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Article ; Online: Shiny-SoSV: A web-based performance calculator for somatic structural variant detection.

Gong, Tingting / Hayes, Vanessa M / Chan, Eva K F

PloS one

2020 Volume 15, Issue 8, Page(s) e0238108

Abstract: Somatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools ...

Abstract	Somatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools for guiding study design nor are there applications that could predict the performance of somatic structural variant detection. To address this gap, we developed Shiny-SoSV, a user-friendly web-based calculator for determining the impact of common variables on the sensitivity, precision and F1 score of somatic structural variant detection, including choice of variant detection tool, sequencing depth of coverage, variant allele fraction, and variant breakpoint resolution. Using simulation studies, we determined singular and combinatoric effects of these variables, modelled the results using a generalised additive model, allowing structural variant detection performance to be predicted for any combination of predictors. Shiny-SoSV provides an interactive and visual platform for users to easily compare individual and combined impact of different parameters. It predicts the performance of a proposed study design, on somatic structural variant detection, prior to the commencement of benchwork. Shiny-SoSV is freely available at https://hcpcg.shinyapps.io/Shiny-SoSV with accompanying user's guide and example use-cases.
MeSH term(s)	Algorithms ; Carcinogenesis/genetics ; Computational Biology/methods ; Genetic Variation/genetics ; Genome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Internet ; Neoplasms/genetics ; Software
Language	English
Publishing date	2020-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0238108
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Article ; Online: Detection of somatic structural variants from short-read next-generation sequencing data.

Gong, Tingting / Hayes, Vanessa M / Chan, Eva K F

Briefings in bioinformatics

2020 Volume 22, Issue 3

Abstract: Somatic structural variants (SVs), which are variants that typically impact >50 nucleotides, play a significant role in cancer development and evolution but are notoriously more difficult to detect than small variants from short-read next-generation ... ...

Abstract	Somatic structural variants (SVs), which are variants that typically impact >50 nucleotides, play a significant role in cancer development and evolution but are notoriously more difficult to detect than small variants from short-read next-generation sequencing (NGS) data. This is due to a combination of challenges attributed to the purity of tumour samples, tumour heterogeneity, limitations of short-read information from NGS and sequence alignment ambiguities. In spite of active development of SV detection tools (callers) over the past few years, each method has inherent advantages and limitations. In this review, we highlight some of the important factors affecting somatic SV detection and compared the performance of seven commonly used SV callers. In particular, we focus on the extent of change in sensitivity and precision for detecting different SV types and size ranges from samples with differing variant allele frequencies and sequencing depths of coverage. We highlight the reasons for why some SV callers perform well in some settings but not others, allowing our evaluation findings to be extended beyond the seven SV callers examined in this paper. As the importance of large SVs become increasingly recognized in cancer genomics, this paper provides a timely review on some of the most impactful factors influencing somatic SV detection that should be considered when choosing SV callers.
MeSH term(s)	Gene Frequency ; Genetic Variation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Sequence Analysis, DNA/methods
Language	English
Publishing date	2020-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2068142-2
ISSN	1477-4054 ; 1467-5463
ISSN (online)	1477-4054
ISSN	1467-5463
DOI	10.1093/bib/bbaa056
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Article ; Online: Blinatumomab with donor lymphocyte infusions post haploidentical hematopoietic stem cell transplantation as salvage therapy for relapsed refractory acute lymphoblastic leukemia post chimeric antigen receptor T-cell therapy.

Chan, Wilson Y K / Lee, Pamela P W / Cheuk, Daniel K L / Yeung, Eva W M / Wong, Kenneth C W / Li, C K / Chan, Godfrey C F / Leung, Wing

Pediatric blood & cancer

2022 Volume 70, Issue 1, Page(s) e29852

MeSH term(s)	Humans ; Salvage Therapy ; Receptors, Chimeric Antigen ; Antibodies, Bispecific/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Lymphocytes
Chemical Substances	blinatumomab (4FR53SIF3A) ; Receptors, Chimeric Antigen ; Antibodies, Bispecific
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Letter
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.29852
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Article ; Online: Impaired cerebral blood flow in type 2 diabetes mellitus – A comparative study with subjective cognitive decline, vascular dementia and Alzheimer’s disease subjects

Anson C.M. Chau / Eva Y.W. Cheung / K.H. Chan / W.S. Chow / Y.F. Shea / Patrick K.C. Chiu / Henry K.F. Mak

NeuroImage: Clinical, Vol 27, Iss , Pp 102302- (2020)

2020

Abstract: ... clinic also had 18-F Flutametamol PET-CT scanning to look for any amyloid burden. Pseudocontinuous ...

Abstract	The link between non-demented type 2 diabetes mellitus (T2DM) and different types of cognitive impairment is controversial. By controlling for co-morbidities such as cerebral macrovascular and microvascular changes, cerebral atrophy, amyloid burden, hypertension or hyperlipidemia, the current study investigated the cerebral blood flow of T2DM individuals as compared to cognitively impaired subjects recruited from a memory clinic.15 healthy control (71.8 ± 6.1 years), 18 T2DM (62.5 ± 3.7 years), as well as 8 Subjective Cognitive Decline (69.5 ± 7.5 years), 12 Vascular Dementia (79.3 ± 4.2 years) and 17 Alzheimer’s Disease (75.1 ± 8.2 years) underwent multi-parametric MRI brain scanning. Subjects with T2DM and from the memory clinic also had 18-F Flutametamol PET-CT scanning to look for any amyloid burden. Pseudocontinuous Arterial Spin Labeling (PCASL), MR Angiography Head, 3D FLAIR and 3D T1-weighted sequences were used to quantify cerebral blood flow, cerebrovascular changes, white matter hyperintensities and brain atrophy respectively. Vascular risk factors were retrieved from the medical records. The 37 subjects from memory clinic were classified into subjective cognitive decline (SCD), vascular dementia (VD) and Alzheimer’s disease (AD) subgroups by a multi-disciplinary panel consisting of a neuroradiologist, and 2 geriatricians.Absolute cortical CBF in our cohort of T2DM, SCD, VD and AD was significantly decreased (p < 0.01) as compared to healthy controls (HC) in both whole brain and eight paired brain regions, after age, normalized grey matter volume and gender adjustment and Bonferroni correction.Subgroup analysis between T2DM, SCD, VD, and AD revealed that CBF of T2DM was not significantly different from AD, VD or SCD. By controlling for co-morbidities, impaired cortical CBF in T2DM was not related to microangiopathy or amyloid deposition, but to the interaction of triple risk factors (such as diabetes mellitus, hypertension, and hyperlipidemia).There was statistically significant negative ...
Keywords	Type 2 diabetes mellitus ; Cerebral blood flow ; Arterial spin labeling ; Subjective cognitive decline ; Dementia ; Cerebral autoregulation ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Anesthetic Management for Squamous Cell Carcinoma of the Esophagus.

Chan, Eva Y F / Ip, Danny K Y / Irwin, Michael G

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2129, Page(s) 359–383

Abstract: While surgery plays a major role in the treatment and potential cure of esophageal cancers, esophagectomy remains a high-risk operation with significant perioperative morbidity and mortality compared to other oncosurgical procedures. Perioperative ... ...

Abstract	While surgery plays a major role in the treatment and potential cure of esophageal cancers, esophagectomy remains a high-risk operation with significant perioperative morbidity and mortality compared to other oncosurgical procedures. Perioperative management for esophagectomy is complex, and close attention to detail in various areas of anesthetic and perioperative management is crucial to improve postoperative outcomes. Patients undergoing esophagectomy should be offered an evidence-based risk assessment for their postoperative outcomes to allow active participation and informed, shared-decision making. Novel perioperative risk scores have been developed to predict both short-term and long-term outcomes in patients with esophageal cancer, although independent validation of such scoring systems is still required. Apart from accurate preoperative risk assessment, further efforts to improve morbidity and mortality from esophagectomy is achieved through comprehensive Enhanced Recovery after Surgery (ERAS) protocols, which comprise an individualized bundle of care throughout the perioperative journey for each patient and should be implemented as a standard practice. Furthermore, anesthetic practice and perioperative anesthetic drug usage can potentially affect cancer progression and recurrence. This chapter reviews current evidence for various factors that contribute to the improvement of perioperative outcomes, including prehabilitation, preoperative optimization of anemia, thoracic epidural analgesia, intraoperative protective ventilatory strategies, goal-directed fluid therapy, as well as special attention to other perioperative issues that potentially reduce anastomotic and cardiopulmonary complications. In summary, it is difficult to show a measurable benefit from any one single intervention, and a multidisciplinary approach that encompasses multiple aspects of perioperative care is necessary to improve outcomes after esophagectomy.
MeSH term(s)	Adenocarcinoma/pathology ; Anesthesia/methods ; Anesthetics/therapeutic use ; Carcinoma, Squamous Cell/pathology ; Esophageal Neoplasms/pathology ; Esophageal Squamous Cell Carcinoma/metabolism ; Esophageal Squamous Cell Carcinoma/pathology ; Esophageal Squamous Cell Carcinoma/surgery ; Esophagectomy/adverse effects ; Esophagectomy/methods ; Esophagus/pathology ; Female ; Head and Neck Neoplasms/pathology ; Humans ; Male ; Mouth Neoplasms/pathology ; Perioperative Care/methods ; Postoperative Complications/etiology ; Risk Factors
Chemical Substances	Anesthetics
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0377-2_26
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Article ; Online: Shiny-SoSV

Tingting Gong / Vanessa M Hayes / Eva K F Chan

PLoS ONE, Vol 15, Iss 8, p e

A web-based performance calculator for somatic structural variant detection.

2020 Volume 0238108

Abstract	Somatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools for guiding study design nor are there applications that could predict the performance of somatic structural variant detection. To address this gap, we developed Shiny-SoSV, a user-friendly web-based calculator for determining the impact of common variables on the sensitivity, precision and F1 score of somatic structural variant detection, including choice of variant detection tool, sequencing depth of coverage, variant allele fraction, and variant breakpoint resolution. Using simulation studies, we determined singular and combinatoric effects of these variables, modelled the results using a generalised additive model, allowing structural variant detection performance to be predicted for any combination of predictors. Shiny-SoSV provides an interactive and visual platform for users to easily compare individual and combined impact of different parameters. It predicts the performance of a proposed study design, on somatic structural variant detection, prior to the commencement of benchwork. Shiny-SoSV is freely available at https://hcpcg.shinyapps.io/Shiny-SoSV with accompanying user's guide and example use-cases.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction: Human origins in a southern African palaeo-wetland and first migrations.

Chan, Eva K F / Timmermann, Axel / Baldi, Benedetta F / Moore, Andy E / Lyons, Ruth J / Lee, Sun-Seon / Kalsbeek, Anton M F / Petersen, Desiree C / Rautenbach, Hannes / Förtsch, Hagen E A / Bornman, M S Riana / Hayes, Vanessa M

Nature

2021 Volume 592, Issue 7852, Page(s) E7

Language	English
Publishing date	2021-03-16
Publishing country	England
Document type	Published Erratum
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-03156-w
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Article ; Online: Psychometric evaluation of the Symptoms of Infection with Coronavirus-19 (SIC): results from a cross-sectional study and a phase 3 clinical trial.

Chan, Eric K H / Williams, Valerie / Romano, Carla / Fehnel, Sheri / Slagle, Ashley F / Stoddard, Jeffrey / Sadoff, Jerald / Mayorga, Margaret / Lewis, Sandy / Yarr, Stuart / Ma, Jia / Liu, Yan / Katz, Eva G / McNulty, Pauline / van Dromme, Ilse / McQuarrie, Kelly

Journal of patient-reported outcomes

2023 Volume 7, Issue 1, Page(s) 45

Abstract: Background: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and ... ...

Abstract	Background: The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure scored by body system composites to assess signs/symptoms of coronavirus disease 2019 (COVID-19). In addition to cross-sectional and longitudinal psychometric evaluations, qualitative exit interviews were conducted to support the content validity of the SIC. Methods: In a cross-sectional study, adults diagnosed with COVID-19 in the United States completed the web-based SIC and additional PRO measures. A subset was invited to participate in phone-based exit interviews. Longitudinal psychometric properties were assessed in ENSEMBLE2, a multinational, randomized, double-blind, placebo-controlled, phase 3 trial of the Ad26.COV2.S COVID-19 vaccine. Psychometric properties evaluated included structure, scoring, reliability, construct validity, discriminating ability, responsiveness, and meaningful change thresholds of SIC items and composite scores. Results: In the cross-sectional study, 152 participants completed the SIC (mean age, 51.0 ± 18.6 years) and 20 completed follow-up interviews. Fatigue (77.6%), feeling unwell (65.8%), and cough (60.5%) were symptoms most frequently reported. SIC inter-item correlations were all positive and mostly moderate (r ≥ 0.3) and statistically significant. SIC items and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) scores correlated as hypothesized (all r ≥ 0.32). Internal consistency reliabilities of all SIC composite scores were satisfactory (Cronbach's alpha, 0.69-0.91). SIC composite scores correlated moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) with PROMIS-29 scores and Patient Global Impression of Severity (PGIS) ratings (all P < 0.01). A variety of signs/symptoms were cited in exit interviews, and participants considered the SIC straightforward, comprehensive, and easy to use. From ENSEMBLE2, 183 participants with laboratory-confirmed moderate to severe/critical COVID-19 were included (51.5 ± 14.8 years). Strong test-retest reliabilities were observed for most SIC composite scores (intraclass correlations ≥ 0.60). Statistically significant differences across PGIS severity levels were found for all but 1 composite score, supporting known-groups validity. All SIC composite scores demonstrated responsiveness based on changes in PGIS. Conclusions: The psychometric evaluations provided strong evidence for the reliability and validity of the SIC for measuring COVID-19 symptoms, supporting its use in vaccine and treatment trials. In exit interviews, participants described a broad range of signs/symptoms consistent with previous research, further supporting the content validity and format of the SIC.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Aged ; Cross-Sectional Studies ; Psychometrics/methods ; Reproducibility of Results ; Ad26COVS1 ; COVID-19 Vaccines ; Surveys and Questionnaires ; COVID-19
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; COVID-19 Vaccines
Language	English
Publishing date	2023-05-17
Publishing country	Germany
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2509-8020
ISSN (online)	2509-8020
DOI	10.1186/s41687-023-00581-z
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Article ; Online: Quality of life in patients with malignant spinal cord compression: a systematic review.

Gojsevic, Milena / Shariati, Saba / Chan, Adrian Wai / Bonomo, Pierluigi / Zhang, Elwyn / Kennedy, Samantha K F / Rajeswaran, Thenugaa / Rades, Dirk / Vassiliou, Vassilios / Soliman, Hany / Lee, Shing-Fung / Wong, Henry C Y / Rembielak, Agata / Oldenburger, Eva / Akkila, Shereen / Azevedo, Lucas / Chow, Edward

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

2023 Volume 31, Issue 12, Page(s) 736

Abstract: Introduction: Malignant spinal cord compression (MSCC) is an oncological emergency that may result in a devastating combination of malignancy and disability. Existing quality of life (QoL) questionnaires commonly used in MSCC literature (EORTC QLQ-C30, ... ...

Abstract	Introduction: Malignant spinal cord compression (MSCC) is an oncological emergency that may result in a devastating combination of malignancy and disability. Existing quality of life (QoL) questionnaires commonly used in MSCC literature (EORTC QLQ-C30, BM-22, Brief Pain Inventory, and Spine Oncology Study Group Outcomes) may not capture all the commonly reported symptoms and lack specificity to MSCC. The primary objective of this systematic review is to determine unmet patient needs and underreported QoL issues and compile a comprehensive list of QoL issues. The secondary objective of this review is to compile all existing QoL tools and questionnaires and determine whether any QoL issues are not addressed in the existing tools currently used in the literature. Methods: A literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and February 6, 2023, to compile all QoL issues and existing questionnaires used to assess QoL in patients with MSCC. All study designs were included given that they discussed QoL issues specific to patients with MSCC. Results: The results of this systematic review identified the most frequently discussed QoL issues in the literature studying MSCC. This included direct symptoms of MSCC such as back pain, paralysis, limb weakness/numbness, and urinary/bowel incontinence. Indirect symptoms coming from radiotherapy treatment such as dysphagia, painful swallowing, mouth pain, dry mouth, diarrhea, fatigue, and nausea/vomiting were also noted. Other symptoms resulting from corticosteroid treatment included difficulty sleeping, blurring of vision, weight gain, and mood disturbance. Patients also experienced psychosocial issues such as anxiety, depression, emotional distress, low self-esteem, concerns about dependence on others, concerns about getting home, and fear about their prognosis and future. Conclusion: This review highlights the QoL issues specific to patients with MSCC and QoL tools capturing these issues. Relevance of QoL issues identified in this systematic review must be prospectively validated by patients and healthcare professionals with experience in treating MSCC.
MeSH term(s)	Humans ; Quality of Life ; Spinal Cord Compression/etiology ; Pain ; Patients ; Spine
Language	English
Publishing date	2023-12-01
Publishing country	Germany
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	1134446-5
ISSN	1433-7339 ; 0941-4355
ISSN (online)	1433-7339
ISSN	0941-4355
DOI	10.1007/s00520-023-08186-4
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Article ; Online: Impaired cerebral blood flow in type 2 diabetes mellitus - A comparative study with subjective cognitive decline, vascular dementia and Alzheimer's disease subjects.

Chau, Anson C M / Cheung, Eva Y W / Chan, K H / Chow, W S / Shea, Y F / Chiu, Patrick K C / Mak, Henry K F

NeuroImage. Clinical

2020 Volume 27, Page(s) 102302

Abstract: ... clinic also had 18-F Flutametamol PET-CT scanning to look for any amyloid burden. Pseudocontinuous ...

Abstract	The link between non-demented type 2 diabetes mellitus (T2DM) and different types of cognitive impairment is controversial. By controlling for co-morbidities such as cerebral macrovascular and microvascular changes, cerebral atrophy, amyloid burden, hypertension or hyperlipidemia, the current study investigated the cerebral blood flow of T2DM individuals as compared to cognitively impaired subjects recruited from a memory clinic. 15 healthy control (71.8 ± 6.1 years), 18 T2DM (62.5 ± 3.7 years), as well as 8 Subjective Cognitive Decline (69.5 ± 7.5 years), 12 Vascular Dementia (79.3 ± 4.2 years) and 17 Alzheimer's Disease (75.1 ± 8.2 years) underwent multi-parametric MRI brain scanning. Subjects with T2DM and from the memory clinic also had 18-F Flutametamol PET-CT scanning to look for any amyloid burden. Pseudocontinuous Arterial Spin Labeling (PCASL), MR Angiography Head, 3D FLAIR and 3D T1-weighted sequences were used to quantify cerebral blood flow, cerebrovascular changes, white matter hyperintensities and brain atrophy respectively. Vascular risk factors were retrieved from the medical records. The 37 subjects from memory clinic were classified into subjective cognitive decline (SCD), vascular dementia (VD) and Alzheimer's disease (AD) subgroups by a multi-disciplinary panel consisting of a neuroradiologist, and 2 geriatricians. Absolute cortical CBF in our cohort of T2DM, SCD, VD and AD was significantly decreased (p < 0.01) as compared to healthy controls (HC) in both whole brain and eight paired brain regions, after age, normalized grey matter volume and gender adjustment and Bonferroni correction. Subgroup analysis between T2DM, SCD, VD, and AD revealed that CBF of T2DM was not significantly different from AD, VD or SCD. By controlling for co-morbidities, impaired cortical CBF in T2DM was not related to microangiopathy or amyloid deposition, but to the interaction of triple risk factors (such as diabetes mellitus, hypertension, and hyperlipidemia). There was statistically significant negative correlation (p ≤ 0.05) between adjusted CBF and HbA1c in all brain regions of T2DM and HC (with partial correlation ranging from -0.30 to -0.46). Taken together, altered cerebral blood flow in T2DM might be related to disruption of cerebrovascular autoregulation related to vascular risk factors, and such oligemia occurred before clinical manifestation due to altered glycemic control.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Brain/blood supply ; Brain/physiopathology ; Cerebrovascular Circulation/physiology ; Cognitive Dysfunction/pathology ; Cognitive Dysfunction/physiopathology ; Dementia, Vascular/pathology ; Dementia, Vascular/physiopathology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/pathology ; Diabetes Mellitus, Type 2/physiopathology ; Female ; Humans ; Male ; Memory/physiology ; Middle Aged ; Positron Emission Tomography Computed Tomography/methods
Language	English
Publishing date	2020-05-28
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2020.102302
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