bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoking patterns and the intention to quit in German patients with cancer: study protocol for a cross-sectional observational study
Authors: Bokemeyer Frederike , Lebherz Lisa , Schulz Holger , Bokemeyer Carsten , Gali Kathleen , Bleich Christiane 
Published: April 2023

IntroductionPatients who continue to smoke cigarettes after a cancer diagnosis can experience poorer treatment tolerance and outcomes than those who quit immediately. Identifying risk factors specific to patients with cancer who smoke, as well as their smoking behaviours (eg, frequency of use, types of tobacco products), dependency level and quit intentions, is necessary to better inform patients and encourage quitting smoking after a cancer diagnosis. This study aims to examine the occurrence of smoking in patients with cancer treated at specialised oncology departments and outpatient clinics based within the metropolitan region of Hamburg, Germany, and presents an analysis of their smoking patterns. This understanding is the first step in developing an adequate smoking cessation intervention and shall contribute to a sustainable improvement in the treatment results, long-term survival and quality of life of patients with cancer.Methods and analysisA questionnaire will be administered to patients with cancer (N=865) aged 18 years and above in the catchment area of Hamburg, Germany. Data acquisition includes sociodemographic, medical and psychosocial data as well as information on current smoking patterns. To identify the associations between smoking patterns and sociodemographic characteristics, disease-related variables, and psychological risk factors, descriptive statistics and multiple logistic as well as multinomial regressions will be performed.Ethics and disseminationThis study was registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/PGBY8). It was approved by the ethics committee of the local psychological Ethic committee at the centre of psychosocial medicine Hamburg, Germany (LPEK) (tracking number: LPEK-0212). The study will be carried out in accordance with the Code of Ethics of the Declaration of Helsinki. The results will be published in peer-reviewed scientific journals.
Factors influencing the choice-of-care pathway and survival in the fetus with hypoplastic left heart syndrome in New Zealand: a population-based cohort study
Authors: Soszyn Natalie , Cloete Elza , Sadler Lynn , de Laat Monique W M , Crengle Sue , Bloomfield Frank , Finucane Kirsten , Gentles Thomas L 
Published: April 2023

ObjectivesTo better understand the relative influence of fetal and maternal factors in determining the choice-of-care pathway (CCP) and outcome in the fetus with hypoplastic left heart syndrome (HLHS).DesignA retrospective, population-based study of fetuses with HLHS from a national dataset with near-complete case ascertainment from 20 weeks’ gestation. Fetal cardiac and non-cardiac factors were recorded from the patient record and maternal factors from the national maternity dataset. The primary endpoint was a prenatal decision for active treatment after birth (intention-to-treat). Factors associated with a delayed diagnosis (≥24 weeks’ gestation) were also reviewed. Secondary endpoints included proceeding to surgical treatment, and 30-day postoperative mortality in liveborns with an intention-to-treat.SettingNew Zealand population-wide.ParticipantsFetuses with a prenatal diagnosis of HLHS between 2006 and 2015.ResultsOf 105 fetuses, the CCP was intention-to-treat in 43 (41%), and pregnancy termination or comfort care in 62 (59%). Factors associated with intention-to-treat by multivariable analysis included a delay in diagnosis (OR: 7.8, 95% CI: 3.0 to 20.6, p<0.001) and domicile in the maternal fetal medicine (MFM) region with the most widely dispersed population (OR: 5.3, 95% CI: 1.4 to 20.3, p=0.02). Delay in diagnosis was associated with Māori maternal ethnicity compared with European (OR: 12.9, 95% CI: 3.1 to 54, p<0.001) and greater distance from the MFM centre (OR: 3.1, 95% CI: 1.2 to 8.2, p=0.02). In those with a prenatal intention-to-treat, a decision not to proceed to surgery was associated with maternal ethnicity other than European (p=0.005) and the presence of major non-cardiac anomalies (p=0.01). Thirty-day postoperative mortality occurred in 5/32 (16%) and was more frequent when there were major non-cardiac anomalies (p=0.02).ConclusionsFactors associated with the prenatal CCP relate to healthcare access. Anatomic characteristics impact treatment decisions after birth and early postoperative mortality. The association of ethnicity with delayed prenatal diagnosis and postnatal decision-making suggests systemic inequity and requires further investigation.
Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) in adults with chronic stroke: protocol of a randomised controlled trial
Authors: Ebner-Karestinos Daniela , Gathy Estelle , Carton de Tournai Astrid , Herman Enimie , Araneda Rodrigo , Dricot Laurence , Macq Benoît , Vandermeeren Yves , Bleyenheuft Yannick 
Published: April 2023

IntroductionStroke causes multiple deficits including motor, sensitive and cognitive impairments, affecting also individual’s social participation and independence in activities of daily living (ADL) impacting their quality of life. It has been widely recommended to use goal-oriented interventions with a high amount of task-specific repetitions. These interventions are generally focused only on the upper or lower extremities separately, despite the impairments are observed at the whole-body level and ADL are both frequently bimanual and may require moving around. This highlights the need for interventions targeting both upper and lower extremities. This protocol presents the first adaptation of Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for adults with acquired hemiparesis.Methods and analysisThis randomised controlled trial will include 48 adults with chronic stroke, aged ≥40 years. This study will compare the effect of 50 hours of HABIT-ILE against usual motor activity and regular rehabilitation. HABIT-ILE will be provided in a 2-week, adult’s day-camp setting, promoting functional tasks and structured activities. These tasks will continuously progress by increasing their difficulty. Assessed at baseline, 3 weeks after and at 3 months, the primary outcome will be the adults-assisting-hand-assessment stroke; secondary outcomes include behavioural assessments for hand strength and dexterity, a motor learning robotic medical device for quality of bimanual motor control, walking endurance, questionnaires of ADL, stroke impact on participation and self-determined patient-relevant goals, besides neuroimaging measures.Ethics and disseminationThis study has full ethical approval from theComité d’éthique Hospitalo-Facultaire/Université catholique de Louvain, Brussels (reference number: 2013/01MAR/069) and the local medical Ethical Committee of the CHU UCL Namur-site Godinne. Recommendations of the ethical board and the Belgian law of 7 May 2004, concerning human experiments will be followed. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.Trial registration numberNCT04664673.
Long-term consequences of neonatal encephalopathy in the hypothermia era: protocol for a follow-up cohort study at 9 years of age
Authors: Brossard-Racine Marie , Rampakakis Emmanouille , Tardif Christine Lucas , Gilbert Guillaume , White Angela , Luu Thuy Mai , Gallagher Anne , Pinchefsky Elana , Montreuil Tina , Simard Marie-Noelle , Wintermark Pia 
Published: April 2023

IntroductionTherapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective in reducing mortality and the incidence of severe developmental disabilities, the recent literature converges in reporting frequent cognitive and behavioural difficulties at school entry in children with NE-TH. Although these challenges are deemed minor compared with cerebral palsy and intellectual disability, their impacts on a child’s self-determination and family’s well-being are quite significant. Therefore, the nature and extent of these difficulties need to be comprehensively described so that appropriate care can be offered.Methods and analysisThe current study will be the largest follow-up study of neonates with NE treated with TH to characterize their developmental outcomes and associated brain structural profiles at 9 years of age. Specifically, we will compare executive function, attention, social cognition, behaviour, anxiety, self-esteem, peer problems, brain volume, cortical features, white matter microstructure and myelination between children with NE-TH and matched peers without NE. Associations of perinatal risk factors and structural brain integrity with cognitive, behavioural and psycho-emotional deficits will be evaluated to inform about the potential aggravating and protective factors associated with function.Ethics and disseminationThis study is supported by the Canadian Institute of Health Research (202203PJT-480065-CHI-CFAC-168509), and received approval from the Pediatric Ethical Review Board of the McGill University Health Center (MP-37-2023-9320). The study findings will be disseminated in scientific journals and conferences and presented to parental associations and healthcare providers to inform best practices.Trial registration numberNCT05756296.
Doctors Improving Referrals project: a referrals toolkit for junior doctors
Authors: Thorley Emma V , Doshi Akash , Turner Benedict R H 
Published: April 2023

Every day in hospitals around the world, millions of interspecialty referrals are made to obtain advice on the optimal care and management of patients. In the UK, the brunt of this work is undertaken by junior doctors with less clinical experience than the specialist colleagues to which they refer. A survey of 283 junior doctors revealed that colleagues were underconfident when making referrals and struggled to know which specialty to contact, how to reach the specialty and what clinical information to include in the referral. More concerningly, 10% of those surveyed had experienced bullying or belittling behaviours and verbal aggression from colleagues when referring.The aim of this project was to design and implement a referrals toolkit for junior doctors to improve confidence making referrals and time to interspecialty advice, to improve patient care. Process mapping to understand the constituents of good referrals was combined with a failure modes and effects analysis describing how referrals fail to identify areas for intervention.A specialty referrals guide with all specialty contact information was created at the trust, demonstrating an increase in junior doctor median confidence from 3/5 (n=20) to 5/5 (n=23) (p<0.001); 65% found it quicker to refer with the guide and 81% found an improved time to discharge. A referrals cheat sheet was also created, containing specialty-specific information to be included when making a referral. This has been downloaded over 23 000 times from around the globe. Of survey respondents (n=43), 74% noted improved confidence in making referrals, 26% noted faster time to specialty advice and 19% found a positive impact on patient discharges. Overall, the referrals toolkit has been beneficial for both junior doctors and the patients for which they care and has been accessed by over 50% of new foundation doctors in 2021 and 2022.
Lumbar spine bone mineral adaptation: cricket fast bowlers versus controls
Authors: Keylock Laura , Alway Peter , Johnson William , Crabtree Nicola , King Mark , Peirce Nicholas , Brooke-Wavell Katherine 
Published: April 2023

Elite adult male fast bowlers have high lumbar spine bone mineral, particularly on the contralateral side to their bowling arm. It is thought that bone possesses its greatest ability to adapt to loading during adolescence, but it is unknown at what age the greatest changes in lumbar bone mineral and asymmetry develops in fast bowlers.ObjectivesThis study aims to evaluate the adaptation of the lumbar vertebrae in fast bowlers compared to controls and how this is associated with age.Methods91 male fast bowlers and 84 male controls aged 14–24 years had between one and three annual anterior-posterior lumbar spine dual-energy-X-ray absorptiometry scans. Total (L1-L4) and regional ipsilateral and contralateral L3 and L4 (respective to bowling arm) bone mineral density and content (BMD/C) were derived. Multilevel models examined the differences in lumbar bone mineral trajectories between fast bowlers and controls.ResultsAt L1-L4 BMC and BMD, and contralateral BMD sites, fast bowlers demonstrated a greater negative quadratic pattern to their accrual trajectories than controls. Fast bowlers had greater increases in BMC in L1-L4 between 14 and 24 years of 55% compared with controls (41%). Within vertebra, asymmetry was evident in all fast bowlers and increased by up to 13% in favour of the contralateral side.ConclusionsLumbar vertebral adaptation to fast bowling substantially increased with age, particularly on the contralateral side. The greatest accrual was during late adolescence and early adulthood, which may correspond with the increasing physiological demands of adult professional sport.
Diagnostic significance of antineutrophil cytoplasmic antibody (ANCA) titres: a retrospective case-control study
Authors: Merindol Julie , Levraut Michael , Seitz-Polski Barbara , Morand Lucas , Martis Nihal 
Published: April 2023

ObjectivesTo investigate the reliability of elevated titres of antineutrophil cytoplasmic antibody (ANCA) and to identify a cut-off titre in discriminating between ANCA-associated vasculitides (AAV) and its mimickers.MethodsThis retrospective observational single-centre study included patients over 18 years with positive myeloperoxidase (MPO)-ANCA and/or proteinase 3 (PR3)-ANCA immunoassays over an 8-year period (January 2010 to December 2018), via their electronic medical files. Patients were classified according to the 2022 ACR/EULAR criteria and alternative diagnoses categorised either as non-AAV autoimmune disorders (ANCA-AI) or disorders without autoimmune features (ANCA-O). Findings from the AAV group were compared with those of ANCA-AI and ANCA-O groups and followed by a multivariate logistic stepwise regression analysis of features associated with AAV.Results288 ANCA-positive patients of which 49 had AAV were altogether included. There was no difference between patients between the ANCA-AI (n=99) and the ANCA-O (n=140) groups. The AUC for titres discriminating AAV from mimickers was 0.83 (95% CI, 0.79 to 0.87). The best threshold titre, irrespective of PR3-ANCA or MPO-ANCA, was 65 U/mL with a negative predictive value of 0.98 (95% CI, 0.95 to 1.00). On multivariate analysis, an ANCA titre ≥65 U/mL was independently associated with AAV with an OR of 34.21 (95% CI 9.08 to 129.81; p<0.001). Other risk factors were: pulmonary fibrosis (OR, 11.55 (95% CI, 3.87 to 34.47, p<0.001)), typical ear nose and throat involvement (OR, 5.67 (95% CI, 1.64 to 19.67); p=0.006) and proteinuria (OR, 6.56 (95% CI, 2.56 to 16.81; p<0.001)).ConclusionHigh PR3/MPO-ANCA titres can help to discriminate between AAV and their mimickers in patients presenting with small-calibre vasculitides, with a threshold titre of 65 U/mL and above.
End-to-End Security for Distributed Event-driven Enclave Applications on Heterogeneous TEEs
Authors: Scopelliti Gianluca , Pouyanrad Sepideh , Noorman Job , Alder Fritz , Baumann Christoph , Piessens Frank , Mühlberg Jan Tobias 
Published: April 2023

This article presents an approach to provide strong assurance of the secure execution of distributed event-driven applications on shared infrastructures, while relying on a small Trusted Computing Base. We build upon and extend security primitives provided by Trusted Execution Environments (TEEs) to guarantee authenticity and integrity properties of applications, and to secure control of input and output devices. More specifically, we guarantee that if an output is produced by the application, it was allowed to be produced by the application’s source code based on an authentic trace of inputs.
We present an integrated open-source framework to develop, deploy, and use such applications across heterogeneous TEEs. Beyond authenticity and integrity, our framework optionally provides confidentiality and a notion of availability, and facilitates software development at a high level of abstraction over the platform-specific TEE layer. We support event-driven programming to develop distributed enclave applications in Rust and C for heterogeneous TEE, including Intel SGX, ARM TrustZone, and Sancus.
In this article we discuss the workings of our approach, the extensions we made to the Sancus processor, and the integration of our development model with commercial TEEs. Our evaluation of security and performance aspects show that TEEs, together with our programming model, form a basis for powerful security architectures for dependable systems in domains such as Industrial Control Systems and the Internet of Things, illustrating our framework’s unique suitability for a broad range of use cases which combine cloud processing, mobile and edge devices, and lightweight sensing and actuation.
Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco 
Published: April 2023

Abstract

Purpose:
mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy.

Experimental Design:
lncRNA expression profile was analyzed in one cohort of patients with melanoma and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells.

Results:
We identified the lncRNA NEAT1 as commonly upregulated between patients with melanoma with complete therapeutic response and patients with GBM with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the IFNγ pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNFα/NFκB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNFα and other inflammatory cytokines.

Conclusions:
These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.
Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers
Authors: Venkadakrishnan Varadha Balaji , Yamada Yasutaka , Weng Kenny , Idahor Osasenaga , Beltran Himisha 
Published: April 2023

Abstract
Cancer cells can undergo plasticity in response to environmental stimuli or under selective therapeutic pressures that result in changes in phenotype. This complex phenomenon of phenotypic plasticity is now recognized as a hallmark of cancer. Lineage plasticity is often associated with loss of dependence on the original oncogenic driver and is facilitated, in part, by underlying genomic and epigenetic alterations. Understanding the molecular drivers of cancer plasticity is critical for the development of novel therapeutic strategies. The retinoblastoma gene RB1 (encoding RB) is the first tumor suppressor gene to be discovered and has a well-described role in cell-cycle regulation. RB is also involved in diverse cellular functions beyond cell cycle including differentiation. Here, we describe the emerging role of RB loss in unlocking cancer phenotypic plasticity and driving therapy resistance across cancer types. We highlight parallels in cancer with the noncanonical role of RB that is critical for normal development and lineage specification, and the downstream consequences of RB loss including epigenetic reprogramming and chromatin reorganization that can lead to changes in lineage program. Finally, we discuss potential therapeutic approaches geared toward RB loss cancers undergoing lineage reprogramming.
Genome-wide CRISPR Screen Reveals RAB10 as a Synthetic Lethal Gene in Colorectal and Pancreatic Cancers Carrying SMAD4 Loss
Authors: Erasimus Hélène , Kolnik Vanessa , Lacroix Frédéric , Sidhu Sukhvinder , D'Agostino Stéphane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe 
Published: April 2023

The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. SMAD4 acts as a tumor suppressor and its loss is associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions with SMAD4 deficiency to find novel therapeutic strategies for the treatment of patients with SMAD4-deficient colorectal or pancreatic cancers. Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens in Cas9-expressing colorectal and pancreatic cancer cells harboring altered or wild-type SMAD4. The small GTPase protein RAB10 was identified and validated as a susceptibility gene in SMAD4-altered colorectal and pancreatic cancer cells. Rescue assays showed that RAB10 reintroduction reversed the antiproliferative effects of RAB10 knockout in SMAD4-negative cell lines. Further investigation is necessary to shed light on the mechanism by which RAB10 inhibition decreases cell proliferation of SMAD4-negative cells.

Significance:
This study identified and validated RAB10 as new synthetic lethal gene with SMAD4. This was achieved by conducting a whole-genome CRISPR screens in different colorectal and pancreatic cell lines. A future RAB10 inhibitors could correspond to a new therapeutic solution for patients with cancer with SMAD4 deletion.