bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analyses reveal two molecularly and clinically distinct subtypes of H3 K27M-mutant diffuse midline gliomas with prognostic significance
Authors: Stegat Lotte , Eckhardt Alicia , Gocke Antonia , Neyazi Sina , Pohl Lara , Schmid Simone , Dottermusch Matthias , Frank Stephan , Pinnschmidt Hans , Herms Jochen , Glatzel Markus , Snuderl Matija , Schweizer Leonille , Thomas Christian , Neumann Julia , Dorostkar Mario M. , Schüller Ulrich , Wefers Annika K. 
Published: September 2024

AbstractH3 K27M-altered diffuse midline gliomas (DMGs) are highly malignant tumours that arise in the midline structures of the CNS. Most DMGs carry an H3 K27M-mutation in one of the genes encoding for histone H3. Recent studies suggested that epigenetic subgroups of DMGs can be distinguished based on alterations in the MAPK-signalling pathway, tumour localisation, mutant H3-gene, or overall survival (OS). However, as these parameters were studied individually, it is unclear how they collectively influence survival. Hence, we analysed dependencies between different parameters, to define novel epigenetic, clinically meaningful subgroups of DMGs. We collected a multifaceted cohort of 149 H3 K27M-mutant DMGs, also incorporating data of published cases. DMGs were included in the study if they could be clearly allocated to the spinal cord (n = 31; one patient with an additional sellar tumour), medulla (n = 20), pons (n = 64) or thalamus (n = 33), irrespective of further known characteristics. We then performed global genome-wide DNA methylation profiling and, for a subset, DNA sequencing and survival analyses. Unsupervised hierarchical clustering of DNA methylation data indicated two clusters of DMGs, i.e. subtypes DMG-A and DMG-B. These subtypes differed in mutational spectrum, tumour localisation, age at diagnosis and overall survival. DMG-A was enriched for DMGs with MAPK-mutations, medullary localisation and adult age. 13% of DMG-A had a methylated MGMT promoter. Contrarily, DMG-B was enriched for cases with TP53-mutations, PDGFRA-amplifications, pontine localisation and paediatric patients. In univariate analyses, the features enriched in DMG-B were associated with a poorer survival. However, all significant parameters tested were dependent on the cluster attribution, which had the largest effect on survival: DMG-A had a significantly better survival compared to DMG-B (p < 0.001). Hence, the subtype attribution based on two methylation clusters can be used to predict survival as it integrates different molecular and clinical parameters.
GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)
Authors: Katzdobler Sabrina , Nübling Georg , Klietz Martin , Fietzek Urban M. , Palleis Carla , Bernhardt Alexander M. , Wegner Florian , Huber Meret , Rogozinski Sophia , Schneider Luisa-Sophie , Spruth Eike Jakob , Beyle Aline , Vogt Ina R. , Brandt Moritz , Hansen Niels , Glanz Wenzel , Brockmann Kathrin , Spottke Annika , Hoffmann Daniel C. , Peters Oliver , Priller Josef , Wiltfang Jens , Düzel Emrah , Schneider Anja , Falkenburger Björn , Klockgether Thomas , Gasser Thomas , Nuscher Brigitte , Haass Christian , Höglinger Günter , Levin Johannes 
Published: September 2024

Abstract
Background
Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA.

Methods
GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson’s disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores).

Results
In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90–1.00; plasma: AUC = 0.90, 95% CI 0.81–1.00).

Discussion
In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.
Salt-sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity
Authors: Verouti S. , Aeschlimann G. , Wang Q. , Del Olmo D. Ancin , Peyter A. C. , Menétrey S. , Winter D. V. , Odermatt A. , Pearce D. , Hummler E. , Vanderriele P. E. 
Published: September 2024

AbstractIn humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/− rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active polyunsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregulated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.
Gross lesions associated with Sarcocystis miescheriana in a wild boar hunted for human consumption: the importance of trained hunters to ensure animal health surveillance and food safety
Authors: Vieira-Pinto Madalena , Chiesa Francesco , Pires Isabel Cristina Ribeiro , Duarte Carmen Gonzalez , Rubiola Selene 
Published: September 2024

AbstractSarcocystis is a genus of protozoa with a worldwide distribution infecting a wide range of animals, including humans. Wild boars can harbor at least two species of Sarcocystis, that is, the zoonotic Sarcocystis suihominis, using humans as definitive hosts, and Sarcocystis miescheriana, for which wild and domestic canids serve as definitive hosts. In Portugal, hunting holds significant economic and social importance, and wild boars are among the most appreciated hunted species. As the consumption of wild boar meat can expose humans to several foodborne pathogens, the presence of trained hunters can make a difference in ensuring animal health surveillance and food safety. Herein, we report the detection of macroscopic cystic lesions associated with S. miescheriana in a wild boar hunted for human consumption, resulting in carcass condemnation. To the best of the authors’ knowledge, the presence of S. miescheriana in wild boar tissues has never been associated with macroscopic pathological alterations before. Although S. miescheriana cannot infect humans, carcasses affected by grossly visible pathological changes must be declared unfit for consumption. Therefore, our finding points out the potential economic damage associated with carcass rejection due to the presence of gross lesions associated with generalized sarcocystosis. Nonetheless, further studies are required to investigate these alterations that currently appear to be occasional findings.
Palliative care in terminally ill advanced chronic liver disease patients
Authors: Pomej Katharina , Masel Eva Katharina , Kreye Gudrun 
Published: September 2024

SummaryWhile mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have a comparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, a lack of confidence in prescribing medication and a lack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.
Management of hip osteoarthritis: harnessing the potential of mesenchymal stem cells—a systematic review
Authors: Giorgino Riccardo , Alessandri Bonetti Mario , Migliorini Filippo , Nannini Alessandra , Vaienti Luca , Peretti Giuseppe Michele , Mangiavini Laura 
Published: September 2024

Abstract
Introduction
Hip osteoarthritis (OA) is a prevalent and debilitating condition, necessitating effective and safe treatment options. This systematic review aims to explore the potential of intra-articular mesenchymal stem cell (MSC) infiltrations as a therapeutic approach for hip OA.

Methods
Following PRISMA guidelines, a systematic review was conducted, encompassing PubMed, Embase, and Cochrane Library databases. Inclusion criteria involved studies focusing on intra-articular MSC injections in patients with hip OA and reporting pain relief as an outcome measure. Quality assessment utilized the Newcastle–Ottawa scale and methodological index for non-randomized studies.

Results
Ten studies were included in the review, exhibiting varied designs and sample sizes (316 patients). Outcome measures consisted of cartilage repair assessed through MRI and radiographies, pain scores (WOMAC, VAS, NRS), and functional improvements (HOS-ADL, OHS, FRI, PDQQ, LEFS). The studies reported favorable improvements in functional scores, pain relief, and cartilage repair/radiographic findings, with minimal reported adverse events.

Conclusions
Intra-articular MSC infiltrations demonstrate promise as an effective and safe therapeutic intervention for managing hip OA, offering pain relief and functional enhancements. Nevertheless, limited high-quality studies and outcome measure variations underscore the need for further research to establish definitive treatment guidelines. Future investigations should address optimal MSC utilization, long-term outcomes, and potential complications to ensure the success of MSC-based therapies for hip OA management, ultimately improving patient outcomes. The findings provide valuable insights into the potential of MSC-based treatments for hip OA, advocating further rigorous research in this field.

Trial Registration
The protocol was registered on PROSPERO database (CRD42023436973).
A comparison of climate drivers’ impacts on silage maize yield shock in Germany
Authors: Stainoh Federico , Moemken Julia , Gouveia Celia M. , Pinto Joaquim G. 
Published: September 2024

AbstractExtreme weather events have become more frequent and severe with ongoing climate change, with a huge implication for the agricultural sector and detrimental effects on crop yield. In this study, we compare several combinations of climate indices and utilized the Least Absolute Shrinkage and Selection Operator (LASSO) to explain the probabilities of substantial drops in silage maize yield (here defined as “yield shock” by using a 15th percentile as threshold) in Germany between 1999 and 2020. We compare the variable importance and the predictability skill of six combinations of climate indices using the Matthews Correlation Coefficient (MCC). Finally, we delve into year-to-year predictions by comparing them against the historical series and examining the variables contributing to high and low predicted yield shock probabilities. We find that cold conditions during April and hot and/or dry conditions during July increase the chance of silage maize yield shock. Moreover, a combination of simple variables (e.g. total precipitation) and complex variables (e.g. cumulative cold under cold nights) enhances predictive accuracy. Lastly, we find that the years with higher predicted yield shock probabilities are characterized mainly by relatively hotter and drier conditions during July compared to years with lower yield shock probabilities. Our findings enhance our understanding of how weather impacts maize crop yield shocks and underscore the importance of considering complex variables and using effective selection methods, particularly when addressing climate-related events.
Do Children Cause the Cognitive Stimulation they Receive? Modelling the Direction of Causality
Authors: Starr Alexandra , Oginni Olakunle , von Stumm Sophie 
Published: September 2024

AbstractWe tested the directionality of associations between children’s early-life cognitive development and the cognitive stimulation that they received from their parents. Our sample included up to 15,314 children from the Twins Early Development Study (TEDS), who were born between 1994 and 1996 in England and Wales and assessed at ages 3 and 4 years on cognitive development and cognitive stimulation, including singing rhymes, reading books, and playing games. Using genetically informative cross-lagged models, we found consistent, bidirectional effects from cognitive development at age 3 to cognitive stimulation at age 4, and from cognitive stimulation at age 3 to cognitive development at age 4. These cross-lagged longitudinal effects were largely explained by underlying common genetic and shared environmental factors, rather than reflecting causal mechanisms. Our findings emphasize the active role that children play in constructing their own learning experiences.
Feasibility study on virtual reality-based training for skin cancer screening: Bridging the gap in dermatological education
Authors: Mergen Marvin , Will Lisa , Graf Norbert , Meyerheim Marcel 
Published: September 2024

AbstractDespite growing interest in the inclusion of virtual reality (VR) in medical education, its full potential for immersive and interactive training remains underutilized, particularly in dermatology. As part of a multidisciplinary project, we tested the feasibility of integrating a VR training scenario for a complete skin cancer screening into the curriculum with 58 medical students. The evaluation focused on simulation usability, cognitive task load, immersion, change in perceived competence, suitability, and cybersickness using established and adapted questionnaires. Participants reported rather high levels of system usability and immersion and medium cognitive task load. Self-assessed competence in performing a skin cancer screening increased significantly after the training simulation.Prior skin cancer screening experience correlated positively with self-assessed competence and theoretical knowledge, which themselves were neither related to gender nor age. Age correlated negatively with perceived usability and immersion, enjoyment of learning during the simulation and assessed appropriateness of the simulation to learn a dermatological full-body examination while being positively correlated with perceived cybersickness. Gender was significantly associated with the need for technical help during the simulation and openness to new technologies.As a blueprint of a feasibility evaluation, this study can contribute to further refinement of the presented and relatable VR applications in medical curricula.
An integrated strategy for pathogen surveillance unveiled Xylella fastidiosa ST1 outbreak in hidden agricultural compartments in the Apulia region (Southern Italy)
Authors: Cornara Daniele , Boscia Donato , D’Attoma Giusy , Digiaro Michele , Ligorio Angela Maria , Loconsole Giuliana , Minutillo Serena Anna , Montilon Vito , Palmisano Francesco , Ragone Gianvito , Silletti Maria Rosaria , Verrastro Vincenzo , Zaza Claudio , Saponari Maria 
Published: September 2024

Abstract
Annual surveillance programs for the plant pathogenic bacterium Xylella fastidiosa are implemented in Europe as part of the preventive phytosanitary strategies enforced to face the emergence of the detrimental infections reported in olives in southern Italy. The programs include inspections and sampling of host plants by prioritizing those showing suspicious symptoms or those known to be highly susceptible to different strains and subspecies of the bacterium. In the framework of these programs numerous outbreaks have been unraveled, with several strains and subspecies found to infect a relatively large host range in France, Spain, Portugal and Italy. Here we report the results of an integrated surveillance approach implemented in the Apulia Region (southern Italy), where a conventional survey program on host plants is complemented by monitoring and testing for X. fastidiosa the insect vectors. In the framework of this program, bacterium-positive spittlebugs were intercepted in the Xylella-free area of the region, close to one of the most relevant Italian table grape production district. Such findings prompted further investigation to identify the bacterial reservoir in the host plants. Almond and grapevine were found to be the most frequently infected hosts, with infections caused by isolates of X. fastidiosa subspecies fastidiosa ST1. Investigations are ongoing to assess the extent and history of the outbreak, to assess and estimate the potential impacts, and define the best options for its containment.
Early sex identification by leaflet distance in plantlets of Cycas revoluta
Authors: De Luca Ylenia , Cozzolino Salvatore , Cristaudo Antonia , Widmer Alex , Cafasso Donata 
Published: September 2024

AbstractIn dioecious plants, the process of sex determination usually occurs during the reproductive stage. However, it can be challenging to determine the sex of long-lived plants with long generation times. This is true for Cycas revoluta, which produces toxic seeds in female plants, leading to a preference for male plants in public green spaces. In this study we aim to identify a morphological trait that can be used to distinguish between the sexes in C. revoluta at a very early stage of plant growth. We sampled C. revoluta seedlings/plantlets at three different early growth stages and identified the sex of individuals by PCR amplification of a male-specific molecular marker. On the same plants, we measured morphological traits, including the distance between leaflets on the leaf rachis, perimeter, area, number of indents, and leaf complexity, and evaluated their correlation with the sex of the individuals. Among all measured traits, the medium distance between leaflets on the leaf rachis was found to be a sexually dimorphic morphological trait in Cycas plantlets in all three growth stages. In particular, the distance between leaflets on the leaf rachis in the upper part of the leaf in the first stage revealed no overlap between the sexes. Whenever available, morphological traits for sex differentiation in greenhouses and plant nurseries can represent a rapid and economic tool when coupled with automatized image recognition systems.
The Kynurenine Pathway in Gut Permeability and Inflammation
Authors: Kearns Rowan 
Published: September 2024

AbstractThe gut-brain axis (GBA) is a crucial communication network linking the gastrointestinal (GI) tract and the central nervous system (CNS). The gut microbiota significantly influences metabolic, immune, and neural functions by generating a diverse array of bioactive compounds that modulate brain function and maintain homeostasis. A pivotal mechanism in this communication is the kynurenine pathway, which metabolises tryptophan into various derivatives, including neuroactive and neurotoxic compounds. Alterations in gut microbiota composition can increase gut permeability, triggering inflammation and neuroinflammation, and contributing to neuropsychiatric disorders. This review elucidates the mechanisms by which changes in gut permeability may lead to systemic inflammation and neuroinflammation, with a focus on the kynurenine pathway. We explore how probiotics can modulate the kynurenine pathway and reduce neuroinflammation, highlighting their potential as therapeutic interventions for neuropsychiatric disorders. The review integrates experimental data, discusses the balance between neurotoxic and neuroprotective kynurenine metabolites, and examines the role of probiotics in regulating inflammation, cognitive development, and gut-brain axis functions. The insights provided aim to guide future research and therapeutic strategies for mitigating GI complaints and their neurological consequences.