bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenomenological experience of a negative event when an older self is imagined
Authors: Özdemir Haksever Nilay , Ikier Simay
Published: February 2025

When individuals become older, they sometimes interpret their autobiographical memories in perspective and remember them more positively. In the present study, we investigated whether simulating an autobiographical memory as if an older individual experienced it would change its phenomenological experience. In the first session of the experiment, young participants retrieved and phenomenologically rated an important negative event (original memory). One week later, in the second session, half of the participants simulated themselves as older (older-self condition) and the other half simulated another older individual (older-other condition) and imagined that this simulated individual experienced the event at the same age that they did (simulated memory). They provided the same phenomenological experience ratings for the simulated memory. Lastly, they rated the original memory once more as their current selves (post-simulation memory) on the same scales. The positivity of the memories was higher in the older-self condition than in the older-other condition. Compared to the original memory, participants experienced reduced negative affect for the simulated memory, which remained for the post-simulation memory. The simulated memory was less likely to be viewed from a field perspective and it revealed lower vividness and reliving ratings than the original and post-simulation memory. The emotional intensity of the simulated memory was lower than the original memory, but the intensity of the original and the post-simulation memory did not differ. The present study highlights the strong relationship between self and memory, showing how age-related distancing from the current self can be reflected in the phenomenological experience of memories.
Estimating relative uncertainty of geological 3D models with low density of input data in geologically complex regions
Authors: Staněk František , Franěk Jan , Jelínek Jan , Žáček Vladimír
Published: February 2025

This paper addresses uncertainty quantification in manually created 3D geological models of complex regions with sparse data, crucial for e.g. safety and exploration planning. Current models lack such assessments, which is particularly problematic for non-expert stakeholders. The Czech Geological Survey (CGS) developed a workflow to evaluate and visualize uncertainty in such models. Unlike models of geologically simpler areas with rich input data, these models based on sparse input data are created manually and rely on specific model-based interpretations that assume certain tectonic regime or deformation style known from a broader region and from field studies of rock outcrops. The classic uncertainty calculation based on the comparison of a range of (semi-) automatically created models cannot be employed for manually-created stand-alone geological models, and no suitable methodology has yet been determined for such cases. The methodology presented by the CGS considers three sources of uncertainty: the local lithological complexity, the distance to faults, and the so-called general uncertainty - a coefficient that increases with depth. The resulting uncertainty, normalized to the interval < 0;1>, is then reduced in the vicinity of available input data sources (boreholes, geological/geophysical profiles, etc.). The result comprises a 3D grid of the relative uncertainty of the given geological model, which can then be imported into the 3D software tools available to the users of the respective geological model. Demonstrated on the Čertovka site, a potential deep geological repository of high-level radioactive waste, the resulting uncertainty 3D grid guides users in understanding model limitations and can guide subsequent geological explorations.
Carbonate and Nutrient Dynamics in a Mississippi River Influenced Eutrophic Estuary
Authors: He Songjie , Gordon Sean , Maiti Kanchan
Published: February 2025

There is limited information on how the nutrient and freshwater input affects water column carbonate chemistry in the estuaries along the northern Gulf of Mexico. In this study, we assess the seasonal and spatial variability in carbonate chemistry in the Barataria Basin, a eutrophic estuary adjacent to the mouth of the Mississippi River. Eleven stations were sampled along a salinity gradient during the winter (January), spring (April), summer (July), and fall (October) of 2021. Surface and bottom water samples were collected for the analyses of dissolved inorganic carbon (DIC); total alkalinity (TA); and nitrite plus nitrate (NO2 + NO3), phosphate (PO4), and dissolved silica (SiO4). Dissolved CO2 (pCO2) was measured in the surface water. Seasonal surface DIC and TA values ranged from 1553 to 2582 μmol kg−1 and 1217 to 2217 μmol kg−1, respectively. DIC and TA varied seasonally and showed an increasing trend from fresh stations to saline stations. The highest DIC and TA values were observed during the fall season, likely due to the increased contribution of DIC and TA from adjacent marshes as a result of enhanced porewater exchange. In contrast to DIC and TA, pCO2 decreased with the increase of salinity. The seasonal and spatial patterns in carbonate chemistry could not be explained solely by physical mixing and reflected complex interactions between biogeochemical processes driven by nutrient supply and temperature as well as tidal flushing and material exchanges with adjacent marshes.
Solving the puzzle of neanderthal occupations: a reassessment of temporal indicators of occupation duration
Authors: Lubrano Valentina , Rufà Anna , Blasco Ruth , Rivals Florent , Rosell Jordi
Published: February 2025

The identification of the duration of Neanderthal occupations is a tricky topic by the palimpsest nature of archaeological assemblages. This study explores the challenges associated with distinguishing between long and short-term occupations, using qualitative and quantitative data from relevant archaeological sites in the Late Middle Palaeolithic in Spain and south-eastern France. We highlight the proposed occupation models and their specific characteristics, considering the heterogeneity of archaeological evidence and the limitations of current methodologies. The article offers a reassessment of the topic, critically analysing the current indicators used to determine the duration of Neanderthal occupations. Furthermore, we discuss the complexity in defining the concepts of short and long-term occupation, emphasising the need for a multidisciplinary approach to fully understand the complexity of the practices of the Late Neanderthals.
Effect of Biochar Addition in Two Different Phases of the Co-Composting of Green Waste and Food Waste: An Analysis of the Process, Product Quality and Microbial Community
Authors: Oviedo-Ocaña Edgar Ricardo , Soto-Paz Jonathan , Parra-Orobio Brayan Alexis , Zafra Germán , Maeda Toshinari , Galezo-Suárez Andrea Carolina , Diaz-Larotta Judy Tatiana , Sanchez-Torres Viviana
Published: February 2025

Green waste (GW) contains lignocellulosic substances that are resistant to degradation and prolong the composting process. Different strategies have been used to improve GW composting, including adding co-substrates and additives like food waste (FW) and biochar (Bc). FW offers advantages such as its constant availability in MSW streams, its high content of readily degradable organic matter, and its contribution of essential nutrients like nitrogen and potassium. On the other hand, Bc is incorporated at the beginning of the process. However, the effect of its addition in the phase of greatest biological activity has not been studied. This article compares the effect on the process, product quality, and the compost microbial community of adding 2% Bc in two different phases of the co-composting GW with food waste (FW). Two treatments were evaluated using the same mixture of substrates (wet/ weight) (i.e., 48%GW + 35%FW + 13%Sawdust + 2% Phosphate Rock + 2%Bc), but Bc was added in the mesophilic phase for T1 and the thermophilic phase for T2. With the addition of Bc at the mesophilic phase, higher temperatures were reached in the thermophilic phase, with a maximum temperature of 52.5 °C for T1 and 47.7 °C for T2. T1 final product had higher nutrient content (i.e., 28.30% TOC, 1.91% TN, and 4.69% TP in T1 compared to 15.80% TOC, 1.14% TN, and 4.29% TP in T2) and achieved a higher fertility index. Streptomyces and Nonomuraea were more abundant in T1 than T2, while Rhizobium, Roseiflexus, and Chloroflexus were significantly more abundant in T2 than in T1. These results suggest that T1 presents a microbial community that is more robust in degrading complex organic materials. This article demonstrated increased biological activity, lignocellulosic degradation, and nutrient content in the product when biochar is added from the beginning of the process.
Computational Study of Simultaneous Memristive Effect and Biosensing for Prostate-Specific Antigen Detection
Authors: Chen Junrui , Carrara Sandro
Published: February 2025

Over the past decade, memristive biosensors have demonstrated remarkable capabilities in biological detection. However, a notable limitation has been the loss of the memristive effect during biosensing operations. In this study, we introduce a memristive biosensor that successfully integrates resistive switching behavior with biosensing functionality, for the detection of Prostate-Specific Antigen (PSA). The proposed device incorporates dual Schottky contacts and stacked Silicon Nanowires (SiNWs), which act as biomolecule binding sites. Upon bio-functionalization, a distinct voltage difference-termed the Voltage Gap (Vg)-emerges between current minima during forward and backward voltage sweeps in Current–Voltage (I-V) characteristics, serving as a reliable indicator of target molecule binding. Crucially, the device retains its resistive switching properties even during molecular sensing, addressing a key challenge in existing designs. To explain the electrical behavior of this dual-functional memristive biosensor, we developed a capacitively coupled memristive model. The close alignment of simulation results with experimental data provides valuable insights for optimizing the design and performance of memristive biosensors. These advancements highlight the device’s potential for a wide range of biomedical applications, aiming to investigate the feasibility of simultaneously integrating biosensing and memristive switching, thereby paving the way for advanced applications such as in-sensor computing and in-memory sensing.
Anti-tumor potential of Harmine and its derivatives: recent trends and advancements
Authors: Joshi Hemant , Bhushan Sakshi , Dimri Tanisha , Sharma Deepak , Sak Katrin , Chauhan Abhishek , Chauhan Ritu , Haque Shafiul , Ahmad Faraz , Kumar Manoj , Tuli Hardeep Singh , Kaur Damandeep
Published: February 2025

Harmine is a β-carboline alkaloid derived from Peganum harmala, showing a solid antitumor potential in different types of human cancer cells. Unfortunately, the clinical application of this natural alkaloid has been impeded till now by severe toxic side effects, especially neurotoxicity, besides its poor water solubility. Therefore, over the recent years, several semisynthetic derivatives of harmine have been prepared and studied concerning their abilities to inhibit tumor cell proliferation, survival, angiogenesis, migration, and invasion in diverse preclinical models. This review article summarizes the anticancer effects of harmine and its synthetic derivatives, demonstrating their high potential to be developed as novel anticancer drugs to supplement our current therapeutic arsenal in the fight against the globally increasing rate of malignant disorders.
Lower estimate of blow-up time and blow-up rate for non-local curvature flows for plane curves
Authors: Nagasawa Takeyuki
Published: February 2025

This study examines several non-local curvature flows for plane curves with general rotation number. The flows investigated here are the area-preserving flow, the length-preserving flow, and the gradient flow of isoperimetric deficit. In a previous study, sufficient conditions for finite-time blow-up have been presented, and an upper bound for the blow-up time have been proposed. Here, we give estimates for solutions including at least two important applications. First, a lower bound for the blow-up time for the blow-up solutions is derived. Second, our estimate improves the blow-up rate of the blow-up solutions.
Load monitoring of a helicopter inceptor through efficient FBG sensors placement
Authors: Ballarin Pietro , Marchesoli Davide , Zanet Davide Pio Loco , Rigamonti Daniela , Zanoni Andrea
Published: February 2025

The implementation of fly-by-wire technologies on rotorcraft requires the knowledge of the loads exerted by the pilot on the command chain during the flight; however, it is not easy to retrieve such information. In this work, a novel composite sensorized helicopter inceptor is developed aimed at monitoring the loads applied by the pilot during the flight for the entire helicopter lifecycle. The inceptor is produced using a soluble mandrel, and the connection elements are produced in polymeric material, allowing the connection of the optical fiber carrying the fiber Bragg grating (FBG) sensors to the interrogation system. Two prototypes of inceptor are manufactured, the first is produced with the aim to calibrate the Finite Element (FE) model of the component. Then the model is exploited to perform a sensor placement optimization based on the minimization of the condition number of the system using a Genetic Algorithm. The second prototype is produced positioning the FBG sensors according to the output of the optimization. Results show that a satisfactory load identification capability is obtained using only two sensors positioned according to the optimization technique. A comparison is also performed using the first prototype equipped with four strain gauges positioned using qualitative criteria: results show that a better load identification quality is obtained with only two sensors positioned according to the placement optimization technique. This work demonstrates the feasibility of a composite sensorized helicopter inceptor, characterized by a complex geometry, capable to provide satisfactory load identification quality with a limited number of sensors.
Microbiological diversity among patients with Lemierre syndrome and clinical implications: an individual patient-level analysis
Authors: Frehner Maurus , Fumagalli Riccardo M. , Brugger Silvio D. , Cardi Silvia , Catalani Filippo , Trinchero Alice , Pecci Alessandro , Kucher Nils , Valerio Luca , Barco Stefano
Published: February 2025

Purpose

Lemierre syndrome is a rare condition traditionally defined by bacterial infection of the head/neck region, local thrombophlebitis, and septic embolism. Although in most cases Fusobacterium necrophorum is isolated, it is questionable whether the presence of this microbe is mandatory for diagnosis. In this study, we investigated microorganisms isolated in cases of Lemierre syndrome and their association with demographical and clinical features.

Methods

We conducted an analysis of individual patient data from 712 patients diagnosed with Lemierre syndrome. Demographics, clinical presentation, treatment strategies, and outcomes according to different pathogens were evaluated.

Results

Among a total of 712 patients, in 574 cases bacterial growth was detected. In 415 patients Fusobacterium spp. was isolated, in 108 either Streptococcus spp. or Staphylococcus spp., and in 51 other bacteria. Patients with different bacteria differed markedly in age, site of preceding infections, clinical presentation, and treatment. Fusobacterium spp. was typically isolated in younger patients (69% of patients aged 16 to 30 years) while Streptococcus spp. and Staphylococcus spp. were more prevalent in older subjects (30% of patients aged over 45 years). Of all cases with Fusobacterium spp., 63% had a thrombosis of the internal jugular vein and 91% septic embolism, compared with 94% and 69%, respectively, in cases with Streptococcus spp. or Staphylococcus spp.

Conclusion

In contrast to the available literature, our study suggests that Lemierre syndrome may be caused by multiple bacterial species, and that the clinical presentation and course may vary according to the specific bacterial species involved.
Evaluation of fluid status in patients with acromegaly through bioelectrical impedance vector analysis: a cross-sectional study
Authors: Varaldo Emanuele , Prencipe Nunzia , Berton Alessandro Maria , Cuboni Daniela , Aversa Luigi Simone , Sibilla Michela , Mocellini Francesca , Bioletto Fabio , Ghigo Ezio , Gasco Valentina , Grottoli Silvia
Published: February 2025

Purpose

The acromegalic state is associated with an increase in total body water and sodium. The aim of our study was to assess the hydration status of patients with acromegaly using bioimpedance vector analysis (BIVA), differentiating patients according to their disease status (active, medically controlled or cured) and to compare the confidence and tolerance ellipses of BIVA in those patients in relation to a reference healthy population.

Methods

We analyzed data from 73 consecutive patients aged 18 years or older, diagnosed with acromegaly and undergoing regular follow-up at our Division for whom a BIVA analysis was available. Patients were evaluated through BIVA and insulin-like growth factor I (IGF-I), growth hormone (GH), serum sodium and potassium, creatinine, glucose, HbA1c and plasma and urine osmolality were collected. Exclusion criteria were concurrent presence of arginine-vasopressin deficiency, dysnatremia or the presence of pathologies known to significantly alter the extracellular fluid.

Results

Sixty-nine patients (M/F 34/35, age 60 ± 14 years) were enrolled in the study. As expected, patients with active disease (n = 22) presented higher IGF-I and GH levels compared to other subjects. Patients with controlled disease (n = 33) were significantly older than other individuals (p = 0.028 vs. active disease, p = 0.024 vs. cured disease). Compared to a reference healthy population, patients with either active or medically controlled disease showed significant fluid overload (p < 0.0001 for both males and females) and BIVA confidence analysis demonstrated that there were no significant differences in hydration status between the two groups (p = 0.363). On the other hand, patients with cured disease (n = 14) showed reduced hydration status compared to patients with active disease (p = 0.016), although no difference was observed compared to patients with controlled disease (p = 0.308).

Conclusion

The results of our study demonstrate that patients with either active or medically controlled acromegaly present a significant overhydration compared to a healthy reference population and that alterations in body water content usually improve in individuals with cured disease.
Fire-weather conditions during two fires in Southern Portugal: Meteorology, Orography, and Fuel Characteristics
Authors: Purificação Carolina , Santos Filippe L. M. , Henkes Alice , Kartsios Stergios , Couto Flavio Tiago
Published: February 2025

The interactions between meteorology, orography and fuel have a major impact on fire dynamics, influencing its behaviour. This study presents the results about the atmospheric environment and surface aspects of two wildfires that occurred in Southern Portugal. Two numerical simulations were performed by the Meso-NH atmospheric model using a two-way nested domain configuration with horizontal resolutions of 2500 m and 500 m, respectively. Furthermore, observations of land use/land cover and live fuel moisture content analysis for each wildfire were used to understand the land occupation and vegetation dynamics. Both cases present significant fuel variability with low live fuel moisture content, showing high probability of fire occurrence over the region. The analysis of Castro Marim’s fire with ignition during the nighttime, presented critical fire weather conditions, namely high air temperatures and low relative humidity, even overnight. Furthermore, the interaction of the northerly flow with the local terrain led to the spread of the fire to southeast and south westward. In the second case study, Odemira’s fire exhibited a complex environment marked by continual shifts in wind direction. However, the study highlights the strong southeasterly flow prevailing from the Gibraltar Strait reaching the Algarve region and producing intense winds in the local mountains. Algarve region contains forest species such as maritime pine and eucalyptus in large variations of altitude that are highly susceptible to the occurrence of wildfires if the forests are not adequately manage, significantly threatening the safety of front-line firefighters. In a regional context, the present study shows that the use of atmospheric modelling can be useful in assessing fire risk when also the surface aspects obtained from remote sensing observations are considered.
Animal Bodies and Futures: Rethinking Ethical Implications of Cultivated Meat and Fish
Authors: Ferrari Arianna
Published: February 2025

This paper critically examines the ethical discourse surrounding cultivated meat and fish, arguing that it has largely remained confined to theoretical or speculative discussions, neglecting the practical and evolving implications of this emerging technology—particularly in relation to the continued involvement of animals in its production. I demonstrate that a significant gap exists in the assessment of the impact on animal bodies during cell harvesting and cultivation, leading to a distorted or incomplete understanding of the normative dimensions of this innovation. The paper further addresses the often-overlooked issue of “animal futures,” particularly the treatment of animals post-biopsy, and the ethical concerns surrounding the breeding of animals specifically for stem cell production. It critiques the lack of foresight in current ethical discussions, which fail to adequately consider the long-term lives of animals involved in the production of cultivated meat. Advocating for a more comprehensive ethical framework, the paper calls for a deeper, more nuanced consideration of both the immediate and future welfare of these animals. In doing so, the paper stresses that ethical reflection should not be an afterthought but an integral part of technological development—one that must influence both its design and its evolution. Through this analysis, the paper aims to contribute meaningfully to the ongoing discourse on the ethics of cultivated meat, urging a rethinking of the relationship between technological progress and animal welfare and rights.
Evaluating ChatGPT’s Accuracy and Helpfulness in Gastroesophageal Reflux Disease Queries Compared to Traditional Search Engines: A New Era of Health Information Retrieval
Authors: Lahoud Chloe , Tawfik Mark , Di Pietro Gaetano , Andrawes Sherif
Published: February 2025

The use of Artificial Intelligence (AI) is exponentially growing across medical specialties, offering numerous advantages over traditional search engines. This manuscript aims to fill this gap by evaluating the performance of the AI system ChatGPT in the context of Gastroesophageal Reflux Disease (GERD) related queries compared to traditional search engine responses. We compared the AI system ChatGPT 3.5 with the traditional search engine Google. Six standardized queries on GERD topics (definition, risk factors, diagnosis, symptoms, and management) were generated using Google’s auto-completions. Responses from ChatGPT 3.5 and Google were evaluated for accuracy and helpfulness using a five-point Likert scale by three independent gastroenterology experts. Statistical analysis was performed using Python. For accuracy, ChatGPT received average ratings of 5, 4.67, and 4.67, while traditional search engines scored 4.83, 4.33, and 3.33 (p-values 0.363, 0.105, 0.001). For helpfulness, ChatGPT was rated 5, 4.67, and 4.83, compared to 4.33, 4, and 3.33 for traditional search engines (p-values 0.012, 0.025, 0.004). Evaluator 3 found ChatGPT significantly more accurate, while evaluators 1 and 2 saw no significant difference. All three evaluators rated ChatGPT as significantly more helpful. Overall, ChatGPT received higher ratings for both accuracy and helpfulness. This study demonstrates that AI systems like ChatGPT 3.5 provide more accurate and useful information on GERD than traditional search engines like Google. AI can enhance patient education and decision-making, though further research is needed to confirm its reliability across other topics.
Molecular mechanisms of Mmd2 gene in regulating growth of the Pacific white shrimp Litopenaeus vannamei
Authors: Si Shuqing , Zhang Xiaojun , Yu Yang , Zhong Xiaoyun , Zhang Xiaoxi , Yuan Jianbo , Chu Ka Hou , Li Fuhua
Published: February 2025

Growth of the Pacific white shrimp Litopenaeus vannamei, the most important farmed crustacean, has consistently been a focal point for breeders. Over the past decades, some candidate genes for shrimp growth have been identified. However, further research is needed to elucidate the molecular regulatory mechanism of these genes. LvMmd2 was previously identified as a candidate gene that may inhibit the growth of L. vannamei. In this study, we analyzed the genotype and expression of the LvMmd2 gene in a breeding family and indicated its role as a growth-inhibiting gene. We found that LvMmd2 co-localized with its homolog LvPAQR3 at the Golgi apparatus. Using co-immunoprecipitation (Co-IP) and DUAL membrane system yeast two-hybrid (MbY2H), we indicated the interactions between LvMmd2 and LvPAQR3, LvPAQR3 and LvRaf1, as well as LvMmd2 and LvRho. These results suggest that LvMmd2 directly and indirectly regulates the Ras signaling pathway. Furthermore, we show that the LvMmd2 gene may indirectly affect the PI3K/AKT, insulin, and Hippo signaling pathways to regulate cell proliferation and differentiation via LvPAQR3 and LvRaf1. Through transcriptome and MbY2H analyses, we have also revealed the interaction between LvMmd2 and proteins involved in growth, immunity, protein transport, synthesis, and modification. These findings demonstrate the various molecular pathways through which LvMmd2 regulates L. vannamei growth. This study provides insights into the mechanism of shrimp growth regulated by Mmd2, enhances our understanding of LvMmd2 function, and highlights its potential application in shrimp breeding.
Young infants’ exposure to parabens: lotion use as a potential source of exposure
Authors: Boxer Elizabeth , Zhong Yilin , Levasseur Jessica , Stapleton Heather M. , Hoffman Kate
Published: February 2025

Background

Parabens are widely used as antimicrobials in personal care products and pharmaceuticals. While previous studies demonstrate paraben exposure is ubiquitous, data investigating infants’ exposure is limited.

Objective

We sought to characterize infants’ exposure to parabens and identify factors associated with higher levels of exposure.

Methods

Families enrolled in the CHildren’s Immune ResPonse Study between 2016-2018. Parents completed questionnaires, providing information on demographics and lifestyle factors. Urine samples were collected when infants were 1 to 3 months old (n = 71) and 12 months old (n = 29), with 18 infants evaluated at both ages. Parabens were measured in urine samples using liquid chromatography tandem mass spectrometry and served as an indicator of exposure.

Results

Methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were detected in >70% of urine samples, and concentrations ranged several orders of magnitude (specific-gravity-corrected medians: MP = 25.4 PP = 3.55; EP = 0.90 ng/mL). Butylparaben was detected less frequently (<50%). Paraben concentrations were lower than those reported for older children and adults; however, we did not find statistically significant differences in paraben concentrations by infant age. Correlations between measurements taken over time were poor, suggesting paraben exposure is variable, and multiple measurements are needed to capture cumulative exposure information. We observed differences in exposure by race/ethnicity and socioeconomic status; non-White infants and infants whose parents completed less education had higher paraben exposure. Recent lotion usage strongly predicted paraben exposure in 1–3-month-olds. For example, infants using lotion in the past seven days had urinary MP concentrations 355% higher than infants without lotion usage (eß = 4.55, 95% Confidence Interval = 1.68, 12.55, p < 0.001). Together, our results suggest infants are ubiquitously exposed to parabens and personal care product use may be an important source of exposure.

Impact

To the best of our knowledge, this is the first paper to report paraben levels and evaluate predictors of exposure in infants. This study supports the hypothesis that universal exposure to parabens extends to infants, as indicated by urinary biomarker concentrations. Of the predictors evaluated, lotion use in the last seven days was the strongest predictor of exposure in 1-3-month-olds. Given infant paraben levels are strongly correlated to lotion use, there may be an opportunity for parents to reduce paraben exposure by limiting its application or consulting ingredient labels to ensure no parabens are present.
REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression
Authors: Kheirkhah Mina , Duncan Wallace C. , Yuan Qiaoping , Wang Philip R. , Jamalabadi Hamidreza , Leistritz Lutz , Walter Martin , Goldman David , Zarate Carlos A. , Hejazi Nadia S.
Published: February 2025

Abnormalities during rapid eye movement (REM) sleep contribute to the pathophysiology of major depressive disorder (MDD), but few studies have explored the relationship between REM sleep and treatment-resistant depression (TRD). In MDD, REM sleep abnormalities often manifest as alterations in total night REM Density (RD), RD in the first REM period (RD1), and REM Latency (RL). Among these, RD1 is notably considered a potential endophenotype of depression. This study compared REM sleep markers between 63 drug-free individuals with TRD (39 F/24 M) and 41 healthy volunteers (25 F/16 M). It also investigated the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on these REM sleep variables. Specifically, the study investigated whether RD1 could predict antidepressant response to ketamine. TRD participants showed higher RD1 and shorter RL at baseline compared to HVs, as assessed via non-parametric tests, but Total Night RD did not differ between the two groups. Ketamine treatment decreased RD1 in TRD participants but did not affect Total Night RD or RL. As assessed via the Support Vector Machine (SVM) algorithm, baseline RD1 level moderately predicted antidepressant response to ketamine versus non-response (area under the receiver operating characteristic (ROC) curve (AUC) = 0.73, with a median accuracy of 0.75), wherein TRD participants with higher baseline RD1 were more likely to respond to ketamine. These results underscore the utility of RD1 for identifying individuals most likely to benefit from ketamine treatment, enabling more targeted and effective therapeutic strategies. Clinical Trials Identifier: NCT00088699, NCT01204918.
Nucleolar NOL9 regulated by DNA methylation promotes hepatocellular carcinoma growth through activation of Wnt/β-catenin signaling pathway
Authors: Chen Xiyao , Song Xin , Zheng Xingrong , Qian Tinglin , Zhang Boxiang , Wu Lina , Lian Qinghai , Chen Jia , Luo Qiumin , Xu Wenxiong , Peng Liang , Xie Chan
Published: February 2025

Ribosome biogenesis (RiboSis) and ribosomal stress are critical in tumor progression, positioning RiboSis as a promising therapeutic target for cancer treatment and for overcoming drug resistance. In this study, we examined the role of RiboSis in the progression from hepatitis B virus (HBV) infection to HBV-related hepatocellular carcinoma (HCC), focusing specifically on nucleolar protein 9 (NOL9) and its influence on HCC pathogenesis and therapeutic response. Our findings showed that NOL9 was significantly upregulated in HCC tissues, correlating with larger tumor sizes and more advanced pathological grades. High levels of NOL9 expression were associated with unfavorable prognosis in both the TCGA-LIHC and our HCC cohorts. Functional assays indicated that NOL9 regulated HCC cell proliferation and apoptosis; specifically, NOL9 knockdown inhibited cell proliferation and promoted apoptosis, while overexpression enhanced these processes. In vivo studies confirmed that NOL9 depletion reduced tumor growth. Mechanistically, NOL9 expression was regulated by DNA methylation and the transcription factor ZNF384. Our DNA methylation analysis revealed an inverse correlation between NOL9 expression and methylation at specific CpG sites, implicating DNMT1 in its epigenetic regulation. Additionally, NOL9-mediated cell proliferation was dependent on activation of the Wnt/β-catenin signaling pathway. This study highlights the multifaceted role of NOL9 in HCC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target.
The integrated stress response engages a cell-autonomous, ligand-independent, DR5-driven apoptosis switch
Authors: Zappa Francesca , Muniozguren Nerea L. , Conrad Julia E. , Acosta-Alvear Diego
Published: February 2025

The integrated stress response (ISR) is a fundamental signaling network that leverages the cell’s biosynthetic capacity against different stresses to restore homeostasis. However, when homeostasis is unattainable, the ISR switches to drive cell death and eliminate irreparably damaged cells. Previous work has shown that persistent activity of the ISR kinase PERK during unyielding endoplasmic reticulum (ER) stress induces apoptosis downstream of death receptor 5 (DR5) [1]. ER stress provides activating signals that engage the ectodomain (ED) of DR5 to drive its unconventional activation in the Golgi apparatus [1, 2]. Here, using chemical genetics to uncouple stress sensing from ISR activation, we found that DR5 signaling from the Golgi apparatus is integral to the ISR and not specific to ER stress. Furthermore, we show that DR5 activation can be driven solely by increased expression and does not require its ED. These findings indicate that a general ISR kill switch eliminates irreversibly injured cells.
CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells
Authors: Khamidullina Alvina I. , Yastrebova Margarita A. , Bruter Alexandra V. , Nuzhina Julia V. , Vorobyeva Nadezhda E. , Khrustaleva Anastasia M. , Varlamova Ekaterina A. , Tyakht Alexander V. , Abramenko Iaroslav E. , Ivanova Ekaterina S. , Zamkova Maria A. , Li Jing , Lim Chang-Uk , Chen Mengqian , Broude Eugenia V. , Roninson Igor B. , Shtil Alexander A. , Tatarskiy Victor V.
Published: February 2025

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment. However, activation of circumventing signaling pathways and quiescence may limit BCR-ABLi efficacy. CDK8/19 Mediator kinases have been implicated in the emergence of non-genetic drug resistance. Dissecting the effects of pharmacological CDK8/19 inhibition on CML survival in response to BCR-ABLi, we found that a selective, non-toxic CDK8/19 inhibitor (CDK8/19i) Senexin B (SenB) and other CDK8/19i sensitized K562 cells to different BCR-ABLi via attenuation of cell cycle arrest. In particular, SenB prevented IM-induced upregulation of genes that negatively regulate cell cycle progression. SenB also antagonized IM-activated p27Kip1 elevation thereby diminishing the population of G1-arrested cells. After transient G1 arrest, cells treated with IM + SenB re-entered the S phase, where they were halted and underwent replicative stress. Consequently, the combination of IM and SenB intensified apoptotic cell death, measured by activation of caspase 9 and 3, subsequent cleavage of poly(ADPriboso)polymerase 1, positive Annexin V staining and increase of subG1 fraction. In contrast, IM-treated BCR-ABL-positive KU812 CML cells, which did not induce p27Kip1, readily died regardless of SenB treatment. Thus, CDK8/19i prevent the quiescence-mediated escape from BCR-ABLi-induced apoptosis, suggesting a strategy for avoiding the CML relapse.
Prescribing carbonic anhydrase inhibitors to patients with “sulfa” antibiotics allergy: do we dare?
Authors: Quintanilla Raquel , van Leeuwen Luke , Sharma Arjun , Chang Ta Chen , Hodapp Elizabeth , McSoley John , Grajewski Alana , Bitrian Elena
Published: February 2025

Objective

To evaluate if provider characteristics affect attitude toward carbonic anhydrase inhibitors (CAI) prescription for patients with history of sulfonamide antibiotic (SA) hypersensitivity.

Methods

A survey querying providers’ attitudes toward CAI prescription in hypothetical patients with prior SA hypersensitivity was distributed to four ophthalmology and optometry organizations. Logistic regression was used to assess the relationship between avoiding CAI and profession, specialty, organizational affiliation, and years in practice.

Results

Of 250 respondents, 27% and 52% would avoid topical and oral CAI, respectively, in patients with prior SA rash and/or urticaria. >90% would avoid oral CAI in patients with prior severe SA hypersensitivity. Respondents with >10 years in practice were more likely to avoid oral CAI in patients with prior SA rash and/or urticaria than those with ≤10 (OR 2.27, p = 0.002). Respondents affiliated with non-glaucoma organizations were more likely to avoid oral CAI in patients with prior SA rash and/or urticaria than those affiliated with glaucoma organizations (p = 0.03). Providers without glaucoma training were more likely to avoid topical CAI in patients with prior SA rash and/or urticaria (p = 0.004) and anaphylaxis (p = 0.01) than glaucoma-trained providers.

Conclusions

Despite no supporting evidence, a significant number of respondents would avoid CAI in patients with prior SA hypersensitivity. Respondents without glaucoma training, no affiliation with a glaucoma organization, and >10 years in practice are more likely to avoid CAI in patients with type I SA hypersensitivity. Providers should be informed of the low cross-reactivity risk between CAI and SA so more patients may benefit from these drugs.
A systematic review of determinants of breast cancer risk among women with benign breast disease
Authors: Burke Aileen , O’Driscoll Jessica , Abubakar Mustapha , Bennett Kathleen E. , Carmody Emma , Flanagan Fidelma , Gierach Gretchen L. , Mullooly Maeve
Published: February 2025

Benign breast disease (BBD) is associated with heterogeneous breast cancer risk. Identifying key breast cancer risk factors for this population may inform breast cancer prevention or early detection strategies. We systematically searched literature databases PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify studies reporting associations of demographic, lifestyle, reproductive, and radiological factors with risk of breast cancer among women with biopsy-confirmed BBD. 67 studies met eligibility criteria. Variation was observed for study time period, exposure measurement, comparison groups, outcomes, and adjustment for confounders, precluding meta-analysis. The literature suggested positive risk associations for age at biopsy, family history, mammographic breast density, and time since biopsy, and no association for body mass index, alcohol, smoking, age at menarche, and use of hormonal contraceptives. More research is needed to understand risk factor associations among women with BBD, particularly studies that account for heterogeneity within BBD and breast cancer.
Outlier-detection for reactive machine learned potential energy surfaces
Authors: Vazquez-Salazar Luis Itza , Käser Silvan , Meuwly Markus
Published: February 2025

Uncertainty quantification (UQ) to detect samples with large expected errors (outliers) is applied to reactive molecular potential energy surfaces (PESs). Three methods–Ensembles, deep evidential regression (DER), and Gaussian Mixture Models (GMM)—were applied to the H-transfer reaction between syn-Criegee and vinyl hydroxyperoxide. The results indicate that ensemble models provide the best results for detecting outliers, followed by GMM. For example, from a pool of 1000 structures with the largest uncertainty, the detection quality for outliers is ~90% and ~50%, respectively, if 25 or 1000 structures with large errors are sought. On the contrary, the limitations of the statistical assumptions of DER greatly impact its prediction capabilities. Finally, a structure-based indicator was found to be correlated with large average error, which may help to rapidly classify new structures into those that provide an advantage for refining the neural network.
Mathematical modeling of multicellular tumor spheroids quantifies inter-patient and intra-tumor heterogeneity
Authors: Malik Adam A. , Nguyen Kyle C. , Nardini John T. , Krona Cecilia C. , Flores Kevin B. , Nelander Sven
Published: February 2025

In the study of brain tumors, patient-derived three-dimensional sphere cultures provide an important tool for studying emerging treatments. The growth of such spheroids depends on the combined effects of proliferation and migration of cells, but it is challenging to make accurate distinctions between increase in cell number versus the radial movement of cells. To address this, we formulate a novel model in the form of a system of two partial differential equations (PDEs) incorporating both migration and growth terms, and show that it more accurately fits our data compared to simpler PDE models. We show that traveling-wave speeds are strongly associated with population heterogeneity. Having fitted the model to our dataset we show that a subset of the cell lines are best described by a “Go-or-Grow”-type model, which constitutes a special case of our model. Finally, we investigate whether our fitted model parameters are correlated with patient age and survival.
Transcriptomics and epigenomics datasets of primary brain cancers in formalin-fixed paraffin embedded format
Authors: García-Heredia Anabel , Guerra-Núñez Luna , Martín-Climent Paula , Rojas Estefanía , López-Domínguez Raúl , Alcántara-Domínguez Clara , Alenda Cristina , Valor Luis M.
Published: February 2025

The access of public omics-based datasets is of paramount importance in brain cancer research as allows the proposal and validation of both biomarkers and therapeutic targets in gliomas, especially in the most prevalent and aggressive glioblastomas. Taking profit of current advances in next generation sequencing and DNA methylation profiling, we have created datasets from approximately 150 formalin-fixed paraffin embedded (FFPE) tumours. These datasets enable for the first time integrative transcriptional and epigenetics studies in a context that consider the degradation and fixation-derived chemical alterations of the most extended archiving format in hospitals, and provide an independent cohort from current public databases for further validation of putative novel biomarkers. Alongside with the most profusely known glioblastomas, astrocytomas and oligodendrogliomas, we have also included for comparison purposes few examples of rare tumours that are often neglected in brain cancer research. Taken together, we provide a valuable tool to explore combined gene expression and DNA methylation patterns in the study of gliomas and glioneuronal tumours.
Machine learning enhanced grey box soft sensor for melt viscosity prediction in polymer extrusion processes
Authors: Perera Yasith S. , Li Jie , Abeykoon Chamil
Published: February 2025

Melt viscosity is regarded as a key quality indicator of the polymer melt in polymer extrusion processes. However, limitations such as disturbances to the melt flow and measurement delays of the existing in-line and side-stream rheometers prevent the monitoring and controlling of this key parameter in real time. Soft sensors can be employed to monitor physical parameters that are difficult to measure using hardware sensing instruments. This study presents a grey-box soft sensing solution to predict the melt viscosity in real time, which combines physics-based knowledge with machine learning. A fine-tuned physics-based mathematical model is used to make melt viscosity predictions, and a deep neural network is employed to compensate for its prediction errors. The proposed soft sensor model reported a normalised root mean square error of 2.2
$$\:\times\:$$
10−3 (0.22%), outperforming fully data-driven soft sensor models based on multilayer perceptron and long short-term memory neural networks. Furthermore, it exhibited an improvement of approximately 95% in terms of predictive performance, compared to a soft sensor based on a radial basis function neural network reported in a previous study. The proposed soft sensor can monitor viscosity changes caused by changes in operating conditions but not suitable for detecting viscosity changes due to changes in material properties. The findings of this study can aid in enhancing process monitoring and control in polymer extrusion processes.
Efficient WSI classification with sequence reduction and transformers pretrained on text
Authors: Pisula Juan I. , Bozek Katarzyna
Published: February 2025

From computer vision to protein fold prediction, Language Models (LMs) have proven successful in transferring their representation of sequential data to a broad spectrum of tasks beyond the domain of natural language processing. Whole Slide Image (WSI) analysis in digital pathology naturally fits to transformer-based architectures. In a pre-processing step analogous to text tokenization, large microscopy images are tessellated into smaller image patches. However, due to the massive size of WSIs comprising thousands of such patches, the problem of WSI classification has not been addressed via deep transformer architectures, let alone via available text-pre-trained deep transformer language models. We introduce SeqShort, a multi-head attention-based sequence shortening layer that summarizes a large WSI into a fixed- and short-sized sequence of feature vectors by removing redundant visual information. Our sequence shortening mechanism not only reduces the computational costs of self-attention on large inputs, it also allows to include standard positional encodings to the previously unordered bag of patches that compose a WSI. We use SeqShort to effectively classify WSIs in different digital pathology tasks using a deep, text pre-trained transformer model while fine-tuning less than 0.1% of its parameters, demonstrating that their knowledge about natural language transfers well to this domain.
Effect of neoadjuvant chemotherapy on CD14 + CD16 + monocytes and soluble CD163 in Egyptian breast cancer patients
Authors: Youssry Sara , Ghoneim Hossam , Barakat Riham , ElAlfy Eman
Published: February 2025

Neoadjuvant chemotherapy (NACT) influences the anticancer response by favourably altering the immune microenvironment. However, the effects of NACT on peripheral monocytes and their prognostic contribution to the NACT response have not yet been clarified. We aimed to evaluate the potential therapeutic responses and possible predictive value of double-positive (CD14 + CD16 +) monocytes and soluble CD163 (sCD163) in Egyptian breast cancer patients. Blood samples were obtained before and after neoadjuvant therapy from 30 patients with invasive breast cancer, and the expression of CD14 and CD16 was assessed via flow cytometry. The patients’ sCD163 levels were also determined in both the serum and culture supernatant using enzyme-linked immunosorbent assay (ELISA). The results revealed that NACT was associated with a significant decrease in double-positive monocytes and sCD163 levels. In addition, both double-positive monocytes and serum sCD163 were significantly associated with a partial clinical response. Double-positive monocytes and serum sCD163 levels may be related to therapeutic response, suggesting their possible predictive value in breast cancer patients receiving NACT.