bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanoma stimulates the proteolytic activity of HaCaT keratinocytes
Authors: Mazurkiewicz Justyna , Simiczyjew Aleksandra , Dratkiewicz Ewelina , Kot Magdalena , Pietraszek-Gremplewicz Katarzyna , Wilk Dominika , Ziętek Marcin , Matkowski Rafał , Nowak Dorota 
Published: September 2022

Abstract
Background
Keratinocytes constitute a major part of the melanoma microenvironment, considering their protective role towards melanocytes in physiological conditions. However, their interactions with tumor cells following melanomagenesis are still unclear.

Methods
We used two in vitro models (melanoma-conditioned media and indirect co-culture of keratinocytes with melanoma cells on Transwell inserts) to activate immortalized keratinocytes towards cancer-associated ones. Western Blotting and qPCR were used to evaluate keratinocyte markers and mediators of cell invasiveness on protein and mRNA expression level respectively. The levels and activity of proteases and cytokines were analysed using gelatin-FITC staining, gelatin zymography, chemiluminescent enzymatic test, as well as protein arrays. Finally, to further study the functional changes influenced by melanoma we assessed the rate of proliferation of keratinocytes and their invasive abilities by employing wound healing assay and the Transwell filter invasion method.

Results
HaCaT keratinocytes activated through incubation with melanoma-conditioned medium or indirect co-culture exhibit properties of less differentiated cells (downregulation of cytokeratin 10), which also prefer to form connections with cancer cells rather than adjacent keratinocytes (decreased level of E-cadherin). While they express only a small number of cytokines, the variety of secreted proteases is quite prominent especially considering that several of them were never reported as a part of secretome of activated keratinocytes’ (e.g., matrix metalloproteinase 3 (MMP3), ADAM metallopeptidase with thrombospondin type 1 motif 1). Activated keratinocytes also seem to exhibit a high level of proteolytic activity mediated by MMP9 and MMP14, reduced expression of TIMPs (tissue inhibitor of metalloproteinases), upregulation of ERK activity and increased levels of MMP expression regulators-RUNX2 and galectin 3. Moreover, cancer-associated keratinocytes show slightly elevated migratory and invasive abilities, however only following co-culture with melanoma cells on Transwell inserts.

Conclusions
Our study offers a more in-depth view of keratinocytes residing in the melanoma niche, drawing attention to their unique secretome and mediators of invasive abilities, factors which could be used by cancer cells to support their invasion of surrounding tissues.
Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis
Authors: Han Ping , Lei Yu , Liu Jingmei , Liu Jiqiao , Huang Huanjun , Tian Dean , Yan Wei 
Published: September 2022

Abstract
Background
Tumor cells detachment from primary lesions is an early event for hepatocellular carcinoma (HCC) metastasis, in which cell adhesion molecules play an important role. The role of mechanical crowding has attracted increasing attention. Previous studies have found that overcrowding can induce live cells extrusion to maintain epithelial cell homeostasis, and normally, live extruded cells eventually die through a process termed anoikis, suggesting the potential of tumor cells resistant to anoikis might initiate metastasis from primary tumors by cell extrusion. We have demonstrated transmembrane adhesion molecule blood vessel epicardial substance (BVES) suppression as an early event in HCC metastasis. However, whether its suppression is involved in HCC cell extrusion, especially in HCC metastasis, remains unknown. This study aims to investigate the role of BVES in tumor cells extrusion in HCC metastasis, as well as the underlying mechanisms.

Methods
Cells extrusion was observed by silicone chamber, petri dish inversion, and three-dimensional cell culture model. Polymerase chain reaction, western blotting, immunohistochemistry, immunofluorescence, co-immunoprecipitation, and RhoA activity assays were used to explore the underlying mechanisms of cell extrusion regulated by BVES. An orthotopic xenograft model was established to investigate the effects of BVES and cell extrusion in HCC metastasis in vivo.

Results
Tumor cell extrusion was observed in HCC cells and tissues. BVES expression was decreased both in HCC and extruded tumor cells. BVES overexpression led to the decrease in HCC cells extrusion in vitro and in vivo. Moreover, our data showed that BVES co-localized with ZO-1 and GEFT, regulating ZO-1 expression and localization, and GEFT distribution, thus modulating RhoA activity.

Conclusion
The present study revealed that BVES downregulation in HCC enhanced tumor cells extrusion, thus promoting HCC metastasis, which contributed to a more comprehensive understanding of tumor metastasis, and provided clues for developing novel HCC therapy strategies.
Ethnobotanical investigation of medicinal plants in Buska Mountain range, Hamar district, Southwestern Ethiopia
Authors: Bekele Melese , Woldeyes Feleke , Lulekal Ermias , Bekele Tamrat , Demissew Sebsebe 
Published: September 2022

Abstract
Background
Despite the fact that ethnobotanical studies have been conducted in various parts of Ethiopia, compared with the existence of the multitude and diverse ethnic groups and their associated traditional knowledge, the studies are not comprehensive enough for all the localities and communities in the country. This is also true for the Hamar community of Southwestern Ethiopia, who are totally dependent on plants and plant products for their livelihood. Hence, this investigation was done to identify and record medicine plants and the native wisdom of the community in the area.

Methods
Three hundred twenty six (326) informants were selected from the 12 lowest governmental units (Kebeles) applying Cochran’s formula through stratified random sampling technique. From the total informants, 74 (48 males and 26 females) were purposively selected for in-depth discussion. Semi-structured interviews, focus group discussions, guided field walks as well as market surveys were used for data collection. Standard ethnobotanical analytical tools comprising ranking and comparison were used for the analysis. Preference ranking, pair-wise comparison, informant consensus factor, direct matrix ranking, Cultural Significance Index (CSI) and Jaccard’s similarity coefficient (JCS) as well as Analysis of Variances (ANOVA), applying SPSS (version 20) were computed.

Results
A total of 145 species practical to cure about 72 ailments of livestock and humans were recorded. Families Fabaceae (with 22% of species), Asteraceae (11%), and Lamiaceae (9%) were discovered as the most dominant families in the area. Shrubs contributed the most (40%) to the growth forms followed by herbs (26.5%). Fresh leaves of the plants were parts that are used most frequently in the area. The highest ICF value (0.94) was recorded for reproductive problem categories. There was a relatively very high dependence of the community on plants and plant products together with a hoarded indigenous knowledge in the area that positively correlated with age (r = 0.82).

Conclusion
The study's findings revealed that Buska Mountain range is a home for highly diverse and most dependable plant species and associated indigenous knowledge. However, because of the realized environmental threats in the area, the conservation efforts of the community should be invigorated and supported in order to sustain the biodiversity in general and the medicinal plant species in particular.
Metabolic shift towards increased biohydrogen production during dark fermentation in the anaerobic fungus Neocallimastix cameroonii G341
Authors: Stabel Marcus , Haack Karoline , Lübbert Hannah , Greif Meike , Gorenflo Pascal , Aliyu Habibu , Ochsenreither Katrin 
Published: September 2022

Abstract
Background
Anaerobic fungi of the phylum Neocallimastigomycota have a high biotechnological potential due to their robust lignocellulose degrading capabilities and the production of several valuable metabolites like hydrogen, acetate, formate, lactate, and ethanol. The metabolism of these fungi, however, remains poorly understood due to limitations of the current cultivation strategies in still-standing bottles, thereby restricting the comprehensive evaluation of cultivation conditions.

Results
We describe the analysis of growth conditions and their influence on the metabolism of the previously isolated fungus Neocallimastix cameroonii G341. We established a bioreactor process in a stirred tank, enabling cultivation under defined conditions. The optimal growth temperature for the fungus was between 38.5 °C and 41.5 °C, while the optimal pH was 6.6–6.8. Like other dark fermentation systems, hydrogen production is dependent on the hydrogen partial pressure and pH. Shaking the bottles or stirring the fermenters led to an increase in hydrogen and a decrease in lactate and ethanol production. Regulation of the pH to 6.8 in the fermenter nearly doubled the amount of produced hydrogen.

Conclusions
Novel insights into the metabolism of Neocallimastix cameroonii were gained, with hydrogen being the preferred way of electron disposal over lactate and ethanol. In addition, our study highlights the potential application of the fungus for hydrogen production from un-pretreated biomass. Finally, we established the first cultivation of an anaerobic fungus in a stirred tank reactor system.
Improvement in l-ornithine production from mannitol via transcriptome-guided genetic engineering in Corynebacterium glutamicum
Authors: Nie Libin , He Yutong , Hu Lirong , Zhu Xiangdong , Wu Xiaoyu , Zhang Bin 
Published: September 2022

Abstract
Background
l-Ornithine is an important medicinal intermediate that is mainly produced by microbial fermentation using glucose as the substrate. To avoid competition with human food resources, there is an urgent need to explore alternative carbon sources for l-ornithine production. In a previous study, we constructed an engineered strain, Corynebacterium glutamicum MTL13, which produces 54.56 g/L of l-ornithine from mannitol. However, compared with the titers produced using glucose as a substrate, the results are insufficient, and further improvement is required.

Results
In this study, comparative transcriptome profiling of MTL01 cultivated with glucose or mannitol was performed to identify novel targets for engineering l-ornithine-producing strains. Guided by the transcriptome profiling results, we modulated the expression of qsuR (encoding a LysR-type regulator QsuR), prpC (encoding 2-methylcitrate synthase PrpC), pdxR (encoding a MocR-type regulator PdxR), acnR (encoding a TetR-type transcriptional regulator AcnR), CGS9114_RS08985 (encoding a hypothetical protein), and CGS9114_RS09730 (encoding a TetR/AcrR family transcriptional regulator), thereby generating the engineered strain MTL25 that can produce l-ornithine at a titer of 93.6 g/L, representing a 71.6% increase as compared with the parent strain MTL13 and the highest l-ornithine titer reported so far for C. glutamicum.

Conclusions
This study provides novel indirect genetic targets for enhancing l-ornithine accumulation on mannitol and lays a solid foundation for the biosynthesis of l-ornithine from marine macroalgae, which is farmed globally as a promising alternative feedstock.
Translation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer
Authors: Palanca-Ballester Cora , Hervas David , Villalba Maria , Valdes-Sanchez Teresa , Garcia Diana , Alcoriza-Balaguer Maria Isabel , Benet Marta , Martinez-Tomas Raquel , Briones-Gomez Andres , Galbis-Caravajal Jose , Calvo Alfonso , Juan Oscar , Lahoz Agustin , Cases Enrique , Sandoval Juan 
Published: September 2022

AbstractLung cancer patients are diagnosed at late stages when curative treatments are no longer possible; thus, molecular biomarkers for noninvasive detection are urgently needed. In this sense, we previously identified and validated an epigenetic 4-gene signature that yielded a high diagnostic performance in tissue and invasive pulmonary fluids. We analyzed DNA methylation levels using the ultrasensitive digital droplet PCR in noninvasive samples in a cohort of 83 patients. We demonstrated that BCAT1 is the candidate that achieves high diagnostic efficacy in circulating DNA derived from plasma (area under the curve: 0.85). Impact of potentially confounding variables was also explored.
Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis
Authors: Muscatello Rachael A. , Rafatjoo Emma , Mirpuri Karan K. , Kim Ahra , Vandekar Simon , Corbett Blythe A. 
Published: September 2022

Abstract
Background
Puberty is characterized by significant physical, hormonal, and psychological changes, which may be especially challenging for individuals with autism spectrum disorder (ASD). Although the etiology of ASD remains uncertain, studies suggest imbalances in hormones, such as testosterone, may modulate the autism phenotype. While differences in fetal and postnatal testosterone have been reported, there is limited literature regarding testosterone variations during adolescence in ASD. We investigated morning salivary testosterone levels in youth with ASD and typical development (TD) to explore hypothesized differences, expecting elevated hormonal levels in ASD compared to TD.

Methods
Youth with ASD (n = 140) and TD (n = 104), ages 10 to 13 years, were enrolled as part of a longitudinal study on pubertal development. Pubertal stage was determined by gold standard physical examination, and salivary testosterone was collected in the morning immediately upon waking and 30 min after waking and averaged across 3 days. Diagnostic (ASD/TD) and sex (male/female) differences, as well as interactions with age and puberty, were examined using robust linear mixed effect models.

Results
Youth with ASD showed significantly elevated testosterone concentrations compared to same-age TD peers. After the inclusion of natural cubic splines to account for nonlinearity in age, a significant age-by-sex interaction emerged with distinct developmental slopes for males and females. At younger ages, females had higher testosterone, until about 11.5 years of age, when levels began to plateau, while male testosterone concentrations continued to rapidly increase and surpass females. As expected, more advanced pubertal development was associated with elevated testosterone. In contrast, no significant effect of parent-reported social communication symptoms was observed.

Limitations
Limitations include an unequal sex distribution, non-representative sample (e.g., cognition and race/ethnicity), and inability to examine afternoon/evening testosterone due to detection limits.

Conclusions
Testosterone may play a unique role in the presentation of ASD, especially during periods of dynamic hormonal changes including puberty. Inherent developmental (age, puberty) and sex-based (male, female) factors play a more prominent role in changes in testosterone levels during adolescence. Even so, future research is warranted to determine the differential expression and impact of exposure to excess testosterone during the pubertal transition for youth with ASD.
Biofilm of Klebsiella pneumoniae minimize phagocytosis and cytokine expression by macrophage cell line
Authors: Rathore Sudarshan Singh , Cheepurupalli Lalitha , Gangwar Jaya , Raman Thiagarajan , Ramakrishnan Jayapradha 
Published: September 2022

AbstractInfectious bacteria in biofilm mode are involved in many persistent infections. Owing to its importance in clinical settings, many in vitro and in vivo studies are being conducted to study the structural and functional properties of biofilms, their drug resistant mechanism and the s urvival mechanism of planktonic and biofilm cells. In this regard, there is not sufficient information on the interaction between Klebsiella biofilm and macrophages. In this study, we have attempted to unravel the interaction between Klebsiella biofilm and macrophages in terms of phagocytic response and cytokine expression. In vitro phagocytosis assays were performed for heat inactivated and live biofilms of K. pneumoniae, together with the expression analysis of TLR2, iNOS, inflammatory cytokines such as IL-β1, IFN-γ, IL-6, IL-12, IL-4, TNF-α and anti-inflammatory cytokine, IL-10. A phagocytic rate of an average of 15% was observed against both heat inactivated and live biofilms when LPS + IFN-γ activated macrophages were used. This was significantly higher than non-activated macrophages when tested against heat inactivated and live biofilms (average 8%). Heat-inactivated and live biofilms induced similar phagocytic responses and up-regulation of pro-inflammatory genes in macrophages, indirectly conveying that macrophage responses are to some extent dependent on the biofilm matrix.
Cloud failure prediction based on traditional machine learning and deep learning
Authors: Tengku Asmawi Tengku Nazmi , Ismail Azlan , Shen Jun 
Published: September 2022

AbstractCloud failure is one of the critical issues since it can cost millions of dollars to cloud service providers, in addition to the loss of productivity suffered by industrial users. Fault tolerance management is the key approach to address this issue, and failure prediction is one of the techniques to prevent the occurrence of a failure. One of the main challenges in performing failure prediction is to produce a highly accurate predictive model. Although some work on failure prediction models has been proposed, there is still a lack of a comprehensive evaluation of models based on different types of machine learning algorithms. Therefore, in this paper, we propose a comprehensive comparison and model evaluation for predictive models for job and task failure. These models are built and trained using five traditional machine learning algorithms and three variants of deep learning algorithms. We use a benchmark dataset, called Google Cloud Traces, for training and testing the models. We evaluated the performance of models using multiple metrics and determined their important features, as well as measured their scalability. Our analysis resulted in the following findings. Firstly, in the case of job failure prediction, we found that Extreme Gradient Boosting produces the best model where the disk space request and CPU request are the most important features that influence the prediction. Second, for task failure prediction, we found that Decision Tree and Random Forest produce the best models where the priority of the task is the most important feature for both models. Our scalability analysis has determined that the Logistic Regression model is the most scalable as compared to others.
Formulation of abamectin and plant oil-based nanoemulsions with efficacy against the two-spotted spider mite Tetranychus urticae (Acari: Tetranychidae) under laboratory and field conditions
Authors: Ismail Tamer , Keratum Attia , El-Hetawy Lamia 
Published: September 2022

AbstractDue to the harmful effects of synthetic chemical acaricides on ecosystems and human health, there is increasing interest in the use of nanotechnology to fabricate eco-friendly nanoemulsions based on plant oils in the field of spider mite control. In this study, nanoemulsions of abamectin, garlic, and neem oils were prepared by a high-energy approach and characterized by transmission electron microscopy. The droplet sizes of all tested nanoemulsions were less than 100 nm. The acaricidal activities of the prepared nanoemulsions compared to abamectin were evaluated against a susceptible laboratory strain of Tetranychus urticae Koch (Acari: Tetranychidae) under laboratory and field conditions. The results showed that abamectin nanoemulsion was the most toxic compound against adult females of T. urticae followed by abamectin emulsion. Neem nanoemulsion had moderate toxicity and garlic nanoemulsion had the lowest toxicity. The effects of tested compound residues on egg deposition and egg hatching in descending order were as follows: abamectin nanoemulsion > abamectin emulsion > neem oil nanoemulsion < garlic oil nanoemulsion. In the field experiment, all tested compounds were effective in reducing the population density of T. urticae in the motile stage, with mean reductions ranging between 66.08% and 95.24% for all compounds. The most effective compound was abamectin nanoemulsion. The results of the present study demonstrate that nanoemulsion enhanced the biological activity of abamectin. Further, neem and garlic oil nanoemulsions have potential utility as environmentally friendly acaricides in integrated pest management programs.
Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants
Authors: Baccelli Francesco , Leardini Davide , Muratore Edoardo , Messelodi Daria , Bertuccio Salvatore Nicola , Chiriaco Maria , Cancrini Caterina , Conti Francesca , Castagnetti Fausto , Pedace Lucia , Pession Andrea , Yoshimi Ayami , Niemeyer Charlotte , Tartaglia Marco , Locatelli Franco , Masetti Riccardo 
Published: September 2022

AbstractBackgroundCBL syndrome is a RASopathy caused by heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. It is characterized by heterogeneous clinical phenotype, including developmental delay, facial dysmorphisms, cardiovascular malformations and an increased risk of cancer development, particularly juvenile myelomonocytic leukemia (JMML). Although the clinical phenotype has been progressively defined in recent years, immunological manifestations have not been well elucidated to date.MethodsWe studied the genetic, immunological, coagulative, and clinical profile of a family with CBL syndrome that came to our observation after the diagnosis of JMML, with homozygous CBL mutation, in one of the members.ResultsVariant analysis revealed the co-occurrence of CBL heterozygous mutation (c.1141 T > C) andSH2B3mutation (c.1697G > A) in two other members. Patients carrying both mutations showed an ALPS-like phenotype characterized by lymphoproliferation, cytopenia, increased double-negative T-cells, impaired Fas-mediated lymphocyte apoptosis, altered cell death in PBMC and low TRECs expression. A coagulative work-up was also performed and showed the presence of subclinical coagulative alterations in patients carrying both mutations.ConclusionIn the reported family, we described immune dysregulation, as part of the clinical spectrum of CBL mutation with the co-occurrence of SH2B3.