bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau- and α-synuclein-targeted gold nanoparticles: applications, opportunities, and future outlooks in the diagnosis and therapy of neurodegenerative diseases
Authors: Tapia-Arellano Andreas , Cabrera Pablo , Cortés-Adasme Elizabeth , Riveros Ana , Hassan Natalia , Kogan Marcelo J. 
Published: May 2024

AbstractThe use of nanomaterials in medicine offers multiple opportunities to address neurodegenerative disorders such as Alzheimer's and Parkinson's disease. These diseases are a significant burden for society and the health system, affecting millions of people worldwide without sensitive and selective diagnostic methodologies or effective treatments to stop their progression. In this sense, the use of gold nanoparticles is a promising tool due to their unique properties at the nanometric level. They can be functionalized with specific molecules to selectively target pathological proteins such as Tau and α-synuclein for Alzheimer’s and Parkinson’s disease, respectively. Additionally, these proteins are used as diagnostic biomarkers, wherein gold nanoparticles play a key role in enhancing their signal, even at the low concentrations present in biological samples such as blood or cerebrospinal fluid, thus enabling an early and accurate diagnosis. On the other hand, gold nanoparticles act as drug delivery platforms, bringing therapeutic agents directly into the brain, improving treatment efficiency and precision, and reducing side effects in healthy tissues. However, despite the exciting potential of gold nanoparticles, it is crucial to address the challenges and issues associated with their use in the medical field before they can be widely applied in clinical settings. It is critical to ensure the safety and biocompatibility of these nanomaterials in the context of the central nervous system. Therefore, rigorous preclinical and clinical studies are needed to assess the efficacy and feasibility of these strategies in patients. Since there is scarce and sometimes contradictory literature about their use in this context, the main aim of this review is to discuss and analyze the current state-of-the-art of gold nanoparticles in relation to delivery, diagnosis, and therapy for Alzheimer’s and Parkinson’s disease, as well as recent research about their use in preclinical, clinical, and emerging research areas.
Graphical Abstract
The TransFORmation of IndiGEnous PrimAry HEAlthcare Delivery (FORGE AHEAD): economic analysis
Authors: Stanimirovic Aleksandra , Francis Troy , Webster-Bogaert Susan , Harris Stewart , Rac Valeria ,   the LIONESS study group
Published: May 2024

Abstract
Background
Indigenous populations have increased risk of developing diabetes and experience poorer treatment outcomes than the general population. The FORGE AHEAD program partnered with First Nations communities across Canada to improve access to resources by developing community-driven primary healthcare models.

Methods
This was an economic assessment of FORGE AHEAD using a payer perspective. Costs of diabetes management and complications during the 18-month intervention were compared to the costs prior to intervention implementation. Cost-effectiveness of the program assessed incremental differences in cost and number of resources utilization events (pre and post). Primary outcome was all-cause hospitalizations. Secondary outcomes were specialist visits, clinic visits and community resource use. Data were obtained from a diabetes registry and published literature. Costs are expressed in 2023 Can$.

Results
Study population was ~ 60.5 years old; 57.2% female; median duration of diabetes of 8 years; 87.5% residing in non-isolated communities; 75% residing in communities < 5000 members. Total cost of implementation was $1,221,413.60 and cost/person $27.89. There was increase in the number and cost of hospitalizations visits from 8/$68,765.85 (pre period) to 243/$2,735,612.37. Specialist visits, clinic visits and community resource use followed this trend.

Conclusion
Considering the low cost of intervention and increased care access, FORGE AHEAD represents a successful community-driven partnership resulting in improved access to resources.
Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer
Authors: Kim Baek Gil , Lee Sung Hwan , Jang Yeonsue , Kang Suki , Kang Chang Moo , Cho Nam Hoon 
Published: May 2024

Abstract
Background
The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography—a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer.

Methods
Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5 < 4.5, MTV-high: MTV2.5 ≥ 4.5). Gene expression fold change was first calculated in cancer tissue compared to its normal counter and then compared between low and high MTV groups to obtain significant DEGs. To assess the suitability of the DEGs for clinical application, the correlation of the DEGs with tumor grades and clinical outcomes was analyzed in TCGA-PAAD, a large dataset without MTV information.

Results
Total RNA-sequencing (MTV RNA-Seq) revealed that 44 genes were upregulated and 56 were downregulated in the high MTV group. We selected the 29 genes matching MTV RNA-seq patterns in the TCGA-PAAD dataset, a large clinical dataset without MTV information, as MTV-associated genes (MAGs). In the analysis with the TCGA dataset, MAGs were significantly associated with patient survival, treatment outcomes, TCGA-PAAD-suggested markers, and CEACAM family proteins. Some MAGs showed an inverse correlation with miRNAs and were confirmed to be differentially expressed between normal and cancerous pancreatic tissues. Overexpression of KIF11 and RCC1 and underexpression of ADCY1 and SDK1 were detected in ~ 60% of grade 2 pancreatic cancer patients and associated with ~ 60% mortality in stages I and II.

Conclusions
MAGs may serve as diagnostic markers and miRNA therapeutic targets for pancreatic cancer. Among the MAGs, KIF11, RCC1, ADCY, and SDK1 may be early diagnostic markers.
Estetrol/GPER/SERPINB2 transduction signaling inhibits the motility of triple-negative breast cancer cells
Authors: Cirillo Francesca , Spinelli Asia , Talia Marianna , Scordamaglia Domenica , Santolla Maria Francesca , Grande Fedora , Rizzuti Bruno , Maggiolini Marcello , Gérard Céline , Lappano Rosamaria 
Published: May 2024

Abstract
Background
Estetrol (E4) is a natural estrogen produced by the fetal liver during pregnancy. Due to its favorable safety profile, E4 was recently approved as estrogenic component of a new combined oral contraceptive. E4 is a selective ligand of estrogen receptor (ER)α and ERβ, but its binding to the G Protein-Coupled Estrogen Receptor (GPER) has not been described to date. Therefore, we aimed to explore E4 action in GPER-positive Triple-Negative Breast Cancer (TNBC) cells.

Methods
The potential interaction between E4 and GPER was investigated by molecular modeling and binding assays. The whole transcriptomic modulation triggered by E4 in TNBC cells via GPER was explored through high-throughput RNA sequencing analyses. Gene and protein expression evaluations as well as migration and invasion assays allowed us to explore the involvement of the GPER-mediated induction of the plasminogen activator inhibitor type 2 (SERPINB2) in the biological responses triggered by E4 in TNBC cells. Furthermore, bioinformatics analysis was aimed at recognizing the biological significance of SERPINB2 in ER-negative breast cancer patients.

Results
After the molecular characterization of the E4 binding capacity to GPER, RNA-seq analysis revealed that the plasminogen activator inhibitor type 2 (SERPINB2) is one of the most up-regulated genes by E4 in a GPER-dependent manner. Worthy, we demonstrated that the GPER-mediated increase of SERPINB2 is engaged in the anti-migratory and anti-invasive effects elicited by E4 in TNBC cells. In accordance with these findings, a correlation between SERPINB2 levels and a good clinical outcome was found in ER-negative breast cancer patients.

Conclusions
Overall, our results provide new insights into the mechanisms through which E4 can halt migratory and invasive features of TNBC cells.
The largest European forest carbon stocks are in the Dinaric Alps old-growth forests: comparison of direct measurements and standardised approaches
Authors: Bono Alessia , Alberti Giorgio , Berretti Roberta , Curovic Milic , Dukic Vojislav , Motta Renzo 
Published: May 2024

AbstractBackgroundCarbon (C) sink and stock are among the most important ecosystem services provided by forests in climate change mitigation policies. In this context, old-growth forests constitute an essential reference point for the development of close-to-nature silviculture, including C management techniques. Despite their small extent in Europe, temperate old-growth forests are assumed to be among the most prominent in terms of biomass and C stored. However, monitoring and reporting of C stocks is still poorly understood. To better understand the C stock amount and distribution in temperate old-growth forests, we estimated the C stock of two old-growth stands in the Dinaric Alps applying different assessment methods, including direct and indirect approaches (e.g., field measurements and allometric equations vs. IPCC standard methods). This paper presents the quantification and the distribution of C across the five main forest C pools (i.e., aboveground, belowground, deadwood, litter and soil) in the study areas and the differences between the applied methods.ResultsWe report a very prominent C stock in both study areas (507 Mg C ha− 1), concentrated in a few large trees (36% of C in 5% of trees). Moreover, we found significant differences in C stock estimation between direct and indirect methods. Indeed, the latter tended to underestimate or overestimate depending on the pool considered.ConclusionsComparison of our results with previous studies and data collected in European forests highlights the prominence of temperate forests, among which the Dinaric Alps old-growth forests are the largest. These findings provide an important benchmark for the development of future approaches to the management of the European temperate forests. However, further and deeper research on C stock and fluxes in old-growth stands is of prime importance to understand the potential and limits of the climate mitigation role of forests.
DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes
Authors: Salama Ola E. , Hizon Nikho , Del Vecchio Melissa , Kolsun Kurt , Fonseca Mario A. , Lin David T. S. , Urtatiz Oscar , MacIsaac Julia L. , Kobor Michael S. , Sellers Elizabeth A. C. , Dolinsky Vernon W. , Dart Allison B. , Jones Meaghan J. , Wicklow Brandy A. 
Published: May 2024

Abstract
Objective
Youth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes.

Methods
We performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry.

Results
We identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth.

Conclusion
Our findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.
Long-lasting severe anemia following treatment with natalizumab for relapsing–remitting multiple sclerosis: a case report
Authors: Hamnvik Lars Henrik Dahl , Tjønnfjord Geir E. , Spetalen Signe , Dalgaard Jakob 
Published: May 2024

Abstract
Background
Natalizumab is a monoclonal antibody used to treat patients with relapsing–remitting multiple sclerosis. Anemia is a recognized side effect, but it is usually mild and of a short duration when natalizumab is stopped. Here, we describe a case of a young woman with severe and especially long lasting anemia associated with treatment with natalizumab, persisting up to a year after treatment was stopped.

Case presentation
A 24 year-old Caucasian woman with relapsing–remitting multiple sclerosis developed severe transfusion dependent anemia after 27 infusions with natalizumab, which was her first and only treatment for her multiple sclerosis. Extensive hematologic diagnostics did not reveal any malignant cause or any other plausible non-malignant cause for her anemia. The bone marrow was found to be hypercellular, with a maturation arrest of the erythropoiesis and with grade 1–2 fibrosis. No specific treatment for the anemia was given. The hemoglobin level showed signs of spontaneous increase after nearly one year after natalizumab was discontinued.

Conclusion
Severe anemia can be caused by treatment with natalizumab. This case adds information to the few other similar reported cases, demonstrating the potential duration of the anemia, as well as detailed description of hematologic findings. The mechanism is most likely due to inhibition of α4 subunit of the α4β1-integrin, which is present on both lymphocytes and erythroid precursor cells.
Optimal station placement based on grey wolf optimizer for regional target localization
Authors: Wang Zewen , Hu Dexiu , Huang Jie , Xie Min , Zhao Chuang 
Published: May 2024

AbstractThe accuracy of target passive localization is influenced by the placement of signal receiving stations; therefore, many studies have been performed to optimize station placement. However, most of the present placement methods focus on the localization error of one target, and if the exact position of the target cannot be determined, but only the range of the target activity is known, how to study the localization station placement in a region is a problem that needs to be solved. This paper proposes a grey wolf optimization algorithm based on the regional target error model to solve the optimal station placement problem. Firstly, a regional target localization error model is established using the measured TDOA, and the overall error matrix within a region is derived. Then, by taking the trace of the error matrix as a criterion, the objective function is established to find the optimal location of the receiving station by grey wolf optimizer. The optimization parameters are also improved to increase the global search ability of the algorithm. Finally, the feasibility and reliability of the overall error model and the grey wolf algorithm proposed are verified by experiments from multiple perspectives. The station placement method proposed in this paper can effectively solve the localization problem of targets that are only known to be in a general activity region in advance, which is more realistic.
Aerobic anoxygenic phototrophs play important roles in nutrient cycling within cyanobacterial Microcystis bloom microbiomes
Authors: Cai Haiyuan , McLimans Christopher J. , Jiang Helong , Chen Feng , Krumholz Lee R. , Hambright K. David 
Published: May 2024

Abstract

Background
During the bloom season, the colonial cyanobacterium Microcystis forms complex aggregates which include a diverse microbiome within an exopolymer matrix. Early research postulated a simple mutualism existing with bacteria benefitting from the rich source of fixed carbon and Microcystis receiving recycled nutrients. Researchers have since hypothesized that Microcystis aggregates represent a community of synergistic and interacting species, an interactome, each with unique metabolic capabilities that are critical to the growth, maintenance, and demise of Microcystis blooms. Research has also shown that aggregate-associated bacteria are taxonomically different from free-living bacteria in the surrounding water. Moreover, research has identified little overlap in functional potential between Microcystis and members of its microbiome, further supporting the interactome concept. However, we still lack verification of general interaction and know little about the taxa and metabolic pathways supporting nutrient and metabolite cycling within Microcystis aggregates.

Results
During a 7-month study of bacterial communities comparing free-living and aggregate-associated bacteria in Lake Taihu, China, we found that aerobic anoxygenic phototrophic (AAP) bacteria were significantly more abundant within Microcystis aggregates than in free-living samples, suggesting a possible functional role for AAP bacteria in overall aggregate community function. We then analyzed gene composition in 102 high-quality metagenome-assembled genomes (MAGs) of bloom-microbiome bacteria from 10 lakes spanning four continents, compared with 12 complete Microcystis genomes which revealed that microbiome bacteria and Microcystis possessed complementary biochemical pathways that could serve in C, N, S, and P cycling. Mapping published transcripts from Microcystis blooms onto a comprehensive AAP and non-AAP bacteria MAG database (226 MAGs) indicated that observed high levels of expression of genes involved in nutrient cycling pathways were in AAP bacteria.

Conclusions
Our results provide strong corroboration of the hypothesized Microcystis interactome and the first evidence that AAP bacteria may play an important role in nutrient cycling within Microcystis aggregate microbiomes.
The big five factors as differential predictors of self-regulation, achievement emotions, coping and health behavior in undergraduate students
Authors: Fuente Jesús de la , Sander Paul , Garzón Umerenkova Angélica , Urien Begoña , Pachón-Basallo Mónica , O Luis Elkin 
Published: May 2024

Abstract
Background
The aim of this research was to analyze whether the personality factors included in the Big Five model differentially predict the self-regulation and affective states of university students and health.

Methods
A total of 637 students completed validated self-report questionnaires. Using an ex post facto design, we conducted linear regression and structural prediction analyses.

Results
The findings showed that model factors were differential predictors of both self-regulation and affective states. Self-regulation and affective states, in turn, jointly predict emotional performance while learning and even student health. These results allow us to understand, through a holistic predictive model, the differential predictive relationships of all the factors: conscientiousness and extraversion were predictors regulating positive emotionality and health; the openness to experience factor was non-regulating; nonregulating; and agreeableness and neuroticism were dysregulating, hence precursors of negative emotionality and poorer student health.

Conclusions
These results are important because they allow us to infer implications for guidance and psychological health at university.
An up-scaled biotechnological approach for phosphorus-depleted rye bran as animal feed
Authors: Widderich Niklas , Stotz Johanna , Lohkamp Florian , Visscher Christian , Schwaneberg Ulrich , Liese Andreas , Bubenheim Paul , Ruff Anna Joëlle 
Published: May 2024

AbstractSide streams from the milling industry offer excellent nutritional properties for animal feed; yet their use is constrained by the elevated phosphorus (P) content, mainly in the form of phytate. Biotechnological P recovery fosters sustainable P management, transforming these streams into P-depleted animal feed through enzymatic hydrolysis. The enzymatic P mobilization not only enables P recovery from milling by-products but also supports the valorization of these streams into P-depleted animal feeds. Our study presents the scalability and applicability of the process and characterizes the resulting P-depleted rye bran as animal feed component. Batch mode investigations were conducted to mobilize P from 100 g to 37.1 kg of rye bran using bioreactors up to 400 L. P reductions of 89% to 92% (reducing from 12.7 gP/kg to 1.41–1.28 gP/kg) were achieved. In addition, High Performance Ion Chromatography (HPIC) analysis showed complete depletion of phytate. The successful recovery of the enzymatically mobilized P from the process wastewater by precipitation as struvite and calcium hydrogen phosphate is presented as well, achieving up to 99% removal efficiency. Our study demonstrates a versatile process that is easily adaptable, allowing for a seamless implementation on a larger scale.
Graphical Abstract
Effective relax acquisition: a novel approach to classify relaxed state in alpha band EEG-based transformation
Authors: Risqiwati Diah , Wibawa Adhi Dharma , Pane Evi Septiana , Yuniarno Eko Mulyanto , Islamiyah Wardah Rahmatul , Purnomo Mauridhi Hery 
Published: May 2024

AbstractA relaxed state is essential for effective hypnotherapy, a crucial component of mental health treatments. During hypnotherapy sessions, neurologists rely on the patient’s relaxed state to introduce positive suggestions. While EEG is a widely recognized method for detecting human emotions, analyzing EEG data presents challenges due to its multi-channel, multi-band nature, leading to high-dimensional data. Furthermore, determining the onset of relaxation remains challenging for neurologists. This paper presents the Effective Relax Acquisition (ERA) method designed to identify the beginning of a relaxed state. ERA employs sub-band sampling within the Alpha band for the frequency domain and segments the data into four-period groups for the time domain analysis. Data enhancement strategies include using Window Length (WL) and Overlapping Shifting Windows (OSW) scenarios. Dimensionality reduction is achieved through Principal Component Analysis (PCA) by prioritizing the most significant eigenvector values. Our experimental results indicate that the relaxed state is predominantly observable in the high Alpha sub-band, particularly within the fourth period group. The ERA demonstrates high accuracy with a WL of 3 s and OSW of 0.25 s using the KNN classifier (90.63%). These findings validate the effectiveness of ERA in accurately identifying relaxed states while managing the complexity of EEG data.
Graphical abstract