bluuebunny/crossref_metadata_2025_split huggingface dataset:
The KOMPACT-P study: Knee Osteoarthritis Management with Physiotherapy informed by Acceptance and Commitment Therapy—Pilot study protocol
Authors: March Marie K , Harmer Alison , Godfrey Emma , Venkatesh Shruti , Thomas Bijoy , Dennis Sarah 
Published: June 2020

IntroductionIncidence of total knee arthroplasty (TKA) is projected to rise 276% in 2030, and psychological distress affects up to 42% of people with knee osteoarthritis undergoing TKA, with demonstrated detrimental effects on postoperative outcomes. Few studies have assessed psychological treatment in people awaiting TKA, and these have been psychologist-delivered treatments. No evidence exists regarding psychologically-informed interventions delivered by health professionals currently embedded in TKA clinical pathways. The primary aim of this pilot study is to explore the safety, acceptability and feasibility of the Knee Osteoarthritis Management with Physiotherapy informed by Acceptance and Commitment Therapy (KOMPACT) approach in people awaiting TKA.Methods and analysis51 community-dwelling adults scheduled for a primary TKA at two hospitals will be recruited to this pilot, mixed-methods, prospective randomised controlled trial with assessor blinding. Participants will be randomised in a 1:2 ratio to either usual care (education class) or usual care plus KOMPACT (2 hours 20 min of preoperative physiotherapy informed by Acceptance and Commitment Therapy). Our primary outcome measures are safety (length of stay, complications and psychological health after KOMPACT), acceptability (treatment credibility and qualitative data) and feasibility (recruitment, retention and intervention fidelity) of the KOMPACT approach. Secondary outcomes include health service outcomes, patient-reported physical and psychological outcomes, and physical performance measures. Quantitative data collection was conducted at baseline, 1–2 weeks before TKA, 6 weeks after TKA and 6 months after TKA. Qualitative data collection is 1–2 weeks before TKA. Data analysis will take a quantitative-led approach with triangulation after thematic analysis of the qualitative data.Ethics and disseminationThis study has full ethics approval (HREC/18/WMEAD/440). Results from this study will be published in peer-reviewed journals and presented at local and international conferences.Trial registration numberAustralia New Zealand Clinical Trials Registry (ACTRN12618001867280p).
Point-of-care tests for urinary tract infections: protocol for a systematic review and meta-analysis of diagnostic test accuracy
Authors: Fraile Navarro David , Sullivan Frank , Azcoaga-Lorenzo Amaya , Hernandez Santiago Virginia 
Published: June 2020

IntroductionUrinary tract infections (UTIs) are the second most common type of infection worldwide, accounting for a large number of primary care consultations and antibiotic prescribing. Current diagnosis is based on an empirical approach, relying on symptoms and occasional use of urine dipsticks. The diagnostic reference standard is still urine culture, although it is not routinely recommended for uncomplicated UTIs in the community, due to time to diagnosis (48 hours). Faster point-of-care tests have been developed, but their diagnostic accuracy has not been compared. Our objective is to systematically review and meta-analyse the diagnostic accuracy of currently available point-of-care tests for UTIs.Methods and analysisStudies evaluating the diagnostic accuracy of point-of-care tests for UTIs will be included. PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to 1 June 2019. Data extraction and risk-of-bias assessment will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis will be performed depending on data availability and heterogeneity.Ethics and disseminationThis is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers, and will also be presented and national and international conferences.PROSPERO registration numberCRD42018112019.
Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial
Authors: Wang Juan , Wu Dong Xue , Meng Lu , Ji Gang 
Published: June 2020

IntroductionAnlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.Methods and analysisThis study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients’ demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.Ethics and disseminationEthics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.Trial registration numberChiCTR1900026291 (registration date: 29 September 2019).
Assessment of visually guided reaching in prodromal Alzheimer’s disease: a cross-sectional study protocol
Authors: Mitchell Alexandra G , McIntosh Robert D , Rossit Stephanie , Hornberger Michael , Pal Suvankar 
Published: June 2020

IntroductionRecent evidence has implicated the precuneus of the medial parietal lobe as one of the first brain areas to show pathological changes in Alzheimer’s disease (AD). Damage to the precuneus through focal brain injury is associated with impaired visually guided reaching, particularly for objects in peripheral vision. This raises the hypothesis that peripheral misreaching may be detectable in patients with prodromal AD. The aim of this study is to assess the frequency and severity of peripheral misreaching in patients with mild cognitive impairment (MCI) and AD.Methods and analysisPatients presenting with amnestic MCI, mild-to-moderate AD and healthy older-adult controls will be tested (target N=24 per group). Peripheral misreaching will be assessed using two set-ups: a tablet-based task of lateral reaching and motion-tracked radial reaching (in depth). There are two versions of each task, one where participants can look directly at targets (free reaching), another wheren they must maintain central fixation (peripheral reaching). All tasks will be conducted first on their dominant, and then their non-dominant side. For each combination of task and side, a Peripheral Misreaching Index (PMI) will be calculated as the increase in absolute reaching error between free and peripheral reaching. Each patient will be classified as showing peripheral misreaching if their PMI is significantly abnormal, by comparison to control performance, on either side of space. We will then test whether the frequency of peripheral misreaching exceeds the chance level in each patient group and compare the overall severity of misreaching between groups.Ethics and disseminationEthical approval was provided by the National Health Service (NHS) East of England, Cambridge Central Research Ethics Committee (REC 19/EE/0170). The results of this study will be published in a peer-reviewed journal and presented at academic conferences.
Spirituality and religiosity in a palliative medicine population: mixed-methods study
Authors: O'Callaghan Clare C , Georgousopoulou Ekavi , Seah Davinia , Clayton Josephine M , Kissane David , Michael Natasha 
Published: June 2020

BackgroundSpiritual care allows palliative care patients to gain a sense of purpose, meaning and connectedness to the sacred or important while experiencing a serious illness. This study examined how Australian patients conceptualise their spirituality/religiosity, the associations between diagnosis and spiritual/religious activities, and views on the amount of spiritual support received.MethodsThis mixed-methods study used anonymous semistructured questionnaires, which included the Functional Assessment of Chronic Illness Therapy-Spiritual Scale-12 (FACIT-SP-12) and adapted and developed questions examining religion/spirituality’s role and support.ResultsParticipants numbered 261, with a 50.9% response rate. Sixty-two per cent were affiliated with Christianity and 24.2% with no religion. The mean total FACIT-SP-12 score was 31.9 (SD 8.6). Patients with Christian affiliation reported a higher total FACIT-SP-12 score compared with no religious affiliation (p=0.003). Those with Christian and Buddhist affiliations had higher faith subscale scores compared with those with no religious affiliation (p<0.001). Spirituality was very important to 39.9% and religiosity to 31.7% of patients, and unimportant to 30.6% and 39.5%, respectively. Following diagnosis, patients prayed (p<0.001) and meditated (p<0.001) more, seeking more time, strength and acceptance. Attendance at religious services decreased with frailty (p<0.001), while engagement in other religious activities increased (p=0.017). Patients who received some level of spiritual/religious support from external religious/faith communities and moderate to complete spiritual/religious needs met by the hospitals reported greater total FACIT-SP-12 spirituality scores (p<0.001).ConclusionRespectful inquiry into patients spiritual/religious needs in hospitals allows for an attuned approach to addressing such care needs while considerately accommodating those disinterested in such support.
Female Athlete Triad Coalition cumulative risk assessment tool: proposed alternative scoring strategies
Authors: Koltun Kristen J. , Williams Nancy I. , De Souza Mary Jane 
Published: June 2020

We (i) identified alternative scoring strategies for the Female Athlete Triad Coalition cumulative risk assessment (CRA) tool to be utilized when particular risk factors (bone mineral density (BMD), oligomenorrhea/amenorrhea) cannot be determined; (ii) objectively defined dietary restriction for use in the CRA tool; and (iii) explored proxy measures of energy deficiency. This cross-sectional investigation of exercising women (n = 166) utilized an existing database derived from multiple studies designed to assess health, exercise, and menstrual function. Data from the screening/baseline period of each study included: anthropometrics, dual-energy X-ray absorptiometry, disordered eating questionnaires, descriptive data, and proxy measures of energy deficiency (total triiodothyronine (TT3) and ratio of measured-to-predicted resting metabolic rate (mRMR/pRMR)). Substituting delayed menarche for BMD was the best-fit replacement resulting in 15 (9%) participants being categorized in different clearance categories. When menstrual status cannot be assessed, such as during hormonal contraceptive use, low energy availability (EA) determined using self-report and disordered eating questionnaires was the best substitution, resulting in 34 (20%) participants being categorized in different clearance categories. Based on original clearance categorizations, the provisional group had lower TT3 (78.3 ± 2.2 ng/dL; 92.7 ± 2.7 ng/dL) and Harris–Benedict mRMR/pRMR (0.85 ± 0.01; 0.90 ± 0.01) than the full group. Until an updated risk assessment tool is developed, delayed menarche can substitute for low BMD and low EA for oligomenorrhea/amenorrhea. Novelty This investigation addresses previous limitations of the Triad CRA tool. Disordered eating questionnaires can be used to objectively identify dietary restriction for the low EA risk factor. When a risk factor cannot be assessed, delayed menarche can substitute for low BMD and low EA for oligomenorrhea/amenorrhea.
FCC-ee interaction region backgrounds
Authors: Voutsinas G. , Elsener K. , Janot P. , El Khechen D. , Kolano A. , Leogrande E. , Perez E. F. , Tehrani N. A. , Viazlo O. , Boscolo M. , Blanco O. , Collamati F. , Bacchetta N. , Dam M. , Sullivan M. K. 
Published: June 2020

The FCC-ee machine induced backgrounds on the two proposed detectors (CLD and IDEA) have been studied in detail. Synchrotron Radiation (SR) considerations dictate the Interaction Region (IR) optimization. An asymmetric IR design limits the final bend critical energy to 100 keV. Masks placed before the final focus quadrupole protect the detector from direct hits, and a shield placed around the beam pipe from secondary particles, keeping the effect of SR on the detector to negligible levels. The most important source of background is expected to be the Incoherent Pair Creation (IPC). Its effect has been studied in full simulation and reconstruction, and it was shown that it will not pose a problem for the detector, even if conservative estimations for the time resolution of the detector sensors are assumed. Moreover, the [Formula: see text], radiative Bhabhas and beam-gas interaction induced backgrounds were studied. All were found to have small to negligible effect on the detector. Overall, the FCC–ee interaction region backgrounds are not expected to compromise the detector performance.
Abstract A08: Modeling melanomagenesis
Authors: Moon Hyeongsun , Donahue Leanne , White Andrew C. 
Published: June 2020

Abstract
Despite recent advances in therapy, cutaneous melanoma remains a deadly form of skin cancer. Ultraviolet radiation is a known risk factor that can be reduced by the use of sunscreen; nevertheless, melanoma incidence continues to rise. Determining how a cell that contains all the mutations required for cancer resists forming a tumor could suggest novel means of prevention. Conversely, understanding an identical cancer cell of origin that has switched to a proliferative expansion state can provide invaluable insight into tumor initiation. We have generated a method of inducing melanoma from melanocyte stem cells in a spatially specific manner by altering the exterior environment, in the context of a previously established genetically engineered mouse model of melanoma. Specifically, exposure to ultraviolet radiation B can provide a proinflammatory microenvironment that stimulates this switch from a quiescent cancer cell of origin to a proliferative cancer cell. Moreover, this model shows tumor development from the interfollicular epidermis, similar to human melanoma initiation and progression. This represents an evolution from previous mouse models of melanoma and presents a new method that can be exploited for stage-specific precision targeting for both initiation prevention and progression intervention.
Citation Format: Hyeongsun Moon, Leanne Donahue, Andrew C. White. Modeling melanomagenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A08.
Abstract A32: Targeting RON-mediated metabolic vulnerabilities in recurrent/progressive breast cancer
Authors: Hunt Brian G. , Wicker Christina A. , Bourn Jennifer , Lower Elyse , Takiar Vinita , Waltz Susan E. 
Published: June 2020

Abstract
Despite advances in clinical detection, molecular subtyping, and targeted therapeutics, breast cancer (BC) is the second leading cause of cancer-related death in women. Recurrent and metastatic disease is the underlying cause of BC mortality. Due to fear of recurrence, BC is the most overtreated cancer, creating significant ethical and financial burdens. Through a discovery-based genomics approach, the RON receptor tyrosine kinase was identified as a predictor of BC recurrence. We and others have shown that RON overexpression occurs in more than half of all BCs and that RON levels are a predictor of metastasis and poor survival. Through evaluation of human breast tumor tissue, we provide the first line of evidence that RON overexpression occurs independent of molecular subtype and provide prognostic evidence of RON expression as a biomarker of BC recurrence. Further, we identified glycolysis and cholesterol biosynthesis, two potentially therapeutically targetable processes, as being significantly upregulated by RON. To test the efficacy of reducing cholesterol as a therapy for BC with RON expression, we treated two independent, spontaneous murine breast cancer models with inhibitors directed at RON and/or cholesterol biosynthesis (atorvastatin). Our studies show that either RON or cholesterol inhibition reduced BC progression and that combination treatments blocked progression further. Current studies are under way to determine the mechanisms by which RON promotes metabolic pathway dependency and to directly test in a novel murine model of BC recurrence if targeting these pathways provides a survival benefit. We anticipate that our studies will serve as the scientific underpinnings for rationally designed new combinatorial therapeutic strategies to decrease the morbidity and mortality associated with advanced breast cancer.
Citation Format: Brian G. Hunt, Christina A. Wicker, Jennifer Bourn, Elyse Lower, Vinita Takiar, Susan E. Waltz. Targeting RON-mediated metabolic vulnerabilities in recurrent/progressive breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A32.
Abstract B02: Association of APC, BRAF, and TCF7L2 mutations with tumor mutation load and survival outcomes in patients with metastatic colorectal cancer
Authors: Xu Liang , He Xiao-Sheng , Lan Ping 
Published: June 2020

Abstract
Objective: To investigate whether APC, BRAF, and TCF7L2 mutations are associated with prognosis in patients with mCRC.
Methods: Statistical analysis of genomic data from 980 metastatic colorectal cancer samples obtained from the cbioportal database was performed. The cbioportal cohort was used as a discovery set. Logistic regression models and Kaplan-Meier survival analysis and multivariate analysis and nomogram analysis were applied. The lasso regression was used to identify significantly mutant genes.
Results: We identified 25 mutant genes related to survival outcomes by using lasso regression. These mutated genes were generated to classify mCRC patients into high-risk and low-risk groups. Patients with high-risk scores in the training cohort had shorter survival (hazard ratio [HR] 2.735, 95% CI 2.206-3.390; p&lt;0.0001) than patients with low-risk scores. These 25 genes and mutant gene with mutation frequencies more than 5% were analyzed by univariate and multivariate analysis. Three mutant genes could be regarded as independent prognostic factors for overall survival in mCRC patients: APC, BRAF, and TCF7L2. APC and TCF7L2 mutation were favorable factors, while BRAF mutation was an unfavorable factor. The combined Kaplan-Meier analysis showed 5 groups were significantly associated with prognosis in mCRC and found that these 5 groups were associated with tumor location, molecular subtype, survival, tumor grade, and hypermutation. In TCF7L2 and BRAF mutant group, other mutant gene had a much higher mutation frequency than wild-type group. We speculated that BRAF and TCF7L2 mutation were two important mutation points during CRC metastasis.
Conclusions: These findings indicate that APC, BRAF, and TCF7L2 mutations were associated with tumor mutation load and survival outcomes. These findings may be applicable for patients with mCRC.
Note: This abstract was not presented at the conference.
Citation Format: Liang Xu, Xiao-Sheng He, Ping Lan. Association of APC, BRAF, and TCF7L2 mutations with tumor mutation load and survival outcomes in patients with metastatic colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B02.
Abstract B14: Engineering a long-term in vitro model of breast cancer tumor resistance for high-throughput predictive drug screening
Authors: Weathered Rachel , Zhou Ruolan , Swartz Melody A. 
Published: June 2020

Abstract
Solid tumors often show high levels of heterogeneity, making targeted therapeutics especially challenging. In breast cancer, for example, the primary cancer type may be eradicated with targeted therapy, but the minority subclones that are drug resistant can emerge as the new majority clones. Here, we present an in vitro model for long-term culture of ex vivo tumors (e.g., from biopsies) that maintain the tumor microenvironment such that tumors can be dramatically reduced with drugs yet maintained to observe long-term drug resistance. Our in vitro “avatars” (“ivitars”) utilize perfused 3D cultures in a high-throughput, robust, and easily maintained format. We demonstrate in vivo relevance with heterogeneous tumors composed of human breast cancer cell lines MCF-7 and LCC9, with sublines that are tamoxifen sensitive or resistant, in combination with stromal cells. Our results indicate that stromal cells, extracellular matrix components, and relevant biophysical stimuli such as fluid flow in the tumor microenvironment enhance tumor resistance to tamoxifen, even in tamoxifen-sensitive tumor cells. Together, our results suggest that the model can be used as a robust and high-throughput system for studying tumor resistance and will be further investigated for use in patient-specific testing.
Citation Format: Rachel Weathered, Ruolan Zhou, Melody A. Swartz. Engineering a long-term in vitro model of breast cancer tumor resistance for high-throughput predictive drug screening [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B14.