bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring multidimensional aspects of quality of life after cancer immunotherapy: protocol for the international multicentre, observational QUALITOP cohort study
Authors: Vinke Petra C. , Combalia Marc , de Bock Geertruida H , Leyrat Clémence , Spanjaart Anne Mea , Dalle Stephane , Gomes da Silva Maria , Fouda Essongue Aurore , Rabier Aurélie , Pannard Myriam , Jalali Mohammad S , Elgammal Amal , Papazoglou Mike , Hacid Mohand-Said , Rioufol Catherine , Kersten Marie-José , van Oijen Martijn GH , Suazo-Zepeda Erick , Malhotra Ananya , Coquery Emmanuel , Anota Amélie , Preau Marie , Fauvernier Mathieu , Coz Elsa , Puig Susana , Maucort-Boulch Delphine 
Published: April 2023

IntroductionImmunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy, have significantly improved the clinical outcomes of various malignancies. However, they also cause immune-related adverse events (irAEs) that can be challenging to predict, prevent and treat. Although they likely interact with health-related quality of life (HRQoL), most existing evidence on this topic has come from clinical trials with eligibility criteria that may not accurately reflect real-world settings. The QUALITOP project will study HRQoL in relation to irAEs and its determinants in a real-world study of patients treated with immunotherapy.Methods and analysisThis international, observational, multicentre study takes place in France, the Netherlands, Portugal and Spain. We aim to include about 1800 adult patients with cancer treated with immunotherapy in a specifically recruited prospective cohort, and to additionally obtain data from historical real-world databases (ie, databiobanks) and medical administrative registries (ie, national cancer registries) in which relevant data regarding other adult patients with cancer treated with immunotherapy has already been stored. In the prospective cohort, clinical health status, HRQoL and psychosocial well-being will be monitored until 18 months after treatment initiation through questionnaires (at baseline and 3, 6, 12 and 18 months thereafter), and by data extraction from electronic patient files. Using advanced statistical methods, including causal inference methods, artificial intelligence algorithms and simulation modelling, we will use data from the QUALITOP cohort to improve the understanding of the complex relationships among treatment regimens, patient characteristics, irAEs and HRQoL.Ethics and disseminationAll aspects of the QUALITOP project will be conducted in accordance with the Declaration of Helsinki and with ethical approval from a suitable local ethics committee, and all patients will provide signed informed consent. In addition to standard dissemination efforts in the scientific literature, the data and outcomes will contribute to a smart digital platform and medical data lake. These will (1) help increase knowledge about the impact of immunotherapy, (2) facilitate improved interactions between patients, clinicians and the general population and (3) contribute to personalised medicine.Trial registration numberNCT05626764.
Trends in prevalence and clustering of modifiable cardiovascular disease risk factors across socioeconomic spectra in rural southwest China: a cross-sectional study
Authors: Le Cai , Liu Lan , Li Guo-hui , Zhao Yi , Wu Xia , Rabkin Golden Allison 
Published: April 2023

ObjectivesThis study aimed to determine the changing prevalence of clustering of cardiovascular disease (CVD) risk factors across socioeconomic spectra in rural southwest China.DesignData were collected from two waves of cross-sectional health interviews and examinations among individuals aged ≥35 years in rural China. Anthropometric measurements, blood pressure and fasting blood sugar levels were recorded for each participant.SettingThis study was conducted in rural Yunnan Province of China.Participants8187 individuals in 2011 and 7572 in 2021 consented to participate in this study.ResultsFrom 2011 to 2021, prevalence increased of hypertension (26.1% vs 41.6%), diabetes mellitus (5.9% vs 9.8%), obesity (5.9% vs 12.0%) and central obesity (50.0% vs 58.3%) (p<0.01), while prevalence decreased of current smoking (35.2% vs 29.6%), secondhand smoke exposure (42.6% vs 27.4%) and current drinking (26.6% vs 29.6%) (p<0.01). This decade also saw an increase in the prevalence of participants with clustering of ≥2 (61.8% vs 63.0%) and ≥3 CVD risk factors (28.4% vs 32.2%) (p<0.05). These increasing rates were also observed among subgroups categorised by sex, ethnicity, education level, income level and those ≥45 years of age (p<0.05). In both 2011 and 2021, male participants and participants with a lower education level had higher prevalence of clustering of ≥2 and ≥3 CVD risk factors than their counterparts (p<0.01). Ethnic minority participants and participants with higher annual income had higher prevalence of clustering of CVD risk factors in 2011 but presented opposite associations in 2021 (p<0.01).ConclusionThe prevalence of clustering of CVD risk factors increased substantially across all socioeconomic spectra in rural southwest China from 2011 to 2021. Future efforts to implement comprehensive lifestyle interventions to promote the prevention and control of CVD should in particular focus on men, those of Han ethnicity and those with low socioeconomic status.
Early, very high-titre convalescent plasma therapy in clinically vulnerable individuals with mild COVID-19 (COVIC-19): protocol for a randomised, open-label trial
Authors: Desmarets Maxime , Hoffmann Simone , Vauchy Charline , Rijnders Bart J A , Toussirot Eric , Durrbach Antoine , Körper Sixten , Schrezenmeier Eva , van der Schoot C Ellen , Harvala Heli , Brunotte Gaëlle , Appl Thomas , Seifried Erhard , Tiberghien Pierre , Bradshaw Daniel , Roberts David J , Estcourt Lise J , Schrezenmeier Hubert 
Published: April 2023

IntroductionCOVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients.Methods and analysisCOVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle.Ethics and disseminationEthical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.Trial registrationClinical Trials.gov (NCT05271929), EudraCT (2021-006621-22)
Protocol for a realist and social return on investment evaluation of the use of patient-reported outcomes in four value-based healthcare programmes
Authors: Roberts Gareth , Cahill Adele , Lawthom Charlotte , Price Martine , Blyth Christopher , Jones Carys , Mc Laughlin Leah , Noyes Jane 
Published: April 2023

IntroductionThere is growing recognition that in order to remain sustainable, the UK’s National Health Service must deliver the best patient outcomes within available resources. This focus on outcomes relative to cost is the basis of value-based healthcare (VBHC) and has led to interest in the recording of patient-reported outcome measures (PROMs) to measure patient perspectives on the impact of a health condition on their lives. Every health board in Wales is now required to collect PROMS as part of routine care. We will evaluate the VBHC programme implemented in a lead health board. The study aim is to understand what works about PROMs collection, for whom, in what contexts and why in a VBHC context. In addition, we will assess the social value of integrating PROMs collection into routine care.Methods and analysisA three-stage mixed-methods study comprising a realist evaluation integrated with social return on investment (SROI) analysis across four conditions; Parkinson’s disease, epilepsy, heart failure and cataract surgery. Workstream 1: Development of logic models, informed by a scoping review, documentary analysis, patient and public involvement (PPI), staff and key stakeholder engagement. Workstream 2: Realist evaluation building on multiple data sources from stages 1 to 3 to test and refine the programme theories that arise from the logic model development. Workstream 3: SROI analysis using interview data with patients, staff and carers, stakeholder and PPI engagement, anonymised routinely collected data, and questionnaires to populate a model that will explore the social value generated by the implementation of PROMs. Findings across stages will be validated with key stakeholders.Ethics and disseminationThe study is approved by Wales Research Ethics Committee #5 (22/WA/0044). Outcomes will be shared with key stakeholders, published in peer-reviewed journals and presented at national and international conferences.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.
Development of machine learning-based models to predict 10-year risk of cardiovascular disease: a prospective cohort study
Authors: You Jia , Guo Yu , Kang Ju-Jiao , Wang Hui-Fu , Yang Ming , Feng Jian-Feng , Yu Jin-Tai , Cheng Wei 
Published: April 2023

BackgroundPrevious prediction algorithms for cardiovascular diseases (CVD) were established using risk factors retrieved largely based on empirical clinical knowledge. This study sought to identify predictors among a comprehensive variable space, and then employ machine learning (ML) algorithms to develop a novel CVD risk prediction model.MethodsFrom a longitudinal population-based cohort of UK Biobank, this study included 473 611 CVD-free participants aged between 37 and 73 years old. We implemented an ML-based data-driven pipeline to identify predictors from 645 candidate variables covering a comprehensive range of health-related factors and assessed multiple ML classifiers to establish a risk prediction model on 10-year incident CVD. The model was validated through a leave-one-center-out cross-validation.ResultsDuring a median follow-up of 12.2 years, 31 466 participants developed CVD within 10 years after baseline visits. A novel UK Biobank CVD risk prediction (UKCRP) model was established that comprised 10 predictors including age, sex, medication of cholesterol and blood pressure, cholesterol ratio (total/high-density lipoprotein), systolic blood pressure, previous angina or heart disease, number of medications taken, cystatin C, chest pain and pack-years of smoking. Our model obtained satisfied discriminative performance with an area under the receiver operating characteristic curve (AUC) of 0.762±0.010 that outperformed multiple existing clinical models, and it was well-calibrated with a Brier Score of 0.057±0.006. Further, the UKCRP can obtain comparable performance for myocardial infarction (AUC 0.774±0.011) and ischaemic stroke (AUC 0.730±0.020), but inferior performance for haemorrhagic stroke (AUC 0.644±0.026).ConclusionML-based classification models can learn expressive representations from potential high-risked CVD participants who may benefit from earlier clinical decisions.
Emergence of high-energy dynamics from cascade-baryon detections at the LHC
Authors: Celiberto Francesco Giovanni 
Published: April 2023

AbstractWe propose the inclusive detection at the LHC of a cascade$$\Xi ^-/\bar{\Xi }^+$$Ξ-/Ξ¯+baryon in association with a jet, as a novel probe channel for the QCD dynamics at high energies. We investigate the behavior of a selection of distributions, differential in rapidity, azimuthal angle and/or transverse momenta, calculated via the hybrid high-energy/collinear factorization encoding the full next-to-leading BFKL resummation of energy logarithms. We come out with the conclusion that the fragmentation mechanism underlying the production of$$\Xi ^-/\bar{\Xi }^+$$Ξ-/Ξ¯+baryon states leads to stabilization effects of the resummation, similar to those recently observed in the context of heavy-flavor studies within the same formalism.
Spectral interactions between strings in the Higgs background
Authors: Bochniak Arkadiusz , Sitarz Andrzej 
Published: April 2023

AbstractWe derive the exact form of the spectral interaction of two strings mediated by a constant scalar field using methods derived from noncommutative geometry. This is achieved by considering a non-product modification of the Connes–Lott model with two-dimensional manifolds. The analogy with the latter construction justifies the interpretation of the scalar field as being of Higgs type. Working in dimension two requires the use of the spectral zeta function instead of the Wodzicki residue techniques applicable to four-dimensional models. In the latter case, an analogous non-product geometry construction leads, for specific choices of metrics, to the so-called “doubled geometry models”, which can be thought of as a spectral modification of the Hassan–Rosen bimetric theory. We find that in dimension two, the interaction term depends explicitly on zweibeins defining the Dirac operators and only in some special cases can they be expressed solely using the metrics. The computations can be performed analytically for an arbitrary choice of zweibeins defining geometry on the two strings.
Geological disposal of radioactive waste in deep clay formations: celebrating 40 years of RD&D in the Belgian URL HADES
Authors: Van Geet Maarten , Bruggeman Christophe , De Craen Mieke 
Published: April 2023

Abstract

The option of disposing of radioactive waste deep underground has been studied in Belgium by SCK CEN since the 1970s. This led in 1980 to the construction of the HADES underground research laboratory (URL) in a clay formation, the Boom Clay, at a depth of 225 m under the premises of SCK CEN in Mol. Over the last four decades, many
in situ
experiments have been conducted in the HADES URL. These have made a significant contribution to ONDRAF/NIRAS’ research, development and demonstration (RD&D) efforts demonstrating that disposal in Boom Clay can offer a safe solution for the long-term management of high-level and/or long-lived radioactive waste. Moreover, the construction of the HADES URL itself is a demonstration that shafts and galleries can be constructed in clay at that depth. However, the HADES URL did not only contribute to the Belgian programme. Many of the
in situ
experiments have been part of international research and the laboratory has provided valuable input to the research programmes of other URLs, such as the Meuse/Haute-Marne URL in France and the Mont Terri rock laboratory in Switzerland. This paper gives a brief overview of the main contributions of the HADES URL to both national and international research into geological disposal.
N6-Methyladenosine Promotes Translation of VEGFA to Accelerate Angiogenesis in Lung Cancer
Authors: Zhang Haisheng , Zhou Jiawang , Li Jiexin , Wang Zhaotong , Chen Zhuojia , Lv Ziyan , Ge Lichen , Xie Guoyou , Deng Guoming , Rui Yalan , Huang Hongbing , Chen Likun , Wang Hongsheng 
Published: April 2023

Abstract

Angiogenesis is hijacked by cancer to support tumor growth. RNA modifications such as N6-methyladenosine (m6A) can regulate several aspects of cancer, including angiogenesis. Here, we find that m6A triggers angiogenesis in lung cancer by upregulating VEGFA, a central regulator of neovasculature and blood vessel growth. m6A-sequencing and functional studies confirmed that m6A modification of the 5′UTR (untranslated region) of VEGFA positively regulates its translation. Specifically, methylation of a 5′UTR internal ribosome entry site (IRES) recruited the YTHDC2/eIF4GI complex to trigger cap-independent translation initiation. Intriguingly, the m6A methylation site A856 of the 5′UTR was located within the conserved upstream open reading frame (uORF) of VEGFA IRES-A, which overcomes uORF-mediated translation suppression while facilitating G-quadruplex–induced translation of VEGFA. Targeted specific demethylation of VEGFA m6A significantly decreased expression of VEGFA and reduced lung cancer cell–driven angiogenesis. In vivo and clinical data confirmed the positive effects of m6A modification of VEGFA on angiogenesis and tumor growth of lung cancer. This study not only reveals that the m6A/VEGFA axis is a potential target for lung cancer therapy but also expands our understanding of the impact of m6A modification of IRES in the 5′UTR of mRNA on translation regulation.

Significance:
Methylation of the 5′UTR IRES of VEGFA mRNA increases cap-independent translation via recruitment of the YTHDC2/eIF4GI complex, which stimulates angiogenesis to promote lung tumor growth.
Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103
Authors: Shen Fei , Jiang Guanglong , Philips Santosh , Gardner Laura , Xue Gloria , Cantor Erica , Ly Reynold C. , Osei Wilberforce , Wu Xi , Dang Chau , Northfelt Donald , Skaar Todd , Miller Kathy D. , Sledge George W. , Schneider Bryan P. 
Published: May 2023

Abstract

Purpose:
Paclitaxel is a widely used anticancer therapeutic. Peripheral neuropathy is the dose-limiting toxicity and negatively impacts quality of life. Rare germline gene markers were evaluated for predicting severe taxane-induced peripheral neuropathy (TIPN) in the patients of European ancestry. In addition, the impact of Cytochrome P450 (CYP) 2C8, CYP3A4, and CYP3A5 metabolizer status on likelihood of severe TIPN was also assessed.

Experimental Design:
Whole-exome sequencing analyses were performed in 340 patients of European ancestry who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Patients who experienced grade 3–4 (n = 168) TIPN were compared to controls (n = 172) who did not experience TIPN. For the analyses, rare variants with a minor allele frequency ≤ 3% and predicted to be deleterious by protein prediction programs were retained. A gene-based, case–control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of severe TIPN. CYP star alleles for CYP2C8, CYP3A4, and CYP3A5 were called. An additive logistic regression model was performed to test the association of CYP2C8, CYP3A4, and CYP3A5 metabolizer status with severe TIPN.

Results:
Cytochrome P450 oxidoreductase (POR) was significantly associated with severe TIPN (P value = 1.8 ×10−6). Six variants were predicted to be deleterious in POR. There were no associations between CYP2C8, CYP3A4, or CYP3A5 metabolizer status with severe TIPN.

Conclusions:
Rare variants in POR predict an increased risk of severe TIPN in patients of European ancestry who receive paclitaxel.
Maveropepimut-S, a DPX-Based Immune-Educating Therapy, Shows Promising and Durable Clinical Benefit in Patients with Recurrent Ovarian Cancer, a Phase II Trial
Authors: Dorigo Oliver , Oza Amit M. , Pejovic Tanja , Ghatage Prafull , Ghamande Sharad , Provencher Diane , MacDonald Lisa D. , Torrey Heather , Kaliaperumal Valarmathy , Ebrahimizadeh Walead , Hirsch Heather A. , Bramhecha Yogesh , Villella Jeannine , Fiset Stephan 
Published: May 2023

Abstract

Purpose:
Patients with platinum-resistant ovarian cancer respond poorly to existing therapies. Hence there is a need for more effective treatments.

Patients and Methods:
The DeCidE1 trial is a multicenter, randomized, open-label, single-arm phase II study to evaluate the safety and effectiveness of maveropepimut-S with cyclophosphamide in patients with recurrent ovarian cancer. Median follow-up for evaluable subjects was 4.4 months. Data were collected from March 2019 to June 2021. Subjects received two injections of 0.25 mL maveropepimut-S 3 weeks apart, followed by one 0.1-mL doses, every 8 weeks up to progression. Oral cyclophosphamide, 50 mg twice daily, was administered in repeating weekly on and off cycles.

Results:
Twenty-two patients were enrolled. Median age was 58 years (38–78 years). Among the evaluable population, the objective response rate (ORR) was 21% [90% confidence interval (CI), 7.5%–41.9%], with a disease control rate (DCR) of 63% (90% CI, 41.8%–81.3%), including 4 (21%) patients with partial responses, 8 (42%) stable disease, and 7 (37%) progressive disease. The ORRs were consistent across subgroups based on platinum sensitivity, and DCR was higher in the platinum-resistant subpopulation. Four SD patients maintained clinical benefit up to 25 months. Most treatment-related adverse events (TRAE) were grade 1 and 2 (87% of unique events). Most common AEs were injection site reactions. Eight subjects reported grade 3 and no grade 4 AEs. Survivin-specific T-cell responses were observed in treated patients with clinical benefit.

Conclusions:
Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer. Observed responses are irrespective of the platinum status.