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Fulltext Editorial: Advancements of deep learning in medical imaging for neurodegenerative diseases

Gaur L, Siarry P, Abraham A, Castillo O

Front Neurosci, 2024;18:1361055.
PMID: 38312932 DOI: 10.3389/fnins.2024.1361055
Mesenchymal chondrosarcoma - A rare cause of pleural effusion

Cheo SW, Abraham AD, Madatang A, Low QJ

Med J Malaysia, 2020 07;75(4):458-460.
PMID: 32724019

Mesenchymal chondrosarcoma is a malignant neoplasm arising from cartilaginous bone or soft tissue. It is uncommon yet devastating. Our patient was a 21-year-old man who presented with pleuritic chest pain and weight loss. His chest radiograph showed left pleural effusion. His pleural effusion analysis was consistent with exudative pleural effusion. Tuberculosis workup was negative. Pleural fluid cytology did not yield malignant cells. Subsequently, his computed tomography of thorax showed left rib sclerotic lesion with soft tissue component. Biopsy of the soft tissue eventually confirmed the diagnosis of mesenchymal chondrosarcoma. He succumbed to his illness before the diagnosis was confirmed. We hope that through this case report, we are able to provide some insight into this rare condition.
A novel nonlinear time-varying sigmoid transfer function in binary whale optimization algorithm for descriptors selection in drug classification

Mohd Yusof N, Muda AK, Pratama SF, Abraham A

Mol Divers, 2023 Feb;27(1):71-80.
PMID: 35254585 DOI: 10.1007/s11030-022-10410-y

In computational chemistry, the high-dimensional molecular descriptors contribute to the curse of dimensionality issue. Binary whale optimization algorithm (BWOA) is a recently proposed metaheuristic optimization algorithm that has been efficiently applied in feature selection. The main contribution of this paper is a new version of the nonlinear time-varying Sigmoid transfer function to improve the exploitation and exploration activities in the standard whale optimization algorithm (WOA). A new BWOA algorithm, namely BWOA-3, is introduced to solve the descriptors selection problem, which becomes the second contribution. To validate BWOA-3 performance, a high-dimensional drug dataset is employed. The proficiency of the proposed BWOA-3 and the comparative optimization algorithms are measured based on convergence speed, the length of the selected feature subset, and classification performance (accuracy, specificity, sensitivity, and f-measure). In addition, statistical significance tests are also conducted using the Friedman test and Wilcoxon signed-rank test. The comparative optimization algorithms include two BWOA variants, binary bat algorithm (BBA), binary gray wolf algorithm (BGWOA), and binary manta-ray foraging algorithm (BMRFO). As the final contribution, from all experiments, this study has successfully revealed the superiority of BWOA-3 in solving the descriptors selection problem and improving the Amphetamine-type Stimulants (ATS) drug classification performance.
Fulltext A preliminary investigation of user perception and behavioral intention for different review types: customers and designers perspective

Qazi A, Raj RG, Tahir M, Waheed M, Waheed M, Khan SU, et al.

ScientificWorldJournal, 2014;2014:872929.
PMID: 24711739 DOI: 10.1155/2014/872929

Existing opinion mining studies have focused on and explored only two types of reviews, that is, regular and comparative. There is a visible gap in determining the useful review types from customers and designers perspective. Based on Technology Acceptance Model (TAM) and statistical measures we examine users' perception about different review types and its effects in terms of behavioral intention towards using online review system. By using sample of users (N = 400) and designers (N = 106), current research work studies three review types, A (regular), B (comparative), and C (suggestive), which are related to perceived usefulness, perceived ease of use, and behavioral intention. The study reveals that positive perception of the use of suggestive reviews improves users' decision making in business intelligence. The results also depict that type C (suggestive reviews) could be considered a new useful review type in addition to other types, A and B.
Fulltext Corrigendum to "A preliminary investigation of user perception and behavioral intention for different review types: customers and designers perspective"

Qazi A, Raj RG, Tahir M, Waheed M, Khan SU, Abraham A

ScientificWorldJournal, 2015;2015:258150.
PMID: 25945359 DOI: 10.1155/2015/258150
Phase 3 Trial of Concizumab in Hemophilia with Inhibitors

Matsushita T, Shapiro A, Abraham A, Angchaisuksiri P, Castaman G, Cepo K, et al.

N Engl J Med, 2023 Aug 31;389(9):783-794.
PMID: 37646676 DOI: 10.1056/NEJMoa2216455

BACKGROUND: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody designed to achieve hemostasis in all hemophilia types, with subcutaneous administration. A previous trial of concizumab (explorer4) established proof of concept in patients with hemophilia A or B with inhibitors.
METHODS: We conducted the explorer7 trial to assess the safety and efficacy of concizumab in patients with hemophilia A or B with inhibitors. Patients were randomly assigned in a 1:2 ratio to receive no prophylaxis for at least 24 weeks (group 1) or concizumab prophylaxis for at least 32 weeks (group 2) or were nonrandomly assigned to receive concizumab prophylaxis for at least 24 weeks (groups 3 and 4). After a treatment pause due to nonfatal thromboembolic events in three patients receiving concizumab, including one from the explorer7 trial, concizumab therapy was restarted with a loading dose of 1.0 mg per kilogram of body weight, followed by 0.2 mg per kilogram daily (potentially adjusted on the basis of concizumab plasma concentration as measured at week 4). The primary end-point analysis compared treated spontaneous and traumatic bleeding episodes in group 1 and group 2. Safety, patient-reported outcomes, and pharmacokinetics and pharmacodynamics were also assessed.
RESULTS: Of 133 enrolled patients, 19 were randomly assigned to group 1 and 33 to group 2; the remaining 81 were assigned to groups 3 and 4. The estimated mean annualized bleeding rate in group 1 was 11.8 episodes (95% confidence interval [CI], 7.0 to 19.9), as compared with 1.7 episodes (95% CI, 1.0 to 2.9) in group 2 (rate ratio, 0.14 [95% CI, 0.07 to 0.29]; P<0.001). The overall median annualized bleeding rate for patients receiving concizumab (groups 2, 3, and 4) was 0 episodes. No thromboembolic events were reported after concizumab therapy was restarted. The plasma concentrations of concizumab remained stable over time.
CONCLUSIONS: Among patients with hemophilia A or B with inhibitors, the annualized bleeding rate was lower with concizumab prophylaxis than with no prophylaxis. (Funded by Novo Nordisk; explorer7 ClinicalTrials.gov number, NCT04083781.).
Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score

Huynh-Le MP, Karunamuni R, Fan CC, Asona L, Thompson WK, Martinez ME, et al.

Prostate Cancer Prostatic Dis, 2022 Apr;25(4):755-761.
PMID: 35152271 DOI: 10.1038/s41391-022-00497-7

BACKGROUND: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.
METHODS: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.
RESULTS: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.
CONCLUSIONS: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
Fulltext Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, et al.

Nat Genet, 2023 Dec;55(12):2065-2074.
PMID: 37945903 DOI: 10.1038/s41588-023-01534-4

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.