bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised controlled trial of tailored support to increase physical activity and reduce smoking in smokers not immediately ready to quit: protocol for the Trial of physical Activity-assisted Reduction of Smoking (TARS) Study
Authors: Taylor Adrian , Thompson Tom P , Ussher Michael , Aveyard Paul , Murray Rachael L , Harris Tess , Creanor Siobhan , Green Colin , Streeter Adam Justin , Chynoweth Jade , Ingram Wendy , Greaves Colin J , Hancocks Helen , Snowsill Tristan , Callaghan Lynne , Price Lisa , Horrell Jane , King Jennie , Gude Alex , George Mary , Wahlich Charlotte , Hamilton Louisa , Cheema Kelisha , Campbell Sarah , Preece Dan 
Published: April 2023

IntroductionSmoking reduction can lead to increased success in quitting. This study aims to determine if a client-focused motivational support package for smoking reduction (and quitting) and increasing (or otherwise using) physical activity (PA) can help smokers who do not wish to quit immediately to reduce the amount they smoke, and ultimately quit. This paper reports the study design and methods.Methods and analysisA pragmatic, multicentred, parallel, two group, randomised controlled superiority clinical trial, with embedded process evaluation and economics evaluation. Participants who wished to reduce smoking with no immediate plans to quit were randomised 1:1 to receive either (1) tailored individual health trainer face-to-face and/or telephone support to reduce smoking and increase PA as an aid to smoking reduction (intervention) or (2) brief written/electronic advice to reduce or quit smoking (control). Participants in both arms of the trial were also signposted to usual local support for smoking reduction and quitting. The primary outcome measure is 6-month carbon monoxide-confirmed floating prolonged abstinence following participant self-reported quitting on a mailed questionnaire at 3 and 9 months post-baseline. Participants confirmed as abstinent at 9 months will be followed up at 15 months.Ethics and disseminationApproved by SW Bristol National Health Service Research Committee (17/SW/0223). Dissemination will include publication of findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will be disseminated to trial participants and healthcare providers.Trial registration numberNCT47776579.
Study protocol for a pilot trial analysing the usability, validity and safety of an interventional health app programme for the structured prehabilitation of patients before major surgical interventions: the PROTEGO MAXIMA trial
Authors: Faqar-Uz-Zaman Sara Fatima , Sliwinski Svenja , Detemble Charlotte , Filmann Natalie , Zmuc Dora , Mohr Lisa , Dreilich Julia , Bechstein Wolf O , Fleckenstein Johannes , Schnitzbauer Andreas A 
Published: April 2023

IntroductionMajor surgery is associated with a high risk for postoperative complications, leading to an increase in mortality and morbidity, particularly in frail patients with a reduced cardiopulmonary reserve. Prehabilitation, including aerobic exercise training, aims to improve patients’ physical fitness before major surgery and reduce postoperative complications, length of hospital stay and costs. The purpose of the study is to assess the usability, validity and safety of an app-based endurance exercise software in accordance with the Medical Device Regulation using wrist-worn wearables to measure heart rate (HR) and distance.Methods and analysisThe PROTEGO MAXIMA trial is a prospective, interventional study with patients undergoing major elective surgery, comprising three tasks. Tasks I and II aim to assess the usability of the app, using evaluation questionnaires and usability scenarios. In Task IIIa, patients will undergo a structured risk assessment by the Patronus App, which will be correlated with the occurrence of postoperative complications after 90 days (non-interventional). In Task IIIb, healthy students and patients will perform a supervised 6 min walking test and a 37 min interval training on a treadmill based on HR reserve, wearing standard ECG limb leads and two smartwatches, which will be driven by the test software. The aim of this task is to assess the accuracy of HR measurement by the wearables and the safety, using specific alarm settings of the devices and lab testing of the participants (interventional).Ethics and disseminationEthical approval was granted by the Institutional Review Board of the University Hospital of Frankfurt and by the Federal Institute for Pharmaceuticals and Medical Products (BfArM, reference number 94.1.04-5660-13655) on 7 February 2022. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration numbersEuropean Database on Medical Devices (CIV-21-07-037311) and German Clinical Trial Registry (DRKS00026985).
Aerobic adaptations following two iso-effort training programs: an intense continuous and a high-intensity interval
Authors: Myrkos Aristides , Smilios Ilias , Zafeiridis Andreas , Kokkinou Maria-Eleni , Tzoumanis Apostolos , Douda Helen 
Published: April 2023

The intensity of the training stimulus and the effort exerted (regarded as an index of internal load) to complete an exercise session are driving forces for physiological processes and long-term training adaptations. This study compared the aerobic adaptations following two iso-effort, ratings of perceived exertion (RPE)-based training programs, an intense continuous (CON) and a high-intensity interval (INT). Young adults were assigned to a CON ( n = 11) or an INT ( n = 13) training group to perform 14 training sessions within 6 weeks. The INT group performed running bouts (9.3 ± 4.4 repetitions) at 90% of peak treadmill velocity (PTV) with bout duration equal to 1/4 of time to exhaustion at this speed (134.2 ± 27.9 s). The CONT group ran (1185.0 ± 487.6 s) at a speed corresponding to −2.5% of critical velocity (CV; 80.1% ± 3.0% of PTV). Training-sessions were executed until RPE attained 17 on the Borg scale. VO2max, PTV, CV, lactate threshold velocity (vLT), and running economy were assessed pre-, mid-, and post-training. Both CONT and INT methods increased ( p < 0.05) VO2max (INT: 57.7 ± 8.1–61.41 ± 9.2; CONT: 58.1 ± 7.5–61.1 ± 6.3 mL kg−1 min−1), PTV (INT: 14.6 ± 1.8–15.7 ± 2.1; CONT: 15.0 ± 1.7–15.7 ± 1.8 km h−1), CV (INT: 11.8 ± 1.4–12.8 ± 1.8; CONT: 12.2 ± 1.6–12.9 ± 1.7 km h−1), and vLT (INT: 9.77 ± 1.1–10.8 ± 1.4; CONT: 10.4 ± 1.4–11.0 ± 1.8 km h−1) with no differences ( p > 0.05) between them; running economy remained unchanged. The continuous training method, when matched for effort and executed at relatively high intensity at the upper boundaries of the heavy-intensity domain (∼80% of PTV), confers comparable aerobic adaptations to those attained after a high-intensity interval protocol following a short-term training period.
Investigating the Rydberg states and photodissociation dynamics of Kr2using velocity map imaging
Authors: Stienstra Cailum M.K. , Coughlan Neville J.A. , Haack Alexander , Carr Patrick J.J. , Crouse Jeff , Featherstone Joshua , Hopkins W. Scott 
Published: April 2023

Although the krypton dimer, Kr2, is a prototypical weakly bound van der Waals complex in its ground electronic state, the excited states of Kr2exhibit many and various interactions. Resonance-enhanced multiphoton ionization and velocity map imaging provide an avenue to explore the electronic structure and photofragmentation dynamics of Kr2in the vacuum ultraviolet region. By monitoring photofragmentation product channels and recoil anisotropy distributions, one can gain insights into excited state symmetries and lifetimes, which can aid in interpreting spectroscopy. Here, we study the spectroscopy and photodissociation dynamics of Kr2in the 91 000–94 500 cm−1region. We record and assign photofragment product channels for 32 vibronic bands corresponding to seven electronic transitions. We also identify two previously unobserved vibronic band systems, which we assign as the Kr2 5p [5/2]3 [Formula: see text] and 5p [3/2]2[Formula: see text] transitions. Velocity map images show photofragments arising from predissociation of the neutral Rydberg states and from dissociative photoionization at the n > 2 photon level. We also observe variation in branching ratios between the predissociative and dissociative photoionization channels depending on the lifetime of the intermediate; longer lived states favour higher dissociative photoionization yields and exhibit β6anisotropy parameters for predissociation product channels, indicating “rotational smearing” of the product angular distributions.
Petrology of the explosive deposits from the April 2021 eruption of La Soufrière volcano, St Vincent: a time-series analysis of microlites
Authors: Frey Holli M. , Manon Matthew R. , Barclay Jenni , Davies Bridie V. , Walters Sydney A. , Cole Paul D. , Christopher Thomas E. , Joseph Erouscilla P. 
Published: April 2023

Abstract

After more than three months of lava dome extrusion, La Soufrière (St Vincent) transitioned to a series of explosive eruptions in April 2021. Here we present a time-series petrologic analysis of the phenocryst and microlite populations during the first
c.
48 h of explosivity to constrain ascent conditions and processes that drove changes in behaviour. Primary eruptive products were crystal-rich (45–50 vol%) basaltic andesites with similar phenocryst phase assemblages and compositions. The change in eruptive style is consistent with overpressurization as a consequence of second boiling from anhydrous microlite crystallization. The microlites display variation between the explosive phases, with two populations: (1) ‘inherited’ − normally zoned high-An plagioclase (>An
70
) + olivine (Fo
62–79
) + clinopyroxene + titanomagnetite, inferred to have crystallized at depths >15 km and high water pressures; (2) ‘juvenile’ − unzoned plagioclase (An
45–65
) + clinopyroxene + orthopyroxene + intermediate pyroxene (Wo
12–38
) + titanomagnetite, inferred to have crystallized upon ascent due to decompression and degassing. Scoria from the first explosions featured extensive groundmass crystallization and a significant ‘inherited’ microlite population. Later explosions had a more abundant ‘juvenile’ microlite population and lower crystallinity, consistent with more rapid ascent from depth, initiated by decompression following initial blasts and destruction of the lava dome.
Abstract 3957: Anticancer effect of novel 1,4-benzodiazepine derivatives through tubulin polymerization inhibition
Authors: Srovnalova Alzbeta , Rehulka Jiri , Gurska Sona , Polyshchuk Pavel , Bachinsky Sergey , Dzubak Petr , Hajduch Marian 
Published: April 2023

Abstract
Benzodiazepines are well known as a key scaffold in medicinal chemistry, providing bioactive compounds for a wide variety of biological targets. Among their primary use as anxiolytics and sedatives, the 1,4-benzodiazepine derivatives and their metabolites play a role as antitumor, antithrombotic, antiviral and antimalarial agents. Recent studies revealed the influence of the benzodiazepine derivatives on microtubule assembly or stability with subsequent mitotic failure. These microtubule-targeting effects were evaluated in novel benzodiazepine derivatives. The antiproliferative activities of novel derivatives were tested against a panel of 10 cancer cell lines and 2 non-cancer cell lines. The compounds with IC50&lt;10 µM were further analyzed for the cell cycle. Flow cytometry and fluorescent cell cycle indicator (FUCCI) assays were performed to evaluate the effects of derivatives on the cell cycle phases. The immunofluorescence alpha-tubulin assay and tubulin polymerization assay were accomplished to detect the changes in the mitosis. Implementation of molecular docking revealed the specific binding site of the derivatives. All tested derivatives reveal the G2/M block in the cell cycle and 3 of them were identified as M-phase blockers. The immunofluorescence alpha-tubulin assay detected the disruption of the cellular microtubule network, and the tubulin polymerization assay uncovered the potential of the tested compounds to inhibit tubulin polymerization. Molecular docking confirms that benzodiazepine derivatives fit the colchicine site best and are partially overlaid with the native colchicine binding pose. This suggests that these compounds may adapt to the tubulin binding site in a conformation induced by colchicine The inhibition of tubulin polymerization by novel derivatives is one of their possible mechanisms of action on antiproliferative effect on cancer cell lines. More rigorous studies will be performed further to establish pose stability and explain structure-activity relationships. This work was supported by European Union - Programme EXCELES, ID Project No. LX22NPO5102, the Czech Ministry of Education, Youth and Sports (CZ-OPENSCREEN - LM2018130, EATRIS-CZ - LM2018133), and by the internal grant of Palacky University Olomouc (IGA_LF_2022_033) and European Regional Development Fund - Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868).
Citation Format: Alzbeta Srovnalova, Jiri Rehulka, Sona Gurska, Pavel Polyshchuk, Sergey Bachinsky, Petr Dzubak, Marian Hajduch. Anticancer effect of novel 1,4-benzodiazepine derivatives through tubulin polymerization inhibition. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3957.
Abstract 4: A novel humanized mouse model for study of T cells and NK cells in the tumor microenvironment
Authors: Arora Jyoti , Lemke-Miltner Caitlin D. , Weiner George J. 
Published: April 2023

Abstract
Humanized mouse models can be useful for in vivo preclinical evaluation of mechanisms underlying cancer immunotherapy. Most such models involve systemic engraftment of immunocompromised mice with human lymphoid and hematopoietic cells, often using normal donor peripheral blood mononuclear cells (PBMCs), followed by inoculation with human tumor. The ability to control and modify immune cells within the tumor microenvironment (TME), especially human NK cells, is limited in such models. Here, we report the development of a mouse model designed to control the number of human T cells and NK cells in the TME. 18 mice and pre-validated PBMCs were obtained from Charles River. Six groups of 3 mice each were inoculated with Raji lymphoma cells. Group 1 was inoculated with Raji cells only and received no PBMCs. Raji cells were mixed PBMCs for groups 2-4. Group 5 was systemically engrafted with PBMCs 12 days prior to Raji inoculation and Group 6 was systemically engrafted with PBMCs 10 days after Raji inoculation. All mice developed tumors with similar growth characteristics. Serial fine needle aspirates (FNAs) of the resulting tumors were evaluated by flow cytometry. Results of FNAs are summarized below.
Tumors were harvested at the end of experiment, typically 27 days after tumor inoculation, and evaluated by immunohistochemistry. Both T cells and NK cells were evenly distributed within tumors at the time of harvest. We conclude co-injection of tumor and PBMCs results in engraftment of both T cells and NK cells within the TME for up to 27 days, with T cells and NK cells distributed evenly within the tumor. Mixing higher numbers of PBMCs with tumor cells resulted in increased numbers of T cells and NK cells in the TME throughout the experiment. Matrigel did not improve engraftment or persistence of T or NK cells in the TME. We conclude mixing PBMCs with Raji tumor cells prior to tumor inoculation into immunocompromised mice is an effective approach when a humanized model with human T cells and NK cells within the TME is desired.
Group Description % T cells in tumor at 17 days % NK cells in tumor at 17 days 1 No PBMCs 0 0 2 PBMCs mixed with Raji at 10:1 ratio 8.6 1.5 3 PBMCs mixed with Raji at 2:1 ratio 20.3 2.7 4 PBMCs and Raji in matrigel 9.2 0.6 5 PBMCs systemically engrafted 12 days before Raji inoculation 23.2 0.1 6 PBMCs systemically engrafted 10 days after Raji inoculation 19.6 0.2
Citation Format: Jyoti Arora, Caitlin D. Lemke-Miltner, George J. Weiner. A novel humanized mouse model for study of T cells and NK cells in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4.
Abstract 4059: Developing an allogeneic iPSC derived macrophage cell therapy for oncology
Authors: Wang Huafeng , Sumi May , Huh Christine , Parviz Fereshteh , Mastroianni Jessica , Healy Jane , Stevens Nicole , Mitchell Leah , Lang Susanne , Kaufman Dan , Hollingsworth Robert , Rodgers David T. 
Published: April 2023

Abstract
The full potential of cell therapy has yet to be realized in solid tumor indications and new approaches are urgently required. Macrophages are innate immune cells that can kill tumor cells and orchestrate the anti-tumor immune response. Macrophage cell therapy is an exciting new approach to treat cancer with the aim to harness the powerful activity of macrophages to reignite the immune system. Patient derived macrophages, however, are difficult to genetically engineer and do not proliferate, which makes generating high-quality cells at clinically relevant scales challenging. To address this, we have developed an induced pluripotent stem cell (iPSC) approach to macrophage cell therapy. These cells can be genetically engineered at the iPSC stage and then differentiated into billions of highly functional iPSC derived macrophages (iMACs). This allogenic cell therapy product can then be cryopreserved and stored for immediate use in the clinic when the patient is ready.
Here we show that iMACs function like normal macrophages. They migrate towards tumor cells, respond to challenges through innate immune receptors, and produce immune recruiting and activating cytokines and chemokines. iMACs also express high levels of antibody receptors and we show that these cells can be directed to kill tumors in vitro and in vivo via antibody dependent cellular phagocytosis. Furthermore, we have conducted a robust screen to develop a novel CAR that is optimized for use in iMACs. These receptors can be engineered into iMACs at the iPSC stage and trigger robust tumor cell killing. In summary, these data highlight the therapeutic potential of iMACs in oncology and support the further development of this technology for clinical use.
Citation Format: Huafeng Wang, May Sumi, Christine Huh, Fereshteh Parviz, Jessica Mastroianni, Jane Healy, Nicole Stevens, Leah Mitchell, Susanne Lang, Dan Kaufman, Robert Hollingsworth, David T. Rodgers. Developing an allogeneic iPSC derived macrophage cell therapy for oncology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4059.
Abstract 451: AICAR targets oncogenic signaling pathways of MUC1-CT
Authors: Aftab Fareesa , Rodriguez-Fuguet Alice , Silva Luis , Kobayashi Ikei S. , Sun Jiao , Politi Katerina , Levantini Elena , Zhang Wei , Kobayashi Susumu S. , Zhang Wen Cai 
Published: April 2023

Abstract
Lung cancer cells overexpress oncogenic mucin 1 (MUC1), whose C-terminal active subunit (MUC1-CT) is involved in lung tumor formation. Although a specific peptide against MUC1-CT has effectively blocked the MUC1 signaling pathway, intrinsic metabolites targeting MUC1 were not well studied. 5-aminoimidazole-4-carboxamide riboside (AICAR) is a purine biosynthesis intermediate and an analog of adenosine. Our study showed that high AICAR reduced lung tumor cell growth by increasing DNA damage and cell apoptosis. MUC1 was validated as one of the leading AICAR-binding proteins by virtual target screening and thermal stability assay. AICAR treatment dramatically degraded MUC1-CT at protein levels. Whole transcriptome analysis demonstrated that AICAR negatively regulated the Janus kinase (JAK) signaling pathway. Duolink proximity ligation assay revealed that JAK1 interacted with MUC1 directly, and AICAR treatment impaired this protein-protein interaction. Increased epidermal growth factor receptor (EGFR) activity was linked to upregulated expression of MUC1-CT in tissues from an EGFR transgenic mouse lung cancer model. AICAR treatment reduced phosphorylated EGFR, JAK1, and MUC1-CT in lung cancer cells. A mono-treatment with AICAR reduced tumor formation in a mouse lung xenograft model. Combination therapy with AICAR and small-molecule inhibitors against JAK1 or mutant EGFR reduced the growth of lung tissue-derived tumor organoids. Thus, our study has first disclosed a new ligand repressing the MUC1 activity in lung cancer that disrupts protein-protein interactions between MUC1-CT and other oncogenic proteins.
Citation Format: Fareesa Aftab, Alice Rodriguez-Fuguet, Luis Silva, Ikei S. Kobayashi, Jiao Sun, Katerina Politi, Elena Levantini, Wei Zhang, Susumu S. Kobayashi, Wen Cai Zhang. AICAR targets oncogenic signaling pathways of MUC1-CT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 451.
Abstract 513: Suppressing YBX1 with a small molecule inhibitor sensitizes lung cancer to chemotherapy
Authors: Lee Jee Min , Malhotra Sanjay 
Published: April 2023

Abstract
Y-box binding protein-1 (YBX1) is a multifunctional protein that regulates genes by binding to their DNA and/or RNA. YBX1 is known to contribute to tumorigenesis, disease progression and resistance by stabilizing the mRNAs of genes that are involved in cell growth and survival. High expression of YBX1 has been associated with poor clinical outcomes and decreased overall survival in over 20 cancer types including lung cancer. Given its critical roles in cancer progression and significant correlation with poor cancer prognosis, we hypothesized that inhibition of YBX1 may sensitize the cancer cells to chemotherapeutic agents. To profile the relationship between YBX1 and chemo-response, we aim to investigate the synergistic effect of YBX1 inhibition with standard of care chemotherapy drugs including cisplatin, in lung cancer using animal models and omics analysis. Our studies have found that SU056, a small molecule YBX1 inhibitor, effectively inhibits YBX1 expression in human lung adenocarcinoma cell lines and halts their cell proliferation and clonogenic potential, whereas overexpression of YBX1 promotes cell proliferation. SU056-mediated YBX1 inhibition also led to G2/M cell cycle arrest in these cells followed by apoptotic cell death. These results were further confirmed in A549 lung tumor xenograft model, where inhibitor treatment delayed tumor progression. We will present collective data from in vitro and in vivo studies with YBX1 inhibitor, combination studies with known chemotherapeutic drugs and omics analysis to suggest that targeting YBX1 has therapeutic potential to increase the efficacy of chemotherapeutic agents.
Citation Format: Jee Min Lee, Sanjay Malhotra. Suppressing YBX1 with a small molecule inhibitor sensitizes lung cancer to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 513.