bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity
Authors: Ibrahim Aya Saber , El-Shinawi Mohamed , Sabet Salwa , Ibrahim Sherif Abdelaziz , Mohamed Mona Mostafa 
Published: August 2022

Abstract
Background
Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease.

Methods
This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t-test.

Results
The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell.

Conclusions
This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.
Postprandial triglyceride levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants
Authors: Stenkula Karin G. , Klemendz Lisa Esbjörnsson , Fryklund Claes , Wierup Nils , Alsalim Wathik , Landin-Olsson Mona , Trinh Lena , Månsson Sven , Bennet Louise 
Published: August 2022

Abstract
Purpose
Previous studies have shown that at a similar body mass index, Middle Eastern immigrants are more insulin resistant and at higher risk for type 2 diabetes (T2D) than native Europeans. Insulin resistance is strongly associated with disturbed fat metabolism and cardiovascular disease (CVD). However, fat metabolism is poorly investigated comparing Middle Eastern and European ethnicities.

Methods
This observational study included 26 Iraqi and 16 Swedish-born men without T2D or clinical risk factors for CVD. An oral fat tolerance test (OFTT) was performed, where plasma triglycerides (p-TG) were measured for 6 h. mRNA expression and adipocyte size were measured in subcutaneous adipose tissue biopsies collected prior to OFTT, and magnetic resonance imaging was conducted to assess body fat distribution.

Results
The median p-TG accumulation was higher and the clearance slower among Iraqis than Swedes. None of the groups reached their fasting p-TG (Iraqis 1.55 mmol/l; Swedes 0.95 mmol/l) after 6 h (Iraqis p-TG 3.10 mmol/l; Swedes p-TG 1.50 mmol/l). Adipocyte size, mRNA expression, and fat accumulation in the liver, muscle and abdomen were similar in both groups.

Conclusion
Postprandial p-TG levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants without CVD risk factors.
Novel approach to analysis of the immune system using an ungated model of immune surface marker abundance to predict health outcomes
Authors: Provost G. , Lavoie F. B. , Larbi A. , Ng TP. , Ying C. Tan Tze , Chua M. , Fulop T. , Cohen A. A. 
Published: August 2022

AbstractTraditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a new way of looking at immune data, which is by looking directly at the values of the surface markers without dividing the cells into different subtypes. To assess the merit of this approach, we compared it with manual gating using cytometry data from the Singapore Longitudinal Aging Study (SLAS) database. We used two different neural networks (one for each method) to predict the presence of several health conditions. We found that the model built using raw surface marker abundance outperformed the manual gating one and we were able to identify some markers that contributed more to the predictions. This study is intended as a brief proof-of-concept and was not designed to predict health outcomes in an applied setting; nonetheless, it demonstrates that alternative methods to understand the structure of immune variation hold substantial progress.
Protection against MIS-C outweighs the risk of myocarditis after Covid-19 vaccination in children
Authors: Mariani Marcello , Caorsi Roberta , Consolaro Alessandro , Brisca Giacomo , Sticchi Camilla , Gattorno Marco , Castagnola Elio , Ravelli Angelo 
Published: August 2022

AbstractFrom March 2020 to July 2022, in Liguria region (North-West Italy) incidence of MIS-C among pediatric patients infected by SARS-CoV-2 was 38.7/100.000, which is higher than that of myocarditis after COVID-19 vaccination. In our opinion severity of MIS-C-related cardiac disease outweigh the risk of myocarditis after COVID-19 vaccine.
Methylome decoding of RdDM-mediated reprogramming effects in the Arabidopsis MSH1 system
Authors: Kundariya Hardik , Sanchez Robersy , Yang Xiaodong , Hafner Alenka , Mackenzie Sally A. 
Published: August 2022

Abstract
Background
Plants undergo programmed chromatin changes in response to environment, influencing heritable phenotypic plasticity. The RNA-directed DNA methylation (RdDM) pathway is an essential component of this reprogramming process. The relationship of epigenomic changes to gene networks on a genome-wide basis has been elusive, particularly for intragenic DNA methylation repatterning.

Results
Epigenomic reprogramming is tractable to detailed study and cross-species modeling in the MSH1 system, where perturbation of the plant-specific gene MSH1 triggers at least four distinct nongenetic states to impact plant stress response and growth vigor. Within this system, we have defined RdDM target loci toward decoding phenotype-relevant methylome data. We analyze intragenic methylome repatterning associated with phenotype transitions, identifying state-specific cytosine methylation changes in pivotal growth-versus-stress, chromatin remodeling, and RNA spliceosome gene networks that encompass 871 genes. Over 77% of these genes, and 81% of their central network hubs, are functionally confirmed as RdDM targets based on analysis of mutant datasets and sRNA cluster associations. These dcl2/dcl3/dcl4-sensitive gene methylation sites, many present as singular cytosines, reside within identifiable sequence motifs. These data reflect intragenic methylation repatterning that is targeted and amenable to prediction.

Conclusions
A prevailing assumption that biologically relevant DNA methylation variation occurs predominantly in density-defined differentially methylated regions overlooks behavioral features of intragenic, single-site cytosine methylation variation. RdDM-dependent methylation changes within identifiable sequence motifs reveal gene hubs within networks discriminating stress response and growth vigor epigenetic phenotypes. This study uncovers components of a methylome “code” for de novo intragenic methylation repatterning during plant phenotype transitions.
RNA sequencing reveals dynamic expression of spleen lncRNAs and mRNAs in Beagle dogs infected by Toxocara canis
Authors: Xu Yue , Zheng Wen-Bin , Li Hao-Yu , Cai Lang , Zou Yang , Xie Shi-Chen , Zhu Xing-Quan , Elsheikha Hany M. 
Published: August 2022

Abstract
Background
Toxocara canis is a cosmopolitan parasite with a significant adverse impact on the health of humans and animals. The spleen is a major immune organ that plays essential roles in protecting the host against various infections. However, its role in T. canis infection has not received much attention.

Methods
We performed sequencing-based transcriptome profiling of long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression in the spleen of Beagle puppies at 24 h post-infection (hpi), 96 hpi and 36 days post-infection (dpi). Deep sequencing of RNAs isolated from the spleen of six puppies (three infected and three control) at each time point after infection was conducted.

Results
Our analysis revealed 614 differentially expressed (DE) lncRNAs and 262 DEmRNAs at 24 hpi; 726 DElncRNAs and 878 DEmRNAs at 96 hpi; and 686 DElncRNAs and 504 DEmRNAs at 36 dpi. Of those, 35 DElncRNA transcripts and 11 DEmRNAs were detected at all three time points post-infection. Many DE genes were enriched in immune response, such as ifit1, ifit2 and rorc. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that some genes (e.g. prkx and tnfrsf11a) were involved in the T cell receptor signaling pathway, calcium signaling pathway, Ras signaling pathway and NF-κB signaling pathway.

Conclusions
The findings of this study show marked alterations in the expression profiles of spleen lncRNAs and mRNAs, with possible implications in the pathophysiology of toxocariasis.

Graphical Abstract
Circulating osteocalcin is associated with time in range and other metrics assessed by continuous glucose monitoring in type 2 diabetes
Authors: Liu Jun , Wei Yinghua , Zang Pu , Wang Wei , Feng Zhouqin , Yuan Yanyu , Zhou Hui , Zhang Zhen , Lei Haiyan , Yang Xinyi , Liu Jun , Lu Bin , Shao Jiaqing 
Published: August 2022

Abstract
Background
Osteocalcin, a protein secreted mainly by mature osteoblasts, has been shown to be involved in glucose metabolism through various pathways. However, few studies has explored the association between osteocalcin and Time in range (TIR). Continuous glucose monitoring (CGM) -derived metrics, such as TIR and other indexes have been gradually and widely used in clinical practice to assess glucose fluctuations. The main purpose of this study was to investigate the correlation between osteocalcin and indexes from CGM in patients with type 2 diabetes mellitus (T2DM).

Method
The total number of 376 patients with T2D were enrolled, all of them performed three consecutive days of monitoring. They were divided into four groups on account of the quartile of osteocalcin. Time in range, Time below range (TBR), Time above range(TAR) and measures of glycemic variability (GV) were assessed for analysing. After a 100 g standard steamed bread meal, blood glucose (Glu0h Glu0.5 h, Glu1h, Glu2h, GLu3h), C-peptide (Cp0h, Cp0.5 h, Cp1h, Cp2h, Cp3h), serum insulin (INS0h, INS0.5 h, INS1h, INS2h, INS3h) concentrations at different time points were obtained. HOMA-IS, HOMA-βwas calculated to evaluate insulin sensitivity and insulin secreting of the participants.

Results
Patients with higher osteocalcin level had higher TIR (P < 0.05). Spearman correlation analysis showed that osteocalcin was positively correlated with TBR (although the P value for TBR was greater than 0.05) (r = 0.227, P < 0.001 r = 0.068, P = 0.189) and negatively correlated with TAR (− 0.229, P < 0.001). Similarly, there was a negative correlation between osteocalcin and glycemic variability (GV) indicators, including SD, MBG, MODD, ADDR, and MAGE (P value of MAGE > 0.05). Multiple stepwise regression showed that osteocalcin was an independent contributor to TIR, TAR and HOMA-IS.

Conclusion
Circulating osteocalcin is positively correlated with TIR and negatively correlated with MODD, ADDR, and MAGE. Osteocalcin may have a beneficial impact on glucose homeostasis in T2DM patients.
Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models
Authors: He Chunrong , Clark Karen L. , Tan Jian , Zhou Hecheng , Tuan Rocky S. , Lin Hang , Wu Song , Alexander Peter G. 
Published: August 2022

Abstract
Background
Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models.

Methods
Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-β3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1β, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed.

Results
Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1β treatment.

Conclusions
Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.
Validation of the Arabic version of the modified Yale Food Addiction Scale in the general population in Lebanon
Authors: Hallit Souheil , Brytek-Matera Anna , Malaeb Diana , Obeid Sahar 
Published: August 2022

Abstract
Background
Although the definition of food addiction is not agreed upon, it is characterized by eating more than expected without being hungry, not being able to visit certain places associated with overeating or unsuccessfully trying to cut down on the consumption of certain foods. The modified YFAS (mYFAS 2.0) version, instrument available to evaluate food addiction, was shown to have good psychometric properties. Our objective was to assess the psychometric properties of the Arabic version of the mYFAS (mYFAS-Ar-Leb) in the Lebanese population.

Methods
This cross-sectional study enrolled 1268 persons residing in Lebanon (September–November 2020). The mean age of the participants was 26.18 years (SD = 11.17; min: 18; max: 85), with 65.1% females. The percentage of participants with food addiction was 226 (17.8%) in the total sample. A confirmatory factor analysis was run on the one-factor structure among the total sample.

Results
The fit indices of the confirmatory factor analysis of the scale were excellent. The Cronbach’s alpha value was good for the total scale. The mYFAS-Ar-Leb score was positively and strongly associated with stress, anxiety and depression.

Conclusion
Our study findings highlighted that the use of the mYFAS-Ar-Leb in Lebanese population might help estimate food addiction prevalence and stress on the need for effective treatment and preventive measures to craving for addictive foods.
Personal recovery in forensic institutions as a political process: the significance of frameworks for clinical practice
Authors: Shepherd Andrew , Shaw Jenny 
Published: August 2022

Summary
Support of personal recovery has been a stated goal for many mental health services since the early 2000s. Frameworks such as the CHIME-S described in this issue of BJPsych Open provide useful tools for the operationalisation of this in clinical practice. It is important, however, that through this act of normalisation we do not lose sight of the radical implications of personal recovery as a personal and political process taking place within a social world.
Breast Cancer and Prolactin – New Mechanisms and Models
Authors: Clevenger Charles V , Rui Hallgeir 
Published: August 2022

Abstract
The pathogenesis of breast cancer is driven by multiple hormones and growth factors. One of these, prolactin (PRL), contributes to both mammary differentiation and oncogenesis, and yet the basis for these disparate effects has remained unclear. The focus of this review is to examine and place into context 2 recent studies that have provided insight into the roles of PRL receptors and PRL in tumorigenesis and tumor progression. One study provides novel evidence for opposing actions of PRL in the breast being mediated in part by differential PRL receptor (PRLr) isoform utilization. Briefly, homomeric complexes of the long isoform of the PRLr (PRLrL-PRLrL) promotes mammary differentiation, while heteromeric complexes of the intermediate and long PRLr (PRLrI-PRLrL) isoforms trigger mammary oncogenesis. Another study describes an immunodeficient, prolactin-humanized mouse model, NSG-Pro, that facilitates growth of PRL receptor-expressing patient-derived breast cancer xenografts. Evidence obtained with this model supports the interactions of physiological levels of PRL with estrogen and ERBB2 gene networks, the modulatory effects of PRL on drug responsiveness, and the pro-metastatic effects of PRL on breast cancer. This recent progress provides novel concepts, mechanisms and experimental models expected to renew interest in harnessing/exploiting PRLr signaling for therapeutic effects in breast cancer.
Optogenetically induced reward and ‘frustration’ memory in larval Drosophila melanogaster
Authors: Thoener Juliane , Weiglein Aliće , Gerber Bertram , Schleyer Michael 
Published: August 2022

ABSTRACT
Animals, including humans, form oppositely valenced memories for stimuli that predict the occurrence versus the termination of a reward: appetitive ‘reward’ memory for stimuli associated with the occurrence of a reward and aversive ‘frustration’ memory for stimuli that are associated with its termination. We characterized these memories in larval Drosophila melanogaster using a combination of Pavlovian conditioning, optogenetic activation of the dopaminergic central-brain DAN-i1864 neuron, and high-resolution video-tracking. This reveals their dependency on the number of training trials and the duration of DAN-i1864 activation, their temporal stability, and the parameters of locomotion that are modulated during memory expression. Together with previous results on ‘punishment’ versus ‘relief’ learning by DAN-f1 neuron activation, this reveals a 2×2 matrix of timing-dependent memory valence for the occurrence/termination of reward/punishment. These findings should aid the understanding and modelling of how brains decipher the predictive, causal structure of events around a target reinforcing occurrence.
Kawasaki disease: a comprehensive review
Authors: Osiejewska Aleksandra , Wojtachnio Dominika , Bartoszewicz Jakub , Grądzik Anna , Nowakowska Izabela , Kudan Małgorzata , Gorajek Anna 
Published: August 2022

Introduction and purpose: Kawasaki disease is an acute, self-limited vasculitis of medium arteries, and it affects children under 5 years old. It can lead to coronary artery aneurysms.
Brief description of the state of knowledge: Pathogenesis of Kawasaki disease is unclear. The diagnosis is based on the clinical findings. The characteristic symptoms are polymorphous skin rashes, conjunctivitis, erythema, dryness, cracking and bleeding of the lips, erythema and swelling of palms and soles and cervical lymphadenopathy. Kawasaki disease is defined as a fever for 5 days accompanied by 4 or more of the diagnostic symptoms described above. The classic diagnosis is based on the exclusion of other diseases too. The diagnosis of incomplete Kawasaki disease is suggested if less than 4 main clinical features are found. It is the most common cause of acquired heart disease in children. Kawasaki disease can lead to coronary artery aneurysm, myocarditis and pericarditis so it is very important to treat this illness correctly. Basic treatment is a single infusion of intravenous immunoglobulin and high-dose aspirin. Recurrent Kawasaki disease (persistent fever after first line treatment with IVIG and aspirin) requires the same treatment as used for the first episode. Corticosteroids and immune-modulating therapies can be used as second and third line options. Quick recognition and early treatment result in a reduction of coronary artery abnormalities.
Conclusion: This article reviews basic informations, history, epidemiology, pathophysiology, clinical presentation, diagnostic criteria, complications and treatment of Kawasaki disease.