bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnoprimatology of the Shipibo of the upper Ucayali River, Perú
Authors: Anca Evelyn , Shanee Sam , Svensson Magdalena S. 
Published: October 2023

AbstractIn the Anthropocene, primate conservation can only take place when considering human culture, perspectives, and needs. Such approaches are increasingly important under the growing impact of anthropogenic activities and increasing number of threatened primates. The Amazon rainforest, rich in cultural and biological diversity, where indigenous people play a crucial role in primate conservation, provides ample opportunity to study human–primate interactions and the sociocultural context in which they occur. Human activities threaten the Amazon’s fragile ecosystems and its primates, which play a key role in its maintenance and regeneration. This study focuses on one of the largest indigenous groups in the Peruvian Amazon: the Shipibo. Interviews and participant observation were used to investigate local perceptions of animal presence and depletion, food preferences, and how primates are incorporated into daily life and culture. Since time immemorial and still today, primates remain important in Shipibo culture, mythology, and subsistence. Local Shipibo participants consistently identified the presence of 13 species of primate. Primates were among the preferred species for consumption, pet keeping, and held a fundamental role in mythology, traditional knowledge, and storytelling. Large-bodied primates were often mentioned as being locally extinct, with reports and observations suggesting increasing consumption of smaller-bodied primates. Commonly perceived reasons for primate depletion include noise disturbance, hunting, and population growth, often in parallel. This study sheds light on the cultural context of an area rich in biodiversity, where primates, essential for ecological balance and integral to Shipibo lives and identity, are being depleted. We highlight the need for an inclusive ethnoprimatological approach to conserving primates and preserving indigenous heritage while improving local livelihoods.
Regulation of cortical hyperexcitability in amyotrophic lateral sclerosis: focusing on glial mechanisms
Authors: Xie Manling , Pallegar Praveen N. , Parusel Sebastian , Nguyen Aivi T. , Wu Long-Jun 
Published: October 2023

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, resulting in muscle weakness, atrophy, paralysis, and eventually death. Motor cortical hyperexcitability is a common phenomenon observed at the presymptomatic stage of ALS. Both cell-autonomous (the intrinsic properties of motor neurons) and non-cell-autonomous mechanisms (cells other than motor neurons) are believed to contribute to cortical hyperexcitability. Decoding the pathological relevance of these dynamic changes in motor neurons and glial cells has remained a major challenge. This review summarizes the evidence of cortical hyperexcitability from both clinical and preclinical research, as well as the underlying mechanisms. We discuss the potential role of glial cells, particularly microglia, in regulating abnormal neuronal activity during the disease progression. Identifying early changes such as neuronal hyperexcitability in the motor system may provide new insights for earlier diagnosis of ALS and reveal novel targets to halt the disease progression.
The role of endotoxin in septic shock
Authors: Kellum John A. , Ronco Claudio 
Published: October 2023

AbstractSeptic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5–7 million patients worldwide develop sepsis with very high endotoxin activity in the blood and more than half die. The term endotoxic septic shock has been used for these patients but it is important to emphasize that endotoxin may be a factor in all forms of septic shock including non-bacterial etiologies like COVID-19 since translocation of bacterial products is a common feature of septic shock. A pattern of organ failure including hepatic dysfunction, acute kidney injury and various forms of endothelial dysfunction ranging from disseminated intravascular coagulation to thrombotic microangiopathy characterize endotoxic septic shock. However, while characteristic, the clinical phenotype is not unique to patients with high endotoxin, and the diagnosis relies on the measurement of endotoxin activity in addition to clinical assessment. Therapies for endotoxic septic shock are limited with immune modulating therapies under investigation and extracorporeal blood purification still controversial in many parts of the world.
Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome
Authors: Costeira Ricardo , Evangelista Laila , Wilson Rory , Yan Xinyu , Hellbach Fabian , Sinke Lucy , Christiansen Colette , Villicaña Sergio , Masachs Olatz M. , Tsai Pei-Chien , Mangino Massimo , Menni Cristina , Berry Sarah E. , Beekman Marian , van Heemst Diana , Slagboom P. Eline , Heijmans Bastiaan T. , Suhre Karsten , Kastenmüller Gabi , Gieger Christian , Peters Annette , Small Kerrin S. , Linseisen Jakob , Waldenberger Melanie , Bell Jordana T. 
Published: October 2023

Abstract
Background
B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants.

Results
Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites — pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) — were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E−09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals.

Conclusion
Metabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.
Pharmacological EZH2 inhibition combined with retinoic acid treatment promotes differentiation and apoptosis in rhabdomyosarcoma cells
Authors: O’Brien Eleanor , Tse Carmen , Tracy Ian , Reddin Ian , Selfe Joanna , Gibson Jane , Tapper William , Pengelly Reuben J. , Gao Jinhui , Aladowicz Ewa , Petts Gemma , Thway Khin , Popov Sergey , Kelsey Anna , Underwood Timothy J. , Shipley Janet , Walters Zoë S. 
Published: October 2023

Abstract
Background
Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign. The histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2) suppresses normal skeletal muscle differentiation and is highly expressed in RMS tumours.

Results
We demonstrate combining inhibition of the epigenetic modulator EZH2 with the differentiating agent retinoic acid (RA) is more effective at reducing cell proliferation in RMS cell lines than single agents alone. In PAX3-FOXO1 positive RMS cells this is due to an RA-driven induction of the interferon pathway resulting in apoptosis. In fusion negative RMS, combination therapy led to an EZH2i-driven upregulation of myogenic signalling resulting in differentiation. In both subtypes, EZH2 is significantly associated with enrichment of trimethylated lysine 27 on histone 3 (H3K27me3) in genes that are downregulated in untreated RMS cells and upregulated with EZH2 inhibitor treatment. These results provide insight into the mechanism that drives the anti-cancer effect of the EZH2/RA single agent and combination treatment and indicate that the reduction of EZH2 activity combined with the induction of RA signalling represents a potential novel therapeutic strategy to treat both subtypes of RMS.

Conclusions
The results of this study demonstrate the potential utility of combining EZH2 inhibitors with differentiation agents for the treatment of paediatric rhabdomyosarcomas. As EZH2 inhibitors are currently undergoing clinical trials for adult and paediatric solid tumours and retinoic acid differentiation agents are already in clinical use this presents a readily translatable potential therapeutic strategy. Moreover, as inhibition of EZH2 in the poor prognosis FPRMS subtype results in an inflammatory response, it is conceivable that this strategy may also synergise with immunotherapies for a more effective treatment in these patients.
Longitudinal resting-state EEG in amyloid-positive patients along the Alzheimer’s disease continuum: considerations for clinical trials
Authors: Scheijbeler Elliz P. , de Haan Willem , Stam Cornelis J. , Twisk Jos W. R. , Gouw Alida A. 
Published: October 2023

Abstract
Background
To enable successful inclusion of electroencephalography (EEG) outcome measures in Alzheimer’s disease (AD) clinical trials, we retrospectively mapped the progression of resting-state EEG measures over time in amyloid-positive patients with mild cognitive impairment (MCI) or dementia due to AD.

Methods
Resting-state 21-channel EEG was recorded in 148 amyloid-positive AD patients (MCI, n = 88; dementia due to AD, n = 60). Two or more EEG recordings were available for all subjects. We computed whole-brain and regional relative power (i.e., theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-13 Hz), beta (13-30 Hz)), peak frequency, signal variability (i.e., theta permutation entropy), and functional connectivity values (i.e., alpha and beta corrected amplitude envelope correlation, theta phase lag index, weighted symbolic mutual information, inverted joint permutation entropy). Whole-group linear mixed effects models were used to model the development of EEG measures over time. Group-wise analysis was performed to investigate potential differences in change trajectories between the MCI and dementia subgroups. Finally, we estimated the minimum sample size required to detect different treatment effects (i.e., 50% less deterioration, stabilization, or 50% improvement) on the development of EEG measures over time, in hypothetical clinical trials of 1- or 2-year duration.

Results
Whole-group analysis revealed significant regional and global oscillatory slowing over time (i.e., increased relative theta power, decreased beta power), with strongest effects for temporal and parieto-occipital regions. Disease severity at baseline influenced the EEG measures’ rates of change, with fastest deterioration reported in MCI patients. Only AD dementia patients displayed a significant decrease of the parieto-occipital peak frequency and theta signal variability over time. We estimate that 2-year trials, focusing on amyloid-positive MCI patients, require 36 subjects per arm (2 arms, 1:1 randomization, 80% power) to detect a stabilizing treatment effect on temporal relative theta power.

Conclusions
Resting-state EEG measures could facilitate early detection of treatment effects on neuronal function in AD patients. Their sensitivity depends on the region-of-interest and disease severity of the study population. Conventional spectral measures, particularly recorded from temporal regions, present sensitive AD treatment monitoring markers.
Cutaneous metastasis from cervical cancer to the scalp and trunk: a case report and review of the literature
Authors: Dai Ying , Zhang Yufei , Ke Xue , Liu Yunqin , Zang Chunbao 
Published: October 2023

Abstract
Background
An estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with an incidence of 0.1–1.3% and typically a preterminal occurrence. Scalp metastasis from cervical cancer is exceptionally anecdotal, with only a dozen examples well documented.

Case presentation
The patient is a 33-year-old Chinese woman who was diagnosed with International Federation of Gynecology and Obstetrics stage IVB cervical cancer in November 2021. From December 2021 to April 2022, the patient was enrolled in the clinical trial of sintilimab combined with chemotherapy and radiotherapy for treatment of stage IV cervical cancer and underwent six cycles of immunotherapy and chemotherapy (sintilimab plus paclitaxel liposome and cisplatin). Treatment was well tolerated and led to a partial response. The masses adjacent to the spine and iliac bone was largely reduced. Thus, radiotherapy of the metastatic residues was carried out and followed by radiotherapy to the primary tumor at the cervix uteri. However, by the time of the radiotherapy completion in October 2022, the patient noticed painless nodules at the left scapular region and the right hypochondrium. The following month, more nodules occurred on the scalp and trunk, including the left axilla, anterior abdomen, and left back, along with a lesion invading the sternum that caused acute bone pain. The cutaneous masses were white, discrete with a rubbery consistency, and fixed to the skin. Several nodules increased in size and eventually ulcerated. Fine‑needle aspiration cytology of the left back swellings revealed metastatic squamous cell carcinoma, P16 positive. No visceral or brain metastasis was observed at this point.

Conclusions
Cervical cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. So far, there is no clear guideline regarding skin metastases treatment. Such skin lesions warrant a thorough radiologic and pathologic workup to form a comprehensive management plan.
Context-based refinement of mappings in evolving life science ontologies
Authors: Yamamoto Victor Eiti , Destro Juliana Medeiros , dos Reis Julio Cesar 
Published: October 2023

Abstract
Background
Biomedical computational systems benefit from ontologies and their associated mappings. Indeed, aligned ontologies in life sciences play a central role in several semantic-enabled tasks, especially in data exchange. It is crucial to maintain up-to-date alignments according to new knowledge inserted in novel ontology releases. Refining ontology mappings in place, based on adding concepts, demands further research.

Results
This article studies the mapping refinement phenomenon by proposing techniques to refine a set of established mappings based on the evolution of biomedical ontologies. In our first analysis, we investigate ways of suggesting correspondences with the new ontology version without applying a matching operation to the whole set of ontology entities. In the second analysis, the refinement technique enables deriving new mappings and updating the semantic type of the mapping beyond equivalence. Our study explores the neighborhood of concepts in the alignment process to refine mapping sets.

Conclusion
Experimental evaluations with several versions of aligned biomedical ontologies were conducted. Those experiments demonstrated the usefulness of ontology evolution changes to support the process of mapping refinement. Furthermore, using context in ontological concepts was effective in our techniques.
Exploring the potential of vagus nerve stimulation in treating brain diseases: a review of immunologic benefits and neuroprotective efficacy
Authors: Jin Zeping , Dong Jing , Wang Yang , Liu Yunpeng 
Published: October 2023

AbstractThe vagus nerve serves as a critical connection between the central nervous system and internal organs. Originally known for its effectiveness in treating refractory epilepsy, vagus nerve stimulation (VNS) has shown potential for managing other brain diseases, including ischaemic stroke, traumatic brain injury, Parkinson's disease, and Alzheimer's disease. However, the precise mechanisms of VNS and its benefits for brain diseases are not yet fully understood. Recent studies have found that VNS can inhibit inflammation, promote neuroprotection, help maintain the integrity of the blood-brain barrier, have multisystemic modulatory effects, and even transmit signals from the gut flora to the brain. In this article, we will review several essential studies that summarize the current theories of VNS and its immunomodulatory effects, as well as the therapeutic value of VNS for brain disorders. By doing so, we aim to provide a better understanding of how the neuroimmune network operates and inspire future research in this field.
Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition
Authors: Holt Amy K. , Najumudeen Arafath K. , Collard Tracey J. , Li Hao , Millett Laura M. , Hoskin Ashley J. , Legge Danny N. , Mortensson Eleanor M. H. , Flanagan Dustin J. , Jones Nicholas , Kollareddy Madhu , Timms Penny , Hitchings Matthew D. , Cronin James , Sansom Owen J. , Williams Ann C. , Vincent Emma E. 
Published: October 2023

Abstract
Background
To support proliferation and survival within a challenging microenvironment, cancer cells must reprogramme their metabolism. As such, targeting cancer cell metabolism is a promising therapeutic avenue. However, identifying tractable nodes of metabolic vulnerability in cancer cells is challenging due to their metabolic plasticity. Identification of effective treatment combinations to counter this is an active area of research. Aspirin has a well-established role in cancer prevention, particularly in colorectal cancer (CRC), although the mechanisms are not fully understood.

Methods
We generated a model to investigate the impact of long-term (52 weeks) aspirin exposure on CRC cells, which has allowed us comprehensively characterise the metabolic impact of long-term aspirin exposure (2–4mM for 52 weeks) using proteomics, Seahorse Extracellular Flux Analysis and Stable Isotope Labelling (SIL). Using this information, we were able to identify nodes of metabolic vulnerability for further targeting, investigating the impact of combining aspirin with metabolic inhibitors in vitro and in vivo.

Results
We show that aspirin regulates several enzymes and transporters of central carbon metabolism and results in a reduction in glutaminolysis and a concomitant increase in glucose metabolism, demonstrating reprogramming of nutrient utilisation. We show that aspirin causes likely compensatory changes that render the cells sensitive to the glutaminase 1 (GLS1) inhibitor—CB-839. Of note given the clinical interest, treatment with CB-839 alone had little effect on CRC cell growth or survival. However, in combination with aspirin, CB-839 inhibited CRC cell proliferation and induced apoptosis in vitro and, importantly, reduced crypt proliferation in Apcfl/fl mice in vivo.

Conclusions
Together, these results show that aspirin leads to significant metabolic reprogramming in colorectal cancer cells and raises the possibility that aspirin could significantly increase the efficacy of metabolic cancer therapies in CRC.
Myopathologic trajectory in Duchenne muscular dystrophy (DMD) reveals lack of regeneration due to senescence in satellite cells
Authors: Cardone Nastasia , Taglietti Valentina , Baratto Serena , Kefi Kaouthar , Periou Baptiste , Gitiaux Ciryl , Barnerias Christine , Lafuste Peggy , Pharm France Leturcq , Pharm Juliette Nectoux , Panicucci Chiara , Desguerre Isabelle , Bruno Claudio , Authier François-Jerome , Fiorillo Chiara , Relaix Frederic , Malfatti Edoardo 
Published: October 2023

AbstractDuchenne muscular dystrophy (DMD) is a devastating X-linked muscular disease, caused by mutations in the DMD gene encoding Dystrophin and affecting 1:5000 boys worldwide. Lack of Dystrophin leads to progressive muscle wasting and degeneration resulting in cardiorespiratory failure. Despite the absence of a definitive cure, innovative therapeutic avenues are emerging. Myopathologic studies are important to further understand the biological mechanisms of the disease and to identify histopathologic benchmarks for clinical evaluations. We conducted a myopathologic analysis on twenty-four muscle biopsies from DMD patients, with particular emphasis on regeneration, fibro-adipogenic progenitors and muscle stem cells behavior. We describe an increase in content of fibro-adipogenic progenitors, central orchestrators of fibrotic progression and lipid deposition, concurrently with a decline in muscle regenerative capacity. This regenerative impairment strongly correlates with compromised activation and expansion of muscle stem cells. Furthermore, our study uncovers an early acquisition of a senescence phenotype by DMD-afflicted muscle stem cells. Here we describe the myopathologic trajectory intrinsic to DMD and establish muscle stem cell senescence as a pivotal readout for future therapeutic interventions.