bluuebunny/crossref_metadata_2025 huggingface dataset:
Speciation-dependent molecular mechanism of electron transfer from the c-type cytochrome MtrC to U(VI)-ligand complexes
Authors: Molinas Margaux , Lederballe Meibom Karin , Brown Ashley , Abriata Luciano A. , Prüßmann Tim , Bernier-Latmani Rizlan
Published: February 2025

Members of the Shewanella genus transfer electrons to metal and actinide electron acceptors such as hexavalent uranium, U(VI), via c-type cytochromes. The intracellular mechanism of electron transfer is well studied but the delivery of electrons to external electron acceptors less well so. MtrC, a decaheme c-type cytochrome located on the cell surface side of the outer membrane of many Shewanella species, and extending to the extracellular medium, transfers electrons to U(VI), both in vivo and in vitro when purified. However, it is unclear how the electron transfer between the terminal heme(s) of the protein and extracellular U(VI) occurs. In particular, the type of interaction between MtrC and U(VI), and the parameters controlling electron transfer remain to be elucidated. Here, we investigated the kinetics of U(VI) reduction by S. baltica MtrC in solution for U(VI) complexed with one of five ligands: carbonate, hydroxyl, citrate, nitrilotriacetic acid (NTA) or ethylenediaminetetraacetic acid (EDTA). We observed two initial reaction rates, one more rapid for U-citrate, U-NTA and U-EDTA, and another slower for U-carbonate and U-hydroxo. By combining Nuclear Magnetic Resonance spectroscopy and M4-edge High Resolution X-ray Absorption Near Edge Structure spectroscopy, we attributed these differences to the type of interaction between the U-ligand complex and MtrC, i.e., probably electrostatic interaction with the ligand of U-EDTA, hydrogen bonding to the ligand of U-citrate and U-NTA, and covalent bonding with U-carbonate and U-hydroxo. We also demonstrate the persistence of U(V) in the U-carbonate system when interacting with MtrC. Overall, we showed that the mechanism of electron transfer depended on the chemistry of the soluble U(VI) complex serving as the substrate.
X-linked sideroblastic anemia in females
Authors: Ducamp Sarah , Campagna Dean R , Sendamarai Anoop , Schmidt Paul , Tsai Harrison K. , Heeney Matthew M , Bottomley Sylvia S , Fleming Mark Daniel
Published: February 2025

X-linked sideroblastic anemia (XLSA) in carrier females of ALAS2 mutations is not uncommon. We describe unique features and genotype/phenotype correlations in XLSA females and evaluate the contributions of X-chromosome skewing and clonal hematopoiesis, emphasizing the importance of distinguishing it from myelodysplastic syndromes with ring sideroblasts.
PSTK inhibition activates cGAS-STING, precipitating ferroptotic cell death in leukemic stem cells
Authors: He Lingli , Zhao Ting , Leong Wei Zhong , Sharda Azeem , Mayerhofer Christina , Mei Shenglin , Bonilla Gracia M. , Menendez-Gonzalez Juan Bautista , Gustafsson Karin , Fukushima Tsuyoshi , Kristiansen Trine A. , Lee Ji-Won , Xu Yanxin , Chen Lei , Xia Jun , Orozco Luis Angel , Budnik Bogdan , Sadreyev Ruslan , Dou Zhixun , Sykes David B. , Scadden David T
Published: February 2025

Differentiation arrest and dependence on oxidative metabolism are features shared among genetically diverse acute myeloid leukemias (AML). A phenotypic CRISPR-Cas9 screen in AML identified dependence on phosphoseryl-tRNA kinase (PSTK), an atypical kinase required for the biosynthesis of all selenoproteins. In vivo, PSTK inhibition (PSTKi) impaired AML cell growth and leukemic stem cell self-renewal. Notably, timed pharmacologic PSTKi effectively targeted chemo-resistant AML in murine and patient-derived xenograft models, showing selectivity for malignant cells over normal hematopoietic cells. Mechanistically, PSTKi-induced reactive oxygen species (ROS) triggering mitochondrial DNA release into the cytosol and activated cGAS-STING. This activation in turn disrupted iron metabolism augmenting ROS generation and amplifying ferroptosis. Together, these findings reveal a self-reinforcing PSTK-cGAS-STING-ROS loop culminating in an oxidative crisis and ferroptotic cell death of leukemic stem cells. The data highlight the potential for augmenting standard cancer chemotherapies using timed metabolic intervention to eliminate chemopersisting cells and thereby impede disease relapse.
Impact of new medications on the treatment of Immune TTP
Authors: Scully Marie , Howells Lara , Lester William A
Published: February 2025

The last decade has seen the introduction of two new licensed therapies for thrombotic thrombocytopenic purpura (TTP)-caplacizumab and recombinant ADAMTS 13 (rADAMTS 13), for immune (iTTP) and congenital TTP (cTTP) respectively. They improve acute TTP outcomes, reduce the need for plasma therapy, time to clinical response and treatment burden. Future pathways need to replace plasma exchange in acute TTP and optimise/personalise rADAMTS 13 in cTTP. Future emphasis should focus on additional monoclonals/treatments to tackle ADAMTS 13 antibodies.
Fluorine-rich hydrogarnet, prehnite and pumpellyite in monzodioritic basement of the Rhine Rift Valley produced by in-situ low-grade metamorphism at 200 °C and 5 km depth
Authors: Bucher Kurt , Hofer Moritz , Ladner Florentin , Stober Ingrid
Published: February 2025

The Basel-1 geothermal deep well has been drilled in 2006 to a final depth of 5 km. The recovered core material from 4.9 km depth shows coarse grained biotite-hornblende quartz-monzodiorite from the Variscan basement. The primary igneous rock is locally altered and contains prehnite, pumpellyite, mica and chlorite as major alteration products. Locally small amounts of hydrogarnet formed from pyrite oxidation and fluorine derived from the alteration of primary F-rich biotite. The local low-grade alteration products are consistent with the in-situ measured temperature of about 200 °C. The assemblage of low-grade minerals formed in distinct zones separated by sharp reaction fronts from the primary monzodiorite. The bulk of the alteration zones may have formed from reaction of the monzodiorite with the pre-drilling formation fluid. However, also the external stimulation fluid rapidly readjusted its composition by reaction with the rock at depth. This follows from the temperature derived from fluid composition thermometers applied to recovered stimulation fluid which is consistent with measured temperatures at depth.
Machine learning reveals sex differences in distinguishing between conduct-disordered and neurotypical youth based on emotion processing dysfunction
Authors: Kohls Gregor , Elster Erik M. , Tino Peter , Fairchild Graeme , Stadler Christina , Popma Arne , Freitag Christine M. , De Brito Stephane A. , Konrad Kerstin , Pauli Ruth
Published: February 2025

Background

Theoretical models of conduct disorder (CD) highlight that deficits in emotion recognition, learning, and regulation play a pivotal role in CD etiology. With CD being more prevalent in boys than girls, various theories aim to explain this sex difference. The “differential threshold” hypothesis suggests greater emotion dysfunction in conduct-disordered girls than boys, but previous research using conventional statistical analyses has failed to support this hypothesis. Here, we used novel analytic techniques such as machine learning (ML) to uncover potentially sex-specific differences in emotion dysfunction among girls and boys with CD compared to their neurotypical peers.

Methods

Multi-site data from 542 youth with CD and 710 neurotypical controls (64% girls, 9–18 years) who completed emotion recognition, learning, and regulation tasks were analyzed using a multivariate ML classifier to distinguish between youth with CD and controls separately by sex.

Results

Both female and male ML classifiers accurately predicted (above chance level) individual CD status based solely on the neurocognitive features of emotion dysfunction. Notably, the female classifier outperformed the male classifier in identifying individuals with CD. However, the classification and identification performance of both classifiers was below the clinically relevant 80% accuracy threshold (although they still provided relatively fair and realistic estimates of ~ 60% classification performance), probably due to the substantial neurocognitive heterogeneity within such a large and diverse, multi-site sample of youth with CD (and neurotypical controls).

Conclusions

These findings confirm the close association between emotion dysfunction and CD in both sexes, with a stronger association observed in affected girls, which aligns with the “differential threshold” hypothesis. However, the data also underscore the heterogeneity of CD, namely that only a subset of those affected are likely to have emotion dysfunction and that other neurocognitive domains (not tested here) probably also contribute to CD etiology.

Clinical trial number

Not applicable.
Investigating mental health disparities in rural sexual and gender minority adults: protocol for the rural exploration and approaches to LGBTQ + Mental Health (REALM) prospective cohort study
Authors: Fine Shoshanna L. , Willis Kalai , Lucas Iaah L. , Siebach Kirsten F. , Glick Jennifer L. , Valentine-Graves Mariah , Winter Savannah , Smith Michael , Waltz Thomas , Herring Gina Bailey , Hannah Marissa , Wilcox Holly C. , Sanchez Travis , Baral Stefan D. , Murray Sarah M.
Published: February 2025

Background

Sexual and gender minority (SGM) persons experience substantial mental health disparities throughout the life course, including increased vulnerability to depression and suicide. Few existing studies, however, have explored how pervasive experiences of SGM-related stigma, discrimination, and trauma (i.e., minority stress) contribute to adverse mental health outcomes among diverse sub-populations of SGM adults living in rural areas of the United States. This paper describes the protocol for a prospective cohort study, “Rural Exploration and Approaches for LGBTQ + Mental Health (REALM),” that will explore minority stress in relation to mental health conditions and suicidal behaviors among rural SGM adults.

Methods

Online processes will be used to recruit and enroll a diverse sample of up to 2,500 SGM adults aged 18 + living in rural counties and small metropolitan areas in the United States to complete an online baseline survey. This will include: up to 1,000 cisgender sexual minority persons (up to n = 500 each cisgender women and cisgender men); and up to 1,500 gender minority persons (up to n = 500 persons who were assigned male at birth and identify as a woman, female, and/or transfeminine; up to n = 500 persons who were assigned female at birth and identify as a man, male, and/or transmasculine; and up to n = 500 persons who identify as some other gender, including non-binary, gender non-conforming, and/or agender regardless of sex assigned at birth). All enrolled participants will subsequently be followed over a 12-month period, with repeated surveys at three-month intervals. Included survey measures will focus on sociodemographic information, mental health, substance use, suicidal behaviors, minority stressors, psychological processes, and other related risk and protective factors.

Discussion

This study presents a critical opportunity to better understand how minority stress contributes to adverse mental health outcomes among populations that remain underrepresented in research and programs in 2024. Results will be used to create more targeted, acceptable, and impactful intervention content and strategies that mitigate stigma, promote mental health, and prevent suicidal behaviors among rural SGM adults.
Psychosocial work characteristic profiles and health outcomes in registered nurses at different stages of their careers: a cross-sectional study
Authors: Lönnqvist Katri , Sinervo Timo , Kaihlanen Anu-Marja , Elovainio Marko
Published: February 2025

Background

Individual psychosocial work characteristics have been associated with the health and well-being of registered nurses. However, it remains to be determined whether different types of psychosocial work characteristics form patterned profiles and whether the profiles are associated with registered nurses’ health and welfare at different stages of their careers. The purpose of this study was to identify latent psychosocial work characteristic profiles and examine whether the profiles are associated with a certain career stage and health outcomes.

Methods

This cross-sectional study was conducted with 624 early-career registered nurses and 1,016 later-career registered nurses. Data were collected using an electronic survey with internationally validated measures including the Organizational Justice Scale, the Nurse Stress Index Scale, the Job Content Questionnaire, the Team Climate Inventory, the Psychological Distress Questionnaire, the Sleep Problems Questionnaire, and the Self-Rated Health Questionnaire. Latent profile analysis was conducted to identify subgroups with similar psychosocial work characteristic profiles. Multinomial and linear regression analyses were used to examine the association between latent work characteristics profiles, stage of career, and health outcomes.

Results

We identified five profiles. The profiles were named based on class descriptions. The low strain/high support profile group and the moderate strain/high support profile group had statistically better self-rated health (p = < 0.001), less psychological distress (p = < 0.001) and less sleep problems (p = < 0.001) compared to the high strain/low support profile group.

Conclusions

Low to moderate strain, high interactional and procedural justice, and participative safety in teams form patterned profiles associated with better health in registered nurses. High strain, a lack of justice and a lack of participation safety form a risk combination pattern profile that may lead to health problems in registered nurses. Promoting procedural and interactional justice, and participation safety in teams seems efficient in enhancing the health and well-being of registered nurses. The findings indicate no significant correlation between career stages and work characteristic profiles. It is crucial to identify stressors specific for career stages and develop tailored interventions.
Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility
Authors: Nakada Shinya , Ward Joey , Strawbridge Rona J. , Welsh Paul , Celis-Morales Carlos , Ho Frederick K. , Pell Jill P.
Published: February 2025

Background

Associations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. This study investigated how genetic susceptibility to CAD alters these associations with incident CAD, comparing and combining anxiety disorder and depression.

Methods

This is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRSCAD) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety disorder and depression and CAD.

Results

Both anxiety disorder (HR 2.31, 95% CI 1.92–2.78) and depression (HR 2.15, 95% CI 1.90–2.24) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRSCAD (RERI 0.97, 95% CI 0.12–1.81) such that the association between depression and CAD was strongest among those with a high PRSCAD whilst there was no such evidence for anxiety disorder. Anxiety disorder only (HR 1.68, 95% 1.16–2.44), depression only (HR 2.13, 95% CI 1.72–2.64), and concomitant anxiety disorder and depression (HR 3.85, 95% CI 2.48–5.98) were associated with CAD even among people with a low PRSCAD. Adjusting for potential mediators attenuated all these associations across PRS categories.

Conclusions

CAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.
HIV, smoking, and the brain: a convergence of neurotoxicities
Authors: Orlinick Benjamin L. , Farhadian Shelli F.
Published: February 2025

Purpose of review

The purpose of this review is to characterize the combined effects of tobacco smoking and human immunodeficiency virus (HIV) infection in people with HIV (PWH) and identify possible therapeutic targets through shared mechanisms for neurotoxicity.

Recent findings

HIV and tobacco smoke can exert neurotoxicity through shared mechanisms such as brain volume changes, microglial dysregulation, and dysregulation of the cholinergic anti-inflammatory pathway (CAP) through the alpha7-nicotinic acetylcholine receptor (nAChR). Evidence also suggests the potential for synergistic effects of HIV and tobacco smoking on neurotoxicity.

People with HIV (PWH) are disproportionately affected by both neurocognitive impairment (NCI) and tobacco smoking compared to the general population. Both HIV and tobacco smoking are known to have neurotoxic effects and have the potential for clinically significant impacts on brain health and cognitive functioning. Less, however, is known about how PWH may be uniquely affected by the interactive neurotoxic effects of both HIV and tobacco smoking. Evidence suggests that smoking and HIV can have synergistic effects on neurotoxicity and NCI in PWH. Some mechanisms for neurotoxicity include increased oxidative stress from microglial activation and dysfunction in the alpha7- nAChR cholinergic anti-inflammatory pathway leading to increased neuroinflammation and neuronal apoptosis. Mechanisms may vary by cell type and brain region, however, and there is a need for more human-facing, longitudinal studies on smoking in PWH.
Severe subcutaneous infection with Clostridium septicum in a herd of native Icelandic horses
Authors: Oddsdóttir Charlotta , Sigurðardóttir Ólöf G. , Friðriksdóttir Vala , Svansson Vilhjálmur , Bragason Birkir Þór , Björnsdóttir Sigríður
Published: February 2025

Background

Cellulitis due to infection with clostridia has not been documented in horses in Iceland. However, clostridia are well-known pathogens in Icelandic sheep, which have traditionally shared grazing land with horses. Clostridial infections of equine muscle or subcutis following injection with medicinal products have been described in other countries but have never been reported in Iceland. In this case report, we present the first documented outbreak of subcutaneous clostridial infection in horses in Iceland following subcutaneous injection.

Case presentation

In November 2022, 16 out of 32 horses, that some days earlier had received a subcutaneous injection of Noromectin® 1% injectable solution, developed clinical signs indicating malignant oedema. The clinical signs included pyrexia, depression, swollen limbs, chest and neck, reluctance to move and dyspnoea, leading to the death or euthanasia of five horses. In addition, one horse was found dead with no previously noted clinical signs. Necropsy of one of the five horses revealed severe, acute cellulitis in the neck region, as well as lymphadenitis in regional lymph nodes. Abscesses, some with subsequent spontaneous drainage of seropurulent material, were observed at the presumed injection site on eight surviving horses approximately 2 weeks post-injection. Bacterial culture of samples from the necropsied horse and from abscesses from three surviving horses yielded the growth of C. septicum. Analysis of water samples from the pasture where the herd was kept also revealed the presence of C. septicum. Whole genome sequencing suggested that the isolates from the diseased horses contained the same C. septicum strain, whereas the strain isolated from the water samples differed from the disease-causing isolates.

Conclusions

Clinical signs compatible with serious subcutaneous C. septicum infection were seen in over half of 32 horses injected with an ivermectin product, with the subsequent death of six of the horses. In the absence of other obvious sources, the outbreak suggests that C. septicum spores on the skin of these horses were introduced under the skin when they were injected. Such infections have not been reported in Iceland, although ivermectin products formulated for subcutaneous injection have been widely used for more than 30 years. The outbreak warrants further investigation into C. septicum in the environment of grazing horses in Iceland.
Assessment of recruitment from CT to the bedside: challenges and future directions
Authors: Giovanazzi Stefano , Nocera Domenico , Catozzi Giulia , Collino Francesca , Cressoni Massimo , Ball Lorenzo , Moerer Onnen , Quintel Michael , Camporota Luigi , Gattinoni Luciano
Published: February 2025

Assessing and quantifying recruitability are important for characterizing ARDS severity and for reducing or preventing the atelectrauma caused by the cyclic opening and closing of pulmonary units. Over the years, several methods for recruitment assessment have been developed, grouped into three main approaches: 1) Quantitative CT Scanning: This method accurately measures the amount of atelectatic lung tissue that regains aeration; 2) Regional Gas Volume Measurement: Based on anatomical markers, this approach assesses gas volume within a specified lung region; 3) Compliance-Based Gas Volume Measurement: This technique compares actual gas volume at a given pressure to expected values, assuming respiratory system compliance is constant within the explored pressure range. Additional methods, such as lung ultrasonography and electrical impedance variation, have also been explored. This paper details the distribution of opening and closing pressures throughout the lung parenchyma, which underpin the concept of recruitability. The distribution of recruitable regions corresponds to atelectasis distribution, with the pressure needed for recruitment varying according to whether the atelectasis is “loose” or “sticky.” We also discuss the effects of different PEEP levels on preventing atelectrauma, the importance of keeping some lung areas closed throughout the respiratory cycle, and briefly cover the roles of sigh ventilation, prone positioning, and the closed lung approach.
TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial
Authors: Zaloumis Sophie , Summers Matthew J. , Presneill Jeffrey J. , Bellomo Rinaldo , Chapple Lee-anne S. , Chapman Marianne J. , Deane Adam M. , Ferrie Suzie , French Craig , Hurford Sally , Kakho Nima , Maiden Matthew J. , O’Connor Stephanie N. , Peake Sandra L. , Ridley Emma J. , Tran-Duy An , Williams Patricia J. , Young Paul J. , Karahalios Amalia ,   on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group
Published: February 2025

Background

The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care.

Objective

To describe the statistical analysis plan for the TARGET Protein trial.

Methods

TARGET Protein is a cluster randomized, cross-sectional, double cross-over, open-label, registry-embedded, pragmatic clinical trial conducted across Australia and New Zealand. The trial randomized eight intensive care units (ICU) to receive enteral formula containing either higher dose enteral protein (augmented protein) or usual dose protein in a 1:1 ratio. Each ICU received one trial formula for a 3-month period and then switched to the alternate formulae. This sequence was repeated, for a total trial length of 12 months. The primary outcome is the number of days free of the index hospital and alive at day 90. Secondary outcomes include proportion of patients alive at day 90, survivor-only analysis of days free of the index hospital at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. The statistical methods and models which will be used to estimate the effects for the primary and secondary outcomes are described. All statistical models will account for the cluster-randomized cross-over design to ensure correct estimation of the 95% confidence intervals. Trial enrolment is complete with 3412 patients enrolled. Data linkage is ongoing.

Conclusion

This statistical analysis plan enables transparent reporting of the TARGET Protein trial. It will reduce the risk of potential selective reporting biases.

Trial registration

Australian New Zealand Clinical Trials Registry (ACTRN12621001484831). Registered on November 1, 2021.
Phytochrome-mediated shade avoidance responses impact the structure and composition of the bacterial phyllosphere microbiome of Arabidopsis
Authors: O’Rourke James A. , Vincent Stacey A. , Williams Isabel E. I. , Gascoyne Eleanor L. , Devlin Paul F.
Published: February 2025

The shade avoidance response triggers a dramatic promotion of elongation growth, accompanied by a significant reprogramming of metabolic pathways as plants seek to prevent overtopping and adapt to vegetative shade. Here we demonstrate that simulated vegetative shade results in significant changes in the structure and composition of the phyllosphere bacterial microbiome. Our study uncovered significant shifts in the diversity, occurrence, abundance and activity of bacteria within the phyllosphere microbiome. A comparison of responses in both wild-type plants and phytochrome mutants, which inherently exhibit a shade-avoidance phenotype, revealed both indirect responses to host plant physiology and direct responses to light among the microbiota. Hierarchical clustering of response patterns further suggested that over a third of the taxa constituting the core phyllosphere microbiome in our assay show some degree of response to vegetative shade. Bacteria that increased in abundance on plants with a shade-avoidance phenotype corresponded to genera associated with beneficial traits such as enhanced disease resistance and growth promotion. Our findings suggests that plants manipulate their phyllosphere microbiome under shade conditions as a strategy to optimise fitness when competing for light. We discuss the implications of our findings in terms of furthering our understanding of plant-microbe signalling in the shaping of the phyllosphere microbiome and the possibility of manipulating the phyllosphere microbiome for plant health in an agricultural setting at high planting densities.
Artificial intelligence in the service of entrepreneurial finance: knowledge structure and the foundational algorithmic paradigm
Authors: Kudelić Robert , Šmaguc Tamara , Robinson Sherry
Published: February 2025

The study conducts a bibliometric review of artificial intelligence applications in two areas: the entrepreneurial finance literature, and the corporate finance literature with implications for entrepreneurship. A rigorous search and screening of the web of science core collection identified 1,890 journal articles for analysis. The bibliometrics provide a detailed view of the knowledge field, indicating underdeveloped research directions. An important contribution comes from insights through artificial intelligence methods in entrepreneurship. The results demonstrate a high representation of artificial neural networks, deep neural networks, and support vector machines across almost all identified topic niches. In contrast, applications of topic modeling, fuzzy neural networks, and growing hierarchical self-organizing maps are rare. Additionally, we take a broader view by addressing the problem of applying artificial intelligence in economic science. Specifically, we present the foundational paradigm and a bespoke demonstration of the Monte Carlo randomized algorithm.
Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
Authors: Luo Xiaoqin , Li Chao , Qin Gang
Published: February 2025

Background

Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on the molecular heterogeneity of HNSCC is essential to enhance therapeutic efficacy and prognosis.

Methods

We integrated four HNSCC datasets (TCGA-HNSCC, GSE27020, GSE41613, and GSE65858) from TCGA and GEO databases. Using 10 multi-omics consensus clustering algorithms via the MOVICS package, we identified two molecular subtypes (CS1 and CS2) and validated their stability. A machine learning-driven prognostic signature was constructed by combining 101 algorithms, ultimately selecting 30 prognosis-related genes (PRGs) with the Elastic Net model. This signature was further linked to immune infiltration, functional pathways, and therapeutic sensitivity.

Results

CS1 exhibited superior survival outcomes in both TCGA and META-HNSCC cohorts. The PRG-based signature stratified patients into low- and high-risk groups, with the low-risk group showing prolonged survival, enhanced immune cell infiltration (B cells, T cells, monocytes), and activated immune functions (cytolytic activity, T cell co-stimulation). High-risk patients were more sensitive to radiotherapy and chemotherapy (e.g., Cisplatin, 5-Fluorouracil), while low-risk patients responded better to immunotherapy and targeted therapies.

Conclusion

Our study delineates two molecular subtypes of HNSCC and establishes a robust prognostic model using multi-omics data and machine learning. These findings provide a framework for personalized treatment selection, offering clinical insights to optimize therapeutic strategies for HNSCC patients.
CX3CR1+ age-associated CD4+ T cells contribute to synovial inflammation in late-onset rheumatoid arthritis
Authors: Akiyama Mitsuhiro , Wakasugi Sohma , Yoshimoto Keiko , Saito Koichi , Ishigaki Sho , Inukai Risa , Matsuno Yoshiyuki , Alshehri Waleed , Kondo Yasushi , Kaneko Yuko
Published: February 2025

Background

Recent evidence suggests that clonally expanded cytotoxic T cells play a role in various autoimmune diseases. Late-onset rheumatoid arthritis (LORA) exhibits unique characteristics compared to other RA forms, suggesting distinct immunological mechanisms. This study aimed to examine the involvement of cytotoxic T cells in LORA.

Methods

Fresh peripheral blood samples were collected from 78 treatment-naïve active RA patients, 12 with difficult-to-treat RA, and 16 healthy controls. Flow cytometry was employed to measure the proportions of CX3CR1+cytotoxic CD4+ and CD8+ T cells in these samples. Additionally, immunohistochemical staining was performed on lymphoid node and synovial biopsy samples from patients with RA.

Results

CX3CR1+cytotoxic CD4+ T cells were specifically increased in untreated, active patients with LORA, displaying features of CXCR3mid age-associated T helper cells known as “ThA”. CX3CR1⁺CD4⁺ T cells were identified as a cytotoxic ThA subset, as nearly all of these cells specifically expressed granzyme B. These cells were observed in enlarged lymph nodes and were found to infiltrate synovial tissues from patients with LORA. The proportions of CX3CR1+CD4+ T cells positively correlated with arthritis activity in LORA. The number of cells decreased after treatment with methotrexate, tumor necrosis factor inhibitors, and interleukin-6 inhibitors, whereas T-cell activation modulators did not affect them. Moreover, PD-1+CD38+CX3CR1+CD4+ T cells were identified as a treatment-resistant T cell subset that was characteristically increased in difficult-to-treat RA. CX3CR1+CD8+ T cells showed no significant difference between RA patients and healthy individuals, and no correlation with disease activity was observed. However, a correlation with age was observed in RA patients.

Conclusions

Our findings suggest that the immunopathogenesis of RA differs by age of onset, with CX3CR1+ age-associated cytotoxic CD4+ T cells playing a significant role in LORA. Additionally, the presence of a specific CX3CR1+ T cell subset may be linked to treatment resistance.
Distinguishing glioblastoma from brain metastasis; a systematic review and meta-analysis on the performance of machine learning
Authors: Habibi Mohammad Amin , Omid Reza , Asgarzade Shafaq , Derakhshandeh Sadaf , Soltani Farsani Ali , Tajabadi Zohreh
Published: February 2025

Background

The discrimination of glioblastoma and solitary metastasis brain tumor is challenging. Up now, several conventional and advanced imaging modalities were used for distinguishing between these tumors with different success rates. We systematically reviewed the studies reported the performance of machine learning (ML) algorithms for accurately discrimination of these two entities.

Method

The search was conducted from inception to 1 June, 2023, in PubMed/Medline, Embase, Scopus, and Web of Science to find out the studies investigated the performance of ML-based algorithm for differentiation of glioblastoma and metastatic brain tumor.

Results

This study included 28 studies comprising a total of 2,860 patients. The meta-analysis model results revealed a pooled sensitivity and specificity estimate of 0.83 [0.80–0.86] and 0.87 [0.83–0.90], respectively, indicating a commendable overall diagnostic accuracy across all the studies. ResNet50 and ResNet50-LSTM have shown promising results with single-study sensitivities of up to 88.9% and 88.2%, respectively. Furthermore, the integration of CNNs and RNNs has demonstrated improved performance compared to standalone models in a significant portion of the studies. The ROC curve area was 0.90, indicating high discriminative ability. The positive likelihood ratio was 6.2, and the negative likelihood ratio was 0.20, providing helpful information on how test results modified pretest probability.

Conclusion

ML applied to routine neuroimaging shows high diagnostic potential for glioblastoma detection. While more research is needed before clinical deployment, preliminary results are encouraging.
Percutaneous large-bore mechanical thrombectomy for macroscopic fat pulmonary embolism: a case report
Authors: Chan James M. , Aljeboori Zeyad , Ghosh Angajendra , Peake Benjamin , Rush Moira N. , Du Guesclin Alexandra , Lim Hui Yin , Siemienowicz Miranda , Kok Hong Kuan , Mitreski Goran
Published: February 2025

Background

Macroscopic fat pulmonary embolism is extremely uncommon. Most cases occur in the context of fat grafting or long bone fractures. Macroscopic fat pulmonary embolism may be associated with cardiopulmonary compromise and is associated with high mortality. Mechanical thrombectomy is an emerging technique in interventional radiology, primarily investigated as a therapeutic approach for thrombotic pulmonary embolism.

Case presentation

We present a case report of a 73-year-old woman with macroscopic fat pulmonary embolism after a neck of femur fracture. Initially, she had severe circulatory shock, requiring multiple vasopressors and admission to the Intensive Care Unit. A percutaneous large-bore mechanical thrombectomy was performed, after which notable improvements to haemodynamic function and overall clinical trajectory were observed.

Conclusions

To our knowledge, this is the first report of mechanical thrombectomy in macroscopic fat pulmonary embolism. Further research is required to better delineate the role of mechanical thrombectomy in this rare condition.
Case report: identification of novel variant in SLC26A2 gene and preimplantation genetic testing for monogenic disorders in preventing diastrophic dysplasia
Authors: Tonyan Ziravard N. , Nasykhova Yulia A. , Danilova Maria M. , Shabanova Elena S. , Bespalova Olesya N. , Kogan Igor Y. , Glotov Andrey S.
Published: February 2025

Background

Diastrophic dysplasia is a rare autosomal recessive disorder characterized by abnormalities in bone and cartilage development, caused by pathogenic variants in the SLC26A2 gene.

Case presentation

This article presents a clinical case of preimplantation genetic testing for monogenic disorders (PGT-M) conducted for a family with two previous pregnancy losses due to diastrophic dysplasia in the fetus. We report a previously uncharacterized variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. We detail the approach to performing PGT-M in the absence of material from the proband and close relatives from one partner for analysis. A testing system was developed to analyze pathogenic variants in the SLC26A2 gene, alongside with indirect markers such as short tandem repeats and single nucleotide polymorphisms. This allowed us to identify linkage groups associated with the analyzed pathogenic variants during the in vitro fertilization cycle with PGT-M, enabling the selection of an embryo that did not inherit pathogenic variants from either parent. The transfer of this embryo resulted in a successful pregnancy, resulting in the birth of a healthy child.

Conclusion

To our knowledge, this is a first report of variant c.1358C > T in the SLC26A2 gene associated with diastrophic dysplasia. The successful application of PGT-M enabled the selection of an embryo free from inherited pathogenic variants from both parents, highlighting the importance of PGT-M in improving reproductive outcomes for affected families.
Primary hyperparathyroidism and psychiatry: manifestations, causes and management
Authors: Singh Sukhmeet , Stokes Victoria , El Kaubaisy Al Hakam , Rubinsztein Judy S.
Published: February 2025

Primary hyperparathyroidism (PHPT) is the presence of hypercalcaemia with an elevated or inappropriately normal parathyroid hormone level. In clinical psychiatry this is often detected on routine blood investigations. This article aims to help mental health professionals understand the relevance of PHPT to psychiatry and offers some guidance about further management of patients presenting with this endocrine abnormality in mental health settings. PHPT can be associated with both mental and physical health problems in some individuals, making it a crucial diagnosis that should not be overlooked.
Tuer l’auteur
Authors: Uhlig Marion
Published: February 2025

L’article interroge la présence et les fonctions de la métalepse dans la littérature médiévale en français de tradition épique et historiographique par l’étude de deux exemples mettant en scène le meurtre de l’auteur par les personnages de l’histoire qui lui est attribuée. La Chanson de Roland et la Chronique du pseudo-Turpin (XIIe s.) ainsi que la chanson de Raoul de Cambrai (fin XIIe s.) modulent différentes variations autour de ce motif. Quelles sont les spécificités de ces métalepses médiévales ? Elles possèdent, et c’est l’hypothèse du présent article, une fonction de légitimation du texte dans la mesure où la mort de l’auteur représentée à l’intérieur même de l’œuvre fonde le prestige et la valeur de celle-ci.
Scenes of Misrecognition (Koltès, Duras)
Authors: Killeen Marie-Chantal
Published: February 2025

What is it about confession scenes that makes them such a productive heuristic device in late twentieth-century French theater, given that so many playwrights only tease audiences with the tantalizing prospect of confession’s truth-telling potential, all the better to quash it? Whether these disclosures are extracted under the glare of courtroom or police interrogations, or elicited in the more intimate settings of the bedroom or the analyst’s couch, modern theater’s interest in confessions appears to reside less in their probative value than in the questions they raise about the dramatic form and our investment in it. This article’s author proposes to pursue this inquiry through a discussion of two plays: Marguerite Duras’s oft-staged récit from 1982, La Maladie de la mort, and Bernard-Marie Koltès’s 1986 play Dans la solitude des champs de coton. What is most fascinating about these works is the curious way in which they appear to bear all the markings of confessions yet pointedly refuse to behave like them, thwarting the desire for revelation, catharsis, and closure at every turn. As performative utterances, these abortive confessions ultimately perform little apart from their own undoing. This failure is due in no small part to the persistence with which they direct one’s focus elsewhere: instead of the familiar spectacle of a character’s full and frank confession (assuming such a thing were even possible), the disquieting theater of Koltès and Duras demands instead that one attend to what one disavows.
Mitophagy is induced in human engineered heart tissue after simulated ischemia and reperfusion
Authors: Nàger Mireia , Larsen Kenneth B. , Bhujabal Zambarlal , Kalstad Trine B. , Rössinger Judith , Myrmel Truls , Weinberger Florian , Birgisdottir Asa B.
Published: February 2025

The paradoxical exacerbation of cellular injury and death during reperfusion remains a problem in treatment of myocardial infarction. Mitochondrial dysfunction plays a key role in the pathogenesis of myocardial ischemia and reperfusion injury. Dysfunctional mitochondria can be removed by mitophagy, culminating in their degradation within acidic lysosomes. Mitophagy is pivotal in maintaining cardiac homeostasis and emerges as a potential therapeutic target. Here we employ beating human engineered heart tissue (EHT) to assess mitochondrial dysfunction and mitophagy during ischemia and reperfusion simulation. Our data indicate adverse ultrastructural changes in mitochondrial morphology and impairment of mitochondrial respiration. Furthermore, our pH-sensitive mitophagy reporter EHTs, generated by CRISPR/Cas9 endogenous knock-in strategy, reveal induced mitophagy flux in EHTs after ischemia and reperfusion simulation. The induced flux requires the activity of the protein kinase ULK1, a member of the core-autophagy machinery. Our results demonstrate the applicability of the reporter EHTs for mitophagy assessment in a clinically relevant setting. Deciphering mitophagy in the human heart will facilitate development of novel therapeutic strategies.
The Appreciative Ontology of the Human, Social, Natural and Cosmic Worlds
Authors: Varona Federico
Published: February 2025

Appreciative Ontology refers to our understanding of human beings, the organizational world, and the natural and cosmic worlds, shaped through the development of theories that explain them. It is one facet of the Appreciative Paradigm, along with appreciative research (epistemology), transformation (praxis), values (axiology) and language. In this final article in the series, the author identifies the fundamental characteristics of the three components of Appreciative Ontology and argues that every appreciative inquiry and every human activity aimed at personal and social change is inspired by and grounded in an ontology.
Soft skills and the perceived necessity of a college degree for the paramedic profession
Authors: Egnatovich Jeffrey P , Jasmine Joanne
Published: February 2025

Using the views of paramedics and paramedic employers in the United States, this mixed-methodology study explored the perceived necessity for a college degree in the paramedic profession – specifically, the soft skills attained through studying for one. The researchers surveyed more than 3900 paramedics and over 400 employers. The surveys included personal, professional and educational demographic information, as well as Likert-style statements regarding degrees and soft skills commonly used in paramedicine. In addition, an open-ended survey was used to gain a better understanding of how taking a degree contributed to specific soft skills in paramedic practice. Paramedics with a degree were more likely to believe that their college education contributed to developing their soft skills. This belief increased as the level of completed education increased, and was consistent between states that require a degree for new paramedic certification and those that do not.
The theory of event medicine: a literature review
Authors: Shelswell Robert
Published: February 2025

Background:

Event medicine is a field of medicine that encompasses the provision of healthcare to spectators/attendees at sports stadiums, music events, and festivals. This article explores existing theory to understand the evidence base currently afforded to operational practice.

Aim:

The study aim is to explore the current literature on event medicine to identify collective themes and areas for future research, prompt clinician reflective practice, and inform future standards of professional practice.

Methods:

A six-stage thematic-analysis-based literature review was conducted. The electronic databases of Google Scholar, Medline and PubMed were searched between January and April 2024. The search terms used were ‘event medicine’, ‘mass gathering medicine’, stadium medicine’, and crowd medicine’. Articles prior to January 2004 were excluded. The search included English language full-text articles.

Findings:

A total of 32 articles were selected. They originated from Europe, Northern America, Southern Africa, and Asia, across a variety of sporting, outdoor festival, and music events. From their analysis, five main themes were identified: patient presentations; medical resource skill mix; predictive modelling; transfer to hospital rates; and acute cardiac events.

Conclusion:

Event medicine operational practice is under-researched, and essentially affords a large theory-practice gap in event medical service planning, provision, and application. Event-medicine clinicians should aim to deliver prehospital medical care that reflects the complexity of the five identified themes, as well as critically analyse existing event medical data, challenge their conceptual roles, and seek to develop future improved core standards of event medicine with a view to developing safer models of care for event spectators/attendees.
Ethnomedicinal plants used by Manobo Tribe in Ugnop Cave Landscape Forest Reserve, Agusan del Sur, Philippines
Authors: PARAGUISON LYN D. , SALAMANES JULIUS JOHN DP. , DAPAR MARK LLOYD G. , ALEJANDRO GRECEBIO JONATHAN D.
Published: February 2025

Abstract. Paraguison LD, Salamanes JJDP, Dapar MLG, Alejandro GJD. 2024. Ethnomedicinal plants used by Manobo Tribe in Ugnop Cave Landscape Forest Reserve, Agusan del Sur, Philippines. Biodiversitas 25: 4223-4232. As a protected and conserved area, Upland Prosperidad in Agusan del Sur, harbors medicinal plants traditionally used by local communities and indigenous groups. This study investigates the ethnomedicinal practices of the Manobo tribe in the Ugnop Cave Landscape Forest Reserve, Prosperidad, Agusan del Sur. Data were gathered through semi-structured interviews, guided field walks, and focus group discussions with 150 key informants. A total of 57 medicinal plants, belonging to 31 families and 49 genera, were documented for their use in treating various diseases and ailments. The Fabaceae family dominated with five species reported for medicinal use. Piperaceae (FIV=98.67) and Asteraceae (FIV=96.66) were identified as the families with the highest Family Importance Value, receiving the most citation reports from key informants. The most frequently reported plant species was Piper aduncum L., traditionally used for treating cuts and wounds. Leaves were the most commonly used plant part, constituting 32% of usage. Decoction was the most common mode of preparation (55%), followed by poultice (22%) and direct eating (16%). The forest reserve was found to be rich in medicinal plant knowledge and resources among the locals and indigenous communities, emphasizing the need for ongoing protection and conservation of these valuable genetic resources.