bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowerment and enablement as predictors of change in health-related quality of life among patients participating in a Supported OsteoArthritis Self-Management Programme – a prospective observational study
Authors: Åkesson Karin Sturesdotter , Sundén Anne , Stigmar kjerstin , Eek Frida , Pawlikowska Teresa , Hansson Eva Ekvall
Published: March 2022

Background: Osteoarthritis is a leading cause of disability worldwide. Current treatment supports coping strategies to improve health-related quality of life (HRQoL). The need to predict response to treatment has been raised to personalise care. This study aims to examine change in HRQoL from baseline to three and nine months follow-up after participating in a Supported OsteoArthritis Self-Management Programme (SOASP) and to examine if empowerment and/or enablement could predict change in HRQoL among patients participating in a SOASP. Methods: Patients participating in a SOASP were recruited consecutively between April 2016 and June 2018. The EQ-5D was used to measure HRQoL, the SWE-RES-23 23 (score range 1–5) to measure empowerment and the PEI (score range 0–12) to measure enablement. The instruments were answered before (EQ-5D, SWE-RES-23) and after (EQ-5D, SWE-RES-23, PEI) the SOASP. A patient partner was engaged to enhance the patient perspective. Changes in outcome were examined with paired sample t-test and standardized effect sizes (Cohen´s d). Potential predictive variables were tested with multiple linear regression analysis. Results: In total, 143 patients participated in baseline measurement. The mean EQ-5D-5L index score increased significantly from baseline to three months corresponding to a standardised effect size (Cohen´s d) of d=.43, 95 % CI [.24, .63] (n=109), and from baseline to nine months d=.19, 95 % CI [.01, .37] (n=119). The average EQ VAS score increased significantly from baseline to three months corresponding to a standardised effect size of d=.26, 95 % CI [.07, .45] (n=109), and from baseline to nine months d=.18, 95 % CI [.00, .36] (n=119). Neither the SWE-RES-23 nor the PEI at three months follow-up or the change in the SWE-RES-23 score from baseline to three months follow-up predicted change in either EQ-5D-5L index (p>.05) or the EQ VAS (p>.05). Conclusions: Health-related quality of life increased after participating in a SOASP. Empowerment and enablement as measured with the SWE-RES-23 and the PEI respectively could not predict change in HRQoL among patients participating in a SOASP. Trial registration: ClinicalTrials.gov. Identification number: NCT 02974036. First registration 28/11/2016, retrospectively registered.
Scale-Up Production Of Extracellular Vesicles From Mesenchymal Stromal Cells Isolated From Pre-Implantation Equine Embryos
Authors: Tasma Zoe , Hou Weilin , Damani Tanvi , Seddon Katy , Kang Matthew , Ge Yi , Hanlon David , Hollinshead Fiona , Hisey Colin L. , Chamley Lawrence W.
Published: March 2022

Mesenchymal stromal cells (MSC) have recently been explored for their potential use as therapeutics in veterinary medicine applications. Alternatively, MSC-derived extracellular vesicles (EVs) may also provide therapeutic benefits but as an off-the-shelf solution, provided they can be produced in large enough quantities and without the risk of contamination from bovine EVs contained in fetal bovine serum that is a common component of cell culture media. Towards this aim, we demonstrated the successful isolation and characterisation of equine MSCs from pre-implantation embryos. We also demonstrate that many of these lines can be propagated long-term in culture and conducted a head-to-head comparison of two bioreactor systems for scalable EV production including in serum-free conditions. Based on our findings, the CELLineTM AD 1000 flasks enabled higher cell density cultures and significantly more EV production than the FibercellTM system or conventional culture flasks. These findings will enable future isolation of equine MSCs and the scalable culture of their EVs for a wide range of applications in this rapidly growing field.
An Equation of State Unifies Diversity, Productivity, Abundance and Biomass
Authors: Harte John , Brush Micah , Newman Erica , Umemura Kaito
Published: March 2022

To advance understanding of biodiversity and ecosystem function, ecologists seek widely applicable relationships among species diversity and other ecosystem characteristics such as species productivity, biomass, and abundance1-4. These metrics vary widely across ecosystems and no relationship among any combination of them that is valid across habitats, taxa, and spatial scales, has heretofore been found. Here we derive such a relationship, an equation of state, among species richness, energy flow, biomass and abundance by combining results from the Maximum Entropy Theory of Ecology5-7 and the Metabolic Theory of Ecology8,9. It accurately captures the relationship among these state variables in 42 data sets, including vegetation and arthropod communities, that span a wide variety of spatial scales and habitats. The success of our ecological equation of state opens opportunities for predicting difficult-to-measure state variables from measurements of others, adds support for two current theories in ecology, and is a step toward unification in ecology.
Differences in Global Functional Connectivity During Sound Location Processing: An Auditory MMN Study
Authors: Wang Songjian , Li Chunlin , Zhen Li , Wang Mengyue , Lin Meng , Qian Si , Hu Jiong , Pugh Esther , Zhang Xu , Wang Shuo
Published: March 2022

Our ability to localize low-frequency sounds relies on interaural time differences (ITD), the sensitivity to which underlies our ability to localize sound sources in azimuth and to segregate competing sound sources across a wide range of situations. However, the cortical representation of ITD has not been well characterized. To investigate differences in evoked cortical potentials and global functional connectivity during the unattended processing of sound localization on the horizontal plane, auditory mismatch negativity (MMN) was recorded and analyzed in adults using a deviant-standard oddball paradigm. A central sound source at the centerline of the horizontal plane (ITD = 0μs) was used as the standard stimulus and lateralized sounds with various ITDs were used as deviant stimuli. Characteristics of event-related potentials (ERP) and MMN obtained from young adults were compared between different deviant stimulus groups. The time-frequency (TF) power at each electrode associated with standard and deviant conditions were calculated. Distribution differences of electrode power between standard and deviant stimuli among oddball experiments were compared. Phase lag index (PLI) was also calculated to examine the dynamics of functional connectivity in various deviant stimulus groups. Network topological parameters were calculated to examine the global efficiency of information transfer in different deviant stimulus groups. Results of MMN analysis indicated that sounds with larger deviations from centerline elicited MMNs with greater amplitudes and shorter latencies and the MMN response was stronger in the hemisphere contralateral to the deviant stimulus. Results from the TF analysis showed a significant event-related synchronization (ERS) in the theta frequency band. Results of PLI functional connectivity suggested that the deviant stimulus resulted in a global increase in connectivity in theta band. Increased functional connectivity was found in frontal electrode pairs in sound stimuli towards the central rather than peripheral sound stimuli, and the peripheral sound stimuli revealed a higher global efficiency. This study suggests that the auditory system response in horizontal sound localization appeared to originate from the activity of the theta band. Sound sources with larger deviations from the centerline revealed higher brain network efficiency.
Couple-based Study on the Association Between Chronic Diseases and Depressive Symptoms in China: a Cross-section Study
Authors: Zhou Yang , Ren Wen-Long , Chen Lun-Wen , Yan Guo-Dong , Yang Xiao-Hua , Chen Jie , Cao Li-Na , Gu Yun-Juan , Xiao Jing
Published: March 2022

Background: We explored the association between several chronic diseases and depressive symptoms (DSs) at individual and couple levels.Methods: Data were derived from the 2018 China Health and Retirement Longitudinal Study, including 5365 middle-aged and elderly couples. DSs were measured using the 10-item Center for Epidemiological Studies Depression Scale, and chronic diseases were determined by self-report and doctor diagnosis. Multivariate logistic regression models were used to estimate the association between chronic diseases and DSs.Results: Couples’ unilaterality with different numbers of chronic diseases had increased 16%–289% risk on their own DSs and 24%–39% risk on spousal DSs. Couples with different numbers of chronic diseases increased their co-depression by 183%–834%, which was mainly increased in wives’ depressive symptoms (WDSs) by 51%–301%, more severe than husbands’ depressive symptoms (HDSs). WDSs and HDSs increased by 13%–111% in couples with unilateral respiratory disease, dyslipidaemia, digestive disease, arthritis, kidney disease, stroke, memory-related disease and by 24%–244% in couples’ co-morbidity of respiratory, metabolic, and digestive diseases, arthritis, heart problem, kidney disease, stroke. Further, co-depression increased by 34%–458% in couples with unilaterality/co-morbidity of these chronic diseases.Conclusions: Couples’ unilaterality/co-morbidity of most chronic diseases were associated with WDSs, HDSs, and co-depression. WDSs were more susceptible to chronic diseases than HDSs. Physical health of an individual could predict not only his/her own mental health but also his/her spouse’s mental health.
Incorporating Social Determinants of Health into the Mathematical Modeling of HIV/AIDS
Authors: Oliveira Robson , Rubio Felipe , Anderle Rodrigo , Sanchez Mauro , de Souza Luis , Macinko James , Dourado Ines , Rasella Davide
Published: March 2022

Background
Currently, it is estimated that 37.6 million people are living with the HIV/AIDS virus worldwide, placing HIV/AIDS among the 10 leading causes of death, mostly among low- and lower-middle-income countries. Despite the effective intervention in the prevention and treatment, this reduction did not occur equally among populations, subpopulations and geographic regions. This difference in the occurrence of the disease is associated with the social determinants of health (SDH), which could affect the transmission and maintenance of HIV. With the recognition of the importance of SDH in HIV transmission, the development of mathematical models that incorporate these determinants could increase the accuracy and robustness of the modeling. This article aims to propose a theoretical and conceptual way of including SDH in the mathematical modeling of HIV/AIDS.
Methods
The theoretical mathematical model with the Social Determinants of Health has been developed in stages. For the selection of SDH that were incorporated into the model, a narrative literature review was conducted. Secondly, we proposed an extended model in which the population (N) is divided into Susceptible (S), HIV-positive (I), Individual with AIDS (A) and individual under treatment (T). Each SDH had a different approach to embedding in the model.
Results
A total of 31 SDH were obtained in the review, divided into 4 groups: Individual Factors, Socioeconomic Factors, Social Participation, and Health Services. In the end, 4 determinants were selected for incorporation into the model: Education, Poverty, Use of Drugs and Alcohol abuse, and Condoms Use.
Conclusions
The equations presented with the chosen SDH exemplify some approaches that we can adopt when thinking about modeling social effects on the occurrence of HIV. The recognition of the importance of including the SDH in the modeling and studies on HIV/AIDS is evident, due to its complexity and multicausality. Models that do not take into account in their structure, will probably miss a great part of the real trends, especially in periods, as the current on, of economic crisis and strong socioeconomic changes.
Feasibility and Safety of Oncoplastic Breast-Conserving Surgery Through an Inframammary Incision
Authors: Fayed Haytham Mahmoud , Yousry Joseph , El-Fayomi Tarek , Al-Husseini Mahmoud
Published: March 2022

Background: Breast-conserving therapy (BCT) became the treatment of choice for early breast cancer due to a better understanding of the disease's biological activity and natural history. With the addition of oncoplastic breast surgery (OPS), conservation could be conducted in relatively large tumors with the best possible cosmetic results and without jeopardizing oncological safety. OPS procedures are by incising the skin envelop of the breast then dissection of the dermoglandular breast tissue. An inframammary crease incision is a suitable choice as a hidden scar in the breast envelope because one of the primary considerations for good oncoplastic methods is the cosmetic outcome. It also provides easy access to the retromammary region. This study aims to assess the feasibility of adopting the retro glandular approach for breast-conserving surgery by making a skin incision in the inframammary fold (IMF)Patients and methods: This study involved 67 female patients with breast cancer who were candidates for BCS and had tumors deeply seated between January 2019 and July 2021. An incision is made in the inframammary fold, its length depends on the tumor site, the tumor was excised after retroglandular exploration. Reapproximation of the glandular pillars was done and the wound was closed after a closed suction drain was inserted. SPSS software package version 20.0 was used for statistical analysis.Results: All patients were presented with mass, most of them (53.7%) had breast cup size B. 55.3% of cases had their tumor in the lower half of the breast. The median operative time was 125 (110 – 140) minutes. Seroma was the most common complication (8.9% of cases). 62.7% of cases had excellent results as judged by breast surgeons other than the operating surgeon. 82.1% of patients were satisfied with the aesthetic results.Conclusion:The Inframammary approach for breast-conserving surgery is feasible and safe for surgical treatment of patients presented with deeply seated breast cancer.Trial registration: This study protocol was reviewed and approved by the Ethical Committee of Alexandria Faculty of Medicine on 16- 7- 2020. Approval number: 0106451.
The Diversity Of Wild Medicinal Plants Of Lufeng In Eastern Guangdong, China
Authors: Yang Jun , Huang Junkai , Shen Hongkang , Qin Xinsheng
Published: March 2022

Backgrounds: Lufeng is located in the most backward coastal city in Guangdong, but it is a good place for medicinal plant cultivation because of the richness of plant species and the variety of land types, potential and adaptability. However, there are few comprehensive reports on the existing wild medicinal plants in Lufeng City. Relying on the fourth national census of Chinese medicine resources, this study aims to document the diversity of wild medicinal plant resources, medicinal properties, flavors, and effects, as well as the comprehensive value of key medicinal plants in Lufeng City.Methods: By consulting literature, collecting medicinal plants specimens, and field investigation, 36 sample sites and 32 sample lines in Lufeng were studied. For each described plant species, the composition of the family and genus, life forms, medicinal properties and flavors, the part of the plant used in medicine, and the medicinal uses were recorded. Key medicinal plants shall be determined by the catalog of the National Census of Chinese Medicinal Resources focused on the investigation of Chinese medicinal resources (Chinese herbal medicine), and the key medicinal plants with high comprehensive value in the city shall be determined by calculating the comprehensive value (SVMP).Results: 410 species of wild medicinal plants were identified, belonging to 304 genera and 118 families. Perennial herbs and shrubs were the main life forms. In terms of medicinal parts, the most are roots and rhizomes, accounting for 49.02%. WMPs with flat property (33.17%) took the largest proportion. These medicines mainly had three medicinal flavors, including sweet (39.27%) bitter (35.37%), and pungent (31.71%). The main uses of them were clearing heat (38.29%). The comprehensive value of imperative WMPs is high, but the development and utilization rate is low. Conclusion: Lufeng city is rich in the kinds of WMPs. In the future, in order to promote the local economic development, wild medicinal plants with high comprehensive value: Sargentodoxa cuneata, Plantago asiatica, Mentha canadensis, Juncus effusus and Turpinia montana should be developed. At the same time, the WMPs should be carefully considered in future development plans aimed at promoting sustainability.
Plasma Cell-free DNA 5-Hydroxymethylcytosine and Whole-Genome Sequencing Signatures for Early Detection of Esophageal Cancer
Authors: Lu Di , Wu Xuanzhen , Wu Shuangxiu , Li Hui , Yan Xuebin , Zhai Jianxue , Dong Xiaoying , Feng Siyang , Sun Fuming , Wang Shaobo , Zhang Xueying , Cai Kaican
Published: March 2022

Background
Esophageal cancer is one of globally high incidence and mortality disease. Its early stage has rarely obvious symptoms. Compared to conventional endoscopy diagnosis, liquid biopsy is an emerging non-invasive method for cancer early detection.
Methods
We enrolled 100 esophageal squamous cell carcinoma (ESCC) patients and 71 healthy individuals as a Southern China cohort and performed 5-hydroxymethylcytosine (5hmC) sequencing on their plasma cell-free DNA (cfDNA). A Northern cohort of cfDNA 5hmC dataset with 150 ESCC patients and 183 health individuals were downloaded for validation. A diagnostic model was firstly developed based on cfDNA 5hmC signatures and then improved by low-pass whole genome sequencing (WGS) features of cfDNA.
Results
Conserved cfDNA 5hmC modification motifs were observed in the two independent ESCC cohorts. A diagnostic model with 273 5hmC features based on randomly-selected two-thirds samples of the Southern China cohort was validated independently in the left one-thirds samples and the whole Northern China cohort, achieved an AUC of 0.810 and 0.862 with sensitivities of 69.3–74.3% and specificities of 82.4–90.7%, respectively. The performance was well maintained in Stage I to Stage IV, with accuracy of 70%-100%, but low in Stage 0, with accuracy of 33.3%. Low-pass WGS of cfDNA improved the AUC to 0.934 with a sensitivity of 82.4%, a specificity of 88.2% and an accuracy of 84.3%, particularly significantly in Stage 0 with the accuracy up to 80%.
Conclusions
This study suggests that the blood-based 5hmC integrated with low-pass WGS model could improve the accurate diagnosis of early stage ESCC, particularly for very early stage ESCC.
Predictive Blood Biomarkers of Sheep Pregnancy and Litter Size
Authors: Goldansaz Seyed Ali , Markus Susan , Plastow Graham , Wishart David S.
Published: March 2022

Early detection of sheep pregnancy and the prediction of how many lambs a pregnant ewe delivers affects sheep farmers in a number of ways, most notably with regard to feed management, lambing rate, and sheep/lamb health. The standard practice for direct detection of sheep pregnancy and litter size (PLS) is ultrasonography. However, this approach has a number of limitations. Indirect measurement of PLS using blood biomarkers could offer a simpler, faster and earlier route to PLS detection. Therefore, we undertook a large-scale metabolomics study to identify and validate predictive serum biomarkers of sheep PLS. We conducted a longitudinal experiment that analyzed 131 serum samples over five timepoints (from seven days pre-conception to 70 days post-conception) from six commercial flocks in Alberta and Ontario, Canada. Using LC-MS/MS and NMR, we identified and quantified 107 metabolites in each sample. We also identified three panels of serum metabolite biomarkers that can predict ewe PLS as early as 50 days after breeding. These biomarkers were then validated in separate flocks consisting of 243 animals yielding areas-under-the-receiver-operating-characteristic-curve (AU-ROC) of 0.81–0.93. The identified biomarkers could lead to the development of a simple, low-cost blood test to measure PLS at an early stage of pregnancy. This could help optimize reproductive management on sheep farms.
How the Iranian Health Transformation Plan has changed inequality in healthcare financing in Iran?
Authors: Moeeni Maryam , Nosratnejad Shirin , Ponnet Koen , Rostampour Manizhe
Published: March 2022

Introduction One of the major goals of health is providing a financing system without inequality; it has a significant impact on people’s access to healthcare. The present study aimed to investigate the inequality in households’ financial contribution to health expenditure before and after implementation of the Iranian Health Transformation Plan(HTP). Methods The present study is a secondary analysis of two waves of a national cross-sectional survey conducted in Iran. The data collected from the Households Income and Expenditure Survey(HIES) in 2013 and 2015. The research sample included 76,195 Iranian households. The inequality in households’ financial contributions to the health system(HFC) was assessed using the Gini coefficient, and the concentration index(CI). In addition, by using econometric modeling, the relationship between the implementation of the HTP and inequality in HFC was studied. The households’ financial included healthcare and health insurance prepayments. Results The Gini coefficient values were 0.67 and 0.65 in 2013 and 2015, respectively, which indicated a medium degree of inequality in HFC in both years. The CI values were 0.54 and 0.56 in 2013 and 2015, respectively, suggesting that inequalities in HFC were in favor of higher income quintiles in the years before and after the implementation of the HTP. Regression analysis showed Households with a female head, with an unemployed head, and with a head having income without a job were more contribution to financing health expenditure. The presence of a household member over the age of 65 was associated to higher level of HFC. The implementation of the HTP had a negative relationship with HFC. Discussion and conclusion The HTP, which aimed to provide an equal financing system, did not achieve the intended goal as enough. The implementation of HTP neglected factors at the individual and household levels, such as the presence of members older than age 60 in the family, a female household head, and unemployment; this resulted in a failure to reduce the inequality of HFC. We suggest that policy makers take into account individual factors and features of the household level to reduce inequality in HFC.
3D Deep Learning Versus the Current Methods for Predicting Tumor Invasiveness of Lung Adenocarcinoma
Authors: Lv Yilv , Wei Ying , Xu Kuan , Zhang Xiaobin , Hua Rong , Huang Jia , Li Min , Tang Cui , Yang Long , Liu Bingchun , Yuan Yonggang , Li Siwen , Gao Yaozong , Zhang Xianjie , Wu Yifan , Han Yuchen , Shang Zhanxian , Yu Hong , Zhan Yiqiang , Shi Feng , Ye Bo
Published: March 2022

Background: Different pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma in situ and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach on the classification of tumor invasiveness and compare it with the performances of currently available approaches.Methods: In this study, we propose a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules. A total of 901 early-stage non-small cell lung cancer patients who underwent surgical treatment at Shanghai Chest Hospital between November 2015 and March 2017 were retrospectively included and randomly assigned to a training set (n=814) or testing set 1 (n=87). We subsequently included 116 patients who underwent surgical treatment and intraoperative frozen section between April 2019 and January 2020 to form testing set 2. We compared the performance of our deep learning approach in predicting tumor invasiveness with that of intraoperative frozen section analysis and human experts (radiologists and surgeons).Results: The deep learning approach yielded an area under the receiver operating characteristic curve (AUC) of 0.946 for distinguishing preinvasive adenocarcinoma from invasive lung adenocarcinoma in testing set 1, which is significantly higher than the AUCs of human experts (P<0.05). In testing set 2, the deep learning approach distinguished invasive adenocarcinoma from preinvasive adenocarcinoma with an AUC of 0.862, which is higher than that of frozen section analysis (0.755, P=0.043), senior thoracic surgeons (0.720, P=0.006), radiologists (0.766, P>0.05) and junior thoracic surgeons (0.768, P>0.05).Conclusions: We developed a deep learning approach that achieved comparable performance to intraoperative frozen section analysis in determining tumor invasiveness. The proposed method may contribute to clinical decisions related to the extent of surgical resection.
Near-infrared light reduces β-amyloid-stimulated microglial toxicity and enhances survival of neurons: Mechanisms of light therapy for Alzheimer's disease
Authors: Stepanov Yurii V. , Golovynska Iuliia , Zhang Renlong , Golovynskyi Sergii , Stepanova Liudmyla I. , Gorbach Oleksandr , Dovbynchuk Taisa , Garmanchuk Liudmyla V. , Ohulchanskyy Tymish Y. , Qu Junle
Published: March 2022

Background.
Low-intensity light can decelerate neurodegenerative disease progression and reduce amyloid β (Aβ) levels in the cortex, though, the cellular and molecular mechanisms by which photobiomodulation protects against neurodegeneration are still in the early stages. Microglia cells play a key role in the pathology of Alzheimer's disease by causing chronic inflammation. We present new results concerning the photobiomodulation of both oxidative stress and microglia metabolism associated with the activation of metabolic processes by 808 nm near-infrared light.
Methods.
The studies were carried out using healthy male mice to obtain the microglial cell suspension from the hippocampus. Oligomeric β-amyloid (1–42) was prepared and used to treat microglia cells. Light irradiation of cells was performed using diode lasers emitting at 808 nm (30 mW/cm2 for 5 min, resulting in the dose of 10 J/cm2). Mitochondrial membrane potential, ROS level studies, cell viability, apoptosis and necrosis assays were performed using epifluorescence microscopy. Phagocytosis, nitric oxide and H2O2 production, arginase and glucose 6-phosphate dehydrogenase activities were measured using standard assays. Cytokines, glucose, lactate, and ATP were measurements with ELISA. As our data were normally distributed, Student’s t-test was used.
Results.
The light induces a metabolic shift from glycolysis to mitochondrial activity in pro-inflammatory microglia affected by oligomeric Aβ. Thereby, the level of anti-inflammatory microglia increases. This process is accompanied by a decrease in pro-inflammatory cytokines and an activation of phagocytosis. Light exposure decreases the Aβ-induced activity of glucose-6-phosphate dehydrogenase, an enzyme that regulates the rate of the pentose phosphate pathway, which activates nicotinamide adenine dinucleotide phosphate oxidases to further produce ROS. During co-cultivation of neurons with microglia, light prevents the death of neurons, which is caused by ROS produced by Aβ-altered microglia.
Conclusions.
These original data clarify reasons for how photobiomodulation protects against neurodegeneration and support the use of light for therapeutic research in the treatment of Alzheimer's disease.
Optimize Data-Driven Multi-Agent Simulation for COVID-19 Transmission
Authors: Jin Chao , Zhang Hao , Yin Ling , Zhang Yong , Feng Sheng-zhong
Published: March 2022

Background:
Multi-Agent Simulation is an essential technique for exploring complex systems. In researches of contagious diseases, it is widely exploited to analyze their spread mechanisms, especially for preventing COVID-19. Nowadays, transmission dynamics and interventions of COVID-19 have been elaborately established by this method, but its computation performance is seldomly concerned. As it usually suffers from inadequate CPU utilization and pour data locality, optimizing the performance is challenging.

Results:
This paper explores approaches to optimize multi-agent simulation for COVID-19 disease. The focus of this work is on the algorithm and data structure designs for improving performance, as well as its parallelisation strategies. We propose two successive methods to optimize the computation. We construct a case-focused iteration algorithm to improve data locality, and create a thread-safe data-mapping paradigm called hierachical hash table to accelerate hash operations.

Conclusions:
Our performance results demonstrate capabilities of these methods exhibiting significant improvements of system performance. The case-focused method degrades $\sim 90 \%$ cache references and achieves $\times 4.3$ speedup. Hierachical hash table can further boost computation speed by 47\%. And parallel implementation with 20 threads on CPU achieves $\times 81$ speedup consequently.
A Seven-Year Surveillance of Epidemiological Trends of Serratia Marcescens with Different Infection Types in a Tertiary Hospital in China
Authors: Zhu Qingtang , Chen Caiyun , Ge Zijun , Zang Feng , Zhang Yongxiang , Liu Bo
Published: March 2022

Objective: To explore the trend of detection and antimicrobial resistance of Serratia marcescens with different infection types for 7 consecutive years, to provide a reference for future studies for the control of S. marcescens infections and a rational selection of antibiotics.Methods: S. marcescens isolates were collected from 2014 to 2020, and the trend of detection and antimicrobial resistance were analyzed according to different types of infection.Results: For 7 consecutive years, the data showed that patients with S. marcescens infections were mainly from the intensive care unit (ICU) (384 isolates, 40.98%), and the isolates recovered were mainly from sputum samples (743 isolates, 79.30%). The number of isolated strains increased every year, and the average rate of detection ranged from 0.60% to 0.80%. The detection rate of S. marcescens with hospital-acquired infections (HAI) showed a downward trend and that of S. marcescens with colonization showed an upward trend. The detection rate of multidrug-resistant S. marcescens fluctuated between 8.33%–16.89%. The resistance rate of S. marcescens to piperacillin was 17.0%–29.06% and the resistance rate to piperacillin tazobactam was 2.95%–13.13%. For cephalosporin antibiotics, the resistance rates of S. marcescens to cefuroxime and cefazolin were >99% and the resistance rates to ceftazidime and cefepime were <13%. The resistance rate of S. marcescens to aminoglycoside antibiotics, especially amikacin, was the lowest. The resistance rate of S. marcescens with community-acquired infections (CAI) to carbapenems was higher than that with HAI and colonization.Conclusion: The different infection types of S. marcescens have different detection and epidemic trends. In addition, resistance to carbapenems is different across the strains.
TMEM205 Reduces the Sensitivity of Gastric Cancer to Cisplatin Through TAM/M2 Polarization
Authors: Wu Xuwei , Meng Ziqi , Zhang Rui , Zhang Meihua , Piao Zhengri , Jin Tiefeng
Published: March 2022

Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find an effective therapeutic target to enhance the sensitivity of GC to DDP. Transmembrane protein 205 (TMEM205) plays significant roles in DDP resistance, but the specific mechanism of TMEM205 in DDP-resistant GC has not been studied. Databases showed that TMEM205 overexpresses in GC. In vitro results showed that TMEM205 enhances proliferation, stemness, epithelial-mesenchymal transition (EMT) process, migration and angiogenesis of SGC-7901/DDP cells by activating the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment.
Associations of Serum Phosphorus Concentrations with Insulin Resistance and Hyperandrogenemia in Normal Weight Women with Polycystic Ovary Syndrome
Authors: Wu Xiao-ke , Zhang Shi-ke , He Hui , Wang Yu , Li Jian , Gao Jing-shu , Cong Jing , Feng Jia-xing , Zhu Meng-yi
Published: March 2022

Purpose: Serum phosphorus is reported to be associated with insulin resistance (IR) and testosterone in many populations. However, studies exploring the role of serum phosphorus in polycystic ovary syndrome (PCOS) patients are rare. Thus, we aimed to investigate the associations of serum phosphorus concentrations with IR and hyperandrogenemia (HA) in women with PCOS.Methods: This was a secondary analysis of a multicenter and large-sample clinical trial including 1000 PCOS subjects diagnosed by the modified Rotterdam criteria. A total of 508 normal-weight PCOS patients with available serum phosphorus data were enrolled in the present study. Serum phosphorus, metabolic indices, and total testosterone (TT) concentration were measured. IR status was defined by a homeostasis model assessment of insulin resistance (HOMA‐IR) ≥ 2.69, and HA status was defined as a TT level ≥ 1.67 nmol/L. Multivariable linear regression and logistic regression models were used to evaluate the associations of serum phosphorus with IR and HA.Results: Multiple linear regression analysis showed that the serum phosphorus concentration was inversely correlated with fasting plasma glucose (FPG), fasting insulin (FIN), HOMA‐IR, and TT (P trend < 0.05 for all) after adjusting for confounding factors. Logistic regression showed that the serum phosphorus concentration was negatively correlated with IR and HA status. The multivariable-adjusted odds ratios with 95% confidence intervals for IR and HA status for the lowest vs. the highest quartiles of serum phosphorus were 2.26 (1.17-4.35, P trend = 0.009) and 2.58 (1.48–4.51, P trend = 0.002), respectively. Conclusion: Our results demonstrated that lower serum phosphorus concentrations were associated with higher risk of IR and worsened HA in normal-weight women with PCOS.
Intervention programs targeting the mental health, professional burnout, or wellbeing of school teachers: A systematic review and meta-analyses
Authors: Beames Joanne , Spanos Samantha , Roberts Anna , McGillivray Lauren , Li Sophie , Newby Jill , O'Dea Bridianne , Werner-Seidler Aliza
Published: March 2022

This paper outlines a systematic review and meta-analyses to identify, describe, and evaluate randomised and non-randomised controlled trials of psychological programs targeting the mental health, professional burnout, or wellbeing of school classroom teachers. Eighty-two unique studies were identified for inclusion in the review, and of those 39 were included in the meta-analyses (19 randomised controlled trials). In randomised controlled trials, the programs examined had significant large effects on stress (g=1.16), and moderate effects on burnout (g=0.58) and wellbeing (g=0.68). In non-randomised controlled trials, programs had significant moderate effects on stress (g=0.62), and small to moderate effects on anxiety (g=0.42), depression (g=0.36), and wellbeing (g=0.44). Studies were heterogeneous in design and methodological quality was generally poor, particularly in non-randomised controlled trials. There was an inadequate number of comparisons to perform sub-group analyses, meta-regression, or publication bias analyses. Most of the programs examined required significant time, effort, and resources to deliver and complete. These programs may not translate well outside of research trials to real-world contexts due to teachers being time poor. Priorities for research include using methodologically rigorous designs, developing programs for teachers with teachers (i.e., co-design), and considering implementation factors to ensure feasibility, acceptability, and uptake. Systematic Review Registration Number: PROPSERO - CRD42020159805.
Does the regulatory effect of vitamin D allow to reduce the cisplatin dose in T24 bladder cancer cell line?
Authors: Özgen Özge , Eroğlu Güneş Özen , Akdeniz Nilgün , Hepokur Ceylan , Kuruca Serap , Yaylım İlhan
Published: March 2022

1,25(OH)2D3 (Calcitriol, active form of Vitamin D), which is a broad regulatory molecule, plays a role in changing the efficacy of chemotherapeutic drugs. In bladder cancer, effectiveness of the treatment and reducing the resistance to chemotherapeutics such as cisplatin are of great importance. Cisplatin usage is one of a current standard chemotherapy regimen for bladder cancer. In our study T24, ECV-304 and HUVEC cell lines were treated with calcitriol and cisplatin individually and with combination. MTT assays were used for optimal dose determination. It was aimed to determine the possible potential of the combined use of cisplatin with calcitriol. Determined doses and combination treatments of calcitriol and cisplatin on all cell lines were evaluated for cytotoxicity, apoptosis and drug resistance. Also calcitriol and cisplatin interaction with p53 protein was assessed by molecular docking analysis. Datas showed that combination treatment increased the anti-proliferative efficacy compared to cisplatin alone (p=0.0108) in T24 cells. Also it reduced the cytotoxicity in the HUVEC compared to cisplatin alone (p< 0.0001). Combination treatment achieved slightly higher apoptosis rate in T24 cells than treatment of cisplatin alone (p=0.0005). It was determined that the rate of apoptosis and P-gp levels did not change significantly in the ECV-304 cells. However it decreased in HUVEC healthy control cell line (p=0.0082). P-gp ratios were increased in HUVEC (p < 0.0001) and decreased in T24 cells (74.47% p<0.0001) compare to control. The data obtained in this study show that the combination of calcitriol and cisplatin allows the use of cisplatin at lower doses.
Evaluation of Auto-segmentation for External Radiotherapy Planning Structures:A Part of Deep Learning Based Workflow in Cervical Cancer
Authors: Wang Jiahao , Chen Yuanyuan , Xie Hongling , Luo Lumeng , Tang Qiu
Published: March 2022

Objective:Deep learning (DL) based approach aims to construct a full workflow solution for cervical cancer with external radiotherapy (EBRT) and brachytherapy (BT).The purpose of this study was to evaluate the accuracy of EBRT planning structures derived from DL based auto-segmentation which would be a part implemented in the workflow of cervical cancer.Methods:Clinical target volumes (CTVs) and organs at risk (OARs) of 75 cervical cancer patients were manually delineated by senior radiation oncologists and auto-segmented by DL based method.The accuracy of DL based auto-segmented contours were evaluated using geometric and dosimetric metrics including dice similarity coefficient (DSC),95%hausdorf distance (95%HD),jaccard coefficient (JC) and dose-volume index (DVI).The correlation between geometric metrics and dosimetric difference was performed by Spearman’s correlation analysis. Results:The DL based auto-segmentation generated similar geometric performance in right kidney,left kidney,bladder,right femoral head and left femoral head with mean DSC of 0.88-0.93,95%HD of 1.03-2.96mm and JC of 0.78-0.88. Wilcoxon’s signed-rank test indicated significant dosimetric differences between manual and DL based auto-segmentation in CTV,spinal cord and pelvic bone (P<0.001). A strong correlation between the mean dose of pelvic bone and its 95%HD (R=0.843, P=0.000) was found in Spearman’s correlation analysis, and the remaining structures showed weak link between dosimetric difference and all of geometric metrics.Conclusion:Auto-segmentation achieved a satisfied agreement for most EBRT planning structures,although the dosimetric consistency of CTV was a concern. DL based auto-segmentation was an essential component in cervical cancer workflow which would generate the accurate contouring.
Warming-induced increase in carbon uptake leads to earlier spring phenology
Authors: Gu Hongshuang , Qiao Yuxin , Xi Zhenxiang , Rossi Sergio , Smith Nicholas , Liu Jianquan , Chen Lei
Published: March 2022

Under global warming, advances in spring phenology due to rising temperatures have been widely reported. However, the physiological mechanisms underlying the warming-induced earlier spring phenology remain poorly understood. Here, using multiple long-term and large-scale phenological datasets between 1951 and 2018, we show that warmer temperatures during the previous growing season led to earlier spring phenology in the Northern Hemisphere, with an average advancement of 2.5 days °C− 1. Correspondingly, we observed an earlier spring phenology with the increase in photosynthesis of previous growing season. Furthermore, we found a significant decline in the advancing effect of warming in previous growing season on spring phenology from cold to warm periods. These findings reveal that the observed warming-induced earlier spring phenology is driven by increased photosynthetic carbon assimilation in the previous growing season, while the slowdown in the advanced spring phenology may arise from decreased carbon assimilation when warming exceeds optimal temperatures for photosynthesis. Therefore, the vital role of warming-induced changes in carbon assimilation should be considered to accurately project spring phenology and carbon cycling under future climate warming conditions.
A study of Human pupil orbit model estimation method for the eye-gaze tracking.
Authors: Lee Seung Bong , Jeong Jae Hoon , Kim Dae Chang , Kim Sung Min
Published: March 2022

Background: Eye tracking is a technology that detects the direction of the user's gaze in real time. This technology is used in various fields such as analyzing user emotions and behaviors by analyzing the length of time the gaze stays in a specific direction or the path of movement. Recently, Eye-gaze tracking is a popular to a non-contact interaction technique for the minimization of covid-19 infection. A study conducted in the past have a limitation in that the ocular rotational center point (ORCP) cannot be found in common. For this reason, each research is continuously researching to overcome this problem by using various sensors, structures, and phenomena. In spite of, a tiny movement of the subject cause an error in accuracy during the process of Eye-gaze tracking. In this paper, we propose a novel method for Eye-gaze tracking under the condition of photographing the front of the face using a camera. We named this position set as Human pupil orbit model (HPOM) and it can express as a spherical equation because it looks like a sphere in 3-dimensional coordinate.Results: A simulation experiment was performed to confirm the performance of the proposed method. The error of HPOM estimation appears under 1 pixel in the first experiment both ORCP and a radius. In addition, it was confirmed that the process of estimating HPOM can be conducted as a real time in the second experiment.Conclusions: The proposed method was able to overcome the common problem of existing studies that could not find the rotational center of an eye-ball. In addition, HPOM may be secured in real time even if the subject moves.
Arterial Chemoembolization For Patients With Hepatocellular Carcinoma And Elevated Lactate Dehydrogenase Is Associated With Low Survival: A Cohort Study
Authors: Zhuang Genghui , Xie Yuping , Hong Junfeng , Lin Shan , Chen Tingting , Fang Wenzheng
Published: March 2022

Purpose: Serum lactate dehydrogenase (LDH) concentration has been used for the evaluation and prediction of prognosis of several tumors, including hepatocellular carcinoma (HCC). However, the relationship between changes in LDH after treatment (ΔLDH) and prognosis is still unclear. Herein, we aimed to determine this association in patients with HCC.Methods: Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (95%CIs) for HCC were obtained by Cox proportional hazard regression models. As for ΔLDH and overall survival (OS), the nonlinear relationship was evaluated through a restricted cubic spline regression analysis, and threshold effects were further calculated using a two-piece-wise Cox proportional hazard model.Results: The study finally selected 749 patients with HCC treated by transarterial chemoembolization (TACE) for the secondary analysis. Considering the ΔLDH within ±80 U/L group as the baseline, the risk of death in the ΔLDH≥80 U/L group was significantly increased by 131% (95%CI: 1.74–3.06), and the risk of death in the ΔLDH≤- 80 U/L group was increased by 24% (HR: 1.23, 95%CI: 0.99–1.55). However, this difference was not statistically significant. Furthermore, with ΔLDH=0 (100 U/L) as the turning point, an upward U-shaped curve could be formed between ΔLDH and OS. After adjusting for confounders, ΔLDH still had a significant effect on the threshold of OS (P=0.021).Conclusion: After TACE, with the increase of LDH index, HCC patients will be closely related to worse OS.
Relationship between the Level of Sacral Resection and Short-Term Outcomes in Patients Undergoing Total Pelvic Exenteration Combined with Sacral Resection for Rectal Cancer
Authors: Komori Koji , Tsukushi Satoshi , Yoshida Masahiro , Kinoshita Takashi , Sato Yusuke , Ouchi Akira , Ito Seiji , Abe Tetsuya , Misawa Kazunari , Ito Yuichi , Natsume Seiji , Higaki Eiji , Okuno Masataka , Fujieda Hironori , Kawakatsu Shoji , Kunitomo Aina , Oki Satoshi , Maeda Shingo , Nagao Takuya , Aritake Tsukasa , Tawada Kakeru , Akaza Satoru , Shimizu Yasuhiro
Published: March 2022

Background: This retrospective study aimed to elucidate the relationships between short-term outcomes following total pelvic exenteration combined with sacral resection (TPES) and operative techniques in patients with rectal cancer.Methods: Data regarding sex, age, body mass index, neoadjuvant therapy, location of sacral resection (“Upper” or “Lower” relative to the level between the 3rd and 4th sacral segment), operative time, bleeding, and curability (R0/R1) were collected and compared to determine their association with complications exhibiting a Clavien–Dindo grade higher than III. Results: The complication rate was significantly higher for recurrent cancers than for primary cancers (p=0.007), and for “Upper” resection than for “Lower” resection (p=0.078). Significant differences were observed when complication rates for “Upper” and “Lower” resection were compared between primary and recurrent cancers (p=0.007).Conclusion: In patients with recurrent rectal cancer, “Upper” sacral resection during TPES is associated with a high complication rate, highlighting the need for careful monitoring.