bluuebunny/crossref_metadata_2025_split huggingface dataset:
Level of vital and laboratory values on arrival, and increased risk of 7-day mortality among adult patients in the emergency department: a population-based cohort study
Authors: Pedersen Peter Bank , Henriksen Daniel Pilsgaard , Brabrand Mikkel , Lassen Annmarie Touborg 
Published: November 2020

ObjectivesThe aim of the study was to provide evidence for, at which vital and laboratory values, increased risk of 7-day mortality in acute adult patients on arrival to an emergency department (ED).DesignA population-based cohort study.SettingED at Odense University Hospital, Denmark.ParticipantsAll patients ≥18 years with a first-time contact within the study period, 1 April 2012 to 31 March 2015.Primary and secondary outcome measuresPrimary outcome was 7-day all-cause mortality.Variables were first recorded vital and laboratory values included in risk stratification scores; respiratory frequency, blood pressure, heart rate, Glasgow Coma Scale, temperature, saturation, creatinine, PaO2, platelet count and bilirubin. The association between values and mortality was described using a restricted cubic spline. A predefined 7-day mortality of 2.5% was chosen as a relevant threshold.ResultsWe included 40 423 patients, 52.5% women, median age 57 (IQR 38–74) years and 7-day mortality 2.8%. Seven-day mortality of 2.5% had thresholds of respiratory frequency <12 and >18/min, systolic blood pressure <112 and >192 mm Hg, heart rate <54 and >102 beats/min, temperature <36.0°C and >39.8°C, saturation <97%, Glasgow Coma Scale score <15, creatinine <41 and >98 µmol/L for PaO2 <9.9 and >12.3 kPa, platelet count <165 and >327×109/L and bilirubin >12 µmol/L.ConclusionVital values on arrival, outside the normal ranges for the measures, are indicative of increased risk of short-term mortality, and most of the value thresholds are included in the lowest urgency level in triage and risk stratification scoring systems.
Disease composition and epidemiological characteristics of primary care visits in Pudong New Area, Shanghai: a longitudinal study, 2016–2018
Authors: Gong Xin , Wang Xiaoli , Shi Tianxing , Shi Jianwei , Yu Wenya , Zhou Liang , Chen Ning , Huang Jiaoling , Wang Zhaoxin 
Published: November 2020

ObjectivesThis study aims to analyse the disease composition of primary care visits rather than specialist visits, the former of which had scarcely been studied. We adopted specific disease classification (International Statistical Classification of Diseases and Related Health Problems, 10th Revision), disease system and communicable/non-communicable/injury disease classification, and variations of sex and age were also analysed.SettingWe extracted data from all community health service centres (CHSCs) and community health service stations in Pudong, Shanghai, from 2016 to 2018 using the electronic health record systems of the Pudong health information centre.ParticipantsOur data included all 46 720 972 primary care visits from 2016 to 2018 in CHSCs in Pudong.ResultsWe found that the top five diseases in primary care visits continued to be primary hypertension, problems related to medical facilities, chronic ischaemic heart disease, unspecified diabetes mellitus and acute upper respiratory infection. Lipoprotein metabolism disorder visits continued to increase over the study years. The numbers and proportions of patients with hypertension and unspecified diabetes were higher among men than women, and other cerebrovascular diseases were higher among women than men. The top five disease systems were circulatory system diseases, respiratory system diseases, endocrine/nutritional/metabolic diseases, factors influencing health status and digestive system diseases. The rankings of respiratory system and endocrine/nutritional/metabolic diseases rose over time. Non-communicable diseases (NCDs) accounted for approximately 90% of the primary care visits—a much higher percentage than other causes. The top five NCDs in primary care visits were cardiovascular and circulatory diseases, musculoskeletal disorders, diabetes, digestive diseases and urogenital diseases. Compared with women, men suffered from cardiovascular diseases at an earlier age.ConclusionsDifferent from specialist visits, common diseases, especially NCDs, were the main disease composition of current primary healthcare visits while the former focused on intractable diseases such as tumours, indicating that primary healthcare had played the role of gatekeeper of the healthcare system.
Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study
Authors: Lai Alvina G , Pasea Laura , Banerjee Amitava , Hall Geoff , Denaxas Spiros , Chang Wai Hoong , Katsoulis Michail , Williams Bryan , Pillay Deenan , Noursadeghi Mahdad , Linch David , Hughes Derralynn , Forster Martin D , Turnbull Clare , Fitzpatrick Natalie K , Boyd Kathryn , Foster Graham R , Enver Tariq , Nafilyan Vahe , Humberstone Ben , Neal Richard D , Cooper Matt , Jones Monica , Pritchard-Jones Kathy , Sullivan Richard , Davie Charlie , Lawler Mark , Hemingway Harry 
Published: November 2020

ObjectivesTo estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.MethodsWe employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.ResultsDeclines in urgent referrals (median=−70.4%) and chemotherapy attendances (median=−41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=−44.5%) and chemotherapy attendances (median=−31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.ConclusionsDramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.
Comparison of active versus passive surveillance adverse event reporting in a paediatric ambulatory chiropractic care setting: a cluster randomised controlled trial
Authors: Pohlman Katherine A , Carroll Linda , Tsuyuki Ross T , Hartling Lisa , Vohra Sunita 
Published: November 2020

ObjectivesThis pragmatic, cluster, stratified randomised controlled trial (RCT) compared the quantity and quality of adverse event (AE) reports after chiropractic manual therapy in children less than 14 years of age, using active versus passive surveillance reporting systems.MethodData were collected between November 2014 and July 2017 from 60 consecutive paediatric patient visits to participating chiropractors. Those allocated to active surveillance collected AE information with three paper-based questionnaires (two from patients, one from chiropractors) to identify any new or worsening symptoms after treatment. Passive surveillance involved AE information reported by chiropractors on a web-based system. To assess quality of reporting, AE reports greater than mild were reviewed by content experts. The primary outcome was the cumulative incidence of AE reports in active versus passive surveillance.ResultsNinety-six chiropractors agreed to participate and enrolled in the study: 34 chiropractors in active surveillance with 1894 patient visits from 1179 unique patients and 35 chiropractors in passive surveillance with 1992 patient visits from 1363 unique patients. In the active arm, AEs were reported in 8.8% (n=140, 95% CI 6.72% to 11.18%) of patients/caregivers, compared with 0.1% (n=2, 95% CI 0.02% to 0.53%) in the passive arm (p<0.001). The quality of AE reports was not evaluated because the five AE reports reviewed by the content experts were determined to be of mild severity.ConclusionWe found that active surveillance resulted in significantly more AE reports than passive surveillance. Further prospective active surveillance research studies should be conducted with children receiving chiropractic manual therapy to understand mechanisms and risk factors for moderate and severe AEs, and to further explore how and when to solicit patient safety information.
EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers
Authors: Smyth Elizabeth C , Vlachogiannis Georgios , Hedayat Somaieh , Harbery Alice , Hulkki-Wilson Sanna , Salati Massimiliano , Kouvelakis Kyriakos , Fernandez-Mateos Javier , Cresswell George D , Fontana Elisa , Seidlitz Therese , Peckitt Clare , Hahne Jens C , Lampis Andrea , Begum Ruwaida , Watkins David , Rao Sheela , Starling Naureen , Waddell Tom , Okines Alicia , Crosby Tom , Mansoor Was , Wadsley Jonathan , Middleton Gary , Fassan Matteo , Wotherspoon Andrew , Braconi Chiara , Chau Ian , Vivanco Igor , Sottoriva Andrea , Stange Daniel E , Cunningham David , Valeri Nicola 
Published: November 2020

ObjectiveEpidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome andEGFRcopy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785).DesignEGFRCN by either fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients.ResultsEGFRamplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significantEGFRCN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cyclin B1 downregulation and cyclin E1 upregulation, selectively in organoids fromEGFR-amplified aGEA.ConclusionEGFRCN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials.
Bouncing cosmology in f(Q) symmetric teleparallel gravity
Authors: Bajardi Francesco , Vernieri Daniele , Capozziello Salvatore 
Published: November 2020

AbstractWe consider f(Q) extended symmetric teleparallel cosmologies, where Q is the non-metricity scalar, and constrain its functional form through the order reduction method. By using this technique, we are able to reduce and integrate the field equations and thus to select the corresponding models giving rise to bouncing cosmology. The selected Lagrangian is then used to develop the Hamiltonian formalism and to obtain the Wave Function of the Universe which suggests that classical observable universes can be recovered according to the Hartle Criterion.
The effect of methyl ammonium chloride doping for perovskite solar cells on structure, crystallization and power conversion efficiency
Authors: Gao Jing , Liao Chujian , Guo Yanqun , Zhou Difan , Zeng Zhigang , Cai Chuanbing 
Published: November 2020

The perovskite membrane with large particle size, uniform coverage and high quality is the prerequisite for the preparation of efficient and stable perovskite solar cells. Various additives have been used to increase the grain size and improve the film morphology and crystal quality. In this paper, methylammonium chloride (MACl) was proposed to obtain high crystalline quality of [Formula: see text] perovskite absorption layer. The results show that the adding ammonium methyl chloride into the precursor of tricationic perovskite not only passivates surface defects to form high-quality and large-grain perovskite films, but also facilitates the formation of pure [Formula: see text]-phase [Formula: see text]. Meanwhile, the designed perovskite precursor solutions were used to fabricate mesoporous perovskite solar cells (PSCs). Owing to the perovskite layer consisting of optimized MACl doping, the short-circuit current density [Formula: see text] of PSCs reaches 23.81 mA/cm2, which is 2.73 mA/cm2 higher than the primary [Formula: see text] based on PSCs. The obtained power conversion efficiency (PCE) increases from 13.67% to 17.59%.
2-Hydroxylation of Fatty Acids Represses Colorectal Tumorigenesis and Metastasis via the YAP Transcriptional Axis
Authors: Sun Liang , Yang Xiaoqin , Huang Xiaoheng , Yao Yizhou , Wei Xiangyu , Yang Shugao , Zhou Diyuan , Zhang Wei , Long Zhimin , Xu Xiaoyan , Zhu Xinguo , He Songbing , Su Xiong 
Published: November 2020

Abstract

Alteration in lipid composition is an important metabolic adaptation by cancer cells to support tumorigenesis and metastasis. Fatty acid 2-hydroxylase (FA2H) introduces a chiral hydroxyl group at the second carbon of fatty acid (FA) backbones and influences lipid structures and metabolic signaling. However, the underlying mechanisms through which FA 2-hydroxylation is coupled to metabolic adaptation and tumor growth remain elusive. Here, we show that FA2H regulates specific metabolic reprogramming and oncogenic signaling in the development of colorectal cancer. FA2H is highly expressed in normal colorectal tissues. Assessments through deciphering both published high-throughput data and curated human colorectal cancer samples revealed significant suppression of FA2H in tumors, which is correlated with unfavorable prognosis. Experiments with multiple models of genetic manipulation or treatment with an enzymatic product of FA2H, (R)-2-hydroxy palmitic acid, demonstrated that FA 2-hydroxylation inhibits colorectal cancer cell proliferation, migration, epithelial-to-mesenchymal transition progression, and tumor growth. Bioinformatics analysis suggested that FA2H functions through AMP-activated protein kinase/Yes-associated protein (AMPK/YAP) pathway, which was confirmed in colorectal cancer cells, as well as in tumors. Lipidomics analysis revealed an accumulation of polyunsaturated fatty acids in cells with FA2H overexpression, which may contribute to the observed nutrient deficiency and AMPK activation. Collectively, these data demonstrate that FA 2-hydroxylation initiates a metabolic signaling cascade to suppress colorectal tumor growth and metastasis via the YAP transcriptional axis and provides a strategy to improve colorectal cancer treatment.

Significance:
These findings identify a novel metabolic mechanism regulating the tumor suppressor function of FA 2-hydroxylation in colorectal cancer.
Abstract IA-04: Pancreatic cancer cells assemble a CXCL12-keratin 19 coating to resist immunotherapy
Authors: Fearon Douglas , Wang Zhikai 
Published: November 2020

Abstract
How pancreatic ductal adenocarcinoma (PDA) cells stimulate CXCR4 to exclude T cells and resist T cell checkpoint inhibitors is not known. We find that CXCL12, the ligand forCXCR4 that is produced by the cancer-associated fibroblast, “coats” human PDA and colorectal cancer cells as covalent heterodimers with keratin 19 (KRT19). Modeling the formation of the heterodimer with three proteins shows that KRT19 binds CXCL12 and transglutaminase-2 (TGM2), and that TGM2 converts the reversible KRT19-CXCL12 complex into the covalent heterodimer. This model is validated by showing that cancer cells in mouse PDA tumors must express KRT19 and TGM2 to become coated with CXCL12, exclude T cells, and resist immunotherapy with anti-PD-1 antibody. Thus, PDA cells have a cell-autonomous means by which they capture CXCL12 to mediate immune suppression, which is potentially amenable to therapy.
Citation Format: Douglas Fearon, Zhikai Wang. Pancreatic cancer cells assemble a CXCL12-keratin 19 coating to resist immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-04.
Abstract IA-06: Heterotypic 3D bioprinted tissues to study pancreatic cancer
Authors: Langer Ellen M , Allen-Petersen Brittany L , English Isabel A , Link Jason M , Sears Rosalie C 
Published: November 2020

Abstract
Crosstalk between tumor cells and the tumor microenvironment contributes critically to tumor initiation, tumor progression, and therapeutic response. The tumor microenvironment (TME) is composed of multiple cell types (e.g. fibroblast, vascular, and immune cells) that are temporally and spatially dynamic. Stromal cells in the TME respond not only to the growing tumor cells, but are also affected by concurrent changes in the accessibility and composition of the extracellular matrix (ECM), signaling molecules, nutrients and oxygen. Together, the interactions of tumor cells and stromal cells regulates the tumor phenotype and, ultimately, affects patient outcomes. As more is understood about the dynamic relationship of multiple cell types in the tumor microenvironment, it has become clear that better models of human cancer are needed. In order to understand the impact of heterotypic crosstalk on tumor behaviors such as initiation, progression, and response to therapies, we recently developed heterotypic, scaffold-free tissue models of advanced cancer using an extrusion-based bioprinter system. Multiple cell types including cancer cells, fibroblasts, endothelial cells, mesenchymal stem cells, and immune cells can be incorporated into bioprinted tissues with defined spatial architecture, and the system is compatible with patient-derived cells. Within these structures, cells exhibit a tissue-like cellular density, deposit ECM, and self-organize to form complex structures, as illustrated by formation of nascent endothelial networks. Cell intrinsic, extrinsic, and spatial phenotypes, including cell survival, cell proliferation, differentiation state, ECM deposition, and cellular migration, can be assessed within these tissues following exposure to extrinsic signals or therapies. Our current work is focused in three main areas. First, we aim to understand the signaling between tumor and stromal cell types in early cancer development that contributes to malignant progression. Second, we are working to understand the influence of fibroblast heterogeneity on tumor cell phenotypes, using genetic or non-genetic perturbagens to alter fibroblast activation. Finally, we are building tissues comprising patient-derived cells to understand how the microenvironment influences therapeutic response. Together, our work demonstrates that bioprinted tumor tissues recapitulate many aspects of in vivo neoplastic tissues, and provides a manipulable model system to interrogate molecular mechanisms of tumor development, progression, and treatment response.
Citation Format: Ellen M Langer, Brittany L Allen-Petersen, Isabel A English, Jason M Link, Rosalie C Sears. Heterotypic 3D bioprinted tissues to study pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-06.
Abstract PO-014: Interleukin 17 induced- neutrophil extracellular traps (NETs) mediate resistance to checkpoint blockade in pancreatic cancer
Authors: Chandra Vidhi , Zhang Yu , Riquelme Erick , Dutta Prasanta , Quesada Pompeyo R. , Rakoski Amanda , Zoltan Michelle , Arora Nivedita , Baydogan Seyda , Horne William , Burks Jared , Xu Hanwen , Hussain Perwez , Wang Huamin , Gupta Sonal , Maitra Anirban , Bailey Jennifer M. , Moghaddam Seyed J. , Banerjee Sulagna , Sahin Ismet , Bhattacharya Pratip , McAllister Florencia 
Published: November 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) continues to be an aggressive disease with an immunosuppressive tumor microenvironment, which is recalcitrant to most therapies. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been implicated in initiation of pancreatic premalignant lesions but its role in invasive PDAC has not been widely explored. We hypothesized that IL-17 triggers and sustains immunosuppression during PDAC. We employed pharmacological and genetic strategies to inhibit IL-17/IL-17RA signaling axis and characterized the tumor microenvironment with RNA sequencing, mass & flow cytometry and quantitative multiplex immunofluorescence. Our analysis revealed that IL-17 signaled through tumor cells to recruit neutrophils into the tumor microenvironment and spatially exclude cytotoxic CD8 T cells. Furthermore, IL-17 signaling in tumor cells triggered neutrophils to form extracellular traps (NETs), a primary mechanism mediating PDAC immunosuppression. Genetic or pharmacological inhibition of IL-17 overcame resistance to immune checkpoint blockade (PD-1, CTLA-4), in a CD8 T cell dependent manner. Inhibition of neutrophils or Padi4-dependent NETosis phenocopied IL-17 neutralization. Higher expression of IL-17 and PADI4 in human PDAC corresponded with poorer prognosis, according to TCGA data. Serum from PDAC patients had a higher capacity for NET formation and diminished ability for NET degradation in control neutrophils, in comparison to serum from healthy donors. In conclusion, the cross-talk of IL-17 with pancreatic cancer cells orchestrates neutrophil recruitment and activation of Padi4 dependent NETosis, ultimately resulting in spatial remodeling of the stroma and immunosuppression. IL-17 inhibition overcomes resistance to checkpoint blockade in a CD8 T cell dependent fashion. Clinical studies with IL-17 inhibitors and checkpoint blockade represent a promising novel combinatorial therapy for this lethal disease.
Citation Format: Vidhi Chandra, Yu Zhang, Erick Riquelme, Prasanta Dutta, Pompeyo R. Quesada, Amanda Rakoski, Michelle Zoltan, Nivedita Arora, Seyda Baydogan, William Horne, Jared Burks, Hanwen Xu, Perwez Hussain, Huamin Wang, Sonal Gupta, Anirban Maitra, Jennifer M. Bailey, Seyed J. Moghaddam, Sulagna Banerjee, Ismet Sahin, Pratip Bhattacharya, Florencia McAllister. Interleukin 17 induced- neutrophil extracellular traps (NETs) mediate resistance to checkpoint blockade in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-014.