141 results on '"Tran TC"'
Search Results
2. Management strategy after diagnosis of Abernethy malformation: a case report
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Witjes Caroline DM, Ijzermans Jan NM, Noordegraaf Anton, and Tran TC
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hepatocellular carcinoma ,arteriovenous malformation ,Abernethy malformation ,pulmonary hypertension ,Medicine - Abstract
Abstract Introduction The Abernethy malformation is a rare anomaly with a widely variable clinical presentation. Many diagnostic dilemmas have been reported. Nowadays, with the evolution of medical imaging, diagnosis can be made more easily, but management of patients with an Abernethy malformation is still open for discussion. Case presentation In this case study, we describe a 34-year-old Caucasian man who presented with a large hepatocellular carcinoma in the presence of an Abernethy malformation, which was complicated by the development of pulmonary arterial hypertension. Conclusion This case underlines the importance of regular examination of patients with an Abernethy malformation, even in older patients, to prevent complications and to detect liver lesions at an early stage.
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- 2012
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3. Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial
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Alwayn Ian PJ, zur borg Ingrid RAM, Langenhuijsen Johan F, d'Ancona Frank CH, Tran TC Khe, Terkivatan Turkan, Kok Niels FM, Dols Leonienke FC, Hendriks Mark P, Dooper Ine M, Weimar Willem, and IJzermans Jan NM
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Surgery ,RD1-811 - Abstract
Abstract Background Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. Methods/design The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. Discussion This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. Trial Registration Dutch Trial Register NTR1433
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- 2010
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4. GENETIC IMPROVEMENT FOR WOOD PRODUCTION IN MELALEUCA CAJUPUTI
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Nguyen, THH, Konda, R, Kieu, TD, Tran, TC, Phung, VK, Tran, TH, and Wu, HX
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- 2019
5. Current use of imaging after primary treatment of prostate cancer
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Hussein, AA, Punnen, S, Zhao, S, Cowan, JE, Leapman, M, Tran, TC, Washington, SL, Truesdale, MD, Carroll, PR, and Cooperberg, MR
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Urology & Nephrology ,Clinical Sciences - Abstract
Purpose Data are limited on imaging after primary treatment of localized prostate cancer. Materials and Methods We identified 8,435 men newly diagnosed with nonmetastatic prostate cancer in 1995 to 2012 who were enrolled in CaPSURE™. Patients were followed after primary treatment with radical prostatectomy, cryosurgery, brachytherapy, external beam radiation therapy or androgen deprivation therapy. We assessed the use of bone scan, computerized tomography and magnetic resonance imaging after primary treatment. Factors associated with posttreatment outcomes (number of imaging tests, and time to first imaging and salvage treatment) were evaluated with multivariate Poisson regression and Cox proportional hazards regression. Results The incidence of posttreatment bone scan, computerized tomography and magnetic resonance imaging was 20% or less. Last posttreatment log(prostate specific antigen) was associated with multiple posttreatment imaging. Management by radical prostatectomy, cryosurgery, external beam radiation therapy or brachytherapy vs androgen deprivation therapy was associated with a lower likelihood of posttreatment imaging. Of patients who were imaged after treatment 25% with radical prostatectomy and 9% with radiation underwent imaging before prostate specific antigen failure. The 5-year salvage treatment-free survival rate was 81%. Positive findings on posttreatment imaging were associated with a higher risk of salvage treatment. Conclusions Patients treated with androgen deprivation therapy for localized disease were most likely to be imaged, primarily by bone scan. Men treated with other therapies were less likely to be imaged and tended to undergo computerized tomography. Imaging may add value to posttreatment prostate specific antigen monitoring to identify disease recurrence and progression. Further studies are needed to establish guidelines for the optimal frequency and imaging type to monitor the treatment response.
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- 2015
6. Model predictive control and stabilisation of interconnected systems
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Tran, TC
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Model predictive control ,Constraints ,Large scale systems ,Stability - Abstract
University of Technology, Sydney. Faculty of Engineering and Information Technology. The attraction of having higher efficiency and quality, as well as increasing reliability and flexibility for industrial plants and network systems has created opportunities for new research in the control and optimisation fields. Among various design methods, model predictive control (MPC) strategies have proved to be effective in industrial applications. Whilst found widespread used with stand-alone controllers in the refining and many other industries, the field of orchestrating non-centralised MPCs and distributed MPCs is evaluated as still in its infancy. The work in this thesis is concerned with stabilising methods for the control of complex interconnected systems with mixed connection configurations employing distributed and decentralised model predictive control schemes. Inheriting the advantage of the MPC strategy, the control and state constraints are naturally dealt with by the employed methods. As a result, the novel concept of asymptotically positive realness constraint (APRC) and the segregation and integration constructive methods for the constrained stabilisation of interconnected systems are introduced and developed. The MPC is formulated with state space models and stabilising constraints within the open-loop paradigm in this thesis. By having the control inputs entirely decoupled between subsystems and no additional constraints imposed on the interactive variables rather than the coupling constraint itself, the proposed approaches outreach various types of systems and applications. For parallel connections that emulate parallel redundant structures and have unknown splitting ratios, a fully decentralised control strategy is developed as an alternative to the hybrid approaches. For the semi-automatic control systems, which is involved with both closed-loop and humanin- the-loop regulatory controls, the stability-guaranteed method of decentralised stabilising agents which are interoperable with different control algorithms is germinated and implemented for each single subsystem.
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- 2011
7. GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cellsex vivo
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Pedroza-Gonzalez, Alexander, primary, Zhou, Guoying, additional, Singh, Simar Pal, additional, Boor, Patrick PC, additional, Pan, Qiuwei, additional, Grunhagen, Dirk, additional, de Jonge, Jeroen, additional, Tran, TC Khe, additional, Verhoef, Cornelis, additional, IJzermans, Jan NM, additional, Janssen, Harry LA, additional, Biermann, Katharina, additional, Kwekkeboom, Jaap, additional, and Sprengers, Dave, additional
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- 2015
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8. Temporal Fluctuation of Multidrug Resistant Salmonella Typhi Haplotypes in the Mekong River Delta Region of Vietnam
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Diemert, DJ, Holt, KE, Dolecek, C, Tran, TC, Pham, TD, Tran, TPL, Nguyen, VMH, Tran, VTN, Campbell, JI, Bui, HM, Nguyen, VVC, Tran, TH, Farrar, J, Dougan, G, Baker, S, Diemert, DJ, Holt, KE, Dolecek, C, Tran, TC, Pham, TD, Tran, TPL, Nguyen, VMH, Tran, VTN, Campbell, JI, Bui, HM, Nguyen, VVC, Tran, TH, Farrar, J, Dougan, G, and Baker, S
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BACKGROUND: typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. PRINCIPAL FINDINGS: the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. SIGNIFICANCE: the H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam.
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- 2011
9. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens
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Tran, VTN, Karkey, A, Dongol, S, Hang, NT, Dunstan, S, Holt, K, Le, TPT, Campbell, JI, Tran, TC, Nguyen, VVC, Arjyal, A, Koirala, S, Basnyat, B, Dolecek, C, Farrar, J, Baker, S, Tran, VTN, Karkey, A, Dongol, S, Hang, NT, Dunstan, S, Holt, K, Le, TPT, Campbell, JI, Tran, TC, Nguyen, VVC, Arjyal, A, Koirala, S, Basnyat, B, Dolecek, C, Farrar, J, and Baker, S
- Abstract
BACKGROUND: PCR amplification for the detection of pathogens in biological material is generally considered a rapid and informative diagnostic technique. Invasive Salmonella serovars, which cause enteric fever, can be commonly cultured from the blood of infected patients. Yet, the isolation of invasive Salmonella serovars from blood is protracted and potentially insensitive. METHODS: We developed and optimised a novel multiplex three colour real-time PCR assay to detect specific target sequences in the genomes of Salmonella serovars Typhi and Paratyphi A. We performed the assay on DNA extracted from blood and bone marrow samples from culture positive and negative enteric fever patients. RESULTS: The assay was validated and demonstrated a high level of specificity and reproducibility under experimental conditions. All bone marrow samples tested positive for Salmonella, however, the sensitivity on blood samples was limited. The assay demonstrated an overall specificity of 100% (75/75) and sensitivity of 53.9% (69/128) on all biological samples. We then tested the PCR detection limit by performing bacterial counts after inoculation into blood culture bottles. CONCLUSIONS: Our findings corroborate previous clinical findings, whereby the bacterial load of S. Typhi in peripheral blood is low, often below detection by culture and, consequently, below detection by PCR. Whilst the assay may be utilised for environmental sampling or on differing biological samples, our data suggest that PCR performed directly on blood samples may be an unsuitable methodology and a potentially unachievable target for the routine diagnosis of enteric fever.
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- 2010
10. A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam
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Frenck, R, Dolecek, C, Tran, TPL, Nguyen, NR, Le, TP, Ha, V, Phung, QT, Doan, CD, Nguyen, TBB, Duong, TL, Luong, BH, Nguyen, TB, Nguyen, TAH, Pham, ND, Mai, NL, Phan, VBB, Vo, AH, Nguyen, VMH, Tran, TTN, Tran, TC, Schultsz, C, Dunstan, SJ, Stepniewska, K, Campbell, JI, To, SD, Basnyat, B, Nguyen, VVC, Nguyen, VS, Nguyen, TC, Tran, TH, Farrar, J, Frenck, R, Dolecek, C, Tran, TPL, Nguyen, NR, Le, TP, Ha, V, Phung, QT, Doan, CD, Nguyen, TBB, Duong, TL, Luong, BH, Nguyen, TB, Nguyen, TAH, Pham, ND, Mai, NL, Phan, VBB, Vo, AH, Nguyen, VMH, Tran, TTN, Tran, TC, Schultsz, C, Dunstan, SJ, Stepniewska, K, Campbell, JI, To, SD, Basnyat, B, Nguyen, VVC, Nguyen, VS, Nguyen, TC, Tran, TH, and Farrar, J
- Abstract
BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azit
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- 2008
11. DO METEOROLOGICAL CONDITIONS PLAY A ROLE IN OCCURENCE OF PREECLAMPSIA?
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Tran, TC., primary, Boumendil, A., additional, Rozenberg, P., additional, and Aegerter, P., additional
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- 2011
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12. Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial
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Dols, Leonienke FC, primary, Kok, Niels FM, additional, Terkivatan, Turkan, additional, Tran, TC Khe, additional, d'Ancona, Frank CH, additional, Langenhuijsen, Johan F, additional, zur borg, Ingrid RAM, additional, Alwayn, Ian PJ, additional, Hendriks, Mark P, additional, Dooper, Ine M, additional, Weimar, Willem, additional, and IJzermans, Jan NM, additional
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- 2010
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13. The Need for a Prophylactic Gastrojejunostomy for Unresectable Periampullary Cancer
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Van Heek, N Tjarda, primary, De Castro, Steve M.M., additional, van Eijck, Casper H., additional, van Geenen, Rutger C.I., additional, Hesselink, Eric J., additional, Breslau, Paul J., additional, Tran, TC Khe, additional, Kazemier, Geert, additional, Visser, Mechteld R.M., additional, Busch, Olivier R.C., additional, Obertop, Hugo, additional, and Gouma, Dirk J., additional
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- 2003
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14. Impact of case volume on survival of septic shock in patients with malignancies.
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Zuber B, Tran TC, Aegerter P, Grimaldi D, Charpentier J, Guidet B, Mira JP, Pène F, and CUB-Réa Network
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OBJECTIVE: Septic shock is a frequent and severe complication in the course of malignancies. In a large multicenter cohort of septic shock patients with hematologic malignancies and solid tumors, we assessed the temporal trend in survival and the prognostic factors, with particular emphasis on case volume. DESIGN: A 12-yr multicenter retrospective cohort study of prospectively collected data. PATIENTS AND METHODS: Cancer patients with septic shock were selected over a 12-yr period (1997-2008) from a French regional database (CUB-Réa). The following variables were extracted: demographic characteristics, type of malignancy, characteristics of infection, severity-of-illness score (Simplified Acute Physiology Score II), organ failure supports, and vital status. For each unit, a running mean annual volume of admissions was calculated for the purpose of categorization into volume tertiles. Prognostic factors were analyzed by a conditional multivariate logistic model after matching on a propensity score of being admitted to a high-volume unit and on the year of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 3,437 patients were included in the study. The intensive care unit mortality rate dramatically dropped over time (from 70.4% in 1997 to 52.5% in 2008, relative decrease 25.4%, p < .001). Participating units were distributed into low-volume (< five patients per year), medium-volume (five to 12 patients per year), and high-volume (>= 13 patients per year) tertiles. A medical cause for intensive care unit admission, Simplified Acute Physiology Score II, invasive mechanical ventilation, renal replacement therapy, fungal infections, and unknown microorganism were identified as poor prognostic factors. Case volume demonstrated a strong influence on survival, admission in a high-volume unit being associated with a marked decrease in mortality as compared to low-volume units (adjusted odds ratio 0.63; 95% confidence interval [0.46-0.87], p = .002). CONCLUSIONS: Survival of septic shock patients with malignancies markedly increased over the recent years. Furthermore, we identified case volume as a major prognostic factor in this setting. [ABSTRACT FROM AUTHOR]
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- 2012
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15. GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cells ex vivo.
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Pedroza-Gonzalez, Alexander, Zhou, Guoying, Singh, Simar Pal, Boor, Patrick PC, Pan, Qiuwei, Grunhagen, Dirk, de Jonge, Jeroen, Tran, TC Khe, Verhoef, Cornelis, IJzermans, Jan NM, Janssen, Harry LA, Biermann, Katharina, Kwekkeboom, Jaap, and Sprengers, Dave
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LIVER cancer ,LIVER tumors ,T cells ,GLUCOCORTICOID receptors - Abstract
In liver cancer tumor-infiltrating regulatory T cells (Ti-Treg) are potent suppressors of tumor-specific T-cell responses and express high levels of the Treg-associated molecules cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor receptor (GITR). In this study, we have evaluated the capacity of GITR-ligation, CTLA-4-blockade and a combination of both treatments to alleviate immunosuppression mediated by Ti-Treg. Usingex vivoisolated cells from individuals with hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (LM-CRC) we show that treatment with a soluble form of the natural ligand of GITR (GITRL), or with blocking antibodies to CTLA-4, reduces the suppression mediated by human liver tumor-infiltrating CD4+Foxp3+ Treg, thereby restoring proliferation and cytokine production by effector T cells. Importantly, combined treatment with low doses of both molecules exhibited stronger recovery of T cell function compared with either treatment alone. Our data suggest that in patients with primary and secondary liver cancer both GITR-ligation and anti-CTLA-4 mAb can improve the antitumor immunity by abrogating Ti-Treg mediated suppression. [ABSTRACT FROM AUTHOR]
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- 2015
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16. Cardiovascular events in patients with fabry disease natural history data from the fabry registry.
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Patel MR, Cecchi F, Cizmarik M, Kantola I, Linhart A, Nicholls K, Strotmann J, Tallaj J, Tran TC, West ML, Beitner-Johnson D, and Abiose A
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- 2011
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17. PheWAS analysis on large-scale biobank data with PheTK.
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Tran TC, Schlueter DJ, Zeng C, Mo H, Carroll RJ, and Denny JC
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Summary: With the rapid growth of genetic data linked to electronic health record data in huge cohorts, large-scale phenome-wide association study (PheWAS) have become powerful discovery tools in biomedical research. PheWAS is an analysis method to study phenotype associations utilizing longitudinal electronic health record (EHR) data. Previous PheWAS packages were developed mostly with smaller data sets and with earlier PheWAS approaches. PheTK was designed to simplify analysis and efficiently handle biobank-scale data. PheTK uses multithreading and supports a full PheWAS workflow including extraction of data from OMOP databases and Hail matrix tables as well as PheWAS analysis for both phecode version 1.2 and phecodeX. Benchmarking results showed PheTK took 64% less time than the R PheWAS package to complete the same workflow. PheTK can be run locally or on cloud platforms such as the All of Us Researcher Workbench (All of Us) or the UK Biobank (UKB) Research Analysis Platform (RAP)., Availability and Implementation: The PheTK package is freely available on the Python Package Index, on GitHub under GNU General Public License (GPL-3) at https://github.com/nhgritctran/PheTK, and on Zenodo, DOI 10.5281/zenodo.14217954, at https://doi.org/10.5281/zenodo.14217954. PheTK is implemented in Python and platform independent., Supplementary Information: Supplementary data are available at Bioinformatics online., (Published by Oxford University Press 2024.)
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- 2024
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18. Racial and Ethnic Disparities in Antihypertensive Medication Prescribing Patterns and Effectiveness.
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Goleva SB, Williams A, Schlueter DJ, Keaton JM, Tran TC, Waxse BJ, Ferrara TM, Cassini T, Mo H, and Denny JC
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- Adult, Aged, Female, Humans, Male, Middle Aged, Black or African American, Blood Pressure drug effects, Ethnicity, Hispanic or Latino, Longitudinal Studies, Treatment Outcome, United States, White, Antihypertensive Agents therapeutic use, Healthcare Disparities ethnology, Hypertension drug therapy, Hypertension ethnology, Practice Patterns, Physicians' statistics & numerical data
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Variability in drug effectiveness and provider prescribing patterns have been reported in different racial and ethnic populations. We sought to evaluate antihypertensive drug effectiveness and prescribing patterns among self-identified Hispanic/Latino (Hispanic), Non-Hispanic Black (Black), and Non-Hispanic White (White) populations that enrolled in the NIH All of Us Research Program, a US longitudinal cohort. We employed a self-controlled case study method using electronic health record and survey data from 17,718 White, Hispanic, and Black participants who were diagnosed with essential hypertension and prescribed at least one of 19 commonly used antihypertensive medications. Effectiveness was determined by calculating the reduction in systolic blood pressure measurements after 28 or more days of drug exposure. Starting systolic blood pressure and effectiveness for each medication were compared for self-reported Black, Hispanic, and White participants using adjusted linear regressions. Black and Hispanic participants were started on antihypertensive medications at significantly higher SBP than White participants in 13 and 7 out of 19 medications, respectively. More Black participants were prescribed multiple antihypertensive medications (58.46%) than White (52.35%) or Hispanic (49.9%) participants. First-line HTN medications differed by race and ethnicity. Following the 2017 American College of Cardiology and the American Heart Association High Blood Pressure Guideline release, around 64% of Black participants were prescribed a recommended first-line antihypertensive drug compared with 76% of White and 82% of Hispanic participants. Effect sizes suggested that most antihypertensive drugs were less effective in Hispanic and Black, compared with White, participants, and statistical significance was reached in 6 out of 19 drugs. These results indicate that Black and Hispanic populations may benefit from earlier intervention and screening and highlight the potential benefits of personalizing first-line medications., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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19. Corrigendum to "Transforming medical education to strengthen the health professional training in Viet Nam: a case study" [ The Lancet Regional Health - Western Pacific, volume 27 (2022)/S2666606522001584].
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Tran TD, Vu PM, Pham HTM, Au LN, Do HP, Doan HTT, Huynh N, Huynh QTV, Le BK, Ngo DQ, Nguyen HTM, Nguyen KD, Nguyen NA, Nguyen PH, Nguyen TA, Tran TC, Chau HN, Vuong LN, and Vu NV
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[This corrects the article DOI: 10.1016/j.lanwpc.2022.100543.]., (© 2024 The Author(s).)
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- 2024
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20. Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.
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Mo H, Channa Y, Ferrara TM, Waxse BJ, Schlueter DJ, Tran TC, Awan AH, Goleva SB, Williams A, Babbar A, Stubblefield O, Keaton JM, Larson EA, Wilke RA, and Denny JC
- Abstract
Selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and norepinephrine-dopamine reuptake inhibitor (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks of hyponatremia associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) and NRI (bupropion), as well as omeprazole as a reference, with a retrospective observational cohort study in the All of Us Research Program, a national multicenter research cohort containing de-identified electronic health records (EHR). Participants who had been prescribed monotherapy with any of eight common antidepressants were included, with each drug considered as a separate arm indexed with a start date. Events were defined as the first occurrence of a low plasma sodium measurement or a clinical diagnosis recorded for either hyponatremia or SIADH. Those who did not have events were censored at their last plasma sodium measurement. A total of 17,439 individuals were exposed to one of the eight antidepressants as monotherapy. The overall incidences for hyponatremia were 0.87% in the first 30 days and 10.5% in the first 3 years in the antidepressant arms. Compared to sertraline, duloxetine (hazard ratio [HR] = 1.37 [1.19-1.58]) and escitalopram (HR = 1.16 [1.01-1.33]) were associated with the highest overall risk of hyponatremia, and bupropion (HR = 0.83 [0.73-0.94]) and paroxetine (HR = 0.78 [0.65-0.93]) were associated with the lowest risk. The risks were unchanged after adjusting for comorbidity and polypharmacy. Such information could help guide providers in managing patients and their risks of hyponatremia when on common antidepressants., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2024
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21. Altered interactions between cis-regulatory elements partially resolve BLADE-ON-PETIOLE genetic redundancy in Capsella rubella.
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Tran TC, Mähl K, Kappel C, Dakhiya Y, Sampathkumar A, Sicard A, and Lenhard M
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- Plants, Genetically Modified, Flowers genetics, Flowers growth & development, Genes, Plant, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism, Regulatory Sequences, Nucleic Acid genetics, Gene Duplication, Genes, Duplicate genetics, Capsella genetics, Arabidopsis genetics, Gene Expression Regulation, Plant, Plant Proteins genetics, Plant Proteins metabolism, Promoter Regions, Genetic genetics
- Abstract
Duplicated genes are thought to follow one of three evolutionary trajectories that resolve their redundancy: neofunctionalization, subfunctionalization, or pseudogenization. Differences in expression patterns have been documented for many duplicated gene pairs and interpreted as evidence of subfunctionalization and a loss of redundancy. However, little is known about the functional impact of such differences and about their molecular basis. Here, we investigate the genetic and molecular basis for the partial loss of redundancy between the two BLADE-ON-PETIOLE genes BOP1 and BOP2 in red shepherd's purse (Capsella rubella) compared to Arabidopsis (Arabidopsis thaliana). While both genes remain almost fully redundant in A. thaliana, BOP1 in C. rubella can no longer ensure wild-type floral organ numbers and suppress bract formation, due to an altered expression pattern in the region of the cryptic bract primordium. We use two complementary approaches, transgenic rescue of A. thaliana atbop1 atbop2 double mutants and deletions in the endogenous AtBOP1 promoter, to demonstrate that several BOP1 promoter regions containing conserved noncoding sequences interact in a nonadditive manner to control BOP1 expression in the bract primordium and that changes in these interactions underlie the evolutionary divergence between C. rubella and A. thaliana BOP1 expression and activity. Similarly, altered interactions between cis-regulatory regions underlie the divergence in functional promoter architecture related to the control of floral organ abscission by BOP1. These findings highlight the complexity of promoter architecture in plants and suggest that changes in the interactions between cis-regulatory elements are key drivers for evolutionary divergence in gene expression and the loss of redundancy., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)
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- 2024
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22. Phenome-Wide Association of APOE Alleles in the All of Us Research Program.
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Khajouei E, Ghisays V, Piras IS, Martinez KL, Naymik M, Ngo P, Tran TC, Denny JC, Wheeler TJ, Huentelman MJ, Reiman EM, and Karnes JH
- Abstract
Background: Genetic variation in APOE is associated with altered lipid metabolism, as well as cardiovascular and neurodegenerative disease risk. However, prior studies are largely limited to European ancestry populations and differential risk by sex and ancestry has not been widely evaluated. We utilized a phenome-wide association study (PheWAS) approach to explore APOE -associated phenotypes in the All of Us Research Program., Methods: We determined APOE alleles for 181,880 All of Us participants with whole genome sequencing and electronic health record (EHR) data, representing seven gnomAD ancestry groups. We tested association of APOE variants, ordered based on Alzheimer's disease risk hierarchy (ε2/ε2<ε2/ε3<ε3/ε3<ε2/ε4<ε3/ε4<ε4/ε4), with 2,318 EHR-derived phenotypes. Bonferroni-adjusted analyses were performed overall, by ancestry, by sex, and with adjustment for social determinants of health (SDOH)., Findings: In the overall cohort, PheWAS identified 17 significant associations, including an increased odds of hyperlipidemia (OR 1.15 [1.14-1.16] per APOE genotype group; P =1.8×10
-129 ), dementia, and Alzheimer's disease (OR 1.55 [1.40-1.70]; P =5×10-19 ), and a reduced odds of fatty liver disease (OR 0.93 [0.90-0.95]; P =1.6×10-9 ) and chronic liver disease. ORs were similar after SDOH adjustment and by sex, except for an increased number of cardiovascular associations in males, and decreased odds of noninflammatory disorders of vulva and perineum in females (OR 0.89 [0.84-0.94]; P =1.1×10-5 ). Significant heterogeneity was observed for hyperlipidemia and mild cognitive impairment across ancestry. Unique associations by ancestry included transient retinal arterial occlusion in the European ancestry group, and first-degree atrioventricular block in the American Admixed/Latino ancestry group., Interpretation: We replicate extensive phenotypic associations with APOE alleles in a large, diverse cohort, despite limitations in accuracy for EHR-derived phenotypes. We provide a comprehensive catalog of APOE -associated phenotypes and present evidence of unique phenotypic associations by sex and ancestry, as well as heterogeneity in effect size across ancestry.- Published
- 2024
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23. Gα13 restricts nutrient driven proliferation in mucosal germinal centers.
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Nguyen HT, Li M, Vadakath R, Henke KA, Tran TC, Li H, Yamadi M, Darbha S, Yang Y, Kabat J, Albright AR, Centeno EG, Phelan JD, Roulland S, Huang DW, Kelly MC, Young RM, Pittaluga S, Difilippantonio S, and Muppidi JR
- Subjects
- Animals, Mice, Lymph Nodes metabolism, Lymph Nodes immunology, Nutrients metabolism, Signal Transduction, Glutamine metabolism, Mice, Inbred C57BL, Proto-Oncogene Proteins c-myc metabolism, Proto-Oncogene Proteins c-myc genetics, Intestinal Mucosa metabolism, Intestinal Mucosa immunology, Mucous Membrane metabolism, Mucous Membrane immunology, Germinal Center immunology, Germinal Center metabolism, Cell Proliferation, B-Lymphocytes immunology, B-Lymphocytes metabolism, GTP-Binding Protein alpha Subunits, G12-G13 metabolism, GTP-Binding Protein alpha Subunits, G12-G13 genetics, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Knockout
- Abstract
Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Published
- 2024
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24. Convergence and molecular evolution of floral fragrance after independent transitions to self-fertilization.
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Woźniak NJ, Sartori K, Kappel C, Tran TC, Zhao L, Erban A, Gallinger J, Fehrle I, Jantzen F, Orsucci M, Ninkovic V, Rosa S, Lenhard M, Kopka J, and Sicard A
- Subjects
- Pollination, Alkenes metabolism, Plant Proteins genetics, Plant Proteins metabolism, Acyclic Monoterpenes, Flowers genetics, Self-Fertilization genetics, Evolution, Molecular, Odorants analysis
- Abstract
Studying the independent evolution of similar traits provides valuable insights into the ecological and genetic factors driving phenotypic evolution.
1 The transition from outcrossing to self-fertilization is common in plant evolution2 and is often associated with a reduction in floral attractive features such as display size, chemical signals, and pollinator rewards.3 These changes are believed to result from the reallocation of the resources used for building attractive flowers, as the need to attract pollinators decreases.2 , 3 We investigated the similarities in the evolution of flower fragrance following independent transitions to self-fertilization in Capsella.4 , 5 , 6 , 7 , 8 , 9 We identified several compounds that exhibited similar changes in different selfer lineages, such that the flower scent composition reflects mating systems rather than evolutionary history within this genus. We further demonstrate that the repeated loss of β-ocimene emission, one of the compounds most strongly affected by these transitions, was caused by mutations in different genes. In one of the Capsella selfing lineages, the loss of its emission was associated with a mutation altering subcellular localization of the ortholog of TERPENE SYNTHASE 2. This mutation appears to have been fixed early after the transition to selfing through the capture of variants segregating in the ancestral outcrossing population. The large extent of convergence in the independent evolution of flower scent, together with the evolutionary history and molecular consequences of a causal mutation, suggests that the emission of specific volatiles evolved as a response to changes in ecological pressures rather than resource limitation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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25. Influenza and pneumococcal vaccination in patients with COPD from 3 French cohorts: Insufficient coverage and associated factors.
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Raherison C, Aguilaniu B, Zysman M, Burgel PR, Hess D, Ouaalaya EH, Tran TC, and Roche N
- Abstract
Background: Low vaccination rates against influenza and Streptococcus (S.) pneumoniae infections in COPD could impair outcomes. Understanding underlying factors could help improving implementation., Objectives: To describe vaccination rates at inclusion in COPD cohorts and analyze associated factors., Methods: Between 2012 and 2018, 5927 patients with sufficient data available were recruited in 3 French COPD cohorts (2566 in COLIBRI-COPD, 2653 in PALOMB and 708 in Initiatives BPCO). Data at inclusion were pooled to describe vaccination rates and analyze associated factors., Results: Mean age was 66 years, 34 % were women, 35 % were current smokers, mean FEV1 was 58 % predicted, 22 % reported ≥2 exacerbations in the year prior to inclusion, mMRC dyspnea grade was ≥2 in 59 %, 52 % had cardiovascular comorbidities and 9 % a history of asthma. Vaccinations rates in the year prior to study entry were 34.4 % for influenza + S. pneumoniae, 17.5 % for influenza alone and 8.9 % for S. pneumoniae alone. In multivariate analyses, influenza vaccination rate was greater in older age, smoking status, low FEV1, exacerbation history, mMRC dyspnea>2, asthma history, hypertension, diabetes mellitus, and the year of inclusion. SP vaccination was associated with type of practice of the respiratory physician, age, smoking status, FEV1, exacerbation history, dyspnea grade, asthma history and the year of inclusion., Conclusion: Rates of vaccination against influenza and S. pneumoniae infection at inclusion in COPD cohorts remain insufficient and vaccination appears restricted to patients with specific features especially regarding severity and comorbidities, which is not consistent with current recommendations., Competing Interests: Declaration of competing interest All authors have nothing to disclose related to this work., (Copyright © 2024 SPLF and Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
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26. Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022.
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Del Prete R, Nesta D, Triggiano F, Lorusso M, Garzone S, Vitulano L, Denicolò S, Indraccolo F, Mastria M, Ronga L, Inchingolo F, Aityan SK, Nguyen KCD, Tran TC, Gargiulo Isacco C, and Santacroce L
- Abstract
Background: The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data., Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males., Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41-50 and 51-60 years old, and finally, 44% of subjects were >60 years old., Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism.
- Published
- 2024
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27. Comparison of phenomic profiles in the All of Us Research Program against the US general population and the UK Biobank.
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Zeng C, Schlueter DJ, Tran TC, Babbar A, Cassini T, Bastarache LA, and Denny JC
- Subjects
- Humans, Biological Specimen Banks, UK Biobank, Phenotype, United Kingdom epidemiology, Phenomics, Population Health
- Abstract
Importance: Knowledge gained from cohort studies has dramatically advanced both public and precision health. The All of Us Research Program seeks to enroll 1 million diverse participants who share multiple sources of data, providing unique opportunities for research. It is important to understand the phenomic profiles of its participants to conduct research in this cohort., Objectives: More than 280 000 participants have shared their electronic health records (EHRs) in the All of Us Research Program. We aim to understand the phenomic profiles of this cohort through comparisons with those in the US general population and a well-established nation-wide cohort, UK Biobank, and to test whether association results of selected commonly studied diseases in the All of Us cohort were comparable to those in UK Biobank., Materials and Methods: We included participants with EHRs in All of Us and participants with health records from UK Biobank. The estimates of prevalence of diseases in the US general population were obtained from the Global Burden of Diseases (GBD) study. We conducted phenome-wide association studies (PheWAS) of 9 commonly studied diseases in both cohorts., Results: This study included 287 012 participants from the All of Us EHR cohort and 502 477 participants from the UK Biobank. A total of 314 diseases curated by the GBD were evaluated in All of Us, 80.9% (N = 254) of which were more common in All of Us than in the US general population [prevalence ratio (PR) >1.1, P < 2 × 10-5]. Among 2515 diseases and phenotypes evaluated in both All of Us and UK Biobank, 85.6% (N = 2152) were more common in All of Us (PR >1.1, P < 2 × 10-5). The Pearson correlation coefficients of effect sizes from PheWAS between All of Us and UK Biobank were 0.61, 0.50, 0.60, 0.57, 0.40, 0.53, 0.46, 0.47, and 0.24 for ischemic heart diseases, lung cancer, chronic obstructive pulmonary disease, dementia, colorectal cancer, lower back pain, multiple sclerosis, lupus, and cystic fibrosis, respectively., Discussion: Despite the differences in prevalence of diseases in All of Us compared to the US general population or the UK Biobank, our study supports that All of Us can facilitate rapid investigation of a broad range of diseases., Conclusion: Most diseases were more common in All of Us than in the general US population or the UK Biobank. Results of disease-disease association tests from All of Us are comparable to those estimated in another well-studied national cohort., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)
- Published
- 2024
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28. New species of the eel genera Dysomma and Dysommina from Vietnam, South China Sea (Anguilliformes: Synaphobranchidae).
- Author
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Vo VQ, Ho HC, Dao HV, and Tran TC
- Subjects
- Animals, Vietnam, Spine, China, Eels, Head
- Abstract
Two new cutthroat eel species are described from Vietnam. Dysomma intermedium sp. nov. has a relatively long trunk, being about half of head length and anal-fin origin more than twice pectoral-fin length behind the pectoral-fin tip; pectoral fin well developed; dorsal-fin origin over or slightly in front of base of pectoral fin; two intermaxillary teeth; four or five compound teeth on ethmovomer; single row of seven or eight teeth on lower jaw; total lateral-line pores 70-76; and 21 pre-anal and 118-124 total vertebrae. Dysommina brevis sp. nov. differs from congeners by having a trunk shorter than head length, its length 11.1%-11.8% TL; a short pre-anal length 24.6%-25.6% TL, eye diameter 11.8%-12.3% head length; three large and one or two small teeth on ethmovomer; and fewer teeth on the upper and lower jaws. In addition, a specimen representing the first record of Dysommina orientalis in Vietnamese water is documented., (© 2024 Fisheries Society of the British Isles.)
- Published
- 2024
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29. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.
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Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X, Lorenz KM, Mandla R, Huerta-Chagoya A, Melloni GEM, Kanoni S, Rayner NW, Bocher O, Arruda AL, Sonehara K, Namba S, Lee SSK, Preuss MH, Petty LE, Schroeder P, Vanderwerff B, Kals M, Bragg F, Lin K, Guo X, Zhang W, Yao J, Kim YJ, Graff M, Takeuchi F, Nano J, Lamri A, Nakatochi M, Moon S, Scott RA, Cook JP, Lee JJ, Pan I, Taliun D, Parra EJ, Chai JF, Bielak LF, Tabara Y, Hai Y, Thorleifsson G, Grarup N, Sofer T, Wuttke M, Sarnowski C, Gieger C, Nousome D, Trompet S, Kwak SH, Long J, Sun M, Tong L, Chen WM, Nongmaithem SS, Noordam R, Lim VJY, Tam CHT, Joo YY, Chen CH, Raffield LM, Prins BP, Nicolas A, Yanek LR, Chen G, Brody JA, Kabagambe E, An P, Xiang AH, Choi HS, Cade BE, Tan J, Broadaway KA, Williamson A, Kamali Z, Cui J, Thangam M, Adair LS, Adeyemo A, Aguilar-Salinas CA, Ahluwalia TS, Anand SS, Bertoni A, Bork-Jensen J, Brandslund I, Buchanan TA, Burant CF, Butterworth AS, Canouil M, Chan JCN, Chang LC, Chee ML, Chen J, Chen SH, Chen YT, Chen Z, Chuang LM, Cushman M, Danesh J, Das SK, de Silva HJ, Dedoussis G, Dimitrov L, Doumatey AP, Du S, Duan Q, Eckardt KU, Emery LS, Evans DS, Evans MK, Fischer K, Floyd JS, Ford I, Franco OH, Frayling TM, Freedman BI, Genter P, Gerstein HC, Giedraitis V, González-Villalpando C, González-Villalpando ME, Gordon-Larsen P, Gross M, Guare LA, Hackinger S, Hakaste L, Han S, Hattersley AT, Herder C, Horikoshi M, Howard AG, Hsueh W, Huang M, Huang W, Hung YJ, Hwang MY, Hwu CM, Ichihara S, Ikram MA, Ingelsson M, Islam MT, Isono M, Jang HM, Jasmine F, Jiang G, Jonas JB, Jørgensen T, Kamanu FK, Kandeel FR, Kasturiratne A, Katsuya T, Kaur V, Kawaguchi T, Keaton JM, Kho AN, Khor CC, Kibriya MG, Kim DH, Kronenberg F, Kuusisto J, Läll K, Lange LA, Lee KM, Lee MS, Lee NR, Leong A, Li L, Li Y, Li-Gao R, Ligthart S, Lindgren CM, Linneberg A, Liu CT, Liu J, Locke AE, Louie T, Luan J, Luk AO, Luo X, Lv J, Lynch JA, Lyssenko V, Maeda S, Mamakou V, Mansuri SR, Matsuda K, Meitinger T, Melander O, Metspalu A, Mo H, Morris AD, Moura FA, Nadler JL, Nalls MA, Nayak U, Ntalla I, Okada Y, Orozco L, Patel SR, Patil S, Pei P, Pereira MA, Peters A, Pirie FJ, Polikowsky HG, Porneala B, Prasad G, Rasmussen-Torvik LJ, Reiner AP, Roden M, Rohde R, Roll K, Sabanayagam C, Sandow K, Sankareswaran A, Sattar N, Schönherr S, Shahriar M, Shen B, Shi J, Shin DM, Shojima N, Smith JA, So WY, Stančáková A, Steinthorsdottir V, Stilp AM, Strauch K, Taylor KD, Thorand B, Thorsteinsdottir U, Tomlinson B, Tran TC, Tsai FJ, Tuomilehto J, Tusie-Luna T, Udler MS, Valladares-Salgado A, van Dam RM, van Klinken JB, Varma R, Wacher-Rodarte N, Wheeler E, Wickremasinghe AR, van Dijk KW, Witte DR, Yajnik CS, Yamamoto K, Yamamoto K, Yoon K, Yu C, Yuan JM, Yusuf S, Zawistowski M, Zhang L, Zheng W, Raffel LJ, Igase M, Ipp E, Redline S, Cho YS, Lind L, Province MA, Fornage M, Hanis CL, Ingelsson E, Zonderman AB, Psaty BM, Wang YX, Rotimi CN, Becker DM, Matsuda F, Liu Y, Yokota M, Kardia SLR, Peyser PA, Pankow JS, Engert JC, Bonnefond A, Froguel P, Wilson JG, Sheu WHH, Wu JY, Hayes MG, Ma RCW, Wong TY, Mook-Kanamori DO, Tuomi T, Chandak GR, Collins FS, Bharadwaj D, Paré G, Sale MM, Ahsan H, Motala AA, Shu XO, Park KS, Jukema JW, Cruz M, Chen YI, Rich SS, McKean-Cowdin R, Grallert H, Cheng CY, Ghanbari M, Tai ES, Dupuis J, Kato N, Laakso M, Köttgen A, Koh WP, Bowden DW, Palmer CNA, Kooner JS, Kooperberg C, Liu S, North KE, Saleheen D, Hansen T, Pedersen O, Wareham NJ, Lee J, Kim BJ, Millwood IY, Walters RG, Stefansson K, Ahlqvist E, Goodarzi MO, Mohlke KL, Langenberg C, Haiman CA, Loos RJF, Florez JC, Rader DJ, Ritchie MD, Zöllner S, Mägi R, Marston NA, Ruff CT, van Heel DA, Finer S, Denny JC, Yamauchi T, Kadowaki T, Chambers JC, Ng MCY, Sim X, Below JE, Tsao PS, Chang KM, McCarthy MI, Meigs JB, Mahajan A, Spracklen CN, Mercader JM, Boehnke M, Rotter JI, Vujkovic M, Voight BF, Morris AP, and Zeggini E
- Subjects
- Humans, Adipocytes metabolism, Chromatin genetics, Chromatin metabolism, Coronary Artery Disease complications, Coronary Artery Disease genetics, Diabetic Nephropathies complications, Diabetic Nephropathies genetics, Endothelial Cells metabolism, Enteroendocrine Cells, Epigenomics, Islets of Langerhans metabolism, Multifactorial Inheritance genetics, Peripheral Arterial Disease complications, Peripheral Arterial Disease genetics, Single-Cell Analysis, Diabetes Mellitus, Type 2 classification, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 pathology, Diabetes Mellitus, Type 2 physiopathology, Disease Progression, Genetic Predisposition to Disease genetics, Genome-Wide Association Study
- Abstract
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes
1,2 and molecular mechanisms that are often specific to cell type3,4 . Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8 ) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care., (© 2024. The Author(s).)- Published
- 2024
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30. Epilepsy self-management mobile health application: A needs assessment in people with epilepsy and caregivers in Viet Nam.
- Author
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Tran TC, Duong HD, Truong LHK, Bui CK, Nguyen QH, Huynh HT, Le NN, Sor K, Truong TQ, Cu VT, Le NQ, Nguyen TTK, and Le MT
- Subjects
- Humans, Vietnam, Caregivers, Needs Assessment, Seizures, Surveys and Questionnaires, Self-Management, Epilepsy epidemiology, Epilepsy therapy, Telemedicine, Southeast Asian People
- Abstract
Objectives: This study aimed to determine (1) the needsof Vietnamese people with epilepsy (PWE) and their caregivers for self-management mobile health applications and (2) the self-management features expected to be included in an application., Methods: The survey consisted of an anonymous self-administered questionnaire that was distributed to PWE and caregivers from the age of 18 in Vietnam through online platforms and onsite at Nguyen Tri Phuong Hospital and University Medical Center, Ho Chi Minh City, from February 2022 to May 2022. The questionnaire assessed the participants' attitudes toward epilepsy self-management mobile applications, their willingness to use applications, and their expectations of the contents of an application., Results: Responses from 103 participants were submitted. Eighty-one participants (78.6%) reported using a smartphone, but only 50.6% of those claimed to know about self-management applications. Most respondents (70.9%) thought the applications would be useful for disease self-management, and 68.9% were willing to use epilepsy self-management applications. In addition, the most expected features to be included in self-management applications were epilepsy information, seizure first aid, connecting with medical professionals, and a seizure diary., Conclusion: Most Vietnamese PWE and caregivers had a willingness to use epilepsy self-management applications.The expected features are related to all aspects of self-management, including information, seizure, medication, and safety management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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31. Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program.
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Schlueter DJ, Sulieman L, Mo H, Keaton JM, Ferrara TM, Williams A, Qian J, Stubblefield O, Zeng C, Tran TC, Bastarache L, Dai J, Babbar A, Ramirez A, Goleva SB, and Denny JC
- Subjects
- Humans, Phenotype, Polymorphism, Single Nucleotide, Smoking, Genome-Wide Association Study methods, Population Health
- Abstract
Objective: The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations., Materials and Methods: We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals., Results: PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10-5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated., Discussion: Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results., Conclusion: This study demonstrated the feasibility of studying common exposures using All of Us data., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2023.)
- Published
- 2023
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32. Plasma cell-free RNA profiling of Vietnamese Alzheimer's patients reveals a linkage with chronic inflammation and apoptosis: a pilot study.
- Author
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Cao THM, Le APH, Tran TT, Huynh VK, Pham BH, Le TM, Nguyen QL, Tran TC, Tong TM, Than THN, Nguyen TTT, and Ha HTT
- Abstract
Introduction: Circulating cell-free RNA (cfRNA) is a potential hallmark for early diagnosis of Alzheimer's Disease (AD) as it construes the genetic expression level, giving insights into the pathological progress from the outset. Profiles of cfRNA in Caucasian AD patients have been investigated thoroughly, yet there was no report exploring cfRNAs in the ASEAN groups. This study examined the gap, expecting to support the development of point-of-care AD diagnosis., Methods: cfRNA profiles were characterized from 20 Vietnamese plasma samples (10 probable AD and 10 age-matched controls). RNA reads were subjected to differential expression (DE) analysis. Weighted gene correlation network analysis (WGCNA) was performed to identify gene modules that were significantly co-expressed. These modules' expression profiles were then correlated with AD status to identify relevant modules. Genes with the highest intramodular connectivity (module membership) were selected as hub genes. Transcript counts of differentially expressed genes were correlated with key AD measures-MMSE and MTA scores-to identify potential biomarkers., Results: 136 genes were identified as significant AD hallmarks ( p < 0.05), with 52 downregulated and 84 upregulated in the AD cohort. 45.6% of these genes are highly expressed in the hippocampus, cerebellum, and cerebral cortex. Notably, all markers related to chronic inflammation were upregulated, and there was a significant shift in all apoptotic markers. Three co-expressed modules were found to be significantly correlated with Alzheimer's status ( p < 0.05; R
2 > 0.5). Functional enrichment analysis on these modules reveals an association with focal adhesion, nucleocytoplasmic transport, and metal ion response leading to apoptosis, suggesting the potential participation of these pathways in AD pathology. 47 significant hub genes were found to be differentially expressed genes with the highest connectivity. Six significant hub genes ( CREB1, YTHDC1, IL1RL1, PHACTR2, ANKRD36B, RNF213 ) were found to be significantly correlated with MTA and MMSE scores. Other significant transcripts ( XRN1, UBB, CHP1, THBS1, S100A9 ) were found to be involved in inflammation and neuronal death. Overall, we have identified candidate transcripts in plasma cf-RNA that are differentially expressed and are implicated in inflammation and apoptosis, which can jumpstart further investigations into applying cf-RNA as an AD biomarker in Vietnam and ASEAN countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Le, Tran, Huynh, Pham, Le, Nguyen, Tran, Tong, Than, Nguyen and Ha.)- Published
- 2023
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33. The complete genome sequence of Neckar River virus confirms it to be a distinct member of the genus Tombusvirus in the family Tombusviridae.
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Tran TC, Maiss E, and Rose H
- Subjects
- DNA, Complementary, Phylogeny, Genome, Viral, Open Reading Frames, RNA, Viral genetics, Tombusvirus genetics, Tombusviridae genetics
- Abstract
Neckar River virus (NRV), first isolated from a water sample of the Neckar River (Germany) in the 1980s, was serologically characterized as a novel tombusvirus. In this study, the complete genome sequence was determined, and an infectious full-length cDNA clone was constructed. The genome organization of NRV (DSMZ PV-0270) resembles that of tombusviruses. The genome consists of 4739 nucleotides and contains five open reading frames (ORFs) and one additional putative ORF (pX) in the 3'-terminal region. Phylogenetic analysis and sequence comparisons confirmed NRV to be a member of the species Tombusvirus neckarfluminis in the genus Tombusvirus. The infectious full-length cDNA clone was constructed using Gibson assembly and subsequent infection of Nicotiana benthamiana plants by Rhizobium radiobacter inoculation. The virus derived from the full-length cDNA clone caused symptoms resembling those caused by the wild-type virus, but slightly milder., (© 2023. The Author(s).)
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- 2023
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34. Drug-Induced Liver Injury with Commonly Used Antibiotics in the All of Us Research Program.
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Gu S, Rajendiran G, Forest K, Tran TC, Denny JC, Larson EA, and Wilke RA
- Subjects
- Humans, United States epidemiology, Anti-Bacterial Agents adverse effects, Azithromycin adverse effects, Retrospective Studies, Amoxicillin-Potassium Clavulanate Combination adverse effects, Amoxicillin, Ciprofloxacin adverse effects, Cephalexin, Population Health, Chemical and Drug Induced Liver Injury diagnosis, Chemical and Drug Induced Liver Injury epidemiology, Chemical and Drug Induced Liver Injury etiology
- Abstract
Antibiotics are a known cause of idiosyncratic drug-induced liver injury (DILI). According to the Centers for Disease Control and Prevention, the five most commonly prescribed antibiotics in the United States are azithromycin, ciprofloxacin, cephalexin, amoxicillin, and amoxicillin-clavulanate. We quantified the frequency of acute DILI for these common antibiotics in the All of Us Research Program, one of the largest electronic health record (EHR)-linked research cohorts in the United States. Retrospective analyses were conducted applying a standardized phenotyping algorithm to de-identified clinical data available in the All of Us database for 318,598 study participants. Between February 1984 and December 2022, more than 30% of All of Us participants (n = 119,812 individuals) had been exposed to at least 1 of our 5 study drugs. Initial screening identified 591 potential case patients that met our preselected laboratory-based phenotyping criteria. Because DILI is a diagnosis of exclusion, we then used phenome scanning to narrow the case counts by (i) scanning all EHRs to identify all alternative diagnostic explanations for the laboratory abnormalities, and (ii) leveraging International Classification of Disease 9th revision (ICD)-9 and ICD 10th revision (ICD)-10 codes as exclusion criteria to eliminate misclassification. Our final case counts were 30 DILI cases with amoxicillin-clavulanate, 24 cases with azithromycin, 24 cases with ciprofloxacin, 22 cases with amoxicillin alone, and < 20 cases with cephalexin. These findings demonstrate that data from EHR-linked research cohorts can be efficiently mined to identify DILI cases related to the use of common antibiotics., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
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- 2023
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35. Correction: The ability of Interleukin-10 to negate haemozoin-related pro-inflammatory effects has the potential to restore impaired macrophage function associated with malaria infection.
- Author
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Tembo D, Harawa V, Tran TC, Afran L, Molyneux ME, Taylor TE, Seydel KB, Nyirenda T, Russell DG, and Mandala W
- Published
- 2023
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36. Typhoid fever, complicated by syncope due to relative bradycardia: A case report.
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Nguyen TV, Le QV, Nguyen HT, Tu Q, Hoang TT, Ta TB, Tran TV, Dinh Le T, Tran TC, Nguyen LG, Nghiem TD, Tien Nguyen S, Van Nguyen A, Dinh Hoang K, and Nguyen KX
- Abstract
In a United Nations (UN) staff member headquarters in South Sudan, we present a rare typhoid fever complicated by syncope due to relative bradycardia. A 25-year-old male presented to our hospital with a high fever, diarrhea, and no vomiting. He had no substantial medical background. He was diagnosed with an unspecified digestive disorder and received initial treatment. Two syncope episodes were recorded in the Level 1 hospital. He was referred to our hospital at the 30th hour and the third fainting occurred. Electrocardiogram showed bradycardia with a heart rate of 40 beats/min. The atropine test was negative; the initial diagnosis was sinus sickness syndrome. Microbiology tests later suggested typhoid infection. Then, the diagnosis changed to relative bradycardia caused by Salmonella typhi ; and he was orally treated with the third-generation Quinolone antibiotic. He significantly improved and got discharged on the seventh day. In conclusion, typhoid remains a real and present threat to UN staff and civilians in South Sudan., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
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- 2023
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37. The ability of Interleukin-10 to negate haemozoin-related pro-inflammatory effects has the potential to restore impaired macrophage function associated with malaria infection.
- Author
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Tembo D, Harawa V, Tran TC, Afran L, Molyneux ME, Taylor TE, Seydel KB, Nyirenda T, Russell DG, and Mandala W
- Subjects
- Humans, Interleukin-10, Convalescence, Cytokines, Tumor Necrosis Factor-alpha, Interferon-gamma, Plasmodium falciparum, Macrophages metabolism, Inflammation, Malaria, Falciparum, Malaria, Cerebral
- Abstract
Background: Although pro-inflammatory cytokines are involved in the clearance of Plasmodium falciparum during the early stages of the infection, increased levels of these cytokines have been implicated in the pathogenesis of severe malaria. Amongst various parasite-derived inducers of inflammation, the malarial pigment haemozoin (Hz), which accumulates in monocytes, macrophages and other immune cells during infection, has been shown to significantly contribute to dysregulation of the normal inflammatory cascades., Methods: The direct effect of Hz-loading on cytokine production by monocytes and the indirect effect of Hz on cytokine production by myeloid cells was investigated during acute malaria and convalescence using archived plasma samples from studies investigating P. falciparum malaria pathogenesis in Malawian subjects. Further, the possible inhibitory effect of IL-10 on Hz-loaded cells was examined, and the proportion of cytokine-producing T-cells and monocytes during acute malaria and in convalescence was characterized., Results: Hz contributed towards an increase in the production of inflammatory cytokines, such as Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF) and Interleukin 2 (IL-2) by various cells. In contrast, the cytokine IL-10 was observed to have a dose-dependent suppressive effect on the production of TNF among other cytokines. Cerebral malaria (CM) was characterized by impaired monocyte functions, which normalized in convalescence. CM was also characterized by reduced levels of IFN-γ-producing T cell subsets, and reduced expression of immune recognition receptors HLA-DR and CD 86, which also normalized in convalescence. However, CM and other clinical malaria groups were characterized by significantly higher plasma levels of pro-inflammatory cytokines than healthy controls, implicating anti-inflammatory cytokines in balancing the immune response., Conclusions: Acute CM was characterized by elevated plasma levels of pro-inflammatory cytokines and chemokines but lower proportions of cytokine-producing T-cells and monocytes that normalize during convalescence. IL-10 is also shown to have the potential to indirectly prevent excessive inflammation. Cytokine production dysregulated by the accumulation of Hz appears to impair the balance of the immune response to malaria and exacerbates pathology., (© 2023. The Author(s).)
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- 2023
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38. Synergistic effect of miscible cellulose-based microparticles and pH modulators on the bioavailability of a weakly basic drug and its metabolites.
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Tung NT, Tran CS, Nguyen TH, Tran TC, Nguyen KT, Pham TA, Trinh TV, and Ngo TN
- Subjects
- Animals, Rabbits, Biological Availability, Solubility, Hydrogen-Ion Concentration, Calorimetry, Differential Scanning, Spectroscopy, Fourier Transform Infrared, Cellulose, Itraconazole pharmacology
- Abstract
This study aimed to evaluate the miscibility of cellulose derivatives to improve the release rate and stability of microparticles containing the weakly basic drug itraconazole (ITZ). We also investigated the effect of some organic acids on the microenvironmental pH (pH
m ) and the release rate of ITZ from the cellulose-based microparticles. The synergistic effect of cellulose-based microparticles and pHm modulators on the bioavailability of ITZ compared with the reference product was investigated in a rabbit model. Differential scanning calorimetry and Fourier-transform infrared spectroscopy (FTIR) analysis showed that ITZ, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose phthalate were miscible at a ratio of 1.5:3:1 (w/w/w), and the stability of the microparticles was maintained for 6 months under accelerated conditions. In addition, X-ray diffraction, FTIR, and scanning electron microscopy were used to characterize the properties of the microparticles. Through the titration technique and determination of pHm , the combination of fumaric acid and maleic acid (1:2, w/w) was found to be the most effective pHm modulator for microparticles. The integration of cellulose-based microparticles and pHm modulators showed a synergistic effect on the flux and relative bioavailability of ITZ and its active metabolite OH-ITZ (182.60 % and 217.67 %, respectively) when compared with the reference product., Competing Interests: Declaration of competing interest The authors do not have any personal conflict of interest that may arise from submission of our research., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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39. Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.
- Author
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Suzuki K, Hatzikotoulas K, Southam L, Taylor HJ, Yin X, Lorenz KM, Mandla R, Huerta-Chagoya A, Rayner NW, Bocher O, Arruda ALSV, Sonehara K, Namba S, Lee SSK, Preuss MH, Petty LE, Schroeder P, Vanderwerff B, Kals M, Bragg F, Lin K, Guo X, Zhang W, Yao J, Kim YJ, Graff M, Takeuchi F, Nano J, Lamri A, Nakatochi M, Moon S, Scott RA, Cook JP, Lee JJ, Pan I, Taliun D, Parra EJ, Chai JF, Bielak LF, Tabara Y, Hai Y, Thorleifsson G, Grarup N, Sofer T, Wuttke M, Sarnowski C, Gieger C, Nousome D, Trompet S, Kwak SH, Long J, Sun M, Tong L, Chen WM, Nongmaithem SS, Noordam R, Lim VJY, Tam CHT, Joo YY, Chen CH, Raffield LM, Prins BP, Nicolas A, Yanek LR, Chen G, Brody JA, Kabagambe E, An P, Xiang AH, Choi HS, Cade BE, Tan J, Broadaway KA, Williamson A, Kamali Z, Cui J, Adair LS, Adeyemo A, Aguilar-Salinas CA, Ahluwalia TS, Anand SS, Bertoni A, Bork-Jensen J, Brandslund I, Buchanan TA, Burant CF, Butterworth AS, Canouil M, Chan JCN, Chang LC, Chee ML, Chen J, Chen SH, Chen YT, Chen Z, Chuang LM, Cushman M, Danesh J, Das SK, de Silva HJ, Dedoussis G, Dimitrov L, Doumatey AP, Du S, Duan Q, Eckardt KU, Emery LS, Evans DS, Evans MK, Fischer K, Floyd JS, Ford I, Franco OH, Frayling TM, Freedman BI, Genter P, Gerstein HC, Giedraitis V, González-Villalpando C, González-Villalpando ME, Gordon-Larsen P, Gross M, Guare LA, Hackinger S, Han S, Hattersley AT, Herder C, Horikoshi M, Howard AG, Hsueh W, Huang M, Huang W, Hung YJ, Hwang MY, Hwu CM, Ichihara S, Ikram MA, Ingelsson M, Islam MT, Isono M, Jang HM, Jasmine F, Jiang G, Jonas JB, Jørgensen T, Kandeel FR, Kasturiratne A, Katsuya T, Kaur V, Kawaguchi T, Keaton JM, Kho AN, Khor CC, Kibriya MG, Kim DH, Kronenberg F, Kuusisto J, Läll K, Lange LA, Lee KM, Lee MS, Lee NR, Leong A, Li L, Li Y, Li-Gao R, Lithgart S, Lindgren CM, Linneberg A, Liu CT, Liu J, Locke AE, Louie T, Luan J, Luk AO, Luo X, Lv J, Lynch JA, Lyssenko V, Maeda S, Mamakou V, Mansuri SR, Matsuda K, Meitinger T, Metspalu A, Mo H, Morris AD, Nadler JL, Nalls MA, Nayak U, Ntalla I, Okada Y, Orozco L, Patel SR, Patil S, Pei P, Pereira MA, Peters A, Pirie FJ, Polikowsky HG, Porneala B, Prasad G, Rasmussen-Torvik LJ, Reiner AP, Roden M, Rohde R, Roll K, Sabanayagam C, Sandow K, Sankareswaran A, Sattar N, Schönherr S, Shahriar M, Shen B, Shi J, Shin DM, Shojima N, Smith JA, So WY, Stančáková A, Steinthorsdottir V, Stilp AM, Strauch K, Taylor KD, Thorand B, Thorsteinsdottir U, Tomlinson B, Tran TC, Tsai FJ, Tuomilehto J, Tusie-Luna T, Udler MS, Valladares-Salgado A, van Dam RM, van Klinken JB, Varma R, Wacher-Rodarte N, Wheeler E, Wickremasinghe AR, van Dijk KW, Witte DR, Yajnik CS, Yamamoto K, Yamamoto K, Yoon K, Yu C, Yuan JM, Yusuf S, Zawistowski M, Zhang L, Zheng W, Raffel LJ, Igase M, Ipp E, Redline S, Cho YS, Lind L, Province MA, Fornage M, Hanis CL, Ingelsson E, Zonderman AB, Psaty BM, Wang YX, Rotimi CN, Becker DM, Matsuda F, Liu Y, Yokota M, Kardia SLR, Peyser PA, Pankow JS, Engert JC, Bonnefond A, Froguel P, Wilson JG, Sheu WHH, Wu JY, Hayes MG, Ma RCW, Wong TY, Mook-Kanamori DO, Tuomi T, Chandak GR, Collins FS, Bharadwaj D, Paré G, Sale MM, Ahsan H, Motala AA, Shu XO, Park KS, Jukema JW, Cruz M, Chen YI, Rich SS, McKean-Cowdin R, Grallert H, Cheng CY, Ghanbari M, Tai ES, Dupuis J, Kato N, Laakso M, Köttgen A, Koh WP, Bowden DW, Palmer CNA, Kooner JS, Kooperberg C, Liu S, North KE, Saleheen D, Hansen T, Pedersen O, Wareham NJ, Lee J, Kim BJ, Millwood IY, Walters RG, Stefansson K, Goodarzi MO, Mohlke KL, Langenberg C, Haiman CA, Loos RJF, Florez JC, Rader DJ, Ritchie MD, Zöllner S, Mägi R, Denny JC, Yamauchi T, Kadowaki T, Chambers JC, Ng MCY, Sim X, Below JE, Tsao PS, Chang KM, McCarthy MI, Meigs JB, Mahajan A, Spracklen CN, Mercader JM, Boehnke M, Rotter JI, Vujkovic M, Voight BF, Morris AP, and Zeggini E
- Abstract
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance ( P <5×10
-8 ) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care., Competing Interests: R.A.S. is now an employee of GlaxoSmithKline. G.T. is an employee of deCODE genetics/Amgen Inc. A.S.B. reports institutional grants from AstraZeneca, Bayer, Biogen, BioMarin, Bioverativ, Novartis, Regeneron and Sanofi. J.Danesh serves on scientific advisory boards for AstraZeneca, Novartis, and UK Biobank, and has received multiple grants from academic, charitable and industry sources outside of the submitted work. L.S.E. is now an employee of Bristol Myers Squibb. J.S.F. has consulted for Shionogi Inc. T.M.F. has consulted for Sanofi, Boehringer Ingelheim, and received funding from GlaxoSmithKline. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care; reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Roche, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Pfizer, Sanofi, Kowa and Hanmi.lth Institute Chair in Diabetes Research and Care; reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; and consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Janssen, Sanofi, and Kowa. M.Ingelsson is a paid consultant to BioArctic AB. R.L.-G. is a part-time consultant of Metabolon Inc. A.E.L. is now an employee of Regeneron Genetics Center LLC and holds shares in Regeneron Pharmaceuticals. M.A.N. currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc. S.R.P. has received grant funding from Bayer Pharmaceuticals, Philips Respironics and Respicardia. N.Sattar has consulted for or been on speakers bureau for Abbott, Amgen, Astrazeneca, Boehringer Ingelheim, Eli Lilly, Hanmi, Novartis, Novo Nordisk, Sanofi and Pfizer and has received grant funding from Astrazeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics. V.S. is now an employee of deCODE genetics/Amgen Inc. A.M.S. receives funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. U.T. is an employee of deCODE genetics/Amgen Inc. E.Ingelsson is now an employee of GlaxoSmithKline. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. R.C.W.M. reports research funding from AstraZeneca, Bayer, Novo Nordisk, Pfizer, Tricida Inc. and Sanofi, and has consulted for or received speakers fees from AstraZeneca, Bayer, Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. D.O.M.-K. is a part-time clinical research consultant for Metabolon Inc. S.Liu reports consulting payments and honoraria or promises of the same for scientific presentations or reviews at numerous venues, including but not limited to Barilla, by-Health Inc, Ausa Pharmed Co.LTD, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital and Academy of Medical Sciences, Consulting member for Novo Nordisk, Inc; member of the Data Safety and Monitoring Board for a trial of pulmonary hypertension in diabetes patients at Massachusetts General Hospital; receives royalties from UpToDate; receives an honorarium from the American Society for Nutrition for his duties as Associate Editor. K.Stefansson is an employee of deCODE genetics/Amgen Inc. M.I.M. has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda; and is now an employee of Genentech and a holder of Roche stock. J.B.M. is an Academic Associate for Quest Diagnostics R&D. A.Mahajan is an employee of Genentech, and a holder of Roche stock.- Published
- 2023
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40. Pollen-stigma incompatibility within and between species: Tread lightly, sedate the dogs, and don't wake the guards!
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Tran TC and Lenhard M
- Subjects
- Reproduction, Hybridization, Genetic, Flowers genetics, Magnoliopsida genetics, Magnoliopsida physiology, Pollen genetics, Pollination genetics, Pollination physiology, Germination physiology, Crosses, Genetic
- Abstract
In a recent issue of Nature, Huang et al. identify and show how to overcome the barriers to successful pollen germination after interspecific crosses.
1 Their findings answer a long-standing question about reproductive barriers in flowering plants and open the door to harnessing genetic diversity of distant relatives for crop improvement., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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41. Designing and developing a mobile app (BeBo) in a randomized controlled trial study to promote breastfeeding among Vietnamese mothers.
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Doan TTD, Tran TC, Pham NM, Zhao Y, Dinh TPH, Hoai NX, Lee A, Binns C, and Bui TTH
- Subjects
- Female, Humans, Infant, Pregnancy, Mothers psychology, Vietnam, Breast Feeding psychology, Mobile Applications
- Abstract
Background: Breastfeeding should begin as soon as possible after birth and continue exclusively to 6 months of age. In Vietnam, as in many other countries, breastfeeding is decreasing because of modern lifestyles and the promotion of infant formula. It is important to provide mothers, family members, and the community with the knowledge and strategies to improve breastfeeding rates. Smartphones are almost ubiquitous in Vietnam and of the potential to provide information about breastfeeding. This study aimed to document the process of designing and developing a mobile app to increase breastfeeding rates in Vietnamese women., Methods: We used a four-step mixed methods approach with a literature review, formative research (22 in-depth interviews and 49 self-administered online questionnaires), and testing of prototype apps (3 focus groups discussion and external experts). Formative research and focus group discussion involved 99 participants. Finally, the revisions of the app were tested. All of the formative research was undertaken in Hanoi in 2019-2020. Target behaviors followed by key determinants, to improve breastfeeding self-efficacy were studied and this information was then applied in developing the messages and library content. Barriers and facilitators to breastfeeding were identified from literature reviews and qualitative research. The messages were targeted at not only mothers but also included fathers, mothers-in-law, or families., Results: Mothers were mostly concerned about the initiation of breastfeeding, preventing and reducing difficulties encountered during breastfeeding, and nutrition for breastfeeding mothers. Mental health and well-being in the postnatal period are also concerns. Three key features to be included in the app were identified from the formative research: (1) notifications; (2) an information library; and (3) a searching function. The research found that the app should be installed during pregnancy rather than after delivery (81% vs 17%, respectively). Notifications that convey breastfeeding messages should be sent 2-3 times per week., Conclusion: The development of the app followed a best practice approach, including the involvement of stakeholders and grounding in behavior change theory. The next step is to evaluate the effectiveness of the BeBo mobile app in a well-conducted randomized controlled trial., Trial Registration: ACTRN12619000531112., (© 2023. The Author(s).)
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- 2023
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42. The Anti-Viral Activity of Stem Cells: A Rational Explanation for their Use in Clinical Application.
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Balzanelli MG, Distratis P, Lazzaro R, Pham VH, Tran TC, Dipalma G, Inchingolo F, Serlenga EM, Aityan SK, Ballini A, Nguyen KCD, and Isacco CG
- Subjects
- Adult, Humans, Antiviral Agents, Stem Cells, Interferons
- Abstract
It is well established the importance of stem cells (SCs) in tissue growth, regeneration and repair, given their ability to self-renew and differentiate into mature cells. Stem cells are present in all individuals and are potentially active to the end of life. However, less is known about their unique function within the immune system as immune regulators and their important task in viral protection. Antiviral resistance is a common mechanism in all cells though stem cells utilize an antiviral RNA interference (RNAi) mechanism, while adult cells react by using the interferondependent repression pathway via interferon-associated protein-based response to induce an antiviral response. Therefore, the idea behind this review is to highlight the mechanisms of viral evasion of host defense, which would then allow us to highlight the rationale use of autologous stem cells and their biochemical and immunological ability to reset the subverted immune responses. Recently, scientists have highlighted their use in the field of immune-therapy, establishing the possibilities of using them outside the conventional protocol with the advancement in manipulating these cells in such a way that specific body activity can be restored. This paper describes the remarkable SCs profile and discusses some ideas regarding their promising use in vivo., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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43. Genetic analysis of Vietnamese patients with early-onset Alzheimer's disease.
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Tong TM, Dao TTH, Doan LP, Nguyen DT, Nguyen QT, Do TT, Truong KD, Phan MD, Nguyen HN, Tran TC, and Giang H
- Subjects
- Humans, Aged, Presenilin-1 genetics, Amyloid beta-Protein Precursor genetics, Genetic Testing, Mutation genetics, Asian People genetics, Age of Onset, Alzheimer Disease epidemiology, Alzheimer Disease genetics
- Abstract
Purpose of the study: Alzheimer's disease (AD) is the most common type of dementia and its prevalence is rapidly increasing worldwide. Early-onset Alzheimer's disease (EOAD) constitutes of patients with age of onset earlier than 65 year-old and is known to be associated with genetic mutations. In this study, we reported the first genetic analysis of Vietnamese patients with EOAD. Materials and methods: We analyzed targeted sequencing data obtained from a cohort of 51 Vietnamese EOAD patients to identify pathogenic variants in twenty nine well-characterized neurodengerative genes. Results: We identified four missense mutations in APP/PSEN1 genes from six individuals, which accounts for 11.8% of all tested cases. Three of these mutations were previously reported as pathogenic and one mutation in the APP gene was newly identified and might be specific for Vietnamese patients. Our study also found eight individuals carrying homozygous APOE ε4 allele, the main risk factor gene for late-onset AD. Conclusions: Our findings showed that mutation rate in APP/PSEN genes in Vietnamese EOAD patients is consistent with that in other ethnic groups. Although further functional studies are required to validate the pathogenesis of the new mutations, our study demonstrated the necessity of genetic screening for EOAD patients as well as additional genetic data collection in Vietnamese population.
- Published
- 2022
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44. Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection.
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Balzanelli MG, Distratis P, Lazzaro R, Pham VH, Tran TC, Dipalma G, Bianco A, Serlenga EM, Aityan SK, Pierangeli V, Nguyen KCD, Inchingolo F, Tomassone D, and Isacco CG
- Abstract
Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual's responses to the virus and the high differences of effect that the virus may cause to some. While a person's preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts' genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO
2 and carbon dioxide-SpCO2 ) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.- Published
- 2022
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45. The Sub-Molecular and Atomic Theory of Cancer Beginning: The Role of Mitochondria.
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Balzanelli MG, Distratis P, Lazzaro R, Pham VH, Tran TC, Dipalma G, Inchingolo F, Tomassone D, Aityan SK, Vergara S, Nguyen KCD, and Isacco CG
- Abstract
Life as we know it is made of strict interaction of atom, metabolism, and genetics, made around the chemistry of the most common elements of the universe: hydrogen, oxygen, nitrogen, sulfur, phosphorus, and carbon. The interaction of atomic, metabolic, and genetic cycles results in the organization and de-organization of chemical information of what we consider living entities, including cancer cells. In order to approach the problem of the origin of cancer, it is therefore reasonable to start from the assumption that the atomic structure, metabolism, and genetics of cancer cells share a common frame with prokaryotic mitochondria, embedded in conditions favorable for the onset of both. Despite years of research, cancer in its general acceptation remains enigmatic. Despite the increasing efforts to investigate the complexity of tumorigenesis, complementing the research on genetic and biochemical changes, researchers face insurmountable limitations due to the huge presence of variabilities in cancer and metastatic behavior. The atomic level of all biological activities it seems confirmed the electron behavior, especially within the mitochondria. The electron spin may be considered a key factor in basic biological processes defining the structure, reactivity, spectroscopic, and magnetic properties of a molecule. The use of magnetic fields (MF) has allowed a better understanding of the grade of influence on different biological systems, clarifying the multiple effects on electron behavior and consequently on cellular changes. Scientific advances focused on the mechanics of the cytoskeleton and the cellular microenvironment through mechanical properties of the cell nucleus and its connection to the cytoskeleton play a major role in cancer metastasis and progression. Here, we present a hypothesis regarding the changes that take place at the atomic and metabolic levels within the human mitochondria and the modifications that probably drive it in becoming cancer cell. We propose how atomic and metabolic changes in structure and composition could be considered the unintelligible reason of many cancers' invulnerability, as it can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between this sub-molecular organized dynamic structure, nuclear mechanics, and metastatic progression may have powerful implications in cancer diagnostics and therapy disclosing innovation in targets of cancer cell invasion.
- Published
- 2022
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46. Transforming medical education to strengthen the health professional training in Viet Nam: A case study.
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Tran TD, Vu PM, Pham HTM, Au LN, Do HP, Doan HTT, Huynh N, Huynh QTV, Le BK, Ngo DQ, Nguyen HTM, Nguyen KD, Nguyen NA, Nguyen PH, Nguyen TA, Tran TC, Chau HN, Vuong LN, and Vu NV
- Abstract
The competency-based undergraduate curriculum reform at the University of Medicine and Pharmacy at Ho Chi Minh City, Faculty of Medicine (UMP-FM) is detailed and reviewed in reference to the instructional and institutional reforms, and enabling actions recommended by the Lancet 2010 Commission for Health Professional Education. Key objectives are to: revise the overall 6-year curriculum to be more integrated and competency-based; reinforce students' knowledge application, problem-solving, clinical competence, self-directed learning and soft skills; develop a comprehensive and performance-based student assessment programme; and establish a comprehensive quality monitoring programme to facilitate changes and improvements. New features include early introduction to the practice of medicine, family- and community-based medicine, professionalism, interprofessional education, electives experiences, and a scholarly project. Institutional reform introduces a faculty development programme, joint planning mechanism, a "culture of critical inquiry", and a transparent faculty reward system. Lessons learnt from the curriculum reform at UMP-FM could be helpful to medical schools from low- and middle-income countries considering transitioning from a traditional to a competency-based curriculum., Funding: This work receives no external funding., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)
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- 2022
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47. Vietnamese Version of Cornell Scale for Depression in Dementia at an Outpatient Memory Clinic: A Reliability and Validity Study.
- Author
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Huynh TT, Nguyen NTT, Nguyen TDP, and Tran TC
- Abstract
Background: In Vietnam, there has been, currently, no standardized tool for depression assessment for people with dementia (PWD). Cornell Scale for Depression in Dementia (CSDD) is a widely studied and used scale for PWD worldwide., Objectives: The aim of this study was to standardize the Vietnamese version of the CSDD (V-CSDD) in depression assessment in PWD through reliability and validity examination., Methods: V-CSDD was rated in terms of reliability and validity with gold standard regarding "major depressive episode" and "major depressive-like episode" of DSM-5. Cronbach's α, ICC, exploratory factor analysis (EFA), and receiver operating characteristic analysis were performed., Results: V-CSDD was found to have a high internal consistency reliability (Cronbach's α = 0.80), inter-rater reliability at sound ranking (ICC = 0.89; 95% CI = 0.81-0.94), maximum cut-off mark of 13 (sensitivity = 70%, specificity = 92%), and EFA, which suggested that V-CSDD may comprise 5 factors., Conclusions: Results indicate the V-CSDD to be a reliable and valid assessment and to be beneficial in classifying and diagnosing depression in dementia outpatients in clinical contexts., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)
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- 2022
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48. Mosquitoes (Diptera: Culicidae) from Villages and Forest Areas of Rural Communes in Khanh Hoa and Binh Phuoc Provinces, Vietnam.
- Author
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Vu NS, Hertz JC, Martin NJ, Tran TC, Fiorenzano JM, Tran PV, Nguyen HV, Dang AD, Tran DN, and Motoki MT
- Subjects
- Animals, Culicidae classification, Culicidae growth & development, Larva classification, Larva growth & development, Larva physiology, Vietnam, Animal Distribution, Culicidae physiology
- Abstract
This study presents the diversity of mosquitoes collected from communes, endemic with malaria and dengue, located in Khanh Hoa and Binh Phuoc Provinces, Vietnam. A total of 10,288 mosquitoes were collected in the village and forested sites using standard larval dippers, cow-baited traps, ultra-violet light traps, and mechanical aspirators. Mosquito taxa were identified morphologically and species complexes/groups were further characterized molecularly. Five genera of mosquitoes were morphologically identified: Anopheles Meigen (21 species), Aedes Meigen (2 species), Culex Linnaeus (5 species), Mansonia Blanchard sp., and Armigeres Theobald sp. The PCR-based identification methods allowed the distinction of members of Maculatus Group, Funestus Group, and Dirus Complex; and DNA barcodes enabled the further identification of the Barbirostris Complex. Data reported here include the first report of An. saeungae Taai & Harbach and An. wejchoochotei Taai & Harbach from Vietnam, and re-emphasizes the significance of using molecular data in an integrated systematic approach to identify cryptic species and better understand their role in disease transmission., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America.)
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- 2021
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49. Metal salt-modified biochars derived from agro-waste for effective congo red dye removal.
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Nguyen DLT, Binh QA, Nguyen XC, Huyen Nguyen TT, Vo QN, Nguyen TD, Phuong Tran TC, Hang Nguyen TA, Kim SY, Nguyen TP, Bae J, Kim IT, and Van Le Q
- Subjects
- Adsorption, Charcoal, Metals, Congo Red, Water Pollutants, Chemical
- Abstract
Anionic Congo red dye (CR) is not effectively removed by conventional adsorbents. Three novel biochars derived from agro-waste (Acacia auriculiformis), modified with metal salts of FeCl
3 , AlCl3 , and CaCl2 at 500 °C pyrolysis have been developed to enhance CR treatment. These biochars revealed significant differences in effluents compared to BC, which satisfied initial research expectations (P < 0.05). The salt concentration of 2 M realized optimal biochars with the highest CR removal of 96.8%, for AlCl3 -biochar and FeCl3 -biochar and 70.8% for CaCl2 -biochar. The modified biochars were low in the specific surface area (137.25-380.78 m2 g-1 ) compared normal biochar (393.15 m2 g-1 ), had more heterogeneous particles and successfully integrated metal oxides on the surface. The CR removal increased with a decrease in pH and increase in biochar dosage, which established an optimal point at an initial loading of 25 mg g-1 . Maximum adsorption capacity achieved 130.0, 44.86, and 30.80 mg g-1 for BFe, BCa, and BAl, respectively. As magnetic biochar, which is easily separated from the solution and achieves a high adsorption capacity, FeCl3 -biochar is the preferred biochar for CR treatment application., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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50. Maternal and neonatal outcomes related to Zika virus in pregnant women in Southern Vietnam: An epidemiological and virological prospective analysis.
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Grant R, Nguyen TTT, Dao MH, Pham HTT, Piorkowski G, Pham TDT, Cao TM, Huynh LTK, Nguyen QH, Vien LDK, Lemoine F, Zhukova A, Hoang DTN, Nguyen HT, Nguyen NT, Le LB, Ngo MNQ, Tran TC, Le NNT, Nguyen MN, Pham HT, Hoang TTD, Dang TV, Vu AT, Nguyen QNT, de Lamballerie X, Pham QD, Luong QC, and Fontanet A
- Abstract
Background: In 2016-2017, 68 women in Southern Vietnam had RT-PCR confirmed Zika virus (ZIKV) infection during pregnancy. We report here the outcomes of the pregnancies and the virological analyses related to this outbreak., Methods: We collected clinical and epidemiological information from the women who were enrolled in the study. Medical records related to the pregnancy in 2016-2017 were retrieved for those who were not able to be enrolled in the study. Children born to women with ZIKV infection during pregnancy were also enrolled. Serum samples were evaluated for presence of ZIKV antibodies. Phylogenetic analyses were performed on Zika virus genomes sequenced from the 2016-2017 serum samples., Findings: Of the 68 pregnancies, 58 were livebirths and 10 were medically terminated. Four of the medical records from cases of fetal demise were able to be retrieved, of which one was consistent with congenital ZIKV infection. Of the 58 women with a livebirth, 21 participated in the follow-up investigation. All but two women had serologic evidence of ZIKV infection. Of the 21 children included in the study (mean age: 30.3 months), 3 had microcephaly at birth. No other clinical abnormalities were reported and no differences in neurodevelopment were observed compared to a control group. Phylogenetic analysis revealed a clade within the ZIKV Asian lineage and branch at the root of samples from the 2013-2014 French Polynesian outbreak. The prM S139N mutation was not observed., Interpretation: We have been able to demonstrate a clade within the ZIKV Asian lineage implicated in adverse pregnancy outcomes in Southern Vietnam., Funding: INCEPTION project (PIA/ANR-16-CONV-0005) and a grant received from BNP Paribas Simplidon., Competing Interests: All authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)
- Published
- 2021
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