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Article: Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma.

Norquest, Carissa J / Rogic, Anita / Gimotty, Phyllis A / Maitz, Charles A / Rindt, Hansjorg / Ashworth, Hayley L / Bryan, Jeffrey N / Donnelly, Lindsay L / McCleary-Wheeler, Angela L / Flesner, Brian K

Frontiers in veterinary science

2024 Volume 11, Page(s) 1237084

Abstract: ... ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks).: Results: We found ... G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL ...

Abstract	Introduction: Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM). In human medicine, ZOL provides improved bone pain relief and prolonged time to skeletal-related events compared to its older generational counterparts. Preclinical studies have investigated its role as an anti-neoplastic agent, both independently and synergistically, with radiation therapy (RT). ZOL and RT act synergistically in several neoplastic human cell lines: prostate, breast, osteosarcoma, and fibrosarcoma. However, the exact mechanism of ZOL's radiosensitization has not been fully elucidated. Methods: We investigated ZOL's ability to induce apoptosis in canine osteosarcoma cell lines treated with various doses of megavoltage external beam radiotherapy. Second, we evaluated cell cycle arrest in ZOL-treated cells to assess several neo-adjuvant time points. Finally, we treated 20 dogs with naturally occurring appendicular OS with 0.1 mg/kg ZOL IV 24 h before receiving 8 Gy of RT (once weekly fraction x 4 weeks). Results: We found that apoptosis was increased in all ZOL-treated cell lines compared to controls, and the combination of ZOL and RT resulted in dissimilar apoptosis between Abrams and D-17 and HMPOS cell lines. Cell cycle arrest (G2/M phase) was minimal and variable between cell lines but perhaps greatest at 48 h post-ZOL treatment. Only 10% of dogs treated with ZOL and RT developed pathologic fractures, compared to 44% of dogs historically treated with PAM and RT ( Discussion: ZOL and RT appear to be a well-tolerated combination treatment scheme for non-surgical candidates; future studies must elucidate the ideal timing of ZOL.
Language	English
Publishing date	2024-01-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2024.1237084
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Article ; Online: The impact of COVID-19 on young people's mental health, wellbeing and routine from a European perspective: A co-produced qualitative systematic review.

Dewa, Lindsay H / Roberts, Lily / Choong, Elizabeth / Crandell, Caroline / Demkowicz, Ola / Ashworth, Emma / Branquinho, Catia / Scott, Steph

PloS one

2024 Volume 19, Issue 3, Page(s) e0299547

Abstract: Background: The impact of the Covid-19 pandemic on young people's (YP) mental health has been mixed. Systematic reviews to date have focused predominantly on quantitative studies and lacked involvement from YP with lived experience of mental health ... ...

Abstract	Background: The impact of the Covid-19 pandemic on young people's (YP) mental health has been mixed. Systematic reviews to date have focused predominantly on quantitative studies and lacked involvement from YP with lived experience of mental health difficulties. Therefore, our primary aim was to conduct a qualitative systematic review to examine the perceived impact of the Covid-19 pandemic on YP's (aged 10-24) mental health and wellbeing across Europe. Methods and findings: We searched MEDLINE, PsycINFO, Embase, Web of Science, MEDRXIV, OSF preprints, Google, and voluntary sector websites for studies published from 1st January 2020 to 15th November 2022. European studies were included if they reported qualitative data that could be extracted on YP's (aged 10-24) own perspectives of their experiences of Covid-19 and related disruptions to their mental health and wellbeing. Screening, data extraction and appraisal was conducted independently in duplicate by researchers and YP with lived experience of mental health difficulties (co-researchers). Confidence was assessed using the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) approach. We co-produced an adapted narrative thematic synthesis with co-researchers. This study is registered with PROSPERO, CRD42021251578. We found 82 publications and included 77 unique studies in our narrative synthesis. Most studies were from the UK (n = 50; 65%); and generated data during the first Covid-19 wave (March-May 2020; n = 33; 43%). Across the 79,491 participants, views, and experiences of YP minoritised by ethnicity and sexual orientation, and from marginalised or vulnerable YP were limited. Five synthesised themes were identified: negative impact of pandemic information and restrictions on wellbeing; education and learning on wellbeing; social connection to prevent loneliness and disconnection; emotional, lifestyle and behavioural changes; and mental health support. YP's mental health and wellbeing across Europe were reported to have fluctuated during the pandemic. Challenges were similar but coping strategies to manage the impact of these challenges on mental health varied across person, study, and country. Short-term impacts were related to the consequences of changing restrictions on social connection, day-to-day lifestyle, and education set-up. However, YP identified potential issues in these areas going forward, and therefore stressed the importance of ongoing long-term support in education, learning and mental health post-Covid-19. Conclusions: Our findings map onto the complex picture seen from quantitative systematic reviews regarding the impact of Covid-19 on YP's mental health. The comparatively little qualitative data found in our review means there is an urgent need for more high-quality qualitative research outside of the UK and/or about the experiences of minoritised groups to ensure all voices are heard and everyone is getting the support they need following the pandemic. YP's voices need to be prioritised in decision-making processes on education, self-care strategies, and mental health and wellbeing, to drive impactful, meaningful policy changes in anticipation of a future systemic crisis.
MeSH term(s)	Humans ; Male ; Female ; Adolescent ; Mental Health ; COVID-19/epidemiology ; Pandemics ; Qualitative Research ; Learning
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0299547
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Article: Activation of fluoride anion as nucleophile in water with data-guided surfactant selection.

Sharma, Krishna / McCorry, Alison / Boobier, Samuel / Mottram, James / Napier, Rachel / Ashworth, Ian W / Blacker, A John / Kapur, Nikil / Warriner, Stuart L / Wright, Megan H / Nguyen, Bao N

Chemical science

2024 Volume 15, Issue 15, Page(s) 5764–5774

Abstract: A principal ... ...

Abstract	A principal component
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2559110-1
ISSN	2041-6539 ; 2041-6520
ISSN (online)	2041-6539
ISSN	2041-6520
DOI	10.1039/d3sc06311a
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Article ; Online: The usefulness of electrodiagnostic studies in the diagnosis and management of neuromuscular disorders.

Lindstrom, Heather / Ashworth, Nigel L

Muscle & nerve

2018 Volume 58, Issue 2, Page(s) 191–196

Abstract: Introduction: This study seeks to evaluate the usefulness of electrodiagnostic (EDX) studies in terms of the patient's diagnosis and subsequent management and to identify patient groups in which EDX is particularly useful.: Methods: The records of ... ...

Abstract	Introduction: This study seeks to evaluate the usefulness of electrodiagnostic (EDX) studies in terms of the patient's diagnosis and subsequent management and to identify patient groups in which EDX is particularly useful. Methods: The records of new patients referred to a single tertiary hospital EDX laboratory during 1 calendar year were reviewed to determine whether results of EDX studies led to a changed diagnosis and/or management plan. Logistic regression was used to determine whether any factors were associated with changed diagnosis or management. Results: Results of EDX studies led to a change in diagnosis and a confirmation in diagnosis in 51.5% and 46.5% of the cases, respectively. Results of EDX studies led to a change in the management plan in 63.4% of all cases. The diagnosis and management plan were more likely to be changed in older patients and patients referred in hospital. Discussion: EDX studies seem useful for confirming or changing the diagnosis and in guiding management in patients with suspected neuromuscular disorders. Muscle Nerve 58: 191-196, 2018.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Disease Management ; Electrodiagnosis/methods ; Electromyography ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Neuromuscular Diseases/diagnosis ; Neuromuscular Diseases/therapy ; Patient Care Planning ; Predictive Value of Tests ; Referral and Consultation ; Reproducibility of Results ; Sensitivity and Specificity ; Young Adult
Language	English
Publishing date	2018-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.26126
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Zs.A 1449: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cancer detection via primary care urgent referral and association with practice characteristics: a retrospective cross-sectional study in England from 2009/2010 to 2018/2019.

Round, Thomas / Ashworth, Mark / L'Esperance, Veline / Møller, Henrik

The British journal of general practice : the journal of the Royal College of General Practitioners

2021 Volume 71, Issue 712, Page(s) e826–e835

Abstract: Background: There is substantial variation in the use of urgent suspected cancer referral (2-week wait [2WW]) between practices.: Aim: To examine the change in use of 2WW referrals in England over 10 years (2009/2010 to 2018/2019) and the practice ... ...

Abstract	Background: There is substantial variation in the use of urgent suspected cancer referral (2-week wait [2WW]) between practices. Aim: To examine the change in use of 2WW referrals in England over 10 years (2009/2010 to 2018/2019) and the practice and population factors associated with cancer detection. Design and setting: Retrospective cross-sectional study of English general practices and their 2WW referral and Cancer Waiting Times database detection data (all cancers other than non-melanoma skin cancers) from 2009/2010 to 2018/2019. Method: A retrospective study conducted using descriptive statistics of changes over 10 years in 2WW referral data. Yearly linear regression models were used to determine the association between cancer detection rates and quintiles of practice and population characteristics. Predicted cancer detection rates were calculated, as well as the difference between lowest to highest quintiles. Results: Over the 10 years studied there were 14.89 million 2WW referrals (2.24 million in 2018/2019), and 2.68 million new cancer diagnoses, of which 1.26 million were detected following 2WW. The detection rate increased from 41% to 52% over the time period. In 2018/2019 an additional 66 172 cancers were detected via 2WW compared with 2009/2010. Higher cancer detection via 2WW referrals was associated with larger practices and those with younger GPs. From 2016/2017 onwards more deprived practice populations were associated with decreased cancer detection. Conclusion: From 2009/2010 to 2018/2019 2WW referrals increased on average by 10% year on year. The most consistent association with higher cancer detection was found for larger practices and those with younger GPs, though these differences became attenuated over time. The more recent association between increased practice deprivation and lower cancer detection is a cause for concern. The COVID-19 pandemic has led to significant impacts on 2WW referral activity and the impact on patient outcomes will need to be studied.
MeSH term(s)	COVID-19 ; Cross-Sectional Studies ; Early Detection of Cancer ; England/epidemiology ; Humans ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Pandemics ; Primary Health Care ; Referral and Consultation ; Retrospective Studies ; SARS-CoV-2
Language	English
Publishing date	2021-10-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1043148-2
ISSN	1478-5242 ; 0035-8797 ; 0960-1643
ISSN (online)	1478-5242
ISSN	0035-8797 ; 0960-1643
DOI	10.3399/BJGP.2020.1030
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Article ; Online: Hypertension prevalence, coding and control in an urban primary care setting in the UK between 2014 and 2021.

Basta, Karol / Ledwaba-Chapman, Lesedi / Dodhia, Hiten / Ashworth, Mark / Whitney, David / Dalrymple, Kathryn / Wang, Yanzhong

Journal of hypertension

2023 Volume 42, Issue 2, Page(s) 350–359

Abstract: Objective: Hypertension is a leading preventable cause of mortality, yet high rates of undiagnosed and uncontrolled hypertension continue. The burden falls most heavily on some ethnic minorities and the socially deprived, with the COVID-19 pandemic ... ...

Abstract	Objective: Hypertension is a leading preventable cause of mortality, yet high rates of undiagnosed and uncontrolled hypertension continue. The burden falls most heavily on some ethnic minorities and the socially deprived, with the COVID-19 pandemic having further widened inequalities. We sought to determine the prevalence and predictors of unmeasured blood pressure (BP), uncoded elevated BP and uncontrolled hypertension in primary care across 2014-2021. Methods: A population-based cohort study using data from all 41 general practices in a socioeconomically diverse inner-city borough. BP measurements, sociodemographic, lifestyle and clinical factors were extracted from anonymized primary care data. Hypertension and BP control were defined using NICE guidelines. Associations between patient characteristics and hypertension outcomes were identified using logistical regression modelling. Results: Of 549 082 patients, 39.5% had unmeasured BP; predictors included male sex [AOR 2.40, 95% confidence interval (95% CI) 2.26-2.43] and registration in the pandemic years. Of 71 970 adults with elevated BP, 36.0% were uncoded; predictors included obesity (AOR 2.51, 95% CI 2.42-2.60) and increasing age. Of 44 648 adults on the hypertension register, 46.8% had uncontrolled hypertension; predictors included black ethnicity compared to white (AOR 1.54, 95% CI 1.41-1.68) and cardiovascular co-morbidities (AOR 1.23, 95% CI 1.21-1.25). Social deprivation was only weakly or not significantly associated with hypertension outcomes. Conclusion: The burden of uncoded elevated BP and uncontrolled hypertension is high. Obesity and male sex were associated with uncoded elevated BP and uncontrolled hypertension. Black ethnicity was associated with uncontrolled hypertension. Initiatives are needed to optimize hypertension coding and control, with an emphasis on specific population subgroups.
MeSH term(s)	Adult ; Humans ; Male ; Cohort Studies ; Prevalence ; Pandemics ; Hypertension ; Blood Pressure ; Obesity/epidemiology ; Autonomic Nervous System Diseases ; Primary Health Care ; United Kingdom/epidemiology
Language	English
Publishing date	2023-09-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000003584
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Article ; Online: De novo design of drug-binding proteins with predictable binding energy and specificity.

Lu, Lei / Gou, Xuxu / Tan, Sophia K / Mann, Samuel I / Yang, Hyunjun / Zhong, Xiaofang / Gazgalis, Dimitrios / Valdiviezo, Jesús / Jo, Hyunil / Wu, Yibing / Diolaiti, Morgan E / Ashworth, Alan / Polizzi, Nicholas F / DeGrado, William F

Science (New York, N.Y.)

2024 Volume 384, Issue 6691, Page(s) 106–112

Abstract: The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening and optimization after computational design. We developed a ... ...

Abstract	The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening and optimization after computational design. We developed a computational procedure to design a protein that recognizes a common pharmacophore in a series of poly(ADP-ribose) polymerase-1 inhibitors. One of three designed proteins bound different inhibitors with affinities ranging from <5 nM to low micromolar. X-ray crystal structures confirmed the accuracy of the designed protein-drug interactions. Molecular dynamics simulations informed the role of water in binding. Binding free energy calculations performed directly on the designed models were in excellent agreement with the experimentally measured affinities. We conclude that de novo design of high-affinity small molecule-binding proteins with tuned interaction energies is feasible entirely from computation.
MeSH term(s)	Binding Sites ; Drug Design/methods ; Ligands ; Molecular Dynamics Simulation ; Poly(ADP-ribose) Polymerase Inhibitors/chemistry ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Protein Binding ; Proteins/chemistry ; Humans
Chemical Substances	Ligands ; Poly(ADP-ribose) Polymerase Inhibitors ; Proteins
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adl5364
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Article ; Online: Cooling dynamics of energized naphthalene and azulene radical cations.

Lee, Jason W L / Stockett, Mark H / Ashworth, Eleanor K / Navarro Navarrete, José E / Gougoula, Eva / Garg, Diksha / Ji, MingChao / Zhu, Boxing / Indrajith, Suvasthika / Zettergren, Henning / Schmidt, Henning T / Bull, James N

The Journal of chemical physics

2023 Volume 158, Issue 17

Abstract: Naphthalene and azulene are isomeric polycyclic aromatic hydrocarbons (PAHs) and are topical in the context of astrochemistry due to the recent discovery of substituted naphthalenes in the Taurus Molecular Cloud-1 (TMC-1). Here, the thermal- and photo- ... ...

Abstract	Naphthalene and azulene are isomeric polycyclic aromatic hydrocarbons (PAHs) and are topical in the context of astrochemistry due to the recent discovery of substituted naphthalenes in the Taurus Molecular Cloud-1 (TMC-1). Here, the thermal- and photo-induced isomerization, dissociation, and radiative cooling dynamics of energized (vibrationally hot) naphthalene (Np+) and azulene (Az+) radical cations, occurring over the microsecond to seconds timescale, are investigated using a cryogenic electrostatic ion storage ring, affording "molecular cloud in a box" conditions. Measurement of the cooling dynamics and kinetic energy release distributions for neutrals formed through dissociation, until several seconds after hot ion formation, are consistent with the establishment of a rapid (sub-microsecond) Np+ ⇌ Az+ quasi-equilibrium. Consequently, dissociation by C2H2-elimination proceeds predominantly through common Az+ decomposition pathways. Simulation of the isomerization, dissociation, recurrent fluorescence, and infrared cooling dynamics using a coupled master equation combined with high-level potential energy surface calculations [CCSD(T)/cc-pVTZ], reproduce the trends in the measurements. The data show that radiative cooling via recurrent fluorescence, predominately through the Np+ D0 ← D2 transition, efficiently quenches dissociation for vibrational energies up to ≈1 eV above dissociation thresholds. Our measurements support the suggestion that small cations, such as naphthalene, may be more abundant in space than previously thought. The strategy presented in this work could be extended to fingerprint the cooling dynamics of other PAH ions for which isomerization is predicted to precede dissociation.
Language	English
Publishing date	2023-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0147456
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Article: Nasal angiofibroma treatment outcome using intensity‐modulated radiation therapy in a dog

L. Ashworth, Hayley / K. Flesner, Brian / J. Norquest, Carissa / A. Maitz, Charles

Veterinary radiology & ultrasound. 2021 July, v. 62, no. 4

2021

Abstract: A 6‐year‐old dog presented with a modified Adams stage 3 angiofibroma of the right nasal cavity, causing fluid accumulation along the right frontal sinus. Treatment consisted of step‐and‐shoot intensity‐modulated radiation therapy in 12 daily treatments ... ...

Abstract	A 6‐year‐old dog presented with a modified Adams stage 3 angiofibroma of the right nasal cavity, causing fluid accumulation along the right frontal sinus. Treatment consisted of step‐and‐shoot intensity‐modulated radiation therapy in 12 daily treatments of 3.5 Gy, for a total dose of 42 Gy to 95% of the planning target volume. The dog developed self‐limiting grade 2 oral mucositis which resolved within 2 weeks of course completion. A recheck exam 668 days after treatment confirmed a stable disease response by RECIST and a tumor volume decrease of 55.4%.
Keywords	dogs ; nasal cavity ; neoplasms ; radiology ; radiotherapy ; ultrasonics
Language	English
Dates of publication	2021-07
Size	p. e40-e43.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2142058-0
ISSN	1740-8261 ; 1058-8183
ISSN (online)	1740-8261
ISSN	1058-8183
DOI	10.1111/vru.12961
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Article ; Online: Combined polygenic scores for ischemic stroke risk factors aid risk assessment of ischemic stroke.

Huang, Sarah / Joshi, Abhishek / Shi, Zhuqing / Wei, Jun / Tran, Huy / Zheng, S Lilly / Duggan, David / Ashworth, Annabelle / Billings, Liana / Helfand, Brian T / Qamar, Arman / Bulwa, Zachary / Tafur, Alfonso / Xu, Jianfeng

International journal of cardiology

2024 Volume 404, Page(s) 131990

Abstract: Background: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGS: Methods: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS ... ...

Abstract	Background: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGS Methods: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGS Results: During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGS Conclusions: Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.
MeSH term(s)	Humans ; Ischemic Stroke ; Stroke/diagnosis ; Stroke/epidemiology ; Stroke/genetics ; Diabetes Mellitus, Type 2/complications ; Risk Factors ; Risk Assessment ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/genetics ; Obesity/diagnosis ; Obesity/epidemiology ; Obesity/genetics
Language	English
Publishing date	2024-03-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2024.131990
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