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Are the Radiological and Molecular Features of Pediatric Medulloblastomas Valuable Prognostic Indicators? A 10-year Retrospective Review in the Middle East

Alhaj AK, Burhamah T, Mohammad F, Almutawa M, Dashti F, Almurshed M, et al.

World Neurosurg, 2024 Apr 16.
PMID: 38636638 DOI: 10.1016/j.wneu.2024.04.057

BACKGROUND: Medulloblastomas are the most common malignant brain tumors in the pediatric population. Based on the idea that tumors with identical radio-genomic features should behave similarly, the four molecular subtypes are now widely accepted as a guide for the management and prognosis. The radiological features of medulloblastomas can predict the molecular subtype; thus, anticipating the subsequent disease progression. However, this has not been evaluated comprehensively.
PURPOSE: We aim to thoroughly study the association between the molecular subtypes and radiological features of medulloblastomas. Moreover, we aim to investigate the efficacy of this correlation with the use of progression-free survival (PFS) and five-year survival rates.
METHODS: A retrospective analysis was conducted for all histopathological confirmed medulloblastomas in pediatric patients (<16 years old) that were operated on in Kuwait over the past ten years (n=44). The radiological, histological, and molecular characteristics were justifiably evaluated and analyzed in our sample.
RESULTS: The overall progression-free survival after one year was noticed among 27 cases (≈44%) and the non-specific five-year survival was seen in 31 cases (≈70%) after a five-year follow-up. SHH and WNT had the best outcomes, while group 3 showed the worst outcomes.
CONCLUSION: Our findings did not support the association between most of the typical MRI characteristics and survival rate. We further established that SHH and WNT biological types have a better prognosis. There was no association observed between the radiographic features, specifically the location, and the molecular subtype.
A nationwide survey on awareness and knowledge about Bronchial Provocation Test amongst doctors in Malaysia

Ng KL, Huan NC, Mohammad FA, Mohd Aminudin NH, Mohammad FA, Abdul Rahaman JA

Med J Malaysia, 2022 Jan;77(1):33-40.
PMID: 35086992

BACKGROUND: Bronchial provocation test (BPT) is widely used internationally not only to evaluate bronchial responsiveness in conditions especially asthma, but is also utilized as a marker of control, severity and prognosis for asthma. However, the uptake of BPT in certain countries including Malaysia remains low. We aimed to explore this lack of knowledge by assessing the current level of awareness and knowledge on BPT amongst doctors in Malaysia.
MATERIALS AND METHODS: A nationwide web-based questionnaire targeting doctors was sent through social media (Facebook, WhatsApp and Telegram) and Malaysian Medical Association (MMA) mailing lists between 1 October 2020 - 5 February 2021.
RESULTS: In all 415 survey responses were analysed from doctors of various grades namely medical officers to consultants. A total of 404 (97.35%) encountered patients with asthma in their daily practice. According to specialty: 169 (40.72%) were from primary care, 121 (29.16%) internal medicine, 50 (12.05%) pulmonary medicine and 75 (18.07%) others. Only 163 (39.28%) were aware of BPT as a tool to diagnose asthma. 232 (55.90%) and 124 (29.88%) regarded BPT as an important test and felt confident to refer patients for BPT respectively. Of those participants who were not confident to refer: 35.17% were unsure of BPT indications, 33.21% were unsure of centres providing BPT, 8.17% cited logistic reasons, 6.04% were concerned of possible BPT side effects. 387 (93.25%) wanted more training in BPT. The median BPT knowledge score was 20% (1 out of 5). Awareness and knowledge were affected by specialty but not by: region of practice, gender, age and grade from logistic regression analysis.
CONCLUSION: Various national level programs and targeted local interventions are much needed to increase the awareness, knowledge and uptake of BPT in Malaysia.
Fulltext Using a Deep Learning Method and Data from Two-Dimensional (2D) Marker-Less Video-Based Images for Walking Speed Classification

Sikandar T, Rabbi MF, Ghazali KH, Altwijri O, Alqahtani M, Almijalli M, et al.

Sensors (Basel), 2021 Apr 17;21(8).
PMID: 33920617 DOI: 10.3390/s21082836

Human body measurement data related to walking can characterize functional movement and thereby become an important tool for health assessment. Single-camera-captured two-dimensional (2D) image sequences of marker-less walking individuals might be a simple approach for estimating human body measurement data which could be used in walking speed-related health assessment. Conventional body measurement data of 2D images are dependent on body-worn garments (used as segmental markers) and are susceptible to changes in the distance between the participant and camera in indoor and outdoor settings. In this study, we propose five ratio-based body measurement data that can be extracted from 2D images and can be used to classify three walking speeds (i.e., slow, normal, and fast) using a deep learning-based bidirectional long short-term memory classification model. The results showed that average classification accuracies of 88.08% and 79.18% could be achieved in indoor and outdoor environments, respectively. Additionally, the proposed ratio-based body measurement data are independent of body-worn garments and not susceptible to changes in the distance between the walking individual and camera. As a simple but efficient technique, the proposed walking speed classification has great potential to be employed in clinics and aged care homes.
Fulltext Immuno Nanosensor for the Ultrasensitive Naked Eye Detection of Tuberculosis

Mohd Bakhori N, Yusof NA, Abdullah J, Wasoh H, Md Noor SS, Ahmad Raston NH, et al.

Sensors (Basel), 2018 Jun 14;18(6).
PMID: 29899214 DOI: 10.3390/s18061932

In the present study, a beneficial approach for the ultrasensitive and affordable naked eye detection and diagnosis of tuberculosis (TB) by utilizing plasmonic enzyme-linked immunosorbent assay (ELISA) via antibody-antigen interaction was studied. Here, the biocatalytic cycle of the intracellular enzymes links to the formation and successive growth of the gold nanoparticles (GNPs) for ultrasensitive detection. The formation of different colored solutions by the plasmonic nanoparticles in the presence of enzyme labels links directly to the existence or non-existence of the TB analytes in the sample solutions. For disease detection, the adapted protocol is based mainly on the conventional ELISA procedure that involves catalase-labeled antibodies, i.e., the enzymes consume hydrogen peroxide and further produce GNPs with the addition of gold (III) chloride. The amount of hydrogen peroxide remaining in the solution determines whether the GNPs solution is to be formed in the color blue or the color red, as it serves as a confirmation for the naked eye detection of TB analytes. However, the conventional ELISA method only shows tonal colors that need a high concentration of analyte to achieve high confidence levels for naked eye detection. Also, in this research, we proposed the incorporation of protein biomarker, Mycobacterium tuberculosis ESAT-6-like protein esxB (CFP-10), as a means of TB detection using plasmonic ELISA. With the use of this technique, the CFP-10 detection limit can be lowered to 0.01 µg/mL by the naked eye. Further, our developed technique was successfully tested and confirmed with sputum samples from patients diagnosed with positive TB, thereby providing enough evidence for the utilization of our technique in the early diagnosis of TB disease.
Fulltext Thiolate-Capped CdSe/ZnS Core-Shell Quantum Dots for the Sensitive Detection of Glucose

Abd Rahman S, Ariffin N, Yusof NA, Abdullah J, Mohammad F, Ahmad Zubir Z, et al.

Sensors (Basel), 2017 Jul 01;17(7).
PMID: 28671559 DOI: 10.3390/s17071537

A semiconducting water-soluble core-shell quantum dots (QDs) system capped with thiolated ligand was used in this study for the sensitive detection of glucose in aqueous samples. The QDs selected are of CdSe-coated ZnS and were prepared in house based on a hot injection technique. The formation of ZnS shell at the outer surface of CdSe core was made via a specific process namely, SILAR (successive ionic layer adsorption and reaction). The distribution, morphology, and optical characteristics of the prepared core-shell QDs were assessed by transmission electron microscopy (TEM) and spectrofluorescence, respectively. From the analysis, the results show that the mean particle size of prepared QDs is in the range of 10-12 nm and that the optimum emission condition was displayed at 620 nm. Further, the prepared CdSe/ZnS core shell QDs were modified by means of a room temperature ligand-exchange method that involves six organic ligands, L-cysteine, L-histidine, thio-glycolic acid (TGA or mercapto-acetic acid, MAA), mercapto-propionic acid (MPA), mercapto-succinic acid (MSA), and mercapto-undecanoic acid (MUA). This process was chosen in order to maintain a very dense water solubilizing environment around the QDs surface. From the analysis, the results show that the CdSe/ZnS capped with TGA (CdSe/ZnS-TGA) exhibited the strongest fluorescence emission as compared to others; hence, it was tested further for the glucose detection after their treatment with glucose oxidase (GOx) and horseradish peroxidase (HRP) enzymes. Here in this study, the glucose detection is based on the fluorescence quenching effect of the QDs, which is correlated to the oxidative reactions occurred between the conjugated enzymes and glucose. From the analysis of results, it can be inferred that the resultant GOx:HRP/CdSe/ZnS-TGA QDs system can be a suitable platform for the fluorescence-based determination of glucose in the real samples.
Fulltext Annual Southeast Asia haze increases respiratory admissions: A 2-year large single institution experience

Ming CR, Ban Yu-Lin A, Abdul Hamid MF, Latif MT, Mohammad N, Hassan T

Respirology, 2018 10;23(10):914-920.
PMID: 29923364 DOI: 10.1111/resp.13325

BACKGROUND AND OBJECTIVE: The Southeast Asia (SEA) haze is an annual problem and at its worst could produce respirable particles of concentrations up to 500 μg/m3 which is five times the level considered as 'unhealthy'. However, there are limited reports examining the direct clinical impact of the annual haze. This study examines the effects of the SEA haze on respiratory admissions.
METHODS: Data from all respiratory admissions in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2014 to 31st December 2015 were collected retrospectively from chart and electronic database. A total of 16 weeks of haze period had been formally dated by the Department of Environment using the definition of weather phenomenon leading to atmospheric visibility of less than 10 km. Multivariable regression analyses were performed to estimate rate ratios and 95% CI.
RESULTS: There were 1968 subjects admitted for respiratory admissions in UKMMC during the study period. Incidence rates per week were significantly different between the two groups with 27.6 ± 9.2 cases per week during the haze versus 15.7 ± 6.7 cases per week during the non-haze period (P < 0.01). A total of 4% versus 2% was admitted to the intensive care unit in the haze and the non-haze groups, respectively (P = 0.02). The mean ± SD lengths of stay was 12.1 ± 5.2 days; the haze group had a longer stay (18.2 ± 9.7 days) compared to the non-haze groups (9.7 ± 3.9) (P < 0.001).
CONCLUSION: The annual SEA haze is associated with increased respiratory admissions.
Fulltext Hydrophobically Grafted Pullulan Nanocarriers for Percutaneous Delivery: Preparation and Preliminary In Vitro Characterisation

Bostanudin MF, Barbu E, Liew KB

Polymers (Basel), 2021 Aug 25;13(17).
PMID: 34502895 DOI: 10.3390/polym13172852

Polymeric colloidal nanocarriers formulated from hydrophobically grafted carbohydrates have been the subject of intensive research due to their potential to increase the percutaneous penetration of hydrophilic actives. To this goal, a series of hydrophobically grafted pullulan (BMO-PUL) derivatives with varying degree of grafting (5-64%) was prepared through functionalisation with 2-(butoxymethyl)oxirane. The results demonstrated that monodispersed BMO-PUL nanocarriers (size range 125-185 nm) could be easily prepared via nanoprecipitation; they exhibit close-to-spherical morphology and adequate stability at physiologically relevant pH. The critical micellar concentration of BMO-PUL was found to be inversely proportional to their molecular weight (Mw) and degree of grafting (DG), with values of 60 mg/L and 40 mg/L for DG of 12.6% and 33.8%, respectively. The polymeric nanocarriers were loaded with the low Mw hydrophilic active α-arbutin (16% loading), and the release of this active was studied at varying pH values (5 and 7), with a slightly faster release observed in acidic conditions; the release profiles can be best described by a first-order kinetic model. In vitro investigations of BMO-PUL nanocarriers (concentration range 0.1-4 mg/mL) using immortalised skin human keratinocytes cells (HaCaT) evidenced their lack of toxicity, with more than 85% cell viability after 24 h. A four-fold enhance in arbutin permeation through HaCaT monolayers was recorded when the active was encapsulated within the BMO-PUL nanocarriers. Altogether, the results obtained from the in vitro studies highlighted the potential of BMO-PUL nanocarriers for percutaneous delivery applications, which would warrant further investigation in vivo.
Fulltext Evaluation of porogen factors for the preparation of ion imprinted polymer monoliths used in mercury removal

Rahman SKA, Yusof NA, Abdullah AH, Mohammad F, Idris A, Al-Lohedan HA

PLoS One, 2018;13(4):e0195546.
PMID: 29649325 DOI: 10.1371/journal.pone.0195546

In the present study, ion imprinted polymer monoliths (IIPMs) were developed to overcome the limitations of ion imprinted polymer particles (IIPPs) used for the removal of Hg(II) ions from waste water samples. The adsorbents preparation, characterization and Hg(II) removal were very well reported. The IIPMs on porogen optimization was prepared using the molding technique with Hg(II) as a template ion, [2-(methacryloyloxy)ethyl]trimethylammonium cysteine (MAETC) as ligand, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylamide (EGDMA) as cross-linker, benzoyl peroxide as an initiator and methanol and acetonitrile as porogen in the polypropylene tube (drinking straw) as mold. The IIPMs prepared with higher volumes of porogen were indicated to have a good adsorption rate for the Hg(II) removal along with good water permeability and larger porosity as compared to a lower volume of porogen. The IIPMs prepared using the binary porogen were able to improve the porosity and surface area of the monolithic polymers as compared to the single porogen added IIPMs. Finally, we indicate from our analysis that the IIPM having the efficient capacity for the Hg(II) ions is easy to prepare, and has higher water permeability along with high porosity and high adsorption capacity and all these factors making it one of the suitable adsorbent for the successful removal of Hg(II) ions.
Fulltext Depression, anxiety, and stress among university students in Selangor, Malaysia during COVID-19 pandemics and their associated factors

Wong SS, Wong CC, Ng KW, Bostanudin MF, Tan SF

PLoS One, 2023;18(1):e0280680.
PMID: 36696454 DOI: 10.1371/journal.pone.0280680

INTRODUCTION: This study aims to assess the impacts of COVID-19 pandemics among university students in Malaysia, by identifying the prevalence of depression, anxiety and stress among them and their respective predictors.
METHODOLOGY: An online cross-sectional study was conducted via non-probabilistic convenience sampling. Data were collected on sociodemographic characteristics, lifestyle, COVID-19 related influences. Mental health status was assessed with depression, anxiety, and stress scale (DASS-21).
RESULTS: 388 students participated this study (72.4% female; 81.7% Bachelor's student). The prevalence of moderate to severe depression, anxiety and stress among university students are 53.9%, 66.2% and 44.6%, respectively. Multivariable logistic regression analysis found that the odds of depression were lower among students who exercise at least 3 times per week (OR: 0.380, 95% CI: 0.203-0.711). The odd ratio of student who had no personal history of depression to had depression, anxiety and stress during this pandemic was also lower in comparison (OR: 0.489, 95% CI: 0.249-0.962; OR: 0.482, 95% CI: 0.241-0.963; OR: 0.252, 95% CI: 0.111-0.576). Surprisingly, students whose are currently pursuing Master study was associated with lower stress levels (OR: 0.188, 95% CI: 0.053-0.663). However, student who had poorer satisfaction of current learning experience were more likely to experience stress (OR: 1.644, 95% CI: 1.010-2.675).
LIMITATIONS: It is impossible to establish causal relationships between variables on mental health outcomes, and there is a risk of information bias.
CONCLUSION: The prevalence of mental health issues among university students is high. These findings present essential pieces of predictive information when promoting related awareness among them.
Fulltext Drug Release Profiles of Mitomycin C Encapsulated Quantum Dots-Chitosan Nanocarrier System for the Possible Treatment of Non-Muscle Invasive Bladder Cancer

Manan FAA, Yusof NA, Abdullah J, Mohammad F, Nurdin A, Yazan LS, et al.

Pharmaceutics, 2021 Aug 31;13(9).
PMID: 34575455 DOI: 10.3390/pharmaceutics13091379

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated chitosan (CS)-based nanocarrier system encapsulated with Mitomycin C (MMC) drug. This fabricated nanocarrier, MMC@CS-Mn:ZnS, has been tested thoroughly for the drug loading capacity, drug encapsulation efficiency, and release properties at a fixed wavelength (358 nm) using a UV-Vis spectrophotometer. Followed by the physicochemical characterization, the cumulative drug release profiling data of MMC@CS-Mn:ZnS nanocarrier (at pH of 6.5, 6.8, 7.2, and 7.5) were investigated to have the highest release of 56.48% at pH 6.8, followed by 50.22%, 30.88%, and 10.75% at pH 7.2, 6.5, and 7.5, respectively. Additionally, the drug release studies were fitted to five different pharmacokinetic models including pesudo-first-order, pseudo-second-order, Higuchi, Hixson-Crowell, and Korsmeyers-Peppas models. From the analysis, the cumulative MMC release suits the Higuchi model well, revealing the diffusion-controlled mechanism involving the correlation of cumulative drug release proportional to the function square root of time at equilibrium, with the correlation coefficient values (R2) of 0.9849, 0.9604, 0.9783, and 0.7989 for drug release at pH 6.5, 6.8, 7.2, and 7.5, respectively. Based on the overall results analysis, the formulated nanocarrier system of MMC synergistically envisages the efficient delivery of chemotherapeutic agents to the target cancerous sites, able to sustain it for a longer time, etc. Consequently, the developed nanocarrier system has the capacity to improve the drug loading efficacy in combating the reoccurrence and progression of cancer in non-muscle invasive bladder diseases.
Fulltext Aptasensor for the Detection of Mycobacterium tuberculosis in Sputum Utilising CFP10-ESAT6 Protein as a Selective Biomarker

Azmi UZM, Yusof NA, Abdullah J, Mohammad F, Ahmad SAA, Suraiya S, et al.

Nanomaterials (Basel), 2021 Sep 20;11(9).
PMID: 34578762 DOI: 10.3390/nano11092446

A portable electrochemical aptamer-antibody based sandwich biosensor has been designed and successfully developed using an aptamer bioreceptor immobilized onto a screen-printed electrode surface for Mycobacterium tuberculosis (M. tuberculosis) detection in clinical sputum samples. In the sensing strategy, a CFP10-ESAT6 binding aptamer was immobilized onto a graphene/polyaniline (GP/PANI)-modified gold working electrode by covalent binding via glutaraldehyde linkage. Upon interaction with the CFP10-ESAT6 antigen target, the aptamer will capture the target where the nano-labelled Fe3O4/Au MNPs conjugated antibody is used to complete the sandwich format and enhance the signal produced from the aptamer-antigen interaction. Using this strategy, the detection of CFP10-ESAT6 antigen was conducted in the concentration range of 5 to 500 ng/mL. From the analysis, the detection limit was found to be 1.5 ng/mL, thereby demonstrating the efficiency of the aptamer as a bioreceptor. The specificity study was carried out using bovine serum albumin (BSA), MPT64, and human serum, and the result demonstrated good specificity that is 7% higher than the antibody-antigen interaction reported in a previous study. The fabricated aptasensor for M. tuberculosis analysis shows good reproducibility with an relative standard deviation (RSD) of 2.5%. Further analysis of M. tuberculosis in sputum samples have shown good correlation with the culture method with 100% specificity and sensitivity, thus making the aptasensor a promising candidate for M. tuberculosis detection considering its high specificity and sensitivity with clinical samples.
Fulltext Preparation, Characterization, and Radiolabeling of [68Ga]Ga-NODAGA-Pamidronic Acid: A Potential PET Bone Imaging Agent

Ashhar Z, Yusof NA, Ahmad Saad FF, Mohd Nor SM, Mohammad F, Bahrin Wan Kamal WH, et al.

Molecules, 2020 Jun 09;25(11).
PMID: 32526838 DOI: 10.3390/molecules25112668

Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of image-guided radiopharmaceuticals are being employed as an alternative to traditional biopsies. Hence, in the present work, we tested the efficacy of a gallium-68 (68Ga)-based compound as a radiopharmaceutical agent towards the bone imaging in positron emitting tomography (PET). For that, we prepared, thoroughly characterized, and radiolabeled [68Ga]Ga-NODAGA-pamidronic acid radiopharmaceutical, a 68Ga precursor for PET bone cancer imaging applications. The preparation of NODAGA-pamidronic acid was performed via the N-Hydroxysuccinimide (NHS) ester strategy and was characterized using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MSn). The unreacted NODAGA chelator was separated using the ion-suppression reverse phase-high performance liquid chromatography (RP-HPLC) method, and the freeze-dried NODAGA-pamidronic acid was radiolabeled with 68Ga. The radiolabeling condition was found to be most optimum at a pH ranging from 4 to 4.5 and a temperature of above 60 °C. From previous work, we found that the pamidronic acid itself has a good bone binding affinity. Moreover, from the analysis of the results, the ionic structure of radiolabeled [68Ga]Ga-NODAGA-pamidronic acid has the ability to improve the blood clearance and may exert good renal excretion, enhance the bone-to-background ratio, and consequently the final image quality. This was reflected by both the in vitro bone binding assay and in vivo animal biodistribution presented in this research.
Fulltext Production of Biodegradable Polymer from Agro-Wastes in Alcaligenes sp. and Pseudomonas sp

Sayyed RZ, Shaikh SS, Wani SJ, Rehman MT, Al Ajmi MF, Haque S, et al.

Molecules, 2021 Apr 22;26(9).
PMID: 33922162 DOI: 10.3390/molecules26092443

The present study was aimed to evaluate the suitability of agro-wastes and crude vegetable oils for the cost-effective production of poly-β-hydroxybutyrate (PHB), to evaluate growth kinetics and PHB production in Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1 with these carbon substrates and to study the biodegradation of PHB accumulated by these cultures. Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1 accumulates higher amounts of PHB corn (79.90% of dry cell mass) and rice straw (66.22% of dry cell mass) medium respectively. The kinetic model suggests that the Pseudomonas sp. RZS1 follows the Monod model more closely than A. faecalis RZS4. Both the cultures degrade their PHB extract under the influence of PHB depolymerase. Corn waste and rice straw appear as the best and cost-effective substrates for the sustainable production of PHB from Alcaligenes faecalis RZS4 and Pseudomonas sp. RZS1. The biopolymer accumulated by these organisms is biodegradable in nature. The agro-wastes and crude vegetable oils are good and low-cost sources of nutrients for the growth and production of PHB and other metabolites. Their use would lower the production cost of PHB and the low-cost production will reduce the sailing price of PHB-based products. This would promote the large-scale commercialization and popularization of PHB as an ecofriendly bioplastic/biopolymer.
Fulltext DNA Adsorption Studies of Poly(4,4'-Cychlohexylidene Bisphenol Oxalate)/Silica Nanocomposites

Al Balawi AN, Yusof NA, Kamaruzaman S, Mohammad F, Wasoh H, Al-Lohedan HA

Materials (Basel), 2019 Apr 11;12(7).
PMID: 30978916 DOI: 10.3390/ma12071178

The present study deals with the synthesis, characterization, and DNA extraction of poly(4,4'-cyclohexylidene bisphenol oxalate)/silica (Si) nanocomposites (NCs). The effects of varying the monomer/Si (3.7%, 7%, and 13%) ratio towards the size and morphology of the resulting NC and its DNA extraction capabilities have also been studied. For the NC synthesis, two different methods were followed, including the direct mixing of poly(4,4'-cyclohexylidene bisphenol oxalate) with fumed Si, and in situ polymerization of the 4,4'-cyclohexylidene bisphenol monomer in the presence of fumed silica (11 nm). The formed NCs were thoroughly investigated by using different techniques such as scanning electron microscopy (SEM), fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powdered X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) analysis where the results supported that there was the successful formation of poly(4,4'-cyclohexylidene bisphenol oxalate)/Si NC. Within the three different NC samples, the one with 13% Si was found to maintain a very high surface area of 12.237 m²/g, as compared to the other two samples consisting of 7% Si (3.362 m²/g) and 3.7% Si (1.788 m²/g). Further, the solid phase DNA extraction studies indicated that the efficiency is strongly influenced by the amount of polymer (0.2 g > 0.1 g > 0.02 g) and the type of binding buffer. Among the three binding buffers tested, the guanidine hydrochloride/EtOH buffer produced the most satisfactory results in terms of yield (1,348,000 ng) and extraction efficiency (3370 ng/mL) as compared to the other two buffers of NaCl (2 M) and phosphate buffered silane. Based on our results, it can be indicated that the developed poly(4,4'-cyclohexylidene bisphenol oxalate)/Si NC can serve as one of the suitable candidates for the extraction of DNA in high amounts as compared to other traditional solid phase approaches.
Formulation and In-Vitro Characterisation of Cross-Linked Amphiphilic Guar Gum Nanocarriers for Percutaneous Delivery of Arbutin

Bostanudin MF, Salam A, Mahmood A, Arafat M, Kaharudin AN, Sahudin S, et al.

J Pharm Sci, 2021 Dec;110(12):3907-3918.
PMID: 34403653 DOI: 10.1016/j.xphs.2021.08.014

Nano-colloidal systems formulated from amphiphilically-modified polysaccharides (degree of modification 16.6%) are focus of prominent study due to their potential to augment active penetration across the skin. Here we report the synthesis of amphiphilically-modified guar gum (GBE-GG) prepared by grafting with glycidol butyl ether (GBE), which were subsequently formed into nanocarriers and loaded with α-arbutin (22.3% loading). The monodispersed and close-to-spherical nanocarriers (size range 239-297 nm) formed via cross-linking were adequately stable mainly at low temperature (4 °C) under physiological pH condition. α-arbutin was released from GBE-GG NPs in a more sustained manner and the release profiles can be accurately represented by the 1st order kinetic model. In-vitro interactions on immortalised human keratinocytes (HaCaT) cells revealed an increase in biological membrane permeability as well as the absence of cellular toxicity at application pertinent concentrations. No substantial haemolytic activity appeared and flow cytometry analysis revealed effective cellular uptake, suggesting their potential as promising nanocarriers for percutaneous delivery that warrants further comprehensive research.
Tumor Budding Detection System in Whole Slide Pathology Images

Fauzi MFA, Chen W, Knight D, Hampel H, Frankel WL, Gurcan MN

J Med Syst, 2019 Dec 18;44(2):38.
PMID: 31853654 DOI: 10.1007/s10916-019-1515-y

Tumor budding is defined as the presence of single tumor cells or small tumor clusters (less than five cells) that 'bud' from the invasive front of the main tumor. Tumor budding (TB) has recently emerged as an important adverse prognostic factor for many different cancer types. In colorectal carcinoma (CRC), tumor budding has been independently associated with lymph node metastasis and poor outcome. Pathologic assessment of tumor budding by light microscopy requires close evaluation of tumor invasive front on intermediate to high power magnification, entailing locating the 'hotspot' of tumor budding, counting all TB in one high power field, and generating a tumor budding score. By automating these time-consuming tasks, computer-assisted image analysis tools can be helpful for daily pathology practice, since tumor budding reporting is now recommended on select cases. In this paper, we report our work on the development of a tumor budding detection system in CRC from whole-slide Cytokeratin AE1/3 images, based on de novo computer algorithm that automates morphometric analysis of tumor budding.
Histological analysis of anti-cancer drug loaded, targeted Mn:ZnS quantum dots in metastatic lesions of 4T1 challenged mice

Birma Bwatanglang I, Mohammad F, Yusof NA, Elyani Mohammed N, Abu N, Alitheen NB, et al.

J Mater Sci Mater Med, 2017 Aug 08;28(9):138.
PMID: 28791524 DOI: 10.1007/s10856-017-5949-9

5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs. The 5-FU@FACS-Mn:ZnS composite induced anti-proliferative properties in these organs as compared to the free 5-FU drug. Unlike the 5-FU@FACS-Mn:ZnS treated groups which showed some specific morphological changes such as cell shrinkage without obvious presence of adipocytes, the excised section of the tumor in the untreated control group and the free 5-FU drug treated group showed necrotic and degenerated cells; these cells are multifocally distributed in the tumor mass with evidence of widely distributed adipocytes within the tumor mass. These findings suggest that the 5-FU@FACS-Mn:ZnS composite has a superior role during the induction of apoptosis in the 4T1 cells as compared to the free 5-FU drug treated groups. The results of the study therefore suggest that the impregnation of 5-FU anti-cancer drug within the FACS-Mn:ZnS system significantly improves its selective targeting efficacy, in addition to improving the anti-proliferative properties and attenuate possible tumor resistances to the 5-FU drug. The work discusses about the anti-metastatic effects of folic acid-bound 5-Fluororacil loaded Mn:ZnS quantum dots towards 4T1 cell line proliferation in mice based on the histological analysis.
Fulltext Degraded Historical Document Binarization: A Review on Issues, Challenges, Techniques, and Future Directions

Sulaiman A, Omar K, Nasrudin MF

J Imaging, 2019 Apr 12;5(4).
PMID: 34460486 DOI: 10.3390/jimaging5040048

In this era of digitization, most hardcopy documents are being transformed into digital formats. In the process of transformation, large quantities of documents are stored and preserved through electronic scanning. These documents are available from various sources such as ancient documentation, old legal records, medical reports, music scores, palm leaf, and reports on security-related issues. In particular, ancient and historical documents are hard to read due to their degradation in terms of low contrast and existence of corrupted artefacts. In recent times, degraded document binarization has been studied widely and several approaches were developed to deal with issues and challenges in document binarization. In this paper, a comprehensive review is conducted on the issues and challenges faced during the image binarization process, followed by insights on various methods used for image binarization. This paper also discusses the advanced methods used for the enhancement of degraded documents that improves the quality of documents during the binarization process. Further discussions are made on the effectiveness and robustness of existing methods, and there is still a scope to develop a hybrid approach that can deal with degraded document binarization more effectively.
Doxorubicin-loaded magnetic gold nanoshells for a combination therapy of hyperthermia and drug delivery

Mohammad F, Yusof NA

J Colloid Interface Sci, 2014 Nov 15;434:89-97.
PMID: 25170601 DOI: 10.1016/j.jcis.2014.07.025

In the present work, nanohybrid of an anticancer drug, doxorubicin (Dox) loaded gold-coated superparamagnetic iron oxide nanoparticles (SPIONs@Au) were prepared for a combination therapy of cancer by means of both hyperthermia and drug delivery. The Dox molecules were conjugated to SPIONs@Au nanoparticles with the help of cysteamine (Cyst) as a non-covalent space linker and the Dox loading efficiency was investigated to be as high as 0.32 mg/mg. Thus synthesized particles were characterized by HRTEM, UV-Vis, FT-IR, SQUID magnetic studies and further tested for heat and drug release at low frequency oscillatory magnetic fields. The hyperthermia studies investigated to be strongly influenced by the applied frequency and the solvents used. The Dox delivery studies indicated that the drug release efficacy is strongly improved by maintaining the acidic pH conditions and the oscillatory magnetic fields, i.e. an enhancement in the Dox release was observed from the oscillation of particles due to the applied frequency, and is not effected by heating of the solution. Finally, the in vitro cell viability and proliferation studies were conducted using two different immortalized cell lines containing a cancerous (MCF-7 breast cancer) and non-cancerous H9c2 cardiac cell type.
In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system

Bwatanglang IB, Mohammad F, Yusof NA, Abdullah J, Alitheen NB, Hussein MZ, et al.

J Colloid Interface Sci, 2016 Oct 15;480:146-58.
PMID: 27428851 DOI: 10.1016/j.jcis.2016.07.011

In this study, we modulated the anti-cancer efficacy of 5-Fluorouracil (5-FU) using a carrier system with enhanced targeting efficacy towards folate receptors (FRs) expressing malignant tissues. The 5-FU drug was loaded onto Mn-ZnS quantum dots (QDs) encapsulated with chitosan (CS) biopolymer and conjugated with folic acid (FA) based on a simple wet chemical method. The formation of 5-FU drug loaded composite was confirmed using Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore, the in vivo biodistribution and tumor targeting specificity of the 5-FU@FACS-Mn:ZnS in the tumor-bearing mice was conducted based on the Zn(2+) tissue bioaccumulation using inductively coupled plasma (ICP) spectroscopy. In addition to the characterization, the in vitro release profile of 5-FU from the conjugates investigated under diffusion controlled method demonstrated a controlled release behaviour as compared against the release behaviour of free 5-FU drug. The as-synthesized 5-FU@FACS-Mn:ZnS nanoparticle (NP) systemically induced higher level of apoptosis in breast cancer cells in vitro as compared to cells treated with free 5-FU drug following both cell cycle and annexin assays, respectively. Also, the in vivo toxicity assessment of the 5-FU@FACS-Mn:ZnS NPs as compared to the control did not cause any significant increase in the activities of the liver and kidney function biomarkers, malondialdehyde (MDA) and nitric oxide (NO) levels. However, based on the FA-FRs chemistry, the 5-FU@FACS-Mn:ZnS NPs specifically accumulated in the tumor of the tumor-bearing mice and thus contributed to the smaller tumor size and less event of metastasis was observed in the lungs when compared to the tumor-bearing mice groups treated with the free 5-FU drug. In summary, the results demonstrated that the 5-FU@FACS-Mn:ZnS QDs exhibits selective anti-tumor effect in MDA-MB231 breast cancer cells in vitro and 4TI breast cancer cells in vivo, providing a blueprint for improving the 5-FU efficacy and tumor targeting specificity with limited systemic toxicity.

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