bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy of a virtual reality tool for the treatment of obesity: study protocol of a randomised controlled trial
Authors: Anastasiadou Dimitra , Slater Mel , Spanlang Bernhard , Cano Porras Desiderio , Comas Marta , Ciudin Andreea , Puig Gemma Parramon , Vázquez-De Sebastián Julia , Ramos-Quiroga Jose Antonio , Lusilla-Palacios Pilar 
Published: June 2022

IntroductionPrevious research has shown that it is feasible to integrate motivational interviewing techniques with behavioural and psychological interventions for the treatment of obesity. Moreover, these combined interventions have the potential to improve health-related outcomes of people living with obesity (PLWO) and to afford maintenance of behavioural changes over time. In addition, the use of virtual reality (VR) embodiment techniques in the treatment of eating disorders and obesity has promising preliminary effectiveness. The objective of this study is to assess the clinical efficacy of a VR intervention that uses embodiment and body-swapping techniques and has been specifically developed to cover the needs of PLWO.Methods and analysisA randomised control trial will be carried out with an estimated sample of 96 participants with body mass index (BMI)>30. The whole duration of the trial will be 12 months. Participants will be recruited from the external consultations of the Vall d'Hebron University Hospital and be randomly assigned to three groups. The experimental group 1 will engage in a virtual self-conversation using the ConVRself platform, the experimental group 2 will participate in a ‘pre-established discourse’ provided by the virtual counsellor, who will give psychoeducation advice, and the control group will continue with treatment as usual. Readiness to change, BMI, eating habits and physical activity, psychological well-being, body image satisfaction, quality of life in relation to body image, and weight bias internalisation will be assessed at baseline, post intervention, 1-week and 4-week follow-up. Finally, variables related to adherence and satisfaction with the VR tool will be evaluated for the experimental groups.Ethics and disseminationThis study was approved by the Research Projects Committee of the Vall d’Hebron University Hospital. Findings will be disseminated through peer-reviewed journals, reports to the funding body, conferences and other events for the scientific and clinical community, and the general public.Trial registration numberNCT05094557.
Estimating BMI distributions by age and sex for local authorities in England: a small area estimation study
Authors: Amies-Cull Ben , Wolstenholme Jane , Cobiac Linda , Scarborough Peter 
Published: June 2022

ObjectivesRates of overweight and obesity vary across England, but local rates have not been estimated for over 10 years. We aimed to produce new small area estimates of body mass index (BMI) by age and sex for each lower tier and unitary local authority in England, to provide up-to-date and more detailed estimates for the use of policy-makers and academics working in non-communicable disease risk and health inequalities.DesignWe used generalised linear modelling to estimate the relationship between BMI with social/demographic markers in a cross-sectional survey, then used this model to impute a BMI for each adult in locally-representative populations. These groups were then disaggregated by 5-year age group, sex and local authority group.SettingThe Health Survey for England 2018 (cross-sectional BMI data for England) and Census microdata 2011 (locally representative).ParticipantsA total of 6174 complete cases aged 16 and over were included.Outcome measuresModelled group-level BMI as mean and SD of log-BMI. Extensive internal validation was performed, against the original data and external validation against the National Diet and Nutrition Survey and Active Lives Survey and previous small area estimates.ResultsIn 94% of age–sex are groups, mean BMI was in the overweight or obese ranges. Older and more deprived areas had the highest overweight and obesity rates, which were particularly in coastal areas, the West Midlands, Yorkshire and the Humber. Validation showed close concordance with previous estimates by local area and demographic groups.ConclusionThis work updated previous estimates of the distribution of BMI in England and contributes considerable additional detail to our understanding of the local epidemiology of overweight and obesity. Raised BMI now affects the vast majority of demographic groups by age, sex and area in England, regardless of geography or deprivation.
Resident integration with inpatient clinical documentation improvement: a quality improvement project
Authors: Rouse Michael , Jones Matthew , Zogleman Brice , May Rebekah , Ekilah Tanya , Gibson Cheryl 
Published: June 2022

BackgroundClinical documentation improvement (CDI) is an increasing part of health system quality and patient care with clinical documentation integrity specialists (CDIS) expanding into daily physician workflow. This integration can be especially challenging for resident teams due to increased team size, lack of documentation experience, and misunderstanding of both CDIS and CDI purpose.ProblemThe University of Kansas Health System Internal Medicine residency programme reported challenges with CDIS and resident workflow integration specifically in navigating and understanding CDIS documentation queries, CDIS interruption of interdisciplinary huddles, and general misunderstanding of CDI and the role of CDIS.MethodsA quality improvement project was undertaken to integrate CDIS more effectively into resident workflow. Combined with a resident debrief session to identify general areas of concern, surveys were administered to internal medicine residents, resident rounding faculty and CDIS team members to identify specific barriers to CDIS–physician integration.InterventionA collective group of CDIS member teams, internal medicine chief residents and faculty physicians was formed. Changes made to the CDI process based on survey feedback included (1) improving formatting of CDIS electronic query templates, (2) standardisation of timing for CDIS verbal queries during interdisciplinary huddles, and (3) development of a resident didactic session focused on the role of CDIS and documentation’s impact on quality, safety and outcomes as related to the hospital, provider and patient.ResultsSurveys completed after implementation showed a positive impact on electronic query template changes and perception of CDIS at interdisciplinary huddles. The didactic curriculum was effective in helping residents understand the role and limitations of CDIS and how documentation affects quality of care.ConclusionCDIS–physician integration into resident teams can occur through a collaborative focus on specific aspects of physician workflow and improving understanding of the impact of CDI on patient safety and quality of care.
Perceived stigma and quality of life in Parkinson’s disease with additional health conditions
Authors: Islam Samia S , Neargarder Sandy , Kinger Shraddha B , Fox-Fuller Joshua T , Salazar Robert D , Cronin-Golomb Alice 
Published: June 2022

BackgroundParkinson’s disease (PD) is associated with perceived stigma and affects quality of life (QoL). Additional health conditions may influence these consequences of PD.AimsThis study assessed the impact of health conditions on perceived stigma and QoL in persons with PD. We hypothesised that individuals with more health conditions would report more stigma and poorer QoL. We also examined the contributions of demographic and clinical characteristics to the correlations between health conditions and perceived stigma/QoL.MethodsWe identified 196 eligible participants from the Boston University Online Survey Study of Parkinson’s Disease and examined their health history, performance on multiple stigma measures, and scores on the 39-item Parkinson’s Disease Questionnaire assessing QoL.ResultsAt least one health condition was reported by 79% of the sample, with a median of 2 and a range of 0–7 health conditions. More perceived stigma and poorer QoL were associated with thyroid disease, depression, anxiety, and the total number of health conditions. These correlations were related to younger age, less education, and earlier disease onset. Other health conditions (high blood pressure, back/leg surgery, headache, cancer/tumours, and heart disease) were not significantly correlated with stigma or QoL.ConclusionsHaving more health conditions, or thyroid disease, depression, or anxiety, was associated with more perceived stigma and poorer QoL, with younger age, less education, and earlier disease onset affecting the associations. It is important to consider the burden of health conditions and how they affect persons with PD with specific clinical characteristics.
Collective strategy condensation towards class-separated societies
Authors: Gros Claudius 
Published: June 2022

Abstract
In physics, the wavefunctions of bosonic particles collapse when the system undergoes a Bose–Einstein condensation. In game theory, the strategy of an agent describes the probability to engage in a certain course of action. Strategies are expected to differ in competitive situations, namely when there is a penalty to do the same as somebody else. We study what happens when agents are interested how they fare not only in absolute terms, but also relative to others. This preference, denoted envy, is shown to induce the emergence of distinct social classes via a collective strategy condensation transition. Members of the lower class pursue identical strategies, in analogy to the Bose–Einstein condensation, with the upper class remaining individualistic.

Graphical abstract
Optimal Qubit Assignment and Routing via Integer Programming
Authors: Nannicini Giacomo , Bishop Lev S. , Günlük Oktay , Jurcevic Petar 
Published: June 2022

We consider the problem of mapping a logical quantum circuit onto a given hardware with limited 2-qubit connectivity. We model this problem as an integer linear program, using a network flow formulation with binary variables that includes the initial allocation of qubits and their routing. We consider several cost functions: an approximation of the fidelity of the circuit, its total depth, and a measure of cross-talk, all of which can be incorporated in the model. Numerical experiments on synthetic data and different hardware topologies indicate that the error rate and depth can be optimized simultaneously without significant loss. We test our algorithm on a large number of quantum volume circuits, optimizing for error rate and depth; our algorithm significantly reduces the number of CNOTs compared to Qiskit’s default transpiler SABRE [
19
] and produces circuits that, when executed on hardware, exhibit higher fidelity.
Treatment Represents a Key Driver of Metastatic Cancer Evolution
Authors: Christensen Ditte S. , Ahrenfeldt Johanne , Sokač Mateo , Kisistók Judit , Thomsen Martin K. , Maretty Lasse , McGranahan Nicholas , Birkbak Nicolai J. 
Published: June 2022

Abstract

Metastasis is the main cause of cancer death, yet the evolutionary processes behind it remain largely unknown. Here, through analysis of large panel-based genomic datasets from the AACR Genomics Evidence Neoplasia Information Exchange project, including 40,979 primary and metastatic tumors across 25 distinct cancer types, we explore how the evolutionary pressure of cancer metastasis shapes the selection of genomic drivers of cancer. The most commonly affected genes were TP53, MYC, and CDKN2A, with no specific pattern associated with metastatic disease. This suggests that, on a driver mutation level, the selective pressure operating in primary and metastatic tumors is similar. The most highly enriched individual driver mutations in metastatic tumors were mutations known to drive resistance to hormone therapies in breast and prostate cancer (ESR1 and AR), anti-EGFR therapy in non–small cell lung cancer (EGFR T790M), and imatinib in gastrointestinal cancer (KIT V654A). Specific mutational signatures were also associated with treatment in three cancer types, supporting clonal selection following anticancer therapy. Overall, this implies that initial acquisition of driver mutations is predominantly shaped by the tissue of origin, where specific mutations define the developing primary tumor and drive growth, immune escape, and tolerance to chromosomal instability. However, acquisition of driver mutations that contribute to metastatic disease is less specific, with the main genomic drivers of metastatic cancer evolution associating with resistance to therapy.

Significance:
This study leverages large datasets to investigate the evolutionary landscape of established cancer genes to shed new light upon the mystery of cancer dissemination and expand the understanding of metastatic cancer biology.
DLGAP1-AS2–Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma
Authors: Nan Yabing , Luo Qingyu , Wu Xiaowei , Liu Shi , Zhao Pengfei , Chang Wan , Zhou Aiping , Liu Zhihua 
Published: June 2022

AbstractSquamous cell carcinomas (SCC) constitute a group of human malignancies that originate from the squamous epithelium. Most patients with SCC experience treatment failure and relapse and have a poor prognosis due to de novo and acquired resistance to first-line chemotherapeutic agents. To identify chemoresistance mechanisms and to explore novel targets for chemosensitization, we performed whole-transcriptome sequencing of paired resistant and parental SCC cells. We identified DLGAP1 antisense RNA 2 (D-AS2) as a crucial noncoding RNA that contributes to chemoresistance in SCC. Mechanistically, D-AS2 affected chromatin accessibility around the histone mark H3K27ac of FAM3 metabolism regulating signaling molecule D (FAM3D), reducing FAM3D mRNA transcription and extracellular protein secretion. FAM3D interacted with the Gαi-coupled G protein–coupled receptors formyl peptide receptor 1 (FPR1) and FPR2 to suppress phospholipase D (PLD) activity, and reduced FAM3D increased PLD signaling. Moreover, activated PLD promoted phosphatidic acid (PA) production and subsequent nuclear translocation of yes-associated protein (YAP). Accordingly, in vivo administration of a D-AS2–targeting antisense oligonucleotide sensitized SCC to cisplatin treatment. In summary, this study shows that D-AS2/FAM3D-mediated PLD/PA lipid signaling is essential for SCC chemoresistance, suggesting D-AS2 can be targeted to sensitize SCC to cytotoxic chemotherapeutic agents.Significance:This study identifies D-AS2 as a targetable lipid-related long noncoding RNA that increases phospholipase D activity to promote YAP signaling, triggering chemoresistance in SCC.
Abstract A06: Differential response to autophagy in primary versus melanoma cells
Authors: Morehead Lauren C. , Tackett Alan J. , Miousse Isabelle R. 
Published: June 2022

Abstract
Autophagy is a cellular recycling mechanism triggered by nutrient scarcity. Upregulation of autophagy is associated with lifespan extension, DNA repair, and improved cancer immune recognition. Cancer cells can also utilize this mechanism to cope with nutrient-limited conditions. Chloroquine, an inhibitor of autophagy, has shown promising results alone and in combination with other anticancer agents in various types of cancer. However, several promoters of autophagy have also been shown to display potent anticancer properties. To better understand the relationship between autophagy and cancer, we tested promoters and inhibitors of autophagy in a metastatic melanoma cell line (B16F10) and compared the results with primary human dermal fibroblasts (HDF). After 48h, all tested promoters and inhibitors of autophagy decreased the number of live cells in the B16F10 melanoma cell line compared to untreated controls. In primary cells, promotion of autophagy with methionine restriction (25 μM versus 100 μM in control), complete methionine replacement with homocysteine, and 50 μM of the polyamine spermidine did not affect the number of live cells. Sulforaphane (10 μM) and serum starvation significantly decreased the number of live primary cells. Inhibition of autophagy with 6.25 μM chloroquine did not affect primary cell numbers, while there was a significant decrease in cell numbers associated with a dose of 10 μM of chloroquine and 0.1 μM bafilomycin A1. Cell numbers remained unaffected by longer incubations (96h with replenishment after 48h) of HDF cells with methionine restriction, replacement of methionine with homocysteine, and 6.25 μM chloroquine. These data suggest that cancer cells are more sensitive to both promotion and inhibition of autophagy than primary cells. Interesting compound-specific differences were noted in primary cells. Ongoing preclinical studies evaluate the potential of modulating autophagy as an adjuvant cancer therapy for immune checkpoint inhibitors in metastatic melanoma.
Citation Format: Lauren C. Morehead, Alan J. Tackett, Isabelle R. Miousse. Differential response to autophagy in primary versus melanoma cells [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A06.
Abstract A18: Ccn1 expression by fibroblasts is required for melanoma metastasis
Authors: Hutchenreuther James , Quensel Katherine , Vincent Krista , Posrovit Lynne-Marie , Leask Andrew 
Published: June 2022

Abstract
Metastatic melanoma is highly fatal. Within the tumor microenvironment, the role of cancer-associated fibroblasts (CAFs) in melanoma metastasis and progression is relatively understudied. Matricellular proteins of the CCN family are emerging targets for cancer therapy. Anti-CCN2 (CTGF) strategies are under clinical development; however, the role of CCN1 (cyr61) in cancers is unclear. Herein, we use bioinformatic analyses to report that the CCN1 is overexpressed, in a fashion independent of BRAF mutational status, in melanoma. In human melanoma patients, CCN1 expression negatively correlates with overall survival, disease-free, and metastasis-free survival (p&lt;0.03). CCN1 expression positively correlates with expression of stroma and neovascularization markers. To assess the role of CAFs in melanoma progression, we used C57BL/6 mice expressing a tamoxifen-dependent cre recombinase expressed under the control of a fibroblast-specific promoter/enhancer (COL1A2) to delete CCN1 postnatally in fibroblasts. Mice deleted or not for CCN1 in fibroblasts were injected subcutaneously with B16-F10 melanoma cells. Loss of CCN1 in CAFs did not result in reduced CAF activation, as detected by staining with anti-α-smooth muscle actin antibodies, but resulted in reduced extracellular matrix surrounding tumors, as detected by trichrome stain, and reduced tumor-induced neovascularization, as detected by staining with anti-CD31 antibodies. CCN1-deficient skin showed reduced expression of mRNAs encoding collagen crosslinking enzymes (PLOD2 and LOX) and impaired formation of collagen fibers, as determined by electron microscopy. Tumor growth was not affected by loss of CCN1 from tumor stroma; however, micrometastasis to the lung was severely impaired (p&lt;0.001). Our results provide new insights into the crosstalk among different cell types in the tumor microenvironment and confirm the essential role of CAFs in metastasis and tumor neovascularization. Our data are consistent with the hypothesis that CAFs are essential for melanoma metastasis and that CCN1 is a therapeutic target for melanoma.
Citation Format: James Hutchenreuther, Katherine Quensel, Krista Vincent, Lynne-Marie Posrovit, Andrew Leask. Ccn1 expression by fibroblasts is required for melanoma metastasis [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A18.
Abstract A23: Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse
Authors: Mok Stephen , Duffy Colm R. , Anang Nana-Ama A. , Allison James P. 
Published: June 2022

Abstract
Both anti-CTLA-4 and anti-PD-1 mediate significant response rates in cancer patients. As a hallmark of successful immunotherapies, they also mediate durable responses that last for years. For example, anti-CTLA-4 mediates a 22% 10-year overall survival rate, while anti-PD-1 mediates a 34% 5-year overall survival rate. Because of the broader uses of immunotherapies, the number of patients who have tumor relapse also increases. About 25% of patients who initially responded to anti-PD-1 have tumor relapse within 24 months. However, the relationship between tumor relapse and long-term effect of immunotherapies is still not clear. The goal of this study is to understand the differential effect of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation in murine tumor models. By rechallenging mice with tumor cells that have had tumors previously eradicated by either treatment, our results have shown that anti-CTLA-4 induces a more durable memory antitumor response compared to that treated with anti-PD-1. By tracing the antigen-specific CD8 T-cells throughout the memory phase, anti-CTLA-4 increases the frequency and cytokine production of antigen-specific T cells compared with anti-PD-1. We have also found that anti-CTLA-4 induces the population of KLRG1+ effector CD8 T cells among the effectors compared with anti-PD-1 during rechallenge, despite the ratio between central memory and effectors remaining the same. Our studies enable us to identify the long-term effect of immunotherapies on immune system.
Citation Format: Stephen Mok, Colm R. Duffy, Nana-Ama A. Anang, James P. Allison. Effects of anti-CTLA-4 and anti-PD-1 on memory T-cell differentiation and resistance to tumor relapse [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A23.