bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB524: Discovery of highly selective RON kinase inhibitors
Authors: Ham Young Jin , Kim GyeongHwan , Lee Juhyun , Lee Jaeyoung , Kim Min Kyung , Kim Sunhong , Kim Woosook , Kim Han Byoul , Jang Sung Woong , Park Hee Dong , Jeon Seonguk , Kim Seok-Joo , Cho Joongheui , Kim Jungjoon , Yoon Hong bin , Kwak Youngshin 
Published: June 2022

Abstract
RON is a receptor tyrosine kinase of the MET proto-oncogene family, known as macrophage stimulating 1 receptor (MST1R) that recognizes macrophage-stimulating protein (MSP). RON has been known to be highly expressed in several epithelial tumors, promoting tumor progression and metastasis, and on macrophages surface, facilitating M2-like phenotype polarization of tumor-associated macrophages (TAM) to impair anti-tumor functions of CD8+ T cells. Although pharmacological inhibition of RON kinase has received attention from many research groups, monoclonal antibody drug showed a limited clinical efficacy due to RON variant of receptor region. Because the structure homology of kinase domain between RON and MET is 80%, discovery of RON-specific small molecule inhibitor is considered to be highly challenging to achieve. At first, we discovered a lead compound with about 50-fold of RON selectivity against MET kinase. Our medicinal chemistry efforts elevated RON/MET selectivity up to 500~10,000-fold (IC50 = 1~50 nM in RON enzyme assay), and the target specificity was proved through a panel assay of 372 kinases (Reaction Biology Corp.). A series of compounds effectively modulated p-RON and downstream signals (e.g. p-ERK and p-AKT) in MDA-MB-453, and inhibited cell proliferation of Ba/F3 cell-line engineered with human RON kinase. Significant anti-tumor effects were shown in syngeneic mouse models compared to a control group after oral administration, and studies related to immuno-oncology are ongoing in in-vitro or ex-/in-vivo assay systems. In conclusion, we have identified RON selective small molecule inhibitors that will be useful to figure out the biology following RON selective inhibition against MET kinase, and to validate the translational potential of RON kinase as a therapeutic target for human diseases including cancer.
Citation Format: Young Jin Ham, GyeongHwan Kim, Juhyun Lee, Jaeyoung Lee, Min Kyung Kim, Sunhong Kim, Woosook Kim, Han Byoul Kim, Sung Woong Jang, Hee Dong Park, Seonguk Jeon, Seok-Joo Kim, Joongheui Cho, Jungjoon Kim, Hong bin Yoon, Youngshin Kwak. Discovery of highly selective RON kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB524.
Abstract LB539: Development of GB2102, a novel and highly differentiated anti-FGFR2b antibody for the treatment of gastric cancer
Authors: Zhou Tiantian , Du Qinglin , Yang Xueyan , Peng Fei , Li James , Han Shuhua 
Published: June 2022

Abstract
Background: Gastric cancer (GC) is a complex and heterogeneous disease with limited available treatment options. Fibroblast growth factor receptor-2b (FGFR2b) is overexpressed in approximately 2-30% of GC and associated with worse prognosis. Bemarituzumab is an afucosylated humanized monoclonal antibody that specifically inhibits FGFR2b. In the FIGHT trial, bemarituzumab showed beneficial response in GC, but appeared to cause high corneal adverse events. It was hypothesized that FGF10 inhibition may be the mechanism of corneal toxicity by bemarituzumab. We have recently generated a monoclonal antibody against FGFR2b with potent FGF7 blocking activity but weak inhibition activity for FGF10. Thus, GB2102 may represent a differentiated antibody therapeutics that has a potential to decrease the adverse effects in the eyes. Methods: GB2102 was generated by immunization of FGFR2b protein in mice followed by hybridoma technique. FGF7 and FGF10 ligand blocking was assessed by ELISA. FGF7-induced FGFR2b phosphorylation and cell proliferation were studied in SNU-16 gastric cancer tumor cell line. Antibody-dependent cell-mediated cytotoxicity (ADCC) function was evaluated by IL-2-activated NK cell-induced lysis of target cells. Results: GB2102 displayed potent blocking of FGF7-FGFR2b pathway by inhibition of FGF7-induced FGFR2b phosphorylation and tumor cell proliferation. But GB2102 showed weak blocking of FGF10 binding to FGFR2b compared with benchmark, suggesting that GB2102 may have better safety profile in corneal toxicity. In ADCC function assay, GB2102 induced potent ADCC effects by primary human NK cells to kill FGFR2b-expressing tumor cells. Conclusions: In summary, preclinical studies showed that GB2102 is an anti-FGFR2b antibody with potent ADCC effect and strong FGF7 blocking but weak FGF10 inhibition. These results suggest that GB2102 is potentially a safe and effective candidate for the treatment of FGFR2b positive gastric cancer.
Citation Format: Tiantian Zhou, Qinglin Du, Xueyan Yang, Fei Peng, James Li, Shuhua Han. Development of GB2102, a novel and highly differentiated anti-FGFR2b antibody for the treatment of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB539.
Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial
Authors: Ihl Thomas , Ahmadi Michael , Laumeier Inga , Steinicke Maureen , Ferse Caroline , Klyscz Philipp , Endres Matthias , Hastrup Sidsel , Poppert Holger , Palm Frederick , Kandil Farid I. , Weber Joachim E. , von Weitzel-Mudersbach Paul , Wimmer Martin L.J. , Audebert Heinrich J. 
Published: June 2022

Background:
The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes.

Methods:
In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up.

Results:
Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5–43.5); 36.1 after 2 years (95% CI, 13.1–59.7) and 29.6 (95% CI, 2.0–57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03–1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96–1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95–1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up.

Conclusions:
Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01586702.
A Centimeter-Wavelength Snowfall Retrieval Algorithm Using Machine Learning
Authors: King Fraser , Duffy George , Fletcher Christopher G. 
Published: June 2022

Abstract
Remote sensing snowfall retrievals are powerful tools for advancing our understanding of global snow accumulation patterns. However, current satellite-based snowfall retrievals rely on assumptions about snowfall particle shape, size, and distribution that contribute to uncertainty and biases in their estimates. Vertical radar reflectivity profiles provided by the vertically pointing X-band radar (VertiX) instrument in Egbert, Ontario, Canada, are compared with in situ surface snow accumulation measurements from January to March 2012 as a part of the Global Precipitation Measurement (GPM) Cold Season Precipitation Experiment (GCPEx). In this work, we train a random forest (RF) machine learning model on VertiX radar profiles and ERA5 atmospheric temperature estimates to derive a surface snow accumulation regression model. Using event-based training–testing sets, the RF model demonstrates high predictive skill in estimating surface snow accumulation at 5-min intervals with a low mean-square error of approximately 1.8 × 10−3 mm2 when compared with collocated in situ measurements. The machine learning model outperformed other common radar-based snowfall retrievals (Ze–S relationships) that were unable to accurately capture the magnitudes of peaks and troughs in observed snow accumulation. The RF model also displayed consistent skill when applied to unseen data at a separate experimental site in South Korea. An estimate of predictor importance from the RF model reveals that combinations of multiple reflectivity measurement bins in the boundary layer below 2 km were the most significant features in predicting snow accumulation. Nonlinear machine learning–based retrievals like those explored in this work can offer new, important insights into global snow accumulation patterns and overcome traditional challenges resulting from sparse in situ observational networks.
To Warn or Not to Warn: Factors Influencing National Weather Service Warning Meteorologists’ Tornado Warning Decisions
Authors: Kim Jiyoun , Seate Anita Atwell , Liu Brooke F. , Hawblitzel Daniel , Funk Theodore 
Published: June 2022

Abstract
Weather warnings are critical risk communication messages because they have the potential to save lives and property during emergencies. However, making warning decisions is challenging. While there have been significant advances in technological weather forecasting, recent research suggests that social factors, including communication, influence warning meteorologists’ decisions to warn. We examine the roles of both scientific and social factors in predicting warning meteorologists’ decisions to warn on tornadoes. To do so, we conducted a cross-sectional survey of National Weather Service forecasters and members of management in the southern and the central regions of the United States, as well as conducted a retrospective data analysis of cross-sectional survey data from the central region Tornado Warning Improvement Project. Results reveal that dependency on radar velocity couplet and a variety of social factors predicted decisions to warn.
Recent Levels of Evidence in Otolaryngology Journals
Authors: Chia Clemente , Cheung Priscilla , Wibowo Joshua , Dubrava Adam , Manji Jamil , Paddle Paul 
Published: June 2022

Objective: The development of evidence-based medicine has contributed to improved patient outcomes. This study aims to identify the trends in levels of evidence in otolaryngology journals over time, as represented by the 4 most widely circulated peer-reviewed otolaryngology journals. Methods: A review of all articles from 2007, 2010, 2013, 2016, and 2019, in 4 major otolaryngology journals. Data points included journal source, year of publication, country of origin, first author sex, and subspecialty category within otolaryngology. Level of evidence was determined based on the study’s primary research question and was graded on a scale of 1 (strongest) to 4 (weakest) based on the Oxford Centre of Evidence-based Medicine - Levels of Evidence guideline. Comparison of levels of evidence was performed using Kruskal-Wallis analysis of variance for ordinal data. Results: About 4297 articles were identified over 12 years. The number of research articles remained consistent over the 12 years of this study. Clinical research increased from 78.6% to 85.1%. Female first authorship increased from 20.3% in 2007 to 31.0% in 2019. Of 3558 articles that constituted clinical research from 2007 to 2019, level 1 studies increased from 0.9% to 3.6%, with level 4 studies remaining stable at an overall rate of 60.3%. Randomized controlled trials remained stable at 4.6% of all studies. Systematic reviews increased from 3.2% to 8.4%. Conclusion: This article provides an update on the levels of evidence to allow for an honest self-assessment of otolaryngology as a scientific field.
Balloon Sinus Dilation Versus Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis: Systematic Review and Meta-Analysis
Authors: Sinha Parul , Tharakan Theresa , Payne Spencer , Piccirillo Jay F. 
Published: June 2022

Objective: To determine the efficacy of balloon sinus dilation (BSD) compared to functional endoscopic sinus surgery (FESS) or medical management for chronic rhinosinusitis (CRS). Methods: A qualified medical librarian conducted a literature search for relevant publications that evaluate efficacy of BSD. Studies were assessed independently by 2 reviewers for inclusion in the systematic review and meta-analysis. Results: From 315 abstracts reviewed, 18 studies were included in qualitative review, and 7 were included in meta-analysis. Quantitative analysis included 4 randomized clinical trials (RCTs) and 3 cohort studies comparing baseline and post-operative Sinonasal Outcome Test (SNOT)—20 scores in BSD and FESS. A meta-analysis restricted to the studies reporting SD for changes from baseline (2 RCTs, 1 cohort) showed the pooled difference in means to be 0.435, less than a clinically meaningful difference of 0.8. A separate sensitivity analysis of the studies including 4 additional studies with imputed values of SD for changes from baseline showed the pooled difference of means to be 0.237 assuming the highest level of correlation ( Corr .8) between the pre- and post-intervention scores. Conclusions: There is limited high-quality evidence that assesses the efficacy of BSD versus FESS in the management of CRS patients. To better inform CRS management, future studies should compare BSD with endoscopic sinus surgery, hybrid procedures, and/or medical management alone using validated objective and patient-reported outcome measures.
Virtual Reality and Powerpoint Grocery Store Tours: Equally Effective in Improving Self-efficacy in Randomised Control Trial
Authors: Pilut Jennifer , Hollis James , Lanningham-Foster Lorraine , Pitchford E. Andrew , Litchfield Ruth 
Published: June 2022

Purpose Compare computer-based virtual reality (CBVR) and voice-over PowerPoint (PP) grocery store tours (GST) on adult nutrition literacy (NL) and healthful food purchasing self-efficacy (HFPSE). Design Participants (n = 68) recruited from University worksite wellness program and randomly assigned to CBVR or PP (CBVR = 35; PP = 33). Intervention Four-week culinary/nutrition education program. Initial three weeks provided identical education for both groups. Week four implemented GST intervention using CBVR or PP. Measures NL and HFPSE surveys before, after, and three-months post from the start of program. Analysis Intent-to-treat (ITT) analysis with RMANOVA (95% confidence intervals [CI] and effect sizes) to examine change in NL and HFPSE between CBVR and PP groups over 4-week intervention and 3-month retention period. Results 43 of 68 participants [CBVR (n = 19) and PP (n = 24)] were included in analyses. Both groups significantly improved HFPSE over time (P<.001, CBVR = 46.23% PP = 33.34%), but there were no differences between groups ( P = .21) or group by time interaction ( P = .31). NL did not change for either group ( P = .83, CBVR = 1.11%; PP = .12%) nor were there differences between groups ( P = .07). Conclusions CBVR and PP GST significantly improved and maintained higher HFPSE scores.
Estrogen Receptor- And Progesterone Receptor-Positive Thresholds in Predicting the Recurrence of Early Low-Risk Endometrial Cancer
Authors: Li Ning , Jiang Peng , Huang Yuzhen , TU Yuan , Kong Wei , Jiang Shan , Zhang Jingni , Wu Yijun , Zhang Xiaorong , Xie Qingning , Yuan Rui 
Published: June 2022

Background: Estrogen receptors (ER) and progesterone receptors (PR) have important prognostic value in endometrial cancer, but there is no recognized positive immunohistochemical threshold for predicting the recurrence of early low-risk endometrial cancer. The purpose of this study was to clarify the optimal positive thresholds of the immunohistochemical parameters the ER and PR in early low-risk endometrial cancer. Methods: A total of 332 patients with stage IA endometrial cancer were enrolled from the First Affiliated Hospital of Chongqing Medical University and People’s Hospital of Sha ping ba District in Chongqing between January 2013 and December 2018. First, univariate and multivariate Cox regression analyses were used to analyze the correlation between various clinical factors and the prognosis of early low-risk endometrial cancer. Then, the receiver operating characteristic curve (ROC curve) and Youden index were used to determine the positive thresholds of ER and PR. Results: The positive thresholds of ER and PR for predicting the recurrence of early low-risk endometrial cancer were 12% and 8%, respectively. Multivariate analysis showed that ER ( P = 0.004), PR ( P = 0.026), and p53 ( P = 0.021) were risk factors for the prognosis of patients with early low-risk endometrial cancer. The recurrence-free survival and the overall survival in the low ER group and PR group were much lower than those in the high ER group and PR group ( P < 0.001 of all). Conclusions: ER and PR positive thresholds of 12% and 8%, respectively, are the most suitable for predicting the recurrence of early low-risk endometrial cancer.
Quantifying the health needs of migrants in vulnerable circumstances registered with a nurse-led primary care service
Authors: Clark Emily , Fox Hannah , Gillam Tara B , Clarry Clodagh 
Published: June 2022

Background As of the end of 2019, at least 79.5 million people worldwide have been forced to flee their homes. Those seeking asylum face adversity before, during and after arrival in the UK, resulting in complex health and social needs. The study setting was a nurse-led asylum seeker service in a dispersal city, commissioned to provide an initial health assessment, immunisations and support to register with a general practitioner. Aims The aim was to quantify the health needs of migrants in vulnerable circumstances registered with a nurse-led primary care service by clinical audit. Methods In June 2018, 80 electronic records were reviewed by seven auditors to analyse documentation of demographics, asylum status, service use, barriers to care, physical and mental health. Results Where data were available, 86% migrated due to persecution or trafficking, 59% had a chronic physical illness, 51% had a mental health condition and 49% experienced barriers to accessing a mainstream general practitioner. Conclusions Although a small sample, this survey demonstrated high physical and mental health needs that are often unmet in mainstream services. There was a high level of unknown need, for example of torture rates. These findings informed quality improvement in documentation and health assessments, and further research.
The history of disaster nursing: from Nightingale to nursing in the 21st century
Authors: Fletcher Kelsie A , Reddin Karen , Tait Desiree 
Published: June 2022

Background Nurses have a rich history in performing their duty both domestically and internationally in response to a disaster. Comprising the largest proportion of the healthcare workforce, nurses possess a unique opportunity to inform disaster planning and management. With the ongoing threat from COVID-19 and continuing conflict, humanitarian aid needs, epidemics and natural disasters; the capacity of nurses to continue to respond in times of global need is unparalleled. Aims The aim of this paper is to explore the developments in the field of disaster nursing. Mapping key changes in policy, practice and outcomes. Methods A qualitative interpretive historical review was conducted to examine core developments in the history of disaster nursing, examining key organisations (e.g. World Health Organization, International Council of Nurses), national and international policies and historical accounts. Results 29 articles were analysed, and politics, strategic perspectives and nursing identity (‘sense of duty’ and roles) emerged from the literature. The influence of professionalisation and public health/health promotion emerged next. A total of 10 articles refer to disaster nursing specifically, of which 4 of these are reports/policy. Conclusions Nurses have spent centuries building the trust and legitimacy of the profession. Disaster nursing goes beyond the expectations of a registered nurse. The responsibilities of a disaster nurse encompass wider community health promotion, critical decision-making beyond the individual patient, resilience and ethical challenges. Whilst significant advancements have emerged in the last 30 years, further research, and representation of the profession at a strategic and political level could enhance the effectiveness of nurses’ roles in the 4 phases of disaster response: mitigation, preparation, response and recovery.
Fluctuating power: an exploration of refugee health nursing within the resettlement context in Victoria, Australia
Authors: Hughes Emma , Kean Susanne , Cuthill Fiona 
Published: June 2022

Background The Refugee Health Program (RHP) is a nurse-led community initiative, introduced in 2005 with the aim of responding to complex health issues of refugees arriving in Victoria, Australia. Little is known about refugee health nursing in the resettlement context and the impact of dedicated refugee healthcare. Aim To explore the experiences and perspectives of Refugee Health Nurses (RHNs), Refugee Health Managers (managers) and refugees, gaining insight into professional relationships and the complexities of offering a specialised refugee health service. Method A focused ethnographic approach incorporated semi-structured interviews with five RHNs, two managers and eight refugees, two focus groups with refugees and participant observation within the RHP during April 2017 to December 2017. Data collection was undertaken across two sites and interviews, focus groups and observations were transcribed and thematically analysed. Social constructionism asserts that the focus of enquiry should be on interaction, group processes and social practices. Emphasis is placed upon relationships between RHNs, managers and refugees, with knowledge viewed as relational and interactional. Results Professional relationships between RHNs and refugees are complex, with power oscillating between them. Contrary to discourses of ‘vulnerability’ of refugees, both RHNs and refugees demonstrated power in their relationships with each other. Nurses also suggested that these relationships were stressful and could lead to burnout. Key themes were developed: (1) nursing autonomy and gatekeeping; (2) vicarious trauma and burnout; and (3) refugee negotiation of care. Conclusions The balance of power is central to therapeutic relationships. In relationships between RHNs and refugees, power fluctuates as RHNs are exposed to vicarious trauma and symptoms of burnout, while refugees exercise agency by recognising benefits to specialised care. In developing effective therapeutic relationships between RHNs and refugees, attention should be paid to how care is delivered to protect RHNs from burnout while ensuring that refugees receive appropriate care.