bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large language models in cancer: potentials, risks, and safeguards
Authors: Zitu Md Muntasir , Le Tuan Dung , Duong Thanh , Haddadan Shohreh , Garcia Melany , Amorrortu Rossybelle , Zhao Yayi , Rollison Dana E , Thieu Thanh 
Published: December 2024

Abstract
This review examines the use of large language models (LLMs) in cancer, analysing articles sourced from PubMed, Embase, and Ovid Medline, published between 2017 and 2024. Our search strategy included terms related to LLMs, cancer research, risks, safeguards, and ethical issues, focusing on studies that utilized text-based data. 59 articles were included in the review, categorized into 3 segments: quantitative studies on LLMs, chatbot-focused studies, and qualitative discussions on LLMs on cancer. Quantitative studies highlight LLMs’ advanced capabilities in natural language processing (NLP), while chatbot-focused articles demonstrate their potential in clinical support and data management. Qualitative research underscores the broader implications of LLMs, including the risks and ethical considerations. Our findings suggest that LLMs, notably ChatGPT, have potential in data analysis, patient interaction, and personalized treatment in cancer care. However, the review identifies critical risks, including data biases and ethical challenges. We emphasize the need for regulatory oversight, targeted model development, and continuous evaluation. In conclusion, integrating LLMs in cancer research offers promising prospects but necessitates a balanced approach focusing on accuracy, ethical integrity, and data privacy. This review underscores the need for further study, encouraging responsible exploration and application of artificial intelligence in oncology.
In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson’s disease
Authors: Cortés Adriana , Phung Toan K , de Mena Lorena , Garrido Alicia , Infante Jon , Ruíz-Martínez Javier , Galmés-Ordinas Miquel À , Glendinning Sophie , Pérez Jesica , Roig Ana , Soto Marta , Cosgaya Marina , Ravasi Valeria , Fernández Manel , Rubiano-Castro Alejandro , Díaz Ramón , Hernández-Eguiazu Haizea , Sánchez-Quintana Coro , Vinagre-Aragón Ana , Mondragón Elisabet , Croitoru Ioana , Rivera-Sánchez María , Corrales-Pardo Andrea , Sierra María , Tolosa Eduardo , Malagelada Cristina , Nirujogi Raja S , Fernández-Irigoyen Joaquín , Santamaría Enrique , Alessi Dario R , J Martí María , Ezquerra Mario , Fernández-Santiago Rubén 
Published: December 2024

Abstract
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson’s disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients.
Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174). The groups of study encompassed G2019S L2PD patients (n=37), non-manifesting LRRK2 mutation carriers of G2019S, here, G2019S L2NMCs (n=27), R1441G L2PD patients (n=14), R1441G L2NMCs (n=11), iPD patients (n=40), and healthy controls (n=45).
We identified 207 differential proteins in G2019S L2PD compared to controls (39 up/168 down) and 67 in G2019S L2NMCs (10 up/57 down). G2019S down-regulated proteins affected the endolysosomal pathway, proteostasis, and mitochondria, e.g., ATIC, RAB9A, or LAMP1. At the phospho-proteome level, we observed increases in endogenous phosphorylation levels of pSer106 RAB12 in G2019S carriers, which were validated by immunoblotting after 1 year of follow-up (n=48). Freshly collected PBMCs from 3 G2019S L2PD, 1 R1441G L2PD, 1 iPD, and 5 controls (n=10) showed strong diminishment of pSer106 RAB12 phosphorylation levels after in-vitro administration of the MLi-2 LRRK2 inhibitor. Using machine learning, we identified an 18-feature G2019S phospho-/protein signature discriminating G2019S L2PD, L2NMCs, and controls with 96% accuracy that correlated with disease severity, i.e., UPDRS-III motor scoring.
Using easily accessible PBMCs from a LRRK2 clinical cohort, we identified elevated levels of pSer106 RAB12 as an endogenous biomarker of G2019S carriers. Our data suggest that monitoring pSer106 RAB12 phosphorylation could be a relevant biomarker for tracking LRRK2 activation, particularly in G2019S carriers. Future work may determine whether pSer106 RAB12 could help with patient enrichment and monitoring drug efficacy in LRRK2 clinical trials.
Arousal effects on oscillatory dynamics in the non-human primate brain
Authors: Anand Shashank A , Sogukpinar Fatih , Monosov Ilya E 
Published: December 2024

Abstract
Arousal states are thought to influence many aspects of cognition and behavior by broadly modulating neural activity. Many studies have observed arousal-related modulations of alpha (~8 to 15 Hz) and gamma (~30 to 50 Hz) power and coherence in local field potentials across relatively small groups of brain regions. However, the global pattern of arousal-related oscillatory modulation in local field potentials is yet to be fully elucidated. We simultaneously recorded local field potentials in numerous cortical and subcortical regions in the primate brain and assessed oscillatory activity and inter-regional coherence associated with arousal state. In high arousal states, we found a uniquely strong and coherent gamma oscillation between the amygdala and basal forebrain. In low arousal rest-like states, a relative increase in coherence at alpha frequencies was present across sampled brain regions, with the notable exception of the medial temporal lobe. We consider how these patterns of activity may index arousal-related brain states that support the processing of incoming sensory stimuli during high arousal states and memory-related functions during rest.
Post–Coronavirus Disease 2019 (COVID-19) Condition Risk Factors and Symptom Clusters and Associations With Return to Pre–COVID-19 Health—Results From a 2021 Multistate Survey
Authors: Konkle Stacey L , Magleby Reed , Bonacci Robert A , Segaloff Hannah E , Dimitrov Lina V , Mahale Parag , Katic Bozena , Nji Miriam , Cadwell Betsy , Ko Jean Y , Bushman Dena , Rushmore Julie , Cope Jennifer , Saydah Sharon 
Published: December 2024

Abstract

Background
Little is known about how symptoms or symptom clusters of post–coronavirus disease 2019 (COVID-19) conditions (PCCs) impact an individual's return to pre–COVID-19 health.

Methods
We used 4 state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCCs and associations with an individual's return to pre–COVID-19 health after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants had a positive SARS-CoV-2 test between March 2020 and December 2020. Weighted regression models were used to estimate prevalence of PCCs, identify risk factors associated with developing PCCs, and examine associations between PCC symptom clusters and return to pre–COVID-19 health. Factor analysis was used to identify post–COVID-19 symptom clusters.

Results
Prevalence of PCCs in this population-based sample was 29.9% for persons with SARS-CoV-2 infection during the pre-Delta variant period (March 2020–December 2020); 77.2% of persons who experienced PCCs had not returned to pre–COVID-19 health within 8–60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of preexisting comorbidities were significant risk factors associated with PCCs. Myalgic encephalomyelitis/chronic fatigue syndrome–like symptoms, upper respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre–COVID-19 health.

Conclusions
Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCCs, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCCs can help measure impacts of COVID-19 vaccination and acute COVID-19–specific treatments on reducing PCCs in the United States.
Performance of Diagnostic Algorithms in Patients With Invasive Pulmonary Aspergillosis
Authors: Hatzl Stefan , Geiger Christina , Kriegl Lisa , Scholz Laura , Reisinger Alexander C , Kreuzer Philipp , Fruhwald Sonja , Wölfler Albert , Reinisch Andreas , von Lewinski Dirk , Schilcher Gernot , Hoenigl Martin , Eller Philipp , Krause Robert 
Published: December 2024

Abstract

Background
Invasive pulmonary aspergillosis (IPA), once limited to immunocompromised patients, is now a severe complication in critically ill ICU patients without classic risk factors. Due to the difficulty of obtaining histological evidence, diagnosis relies on poorly tested algorithms in real-world settings.

Methods
We conducted a retrospective multicenter (n = 9) cohort study including 202 patients with IPA. Patients were classified using a multistep process based on the EuropeanOrganization- for-the-Research-and-Treatment-of-Cancer/Mycosis-Study Group (EORTC-MSG), Invasive-Fungal-Diseases-in-Adult-Patients-in-Intensive-Care-Unit (FUNDICU), Aspergillus-ICU (Asp-ICU), and Asp-ICU with biomarkers (Asp-ICU-BM) criteria. We then evaluated the predictive performance of these criteria against the clinical cohort and histologically proven cases.

Results
Among 202 patients, 78 had EORTC-MSG host factors and were classified accordingly, with EORTC-MSG criteria achieving 100% agreement in identifying clinical and histologically proven cases. In 112 ICU patients without EORTC-MSG host factors, overall agreement was 53% for FUNDICU, 4% for Asp-ICU, and 26% for Asp-ICU-BM versus the clinical cohort. Validation against histologically proven cases showed FUNDICU had 44% sensitivity and 75% specificity, Asp-ICU 6% sensitivity and 100% specificity, and Asp-ICU-BM 28% sensitivity and 63% specificity. Adding acute respiratory distress syndrome (ARDS) and post-cardiac surgery to the FUNDICU criteria improved sensitivity to 97% with a specificity of 63%. The remaining 12 patients lacked EORTC-MSG host factors and were not in the ICU, highlighting a novel classification system.

Conclusions
EORTC-MSG and FUNDICU IPA classification systems are useful for the assignment of most patients with IPA. Incorporating postoperative complications after cardiac surgery and ARDS enhanced the diagnostic accuracy of FUNDICU.
Congenital Toxoplasmosis: Fewer Clinical Signs at 3 Years of Age Over the Last 15 Years but Stable Risk of Materno-fetal Transmission
Authors: Wallon Martine , Ksiazek Elea , Journé Antoine , Dupont Damien , Menotti Jean , Peyron François , Binquet Christine 
Published: December 2024

Abstract
The risk and severity of congenital toxoplasmosis were estimated using data from 2455 consecutive mother–child pairs. Clinical signs at 3 years were halved in the 177 children born since 2009 compared with 1996–2008 (odds ratio = .49; 95% CI: .28–.85). Materno-fetal transmission rates remained stable from 1992 to 2021.
Optimal Cutoff Values and Utility of High-Sensitivity Troponin T and NT-proBNP for the Risk Stratification of Patients with Acute Pulmonary Embolism
Authors: Matthews Timothy M , Peters Gregory A , Wang Grace , Horick Nora , Chang Kyle E , Harshbarger Savanah , Prucnal Christiana , Birrenkott Drew A , Stannek Karsten , Lee Eun Sang , Dhar Isabel , Wrenn Jesse O , Stubblefield William B , Kabrhel Christopher 
Published: December 2024

Abstract

Background
Guidelines recommend using high-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE). However, there are no evidence-based cutoff values defined for this clinical application.

Methods
We performed a single-center, retrospective cohort study of patients with imaging-confirmed PE and hsTnT and/or NT-proBNP (ElecsysTM, Roche) measured 12 h before or 24 h after PE Response Team (PERT) activation. We excluded hypotensive patients. Our primary outcome was a composite of adverse outcomes or critical interventions within 7 days. We calculated the area under the receiver operating curve (AUC, ROC) for hsTnT and NT-proBNP and determined the optimal cutoffs using the distance from (0,1). We performed a subgroup analysis on patients with PE and right ventricular dysfunction on imaging.

Results
Two hundred thirty-four patients were included in the hsTnT analysis, and 727 in the NT-proBNP analysis. Mean age was 62 years (SD = 17) and 47% were female. The AUC for hsTnT was 0.64 (95% CI, 0.56–0.71) with an optimal cutoff of 46 ng/L, corresponding to a sensitivity of 59% (95% CI, 49–69) and a specificity of 61% (95% CI, 53–69). The AUC for NT-proBNP was 0.56 (95% CI, 0.51–0.61) with an optimal cutoff of 1092 pg/mL, corresponding to a sensitivity of 53% (95% CI, 45–61) and a specificity of 59% (95% CI, 55–63).

Conclusion
We identified an optimal cutoff of 46 ng/L for hsTnT and 1092 pg/mL for NT-proBNP, though the AUC for both markers suggests low to moderate performance for the risk stratification of initially hemodynamically stable PERT patients. Use of these biomarkers to risk stratify PE may require reconsideration.
Early Onset Active Inflammatory Bowel Disease Is Associated With Psychiatric Comorbidities: A Multi-Network Propensity-Matched Cohort Study
Authors: Nadeem Ahmed , Donohue Sydney , Shah Fatima Zehra , Perez Jaime Abraham , Harper Elleson , Sinh Preetika , Padival Ruthvik , Cooper Gregory , Katz Jeffry , Cominelli Fabio , Regueiro Miguel , Mansoor Emad 
Published: December 2024

Abstract

Background
Psychiatric disease burden in patients with Inflammatory bowel disease (IBD) has risen substantially over the past few decades. However, there is limited data on the relationship between IBD disease activity and the incidence of psychiatric comorbidities. We sought to conduct a population-based study to investigate the impact of early onset disease activity in newly diagnosed IBD patients on psychiatric disease diagnoses and medication usage.

Methods
We performed a retrospective cohort study using the TriNetX database. We identified all adult patients diagnosed with IBD and documented IBD-specific medication use. We stratified these IBD patients into 2 cohorts based on IBD Disease Activity, occurring 6 months to 1 year after initial IBD diagnosis. Active IBD was defined as the utilization of steroids and/or elevated fecal calprotectin [≥200 µg/g] occurring 6 months to 1 year after initial IBD diagnosis. We examined the outcomes of psychiatric disease diagnoses and psychotropic medication prescriptions occurring 1 year after the initial diagnosis.

Results
Out of 69 105 patients with an IBD diagnosis during the study period, after propensity score matching, 16 922 IBD patients each were included in the 2 cohorts based on disease activity. Patients with active IBD had significantly higher odds of developing major depressive disorder, anxiety disorder, bipolar disorder, alcohol use disorder, opiate use disorder, attention deficit hyperactivity disorder, and obsessive-compulsive disorder. Additionally, patients with active IBD also had significantly higher odds of using all studied psychotropic medications, including antidepressants, antipsychotic medications, anxiolytics, sedatives, hypnotic medications, mood stabilizers, stimulant medications, and medications used for substance use disorders (including alcohol, opioid, and tobacco use).

Conclusions
Active IBD shortly after the IBD diagnosis is associated with a higher incidence of psychiatric comorbidities. Awareness of behavioral health in IBD is important, and proper treatment is necessary.
Novel algorithm for non-invasive estimation of left atrial pressure in patients with atrial fibrillation
Authors: Seo Jiwon , Yu Hee Tae , Kim In-Soo , Kim Tae-Hoon , Joung Boyoung , Pak Hui-Nam , Cho Iksung , Shim Chi Young , Hong Geu-Ru , Ha Jong-Won 
Published: December 2024

Abstract

Aims
Determining elevated left atrial (LA) pressure is crucial in patients with atrial fibrillation (AF), yet non-invasive estimation using echocardiography remains unclear. This study aimed to identify useful echocardiographic indices for identifying elevated LA pressure in patients with AF.

Methods and results
Patients with paroxysmal or persistent AF referred for catheter ablation at two tertiary hospitals were prospectively enrolled. Mean LA pressure was measured immediately after transseptal puncture. Elevated mean LA pressure was defined as ≥15 mmHg. Transthoracic echocardiography was performed to acquire the guideline-recommended parameters. A total of 176 patients were included, and 63 (36%) patients had a mean LA pressure ≥15 mmHg. Patients with elevated LA pressure had more frequent hypertension, larger LA, higher septal E/e′, and worse LA strain than the remaining patients. The correlations between mean LA pressure and each echocardiographic parameter were weak. Septal E/e′ ratio showed the best correlation with mean LA pressure (r = 0.351, P &lt; 0.001), and septal E/e′ ratio ≥11 was the best parameter (area under the curve = 0.7, sensitivity = 65%, specificity = 73%, accuracy = 70%) to identify elevated mean LA pressure. A hierarchical algorithm consisting of septal E/e′ ratio, LA reservoir strain, and LA volume index improved identification of patients with elevated mean LA pressure (sensitivity = 61%, specificity = 91%, accuracy = 80%).

Conclusion
In patients with AF, the septal E/e′ ratio was the best single parameter for identifying elevated mean LA pressure. A hierarchical algorithm combining the septal E/e′ ratio, LA reservoir strain, and LA volume index helps identify elevated LA pressure in patients with AF.
Safety of prolonged bilateral antegrade cerebral perfusion in aortic arch surgery with moderate hypothermia
Authors: Hohri Yu , Rajesh Kavya , Murana Giacomo , Castagnini Sabrina , Bianco Edoardo , Zhao Yanling , Kurlansky Paul , Pacini Davide , Takayama Hiroo 
Published: December 2024

Abstract

OBJECTIVES
This study investigates the impact of bilateral antegrade cerebral perfusion (ACP) time on outcomes in aortic arch surgery.

METHODS
In total, 961 patients underwent either hemiarch (n = 385) or total arch replacement (n = 576) with bilateral ACP and moderate hypothermia management between 2006 and 2020 across 2 aortic centres. ACP time was categorized into 4 groups (≤30 min: n = 169, 30–60 min: n = 298, 60–90 min: n = 261, &gt;90 min: n = 233). Inverse probability of treatment weighting yielded a well-balanced cohort among the 4 groups except for the cannulation site. Adjusted cubic spline and multivariable logistic analysis were performed, controlling for surgical procedure, cannulation site and cardiopulmonary bypass (CPB) time, to identify the relationship between ACP time and major in-hospital complications including mortality, stroke, acute renal failure and prolonged ventilation.

RESULTS
There remained a significant difference in surgical procedures and CPB time in the matched cohort. The incidences of mortality and stroke did not show significant trend (P = 0.052 and 0.717, respectively). Cubic spline curves showed that odds ratios did not increase linearly for any complications with increasing ACP time. Furthermore, ACP time, even exceeding 90 min, was not associated with complication rates [mortality: odds ratio = 1.459 (0.368–6.049), P = 0.595; stroke: 0.310 (0.058–1.635), P = 0.166; renal failure: 1.744 (0.521–6.094), P = 0.374; prolonged ventilation: 1.502 (0.535–4.286), P = 0.442], whereas CPB time was associated with mortality and prolonged ventilation.

CONCLUSIONS
Even when ACP time exceeded 90 min, it was not associated with major in-hospital complications, questioning its validity as a marker for surgical insult.
Herbivory and water availability interact to shape the adaptive landscape in the perennial forb, Boechera stricta
Authors: Jameel M Inam , Duncan Lisa , Mooney Kailen , Anderson Jill T 
Published: December 2024

Abstract
Abiotic and biotic factors interact to influence phenotypic evolution; however, identifying the causal agents of selection that drive the evolution and expression of traits remains challenging. In a field common garden, we manipulated water availability and herbivore abundance across 3 years, and evaluated clinal variation in functional traits and phenology, phenotypic plasticity, local adaptation, and selection using diverse accessions of the perennial forb, Boechera stricta. Consistent with expectations, drought stress exacerbated damage from herbivores. We found significant plasticity and genetic clines in foliar and phenological traits. Water availability and herbivory interacted to exert selection, even on traits like flowering duration, which showed no clinal variation. Furthermore, the direction of selection on specific leaf area in response to water availability mirrored the genetic cline and plasticity, suggesting that variation in water levels across the landscape influences the evolution of this trait. Finally, both herbivory and water availability likely contribute to local adaptation. This work emphasizes the additive and synergistic roles of abiotic and biotic factors in shaping phenotypic variation across environmental gradients.
The GATA factor AreB regulates nitrogen metabolism, fungal development, and aflatoxin production in Aspergillus flavus
Authors: Zhi Qing-Qing , Wang Zhen-Long , Yuan Pei-Bo , He Lei , He Zhu-Mei 
Published: December 2024

Abstract
Nitrogen is important for fungal growth and development, and the GATA transcription factor AreA has been widely studied as a key regulator of nitrogen catabolite repression (NCR) in many fungi. However, AreB, another GATA transcription factor in the NCR pathway, remains less studied, and its role in Aspergillus flavus is still unclear. In this study, we characterized areB in A. flavus and investigated its role in regulating nitrogen utilization, fungal growth, and aflatoxin production. The areB gene produces three transcripts, with areB-α being the most abundantly expressed, particularly under nitrogen-limited conditions. Gene expression analysis via qPCR confirmed that areB acts as a negative regulator of NCR, as its deletion led to the upregulation of NCR-related genes under nitrogen-limiting conditions. Gene function analysis of areB revealed that its deletion impaired hyphal growth, reduced conidia production, and delayed conidial germination. Additionally, deletion of areB led to increased aflatoxin production, particularly under less favorable nitrogen sources, while overexpression of areB reduced aflatoxin levels. Furthermore, areB influenced sclerotia formation in a nitrogen-source-dependent manner. These findings reveal the multifaceted role of areB in nitrogen regulation, fungal development, and secondary metabolism, offering insights for controlling aflatoxin contamination and fungal growth.