bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Effect of PARP Inhibitor and BRD4 Inhibitor in Multiple Models of Ovarian Cancer
Authors: Huang Han Yu , Liu Chen , You Xin Li , Li Xi , Sun Yang chao , Chen Gang 
Published: December 2021

Abstract
Background: Ovarian cancer has the highest fatality rate among patients with gynaecological tumours. Current therapies including poly-ADP ribose polymerase (PARP) inhibitors have limitations due to the frequent recurrence of ovarian cancer after treatment and resistance to therapy.Methods: In this study, we used multiple models with different genetic backgrounds to investigate the potential synergism effect and mechanism between the bromodomain-containing protein 4 (BRD4) inhibitor AZD5153 and the PARP inhibitor Olaparib. The models were two-dimensional (2D) and 3D cell lines, patient-derived organoids (PDO) and patient-derived xenografts (PDX). Results: Cotreatment with Olaparib and AZD5153 exhibited marked synergistic effects, and significantly attenuated cell viability, whereas it increased DNA replication fork instability, chromosomal breakage and apoptosis compared to treatment with either drug alone. Mechanistically, the tumor upregulates PTEN after Olaparib treatment to make its DNA and chromosome more stable and therefore induces Olaparib resistance. AZD5153 can downregulate PTEN to reverse Olaparib resistance and thus increase joint lethal effect with Olaparib.Conclusion: This study reveals that AZD5153 can downregulate PTEN to reverse Olaparib resistance and thus increase joint lethal effect on DNA replication fork instability, chromosomal breakage, and apoptosis with Olaparib.
Extended Fractional Singular Kalman Filter
Authors: Nosrati Komeil , Belikov Juri , Tepljakov Aleksei , Petlenkov Eduard 
Published: December 2021

Abstract
Effective and accurate state estimation is a staple of modern modeling. On the other hand, nonlinear fractional-order singular (FOS) systems are an attractive modeling tool as well since they can provide accurate descriptions of systems with complex dynamics. Consequently, developing accurate state estimation methods for such systems is highly relevant since it provides vital information about the system including related memory effects and long interconnection properties with constraint elements. However, missing features in transforming structures such as violation of constraints in non-singular versions of such systems may affect the performance of the estimation result. This paper proposes the state estimation algorithm design for the original and non-transformed stochastic nonlinear FOS system. We introduce a deterministic data-fitting based framework which helps us to take steps directly towards Kalman filter (KF) derivation of the system, called extended fractional singular KF (EFSKF). Using stochastic reasoning, we demonstrate how to construct recursive form of the filter. Analysis of the filter shows how the proposed algorithm reduces to the nominal nonlinear filters when the system is in its usual state-space form making said algorithm highly flexible. Finally, simulation results verify that the estimation of nonlinear states can be accomplished with the proposed EFSKF algorithm with a reasonable performance.
Health Seeking Behavioural Practices of the Elderly in Rural Community of Ekiti State, South-western Nigeria
Authors: ADEWOYE Kayode Rasaq , AREMU Shuaib Kayode , Ekpo David Sylvanus , AKANBI Sikiru Adekunle , Ibrahim Tayo 
Published: December 2021

Abstract
BackgroundThe ageing process increases the risks of contracting a disease among elderly people. Health-seeking behaviour is poor among the aged in sub-Saharan countries like Nigeria, escalating the burden of Non-communicable diseases and the cost of healthcare which further impact the utilization of Orthodox medicine. This study aims to assess the healthcare-seeking behavioural practices and associated factors among elderly people in Ido-Ekiti.MethodA descriptive cross-sectional study was conducted amongst 420 elderly respondents in Ido-Ekiti. An interviewer-administered semi-structured questionnaire was used to collect information. The data collected were analyzed using SPSS version 25 and results were presented in form of tables and bar charts. Chi-square tests were used to test for associations. All data analysis was done at a 5% level of significance.ResultsThe age range of respondents was between 65-95 years with a mean age of 73.88 +/- 6.84 years and 64.0% within the age range 65-75 years. About 63.3% of the respondents have had an episode of illness in the last year preceding the study and only 35.3% consulted a doctor for treatment (Good Health seeking behaviour), however, 57.9% admitted utilizing any of the following; self-medication, consult spiritualist, use of herbal medicine (poor health-seeking behaviour). The factors statistically significantly associated with respondents’ health-seeking behavioural practices are employment status(p<0.001), educational level (p<0.002), cost of health care, access to the health facility, length of time before consultation, beliefs, and lack of support from relations(p<001). ConclusionThis study shows the majority of elderlies had poor health-seeking behaviour due to educational and .economic factors. Making the free or subsidized cost of health care for the elderly in rural communities and the provision of monthly financial support to the aged by the government will promote and encourage good health-seeking behaviour of old people.
Epidemiology and Risk Factors for Resistance to Treatment of Kawasaki Disease in Cyprus.
Authors: Koliou Maria G , Aristidou Athina , Mazeri Stella , Georgiou Elena , Agathocleous Maria , Kousparou Marianna , Elia Avraam , Jossif Antonis 
Published: December 2021

Abstract
Background: Kawasaki disease (KD) is one of the most common vasculitides of early childhood and the first cause of acquired heart disease in developed countries. There are no previous studies on KD in Cyprus. The aim of this study was to evaluate the epidemiology of KD in Cyprus, risk factors for resistance to treatment and the development of cardiac complications. Lastly, the Kobayashi and Egami scoring systems were evaluated in our population.Methods: This is a retrospective multicenter study of pediatric patients with KD hospitalized between January 2000 and-December 2019. The data were collected from medical records. Results: A total of 136 patients with KD were included in the study. 83% of patients were <5 years of age and 10% were <6 months. Median duration of fever before treatment was 6 days. 108/129 patients responded to initial treatment with IVIG. Thirty patients (22%) developed coronary artery lesions. Serum sodium ≤133mmol/L, albumin ≤ 3.2 g/dl, ALT≥ 80 U/L and neutrophils percentage≥ 80% at diagnosis, were identified as risk factors for resistance to IVIG. The Kobayashi and Egami scoring systems had low sensitivity of 57% and 62% respectively and a medium specificity of 76% and 76% respectively in predicting IVIG resistance.Conclusion: Clinical and epidemiological characteristics of KD in Cyprus population were similar to those reported in the literature. Although the majority of cases received appropriate treatment in time, cardiac complications still occurred. The Kobayashi and Egami scoring systems cannot be used in our population in order to predict responsiveness to IVIG.
Monovalent Copper Ions Inhibit Enzymatic Systems
Authors: Saphier Magal , Moshkovich Lea , Popov Stanislav , Shotland Yoram , Silberstein Eldad , Saphier Oshra 
Published: December 2021

Abstract
The effect of monovalent copper ions on enzymatic systems has hardly been studied to date; this is due to the low stability of monovalent copper ions in aqueous solutions, which led to the assumption that their concentration is negligible in biological systems. However, in an anaerobic atmosphere, and in the presence of a ligand that stabilizes the monovalent copper ions over the divalent copper ions, high and stable concentrations of monovalent copper ions can be reached. Moreover, the cell cytoplasm has a substantial concentration of potential stabilizers that can explain significant concentrations of monovalent copper ions in the cytoplasm. This study demonstrates the effect of monovalent and divalent copper ions on DNA polymerase, ligaseT4 DNA, the restriction enzymes EcoP15I and EcoR I, acid phosphatase, and α and βamylase enzymes. These systems were chosen because they can be monitored under conditions necessary for maintaining a stable concentration of monovalent copper ions, and since they exhibit a wide range of dependency on ATP. Previous studies indicated that ATP interacts with monovalent and divalent copper ions and stabilizing monovalent copper ions over divalent copper ions. The results showed that monovalent copper ions dramatically inhibit DNA polymerase and acid phosphatase, inhibit ligaseT4 DNA and the restriction enzyme EcoP15I, moderately inhibit α and β amylase, and have no effect on the restriction enzyme EcoR I. From the results presented in this work, it can be concluded that the mechanism is not one of oxidative stress, even though monovalent copper ions generate reactive oxygen species (ROS). Molecular oxygen in the medium, which is supposed to increase the oxidative stress, impairs the inhibitory effect of monovalent and divalent copper ions, and the kinetics of the inhibition is not suitable for the ROS mechanism.ATP forms a complex with copper ions (di and monovalent ions, where the latter is more stable) in which the metal ion is bound both to the nitrogen base and to the oxygen charged on the phosphate groups, forming an unusually distorted complex. The results of this study indicate that these complexes have the ability to inhibit enzymatic systems that are dependent on ATP.This finding can provide an explanation for the strong antimicrobial activity of monovalent copper ions, suggesting that rapid and lethal metabolic damage is the main mechanism of monovalent copper ions’ antimicrobial effect.
Pathogenesis of Aquatic Bird Bornavirus in Muscovy Ducks
Authors: Iverson Melanie , Leacy Alexander , Pham Phuc H. , Che Sunoh , Brouwer Emily , Nagy Eva , Lillie Brandon N. , Susta Leonardo 
Published: December 2021

Abstract
Aquatic bird bornavirus (ABBV), a type of avian bornavirus, has been associated with inflammation of the central and peripheral nervous systems and neurological disease in wild waterfowl in North America and Europe. The potential of ABBV to infect and cause lesions in commercial waterfowl species is unknown. The aim of this study was to determine the ability of ABBV to infect and cause disease in day-old Muscovy ducks (n = 174), selected as a representative domestic waterfowl. Ducklings became infected with ABBV through both intracranial and intramuscular infection routes: upon intramuscular infection, the virus spread centripetally to the central nervous system (brain and spinal cord), while intracranial infection led to virus spread to the spinal cord, kidneys, proventriculus, and gonads (centrifugal spread). Infected birds developed both encephalitis and myelitis by 4 weeks post infection (wpi), which progressively subsided by 8 and 12 wpi. Despite development of microscopic lesions, clinical signs were not observed. Only five birds had choanal and/or cloacal swabs positive for ABBV, suggesting a moderate potential of Muscovy ducks to shed the virus. This is the first study to document the pathogenesis of ABBV in poultry species, and confirms the ability of ABBV to infect commercial waterfowl.
Ultrastructure and Function of Setae of a Planktonic Diatom, Chaetoceros Coarctatus
Authors: Owari Yuka , Nakamura Fumi , Oaki Yuya , Tsuda Hiroyuki , Shimode Shinji , Imai Hiroaki 
Published: December 2021

Abstract
Silica frustules of most planktonic diatoms have many shallow holes in which the length (L) is smaller than the width (W). The present study focuses on a silicic ultrastructure of the setae of a planktonic diatom having deep (L/W > 1) holes. Here, we characterized nanoholes on the silica walls of hollow setae of a colony of Chaetoceros coarctatus. Basically, tetragonal poroid arrangements with and without a costa pattern are observed on the inner and outer surfaces, respectively, for three kinds of curving hollow setae. Deep nanoholes ∼90 nm wide are elongated from 150 to 1500 nm (L/W ∼17) with an increase in the wall thickness of the polygonal tubes of the setae. The inside poroid array, with a period of 190 nm in the extension direction of setae, is lined by parallel plates of the costae. However, the poroid arrangement on the outer surface is disordered, with several holes obstructed with increasing wall thickness of the posterior terminal setae. According to the movement of a colony in a fluid microchannel, the thick curving terminal setae is suggested to involve attitude control and mechanical protection. Using an optical simulation, the patterned deep through-holes on the intercalary setae were inferred to contribute anti-reflection of blue light for the promotion of photosynthesis in seawater.
Neoadjuvant chemo-free combination of camrelizumab and apatinib for locally advanced resectable oral squamous cell carcinoma – A pilot study
Authors: Ju Wu-tong , Xia Rong-hui , Zhu Dong-wang , Dou Sheng-jin , Zhu Guo-pei , Dong Min-jun , Wang Li-zhen , Sun Qi , Zhao Tong-chao , Zhou Zhi-hang , Liang Si-yuan , Huang Ying-ying , Tang Yong , Wu Si-cheng , Xia Jing , Chen Shiqing , Bai Yuezong , Li Jiang , Zhu Qi , Zhong Lai-ping 
Published: December 2021

Abstract
Novel neoadjuvant therapy regimens are needed to improve the outcomes of patients with locally advanced resectable oral squamous cell carcinoma (OSCC). We conducted a prospective, open-label, single-arm trial (n = 21, NCT04393506) to determine the safety and feasibility of neoadjuvant camrelizumab (an anti-PD-1 antibody) plus apatinib (a VEGFR inhibitor) for locally advanced resectable OSCC. The primary endpoints were safety and major pathological response (MPR). Neoadjuvant camrelizumab plus apatinib was well-tolerated and the MPR rate was 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃ 10 had MPR. Additionally, patients achieving MPR showed more CD4+ T cell infiltration and a higher CD8+/FoxP3+ ratio than those without MPR (p < 0.05), and decreased CD31 and ɑ-SMA expression were observed after neoadjuvant therapy. Our findings demonstrate that neoadjuvant therapy with a chemo-free combination of camrelizumab and apatinib is safe and yields a promising MPR rate, supporting further trials.
Limited Genetic Diversity and High Differentiation in Angelica Dahurica Resulted by Domestication: Insights to Breeding and Conservation
Authors: Huang Rong , Liu Yinrong , Chen Jianling , Lu Zuyu , Wang Jiajia , He Wei , Chao Zhi , Tian Enwei 
Published: December 2021

Abstract
Background： Angelica dahurica, belonging to the Apiaceae family, whose dry root is a famous traditional Chinese medicine named as “Bai zhi”. There are two cultivars (A. dahurica cv. ‘Hangbaizhi’ and A. dahurica cv. ‘Qibaizhi’), which have been domesticated for thousands of years. Long term artificial selection has led to great changes in root phenotypes of the two cultivars, and also decreased their adaptability to environment. We proposed hypothesis that the cultivars may lose some genetic diversity and highly differentiate from wild A. dahurica during the domestication process. However, few studies have been carried out on how domestication affects the genetic variation of this species. Here, we accessed the levels of genetic variation and differentiation within and between wild A. dahurica and its cultivars using 12 SSR markers. Results: The results revealed that the genetic diversity of the cultivars was much lower than that of wild A. dahurica, and A. dahurica cv. ‘Qibaizhi’ had lower genetic diversity compared to A. dahurica cv. ‘Hangbaizhi’. AMOVA analysis showed significant genetic diﬀerentiation between the wild and cultivated A. dahurica, and between A. dahurica cv. ‘Hangbaizhi’ and A. dahurica cv. ‘Qibaizhi’. The results of Bayesian, UPGMA, NJ and PcoA clustering analysis indicated that all 15 populations were assigned to two genetic clusters corresponding to the wild and cultivated resources. Bayesian clustering analysis further divided the cultivated resources into two sub-clusters corresponding to the two cultivars. Conclusions：Our study suggests that domestication process is likely the major factor resulting in the loss of genetic diversity in cultivated A. dahurica and significant genetic differentiation from the wild resources due to founder effect and/or artificially directional selections. This large-scale analysis of population genetics could provide valuable information for genetic resources conservation and breeding programs of Angelica dahurica.
Monitoring of Kidney Functions, Electrolytes and Volemia Analyzed by Application Example of Artificial Intelligence in Patients with Heart Failure
Authors: Tasić Danijela , Đorđević Katarina , Galović Slobodanka , Furudžić Draško , Dimitrijević Zorica , Radenković Sonja 
Published: December 2021

Abstract
Basal renal function is a predictor of response to diuretic therapy and marker of poor prognosis. Simultaneous changes in renal function, sodium, potassium values and their interdependence are key parameters in addition to volemia for the assessment of cardiorenal balance. In our paper, an analysis of volemia, electrolytes, and renal function in heart failure was performed using an algorithm based on the ANFIS (Adoptive Neural Fuzzy Inference System), an intelligent approach to renal and heart function monitoring. The study included 90 subjects who were divided into two groups: clinical (n-80) and control (n-10). The base is composed of parameters B-type natriuretic peptide (NT-proBNP), sodium (Na), potassium (K), ejection fraction (EF), EPI creatinine-cystatin C formula and ANFIS expert system combined in neural network and fuzzy logic network. The results showed that the overall trend of data verification in the network with NT-proBNP, Na and K that we formed is approximately 15%, with which subjects can be classified according to the severity of hypervolemia, electrolyte disturbance and renal function. NT-proBNP (pg/mL) had the most influence on the EPI creatinine-cystatin C formula. Serum sodium (Na) has the most influence on the ejection fraction (EF).
2D Heat Transfer Simulation of an Injection Mold: Comparison Between ANSYS Workbench and ANSYS Mechanical APDL
Authors: Silva Hugo Miguel , Rodrigues Hugo Luís , Noversa João Tiago , Fernandes Leandro , Pontes António José 
Published: December 2021

Abstract
The fabrication of conformal cooling channels (CCC's) has become easier and more affordable due to recent developments in additive manufacturing. The use of CCC's allows better cooling performance than the conventional (straight drilled) channels, in the injection molding process. The main reason for this is that the CCC's can follow the paths of the molded geometry, whereas the conventional channels made by conventional machining techniques are not able to do so. CCCs can help to reduce thermal strains and warpage by reducing cycle time and allowing for a more uniform temperature distribution. CCC, on the other hand, has a more complicated design procedure than traditional channels. Computer-Aided Engineering (CAE) simulations) are crucial to achieve an effective and cost-efficient design. This article focuses the comparison of two ANSYS modules, for results validation. The relative error between ANSYS Workbench and ANSYS Mechanical APDL varied from close to 0 to below 1 %, in the case of maximum temperature Tmax, and between 1.5 to 5.5 approximately, for the average temperature Tavg. It can be concluded that, for the most refined mesh studied, the results are close by the two modules. Therefore, the ANSYS module to work on should be used based on the purpose of the work, as well as the complexity of the CAD geometry.
Family Planning Knowledge, Attitudes and Practices Among Rohingya Women Living in Refugee Camps in Bangladesh: A Cross-Sectional Study
Authors: Azad Md. Abul Kalam , Zakaria Muhammad , Nachrin Tania , Das Madhab Chandra , Cheng Feng , Xu Junfang 
Published: December 2021

Abstract
Background: Considering more than 720,000 Rohingya into Bangladesh, unplanned pregnancy, and serious complications of pregnancy among refugees, this study aims to explore the knowledge, attitude, and practice (KAP) of family planning (FP) and associated factors among the Rohingya women living in the refugee camps in Cox’s Bazar, Bangladesh. Methods: Four hundred Rohingya women were investigated, and data were collected using a structured questionnaire, which included socio-demographic characteristics, awareness of contraceptive methods, knowledge, attitudes and practices on FP. Linear regression analysis was performed to identify the predictors of outcome variables. Results: Of the Rohingya refugee women, 60% were unaware that there is no physical harm in adopting a permanent method of birth control. Half of them lack proper knowledge of whether a girl was eligible for marriage before the age of 18. More than two-thirds think family planning methods should not be used without the husband’s permission. Besides, 40% were ashamed and afraid to discuss family planning matters with their husbands, considering it as a sin. Of them, 58% had the opinion that a couple should continue bearing children until a son is born. Linear regression analyses demonstrated that Racidong in Myanmar as the region of residence, being professional, number of children, physician/nurse being the source of FP knowledge, having FP interventions in the camp, participating in a FP program, visiting a health facility, and talking with a health care provider on FP were significantly associated with Rohingya women’s better KAP of FP. Conclusions: The study showed that Rohingya refugee women are a marginalized population in family planning and the comprehensive FP-KAP capability was low. Contraceptives among the Rohingyas are unpopular, mainly due to a lack of education and family planning awareness. In addition, family planning initiatives among Rohingya refugees were limited by some traditional cultural and religious beliefs. Therefore, strengthening FP interventions and increasing the accessibility to essential health services and education are indispensable in order to improve maternal health among refugees.