bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Demographic Predictors of Early Clozapine Discontinuation Across Mood and Psychotic Disorders
Authors: Ercis Mete , Cole Kristin C. , Dierkhising Ross A. , Ozerdem Aysegul , Markota Matej , Singh Balwinder , McElroy Susan L. , Frye Mark A. , Leung Jonathan G. 
Published: January 2025

Abstract

Background
Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but is often discontinued due to adverse effects. This study compared early clozapine discontinuation rates and reasons in patients with mood and psychotic disorders.

Methods
Data from all individuals with mood or psychotic disorders who initiated clozapine for the first time at the inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 and 2022 were retrospectively analyzed. Early clozapine discontinuation, defined as discontinuation within 90 days of initiation, was the primary outcome. Cox proportional hazards regression was used to assess factors associated with discontinuation.

Results
Of 83 patients (mood group n = 37, psychosis group n = 46), those in the mood group were older (P = 0.022) and more likely to be nonsmokers (P = 0.034). The overall 90-day clozapine discontinuation rate was 45.7%. Early discontinuation was significantly higher in the mood group than in the psychosis group (hazard ratio = 2.41, 95% confidence interval = 1.26–4.64, P = 0.008). Other factors associated with early discontinuation were female sex (P = 0.033), older age (P = 0.026), and nonsmoking (P = 0.001). In multivariable analysis, smoking status was the only factor significantly inversely associated with early clozapine discontinuation (hazard ratio = 0.47, 95% confidence interval = 0.22–0.99, P = 0.048), while diagnostic group, sex, and age did not show significant associations (all P > 0.05). Discontinuations were primarily due to adverse drug reactions in both groups.

Conclusions
Nearly half of the patients discontinued clozapine early, with higher rates in the mood group. Studies should further explore potential pharmacodynamic and pharmacokinetic factors associated with discontinuation, including the influence of smoking. Careful monitoring and personalized management of side effects are crucial for optimizing clozapine therapy and improving treatment outcomes.
Posttranslational histone 3 modification patterns in experimental septic and cardiogenic shock
Authors: Su Fuhong , Herpain Antoine , Garcia Bruno , Moiroux-Sahraoui Alexander , Manicone Francesca , Moreau Anthony , Annoni Filippo , Giuseppe Casu , Picod Adrien , Vincent Jean-Louis , Creteur Jacques , Taccone Fabio Silvio 
Published: January 2025

Background:
Histones are released during cellular damage and cell death. In addition to their intrinsic toxicity, posttranslational modifications (PTMs) in histones impact the sepsis response. Histone PTMs in cardiogenic shock (CS) remain unclear. We explored the temporal dynamics of nucleosomes and histone 3 (H3) PTM patterns in septic shock (SS) and CS and whether histone neutralization by the administration of sodium-β-O-methyl cellobioside sulfate (mCBS) could influence H3 PTMs in SS.

Methods:
Two experiments were conducted. In the first, SS was induced in 24 female sheep by fecal peritonitis. These animals were randomized into three groups: control, early mCBS, and late mCBS (n = 8 each), with mCBS given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) immediately after sepsis induction (early group) or 4 h later (late group). The experiment lasted 24 h, during which plasma samples were collected at baseline and every 4 h. In the second experiment, CS was induced in 8 pigs by partial occlusion of the anterior interventricular and circumflex arteries for 120 min using two angioplasty balloons. The CS experiment lasted 12 h, with serum samples collected at baseline, post-ischemia, and thereafter every 4 h. All animals were mechanically ventilated, hemodynamically monitored, fluid resuscitated, and received norepinephrine throughout the experiment. Concentrations of nucleosomes and H3 PTMs (H3K27ac, H3K27me3, and H3R8Cit) were measured using an enzyme-linked immunoassay.

Results:
Circulating nucleosome levels increased in SS but not in CS. H3K27ac and H3R8Cit reached peak levels rapidly following the onset of sepsis, whereas H3K27me3 showed a gradual increase during the later phases of SS. During CS, there were no significant changes in H3R8Cit, H3K27ac, or H3K27me3 levels. The mCBS treatment was associated with a nonsignificant reduction in H3 PTM levels.

Conclusion:
In these experimental models, the H3 PTM patterns differed in SS and CS. The administration of mCBS did not significantly reduce H3 PTM levels during sepsis.
Cerebrospinal Fluid Biomarkers and Cognition in Alzheimer Disease and Frontotemporal Dementia in a Memory Clinic Setting
Authors: Cayir Salih , Sadabad Faranak Ebrahimian , Mecca Adam P. , Matuskey David , Fesharaki-Zadeh Arman 
Published: January 2025

Objective:
Currently available literature on the relationships between cerebrospinal fluid (CSF) biomarkers and cognitive performance in frontotemporal dementia (FTD) is very limited and inconclusive. In this study, we investigated the association of cognitive symptoms, as measured with Montreal Cognitive Assessment (MoCA), with CSF levels of total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and amyloid β 1–42 (Aβ1–42) in a group of patients with probable FTD and Alzheimer disease (AD).

Methods:
We conducted a retrospective cohort study with participants selected from the electronic records of patients seen at Yale New Haven Hospital’s Memory Clinic, CT. A total of 61 patients, 28 with FTD (mean age=64.1) and 33 with AD (mean age=66.8), with available CSF results and cognitive test scores in their chart were included in analyses.

Results:
T-tau levels negatively and significantly correlated with total MoCA scores as well as the different MoCA index scores in patients with FTD (r=−0.47, P=0.04). There were no significant associations between MoCA scores and p-tau181 levels in patients with FTD (r=−0.22, P=0.25). Patients with AD exhibited significant correlations between MoCA scores and both t-tau (r=−0.54, P<0.01) and p-tau (r=−0.55, P<0.01) levels. Also, Aβ1–42 levels were not significantly correlated with MoCA scores in either of the FTD and AD groups.

Conclusion:
CSF concentrations of t-tau are inversely correlated to cognitive performance in patients with FTD and both t-tau and p-tau181 in AD. This study provides valuable insights into the relationship between clinical cognitive performance and tau-related pathology in FTD in comparison with AD.
Oral hygiene of stroke patients in a stroke unit: a best practice implementation project
Authors: Ferreira Salomé , Lima Andreia , Araújo Paula , Carneiro Silvia , Moreira Teresa , Cardoso Ana Filipa 
Published: January 2025

ABSTRACT

Introduction:
People with stroke are at risk of poor oral hygiene caused by neurological deficits, which can be motor, sensory, or cognitive. Good oral hygiene has been shown to reduce adverse events and improve the patient's quality of life. Although nurses recognize the benefits of oral hygiene, evidence shows that this area of care is frequently overlooked.

Aim:
This evidence implementation project aimed to improve oral hygiene in stroke patients through the application of best practices.

Methods:
This project was conducted in a stroke unit in a hospital in northern Portugal. The project followed the JBI Evidence Implementation Framework, which is grounded in an audit, feedback, and re-audit process. Four audit criteria were used in the baseline and follow-up audits. Observation of nursing care and analysis of nursing records were used to assess current practice against best practice recommendations. Nurses were engaged in the project through brainstorming to identify barriers, co-create strategies to address the barriers, and ensure project sustainability.

Results:
The baseline audit revealed low compliance with the four audit criteria. The follow-up audit showed increased compliance, with Criterion 1 improving from 0% to 100%, with all nurses receiving training on oral hygiene assessment and management. Compliance increased by 40% for Criterion 2 and 36.7% for Criteria 3 and 4, respectively.

Conclusions:
The project successfully promoted compliance with best practice recommendations and increased evidence-based practice for oral hygiene in patients with stroke in a stroke unit.

Spanish abstract:

http://links.lww.com/IJEBH/A302
Urban air pollution and child neurodevelopmental conditions: a systematic bibliometric review
Authors: Kefas Rosalyn , Roy Raymond , D’Angiulli Amedeo 
Published: January 2025

Purpose of review
Using advanced bibliometric analysis, we systematically mapped the most current literature on urban air pollution and neurodevelopmental conditions to identify key patterns and associations. Here, we review the findings from the broader literature by discussing a distilled, validated subset of 44 representative studies.

Recent findings
Literature highlights a complex relationship between environmental toxins, neurodevelopmental disorders in children, and neurobehavioral pathways involving oxidative stress, neuroinflammation, and protein aggregation. Chronic prenatal and postnatal exposure to airborne pollutants – such as particulate matter and heavy metals – may contribute to early formation of amyloid plaques through preadolescence. These processes may compromise synaptic plasticity and neural integrity, which can progressively induce cognitive, emotional, and behavioral dysregulation, sharing some pathological features traditionally associated with adult neurodegenerative diseases.

Summary
The interactions between air pollution exposure levels, developmental timing, and factors such as genetic vulnerability associated with neurodevelopmental disorders are still undetermined. However, accelerated neurodegenerative processes leading to cognitive decline and suboptimal mental health in children and adolescents seem most likely linked with pollutants penetrating the blood–brain barrier, and inducing oxidative stress and neuroinflammation. Urgent precautionary action might reduce environmental exposures during critical early developmental periods, thereby safeguarding children's cognitive function and mental health.
Breaking boundaries: fungi in the “rhizoctonia” species complex exhibit systemic colonization in three terrestrial orchid species
Authors: Jacopo Calevo , Pasquale Alibrandi , Samuele Voyron , Mariangela Girlanda , Silvia Perotto 
Published: January 2025

SummaryMost green orchids associate with orchid mycorrhizal (OrM) fungi belonging to the ‘rhizoctonia’ complex, a polyphyletic group of Tulasnellaceae, Ceratobasidiaceae and Serendipitaceae (Agaricomycotina), which are generally assumed to live as saprotrophs in soil. However, OrM rhizoctonias were rarely detected by metabarcoding in soil around orchid roots, and we have tested the hypothesis that these fungi may use adult orchid plants as a niche by colonizing not only their roots, but also other organs.The occurrence of OrM rhizoctonias inside roots, stems and leaves of three terrestrial orchid species (Spiranthes spiralis,Serapias vomeraceaandNeottia ovata) was therefore investigated by metabarcoding. To test the possibility of a vertical transmission of OrM fungi, reproductive structures (capsules, as well as seeds inS. spiralis) were also analyzed in a subset of plants.In all orchid species, a broad majority of OrM fungi found in roots was also detected in either stems or leaves of the same plant. OrM fungi were also detected in capsules/seeds.Systemic colonization of orchid tissues by OrM symbionts is a novel finding that raises important questions on the plant-fungus relationship in the aerial organs and opens intriguing perspectives on the potential modes of fungal transmission to the orchid progeny.
Tie that binds- Hill-Robertson Interference can produce signals of sexual antagonism even in the absence of sexually antagonistic selection
Authors: Arun Manas Geeta 
Published: January 2025

1AbstractSexually antagonistic (SA) selection on a trait with a shared genetic basis between the sexes is thought to lead to Intralocus Sexual Conflict (IaSC). A common way of measuring IaSC involves characterising the joint distribution of breeding values of male and female fitness using the intersexual additive genetic correlation for fitness (rmf,W). However, there is considerable variation in the empirical estimates ofrmf,W- with estimates ranging from significantly negative (suggestive of strong IaSC) to significantly positive (suggesting an absence of IaSC) - even among closely related populations of the same species. Here, we investigate whether SA selection is even necessary forrmf,Wto be negative. We first highlight that the sign ofrmf,Wdepends on a term that describes direct sex-specific selection, and another that describes indirect selection mediated by linkage disequilibria (LD). We show thatrmf,Wcan be negative if (1) selection is perfectly sex-limited - such that every locus affects the fitness of one sex only - and (2) the LD between closely-linked male-beneficial and female-beneficial alleles is on average negative as predicted under Hill-Robertson Interference (HRI). We test this idea using individual-based simulations. Our results suggest that populations evolving under purely sex-limited selection exhibit a prominent negative bias inrmf,Wthat gets strengthened by a reduction in the recombination rate. Therefore, HRI can drivermf,Wto be negative even in the absence of SA selection suggesting that negative estimates ofrmf,Wshould not automatically be considered as evidence of IaSC.
Exosomal miR-145-5p promotes apoptosis of renal tubule epithelial cells through the JNK signalling pathway
Authors: Deng Xiao-long , Yan Le-ping , Lan Yuan , Guo Jun-miao , Yuan Run-qi , Zhang Rong , Mao Pu 
Published: January 2025

AbstractAcute kidney injury (AKI) is the most prevalent extrapulmonary organ failure observed in patients with acute respiratory distress syndrome (ARDS). However, the underlying mechanisms leading to AKI in ARDS remain unclear. Exosomes facilitate intercellular and inter-organ communication via exosomal microRNAs (miRNAs), which potentially contribute to the crosstalk between the lung and kidney in ARDS. Therefore, the purposes of our study were to investigate the involvement of exosomal miRNAs in the development of AKI in ARDS. In current study, Sprague-Dawley rats were induced to develop ARDS via hydrochloric acid aspiration. Nanoparticle tracking analysis, Transmission electron microscopy and western blotting were conducted to analyse the exosomes. Quantitative reverse transcription-polymerase chain reaction andin situhybridisation showed elevated expression level of miR-145-5p in the circulating exosomes and lung tissue of ARDS rats. Overexpression of miR-145-5p disrupted the proteomic profile of renal proximal tubule epithelial cells, leading to impacts on proteins associated with various biological processes, including apoptosis. We further demonstrate that miR-145-5p overexpression enhanced JNK phosphorylation by directly repressing RBM3 expression and promoted cell apoptosis.Invivo, administration of agomiR-145-5p injection via intravenous route, which subsequently induced renal tubular cell apoptosis. These findings have revealed that miR-145-5p may serve as a novel mediator for the apoptosis of renal cell in the context of ARDS.
Viscoelastic HyA Hydrogel Promotes Recovery of Muscle Quality and Vascularization in a Murine Model of Delayed Rotator Cuff Repair
Authors: Pfaff Morgan R. , Wague Aboubacar , Davies Michael , Killaars Anouk R. , Ning Derek , Garcia Steven , Nguyen Anthony , Nuthalapati Prashant , Liu Mengyao , Liu Xuhui , Feeley Brian T. , Healy Kevin E. 
Published: January 2025

AbstractRotator cuff tears are among the most common musculotendinous injuries with high risk of permanent functional disability. Following surgical repair, sub-optimal patient outcomes are directly correlated with poor muscle quality; namely, injury site fatty infiltration (FI), fibrosis, and muscle atrophy. Muscle resident fibro-adipogenic progenitor cells (FAPs) have been identified as key regulators of post-injury skeletal muscle regeneration and repair by maintaining a promyogenic environment. In this work, human-derived FAPs (hFAPs) were encapsulated into hyaluronic acid (HyA)-based hydrogels functionalized with bsp-RGD(15) cell adhesion peptide, heparin, and a matrix metalloproteinase (MMP)-cleavable crosslinker. Hydrogel-encapsulated hFAPs increased expression of the promyogenic marker UCP1 and production of the anti-inflammatory cytokine IL-10, while downregulating the expression of the fibrotic marker αSMA over time. A murine model of unilateral rotator cuff transection, denervation, and delayed repair was treated with the HyA hydrogel or PBS and compared to a contralateral, non-injured control limb. Muscle histology 6 weeks post-repair revealed that the hydrogel reduced fibrosis, FI, and muscle atrophy while supporting vascularization of the injured tissue region. Collectively, these results suggest that the hydrogel alone can promote muscle regeneration in a clinically relevant delayed repair model of rotator cuff tear, which we hypothesize is due to controlled FAP differentiation into promyogenic lineages.
Nuclear pore complex distribution on the nuclear envelope: insights into curvature, chromatin, and actin contributions
Authors: Lachuer Hugo , Faklaris Orestis , Hénon Sylvie , Montel Fabien , Pereira David 
Published: January 2025

AbstractThe Nuclear Pore Complex (NPC) is an ancestral feature of eukaryotic cells, essential for the exchange of material and information between cytoplasm and nucleoplasm. While, typical eukaryotic cells harbor thousands of NPCs covering the nucleus surface, a quantitative characterization of their spatial distribution remains lacking. Taking advantage of super-resolution microscopy, we imaged and segmented individual NPCs in myoblast cells to reconstruct the nuclear surface. Our spatial statistics analysis of NPCs on the nuclear surface reveals the existence of a 400nm repulsion length between NPCs, likely reflecting the mesh size of the underlying lamin network. Furthermore, we identify three key correlates of NPC density. (1) Myoblast actin fibres, which can indent the nucleus, correlate with a decrease in NPC surface density, contrary to what was reported in previous studies; (2) Regions of the nuclear envelope near large heterochromatin domains exhibit reduced NPC surface density; and (3) There is a non-monotonous relationship between NPC density and the nuclear envelope curvature. This last observation is consistent with the existence of NPC-preferred curvature suggesting curvature sensing properties. In conclusion, this study provides new insights into the spatial distribution of NPCs, shedding light on possible new determinants of NPC spatial distribution.
Linking Molecular Tension and Cellular Tractions: A Multiscale Approach to Focal Adhesion Mechanics
Authors: Aytekin Samet , Kimps Laurens , Coucke Quinten , Linhares Débora , Deodhar Swaraj , Cardinaels Ruth , Cóndor Mar , Barrasa-Fano Jorge , Oosterwyck Hans Van , Rocha Susana 
Published: January 2025

AbstractFocal adhesions (FAs) are mechanosensitive structures that mediate force transmission between cells and the extracellular matrix. While Traction Force Microscopy (TFM) quantifies cellular tractions exerted on deformable substrates, Förster Resonance Energy Transfer (FRET)-based tension probes, such as Vinculin Tension Sensors (VinTS), measure molecular-scale forces within FA proteins. Despite their potential synergy, these methods have rarely been combined to explore the interplay between molecular tension and cellular tractions. Here, we introduce a framework integrating TFM and VinTS to investigate FA mechanics across scales. At cell level, tractions and vinculin tension increased with substrate stiffness. At FA level, vinculin tension correlated with vinculin density, while tractions scaled with FA area, total vinculin content and vinculin density. Direct comparison of tractions to tension revealed a complex, heterogenous relationship between these forces, possibly linked to diverse cell and FA maturation states. Sub-FA analysis revealed conserved spatial patterns, with tension and traction increasing towards the cell periphery. This multiscale approach provides insights into the multiscale dynamics of FA mechanotransduction, bridging the gap between molecular forces and cellular mechanics.j
Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis
Authors: Jose Anu Chirackal , Syu Yu-Wei , Lai Hao-Wen , Tsai Ming-Yuan , Jiang Yi-Fan , Hsu Shao-Chun , Lin Po-Yen , Huang Wan-Chen , Chu Wei-Chen , Fu Chi-Yu , Lee Yi-Ching 
Published: January 2025

SummaryRegulation of intracellular ascorbic acid (AA) levels is critical for connective tissue development and maintenance, but the underlying mechanisms remain unclear. In this study, we uncover a novel regulatory role of glucose transporter 10 (GLUT10) in AA homeostasis through a noncanonical trafficking pathway from the endomembrane system to mitochondria, traditionally considered as separate entities. We demonstrate that GLUT10 transit from ER to mitochondria through the plasma membrane (PM) and endosomes increases under stress conditions. This PM localization enhances the transport of dehydroascorbic acid (DHA), the oxidized form of AA, thereby maintaining intracellular AA levels. Disruption of this trafficking impairs AA homeostasis. Our findings reveal a previously unrecognized localization of GLUT10 at the PM and endosomes, highlighting a novel communication between endomembrane system and mitochondria for proetin redistribution, which is essential for maintaining intracellular AA homeostasis and facilitating environmental adaptation.Graphical abstract
Autosuggestion and Mental Imagery Bias the Perception of Social Emotions
Authors: Myga Kasia A. , Longo Matthew R. , Kuehn Esther , Azañón Elena 
Published: January 2025

AbstractCognitive processes that modulate social emotion perception are of pivotal interest for psychological and clinical research. Autosuggestion and mental imagery are two candidate processes for such a modulation, however, their precise effects on social emotion perception remain uncertain. Here, we investigated how autosuggestion and mental imagery, employed during an adaptation period, influence the subsequent perception of facial emotions, and to which extent. Separate cohorts of participants took part in five experiments, where they either mentally affirmed (autosuggested, Experiments 1a and 1b) or imagined (Experiment 2) that a neutral face would be expressing a specific emotion (happy or sad). Subsequent facial emotion perception was then assessed by calculating points of subjective equality (PSEs) along a happiness-sadness continuum. Our results show that both autosuggestion and mental imagery induce a bias toward perceiving facial emotions in the direction of the desired emotion, with larger Bayes factors supporting autosuggestion. Experiment 3 confirmed no effects when emotional words were presented instead, suggesting a reduced role of response bias to drive this effect. Finally, experiment 4 validated the experimental setup by demonstrating standard contrastive aftereffects when participants are adapted to actual, physical emotional faces. Together, our findings provide an initial step toward understanding the potential of intentional cognitive processes to modulate social emotions, specifically by biasing emotional face perception. With comparable effect sizes observed for both autosuggestion and mental imagery, both strategies show promise for self-directed interventions. Their practical applicability may vary due to individual responses, preferred cognitive strategies, and potential overlaps in underlying cognitive mechanisms.