bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the credibility of anchor based estimates of minimal important differences for patient reported outcomes: instrument development and reliability study
Authors: Devji Tahira , Carrasco-Labra Alonso , Qasim Anila , Phillips Mark , Johnston Bradley C , Devasenapathy Niveditha , Zeraatkar Dena , Bhatt Meha , Jin Xuejing , Brignardello-Petersen Romina , Urquhart Olivia , Foroutan Farid , Schandelmaier Stefan , Pardo-Hernandez Hector , Vernooij Robin WM , Huang Hsiaomin , Rizwan Yamna , Siemieniuk Reed , Lytvyn Lyubov , Patrick Donald L , Ebrahim Shanil , Furukawa Toshi , Nesrallah Gihad , Schünemann Holger J , Bhandari Mohit , Thabane Lehana , Guyatt Gordon H 
Published: June 2020

Abstract

Objective
To develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of the instrument.

Design
Instrument development and reliability study.

Data sources
Initial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument.

Participants
With the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates.

Main outcome measures
Core credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined.

Results
The credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors.

Conclusions
Researchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.
Protocol for LAsting Symptoms after Oesophageal Resectional Surgery (LASORS): multicentre validation cohort study
Authors: Markar Sheraz Rehan , Griffiths Ewen A , Behrens Paul , Singh Pritam , Vohra Ravi S , Gossage James , Underwood Tim , Hanna George B 
Published: June 2020

IntroductionSurgery is the primary curative treatment for oesophageal cancer, with considerable recent improvements in long-term survival. However, surgery has a long-lasting impact on patient’s health-related quality of life (HRQOL). Through a multicentre European study, our research group was able to identify key symptoms that affect patient’s HRQOL. These symptoms were combined to produce a tool to identify poor HRQOL following oesophagectomy (LAsting Symptoms after Oesophageal Resection (LASOR) tool). The objective of this multicentre study is to validate a six-symptom clinical tool to identify patients with poor HRQOL for use in everyday clinical practice.Methods and analysisIncluded patients will: (1) be aged 18 years or older, (2) have undergone an oesophagectomy for cancer between 2015 and 2019, and (3) be at least 12 months after the completion of adjuvant oncological treatments. Patients will be given the previously created LASOR questionnaire. Each symptom from the LASOR questionnaire will be graded according to impact on quality of life and frequency of the symptom, with a composite score from 0 to 5. The previously developed LASOR symptom tool will be validated against HRQOL as measured by the European Organisation for Research and Treatment of Cancer QLQC30 and OG25.Sample sizeWith a predicted prevalence of poor HRQOL of 45%, based on the previously generated LASOR clinical symptom tool, to validate this tool with a sensitivity and specificity of 80%, respectively, a minimum of 640 patients will need to be recruited to the study.Ethics and disseminationNHS Health Research Authority (North East—York Research Ethics Committee) approval was gained 8 November 2019 (REC reference 19/NE/0352). Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal.
Using a system dynamics model to study the obesity transition by socioeconomic status in Colombia at the country, regional and department levels
Authors: Meisel Jose D , Ramirez Angie M , Esguerra Valentina , Montes Felipe , Stankov Ivana , Sarmiento Olga L. , Valdivia Juan A 
Published: June 2020

ObjectiveWe study the obesity transition by socioeconomic status (SES), gender and age within the Colombian urban population at the country, regional and department levels.DesignThe study is informed by cross-sectional data from the 2005 and 2010 ENSIN survey. We used these data to develop a system dynamics model that simulates the dynamics of obesity by body mass index (BMI) categories, gender and SES at the country, regional and department levels from 2005 to 2030.ParticipantsThe sample size of the 2005 ENSIN comprised 8515 children younger than 5 years, 32 009 children and adolescents aged 5–17 years and 48 056 adults aged 18–64 years. In 2010, the corresponding numbers were 11 368, 32 524 and 64 425, respectively.Primary and secondary outcome measureThe obesity prevalence ratio and prevalence rates for each BMI category.ResultsThe results show, at the country level, transitions from overweight to obesity were projected to increase sharply among lower SES adults, particularly among women, suggesting that these groups will undergo an obesity transition by 2030. The model projections also indicate that the regions of Colombia are in different stages of the obesity transition. In the case of women, five out of the six regions were expected to undergo an obesity transition by SES over time. For men, only one region was expected to undergo an obesity transition. However, at the department level, trends in the burden of obesity varied.ConclusionsWe evidence that the Colombian population could be experiencing an obesity transition where the increase in the GDP could be related to shifts in the burden of obesity from higher to lower SES, especially in women. These patterns support the need for policy planning that considers SES and gender, at the national and subnational levels, as important determinants of overweight and obesity among adults in Colombia.
Integrating physical activity promotion into UK medical school curricula: testing the feasibility of an educational tool developed by the Faculty of Sports and Exercise Medicine
Authors: Pugh Gemma , O'Halloran Patrick , Blakey Laura , Leaver Hannah , Angioi Manuela 
Published: June 2020

BackgroundAt present education on exercise medicine and physical activity (PA) promotion does not feature heavily within the medical curriculum.ObjectivesThe purpose of this study was to test the feasibility of a self-directed educational tool (Faculty of Sports and Exercise Medicine (FSEM) exercise prescription booklet) on medical students’ understanding of PA in disease management.MethodsStudents from 22 UK medical schools were invited to complete a brief online questionnaire before and after being provided access to the FSEM exercise prescription booklet.ResultsA total of 205 students responded to the open invitation to participate. At baseline 59% of students agreed that PA promotion was an important part of a doctor’s job with 86% agreeing that PA was important in the prevention of disease. However, confidence to prescribe PA and knowledge of chief medical officer’s adult PA guidelines was low. Following use of the FSEM booklet students’ (n=53) knowledge of PA guidelines and confidence to advise patients about PA significantly improved (p<0.05). Correct response answers to case scenarios covering PA in disease management (specifically osteoarthritis and cancer) also improved (32% and 44% increase, respectively, p<0.01).ConclusionSelf-guided educational tools have the potential to improve the exercise prescription skills of undergraduate medical students. Future research should compare different methods of delivering education on PA within medical schools to determine the most effective means of integrating PA into the curriculum.
Simulating the impacts of land reclamation and de-reclamation on the morphodynamics of tidal networks
Authors: Chen Lei , Zhou Zeng , Xu Fan , Jimenez Mirian , Tao Jianfeng , Zhang Changkuan 
Published: June 2020

Abstract
The morphodynamic responses of tidal networks to anthropogenic reclamation and de-reclamation projects are investigated through a three-stage numerical simulation. In the first stage, the natural development of tidal networks is modelled in an open coast without any anthropogenic interventions. At the beginning of the second stage, parts of the computational domain are enclosed by sea dikes, which represents the implementation of the reclamation project. These sea dikes are removed or opened in the third stage to simulate the recovery of the tidal networks after de-reclamation. Each stage was set to last 100 years. The model results indicate that land reclamation can lead to three effects on tidal network morphology: (i) completely terminating the development of channels inside the projected area, (ii) hindering the development of the channel network in front of the dikes, and (iii) turning the channel direction near the corners of the dikes. When removing all the sea dikes, the previously reclaimed areas are quickly occupied by tidal networks. However, the morphology cannot be fully restored to its original natural state, although the entire reclaimed areas are returned. The effects of opening breaches are relatively slow, and tree-like network structures are formed inside the reclaimed areas.
The accurate prediction of sweat rate from energy expenditure and air temperature: a proof-of-concept study
Authors: Sollanek Kurt J. , Liu Mia , Carballo Andrei , Caldwell Aaron R. , Cheuvront Samuel N. 
Published: June 2020

This proof-of-concept study used a web application to predict runner sweat losses using only energy expenditure and air temperature. A field study (FS) of n = 37 runners was completed with n = 40 sweat loss observations measured over 1 h (sweat rate, SR). Predictions were also compared with 10 open literature (OL) studies in which individual runner SR was reported (n = 82; 109 observations). Three prediction accuracy metrics were used: for FS, the mean absolute error (MAE) and concordance correlation coefficient (CCC) were calculated to include a 95% confidence interval [CI]; for OL, the percentage concordance (PC) was examined against calculation of accumulated under- and over-drinking potential. The MAE for FS runners was 0.141 kg [0.105, 0.177], which was less than estimated scale weighing error on 85% of occasions. The CCC was 0.88 [0.82, 0.93]. The PC for OL was 96% for avoidance of both under- and over-drinking and 93% overall. All accuracy metrics and their CIs were below acceptable error tolerance. Input errors of ±10% and ±1 °C for energy expenditure and air temperature dropped the PC to between 84% and 90%. This study demonstrates the feasibility of accurately predicting SR from energy expenditure and air temperature alone. Novelty Results demonstrate that accurate runner SR prediction is possible with knowledge of only energy expenditure and air temperature. SR prediction error was smaller than scale weighing error in 85% of observations. Accurate runner SR prediction could help mitigate the common risks of over- and under-drinking.
A systematic study on α-decay chains of superheavy nuclei, Z = 126 & 138
Authors: Naveya G. , Santhosh Kumar S. , Stephen A. 
Published: June 2020

The [Formula: see text]-decay chain of [Formula: see text] and [Formula: see text] is studied using cubic plus proximity potential with improved transfer matrix (CPP-ITM) model. The nuclear mass models DD-PC1, WS4, WS3.3 are employed to evaluate the [Formula: see text]-decay energies. Thus calculated [Formula: see text]-decay half-lives and decay chain lengths are found to be in good agreement with other theoretical formalisms. The spontaneous fission (SF) half-lives are calculated using the formalism of Xu et al. [Phys. Rev. C 71 (2005) 014309; Phys. Rev. C 78 (2008) 044329] to have a vision on the possible decay modes and decay chain lengths, and the most probable decay chains associated with the isotopes of [Formula: see text] [Formula: see text] [Formula: see text]. This paper unveils the mass region that survives fission and also predict the long [Formula: see text]-decay chains of [Formula: see text] [Formula: see text] [Formula: see text] with [Formula: see text] emitting 6[Formula: see text], [Formula: see text] emit 5[Formula: see text] [Formula: see text] [Formula: see text] 4[Formula: see text] particles, while for [Formula: see text] chains will have [Formula: see text] emission. The SF for [Formula: see text] [Formula: see text] [Formula: see text] occur at [Formula: see text] and [Formula: see text]. These current predictions may pave way to detect/synthesize the most probable isotopes of the superheavy elements [Formula: see text] [Formula: see text] [Formula: see text] in the laboratory through future experiments.
Aqueous Ammonia Wetting of Gas-Diffusion Media for Electrochemical Cells
Authors: Santamaria Anthony D. , Mortazavi Mehdi 
Published: June 2020

Increased interest in liquid ammonia (NH3) for hydrogen storage can be attributed to its lack of carbon, high energy density to volume and mass ratios (17.6 wt% hydrogen), a ubiquitous supply and distribution network, and lower cost. Recent progress in direct ammonia fuel cells for power generation, as well as ongoing work on the electrochemical synthesis of ammonia, motivate the need for fundamental investigations of aqueous ammonia interactions with electrode materials. Porous gas-diffusion media (GDM) play a large role in facilitating liquid, gas, and charge transport and are an inherent part of these technologies membrane electrode assemblies (MEA). This work characterizes how key wetting properties such as contact angle, advancing/receding contact angles, adhesion force, and breakthrough pressure are influenced by GDM wet-proofing, thickness, and structure. These properties are studied for aqueous ammonia solutions with 0, 10, 20, and 30 wt% NH3. The higher concentrations of NH3 along an electrode surface can lead to lower contact angles as surface tension is reduced. Wet-proofing with PTFE loadings up to 10 wt% increases hydrophobicity, while higher loadings have diminishing effects. The results are useful to those involved with modeling, design, construction, and optimization of these systems.
Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody–drug Conjugate (ARX788) for Breast Cancer Treatment
Authors: Nagaraja Shastri Prathap , Zhu Jingjing , Skidmore Lillian , Liang Xuejun , Ji Yanping , Gu Yi , Tian Feng , Yao Sulan , Xia Gang 
Published: June 2020

Abstract
Conventional antibody–drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The nonspecific conjugation results in a mixture with variable drug-to-antibody ratios (DAR), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent antitubulin cytotoxic drug-linker, AS269. The site-specific conjugation is achieved by first incorporating the nonnatural amino acid, para-acetyl phenylalanine (pAF), into the antibody, followed by covalent conjugation of AS269 to the pAF to form a highly stable oxime bond resulting in a DAR 2 ADC. ARX788 exhibits significant, dose-dependent antitumor activity against HER2- expressing breast and gastric xenograft tumors. Pharmacokinetic (PK) studies in multiple species showed the highly stable nature of ARX788 with overlapping PK profiles for the intact ADC and total antibody. Metabolism studies demonstrated that pAF-AS269 was the sole major metabolite of ARX788, with no evidence for the release of free drug often observed in conventional ADCs and responsible for adverse side effects. Furthermore, ARX788 demonstrated a favorable safety profile in monkeys with a highest nonseverely toxic dose of 10 mg/kg, which was well above the efficacious dose level observed in preclinical tumor models, thus supporting clinical development of ARX788.
Discovery of New Targets to Control Metastasis in Pancreatic Cancer by Single-cell Transcriptomics Analysis of Circulating Tumor Cells
Authors: Dimitrov-Markov Spas , Perales-Patón Javier , Bockorny Bruno , Dopazo Ana , Muñoz Manuel , Baños Natalia , Bonilla Victoria , Menendez Camino , Duran Yolanda , Huang Ling , Perea Sofia , Muthuswamy Senthil K. , Al-Shahrour Fatima , Lopez-Casas Pedro P. , Hidalgo Manuel 
Published: June 2020

Abstract
Metastasis development is the leading cause of cancer-related mortality in pancreatic ductal adenocarcinoma (PDAC) and yet, few preclinical systems to recapitulate its full spreading process are available. Thus, modeling of tumor progression to metastasis is urgently needed. In this work, we describe the generation of highly metastatic PDAC patient-derived xenograft (PDX) mouse models and subsequent single-cell RNA-sequencing (RNA-seq) of circulating tumor cells (CTC), isolated by human HLA sorting, to identify altered signaling and metabolic pathways, as well as potential therapeutic targets. The mouse models developed liver and lung metastasis with a high reproducibility rate. Isolated CTCs were highly tumorigenic, had metastatic potential, and single-cell RNA-seq showed that their expression profiles clustered separately from those of their matched primary and metastatic tumors and were characterized by low expression of cell-cycle and extracellular matrix–associated genes. CTC transcriptomics identified survivin (BIRC5), a key regulator of mitosis and apoptosis, as one of the highest upregulated genes during metastatic spread. Pharmacologic inhibition of survivin with YM155 or survivin knockdown promoted cell death in organoid models as well as anoikis, suggesting that survivin facilitates cancer cell survival in circulation. Treatment of metastatic PDX models with YM155 alone and in combination with chemotherapy hindered the metastatic development resulting in improved survival. Metastatic PDX mouse model development allowed the identification of survivin as a promising therapeutic target to prevent the metastatic dissemination in PDAC.
First-in-Class Inhibitors of Oncogenic CHD1L with Preclinical Activity against Colorectal Cancer
Authors: Abbott Joshua M. , Zhou Qiong , Esquer Hector , Pike Laura , Broneske Travis P. , Rinaldetti Sébastien , Abraham Adedoyin D. , Ramirez Dominique A. , Lunghofer Paul J. , Pitts Todd M. , Regan Daniel P. , Tan Aik Choon , Gustafson Daniel L. , Messersmith Wells A. , LaBarbera Daniel V. 
Published: June 2020

Abstract
Since the discovery of CHD1L in 2008, it has emerged as an oncogene implicated in the pathology and poor prognosis of a variety of cancers, including gastrointestinal cancers. However, a mechanistic understanding of CHD1L as a driver of colorectal cancer has been limited. Until now, there have been no reported inhibitors of CHD1L, also limiting its development as a molecular target. We sought to characterize the clinicopathologic link between CHD1L and colorectal cancer, determine the mechanism(s) by which CHD1L drives malignant colorectal cancer, and discover the first inhibitors with potential for novel treatments for colorectal cancer. The clinicopathologic characteristics associated with CHD1L expression were evaluated using microarray data from 585 patients with colorectal cancer. Further analysis of microarray data indicated that CHD1L may function through the Wnt/TCF pathway. Thus, we conducted knockdown and overexpression studies with CHD1L to determine its role in Wnt/TCF-driven epithelial-to-mesenchymal transition (EMT). We performed high-throughput screening (HTS) to identify the first CHD1L inhibitors. The mechanism of action, antitumor efficacy, and drug-like properties of lead CHD1L inhibitors were determined using biochemical assays, cell models, tumor organoids, patient-derived tumor organoids, and in vivo pharmacokinetics and pharmacodynamics. Lead CHD1L inhibitors display potent in vitro antitumor activity by reversing TCF-driven EMT. The best lead CHD1L inhibitor possesses drug-like properties in pharmacokinetic/pharmacodynamic mouse models. This work validates CHD1L as a druggable target and establishes a novel therapeutic strategy for the treatment of colorectal cancer.
Macrophage (Drp1) Dynamin-Related Protein 1 Accelerates Intimal Thickening After Vascular Injury
Authors: Umezu Ryuta , Koga Jun-ichiro , Matoba Tetsuya , Katsuki Shunsuke , Wang Lixiang , Hasuzawa Nao , Nomura Masatoshi , Tsutsui Hiroyuki , Egashira Kensuke 
Published: June 2020

Objective:
Mitochondria consistently change their morphology in a process regulated by proteins, including Drp1 (dynamin-related protein 1), a protein promoting mitochondrial fission. Drp1 is involved in the mechanisms underlying various cardiovascular diseases, such as myocardial ischemia/reperfusion injury, heart failure, and pulmonary arterial hypertension. However, its role in macrophages, which promote various vascular diseases, is poorly understood. We therefore tested our hypothesis that macrophage Drp1 promotes vascular remodeling after injury.

Method and Results:
To explore the selective role of macrophage Drp1, we created macrophage-selective Drp1-deficient mice and performed femoral arterial wire injury. In these mice, intimal thickening and negative remodeling were attenuated at 4 weeks after injury when compared with control mice. Deletion of macrophage Drp1 also attenuated the macrophage accumulation and cell proliferation in the injured arteries. Gain- and loss-of-function experiments using cultured macrophages indicated that Drp1 induces the expression of molecules associated with inflammatory macrophages. Morphologically, mitochondrial fission was induced in inflammatory macrophages, whereas mitochondrial fusion was induced in less inflammatory/reparative macrophages. Pharmacological inhibition or knockdown of Drp1 decreased the mitochondrial reactive oxygen species and chemotactic activity in cultured macrophages. Co-culture experiments of macrophages with vascular smooth muscle cells indicated that deletion of macrophage Drp1 suppresses growth and migration of vascular smooth muscle cells induced by macrophage-derived soluble factors.

Conclusions:
Macrophage Drp1 accelerates intimal thickening after vascular injury by promoting macrophage-mediated inflammation. Macrophage Drp1 may be a potential therapeutic target of vascular diseases.