Browse publications by year: 2023

  1. Ng SI, Lim XJ, Hsu HC, Chou CC
    Health Promot Int, 2023 Jun 01;38(3).
    PMID: 35437585 DOI: 10.1093/heapro/daac040
    The purpose of this study was to examine the association between age-friendliness of a city, loneliness and depression moderated by internet use among older people during the coronavirus disease 2019 (COVID-19) pandemic. The survey was from 'The 2020 Survey of Needs Assessment for a Safe Community and Age-Friendly City' in Xinyi District, Taipei, which was conducted by face-to-face interviews with community-based older adults who were aged 65 and above from one district of Taipei City from May to June 2020 (n = 335). Partial least square structural equation modeling and the SPSS PROCESS macro were used for data analysis. Two domains of an age-friendly city (housing and community support and health services) were found to be associated with reduced loneliness, while one (respect and social inclusion) was associated with decreased depression. The age-friendliness of cities mitigates depression through moderator (internet use) and mediation (loneliness) mechanisms. Although some age-friendly domains of the city reduced loneliness and depression directly, the age-friendliness-loneliness-depression mechanism held true only for older adults who used the internet and not for nonusers. Maintaining the age-friendliness of an environment is beneficial to mental health, and internet use is a necessary condition to gain optimum benefits from age-friendly initiatives. Policy suggestions are discussed.
    MeSH terms: Aged; Cities; Depression/epidemiology; Humans; Pandemics
  2. Bagheri R, Farahani FK, Ebrahimi M
    J Interpers Violence, 2023 Aug;38(15-16):9492-9513.
    PMID: 37102584 DOI: 10.1177/08862605231168824
    The objective of this article is to assess the effect of domestic violence on abortion and investigate the mediating role of unwanted pregnancy. A secondary analysis was conducted on the National Family Survey data. This survey was a cross-sectional study conducted across Iran in 2018. The association between domestic violence and abortion was analyzed using the Partial Least Square-Structural Equation Model (PLS-SEM) with WarpPLS version 8.0. From among 1,544 married women (mean age 42.8 years) who participated in this survey, 27% (418 women) reported experiencing at-least one-lifetime of abortion. Overall, two in three women (67.3%) experienced at least one form of domestic violence. Almost half of the women with experience of abortion (49.3%) reported at least one unwanted pregnancy in their life course. The bivariate analysis showed a significant positive relationship between domestic violence and abortion, and there was a positive direct effect of domestic violence on unwanted pregnancy. Moreover, age had a negative direct and indirect effect on unwanted pregnancy and abortion. Although, the direct effect of domestic violence on abortion was not significant in the Structure Equation Model, a positive indirect effect of domestic violence on abortion through unwanted pregnancy was confirmed. The effect of unwanted pregnancy on abortion was particularly strong (β = .395, p 
    MeSH terms: Abortion, Spontaneous*; Abortion, Induced*; Adult; Cross-Sectional Studies; Female; Humans; Iran/epidemiology; Pregnancy; Domestic Violence*
  3. Choon SE, Wright AK, Griffiths CEM, Wong KW, Tey KE, Lim YT, et al.
    Br J Dermatol, 2023 Sep 15;189(4):410-418.
    PMID: 37162007 DOI: 10.1093/bjd/ljad158
    BACKGROUND: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia.

    OBJECTIVES: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors.

    METHODS: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV.

    RESULTS: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV.

    CONCLUSIONS: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.

    MeSH terms: Acute Disease; Adult; Chronic Disease; Female; Humans; Information Systems; Malaysia/epidemiology; Male; Middle Aged; Pregnancy; Skin Diseases, Vesiculobullous*; Cohort Studies; Incidence; Prevalence; Soft Tissue Injuries*; Young Adult; Electronic Health Records
  4. Ibrahim MH, Hamzah N, Mohd Yusop MZ, Septiani NLW, Mohd Yasin MF
    Beilstein J Nanotechnol, 2023;14:741-750.
    PMID: 37377745 DOI: 10.3762/bjnano.14.61
    The growth of carbon nanotubes (CNTs) in a flame requires conditions that are difficult to achieve in a highly heterogeneous environment. Therefore, the analysis of the properties of the reaction zone within the flame is critical for the optimal growth of CNTs. In the present study, a comprehensive comparison between the CNT synthesis using a methane diffusion flame and a premixed flame is conducted regarding the morphology and crystallinity of the as-grown nanotubes. The premixed burner configuration created a flame that is stabilized through axisymmetric stagnation flow through sintered metal with one-dimensional geometry, different from a conventional co-flow flame. The significant difference in temperature distribution between the two flames causes a difference in the characteristics of the growth products. In the diffusion flame, the growth is limited to specific regions at certain height-above-burner (HAB) values with a temperature range of 750 to 950 °C at varying radial locations. The identified growth regions at different HAB values showed similar temperature distributions that yield CNTs of similar characteristics. Interestingly, the growth of CNTs in the premixed flame is dictated by only the HAB because the temperature distribution is relatively uniform along the radial directions but significantly different in the vertical direction. 17.3% variation in temperature in the axial direction successfully led to 44% and 66% variation in CNT diameter and crystallinity, respectively. The morphology control capability demonstrated in the present study is important for CNT functionalization for energy storage, nanosensor, and nanocomposite applications, where diameter and crystallinity are influential properties that govern the overall performance of the components.
  5. Ag Lamat MSN, Abd Rahman MSH, Wan Zaidi WA, Yahya WNNW, Khoo CS, Hod R, et al.
    Front Neurol, 2023;14:1118903.
    PMID: 37377856 DOI: 10.3389/fneur.2023.1118903
    INTRODUCTION: Stroke is a typical medical emergency that carries significant disability and morbidity. The diagnosis of stroke relies predominantly on the use of neuroimaging. Accurate diagnosis is pertinent for management decisions of thrombolysis and/or thrombectomy. Early identification of stroke using electroencephalogram (EEG) in the clinical assessment of stroke has been underutilized. This study was conducted to determine the relevance of EEG and its predictors with the clinical and stroke features.

    METHODS: A cross-sectional study was carried out where routine EEG assessment was performed in 206 consecutive acute stroke patients without seizures. The demographic data and clinical stroke assessment were collated using the National Institutes of Health Stroke Scale (NIHSS) score with neuroimaging. Associations between EEG abnormalities and clinical features, stroke characteristics, and NIHSS scores were evaluated.

    RESULTS: The mean age of the study population was 64.32 ± 12 years old, with 57.28% consisting of men. The median NIHSS score on admission was 6 (IQR 3-13). EEG was abnormal in more than half of the patients (106, 51.5%), which consisted of focal slowing (58, 28.2%) followed by generalized slowing (39, 18.9%) and epileptiform changes (9, 4.4%). NIHSS score was significantly associated with focal slowing (13 vs. 5, p 

  6. Jose J, Suresh V, Magoon R
    Indian J Crit Care Med, 2023 Jun;27(6):452.
    PMID: 37378361 DOI: 10.5005/jp-journals-10071-24454
    How to cite this article: Jose J, Suresh V, Magoon R. Optic Nerve Sheath Diameter in Hyponatremia: A Closer Look. Indian J Crit Care Med 2023;27(6):452.
  7. Roslim NA, Ahmad A, Mansor M, Aung MMT, Hamzah F, Lua PL
    Int J Clin Exp Hypn, 2023;71(3):235-249.
    PMID: 37378644 DOI: 10.1080/00207144.2023.2227237
    Hypnotherapy has been gaining recognition as an alternative treatment for excess weight problems. This qualitative study aims to explore individuals' experiences of losing weight through hypnotherapy and their perceived barriers and facilitators for healthy lifestyle changes. Semistructured interviews were conducted with 15 participants (11 women and 4 men; mean age of 23 years) who recorded having lost ≥5% weight after undergoing 3 hypnotherapy sessions previously at a public university in Terengganu, Malaysia. Each interview was audiotaped, transcribed, and analyzed using thematic analysis. The themes that emerged were the usefulness of hypnotherapy, barriers, and facilitators of healthy lifestyle changes. All participants contended that hypnotherapy played a role in their weight-loss journey through increased mindful eating and enhanced motivation to make lifestyle modifications. Barriers to healthy lifestyle changes included high costs of healthy foods and lack of support for healthy food sources in social and family settings. Hypnotherapy is essential as an adjunct tool in assisting weight loss. However, additional efforts are needed to improve support in the weight management journey.
    MeSH terms: Adult; Female; Humans; Hypnosis*; Male; Motivation; Weight Loss; Qualitative Research; Young Adult
  8. Al-Amshawee SKA, Yunus MYBM, Mohamed HS
    PMID: 37378732 DOI: 10.1007/s11356-023-28433-9
    Electrodialysis desalination is constructed with a number of anion exchange membranes (AEM), cation exchange membranes (CEM), anode, cathode, adjacent silicon gasket integrated membrane spacers, and inlet/outlet holes per cell. At the boundary among an ionic solution and an ion exchange membrane, concentration polarization develops. Spacers placed in between channel's walls function as stream baffles to increase turbulence, improve heat and mass transfer, diminish the laminar boundary layer, and lessen fouling problems. The current study offers a systematic review of membrane spacers, spacer-bulk attack angles, and irregular attack angles. Spacer-bulk attack angle is accountable for variations in the pattern and direction of stream which impact heat-mass transfer and concentration polarization. Irregular attack angles (e.g., 0°, 15°, 30°, 37°, 45°, 55°, 60°, 62°, 70°, 74°, 80°, 90°, 110°, 120°) in the present study were found to provide unique stream patterns due to the spacer's filaments being less or more transverse in respect to the primary solution direction, which may significantly alter heat transfer, mass transport, pressure drop, and overall flow dynamics. Spacer applies shear stress resulting by continuous stream tangent to the membrane exterior, which lessens polarization. In the end, 45° is concluded as the preferred attack angle that offers balanced rates of heat transfer, mass transport, and pressure drop throughout the feed channel while greatly lowering the rate of concentration polarization.
  9. Wan Puteh SE, Abdullah YR, Aizuddin AN
    Asian Pac J Cancer Prev, 2023 Jun 01;24(6):1897-1904.
    PMID: 37378917 DOI: 10.31557/APJCP.2023.24.6.1897
    BACKGROUND: The study investigated healthcare expenditure from the perspective of cancer patients, to determine the level of Catastrophic Health Expenditure (CHE) and its associated factors.

    METHODS: This cross-sectional study was conducted in three Malaysian public hospitals namely Hospital Kuala Lumpur, Hospital Canselor Tuanku Muhriz and the National Cancer Institute using a multi-level sampling technique to recruit 630 respondents from February 2020 to February 2021. CHE was defined as incurring a monthly health expenditure of more than 10% of the total monthly household expenditure. A validated questionnaire was used to collect the relevant data.

    RESULTS: The CHE level was 54.4%. CHE was higher among patients of Indian ethnicity (P = 0.015), lower level education (P = 0.001), those unemployed (P < 0.001), lower income (P < 0.001), those in poverty (P < 0.001), those staying far from the hospital (P < 0.001), living in rural areas (P = 0.003), small household size (P = 0.029), moderate cancer duration (P = 0.030), received radiotherapy  treatment (P < 0.001), had very frequent treatment (P < 0.001), and without a Guarantee Letter (GL) (P < 0.001). The regression analysis identified significant predictors of CHE as lower income aOR 18.63 (CI 5.71-60.78), middle income aOR 4.67 (CI 1.52-14.41), poverty income aOR 4.66 (CI 2.60-8.33), staying far from hospital aOR 2.62 (CI 1.58-4.34), chemotherapy aOR 3.70 (CI 2.01-6.82), radiotherapy aOR 2.99 (CI 1.37-6.57), combination chemo-radiotherapy aOR 4.99 (CI 1.48-16.87), health insurance aOR 3.99 (CI 2.31-6.90), without GL aOR 3.38 (CI 2.06-5.40), and without health financial aids aOR 2.94 (CI 1.24-6.96).

    CONCLUSIONS: CHE is related to various sociodemographic, economic, disease, treatment and presence of health insurance, GL and health financial aids variables in Malaysia.

    MeSH terms: Catastrophic Illness; Cross-Sectional Studies; Developing Countries; Health Expenditures*; Humans; Healthcare Financing
  10. Chong ASS, Ahmad M, Mohd Harizan NB, Alias H, Iqbal Hussain R, Lateh A, et al.
    Asian Pac J Cancer Prev, 2023 Jun 01;24(6):1923-1929.
    PMID: 37378920 DOI: 10.31557/APJCP.2023.24.6.1923
    OBJECTIVE: The caregivers of children diagnosed with acute lymphoblastic leukaemia (ALL) are believed to experience post-traumatic stress symptoms (PTSS), depression and anxiety. This present study endeavoured to explore the prevalence and predictors of PTSS, depression, and anxiety among the caregivers of children with ALL.

    METHODS: Purposive sampling was used to select the 73 caregivers of children with ALL who participated in this cross-sectional study. The Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure psychological distress.

    RESULT: There was a low prevalence (11%) of post-traumatic stress disorder (PTSD) among the participants. Although all the criteria for PTSD were not met, a few post-traumatic symptoms remained, suggesting that PTSS was likely present. Most of the participants reported minimal symptoms of depression (79.5%) and anxiety (65.8%). Anxiety, depression, and ethnicity predicted the PTSS scores (R2 = .77, p =.000). Subsequently, depression predicted the PTSS scores (R2 = 0.42, p =0.000). Participants of 'Other' or 'Indigenous' ethnicity had lower PTSS scores and higher anxiety scores (R2 = 0.75, p =0.000) than participants of Malay ethnicity.

    CONCLUSION: The caregivers of children with ALL experience post-traumatic stress symptoms (PTSS), depression, and anxiety. These variables co-exist and may have different trajectories in different ethnic groups. Therefore, healthcare providers should take ethnicity and psychological distress into consideration when providing paediatric oncology treatment and care.

    MeSH terms: Anxiety/etiology; Anxiety/epidemiology; Child; Cross-Sectional Studies; Depression/etiology; Depression/epidemiology; Humans; Caregivers/psychology; Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  11. Al-Hashimi M, Eke T, Kumar C
    J Cataract Refract Surg, 2023 Sep 01;49(9):1000.
    PMID: 37379052 DOI: 10.1097/j.jcrs.0000000000001252
    MeSH terms: Anesthesia*; Cataract*; Cataract Extraction*; Humans; Registries; Refractive Surgical Procedures*
  12. Moussa AA, Omar FD, Fiidow OA, Ali FH, Babatunde SM
    PLoS One, 2023;18(6):e0284854.
    PMID: 37379300 DOI: 10.1371/journal.pone.0284854
    The novel coronavirus disease (COVID-19) pandemic has affected several countries worldwide, resulting in a considerable strain on healthcare systems and increased trend of self-medication practices. This study aims to evaluate the awareness of COVID-19 and the prevalence of self-medication during the pandemic among residents in Mogadishu, Somalia. A cross-sectional study was conducted using a structured and pretested questionnaire between May 2020 and January 2021. Participants from various disciplines were randomly recruited within the study location and interviewed about their self-medication practices during the pandemic. Descriptive statistics were used to summarise the respondents' information and responses to the questionnaire items. Associations between participants' demographic characteristics and specific items relating to self-medication practices were analysed using the Chi-square test. A total of 350 residents participated in the study. Approximately 63% of the participants reported having practised COVID-19 related self-medication with the main reasons being pharmacists' advice (21.4%) and having an old prescription (13.1%), whereas 37.1% did not report their reasons for self-medication. Most participants (60.4%) engaged in self-medication despite not having any symptoms and 62.9% had taken antibiotics in the last three months. Most participants were aware that no medication has been approved for COVID-19 (81.1%), the negative effects of self-medication (66.6%), and the transmission routes of the virus. Meanwhile, more than 40% of the participants have not worn a mask while outside their homes, and do not follow the international COVID-19 guidelines. The most prevalent drug used by participants for self-medication against COVID-19 was paracetamol (81.1%) and antibiotics (78%). The factors associated with awareness of COVID-19 and self-medication practices included age, gender, educational qualification, and occupation. This study revealed considerable high self-medication practices among Mogadishu residents, thus highlighting the need to promote awareness regarding the adverse effects of self-medication and sanitisation guidelines in addressing COVID-19 at the community level.
    MeSH terms: Acetaminophen; Anti-Bacterial Agents/therapeutic use; Cross-Sectional Studies; Humans; Somalia/epidemiology
  13. Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, et al.
    J Clin Oncol, 2023 Sep 10;41(26):4208-4217.
    PMID: 37379502 DOI: 10.1200/JCO.23.00515
    PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1.

    RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles.

    CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

    MeSH terms: Humans; Mutation; Protein Kinase Inhibitors/adverse effects; ErbB Receptors/genetics
  14. Tsai TF
    Br J Dermatol, 2023 Sep 15;189(4):361-362.
    PMID: 37379585 DOI: 10.1093/bjd/ljad197
    MeSH terms: Chronic Disease; Exanthema*; Humans; Information Systems; Malaysia; Psoriasis*; Cohort Studies; Incidence; Prevalence; Electronic Health Records
  15. Zhang R, Zhang Y, Goei R, Oh WD, Zhang Z, He C
    J Environ Manage, 2023 Oct 15;344:118441.
    PMID: 37379626 DOI: 10.1016/j.jenvman.2023.118441
    To realize sound disposal of hyperaccumulator harvested from phytoremediation, hydrothermal carbonization (HTC) has been employed to obtain superior hydrochar adsorbents for removal of phosphate and ammonium from water body. A series of hydrochars have been prepared under tuned HTC conditions to tailor hydrochar with desired properties. Generally, increased temperature and prolonged reaction time facilitated acidic oxygen functional groups on hydrochars, thereby improving adsorption capacity of hydrochar. In single solute system, a superior hydrochar, derived from HTC under 260 °C for 2 h, achieved a maximum phosphate and ammonium adsorption capacity of 52.46 mg/g and 27.56 mg/g at 45 °C, respectively. In binary system, synergistic adsorption was observed only in lower solute concentration, whereas competitive adsorption occurred under higher solute concentration. Characterization and adsorption kinetics suggested chemisorption may dominate the adsorption process, thus the adsorption capacity could be improved by tuning pHpzc of hydrochar. This study firstly demonstrates the sustainable utilization of hyperaccumulators into nutrients-enriched hydrochar as fertilizer for in-situ phytoremediation of contaminated sites with minimized environmental risks towards circular economy.
    MeSH terms: Adsorption; Carbon; Kinetics; Phosphates; Temperature; Sedum*
  16. Hassanpour M, Hassanpour M, Uddin Khandaker M, Rashed Iqbal Faruque M, Alshahrani B, Osman H
    Appl Radiat Isot, 2023 Sep;199:110910.
    PMID: 37379789 DOI: 10.1016/j.apradiso.2023.110910
    Radiation protection is crucial for the safe utilization of ionizing radiation and minimizing the harmful effect upon exposure, hence some standards have been defined by some relevant organizations for the safe uses of radiation. One of the parameters relevant to the calculation of gamma ray shielding is the half-value layer (HVL), which is normally calculated using the knowledge of linear attenuation coefficient (μ). In this research, an attempt has been made to directly calculate HVL without the knowledge of μ via Monte Carlo simulation technique. For this purpose, in the Monte Carlo N-Particle eXtended (MCNPX) code, F1, F5 and Mesh Popul sequences tallies were defined and the optimal structure for the least measurement error was introduced. The MCNPX calculated values showed reasonable agreement with the experimental findings. According to the obtained results, it is suggested that in order to reduce the error of HVL calculations, in exchange for the MCNPX code, the values of the R parameter and the radiation angle of the source should be considered according to the calculations introduced in this plan. Because the results show that by considering the measurement error between 6 and 20%, the code output can be cited in different energy ranges.
  17. Wang X, Walker A, Revez JA, Ni G, Adams MJ, McIntosh AM, et al.
    Am J Hum Genet, 2023 Jul 06;110(7):1207-1215.
    PMID: 37379836 DOI: 10.1016/j.ajhg.2023.06.006
    In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2, the proportion of total phenotypic variances attributable to all common SNPs) is the theoretical upper limit of the out-of-sample prediction R2. However, in real data analyses R2 has been reported to exceed hSNP2, which occurs in parallel with the observation that hSNP2 estimates tend to decline as the number of cohorts being meta-analyzed increases. Here, we quantify why and when these observations are expected. Using theory and simulation, we show that if heterogeneities in cohort-specific hSNP2 exist, or if genetic correlations between cohorts are less than one, hSNP2 estimates can decrease as the number of cohorts being meta-analyzed increases. We derive conditions when the out-of-sample prediction R2 will be greater than hSNP2 and show the validity of our derivations with real data from a binary trait (major depression) and a continuous trait (educational attainment). Our research calls for a better approach to integrating information from multiple cohorts to address issues of between-cohort heterogeneity.
    MeSH terms: Computer Simulation; Humans; Phenotype; Multifactorial Inheritance/genetics; Genome-Wide Association Study*
  18. Deepak P, Kumar P, Arya DK, Pandey P, Kumar S, Parida BP, et al.
    Int J Pharm, 2023 Jul 25;642:123160.
    PMID: 37379892 DOI: 10.1016/j.ijpharm.2023.123160
    Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvβ3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.
    MeSH terms: Animals; Antineoplastic Agents*; Liposomes/chemistry; Tissue Distribution; Drug Delivery Systems/methods; Cell Line, Tumor; Rats
  19. Lai JY, Corona A, Ng CL, Tramontano E, Choong YS, Lim TS
    Int J Biol Macromol, 2023 Aug 01;245:125571.
    PMID: 37379953 DOI: 10.1016/j.ijbiomac.2023.125571
    Ebola virus is notorious for causing severe and even deadly haemorrhagic fever in infected humans and non-human primates. The high fatality rate of Ebola virus disease (EVD) has highlighted the need for effective diagnosis and treatment. Two monoclonal antibodies (mAbs) have been approved by USFDA for treatment of EVD. Virus surface glycoprotein is the common target for diagnostic and therapy including vaccines. Even so, VP35, a viral RNA polymerase cofactor and interferon inhibitor could be a potential target to curb EVD. The present work describes the isolation of three mAb clones from a phage-displayed human naïve scFv library against recombinant VP35. The clones showed binding against rVP35 in vitro and inhibition of VP35 in luciferase reporter gene assay. Structural modelling analysis was also carried out to identify the binding interactions involved in the antibody-antigen interaction model. This allows some insight into the "fitness" of the binding pocket between the paratope and target epitope which would be useful for the design of new mAbs through in silico means in the future. In conclusion, the information obtained from the 3 isolated mAbs could be potentially useful in the quest to improve VP35 targeting for therapeutic development in the future.
    MeSH terms: Animals; Antibodies, Monoclonal/pharmacology; Epitopes/pharmacology; Humans; Ebolavirus*; Viral Regulatory and Accessory Proteins
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