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Fulltext Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats

Chung KF, Seiffert J, Chen S, Theodorou IG, Goode AE, Leo BF, et al.

ACS Nano, 2017 03 28;11(3):2652-2664.
PMID: 28221763 DOI: 10.1021/acsnano.6b07313

There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 μm) and long (L-AgNWs; 10 μm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.
Fulltext Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium

Gong J, Harris K, Lipnicki DM, Castro-Costa E, Lima-Costa MF, Diniz BS, et al.

Alzheimers Dement, 2023 Aug;19(8):3365-3378.
PMID: 36790027 DOI: 10.1002/alz.12962

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups.
METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models.
RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs.
DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.
Fulltext Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study

Röhr S, Pabst A, Riedel-Heller SG, Jessen F, Turana Y, Handajani YS, et al.

Alzheimers Res Ther, 2020 12 18;12(1):167.
PMID: 33339532 DOI: 10.1186/s13195-020-00734-y

BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.
METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.
RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.
CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO

Chen LT, Martinelli E, Cheng AL, Pentheroudakis G, Qin S, Bhattacharyya GS, et al.

Ann Oncol, 2020 03;31(3):334-351.
PMID: 32067677 DOI: 10.1016/j.annonc.2019.12.001

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
Ethnic differences in the Goodenough-Harris draw-a-man and draw-a-woman tests

Dugdale AE, Chen ST

Arch Dis Child, 1979 Nov;54(11):880-5.
PMID: 393181

The draw-a-man (DAM) and draw-a-woman (DAW) tests were given to 307 schoolchildren in Petaling Jaya, Malaysia. The children were ethnically Malay, Chinese, or Indian (Tamil), and all came from lower socioeconomic groups. The standard scores of the Chinese children averaged 118 in the DAM and 112 in the DAW tests. These scores were significantly better than the American standards. Malay children scored significantly lower than Chinese, and Tamil children scored lower again. The nutritional status of the children had no influence on the scores. Chinese and Tamil children scored better in the DAM than the DAW, while in Malay boys the reverse was true. Malay children tended to emphasise clothing in the DAM, but Chinese and Tamil children scored better on items relating to facial features and body proportions. The Goodenough-Harris draw-a-person tests are obviously not culture-free, but the causes of ethnic differences have not been elucidated.
Incidence of nasal trauma associated with nasal prong versus nasal mask during continuous positive airway pressure treatment in very low birthweight infants: a randomised control study

Yong SC, Chen SJ, Boo NY

Arch. Dis. Child. Fetal Neonatal Ed., 2005 Nov;90(6):F480-3.
PMID: 15941825

To compare the incidence of nasal trauma associated with the use of prong or mask during nasal continuous positive airway pressure (nCPAP) support in very low birthweight (<1501 g) infants.
Milk tolerance among malnourished school children in Malaysia

Chen ST, Domala Z

Asia Pac J Public Health, 1989;3(4):274-7.
PMID: 2638907 DOI: 10.1177/101053958900300405

1,256 malnourished children, aged seven to ten years, were selected for study, 575 from Kuala Langat, 416 from Wilayah Persekutuan and 265 from Ulu Selangor. Ninety-three percent of the children were from low socioeconomic groups with large family size, and most of their parents had only primary or no formal education. During the study period, children in Kuala Langat received daily milk supplementation for five days per week, those in Wilayah Persekutuan for two days per week, while those in Ulu Selangor did not receive any milk supplementation. The study shows that a majority of the malnourished primary school children liked to drink milk and that milk intolerance was not a problem among them.
Impact of a school milk programme on the nutritional status of school children

Chen ST

Asia Pac J Public Health, 1989;3(1):19-25.
PMID: 2497765 DOI: 10.1177/101053958900300104

From the start of the school milk feeding programme in February 1985 to October 1986, a total of 2,766 children aged six to nine years from 12 primary schools in Ulu Selangor were followed-up for about two years. The children's weight and height were monitored at the beginning, in the middle and at the end of the study. The study shows that there is a reduction in the prevalence of protein-energy malnutrition in terms of underweight (15.3% to 8.6%), stunting (16.3% to 8.3%) and wasting (2.6% to 1.7%) from the start of the school feeding programme to two years later. Associated with this there was an improvement in the attendance rate of the children during the same period. As there was no major developmental change in Ulu Selangor during that period, it is likely that the reduction in the prevalence of protein-energy malnutrition and the improvement of the attendance rate among the children are due to the impact of the school milk feeding programme.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

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.
Fulltext Using the 2020 global pandemic as a springboard to highlight the need for amphibian conservation in eastern Asia

Borzée A, Kielgast J, Wren S, Angulo A, Chen S, Magellan K, et al.

Biol Conserv, 2021 Mar;255:108973.
PMID: 35125500 DOI: 10.1016/j.biocon.2021.108973

Emerging infectious diseases are on the rise in many different taxa, including, among others, the amphibian batrachochytrids, the snake fungal disease and the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) virus, responsible for Coronavirus disease 2019 (COVID-19) in mammals. Following the onset of the pandemic linked to COVID-19, eastern Asia has shown strong leadership, taking actions to regulate the trade of potential vector species in several regions. These actions were taken in response to an increase in public awareness, and the need for a quick reaction to mitigate against further pandemics. However, trade restrictions rarely affect amphibians, despite the risk of pathogen transmission, directly, or indirectly through habitat destruction and the loss of vector consumption. Thus, species that help alleviate the risk of zoonoses or provide biological control are not protected. Hence, in view of the global amphibian decline and the risk of zoonoses, we support the current wildlife trade regulations and support measures to safeguard wildlife from overexploitation. The current period of regulation overhaul should be used as a springboard for amphibian conservation. To mitigate risks, we suggest the following stipulations specifically for amphibians. I) Restrictions to amphibian farming in eastern Asia, in relation to pathogen transmission and the establishment of invasive species. II) Regulation of the amphibian pet trade, with a focus on potential vector species. III) Expansion of the wildlife trade ban, to limit the wildlife-human-pet interface. The resulting actions will benefit both human and wildlife populations, as they will lead to a decrease in the risk of zoonoses and better protection of the environment.
Significance statement: There is an increasing number of emerging infectious diseases impacting all species, including amphibians, reptiles and mammals. The latest threat to humans is the virus responsible for COVID-19, and the resulting pandemic. Countries in eastern Asia have taken steps to regulate wildlife trade and prevent further zoonoses thereby decreasing the risk of pathogens arising from wild species. However, as amphibians are generally excluded from regulations we support specific trade restrictions: I) Restrictions to amphibian farming; II) regulation of the amphibian pet trade; III) expansion of the wildlife trade ban. These restrictions will benefit both human and wildlife populations by decreasing the risks of zoonoses and better protecting the environment.
Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Rebbeck TR, Friebel TM, Mitra N, Wan F, Chen S, Andrulis IL, et al.

Breast Cancer Res, 2016 11 11;18(1):112.
PMID: 27836010

BACKGROUND: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.
METHODS: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.
RESULTS: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p
Fulltext Timing of antenatal tetanus immunization for effective protection of the neonate

Chen ST, Edsall G, Peel MM, Sinnathuray TA

Bull World Health Organ, 1983;61(1):159-65.
PMID: 6601539

The relationship between the timing of maternal tetanus toxoid immunization and the presence of protective antitoxin in placental cord blood was investigated among women admitted to the obstetrical service of the University Hospital in Kuala Lumpur, Malaysia. The 1st dose was given between 13-39 weeks of gestation, with a median of 29 weeks. The 2nd dose was given an average of 4 weeks later. Protection was conferred on 80% or more of newborns whose mothers received their 1st tetanus toxoid injection 60 days or more before delivery. Protective levels were seen in all cord blood samples from infants whose mothers had received their 1st injection 90 days before delivery. Similarly,protective titers were found in 100% of cord blood samples when the 2nd maternal injection was give 60 days or more before delivery. There was no significant degree of protection when immunization was carried out less than 20 days before delivery. A single-dose schedule provided no protection when less than 70 days before delivery. Cord and maternal antiotoxin titers differed by no more than 1 2-fold dilution for almost all of the individual paired sera. A cord: maternal antitoxin ratio of 2 was more likely to occur with increasing time between the 2nd injection and delivery. Overall, these findings indicate that the 1st injection of a 2-dose maternal tetanus toxoid schedule should be given at least 60 days and preferably 90 days before delivery.
Fulltext Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, et al.

Cell Death Dis, 2022 Jul 04;13(7):580.
PMID: 35787632 DOI: 10.1038/s41419-022-05034-x

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.
Fulltext Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management

Yang J, Chen S, Duan F, Wang X, Zhang X, Lian B, et al.

Cells, 2022 Nov 06;11(21).
PMID: 36359908 DOI: 10.3390/cells11213511

Mitochondrial cardiomyopathy (MCM) is characterized by abnormal heart-muscle structure and function, caused by mutations in the nuclear genome or mitochondrial DNA. The heterogeneity of gene mutations and various clinical presentations in patients with cardiomyopathy make its diagnosis, molecular mechanism, and therapeutics great challenges. This review describes the molecular epidemiology of MCM and its clinical features, reviews the promising diagnostic tests applied for mitochondrial diseases and cardiomyopathies, and details the animal and cellular models used for modeling cardiomyopathy and to investigate disease pathogenesis in a controlled in vitro environment. It also discusses the emerging therapeutics tested in pre-clinical and clinical studies of cardiac regeneration.
'I have high self-compassion': A face-valid single-item self-compassion scale for resource-limited research contexts

Zhang JW, Howell RT, Chen S, Goold AR, Bilgin B, Chai WJ, et al.

Clin Psychol Psychother, 2022 Jan 26.
PMID: 35083797 DOI: 10.1002/cpp.2714

The original 26-item Self-Compassion Scale (SCS; Neff, 2003) and 12-item Short-Form Self-Compassion Scale (SF-SCS; Raes et al., 2011) are scales commonly used in cross-sectional and longitudinal research to assess the global self-compassion construct and its six facets. We introduce the Single-Item Self-Compassion Scale (SISC; 'I have high self-compassion') to measure the global self-compassion construct in time-, space- and resource-limited contexts (e.g., daily diaries, experience sampling and nationally representative surveys). Additionally, the SISC will expand knowledge about self-compassion by providing researchers whose primary interest is not self-compassion with a convenient, face-valid option to measure self-compassion. Across 10 samples (four cross-sectional, four longitudinal and two 7-day daily diary; N = 2,477), we demonstrated that the SISC has acceptable psychometric properties. Specifically, the SISC was temporally consistent, correlated adequately with the SCS and SF-SCS, exhibited nearly identical correlational patterns when compared with the SCS and SF-SCS with a wide range of criterion measures (e.g., self-esteem, personality, affective and social functioning, mental health and demographic variables) and saved 12 min over a 7-day diary. Results replicated among students, community samples and across the United States, Turkey and Malaysia. Thus, we provide the field with an alternative measure of the global self-compassion construct that complements the SCS and SF-SCS.
Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells

Sweeney S, Leo BF, Chen S, Abraham-Thomas N, Thorley AJ, Gow A, et al.

Colloids Surf B Biointerfaces, 2016 Sep 01;145:167-75.
PMID: 27182651 DOI: 10.1016/j.colsurfb.2016.04.040

Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
Reliability and Validity of the Multidimensional Scale of Perceived Social Support Among Women and Adolescent Girls With Disabilities in Selected Sub-districts of Bangladesh

Murshid ME, Chen S, Rahman MM, Islam MZ, Shimpuku Y, Rahman Era N, et al.

Cureus, 2023 Nov;15(11):e49605.
PMID: 38033436 DOI: 10.7759/cureus.49605

Background Adequate community-based or societal collaboration and cooperation are considerably important for the overall welfare of women and adolescent girls with disabilities. "The Multidimensional Scale of Perceived Social Support (MSPSS)" has not been evaluated for reliability and validity amid women and adolescent girls with disabilities in the Bangladeshi context. Methods A Bangla-translated form of the MSPSS was constructed, and the survey was conducted among 152 women and adolescent girls with disabilities who were purposefully recruited from Bogura Sadar and Chapainawabganj Sadar sub-districts of Bangladesh. Results The Cronbach's alpha of the entire scale was 0.868, indicating high internal consistency. Cronbach's alpha for the family sub-scale was 0.763, the friends sub-scale was 0.820, and the significant others scale was 0.776. The composite reliability for the family sub-scale was 0.849677, the friends sub-scale was 0.881248, and the significant others sub-scale was 0.859668. Convergence reliability was established following sub-scale-wise scores. It affirms the consistency of measurements. The content validity score was >0.62, following the Lawshe approach. The three-factor model was adopted during confirmatory factor analysis when the three-factor model run in SPSS Amos (version 21) CFI (comparative fit index) was 0.919. Conclusions In Bangladesh, to the best of our knowledge, our study is initially to calculate the perceived societal assistance of women and adolescent girls with disabilities. We validated the Bangla-translated form of the MSPSS from the Bangladeshi perspective. Researchers and clinicians may rely on our accurate and validated MSPSS translation into Bangla when working with this group. Based on our findings, this study endorses implementing the MSPSS for assessing professed community-based collaboration using the three-factor model, especially among women and adolescent girls with disabilities.
Fulltext CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

Sun Y, Wu G, Cheng KS, Chen A, Neoh KH, Chen S, et al.

EBioMedicine, 2019 Aug;46:133-149.
PMID: 31375425 DOI: 10.1016/j.ebiom.2019.07.044

BACKGROUND: The evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients.
METHODS: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.
FINDINGS: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC 
Fulltext Rapid Targeted Next-Generation Sequencing Platform for Molecular Screening and Clinical Genotyping in Subjects with Hemoglobinopathies

Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.

EBioMedicine, 2017 Sep;23:150-159.
PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015

Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.

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