bluuebunny/crossref_metadata_2025_split huggingface dataset:
Game Violence and Moral Distress
Authors: Wagener Gary Lee , Melzer André 
Published: June 2024

Abstract: Inflicting virtual violence on others violates internalized moral norms of social interaction and therefore usually triggers feelings of moral distress. However, people play and enjoy violent media, especially violent video games (VVG) in which they commit violent acts. In two experimental studies, we tested why people enjoy violent media and whether personality-related factors like the Dark Tetrad (i.e., Machiavellianism, everyday sadism, psychopathy, and narcissism) play a role in it. In Study 1 ( N = 313, online experiment), watching a violent video game clip or reading a violent text led to greater moral distress than watching a non-violent video. Although Dark Tetrad, VVG preference, and moral disengagement were all positively associated, none of these factors moderated moral distress. In Study 2 ( N = 69, laboratory experiment), participants either played a violent or a non-violent game version. Again, game violence led to comparably greater moral distress. However, in contrast to Study 1 in which participants only watched violent media, Dark Tetrad now significantly moderated the relationship between condition and moral distress. Participants with low Dark Tetrad expressions experienced significantly greater moral distress in the violent condition. Generally, participants with more gaming experience felt less morally distressed after gameplay than inexperienced participants. The present findings corroborate the moral implications of experiencing media violence and the important role of personality-related factors, thus further illustrating the complexity of mechanisms underlying violent media effects.
A Hybrid Normal Mode‐Collocation Method for Finding the Response of Laterally Homogeneous Compressible Maxwell Viscoelastic Earth Models
Authors: Brierley‐Green Connor , James Thomas S. 
Published: June 2024

AbstractNormal mode analysis is a Laplace‐transform method for calculating the surface‐loading response of laterally homogeneous spherical Earth models with linear viscoelasticity which delivers modal decay times and amplitudes. It can locally fail owing to numerical singularities arising from the viscoelastic parameters, leading to an incomplete accounting of the surface‐loading response. Collocation methods were developed to circumvent this issue. The mixed collocation method includes least‐squares fitting to the Laplace‐transformed Earth response to determine amplitudes assuming the normal mode decay times are known, while the pure collocation method assumes a series of logarithmically regularly spaced inverse decay times for which amplitudes are determined numerically. Both collocation methods may determine amplitudes that are physically unrealistic and all three methods produce crustal motion predictions that differ significantly. The hybrid normal mode‐collocation method presented here applies the normal mode analysis, and then applies the pure collocation to the resulting residuals. This retains the modal structure, while providing an improved fit. Our implementation avoids numerical singularities that may arise from Rayleigh‐Taylor instabilities occurring at large times and can be automated. Vertical crustal motions predicted by the hybrid method for North America with the ICE‐6G_C loading model and the VM5a viscosity structure have a root mean square (RMS) of 4.49 mm/yr and RMS differences with the normal mode, pure, and mixed collocation method of 0.06, 0.23, and 0.25 mm/yr, respectively. Maximum differences reach 0.20, 0.87, and 0.63 mm/yr. The differences increase for a viscosity profile with a greater viscosity increase with depth that exhibits stronger singularity issues.
Toward a Unified Understanding of Estimating Evapotranspiration: The Linkage Between Three Effective Parsimonious Models
Authors: Wang Yi , Petrone Richard M. , Kompanizare Mazda 
Published: June 2024

AbstractThe maximum information entropy production model (MaxEnt), the relative humidity at equilibrium approach (ETRHEQ), and the Surface Flux Equilibrium model (SFE) are three recently developed models to estimate evapotranspiration. Although the connection between ETRHEQ and SFE is evident, no attempts have been made to investigate the congruence, distinctions, or potential complementarity between the two models and MaxEnt. Our mathematical analysis demonstrates that minimizing the vertical variance of RH in ETRHEQ is equivalent to minimizing the dissipation function of energy fluxes in MaxEnt, under the assumption of the same eddy diffusivity of heat and water vapor and with a specific expression for the ratio between the thermal inertia terms for H and LE. The connection between ETRHEQ, SFE, and MaxEnt is independent of Monin‐Obukhov similarity theory (MOST)’s extremum solution, and MOST's extreme solution can be viewed as equivalent to introducing a constant correction factor to account for atmospheric stability. While ETRHEQ and MaxEnt can be united within a single hydrometeorological framework, they diverge in their approaches to modeling evapotranspiration, particularly in how they address the roles of vegetation and land surface heterogeneity. More importantly, the unified framework suggests that turbulence fluxes within the atmospheric boundary layer adhere to the principles of maximum information entropy production. The way in which dissipation, along with its associated entropy production, is established using information entropy theory deviates from traditional thermodynamic entropy formulations. Exploring the connection between thermodynamic and information entropy and developing proper formulations of dissipation for energy fluxes presents an appealing avenue for prospective research.
Geochemical Signature of Deep Fluids Triggering Earthquake Swarm in the Noto Peninsula, Central Japan
Authors: Umeda Koji , Yamazaki Yukino , Sumino Hirochika 
Published: June 2024

AbstractOn New Year's Day 2024, a magnitude 7.6 event struck the Noto Peninsula in central Japan. Prior to this event, an intense earthquake swarm had persisted beneath the northeastern peninsula for more than five years. Geophysical evidence provides insight into the upwelling of deep fluids from the uppermost mantle that triggers the seismic swarm activity. The noble gases and their isotopes have been used as geochemical indicators to determine the origin of the fluids associated with the swarms and their upwelling. Gas samples collected from boreholes around the seismic source region are characterized by anomalously high 3He/4He ratios (∼3.9 RAcor), indicating infiltration of mantle fluids from the subcrustal lithosphere. Using a steady‐state advection model, we calculated mantle helium fluxes of 1.1–2.4 × 10−15 mol cm−2 a−1, similar to those estimated for other representative fault zones, such as the San Andreas and North Anatolian faults.
Dynamic Component of the Asthenosphere: Lateral Viscosity Variations Due To Dislocation Creep at the Base of Oceanic Plates
Authors: Patočka V. , Čížková H. , Pokorný J. 
Published: June 2024

AbstractThe asthenosphere is commonly defined as an upper mantle zone with low velocities and high attenuation of seismic waves, and high electrical conductivity. These observations are usually explained by the presence of partial melt, or by a sharp contrast in the water content of the upper mantle. Low viscosity asthenosphere is an essential ingredient of functioning plate tectonics. We argue that a substantial component of asthenospheric weakening is dynamic, caused by dislocation creep at the base of tectonic plates. Numerical simulations of subduction show that dynamic weakening scales with the surface velocity both below the subducting and the overriding plate, and that the viscosity decrease reaches up to two orders of magnitude. The resulting scaling law is employed in an apriori estimate of the lateral viscosity variations (LVV) below Earth's oceans. The obtained LVV help in explaining some of the long‐standing as well as recent problems in mantle viscosity inversions.
Investigation and management of young-onset hypertension: British and Irish hypertension society position statement
Authors: Kulkarni Spoorthy , Faconti Luca , Partridge Sarah , Delles Christian , Glover Mark , Lewis Philip , Gray Asha , Hodson Emma , Macintyre Iain , Maniero Carmen , McEniery Carmel M. , Sinha Manish D. , Walsh Stephen B. , Wilkinson Ian B. 
Published: June 2024

AbstractNational and international hypertension guidelines recommend that adults with young-onset hypertension (aged <40 years at diagnosis) are reviewed by a hypertension specialist to exclude secondary causes of hypertension and optimise therapeutic regimens. A recent survey among UK secondary care hypertension specialist physicians highlighted variations in the investigation of such patients. In this position statement, the British and Irish Hypertension Society seek to provide clinicians with a practical approach to the investigation and management of adults with young-onset hypertension. We aim to ensure that individuals receive consistent and high-quality care across the UK and Ireland, to highlight gaps in the current evidence, and to identify important future research questions.
Association between initial ventilation mode and hospital outcomes for severe congenital diaphragmatic hernia
Authors: Wild K. Taylor , Mathew Leny , Ades Anne M. , Rintoul Natalie E. , Soorikian Leane , Matthews Kelle , Lee Sura , Van Hoose K. Taylor , Kesler Erin , Flohr Sabrina , Bostwick Anna , Reynolds Tom , Hedrick Holly L. , Foglia Elizabeth E. 
Published: June 2024

Abstract
Objective
To determine the association between initial delivery room (DR) ventilator (conventional mechanical ventilation [CMV] versus high frequency oscillatory ventilation [HFOV] and hospital outcomes for infants with severe congenital diaphragmatic hernia (CDH).

Study design
Quasi-experimental design before/after introducing a clinical protocol promoting HFOV. The primary outcome was first blood gas parameters. Secondary outcomes included serial blood gas assessments, ECMO, survival, duration of ventilation, and length of hospitalization.

Results
First pH and CO2 were more favorable in the HFOV group (n = 75) than CMV group (n = 85), median (interquartile range (IQR)) pH 7.18 (7.03, 7.24) vs. 7.05 (6.93, 7.17), adjusted p-value < 0.001; median CO2 62.0 (46.0, 82.0) vs 85.9 (59.0, 103.0), adjusted p-value < 0.001. ECMO, survival, duration of ventilation, and length of hospitalization did not differ between groups in adjusted analysis.

Conclusion
Among infants with severe CDH, initial DR HFOV was associated with improved early gas exchange with no adverse differences in hospital outcomes.
Applications of functional neurotransmitter release imaging with genetically encoded sensors in psychiatric research
Authors: Wright Emily C. , Scott Erin , Tian Lin 
Published: June 2024

AbstractPsychiatric research encompasses diverse methodologies to understand the complex interplay between neurochemistry and behavior in mental health disorders. Despite significant advancements in pharmacological interventions, there remains a critical gap in understanding the precise functional changes underlying psychiatric conditions and the mechanisms of action of therapeutic agents. Genetically encoded sensors have emerged as powerful tools to address these challenges by enabling real-time monitoring of neurochemical dynamics in specific neuronal populations. This prospective explores the utility of neurotransmitter binding genetically encoded sensors in uncovering the nature of neuronal dysregulation underpinning mental illness, assessing the impact of pharmaceutical interventions, and facilitating the discovery of novel treatments.
Differential transcriptional invasion signatures from patient derived organoid models define a functional prognostic tool for head and neck cancer
Authors: Haughton Peter D. , Haakma Wisse , Chalkiadakis Theofilos , Breimer Gerben E. , Driehuis Else , Clevers Hans , Willems Stefan , Prekovic Stefan , Derksen Patrick W. B. 
Published: June 2024

AbstractClinical outcome for patients suffering from HPV-negative head and neck squamous cell carcinoma (HNSCC) remains poor. This is mostly due to highly invasive tumors that cause loco-regional relapses after initial therapeutic intervention and metastatic outgrowth. The molecular pathways governing the detrimental invasive growth modes in HNSCC remain however understudied. Here, we have established HNSCC patient derived organoid (PDO) models that recapitulate 3-dimensional invasion in vitro. Single cell mRNA sequencing was applied to study the differences between non-invasive and invasive conditions, and in a collective versus single cell invading PDO model. Differential expression analysis under invasive conditions in Collagen gels reveals an overall upregulation of a YAP-centered transcriptional program, irrespective of the invasion mode. However, we find that collectively invading HNSCC PDO cells show elevated levels of YAP transcription targets when compared to single cell invasion. Also, collectively invading cells are characterized by increased nuclear translocation of YAP within the invasive strands, which coincides with Collagen-I matrix alignment at the invasive front. Using gene set enrichment analysis, we identify immune cell-like migratory pathways in the single cell invading HNSCC PDO, while collective invasion is characterized by overt upregulation of adhesion and migratory pathways. Lastly, based on clinical head and neck cancer cohorts, we demonstrate that the identified collective invasion signature provides a candidate prognostic platform for survival in HNSCC. By uncoupling collective and single cell invasive programs, we have established invasion signatures that may guide new therapeutic options.
Minimum effective dose of clemastine in a mouse model of preterm white matter injury
Authors: Odell Elizabeth P. , Jabassini Nora , Schniedewind Björn , Pease-Raissi Sarah E. , Frymoyer Adam , Christians Uwe , Green Ari J. , Chan Jonah R. , Ostrem Bridget E. L. 
Published: June 2024

Abstract
Background
Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the myelinating cells of the central nervous system. Clemastine was previously shown to induce oligodendrocyte differentiation and myelination in mouse models of PWMI at a dose of 10 mg/kg/day. The minimum effective dose (MED) of clemastine is unknown. Identification of the MED is essential for maximizing safety and efficacy in neonatal clinical trials. We hypothesized that the MED in neonatal mice is lower than 10 mg/kg/day.

Methods
Mouse pups were exposed to normoxia or hypoxia (10% FiO2) from postnatal day 3 (P3) through P10. Vehicle or clemastine at one of four doses (0.5, 2, 7.5 or 10 mg/kg/day) was given to hypoxia-exposed pups. Myelination was assessed at age P14 and 10 weeks to determine the MED. Clemastine pharmacokinetics were evaluated at steady-state on day 8 of treatment.

Results
Clemastine rescued hypoxia-induced hypomyelination with a MED of 7.5 mg/kg/day. Pharmacokinetic analysis of the MED revealed Cmax 44.0 ng/mL, t1/2 4.6 h, and AUC24 280.1 ng*hr/mL.

Conclusions
Based on these results, myelination-promoting exposures should be achievable with oral doses of clemastine in neonates with PWMI.

Impact

Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates.

Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment.

The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials.

We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.
Mechanisms contributing to inhibition of retinal ganglion cell death by cell permeable peptain-1 under glaucomatous stress
Authors: Johnson Gretchen A. , Kodati Bindu , Nahomi Rooban B. , Pham Jennifer H. , Krishnamoorthy Vignesh R. , Phillips Nicole R. , Krishnamoorthy Raghu R. , Nagaraj Ram H. , Stankowska Dorota L. 
Published: June 2024

AbstractThis study assesses the neuroprotective potential of CPP-P1, a conjugate of an anti-apoptotic peptain-1 (P1) and a cell-penetrating peptide (CPP) in in vitro, in vivo, and ex vivo glaucoma models. Primary retinal ganglion cells (RGCs) were subjected to either neurotrophic factor (NF) deprivation for 48 h or endothelin-3 (ET-3) treatment for 24 h and received either CPP-P1 or vehicle. RGC survival was analyzed using a Live/Dead assay. Axotomized human retinal explants were treated with CPP-P1 or vehicle for seven days, stained with RGC marker RBPMS, and RGC survival was analyzed. Brown Norway (BN) rats with elevated intraocular pressure (IOP) received weekly intravitreal injections of CPP-P1 or vehicle for six weeks. RGC function was evaluated using a pattern electroretinogram (PERG). RGC and axonal damage were also assessed. RGCs from ocular hypertensive rats treated with CPP-P1 or vehicle for seven days were isolated for transcriptomic analysis. RGCs subjected to 48 h of NF deprivation were used for qPCR target confirmation. NF deprivation led to a significant loss of RGCs, which was markedly reduced by CPP-P1 treatment. CPP-P1 also decreased ET-3-mediated RGC death. In ex vivo human retinal explants, CPP-P1 decreased RGC loss. IOP elevation resulted in significant RGC loss in mid-peripheral and peripheral retinas compared to that in naive rats, which was significantly reduced by CPP-P1 treatment. PERG amplitude decline in IOP-elevated rats was mitigated by CPP-P1 treatment. Following IOP elevation in BN rats, the transcriptomic analysis showed over 6,000 differentially expressed genes in the CPP-P1 group compared to the vehicle-treated group. Upregulated pathways included CREB signaling and synaptogenesis. A significant increase in Creb1 mRNA and elevated phosphorylated Creb were observed in CPP-P1-treated RGCs. Our study showed that CPP-P1 is neuroprotective through CREB signaling enhancement in several settings that mimic glaucomatous conditions. The findings from this study are significant as they address the pressing need for the development of efficacious therapeutic strategies to maintain RGC viability and functionality associated with glaucoma.
A panoptic segmentation dataset and deep-learning approach for explainable scoring of tumor-infiltrating lymphocytes
Authors: Liu Shangke , Amgad Mohamed , More Deeptej , Rathore Muhammad A. , Salgado Roberto , Cooper Lee A. D. 
Published: June 2024

AbstractTumor-Infiltrating Lymphocytes (TILs) have strong prognostic and predictive value in breast cancer, but their visual assessment is subjective. To improve reproducibility, the International Immuno-oncology Working Group recently released recommendations for the computational assessment of TILs that build on visual scoring guidelines. However, existing resources do not adequately address these recommendations due to the lack of annotation datasets that enable joint, panoptic segmentation of tissue regions and cells. Moreover, existing deep-learning methods focus entirely on either tissue segmentation or cell nuclei detection, which complicates the process of TILs assessment by necessitating the use of multiple models and reconciling inconsistent predictions. We introduce PanopTILs, a region and cell-level annotation dataset containing 814,886 nuclei from 151 patients, openly accessible at: sites.google.com/view/panoptils. Using PanopTILs we developed MuTILs, a neural network optimized for assessing TILs in accordance with clinical recommendations. MuTILs is a concept bottleneck model designed to be interpretable and to encourage sensible predictions at multiple resolutions. Using a rigorous internal-external cross-validation procedure, MuTILs achieves an AUROC of 0.93 for lymphocyte detection and a DICE coefficient of 0.81 for tumor-associated stroma segmentation. Our computational score closely matched visual scores from 2 pathologists (Spearman R = 0.58–0.61, p < 0.001). Moreover, computational TILs scores had a higher prognostic value than visual scores, independent of TNM stage and patient age. In conclusion, we introduce a comprehensive open data resource and a modeling approach for detailed mapping of the breast tumor microenvironment.
Resilience of anodic biofilm in microbial fuel cell biosensor for BOD monitoring of urban wastewater
Authors: Salvian Anna , Farkas Daniel , Ramirez-Moreno Marina , Torruella-Salas Daniela , Berná Antonio , Avignone-Rossa Claudio , Varcoe John R. , Esteve-Núñez Abraham , Gadkari Siddharth 
Published: June 2024

AbstractEfficient wastewater treatment monitoring is vital for addressing water scarcity. Microbial fuel cells (MFCs) have emerged as real-time biosensors for biochemical oxygen demand (BOD) in urban wastewater. Discrepancies in signal generation may arise due to changes in the composition and metabolism of mixed-culture electroactive biofilms stemming from different wastewater compositions. In this study, 3D-printed MFC-based biosensors were employed to assess the BOD of sterile complex artificial wastewater and untreated urban wastewater. Alterations in the microbial composition of the anode were evaluated using 16S rRNA sequencing and metagenomics analysis. Results show that MFC-based biosensors can be effectively recalibrated for diverse types of wastewater, maintaining consistent sensitivity (0.64 ± 0.10 mA L mg−1 m−2 with synthetic wastewater and 0.78 ± 0.13 mA L mg−1 m−2 with urban wastewater) and limit of detection (49 ± 8 mg L−1 for synthetic wastewater and 44 ± 7 mg L−1 for urban wastewater). Crucially, pre-sterilization, conductivity adjustments, and nitrogen purging of wastewater are not required before its introduction into the biosensor. However, the presence of native aerobic microorganisms in the wastewater might affect the current output. Metagenomics and taxonomic analyses revealed that the alterations in biofilm composition are predominantly in response to the varied chemical and microbiological compositions of different substrates. Despite variations in anodic biofilm composition, the MFC-based biosensor maintains a relative error comparable to the standard BOD test. This highlights the resilience and flexibility of the biosensor when directly used with a variety of wastewater types before full biofilm adjustment.