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  1. Ahmed S, Kreft A, Chowdhury EH, Hossain SM, Galle PR, Neumann H
    PLoS One, 2020;15(10):e0239814.
    PMID: 33002048 DOI: 10.1371/journal.pone.0239814
    BACKGROUND AND STUDY AIMS: Despite major technical advancements, endoscopic surveillance for detecting premalignant lesions in Barrett's esophagus is challenging because of their flat appearance with only subtle morphological changes. Molecular endoscopic imaging (MEI) using nanoparticles (NPs), coupled with fluorescently labeled antibody permits visualization of disease-specific molecular alterations. The aim of this ex vivo study was to assess the diagnostic applicability of MEI with NPs to detect Barrett's metaplasia.

    PATIENTS AND METHODS: Seven patients undergoing endoscopic surveillance of known Barrett's esophagus were recruited. Freshly resected biopsy specimens were incubated with NPs coupled with FITC labeled Muc-2 antibodies and examined with MEI. Fluorescence intensity from Barrett's mucosa and control specimens were compared, followed by histological confirmation.

    RESULTS: Fluorescence signals, indicating the presence of goblet cells, were noted for traditional MEI using Muc-2 antibodies in Barrett's intestinal metaplasia. Significantly stronger fluorescence signals were achieved with NPs coupled with FITC-conjugated Muc-2 antibodies. The results of MEI with NPs for the prediction of Barrett's metaplasia correlated with the final histopathological examination in all the cases.

    CONCLUSIONS: Highly-specific NPs detected Barrett's metaplasia more efficiently than conventional MEI in this first feasibility study. MEI was as effective as standard histopathology for identifying Muc-2 containing goblet cells for diagnosis of Barrett's metaplasia. (DRKS-ID: DRKS00017747).

    Matched MeSH terms: Barrett Esophagus/pathology
  2. Leong XF, Aishah A, Nor Aini U, Das S, Jaarin K
    Arch Med Res, 2008 Aug;39(6):567-72.
    PMID: 18662587 DOI: 10.1016/j.arcmed.2008.04.009
    Palm oil used worldwide contains considerable amounts of antioxidants, namely, vitamin E and carotenes. The purpose of the study was to observe the effect of heated palm oil on blood pressure and observe the cardiac histological changes in rats.
    Matched MeSH terms: Myocardium/pathology
  3. Bakshi HA, Mishra V, Satija S, Mehta M, Hakkim FL, Kesharwani P, et al.
    Inflammation, 2019 Dec;42(6):2032-2036.
    PMID: 31377947 DOI: 10.1007/s10753-019-01065-3
    Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.
    Matched MeSH terms: Colitis/pathology
  4. Ashley SE, Tan HT, Peters R, Allen KJ, Vuillermin P, Dharmage SC, et al.
    Clin Exp Allergy, 2017 Aug;47(8):1032-1037.
    PMID: 28544327 DOI: 10.1111/cea.12942
    BACKGROUND: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.

    OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.

    METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.

    RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.

    CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.

    Matched MeSH terms: Th2 Cells/pathology
  5. Yip CH, Taib NA, Choo WY, Rampal S, Thong MK, Teo SH
    World J Surg, 2009 Oct;33(10):2077-81.
    PMID: 19649760 DOI: 10.1007/s00268-009-0146-8
    Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population.
    Matched MeSH terms: Breast Neoplasms/pathology
  6. Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS
    World J Surg, 2007 May;31(5):1031-40.
    PMID: 17387549
    Breast cancer is the leading cause of cancer-related deaths in Asia, and in recent years is emerging as the commonest female malignancy in the developing Asian countries, overtaking cancer of the uterine cervix. There have been no studies objectively comparing data and facts relating to breast cancer in the developed, newly developed, and developing Asian countries thus far.
    Matched MeSH terms: Breast Neoplasms/pathology
  7. Eng LG, Dawood S, Sopik V, Haaland B, Tan PS, Bhoo-Pathy N, et al.
    Breast Cancer Res Treat, 2016 11;160(1):145-152.
    PMID: 27628191
    PURPOSE: To evaluate breast cancer-specific survival at 10 years in patients who present with primary stage IV breast cancer, and to determine whether survival varies with age of diagnosis.

    METHODS: We retrieved the records of 25,323 women diagnosed with primary stage IV breast cancer in the surveillance, epidemiology, and end results 18 registries database from 1990 to 2012. For each case, we extracted information on age at diagnosis, tumour size, nodal status, oestrogen receptor status, progesterone receptor status, ethnicity, cause of death and date of death. The Cox proportional hazards model was used to estimate the unadjusted and adjusted hazard ratio (HR) of death due to stage IV breast cancer, according to age group.

    RESULTS: Among 25,323 women with stage IV breast cancer, 2542 (10.0 %) were diagnosed at age 40 or below, 5562 (22.0 %) were diagnosed between ages 41 and 50 and 17,219 (68.0 %) were diagnosed between ages 51 and 70. After a mean follow-up of 2.2 years, 16,387 (64.7 %) women died of breast cancer (median survival 2.3 years). The ten-year actuarial breast cancer-specific survival rate was 15.7 % for women ages 40 and below, 14.9 % for women ages 41-50 and 11.7 % for women ages 51 to 70 (p 

    Matched MeSH terms: Breast Neoplasms/pathology*
  8. Hansen-Algenstaedt N, Kwan MK, Algenstaedt P, Chiu CK, Viezens L, Chan TS, et al.
    Spine (Phila Pa 1976), 2017 May 15;42(10):789-797.
    PMID: 27584676 DOI: 10.1097/BRS.0000000000001893
    STUDY DESIGN: Prospective propensity score-matched study.

    OBJECTIVE: To compare the outcomes of minimal invasive surgery (MIS) and conventional open surgery for spinal metastasis patients.

    SUMMARY OF BACKGROUND DATA: There is lack of knowledge on whether MIS is comparable to conventional open surgery in treating spinal metastasis.

    METHODS: Patients with spinal metastasis requiring surgery from January 2008 to December 2010 in two spine centers were recruited. The demographic, preoperative, operative, perioperative and postoperative data were collected and analyzed. Thirty MIS patients were matched with 30 open surgery patients using propensity score matching technique with a match tolerance of 0.02 based on the covariate age, tumor type, Tokuhashi score, and Tomita score.

    RESULTS: Both groups had significant improvements in Eastern Cooperative Oncology Group (ECOG), Karnofsky scores, visual analogue scale (VAS) for pain and neurological status postoperatively. However, the difference comparing the MIS and open surgery group was not statistically significant. MIS group had significantly longer instrumented segments (5.5 ± 3.1) compared with open group (3.8 ± 1.7). Open group had significantly longer decompressed segment (1.8 ± 0.8) than MIS group (1.0 ± 1.0). Open group had significantly more blood loss (2062.1 ± 1148.0 mL) compared with MIS group (1156.0 ± 572.3 mL). More patients in the open group (76.7%) needed blood transfusions (with higher average units of blood transfused) compared with MIS group (40.0%). Fluoroscopy time was significantly longer in MIS group (116.1 ± 63.3 s) compared with open group (69.9 ± 42.6 s). Open group required longer hospitalization (21.1 ± 10.8 days) compared with MIS group (11.0 ± 5.0 days).

    CONCLUSION: This study demonstrated that MIS resulted in comparable outcome to open surgery for patients with spinal metastasis but has the advantage of less blood loss, blood transfusions, and shorter hospital stay.

    LEVEL OF EVIDENCE: 3.

    Matched MeSH terms: Postoperative Hemorrhage/pathology
  9. Walters K, Sarsenov R, Too WS, Hare RK, Paterson IC, Lambert DW, et al.
    BMC Genomics, 2019 Jun 03;20(1):454.
    PMID: 31159744 DOI: 10.1186/s12864-019-5850-7
    BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes in diseases such as cancer, although the functions of most remain poorly understood. To address this, here we apply a novel strategy to integrate gene expression profiles across 32 cancer types, and cluster human lncRNAs based on their pan-cancer protein-coding gene associations. By doing so, we derive 16 lncRNA modules whose unique properties allow simultaneous inference of function, disease specificity and regulation for over 800 lncRNAs.

    RESULTS: Remarkably, modules could be grouped into just four functional themes: transcription regulation, immunological, extracellular, and neurological, with module generation frequently driven by lncRNA tissue specificity. Notably, three modules associated with the extracellular matrix represented potential networks of lncRNAs regulating key events in tumour progression. These included a tumour-specific signature of 33 lncRNAs that may play a role in inducing epithelial-mesenchymal transition through modulation of TGFβ signalling, and two stromal-specific modules comprising 26 lncRNAs linked to a tumour suppressive microenvironment and 12 lncRNAs related to cancer-associated fibroblasts. One member of the 12-lncRNA signature was experimentally supported by siRNA knockdown, which resulted in attenuated differentiation of quiescent fibroblasts to a cancer-associated phenotype.

    CONCLUSIONS: Overall, the study provides a unique pan-cancer perspective on the lncRNA functional landscape, acting as a global source of novel hypotheses on lncRNA contribution to tumour progression.

    Matched MeSH terms: Neoplasms/pathology
  10. Mozar FS, Chowdhury EH
    Curr Pharm Des, 2018;24(28):3283-3296.
    PMID: 30062957 DOI: 10.2174/1381612824666180730161721
    PEG-functionalized nanoparticles as carriers of chemotherapeutics agents have been explored with notable successes in preclinical and clinical stages of cancer treatment, with some already approved by FDA, namely PEGylated liposomes and polymers. Half-life extension of therapeutic agents through PEGylation process improves their pharmacokinetic (PK) profiles, thereby reducing their dosing frequency. Protein corona composition of PEGylated nanoparticles (NPs) confers a tremendous influence on their surface characteristics which directly impact tumor accumulation and clearance properties of the drugs. By controlling the size and complexity of PEG molecules, as well as by attaching targeting moieties, the surface characteristics of NPs can be manipulated to improve their tumor uptake without sacrificing the circulation time. This review focuses on design and applications of PEGylated NPs for tumor targeted drug delivery in animal models and clinical setting.
    Matched MeSH terms: Neoplasms/pathology
  11. Low SC, Tan CY, Md Sari NA, Ahmad-Annuar A, Wong KT, Lin KP, et al.
    Amyloid, 2019 7 26;26(sup1):7-8.
    PMID: 31343308 DOI: 10.1080/13506129.2019.1582479
    Matched MeSH terms: Amyloid Neuropathies, Familial/pathology
  12. Khoo ACH, Yeoh KW
    Clin Nucl Med, 2019 Oct;44(10):808-809.
    PMID: 31348083 DOI: 10.1097/RLU.0000000000002739
    Extramammary Paget's disease (EMPD) is a rare disease with an estimated prevalence of 0.1 to 2.4 per 1,000,000 person-years. Metastatic EMPD has a poor prognosis with a 5-year survival of approximately 7%. Local therapy is the only curative option with surgery being recommended for resectable disease. It is therefore crucial to be able to stage such patients appropriately. The utility of F-FDG PET/CT for this disease is not well established. We share a case on how F-FDG PET/CT was used to stage metastatic EMPD.
    Matched MeSH terms: Paget Disease, Extramammary/pathology*
  13. Acharya UR, Fernandes SL, WeiKoh JE, Ciaccio EJ, Fabell MKM, Tanik UJ, et al.
    J Med Syst, 2019 Aug 09;43(9):302.
    PMID: 31396722 DOI: 10.1007/s10916-019-1428-9
    The aim of this work is to develop a Computer-Aided-Brain-Diagnosis (CABD) system that can determine if a brain scan shows signs of Alzheimer's disease. The method utilizes Magnetic Resonance Imaging (MRI) for classification with several feature extraction techniques. MRI is a non-invasive procedure, widely adopted in hospitals to examine cognitive abnormalities. Images are acquired using the T2 imaging sequence. The paradigm consists of a series of quantitative techniques: filtering, feature extraction, Student's t-test based feature selection, and k-Nearest Neighbor (KNN) based classification. Additionally, a comparative analysis is done by implementing other feature extraction procedures that are described in the literature. Our findings suggest that the Shearlet Transform (ST) feature extraction technique offers improved results for Alzheimer's diagnosis as compared to alternative methods. The proposed CABD tool with the ST + KNN technique provided accuracy of 94.54%, precision of 88.33%, sensitivity of 96.30% and specificity of 93.64%. Furthermore, this tool also offered an accuracy, precision, sensitivity and specificity of 98.48%, 100%, 96.97% and 100%, respectively, with the benchmark MRI database.
    Matched MeSH terms: Brain/pathology*
  14. Musa KI, Keegan TJ
    PLoS One, 2018;13(12):e0208594.
    PMID: 30571691 DOI: 10.1371/journal.pone.0208594
    BACKGROUND: Acute stroke results in functional disability measurable using the well-known Barthel Index. The objectives of the study are to describe the change in the Barthel Index score and to model the prognostic factors for Barthel Index change from discharge up to 3 months post-discharge using the random intercept model among patients with acute first ever stroke in Kelantan, Malaysia.

    METHODS: A total 98 in-hospital first ever acute stroke patients were recruited, and their Barthel Index scores were measured at the time of discharge, at 1 month and 3 months post-discharge. The Barthel Index was scored through telephone interviews. We employed the random intercept model from linear mixed effect regression to model the change of Barthel Index scores during the three months intervals. The prognostic factors included in the model were acute stroke subtypes, age, sex and time of measurement (at discharge, at 1 month and at 3 month post-discharge).

    RESULTS: The crude mean Barthel Index scores showed an increased trend. The crude mean Barthel Index at the time of discharge, at 1-month post-discharge and 3 months post-discharge were 35.1 (SD = 39.4), 64.4 (SD = 39.5) and 68.8 (SD = 38.9) respectively. Over the same period, the adjusted mean Barthel Index scores estimated from the linear mixed effect model increased from 39.6 to 66.9 to 73.2. The adjusted mean Barthel Index scores decreased as the age increased, and haemorrhagic stroke patients had lower adjusted mean Barthel Index scores compared to the ischaemic stroke patients.

    CONCLUSION: Overall, the crude and adjusted mean Barthel Index scores increase from the time of discharge up to 3-month post-discharge among acute stroke patients. Time after discharge, age and stroke subtypes are the significant prognostic factors for Barthel Index score changes over the period of 3 months.

    Matched MeSH terms: Stroke/pathology*
  15. Nasir NAM, Paus R, Ansell DM
    Wound Repair Regen, 2019 01;27(1):126-133.
    PMID: 30575205 DOI: 10.1111/wrr.12688
    Ex vivo wounded human skin organ culture is an invaluable tool for translationally relevant preclinical wound healing research. However, studies incorporating this system are still underutilized within the field because of the low throughput of histological analysis required for downstream assessment. In this study, we use intravital fluorescent dye to lineage trace epidermal cells, demonstrating that wound re-epithelialization of human ex vivo wounds occurs consistent with an extending shield mechanism of collective migration. Moreover, we also report a relatively simple method to investigate global epithelial closure of explants in culture using daily fluorescent dye treatment and en face imaging. This study is the first to quantify healing of ex vivo wounds in a longitudinal manner, providing global assessments for re-epithelialization and tissue contraction. We show that this approach can identify alterations to healing with a known healing promoter. This methodological study highlights the utility of human ex vivo wounds in enhancing our understanding of mechanisms of human skin repair and in evaluating novel therapies to improve healing outcome.
    Matched MeSH terms: Cells, Cultured/pathology*
  16. Sano Y, Chiu HM, Li XB, Khomvilai S, Pisespongsa P, Co JT, et al.
    Dig Endosc, 2019 May;31(3):227-244.
    PMID: 30589103 DOI: 10.1111/den.13330
    BACKGROUND AND AIM: In recent years, the incidence of colorectal cancer has been increasing, and it is now becoming the major cause of cancer death in Asian countries. The aim of the present study was to develop Asian expert-based consensus to standardize the preparation, detection and characterization for the diagnosis of early-stage colorectal neoplasia.

    METHODS: A professional group was formed by 36 experts of the Asian Novel Bio-Imaging and Intervention Group (ANBI2 G) members. Representatives from 12 Asia-Pacific countries participated in the meeting. The group organized three consensus meetings focusing on diagnostic endoscopy for gastrointestinal neoplasia. The Delphi method was used to develop the consensus statements.

    RESULTS: Through the three consensus meetings with debating, reviewing the literature and regional data, a consensus was reached at third meeting in 2016. The consensus was reached on a total of 10 statements. Summary of statements is as follows: (i) Adequate bowel preparation for high-quality colonoscopy; (ii) Antispasmodic agents for lesion detection; (iii) Image-enhanced endoscopy (IEE) for polyp detection; (iv) Adenoma detection rate for quality indicators; (v) Good documentation of colonoscopy findings; (vi) Complication rates; (vii) Cecal intubation rate; (viii) Cap-assisted colonoscopy (CAC) for polyp detection; (ix) Macroscopic classification using indigocarmine spray for characterization of colorectal lesions; and (x) IEE and/or magnifying endoscopy for prediction of histology.

    CONCLUSION: This consensus provides guidance for carrying out endoscopic diagnosis and characterization for early-stage colorectal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early-stage colorectal neoplasia.

    Matched MeSH terms: Colorectal Neoplasms/pathology
  17. Tan HY, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2020 Jan;40(1):25-51.
    PMID: 31435851 DOI: 10.1007/s10571-019-00724-1
    The progressive loss of structure and functions of neurons, including neuronal death, is one of the main factors leading to poor quality of life. Promotion of functional recovery of neuron after injury is a great challenge in neuroregenerative studies. Melatonin, a hormone is secreted by pineal gland and has antioxidative, anti-inflammatory, and anti-apoptotic properties. Besides that, melatonin has high cell permeability and is able to cross the blood-brain barrier. Apart from that, there are no reported side effects associated with long-term usage of melatonin at both physiological and pharmacological doses. Thus, in this review article, we summarize the pharmacological effects of melatonin as neuroprotectant in central nervous system injury, ischemic-reperfusion injury, optic nerve injury, peripheral nerve injury, neurotmesis, axonotmesis, scar formation, cell degeneration, and apoptosis in rodent models.
    Matched MeSH terms: Nervous System Diseases/pathology
  18. Al Hariri YK, Sulaiman SAS, Khan AH, Adnan AS, Al Ebrahem SQ
    J Infect Public Health, 2019 07 04;12(6):751-759.
    PMID: 31281106 DOI: 10.1016/j.jiph.2019.06.014
    Leptospirosis is the most widely spread zoonosis and Leptospirosis Associated Acute Kidney Injury (LAKI) is common and fatal if not properly and swiftly treated. The aim of this review is to evaluate the mortality of LAKI and to identify the risk factors for its development. An electronic search was performed to identify the studies included LAKI patients series. Only studies which investigated mortality or risk factors for LAKI development in adults were included. Twenty-three studies with 24 patients series were included in the final analysis and included 1698 patients. The median series mortality was 10.05% (range 0-33.3%) with a total of 223 death. Only four studies identified the independent risk factors for LAKI development which were oliguria, jaundice, arrhythmia, crackles, elevated direct bilirubin level, elevated activated prothrombin time, hyperbilirubinemia and leukocytosis. Although the mortality of LAKI is high, its predictors are not studied enough in literature.
    Matched MeSH terms: Acute Kidney Injury/pathology*
  19. Heo CC, Rahimi R, Mengual X, M Isa MS, Zainal S, Khofar PN, et al.
    J Forensic Sci, 2020 Jan;65(1):276-282.
    PMID: 31305956 DOI: 10.1111/1556-4029.14128
    A body of an unknown adult female was found within a shallow burial ground in Malaysia whereas the skull was exposed and visible on the ground. During autopsy examination, nine insect larvae were recovered from the interior of the human skull and subsequently preserved in 70% ethanol. The larvae were greyish in appearance, each with a posterior elongated breathing tube. A week after the autopsy, more larvae were collected at the burial site, and some of them were reared into adults. Adult specimens and larvae from the skull and from the burial site were sequenced to obtain DNA barcodes. Results showed all adult flies reared from the burial site, as well as the larvae collected from the skull were identified as Eristalinus arvorum (Fabricius, 1787) (Diptera: Syrphidae). Here, we report the colonization of E. arvorum larvae on a human corpse for the first time.
    Matched MeSH terms: Skull/pathology*
  20. Ghani WMN, Ramanathan A, Prime SS, Yang YH, Razak IA, Abdul Rahman ZA, et al.
    Cancer Invest, 2019;37(7):275-287.
    PMID: 31307249 DOI: 10.1080/07357907.2019.1635614
    Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
    Matched MeSH terms: Mouth Neoplasms/pathology
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