Displaying publications 1 - 20 of 31 in total

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  1. Park SC, Lee MS, Hahn SW, Si TM, Kanba S, Chong MY, et al.
    Acta Neuropsychiatr, 2016 Dec;28(6):337-345.
    PMID: 27305958
    Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) study, we aimed to present the rates and clinical correlates of suicidal thoughts/acts in patients recruited from a total of 40 centres in 10 Asian countries/areas: China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand.
  2. Lee MS, Wahlqvist ML
    Asia Pac J Clin Nutr, 2005;14(4):294-7.
    PMID: 16326634
    The systematic observation of food habits and health amongst the elderly, both cross-sectionally and longitudinally, in the Asia Pacific region is increasing as reflected in the recent collective report of a number of intake and health variables in Taiwanese communities. Most studies are of Chinese and Japanese-speaking populations, with some from elsewhere in Northeast Asia (notably Korea) and Southeast Asia (notably the Philippines, Indonesia, Malaysia and Singapore). These, and other international studies, demonstrate that older people can eat in various ways and yet achieve longevity and minimum morbidity, provided they remain physically and mentally active and eat a variety of relatively intact foods, including fish and pulses (lentils, legumes, beans). Such studies are the foundation of a new generation of food and health policy for the aged, with reference to EBN (evidence-based nutrition) and reflected in FBDGs (food-based dietary guidelines) which acknowledge cultural difference and support sustainable food systems.
  3. Chee KY, Tripathi A, Avasthi A, Chong MY, Sim K, Yang SY, et al.
    Asia Pac Psychiatry, 2015 Dec;7(4):366-74.
    PMID: 25706498 DOI: 10.1111/appy.12176
    Research in prescription pattern of antidepressants in Asia is lacking. This study aims to compare the antidepressants prescription pattern in Asia in 2003-2004 and 2013.
  4. Chee KY, Tripathi A, Avasthi A, Chong MY, Xiang YT, Sim K, et al.
    Asia Pac Psychiatry, 2015 Sep;7(3):276-85.
    PMID: 25641910 DOI: 10.1111/appy.12170
    This study was to assess differences in the symptom profile of depressive illness across various countries/territories in Asia. The study was a part of the Research on Asia Psychotropic Prescription project. The participating countries/territories include China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand.
  5. Treuer T, Liu CY, Salazar G, Kongsakon R, Jia F, Habil H, et al.
    Asia Pac Psychiatry, 2013 Dec;5(4):219-30.
    PMID: 23857712 DOI: 10.1111/appy.12090
    Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence-based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence-based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.
  6. Tang CT, Chua EC, Chew QH, He YL, Si TM, Chiu HF, et al.
    Asia Pac Psychiatry, 2020 Dec;12(4):e12393.
    PMID: 32468725 DOI: 10.1111/appy.12393
    INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.

    METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region.

    RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications.

    DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

  7. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  8. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
  9. Lee MS, 'Azmiyaty Amar Ma' Ruf C, Nadhirah Izhar DP, Nafisah Ishak S, Wan Jamaluddin WS, Ya'acob SNM, et al.
    Biomedicine (Taipei), 2019 Sep;9(3):18.
    PMID: 31453799 DOI: 10.1051/bmdcn/2019090318
    INTRODUCTION: The increasing rate of breast cancer (BC) incidence in Malaysia hints a lack of awareness among Malaysians. One (1) woman out of nineteen (19) is at risk with BC and almost up to fifty percent (50%) of women diagnosed with BC were reported to be under the age of fifty (50). Our main concern is to study the level of awareness among the women on risk factors, clinical manifestations, diagnosis, preventions and treatments.

    METHOD: A cross-sectional study was conducted exclusively among women in the public with total sample of three hundred and forty six (346), questionnaires were distributed using a simple random technique. Data was collected and analyzed by student T test in SPPS version 20.

    RESULTS: Our study reveals insufficient awareness on BC. Overall, awareness on risk factors is inadequate, but good knowledge on the importance of family history and diet as risk factors are discovered. Awareness on the cause and clinical manifestations of BC is required for improvement. As for treatment, alternatives especially surgery and chemotherapy are unclear to public, public is remotely unwitting on cessation of smoking to prevent BC at the early stage.

    CONCLUSION: Malaysian has spaces for improvement on awareness of BC in terms of risk factors, clinical manifestations, diagnosis, treatment and prevention. Early detection can be achieved with good awareness because it leads to better prognosis and lower mortality.

  10. Grover S, Avasthi A, Tripathi A, Tanra AJ, Chee KY, He YL, et al.
    East Asian Arch Psychiatry, 2015 Sep;25(3):99-107.
    PMID: 26429836
    Objective: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia.
    Methods: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort.
    Results: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries.
    Conclusion: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant
    prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.
    Key words: Antidepressive agents; Asia; Comorbidity
  11. Chee KY, Tripathi A, Avasthi A, Chong MY, Xiang YT, Sim K, et al.
    East Asian Arch Psychiatry, 2016 Mar;26(1):10-7.
    PMID: 27086755
    Objective: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia.
    Methods: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked
    collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed.
    Results: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults.
    Conclusion: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.
    Key words: Adolescent; Antidepressive agents; Child; Ethnopsychology
  12. Lee MS, Chang LY
    Expert Rev Vaccines, 2010 Feb;9(2):149-56.
    PMID: 20109026 DOI: 10.1586/erv.09.152
    Enterovirus 71 (EV71) was first isolated in 1969 in California, USA. Several epidemic outbreaks with high mortality rates have occurred in European and Asian Countries (Bulgaria in 1975, Hungary in 1978, Malaysia in 1997, Taiwan in 1998 and China in 2008). EV71 CNS involvement may be associated with neurological sequelae, delayed neurodevelopment and reduced cognitive functioning. Since poliovirus was nearly eradicated by vaccination, EV71 is now considered as one of the top candidates for new vaccine development against human enteroviruses. Recently, several EV71 vaccine candidates, including live-attenuated virus, inactivated whole virus, recombinant viral protein, virus-like particle and DNA vaccines, have been evaluated in animals but no clinical trial has yet been conducted. Based on historical experiences with poliovirus vaccines and animal studies, the inactivated whole-virus vaccines are feasible and could be licensed readily, so these are targeted for preparing clinical trials in several organizations in Asia.
  13. Mózes FE, Lee JA, Selvaraj EA, Jayaswal ANA, Trauner M, Boursier J, et al.
    Gut, 2021 May 17.
    PMID: 34001645 DOI: 10.1136/gutjnl-2021-324243
    OBJECTIVE: Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies.

    DESIGN: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.

    RESULTS: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy.

    CONCLUSION: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.

  14. Pennisi G, Enea M, Falco V, Aithal GP, Palaniyappan N, Yilmaz Y, et al.
    Hepatology, 2023 Jul 01;78(1):195-211.
    PMID: 36924031 DOI: 10.1097/HEP.0000000000000351
    BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D).

    METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH.

    CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

  15. Lim WK, Chew QH, He YL, Si TM, Chiu FH, Xiang YT, et al.
    Hum Psychopharmacol, 2020 11;35(6):1-7.
    PMID: 32738085 DOI: 10.1002/hup.2752
    OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

    METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.

    RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

    CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

  16. Zhong XM, Wang F, Zhang Q, Ungvari GS, Ng CH, Chiu HFK, et al.
    Int Psychogeriatr, 2019 05;31(5):685-691.
    PMID: 29212560 DOI: 10.1017/S1041610217002563
    ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.

    METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.

    RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.

    CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

  17. Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.
    J Clin Psychopharmacol, 2016 Dec;36(6):716-719.
    PMID: 27753726
    In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.
  18. Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, et al.
    J Clin Psychopharmacol, 2017 Apr;37(2):255-259.
    PMID: 28146001 DOI: 10.1097/JCP.0000000000000670
    OBJECTIVE: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries.
    METHODS: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling.
    RESULTS: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose.

    CONCLUSIONS: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.
  19. Kim KM, Lee MS, Suh MS, Selvam HSMS, Tan TH, Cheon GJ, et al.
    Med Phys, 2022 Jan 11.
    PMID: 35014699 DOI: 10.1002/mp.15444
    PURPOSE: Voxel-based dosimetry is potentially accurate than organ-based dosimetry because it considers the anatomical variations in each individual and the heterogeneous radioactivity distribution in each organ. Here, voxel-based dosimetry for 177 Lu-DOTATATE therapy was performed using single and multiple voxel S-value (VSV) methods and compared with Monte Carlo simulations. To verify these methods, we adopted sequential 177 Lu-DOTATATE single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) dataset acquired from Sunway Medical Centre using the major vendor's SPECT/CT scanner (Siemens Symbia Intevo).

    METHODS: The administered activity of 177 Lu-DOTATATE was 7.99 ± 0.36 GBq. SPECT/CT images were acquired 0.5, 4, 24, and 48 h after injection in Sunway Medical Centre. For the multiple VSV method, VSV kernels of 177 Lu in media with various densities were generated by Geant4 Application for Emission Tomography (GATE) simulation first. The second step involved the convolution of the time-integrated activity map with each kernel to produce medium-specific dose maps. Third, each medium-specific dose map was masked using binary medium masks, which were generated from CT-based density maps. Finally, all masked dose maps were summed to generate the final dose map. VSV methods with four different VSV sets (1, 4, 10, and 20 VSVs) were compared. Voxel-wise density correction for the single VSV method was also performed. The absorbed doses in the kidneys, bone marrow, and tumors were analyzed, and the relative errors between the VSV and Monte Carlo simulation approaches were estimated. Organ-based dosimetry using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was also compared.

    RESULTS: The accuracy of the multiple VSV approach increased with the number of dose kernels. The average dose estimation errors of a single VSV with density correction and 20 VSVs were less than 6% in most cases, although organ-based dosimetry using OLINDA/EXM yielded an error of up to 123%. The advantages of the single VSV method with density correction and the 20 VSVs over organ-based dosimetry were most evident in bone marrow and bone-metastatic tumors with heterogeneous medium properties.

    CONCLUSION: The single VSV method with density correction and multiple VSV method with 20 dose kernels enabled fast and accurate radiation dose estimation. Accordingly, voxel-based dosimetry methods can be useful for managing administration activity and for investigating tumor dose responses to further increase the therapeutic efficacy of 177 Lu-DOTATATE.

  20. Chien YS, Chen FJ, Wu HC, Lin CH, Chang WC, Perera D, et al.
    Microbiol Spectr, 2023 Oct 13.
    PMID: 37831475 DOI: 10.1128/spectrum.02507-23
    Enteroviruses (EVs) are a group of viruses that cause various human illnesses. While the CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) method can generate VP1 gene fragments for enterovirus genotyping, it is unable to detect recombinant strains. Recent advances in viral genome sequencing using next-generation sequencing technologies have enabled comprehensive analyses. However, the high cost poses a challenge for widespread adoption. To address this issue, this study proposes a cost-effective approach for generating complete enterovirus genome sequences using the Oxford Nanopore MinION sequencer. This protocol not only facilitates the generation of accurate genome sequences for various enterovirus strains but also allows for the differentiation of co-infections from viral isolates. In addition, the method can generate polyprotein sequences as well as peptide sequences of the upstream ORF (uORF) whose expression can impact virus infection. Through the analysis of complete enterovirus genomes, this study successfully identified seven enterovirus A71 isolates obtained during the 2018 enterovirus outbreak in Malaysia and Taiwan as recombinants between enterovirus A71 and coxsackievirus A2. Furthermore, our study has made a significant discovery by establishing a strong correlation between uORF trees and the epidemics of EVA71. This finding highlights the potential of uORF sequences as valuable indicators for monitoring and understanding the spread of EVA71 infections. We also identified notable amino acid changes in the transmembrane domain of the uORF protein within a newly identified lineage. These findings provide crucial insights into the molecular characteristics and evolutionary dynamics of EVA71, offering valuable information for future research and intervention strategies. IMPORTANCE By employing a cost-effective approach for complete genome sequencing, the study has enabled the identification of novel enterovirus strains and shed light on the genetic exchange events during outbreaks. The success rate of genome sequencing and the scalability of the protocol demonstrate its practical utility for routine enterovirus surveillance. Moreover, the study's findings of recombinant strains of EVA71 and CVA2 contributing to epidemics in Malaysia and Taiwan emphasize the need for accurate detection and characterization of enteroviruses. The investigation of the whole genome and upstream ORF sequences has provided insights into the evolution and spread of enterovirus subgenogroups. These findings have important implications for the prevention, control, and surveillance of enteroviruses, ultimately contributing to the understanding and management of enterovirus-related illnesses.
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