has been proven as one of the techniques with great potential for biomedical and environmental applications. Recently, the underlying principle of particle capture by LGMS, through a process known as magnetophoresis, under the influence of hydrodynamic effect has been widely studied and illustrated. Even though the hydrodynamic effect is very substantial for batch processes, its impact on LGMS operated at continuous flow (CF) condition remained largely unknown. Hence, in this study, the dynamical behaviour of LGMS process operated under CF was being studied. First, the LGMS experiments using poly(sodium 4-styrenesulfonate)-functionalized-MNP as modelled particle system were performed through batchwise (BW) and CF modes at different operating conditions. Here BW operation was used as a comparative study to elucidate the transport mechanism of MNP under the similar environment of CF-LGMS process, and it was found out that the convection induced by magnetophoresis (timescale effective is ∼1200 s) is only significant at far-from-magnet region. Hence, it can be deduced that forced convection is more dominant on influencing the transport behaviour of CF-LGMS (with resident time ≤240 s). Moreover, we found that the separation efficiency of CF-LGMS process can be boosted by the higher number of magnets, the higher MNP concentration and the lower flowrate of MNP solution. To better illustrate the underlying dynamical behaviour of LGMS process, a mathematical model was developed to predict its kinetic profile and separation efficiency (with average error of ∼2.6% compared to the experimental results).
MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord

Lim J, Razi ZR, Law J, Nawi AM, Idrus RB, Ng MH

Cytotherapy, 2016 12;18(12):1493-1502.
PMID: 27727016 DOI: 10.1016/j.jcyt.2016.08.003

BACKGROUND AIMS: Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared.
METHODS: Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed.
RESULTS: hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation potential compared with the other two segments.
CONCLUSIONS: hWJMSCs derived from the maternal and fetal segments of the UC are a good source of MSCs compared with cells from the middle segment because of their higher proliferation rate and viability. Fetal and maternal segments are the preferred cell source for bone regeneration.
Fulltext MUSiC: a model-unspecific search for new physics in proton-proton collisions at s = 13 TeV

CMS Collaboration, Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Bergauer T, et al.

Eur Phys J C Part Fields, 2021;81(7):629.
PMID: 34727144 DOI: 10.1140/epjc/s10052-021-09236-z

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.

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