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Article ; Online: Synthesis of

Nguyen, Hillary M H / Thomas, David C / Hart, Marie A / Steenback, Kaila R / Levy, Jeffrey N / McNally, Andrew

Journal of the American Chemical Society

2024 Volume 146, Issue 5, Page(s) 2944–2949

Abstract: Methods to incorporate stable radioisotopes are integral to pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods to ... ...

Abstract	Methods to incorporate stable radioisotopes are integral to pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods to incorporate
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.3c12445
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Article ; Online: An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases.

Broadhurst, Philip J / Hart, Andrew R

Journal of cancer research and clinical oncology

2020 Volume 146, Issue 5, Page(s) 1369–1375

Abstract: Purpose: Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. ...

Abstract	Purpose: Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. Methods: Patient notes with PDAC were reviewed at a large teaching hospital over 2 years. Study variables were obtained from multiple sources of information. Results: 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. Conclusion: Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin's pharmacodynamic actions needs to be clarified.
MeSH term(s)	Aged ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/pathology ; Clinical Trials, Phase III as Topic ; Cross-Sectional Studies ; Female ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/secondary ; Male ; Metformin/therapeutic use ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/pathology ; Randomized Controlled Trials as Topic ; Retrospective Studies
Chemical Substances	Metformin (9100L32L2N)
Language	English
Publishing date	2020-03-10
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-020-03177-y
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Article: Progressing pancreaticobiliary medicine in the UK.

Hart, Andrew R / Johnson, Gavin / Huggett, Matthew T

Frontline gastroenterology

2019 Volume 10, Issue 3, Page(s) 206–207

Language	English
Publishing date	2019-06-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2521857-8
ISSN	2041-4137
ISSN	2041-4137
DOI	10.1136/flgastro-2019-101192
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Article ; Online: Metastatic Carcinoma of Prostate as a Mimicker of SAPHO Syndrome.

Sehgal, Rahul / Virata, Andrew R / Bansal, Pankaj / Hart, Melissa

Clinical medicine & research

2021 Volume 19, Issue 3, Page(s) 141–147

Abstract: Paraneoplastic arthritides are a group of immune-mediated inflammatory arthropathies associated with occult or manifest malignancy. Musculoskeletal spread of an underlying malignancy may also mimic many rheumatologic conditions. Distinguishing primary ... ...

Abstract	Paraneoplastic arthritides are a group of immune-mediated inflammatory arthropathies associated with occult or manifest malignancy. Musculoskeletal spread of an underlying malignancy may also mimic many rheumatologic conditions. Distinguishing primary rheumatologic condition from paraneoplastic arthritides versus direct musculoskeletal spread of malignancy can be challenging especially in individuals with prior history of cancer and new musculoskeletal complaints. SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is an uncommon, although under recognized autoimmune disorder. Two musculoskeletal manifestations, namely inflammatory osteitis and hyperostosis of anterior chest wall with or without dermatologic manifestations, constitute a unifying feature of SAPHO syndrome. However, diagnosis of SAPHO syndrome is one of exclusion, and a wide variety of disorders including infections, malignancy (chondrosarcoma/osteosarcoma/metastasis), metabolic bone disorders (Paget's disease), osteoarthritis, seronegative spondyloarthropathy (spA) and osteonecrosis form part of a broad differential diagnosis. We present the case of a man, aged 72 years, with signs and symptoms of SAPHO syndrome and skin findings. Detailed history, radiological imaging, dermatology appearance, and role of immunohistochemical markers, especially staining for NKX3.1 protein with a novel antibody, led to a diagnosis of metastatic prostate adenocarcinoma. To our knowledge, this is the first case of metastatic adenocarcinoma of the prostate manifesting as SAPHO syndrome and cutaneous metastasis.
MeSH term(s)	Acquired Hyperostosis Syndrome/diagnosis ; Carcinoma ; Humans ; Hyperostosis ; Male ; Osteitis ; Prostate
Language	English
Publishing date	2021-05-13
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2303793-3
ISSN	1554-6179 ; 1539-4182
ISSN (online)	1554-6179
ISSN	1539-4182
DOI	10.3121/cmr.2021.1539
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Article: Evaluation of Differences in Patellar Height After Patellar Stabilization Procedures Not Intended to Address Patella Alta: A Multicenter Study.

Kreulen, R Timothy / Anderson, Gregory / Yalcin, Sercan / Hart, Joseph M / Shank, Kaitlyn / Fury, Matthew S / Elias, John J / Tanaka, Miho J / Farrow, Lutul D / Diduch, David R / Cosgarea, Andrew J

Orthopaedic journal of sports medicine

2024 Volume 12, Issue 3, Page(s) 23259671241235597

Abstract: Background: Recent studies have reported conflicting results as to whether isolated medial patellofemoral ligament reconstruction (MPFLr) leads to decreased patellar height.: Purpose: To investigate if patellar stabilization surgery not intended to ... ...

Abstract	Background: Recent studies have reported conflicting results as to whether isolated medial patellofemoral ligament reconstruction (MPFLr) leads to decreased patellar height. Purpose: To investigate if patellar stabilization surgery not intended to address patella alta influences patellar height. Study design: Cohort study; Level of evidence, 3. Methods: A multicenter retrospective chart review was conducted, and patients who underwent MPFLr, medializing tibial tuberosity osteotomy (TTO), and/or trochleoplasty between 2016 and 2020 were included. The Caton-Deschamps index (CDI) was calculated from radiographs obtained preoperatively, 2 weeks postoperatively, and 3 months postoperatively. The preoperative CDI value was compared with the 2-week postoperative and 3-month postoperative values according to stabilization procedure (isolated MPFLr, isolated TTO, MPFLr + TTO, MPFLr + trochleoplasty, and MPFLr + trochleoplasty + TTO) using the paired Results: A total of 356 knees were included. Statistically significant pre- to postoperative decreases in CDI were seen in all stabilization procedures analyzed ( Conclusion: The different surgical techniques analyzed in the current study affected patellar height, even when a distalizing TTO was not performed. The decrease was dependent on surgical technique, with a 2-bundle MPFLr leading to a statistically significant decrease and a 1-bundle MPFLr effecting no change.
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2706251-X
ISSN	2325-9671
ISSN	2325-9671
DOI	10.1177/23259671241235597
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Article ; Online: DNA sequencing, microbial indicators, and the discovery of buried kimberlites.

Simister, Rachel L / Iulianella Phillips, Bianca P / Wickham, Andrew P / Cayer, Erika M / Hart, Craig J R / Winterburn, Peter A / Crowe, Sean A

Communications earth & environment

2023 Volume 4, Issue 1, Page(s) 387

Abstract: Population growth and technological advancements are placing growing demand on mineral resources. New and innovative exploration technologies that improve detection of deeply buried mineralization and host rocks are required to meet these demands. Here ... ...

Abstract	Population growth and technological advancements are placing growing demand on mineral resources. New and innovative exploration technologies that improve detection of deeply buried mineralization and host rocks are required to meet these demands. Here we used diamondiferous kimberlite ore bodies as a test case and show that DNA amplicon sequencing of soil microbial communities resolves anomalies in microbial community composition and structure that reflect the surface expression of kimberlites buried under 10 s of meters of overburden. Indicator species derived from laboratory amendment experiments were employed in an exploration survey in which the species distributions effectively delineated the surface expression of buried kimberlites. Additional indicator species derived directly from field observations improved the blind discovery of kimberlites buried beneath similar overburden types. Application of DNA sequence-based analyses of soil microbial communities to mineral deposit exploration provides a powerful illustration of how genomics technologies can be leveraged in the discovery of critical new resources.
Language	English
Publishing date	2023-10-21
Publishing country	England
Document type	Journal Article
ISSN	2662-4435
ISSN (online)	2662-4435
DOI	10.1038/s43247-023-01020-z
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Article ; Online: Computational design of hepatitis C virus immunogens from host-pathogen dynamics over empirical viral fitness landscapes.

Hart, Gregory R / Ferguson, Andrew L

Physical biology

2018 Volume 16, Issue 1, Page(s) 16004

Abstract: Hepatitis C virus (HCV) afflicts 170 million people and kills 700 000 annually. Vaccination offers the most realistic and cost effective hope of controlling this epidemic, but despite 25 years of research, no vaccine is available. A major obstacle is HCV' ...

Abstract	Hepatitis C virus (HCV) afflicts 170 million people and kills 700 000 annually. Vaccination offers the most realistic and cost effective hope of controlling this epidemic, but despite 25 years of research, no vaccine is available. A major obstacle is HCV's extreme genetic variability and rapid mutational escape from immune pressure. Coupling maximum entropy inference with population dynamics simulations, we have employed a computational approach to translate HCV sequence databases into empirical landscapes of viral fitness and simulate the intrahost evolution of the viral quasispecies over these landscapes. We explicitly model the coupled host-pathogen dynamics by combining agent-based models of viral mutation with stochastically-integrated coupled ordinary differential equations for the host immune response. We validate our model in predicting the mutational evolution of the HCV RNA-dependent RNA polymerase (protein NS5B) within seven individuals for whom longitudinal sequencing data is available. We then use our approach to perform exhaustive in silico evaluation of putative immunogen candidates to rationally design tailored vaccines to simultaneously cripple viral fitness and block mutational escape within two selected individuals. By systematically identifying a small number of promising vaccine candidates, our empirical fitness landscapes and host-pathogen dynamics simulator can guide and accelerate experimental vaccine design efforts.
MeSH term(s)	Algorithms ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/virology ; Computer Simulation ; Evolution, Molecular ; Hepacivirus/genetics ; Hepacivirus/immunology ; Hepacivirus/physiology ; Hepatitis C/immunology ; Hepatitis C/virology ; Host-Pathogen Interactions ; Humans ; Immunity ; Models, Immunological ; Mutation ; Viral Hepatitis Vaccines/immunology ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/immunology
Chemical Substances	Viral Hepatitis Vaccines ; Viral Nonstructural Proteins ; NS-5 protein, hepatitis C virus (EC 2.7.7.48)
Language	English
Publishing date	2018-11-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2133216-2
ISSN	1478-3975 ; 1478-3967
ISSN (online)	1478-3975
ISSN	1478-3967
DOI	10.1088/1478-3975/aaeec0
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Article ; Online: Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use.

Broadhurst, Philip J / Hart, Andrew R

Digestive diseases and sciences

2018 Volume 63, Issue 11, Page(s) 2840–2852

Abstract: Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely ... ...

Abstract	Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug-drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress.
MeSH term(s)	Carcinoma, Pancreatic Ductal/drug therapy ; Humans ; Hypoglycemic Agents/pharmacokinetics ; Hypoglycemic Agents/therapeutic use ; Metformin/pharmacokinetics ; Metformin/therapeutic use ; Pancreatic Neoplasms/drug therapy ; Proof of Concept Study ; Randomized Controlled Trials as Topic
Chemical Substances	Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2018-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-018-5233-y
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Article ; Online: Author Correction: Basin-scale reconstruction of euxinia and Late Devonian mass extinctions.

Sahoo, Swapan K / Gilleaudeau, Geoffrey J / Wilson, Kathleen / Hart, Bruce / Barnes, Ben D / Faison, Tytrice / Bowman, Andrew R / Larson, Toti E / Kaufman, Alan J

Nature

2023 Volume 617, Issue 7960, Page(s) E6

Language	English
Publishing date	2023-04-11
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/s41586-023-05999-5
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Article ; Online: The use of wing fray and sex ratios to determine the origin of flies at an indoor crime scene.

Beutler, Meghan / Hart, Andrew / Hall, Martin J R

Forensic science international

2019 Volume 307, Page(s) 110104

Abstract: When adult flies are collected at indoor crime scenes, the question of their origin arises, i.e., whether they originated from the outdoors, coming in to oviposit on the body, or if they developed through the larval and pupal stages from eggs laid on the ...

Abstract	When adult flies are collected at indoor crime scenes, the question of their origin arises, i.e., whether they originated from the outdoors, coming in to oviposit on the body, or if they developed through the larval and pupal stages from eggs laid on the body. This is particularly important if no empty puparia were collected, potentially because they were overlooked, with a consequent impact on the accuracy of the minimum post-mortem interval estimation. This study used two methods to determine if flies sampled in various experimental conditions and at an actual crime scene were wild flies attracted to the body or had developed on the body, i.e., through the assessment of: (1) wing fray and; (2) sex ratio. A template was created to measure the amount of wing fray damage quantitatively in a simple, rapid and efficient manner. The experiments demonstrated that by combining the two methods it is possible to establish the origin of a population of adult flies at a crime scene.
MeSH term(s)	Animals ; Diptera/anatomy & histology ; Feeding Behavior ; Female ; Forensic Entomology/methods ; Image Processing, Computer-Assisted ; Larva ; Male ; Microscopy ; Postmortem Changes ; Pupa ; Sex Ratio ; Wings, Animal/anatomy & histology
Language	English
Publishing date	2019-12-19
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	424042-x
ISSN	1872-6283 ; 0379-0738
ISSN (online)	1872-6283
ISSN	0379-0738
DOI	10.1016/j.forsciint.2019.110104
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