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Article: MET Exon 14 Splice-Site Mutations Preferentially Activate KRAS Signaling to Drive Tumourigenesis.

Lu, Daniel / Nagelberg, Amy / Chow, Justine Lm / Chen, Yankuan T / Michalchuk, Quentin / Somwar, Romel / Lockwood, William W

Cancers

2022 Volume 14, Issue 6

Abstract: Targeted therapies ... ...

Abstract	Targeted therapies for
Language	English
Publishing date	2022-03-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14061378
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Article ; Online: Impact of various night-time period definitions on nocturnal ambulatory blood pressure.

Nolde, Janis M / Hillis, Graham S / Atkins, Emily / Von Huben, Amy / Marschner, Simone / Chan, Justine / Reid, Christopher M / Nelson, Mark R / Figtree, Gemma / Chalmers, John / Usherwood, Tim / Rodgers, Anthony / Chow, Clara K / Schlaich, Markus P

Journal of hypertension

2022 Volume 40, Issue 11, Page(s) 2271–2279

Abstract: Background: Several definitions of night-time BP exist for the calculation of nocturnal blood pressure (BP) based on 24-h BP measurements. How much these methods differ regarding the resulting nocturnal blood pressure values, under which circumstances ... ...

Abstract	Background: Several definitions of night-time BP exist for the calculation of nocturnal blood pressure (BP) based on 24-h BP measurements. How much these methods differ regarding the resulting nocturnal blood pressure values, under which circumstances these differences become clinically meaningful, and under which circumstances diary-adjusted measurements should be used preferentially remains uncertain. Methods: Data of 512 24-h BP recordings were analysed regarding differences in nocturnal BP based on three alternative definitions of night-time: 2300-0700 h, 0100-0500 h, and diary-adjusted measures. Results: Mean systolic nocturnal BP between 2300-0700 h was 2.5 mmHg higher than between 0100 and 0500 h and 1.6 mmHg higher than diary adjusted estimates. Up to 38.3% of individuals showed BP differences of more than 5 mmHg when comparing temporal definitions of night-time, resulting in significant proportions of individuals being re-classified as hypertensive. When diary-derived sleeping patterns differed by less than 2 h from the 2300 to 0700 h fixed time definition, mean BP discrepancies remained below 3 mmHg. Absolute time discrepancies between diary and 2300-0700 h fixed time definition of 2-4, 4-8 or at least 8 h led to SBP/DBP differences of 4.1/3.1, 6.8/6.1, and 14.5/9.1mmHg, respectively. Conclusion: Average differences of nocturnal BP between varying definitions in study/cohort data are small and would be of limited relevance in many settings. However, substantial differences can be observed in individual cases, which may affect clinical decision-making in specific patients. In patients whose sleeping patterns differs by more than 2 h from defined fixed night-times, diaries should be used for adjustment.
MeSH term(s)	Blood Pressure/physiology ; Blood Pressure Monitoring, Ambulatory/methods ; Circadian Rhythm/physiology ; Humans ; Hypertension/diagnosis ; Systole
Language	English
Publishing date	2022-08-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000003255
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Article ; Online: CD38 marks the exhausted CD8

Reolo, Marie J Y / Otsuka, Masayuki / Seow, Justine Jia Wen / Lee, Joycelyn / Lee, Yun Hua / Nguyen, Phuong H D / Lim, Chun Jye / Wasser, Martin / Chua, Camillus / Lim, Tony K H / Leow, Wei Qiang / Chung, Alexander / Goh, Brian K P / Chow, Pierce K H / DasGupta, Ramanuj / Yeong, Joe Poh Sheng / Chew, Valerie

Frontiers in immunology

2023 Volume 14, Page(s) 1182016

Abstract: Introduction: Despite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is ...

Abstract	Introduction: Despite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is widely expressed on tumor-infiltrating leukocytes (TILs), predominantly on CD3 Methods: In this current study, we used cytometry time-of-flight (CyTOF), bulk RNA sequencing on sorted T cells, and single-cell RNA (scRNA) sequencing to interrogate expression of CD38 and its correlation with T cell exhaustion in HCC samples. We also employed multiplex immunohistochemistry (mIHC) for validating our findings. Results: From CyTOF analysis, we compared the immune composition of CD38-expressing leukocytes in TILs, non-tumor tissue-infiltrating leukocytes (NIL), and peripheral blood mononuclear cells (PBMC). We identified CD8 Conclusion: Taken together, the concurrent expression of CD38 with exhaustion markers on CD8
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/pathology ; Liver Neoplasms/pathology ; CD8-Positive T-Lymphocytes ; Leukocytes, Mononuclear/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; CTLA-4 Antigen/metabolism ; Memory T Cells ; CD3 Complex/metabolism ; Tumor Microenvironment
Chemical Substances	Programmed Cell Death 1 Receptor ; CTLA-4 Antigen ; CD3 Complex
Language	English
Publishing date	2023-06-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1182016
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Article ; Online: Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey.

Viruses

2023 Volume 15, Issue 8

Abstract: New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, ...

Abstract	New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (
MeSH term(s)	Humans ; COVID-19/epidemiology ; COVID-19/prevention & control ; SARS-CoV-2/genetics ; New Jersey/epidemiology ; COVID-19 Vaccines ; Pandemics ; Retrospective Studies ; Spike Glycoprotein, Coronavirus ; Breakthrough Infections
Chemical Substances	COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-08-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081699
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Article: Biases underlying species detection using fluorescent amplified-fragment length polymorphisms yielded from roots.

Karst, Justine / Chow, Pak / Landhäusser, Simon M

Plant methods

2015 Volume 11, Page(s) 36

Abstract: Background: Roots of different plant species are typically morphologically indistinguishable. Of the DNA-based techniques, fluorescent amplified-fragment length polymorphisms (FAFLPs) are considered reliable, high throughput, inexpensive methods to ... ...

Abstract	Background: Roots of different plant species are typically morphologically indistinguishable. Of the DNA-based techniques, fluorescent amplified-fragment length polymorphisms (FAFLPs) are considered reliable, high throughput, inexpensive methods to identify roots from mixed species samples. False-negatives, however, are not uncommon and their underlying causes are poorly understood. We investigated several sources of potential biases originating in DNA extraction and amplification. Specifically, we examined the effects of sample storage, tissue, and species on DNA yield and purity, and the effects of DNA concentration and fragment size on amplification of three non-coding chloroplast regions (trnT-trnL intergenic spacer, trnL intron, and trnL-trnF intergenic spacer). Results: We found that sample condition, tissue and species all affected DNA yield. A single freeze-thaw reduces DNA yield, DNA yield is less for roots than shoots, and species vary in the amount of DNA yielded from extractions. The effects of template DNA concentration, species identity, and their interaction on amplicon yield differed across the three chloroplast regions tested. We found that the effect of species identity on amplicon production was generally more pronounced than that of DNA concentration. Though these factors influenced DNA yield, they likely do not have a pronounced effect on detection success of fragments and only underscore the restriction on the use of FAFLPs for measuring species presence rather than their abundance. However, for two of the regions tested-the trnT-trnL intergenic spacer and the trnL intron-size-based fragment competition occurred and the likelihood of detection was higher for smaller than larger fragments. This result reveals a methodological bias when using FAFLPs. Conclusions: To avoid potential bias with the use of FAFLPs, we recommend users check for the disproportionate absence of species detected belowground versus aboveground as a function of fragment size, and explore other regions, aside from the trnT-trnL intergenic spacer and trnL intron, for amplification.
Language	English
Publishing date	2015-06-26
Publishing country	England
Document type	Journal Article
ISSN	1746-4811
ISSN	1746-4811
DOI	10.1186/s13007-015-0079-1
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Article: Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2

Seow, Justine Jia Wen / Pai, Rhea / Mishra, Archita / Shepherdson, Edwin / Lim, Tony Kiat Hon / Goh, Brian K P / Chan, Jerry K Y / Chow, Pierce K H / Ginhoux, Florent / DasGupta, Ramanuj / Sharma, Ankur

Frontiers in medicine

2021 Volume 8, Page(s) 603374

Abstract: The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome ... ...

Abstract	The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2
Language	English
Publishing date	2021-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2021.603374
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Article ; Online: Automatic data extraction from 24 hour blood pressure measurement reports of a large multicenter clinical trial.

Nolde, Janis M / Mian, Ajmal / Schlaich, Luca / Chan, Justine / Lugo-Gavidia, Leslie Marisol / Barrie, Nicola / Gopal, Vishal / Hillis, Graham S / Chow, Clara K / Schlaich, Markus P

Computer methods and programs in biomedicine

2021 Volume 214, Page(s) 106588

Abstract: Background and objectives: Ambulatory blood pressure monitoring (ABPM) is usually reported in descriptive values such as circadian averages and standard deviations. Making use of the original, individual blood pressure measurements may be advantageous, ... ...

Abstract	Background and objectives: Ambulatory blood pressure monitoring (ABPM) is usually reported in descriptive values such as circadian averages and standard deviations. Making use of the original, individual blood pressure measurements may be advantageous, particularly for research purposes, as this increases the flexibility of the analytical process, enables alternative statistical analyses and provide novel insights. Here we describe the development of a new multistep, hierarchical data extraction algorithm to collect raw data from .pdf reports and text files as part of a large multi-center clinical study. Methods: Original reports were saved in a nested file system, from which they were automatically extracted, read and saved into databases with custom made programs written in Python 3. Data were further processed, cleaned and relevant descriptive statistics such as averages and standard deviations calculated according to a variety of definitions of day- and night-time. Additionally, data control mechanisms for manual review of the data and programmatic auto-detection of extraction errors was implemented as part of the project. Results: The developed algorithm extracted 97% of the data automatically, the missing data consisted mostly of reports that were saved incorrectly or not formatted in the specified way. Manual checks comparing samples of the extracted data to original reports indicated a high level of accuracy of the extracted data, no errors introduced due to flaws in the extraction software were detected in the extracted dataset. Conclusions: The developed multistep, hierarchical data extraction algorithm facilitated collection from different file formats and paired with database cleaning and data processing steps led to an effective and accurate assembly of raw ABPM data for further and adjustable analyses. Manual work was minimized while data quality was ensured with standardized, reproducible procedures.
MeSH term(s)	Algorithms ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Databases, Factual ; Software
Language	English
Publishing date	2021-12-17
Publishing country	Ireland
Document type	Journal Article ; Multicenter Study
ZDB-ID	632564-6
ISSN	1872-7565 ; 0169-2607
ISSN (online)	1872-7565
ISSN	0169-2607
DOI	10.1016/j.cmpb.2021.106588
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Article ; Online: Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells

Justine Jia Wen Seow / Rhea Pai / Archita Mishra / Edwin Shepherdson / Tony Kiat Hon Lim / Brian K. P. Goh / Jerry K. Y. Chan / Pierce K. H. Chow / Florent Ginhoux / Ramanuj DasGupta / Ankur Sharma

Frontiers in Medicine, Vol

Implications in Coronavirus Disease 2019-Associated Liver Dysfunction

2021 Volume 8

Abstract	The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.
Keywords	SARS-CoV-2 ; COVID-19 ; ACE2 ; tmprss2 ; Trop2 ; liver ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: scRNA-seq reveals ACE2 and TMPRSS2 expression in TROP2+ Liver Progenitor Cells: Implications in COVID-19 associated Liver Dysfunction

Wen Seow, Justine Jia / Pai, Rhea / Mishra, Archita / Shepherdson, Edwin / Hon Lim, Tony Kiat / Goh, Brian KP / Chan, Jerry KY / Chow, Pierce KH / Ginhoux, Florent / DasGupta, Ramanuj / Sharma, Ankur

bioRxiv

Abstract: The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in ∼170 countries across the globe. Entry of SARS- ...

Abstract	The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in ∼170 countries across the globe. Entry of SARS-CoV-2 into mammalian cells require the binding of viral Spike (S) proteins to the ACE2 (angiotensin converting enzyme 2) receptor. Once entered the S protein is primed by a specialised serine protease, TMPRSS2 (Transmembrane Serine Protease 2) in the host cell. Importantly, beside respiratory symptoms, consistent with other common respiratory virus infection when patients become viraemic, a significant number of COVID-19 patients also develop liver comorbidities. We explored if specific target cell-type in the mammalian liver, could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here we employed single-cell RNA-seq (scRNA-seq) to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We report the co-expression of ACE2 and TMPRSS2 in a TROP2+ liver progenitor population. Importantly, we fail to detect the expression of ACE2 in hepatocyte or any other liver (immune and stromal) cell types. These results indicated that in COVID-19 associated liver dysfunction and cell death, viral infection of TROP2+ progenitors in liver may significantly impaired liver regeneration and could lead to pathology. Highlights - EPCAM+ Liver progenitors co-express ACE2 and TMPRSS2 - ACE2 and TMPRSS2 expression is highest in TROP2high progenitors - ACE2 and TMPRSS2 cells express cholangiocyte biased fate markers - ACE2 and TMPRSS2 positive cells are absent in human fetal liver
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.03.23.002832
Database	COVID19

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Article ; Online: scRNA-seq reveals ACE2 and TMPRSS2 expression in TROP2+ Liver Progenitor Cells: Implications in COVID-19 associated Liver Dysfunction

Seow, Justine Jia Wen / Pai, Rhea / Mishra, Archita / Shepherdson, Edwin / Lim, Tony Kiat Hon / Goh, Brian K P / Chan, Jerry KY / Chow, Pierce KH / Ginhoux, Florent / DasGupta, Ramanuj / Sharma, Ankur

bioRxiv

Abstract: The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in ~170 countries across the globe. Entry of SARS- ...

Abstract	The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in ~170 countries across the globe. Entry of SARS-CoV-2 into mammalian cells require the binding of viral Spike (S) proteins to the ACE2 (angiotensin converting enzyme 2) receptor. Once entered the S protein is primed by a specialised serine protease, TMPRSS2 (Transmembrane Serine Protease 2) in the host cell. Importantly, beside respiratory symptoms, consistent with other common respiratory virus infection when patients become viraemic, a significant number of COVID-19 patients also develop liver comorbidities. We explored if specific target cell-type in the mammalian liver, could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here we employed single-cell RNA-seq (scRNA-seq) to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We report the co-expression of ACE2 and TMPRSS2 in a TROP2+ liver progenitor population. Importantly, we fail to detect the expression of ACE2 in hepatocyte or any other liver (immune and stromal) cell types. These results indicated that in COVID-19 associated liver dysfunction and cell death, viral infection of TROP2+ progenitors in liver may significantly impaired liver regeneration and could lead to pathology.
Keywords	covid19
Language	English
Publishing date	2020-03-25
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2020.03.23.002832
Database	COVID19

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