bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of anger suppression and preoccupied attachment in social anxiety disorder: a cross-sectional study
Authors: Conrad Rupert , Forstner Andreas J. , Chung Man-Long , Mücke Martin , Geiser Franziska , Schumacher Johannes , Carnehl Friederike 
Published: February 2021

Abstract
Background
There is evidence for the relevance of attachment style and anger expression for the manifestation of social anxiety disorder (SAD).

Method
In a cross-sectional study 321 individuals with social anxiety disorder (41% men, age 38.8 ± 13.9) were compared with 94 healthy controls (37% men, age 35.8 ± 15.1) on several questionnaires (Attachment Styles Questionnaire, State Trait Anger Inventory, Social Phobia Inventory, Beck Depression Inventory).

Results
Individuals with SAD showed moderate-sized reduced levels of secure and large-sized increased levels of fearful and preoccupied attachment style compared to healthy controls (all p < 0.001) as well as small-sized increased levels of trait anger (p = 0.03) and moderate-sized increased levels of anger-in (p < 0.001). Attachment style and anger regulation could predict 21% (R2 = 0.21, p < 0.001) of the extent of social anxiety (SPIN) in SAD; secure (β = − 0.196, p < 0.01) and preoccupied attachment style (β = 0.117, p < 0.05), as well as anger-in (β = 0.199, p < 0.01) were significant cross-sectional predictors. Further analysis revealed that the relationship between preoccupied attachment and social anxiety is partially mediated by anger-in.

Conclusion
Study findings confirm the relevance of preoccupied attachment style and anger suppression for social anxiety. Disentangling the role of anger regulation in early attachment patterns has significant therapeutic implications in SAD.
Gene expression in tonsils in swine following infection with porcine reproductive and respiratory syndrome virus
Authors: Dong Qian , Lunney Joan K. , Lim Kyu-Sang , Nguyen Yet , Hess Andrew S. , Beiki Hamid , Rowland Raymond R. R. , Walker Kristen , Reecy James M. , Tuggle Christopher K. , Dekkers Jack C. M. 
Published: February 2021

AbstractBackgroundPorcine reproductive and respiratory syndrome (PRRS) is a threat to pig production worldwide. Our objective was to understand mechanisms of persistence of PRRS virus (PRRSV) in tonsil. Transcriptome data from tonsil samples collected at 42 days post infection (dpi) were generated by RNA-seq and NanoString on 51 pigs that were selected to contrast the two PRRSV isolates used, NVSL and KS06, high and low tonsil viral level at 42 dpi, and the favorable and unfavorable genotypes at a genetic marker (WUR) for the putative PRRSV resistance geneGBP5.ResultsThe number of differentially expressed genes (DEGs) differed markedly between models with and without accounting for cell-type enrichments (CE) in the samples that were predicted from the RNA-seq data. This indicates that differences in cell composition in tissues that consist of multiple cell types, such as tonsil, can have a large impact on observed differences in gene expression. Based on both the NanoString and the RNA-seq data, KS06-infected pigs showed greater activation, or less inhibition, of immune response in tonsils at 42 dpi than NVSL-infected pigs, with and without accounting for CE. This suggests that the NVSL virus may be better than the KS06 virus at evading host immune response and persists in tonsils by weakening, or preventing, host immune responses. Pigs with high viral levels showed larger CE of immune cells than low viral level pigs, potentially to trigger stronger immune responses. Presence of high tonsil virus was associated with a stronger immune response, especially innate immune response through interferon signaling, but these differences were not significant when accounting for CE. Genotype at WUR was associated with different effects on immune response in tonsils of pigs during the persistence stage, depending on viral isolate and tonsil viral level.ConclusionsResults of this study provide insights into the effects of PRRSV isolate, tonsil viral level, and WUR genotype on host immune response and into potential mechanisms of PRRSV persistence in tonsils that could be targeted to improve strategies to reduce viral rebreaks. Finally, to understand transcriptome responses in tissues that consist of multiple cell types, it is important to consider differences in cell composition.
Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications
Authors: Saw Eng Leng , Pearson James T. , Schwenke Daryl O. , Munasinghe Pujika Emani , Tsuchimochi Hirotsugu , Rawal Shruti , Coffey Sean , Davis Philip , Bunton Richard , Van Hout Isabelle , Kai Yuko , Williams Michael J. A. , Kakinuma Yoshihiko , Fronius Martin , Katare Rajesh 
Published: February 2021

Abstract
Background
Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (M2AChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism. Impairment of these functions are hallmarks of diabetic heart disease (DHD). The role of the NNCS in DHD is unknown. The aim of this study was to examine the effect of diabetes on cardiac NNCS and determine if activation of cardiac NNCS is beneficial to the diabetic heart.

Methods
Ventricular samples from type-2 diabetic humans and db/db mice were used to measure the expression pattern of NNCS components (ChAT, CHT1, VAChT, AChE and M2AChR) and glucose transporter-4 (GLUT-4) by western blot analysis. To determine the function of the cardiac NNCS in the diabetic heart, a db/db mouse model with cardiac-specific overexpression of ChAT gene was generated (db/db-ChAT-tg). Animals were followed up serially and samples collected at different time points for molecular and histological analysis of cardiac NNCS components and prosurvival and proangiogenic signaling pathways.

Results
Immunoblot analysis revealed alterations in the components of cardiac NNCS and GLUT-4 in the type-2 diabetic human and db/db mouse hearts. Interestingly, the dysregulation of cardiac NNCS was followed by the downregulation of GLUT-4 in the db/db mouse heart. Db/db-ChAT-tg mice exhibited preserved cardiac and vascular function in comparison to db/db mice. The improved function was associated with increased cardiac ACh and glucose content, sustained angiogenesis and reduced fibrosis. These beneficial effects were associated with upregulation of the PI3K/Akt/HIF1α signaling pathway, and increased expression of its downstream targets—GLUT-4 and VEGF-A.

Conclusion
We provide the first evidence for dysregulation of the cardiac NNCS in DHD. Increased cardiac ACh is beneficial and a potential new therapeutic strategy to prevent or delay the development of DHD.
Production of bio-xylitol from d-xylose by an engineered Pichia pastoris expressing a recombinant xylose reductase did not require any auxiliary substrate as electron donor
Authors: Louie Tai Man , Louie Kailin , DenHartog Samuel , Gopishetty Sridhar , Subramanian Mani , Arnold Mark , Das Shuvendu 
Published: February 2021

Abstract
Background
Xylitol is a five-carbon sugar alcohol that has numerous beneficial health properties. It has almost the same sweetness as sucrose but has lower energy value compared to the sucrose. Metabolism of xylitol is insulin independent and thus it is an ideal sweetener for diabetics. It is widely used in food products, oral and personal care, and animal nutrition as well. Here we present a two-stage strategy to produce bio-xylitol from d-xylose using a recombinant Pichia pastoris expressing a heterologous xylose reductase gene. The recombinant P. pastoris cells were first generated by a low-cost, standard procedure. The cells were then used as a catalyst to make the bio-xylitol from d-xylose.

Results
Pichia pastoris expressing XYL1 from P. stipitis and gdh from B. subtilis demonstrated that the biotransformation was very efficient with as high as 80% (w/w) conversion within two hours. The whole cells could be re-used for multiple rounds of catalysis without loss of activity. Also, the cells could directly transform d-xylose in a non-detoxified hemicelluloses hydrolysate to xylitol at 70% (w/w) yield.

Conclusions
We demonstrated here that the recombinant P. pastoris expressing xylose reductase could transform d-xylose, either in pure form or in crude hemicelluloses hydrolysate, to bio-xylitol very efficiently. This biocatalytic reaction happened without the external addition of any NAD(P)H, NAD(P)+, and auxiliary substrate as an electron donor. Our experimental design & findings reported here are not limited to the conversion of d-xylose to xylitol only but can be used with other many oxidoreductase reactions also, such as ketone reductases/alcohol dehydrogenases and amino acid dehydrogenases, which are widely used for the synthesis of high-value chemicals and pharmaceutical intermediates.
Eliminating Plasmodium falciparum malaria: results from tailoring active case detection approaches to remote populations in forested border areas in north-eastern Cambodia
Authors: Stratil Ann-Sophie , Vernaeve Lieven , Lopes Sergio , Bourny Yves , Mannion Kylie , Hamade Prudence , Roca-Feltrer Arantxa , Tibenderana James K. , Sovannaroth Siv , Debackere Mark 
Published: February 2021

Abstract
Background
Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From January 2018 to December 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of falciparum malaria.

Methods
Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Testing for malaria was conducted independent of fever symptoms. Routine monitoring of programmatic data informed tactical adaptations, while supervision exercises ensured service quality.

Results
Despite operational challenges, service delivery sites were able to maintain consistently high testing rates throughout the implementation period, with each of 45 sites testing a monthly average of 64 (SD 6) people in 2020. In 2020, project MMWs detected only 32 P. falciparum cases. Over the project period, the P. falciparum/P. vivax ratio steadily inversed. Including data from neighbouring health centres and village malaria workers, 45% (80,988/180,732) of all people tested and 39% (1280/3243) of P. falciparum cases detected in the area can be attributed to project MMWs. Remaining challenges of the last elimination phase include maintaining intensified elimination efforts, addressing the issue of detecting low parasitaemia cases and shifting focus to P. vivax malaria.

Conclusions
Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. This case study presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.
A cohort study on risk factors of high-density lipoprotein cholesterol hypolipidemia among urban Chinese adults
Authors: Tang Fang , Wang Jian , Nicholas Stephen , Qian Dongfu , Liu Rugang 
Published: February 2021

Abstract
Background
High-density lipoprotein cholesterol (HDL-C) hypolipidemia, a major type of dyslipidemia, has been associated with many kinds of diseases, such as stroke, coronary heart disease, obesity and diabetes, and has displayed an increasing prevalence in China. This study explores the risk factors of HDL-C hypolipidemia and makes recommendations for controlling and preventing HDL-C hypolipidemia and the diseases caused by it.

Methods
Using a retrospective cohort study design, 26,863 urban adults without dyslipidemia, diabetes, cardiovascular and cerebrovascular diseases, hepatosis, renal insufficiency and thyroid diseases were enrolled in the study between 2010 and 2015. Data on each individual were collected at the 2010 baseline year and at a follow-up medical check. A Cox regression model was constructed to evaluate the influence of potential risk factors on the outcome event- HDL-C hypolipidemia.

Results
The incidence of HDL-C hypolipidemia was 5.7% (1531/26863). Sex, age, body mass index (BMI), HDL-C, triglyceride (TG) and urea nitrogen (UN) were significant risk factors of HDL-C hypolipidemia. Men were more likely to develop HDL-C hypolipidemia than women during follow-up medical checks (HR = 1.258, P = 0.014). The incidence of HDL-C hypolipidemia in the over 65 years old group was higher than that of the ≤65 age group (HR = 1.276, P = 0.009). The incidence of HDL-C hypolipidemia increased with increasing BMI (HR = 1.030, P = 0.002), TG (HR = 1.321, P = 0.001) and UN (HR = 1.054, P = 0.019), while falling with increasing HDL-C in the baseline year (HR = 0.002, P < 0.001).

Conclusions
Men, aged over 65, with high BMI were at the highest risk of developing HDL-C hypolipidemia. Measures should be taken to prevent HDL-C hypolipidemia even for healthy urban adults whose blood biochemical indicators were in the normal range when their level of TG, UN and HDL-C are closed to the border of the normal value range.
L-plastin Ser5 phosphorylation is modulated by the PI3K/SGK pathway and promotes breast cancer cell invasiveness
Authors: Machado Raquel A. C. , Stojevski Dunja , De Landtsheer Sébastien , Lucarelli Philippe , Baron Alexandre , Sauter Thomas , Schaffner-Reckinger Elisabeth 
Published: February 2021

Abstract
Background
Metastasis is the predominant cause for cancer morbidity and mortality accounting for approximatively 90% of cancer deaths. The actin-bundling protein L-plastin has been proposed as a metastatic marker and phosphorylation on its residue Ser5 is known to increase its actin-bundling activity. We recently showed that activation of the ERK/MAPK signalling pathway leads to L-plastin Ser5 phosphorylation and that the downstream kinases RSK1 and RSK2 are able to directly phosphorylate Ser5. Here we investigate the involvement of the PI3K pathway in L-plastin Ser5 phosphorylation and the functional effect of this phosphorylation event in breast cancer cells.

Methods
To unravel the signal transduction network upstream of L-plastin Ser5 phosphorylation, we performed computational modelling based on immunoblot analysis data, followed by experimental validation through inhibition/overexpression studies and in vitro kinase assays. To assess the functional impact of L-plastin expression/Ser5 phosphorylation in breast cancer cells, we either silenced L-plastin in cell lines initially expressing endogenous L-plastin or neoexpressed L-plastin wild type and phosphovariants in cell lines devoid of endogenous L-plastin. The established cell lines were used for cell biology experiments and confocal microscopy analysis.

Results
Our modelling approach revealed that, in addition to the ERK/MAPK pathway and depending on the cellular context, the PI3K pathway contributes to L-plastin Ser5 phosphorylation through its downstream kinase SGK3. The results of the transwell invasion/migration assays showed that shRNA-mediated knockdown of L-plastin in BT-20 or HCC38 cells significantly reduced cell invasion, whereas stable expression of the phosphomimetic L-plastin Ser5Glu variant led to increased migration and invasion of BT-549 and MDA-MB-231 cells. Finally, confocal image analysis combined with zymography experiments and gelatin degradation assays provided evidence that L-plastin Ser5 phosphorylation promotes L-plastin recruitment to invadopodia, MMP-9 activity and concomitant extracellular matrix degradation.

Conclusion
Altogether, our results demonstrate that L-plastin Ser5 phosphorylation increases breast cancer cell invasiveness. Being a downstream molecule of both ERK/MAPK and PI3K/SGK pathways, L-plastin is proposed here as a potential target for therapeutic approaches that are aimed at blocking dysregulated signalling outcome of both pathways and, thus, at impairing cancer cell invasion and metastasis formation.
CircAGAP1 promotes tumor progression by sponging miR-15-5p in clear cell renal cell carcinoma
Authors: Lv Qi , Wang Gangmin , Zhang Yinan , Shen Aijun , Tang Junjun , Sun Yi , Ma Chunhui , Wang Peijun 
Published: February 2021

Abstract
Background
Accumulating evidence has revealed that circular RNAs (circRNAs), as novel noncoding RNAs, play critical roles in carcinogenesis and tumor progression. However, the functions and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) are largely unknown.

Methods
The expression and functions of circAGAP1 were identified in clinical samples, ccRCC cells and in vivo animal models. The molecular mechanism of circAGAP1 was investigated by fluorescence in situ hybridization, RNA immunoprecipitation and luciferase assays.

Results
circAGAP1 (circ0058792) expression was significantly upregulated in ccRCC tissues compared to adjacent nontumor tissues. Moreover, the expression of circAGAP1 was closely related to the tumor size, nuclear grade and clinical stage of ccRCC in patients. Mechanistic studies demonstrated that cytoplasmic circAGAP1 targeted miR-15-5p in an RNA-induced silencing complex. Additionally, miR-15-5p expression was downregulated in ccRCC. Luciferase reporter assays showed that E2F transcription factor 3 (E2F3) was a target of miR-15-5p, and upregulated E2F3 expression was positively correlated with circAGAP1 in ccRCC. Furthermore, the tumor-promoting functions of circAGAP1 could be alleviated by miR-15-5p mimics in vitro and in vivo.

Conclusion
Our results clarify that circAGAP1 exerts its oncogenic functions as a competitive endogenous RNA (ceRNA) by sponging miR-15-5p, which promotes E2F3 expression. Targeting circAGAP1 might be a new attractive therapeutic strategy in ccRCC.
Quarantine due to the COVID-19 pandemic from the perspective of adolescents: the crucial role of technology
Authors: Salzano Giuseppina , Passanisi Stefano , Pira Francesco , Sorrenti Lacrima , La Monica Giuseppa , Pajno Giovanni Battista , Pecoraro Maria , Lombardo Fortunato 
Published: February 2021

Abstract
Background
The year 2020 will be remembered as the “year of the COVID-19 pandemic”. The world population had to familiarize themselves with words as swabs, personal protective equipment, pandemic. To curb the wave of the pandemic, almost all the countries imposed self-isolation and social distancing. We conducted a web-based survey to investigate the behavioural responses during the quarantine due to the COVID-19 pandemic.

Methods
Participants were 1860 youth aged 12–18 years attending lower secondary schools and upper secondary schools. Data were collected on demographic characteristics, lifestyle changes during the quarantine period, and the psychological impact of the lock-down on adolescents’ life.

Results
Most adolescents experienced feelings of fear, discouragement, and anxiety which strongly affected the approach to their daily lifestyles. Most of the surveyed subjects reported having used this period to acquire new skills and to practice physical activities at home. The use of technology was predominant both for recreational activities and educational purposes.

Conclusions
Despite the strong psychological impact of the quarantine, adolescents showed good levels of resilience. Technology played a crucial role during the quarantine for young subjects who have increased the daily use of technological devices to stay connected with the rest of the world.
Potential impact of flooding on schistosomiasis in Poyang Lake regions based on multi-source remote sensing images
Authors: Xue Jing-Bo , Wang Xin-Yi , Zhang Li-Juan , Hao Yu-Wan , Chen Zhe , Lin Dan-Dan , Xu Jing , Xia Shang , Li Shi-Zhu 
Published: February 2021

AbstractBackgroundFlooding is considered to be one of the most important factors contributing to the rebound ofOncomelania hupensis, a small tropical freshwater snail and the only intermediate host ofSchistosoma japonicum, in endemic foci. The aim of this study was to assess the risk of intestinal schistosomiasis transmission impacted by flooding in the region around Poyang Lake using multi-source remote sensing images.MethodsNormalized Difference Vegetation Index (NDVI) data collected by the Landsat 8 satellite were used as an ecological and geographical suitability indicator ofO. hupensishabitats in the Poyang Lake region. The expansion of the water body due to flooding was estimated using dual-polarized threshold calculations based on dual-polarized synthetic aperture radar (SAR). The image data were captured from the Sentinel-1B satellite in May 2020 before the flood and in July 2020 during the flood. A spatial database of the distribution of snail habitats was created using the 2016 snail survey in Jiangxi Province. The potential spread ofO. hupensissnails after the flood was predicted by an overlay analysis of the NDVI maps in the flood-affected areas around Poyang Lake. The risk of schistosomiasis transmission was classified based onO. hupensissnail density data and the related NDVI.ResultsThe surface area of Poyang Lake was approximately 2207 km2in May 2020 before the flood and 4403 km2in July 2020 during the period of peak flooding; this was estimated to be a 99.5% expansion of the water body due to flooding. After the flood, potential snail habitats were predicted to be concentrated in areas neighboring existing habitats in the marshlands of Poyang Lake. The areas with high risk of schistosomiasis transmission were predicted to be mainly distributed in Yongxiu, Xinjian, Yugan and Poyang (District) along the shores of Poyang Lake. By comparing the predictive results and actual snail distribution, we estimated the predictive accuracy of the model to be 87%, which meant the 87% of actual snail distribution was correctly identified as snail habitats in the model predictions.ConclusionsData on water body expansion due to flooding and environmental factors pertaining to snail breeding may be rapidly extracted from Landsat 8 and Sentinel-1B remote sensing images. Applying multi-source remote sensing data for the timely and effective assessment of potential schistosomiasis transmission risk caused by snail spread during flooding is feasible and will be of great significance for more precision control of schistosomiasis.Graphical Abstract
Impulsive control of a class of multiple unstable neural networks
Authors: Jia Songfang , Chen Yanheng 
Published: February 2021

AbstractThis paper addresses the issue of stability of a class of multiple unstable Cohen–Grossberg neural networks(CGNNs) under impulsive control. Some novel sufficient conditions are given to make the unstable equilibrium points of the model locallyμ-stable. An example is offered to demonstrate the effectiveness of the control strategy by comprehensive computer simulations.