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  1. Ansari S, Ansari MS, Satsangee SP, Jain R
    Anal Chim Acta, 2019 Jan 10;1046:99-109.
    PMID: 30482307 DOI: 10.1016/j.aca.2018.09.028
    Ranolazine (RZ) is an anti-anginal drug with a distinct mechanism of action and widely employed in patients with chronic angina. Its measurement is essential in clinical environment to ensure adequate drug level and understand the redox mechanism which gives an idea of in-vivo fate of the drug. In view of this, an exemplary voltammetric approach is proposed here for determination of RZ utilizing glassy carbon electrode (GCE) fabricated with WO3 decorated graphene nanocomposite. The structural and morphological characterizations of modifier were made by employing XRD, FESEM, EDAX, HRTEM, XPS, Raman and FT-IR spectroscopy which revealed successful formation of the nanocomposite. As a result of high electrical conductivity and large effective surface area of WO3 nanoparticles and graphene nanosheets, the developed sensor WO3/Graphene/GCE displayed effectual and unrelenting electron interceding behavior exhibiting higher peak currents at lower potentials for RZ oxidation. Using square wave voltammetry, the drug showcased well-defined voltammetric response in Britton-Robinson buffer at pH 4.5 in concentration range from 0.2-1.4 μM and 1.4-14 μM with the low detection limit of 0.13 μM. The developed protocol was then implemented successfully to quantify RZ in commercially accessible pharmaceutical tablets with satisfactory recovery (99.8%-100.2%). The experimental results illustrated the applicability of the fabricated sensor for drug quality control and clinical analysis along with pharmacokinetic studies.
  2. Ansari M, Othman F, El-Shafie A
    Sci Total Environ, 2020 Jun 20;722:137878.
    PMID: 32199382 DOI: 10.1016/j.scitotenv.2020.137878
    Sewage treatment plants (STPs) keep sewage contamination within safe levels and minimize the risk of environmental disasters. To achieve optimum operation of an STP, it is necessary for influent parameters to be measured or estimated precisely. In this research, six well-known influent chemical and biological characteristics, i.e., biochemical oxygen demand (BOD), chemical oxygen demand (COD), Ammoniacal Nitrogen (NH3-N), pH, oil and grease (OG) and suspended solids (SS), were modeled and predicted using the Sugeno fuzzy logic model. The membership function range of the fuzzy model was optimized by ANFIS, the integrated Genetic algorithms (GA), and the integrated particle swarm optimization (PSO) algorithms. The results were evaluated by different indices to find the accuracy of each algorithm. To ensure prediction accuracy, outliers in the predicted data were found and replaced with reasonable values. The results showed that both integrated GA-FIS and PSO-FIS algorithms performed at almost the same level and both had fewer errors than ANFIS. As the GA-FIS algorithm predicts BOD with fewer errors than PSO-FIS and the aim of this study is to provide an accurate prediction of missing data, GA-FIS was only used to predict the BOD parameter; the other parameters were predicted by PSO-FIS algorithm. As a result, the model successfully could provide outstanding performance for predicting the BOD, COD, NH3-N, OG, pH and SS with MAE equal to 3.79, 5.14, 0.4, 0.27, 0.02, and 3.16, respectively.
  3. Ansari M, Othman F, Abunama T, El-Shafie A
    Environ Sci Pollut Res Int, 2018 Apr;25(12):12139-12149.
    PMID: 29455350 DOI: 10.1007/s11356-018-1438-z
    The function of a sewage treatment plant is to treat the sewage to acceptable standards before being discharged into the receiving waters. To design and operate such plants, it is necessary to measure and predict the influent flow rate. In this research, the influent flow rate of a sewage treatment plant (STP) was modelled and predicted by autoregressive integrated moving average (ARIMA), nonlinear autoregressive network (NAR) and support vector machine (SVM) regression time series algorithms. To evaluate the models' accuracy, the root mean square error (RMSE) and coefficient of determination (R2) were calculated as initial assessment measures, while relative error (RE), peak flow criterion (PFC) and low flow criterion (LFC) were calculated as final evaluation measures to demonstrate the detailed accuracy of the selected models. An integrated model was developed based on the individual models' prediction ability for low, average and peak flow. An initial assessment of the results showed that the ARIMA model was the least accurate and the NAR model was the most accurate. The RE results also prove that the SVM model's frequency of errors above 10% or below - 10% was greater than the NAR model's. The influent was also forecasted up to 44 weeks ahead by both models. The graphical results indicate that the NAR model made better predictions than the SVM model. The final evaluation of NAR and SVM demonstrated that SVM made better predictions at peak flow and NAR fit well for low and average inflow ranges. The integrated model developed includes the NAR model for low and average influent and the SVM model for peak inflow.
  4. Abunama T, Othman F, Ansari M, El-Shafie A
    Environ Sci Pollut Res Int, 2019 Feb;26(4):3368-3381.
    PMID: 30511225 DOI: 10.1007/s11356-018-3749-5
    Leachate is one of the main surface water pollution sources in Selangor State (SS), Malaysia. The prediction of leachate amounts is elementary in sustainable waste management and leachate treatment processes, before discharging to surrounding environment. In developing countries, the accurate evaluation of leachate generation rates has often considered a challenge due to the lack of reliable data and high measurement costs. Leachate generation is related to several factors, including meteorological data, waste generation rates, and landfill design conditions. The high variations in these factors lead to complicating leachate modeling processes. This study aims at identifying the key elements contributing to leachate production and developing various AI-based models to predict leachate generation rates. These models included Artificial Neural Network (ANN)-Multi-linear perceptron (MLP) with single and double hidden layers, and support vector machine (SVM) regression time series algorithms. Various performance measures were applied to evaluate the developed model's accuracy. In this study, input optimization process showed that three inputs were acceptable for modeling the leachate generation rates, namely dumped waste quantity, rainfall level, and emanated gases. The initial performance analysis showed that ANN-MLP2 model-which applies two hidden layers-achieved the best performance, then followed by ANN-MLP1 model-which applies one hidden layer and three inputs-while SVM model gave the lowest performance. Ranges and frequency of relative error (RE%) also demonstrate that ANN-MLP models outperformed SVM models. Furthermore, low and peak flow criterion (LFC and PFC) assessment of leachate inflow values in ANN-MLP model with two hidden layers made more accurate values than other models. Since minimizing data collection and processing efforts as well as minimizing modeling complexity are critical in the hydrological modeling process, the applied input optimization process and the developed models in this study were able to provide a good performance in the modeling of leachate generation efficiently.
  5. Ansari S, Ansari MS, Satsangee SP, Jain R
    J Pharm Anal, 2021 Feb;11(1):57-67.
    PMID: 33717612 DOI: 10.1016/j.jpha.2020.03.013
    In the present work, a chemically modified electrode has been fabricated utilizing Bi2O3/ZnO nanocomposite. The nanocomposite was synthesized by simple sonochemical method and characterized for its structural and morphological properties by using XRD, FESEM, EDAX, HRTEM and XPS techniques. The results clearly indicated co-existence of Bi2O3 and ZnO in the nanocomposite with chemical interaction between them. Bi2O3/ZnO nanocomposite based glassy carbon electrode (GCE) was utilized for sensitive voltammetric detection of an anti-biotic drug (balofloxacin). The modification amplified the electroactive surface area of the sensor, thus providing more sites for oxidation of analyte. Cyclic and square wave voltammograms revealed that Bi2O3/ZnO modified electrode provides excellent electrocatalytic action towards balofloxacin oxidation. The current exhibited a wide linear response in concentration range of 150-1000 nM and detection limit of 40.5 nM was attained. The modified electrode offered advantages in terms of simplicity of preparation, fair stability (RSD 1.45%), appreciable reproducibility (RSD 2.03%) and selectivity. The proposed sensor was applied for determining balofloxacin in commercial pharmaceutical formulations and blood serum samples with the mean recoveries of 99.09% and 99.5%, respectively.
  6. Subramaniam T, Ansari MNM, Krishnan SG, Khalid M
    Chemosphere, 2024 Apr;354:141593.
    PMID: 38460854 DOI: 10.1016/j.chemosphere.2024.141593
    This study presents an innovative method for synthesizing activated carbon with an exceptionally high surface area (3359 m2 g-1) using kenaf fiber-based biochar through chemical activation. The achieved specific surface area surpasses activated carbon derived from other reported fiber-based precursors. The resulting activated carbon was investigated as electrodes for supercapacitors, revealing a remarkable maximum capacitance of 312 F g-1 at a current density of 0.5 A g-1. An aqueous symmetric supercapacitor employing these high-surface-area electrodes exhibited an outstanding energy density of 18.9 Wh kg-1 at a power density of 250 W kg-1. Notably, the supercapacitor retained exceptional capacitance, maintaining 93% of its initial capacitance even after 5000 charge-discharge cycles.
  7. Abunama T, Ansari M, Awolusi OO, Gani KM, Kumari S, Bux F
    J Environ Manage, 2021 Sep 01;293:112862.
    PMID: 34049159 DOI: 10.1016/j.jenvman.2021.112862
    To ensure the safe discharge of treated wastewater to the environment, continuous efforts are vital to enhance the modelling accuracy of wastewater treatment plants (WWTPs) through utilizing state-of-art techniques and algorithms. The integration of metaheuristic modern optimization algorithms that are natlurally inspired with the Fussy Inference Systems (FIS) to improve the modelling performance is a promising and mathematically suitable approach. This study integrates four population-based algorithms, namely: Particle swarm optimization (PSO), Genetic algorithm (GA), Hybrid GA-PSO, and Mutating invasive weed optimization (M-IWO) with FIS system. A full-scale WWTP in South Africa (SA) was selected to assess the validity of the proposed algorithms, where six wastewater effluent parameters were modeled, i.e., Alkalinity (ALK), Sulphate (SLP), Phosphate (PHS), Total Kjeldahl Nitrogen (TKN), Total Suspended Solids (TSS), and Chemical Oxygen Demand (COD). The results from this study showed that the hybrid PSO-GA algorithm outperforms the PSO and GA algorithms when used individually, in modelling all wastewater effluent parameters. PSO performed better for SLP and TKN compared to GA, while the M-IWO algorithm failed to provide an acceptable modelling convergence for all the studied parameters. However, three out of four algorithms applied in this study proven beneficial to be optimized in enhancing the modelling accuracy of wastewater quality parameters.
  8. Ahmed S, Mahmood S, Danish Ansari M, Gull A, Sharma N, Sultana Y
    Int J Pharm, 2021 Sep 25;607:121006.
    PMID: 34391848 DOI: 10.1016/j.ijpharm.2021.121006
    The current work attempted to achieve bypassed hepatic metabolism, controlled release, and boosted brain distribution of agomelatine by loading in NLC and administering via transdermal route. Agomelatine-loaded NLC (AG-NLC) was fabricated employing melt-emulsification technique and optimized using central composite design. The optimized AG-NLC had 183.16 ± 6.82 nm particle size, 0.241 ± 0.0236 polydispersity index, and 83.29 ± 2.76% entrapment efficiency. TEM and FESEM visually confirmed the size and surface morphology of AG-NLC, respectively. DSC thermogram confirmed the conversion of AG from crystalline to amorphous form, which indicates improved solubility of AG when loaded in NLC. For further stability and improved applicability, AG-NLC was converted into a hydrogel. The texture analysis of AG-NLC-Gel showed appropriate gelling property in terms of hardness (142.292 g), cohesiveness (0.955), and adhesiveness (216.55 g.sec). In comparison to AG-suspension-Gel (38.036 ± 6.058%), AG-NLC-Gel (89.440 ± 2.586%) exhibited significantly higher (P 
  9. Hussain A, Zahid A, Malik M, Ansari M, Vaismoradi M, Aslam A, et al.
    Children (Basel), 2021 Nov 04;8(11).
    PMID: 34828720 DOI: 10.3390/children8111007
    Immunization is one of the most cost-effective public health interventions, with considerable impacts on people's health. Parents' perception of their knowledge, attitude, and satisfaction is an important factor, as they may be targeted by interventions for better immunization coverage. Therefore, this study aimed to assess parents' perceptions in terms of their knowledge, attitude, and satisfaction of the immunization of their children aged less than two years of age, in two cities of Pakistan. A descriptive cross-sectional study was conducted in the vicinity of Rawalpindi and Islamabad from March to August 2019. A semi-structured questionnaire was used for the data collection on a convenient sample of parents. The questionnaire was hand-delivered to the parents by data collectors. Descriptive and inferential statistics were used for data analysis via SPSS version 22. A total of n = 382 respondents were included in the data analysis. Statistically significant differences were found between the parents' knowledge scores and their education levels and monthly incomes (p < 0.05). Parents with master's education degrees and low monthly incomes had significantly better knowledge (p < 0.05). Additionally, 96.85% of the respondents believed that child immunization was important. In addition, more than half of the respondents (57.58%) thought that the affordability of vaccines was a principal factor for delays in immunization. Although the parents' knowledge regarding the immunization of their children was not adequate, they had positive perceptions toward it.
  10. Gaaz TS, Sulong AB, Ansari MNM, Kadhum AAH, Al-Amiery AA, Nassir MH
    Materials (Basel), 2017 Jul 10;10(7).
    PMID: 28773134 DOI: 10.3390/ma10070777
    The advancements in material science and technology have made polyurethane (PU) one of the most important renewable polymers. Enhancing the physio-chemical and mechanical properties of PU has become the theme of this and many other studies. One of these enhancements was carried out by adding starch to PU to form new renewable materials called polyurethane-starch composites (PUS). In this study, PUS composites are prepared by adding starch at 0.5, 1.0, 1.5, and 2.0 wt.% to a PU matrix. The mechanical, thermal, and morphological properties of PU and PUS composites were investigated. Scanning electron microscope (SEM) images of PU and PUS fractured surfaces show cracks and agglomeration in PUS at 1.5 wt.% starch. The thermo-mechanical properties of the PUS composites were improved as starch content increased to 1.5 wt.% and declined by more starch loading. Despite this reduction, the mechanical properties were still better than that of neat PU. The mechanical strength increased as starch content increased to 1.5 wt.%. The tensile, flexural, and impact strengths of the PUS composites were found to be 9.62 MPa, 126.04 MPa, and 12.87 × 10(-3) J/mm², respectively, at 1.5 wt.% starch. Thermal studies showed that the thermal stability and crystallization temperature of the PUS composites increased compared to that of PU. The loss modulus curves showed that neat PU crystallizes at 124 °C and at 127 °C for PUS-0.5 wt.% and rises with increasing loading from 0.5 to 2 wt.%.
  11. Poudel P, Sharma S, Ansari MNM, Vaish R, Kumar R, Ibrahim SM, et al.
    Glob Chall, 2023 Apr;7(4):2100140.
    PMID: 37020619 DOI: 10.1002/gch2.202100140
    This paper presents a piezoelectric wind energy harvester that operates by a galloping mechanism with different shaped attachments attached to a bluff body. A comparison is made between harvesters that consist of different shaped attachments on a bluff body; these include triangular, circular, square, Y-shaped, and curve-shaped attachments. Simulation of the pressure field and the velocity field variation around the different shaped bluff bodies is performed and it is found that a high pressure difference creates a high lift force on the bluff body with curve-shaped attachments. A theoretical model based on a galloping mechanism is presented, which is verified by experiments. It is observed that the proposed harvester with curve-shaped attachments provides the best performance, where the harvester with a curve-shaped attachments provides the highest voltage and power output compared to the other shaped harvesters examined in this study. This paper provides a new concept for improving the power performance of the piezoelectric wind energy harvesters with modifications made on the bluff body.
  12. Upadhyay DK, Ibrahim MI, Mishra P, Alurkar VM, Ansari M
    Daru, 2016 Feb 29;24:6.
    PMID: 26926657 DOI: 10.1186/s40199-016-0145-x
    BACKGROUND: Cost is a vital component for people with chronic diseases as treatment is expected to be long or even lifelong in some diseases. Pharmacist contributions in decreasing the healthcare cost burden of chronic patients are not well described due to lack of sufficient evidences worldwide. In developing countries like Nepal, the estimation of direct healthcare cost burden among newly diagnosed diabetics is still a challenge for healthcare professionals, and pharmacist role in patient care is still theoretical and practically non-existent. This study reports the impact of pharmacist-supervised intervention through pharmaceutical care program on direct healthcare costs burden of newly diagnosed diabetics in Nepal through a non-clinical randomised controlled trial approach.
    METHODS: An interventional, pre-post non-clinical randomised controlled study was conducted among randomly distributed 162 [control (n = 54), test 1 (n = 54) and test 2 (n = 54) groups] newly diagnosed diabetics by a consecutive sampling method for 18 months. Direct healthcare costs (direct medical and non-medical costs) from patients perspective was estimated by 'bottom up' approach to identify their out-of-pocket expenses (1USD = NPR 73.38) before and after intervention at the baseline, 3, 6, 9 and 12 months follow-ups. Test groups' patients were nourished with pharmaceutical care intervention while control group patients only received care from physician/nurses. Non-parametric tests i.e. Friedman test, Mann-Whitney U test and Wilcoxon signed rank test were used to find the differences in direct healthcare costs among the groups before and after the intervention (p ≤ 0.05).
    RESULTS: Friedman test identified significant differences in direct healthcare cost of test 1 (p 
  13. Ansari M, Ibrahim MI, Hassali MA, Shankar PR, Koirala A, Thapa NJ
    BMC Res Notes, 2012 Oct 24;5:576.
    PMID: 23095352 DOI: 10.1186/1756-0500-5-576
    BACKGROUND: In developing countries, mothers usually manage diarrhea at home with the pattern of management depending on perceived disease severity and beliefs. The study was carried out with the objective of determining mothers' beliefs and barriers about diarrhea and its management.

    METHODS: Qualitative methods involving two focus group discussions and eight in-depth interviews were used to collect the data. The study was conducted at the following places: Tankisinuwari, Kanchanbari and Pokhariya of Morang district, Nepal during the months of February and March 2010. Purposive sampling method was adopted to recruit twenty mothers based on the inclusion criteria. A semi-structured interview guide was used to conduct the interviews. Written informed consent was obtained from all of the participants before conducting the interviews. The interviews were moderated by the main researcher with the support of an expert observer from Nobel Medical College. The interviews were recorded with the permission of the participants and notes were written by a pre trained note-taker. The recordings were transcribed verbatim. All the transcribed data was categorized and analyzed using thematic content analysis.

    RESULTS: Twenty mothers participated in the interviews and most (80%) of them were not educated. About 75% of the mothers had a monthly income of up to 5000 Nepalese rupees (US$ 60.92). Although a majority of mothers believed diarrhea to be due to natural causes, there were also beliefs about supernatural origin of diarrhea. Thin watery diarrhea was considered as the most serious. There was diversity in mothers' beliefs about foods/fluids and diarrhea management approaches. Similarly, several barriers were noted regarding diarrhea prevention and/or management such as financial weakness, lack of awareness, absence of education, distance from healthcare facilities and senior family members at home. The elderly compelled the mothers to visit traditional healers.

    CONCLUSIONS: There were varied beliefs among the mothers about the types, causes and severity of diarrhea, classification of foods/fluids and beliefs and barriers about preventing or treating diarrhea.

  14. Iqbal J, Numan A, Omaish Ansari M, Jafer R, Jagadish PR, Bashir S, et al.
    Polymers (Basel), 2020 Nov 27;12(12).
    PMID: 33261072 DOI: 10.3390/polym12122816
    In this study, silver (Ag) and cobalt oxide (Co3O4) decorated polyaniline (PANI) fibers were prepared by the combination of in-situ aniline oxidative polymerization and the hydrothermal methodology. The morphology of the prepared Ag/Co3O4@PANI ternary nanocomposite was studied by scanning electron microscopy and transmission electron microscopy, while the structural studies were carried out by X-ray diffraction and X-ray photoelectron spectroscopy. The morphological characterization revealed fibrous shaped PANI, coated with Ag and Co3O4 nanograins, while the structural studies revealed high purity, good crystallinity, and slight interactions among the constituents of the Ag/Co3O4@PANI ternary nanocomposite. The electrochemical performance studies revealed the enhanced performance of the Ag/Co3O4@PANI nanocomposite due to the synergistic/additional effect of Ag, Co3O4 and PANI compared to pure PANI and Co3O4@PANI. The addition of the Ag and Co3O4 provided an extended site for faradaic reactions leading to the high specific capacity. The Ag/Co3O4@PANI ternary nanocomposite exhibited an excellent specific capacity of 262.62 C g-1 at a scan rate of 3 mV s-1. The maximum energy and power density were found to be 14.01 Wh kg-1 and 165.00 W kg-1, respectively. The cyclic stability of supercapattery (Ag/Co3O4@PANI//activated carbon) consisting of a battery type electrode demonstrated a gradual increase in specific capacity with a continuous charge-discharge cycle until ~1000 cycles, then remained stable until 2500 cycles and later started decreasing, thereby showing the cyclic stability of 121.03% of its initial value after 3500 cycles.
  15. R S, Nakkeeran S, Saranya N, Senthilraja C, Renukadevi P, Krishnamoorthy AS, et al.
    Microorganisms, 2021 Dec 03;9(12).
    PMID: 34946111 DOI: 10.3390/microorganisms9122511
    Chemical pesticides have an immense role in curbing the infection of plant viruses and soil-borne pathogens of high valued crops. However, the usage of chemical pesticides also contributes to the development of resistance among pathogens. Hence, attempts were made in this study to identify a suitable bacterial antagonist for managing viral and fungal pathogens infecting crop plants. Based on our earlier investigations, we identified Bacillus amyloliquefaciens VB7 as a potential antagonist for managing Sclerotinia sclerotiorum infecting carnation, tobacco streak virus infecting cotton and groundnut bud necrosis infecting tomato. Considering the multifaceted action of B. amyloliquefaciens VB7, attempts were made for whole-genome sequencing to assess the antiviral activity against tomato spotted wilt virus infecting chrysanthemum and antifungal action against Fusarium oxysporum f. sp. cubense (Foc). Genome annotation of the isolate B. amyloliquefaciens VB7 was confirmed as B. velezensis VB7 with accession number CP047587. Genome analysis revealed the presence of 9,231,928 reads with an average read length of 149 bp. Assembled genome had 1 contig, with a total length of 3,021,183 bp and an average G+C content of 46.79%. The protein-coding sequences (CDS) in the genome was 3090, transfer RNA (tRNA) genes were 85 with 29 ribosomal RNA (rRNA) genes and 21 repeat regions. The genome of B. velezensis VB7 had 506 hypothetical proteins and 2584 proteins with functional assignments. VB7 genome had the presence of flagellin protein FlaA with 987 nucleotides and translation elongation factor TU (Ef-Tu) with 1191 nucleotides. The identified ORFs were 3911 with 47.22% GC content. Non ribosomal pepide synthetase cluster (NRPS) gene clusters in the genome of VB7, coded for the anti-microbial peptides surfactin, butirosin A/butirosin B, fengycin, difficidin, bacillibactin, bacilysin, and mersacidin the Ripp lanthipeptide. Antiviral action of VB7 was confirmed by suppression of local lesion formation of TSWV in the local lesion host cowpea (Co-7). Moreover, combined application of B. velezensis VB7 with phyto-antiviral principles M. Jalapa and H. cupanioides increased shoot length, shoot diameter, number of flower buds per plant, flower diameter, and fresh weight of chrysanthemum. Further, screening for antifungal action of VB7 expressed antifungal action against Foc in vitro by producing VOC/NVOC compounds, including hexadecanoic acid, linoelaidic acid, octadecanoic acid, clindamycin, formic acid, succinamide, furanone, 4H-pyran, nonanol and oleic acid, contributing to the total suppression of Foc apart from the presence of NRPS gene clusters. Thus, our study confirmed the scope for exploring B. velezensis VB7 on a commercial scale to manage tomato spotted wilt virus, groundnut bud necrosis virus, tobacco streak virus, S. sclerotiorum, and Foc causing panama wilt of banana.
  16. Hall HN, Bengani H, Hufnagel RB, Damante G, Ansari M, Marsh JA, et al.
    PLoS One, 2022;17(11):e0268149.
    PMID: 36413568 DOI: 10.1371/journal.pone.0268149
    Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism.
  17. Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, et al.
    J Clin Oncol, 2021 02 01;39(4):295-307.
    PMID: 33332189 DOI: 10.1200/JCO.20.02529
    PURPOSE: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.

    PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).

    RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.

    CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.

  18. Shuy YK, Santharan S, Chew QH, Lin SK, Ouyang WC, Chen CK, et al.
    J Clin Psychopharmacol, 2024 01 16;44(2):117-123.
    PMID: 38230861 DOI: 10.1097/JCP.0000000000001813
    BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons.

    METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling.

    RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not.

    CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

  19. Loo LWJ, Chew QH, Lin SK, Yang SY, Ouyang WC, Chen CK, et al.
    PMID: 37068038 DOI: 10.1097/JCP.0000000000001693
    BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing.

    METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling.

    RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months.

    CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

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