bluuebunny/crossref_metadata_2025_split huggingface dataset:
What are the mental health consequences of austerity measures in public housing? A quasi-experimental study
Authors: Kim Chungah , Teo Celine , Nielsen Andrew , Chum Antony 
Published: June 2022

BackgroundAs governments around the world implement austerity measures to reduce national deficits, there is an urgent need to investigate potential health impacts of specific measures to avoid unintended consequences. In 2013, the UK government implemented the underoccupancy penalty (ie, the bedroom tax) to reduce the national housing benefits bill, by cutting social housing subsidies for households deemed to have excess rooms. We investigated the impact of the bedroom tax on self-reported psychological distress.MethodsUsing data from the UK Household Longitudinal Study (2010–2014), the sample included those who received housing subsidies, aged 16–60, living in England. Control and treatment groupings were identified on their household composition and housing situation. We used matching methods to create an exchangeable set of observations. Difference-in-differences analysis was performed to examine changes across the prereform and postreform psychological distress of the treatment and control groups, using the 12-item General Health Questionnaire.ResultsThe implementation of the reform was associated with a moderate increase in psychological distress (0.88, 95% CI 0.06 to 1.71) among the treatment group, relative to the control group. However, the announcement was not associated with change in psychological distress (0.53, 95% CI 0.21 to 1.27).ConclusionOur study provides evidence that the implementation of housing austerity measures can increase psychological distress among social housing tenants. As the use of austerity measures become more widespread, policy-makers should consider supplementary interventions to ameliorate potential negative health consequences.
Income and outcomes of patients with incident atrial fibrillation
Authors: Biancari Fausto , Teppo Konsta , Jaakkola Jussi , Halminen Olli , Linna Miika , Haukka Jari , Putaala Jukka , Mustonen Pirjo , Kinnunen Janne , Hartikainen Juha , Aro Aapo , Airaksinen Juhani , Lehto Mika 
Published: June 2022

BackgroundSocioeconomic disparities can be associated with adverse outcomes in patients with cardiovascular diseases. The impact of personal income on the outcomes of patients with atrial fibrillation (AF) is unclear.MethodsNationwide observational registry-based study on patients with incident AF in Finland during 2007–2018.Results203 154 patients (mean age 73.0±13.5; females 49.0%) were diagnosed with incident AF during the study period. Overall, 16 272 (8.0%) patients experienced first-ever ischaemic stroke and 63 420 (31.2%) died (mean follow-up 4.3±3.3 years). After adjusting for confounding factors, low personal income was associated with increased risk of overall mortality in all age strata and the incidence of first-ever stroke in patients aged <65 years and 65–74 years, but not in those ≥75 years. The magnitude of this effect was greatest in patients aged <65 years. After propensity score matching of patients <65 years in the lowest and highest quintiles of maximum personal annual income, at 10 years, those in the highest income quintile (≥€54 000) had significantly lower risk of first-ever stroke (subdistribution HR 0.495, 95% CI 0.391 to 0.628) and overall mortality (HR 0.307, 95% CI 0.269 to 0.351) compared with patients in the lowest income quintile (≤€12 000).ConclusionsPersonal annual income has a significant impact on the incidence of first-ever ischaemic stroke and overall mortality among patients with incident AF, particularly among patients of working age. Low-income indicate the need for intervention strategies to improve outcomes of AF.Trial registration numberNCT04645537.
A Conceptual Approach for Business Model Innovation Including Strategic Simulations as Digital Prototypes for Decision Support
Authors: Nawroth Georg , Herrmann Florian , Spath Dieter , Bauer Wilhelm 
Published: June 2022

Business model innovations (BMIs) are a promising approach to be successful in hyper-competition. There are several approaches for the systematic development of BMI. Within these approaches, however, companies are faced with major challenges, especially, in the decision-making process. On the one hand, certain information is not available, and on the other hand, cause-and-effect relationships within the innovation networks or systems are not known. In certain contexts, simulations can close this gap. Thus, this paper addresses the research question of how simulations can be systematically integrated into BMI approaches. Therefore, BMI processes and different simulation applications are reviewed, the aspect of BMI prototyping is identified and an extended BMI approach is developed, which systematically integrates simulations.
Effect of Hematocrit Injury on the Survival Rate of Advanced Malignant Tumors and Its Clinical Significance
Authors: Li Lin , Wu Weibin , Yin Mingdi 
Published: June 2022

Objective. To investigate the effect of logistic multivariate analysis on the survival rate of advanced malignant tumors and to evaluate the effect of erythrocyte storage injury on the survival rate of advanced malignant tumors and its clinical significance. Methods. A retrospective analysis was performed on 120 advanced cancer patients who received blood transfusion in Shaanxi Cancer Hospital from March 2018 to June 2019, and the risk factors for death were analyzed. A total of 72 advanced cancer patients admitted to hospital from March 2019 to June 2021 were included in the study. The patients with red blood cell transfusion storage

time
≤
14

d were the study group (

n
=
36

), and the patients with red blood cell transfusion storage

time
>
14

d were the control group (

n
=
36

). Compare the total efficiency of blood transfusion. The levels of Hb, erythrocyte count, hematocrit (HCT), blood oxygen saturation (SPO2), creatinine (Cr), erythrocyte deformability index, whole blood, erythrocyte, and hemoglobin before and after blood transfusion were compared, and the adverse reactions of blood transfusion were recorded. Results. Dyspnea and delirium were significantly associated with patient survival time (

P
<
0.05

). Red blood cell storage

time
≤
14

days,

Lym
%
<
12
%

, lactate dehydrogenase

LDH

>
500

U/L, and

ALB
<
30

g/L were significantly correlated with survival time. Karnofsky performance status

KPS

<
30

, delirium,

LDH
>
500

U/L, and albumin

ALB

<
30

g/L were independent influencing factors of survival (

P
<
0.05

). The overall effective rate of the research group was higher (

P
<
0.05

). The incidence of adverse reactions in the study group was lower (

P
<
0.05

). The levels of Hb, red blood cell count, and HCT in the study group were higher (

P
<
0.05

). Compared with the control group, the SPO2 level and the red blood cell deformability index were higher in the study group (

P
<
0.05

). After blood transfusion, the level of (diphosphoglycerate) DPG in the study group was higher than that in the control group (

P
<
0.05

). The length of hospital stay in the study group was significantly shortened (

P
<
0.05

). The nosocomial infection rate and case fatality rate in the study group were significantly reduced (

P
<
0.05

). Conclusion. Red blood cell storage

time
≤
14

d,

LYM
%
<
12
%

,

LDH
>
500

U/L, and

ALB
<
30

g/L are all significantly correlated with survival time.

KPS
<
30

, delirium,

LDH
>
500

U/L, and

ALB
<
30

g/L were independent factors for survival (

P
<
0.05

). Transfusion of red blood cells stored for ≤14 days in patients with advanced malignant tumors can significantly increase the effective infusion rate, improve anemia status, shorten hospital stay, and reduce mortality and risk of nosocomial infection and is worthy of clinical promotion.
Macular and Optic Disc Parameters in Children with Amblyopic and Nonamblyopic Eyes under Optical Coherence Tomography Fundus Images
Authors: Zhu Dan , Sun Qiang , Yang Hong , Zou Yangcheng , Liu Chunmei , Xu Yan 
Published: June 2022

The aim of this study was to investigate the characteristics of macular and optic disc parameters in children with amblyopic and nonamblyopic eyes, using fundus images under optical coherence tomography (OCT). 36 patients with anisometropic amblyopia were selected in the experimental group, and another 36 healthy volunteers were selected in the control group, OCT examinations were performed in all groups, and the mean diopter, mean corrected visual acuity (CVA), mean axial length, mean optic disc retinal nerve fiber layer (RNFL) thickness, and mean macular fovea thickness were recorded in the two groups. The results found that the average diopter of the patients in the control group and the experimental group was

+
2.30
±
2.54

D and

+
5.51
±
1.76

D, respectively. The average CVA was

0.86
±
0.07

and

0.22
±
0.16

, respectively; the average eye axial length was

22.41
±
1.20

mm and

21.11
±
0.78

mm, respectively. As

P
<
0.05

, the differences were statistically significant in the three indicators between the two groups. There was no significant difference between the two groups in the average thickness of the RNFL of the optic disc and the average thickness of the central fovea of macula (

P
>
0.05

). There was some correlation among CVA, diopter, eye axial length, RNFL thickness, and average thickness of macular fovea, but the correlation was not significant. It was suggested that there were certain differences in the macular and optic disc parameters between amblyopic and nonamblyopic children, but the difference is little. Thereout, a certain objective basis was provided for the early detection and treatment of amblyopia.
Abstract 1020: Cancer health awareness through screening and education (CHANGE): Understanding community experience accessing cancer care
Authors: Vernon Marlo M. , Jones Samantha , Moore Justin X. , Coughlin Steve S. , Heboyan Vahe , Clarke Shakirah , Idun Barbara , Tingen Martha S. 
Published: June 2022

Abstract
INTRODUCTION. Incidence and mortality rates for breast, prostate, and colorectal cancers all exceed national rates in Georgia and are higher among African Americans (AAs). Ensuring culturally competent and equitable health care delivery relies on creating an educated and engaged health care team. Patient stories are powerful examples of community-learned experiences and can be used to educate better providers and health care students who serve diverse populations, particularly when communicating risk and prevention of cancer. The goal of the CHANGE project is to provide a sustainable model of evidence-based cancer awareness through education - with an emphasis on prevention and early detection behaviors. We will develop a health disparities and culturally competent cancer care e-Learning curriculum for health care professionals, hematology-oncology fellows, residents, and medical students at the Medical College of Georgia.
METHODS. Thirty community members and stakeholders (93% AA, 76% female, all adults) were recruited through public housing, healthcare clinics and providers, and community organizations. Vignettes describing patient access and care interactions were used in semi-structured interviews to guide conversations about experiences accessing care, attitudes towards cancer prevention, and community cancer beliefs. Interviews were recorded, professionally transcribed, and content analyzed using NVivo 12.0 by two independent raters.
RESULTS. Three common themes emerged: accessibility of healthcare (transportation, finances, and difficulties in scheduling were primary barriers); cancer myths and cultural norms (no interpersonal discussion of cancer, seen as “taboo,” cancer will spread if cut into and cancer is contagious); and experience of racial bias in health care (historical racial bias and systemic racism; receipt of treatment and care perceived to be different due to race; lack of AA providers).
CONCLUSION. This sample adequately represented those most at risk for cancer in Augusta, GA area. Their shared experiences will be used to design and inform an e-learning curriculum, in conjunction with education on health disparities across the state and specific to the local community. This will provide a comprehensive approach to provider education that will begin to improve patient care satisfaction and health outcomes.
Citation Format: Marlo M. Vernon, Samantha Jones, Justin X. Moore, Steve S. Coughlin, Vahe Heboyan, Shakirah Clarke, Barbara Idun, Martha S. Tingen. Cancer health awareness through screening and education (CHANGE): Understanding community experience accessing cancer care [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 1020.
Abstract 1095: Establishment and characterization of a topotecan resistant lung cancer NCI H460/TPT10 cell line and a tumor xenograft model
Authors: Teng Qiu-Xu , Lei Zi-Ning , Zhang Wei , Fan Ying-Fang , Wang Jing-Quan , Cai Chao-Yun , Yang Dong-Hua , Wurpel John , Chen Zhe-Sheng 
Published: June 2022

Abstract
While topotecan (TPT) is a chemotherapeutic drug in treating lung cancer, the development of TPT resistance in tumors reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of TPT resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in TPT-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143 and cabozantinib. The NCI-H460/TPT10 and its parental cell line were further used to establish in vivo tumor xenograft mouse models, which verified their capability to serve as clinically relevant models for drug screening and the development of targeted strategies to overcome ABCG2-mediated MDR in NSCLC.
Citation Format: Qiu-Xu Teng, Zi-Ning Lei, Wei Zhang, Ying-Fang Fan, Jing-Quan Wang, Chao-Yun Cai, Dong-Hua Yang, John Wurpel, Zhe-Sheng Chen. Establishment and characterization of a topotecan resistant lung cancer NCI H460/TPT10 cell line and a tumor xenograft model [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 1095.
Abstract 1097: First-line therapy based on kinase inhibitors and antibodies prevents resistance in EGFR-mutated lung cancer
Authors: Marrocco Ilaria , Haga Yuya , Yarden Yosef 
Published: June 2022

Abstract
Introduction: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are commonly used to treat patients with EGFR+ non-small cell lung cancer (NSCLC). Unfortunately, despite the initial response, the long-term efficacy of the five clinically approved TKIs (i.e., gefitinib, erlotinib, afatinib, dacomitinib, osimertinib) is limited by the onset of resistance. Several mechanisms of resistance have been described, including the appearance of new EGFR mutations (e.g., T790M, C797S), activation of bypass pathways (e.g., AXL, HER2, MET and IGF1R) and phenotypic alterations (e.g., epithelial to mesenchymal transition, EMT). Additionally, in vitro treatment using EGFR TKIs leads to the establishment of drug tolerant persisters (DTPs), a cell population that might be responsible for the onset of resistance. In order to prevent resistance, the data we present herein propose to simultaneously target EGFR and other survival receptors (e.g., HER2 or HER3) by combining TKIs and specific monoclonal antibodies.
Materials and methods: Cultures of NSCLC cell lines, patient-derived and cell line xenografts were employed to test the efficacy of the drug combinations. In parallel, to better understand resistance to EGFR-TKIs we established NSCLC dacomitinib resistant (DR) cell lines that were used in vivo and in vitro.
Results: DR cells showed upregulation of AXL and IGF1R, features shared with the persister cells. We also demonstrate that combining TKIs and monoclonal antibodies successfully prevented TKI acquired resistance, by downregulating receptor kinases previously implicated in resistance to TKIs (e.g., MET and AXL), as well as by blocking pathways essential for mitosis (e.g., FOXM1).
Conclusions: Combining kinase inhibitors and antibodies in first line settings effectively avoids TKI resistance in animal models of lung cancer and might represent a long-term solution for EGFR positive NSCLC patients.
Citation Format: Ilaria Marrocco, Yuya Haga, Yosef Yarden. First-line therapy based on kinase inhibitors and antibodies prevents resistance in EGFR-mutated lung 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 1097.
Abstract 1107: Notch activation drives resistance to Kras(G12C) inhibition in lung adenocarcinoma
Authors: Hwang Elizabeth E. , Lee Alex , Leung Stanley , Breese Marcus , Sweet-Cordero Alejandro 
Published: June 2022

Abstract
Approximately one-third of lung adenocarcinoma (LUAD) tumors contain driver mutations in the Kras GTPase, most commonly occurring as Kras(G12C) activating mutations. Despite the promising development of covalent G12C small molecule inhibitors, early-phase clinical trial data indicate most patients will likely demonstrate disease progression through either intrinsic or acquired resistance. Thus, there is an urgent need to identify such resistance mechanisms to targeting Kras. Our lab previously discovered a unique requirement for Notch3 in tumor-propagating cells from the KrasLSL-G12D p53fl/fl LUAD mouse model as well as in patient-derived xenografts. Here we report activated Notch3 as a novel driver of resistance to Kras(G12C) inhibition in LUAD cell lines.
Aiming to study the Notch3 transcriptional signature in LUAD, we developed an inducible model of Notch3 intracellular domain (NICD) expression in Kras-mutant LUAD cell lines. Our data demonstrate that activated NICD modulates downstream RTK signaling pathways to suppress both cell cycle arrest and apoptosis in response to G12C inhibitor treatment. We subsequently performed RNA-sequencing to identify Notch-dependent genes driving resistance and in parallel, used Cut&Run technology to interrogate the global chromatin binding profiles of Notch3 and associated histone marks in NICD-expressing cell lines. We integrate our transcriptomic and epigenomic data to reveal that NICD acts as a key regulator of Rho family genes, which in turn support cell survival upon Kras inhibition. We additionally find enrichment of cell division and morphological signatures in inhibitor treated NICD cell lines and we elucidate the mechanism of direct Notch target genes in mediating the apoptotic response. Finally, we conduct a focused in vitro CRISPRi screen in the H358 LUAD cell line to identify the subset of Notch target genes required for NICD-induced resistance. Our results define a Notch3 transcriptional landscape in LUAD and demonstrate a role for Notch signaling in promoting resistance to small molecule Kras inhibitors.
Citation Format: Elizabeth E. Hwang, Alex Lee, Stanley Leung, Marcus Breese, Alejandro Sweet-Cordero. Notch activation drives resistance to Kras(G12C) inhibition in lung adenocarcinoma [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 1107.
Abstract 1132: A systems biology approach combining ProLiFiler and Cancer Data Miner for an enhanced preclinical characterization of the WEE-1 inhibitor Adavosertib
Authors: Vuaroqueaux Vincent , Feger Daniel , Peille Anne-Lise , Siedentopf Oliver , Panzade Sadhana , Ulrich Sarah , Dempe Sebastian , Fiebig Heinz-Herbert , Ehlert Jan Erik 
Published: June 2022

Abstract
Adavosertib (AZD1775, MK-1775), a clinical stage inhibitor of the tyrosine kinase WEE1, was investigated in a cell proliferation and survival assay with 140 human cancer cell lines (CLs) representing all major tumor types (ProLiFiler platform of Reaction Biology) followed by mechanism of action (MoA) and biomarker analyses using 4HF Biotec’s Cancer Data Miner in silico platform. Adavosertib exhibited a broad anti-cancer activity across all hematological and solid tumor types with IC50 values ranging from 0.06 to 10 µM (median: 0.38 µM), matching the consistently high expression of the WEE1 gene. Among 900 reference compounds, the activity profile of adavosertib correlated best with the profiles of compounds targeting the replication stress response including other WEE1 inhibitors but also inhibitors of checkpoint kinase 1 and 2 (CHK1/2) or ataxia telangiectasia-mutated (ATM). Significant correlations were also seen with compounds blocking mitosis, DNA replication and DNA repair. Interestingly, we observed a subset of cell lines that were resistant to both DNA synthesis and PARP inhibitors but were sensitive to WEE1 inhibition. Moreover, by using multiple datasets of WEE1 inhibitors connected to the molecular annotations of CLs for a data driven biomarker screening, we identified MYC mutations as a predictive marker of sensitivity and PIK3CA or ERBB2 gene amplifications as predictors of resistance. Transcriptome analysis identified up to 900 genes for which higher expression in CLs was associated with CL sensitivity to the compound. Preliminary pathway analysis indicated that these genes are well represented among nuclear factor and Myc-regulated genes. In conclusion, our studies demonstrate broad anticancer activity of adavosertib and confirm its proposed MoA. The biomarkers we identified will facilitate the selection of pre-clinical in vivo tumor models and, if confirmed, even patient selection for clinical trials. The combined use of the ProLiFiler and Cancer Data Miner Platforms has the potential to accelerate and de-risk the development of anti-cancer agents.
Citation Format: Vincent Vuaroqueaux, Daniel Feger, Anne-Lise Peille, Oliver Siedentopf, Sadhana Panzade, Sarah Ulrich, Sebastian Dempe, Heinz-Herbert Fiebig, Jan Erik Ehlert. A systems biology approach combining ProLiFiler and Cancer Data Miner for an enhanced preclinical characterization of the WEE-1 inhibitor Adavosertib [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 1132.