bluuebunny/crossref_metadata_2025 huggingface dataset:
Inequalities in Physical Activity During the COVID-19 Pandemic: Report on 4 Consecutive Population-Based Surveys in Southern Brazil
Authors: Ricardo Luiza Isnardi Cardoso , Knuth Alan G. , Nunes Bruno Pereira , Hallal Pedro C. , Santos Leonardo Pozza , Harter Jenifer , Pellegrini Débora da Cruz Payão , Crochemore-Silva Inácio
Published: January 2022

Background: This study aims to investigate inequalities in leisure-time physical activity (PA) practice amid the COVID-19 pandemic in a southern Brazilian city. Methods: Four repeated population-based surveys were carried out. PA was collected using a questionnaire proposed by the authors and an adapted version of the leisure-time section of the International Physical Activity Questionnaire. The sociodemographic variables were sex, age, skin color, and education level. The participants also answered questions regarding social distancing measures compliance. Descriptive analyses based on proportions and their respective P values for categorical variables were presented. The chi-square test for heterogeneity and linear trend was used. Results: The sample is composed of 1556 individuals (66.1% female). Overall, between rounds 1 and 2, PA prevalence declined, followed by a gradual increase thereafter. PA practice during the pandemic was higher among men, individuals with higher education level, and individuals with white skin color in all rounds. In rounds 2, 3, and 4, PA was lower among individuals who were practicing more social distancing. Conclusion: To tackle the PA inequalities, policymakers and stakeholders need to confront disparities, defending greater availability of public policies that are attentive to inequalities, especially regarding gender, skin color, and educational level, to promote PA as a human right.
Meet Me in the Middle: Median Temperatures Impact Cyanobacteria and Photoautotrophy in Eruptive Yellowstone Hot Springs
Authors: Hamilton Trinity L. , Havig Jeff
Published: January 2022

Hot spring cyanobacteria have long been model systems for examining ecological diversification as well as characterizing microbial adaptation and evolution to extreme environments. These studies have reported cyanobacterial diversification in hot spring outflow channels that can be defined by distinct temperature ranges.
Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis
Authors: Jarvis Helen , O'Keefe Hannah , Craig Dawn , Stow Daniel , Hanratty Barbara , Anstee Quentin M
Published: January 2022

Objectives

Liver disease is a leading cause of premature death, partly driven by the increasing incidence of non-alcohol-related fatty liver disease (NAFLD). Many people with a diagnosis of NAFLD drink moderate amounts of alcohol. There is limited guidance for clinicians looking to advise these patients on the effect this will have on their liver disease progression. This review synthesises the evidence on moderate alcohol consumption and its potential to predict liver disease progression in people with diagnosed NAFLD.

Methods

A systematic review of longitudinal observational cohort studies was conducted. Databases (Medline, Embase, The Cochrane Library and ClinicalTrials.gov) were searched up to September 2020. Studies were included that reported progression of liver disease in adults with NAFLD, looking at moderate levels of alcohol consumption as the exposure of interest. Risk of bias was assessed using the Quality in Prognostic factor Studies tool.

Results

Of 4578 unique citations, 6 met the inclusion criteria. Pooling of data was not possible due to heterogeneity and studies were analysed using narrative synthesis. Evidence suggested that any level of alcohol consumption is associated with worsening of liver outcomes in NAFLD, even for drinking within recommended limits. Well conducted population based studies estimated up to a doubling of incident liver disease outcomes in patients with NAFLD drinking at moderate levels.

Conclusions

This review found that any level of alcohol intake in NAFLD may be harmful to liver health.

Study heterogeneity in definitions of alcohol exposure as well as in outcomes limited quantitative pooling of results. Use of standardised definitions for exposure and outcomes would support future meta-analysis.

Based on this synthesis of the most up to date longitudinal evidence, clinicians seeing patients with NAFLD should currently advise abstinence from alcohol.

PROSPERO registration number

The protocol was registered with PROSPERO (#CRD42020168022).
Perception of pharmacological prevention and subsequent non-adherence to medication in patients with ischaemic heart disease: a population-based cohort study
Authors: Graversen Christina Boesgaard , Valentin Jan Brink , Larsen Mogens Lytken , Riahi Sam , Holmberg Teresa , Zinckernagel Line , Johnsen Søren Paaske
Published: January 2022

Objective

A patient-focused approach is advocated to embody risk of non-adherence to medication and subsequent adverse clinical outcomes following ischaemic heart disease (IHD). This study aimed to explore how patient perceived information on pharmacological prevention was associated with subsequent non-adherence to medication (measured by non-initiation, non-implementation and non-persistence) in patients with incident IHD.

Design

Cohort study.

Setting

Denmark.

Participants

Register-based cohort of 829 patients with incident IHD in 2013.

Measures

Perception covered whether patients’ experienced being adequately informed about their pharmacological prevention. Information on such was obtained from a survey and divided into ‘Well informed’, ‘Moderately informed’ and ‘Poorly informed’. Information on baseline characteristics, and reimbursed prescriptions of medication (antiplatelets, statins, ACE-inhibitors/angiotensin receptor blockers and β-blockers) during follow-up were obtained by linkage to nationwide public registers. Non-initiation and non-implementation of medication, measured as proportion of days covered, were analysed by Poisson regression. Non-persistence to medication, measured as risk of discontinuation, was analysed by multivariable Cox proportional hazard regression.

Primary and secondary outcome measures

Non-implementation and non-persistence to medication up to 365 days of follow-up were primary outcomes. Secondary outcomes included non-initiation as well as non-implementation and non-persistence to medication at 180 days of follow-up.

Results

A dose–response association was in general found between perception of pharmacological prevention and risk of non-implementation and non-persistence. For example, the hazard of non-persistence to antiplatelets was 1.18 (95% CI 0.71 to 1.96) times higher for patients reporting 'Moderately informed' and 1.89 (95% CI 1.10 to 3.25) times higher for patients reporting 'Poorly informed', compared with patients reporting 'Well informed of perception of pharmacological prevention' up to 365 days of follow-up.

Conclusion

Lower levels of perception of pharmacological prevention were associated with subsequent non-implementation and non-persistence to medication in patients with incident IHD.
Simultaneous Scheduling of Machines and Tools in a Multi-Machine FMS with Alternate Machines Using Crow Search Algorithm
Authors: Reddy N. Sivarami , Padma Lalitha M. , Ramamurthy D. V. , Prahlada Rao K.
Published: January 2022

Scheduling jobs and tools is a significant problem for manufacturing systems. Inefficient job scheduling and tool loading planning may result in under utilization of capital intensive machines and a high level of machine idle time. Therefore, efficient scheduling of jobs and tools enables a manufacturing system to increase machines’ utilization and decrease their idle times. This paper addresses machines’ and tools’ joint scheduling with alternate machines in a multimachine flexible manufacturing system (FMS) to minimize makespan (MSN). Only one copy of each type of tool is made available in FMS where tools are expensive. The tools are stored in the central tool magazine (CTM), which shares and serves them to several machines in order to reduce the cost of duplicating the tools in every machine. The problem is to select machines from alternate machines for job-operations, allocation of tools to the job-operations and job-operations’ sequencing on machines for MSN minimization. This paper presents nonlinear mixed integer programming (MIP) formulation to model this simultaneous scheduling problem and crow search algorithm (CSA) built on the crows’ intelligent behavior for solving this problem. The results show that CSA is providing better solutions than Jaya algorithm and the usage of alternate machines for the operations can reduce MSN.
Psychological Status, Compliance, Serum Brain-Derived Neurotrophic Factor, and Nerve Growth Factor Levels of Patients with Depression after Augmented Mindfulness-Based Cognitive Therapy
Authors: Guo Huirong , Ren Yuming , Huang Bailing , Wang Junru , Yang Xuhuang , Wang Yali
Published: January 2022

Objective. Mindfulness-based cognitive therapy (MBCT) is a cost-effective psychosocial program that prevents relapse/recurrence in major depression. The present study aimed to analyze the effects of augmented MBCT along with standard treatment dominated by pharmacotherapy on psychological state, compliance, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) expression levels in patients with depression. Methods. A total of 160 eligible patients with depression in The First Affiliated Hospital of Zhengzhou University were included in this study. The study randomly assigned the patients to the experimental group (n = 80) and control group (n = 80). All participants were assessed with the questionnaires including the 17-item Hamilton Depression Rating Scale (HAMD-17), Rosenberg Self-esteem Scale (RSES), Self-Acceptance Questionnaire (SAQ), and Stigma Scale (Scale of Stigma in People with Mental Illness, SSPM). The serum levels of BDNF and NGF were detected by enzyme-linked immunosorbent assay (ELISA). Results. After 8 weeks of treatment, the experimental group showed significant lower HAMD-17 score, higher RSES, and SAQ score, as well as lower SSPM score compared with the control group (

P
<
0.01

). Furthermore, ELISA revealed that the serum levels of BDNF and NGF remarkably increased in the experimental group after treatment (

P
<
0.001

). Conclusions. Our data showed that augmented MBCT combined with pharmacotherapy contributed to improvement on patients’ psychological state, compliance, and disease recurrence.
Will 14-3-3η Be a New Diagnostic and Prognostic Biomarker in Rheumatoid Arthritis? A Prospective Study of Its Utility in Early Diagnosis and Response to Treatment
Authors: Alashkar Doaa Shawky , Elkhouly Radwa Mostafa , Abd Elnaby Amira Yousef , Nada Doaa Waseem
Published: January 2022

Aim of the Work. To evaluate diagnostic and prognostic capacity of 14-3-3η protein in early RA, investigate its pathogenic and theragnostic role, and find its correlations with disease activity and severity in established RA patients. Subjects and Methods: 80 patients with early RA, 80 patients with established RA, and 80 healthy controls were included in this study. ROC curve analysis of RF, ACCP, and 14-3-3η in early disease was conducted, and serum levels of 14-3-3η were assessed by ELISA and reassessed in early RA patients 6 months after anti-TNF therapy. Correlation of 14-3-3η with parameters of disease activity and severity was analyzed. Results. Serum14-3-3η levels were significantly higher in all RA patients than in controls

P
<
0.001

, its sensitivity was 86.7% and 88.3% in early and established RA patients with a significant difference with RF and ACCP at early disease, and the specificity was 96.7%. There was a significant reduction of 14-3-3η levels 6 months after treatment in the first group

p
=
0.004

, and there was a significant positive correlation between serum 14-3-3η levels and parameters of disease activity and severity. Conclusion. 14-3-3η could be a novel, potent, and efficacious diagnostic, and prognostic marker for RA with high sensitivity, that may become a new therapeutic target for RA.
A Comprehensive Formalization of AADL with Behavior Annex
Authors: Tan Yu , Zhao Yongwang , Ma Dianfu , Zhang Xuejun
Published: January 2022

In safety-critical fields, architectural languages such as AADL (Architecture Analysis and Design Language) have been playing an important role, and the analysis of the languages and systems designed by them is a challenging research topic. At present, a formal method has become one of the main practices in software engineering for strict analysis, and it has been applied on the tools of formalization and analysis. The formal method can be used to find and resolve the problems early by describing the system with precise semantics and validating the system model. This article studies the comprehensive formal specification and verification of AADL with Behavior annex by the formal method. The presentation of this specification and semantics is the aim of this article, and the work is illustrated with an ARINC653 model case study in Isabelle/HOL.
Evolution Process and Supply Chain Adaptation of Smart Contracts in Blockchain
Authors: Wu Yue , Li Junxiang , Zhou Jiru , Luo Shichang , Song Liwei
Published: January 2022

Because of its unique decentralization, encryption, reliability, and tamper‐proof, the block chain system makes smart contracts break through the shackles of the lack of trusted environment, and its application field keeps expanding. We read the source code and official documents of Bitcoin, Ethereum, and Hyperledger to explore the operation principle and implementation mode of smart contract. By analyzing the evolution process of smart contracts in blockchain and the sequence of its function expansion, according to the multirole business process of supply chain, we design a semipublic smart contract chain model based on Ethereum and Hyperledger in order to provide useful inspiration and help for the future research of smart contracts in blockchain applied in supply chain.
Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer
Authors: Ming-Sheng Fu , Mei-Ling Du , Xun-Quan Cai , Yuan-Xin Hu , Wei-Jie Zhang , Qin-Cong Pan
Published: January 2022

Background. This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods. We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan–Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results. A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1–67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions. Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.
Automated Detection Model in Classification of B-Lymphoblast Cells from Normal B-Lymphoid Precursors in Blood Smear Microscopic Images Based on the Majority Voting Technique
Authors: Ghaderzadeh Mustafa , Hosseini Azamossadat , Asadi Farkhondeh , Abolghasemi Hassan , Bashash Davood , Roshanpoor Arash
Published: January 2022

Introduction. Acute lymphoblastic leukemia (ALL) is the most common type of leukemia, a deadly white blood cell disease that impacts the human bone marrow. ALL detection in its early stages has always been riddled with complexity and difficulty. Peripheral blood smear (PBS) examination, a common method applied at the outset of ALL diagnosis, is a time-consuming and tedious process that largely depends on the specialist’s experience. Materials and Methods. Herein, a fast, efficient, and comprehensive model based on deep learning (DL) was proposed by implementing eight well-known convolutional neural network (CNN) models for feature extraction on all images and classification of B-ALL lymphoblast and normal cells. After evaluating their performance, four best-performing CNN models were selected to compose an ensemble classifier by combining each classifier’s pretrained model capabilities. Results. Due to the close similarity of the nuclei of cancerous and normal cells, CNN models alone had low sensitivity and poor performance in diagnosing these two classes. The proposed model based on the majority voting technique was adopted to combine the CNN models. The resulting model achieved a sensitivity of 99.4, specificity of 96.7, AUC of 98.3, and accuracy of 98.5. Conclusion. In classifying cancerous blood cells from normal cells, the proposed method can achieve high accuracy without the operator’s intervention in cell feature determination. It can thus be recommended as an extraordinary tool for the analysis of blood samples in digital laboratory equipment to assist laboratory specialists.
Numerical Simulation of Dynamic Response of Submerged Floating Tunnel under Regular Wave Conditions
Authors: Luo Wenlong , Huang Bo , Tang Yao , Ding Hao , Li Ke , Cheng Liang , Ren Qingyang
Published: January 2022

A submerged floating tunnel (SFT) is considered an innovative alternative to conventional bridges and underground or immersed tunnels for passing through deep water. Assessment of hydrodynamic performance of SFT under regular wave loading is one of the important factors in the design of SFT structure. In this paper, a theoretical hydrodynamic model is developed to describe the coupled dynamic response of an SFT and mooring lines under regular waves. In this model, wave-induced hydrodynamic loads are estimated by the Morison equation for a moving object, and the simplified governing differential equation of the tunnel with mooring cables is solved using the fourth-order Runge–Kutta and Adams numerical method. The numerical results are successfully validated by direct comparison against published experimental data. On this basis, the effects of the parameters such as the cable length, buoyancy-weight ratio, wave period, wave steepness, and water/submergence depth on the dynamic response of the SFT under wave loading are studied. The results show that tunnel motions and cable tensions grow with wave height and period and decrease with submergence depth. The resonance of the tunnel will be triggered when the wave period is close to its natural vibration period, and the estimation formula of wave period corresponding to tunnel resonance is proposed in this paper.
Brain Abscess: A Rare Clinical Case with Oral Etiology
Authors: Pereira André João da Silva Pais Rocha , Tavares Ana Teresa , Prates Marcelo , Ribeiro Natacha , Fonseca Luís Filipe , Marques Maria do Rosário , Proença Francisco
Published: January 2022

Brain abscess is a very rare condition but has a significant mortality rate. The three main routes of inoculation are trauma, contiguous focus, and the hematogenous route. The odontogenic focus is infrequent and is usually a diagnosis of exclusion. This paper presents a brain abscess case proven to be of dental origin, caused by Actinomyces meyeri and Fusobacterium nucleatum. This case highlights the risk underlying untreated dental disease and why oral infectious foci removal and good oral health are essential in primary care.
Upper Bound for Lebesgue Constant of Bivariate Lagrange Interpolation Polynomial on the Second Kind Chebyshev Points
Authors: Liu Juan , Zhu Laiyi
Published: January 2022

In the paper, we study the upper bound estimation of the Lebesgue constant of the bivariate Lagrange interpolation polynomial based on the common zeros of product Chebyshev polynomials of the second kind on the square [−1,1]2. And, we prove that the growth order of the Lebesgue constant is O((n + 2)2). This result is different from the Lebesgue constant of Lagrange interpolation polynomial on the unit disk, the growth order of which is . And, it is different from the Lebesgue constant of the Lagrange interpolation polynomial based on the common zeros of product Chebyshev polynomials of the first kind on the square [−1,1]2, the growth order of which is O((lnn)2).
Risk Factors for Esophageal Collateral Veins in Cirrhosis with and without Previous Endoscopic Esophageal Variceal Therapy
Authors: Li Qianqian , Guo Xiaozhong , Feng Ji , Xu Xiangbo , Chawla Saurabh , Li Hongyu , Qi Xingshun
Published: January 2022

Background. Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear. Methods. We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). Results. Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250,

p

 = 0.026), previous EVL (OR = 1.929,

p

 = 0.044), platelet (OR = 0.993,

p

 = 0.008), and esophageal varices needing treatment (EVNTs) (OR = 2.422,

p

 = 0.006). The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers (OR = 0.294,

p

 = 0.042) and EVNTs (OR = 3.714,

p

 = 0.006) in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively. Conclusions. The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL.
Postoperative Complications of Impacted Mandibular Third Molar Extraction Related to Patient’s Age and Surgical Difficulty Level: A Cross-Sectional Retrospective Study
Authors: Rizqiawan Andra , Lesmaya Yeni Dian , Rasyida Anindita Zahratur , Amir Muhammad Subhan , Ono Shigehiro , Kamadjaja David Buntoro
Published: January 2022

Mandibular third molar surgical extraction, either partially erupted or fully impacted, is the most common surgical procedure in oral and maxillofacial surgery (OMFS). However, this procedure can be associated with many postoperative complications including persistent pain, swelling, trismus, and paresthesia due to nerve injury. This study aimed to identify the correlation of postoperative complications with patient’s age, sex, and surgical difficulty level. This study was a cross-sectional retrospective and single-center research conducted on patients with a history of mandibular third molar surgical extraction in the period between 2017 and 2019 at Dental and Oral Hospital Universitas Airlangga, Surabaya, Indonesia. The researchers assessed the factors of age, sex, and surgical difficulty level regarding postoperative complications on the first day of the surgery and after one week on the 7th day of it. Among 916 respondents, the majority of the sample was females (59%) and the dominant age group (60.9%) was the age group of 21–30 years while the dominant surgical difficulty level was shown by the advanced cases group (77%). The statistical analysis showed that there was a significant correlation between surgical difficulty level and postoperative complications including pain, trismus, and paresthesia on the first-day assessment. On the other hand, age was significantly related to complications like pain, swelling, and trismus on the first-week assessment. Age and surgical difficulty level were the most common risk factors of the mandibular third molar extraction postoperative complications. Dentists should take into consideration that older patients (≥51 years) and patients with complex surgical level are more vulnerable to severe postoperative complications.
Effect of Brewing Water on the Antioxidant Capacity of Green Tea Infusion with DPPH Assay
Authors: Cao Qing-Qing , Fu Yan-Qing , Zhang Cheng-Bin , Zhu Yan , Yin Jun-Feng , Granato Daniel , Putnik Predrag , Xu Yong-Quan
Published: January 2022

Brewing water plays a crucial role in flavor and potential healthy functions of tea infusion. In this study, seven water samples with different physicochemical properties were selected to brew green tea. Results showed that the brewing water with higher minerals level and pH value would reduce the yield of catechins in tea infusion, which in turn caused the decrease of antioxidant activity to a large extent. Besides, it was found that EGCG, as a major contributor to the antioxidant activity of green tea infusion, was influenced differently by different metal ions, among which Ca2+/Mg2+ could enhance the antioxidant activity of EGCG solutions with different concentration through synergistic effect, particularly Ca2+, and the effect was more markable at a higher EGCG concentration. These results offered theoretical direction to the selection of tea brewing water for consumers and gave a new sight to the effects of metal ions on the antioxidant capacity of EGCG.
An Intelligent Mission Planning Model for the Air Strike Operations against Islands Based on Neural Network and Simulation
Authors: Song Zhihua , Zhang Han , Zhao Yongmei , Dong Tao , Zhang Fa
Published: January 2022

Mission planning of air strike operations is hard because it has to give instructions to a large number of units during a relatively long period of time in an uncertain environment. If some instruction parameters can be calculated by an intelligent agent, better strategies can be found more quickly. In a specific combat scenario of air strike operations against islands, an intelligent model is proposed to improve the performance and flexibility of mission planning. The proposed intelligent mission planning model is based on rule‐based decision and uses a fully connected recurrent neural network to calculate some of the decision parameters. The proposed intelligent mission planning model shows better results as compared to rule‐based decision making with randomized parameters, and it performs as good as experts in the test set of the specific combat scenario.
Accurate Digital Marketing Communication Based on Intelligent Data Analysis
Authors: Li ZhuoJun
Published: January 2022

In digital marketing, the core advantages of scientific and technological means such as artificial intelligence and big data analysis gradually appear and pay attention to them. This paper studies the accuracy of digital marketing and proposes an intelligent algorithm based on data analysis, which improves the effect of marketing communication. Through the combination of intelligent algorithms and big data analysis, the data are convincing. Through the comparison and improvement of intelligent algorithm logistic regression and XGBoost, this paper puts forward an improved algorithm of XGBoost based on Bayesian optimization parameters, which can improve the efficiency of digital marketing communication and enhance the social influence of digital marketing.
Sexual Effect of Platelet-to-Lymphocyte Ratio in Predicting Cardiovascular Mortality of Peritoneal Dialysis Patients
Authors: Sheng Hui , Qiu Yagui , Xia Xi , Yi Chunyan , Lin Jianxiong , Yang Xiao , Huang Fengxian
Published: January 2022

Background. The study is aimed at exploring the relationship of platelet-to-lymphocyte (PLR), all-cause, and cardiovascular disease (CVD) mortality in peritoneal dialysis (PD) patients based on gender. Methods. A total of 1438 PD patients from January 1,2007 to December 31, 2014 in PD center at The First Affiliated Hospital, Sun Yat-sen University, were included. Patients were followed up until December 31, 2019. The endpoint was all-cause mortality and CVD mortality. Cox proportional hazards regression models were used to evaluate the association of PLR with all-cause and CVD mortality to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results. After a median of 48.9 (interquartile range [IQR]: 23.4-79.3) months of follow-up, 406 (28.2%) patients died based on all-cause death, among which 200 (49.3%) patients died from CVD. In the multivariate Cox regression model, we found that PLR was independently related to an increased risk of CVD mortality only in female PD patients, with HR of 1.003 (95% CI: 1.001-1.006). Interaction test showed that the correlation between PLR level for all-cause and CVD mortality varied with gender (

p
=
0.042

and

p
=
0.012

, respectively). Conclusion. Higher PLR was associated with a higher risk of CVD mortality in female PD patients.
Dynamic Response Characteristic of Building Structure under Blasting Vibration of underneath Tunnel
Authors: He Ru , Jiang Nan , Li Dong-Wei , Qi Jian-Feng
Published: January 2022

The vibration induced by blasting excavation of the subway tunnel in complex urban environments may cause harmful effects on adjacent buildings. Investigating the dynamic response of adjacent buildings is a key issue to predict and control blasting hazards. In this paper, the blasting excavation of the subway tunnel right below a building was selected as a case study, and the blast vibrations in the field were monitored. The Hilbert–Huang Transform (HHT) model was used to extract and analyze the time-frequency characteristic parameters of blasting dynamic response signals. By substituting intrinsic mode functions (IMF) component frequency and instantaneous energy for main frequency and blasting total input energy, respectively, the characteristics of time-instantaneous frequency-instantaneous energy of buildings under blasting seismic load were analyzed, and the concept of effective duration of vibration was proposed.
Abstract IA05: CAR NK Cells: The future of cancer immunotherapy
Authors: Basar Rafet
Published: January 2022

T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical and toxicity issues. Given these concerns, there is a rapidly growing interest in NK cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the allogeneic setting. Other immune effector cells, such as iNKT cells, γδ T cells and macrophages, are attracting interest as well and eventually may be added to the repertoire of engineered cell therapies against cancer. The pace of these developments will undoubtedly benefit from multiple innovative technologies, such as the CRISPR-Cas gene editing system, which offers great potential to enhance the natural ability of immune effector cells to eliminate refractory cancers.

Citation Format: Rafet Basar. CAR NK Cells: The future of cancer immunotherapy [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA05.
Abstract IA06: Chimeric antigen receptor macrophages for the treatment of solid tumors
Authors: Gill Saar
Published: January 2022

Engineered adoptive cell therapies redirect and augment the ability of immune effector cells to mount an anti-tumor response by introducing novel capabilities and targeting moieties. A prominent example of this approach is the use of T cells engineered to express chimeric antigen receptors (CARs), which have demonstrated significant efficacy against some hematologic malignancies. However, despite sophisticated strategies to harness immune cell function, CAR T cell efficacy against solid tumors has remained disappointing. Macrophages have recently emerged as prominent candidate effector cells for the treatment of solid tumors. Macrophages are innate immune cells that are intrinsically equipped with broad therapeutic effector functions, including homing to tumor sites, phagocytosis, activation of the tumor microenvironment and antigen presentation. In this presentation we will discuss strategies for genetic manipulation of CAR macrophages, illustrated by preclinical results.

Citation Format: Saar Gill. Chimeric antigen receptor macrophages for the treatment of solid tumors [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA06.
Abstract IA15: Targeting tumor associated macrophages for anti-cancer therapy
Authors: Guerriero Jennifer L.
Published: January 2022

Despite objective responses to poly(ADP-ribose) polymerase (PARP) inhibition and improvements in progression-free survival (PFS) compared to standard chemotherapy in patients with BRCA-associated triple-negative breast cancer (TNBC), benefits are transitory. Using high-dimensional single-cell profiling of human TNBC, here we demonstrate that macrophages are the predominant infiltrating immune cell type in breast cancer susceptibility (BRCA)-associated TNBC. Through multi-omics profiling, we show that PARP inhibitors enhance both anti- and pro-tumor features of macrophages through glucose and lipid metabolic reprogramming, driven by the sterol regulatory element-binding protein 1 (SREBF1, SREBP1) pathway. Combining PARP inhibitor therapy with colony-stimulating factor 1 receptor (CSF1R)-blocking antibodies significantly enhanced innate and adaptive antitumor immunity and extended survival in mice with BRCA-deficient tumors in vivo, and this was mediated by CD8+ T cells. Collectively, our results uncover macrophage-mediated immune suppression as a liability of PARP inhibitor treatment and demonstrate that combined PARP inhibition and macrophage-targeting therapy induces a durable reprogramming of the tumor microenvironment (TME), thus constituting a promising therapeutic strategy for TNBC. This work highlights the importance of a deep understanding the tumor microenvironment (TME) before and after therapy.

Citation Format: Jennifer L. Guerriero. Targeting tumor associated macrophages for anti-cancer therapy [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA15.
Abstract IA16: Immune suppression in cancer and strategies for its reversal
Authors: Kaplan Rosandra N.
Published: January 2022

The microenvironment is involved in multiple aspect of cancer progression. Tumor metastasis is a critical step in the progression of solid tumors that is associated with patient mortality, and the metastatic microenvironment is key regulator of this process. The pre-metastatic niche is the microenvironment important for metastatic initiation that is established at distant sites in response to primary tumor factors during cancer progression. We characterized this microenvironment which involves changes in both stromal and immune populations in the lungs of sarcoma-bearing mice and in the liver in pancreatic- bearing mice by flow cytometry and RNA sequencing approaches. We identified a gene signature in pre-metastatic niche formation that demonstrates upregulation of immune suppression genes that is consistent across different metastatic tissue including lung and liver as well as across species with commonalities in murine and human early metastatic microenvironments. Performing single cell RNA sequencing of the pre-metastatic niche revealed key immune suppressive genes were found in the myeloid cell clusters. In addition to the increase of myeloid cells and immunosuppressive pathways, we discovered that T cell populations are reduced in pre-metastatic lungs. We hypothesized that reversing this immunosuppressive environment would restore T cell function and antitumor immunity. We designed a novel approach in which we generated Genetically-Engineered Myeloid cells (GEMys) to deliver IL-12, a potent antitumor molecule, into the pre-metastatic microenvironment. We evaluated the lungs by flow cytometry and observed that IL12-GEMy-treated mice had increased numbers of T cells and enhanced expression of activation markers, resulting in reduced metastasis and increased survival. This model was effective in an aggressive experimental metastasis model of pancreatic liver metastasis and was not only able to limit metastatic progression but was able to cure a subset of mice compared to rapid metastatic progression in the liver within a month in the untreated pancreatic cancer mice. When combined with chemotherapy pre-conditioning, IL12-GEMys cured mice of established tumors and generated long-lived T cell memory, as these mice were immune to subsequent tumor challenge. These studies demonstrate that IL12-GEMys can functionally modulate the core program of immune suppression in the pre-metastatic niche to successfully rebalance the dysregulated metastatic microenvironment in cancer.

Citation Format: Rosandra N. Kaplan. Immune suppression in cancer and strategies for its reversal [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA16.
Abstract IA17: The power of ONE: Immunology in the age of single cell genomics
Authors: Amit Ido
Published: January 2022

The immune system is a complex, dynamic and plastic network composed of various interacting cell types that are constantly sensing and responding to environmental cues. From very early on, the immunology field has invested great efforts to characterize the various immune cell types and elucidate their functions. However, accumulating evidence indicates that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of immune processes. Single cell genomics hold the potential to revolutionize the way we characterize complex immune cell assemblies and study their spatial organization, dynamics, clonal distribution, pathways, and crosstalk. This emerging field can greatly affect basic and translational research of the immune system. I will discuss how recent single cell genomic studies are changing our perspective of various immune related pathologies from cancer to autoimmune disease and neurodegeneration. Finally, I will consider recent and forthcoming technological and analytical advances in single cell genomics and their huge potential impact on the future of immunology research and immunotherapy.

Citation Format: Ido Amit. The power of ONE: Immunology in the age of single cell genomics [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA17.
Abstract IA18: Cancer metabolism: Emerging insights from single cell analysis
Authors: Locasale Jason W.
Published: January 2022

This presentation will focus on cancer metabolism and new insights that can be gained from emerging technologies – notably single cell analysis. I will first provide a brief overview of our laboratory's research program around metabolism, emphasizing the research questions we focus on as well as the technologies we've been developing and implementing. I will next discuss work on the development of computational tools using single cell expression data to investigate metabolic networks and pathway activity in single cells to study metabolism in vivo. I will show how this technology can be used to gain insights into metabolism within the tumor microenvironment in human tumors. I will next present an application of this technology in the study a therapeutic our lab has been studying, digoxin – a cardiac glycoside that is under consideration for repurposing in cancer and which we show to target glucose and central carbon metabolism. As a proof of concept, we demonstrate that remodeling of the immune compartment can be achieved upon introduction of this metabolic agent.

References: Sydney M. Sanderson, Zhengtao Xiao, Amy J. Wisdom, Shree Bose, Maria V. Liberti, Michael A. Reid, EmilyHocke, Simon G. Gregory, David G. Kirsch, Jason W. Locasale The Na+/K+ ATPase Regulates Glycolysis and Modifies Immune Metabolism in TumorsbioRxiv 2020.03.31.018739; doi: https://doi.org/10.1101/2020.03.31.018739 Xiao Z, Dai Z, Locasale JW. Metabolic landscape of the tumor microenvironment at single cell resolution. Nature Communications. 2019;10(1):3763. Epub 2019/08/23. doi: 10.1038/s41467-019-11738-0. PubMed PMID: 31434891; PMCID: PMC6704063.

Citation Format: Jason W. Locasale. Cancer metabolism: Emerging insights from single cell analysis [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA18.
Abstract IA21: Understanding responses to cancer therapy: The tissue is the issue, the scoop is in the poop, and you are what you eat
Authors: Wargo Jennifer A.
Published: January 2022

We have made major advances in cancer treatment using multi-modality therapy, with immunotherapy now playing a major role across cancer types. However, responses to treatment are not universal, and strategies to improve outcomes (and to ultimately prevent cancer altogether) are needed. Tissue-based analyses in neoadjuvant and other studies have yielded important insights into known and novel therapeutic targets, leading to rational combination strategies to improve outcomes to therapy. Additionally, next-generation sequencing approaches have allowed interrogation of the microbiome in the tumor, and also in the gut and other niches. Microbiota within the body have a profound impact on physiology, with emerging evidence that they may contribute to carcinogenesis and therapy response. Importantly, it is not only the microbes that matter, but also the substrate for energy use (i.e. our diet). All of these aspects will be discussed in this talk, and rational combination strategies to improve cancer treatment will be proposed.

Citation Format: Jennifer A. Wargo. Understanding responses to cancer therapy: The tissue is the issue, the scoop is in the poop, and you are what you eat [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA21.
Abstract P013: Germinal center hypoxia in tumor-draining lymph nodes negatively regulates humoral immune responses and affects the activation of tumor-infiltrating T cells
Authors: Firmino Natalie , Bennewith Kevin
Published: January 2022

Efforts to understand intrinsic and acquired resistance to anti-tumor immunotherapies have largely focused on characterizing factors within the primary tumor. However, lymph nodes are specialized hubs of immune response development, and an improved understanding of the microenvironmental conditions impacting immune cell activation in tumor-draining lymph nodes (TDLNs) may yield novel approaches for enhancing responses to anti-tumor immunotherapies. Using mouse models of breast cancer, we identified hypoxic regions amongst the B cell germinal center reactions of TDLNs. Injection of lethally irradiated tumor cells was sufficient to induce GC hypoxia, and hypoxia in TDLNs associated with the frequency of antibody- secreting cells. In vitro, hypoxia impaired the proliferation of activated B cells, and inhibited class-switching to IgG1 and IgA immunoglobulin isotypes. To assess the role of the hypoxic response in tumor-reactive GCs in vivo, we deleted von Hippel- Lindau factor (VHL) in class-switched B cells and found decreased GC B cells in TDLNs, and reduced class-switched and tumor-specific antibodies in the circulation, indicating that the hypoxic response negatively-regulates tumor-induced humoral immune responses. pVHL deletion in class-switched B cells also reduced the expression of activation markers amongst tumor-infiltrating T cells and increased the presence of M2-like macrophages within the primary tumor. We detected the hypoxia marker carbonic anhydrase IX in the GCs of LNs from breast cancer patients, providing the first line of evidence that hypoxia develops within human GCs and validating our observations of hypoxia in TDLNs of pre-clinical mammary tumor models. We conclude that GC hypoxia develops in TDLNs, and that the hypoxic response negatively regulates tumor-induced humoral immune responses in pre-clinical models, with consequent impacts on the phenotype tumor-infiltrating T cells and macrophages.

Citation Format: Natalie Firmino, Kevin Bennewith. Germinal center hypoxia in tumor-draining lymph nodes negatively regulates humoral immune responses and affects the activation of tumor-infiltrating T cells [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P013.