bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA021: Digital patient avatars predict cancer evolution and personalised therapeutic strategies
Authors: Fisher Jasmin 
Published: February 2024

Abstract
Tumour heterogeneity manifested by genetic diversity and interchangeable cell states poses considerable challenges for the design of therapeutic strategies to combat cancer. While many strategies have been proposed to address this problem, using combination treatments and sequential delivery of therapies, the scope of combinations and sequencing order of therapies is enormous and is beyond the capacity of exhaustive testing through experimental models. We therefore propose using computational models to rapidly identify effective therapeutic interventions supported by convincing mechanistic explanations. Digital cancer avatars are computational programs representing oncogenic signalling networks and mapping molecular interactions to cell phenotype, which can be interrogated in silico. These computational programs specify how molecular interactions and perturbations produce cellular responses, such as cell proliferation, cell survival or cell death, and as such are well-suited to provide novel mechanistic insights into cellular behaviours as well as to identify therapeutic strategies for targeting them. In this talk, I will demonstrate the utility of bespoke computational models for triple-negative breast cancer, non-small cell lung cancer and melanoma to study how genomic changes drive tumour evolution and therapeutic response, and how these models are used to identify personalised combination treatments to overcome resistance. I will also present an in silico method applied to these models, to screen tens of millions combinations for effective sequential treatments by mapping the evolution of a tumour in response to a single-agent treatment and determining the optimal second-line treatment that will overcome resistance. Together these studies demonstrate the utility of digital avatars to improve our understanding of the mechanisms driving tumour progression and pave the way for personalised therapeutic strategies for improved cancer patient outcomes.
Citation Format: Jasmin Fisher. Digital patient avatars predict cancer evolution and personalised therapeutic strategies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA021.
Abstract PR018: Adaptive local fitness landscapes for aneuploid karyotypes
Authors: Beck Richard J. , Andor Noemi 
Published: February 2024

Abstract
Aneuploidy, which occurs in most solid tumors, dramatically alters the expression of many genes which in turn has broad phenotypic effects. Recent evidence suggests that specific aneuploid karyotypes confer a selective advantage. However, various questions remain unanswered regarding the magnitude of these selective advantages, as well as the repeatability and predictability of karyotype evolution. We developed ALFA-K (Adaptive Local Fitness landscapes for Aneuploid Karotypes) – the first approach to infer karyotype fitness landscapes in a context-dependent manner. Based on the dynamics of just a few subclones derived from longitudinal single cell sequencing data, our method can extrapolate the fitness of thousands of karyotypes. We validate the predictive power of our method on data from several P53 deficient cell lines which exhibited substantial subclonal evolution across multiple passages in vivo or in vitro. Based on topological analyses of the inferred fitness landscapes we investigated how mis-segregation rate itself shapes the stringency of karyotype evolution and whether karyotype evolution is subject to diminishing returns epistasis, sign epistasis or reciprocal sign epistasis. We adapted metrics from geo-statistics to study the fitness landscape of a P53 deficient 184-hTERT diploid breast epithelial cell line that underwent whole genome doubling (WGD) and found support for the hypothesis that WGD benefits tumor cells by enhancing their robustness against chromosomal instability. The stark phenotypic consequences of karyotype changes emphasize the value of predicting the evolutionary trajectory of karyotype composition when exposing cells to a new environment. Our work contributes to accumulating evidence that karyotype evolution is predictable.
Citation Format: Richard J. Beck, Noemi Andor. Adaptive local fitness landscapes for aneuploid karyotypes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr PR018.
Abstract TP218: Best Practices for Optimizing Door-to-Device Times: Road to Target Stroke Phase III
Authors: Sivapatham Thinesh , Albani Barbara J , Gannon Kimberly P , Nomura Jason T , Huisenga Doug P , Ciechanowski Mary C , McAndrew Reina W 
Published: February 2024

Introduction:
The launch of AHA’s Target: Stroke Phase III in 2019 challenged stroke centers to achieve DTD ≤ 90 minutes (direct arriving patients) or ≤ 60 minutes (transfer patients) in ≥ 50% of patients treated with mechanical thrombectomy (MT). At the time of Phase III launch, we were achieving the DTD goal in 45% of patients at our CSC (> 200 MT/year).

Methods:
Our stroke team, in collaboration with the ED and other relevant departments, analyzed the stroke alert process and implemented changes as needed to improve DTD times:

• Early notification of neurointerventional surgery (NIS) by neurologist upon clinical evaluation for any possible MT candidate
• CT/CTP/CTA completed simultaneously (IV lytics given in CT if eligible)
• Utilization of RAPID.AI platform to allow immediate review of stroke imaging by NIS 24/7
• Decision to upgrade to MT made immediately after imaging completed
• MT code activation alerts nursing supervisor, NCCU, anesthesia, and IR team
• Patient transported immediately from CT to angio suite by ED nurse upon upgrade 24/7
• ED nurse transfers care to IR team and anesthesia during working hours, or to NCCU nurse and anesthesia during off hours (IR nurse assumes care upon arrival)
• Focus on efficient handoff process in angio suite
• Specific roles assigned to each team member
• Timer on wall started upon patient arrival to angio suite, with arrival to puncture goal < 20 min
• Efficiency maintained with simulation MT codes rotating members from IR, ER, NCCU, and anesthesia DTD times were collected at launch of Phase III in 2019, and after changes were implemented.
Objectives were to improve DTD times from baseline, in order to optimize care and achieve Phase III goals.

Results:
Figure 1.

Conclusion:
By implementing collaborative and focused interventions, our CSC was able to improve and optimize the workflow of stroke patients undergoing MT, allowing us to achieve the rigorous Target: Stroke Phase III goals and optimize patient outcomes.
Abstract WMP89: Reperfusion Pattern as a Predictor of Final Infarct Growth in Patients With Anterior Large Vessel Occlusion Ischemic Stroke
Authors: Rodrigo-Gisbert Marc , Canals Pere , Garcia-Tornel Alvaro , Requena Manuel , Rizzo Federica , Olive-Gadea Marta , Muchada Marian , Tanzi Leonardo , Marti Cristian , Salvia Punsoda Victor , Ribo Marc 
Published: February 2024

Aim:
The first pass effect (FPE) and complete sudden recanalization (cSR) have been identified as an indicator of favorable clinical outcome. We aimed to compare final infarct volume (FIV) according to different reperfusion pattern.

Methods:
We included consecutive patients admitted with an anterior LVO stroke (intracranial internal carotid artery, MCA-M1) who underwent endovascular treatment between January 2018 and April 2022. Patients with partial or no-reperfusion (eTICI 0-2b) were excluded. Final complete reperfusion (TICI 2c-3) was categorized as achieved at first pass (FPE) or in subsequent passes as sudden (cSR: from TICI 0-1 to TICI 2c-3 in a single pass) or progressive (PR: interim partial recanalization). FIV was quantified using an automatic segmentation tool (Methinks AI) on 24-hour NCCT. Aggregated infarct distribution heatmaps were generated to compare FIV distribution.

Results:
Of 316 consecutive patients, complete reperfusion was achieved in 202 patients (63.9%). Reperfusion patterns were as follows: FPE (109/202, 54.0%), cSR (28/202, 13.9%) and PR (65/202, 32.1%).

The mean FIV was 28.1mL (95%CI 19.1-37.1), 49.5mL (95%CI 18.8-80.2) and 58.4mL (95% CI 37.6-79.2) in FPE patients, cSR and PR patients, respectively (p=0.014). After adjusting for confounders, FPE and cSR patterns were independently associated with a reduced FIV (FPE: -61.7%, 95%CI -77.2% to -35.8%, p<0.001; cSR: -39.7%, 95%CI -63.8% to 0.6%, p=0.05).
The rate of excellent clinical outcome (mRS 90d 0-1) was higher in FPE (36.1%) and cSR (35.7%) groups compared to the PR group (20.3%, p=0.081).

Conclusion:
Improved clinical outcomes in patients with FPE and cSR patterns seem to be influenced by reduced infarct volume in a stepwise manner (FIV FPE<cSR<PR). PR may reflect clot fragmentation and embolization, contributing to infarct growth and worse outcomes. Reperfusion patterns should be explored for selecting target populations for adjunctive neuroprotective therapies during EVT.
Abstract WP249: Risk for Ischemic and Hemorrhagic Stroke is Increased in Veterans Exposed to Agent Orange and Those With Myeloproliferative Neoplasms
Authors: Mathur Natasha , Tiu Andrew , McKinnell Zoe , Gill Puneet , Antonio Martha , Liu Shanshan , Diao Guoqing , Subrahmanyam Ramesh , Kessler Craig M , Jain Maneesh R 
Published: February 2024

Agent Orange (AO) is a dioxin containing defoliant and carcinogen used in the Korean and Vietnam War. There is limited evidence of the association between AO exposure among Veterans and stroke. Stroke is not yet part of the list of presumptive conditions according to the Promise to Address Comprehensive Toxics (PACT) Act which provides Veterans and their survivors disability compensation for conditions arising from exposure to AO. Myeloproliferative Neoplasms (MPN) are uncommon etiologies of stroke but whether AO exposure increases incidence of stroke in MPN has not been described.
Utilizing the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database, a case-control study was performed from 1/1/2006 – 1/26/2023 on the Veterans from Illinois, the state most representative of the US population. ICD-9 and -10 codes identified Veterans with stroke and MPN. AO exposure was verified on the Veterans’ service duration and location. Qualitative data were compared by chi-square tests.
Among 586,555 Veterans from Illinois, there were 15,455 ischemic stroke (IS), 1,593 hemorrhagic stroke (HS), 2,752 MPN, and 59,393 with AO exposure. Among MPNs, there were 237 IS (41 with AO) and 26 HS (3 with AO). IS and HS were associated with AO exposure, OR 1.34 95% CI 1.28-1.41, p<0.0001, and OR 1.20 95% CI 1.03-1.39, p=0.02, respectively. MPN is associated with IS and HS, OR 3.52, 95% CI 3.08-4.03, and OR 3.54, 95% CI 2.4-5.23, both p<0.0001, respectively. There is no significant association with AO exposure among Veterans with MPN with stroke. Among non-MPN Veterans with AO exposure, there was an earlier median age of IS and HS, 67 vs. 70 and 67 vs. 71, both p<0.0001. There was no difference in median age of stroke among MPN Veterans with or without AO exposure. There were no differences with rates of hypertension, hyperlipidemia, diabetes, smoking, heart failure, and pulmonary hypertension among MPN Veterans with stroke with and without AO exposure.
In conclusion, there is an association of AO exposure with IS and HS with an earlier onset among those exposed. There is a strong association between MPN and stroke independent of AO exposure. The biologic plausibility of endothelial dysfunction and accelerated atherosclerosis from AO exposure warrants further investigation.
Abstract WP86: Data Collection Impacts on Study Costs: A Real-World Analysis
Authors: Tessmer Megan , Staloch Jessica , Streib Christopher D , Silva Luis , Gieseke Jessica , Nierengarten Elizabeth , Staugaitis Abbey 
Published: February 2024

Introduction:
Costs are a major barrier to conducting high-quality clinical trials, yet specific determinants of operational costs are understudied. Budgets are frequently planned assuming additional data fields increase cost in a proportional manner. We compared estimated costs for adding data fields to real-world costs as data fields increase.

Methods:
We studied the impact of data fields on operational costs for three Phase III acute stroke clinical trials of similar design, clinical complexity, and logistics. We retrospectively reviewed records of coordinator time logged for completion of data fields per study during 2021 and 2022. Study data management hours included time for data entry, query resolution, and data verification as requested by the study monitor. Our standard rate per hour was used to calculate actual cost for each clinical trial. We estimated the cost of a single data field by dividing the averaged cost per subject by the total data fields collected for the least expensive study. We used this value to estimate cost and compared that to the actual costs.

Results:
Study 1 was the least expensive study, and thus used to calculate the estimated cost of a single data field. There were 277 data fields and a cost of $513 per patient, the cost per data field was calculated as $1.85.

Study 2 had 775 data fields collected per subject and should have an estimated cost of $1,436.40. The actual cost was $2,291.57 which is 1.6 times higher than expected.
Study 3 had 2245 data fields collected per patient and should have an estimated cost of $4,155.30. The actual cost was $20,176.65 which is 4.86 times higher than expected. Results are summarized in Figure 1.

Conclusion:
Our analysis of real-world study data management costs demonstrate that additional data fields have a disproportionate increase in cost. Assuming a proportional increase could lead to inaccurate estimates with large budget and operational cost impacts when a study is implemented.
Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity
Authors: Kerksick C.M. , Moon J.M. , Walden K.E. , Hagele A.M. , Allen L.E. , Gaige C.J. , Krieger J.M. , Jäger R. , Pane M. , Mumford P. 
Published: February 2024

Abstract
The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved () at various time points with MSP supplementation. Systolic blood pressure in PLA increased () after 6 weeks of supplementation with no change in MSP. No changes () in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation.
Registered at clinicaltrials.gov: NCT05343533
Mating and oviposition of a breeding strain of black soldier fly Hermetia illucens (Diptera: Stratiomyidae): polygynandry and multiple egg-laying
Authors: Muraro T. , Lalanne L. , Pelozuelo L. , Calas-List D. 
Published: February 2024

Abstract
Black soldier fly (BSF), Hermetia illucens, is a promising species to valorise organic wastes and agricultural co-products into nutrient-rich animal feed. Thus, basic knowledge of its reproductive behaviour is needed to optimize its rearing processes and future selection. In this study, we investigated the reproductive behaviour (mating and egg-laying) of a mass-breeding BSF strain to (1) determine whether their females were monandrous or polyandrous, (2) describe the impact of multiple mating on egg production and fertility, and (3) describe where and when caged individuals mate and lay eggs. Newly emerged adults were individually tagged with acrylic paint to monitor their mating and egg-laying behaviour during their entire lifetime. Our results indicate that adults mated on average three times before dying, with different or even former partners. Some of them mated up to nine times. We also provide the first observation of multiple egg-laying for domesticated H. illucens females and show that virgin females can lay unfertilized eggs, in smaller quantities compared to mated ones. Finally, this study provides the first evidences that H. illucens can be polygynandrous and that multi-mated females can lay eggs several times, thus increasing egg production, in mass breeding conditions.
Acceptability of plasma ammonia results when samples are not transported and processed under ideal conditions
Authors: Bowron Ann , Osgood Victoria 
Published: February 2024

Background It is recommended that samples for plasma ammonia analysis are kept chilled and processed promptly as in vitro metabolism causes falsely elevated results. Rejection of unsuitable samples can cause delayed diagnosis and treatment of hyperammonaemia with potentially serious clinical consequences. The Metabolic Biochemistry Network (MetBioNet) hyperammonaemia guideline recommends analysis of samples not collected under ideal conditions and reporting with appropriate comments. An audit found that some laboratories did not follow this guidance. An investigation was performed into whether storage at controlled room temperature and delayed sample processing affected interpretation of plasma ammonia results. Methods Eleven healthy volunteers provided informed consent. Blood was taken from each into 14 paediatric EDTA blood sample tubes, one placed immediately on ice, the others in a rack at room temperature. The chilled and baseline room temperature samples were centrifuged and plasma analysed by the Roche Ammonia (NH3L2) method. Samples stored at room temperature were analysed at 10-min intervals up to 2 h. Results Baseline room temperature ammonia was higher than in the chilled sample (19 ± 6.6 µmol/L [mean ± standard deviation] and 18 ± 6.6 µmol/L, respectively). Ammonia increased further by 0.09 ± 0.02 µmol/L per minute to 30 ± 8.4 µmol/L at 2 h. No result was above the reference range (50 µmol/L). No healthy subject with normal baseline ammonia would have been erroneously identified as having hyperammonaemia. Conclusions Results support MetBioNet guidance that laboratories accept blood samples for ammonia analysis which are not processed under ideal conditions.
Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: An international Delphi study
Authors: Surges Séverine M , Brunsch Holger , Jaspers Birgit , Apostolidis Kathi , Cardone Antonella , Centeno Carlos , Cherny Nathan , Csikós Àgnes , Fainsinger Robin , Garralda Eduardo , Ling Julie , Menten Johan , Mercadante Sebastiano , Mosoiu Daniela , Payne Sheila , Preston Nancy , Van den Block Lieve , Hasselaar Jeroen , Radbruch Lukas 
Published: February 2024

Background: The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability. Aim: To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers. Design: Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure. Setting: European. Participants: International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation. Results: A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided. Conclusions: This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals.
Too Much Hegemony: A Novel Theory of the Unintended Consequences of Dominant Narratives
Authors: Bentley Tom 
Published: February 2024

This article builds on Gramscian conceptualisations of power. It does so by introducing `Hegemonic Excess Theory’ as a tool for understanding political crises. For Antonio Gramsci and his adherents, the political and economic establishment fosters consent and allegiance amongst subordinate classes through the dissemination, inculcation and appropriation of seductive and pacifying ideologies. In this article, I argue that subordinate groups may adopt such ideals too well and to such an extent that it undermines key objectives of the establishment. As such, Hegemonic Excess Theory encapsulates the idea that the leading class’s very success in imparting certain ideals among the population can magnify, become unwieldly, backfire and cause crisis for the political elite. I illustrate this through the 2016 Brexit vote, with a particular focus on how xenophobia and anti-migrant narratives and policy, including from the Remain campaign, played a pivotal role in sections of the electorate voting against the interests of the domestic and transnational establishment’s commitment to the neoliberal enterprise of the EU. While not necessarily insurmountable, this has caused a significant crisis for the ruling class. In the conclusion, I contend that Hegemonic Excess Theory has considerable analytical value in understanding political crises far beyond Brexit. Un excès d’hégémonie : Vers une nouvelle conceptualisation des effets indésirables des discours dominants à travers l’étude de cas du Brexit