bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel protein-based prognostic signature linked to immunotherapeutic efficiency in ovarian cancer
Authors: Chen Shuo-Fu , Wang Liang-Yun , Lin Yi-Sian , Chen Cho-Yi 
Published: September 2024

Abstract

Background
Personalized medicine remains an unmet need in ovarian cancer due to its heterogeneous nature and complex immune microenvironments, which has gained increasing attention in the era of immunotherapy. A key obstacle is the lack of reliable biomarkers to identify patients who would benefit significantly from the therapy. While conventional clinicopathological factors have exhibited limited efficacy as prognostic indicators in ovarian cancer, multi-omics profiling presents a promising avenue for comprehending the interplay between the tumor and immune components. Here we aimed to leverage the individual proteomic and transcriptomic profiles of ovarian cancer patients to develop an effective protein-based signature capable of prognostication and distinguishing responses to immunotherapy.

Methods
The workflow was demonstrated based on the Reverse Phase Protein Array (RPPA) and RNA-sequencing profiles of ovarian cancer patients from The Cancer Genome Atlas (TCGA). The algorithm began by clustering patients using immune-related gene sets, which allowed us to identify immune-related proteins of interest. Next, a multi-stage process involving LASSO and Cox regression was employed to distill a prognostic signature encompassing five immune-related proteins. Based on the signature, we subsequently calculated the risk score for each patient and evaluated its prognostic performance by comparing this model with conventional clinicopathological characteristics.

Results
We developed and validated a protein-based prognostic signature in a cohort of 377 ovarian cancer patients. The risk signature outperformed conventional clinicopathological factors, such as age, grade, stage, microsatellite instability (MSI), and homologous recombination deficiency (HRD) status, in terms of prognoses. Patients in the high-risk group had significantly unfavorable overall survival (p < 0.001). Moreover, our signature effectively stratified patients into subgroups with distinct immune landscapes. The high-risk group exhibited higher levels of CD8 T-cell infiltration and a potentially greater proportion of immunotherapy responders. The co-activation of the TGF-β pathway and cancer-associated fibroblasts could impair the ability of cytotoxic T cells to eliminate cancer cells, leading to poor outcomes in the high-risk group.

Conclusions
The protein-based signature not only aids in evaluating the prognosis but also provides valuable insights into the tumor immune microenvironments in ovarian cancer. Together our findings highlight the importance of a thorough understanding of the immunosuppressive tumor microenvironment in ovarian cancer to guide the development of more effective immunotherapies.
Microwave-assisted organic acids and green hydrogen production during mixed culture fermentation
Authors: Barth Maximilian , Werner Magdalena , Otto Pascal , Richwien Benjamin , Bahramsari Samira , Krause Maximilian , Schwan Benjamin , Abendroth Christian 
Published: September 2024

Abstract
Background
The integration of anaerobic digestion into bio-based industries can create synergies that help render anaerobic digestion self-sustaining. Two-stage digesters with separate acidification stages allow for the production of green hydrogen and short-chain fatty acids, which are promising industrial products. Heat shocks can be used to foster the production of these products, the practical applicability of this treatment is often not addressed sufficiently, and the presented work therefore aims to close this gap.

Methods
Batch experiments were conducted in 5 L double-walled tank reactors incubated at 37 °C. Short microwave heat shocks of 25 min duration and exposure times of 5–10 min at 80 °C were performed and compared to oven heat shocks. Pairwise experimental group differences for gas production and chemical parameters were determined using ANOVA and post–hoc tests. High-throughput 16S rRNA gene amplicon sequencing was performed to analyse taxonomic profiles.

Results
After heat–shocking the entire seed sludge, the highest hydrogen productivity was observed at a substrate load of 50 g/l with 1.09 mol H2/mol hexose. With 1.01 mol H2/mol hexose, microwave-assisted treatment was not significantly different from oven-based treatments. This study emphasised the better repeatability of heat shocks with microwave-assisted experiments, revealing low variation coefficients averaging 29%. The pre-treatment with microwaves results in a high predictability and a stronger microbial community shift to Clostridia compared to the treatment with the oven. The pre-treatment of heat shocks supported the formation of butyric acid up to 10.8 g/l on average, with a peak of 24.01 g/l at a butyric/acetic acid ratio of 2.0.

Conclusion
The results support the suitability of using heat shock for the entire seed sludge rather than just a small inoculum, making the process more relevant for industrial applications. The performed microwave-based treatment has proven to be a promising alternative to oven-based treatments, which ultimately may facilitate their implementation into industrial systems. This approach becomes economically sustainable with high-temperature heat pumps with a coefficient of performance (COP) of 4.3.

Graphical abstract
PRKACB is a novel imprinted gene in marsupials
Authors: Newman Trent , Bond Donna M. , Ishihara Teruhito , Rizzoli Phoebe , Gouil Quentin , Hore Timothy A. , Shaw Geoff , Renfree Marilyn B. 
Published: September 2024

Abstract
Background
Genomic imprinting results in parent-of-origin-specific gene expression and, among vertebrates, is found only in therian mammals: marsupials and eutherians. A differentially methylated region (DMR), in which the methylation status of CpG dinucleotides differs between the two alleles, can mark the parental identity of imprinted genes. We developed a computational pipeline that detected CpG islands (CGIs) marked by both methylated and unmethylated signals in whole genome bisulfite sequencing data. This approach identified candidate marsupial DMRs in a publicly available koala methylome. One of these candidate DMRs was associated with PRKACB, a gene encoding the protein kinase A catalytic subunit beta. Nothing is known about the imprinting status of PRKACB in eutherian mammals although mutations of this gene are associated with endocrine neoplasia and other developmental disorders.

Results
In the tammar wallaby and brushtail possum there was parent-of-origin-specific DNA methylation in the PRKACB DMR in which the maternal allele was methylated and the paternal allele was unmethylated. There were multiple RNAs transcribed from this locus. Allele-specific expression analysis identified paternal expression of a PRKACB lncRNA and an mRNA isoform. Comparison of the PRKACB gene start site between marsupials and eutherians demonstrated that the CGI is longer in marsupials. The PRKACB gene product functions in the same signalling pathway as the guanine nucleotide-binding protein alpha subunit encoded at the GNAS locus, a known eutherian imprinted gene. In a mouse methylome Gnas had three differentially methylated CGIs, while in the koala methylome the GNAS locus had two unmethylated CGIs.

Conclusions
We conclude that PRKACB is a novel, DMR-associated marsupial imprinted gene. Imprinting of PRKACB in marsupials and GNAS in eutherians may indicate a conserved selection pressure for imprinting of the protein kinase A signalling pathway in therians with the two lineages adapting by imprinting different genes.
Small extracellular vesicles derived from synovial fibroblasts contain distinct miRNA profiles and contribute to chondrocyte damage in osteoarthritis
Authors: Asghar Sabha , Litherland Gary J. , Cole John J. , McInnes Iain B. , Meek R. M. D. , Lockhart John C. , Goodyear Carl S. , Crilly Anne 
Published: September 2024

Abstract
Background
Small extracellular vesicles (sEV) derived from synovial fibroblasts (SF) represent a novel molecular mechanism regulating cartilage erosion in osteoarthritis (OA). However, a comprehensive evaluation using disease relevant cells has not been undertaken. The aim of this study was to isolate and characterise sEV from OA SF and to look at their ability to regulate OA chondrocyte effector responses relevant to disease. Profiling of micro (mi) RNA signatures in sEV and parental OA SF cells was performed.

Methods
SF and chondrocytes were isolated from OA synovial membrane and cartilage respectively (n = 9). sEV were isolated from OA SF (± IL-1β) conditioned media by ultracentrifugation and characterised using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Particle size was confirmed by nanoparticle tracking analysis (NTA). sEV regulation of OA chondrocyte and cartilage effector response was evaluated using qPCR, ELISA and sulphated glycosaminoglycan assay (sGAG). RNA-sequencing was used to establish miRNA signatures in isolated sEV from OA SF.

Results
OA SF derived sEV were readily taken up by OA chondrocytes, with increased expression of the catabolic gene MMP 13 (p < 0.01) and decreased expression of the anabolic genes aggrecan and COL2A1 (p < 0.01) observed. Treatment with sEV derived from IL-1β stimulated OA SF significantly decreased expression of aggrecan and COL2A1 (p < 0.001) and increased SOX 9 gene expression (p < 0.05). OA chondrocytes cultured with sEV from either non-stimulated or IL-1β treated OA SF, resulted in a significant increase in the secretion of IL-6, IL-8 and MMP-3 (p < 0.01). Cartilage explants cultured with sEV from SF (± IL-1β) had a significant increase in the release of sGAG (p < 0.01). miRNA signatures differed between parental SF cells and isolated sEV. The recently identified osteoclastogenic regulator miR182, along with miR4472-2, miR1302-3, miR6720, miR6087 and miR4532 were enriched in sEV compared to parental cells, p < 0.01. Signatures were similar in sEVs derived from non-stimulated or IL-1β stimulated SF.

Conclusions
OA SF sEV regulate chondrocyte inflammatory and remodelling responses. OA SF sEV have unique signatures compared to parental cells which do not alter with IL-1β stimulation. This study provides insight into a novel regulatory mechanism within the OA joint which could inform future targeted therapy.
Special Issue: 100 years of scientific excavations at UNESCO World Heritage Site Monte San Giorgio and global research on Triassic marine Lagerstätten
Authors: Klug Christian , Scheyer Torsten M. , Klein Nicole , Liu Jun , Albisetti Daniele , Furrer Heinz , Stockar Rudolf 
Published: October 2024

AbstractOnly a few Swiss fossil localities are known globally and of which, the UNESCO World Heritage Site Monte San Giorgio, which extends from Switzerland into Italy, is the most important one. Following the discovery of the occurrence of articulated skeletons of marine reptiles in the local mines, large excavations were organized by Bernhard Peyer from the University of Zurich starting 1924. With this collection of articles, we commemorate the successful excavations and research, which initiated the publication of a series of monographies, mostly on the vertebrates but also on the invertebrates of this locality. Especially with the discovery of several remarkably similar Konservat-Lagerstätten in China, the discoveries from Monte San Giorgio gained global relevance. New methodologies such as computed tomography produced a wealth of new data, particularly on endocranial anatomy of several tetrapods.
Hepatic transcriptomic analysis reveals differential regulation of metabolic and immune pathways in three strains of chickens with distinct growth rates exposed to mixed parasite infections
Authors: Oladosu Oyekunle John , Reyer Henry , Weikard Rosemarie , Grafl Beatrice , Liebhart Dieter , Metges Cornelia C. , Kühn Christa , Daş Gürbüz 
Published: September 2024

AbstractDuring parasite infections, the liver may prioritise immune-related pathways over its metabolic functions. Intestinal infections caused by Ascaridia galli and Heterakis gallinarum impair feed intake, nutrient absorption, and weight gain. Histomonas meleagridis, vectored by H. gallinarum, can also damage liver tissues, potentially impairing liver functions. This study examined the hepatic gene expression in three strains of chickens: Ross-308 (R), Lohmann Brown Plus (LB), and Lohmann Dual (LD), 2 weeks after an experimental infection (n = 18) with both A. galli and H. gallinarum or kept as uninfected control (n = 12). Furthermore, H. gallinarum infection led to a co-infection with H. meleagridis. The mixed infections reduced feed intake and the average daily weight gain (P < 0.001). The infections also increased the plasma concentrations of alpha (1)-acid glycoprotein and the antibody titre against H. meleagridis (P = 0.049), with no strain differences (P > 0.05). For host molecular response, 1887 genes were differentially expressed in LD, while 275 and 25 genes were differentially expressed in R and LB, respectively. The up-regulated genes in R and LD were mostly related to inflammatory and adaptive immune responses, while down-regulated genes in LD were involved in metabolic pathways, including gluconeogenesis. Despite performance differences among the strains, worm burdens were similar, but hepatic molecular responses differed significantly. Moreover, there was an indication of a shift in hepatic functions towards immune-related pathways. We, therefore, conclude that the liver shifts its functions from metabolic to immune-related activities in chickens when challenged with mixed parasite species.
“To exercise sustainably” – Patients’ experiences of compulsive exercise in eating disorders and the Compulsive Exercise Activity Therapy (LEAP) as a treatment: a qualitative interview study
Authors: Simón Emma Thell , Monell Elin , Lindstedt Katarina , Wiberg Anne-Charlotte , Mantilla Emma Forsén 
Published: October 2024

Abstract
Background
Compulsive exercise is common in eating disorders (EDs), but a systematic treatment model is lacking. The CompuLsive Exercise Activity TheraPy (LEAP) is a cognitive behavioral therapy treatment for compulsive exercise in EDs, delivered by trained therapists in groups over four consecutive weeks (8 groupsessions and 1 individual session), aiming to promote healthy physical activity. LEAP is currently evaluated in a randomized efficacy trial. In parallel, it is crucial to learn more about how it is perceived by qualitatively investigating participants’ subjective experiences.

Methods
Nine patients with various EDs participating in the LEAP trial were interviewed about their experiences of taking part in LEAP and about compulsive exercise as an ED symptom using a semi-structured interview guide. The interview transcripts were analyzed according to thematic analysis.

Results
The informants expressed that compulsive exercise had not been addressed in their standard ED treatment and that LEAP as such provided an important complement, spurring reflection, awareness, and changed feelings and behaviors in relation to compulsive exercise. Initially, increased PA was triggered for some, but this side effect was transitory. A wish for more treatment time, in terms of longer or additional sessions, was expressed.

Conclusions
Overall, LEAP seemed to fill an important treatment need and seemed both acceptable and feasible to patients. However, treatment time and the initial increase in PA may need further investigation and attention in order to optimize this treatment.

Trial registration
The trial is registered with the ISRCTN registry (registration date 20200325), trial ID ISRCTN80711391.
Study Protocol for a Cluster, Randomized, Controlled Community Effectiveness Trial of the Early Start Denver Model (ESDM) Compared to Community Early Behavioral Intervention (EBI) in Community Programs serving Young Autistic Children: Partnering for Autism: Learning more to improve Services (PALMS)
Authors: Stahmer Aubyn C. , Dufek Sarah , Rogers Sally J. , Iosif Ana-Maria 
Published: September 2024

Abstract
Background
The rising number of children identified with autism has led to exponential growth in for-profit applied behavior analysis (ABA) agencies and the use of highly structured approaches that may not be developmentally appropriate for young children. Multiple clinical trials support naturalistic developmental behavior interventions (NDBIs) that integrate ABA and developmental science and are considered best practices for young autistic children. The Early Start Denver Model (ESDM) is a comprehensive NDBI shown to improve social communication outcomes for young autistic children in several controlled efficacy studies. However, effectiveness data regarding NDBI use in community-based agencies are limited.

Methods
This study uses a community-partnered approach to test the effectiveness of ESDM compared to usual early behavioral intervention (EBI) for improving social communication and language in autistic children served by community agencies. This is a hybrid type 1 cluster-randomized controlled trial with 2 conditions: ESDM and EBI. In the intervention group, supervising providers will receive training in ESDM; in the control group, they will continue EBI as usual. We will enroll and randomize 100 supervisors (50 ESDM, 50 EBI) by region. Each supervisor enrolls 3 families of autistic children under age 5 (n = 300) and accompanying behavior technicians (n = 200). The primary outcome is child language and social communication at 6 and 12 months. Secondary outcomes include child adaptive behavior, caregiver use of ESDM strategies, and provider intervention fidelity. Child social motivation and caregiver fidelity will be tested as mediating variables. ESDM implementation determinants will be explored using mixed methods.

Discussion
This study will contribute novel knowledge on ESDM effectiveness, the variables that mediate and moderate child outcomes, and engagement of its mechanisms in community use. We expect results from this trial to increase community availability of this model and access to high-quality intervention for young autistic children, especially those who depend on publicly funded intervention services. Understanding implementation determinants will aid scale-up of effective models within communities.

Trail registration
Clinicaltrials.gov identifier number NCT06005285. Registered on August 21, 2023.

Protocol version
Issue date 6 August 2024; Protocol amendment number: 02.
Geothermal resources in Latin-America and their exploration using electromagnetic methods
Authors: Castillo-Reyes Octavio , Prol-Ledesma Rosa María , Corbo-Camargo Fernando , Rojas Otilio 
Published: September 2024

AbstractThe global priority for sustainable societies drives the transition to green energy, with geothermal power as a promising alternative. Latin-American countries benefit from the active volcanism along the Pacific Rim, which fuels their significant geothermal potential. Geothermal electricity production in the region is steadily growing and currently represents approximately $$11\%$$

11
%

of global output (16 GW). This paper provides details on the installed capacity of electrical generation in the most geothermally significant Latin-American countries, as well as the estimated potential production from existing prospects in the region. We also discuss the multiple challenges that limit the widespread development and exploitation of this valuable resource in Latin-America. As México stands as the top electricity producer in the region and ranks sixth worldwide, we offer an overview of its geothermal potential, the use of electromagnetic imaging technologies to enhance Mexican geothermal resource exploration, and the challenges and limitations associated with traditional exploration techniques. Additionally, we present recent case studies on the combined use of these technologies in México, highlighting best practices and lessons learned. The paper identifies open questions and outlines future research directions, particularly in México, to unlock the geothermal potential of the entire region.
Determination of thermal properties of grouting materials for borehole heat exchangers (BHE)
Authors: Albers Anna , Huttenloch Petra , Zorn Roman , Steger Hagen , Blum Philipp 
Published: September 2024

AbstractThermal properties of grouting materials for borehole heat exchangers (BHE) are currently analysed with varying measurement methods and analysis procedures, resulting in difficulties when comparing values of different studies. This study therefore provides the first comprehensive investigation of different analysis procedures by systematically comparing the influence of the measurement method and the sample preparation on the determination of the thermal conductivity and the volumetric heat capacity. Seven dissimilar grouting materials with varying water–solid ratios (W/S) and compositions are analysed. The thermal conductivities of the materials range between 0.9 and 1.8 W m−1 K−1 (transient plane source method, TPS). The volumetric heat capacities range between 3.01 and 3.63 MJ m−3 K−1 (differential scanning calorimetry, DSC). From the findings of this study, a standardised analysis of grouting materials is provided which suggests mixing of the grouting material at a high mixing speed and sample curing under water for 28 days at room temperature. The benefits of calculating the volumetric heat capacities of grouting materials from the specific heat capacities of dry samples measured with the DSC, the water content and the bulk density are demonstrated. Furthermore, an estimation procedure of volumetric heat capacity from the W/S and suspension density with an uncertainty of smaller ± 5% is provided. Finally, this study contributes to consistency and comparability between existing and future studies on the thermal properties of grouting materials.
Admission neutrophil-to-lymphocyte ratio to predict mortality in burn patients: a meta-analysis
Authors: Awad Mohamed K. A. , Elsahhar Ahmed , Alwakeel Mahmoud , Awad Radwa , Gomaa Nada , Salem Amr Muhammad Abdo , Ramadan Mahmood , Elsahhar Ghada , Abdelbaky Reyad Essam Reyad , Fadell Francois 
Published: October 2024

Abstract
Background
The neutrophil-to-lymphocyte ratio (NLR) proves to be a convenient and cost-effective marker with studies showing that a high NLR can serve as a mortality indicator in burn cases. We conducted a meta-analysis aiming to explore whether on-admission NLR values could serve as predictors of mortality in burn patients.

Methods
PubMed, Web of Science, Scopus and Embase were searched from inception until January 2024. We included all studies investigating burn patients that contain information on the NLR value at the time of hospital admission and mortality outcomes. The studies were critically appraised using the NIH Quality Assessment Tool.

Results
Nine studies fulfilled our criteria with a total population of 1837 participants, including 1526 survivor Burn patients and 311 non-survivor Burn patients. The overall mean difference measured by random model showed a significant increase in NLR by 5.06 (95% CI 3.42, 6.68) p ≤ 0.001 for the non-survivor group over the survivors group with heterogeneity I2 = 67.33%, p ≤ 0.001. A meta-regression was done to investigate the potential source of heterogeneity among studies. The results showed that age (p = 0.394), gender (p = 0.164), and sample size (p = 0.099) did not contribute to the source of heterogeneity, however, the burn surface area contributed significantly (p = 0.002). A leave-one-out meta-analysis was done, showing that omitting Le Qui et al., leads to significantly decrease the heterogeneity to be I2 = 2.73%. Meta-regression repeated to assess the burn surface area again to be found noncontributing (p = 0.404).

Conclusions
Our findings support that elevated NLR values can serve as a mortality indicator in burn cases. This will have a great clinical impact by aiding in stratifying the burn patients on admission.