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Fulltext Corrigendum: Stylopine: a potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.

Front Pharmacol, 2024;15:1343756.
PMID: 38299157 DOI: 10.3389/fphar.2024.1343756

[This corrects the article DOI: 10.3389/fphar.2023.1150270.].
Fulltext Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.

Front Pharmacol, 2023;14:1150270.
PMID: 37056983 DOI: 10.3389/fphar.2023.1150270

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski's rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.
Fulltext Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

Abubakar MB, Usman D, El-Saber Batiha G, Cruz-Martins N, Malami I, Ibrahim KG, et al.

Front Pharmacol, 2021;12:629935.
PMID: 34012391 DOI: 10.3389/fphar.2021.629935

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.
Genetic, historical and linguistic perspectives on the origin of the Kelantanese Malays

Loo KW, Gan SH

Gene, 2014 Jul 15;545(1):1-4.
PMID: 24815047 DOI: 10.1016/j.gene.2014.05.016

The Kelantanese Malays who resided in the remote northeastern regions of the Malay Peninsula in the Kelantan state are believed to have a unique genetic signature. The objective of this review is to analyze the populational sub-structure of the Kelantanese Malays from historical, genetic and linguistic perspectives. Historical data suggest that the Semang were composed of the Jahai, Bateq and Kensiu sub-tribes, whereas the Senoi were composed of only the Temiar sub-tribe. The Mendriq sub-tribe is believed to be the first group of aborigines to land in Kelantan. Subsequently, genetic analysis showed that the Kelantanese Malays are an independent clade at the base of the phylogenetic tree and contain genetic material similar to that of the Semang, specifically the Jahai and the Kensiu sub-tribes. The genetic data are supported by the fact that the Aslian language, a branch of the Austroasiatic languages that is widely spoken by the Semang, was potentially transmitted through agricultural activities. However, the potential limitation of this mini-review is the lack of primary reliable sources covering the historical, linguistic and genetic features of the Kelantanese Malays.
Fulltext The Role of microRNAs in Alzheimer's Disease and Their Therapeutic Potentials

Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH

Genes (Basel), 2018 Mar 21;9(4).
PMID: 29561798 DOI: 10.3390/genes9040174

MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer's disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD.
Fulltext Side effects of CoronaVac® COVID-19 vaccination: Investigation in North Jakarta district public health center communities in Indonesia

Ramatillah DL, Gan SH, Novarticia J, Araminda GN, Michael M, Elnaem M, et al.

Heliyon, 2024 May 15;10(9):e30087.
PMID: 38694099 DOI: 10.1016/j.heliyon.2024.e30087

BACKGROUND: The decreasing prevalence of COVID-19 has highlighted the value of vaccinations. CoronaVac® vaccine was one of the most widely used vaccines in Indonesia, in other Southeast Asian countries, as well as in Latin America. However, to date the safety and side effect profiles of CoronaVac® vaccine among the Indonesian population have not been reported.
OBJECTIVE: In this study, the CoronaVac® safety profiles were determined in a community of a public health center in North Jakarta, Indonesia.
METHOD: This is a descriptive cross-sectional questionnaire-based study on vaccine side effects as recorded in the yellow form (MESO). Patients (n = 300) who received CoronaVac® vaccinations between July and August 2021 were enrolled. SPSS was used to analyze the descriptive data.
RESULTS: Most respondents were women (72.7 %) between the ages of 17 and 21 years. A significantly (p = 0.009) positive correlation was established between the vaccine side effects (namely pain at the injection site) with the female gender. Other side effects such as fatigue (p = 0.034) and headache (p
A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats

Tanvir EM, Afroz R, Chowdhury M, Gan SH, Karim N, Islam MN, et al.

Hum Exp Toxicol, 2016 Sep;35(9):991-1004.
PMID: 26519480 DOI: 10.1177/0960327115614384

This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.
Frontiers of monoclonal antibodies: Applications in medical practices

Ghagane SC, Puranik SI, Gan SH, Hiremath MB, Nerli RB, Ravishankar MV

Hum Antibodies, 2017;26(3):135-142.
PMID: 29060935 DOI: 10.3233/HAB-170331

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.
Fulltext Rapid resolution liquid chromatography method development and validation for simultaneous determination of homocysteine, vitamins B(6), B(9), and B(12) in human serum

Shaik MM, Gan SH

Indian J Pharmacol, 2013 Mar-Apr;45(2):159-67.
PMID: 23716893 DOI: 10.4103/0253-7613.108303

Hyperhomocysteinemia and vitamins B(6), B(9), and B(12) deficiencies usually result in various neurological, vascular, ocular, renal, and pulmonary abnormalities. However, to date, there are no simultaneous detection methods available for determining homocysteine, vitamins B(6), B(9), and B(12) levels in various biological fluids. In this study, we aim to develop a new validated simultaneous detection method for all four compounds to save both cost and time of analysis.
Fulltext Tualang honey adjunct with anastrozole improve parenchyma enhancement of breast tissue in breast cancer patients: A randomized controlled trial

Hizan NS, Hassan NHM, Haron J, Abubakar MB, Mahdi NMN, Gan SH

Integr Med Res, 2018 Dec;7(4):322-327.
PMID: 30591885 DOI: 10.1016/j.imr.2018.07.002

Background: To investigate whether the combination of anastrozole and Tualang honey (T honey) influences background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) of postmenopausal women with breast cancer.
Methods: A total of 30 patients were recruited and randomly divided into control (anastrozole 1 mg daily) and intervention (anastrozole 1 mg + T honey 20 g daily). The BPE of the contralateral breast before and six months following treatment was compared using the sign test.
Results: There was a decrease in BPE in 10% of the women (p = 0.317) who received only anastrozole, which resulted in a change of BPE category from moderate to mild. However, the combination of anastrozole and T honey evoked a decrease in BPE in 42% of the patients (p = 0.034).
Conclusions: The combination of T honey and anastrozole maybe more efficacious than anastrozole alone in decreasing breast BPE in breast cancer patients. These findings support the medicinal value of T honey as an adjuvant treatment to anastrozole.
Mapping the role of pH-adjusted potassium in diabetic ketoacidosis: Hypokalemia and the patient outcomes

Usman A, Mustafa N, Iqbal SP, Hasan MZ, Shaikh MF, Dujaili JA, et al.

Int J Clin Pract, 2021 Aug;75(8):e14315.
PMID: 33934480 DOI: 10.1111/ijcp.14315

BACKGROUND: Incidence of hypokalemia during the management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment.
AIM: We aimed to find the role of pH-adjusted potassium (pHK ) in the development of hypokalemia, and their mutual impact on patient outcomes during DKA management.
METHODOLOGY: Adult DKA patient's admission data of preceding 3 years (2015-2017) were retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (hours), severity of hypokalemia and hospitalisation length (days). Linear regression was used to determine significant associations/predictors.
RESULTS: The study was concluded on 85 patients. Hypokalemia was observed in nearly 3/4th of all admissions and occurred by the time of ED care termination. Each 1 mmol/L increase in pHK significantly (a) reduced the degree of hypokalemia by 0.07 mmol/L, (b) delayed time to develop hypokalemia by 4.58 hours, (c) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each 1 mmol/L reduction in the degree of hypokalemia increased hospitalisation length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalisation length by 0.01 days.
CONCLUSION: pH-adjusted potassium shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measured serum potassium in DKA. Utilising pHK will help to avoid hypokalemia, reduce its severity and shorten ED care which will subsequently reduce hospitalisation length. We expect pHK to improve pharmacoeconomics in the future.
Nonpharmacologic Interventions in Prevention and Treatment of Hypertension

Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S

Int J Hypertens, 2019;2019:6709817.
PMID: 31001431 DOI: 10.1155/2019/6709817
Fulltext Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension"

Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S

Int J Hypertens, 2019 10 13;2019:2907675.
PMID: 31737360 DOI: 10.1155/2019/2907675

[This corrects the article DOI: 10.1155/2019/6709817.].
Fulltext Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells

Haque ST, Islam RA, Gan SH, Chowdhury EH

Int J Mol Sci, 2020 Sep 14;21(18).
PMID: 32937817 DOI: 10.3390/ijms21186721

Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.
Fulltext Biogenic silver nanoparticles using Rhinacanthus nasutus leaf extract: synthesis, spectral analysis, and antimicrobial studies

Pasupuleti VR, Prasad TN, Shiekh RA, Balam SK, Narasimhulu G, Reddy CS, et al.

Int J Nanomedicine, 2013;8:3355-64.
PMID: 24039419 DOI: 10.2147/IJN.S49000

Nanotechnology is gaining momentum due to its ability to transform metals into nanoparticles. The synthesis, characterization, and applications of biologically synthesized nanomaterials have become an important branch of nanotechnology. Plant extracts are a cost-effective, ecologically friendly, and efficient alternative for the large-scale synthesis of nanoparticles. In this study, silver nanoparticles (AgNps) were synthesized using Rhinacanthus nasutus leaf extract. After exposing the silver ions to the leaf extract, the rapid reduction of silver ions led to the formation of AgNps in solution. The synthesis was confirmed by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy. The in vitro antimicrobial activity of the AgNps synthesized using R. nasutus leaf extract was investigated against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, Aspergillus niger, and Aspergillus flavus using a disc diffusion method. The AgNps showed potential activity against all of the bacterial strains and fungal colonies, indicating that R. nasutus has the potential to be used in the development of value-added products in the biomedical and nanotechnology-based industries.
Fulltext Drug Delivery of Natural Products Through Nanocarriers for Effective Breast Cancer Therapy: A Comprehensive Review of Literature

Yap KM, Sekar M, Fuloria S, Wu YS, Gan SH, Mat Rani NNI, et al.

Int J Nanomedicine, 2021;16:7891-7941.
PMID: 34880614 DOI: 10.2147/IJN.S328135

Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants' extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: "Natural Product AND Nanoparticle AND Breast Cancer". Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans.
The burden of stroke in the Lao People's Democratic Republic

Loo KW, Gan SH

Int J Stroke, 2013 Jun;8(4):273-5.
PMID: 22974070 DOI: 10.1111/j.1747-4949.2012.00884.x

In the Lao People's Democratic Republic (Laos), stroke is ranked as the third leading cause of death, with a 9·01% mortality rate. To date, neither the prevalence nor the incidence of stroke has been recorded in Laos. This omission may be attributed to a lack of awareness among Laotians of the signs and symptoms of stroke, incomplete data, or insufficient database recording. The only risk factor for stroke that has been studied extensively is cigarette smoking; studies have found that smokers have twice the risk of stroke. Unfortunately, smoking is increasing among youths, adults, and even healthcare professionals. The Southeast Asia Tobacco Control Alliance stated that 42% of hospitalized stroke patients are smokers. Laos is one of the least developed countries in the world, and the country has only one fully trained neurologist for the growing number of stroke cases. The Laos government should seek help from international bodies, such as the World Health Organization, to monitor and rehabilitate stroke patients and prevent stroke occurrence and recurrence.
Burden of stroke in Cambodia

Loo KW, Gan SH

Int J Stroke, 2013 Aug;8(6):475-8.
PMID: 22973861 DOI: 10.1111/j.1747-4949.2012.00868.x

In Cambodia, stroke is not ranked among the top 10 leading causes of death, but infectious disease are among the top three leading causes of death. This finding could be attributed to a lack of awareness among Cambodians of the signs and symptoms of stroke or to poor reporting, incomplete data, lack of neurologists and neurosurgeons, or low accessibility to the hospitals. The only study of stroke in Cambodia is the Prevalence of Non-Communicable Disease Risk Factors in Cambodia survey, which identified several stroke-related risk factors in the population. Tobacco chewing or smoking is the main risk factor for stroke in Cambodia. Traditional therapies, such as oyt pleung (moxibustion) and jup (cupping), are widely practiced for stroke rehabilitation. In Cambodia, there are few neurologists and few important equipment, such as magnetic resonance imaging machines and computed tomography scanners. The Cambodian government should cooperate with the World Health Organization and the United Nations Children's Fund to attract foreign expertise and technologies to treat stroke patients.
Burden of stroke in the Philippines

Loo KW, Gan SH

Int J Stroke, 2013 Feb;8(2):131-4.
PMID: 22568853 DOI: 10.1111/j.1747-4949.2012.00806.x

Based on disability-adjusted life-years, stroke is the second leading cause of death and among the top five diseases with the greatest burden. Although two community-based studies have been conducted to determine the prevalence of stroke in the Philippines, the incidence has not been nationally recorded to date. The prevalence ranged from 1·9% to 6·59%, and 'Wiihabilitation', a rehabilitation stroke therapy, is widely practiced. A clinical trial for stroke rehabilitation using the Chinese Medicine NeuroAid®, which consists of several herbs, is ongoing in many hospitals across the Philippines. Due to their ready availability, phytomedicines are widely used, especially in the rural areas, for the treatment of hypertension, diabetes mellitus, and hypercholesterolemia, which are predisposing factors for stroke in the Philippines. Due to the increasing number of stroke cases annually, the government of the Philippines should emphasize primary and secondary prevention strategies.
Burden of stroke in Malaysia

Loo KW, Gan SH

Int J Stroke, 2012 Feb;7(2):165-7.
PMID: 22264370 DOI: 10.1111/j.1747-4949.2011.00767.x

Stroke is one of the top five leading causes of death and one of the top 10 causes for hospitalization in Malaysia. Stroke is also in the top five diseases with the greatest burden of disease, based on disability-adjusted life years. However, prospective studies on stroke in Malaysia are limited. To date, neither the prevalence of stroke nor its incidence nationally has been recorded. Hypertension is the major risk factor for stroke. The mean age of stroke patients in Malaysia is between 54.5 and 62.6 years. Traditional medicine is commonly practiced. With the increasing number of stroke cases annually, more government and nongovernment organizations should be involved in primary and secondary prevention strategies.

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