Browse publications by year: 2023

  1. Tan K, Waiho K, Tan K, Qiao Y, Lim LS, Yang X, et al.
    Biochem Biophys Res Commun, 2023 Oct 30;679:66-74.
    PMID: 37673004 DOI: 10.1016/j.bbrc.2023.08.066
    Vitellogenin (Vtg) serves as the precursor of yolk protein and exhibits widespread distribution in tissues, including in the ovary of both vertebrates and invertebrates. Vtg plays a critical role in facilitating oocyte maturation and embryonic development following oviposition. In this study, we have successfully elucidated the complete transcript sequence of TtVtg6-like from an ancient chelicerate Tachypleus tridentatus. The TtVtg6-like transcript encompassed a length of 4887 bp and encoded 1629 amino acids residues. Notably, TtVtg6-like was found to contain 25 exons. Furthermore, the molecular weight and isoelectric point of TtVtg6-like were determined to be 191.6 KDa and 6.73, respectively. Subsequent mRNA expression analysis demonstrated the specific expression of TtVtg6-like in ovary and yellow connective tissue. In addition, TtVtg6-like was located and distributed in both ovary and yellow connective tissue. Intriguingly, employing an siRNA approach to silence TtVtg6-like resulted in a decrease in TtVtg6-like transcription levels. Concomitantly, TtVtg6-like silencing led to increase production of ROS, ultimately resulting in DNA damage and cell apoptosis within the ovarian primary cell. The induction of apoptosis ovarian primary cells due to TtVtg6-like silencing was further corroborated through TUNEL assay and flow cytometry analysis. Overall, our findings underscore the significance of TtVtg6-like in ovarian cell development, revealing its potential association with ovarian cell apoptosis. Consequently, the insights gained from this study contribute to the future exploration of vitellogenesis and ovarian development in T. tridentatus.
  2. Kang J, Peng R, Feng J, Wei J, Li Z, Huang F, et al.
    BMJ Open, 2023 Sep 06;13(9):e075030.
    PMID: 37673450 DOI: 10.1136/bmjopen-2023-075030
    OBJECTIVE: To evaluate the health systems efficiency in China and Association of Southeast Asian Nations (ASEAN) countries from 2015 to 2020.

    DESIGN: Health efficiency analysis using data envelopment analysis (DEA) and stochastic frontier approach analysis.

    SETTING: Health systems in China and ASEAN countries.

    METHODS: DEA-Malmquist model and SFA model were used to analyse the health system efficiency among China and ASEAN countries, and the Tobit regression model was employed to analyse the factors affecting the efficiency of health system among these countries.

    RESULTS: In 2020, the average technical efficiency, pure technical efficiency and scale efficiency of China and 10 ASEAN countries' health systems were 0.700, 1 and 0.701, respectively. The average total factor productivity (TFP) index of the health systems in 11 countries from 2015 to 2020 was 0.962, with a decrease of 1.4%, among which the average technical efficiency index was 1.016, and the average technical progress efficiency index was 0.947. In the past 6 years, the TFP index of the health system in Malaysia was higher than 1, while the TFP index of other countries was lower than 1. The cost efficiency among China and ASEAN countries was relatively high and stable. The per capita gross domestic product (current US$) and the urban population have significant effects on the efficiency of health systems.

    CONCLUSIONS: Health systems inefficiency is existing in China and the majority ASEAN countries. However, the lower/middle-income countries outperformed high-income countries. Technical efficiency is the key to improve the TFP of health systems. It is suggested that China and ASEAN countries should enhance scale efficiency, accelerate technological progress and strengthen regional health cooperation according to their respective situations.

    MeSH terms: Asia; China; Government Programs*; Health Systems Agencies*; Gross Domestic Product
  3. Han HL, Nurcahyanto DA, Muhammad N, Lee YJ, Nguyen TTH, Kim SG, et al.
    Sci Rep, 2023 Sep 06;13(1):14684.
    PMID: 37673882 DOI: 10.1038/s41598-023-35108-5
    In the effort of isolating novel microbial species, the strain PL0132T was isolated from a fallen leaf under fresh water at a stream, which glided when grown on a tap water medium (without nutrients). The strain was determined to be Gram-negative, strictly aerobic, and rod-shaped, which grew optimally at 25 °C, pH 6-7, and the strain tolerates 1% (w/v) NaCl concentration. The complete genome of strain PL0132T comprises one contig with a sequencing depth of 76×, consisting of 8,853,064 base pairs and the genomic DNA G + C content was 46.7% (genome). 16S rRNA gene sequence analysis revealed that strain PL0132T represents a member of the phylum Bacteroidetes and is affiliated with the genus Spirosoma. Based on genomic, phenotypic, and chemotaxonomic characteristics, the strain PL0132T represents a novel species of the genus Spirosoma, for which the name Spirosoma foliorum sp. nov. is proposed (= KCTC 72228 T = InaCC B1447T).
    MeSH terms: RNA, Ribosomal, 16S/genetics; Plant Leaves; Acer*; Bacteroidetes; Cytophagaceae*
  4. Abd El-Aal AAA, Jayakumar FA, Lahiri C, Tan KO, Reginald K
    Sci Rep, 2023 Sep 06;13(1):14673.
    PMID: 37673929 DOI: 10.1038/s41598-023-41581-9
    Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.
    MeSH terms: Animals; Biological Assay; Cations; Biofilms; Penaeidae*
  5. Rajan R, Al Jarallah M, Al-Zakwani I, Dashti R, Sulaiman K, Panduranga P, et al.
    Oman Med J, 2023 Jul;38(4):e529.
    PMID: 37674520 DOI: 10.5001/omj.2023.89
    OBJECTIVES: The Rajan's heart failure (R-hf) score was proposed to aid risk stratification in heart failure patients. The aim of this study was to validate R-hf risk score in patients with acute decompensated heart failure.

    METHODS: R-hf risk score is derived from the product estimated glomerular filtration rate (mL/min), left ventricular ejection fraction (%), and hemoglobin levels (g/dL) divided by N-terminal pro-brain natriuretic peptide (pg/mL). This was a multinational, multicenter, prospective registry of heart failure from seven countries in the Middle East. Univariable and multivariable logistic regression was applied.

    RESULTS: A total of 776 patients (mean age = 62.0±14.0 years, 62.4% males; mean left ventricular ejection fraction = 33.0±14.0%) were included. Of these, 459 (59.1%) presented with acute decompensated chronic heart failure. The R-hf risk score group (≤ 5) was marginally associated with a higher risk of all-cause cumulative mortality at three months (adjusted odds ratio (aOR) = 4.28; 95% CI: 0.90-20.30; p =0.067) and significantly at 12 months (aOR = 3.84; 95% CI: 1.23-12.00; p =0.021) when compared to those with the highest R score group (≥ 50).

    CONCLUSIONS: Lower R-hf risk scores are associated with increased risk of all-cause cumulative mortality at three and 12 months.

  6. Deng H, Zhang R, Wang C, Zhang B, Wang J, Wang S, et al.
    Front Psychiatry, 2023;14:1215963.
    PMID: 37674551 DOI: 10.3389/fpsyt.2023.1215963
    BACKGROUND: This multicenter, three-armed, parallel, single-blind randomized controlled trial (RCT) primarily aims to compare the efficacy of virtual reality exposure therapy (VRET) with that of acceptance and commitment therapy (ACT) and treatment as usual (TAU) to depreciate the degree of alcohol craving among alcohol use disorder patients who have undergone in-patient detoxification across four timelines (t0 = baseline prior to intervention, t1 = 4 weeks after baseline, t2 = 12 weeks after baseline, and t3 = 24 weeks after baseline). The secondary aims of this RCT are to compare the efficacy of VRET with that of ACT and TAU to alleviate the severity of alcohol use disorder, dissipate comorbid depressive and anxiety symptoms, and normalize event-related potential (ERP) in electroencephalogram (EEG) monitoring across the four timelines.

    METHODS: Initially, after 2 weeks of in-patient detoxification, 120 patients with alcohol use disorder will be randomized into three groups (VRET, ACT, and TAU control groups) via stratified permuted block randomization in a 1:1:1 ratio. Baseline assessment (t0) commences, whereby all the participants will be administered with sociodemographic, clinical, and alcohol use characteristics questionnaire, such as Alcohol Use Disorder Identification Test (AUDIT), Penn Alcohol Craving Scale (PACS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), while event-related potential (ERP) detection in electroencephalogram (EEG) will also be carried out. Then, 4 weeks of VRET, ACT, and non-therapeutic supportive activities will be conducted in the three respective groups. For the subsequent three assessment timelines (t1, t2, and t3), the alcohol use characteristic questionnaire, such as AUDIT, PACS, HAM-D, HAM-A, and ERP monitoring, will be re-administered to all participants.

    DISCUSSION: As data on the effects of non-pharmacological interventions, such as VRET and ACT, on the treatment of alcohol craving and preventing relapse in alcohol use disorder are lacking, this RCT fills the research gap by providing these important data to treating clinicians. If proven efficacious, the efficacy of VRET and ACT for the treatment of other substance use disorders should also be investigated in future.

    CLINICAL TRIAL REGISTRATION: NCT05841823 (ClinicalTrials.gov).

  7. Aissa R, Ibourki M, Ait Bouzid H, Bijla L, Oubannin S, Sakar EH, et al.
    J Med Life, 2023 Jun;16(6):822-836.
    PMID: 37675158 DOI: 10.25122/jml-2022-0353
    Saffron, botanically known as Crocus sativus L., is renowned as the world's most expensive spice and has been utilized in various fields since ancient times. Extensive scientific research has been conducted on Crocus sativus (C. sativus), focusing on its phytochemical composition, diverse applications, and biological activities. C. sativus phytochemicals consist mainly of three compounds, namely crocin, picrocrocin, and safranal, which are responsible for most of its properties. Saffron is rich in bioactive compounds, more than 150 of which have been isolated. Owing to its unique composition and properties, saffron is used in various fields, such as the food industry, perfumery, cosmetics, pharmaceutics, and medicine. However, the high economic value of saffron makes it susceptible to adulteration and various fraudulent practices. To deal with this issue, a number of methods and techniques have been developed to authenticate and determine adulterants in saffron. This paper presents a bibliometric study of saffron based on the Web of Science database, analyzing 3,735 studies published between 2000 and 2021. The study also examined author participation and collaboration networks among countries. Production, transformation, chemical composition, methods of adulteration detection, uses, and health properties of saffron are also discussed.
    MeSH terms: Humans; Quality Control; Crocus*
  8. Patwardhan B, Wieland LS, Aginam O, Chuthaputti A, Ghelman R, Ghods R, et al.
    Indian J Med Res, 2023 Aug;158(2):101-105.
    PMID: 37675685 DOI: 10.4103/ijmr.ijmr_1574_23
    MeSH terms: Humans; Medicine, Traditional; Quality of Life*; Global Health*
  9. Lakshmanan C, Ranjit S, Natraj R, Venkatachalapathy P, Kumar VS, Lum LCS
    Pediatr Crit Care Med, 2023 Sep 01;24(9):e409-e416.
    PMID: 37125796 DOI: 10.1097/PCC.0000000000003250
    OBJECTIVES: Hyperferritinemia in the critical phase of dengue infections may correlate with severe dengue ( sd ) disease, and our primary objective was to examine the association between ferritin level on day 1 of PICU admission and 2009 World Health Organization (WHO) criteria for sd . Our secondary objective was outcome in relation to care. It is unclear whether immunomodulatory therapy during the critical phase may restore immune homeostasis and mitigate disease severity.

    DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of children with dengue 1 month to 16 years old with admission ferritin greater than or equal to 500 ng/mL requiring PICU admission. Demographics, clinical, and laboratory parameters, presence of the 2009 WHO sd criteria and outcomes were analyzed. Immunomodulatory therapy was used when there was persistent hyperinflammation beyond the critical phase of plasma leakage.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Fifty-five patients were admitted in the critical phase of dengue with median (interquartile range) ferritin levels of 8,105 ng/mL (2,350-15,765 ng/mL). Patients with at least one WHO sd category had higher ferritin levels compared to those without any sd criteria, with the highest levels in eight patients with all three sd categories. In our cohort of 55, 52 patients (94%) recovered with standard supportive therapy. Recovery was associated with decreased ferritin levels that occurred in parallel with improved circulation and platelet counts; this included 22 of 24 patients with admission ferritin levels greater than or equal to 10,000 ng/mL and two with ferritin greater than 1,00,000 ng/mL. Immunomodulation was used in three patients with unremitting fever, persistent hyperferritinemia, and progressive multiple organ dysfunction beyond the critical phase, of whom two died.

    CONCLUSIONS: Hyperferritinemia in the critical phase of sd is associated with the number of 2009 WHO sd criteria present. Our data also indicate that many patients with sd recover well with supportive care.

    MeSH terms: Child; Ferritins; Humans; Platelet Count; Retrospective Studies; Severe Dengue*
  10. Yaow CYL, Chong B, Chin YH, Kueh MTW, Ng CH, Chan KE, et al.
    Eur J Prev Cardiol, 2023 Sep 06;30(12):1227-1235.
    PMID: 37185913 DOI: 10.1093/eurjpc/zwad133
    BACKGROUND: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed.

    METHODS AND RESULTS: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males.

    CONCLUSIONS: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.

    MeSH terms: Cardiovascular Diseases*; Diabetes Mellitus, Type 2*; Female; Heart; Humans; Male
  11. Yan M, Yang Y, Chen F, Hantoko D, Pariatamby A, Kanchanatip E
    Environ Sci Pollut Res Int, 2023 Oct;30(46):102560-102573.
    PMID: 37668784 DOI: 10.1007/s11356-023-29596-1
    In order to efficiently recycle waste polyethylene terephthalate (PET) bottles, this study aimed to enhance the hydrolysis process to convert PET bottle into valuable terephthalic acid (TPA) by developing effective and reusable Ni/γ-Al2O3 catalysts. A series of Ni/γ-Al2O3 catalyst was prepared by the impregnation method with different Ni loadings (5-15 wt%) and was characterized by various techniques including XRD, SEM-EDX, and N2 adsorption-desorption. The prepared catalysts were employed in the catalytic hydrolysis of PET under varied influencing factors, namely reaction temperature (220-280 °C), reaction time (20-60 min), and Ni loading. The response surface methodology (RSM) was used to optimize the operating condition to produce the maximum TPA yield, and the optimal values were determined as follows: reaction temperature = 267.07 °C, reaction time = 48.54 min, and Ni loading = 12.90 wt%, giving the highest TPA yield of 97.06%. The R2, F-value, and P-value of the analysis of variance (ANOVA) were 0.9982, 424.96, and <0.0001, respectively, indicating a good fit of the model. The results from XRD and FTIR measurement of the produced TPA indicated the high purity and comparable chemical structures to the TPA standard. In addition, the 12.9Ni/Al catalyst exhibited high catalytic activity in repeated cycles of hydrolysis process of PET and could be regenerated by calcination to restore its catalytic activity. This finding could be a promising alternative for an effective TPA recovery from waste plastic bottles.
  12. Aupalee K, Srisuka W, Taai K, Takaoka H, Saeung A
    J Med Entomol, 2023 Nov 14;60(6):1330-1342.
    PMID: 37669777 DOI: 10.1093/jme/tjad118
    Simulium (Asiosimulium) khongchiamense sp. nov. is described based on females, males, pupae, and mature larvae collected from Khong Chiam District, Ubon Ratchathani Province, northeastern Thailand. It is characterized in the female by the medium-long sensory vesicle, scutum with 3 dark longitudinal vittae and elongate cercus; in the male by the number of upper-eye (large) facets in 17 or 18 vertical rows and 18 or 19 horizontal rows, hind basitarsus moderately enlarged and ventral plate with the posterior margin moderately concave medially; in the pupa by the head and thoracic integument sparsely covered with tubercles and gill of arborescent type with 32 or 33 filaments; and in the larva by the postgenal cleft deep, reaching the posterior margin of the hypostoma and sheath of the subesophageal ganglion dark pigmented. DNA analysis based on COI gene of all known species of the subgenus Asiosimulium, except for S. shanense and S. suchitrae, indicated that this new species can be clearly differentiated from all other related species (S. phurueaense, S. oblongum, S. saeungae, S. furvum, and S. wanchaii) with interspecific genetic distances ranging between 4.79% and 19.18%. This is the eighth species of the subgenus Asiosimulium. Taxonomic notes are given to distinguish this new species from the 7 known species members in its same subgenus. Additionally, keys to species of all members in the subgenus Asiosimulium are provided.
    MeSH terms: Animals; Female; Larva/genetics; Male; Phylogeny; Pupa/genetics; Thailand
  13. Aburezq M, Alahmad A, Alsafi R, Al-Tawari A, Ramadan D, Shafik M, et al.
    Orphanet J Rare Dis, 2023 Sep 05;18(1):271.
    PMID: 37670342 DOI: 10.1186/s13023-023-02888-y
    BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenic SLC19A3 variants and is characterized by subacute encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations.

    METHODS: A retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.

    RESULTS: Twenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2-3 years. All cases are still alive receiving high doses of biotin and thiamine.

    CONCLUSION: This is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.

    MeSH terms: Adult; Basal Ganglia Diseases*; Biotin; Brain Diseases*; Child, Preschool; Dysarthria; Dystonia*; Humans; Infant, Newborn; Kuwait; Retrospective Studies; Seizures; Membrane Transport Proteins
  14. Gharanizadeh K, Sharifi AM, Tayyebi H, Heidari R, Amiri S, Noorigaravand S
    BMC Pharmacol Toxicol, 2023 Sep 05;24(1):44.
    PMID: 37670365 DOI: 10.1186/s40360-023-00682-x
    BACKGROUND: Deferoxamine (DFO) angiogenesis induction potential has been demonstrated in earlier studies, but not in the osteonecrosis of the femoral head (ONFH). In this study, we evaluated the outcome of ONFH treated with combined core decompression and local DFO administration loaded on Polylactic Glycolic Acid (PLGA).

    PATIENTS AND METHODS: In a pilot experimental study, six patients (10 hips) with early-stage non-traumatic ONFH were treated by core decompression, and concurrent injection of local DFO loaded on PLGA scaffold into the subchondral femoral head. Outcome measures were evaluated before the surgery and 12 and 24 months after the surgery and included visual analog scale (VAS) for pain, modified Merle d'Aubigné-Postel (MAP) score for hip function by MRI, and rate of osteonecrosis assessed by the modified.

    RESULTS: The mean MPA score was 14.7 ± 1.16 before the surgery and 16.7 ± 1.41 one year after the surgery (P = 0.004). The mean VAS for pain was 4.7 ± 1.25 before the surgery and 1.8 ± 1.03 one year after the surgery (P = 0.005). The mean Kerboul angle was 219 ± 58.64 before the operation and 164.6 ± 41.82 one year after the operation (P 

    MeSH terms: Decompression; Femur Head; Glycols*; Humans; Osteonecrosis*; Pilot Projects
  15. Shankar PR, Azhar T, Nadarajah VD, Er HM, Arooj M, Wilson IG
    Korean J Med Educ, 2023 Sep;35(3):235-247.
    PMID: 37670520 DOI: 10.3946/kjme.2023.262
    PURPOSE: The perception of faculty members about an individually tailored, flexible-length, outcomes-based curriculum for undergraduate medical students was studied. Their opinion about the advantages, disadvantages, and challenges was also noted. This study was done to help educational institutions identify academic and social support and resources required to ensure that graduate competencies are not compromised by a flexible education pathway.

    METHODS: The study was done at the International Medical University, Malaysia, and the University of Lahore, Pakistan. Semi-structured interviews were conducted from 1st August 2021 to 17th March 2022. Demographic information was noted. Themes were identified, and a summary of the information under each theme was created.

    RESULTS: A total of 24 (14 from Malaysia and 10 from Pakistan) faculty participated. Most agreed that undergraduate medical students can progress (at a differential rate) if they attain the required competencies. Among the major advantages mentioned were that students may graduate faster, learn at a pace comfortable to them, and develop an individualized learning pathway. Several logistical challenges must be overcome. Providing assessments on demand will be difficult. Significant regulatory hurdles were anticipated. Artificial intelligence (AI) can play an important role in creating an individualized learning pathway and supporting time-independent progression. The course may be (slightly) cheaper than a traditional one.

    CONCLUSION: This study provides a foundation to further develop and strengthen flexible-length competency-based medical education modules. Further studies are required among educators at other medical schools and in other countries. Online learning and AI will play an important role.

    MeSH terms: Artificial Intelligence; Competency-Based Education; Curriculum; Faculty; Humans; Students, Medical*
  16. Chan MY, Nelson AJ, Ngu LH
    Mol Genet Metab Rep, 2023 Sep;36:100991.
    PMID: 37670899 DOI: 10.1016/j.ymgmr.2023.100991
    Mucopolysaccharidosis (MPS) type II (Hunter syndrome) is a rare X-linked, recessive, lysosomal storage disorder caused by the deficit of the enzyme iduronate 2-sulfatase (IDS), resulting in accumulation of glycosaminoglycans (GAGs) impairing cellular function in multiple organ systems. Idursulfase (Elaprase, Takeda Pharmaceuticals) and idursulfase beta (Hunterase, GC Biopharma Corp.) are the two currently available enzyme replacement therapies (ERT) for MPS II in Malaysia. ERT in patients with MPS II is associated with improvements in somatic symptoms, pulmonary function, endurance, joint mobility, and quality of life. Though mostly well tolerated, infusion-associated reactions (IARs), such as allergic (IgE-mediated) or nonallergic (non- immunologic) reactions can develop during ERT. In certain cases, when patients develop recurrent IARs despite reduced infusion rate and premedication, either interruption or cessation of ERT might be necessary. However, interruption of ERT is associated with worsening of clinical symptoms such as recurrent respiratory infections, difficulty in standing and walking, and increased joint stiffness, emphasizing the need for continuation of ERT. Here we report successful long-term experience with the use of idursulfase beta in two adolescent Malaysian patients with MPS II, who experienced recurrent infusion-associated reactions warranting discontinuation of ERT with idursulfase.
  17. Sayaf AM, Ullah Khalid S, Hameed JA, Alshammari A, Khan A, Mohammad A, et al.
    Front Pharmacol, 2023;14:1202128.
    PMID: 37670941 DOI: 10.3389/fphar.2023.1202128
    Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
  18. Goh KW, Stephen A, Wu YS, Sim MS, Batumalaie K, Gopinath SCB, et al.
    J Cancer, 2023;14(13):2491-2516.
    PMID: 37670975 DOI: 10.7150/jca.85260
    Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.
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