Displaying publications 101 - 120 of 157 in total

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  1. Morita A, Tsai TF, Yee EYW, Okubo Y, Imafuku S, Zheng M, et al.
    J Dermatol, 2023 Feb;50(2):183-194.
    PMID: 36282833 DOI: 10.1111/1346-8138.16609
    Generalized pustular psoriasis is a potentially life-threatening neutrophilic skin disease characterized by recurrent flares of widespread erythema and eruption of sterile pustules. In the Effisayil™ 1 study (NCT03782792), 53 patients with a generalized pustular psoriasis flare were treated with placebo or spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, the first targeted treatment to be studied in a randomized clinical trial. Spesolimab treatment resulted in rapid pustular and skin clearance, with an acceptable safety profile. Here, we evaluate the efficacy and safety of spesolimab in 29 Asian patients in the Effisayil™ 1 study. The primary endpoint, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) at Week 1, was achieved by 10 patients (62.5%) randomized to spesolimab and one patient (7.7%) randomized to placebo (risk difference 54.8, 95% confidence interval [CI] 17.3-79.8). The key secondary endpoint, a GPPGA total score of 0 or 1 (clear or almost clear skin) at Week 1, was achieved by eight (50.0%) and two (15.4%) patients, respectively (risk difference 34.6, 95% CI -3.1-64.7). This was similar to previously published data in the overall population in whom the primary and key secondary endpoints were achieved by 54% versus 6% and 43% versus 11% of patients, respectively. The percentages of Asian patients randomized to spesolimab with a GPPGA pustulation subscore of 0 and GPPGA total score of 0 or 1 were sustained above 60% for up to 12 weeks. In these patients, patient-reported outcomes also improved and markers of systemic inflammation were normalized. Eleven (68.8%) and eight (61.5%) of spesolimab- and placebo-treated patients, respectively, experienced at least one adverse event. In conclusion, spesolimab improved outcomes in Asian patients compared with placebo, supporting its use in the treatment of generalized pustular psoriasis flares.
  2. Barden A, Phillips M, Hill LM, Fletcher EM, Mas E, Loh PS, et al.
    PMID: 30471772 DOI: 10.1016/j.plefa.2018.11.004
    INTRODUCTION: The synthetic glucocorticoid dexamethasone is a commonly administered antiemetic. It has immunosuppressive effects and may alter postoperative blood glucose concentrations. Dexamethasone can effect key enzymes involved in inflammation resolution that is an active process driven by specialised lipid mediators of inflammation resolution (SPM). The purpose of this study in healthy volunteers was to examine whether dexamethasone effects cell populations and synthesis of SPM that are critical for the resolution of inflammation.

    METHODS: Thirty-two healthy volunteers were randomly allocated to receive saline (Control) or dexamethasone 2 mg, 4 mg or 8 mg intravenously. Venous blood samples were collected at baseline before administration of treatment, and at 4 h, 24 h and one-week post-treatment. At each time point, measurements included blood glucose and macrophage migration inhibition factor (MMIF), full blood count including lymphocyte subsets, monocytes, neutrophils, eosinophils and basophils by flow cytometry, and plasma SPM using liquid chromatography tandem mass spectrometry. The effect of dexamethasone dose and time on all measures was analysed using linear mixed models.

    RESULTS: There was a dose-dependent increase in neutrophil count after dexamethasone that persisted for 24 h. In contrast, there was a dose-dependent reduction in counts of monocytes, lymphocytes, basophils and eosinophils 4 h after dexamethasone, followed by a rebound increase in cell counts at 24 h. Seven days after administration of dexamethasone, all cell counts were similar to baseline levels. MMIF concentration, glucose and natural killer cell counts were not significantly affected by dexamethasone. There was a significant gender effect on plasma SPM such that levels of 17-HDHA, RvD1, 17R-RvD1 and RvE2 in females were on average 14%-50% lower than males. In a linear mixed model that adjusted for neutrophil count, there was a significant interaction between the dose of dexamethasone and time, on plasma 17R-RvD1 such that plasma 17R-RvD1 fell in a dose-dependent manner until 4 h after administration of dexamethasone. There were no significant effects of dexamethasone on the other plasma SPM (18-HEPE, RvE2, 17-HDHA, RvD1, RvD2 and 14-HDHA) measured.

    DISCUSSION: This is the first study in healthy volunteers to demonstrate that commonly employed antiemetic doses of dexamethasone affect immune cell populations and plasma levels of 17R-RvD1 an SPM with anti-nociceptive properties. If similar changes occur in surgical patients, then this may have implications for acute infection risk in the post-operative period.

  3. Agarwal D, Hanafi NS, Chippagiri S, Brakema EA, Pinnock H, Khoo EM, et al.
    NPJ Prim Care Respir Med, 2019 05 08;29(1):17.
    PMID: 31068586 DOI: 10.1038/s41533-019-0129-7
    This protocol describes a systematic scoping review of chronic respiratory disease surveys in low/middle-income countries (LMICs) undertaken as part of the Four Country ChrOnic Respiratory Disease (4CCORD) study within the National Institute for Health Research Global Health Research Unit on Respiratory Health (RESPIRE). Understanding the prevalence and burden of chronic respiratory disease (CRD) underpins healthcare planning. We will systematically scope the literature to identify existing strategies (definitions/questionnaires/diagnostics/outcomes) used in surveys of CRDs in adults in low-resource settings. We will search MEDLINE, EMBASE, ISI WoS, Global Health and WHO Global Health Library [search terms: prevalence AND CRD (COPD, asthma) AND LMICs, from 1995], and two reviewers will independently extract data from selected studies onto a piloted customised data extraction form. We will convene a workshop of the multidisciplinary 4CCORD research team with representatives from the RESPIRE partners (Bangladesh, India, Malaysia, Pakistan and Edinburgh) at which the findings of the scoping review will be presented, discussed and interpreted. The findings will inform a future RESPIRE 4CCORD study, which will estimate CRD burden in adults in Asian LMICs.
  4. Tan CL, Fhun LC, Tai EL, Abdul Gani NH, Muhammed J, Tuan Jaafar TN, et al.
    J Trop Med, 2017;2017:7946123.
    PMID: 28265290 DOI: 10.1155/2017/7946123
    Background. Ocular bartonellosis can present in various ways, with variable visual outcome. There is limited data on ocular bartonellosis in Malaysia. Objective. We aim to describe the clinical presentation and visual outcome of ocular bartonellosis in Malaysia. Materials and Methods. This was a retrospective review of patients treated for ocular bartonellosis in two ophthalmology centers in Malaysia between January 2013 and December 2015. The diagnosis was based on clinical features, supported by a positive Bartonella spp. serology. Results. Of the 19 patients in our series, females were predominant (63.2%). The mean age was 29.3 years. The majority (63.2%) had unilateral involvement. Five patients (26.3%) had a history of contact with cats. Neuroretinitis was the most common presentation (62.5%). Azithromycin was the antibiotic of choice (42.1%). Concurrent systemic corticosteroids were used in approximately 60% of cases. The presenting visual acuity was worse than 6/18 in approximately 60% of eyes; on final review, 76.9% of eyes had a visual acuity better than 6/18. Conclusion. Ocular bartonellosis tends to present with neuroretinitis. Azithromycin is a viable option for treatment. Systemic corticosteroids may be considered in those with poor visual acuity on presentation.
  5. Chong YP, Peter EP, Lee FJM, Chan CM, Chai S, Ling LPC, et al.
    Sci Rep, 2022 Jul 19;12(1):12315.
    PMID: 35853996 DOI: 10.1038/s41598-022-16671-9
    As pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) are the two major cell types that comprise the immunosuppressive tumor microenvironment of pancreatic cancer, we aimed to investigate the role of conditioned medium derived from PCCs and PSCs co-culture on the viability of lymphocytes. The conditioned medium (CM) collected from PCCs and/or PSCs was used to treat peripheral blood mononuclear cells (PBMCs) to determine CM ability in reducing lymphocytes population. A proteomic analysis has been done on the CM to investigate the differentially expressed protein (DEP) expressed by two PCC lines established from different stages of tumor. Subsequently, we investigated if the reduction of lymphocytes was directly caused by CM or indirectly via CM-induced MDSCs. This was achieved by isolating lymphocyte subtypes and treating them with CM and CM-induced MDSCs. Both PCCs and PSCs were important in suppressing lymphocytes, and the PCCs derived from a metastatic tumor appeared to have a stronger suppressive effect than the PCCs derived from a primary tumor. According to the proteomic profiles of CM, 416 secreted proteins were detected, and 13 DEPs were identified between PANC10.05 and SW1990. However, CM was found unable to reduce lymphocytes viability through a direct pathway. In contrast, CM that contains proteins secreted by PCC and/or PSC appear immunogenic as they increase the viability of lymphocytes subtypes. Lymphocyte subtype treated with CM-induced MDSCs showed reduced viability in T helper 1 (Th1), T helper 2 (Th2), and T regulatory (Treg) cells, but not in CD8+ T cells, and B cells. As a conclusion, the interplay between PCCs and PSCs is important as their co-culture displays a different trend in lymphocytes suppression, hence, their co-culture should be included in future studies to better mimic the tumor microenvironment.
  6. Choi T, Sarkar M, Bonham M, Brock T, Brooks IA, Diug B, et al.
    Front Med (Lausanne), 2023;10:1146832.
    PMID: 37849488 DOI: 10.3389/fmed.2023.1146832
    INTRODUCTION/BACKGROUND: Course evaluation in health education is a common practice yet few comprehensive evaluations of health education exist that measure the impact and outcomes these programs have on developing health graduate capabilities.

    AIM/OBJECTIVES: To explore how curricula contribute to health graduate capabilities and what factors contribute to the development of these capabilities.

    METHODS: Using contribution analysis evaluation, a six-step iterative process, key stakeholders in the six selected courses were engaged in an iterative theory-driven evaluation. The researchers collectively developed a postulated theory-of-change. Then evidence from existing relevant documents were extracted using documentary analysis. Collated findings were presented to academic staff, industry representatives and graduates, where additional data was sought through focus group discussions - one for each discipline. The focus group data were used to validate the theory-of-change. Data analysis was conducted iteratively, refining the theory of change from one course to the next.

    RESULTS: The complexity in teaching and learning, contributed by human, organizational and curriculum factors was highlighted. Advances in knowledge, skills, attitudes and graduate capabilities are non-linear and integrated into curriculum. Work integrated learning significantly contributes to knowledge consolidation and forming professional identities for health professional courses. Workplace culture and educators' passion impact on the quality of teaching and learning yet are rarely considered as evidence of impact.

    DISCUSSION: Capturing the episodic and contextual learning moments is important to describe success and for reflection for improvement. Evidence of impact of elements of courses on future graduate capabilities was limited with the focus of evaluation data on satisfaction.

    CONCLUSION: Contribution analysis has been a useful evaluation method to explore the complexity of the factors in learning and teaching that influence graduate capabilities in health-related courses.

  7. Song CV, Yip CH, Mohd Taib NA, See MH, Teoh LY, Monninkhof EM, et al.
    JCO Glob Oncol, 2022 Mar;8:e2100314.
    PMID: 35245099 DOI: 10.1200/GO.21.00314
    PURPOSE: Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined.

    METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.

    RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.

    CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.

  8. Mudenda S, Chabalenge B, Daka V, Jere E, Sefah I, Wesangula E, et al.
    JAC Antimicrob Resist, 2024 Jun;6(3):dlae076.
    PMID: 38764535 DOI: 10.1093/jacamr/dlae076
    BACKGROUND: Antimicrobial resistance (AMR) poses a threat to public health globally. Despite its consequences, there is little information about the knowledge, awareness, and practices towards AMR among healthcare workers (HCWs). Therefore, this study assessed the knowledge, awareness and practices regarding antimicrobial use (AMU), AMR and antimicrobial stewardship (AMS) among HCWs who are involved in the implementation of AMS activities across eight hospitals in Zambia.

    METHODS: A cross-sectional study was conducted among 64 HCWs from October to December 2023 using a semi-structured questionnaire. Data were analysed using IBM SPSS version 25.0.

    RESULTS: Of the 64 HCWs, 59.4% were females, 60.9% were aged between 25 and 34 years, 37.5% were nurses, 18.7% were pharmacists, 17.2% were medical doctors and only one was a microbiologist. Overall, 75% of the HCWs had good knowledge, 84% were highly aware and 84% had good practices regarding AMU, AMR and AMS. Most of the HCWs (90.6%) responded that they had a multidisciplinary AMS team at their hospitals and were implementing the use of the WHO AWaRe classification of antibiotics.

    CONCLUSION: This study found good knowledge levels, high awareness and good practices regarding AMU, AMR and AMS among HCWs who were involved in the implementation of AMS activities in hospitals in Zambia. Additionally, most hospitals have been conducting AMS training and implementing the use of the WHO AWaRe classification of antibiotics. However, there is still a need to address some identified gaps in AMU and AMR through the strengthening of AMS activities in hospitals.

  9. Wee NK, Git KA, Lee WJ, Raval G, Pattokhov A, Ho ELM, et al.
    Korean J Radiol, 2024 Jul;25(7):603-612.
    PMID: 38942454 DOI: 10.3348/kjr.2024.0419
    Artificial intelligence (AI) is rapidly gaining recognition in the radiology domain as a greater number of radiologists are becoming AI-literate. However, the adoption and implementation of AI solutions in clinical settings have been slow, with points of contention. A group of AI users comprising mainly clinical radiologists across various Asian countries, including India, Japan, Malaysia, Singapore, Taiwan, Thailand, and Uzbekistan, formed the working group. This study aimed to draft position statements regarding the application and clinical deployment of AI in radiology. The primary aim is to raise awareness among the general public, promote professional interest and discussion, clarify ethical considerations when implementing AI technology, and engage the radiology profession in the ever-changing clinical practice. These position statements highlight pertinent issues that need to be addressed between care providers and care recipients. More importantly, this will help legalize the use of non-human instruments in clinical deployment without compromising ethical considerations, decision-making precision, and clinical professional standards. We base our study on four main principles of medical care-respect for patient autonomy, beneficence, non-maleficence, and justice.
  10. Choorakuttil RM, Kan EYL, Hallinan JTPD, Cuenza TR, Ho ELM, Afrin R, et al.
    Jpn J Radiol, 2025 Jan 18.
    PMID: 39826087 DOI: 10.1007/s11604-024-01729-7
    Magnetic Resonance Imaging (MRI) safety is a critical concern in the Asia-Oceania region, as it is elsewhere in the world, due to the unique and complex MRI environment that demands attention. This call-for-action outlines ten critical steps to enhance MRI safety and promote a culture of responsibility and accountability in the Asia-Oceania region. Key focus areas include strengthening education and expertise, improving quality assurance, fostering collaboration, increasing public awareness, and establishing national safety boards. By implementing these actions, we aim to significantly reduce MRI-related incidents and create a culture of safety across diverse healthcare settings in the Asia-Oceania Region.
  11. Asare EA, Abdul-Wahab D, Asamoah A, Dampare SB, Kaufmann EE, Wahi R, et al.
    Environ Monit Assess, 2024 May 01;196(5):494.
    PMID: 38691200 DOI: 10.1007/s10661-024-12654-7
    This study investigated the impact of soil type, pH, and geographical locations on the accumulation of arsenic (As), lead (Pb), and cadmium (Cd) in rice grains cultivated in Ghana. One hundred rice farms for the sampling of rice grains and soil were selected from two regions in Ghana-Volta and Oti. The concentrations of As, Pb, and Cd were analyzed using ICP-OES. Speciation modeling and multivariate statistics were employed to ascertain the relations among measured parameters. The results showed significant variations in soil-As, Pb, and Cd levels across different soil types and pH ranges, with the highest soil-As and Cd found in alkaline vertisols. For soil-As and Cd, the vertisols with a pH more than 7.0 exhibited the highest mean concentration of As (2.51 ± 0.932 mgkg-1) and Cd (1.00 ± 0.244 mgkg-1) whereas for soil-Pb, the luvisols of soil types with a pH less than 6.0 exhibited the highest mean concentration of Pb (4.91 ± 1.540 mgkg-1). Grain As, Pb, and Cd also varied across soil types and pH levels. In regards to grain-As, the vertisols soil type, with a pH less than 6.0, shows the highest mean concentration of grain As, at 0.238 ± 0.107 mgkg-1. Furthermore, vertisols soil types with a pH level less than 6.0 showed the highest mean concentration of grain Cd, averaging at 0.231 ± 0.068 mgkg-1 while luvisols, with a pH less than 6.0, exhibited the highest mean concentration of grain Pb at 0.713 ± 0.099 mgkg-1. Speciation modeling indicated increased bioavailability of grains Cd2+ and Pb2+ ions in acidic conditions. A significant interaction was found between soil-Cd and pH, affecting grain-As uptake. The average concentrations of soil As, Pb, and Cd aligned with international standards. Generally, the carcinogenic metals detected in grain samples collected from the Volta region are higher than that of the Oti region but the differences are insignificant, and this may be attributed to geographical differences and anthropogenic activities. About 51% of the study area showed a hazard risk associated with grain metal levels, although, no carcinogenic risks were recognized. This study highlights the complex soil-plant interactions governing metal bioaccumulation and emphasizes the need for tailored strategies to minimize metal transfer into grains.
  12. Saputra E, Prawiranegara BA, Nugraha MW, Oh WD, Sugesti H, Evelyn, et al.
    Environ Res, 2023 Oct 01;234:116441.
    PMID: 37331558 DOI: 10.1016/j.envres.2023.116441
    Three specific catalysts, namely ZIF-67 (zeolitic imidazolate framework-67), Co@NCF (Co@Nitrogen-Doped Carbon Framework), and 3D NCF (Three-Dimensional Nitrogen-Doped Carbon Framework), were prepared and studied for pulp and paper mill effluent degradation using heterogeneous activation of peroxymonosulfate (PMS). Numerous characterizations, including scanning electron microscopy (SEM), X-ray diffraction (XRD), and N2 adsorption, were used to characterize the properties of three different catalysts. 3D NCF is remarkably effective at heterogeneous activation of PMS to generate sulfate radicals to degrade pulp and paper mill effluent (PPME) compared to the other as-prepared catalysts. The catalytic activity reveals a sequence of 3D NCF > Co@NCF > ZIF-67.3D NCF could degrade organic pollutants in 30 min at an initial COD concentration of 1146 mg/L of PPME, 0.2 g/L catalysts, 2 g/L PMS, and 50 °C. Consequently, it was observed that the degradation of PPME using 3D NCF followed first-order kinetics, with an activation energy of 40.54 kJ mol-1. Overall, 3D NCF/PMS system reveals promising performance for PPME removal.
  13. Yeoh AEJ, Lu Y, Chin WHN, Chiew EKH, Lim EH, Li Z, et al.
    J Clin Oncol, 2018 09 10;36(26):2726-2735.
    PMID: 30044693 DOI: 10.1200/JCO.2018.78.3050
    Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10-7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1-negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.
  14. Li Z, Jiang N, Lim EH, Chin WHN, Lu Y, Chiew KH, et al.
    Leukemia, 2020 09;34(9):2418-2429.
    PMID: 32099036 DOI: 10.1038/s41375-020-0774-4
    Identifying patient-specific clonal IGH/TCR junctional sequences is critical for minimal residual disease (MRD) monitoring. Conventionally these junctional sequences are identified using laborious Sanger sequencing of excised heteroduplex bands. We found that the IGH is highly expressed in our diagnostic B-cell acute lymphoblastic leukemia (B-ALL) samples using RNA-Seq. Therefore, we used RNA-Seq to identify IGH disease clone sequences in 258 childhood B-ALL samples for MRD monitoring. The amount of background IGH rearrangements uncovered by RNA-Seq followed the Zipf's law with IGH disease clones easily identified as outliers. Four hundred and ninety-seven IGH disease clones (median 2, range 0-7 clones/patient) are identified in 90.3% of patients. High hyperdiploid patients have the most IGH disease clones (median 3) while DUX4 subtype has the least (median 1) due to the rearrangements involving the IGH locus. In all, 90.8% of IGH disease clones found by Sanger sequencing are also identified by RNA-Seq. In addition, RNA-Seq identified 43% more IGH disease clones. In 69 patients lacking sensitive IGH targets, targeted NGS IGH MRD showed high correlation (R = 0.93; P = 1.3 × 10-14), better relapse prediction than conventional RQ-PCR MRD using non-IGH targets. In conclusion, RNA-Seq can identify patient-specific clonal IGH junctional sequences for MRD monitoring, adding to its usefulness for molecular diagnosis in childhood B-ALL.
  15. Covés-Datson EM, King SR, Legendre M, Swanson MD, Gupta A, Claes S, et al.
    Sci Rep, 2021 01 12;11(1):656.
    PMID: 33436903 DOI: 10.1038/s41598-020-80577-7
    Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.
  16. Ni Chin WH, Li Z, Jiang N, Lim EH, Suang Lim JY, Lu Y, et al.
    J Mol Diagn, 2021 10;23(10):1359-1372.
    PMID: 34365011 DOI: 10.1016/j.jmoldx.2021.07.013
    Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.
  17. Hanafi NS, Agarwal D, Chippagiri S, Brakema EA, Pinnock H, Sheikh A, et al.
    J Glob Health, 2021 Jun 19;11:04026.
    PMID: 34221357 DOI: 10.7189/jogh.11.04026
    BACKGROUND: Chronic respiratory diseases (CRDs) contribute significantly towards the global burden of disease, but the true prevalence and burden of these conditions in adults is unknown in the majority of low- and middle-income countries (LMICs). We aimed to identify strategies - in particular the definitions, study designs, sampling frames, instruments, and outcomes - used to conduct prevalence surveys for CRDs in LMICs. The findings will inform a future RESPIRE Four Country ChrOnic Respiratory Disease (4CCORD) study, which will estimate CRD prevalence, including disease burden, in adults in LMICs.

    METHODS: We conducted a scoping review to map prevalence surveys conducted in LMICs published between 1995 and 2018. We followed Arksey and O'Malley's six-step framework. The search was conducted in OVID Medline, EMBASE, ISI Web of Science, Global Health, WHO Global Index Medicus and included three domains: CRDs, prevalence and LMICs. After an initial title sift, eight trained reviewers undertook duplicate study selection and data extraction. We charted: country and populations, random sampling strategies, CRD definitions/phenotypes, survey procedure (questionnaires, spirometry, tests), outcomes and assessment of individual, societal and health service burden of disease.

    RESULTS: Of 36 872 citations, 281 articles were included: 132 from Asia (41 from China). Study designs were cross-sectional surveys (n = 260), cohort studies (n = 11) and secondary data analysis (n = 10). The number of respondents in these studies ranged from 50 to 512 891. Asthma was studied in 144 studies, chronic obstructive pulmonary disease (COPD) in 112. Most studies (100/144) based identification of asthma on symptom-based questionnaires. In contrast, COPD diagnosis was typically based on spirometry findings (94/112); 65 used fixed-ratio thresholds, 29 reported fixed-ratio and lower-limit-of-normal values. Only five articles used the term 'phenotype'. Most studies used questionnaires derived from validated surveys, most commonly the European Community Respiratory Health Survey (n = 47). The burden/impact of CRD was reported in 33 articles (most commonly activity limitation).

    CONCLUSION: Surveys remain the most practical approach for estimating prevalence of CRD but there is a need to identify the most predictive questions for diagnosing asthma and to standardise diagnostic criteria.

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