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1. [X/Fe] Marks the Spot: Mapping Chemical Azimuthal Variations in the Galactic Disk with APOGEE

Author

Hackshaw, Zoe, Hawkins, Keith, Filion, Carrie, Horta, Danny, Laporte, Chervin F. P., Carr, Chris, and Price-Whelan, Adrian M.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Solar and Stellar Astrophysics
Abstract

Chemical cartography of the Galactic disk provides insights to its structure and assembly history over cosmic time. In this work, we use chemical cartography to explore chemical gradients and azimuthal substructure in the Milky Way disk with giant stars from APOGEE DR17. We confirm the existence of a radial metallicity gradient in the disk of $\Delta$[Fe/H]/$\Delta$R $\sim -0.066 \pm 0.0004$ dex/kpc and a vertical metallicity gradient of $\Delta$[Fe/H]/$\Delta$Z $\sim -0.164 \pm 0.001$ dex/kpc. We find azimuthal variations ($\pm0.1$ dex) on top of the radial metallicity gradient that have been previously established with other surveys. The APOGEE giants show strong correlations with stellar age and the intensity of azimuthal variations in iron; older stellar populations show the largest deviations from the radial metallicity gradient. Beyond iron, we show that other elements (e.g., Mg, O) display azimuthal variations at the $\pm0.05$ dex-level across the Galactic disk. We illustrate that moving into the orbit-space could help constrain the mechanisms producing these azimuthal metallicity variations. These results suggest that the spiral arms of the Galaxy are not solely responsible for azimuthal metallicity variations and other Galactic processes are at play., Comment: 19 pages, 11 figures

Published
2024

2. Risk stratification in breast screening workshop

Author

Anderson, Andrew, Visintin, Cristina, Antoniou, Antonis, Pashayan, Nora, Gilbert, Fiona J., Hackshaw, Allan, Bhatt, Rikesh, Hill, Harry, Wright, Stuart, Payne, Katherine, Rogers, Gabriel, Shinkins, Bethany, Taylor-Phillips, Sian, and Given-Wilson, Rosalind

Published
2024
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3. Risk stratification in breast screening workshop

Author

Andrew Anderson, Cristina Visintin, Antonis Antoniou, Nora Pashayan, Fiona J. Gilbert, Allan Hackshaw, Rikesh Bhatt, Harry Hill, Stuart Wright, Katherine Payne, Gabriel Rogers, Bethany Shinkins, Sian Taylor-Phillips, and Rosalind Given-Wilson

Subjects
Breast cancer, Screening, Risk stratification, Epidemiology, Cost-effectiveness, Medicine, Science
Abstract

Abstract Population screening for breast cancer (BC) is currently offered in the UK for women aged 50 to 71 with the aim of reducing mortality. There is additional screening within the national programme for women identified as having a very high risk of BC. There is growing interest in further risk stratification in breast screening, which would require a whole population risk assessment and the subsequent offer of screening tailored to the individual’s risk. Some women would be offered more intensive screening than others or no screening. This might provide a better balance of screening benefits and harms for each individual than the current population age-based programme alone. The UK National Screening Committee (UK NSC) is considering using decision-analytic and other models to evaluate different risk stratification screening strategies and identify remaining gaps in evidence. This paper reports the proceedings of a UK NSC workshop where experts in the field discussed both risk prediction models, as well as decision-analytic models providing a benefit-harm analysis/economic evaluation of risk-stratified screening programmes (see Table 1). The aim of the meeting was to present and discuss the current work of experts, including some data which had not been published at the time of the meeting, to inform the UK NSC. The workshop was not intended to present a balanced evaluation of how to deliver screening in future. Areas for further work identified included methods for comparing models to assess accuracy, the optimum risk assessment tools, the digital screening infrastructure, acceptability of stratification, choice of screening test and reducing inequalities. A move to risk stratification of the whole programme would require a careful phased introduction with continuing assessment of real-world evidence during deployment.

Published
2024
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5. Uranium Abundances and Ages of $R$-process Enhanced Stars with Novel U II Lines

Author

Shah, Shivani P., Ezzeddine, Rana, Ji, Alexander P., Hansen, Terese, Roederer, Ian U., Catelan, Márcio, Hackshaw, Zoe, Holmbeck, Erika M., Beers, Timothy C., and Surman, Rebecca

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

The ages of the oldest stars shed light on the birth, chemical enrichment, and chemical evolution of the Universe. Nucleocosmochronometry provides an avenue to determining the ages of these stars independent from stellar evolution models. The uranium abundance, which can be determined for metal-poor $r$-process enhanced (RPE) stars, has been known to constitute one of the most robust chronometers known. So far, U abundance determination has used a $single$ U II line at $\lambda3859$ \r{A}. Consequently, U abundance has been reliably determined for only five RPE stars. Here, we present the first homogeneous U abundance analysis of four RPE stars using two novel U II lines at $\lambda4050$ \r{A} and $\lambda4090$ \r{A}, in addition to the canonical $\lambda3859$ \r{A} line. We find that the U II lines at $\lambda4050$ \r{A} and $\lambda4090$ \r{A} are reliable and render U abundances in agreement with the $\lambda3859$ U abundance, for all the stars. We, thus, determine revised U abundances for RPE stars, 2MASS J09544277+5246414, RAVE J203843.2-002333, HE 1523-0901, and CS 31082-001, using multiple U II lines. We also provide nucleocosmochronometric ages of these stars based on the newly derived U, Th, and Eu abundances. The results of this study open up a new avenue to reliably and homogeneously determine U abundance for a significantly larger number of RPE stars. This will, in turn, enable robust constraints on the nucleocosmochronometric ages of RPE stars, which can be applied to understand the chemical enrichment and evolution in the early Universe, especially of $r$-process elements., Comment: Resubmitted to ApJ

Published
2023
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6. Discovery of a Metal-Poor Red Giant Star with the Highest Ultra-Lithium Enhancement

Author

Kowkabany, Jeremy, Ezzeddine, Rana, Charbonnel, Corinne, Roederer, Ian U., Wang, Ella Xi, Li, Yangyang, Hackshaw, Zoe, Beers, Timothy C., Frebel, Anna, Hansen, Terese T., Holmbeck, Erika, Placco, Vinicius M., and Sakari, Charli M.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

We present the discovery of 2MASS J05241392-0336543 (hereafter J0524-0336), a very metal-poor ([Fe/H]=-2.43 +- 0.16), highly r-process-enhanced ([Eu/Fe]= +1.34 +- 0.10) Milky Way halo field red giant star, with an ultra high Li abundance of A(Li)(3D,NLTE)= 6.15 +- 0.25 and [Li/Fe]= +7.64 +- 0.25, respectively. This makes J0524-0336 the most lithium-enhanced giant star discovered to date. We present a detailed analysis of the star's atmospheric stellar parameters and chemical abundance determinations. Additionally, we detect indications of infrared excess, as well as observe variable emission in the wings of the H_alpha absorption line across multiple epochs, indicative of a potential enhanced mass-loss event with possible outflows. Our analysis reveals that J0524-0336 lies either between the bump and the tip of the Red Giant Branch (RGB), or on the early-Asymptotic Giant Branch (e-AGB). We investigate the possible sources of lithium enrichment in J0524-0336, including both internal and external sources. Based on current models and on the observational evidence we have collected, our study shows that J0524-0336 may be undergoing the so-called lithium flash that is expected to occur in low-mass stars when they reach the RGB bump and/or the early-AGB., Comment: 25 pages, 4 tables, 10 figures, Accepted for publication in ApJ

Published
2022
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7. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author

Pan, Xiaoxi, AbdulJabbar, Khalid, Coelho-Lima, Jose, Grapa, Anca-Ioana, Zhang, Hanyun, Cheung, Alvin Ho Kwan, Baena, Juvenal, Karasaki, Takahiro, Wilson, Claire Rachel, Sereno, Marco, Veeriah, Selvaraju, Aitken, Sarah J., Hackshaw, Allan, Nicholson, Andrew G., Jamal-Hanjani, Mariam, Swanton, Charles, Yuan, Yinyin, Le Quesne, John, and Moore, David A.

Published
2024
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8. Characteristics and Outcomes of Patients in the Emergency Department with Left Ventricular Assist Devices

Author

Finch, Alexander S., Mohseni, Michael M., Simon, Leslie V., Finch, Jennifer G., Gordon-Hackshaw, Lemuel E., Klassen, Aaron B., Mullan, Aiden F., Barbara, David W., and Sandefur, Benjamin J.

Subjects
emergency department, left ventricular assist device, outcomes, resuscitation
Abstract

Introduction: Left ventricular assist devices (LVAD) are increasingly common among patients with heart failure. The unique physiologic characteristics of patients with LVADs present a challenge to emergency clinicians making treatment and disposition decisions. Despite the increasing prevalence of LVADs, literature describing emergency department (ED) visits among this population is sparse. We aimed to describe clinical characteristics and outcomes among patients with LVADs seen in two quaternary-care EDs in a five-year period. Secondarily, we sought to evaluate mortality rates and ED return rates for bridge to transplant (BTT) and destination therapy (DT) patients.Methods: We conducted a retrospective cohort study of adult patients known to have an LVAD who were evaluated in two quaternary-care EDs from 2013–2017. Data were collected from the electronic health record and summarized with descriptive statistics. We assessed patient outcomes with mixed-effects logistic regression models including a random intercept to account for patients with multiple ED visits.Results: During the five-year study period, 290 ED visits among 107 patients met inclusion criteria. The median patient age was 61 years. The reason for LVAD implantation was BTT in 150 encounters (51.7%) and DT in 140 (48.3%). The most common presenting concerns were dyspnea (21.7%), bleeding (18.6%), and chest pain (11.4%). Visits directly related to the LVAD were infrequent (7.9%). Implantable cardioverter-defibrillator discharge was reported in 3.4% of visits. A majority of patients were dismissed home from the ED (53.8%), and 4.5% required intensive care unit admission. Among all patients, 37.9%returned to the ED within 30 days, with similar rates between DT and BTT patients (32.1 vs 43.3%; P = 0.055). The LVAD was replaced in three cases (1.0%) during hospitalization. No deaths occurred in the ED, and the mortality rate within 30 days was 2.1% among all patients.Conclusion: In this multicenter cohort study of ED visits among patients with an LVAD, dyspnea, bleeding, and chest pain were the most common presenting concerns. Visits directly related to the LVAD were uncommon. Approximately half of patients were dismissed home, although return ED visits were common.

Published
2023

9. Urinary biomarkers in metastatic bone pain: Results from a multicentre randomized trial of ibandronate compared to single dose radiotherapy for localized metastatic bone pain in prostate cancer (RIB)

Author

P.J. Hoskin, Aman Malhi, Krystyna Reczko, and Allan Hackshaw

Subjects
Ibandronate, Radiotherapy, Bisphosphonate, Osteoclasts, Metastatic bone pain, Biomarkers, Diseases of the musculoskeletal system, RC925-935, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: The Radiotherapy IBandronate (RIB) trial compared single dose radiotherapy and a single infusion of ibandronate in 470 bisphosphonate naïve patients with metastatic bone pain from prostate cancer randomised into a non-inferiority two arm study. Results for the primary endpoint of pain score response at 4 weeks showed that the ibandronate arm was non-inferior to single dose radiotherapy. Patients and method: In addition to pain assessments including analgesic use made at baseline, 4, 8, 12, 26 and 52 weeks, urine was collected at baseline, 4 and 12 weeks. It was subsequently analysed for urinary N-telopeptide (NTx) and cystatin C. Linear regression models were used to compare the continuous outcome measures for urinary markers within treatment arms and baseline measurements were included as covariates. Interaction terms were fitted to allow for cross-treatment group comparisons. Results: The primary endpoint of the RIB trial was worst pain response at 4 weeks and there was no treatment difference seen. Urine samples and paired pain scores at 4 weeks were available for 273 patients (radiotherapy 168; ibandronate 159)The baseline samples measured for the RIB trial had an average concentration of 193 nM BCE/mM creatinine (range of 7.3–1871) compared to the quoted normal range of 33 nM BCE/mM creatinine (3 to 63). In contrast the average value of Cystatin C was 66 ng/ml (ranges ND – 1120 ng/ml) compared to the quoted normal range of 62.9 ng/ml (ranges 12.6–188 ng/ml). A statistically significant reduction in NTx concentrations between baseline and 4 weeks was seen in the ibandronate arm but not in the radiotherapy arm. No correlation between pain response and urinary marker concentration was seen in either the ibandronate or radiotherapy cohort at any time point. Conclusion: NTx was significantly raised compared to the normal range consistent with a role as a biomarker for bone metastases from prostate cancer. A significant reduction in NTx 4 weeks after ibandronate is consistent with its action in osteoclast inhibition which was not seen after radiotherapy implying a different mode of action for radiation. There was no correlation between bone biomarker levels and pain response.

Published
2024
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10. Overall and non‐lung cancer incidence and mortality in the National Lung Screening Trial: Opportunities for multi‐cancer early detection

Author

Alpa V. Patel, Ellen T. Chang, Allan Hackshaw, Sam M. Janes, Diana S. M. Buist, Earl Hubbell, Christina A. Clarke, and Graham A. Colditz

Subjects
cancer risk, cancer screening, early detection of cancer, multi‐cancer early detection, National Lung Screening Trial, population health, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Currently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers. Methods The National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009. Results Among 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths. Conclusions In the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality.

Published
2024
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11. Author Correction: The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2024
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12. Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial

Author

Reed, Nicholas, Drake, Anne, Bashir, Faheem, Cook, Audrey, Mandal, Ranajit, Barraclough, Lisa, Dubey, Sidarth, Park, Won-Ho Edward, Pilar, Maria, Gallardo, Dolores, Alamilla-Garcia, Gabriela, Colombo, Nicoletta, Adusumalli, Madhavi, Kent, Christopher, Panades, Miguel, King, Margaret, Wade, Robert, Forrest, Jennifer, Mak, Choi, Anand, Anjana, McGrane, John, Persic, Mojca, Bhana, Rajanee, Lankester, Kate, Chowdhury, Rahul Roy, McFarlane, Vicky, Powell, Melanie, Whitmarsh, Karen, McCormack, Mary, Eminowicz, Gemma, Hudson, Emma, Mathew, Tony, Diez, Patricia, Farrelly, Laura, Mukhopadhyay, Asima, Chávez-Blanco, Adriana, Stobart, Hilary, Feeney, Amanda, Vaja, Simran, Hacker, Anne-Marie, Hackshaw, Allan, and Ledermann, Jonathan Andrew

Published
2024
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16. Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Author

Eschweiler, Simon, Ramírez-Suástegui, Ciro, Li, Yingcong, King, Emma, Chudley, Lindsey, Thomas, Jaya, Wood, Oliver, von Witzleben, Adrian, Jeffrey, Danielle, McCann, Katy, Simon, Hayley, Mondal, Monalisa, Wang, Alice, Dicker, Martina, Lopez-Guadamillas, Elena, Chou, Ting-Fang, Dobbs, Nicola, Essame, Louisa, Acton, Gary, Kelly, Fiona, Halbert, Gavin, Sacco, Joseph, Schache, Andrew, Shaw, Richard, McCaul, James, Paterson, Claire, Davies, Joseph, Brennan, Peter, Singh, Rabindra, Loadman, Paul, Wilson, William, Hackshaw, Allan, Seumois, Gregory, Okkenhaug, Klaus, Thomas, Gareth, Jones, Terry, Ay, Ferhat, Friberg, Greg, Vanhaesebroeck, Bart, Vijayanand, Pandurangan, Ottensmeier, Christian, and Kronenberg, Mitchell

Subjects
Adenosine, Animals, Antineoplastic Agents, Disease Models, Animal, Head and Neck Neoplasms, Humans, Immunotherapy, Mice, Phosphatidylinositol 3-Kinases, Quinolines, T-Lymphocytes, Regulatory
Abstract

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Published
2022

17. Characteristics and Outcomes of Patients in the Emergency Department with Left Ventricular Assist Devices

Author

Alexander S. Finch, Michael M. Mohseni, Leslie V. Simon, Jennifer G. Finch, Lemuel E. Gordon-Hackshaw, Aaron B. Klassen, Aidan F. Mullan, David W. Barbara, and Benjamin J. Sandefur

Subjects
Medicine, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Introduction: Left ventricular assist devices (LVAD) are increasingly common among patients with heart failure. The unique physiologic characteristics of patients with LVADs present a challenge to emergency clinicians making treatment and disposition decisions. Despite the increasing prevalence of LVADs, literature describing emergency department (ED) visits among this population is sparse. We aimed to describe clinical characteristics and outcomes among patients with LVADs seen in two quaternary-care EDs in a five-year period. Secondarily, we sought to evaluate mortality rates and ED return rates for bridge to transplant (BTT) and destination therapy (DT) patients. Methods: We conducted a retrospective cohort study of adult patients known to have an LVAD who were evaluated in two quaternary-care EDs from 2013–2017. Data were collected from the electronic health record and summarized with descriptive statistics. We assessed patient outcomes with mixed-effects logistic regression models including a random intercept to account for patients with multiple ED visits. Results: During the five-year study period, 290 ED visits among 107 patients met inclusion criteria. The median patient age was 61 years. The reason for LVAD implantation was BTT in 150 encounters (51.7%) and DT in 140 (48.3%). The most common presenting concerns were dyspnea (21.7%), bleeding (18.6%), and chest pain (11.4%). Visits directly related to the LVAD were infrequent (7.9%). Implantable cardioverter-defibrillator discharge was reported in 3.4% of visits. A majority of patients were dismissed home from the ED (53.8%), and 4.5% required intensive care unit admission. Among all patients, 37.9% returned to the ED within 30 days, with similar rates between DT and BTT patients (32.1 vs 43.3%; P = 0.055). The LVAD was replaced in three cases (1.0%) during hospitalization. No deaths occurred in the ED, and the mortality rate within 30 days was 2.1% among all patients. Conclusion: In this multicenter cohort study of ED visits among patients with an LVAD, dyspnea, bleeding, and chest pain were the most common presenting concerns. Visits directly related to the LVAD were uncommon. Approximately half of patients were dismissed home, although return ED visits were common.

Published
2023
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19. Surface-Enhanced Raman Spectroscopy Combined with Multivariate Analysis for Fingerprinting Clinically Similar Fibromyalgia and Long COVID Syndromes

Author

Shreya Madhav Nuguri, Kevin V. Hackshaw, Silvia de Lamo Castellvi, Yalan Wu, Celeste Matos Gonzalez, Chelsea M. Goetzman, Zachary D. Schultz, Lianbo Yu, Rija Aziz, Michelle M. Osuna-Diaz, Katherine R. Sebastian, W. Michael Brode, Monica M. Giusti, and Luis Rodriguez-Saona

Subjects
long COVID, fibromyalgia, surface-enhanced Raman spectroscopy, volumetric absorptive micro-sampling, dried bloodspot cards, Biology (General), QH301-705.5
Abstract

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10–20% of individuals following COVID-19 infection. FM and LC share similarities with regard to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface-enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCAs) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n = 48 FM and n = 46 LC) and volumetric absorptive micro-sampling tips (VAMS, n = 39 FM and n = 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra were acquired using SERS with gold nanoparticles (AuNPs). Soft independent modelling of class analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity, achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNP SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

Published
2024
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22. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author

Ng, Kevin W., Boumelha, Jesse, Enfield, Katey S. S., Almagro, Jorge, Cha, Hongui, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Sivakumar, Monica, Young, George, Molina-Arcas, Miriam, de Carné Trécesson, Sophie, Anastasiou, Panayiotis, Fendler, Annika, Au, Lewis, Shepherd, Scott T. C., Martínez-Ruiz, Carlos, Puttick, Clare, Black, James R. M., Watkins, Thomas B. K., Kim, Hyemin, Shim, Seohee, Faulkner, Nikhil, Attig, Jan, Veeriah, Selvaraju, Magno, Neil, Ward, Sophia, Frankell, Alexander M., Al Bakir, Maise, Lim, Emilia L., Hill, Mark S., Wilson, Gareth A., Cook, Daniel E., Birkbak, Nicolai J., Behrens, Axel, Yousaf, Nadia, Popat, Sanjay, Hackshaw, Allan, Hiley, Crispin T., Litchfield, Kevin, McGranahan, Nicholas, Jamal-Hanjani, Mariam, Larkin, James, Lee, Se-Hoon, Turajlic, Samra, Swanton, Charles, Downward, Julian, and Kassiotis, George

Published
2023
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23. The evolution of non-small cell lung cancer metastases in TRACERx

Author

Al Bakir, Maise, Huebner, Ariana, Martínez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas B. K., Pich, Oriol, Moore, David A., Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander M., Bunkum, Abigail, Lim, Emilia L., Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T., Hill, Mark S., Cook, Daniel E., Wilson, Gareth A., Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A., Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R., Blackhall, Fiona H., Cave, Judith, Blyth, Kevin G., Nair, Arjun, Ahmed, Asia, Taylor, Magali N., Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M., Janes, Sam M., Papadatos-Pastos, Dionysis, Forster, Martin D., Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio A., Peggs, Karl S., Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J., Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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24. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, Alexander M., Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L., Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S., Grigoriadis, Kristiana, Moore, David A., Black, James R. M., Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas B. K., Naceur-Lombardelli, Cristina, Cook, Daniel E., Salgado, Roberto, Wilson, Gareth A., Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martínez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G., Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M., Naidu, Babu, Middleton, Gary, Blyth, Kevin G., Fennell, Dean A., Forster, Martin D., Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J., Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G., Lester, Jason F., Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M., Lawrence, David, Navani, Neal, Janes, Sam M., Dive, Caroline, Blackhall, Fiona H., Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A., Peggs, Karl S., Schwarz, Roland F., Van Loo, Peter, Miedema, Daniël M., Birkbak, Nicolai J., Hiley, Crispin T., Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, and Swanton, Charles

Published
2023
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25. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author

Abbosh, Christopher, Frankell, Alexander M., Harrison, Thomas, Kisistok, Judit, Garnett, Aaron, Johnson, Laura, Veeriah, Selvaraju, Moreau, Mike, Chesh, Adrian, Chaunzwa, Tafadzwa L., Weiss, Jakob, Schroeder, Morgan R., Ward, Sophia, Grigoriadis, Kristiana, Shahpurwalla, Aamir, Litchfield, Kevin, Puttick, Clare, Biswas, Dhruva, Karasaki, Takahiro, Black, James R. M., Martínez-Ruiz, Carlos, Bakir, Maise Al, Pich, Oriol, Watkins, Thomas B. K., Lim, Emilia L., Huebner, Ariana, Moore, David A., Godin-Heymann, Nadia, L’Hernault, Anne, Bye, Hannah, Odell, Aaron, Roberts, Paula, Gomes, Fabio, Patel, Akshay J., Manzano, Elizabeth, Hiley, Crispin T., Carey, Nicolas, Riley, Joan, Cook, Daniel E., Hodgson, Darren, Stetson, Daniel, Barrett, J. Carl, Kortlever, Roderik M., Evan, Gerard I., Hackshaw, Allan, Daber, Robert D., Shaw, Jacqui A., Aerts, Hugo J. W. L., Licon, Abel, Stahl, Josh, Jamal-Hanjani, Mariam, Birkbak, Nicolai J., McGranahan, Nicholas, and Swanton, Charles

Published
2023
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26. Genomic–transcriptomic evolution in lung cancer and metastasis

Author

Martínez-Ruiz, Carlos, Black, James R. M., Puttick, Clare, Hill, Mark S., Demeulemeester, Jonas, Larose Cadieux, Elizabeth, Thol, Kerstin, Jones, Thomas P., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Rowan, Andrew, Ward, Sophia, Cubitt, Laura, Athanasopoulou, Foteini, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Colliver, Emma, Castignani, Carla, Dietzen, Michelle, Huebner, Ariana, Al Bakir, Maise, Tanić, Miljana, Watkins, Thomas B. K., Lim, Emilia L., Al-Rashed, Ali M., Lang, Danny, Clements, James, Cook, Daniel E., Rosenthal, Rachel, Wilson, Gareth A., Frankell, Alexander M., de Carné Trécesson, Sophie, East, Philip, Kanu, Nnennaya, Litchfield, Kevin, Birkbak, Nicolai J., Hackshaw, Allan, Beck, Stephan, Van Loo, Peter, Jamal-Hanjani, Mariam, Swanton, Charles, and McGranahan, Nicholas

Published
2023
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27. Lung adenocarcinoma promotion by air pollutants

Author

Hill, William, Lim, Emilia L., Weeden, Clare E., Lee, Claudia, Augustine, Marcellus, Chen, Kezhong, Kuan, Feng-Che, Marongiu, Fabio, Evans, Jr, Edward J., Moore, David A., Rodrigues, Felipe S., Pich, Oriol, Bakker, Bjorn, Cha, Hongui, Myers, Renelle, van Maldegem, Febe, Boumelha, Jesse, Veeriah, Selvaraju, Rowan, Andrew, Naceur-Lombardelli, Cristina, Karasaki, Takahiro, Sivakumar, Monica, De, Swapnanil, Caswell, Deborah R., Nagano, Ai, Black, James R. M., Martínez-Ruiz, Carlos, Ryu, Min Hyung, Huff, Ryan D., Li, Shijia, Favé, Marie-Julie, Magness, Alastair, Suárez-Bonnet, Alejandro, Priestnall, Simon L., Lüchtenborg, Margreet, Lavelle, Katrina, Pethick, Joanna, Hardy, Steven, McRonald, Fiona E., Lin, Meng-Hung, Troccoli, Clara I., Ghosh, Moumita, Miller, York E., Merrick, Daniel T., Keith, Robert L., Al Bakir, Maise, Bailey, Chris, Hill, Mark S., Saal, Lao H., Chen, Yilun, George, Anthony M., Abbosh, Christopher, Kanu, Nnennaya, Lee, Se-Hoon, McGranahan, Nicholas, Berg, Christine D., Sasieni, Peter, Houlston, Richard, Turnbull, Clare, Lam, Stephen, Awadalla, Philip, Grönroos, Eva, Downward, Julian, Jacks, Tyler, Carlsten, Christopher, Malanchi, Ilaria, Hackshaw, Allan, Litchfield, Kevin, DeGregori, James, Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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28. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Bakir, Maise Al, Watkins, Thomas B. K., Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S., Frankell, Alexander M., Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L., Martínez-Ruiz, Carlos, Black, James R. M., Biswas, Dhruva, Campbell, Brittany B., Lee, Claudia, Colliver, Emma, Enfield, Katey S. S., Hessey, Sonya, Hiley, Crispin T., Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J., Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad S., Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R., Rekhtman, Natasha, Travis, William D., Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G., McGranahan, Nicholas, Swanton, Charles, and Jamal-Hanjani, Mariam

Published
2023
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29. Body composition and lung cancer-associated cachexia in TRACERx

Author

Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C., Frankell, Alexander M., Watkins, Thomas B. K., Martínez-Ruiz, Carlos, Puttick, Clare, Black, James R. M., Huebner, Ariana, Bakir, Maise Al, Sokač, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P., Christiani, David C., Mak, Raymond H., Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M., O’Rahilly, Stephen, Birkbak, Nicolai J., Aerts, Hugo J. W. L., Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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30. Aimé Césaire

Author

Walcott-Hackshaw, Elizabeth, author, University of the West Indies publisher, and Walcott-Hackshaw, Elizabeth, author

Published
2021

31. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

Author

Lacas, Benjamin, Carmel, Alexandra, Landais, Cécile, Wong, Stuart J, Licitra, Lisa, Tobias, Jeffrey S, Burtness, Barbara, Ghi, Maria Grazia, Cohen, Ezra EW, Grau, Cai, Wolf, Gregory, Hitt, Ricardo, Corvò, Renzo, Budach, Volker, Kumar, Shaleen, Laskar, Sarbani Ghosh, Mazeron, Jean-Jacques, Zhong, Lai-Ping, Dobrowsky, Werner, Ghadjar, Pirus, Fallai, Carlo, Zakotnik, Branko, Sharma, Atul, Bensadoun, René-Jean, Redda, Maria Grazia Ruo, Racadot, Séverine, Fountzilas, George, Brizel, David, Rovea, Paolo, Argiris, Athanassios, Nagy, Zoltán Takácsi, Lee, Ju-Whei, Fortpied, Catherine, Harris, Jonathan, Bourhis, Jean, Aupérin, Anne, Blanchard, Pierre, Pignon, Jean-Pierre, Group, MACH-NC Collaborative, Adelstein, DJ, Alfonsi, M, Belkacemi, Y, Bar-Ad, V, Bernier, J, Bratland, Å, Calais, G, Campbell, B, Caudell, J, Chabaud, S, Chamorey, E, Chaukar, D, Choi, KN, Choussy, O, Collette, L, Cruz, JJ, Dani, C, Dauzier, E, Forastiere, AA, Garaud, P, Gregoire, V, Hackshaw, A, Haddad, E, Haffty, BG, Hansen, A, Hayoz, S, Horiot, JC, Jeremic, B, Karrison, TG, Langendijk, JA, Lapeyre, M, Lartigau, E, Leong, T, Le, QT, Lee, PPY, Lewin, F, Lin, A, Lopes, A, Mehta, S, Moon, J, Moyal, E, Occéan, BV, Olmi, P, Orecchia, R, O'Sullivan, B, Overgaard, J, Petit, C, Quon, H, Sanguineti, G, Satar, T, Simes, J, Simon, C, Sire, C, Staar, S, Stromberger, C, Strojan, P, Temam, S, Thomson, D, Timochenko, A, Torri, V, and Tseroni, V

Subjects
Cancer, Clinical Trials and Supportive Activities, Rare Diseases, Clinical Research, 6.5 Radiotherapy and other non-invasive therapies, Evaluation of treatments and therapeutic interventions, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, Chemotherapy, Adjuvant, Head and Neck Neoplasms, Humans, Induction Chemotherapy, Randomized Controlled Trials as Topic, Meta-analysis, Review, Individual Patient Data, Randomised Clinical Trials, Chemotherapy, Radiotherapy, Head and Neck Cancer, MACH-NC Collaborative Group, Other Physical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Background and purposeThe Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.Materials and methodsPublished or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.ResultsFor the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p

Published
2021

34. Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort

Author

Anthony Edey, Neal Navani, Andrew W Creamer, Kitty Chan, Graham Robinson, Janine Zylstra, Paul Robinson, Laura Green, Anand Devaraj, Jane Rowlands, Allan Hackshaw, Carolyn Horst, Arjun Nair, Sam M Janes, Kate Davies, Jeannie Eng, Mamta Ruparel, Samantha L Quaife, Jennifer L Dickson, Magali Taylor, Angshu Bhowmik, Karen Sennett, Samantha Quaife, Samuel Janes, Hasti Robbie, Joseph Jacob, Laura Farrelly, Sophie Tisi, Andrew Creamer, Helen Hall, Samanjit Hare, Jon Teague, Thea Buchan, Stephen Ellis, Thomas Callender, Rachael Sarpong, John McCabe, Zaheer Mangera, Ethaar El-Emir, Terry O'Shaughnessy, Nick Screaton, Priyam Verghese, William M Ricketts, Anne-Marie Mullin, Vicky Bowyer, Kylie Gyertson, Fanta Bojang, Claire Levermore, Ruth Prendecki, Amyn Bhamani, Malavika Suresh, Judy Airebamen, Alice Cotton, Kaylene Phua, Elodie Murali, Simranjit Mehta, Karen Parry-Billings, Columbus Ife, April Neville, Zahra Hanif, Helen Kiconco, Ricardo McEwen, Dominique Arancon, Nicholas Beech, Derya Ovayolu, Christine Hosein, Sylvia Patricia Enes, Qin April Neville, Aashna Samson, Urja Patel, Fahmida Hoque, Hina Pervez, Sofia Nnorom, Moksud Miah, Julian McKee, Mark Clark, Anant Patel, Sara Lock, Rajesh Banka, Ugo Ekeowa, Charlotte Cash, Tunku Aziz, Alberto Villanueva, Elena Stefan, Charlie Sayer, Navinah Nundlall, Lyndsey Gallagher, Andrew Crossingham, Tanita Limani, Kate Gowers, James Rusius, Jennifer Dickson, Anne-Marie Hacker, Jonathon Teague, and Andrew Perugia TaniaAnastasiadis

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Background Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol.Methods The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT.Results In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25.Conclusions Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.

Published
2023
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35. Retrospective Observational Study of Outcomes in HER2-Positive Metastatic Breast Cancer (mBC) Patients Treated with Ado-Trastuzumab Emtansine (T-DM1) and Subsequent Treatments After T-DM1 in the United States

Author

Neelima Denduluri, Janet L. Espirito, Michelle D. Hackshaw, Chuck Wentworth, Tamy Recchia, and Winghan J. Kwong

Subjects
Therapeutics. Pharmacology, RM1-950, Pharmacy and materia medica, RS1-441
Abstract

Abstract Background Limited evidence exists on real-world outcomes with ado-trastuzumab emtansine (T-DM1) treatment and the effectiveness of subsequent therapies. Objective This study evaluated treatment patterns and outcomes of patients treated with T-DM1 and post-T-DM1 therapy in the United States. Patients and methods Adult patients with HER2-positive (HER2+) metastatic breast cancer (mBC) initiating treatment with T-DM1 between 1/1/2013 and 9/30/2018 were included and followed through 12/31/2018. Data were obtained from the iKnowMed electronic health record. Demographic, clinical, and pre- and post-T-DM1 treatment characteristics were described. The Kaplan-Meier method was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). Results Of 318 patients treated with T-DM1, 184 (57.9%) had prior treatment with pertuzumab. The median age was 58 years. Most patients had visceral disease (93.4%), and 62.3% had two or more prior treatments for mBC before T-DM1 (range 0–9). The most common subsequent regimens were trastuzumab + vinorelbine (22.5%), HER2-targeted monotherapy (22.5%), and trastuzumab + other chemotherapy (19.6%). Median TTD with T-DM1 was 5.9 months (95% confidence interval [CI] 4.6–6.9); median OS from the start of T-DM1 therapy was 19.2 months (95% CI 16.8–24.5). Conclusions Patients treated with T-DM1 in this study appeared to have more advanced disease than patients in clinical trials and were treated in later lines of therapy. Variability was observed across subsequent therapy selections. Treatment patterns and outcomes appeared comparable for patients who received prior pertuzumab. The short treatment durations and survival with T-DM1 therapy in the real-world setting underscore the need for effective post-trastuzumab therapies.

Published
2022
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36. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author

Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.

Abstract

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.

Published
2024

37. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author

Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., Moore D. A., Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., and Moore D. A.

Abstract

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.

Published
2024

38. Uptake of invitations to a lung health check offering low-dose CT lung cancer screening among an ethnically and socioeconomically diverse population at risk of lung cancer in the UK (SUMMIT): a prospective, longitudinal cohort study

Author

Dickson, Jennifer L, Hall, Helen, Horst, Carolyn, Tisi, Sophie, Verghese, Priyam, Mullin, Anne-Marie, Teague, Jon, Farrelly, Laura, Bowyer, Vicky, Gyertson, Kylie, Bojang, Fanta, Levermore, Claire, Anastasiadis, Tania, McCabe, John, Navani, Neal, Nair, Arjun, Devaraj, Anand, Hackshaw, Allan, Quaife, Samantha L, and Janes, Sam M

Published
2023
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39. Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis

Author

Adelstein, D.J., Agarwal, J., Alfonsi, M., Argiris, A., Aupérin, A., Bacigalupo, A., Bar-Ad, V., Bartelink, H., Beadle, B., Belkacemi, Y., Bensadoun, R.J., Bernier, J., Blanchard, P., Bourhis, J., Bratland, Å., Brizel, D., Budach, V., Budach, W., Burtness, B., Calais, G., Campbell, B., Caudell, J., Chabaud, S., Chamorey, E., Chaukar, D., Cheugoua-Zanetsie, M., Cho, K.H., Choussy, O., Cruz Hernandez, J.J., Denham, J.W., Dobrowsky, W., Dominello, M.M, Driessen, C.M.L., Fallai, C., Forastiere, A.A., Fortpied, C., Fountzilas, G., Garaud, P., Garden, A.S., Gery, B., Ghadjar, P., Ghi, M.G., Ghosh Laskar, S., Graff-Cailleaud, P., Grau, C., Gregoire, V., Hackshaw, A., Haddad, E, Haffty, B.G., Hansen, A., Hay, J.H., Hayoz, S., Horiot, J.C., Hitt, R., Jeremic, B., Johansen, J., Jones, C., Julieron, M., Kristensen, C.A., Kumar, S., Lacas, B., Langendijk, J.A., Lapeyre, M., Lartigau, E., Licitra, L., Le, Q.T., Lee, J.W., Lee, P., Lewin, F., Li, Y., Lopes, A., Lotayef, M., Maciejewski, B., Mazeron, J.J., Mehta, S., Michalski, W., Moon, J., Moon, S.H., Moyal, E., Nankivell, M., Nilsson, P., Olmi, P., Orecchia, R., O'Sullivan, B., Overgaard, J., Parmar, M.K.B., Petit, C., Pignon, J.P., Pointreau, Y., Posner, M.R., Poulsen, M.G., Quon, H., Racadot, S., Rosenthal, D.I., Rovea, P., Ruo Redda, M.G., Sanguineti, G., Shenouda, G., Simes, J., Sharma, A., Simon, C., Sire, C., Skladowski, K., Spencer, S., Staar, S., Strojan, P., Stromberger, C., Suwinski, R., Szutkowski, Z., Takácsi-Nagy, Z., Tao, Y.G., Temam, S., Thomson, D., Tobias, J.S., Torres-Saavedra, P., Torri, V., Tripcony, L., Trotti, A., Tseroni, V., van Herpen, C., van Tinteren, H., Vermorken, J., Viegas, C.M.P., Vokes, E.E., Waldron, J., Wernecke, K.D, Widder, J., Wolf, G.T., Wong, S.J., Wu, J.S., Yamazaki, H., Zaktonik, B., Zackrisson, B., Zhong, L.P., Petit, Claire, Lacas, Benjamin, Pignon, Jean-Pierre, Le, Quynh Thu, Grégoire, Vincent, Grau, Cai, Hackshaw, Allan, Zackrisson, Björn, Parmar, Mahesh K B, Lee, Ju-Whei, Ghi, Maria Grazia, Sanguineti, Giuseppe, Temam, Stéphane, Cheugoua-Zanetsie, Maurice, O'Sullivan, Brian, Posner, Marshall R, Vokes, Everett E, Cruz Hernandez, Juan J, Szutkowski, Zbigniew, Lartigau, Eric, Budach, Volker, Suwiński, Rafal, Poulsen, Michael, Kumar, Shaleen, Ghosh Laskar, Sarbani, Mazeron, Jean-Jacques, Jeremic, Branislav, Simes, John, Zhong, Lai-Ping, Overgaard, Jens, Fortpied, Catherine, Torres-Saavedra, Pedro, Bourhis, Jean, Aupérin, Anne, and Blanchard, Pierre

Published
2021
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41. Discovery of a Metal-poor Red Giant Star with the Highest Ultralithium Enhancement

Author

Jeremy Kowkabany, Rana Ezzeddine, Corinne Charbonnel, Ian U. Roederer, Ella Xi Wang, Yangyang Li, Zoe Hackshaw, Timothy C. Beers, Anna Frebel, Terese T. Hansen, Erika Holmbeck, Vinicius M. Placco, and Charli M. Sakari

Subjects
Chemical abundances, R-process, Lithium stars, Asymptotic giant branch, Red giant bump, Milky Way stellar halo, Astrophysics, QB460-466
Abstract

We present the discovery of 2MASS J05241392−0336543 (hereafter J0524−0336), a very metal-poor ([Fe/H] = −2.43 ± 0.16), highly r -process-enhanced ([Eu/Fe] = +1.34 ± 0.10) Milky Way halo field red giant star, with an ultrahigh Li abundance of A (Li, 3D, NLTE) = 6.15 ± 0.25 and [Li/Fe] = +7.64 ± 0.25, respectively. This makes J0524−0336 the most lithium-enhanced giant star discovered to date. We present a detailed analysis of the star’s atmospheric stellar parameters and chemical abundance determinations. Additionally, we detect indications of infrared excess, as well as observe variable emission in the wings of the H α absorption line across multiple epochs, indicative of a potential enhanced mass-loss event with possible outflows. Our analysis reveals that J0524−0336 lies either between the bump and the tip of the red giant branch (RGB), or on the early asymptotic giant branch (e-AGB). We investigate the possible sources of lithium enrichment in J0524−0336, including both internal and external sources. Based on current models and on the observational evidence we have collected, our study shows that J0524−0336 may be undergoing the so-called lithium flash that is expected to occur in low-mass stars when they reach the RGB bump and/or the e-AGB.

Published
2024
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42. Portable Mid-Infrared Spectroscopy Combined with Chemometrics to Diagnose Fibromyalgia and Other Rheumatologic Syndromes Using Rapid Volumetric Absorptive Microsampling

Author

Shreya Madhav Nuguri, Kevin V. Hackshaw, Silvia de Lamo Castellvi, Haona Bao, Siyu Yao, Rija Aziz, Scott Selinger, Zhanna Mikulik, Lianbo Yu, Michelle M. Osuna-Diaz, Katherine R. Sebastian, M. Monica Giusti, and Luis Rodriguez-Saona

Subjects
fibromyalgia, rheumatic diseases, central sensitization, FT-MIR, OPLS-DA, point-of-care device, Organic chemistry, QD241-441
Abstract

The diagnostic criteria for fibromyalgia (FM) have relied heavily on subjective reports of experienced symptoms coupled with examination-based evidence of diffuse tenderness due to the lack of reliable biomarkers. Rheumatic disorders that are common causes of chronic pain such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and chronic low back pain are frequently found to be comorbid with FM. As a result, this can make the diagnosis of FM more challenging. We aim to develop a reliable classification algorithm using unique spectral profiles of portable FT-MIR that can be used as a real-time point-of-care device for the screening of FM. A novel volumetric absorptive microsampling (VAMS) technique ensured sample volume accuracies and minimized the variation introduced due to hematocrit-based bias. Blood samples from 337 subjects with different disorders (179 FM, 158 non-FM) collected with VAMS were analyzed. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. The OPLS-DA algorithm enabled the classification of the spectra into their corresponding classes with 84% accuracy, 83% sensitivity, and 85% specificity. The OPLS-DA regression plot indicated that spectral regions associated with amide bands and amino acids were responsible for discrimination patterns and can be potentially used as spectral biomarkers to differentiate FM and other rheumatic diseases.

Published
2024
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43. Early Diagnosis of Fibromyalgia Using Surface-Enhanced Raman Spectroscopy Combined with Chemometrics

Author

Haona Bao, Kevin V. Hackshaw, Silvia de Lamo Castellvi, Yalan Wu, Celeste Matos Gonzalez, Shreya Madhav Nuguri, Siyu Yao, Chelsea M. Goetzman, Zachary D. Schultz, Lianbo Yu, Rija Aziz, Michelle M. Osuna-Diaz, Katherine R. Sebastian, Monica M. Giusti, and Luis Rodriguez-Saona

Subjects
fibromyalgia, surface-enhanced Raman spectroscopy, central sensitization syndrome, metabolic fingerprinting, in-clinic disease diagnostics, chemometrics, Biology (General), QH301-705.5
Abstract

Fibromyalgia (FM) is a chronic muscle pain disorder that shares several clinical features with other related rheumatologic disorders. This study investigates the feasibility of using surface-enhanced Raman spectroscopy (SERS) with gold nanoparticles (AuNPs) as a fingerprinting approach to diagnose FM and other rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoarthritis (OA), and chronic low back pain (CLBP). Blood samples were obtained on protein saver cards from FM (n = 83), non-FM (n = 54), and healthy (NC, n = 9) subjects. A semi-permeable membrane filtration method was used to obtain low-molecular-weight fraction (LMF) serum of the blood samples. SERS measurement conditions were standardized to enhance the LMF signal. An OPLS-DA algorithm created using the spectral region 750 to 1720 cm−1 enabled the classification of the spectra into their corresponding FM and non-FM classes (Rcv > 0.99) with 100% accuracy, sensitivity, and specificity. The OPLS-DA regression plot indicated that spectral regions associated with amino acids were responsible for discrimination patterns and can be potentially used as spectral biomarkers to differentiate FM and other rheumatic diseases. This exploratory work suggests that the AuNP SERS method in combination with OPLS-DA analysis has great potential for the label-free diagnosis of FM.

Published
2024
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45. A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Author

Wu, Yin, Biswas, Dhruva, Usaite, Ieva, Angelova, Mihaela, Boeing, Stefan, Karasaki, Takahiro, Veeriah, Selvaraju, Czyzewska-Khan, Justyna, Morton, Cienne, Joseph, Magdalene, Hessey, Sonya, Reading, James, Georgiou, Andrew, Al-Bakir, Maise, McGranahan, Nicholas, Jamal-Hanjani, Mariam, Hackshaw, Allan, Quezada, Sergio A., Hayday, Adrian C., and Swanton, Charles

Published
2022
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46. Metabolic fingerprinting for diagnosis of fibromyalgia and other rheumatologic disorders.

Author

Hackshaw, Kevin, Aykas, Didem, Sigurdson, Gregory, Plans, Marcal, Madiai, Francesca, Yu, Lianbo, Buffington, Charles, Giusti, M, and Rodriguez-Saona, Luis

Subjects
Raman spectroscopy, biomarker, blood, fibromyalgia, fingerprinting, high-performance liquid chromatography (HPLC), infrared spectroscopy (IR spectroscopy), mass spectrometry (MS), pain, Adult, Biomarkers, Chromatography, High Pressure Liquid, Female, Fibromyalgia, Humans, Male, Middle Aged, Pain, Pain Measurement, Spectrophotometry, Infrared, Surveys and Questionnaires
Abstract

Diagnosis and treatment of fibromyalgia (FM) remains a challenge owing to the lack of reliable biomarkers. Our objective was to develop a rapid biomarker-based method for diagnosing FM by using vibrational spectroscopy to differentiate patients with FM from those with rheumatoid arthritis (RA), osteoarthritis (OA), or systemic lupus erythematosus (SLE) and to identify metabolites associated with these differences. Blood samples were collected from patients with a diagnosis of FM (n = 50), RA (n = 29), OA (n = 19), or SLE (n = 23). Bloodspot samples were prepared, and spectra collected with portable FT-IR and FT-Raman microspectroscopy and subjected to metabolomics analysis by ultra-HPLC (uHPLC), coupled to a photodiode array (PDA) and tandem MS/MS. Unique IR and Raman spectral signatures were identified by pattern recognition analysis and clustered all study participants into classes (FM, RA, and SLE) with no misclassifications (p < 0.05, and interclass distances > 2.5). Furthermore, the spectra correlated (r = 0.95 and 0.83 for IR and Raman, respectively) with FM pain severity measured with fibromyalgia impact questionnaire revised version (FIQR) assessments. Protein backbones and pyridine-carboxylic acids dominated this discrimination and might serve as biomarkers for syndromes such as FM. uHPLC-PDA-MS/MS provided insights into metabolites significantly differing among the disease groups, not only in molecular m/z+ and m/z- values but also in UV-visible chromatograms. We conclude that vibrational spectroscopy may provide a reliable diagnostic test for differentiating FM from other disorders and for establishing serologic biomarkers of FM-associated pain.

Published
2019

47. Healthcare Practitioner Relationships, Cultural Health Capital and Breastfeeding Support for Adolescent Mothers

Author

Jamie, Kimberly, O'Neill, Roisin, Bows, Hannah, and Hackshaw-McGeagh, Lucy

Abstract

Objectives: Breastfeeding is the optimal method of infant nutrition. Despite this, rates of breastfeeding in high-income countries are low and mirror wider health inequalities with women from under-served populations being least likely to breastfeed. In the UK, adolescent mothers from areas of high socio-economic deprivation are among the least likely groups to initiate and continue breastfeeding. This study aimed to examine young women's experiences of breastfeeding, with a particular focus on information provision and relationships with healthcare practitioners. Methods, design and setting: Data were collected through qualitative focus groups and interviews with 27 adolescent mothers from areas of socio-economic deprivation in Belfast (Northern Ireland), Bristol (South West England) and Middlesbrough (North East England). Questions focused on the support young mothers receive for breastfeeding with a particular focus on the importance of healthcare practitioners in breastfeeding practices. Results: Although young mothers were well-informed about the benefits of breastfeeding, they lacked basic information which led to early cessation. Moreover, mismatched cultural health capital between healthcare practitioners and adolescent mothers led to perceived strained relationships wherein young mothers felt undermined and not listened to. We suggest that this arises from an intersection of age-related lack of confidence and low cultural health capital arising from differences in socio-economic status. Conclusions: Recommendations are offered for a more holistic approach to young mothers' maternal health and the use of peer supporters.

Published
2020
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50. Metabolic Fingerprinting for the Diagnosis of Clinically Similar Long COVID and Fibromyalgia Using a Portable FT-MIR Spectroscopic Combined with Chemometrics

Author

Kevin V. Hackshaw, Siyu Yao, Haona Bao, Silvia de Lamo Castellvi, Rija Aziz, Shreya Madhav Nuguri, Lianbo Yu, Michelle M. Osuna-Diaz, W. Michael Brode, Katherine R. Sebastian, M. Monica Giusti, and Luis Rodriguez-Saona

Subjects
fibromyalgia, post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, metabolic fingerprinting, in-clinic disease diagnostics, chemometrics, blood, Biology (General), QH301-705.5
Abstract

Post Acute Sequelae of SARS-CoV-2 infection (PASC or Long COVID) is characterized by lingering symptomatology post-initial COVID-19 illness that is often debilitating. It is seen in up to 30–40% of individuals post-infection. Patients with Long COVID (LC) suffer from dysautonomia, malaise, fatigue, and pain, amongst a multitude of other symptoms. Fibromyalgia (FM) is a chronic musculoskeletal pain disorder that often leads to functional disability and severe impairment of quality of life. LC and FM share several clinical features, including pain that often makes them indistinguishable. The aim of this study is to develop a metabolic fingerprinting approach using portable Fourier-transform mid-infrared (FT-MIR) spectroscopic techniques to diagnose clinically similar LC and FM. Blood samples were obtained from LC (n = 50) and FM (n = 50) patients and stored on conventional bloodspot protein saver cards. A semi-permeable membrane filtration approach was used to extract the blood samples, and spectral data were collected using a portable FT-MIR spectrometer. Through the deconvolution analysis of the spectral data, a distinct spectral marker at 1565 cm−1 was identified based on a statistically significant analysis, only present in FM patients. This IR band has been linked to the presence of side chains of glutamate. An OPLS-DA algorithm created using the spectral region 1500 to 1700 cm−1 enabled the classification of the spectra into their corresponding classes (Rcv > 0.96) with 100% accuracy and specificity. This high-throughput approach allows unique metabolic signatures associated with LC and FM to be identified, allowing these conditions to be distinguished and implemented for in-clinic diagnostics, which is crucial to guide future therapeutic approaches.

Published
2023
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