bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder
Authors: Guo Xiaonan , Zhai Guangjin , Liu Junfeng , Cao Yabo , Zhang Xia , Cui Dong , Gao Le 
Published: December 2022

Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical heterogeneity. This study aimed to explore the heterogeneity of ASD based on inter-individual heterogeneity of functional brain networks.

Methods
Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were used in this study for 105 children with ASD and 102 demographically matched typical controls (TC) children. Functional connectivity (FC) networks were first obtained for ASD and TC groups, and inter-individual deviation of functional connectivity (IDFC) from the TC group was then calculated for each individual with ASD. A k-means clustering algorithm was used to obtain ASD subtypes based on IDFC patterns. The FC patterns were further compared between ASD subtypes and the TC group from the brain region, network, and whole-brain levels. The relationship between IDFC and the severity of clinical symptoms of ASD for ASD subtypes was also analyzed using a support vector regression model.

Results
Two ASD subtypes were identified based on the IDFC patterns. Compared with the TC group, the ASD subtype 1 group exhibited a hypoconnectivity pattern and the ASD subtype 2 group exhibited a hyperconnectivity pattern. IDFC for ASD subtype 1 and subtype 2 was found to predict the severity of social communication impairments and the severity of restricted and repetitive behaviors in ASD, respectively.

Limitations
Only male children were selected for this study, which limits the ability to study the effects of gender and development on ASD heterogeneity.

Conclusions
These results suggest the existence of subtypes with different FC patterns in ASD and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.
A decision support tool with health economic modelling for better management of DVT patients
Authors: Lebcir Reda , Yakutcan Usame , Demir Eren 
Published: December 2022

AbstractBackgroundResponding to the increasing demand for Deep Vein Thrombosis (DVT) treatment in the United Kingdom (UK) at times of limited budgets and resources is a great challenge for decision-makers. Therefore, there is a need to find innovative policies, which improve operational efficiency and achieve the best value for money for patients. This study aims to develop a Decision Support Tool (DST) that assesses the impact of implementing new DVT patients’ management and care policies aiming at improving efficiency, reducing costs, and enhancing value for money.MethodsWith the involvement of stakeholders from a number of DVT services in the UK, we developed a DST combining discrete event simulation (DES) for DVT pathways and the Socio Technical Allocation of Resources (STAR) approach, an agile health economics technique. The model was inputted with data from the literature, local datasets from DVT services, and interviews conducted with DVT specialists. The tool was validated and verified by various stakeholders and two policies, namely shifting more patients to community services (CSs) and increasing the usage of the Novel Oral Anticoagulant (NOAC) drug were selected for testing on the model.ResultsSixteen possible scenarios were run on the model for a period of 5 years and generated treatment activity, human resources, costing, and value for money outputs. The results indicated that hospital visits can be reduced by up to 50%. Human resources’ usage can be greatly lowered driven mainly by offering NOAC treatment to more patients. Also, combining both policies can lead to cost savings of up to 50%. The STAR method, which considers both service and patient perspectives, produced findings that implementing both policies provide a significantly higher value for money compared to the situation when neither is applied.ConclusionsThe combination of DES and STAR can help decision-makers determine the interventions that have the highest benefits from service providers' and patients’ perspectives. This is important given the mismatch between care demand and resources and the resulting need for improving operational and economic outcomes. The DST tool has the potential to inform policymaking in DVT services in the UK to improve performance.
Addressing energy poverty through technological and governance innovation
Authors: Varo Anais , Jiglau George , Grossmann Katrin , Guyet Rachel 
Published: December 2022

Abstract
Background
Energy poverty has gained much traction over the last decades, holding both high multidisciplinary conceptual value, but also profound implications from a social policy perspective, being closely linked to the quality of life and well-being. The goal of our study is to evaluate recent measures aimed at tackling energy poverty in Europe by analysing the extent to which they are innovative on technological and governance dimensions. We do so by building an analytical tool which combines evaluation criteria along these two dimensions and by employing it for the analysis of twenty measures aimed at tackling energy poverty that have been designed and employed in ten European countries. These measures were selected with the support of an expert panel.

Results
We identify three categories of innovative measures aimed at alleviating energy poverty: (1) measures with high technological scores, (2) measures with high governance scores, and (3) measures with high scores on both axes. The measures in the third category incorporate a variety of actors in sustainable partnerships and implement monitoring tools throughout the process, complementary to incorporating new technologies into the domestic sphere and promoting consumer awareness and consumption pattern transformation.

Conclusions
Our findings allow for a better perspective on the shape innovation takes in the context of energy poverty policies. Based on our research, we argue that combining technological innovation and governance innovation has a better chance of generating more articulate and scalable, and potentially successful measures with respect to their purpose of tackling energy poverty, since the drivers of energy poverty rarely pertain to only technology or only governance.
ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific, brain-penetrating fusion protein
Authors: Bonvicini Gillian , Syvänen Stina , Andersson Ken G. , Haaparanta-Solin Merja , López-Picón Francisco , Sehlin Dag 
Published: December 2022

Abstract
Background
Hijacking the transferrin receptor (TfR) is an effective strategy to transport amyloid-beta (Aβ) immuno-positron emission tomography (immunoPET) ligands across the blood–brain barrier (BBB). Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβ pathology in mouse models of Alzheimer’s disease (AD). This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands.

Methods
Two affinity variants of the rat TfR antibody, OX26, were chemically conjugated to a F(ab′)2 fragment of the anti-Aβ antibody, bapineuzumab (Bapi), to generate two bispecific fusion proteins: OX265-F(ab′)2-Bapi and OX2676-F(ab′)2-Bapi. Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type (WT) rats. [124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging. Ex vivo distribution of injected [124I]I-OX265-F(ab′)2-Bapi and Aβ pathology were assessed.

Results
More [125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than [124I]I-OX2676-F(ab′)2-Bapi. [124I]I-OX265-F(ab′)2-Bapi PET visualized Aβ pathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβ pathology. The PET signals significantly correlated with Aβ levels in AD animals.

Conclusion
Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB, such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently. Furthermore, bispecific immunoPET imaging of brain Aβ pathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats, suggesting that this immunoPET strategy has the potential to be translated to higher species.
Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity
Authors: Ng Winanto , Ng Shi-Yan 
Published: December 2022

AbstractAmyotrophic lateral sclerosis (ALS) is an adult-onset paralytic disease characterized by progressive degeneration of upper and lower motor neurons in the motor cortex, brainstem and spinal cord. Motor neuron degeneration is typically caused by a combination of intrinsic neuronal (cell autonomous) defects as well as extrinsic (non-cell autonomous) factors such as astrocyte-mediated toxicity. Astrocytes are highly plastic cells that react to their microenvironment to mediate relevant responses. In neurodegeneration, astrocytes often turn reactive and in turn secrete a slew of factors to exert pro-inflammatory and neurotoxic effects. Various efforts have been carried out to characterize the diseased astrocyte secretome over the years, revealing that pro-inflammatory chemokines, cytokines and microRNAs are the main players in mediating neuronal death. As metabolomic technologies mature, these studies begin to shed light on neurotoxic metabolites such as secreted lipids. In this focused review, we will discuss changes in the astrocyte secretome during ALS. In particular, we will discuss the components of the reactive astrocyte secretome that contribute to neuronal death in ALS.
Gut microbiota of the young ameliorates physical fitness of the aged in mice
Authors: Kim Kwang H. , Chung Yusook , Huh Ji-Won , Park Dong Jin , Cho Yejin , Oh Yeseul , Jeong Haengdueng , Yoon Jaekyung , Kang Ju-Hee , Shin Hae-Sol , Kim Hyoung-Chin , Kwon Soon-Kyeong , Seo Kyoung Yul , Oh Seung Hyun , Seong Je Kyung , Ha Sang-Jun , Nam Ki Taek , Kim Jihyun F. 
Published: December 2022

AbstractBackgroundAging is a natural process that an organism gradually loses its physical fitness and functionality. Great efforts have been made to understand and intervene in this deteriorating process. The gut microbiota affects host physiology, and dysbiosis of the microbial community often underlies the pathogenesis of host disorders. The commensal microbiota also changes with aging; however, the interplay between the microbiota and host aging remains largely unexplored. Here, we systematically examined the ameliorating effects of the gut microbiota derived from the young on the physiology and phenotypes of the aged.ResultsAs the fecal microbiota was transplanted from young mice at 5 weeks after birth into 12-month-old ones, the thickness of the muscle fiber and grip strength were increased, and the water retention ability of the skin was enhanced with thickened stratum corneum. Muscle thickness was also marginally increased in 25-month-old mice after transferring the gut microbiota from the young. Bacteria enriched in 12-month-old mice that received the young-derived microbiota significantly correlated with the improved host fitness and altered gene expression. In the dermis of these mice, transcription ofDbn1was most upregulated and DBN1-expressing cells increased twice.Dbn1-heterozygous mice exhibited impaired skin barrier function and hydration.ConclusionsWe revealed that the young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin.Dbn1, for the first time, was found to be induced by the young microbiota and to modulate skin hydration. Our results provide solid evidence that the gut microbiota from the young improves the vitality of the aged.
Spatial implementation of frequency ratio, statistical index and index of entropy models for landslide susceptibility mapping in Al-Balouta river basin, Tartous Governorate, Syria
Authors: Abdo Hazem Ghassan , Almohamad Hussein , Al Dughairi Ahmed Abdullah , Ali Sk Ajim , Parvin Farhana , Elbeltagi Ahmed , Costache Romulus , Mohammed Safwan , Al-Mutiry Motrih , Alsafadi Karam 
Published: December 2022

AbstractLandslide vulnerability prediction maps are among the most important tools for managing natural hazards associated with slope stability in river basins that affect ecosystems, properties, infrastructure and society. Landslide events are among the most hazardous patterns of slope instability in the coastal mountains of Syria. Thus, the main goals of this research are to evaluate the performance of three different statistical outputs: Frequency Ratio (FR), Statistical Index (SI) and Index of Entropy (IoE) and therefore map landslide susceptibility in the coastal region of Syria. To this end, we identified a total of 446 locations of landslide events, based on the preliminary inventory map derived from fieldwork and high-resolution imagery surveys. In this regard, 13 geo-environmental factors that have a high influence on landslides were selected for landslide susceptibility mapping. The results indicated that the FR method outperformed the SI and IoE models with a high AUC of 0.824 and better adaptability, followed by the SI with 0.791. According to the SCAI values, although the FR model achieved the best reliability, the other two models also showed good capability in determining landslide susceptibility. The result of FR-based modelling showed that 18.51 and 19.98% of the study area fall under the high and very high landslide susceptible categories, respectively. In the map generated by the SI method, about 36% of the study area is classified as having high or very high landslide sensitivity. In the IoE method, whereas 14.18 and 25.62% of the study area were classified as “very high susceptible” and “high susceptible,” respectively. The relative importance analysis demonstrated that the slope aspects, lithology and proximity to roads effectively motivated the acceleration of slope material instability and were the most influential in both the FR and SI models. On the other hand, the IoE model indicated that the proximity to faults and roads, along with the lithology factor, were important influences in the formation of landslide events. As a result, the statistical bivariate models-based landslide mapping provided a reliable and systematic approach to guide the long-term strategic planning procedures in the study area.
CT texture analysis and node-RADS CT score of mediastinal lymph nodes - diagnostic performance in lung cancer patients
Authors: Meyer Hans-Jonas , Schnarkowski Benedikt , Pappisch Johanna , Kerkhoff Teresa , Wirtz Hubert , Höhn Anne-Kathrin , Krämer Sebastian , Denecke Timm , Leonhardi Jakob , Frille Armin 
Published: December 2022

Abstract
Background
Texture analysis derived from computed tomography (CT) can provide clinically relevant imaging biomarkers. Node-RADS is a recently proposed classification to categorize lymph nodes in radiological images. The present study sought to investigate the diagnostic abilities of CT texture analysis and Node-RADS to discriminate benign from malignant mediastinal lymph nodes in patients with lung cancer.

Methods
Ninety-one patients (n = 32 females, 35%) with a mean age of 64.8 ± 10.8 years were included in this retrospective study. Texture analysis was performed using the free available Mazda software. All lymph nodes were scored accordingly to the Node-RADS classification. All primary tumors and all investigated mediastinal lymph nodes were histopathologically confirmed during clinical workup.

Results
In discrimination analysis, Node-RADS score showed statistically significant differences between N0 and N1-3 (p < 0.001). Multiple texture features were different between benign and malignant lymph nodes: S(1,0)AngScMom, S(1,0)SumEntrp, S(1,0)Entropy, S(0,1)SumAverg. Correlation analysis revealed positive associations between the texture features with Node-RADS score: S(4,0)Entropy (r = 0.72, p < 0.001), S(3,0) Entropy (r = 0.72, p < 0.001), S(2,2)Entropy (r = 0.72, p < 0.001).

Conclusions
Several texture features and Node-RADS derived from CT were associated with the malignancy of mediastinal lymph nodes and might therefore be helpful for discrimination purposes. Both of the two quantitative assessments could be translated and used in clinical routine.
Auricular cartilage regeneration using different types of mesenchymal stem cells in rabbits
Authors: Hassan Taghreed Ahmed , Maher Mohamed Ahmed , El Karmoty Amr Fekry , Ahmed Zainab Sabry Othman , Ibrahim Marwa A , Rizk Hamdy , Reyad Ayman Tolba 
Published: December 2022

AbstractBackgroundCartilaginous disorders comprise a wide range of diseases that affect normal joint movement, ear and nose shape; and they have great social and economic impact. Mesenchymal stem cells (MSCs) provide a promising regeneration alternative for treatment of degenerative cartilaginous disorders. This study aimed to compare therapeutic potential of different types of laser activated MSCs to promote auricular cartilage regeneration. Twelve adult rabbit allocated equally in four groups, all animals received a surgical mid auricular cartilage defect in one ear; Group I (Positive control) injected sub-perichondrially with phosphate-buffered saline (PBS), Group II (ADMSC-transplanted group) injected adipose-derived MSCs (ADMSCs), Group III (BMMSCs-transplanted group) received bone marrow-derived MSCs (BMMSCs), and Group IV (EMSC-transplanted group) received ear MSCs (EMSCs) in the defected ear. The auricular defect was analyzed morphologically, histopathologically and immunohistochemically after 4 weeks. In addition, a quantitative real-time polymerase chain reaction was used to examine expression of the collagen type II (Col II) and aggrecan as cartilage growth factors.ResultsThe auricles of all treatments appeared completely healed with smooth surfaces and similar tissue color. Histopathologically, defective areas of control positive group, ADMSCs and EMSCs treated groups experienced a small area of immature cartilage. While BMMSCs treated group exhibited typical features of new cartilage formation with mature chondrocytes inside their lacunae and dense extracellular matrix (ECM). In addition, BMMSC treated group showed a positive reaction to Masson’s trichrome and orcein stains. In contrary, control positive, ADMSC and EMSC groups revealed faint staining with Masson’s trichrome and Orcein. Immunohistochemically, there was an intense positive S100 expression in BMMSCs (with a significant increase of area percentage + 21.89 (P < 0.05), a moderate reaction in EMSCs (with an area percentage + 17.97, and a mild reaction in the control group and ADMSCs (area percentages + 8.02 and + 11.37, respectively). The expression of relative col II and aggrecan was substantially highest in BMMSCs (± 0.91 and ± 0.89, respectively). While, Control positive, ADMSCs and EMSCs groups recorded (± 0.41: ± 0.21, ± 0.6: ± 0.44, ± 0.61: ± 0.63) respectively.ConclusionBMMSCs showed the highest chondrogenic potential compared to ADMSCs and EMSCs and should be considered the first choice in treatment of cartilaginous degenerative disorders.
Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression
Authors: Pei Fei , Yao Ren-Qi , Ren Chao , Bahrami Soheyl , Billiar Timothy R. , Chaudry Irshad H. , Chen De-Chang , Chen Xu-Lin , Cui Na , Fang Xiang-Ming , Kang Yan , Li Wei-Qin , Li Wen-Xiong , Liang Hua-Ping , Lin Hong-Yuan , Liu Ke-Xuan , Lu Ben , Lu Zhong-Qiu , Maegele Marc , Peng Tian-Qing , Shang You , Su Lei , Sun Bing-Wei , Wang Chang-Song , Wang Jian , Wang Jiang-Huai , Wang Ping , Xie Jian-Feng , Xie Li-Xin , Zhang Li-Na , Zingarelli Basilia , Guan Xiang-Dong , Wu Jian-Feng , Yao Yong-Ming ,   the Shock and Sepsis Society of Chinese Research Hospital Association,   the China Critical Care Immunotherapy Research Group,   the International Federation of the Shock Societies (IFSS)
Published: December 2022

AbstractEmerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.
Plasma polymerized bio-interface directs fibronectin adsorption and functionalization to enhance “epithelial barrier structure” formation via FN-ITG β1-FAK-mTOR signaling cascade
Authors: Chen Shoucheng , Huang Zhuwei , Visalakshan Rahul Madathiparambil , Liu Haiwen , Bachhuka Akash , Wu You , Dabare Panthihage Ruvini L. , Luo Pu , Liu Runheng , Gong Zhuohong , Xiao Yin , Vasilev Krasimir , Chen Zhuofan , Chen Zetao 
Published: December 2022

Abstract

Background

Transepithelial medical devices are increasing utilized in clinical practices. However, the damage of continuous natural epithelial barrier has become a major risk factor for the failure of epithelium-penetrating implants. How to increase the “epithelial barrier structures” (focal adhesions, hemidesmosomes, etc
.
) becomes one key research aim in overcoming this difficulty. Directly targeting the in situ “epithelial barrier structures” related proteins (such as fibronectin) absorption and functionalization can be a promising way to enhance interface-epithelial integration.

Methods
Herein, we fabricated three plasma polymerized bio-interfaces possessing controllable surface chemistry. Their capacity to adsorb and functionalize fibronectin (FN) from serum protein was compared by Liquid Chromatography-Tandem Mass Spectrometry. The underlying mechanisms were revealed by molecular dynamics simulation. The response of gingival epithelial cells regarding the formation of epithelial barrier structures was tested.

Results
Plasma polymerized surfaces successfully directed distinguished protein adsorption profiles from serum protein pool, in which plasma polymerized allylamine (ppAA) surface favored adsorbing adhesion related proteins and could promote FN absorption and functionalization via electrostatic interactions and hydrogen bonds, thus subsequently activating the ITG β1-FAK-mTOR signaling and promoting gingival epithelial cells adhesion.

Conclusion
This study offers an effective perspective to overcome the current dilemma of the inferior interface-epithelial integration by in situ protein absorption and functionalization, which may advance the development of functional transepithelial biointerfaces.

Graphical Abstract
Tuning the surface chemistry by plasma polymerization can control the adsorption of fibronectin and functionalize it by exposing functional protein domains. The functionalized fibronectin can bind to human gingival epithelial cell membrane integrins to activate epithelial barrier structure related signaling pathway, which eventually enhances the formation of epithelial barrier structure.