bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-morbidity and its association with common cancer diagnoses: a UK Biobank prospective study
Authors: Conroy Megan C. , Reeves Gillian K. , Allen Naomi E. 
Published: July 2023

Abstract
Background
Whilst multi-morbidity is known to be a concern in people with cancer, very little is known about the risk of cancer in multi-morbid patients. This study aims to investigate the risk of being diagnosed with lung, colorectal, breast and prostate cancer associated with multi-morbidity.

Methods
We investigated the association between multi-morbidity and subsequent risk of cancer diagnosis in UK Biobank. Cox models were used to estimate the relative risks of each cancer of interest in multi-morbid participants, using the Cambridge Multimorbidity Score. The extent to which reverse causation, residual confounding and ascertainment bias may have impacted on the findings was robustly investigated.

Results
Of the 436,990 participants included in the study who were cancer-free at baseline, 21.6% (99,965) were multi-morbid (≥ 2 diseases). Over a median follow-up time of 10.9 [IQR 10.0–11.7] years, 9,019 prostate, 7,994 breast, 5,241 colorectal, and 3,591 lung cancers were diagnosed. After exclusion of the first year of follow-up, there was no clear association between multi-morbidity and risk of colorectal, prostate or breast cancer diagnosis. Those with ≥ 4 diseases at recruitment had double the risk of a subsequent lung cancer diagnosis compared to those with no diseases (HR 2.00 [95% CI 1.70–2.35] p for trend < 0.001). These findings were robust to sensitivity analyses aimed at reducing the impact of reverse causation, residual confounding from known cancer risk factors and ascertainment bias.

Conclusions
Individuals with multi-morbidity are at an increased risk of lung cancer diagnosis. While this association did not appear to be due to common sources of bias in observational studies, further research is needed to understand what underlies this association.
Non-pharmacological interventions to manage psychological distress in patients living with cancer: a systematic review
Authors: Paley Carole A. , Boland Jason W. , Santarelli Martina , Murtagh Fliss E. M. , Ziegler Lucy , Chapman Emma J. 
Published: July 2023

Abstract
Background
Psychological distress is common in patients with cancer; interfering with physical and psychological wellbeing, and hindering management of physical symptoms. Our aim was to systematically review published evidence on non-pharmacological interventions for cancer-related psychological distress, at all stages of the disease.

Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered on PROSPERO (CRD42022311729). Searches were made using eight online databases to identify studies meeting our inclusion criteria.
Data were collected on outcome measures, modes of delivery, resources and evidence of efficacy. A meta-analysis was planned if data allowed. Quality was assessed using the Mixed Methods Appraisal Tool (MMAT).

Results
Fifty-nine studies with 17,628 participants were included. One third of studies included mindfulness, talking or group therapies. Half of all studies reported statistically significant improvements in distress. Statistically significant intervention effects on distress were most prevalent for mindfulness techniques. Four of these mindfulness studies had moderate effect sizes (d = -0.71[95% CI: -1.04, -0.37] p < 0.001) (d = -0.60 [95% CI: -3.44, -0.89] p < 0.001) (d = -0.77 [CI: -0.146, -1.954] p < 0.01) (d = -0.69 [CI: -0.18, -1.19] p = 0.008) and one had a large effect size (d = -1.03 [95% CI: -1.51, -0.54] p < 0.001). Heterogeneity of studies precluded meta-analysis. Study quality was variable and some had a high risk of bias.

Conclusions
The majority of studies using a mindfulness intervention in this review are efficacious at alleviating distress. Mindfulness—including brief, self-administered interventions—merits further investigation, using adequately powered, high-quality studies.

Systematic review registration
This systematic review is registered on PROSPERO, number CRD42022311729.
Exploring different stakeholders’ perspectives on ward rounds in paediatric oncology: a qualitative study
Authors: Berndt Lea P. , Sellin Julia , Mücke Urs , Mücke Martin , Conrad Rupert , Grigull Lorenz 
Published: July 2023

Abstract
Rational/Aims and Objectives
Ward rounds are a core routine for interprofessional communication and clinical care planning: Health care professionals and patients meet regularly and it encourages patients to actively participate. In paediatric oncology, the long treatment process, the serious diagnosis, and involvement of both patients and their parents in shared-decision-making require specific ward round skills. Despite its high value for patient-centred care, a universal definition of ward round is lacking. Little is known about attitudes and expectations of different participants towards a ‘good’ ward round. This study aims to capture experiences and expectations of different stakeholders to better understand ward round needs in paediatric oncology and serve as a basis to improve future ward rounds.

Method
Semi-structured interviews were conducted with patients, parents, nurses and medical doctors of a paediatric oncology ward until theoretical saturation (13 interviews). A standardised qualitative analysis using the phenomenological framework defined by Colaizzi was used to identify important aspects in the interviews.

Results
Three major themes were identified in the interviews: [1] Structure and Organisation; [2] Communication; [3] Education. Further analysis revealed 23 categories and elucidated several opportunities and unmet needs recognized by stakeholders: Ward round functions in comforting families in stressful situations, and relationship building. Interviewees expressed their concerns about missing structures. Families pleaded for smaller ward round teams and layperson language. Health care professionals underscored the lack of ward round training. Paediatric patients stated that ward round scared them without proper explanation. All interviewees emphasized the need for professionalization of the ward round in the setting of paediatric oncology.

Conclusion
This study gives important insights into ward round functions and organisational requirements. It addresses special challenges for ward round participants in paediatric oncology, such as consideration of the emotional aspect of cancer treatment or the limits of shared decision making. Furthermore, this study underscores the great significance of ward rounds in paediatric oncology, with an emphasis on communication and relationship-building. Although performed universally, ward rounds are poorly explored or evaluated. This structured analysis synthesizes important expectations of different WR stakeholders, revealing opportunities of improvement and stressing the need for guidelines, training, and preparation.
Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer
Authors: Ye Feng , Dewanjee Saikat , Li Yuehua , Jha Niraj Kumar , Chen Zhe-Sheng , Kumar Ankush , Vishakha  , Behl Tapan , Jha Saurabh Kumar , Tang Hailin 
Published: July 2023

AbstractBreast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.
The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium: a nationwide interrupted time series analysis
Authors: Vandenplas Yannick , Simoens Steven , Van Wilder Philippe , Vulto Arnold G. , Huys Isabelle 
Published: July 2023

Abstract
Background
The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake.

Methods
An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses.

Results
In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI −61.61 to −14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI −880.113 to −19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648–3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797–2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI −203.128 to −100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536–1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant.

Conclusions
The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.
The use of participatory systems mapping as a research method in the context of non-communicable diseases and risk factors: a scoping review
Authors: van den Akker Amber , Fabbri Alice , Alardah Dima I. , Gilmore Anna B. , Rutter Harry 
Published: July 2023

Abstract
Context
Participatory systems mapping is increasingly used to gain insight into the complex systems surrounding non-communicable diseases (NCDs) and their risk factors.

Objectives
To identify and synthesize studies that used participatory systems mapping in the context of non-communicable diseases.

Design
Scoping review.

Eligibility criteria
Peer-reviewed studies published between 2000 and 2022.

Study selection
Studies that focused on NCDs and/or related risk factors, and included participants at any stage of their system’s mapping process, were included.

Categories for analysis
The main categories for analysis were: (1) problem definition and goal-setting, (2) participant involvement, (3) structure of the mapping process, (4) validation of the systems map, and (5) evaluation of the mapping process.

Results
We identified 57 studies that used participatory systems mapping for a variety of purposes, including to inform or evaluate policies or interventions and to identify potential leverage points within a system. The number of participants ranged from 6 to 590. While policymakers and professionals were the stakeholder groups most often included, some studies described significant added value from including marginalized communities. There was a general lack of formal evaluation in most studies. However, reported benefits related mostly to individual and group learning, whereas limitations described included a lack of concrete actions following from systems mapping exercises.

Conclusions
Based on the findings of this review, we argue that research using participatory systems mapping would benefit from considering three different but intertwined actions: explicitly considering how different participants and the power imbalances between them may influence the participatory process, considering how the results from a systems mapping exercise may effectively inform policy or translate into action, and including and reporting on evaluation and outcomes of the process, wherever possible.
Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models
Authors: Zhang Huiyuan , Du Yuchen , Qi Lin , Xiao Sophie , Braun Frank K. , Kogiso Mari , Huang Yulun , Huang Frank , Abdallah Aalaa , Suarez Milagros , Karthick Sekar , Ahmed Nabil M. , Salsman Vita S. , Baxter Patricia A. , Su Jack M. , Brat Daniel J. , Hellenbeck Paul L. , Teo Wan-Yee , Patel Akash J. , Li Xiao-Nan 
Published: July 2023

Abstract
Background
Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It’s capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

Materials and methods
23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage.

Results
PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times.

Conclusion
A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.
PARP1 negatively regulates transcription of BLM through its interaction with HSP90AB1 in prostate cancer
Authors: Huang Mengqiu , Chen Lin , Guo Yingchu , Ruan Yong , Xu Houqiang 
Published: July 2023

Abstract
Background
Prostate cancer (PCa) is a prevalent malignant disease affecting a significant number of males globally. Elevated expression of the Bloom’s syndrome protein (BLM) helicase has emerged as a promising cancer biomarker, being associated with the onset and progression of PCa. Nevertheless, the precise molecular mechanisms governing BLM regulation in PCa remain elusive.

Methods
The expression of BLM in human specimens was analyzed using immnohistochemistry (IHC). A 5′-biotin-labeled DNA probe containing the promoter region of BLM was synthesized to pull down BLM promoter-binding proteins. Functional studies were conducted using a range of assays, including CCK-8, EdU incorporation, clone formation, wound scratch, transwell migration, alkaline comet assay, xenograft mouse model, and H&E staining. Mechanistic studies were carried out using various techniques, including streptavidin-agarose-mediated DNA pull-down, mass spectrometry (MS), immunofluorescence (IF), dual luciferase reporter assay system, RT-qPCR, ChIP-qPCR, co-immunoprecipitation (co-IP), and western blot.

Results
The results revealed significant upregulation of BLM in human PCa tissues, and its overexpression was associated with an unfavorable prognosis in PCa patients. Increased BLM expression showed significant correlations with advanced clinical stage (P = 0.022) and Gleason grade (P = 0.006). In vitro experiments demonstrated that BLM knockdown exerted inhibitory effects on cell proliferation, clone formation, invasion, and migration. Furthermore, PARP1 (poly (ADP-ribose) polymerase 1) was identified as a BLM promoter-binding protein. Further investigations revealed that the downregulation of PARP1 led to increased BLM promoter activity and expression, while the overexpression of PARP1 exerted opposite effects. Through mechanistic studies, we elucidated that the interaction between PARP1 and HSP90AB1 (heat shock protein alpha family class B) enhanced the transcriptional regulation of BLM by counteracting the inhibitory influence of PARP1 on BLM. Furthermore, the combination treatment of olaparib with ML216 demonstrated enhanced inhibitory effects on cell proliferation, clone formation, invasion, and migration. It also induced more severe DNA damage in vitro and exhibited superior inhibitory effects on the proliferation of PC3 xenograft tumors in vivo.

Conclusions
The results of this study underscore the significance of BLM overexpression as a prognostic biomarker for PCa, while also demonstrating the negative regulatory impact of PARP1 on BLM transcription. The concurrent targeting of BLM and PARP1 emerges as a promising therapeutic approach for PCa treatment, holding potential clinical significance.
Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages
Authors: He Weiwei , Huang Yinxiang , Shi Xiulin , Wang Qingxuan , Wu Menghua , Li Han , Liu Qiuhong , Zhang Xiaofang , Huang Caoxin , Li Xuejun 
Published: July 2023

Abstract
Background
There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD.

Methods
To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues.

Results
The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-β signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients.

Conclusion
Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.
Dissemination and genome characterization of a human adenovirus F41 in a patient with B-Cell lymphoma
Authors: Fall Amary , Campodónico Victoria L. , Howard Craig , Gallagher Nicholas , Bailey Gabrielle , Kajon Adriana E. , Mostafa Heba H. 
Published: July 2023

AbstractAdenovirus (HAdV) F41 is a common cause of gastroenteritis and has rarely been reported associated with disseminated disease. In this report, an adult patient with a history of ulcerative colitis, cryptogenic cirrhosis, stage III adenocarcinoma, high-grade diffuse large B-cell lymphoma on chemotherapy was diagnosed with disseminated adenovirus infection. HAdV DNA was quantified in stool, plasma, and urine with viral loads of 7, 4, and 3 log10 copies/mL, respectively. The patient’s course was rapidly progressive and he passed away 2 days after initiation of antiviral therapy. The patient’s infecting virus was characterized as HAdV-F41 by whole genome sequencing.