bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal Biomarkers for Prognosis in Oral Squamous Cell Carcinoma—A Systematic Review of Emerging Technologies
Authors: Abdul Nishath Sayed , Ronsivalle Vincenzo , Shivakumar Sahana , Fiorillo Luca , Minervini Giuseppe 
Published: February 2025

Background:
Oral squamous cell carcinoma (OSCC) is a significant health issue because of its aggressive nature and poor prognosis during the advanced stages. Exosomal biomarkers have emerged as promising entities for facilitating an enhanced existing assessment of diagnosis and prognosis in OSCC, particularly in monitoring the noninvasive behavior of tumors. The authors tried to assess the potential role of these exosomal biomarkers in the prognosis of OSCC through this systematic review.

Methods:
Seven databases, PubMed, Scopus, Web of Science, Embase, Cochrane Library, CINAHL, and ProQuest, were searched systematically. Boolean operators, along with MeSH terms, were utilized for refining the search strings to retrieve the appropriate studies. The authors included studies focusing on exosomal biomarkers derived from OSCC tissues or cell lines, with emphasis on their potential as a prognostic.

Results:
We included 7 studies that probed the role of miRNAs, lncRNAs, and proteins in exosomes. A few particular miRNAs, such as miR-155, miR-21, miR-126, and miR-130a showed significant correlation with the patients' outcomes along with the progression of OSCC. These miRNAs continuously showed association with pathways having activities related to the promotion of tumor growth, regulation of the immune system, and angiogenesis. Interestingly, the studies on proteins like Arginase-1 and CKAP4 demonstrated significance in metastasis via exosomes and could be exploited in the risk assessment for metastasis. Another group of lncRNAs screened in exosomal contents has opened the exciting possibility of uncovering the functions of noncoding RNAs in the pathogenesis of OSCC.

Conclusions:
Our results conclude that exosomal biomarkers, including miRNAs, lncRNAs, and proteins, have great potential to improve the accuracy of prognosis and thus outcomes in OSCC. Some miRNAs were proven to be particularly instrumental for non-invasive diagnostics, whereas proteins and lncRNAs were more informative concerning complicated mechanisms of progression. The above inconsistency in molecular targets between the studies indicates that exosomes play a complex role in OSCC and future studies should focus on combining these different types of biomarkers for further enhancement of potential clinical applications and management of OSCC patients.
The Role of Intraoperative Neurophysiologic Monitoring on Surgical Decision Making and Neurologic Outcomes in Pediatric Patients With Intramedullary Spinal Cord Tumors
Authors: Papadakis Joanna E. , Mosher Amanda , Slingerland Anna L. , Albanese John S. , Staffa Steven J. , Bose Mitali , Toczylowlski Matthew , Fehnel Katie P. 
Published: February 2025

Purpose:
Maximal safe resection is recommended for intramedullary spinal cord tumors (IMSCT). Tools to minimize surgical morbidity are, therefore, critical. We review intraoperative neurophysiologic monitoring (IONM) in a large series of pediatric IMSCTs, focusing on its relationship with functional outcomes and surgical decision making.

Methods:
A single-institution, retrospective review of all IMSCT resections with IONM from 2000 to 2022 was conducted. Univariate analysis evaluated IONM changes with clinical and functional outcomes across an extended follow-up period.

Results:
Among the 59 IMSCT cases with IONM that met inclusion, somatosensory evoked potentials were used in 89.8%, motor evoked potentials in 86.4%, and Direct wave monitoring in 18.6%. Almost a third of patients experienced intraoperative changes in motor evoked potentials, somatosensory evoked potentials, and Direct waves, respectively, depending on the modality of IONM used. Monitoring alerts were more common in older patients (≥15 years) and those with larger tumors, and often led to longer hospital/intensive care unit stays and a higher rate of discharge to inpatient rehabilitation. Motor evoked potential and Direct wave alerts significantly affected the surgeon's decision to stop further resection (p = 0.001 and p = 0.067). Marked somatosensory evoked potential changes were associated with worse immediate postoperative sensory deficits (<6-weeks, p < 0.05). At 1-year follow-up, most patients experienced improved functional outcomes, with favorable motor and sensory recovery.

Conclusions:
Multiple IONM modalities are technically feasible in pediatric IMSCTs and help guide surgical decision making. Intraoperative neurophysiologic monitoring alerts were more common in patients with larger tumors and older ages, significantly affecting the surgeon's decision to stop further resection. Although associated with longer hospital/intensive care unit stays and increased discharge rates to rehabilitation, IONM changes did not significantly affect long-term functional outcomes.
Treatments for weight gain in schizophrenia
Authors: Elman Igor 
Published: February 2025

Purpose of review
Obesity and related metabolic disorders are extremely common in psychiatric patients, particularly in those with schizophrenia. Elucidating this link's neurobiology may inform clinicians and researchers of rational therapeutic approaches necessary to optimize clinical outcomes.

Recent findings
Current literature highlights the pivotal role of the inflammation-oxidative stress-insulin resistance loop in the pathophysiology of both metabolic and neuropsychiatric disorders. The concept of ‘diabetophrenia’ is put forward to highlight the overlapping neurobiological mechanisms underlying metabolic dysfunction and schizophrenia symptoms. Innovative treatments, including the combination of xanomeline with trospium and incretin-based medicines, demonstrate encouraging potential in addressing such complex health challenges.

Summary
The nuanced dynamics of chronic inflammation and psychiatric symptomatology underscore the significance of addressing both metabolic and mental health factors in a cohesive fashion while considering unique psychosocial contexts, dietary preferences, and lifestyle choices. A multidisciplinary strategy is essential for incorporating counseling, dietary interventions, behavioral therapies, and pharmacotherapy into the management of schizophrenia. The ensuing enhanced collaboration among healthcare professionals may render obsolete the prevailing siloed conceptualizations of mental disorders, opening new vistas for generating synergistic insights into the mind-body systems and leading to improved health and quality of life for patients with schizophrenia and other psychiatric conditions.
A machine learning approach to predict treatment efficacy and adverse effects in major depression using CYP2C19 and clinical-environmental predictors
Authors: Calabrò Marco , Fabbri Chiara , Serretti Alessandro , Kasper Siegfried , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Colombo Cristina , Zanardi Raffaella , De Ronchi Diana , Crisafulli Concetta 
Published: February 2025

Background
Major depressive disorder (MDD) is among the leading causes of disability worldwide and treatment efficacy is variable across patients. Polymorphisms in cytochrome P450 2C19 (CYP2C19) play a role in response and side effects to medications; however, they interact with other factors. We aimed to predict treatment outcome in MDD using a machine learning model combining CYP2C19 activity and nongenetic predictors.

Methods
A total of 1410 patients with MDD were recruited in a cross-sectional study. We extracted the subgroup treated with psychotropic drugs metabolized by CYP2C19. CYP2C19 metabolic activity was determined by the combination of *1, *2, *3, and *17 alleles. We tested if treatment response, treatment-resistant depression, and side effects could be inferred from CYP2C19 activity in combination with clinical-demographic and environmental features. The model used for the analysis was based on a decision tree algorithm using five-fold cross-validation.

Results
A total of 820 patients were treated with CYP2C19 metabolized drugs. The predictive performance of the model showed at best.70 accuracy for the classification of treatment response (average accuracy = 0.65, error = ±0.047) and an average accuracy of approximately 0.57 across all the tested outcomes. Age, BMI, and baseline depression severity were the main features influencing prediction across all the tested outcomes. CYP2C19 metabolizing status influenced both response and side effects but to a lower extent than the previously indicated features.

Conclusion
Predictive modeling could contribute to precision psychiatry. However, our study underlines the difficulty in selecting variables with sufficient impact on complex outcomes.
PP4Psy2regulates Rrm3 and Pif1 helicases to facilitate DSB resection across tandem retrotransposons
Authors: Campos Adrián , Pulido Lydia , Iglesias Lydia , Delgado Celia , Sánchez Mar , Villoria María Teresa , Clemente-Blanco Andrés 
Published: February 2025

AbstractDouble-strand break repair is a tightly regulated process that relies on the coordinated activity of kinase and phosphatase complexes. Here we show that the PP4 phosphatase regulatory subunits, Psy2 and Psy4, act as positive and negative regulators of the holoenzyme during DSB repair. Cdk-dependent phosphorylation of Psy2 is crucial for DSB repair but is not required for DNA damage checkpoint inactivation. Lack of Psy2 leads to an asymmetric resection defect on one side of the DSB, a defect that is alleviated by expressing a phosphodeficient H2A variant or by depleting the checkpoint adaptor Rad9. This resection asymmetry is associated to the presence of tandem retrotransposons proximal to the DSB site, underlining the role of PP4Psy2in stimulating resection across repetitive heterochromatic regions. PP4Psy2support resection progression through paired transposable elements by reducing the phosphorylation state of Pif1 and Rrm3 helicases during the DSB response. These findings provide a comprehensive framework for the role of PP4Psy2in resection-mediated DSB repair, highlighting its function in coordinating helicases activity to preserve genomic stability in response to DNA damage.
A Metabolite-Based Resistance Mechanism Against Malaria
Authors: Figueiredo Ana , Rastogi Sonia Trikha , Ramos Susana , Nogueira Fátima , De Villiers Katherine , de Sousa António G. Gonçalves , Votborg-Novél Lasse , von Wedel Cäcilie , Tober-Lau Pinkus , Jentho Elisa , Pagnotta Sara , Mesquita Miguel , Cardoso Silvia , Bortolussi Giulia , Muro Andrés F. , Tranfield Erin M. , Thibaud Jessica , Duarte Denise , Sousa Ana Laura , Pinto Sandra N. , Kitoko Jamil , Mombo-Ngoma Ghyslain , Mischlinger Johannes , Junttila Sini , Alenquer Marta , Amorim Maria João , Vasavda Chirag , Bosma Piter J. , Violante Sara , Drotleff Bernhard , Paixão Tiago , Portugal Silvia , Kurth Florian , Elo Laura L. , Paul Bindu D. , Martins Rui , Soares Miguel P. 
Published: February 2025

AbstractWhether jaundice, a common presentation ofPlasmodium(P.)falciparummalaria (1-3) arising from the accumulation of circulating bilirubin, represents an adaptive or maladaptive response toPlasmodiumspp. infection is not understood (1-3). We found that asymptomaticP. falciparuminfection was associated with a >10-fold higher ratio of unconjugated bilirubin over parasite burden, compared to symptomatic malaria. Genetic suppression of bilirubin synthesis by biliverdin reductase A (BVRA) (4) increased parasite virulence and malaria mortality in mice. Accumulation of unconjugated bilirubin in plasma, via genetic inhibition of hepatic conjugation by UDP glucuronosyltransferase family 1 member A1 (UGT1A1) (5), was protective against malaria in mice. Unconjugated bilirubin inhibitedP. falciparumproliferation in red blood cells (RBC) via a mechanism that suppressed mitochondrial pyrimidine synthesis. Moreover, unconjugated bilirubin inhibited hemozoin (Hz) crystallization and compromised the parasite’s food vacuole. In conclusion, jaundice represents a metabolic response toPlasmodium spp. infection that limits malaria severity.
Implicit and explicit attitudes toward people with physical disabilities in clinicians, rehabilitation assistants, and other occupations: A comparative study
Authors: Boisgontier Matthieu P. 
Published: February 2025

ABSTRACTObjectiveAbleism is driven by attitudes that influence behaviors and decisions toward people with disabilities. To assess whether these attitudes vary by occupation, we compared the preferences for people with or without physical disabilities between healthcare practitioners and individuals in other professions.MethodsData from 213,191 participants collected through Project Implicit were analyzed, including 6445 clinicians, 3482 rehabilitation assistants, and 203,264 individuals in other occupations. Implicit attitudes were assessed using D-scores derived from the Implicit Association Test. Explicit attitudes were assessed using a Likert scale. Multiple linear regression models were conducted to examine the association between occupation groups and attitudes toward people with and without physical disabilities, while controlling for demographic variables.ResultsHealthcare practitioners showed both an implicit and explicit preference for people without physical disabilities. Equivalence tests showed that implicit attitudes of clinicians and rehabilitation assistants were equivalent to those in other occupations. Clinicians had less favorable explicit attitudes toward people with physical disabilities, whereas rehabilitation assistants had more favorable ones. Older age, male sex, and no personal experience of disability were associated with less favorable attitudes toward people with physical disabilities. Associations with education, race, geographic region, and year of data collection were also observed.ConclusionsThis study provides evidence of attitudes against people with physical disabilities among healthcare practitioners. Moreover, implicit attitudes of healthcare practitioners toward people with physical disabilities were not more favorable than those of other occupations; and explicit attitudes of clinicians were even less favorable.ImpactOur findings suggest that despite ongoing educational shifts toward more inclusive approaches, the longstanding framework of disability as an abnormality to be normalized may still affect healthcare practitioners. This underscores the need for continued efforts to address ableism in healthcare by promoting disability-inclusive education and training.DisclosuresNone
The Impact of Virtual Reality Training on Immune-Related Mechanisms in Alzheimer’s Disease
Authors: Yusufu Nazuke , Hongyan Li 
Published: February 2025

AbstractObjectiveThere is currently lack of research on the molecular mechanisms of VR therapy. In this study, we aimed to analyze the differential gene expression profiles and functional pathway enrichment of peripheral blood samples of AD related Mild Cognitive Impairment (MCI)patients before and after VR treatment using high-throughput sequencing methods and compare to normal controls to explore the targeted genes and potential intervention mechanisms of VR treatment.MethodsSelect five AD patients and five normal controls, collect peripheral blood samples, perform whole transcriptome sequencing to screen for differentially expressed mRNA genes before and after VR treatment and in comparison with the control group. Combine with GO and KEGG pathway enhancement to elucidate the underlying biological mechanisms and related pathways to predict the targeted genes and potential intervention mechanisms of VR treatment.ResultsPre- and post-VR treatment group comparisons revealed a total of 1167 significantly differentially expressed genes in the mRNA data, with 165 genes upregulated and 1002 downregulated. Among these, ZFP36, FOS, JUN, FOSB, and PMAIP1 were identified as disease-related genes. Furthermore, immune infiltration analysis indicated that PMAIP1, ZFP36, and FOSB were correlated with immune cells. GO analysis highlighted significant enrichment in immune-related pathways.ConclusionVR treatment may modulate immune and transcriptional regulatory mechanisms, potentially contributing to its therapeutic efficacy in AD. The specific mechanisms require further research and validation.
Randomized Double Blind Inpatient Study of a Gluten-Free Diet in Persons with Schizophrenia
Authors: Kelly Deanna L. , Lee Christopher M. , Roche Daniel J.O. , Talor Monica V. , Clark Sarah , Eaton William W. 
Published: February 2025

SummaryBackgroundSchizophrenia and related disorders (SRD) are characterized by positive and negative symptoms, such as anhedonia and avolition. There are no current FDA approved treatments for negative symptoms, which is a critical gap in our treatment of people with SRDs, since they are a major determinant of functional impairment. An emerging literature suggests that SRDs have a relationship with immune function and inflammation. Recently an SRD subgroup with high inflammation and elevated levels of anti-gliadin antibodies (AGA) of immunoglobulin G type (IgG) hasbeen characterized. Negative symptom improvement has been previously observed with gluten removal in this subgroup in two small clinical trials.MethodsWe conducted a 5-week confirmatory double-blind placebo-controlled trial of a gluten free diet (GFD) versus gluten-containing diet (GCD) for negative symptoms in people with SRD who have elevated AGA IgG (NCT03183609). Participants were between the ages of 18-64 years, had baseline negative symptoms and a diagnosis of schizophrenia or schizoaffective disorder. Those included were screened for an AGA IgG >20 U, no serologic evidence of celiac disease, and stable antipsychotic treatment and dose. All participants were inpatients, received a GFD and were randomized to 30 grams of gluten or rice flour daily delivered in protein shakes. The Clinical Assessment Interview for Negative Symptoms (CAINS) Motivation and Pleasure (MAP) scale was the primary outcome measure. We also examined the CAINS Expressivity (EXP) scale, the Scale for the Assessment of Negative Symptoms (SANS), the Brief Psychiatric Rating Scale (BPRS), the MATRICS Consensus Cognitive Battery (MCCB) and conducted regular side effect screening and laboratory measures for safety.FindingsBetween 2018 and 2024, we included 39 participants (N=21 GFD and N=18 GCD). There was a significant improvement over time in the CAINS MAP (treatment X timedf=30.1,F=2.78,p=0.045) in the GFD compared to GCD, but no significant change in the CAINS EXP, the SANS, BPRS or MCCB. The diet was well tolerated; the most frequently occurring side effects were constipation (38.1% GFD, 33.3% GCD), sedation (33.3% GFD, 50% GCD), dry mouth (33.3% GFD, 33.3% GCD), headache (33.3% GFD, 27.8% GCD), and insomnia (33.3% GFD, 27.8% GCD).InterpretationThis is the first large scale double-blind randomized clinical trial in SRD with AGA IgG+. This replication of smaller studies suggests that negative symptoms, particularly anhedonia and avolition may be improved. However, we did not replicate our previous finding of cognitive improvement and COVID-19 likely impacted the extent of improvement in negative symptoms due to quarantines and lockdowns. More work is needed to determine the mechanism of action of gluten removal in this subgroup with hopes of developing new treatment targets for motivational deficits of this illness.
Reproducible Brain Charts: An open data resource for mapping brain development and its associations with mental health
Authors: Shafiei G , Esper NB , Hoffmann MS , Ai L , Chen AA , Cluce J , Covitz S , Giavasis S , Lane C , Mehta K , Moore TM , Salo T , Tapera TM , Calkins ME , Colcombe S , Davatzikos C , Gur RE , Gur RC , Pan PM , Jackowski AP , Rokem A , Rohde LA , Shinohara RT , Tottenham N , Zuo XN , Cieslak M , Franco AR , Kiar G , Salum GA , Milham MP , Satterthwaite TD 
Published: February 2025

ABSTRACTMajor mental disorders are increasingly understood as disorders of brain development. Large and heterogeneous samples are required to define generalizable links between brain development and psychopathology. To this end, we introduce the Reproducible Brain Charts (RBC), an open data resource that integrates data from 5 large studies of brain development in youth from three continents (N=6,346; 45% Female). Confirmatory bifactor models were used to create harmonized psychiatric phenotypes that capture major dimensions of psychopathology. Following rigorous quality assurance, neuroimaging data were carefully curated and processed using consistent pipelines in a reproducible manner with DataLad, the Configurable Pipeline for the Analysis of Connectomes (C-PAC), and FreeSurfer. Initial analyses of RBC data emphasize the benefit of careful quality assurance and data harmonization in delineating developmental effects and associations with psychopathology. Critically, all RBC data – including harmonized psychiatric phenotypes, unprocessed images, and fully processed imaging derivatives – are openly shared without a data use agreement via the International Neuroimaging Data-sharing Initiative. Together, RBC facilitates large-scale, reproducible, and generalizable research in developmental and psychiatric neuroscience.
Effects of Social Housing on Electrically Stimulated Dopamine Release in the Nucleus Accumbens Core and Shell in Female and Male Rats
Authors: Gonzalez Ivette L. , Becker Jill B. 
Published: February 2025

AbstractDopamine (DA) is a neurotransmitter that is important in the reward system and increased DA release is associated with rewarding properties of drugs. Highly addictive stimulants like methamphetamine (METH) increase DA release and block reuptake, causing the DA to stay in the synapse longer, enhancing its effects. Because the misuse of METH is increasing in the United States, it is important to investigate ways to protect against this highly addictive stimulant. Recent studies have shown that social support can be a protective factor against METH self-administration in females, but not males. Other studies using microdialysis have shown that socially housed females have lower DA release in the nucleus accumbens (NAc) compared to single housed females after treatment with METH. Additionally, researchers have shown that there are sex differences in stimulated DA release. The present study investigates whether social housing affects stimulated DA release after METH treatment. DA release in the NAc core and shell of socially housed and individually housed rats was measured using fast scan cyclic voltammetry (FSCV) with a chronic 16-channel carbon fiber electrode in the NAc. A stimulating electrode was aimed at the ventral tegmental area (VTA) to induce DA release in the NAc. The results showed that social housing enhances electrically stimulated DA release in males and that there was greater DA release in NAc core than shell in single males, but no difference in socially housed males. In females, social housing also enhanced ES DA release. In single females there was greater ES DA release in shell than in core. Additionally, in single housed females there was greater ES DA release over time, while the socially housed females had high ES DA release that remained stable over time. These results suggest that social housing protects females from sensitization, making single females more vulnerable to the addictive properties of METH.