bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stem cells modulate IL-17 and IL-9 production induced by Th17-inducing cytokine conditions in autoimmune arthritis: an explorative analysis
Authors: Riekert Maximilian , Almanzar Giovanni , Schmalzing Marc , Schütze Norbert , Jakob Franz , Prelog Martina 
Published: July 2022

Abstract
Background
The importance of proinflammatory T-cells and their cytokine production in patients with autoimmune arthritis has been widely described. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have come into focus as a potential therapeutic concept. The aim of this study was to investigate the influence of MSCs on the phenotype, cytokine profile, and functionality of naive and non-naive CD4+ T-cells from healthy donors (HD) and patients with autoimmune arthritis under Th17-cytokine polarizing conditions in an explorative way using a transwell system prohibiting any cell-cell-contact.
Methods
Magnetically isolated naive and non-naive CD4+ T-cells were stimulated under Th17-polarizing proinflammatory cytokine conditions in presence and absence of bone marrow derived mesenchymal stromal cells (MSCs). After an incubation period of six days, the proportions of the T-cell subpopulations TEMRA (CD45RA+CD27−), memory (CD45RA−CD27+), effector (CD45RA−CD27−) and naive cells (CD45RA+CD27+) were determined. Quantitative immunofluorescence intensity was used as a measure for IL-9, IL-17 and IFN-γ production in each subpopulation.
Results
In isolated naive CD4+ T-cells from HD and patients, MSCs suppressed the differentiation of naive towards an effector phenotype while memory and naive cells showed higher percentages in culture with MSCs. In patients, MSCs significantly decreased the proportion of IL-9 and IL-17 producing effector T-cells. MSCs also reduced IFN-γ production in the naive and memory phenotype from HD.
Conclusion
The results of the study indicate significant immunomodulatory properties of MSCs, as under Th17-polarizing conditions MSCs are still able to control T-cell differentiation and proinflammatory cytokine production in both HD and patients with autoimmune arthritis.
Tirofiban combined with mechanical thrombectomy may improve the outcome of acute ischemic stroke patients with higher initial NIHSS score: a case control study
Authors: Cai Lingxin , Wang Tingting , Chen Aiqing , Ling Chenhan , Xu Liang , Xu Jing , Qian Cong , Chen Gao 
Published: July 2022

Abstract
Background
Tirofiban has recently shown encouraging efficacy and safety among acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). However, the benefits of tirofiban varied among studies depending on the patient’s condition, which was often not well analyzed. This study aimed to identify the characteristics of patients who may obtain the largest benefits from tirofiban.
Methods
The efficacy endpoint was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0 ~ 2 at 90 days. The safety endpoints were intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Adjusted logistic regression analysis and subgroup analyses were utilized to investigate the factors associated with tirofiban and the outcome.
Results
285 patients fit the inclusion criteria. Tirofiban was associated with a higher rate of favorable outcome (aOR 2.033, 95% CI, 1.002 ~ 4.123, P = 0.043) but not with an increased risk of ICH, sICH or mortality (P > 0.05). Moreover, subgroup analyses revealed that tirofiban was associated with favorable outcomes in patients with NIHSS > 14 (aOR 2.778, 95% CI 1.056 ~ 7.356, P = 0.038) but not in patients with NIHSS ≤ 14 (aOR 1.719, 95% CI 0.646 ~ 4.578, P = 0.278). No significant heterogeneity was found in the effect of tirofiban across the subgroups of age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology (P for interaction > 0.05).
Conclusions
Tirofiban was associated with an increased rate of favorable outcomes in patients with anterior circulation AIS undergoing MT and may be more beneficial for patients with moderate and severe stroke. Further studies are needed to confirm this finding.
Transcript shortening through alternative polyadenylation promotes gene expression during fracture healing
Authors: Elbarbary Reyad , Khajuria Deepak Kumar , Nowak Irena , Leung Ming , Karuppagounder Vengadeshprabhu , Imamura Yuka , Norbury Christopher , Kamal Fadia 
Published: July 2022

Abstract
Maturation of the 3´ end of almost all eukaryotic messenger RNAs (mRNAs) requires cleavage and polyadenylation. Most mammalian mRNAs are polyadenylated at different sites within the last exon, generating alternative polyadenylation (APA) isoforms that have the same coding region but distinct 3´ untranslated regions (UTRs). The 3´UTR contains motifs that regulate mRNA metabolism; thus, changing the 3´UTR length via APA can significantly impact gene expression. Endochondral ossification is a central process in bone healing, and the impact of APA on gene expression during this process is unknown. Here, we report widespread utilization of APA that impacts multiple pathways with established roles in bone healing. Importantly, progression of endochondral ossification is typified by global 3´UTR shortening that is coupled with an increased abundance of shortened transcripts as compared to all other transcripts, underscoring the role of APA in promoting gene expression during endochondral bone formation. Our mechanistic studies of genes that undergo APA in the fracture callus uncover an intricate regulatory network in which APA boosts the expression of collagen, type I, alpha 1 (Col1a1) and Col1a2 genes, which encode the 2 subunits of the abundantly expressed protein collagen 1. APA does so via shortening the 3´UTRs of Col1a1 and Col1a2 mRNAs, which removes the binding sites of miR-29a-3p that otherwise potently triggered the degradation of both transcripts. Taken together, our study takes the lead in characterizing crucial roles of APA in tailoring the 3´UTR landscape and regulating gene expression during fracture healing.
Searcher Struggle Detection via the Reversal Theory
Authors: Luo Jiyun , Yang Yan , Nayak Valerie , Yang Grace Hui 
Published: July 2022

Abstract
Searcher struggle is important feedback to Web search engines. Existing Web search struggle detection methods rely on effort-based features to identify the struggling moments. Their underlying assumption is that the more effort a user spends, the more struggling the user may be. However, recent studies have suggested this simple association might be incorrect. This paper proposes a new feature modulation method for struggle detection and refers to the reversal theory in psychology. The reversal theory (RT) points out that instead of having a static personality trait, people constantly switch between opposite psychological states, complicating the relationship between the efforts they spend and the level of frustration they feel. Supported by the theory, our method modulates the effort-based features based on reversal theory’s bi-modal arousal model. Evaluations on week-long Web search logs confirm that the proposed method can statistically significantly improve state-of-the-art struggle detection methods.
Prediction of Obesity in Early and Late Childhood Based on Growth Trajectory During Infancy
Authors: Moschonis George , Halilagic Anela , Karaglani Eva , Mavrogianni Christina , Collins Clare , Manios Yannis 
Published: July 2022

Abstract
Childhood obesity rates have reached epidemic levels with Mediterranean countries reporting among the highest numbers globally. Evidence suggests early life factors, including infant growth rate, increase the risk of obesity later in childhood. However, optimal rates of infant growth associated with lower future obesity risk remains undetermined. The study aim was to determine the optimal infant growth rate associated with a lower risk of childhood overweight and obesity. Perinatal and anthropometric data collected from 1,778 Greek preschool (2–5 years old) and 2,294 Greek preadolescent (10–12 years old) children participating in the ToyBox and the Healthy Growth Study (HGS) respectively, was combined for examination. Logistic regression models and receiver operating curves were used to determine the association between infant growth rate and development of childhood overweight and obesity, as well as optimal infant growth rate, respectively. Rapid weight gain during the first 6 months of life was positively associated with overweight and obesity in preadolescent children (OR:1.36, 95% CI: 1.13–1.63). Optimal cut-off points for several infancy growth rate indices (i.e., WAZ, WLZ, HAZ, BAZ) associated with a lower risk of overweight and obesity in preschool years and preadolescence were also identified. The current findings have the potential to guide health professionals in monitoring infant growth to prevent childhood overweight and obesity, through timely identification of those at high risk and effective early intervention.
Novel methods for solving Multi-objective Non linear Inventory Model Of Highly Deteriorating Items
Authors: Sahoo Anuradha , Panda Minakshi 
Published: July 2022

Abstract
In this study, multi-objective inventory model of deteriorating and perishable items is developed under space and budget constraints. Demand is stock dependent and power function of time. This model is completely a new model in the sense that the model is applied to those items whose deterioration rate is maximum. Shortages are allowed in each cycle. The main aim of this paper is to find different time points for each cycle where shortage occurs and inventory depletes respectively so that both total cost and shortage cost can be minimized simultaneously. The model is developed in both crisp and fuzzy environment. In fuzzy environment, the objectives are considered as fuzzy constraints. For this the decision maker needs to establish an aspiration level for the objective functions which he wants to achieve as far as possible. This paper aims to use fuzzy non-linear programming (FNLP) and intuitionistic fuzzy optimization (IFO) techniques for the multi-objective inventory model. Comparison is based on different optimization techniques in different environment using numerical examples. Graph of the objective functions are provided. System diagram of the model and algorithm for solving the model are provided. Also, sensitivity analysis is made using different parameters of the model.
Experience of memory: transfer of the motor feeling of fluency linked to our interaction with the environment
Authors: brouillet denis 
Published: July 2022

Abstract
In the field of memory, it is now admitted that an experience of memory is not only the consequence of the activation of a precise content, but also results from an inference associated with the transfer of the manner in which the process was carried out (i.e., fluency) in addition to the transfer of the process itself. The aim of this work was to show that experience of memory is also associated with the fluency that is due to the transfer of a processing carried out in our interactions with our past environment. Firstly, participants performed a perceptual discrimination task (geometric shapes: circle or square) that involves a fluent or a non-fluent gesture to respond. Motor fluency vs. non-fluency was implicitly associated with the colour of the geometric shapes. Secondly, participants had to perform a classical memory recognition task. During the recognition phase, items appeared either with the colour associated with motor fluency or with the colour associated with motor non-fluency. We used a Go-NoGo task to avoid having a confused factor (response space). Results show that items were better recognised with a colour associated with motor fluency than with a colour associated with non-motor fluency. These findings support the idea that an experience of memory is also associated with the transfer of the motor feeling of fluency linked to our interaction with the environment.
Emerging burden of alcohol, drug, and tobacco use initiations among 303,519 school-going adolescents in 92 countries
Authors: Mahumud Rashidul Alam , Rahman Md. Ashfikur , Dawson Angela , Sahle Berhe W. , Kamara Joseph Kihika , Haque Mohammad Enamul , kundu Satyajit , Alam Khorshed , Renzaho Andre M.N. 
Published: July 2022

Abstract
Adolescent alcohol, drug, and tobacco use is an emerging public health concern in low and middle-income countries (LMICs) and high-income countries (HICs). Yet, there is a lack of reliable, national-level data to inform policies and prevention interventions. This study aimed to provide the best available associations of global and regional risk and protective factors of the early initiation of alcohol, drugs, and tobacco use (before 14 years or 14–17 years old) amongst school–going adolescents. A total of 303,519 adolescents participated in this study. They were drawn from 92 countries in the latest Global School–based Student Health Survey of school children aged 14–17 years. Our analysis covered the period between 2003 and 2015 for which data are available, grouped according to the six World Health Organization (WHO) regions. The pooled weighted prevalence of early initiation of alcohol, drug and tobacco use amongst adolescents (aged <14 years) was 15·37% (28·19% for aged 14–17 years), 3·86% (6·78% for aged 14–17 years), and 6·21% (vs. 16·20% for aged 14–17 years), respectively. The prevalence of the initiation of drinking alcohol (42·60%) and drug use (8·30%) were also pronounced among adolescents in high-income countries, HICs compared to low-income countries, LICs (16·07% for drinking alcohol and 5·53% for drug use) and lower-middle income countries, LMICs (15·50% for drinking alcohol and 5·24% for drug use). One in five adolescents (20·53%) had started drinking alcohol before they were 14 years old in the Western Pacific and Americas Regions, followed by 11·91% in the African region and 5·11% in South–East Asian region. The prevalence of drug use was highest for the Americas region (5·66% aged <14 years and 8·14% aged between 14–17 years old) and lowest in the South–East Asia region (1·18% of adolescents aged <14 years and 4·40% of adolescents aged 14–17 years). In addition, the pooled prevalence of tobacco use (adolescents <14 years) was more than double among adolescents in HICs (21·28%) compared to adolescents in LMICs (10·10%) and in LICs (9·63%). The early initiation of alcohol, drug and tobacco use was associated with being physically attacked, physical fighting, high levels of anxiety, feeling lonely, being bullied, a lack of parental support and close friends, poor peer support and high levels of sedentary behaviour. We found similar associations across six WHO regions and country income groups (LICs–HICs). School–based prevention efforts that promote a healthy lifestyle and environmental change are urgently needed.
Novel Method for Establishing a Beagle Dog Model of GI-ARS
Authors: Xu Yin , Zuo Zongchao , Ouyang Zhangyi , Wang Limei , Wang Xinmei , Cong Yuwen 
Published: July 2022

Abstract
The widespread use of nuclear energy and nuclear facilities has dramatically increased the risks associated with nuclear radiation exposure. Effective radioprotective agents that are easy to administer and have low toxicity are urgently needed to minimize the significant harm caused by exposure to nuclear radiation. Appropriate animal models are also required for investigation of the effectiveness of radioprotective agents. However, the animal models presently used to study the intestinal form of acute radiation sickness (ARS) are limited mainly to rodents, and large animal models (for example, Beagle dogs and non-human primates) are still under exploration. We have developed a Beagle model for investigation of GI-ARS in which the head, chest, and extremities are shielded to reduce the possibility of bleeding and/or damage to other more sensitive organs and rehydration support is provided after irradiation of 12.5 Gy with 60Co γ-rays. Significant vomiting and diarrhea were seen in this model, with typical signs of radiation sickness that progressively worsened with time since irradiation. The 6-day mortality rate was 100%, and significant intestinal damage was observed on gross autopsy and histopathology. By reflecting GI-ARS based on relatively objective evaluation of clinical manifestations and histopathological examination, this model provides a new concept and methodology for further experimental evaluation of the effectiveness of radioprotective agents in animals.
A novel method for design and implementation of systolic associative cascaded variable leaky least mean square adaptive filter for denoising of ECG signals
Authors: Manickam Chitra , Govindasamy Murugesan , Muthusamy Suresh , Paramasivam Muneeshwari 
Published: July 2022

Abstract

The most essential diagnostic test for heart disease detection is the electrocardiogram (ECG). It has a low frequency and a small amplitude, making it vulnerable to a variety of stimuli, including high/low-frequency noises. As a result, the diagnostic quality suffers. ECG signal analysis deals with the major problem of removing the noise from ECG signal. Implementation of adaptive filter removes noise from the signal in a better way. Adaptive filters in signal processing plays a major role in biomedical applications for denoising different types of noises such as Power Line Interference (PLI) noise which is generated by the power line electromagnetic field and it exhibits its peak from 50Hz to 60Hz, Baseline Wander (BW) noise which occurs due to the variation of electrode skin impedance, Motion Artifacts (MA) which is generated by the electrode motions away from the contact zone on the skins and Muscle Noise, this is due to the Electromyographic signals (EMG), originating from the skeletal muscle contractions. In order to eliminate the above-mentioned noises, the most common adaptive filters such as Least Mean Square (LMS) and Recursive Least Squares (RLS) are used. In existing method, they used Cascaded Least Mean Square adaptive filters to reduce noises at a much higher rate than the Least Mean Square Adaptive filter and to achieve the higher Signal to Noise Ratio (SNR). The Cascaded RLS filter can be used to obtain faster range of convergence than the Cascaded LMS. But the problem is that while using RLS filters the computational complexity will increase and as well as the delay will also increase. So, in order to counteract these problems, Cascaded Leaky Least Mean Square filter is designed not only to increase the rate of convergence and SNR and stability but also to reduce the computational complexity. The filter is designed with adaptive variable step size which calculates the step size according to the input signal of the filter, this is used to increase the stability of the filter. The systolic architecture and associativity of the VLLMS filter is implemented to reduce the number of adders and multipliers along the critical path of the filter. This systolic architecture increases the SNR of the filter and systolic combined with associativity reduces the delay and area of the filter. The work comprises of designing the 4 tap, 8 tap and 16 tap cascaded systolic associative variable leaky least mean square adaptive filters using Simulink and the SNR comparisons have been made between normal LMS cascaded filter and cascaded VLLMS filter. The area and delay between normal filter and systolic associative filter are compared by converting the Simulink design into Verilog and by implementing in Xilinx.
FUNDC1 Protects against Doxorubicin-Induced Cardiomyocyte PANoptosis through Stabilizing mtDNA via Interaction with TUMF
Authors: Bi Yaguang , Xu Haixia , Zhu Hong , Wang Xiang , Zhang Yingmei , Ren Jun 
Published: July 2022

Abstract
Doxorubicin (DOX) is an effective anti-cancer anthracyclines chemotherapy drug with its potentially life-threatening cardiotoxicity severely limiting its clinical application. Mitochondrial damage-induced cardiomyocyte death is considered an essential cue for DOX cardiotoxicity. FUN14 domain containing 1 (FUNDC1) is a mitochondrial membrane protein participating in the regulation of mitochondrial integrity in multiple diseases although its role in DOX cardiomyopathy remains elusive. Here we examined whether PANoptosis, a novel type of programmed cell death closely associated with mitochondrial damage, was involved in DOX-induced heart injury, and whether FUNDC1 regulated cardiomyocyte PANoptosis. FUNDC1 was downregulated in heart tissues in patients with dilated cardiomyopathy (DCM) and DOX-challenged mice. FUNDC1 deficiency aggravated DOX-induced cardiac dysfunction, mitochondrial injury and cardiomyocyte PANoptosis. Further examination revealed that FUNDC1 countered against cytoplasmic release of mitochondrial DNA (mtDNA) and activation of PANoptosome through interaction with mitochondrial Tu translation elongation factor (TUFM), a key factor in the translational expression and repair of mitochondrial DNA, via its 96–133 amino acid domain. TUFM intervention reversed FUNDC1-elicited protection against DOX-induced mtDNA cytosolic release and cardiomyocyte PANoptosis. These findings shed light towards the protective role of FUNDC1 against DOX cardiotoxicity and cardiomyocyte PANoptosis, which provides a potentially therapeutic approach for Dox induced cardiotoxicity.
Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin
Authors: Gao Chongqing , Chu Zhenzhen , Xiao Yang , Zhou Xingyan , Wu Junru , Yuan Hui , Jiang Yuchuan , Chen Dong , Zhang Ji-chun , Yao Nan , Chen Kaiyun , HONG JIAN 
Published: July 2022

Abstract
Intrahepatic Cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy with limited therapeutic options. Metastasis is one of the main contributors to ICC progression and poor prognosis. However, the underlying mechanism of ICC metastasis remains largely unknown. Here, we showed that TANK-binding kinase 1 (TBK1), a serine/threonine-protein kinase, was significantly upregulated in tumor tissues of ICC patients with larger tumor diameter, lymph node metastasis, and advanced TNM stage. Consistently, during the different stages of Cholangiocarcinoma (CCA) carcinogenesis (hyperplasia, dysplasia, and CCA), TBK1 showed a dynamic increase in spontaneous rat and mouse models. Functional studies showed that enforced expression of TBK1 promoted metastasis both in vitro and in vivo. Mechanistically, TBK1 directly interacts with β-catenin and stimulates its nuclear translocation, further activating the β-catenin-mediated epithelial-mesenchymal transition (EMT) process. Moreover, we demonstrate that the S172 site of TBK1 kinase domain was essential for the interaction between TBK1 and β-catenin as well as for TBK1 mediated β-catenin activation. In addition, high levels of TBK1 in clinical ICC tissues were correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. A TBK1 inhibitor GSK-8612 and the liver-specific accumulation of DNA/RNA heteroduplex oligonucleotide (TBK1-HDO) significantly reduced TBK1 expression of ICC and inhibited its intrahepatic metastasis. In summary, our study demonstrated that TBK1 could activate β-catenin via protein-protein interaction, then promote EMT and ICC metastasis, which might serve as a potential therapeutic target for patients with cholangiocarcinoma.