bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling
Authors: Bobis-Wozowicz Sylwia , Paw Milena , Sarna Michał , Kędracka-Krok Sylwia , Nit Kinga , Błażowska Natalia , Dobosz Anna , Hammad Ruba , Cathomen Toni , Zuba-Surma Ewa , Tyszka-Czochara Małgorzata , Madeja Zbigniew 
Published: July 2024

Abstract
Background
Stem cell-derived extracellular vesicles (EVs) are an emerging class of therapeutics with excellent biocompatibility, bioactivity and pro-regenerative capacity. One of the potential targets for EV-based medicines are cardiovascular diseases (CVD). In this work we used EVs derived from human induced pluripotent stem cells (hiPSCs; hiPS-EVs) cultured under different oxygen concentrations (21, 5 and 3% O2) to dissect the molecular mechanisms responsible for cardioprotection.

Methods
EVs were isolated by ultrafiltration combined with size exclusion chromatography (UF + SEC), followed by characterization by nanoparticle tracking analysis, atomic force microscopy (AFM) and Western blot methods. Liquid chromatography and tandem mass spectrometry coupled with bioinformatic analyses were used to identify differentially enriched proteins in various oxygen conditions. We directly compared the cardioprotective effects of these EVs in an oxygen-glucose deprivation/reoxygenation (OGD/R) model of cardiomyocyte (CM) injury. Using advanced molecular biology, fluorescence microscopy, atomic force spectroscopy and bioinformatics techniques, we investigated intracellular signaling pathways involved in the regulation of cell survival, apoptosis and antioxidant response. The direct effect of EVs on NRF2-regulated signaling was evaluated in CMs following NRF2 inhibition with ML385.

Results
We demonstrate that hiPS-EVs derived from physiological hypoxia at 5% O2 (EV-H5) exert enhanced cytoprotective function towards damaged CMs compared to EVs derived from other tested oxygen conditions (normoxia; EV-N and hypoxia 3% O2; EV-H3). This resulted from higher phosphorylation rates of Akt kinase in the recipient cells after transfer, modulation of AMPK activity and reduced apoptosis. Furthermore, we provide direct evidence for improved calcium signaling and sustained contractility in CMs treated with EV-H5 using AFM measurements. Mechanistically, our mass spectrometry and bioinformatics analyses revealed differentially enriched proteins in EV-H5 associated with the antioxidant pathway regulated by NRF2. In this regard, EV-H5 increased the nuclear translocation of NRF2 protein and enhanced its transcription in CMs upon OGD/R. In contrast, inhibition of NRF2 with ML385 abolished the protective effect of EVs on CMs.

Conclusions
In this work, we demonstrate a superior cardioprotective function of EV-H5 compared to EV-N and EV-H3. Such EVs were most effective in restoring redox balance in stressed CMs, preserving their contractile function and preventing cell death. Our data support the potential use of hiPS-EVs derived from physiological hypoxia, as cell-free therapeutics with regenerative properties for the treatment of cardiac diseases.
Novel drug resistance mechanisms and drug targets in BRAF-mutated peritoneal metastasis from colorectal cancer
Authors: Lund-Andersen Christin , Torgunrud Annette , Kanduri Chakravarthi , Dagenborg Vegar J. , Frøysnes Ida S. , Larsen Mette M. , Davidson Ben , Larsen Stein G. , Flatmark Kjersti 
Published: July 2024

Abstract
Background
Patients with peritoneal metastasis from colorectal cancer (PM-CRC) have inferior prognosis and respond particularly poorly to chemotherapy. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC.

Methods
Tumor samples (230) from a Norwegian national cohort undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations with clinical data were analyzed. mRNA sequencing was conducted on a subset of 30 samples to compare gene expression in tumors harboring BRAF or KRAS mutations and wild-type tumors.

Results
BRAF mutations were detected in 27% of the patients, and the BRAF-mutated subgroup had inferior overall survival compared to wild-type cases (median 16 vs 36 months, respectively, p < 0.001). BRAF mutations were associated with RNF43/RSPO aberrations and low expression of negative Wnt regulators (ligand-dependent Wnt activation). Furthermore, BRAF mutations were associated with gene expression changes in transport solute carrier proteins (specifically SLC7A6) and drug metabolism enzymes (CES1 and CYP3A4) that could influence the efficacy of MMC and irinotecan, respectively. BRAF-mutated tumors additionally exhibited increased expression of members of the novel butyrophilin subfamily of immune checkpoint molecules (BTN1A1 and BTNL9).

Conclusions
BRAF mutations were frequently detected and were associated with particularly poor survival in this cohort, possibly related to ligand-dependent Wnt activation and altered drug transport and metabolism that could confer resistance to MMC and irinotecan. Drugs that target ligand-dependent Wnt activation or the BTN immune checkpoints could represent two novel therapy approaches.
Terrestrial laser scanning and low magnetic field digitization yield similar architectural coarse root traits for 32-year-old Pinus ponderosa trees
Authors: Montagnoli Antonio , Hudak Andrew T. , Raumonen Pasi , Lasserre Bruno , Terzaghi Mattia , Silva Carlos A. , Bright Benjamin C. , Vierling Lee A. , de Vasconcellos Bruna N. , Chiatante Donato , Dumroese R. Kasten 
Published: July 2024

Abstract
Background
Understanding how trees develop their root systems is crucial for the comprehension of how wildland and urban forest ecosystems plastically respond to disturbances such as harvest, fire, and climate change. The interplay between the endogenously determined root traits and the response to environmental stimuli results in tree adaptations to biotic and abiotic factors, influencing stability, carbon allocation, and nutrient uptake. Combining the three-dimensional structure of the root system, with root morphological trait information promotes a robust understanding of root function and adaptation plasticity. Low Magnetic Field Digitization coupled with AMAPmod (botAnique et Modelisation de l’Architecture des Plantes) software has been the best-performing method for describing root system architecture and providing reliable measurements of coarse root traits, but the pace and scale of data collection remain difficult. Instrumentation and applications related to Terrestrial Laser Scanning (TLS) have advanced appreciably, and when coupled with Quantitative Structure Models (QSM), have shown some potential toward robust measurements of tree root systems. Here we compare, we believe for the first time, these two methodologies by analyzing the root system of 32-year-old Pinus ponderosa trees.

Results
In general, at the total root system level and by root-order class, both methods yielded comparable values for the root traits volume, length, and number. QSM for each root trait was highly sensitive to the root size (i.e., input parameter PatchDiam) and models were optimized when discrete PatchDiam ranges were specified for each trait. When examining roots in the four cardinal direction sectors, we observed differences between methodologies for length and number depending on root order but not volume.

Conclusions
We believe that TLS and QSM could facilitate rapid data collection, perhaps in situ, while providing quantitative accuracy, especially at the total root system level. If more detailed measures of root system architecture are desired, a TLS method would benefit from additional scans at differing perspectives, avoiding gravitational displacement to the extent possible, while subsampling roots by hand to calibrate and validate QSM models. Despite some unresolved logistical challenges, our results suggest that future use of TLS may hold promise for quantifying tree root system architecture in a rapid, replicable manner.
A new diagnostic technique for identifying Angiostrongylus spp. larvae in intermediate snail species by examining the buccal cavity
Authors: Zhao Yong-bo , Jiang Ling , Fang Wen , Chen Shao-rong , Liu Yu-hua , Zhao Shen-hua , Andrus Peter S. , Li Tian-mei , Guo Yun-hai 
Published: July 2024

Abstract
Background
Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis.

Methods
In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure.

Results
We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods.

Conclusions
This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.

Graphical Abstract
Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus
Authors: Mostafa Salma Mohamed , Elebrashy Ibrahim , Haddad Hemmat El , Shaker Olfat , Razek Naglaa Abdel , Fayed Ahmed 
Published: July 2024

Abstract
Background
Patients with Type 2 diabetes mellitus (T2DM) have decreased bone health. We aimed to investigate serum levels of bone turnover markers (BTMs) (markers of bone formation and bone resorption) and bone mineral density (BMD) at three sites (lumber, neck femur, and total femur) in middle-aged men with type 2 diabetes and to analyze the relationship between them. Also to evaluate serum osteoglycin as a novel marker and its relation to BTMs, BMD, and diabetic status.

Methods
We recruited seventy-eight patients with T2DM and thirteen non-diabetic, male volunteers as a control group. BMD was measured using a DEXA scan. BTMs (carboxy-terminal crosslinking telopeptide of type 1 collagen [CTX] and procollagen type 1 N propeptide [P1NP]), osteoglycin, PTH, and vitamin D were estimated. Data was compared among subjects and statistical analysis was performed.

Results
Most of the patients were having normal BMD with no significant difference between patients and the controls. BTMs and osteoglycin were significantly higher and vitamin D was significantly lower in the diabetic patients. Serum osteoglycin was positively correlated with DEXA Neck Femur (r = 0.233; p-value < 0.05).

Conclusion
Body mass index and Serum osteoglycin have a significant positive effect on BMD. Both markers of bone formation and bone resorption were increased indicating a state of increased bone turnover in T2DM.
Bacteriological quality and physicochemical analysis of the Kalte River at Wolaita Sodo Town, southern Ethiopia
Authors: Sivalingam Krishna Moorthy , Choramo Israel Solomon , Chutulo Eyob Chukalo 
Published: July 2024

Abstract
Objective
The current research aimed to investigate the physicochemical and bacteriological quality status of the Kalte River in Wolaita Sodo Town, southern Ethiopia.

Methods
A total of 42 water samples were collected using sterile glass bottles from three different river sites: Damota (upstream), Kera (midstream), and Gututo (downstream). All the water samples were examined for the presence of heterotrophic bacteria, total coliform and fecal coliform using direct plate count method and membrane filtration method. Standard methods suggested by American water works association were used to analysis the physicochemical parameters of the water samples.

Results
The results revealed that the total heterotrophic bacteria, total coliform, and fecal coliform count ranged from 8.9 to 12.6 × 104 cfu/ml, 7.5–11.3 × 102 cfu/ml and 5.7–9.7 × 104 cfu/ml, respectively. The bacterial count results indicated that the river water crossed the WHO-recommended limit of potable water. Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella, and Shigella species were the common bacterial pathogens isolated from river water samples. The results of the physicochemical analysis revealed that some of the parameters Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), and turbidity exceeded the maximum permissible limits of WHO and other parameters were below the WHO permissible limits.

Conclusion
Therefore, the presence of bacterial pathogens, fecal coliform indicators, and some physicochemical parameters of the Kalte River exceeding the recommended limits may expose users of the river water to the risk of infection.
Visfatin (NAMPT) affects global gene expression in porcine anterior pituitary cells during the mid-luteal phase of the oestrous cycle
Authors: Dobrzyn Kamil , Kopij Grzegorz , Kiezun Marta , Zaobidna Ewa , Gudelska Marlena , Zarzecka Barbara , Paukszto Lukasz , Rak Agnieszka , Smolinska Nina , Kaminski Tadeusz 
Published: July 2024

Abstract
Background
The pituitary belongs to the most important endocrine glands involved in regulating reproductive functions. The proper functioning of this gland ensures the undisturbed course of the oestrous cycle and affects the female’s reproductive potential. It is believed that visfatin, a hormone belonging to the adipokine family, may regulate reproductive functions in response to the female’s metabolic state. Herein we verified the hypothesis that suggests a modulatory effect of visfatin on the anterior pituitary transcriptome during the mid-luteal phase of the oestrous cycle.

Results
RNA-seq analysis of the porcine anterior pituitary cells revealed changes in the expression of 202 genes (95 up-regulated and 107 down-regulated in the presence of visfatin, when compared to the non-treated controls), assigned to 318 gene ontology terms. We revealed changes in the frequency of alternative splicing events (235 cases), as well as long noncoding RNA expression (79 cases) in the presence of the adipokine. The identified genes were associated, among others, with reproductive system development, epithelial cell proliferation, positive regulation of cell development, gland morphogenesis and cell chemotaxis.

Conclusions
The obtained results indicate a modulatory influence of visfatin on the regulation of the porcine transcriptome and, in consequence, pituitary physiology during the mid-luteal phase of the oestrous cycle.
Secondary carnitine deficiency during refeeding in severely malnourished patients with eating disorders: a retrospective cohort study
Authors: Imaeda Miho , Tanaka Satoshi , Oya-Ito Tomoko , Uematsu Mariko , Fujigaki Hidetsugu , Saito Kuniaki , Ando Masahiko , Ozaki Norio 
Published: July 2024

Abstract
Background
Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes.

Method
In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC).

Results
Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21–35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8–14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214–0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217–0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170–40.833, p = 0.032).

Conclusions
Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.
Maternal insecure attachment representation as a long-term risk factor for disrupted mother–child-interaction and child mental health
Authors: Rost Katharina , Ziegenhain Ute , Fegert Jörg M. , Buchheim Anna , Köhler-Dauner Franziska 
Published: July 2024

AbstractMaternal childhood maltreatment (CM) represents an important factor in the transmission of trauma that may lead to impaired child mental health. Apart from childhood maltreatment insecure attachment has been identified as a risk factor for insensitive caregiving behavior, which may affect child's mental health. The aim of this study is to identify the working mechanisms in the relationship between maternal CM and child mental health, considering maternal attachment representation, mother–child-interaction und maternal helplessness and fear. N = 103 mother–child-dyads from a longitudinal cohort study were examined at four different measuring points. Data was assessed using self and external report questionnaires as well as the AMBIANCE scales during the Strange Situation Procedure and the Adult Attachment Projective Picture System (AAP). Maternal CM experience did not predict an insecure attachment representation (OR = 2.46 [0.98, 6.53], p = .060). Maternal insecure attachment was associated with higher AMBIANCE scores (F(8, 94) = 11.46, p < .001), which indicates more disrupted communication between mother and child. AMBIANCE scores in turn predicted higher self-perceived helplessness (F(9, 93) = 8.62, p < .001) and fear (F(9, 93) = 7.40, p < .001) in mothers. Helplessness and fear both were associated with higher SDQ-scores, indicating more mental health problems in children (F(10, 92) = 3.98, p < .001; F(10, 92) = 3.87, p < .001). The results of this study highlight how even insecure attachment in a low-risk sample has a long-term impact on parenting behavior and child mental health, therefore underlining the need of early intervention programs in affected and at-risk families.
Assessment of visual quality and social perception of cultural landscapes: application to Anyi traditional villages, China
Authors: Kang Ning , Liu Chunqing 
Published: July 2024

Abstract
The assessment of landscape visual quality (LVQ) holds significant importance in the preservation and advancement of traditional villages. One challenge in measuring human perception lies in establishing a connection between public preferences and landscape characteristics. This study conducted an analysis of social media data from Anyi traditional villages in China to address this issue and identified eight human perceptions: naturalness, ancientness, colorfulness, variety, uniqueness, ingenuity, vividness, and pleasantness. A total of thirty characteristic indicators with potential explanations for LVQ were determined by research group through field investigations. A questionnaire survey was developed to assess human’s preferences using 82 traditional village photos, and scores for the eight perceptions were obtained. The logistic regression was employed to establish distinct perception models, with perceptions serving as the dependent variables and characteristic indicators as the independent variables. Nomograms were subsequently utilized to visualize regression results and display the correlation between these two factors. The findings suggest that nomograms facilitate intuitive determination of the weights assigned to characteristic indicators in perceptual models, as well as their influence on LVQ. This work provides a reference for decision-making related to the adaptive protection and development of traditional villages, thereby helping to enhance the competitiveness of tourist destinations.
Microblasting with vegetable and cellulosic media for heritage wood cleaning: effects on surface morphology
Authors: Iglesias-Campos Manuel Ángel , Pitarch Martí Africa , Nualart-Torroja Anna , Bautista-Morenilla Iris 
Published: July 2024

Abstract
In this research, microblasting with powdered vegetable particles (almond and hazelnut husks, cork saw dust and rice husks) and cellulosic fibres was used to analyse their usefulness for cleaning unpainted wooden cultural heritage and their effects on surface morphology. Tests were made on mock-ups of old pine wood from wooden boards with original soiling. Before cleaning powdered particles were characterised by SEM–EDS to analyse their morphology and elemental composition. Wood surfaces were analysed before and after cleaning by means of digital microscope (white and UV light) and SEM–EDS to evaluate cleaning effectiveness, assess effects on the wood surface, and determine eventual soiling and powdered particles larger than 1 µm that might remain in the surface after the procedure. Results indicate that microblasting with powdered vegetable and cellulosic media is a useful and safe technique to remove soiling from wood, including micrometric particles embedded in its texture, with negligible surface changes. Furthermore, residues left after the cleaning procedure are very scarce and chemically compatible with the substrate because they are mainly composed of cellulose, hemicellulose and lignin, the main components of wood.