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Article ; Online: Reply to T. J. A. Dekker, D.-C. Mo et al, and A. Seidman et al.

Saura, Cristina / Oliveira, Mafalda / Kim, Sung-Bae / Yau, Thomas / Takano, Toshimi / Brufsky, Adam

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2020 Volume 39, Issue 3, Page(s) 254–255

Language	English
Publishing date	2020-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.20.02963
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article: Altered chromatin occupancy of patient-associated H4 mutants misregulate neuronal differentiation.

Feng, Lijuan / Barrows, Douglas / Zhong, Liangwen / Mätlik, Kärt / Porter, Elizabeth G / Djomo, Annaelle M / Yau, Iris / Soshnev, Alexey A / Carroll, Thomas S / Wen, Duancheng / Hatten, Mary E / Garcia, Benjamin A / Allis, C David

bioRxiv : the preprint server for biology

2023

Abstract: Chromatin is a crucial regulator of gene expression and tightly controls development across species. Mutations in only one copy of multiple histone genes were identified in children with developmental disorders characterized by microcephaly, but their ... ...

Abstract	Chromatin is a crucial regulator of gene expression and tightly controls development across species. Mutations in only one copy of multiple histone genes were identified in children with developmental disorders characterized by microcephaly, but their mechanistic roles in development remain unclear. Here we focus on dominant mutations affecting histone H4 lysine 91. These H4K91 mutants form aberrant nuclear puncta at specific heterochromatin regions. Mechanistically, H4K91 mutants demonstrate enhanced binding to the histone variant H3.3, and ablation of H3.3 or the H3.3-specific chaperone DAXX diminishes the mutant localization to chromatin. Our functional studies demonstrate that H4K91 mutant expression increases chromatin accessibility, alters developmental gene expression through accelerating pro-neural differentiation, and causes reduced mouse brain size
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.29.560141
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Article ; Online: The health, cost and equity impacts of restrictions on the advertisement of high fat, salt and sugar products across the transport for London network: a health economic modelling study.

Thomas, Chloe / Breeze, Penny / Cummins, Steven / Cornelsen, Laura / Yau, Amy / Brennan, Alan

The international journal of behavioral nutrition and physical activity

2022 Volume 19, Issue 1, Page(s) 93

Abstract: Background: Policies aimed at restricting the marketing of high fat, salt and sugar products have been proposed as one way of improving population diet and reducing obesity. In 2019, Transport for London implemented advertising restrictions on high fat, ...

Abstract	Background: Policies aimed at restricting the marketing of high fat, salt and sugar products have been proposed as one way of improving population diet and reducing obesity. In 2019, Transport for London implemented advertising restrictions on high fat, salt and sugar products. A controlled interrupted time-series analysis comparing London with a north of England control, suggested that the advertising restrictions had resulted in a reduction in household energy purchases. The aim of the study presented here was to estimate the health benefits, cost savings and equity impacts of the Transport for London policy using a health economic modelling approach, from an English National Health Service and personal social services perspective. Methods: A diabetes prevention microsimulation model was modified to incorporate the London population and Transport for London advertising intervention. Conversion of calorie to body mass index reduction was mediated through an approximation of a mathematical model estimating weight loss. Outcomes gathered included incremental obesity, long-term diabetes and cardiovascular disease events, quality-adjusted life years, healthcare costs saved and net monetary benefit. Slope index of inequality was calculated for proportion of people with obesity across socioeconomic groups to assess equity impacts. Results: The results show that the Transport for London policy was estimated to have resulted in 94,867 (4.8%) fewer individuals with obesity, and to reduce incidence of diabetes and cardiovascular disease by 2,857 and 1,915 cases respectively within three years post intervention. The policy would produce an estimated 16,394 additional quality-adjusted life-years and save £218 m in NHS and social care costs over the lifetime of the current population. Greater benefits (e.g. a 37% higher gain in quality-adjusted life-years) were expected to accrue to individuals from the most socioeconomically deprived groups compared to the least deprived. Conclusions: This analysis suggests that there are considerable potential health and economic gains from restricting the advertisement of high fat, salt and sugar products. The population health and economic impacts of the Transport for London advertising restrictions are likely to have reduced health inequalities in London.
MeSH term(s)	Advertising ; Cardiovascular Diseases/prevention & control ; Cost-Benefit Analysis ; Humans ; London ; Obesity/epidemiology ; Obesity/prevention & control ; Sodium Chloride, Dietary ; State Medicine ; Sugars
Chemical Substances	Sodium Chloride, Dietary ; Sugars
Language	English
Publishing date	2022-07-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2134691-4
ISSN	1479-5868 ; 1479-5868
ISSN (online)	1479-5868
ISSN	1479-5868
DOI	10.1186/s12966-022-01331-y
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Article ; Online: Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

Wing, Sara / Thomas, Doneal / Balamchi, Shabnam / Ip, Jane / Naylor, Kyla / Dixon, Stephanie N / McArthur, Eric / Kwong, Jeffrey C / Perl, Jeffrey / Atiquzzaman, Mohammad / Yeung, Angie / Yau, Kevin / Hladunewich, Michelle A / Leis, Jerome A / Levin, Adeera / Blake, Peter G / Oliver, Matthew J

Clinical journal of the American Society of Nephrology : CJASN

2023 Volume 18, Issue 4, Page(s) 491–498

Abstract: Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... ...

Abstract	Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. Methods: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. Results: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). Conclusions: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; COVID-19/epidemiology ; COVID-19/prevention & control ; Retrospective Studies ; SARS-CoV-2 ; Ontario/epidemiology ; RNA, Messenger ; Renal Dialysis
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger
Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.0000000000000108
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Zs.A 6584: Show issues

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Article ; Online: Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements.

European journal of human genetics : EJHG

2024

Abstract: Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does ...

Abstract	Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.
Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/s41431-024-01593-z
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Zs.A 3589: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Mesothelioma: Pleural, Version 1.2024.

Stevenson, James / Ettinger, David S / Wood, Douglas E / Aisner, Dara L / Akerley, Wallace / Bauman, Jessica R / Bharat, Ankit / Bruno, Debora S / Chang, Joe Y / Chirieac, Lucian R / DeCamp, Malcolm / Desai, Aakash / Dilling, Thomas J / Dowell, Jonathan / Durm, Gregory A / Garassino, Marina C / Gettinger, Scott / Grotz, Travis E / Gubens, Matthew A /

Lackner, Rudy P / Lanuti, Michael / Lin, Jules / Loo, Billy W / Lovly, Christine M / Maldonado, Fabien / Massarelli, Erminia / Morgensztern, Daniel / Mullikin, Trey C / Ng, Thomas / Otterson, Gregory A / Owen, Dawn / Patel, Sandip P / Patil, Tejas / Polanco, Patricio M / Riely, Gregory J / Riess, Jonathan / Shapiro, Theresa A / Singh, Aditi P / Tam, Alda / Tanvetyanon, Tawee / Yanagawa, Jane / Yang, Stephen C / Yau, Edwin / Gregory, Kristina / Hang, Lisa

Journal of the National Comprehensive Cancer Network : JNCCN

2024 Volume 22, Issue 2, Page(s) 72–81

Abstract: Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents ... ...

Abstract	Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.
MeSH term(s)	Humans ; Pleura ; Mesothelioma/diagnosis ; Mesothelioma/therapy ; Mesothelioma, Malignant ; Pleural Neoplasms/diagnosis ; Pleural Neoplasms/therapy
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2024.0014
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Zs.A 6365: Show issues

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Article ; Online: C-terminal binding protein (CTBP2) is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma.

Cheung, Coty Hing Yau / Cheng, Chi Keung / Leung, Kam Tong / Zhang, Chi / Ho, Chi Yan / Luo, Xi / Kam, Angel Yuet Fong / Xia, Tian / Wan, Thomas Shek Kong / Pitts, Herbert Augustus / Chan, Natalie Pui Ha / Cheung, Joyce Sin / Wong, Raymond Siu Ming / Zhang, Xiao-Bing / Ng, Margaret Heung Ling

Blood advances

2024

Abstract: ... an unappreciated tumor suppressive role of C-terminal Binding Protein 2 (CTBP2) in MM via strong inhibition ...

Abstract	Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation target IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable" as the majority of small molecule inhibitors suffers from low potency, suboptimal pharmacokinetic properties and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncover an unappreciated tumor suppressive role of C-terminal Binding Protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features and adverse clinical outcomes. Restoration of CTBP2 exhibited potent anti-tumor effects against MM in vitro and in vivo, with marked repression of MYC-IRF4 network genes. Mechanistically, CTBP2 impeded transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac), and indirectly via activation of MYC repressor IFIT3. In addition, activation of interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies revealed contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2 (EZH2), histone deacetylase (HDACs) and DNA methyltransferase (DNMTs) currently under evaluation in clinical trials were effective in restoring CTBP2 expression in MM. Our findings indicated that loss of CTBP2 plays an essential role in myelomagenesis and decipher an additional mechanistic link on MYC-IRF4 dysregulation in MM. We envision that identification of novel critical regulators would facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy.
Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023010218
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Zs.A 7153: Show issues

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Article ; Online: Association Between Household Online Grocery Delivery Service Use and Food and Drink Purchase Behavior in England: Cross-Sectional Analysis.

Yau, Amy / Law, Cherry / Cornelsen, Laura / Adams, Jean / Boyland, Emma / Burgoine, Thomas / de Vocht, Frank / White, Martin / Cummins, Steven

JMIR public health and surveillance

2023 Volume 9, Page(s) e41540

Abstract: Background: Online grocery delivery services (OGDSs) are a popular way of acquiring food. However, it is unclear whether OGDS use is associated with the healthiness of purchases and whether there are sociodemographic differences in OGDS use. If so, the ... ...

Abstract	Background: Online grocery delivery services (OGDSs) are a popular way of acquiring food. However, it is unclear whether OGDS use is associated with the healthiness of purchases and whether there are sociodemographic differences in OGDS use. If so, the increased prevalence of OGDS use may have implications for population diet, and differential OGDS use could contribute to diet inequalities. Objective: This study aimed to examine whether OGDS use varies by sociodemographic characteristics and is associated with the amount and types of groceries purchased. Methods: Item-level take-home food and drink purchase data (n=3,233,920 items) from households in London and the North of England were available from the 2019 UK Kantar fast-moving consumer goods panel (N=1911). Purchases were categorized as being bought online or in-store. We used logistic regression to estimate the likelihood of an above-median frequency of OGDS use by sociodemographic characteristics. We used Poisson regression to estimate the differences in energy and nutrients purchased by households that had above- and below-median OGDS use and the proportion of energy purchased from products high in fat, salt, and sugar (HFSS) online versus in-store among households that used both shopping methods (n=665). Results: In total, 668 (35%) households used OGDSs at least once in 2019. Of the households that used OGDSs, the median use was 5 occasions in 2019. Households were more likely to have above-median use in London versus in the North of England (odds ratio 1.29, 95% CI 1.01-1.65) and if they had a higher annual household income (odds ratio 1.56, 95% CI 1.02-2.38 for ≥£50,000 [US $64,000] vs <£20,000 [$25,600]). Households with above-median OGDS use had a higher weekly mean purchase of energy by 1461 (95% CI 1448-1474) kcal per person compared with households with below-median OGDS use. For households that used a combination of in-store and online shopping, HFSS products made up a lower proportion (-10.1%, 95% CI -12% to -8.1%) of energy purchased online compared to in-store. Conclusions: Differences in grocery purchases between households with above- and below-median OGDS use could have positive or negative consequences. The extra energy purchased among households with above-median OGDS use could lead to overconsumption or food waste, which has negative consequences for population and environmental health. Alternatively, this extra energy may be replacing out-of-home purchasing, which tends to be less healthy, and may be beneficial for the population diet. Households made fewer HFSS purchases when shopping online compared to in-store, which may be due to differences in the shopping environment or experience, such as fewer promotions and advertisements when shopping online or not having to transport and carry purchases home. As higher-income households used OGDS more frequently, the implications of this sociodemographic pattern on dietary inequalities must be explored.
MeSH term(s)	Humans ; Food ; Cross-Sectional Studies ; Refuse Disposal ; Diet ; England
Language	English
Publishing date	2023-12-19
Publishing country	Canada
Document type	Journal Article
ISSN	2369-2960
ISSN (online)	2369-2960
DOI	10.2196/41540
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Article: Duration of Endocrine Treatment for DCIS impacts second events: Insights from a large cohort of cases at two academic medical centers.

O'Keefe, Thomas / Yau, Christina / Iaconetti, Emma / Jeong, Eliza / Brabham, Case / Kim, Paul / McGuire, Joseph / Griffin, Ann / Wallace, Anne / Esserman, Laura / Harismendy, Olivier / Hirst, Gillian

Research square

2024

Abstract: Ductal carcinoma in situ (DCIS) incidence has risen rapidly with the introduction of screening mammography, yet it is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, (RT), endocrine therapy (ET)) versus what ... ...

Abstract	Ductal carcinoma in situ (DCIS) incidence has risen rapidly with the introduction of screening mammography, yet it is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, (RT), endocrine therapy (ET)) versus what constitutes over-treatment. Our goal was to identify the effects of adjuvant RT, or ET+/- RT versus breast conservation surgery (BCS) alone in a large multi-center registry of retrospective DCIS cases (N = 1,916) with median follow up of 8.2 years. We show that patients with DCIS who took less than 2 years of adjuvant ET alone have a similar second event rate as BCS. However, patients who took more than 2 years of ET show a significantly reduced second event rate, similar to those who received either RT or combined ET+RT, which was independent of age, tumor size, grade, or period of diagnosis. This highlights the importance of ET duration for risk reduction.
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3403438/v1
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Article ; Online: Ramucirumab for Patients with Advanced Hepatocellular Carcinoma and Elevated Alpha Fetoprotein Following Non-Sorafenib Systemic Therapy: An Expansion Cohort of REACH-2.

Finn, Richard S / Yau, Thomas / Hsu, Chih-Hung / De Toni, Enrico N / Goyal, Lipika / Galle, Peter R / Qin, ShuKui / Rao, Sujata / Sun, Fangfang / Wang, Chunxiao / Widau, Ryan C / Zhu, Andrew X

The oncologist

2022 Volume 27, Issue 12, Page(s) e938–e948

Abstract: Background: Ramucirumab is indicated for patients with advanced hepatocellular carcinoma (HCC) and α-fetoprotein (AFP) ≥400 ng/mL following sorafenib. Here, we prospectively studied ramucirumab following non-sorafenib systemic therapies.: Materials ... ...

Abstract	Background: Ramucirumab is indicated for patients with advanced hepatocellular carcinoma (HCC) and α-fetoprotein (AFP) ≥400 ng/mL following sorafenib. Here, we prospectively studied ramucirumab following non-sorafenib systemic therapies. Materials and methods: This open-label, non-comparative cohort of REACH-2 enrolled patients with advanced HCC, Child-Pugh class-A liver disease, and AFP ≥400 ng/mL who had received 1-2 lines of therapy, excluding sorafenib or chemotherapy. Ramucirumab was administered 8 mg/kg intravenously Q2W. The primary endpoint was safety. Secondary endpoints were overall survival, progression-free survival, objective response rate (RECIST v1.1), time to progression, pharmacokinetics, and patient-reported outcomes. Final analysis occurred after all enrolled patients completed ≥3 treatment cycles or discontinued treatment. Results: Between April 27, 2018, and March 29, 2021, 47 patients were treated at 21 investigative sites in Asia, Europe, and USA. The most frequently reported grade ≥3 adverse events, regardless of causality, were hypertension (11%), proteinuria (6%), hyponatremia (6%), and AST increased (6%). Two patients died from adverse events (myocardial infarction and upper gastrointestinal hemorrhage), deemed related to treatment. Median progression-free survival, time to progression, and overall survival were 1.7 months, 2.8 months, and 8.7 months, respectively. The objective response rate was 10.6% with a median duration response of 8.3 months. Median time to deterioration in FHSI-8 total score was 4.4 months. Conclusion: Ramucirumab demonstrated consistent and meaningful clinical activity with no new safety signals following non-sorafenib therapies in patients with advanced HCC and AFP ≥400 ng/mL. This represents one of the first sequencing studies for patients with advanced HCC not treated with sorafenib.
MeSH term(s)	Humans ; Sorafenib/therapeutic use ; Carcinoma, Hepatocellular/drug therapy ; alpha-Fetoproteins ; Liver Neoplasms/drug therapy ; Europe
Chemical Substances	Sorafenib (9ZOQ3TZI87) ; alpha-Fetoproteins
Language	English
Publishing date	2022-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac183
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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