bluuebunny/crossref_metadata_2025_split huggingface dataset:
The temporal evolution of cancer hallmarks
Authors: Zapata Luis , Gourmet Lucie , Lam Jie Min , Ramazzotti Daniele , Pennycuick Adam , Mallick Parag , Walker-Samuel Simon 
Published: December 2024

Abstract

Cancer hallmarks describe key physiological characteristics that distinguish cancers from normal tissues. The temporal order in which these hallmarks appear during cancer pathogenesis is of interest from both evolutionary and clinical perspectives but has not been investigated before. Here, we order hallmarks based on the allele frequency and selective advantage of mutations in cancer hallmark genes across > 10K untreated primary tumors and > 8K healthy tissues. Using this novel approach, we identified a common evolutionary trajectory for 27 of 32 cancer types with genomic instability appearing first and immune evasion appearing last. We demonstrated widespread positive selection in cancer and strong negative selection in normal tissues for all hallmarks. Notable exceptions to the hallmark ordering in tumors were melanomas (uveal and skin) suggesting that strong environmental factors could disrupt common evolutionary paths. Clustering of hallmark trajectories across patients revealed 2 clusters defined by early or late genomic instability, with differential prognosis. We finally validated our results in about 3K primary tumors from the PCAWG consortium. Our study is the first to identify the temporal order of cancer hallmarks during tumorigenesis and demonstrate a prognostic value that could be exploited for early detection and risk stratification across multiple cancer types.
Middle cerebral artery embolism can be predicted by CT perfusion
Authors: Sun Hongyang , Luo Yun , Wu Jincheng , Zhao Zhenyu , Gong Jian , Han Hongxing , Wang Xianjun 
Published: December 2024

Abstract

Background
Identifying the etiology of acute middle cerebral artery occlusion (MCAO) is important in endovascular treatment. This study aimed to explore the predictive value of computed tomography perfusion (CTP) for determining the etiology of acute MCAO.
Methods
Clinical data and CTP images of patients with acute M1 segment MCAO who had undergone endovascular treatment at Linyi People’s Hospital from January 2020 to December 2023 were retrospectively analyzed. Patients were categorized based on the location of core infarction on CTP as cortical, subcortical, or mixed infarction. The etiology of MCAO was determined as either intracranial atherosclerotic stenosis (ICAS) or embolism via digital subtraction angiography (DSA).
Results
A total of 360 patients were included (median age 66 years, 63.9% male), of whom 241 had experienced embolism and 119 ICAS. Compared with the embolism group, the ICAS group was younger (p = 0.009), had a higher percentage of hyperlipidemia (p < 0.001), lower rates of coronary heart disease (p = 0.007) and atrial fibrillation (p < 0.001), a longer duration of endovascular treatment (p< 0.001), lower NIHSS scores (p< 0.001), smaller core volumes (p< 0.001), and better collateral compensation (p < 0.001). The two groups also differed in infarction location, with the embolism group primarily showing cortical infarctions (88%) and the ICAS group primarily exhibiting subcortical infarctions (69.7%). Multivariate analysis revealed that atrial fibrillation and cortical infarction were independent predictors of middle cerebral artery embolism (odds ratio = 36.496, 95% confidence interval: 10.732–124.106). Cortical infarction predicted middle cerebral artery embolism with a sensitivity of 88%, specificity of 86.6%, and accuracy of 87.5%.
Conclusion
The location of core infarction on baseline CTP can aid in identifying the etiology of acute MCAO. Cortical infarction is an independent predictor for middle cerebral artery embolism.
Design of allosteric modulators that change GPCR G protein subtype selectivity
Authors: Slosky Lauren , Moore Madelyn , Person Kelsey , Alwin Abigail , Krusemark Campbell , Foster Noah , Ray Caroline , Inoue Asuka , Jackson Michael , Sheedlo Michael , Barak Lawrence , de Velasco Ezequiel Marron Fernandez , Olson Steven 
Published: December 2024

Abstract

G protein-coupled receptors (GPCRs), the largest family of drug targets, can signal through 16 subtypes of Gα proteins. Biased compounds that selectively activate therapy-relevant pathways promise to be safer, more effective medications. The determinants of bias are poorly understood, however, and rationally-designed, G protein-subtype-selective compounds are lacking. Here, using the prototypical class A GPCR neurotensin receptor 1 (NTSR1), we find that small molecules binding the intracellular GPCR-transducer interface change G protein coupling by subtype-specific and predictable mechanisms, enabling rational drug design. We demonstrate that the compound SBI-553 switches NTSR1 G protein preference by acting both as a molecular bumper and a molecular glue. Structurally, SBI-553 occludes G protein binding determinants on NTSR1, promoting association with select G protein subtypes for which an alternative, shallow-binding conformation is energetically favorable. Minor modifications to the SBI-553 scaffold produce allosteric modulators with distinct G protein subtype selectivity profiles. Selectivity profiles are probe-independent, conserved across species, and translate to differences in in vivo activity. These studies demonstrate that G protein selectivity can be tailored with small changes to a single chemical scaffold targeting the receptor-transducer interface and, as this pocket is broadly conserved, present a strategy for pathway-selective drug discovery applicable to the diverse GPCR superfamily.
A Multi-Grained Symmetric Differential Equation Model for Learning Protein-Ligand Binding Dynamics
Authors: Liu Shengchao , Du Weitao , Xu Hannan , Li Yanjing , Li Zhuoxinran , Bhethanabotla Vignesh C. , Yan Divin , Borgs Christian , Anandkumar Anima , Guo Harry , Chayes Jennifer 
Published: December 2024

Abstract

In drug discovery, molecular dynamics (MD) simulation for protein-ligand binding provides a powerful tool for predicting binding affinities, estimating transport properties, and exploring pocket sites. There has been a long history of improving the efficiency of MD simulations through better numerical methods and, more recently, by utilizing machine learning (ML) methods. Yet, challenges remain, such as accurate modeling of extended-timescale simulations. To address this issue, we propose NeuralMD, the first ML surrogate that can facilitate numerical MD and provide accurate simulations in protein-ligand binding dynamics. We propose a principled approach that incorporates a novel physics-informed multi-grained group symmetric framework. Specifically, we propose (1) the BindingNet model that satisfies group symmetry using vector frames and captures the multi-level protein-ligand interactions, and (2) an augmented neural differential equation solver that learns the trajectory under Newtonian mechanics. For the experiment, we design ten single-trajectory and three multi-trajectory binding simulation tasks. We demonstrate the efficiency and effectiveness of NeuralMD, achieving over 1K$\times$ speedup compared to standard numerical MD simulations. NeuralMD also outperforms all other ML approaches, achieving up to 15$\times$ reduction in reconstruction error and 70% increase in validity. Additionally, we qualitatively illustrate that the oscillations in the predicted trajectories align more closely with ground-truth dynamics than those of other machine-learning methods. We believe NeuralMD paves the foundation for a new research paradigm in simulating protein-ligand dynamics.
Control of CO₂ in Closed Ecosystems Using Photosynthetic Organisms and Material Science Solution.
Authors: Castillo Iñaki Del Amo 
Published: December 2024

Abstract

The accumulation of CO₂ in closed ecological systems (CES) remains a critical challenge for sustainability and habitability, as exemplified by historical experiments like Biosphere 2. This study proposes an innovative approach integrating photosynthetic organisms—diatoms, cyanobacteria, and algae—with inert ceramic materials to address CO₂ accumulation while promoting system stability. A mathematical model was developed to simulate CO₂ dynamics and biomass growth, validated experimentally using a small-scale chamber.
Experimental results demonstrated a 45% reduction in CO₂ concentration, stabilizing at 440 ppm after 10 days, alongside a 15% increase in biomass. Ceramic materials showed no measurable interaction with CO₂, confirming their inert properties under humid conditions. These findings validate the theoretical predictions and underscore the system's potential for scalability and adaptability.
This work lays the foundation for applications in extraterrestrial habitats, urban sustainability projects, and advanced CES designs. Future research will focus on extending experimental durations, exploring variations in initial conditions, and optimizing light and nutrient availability to further enhance system performance.
Impact of integrated community-based HIV and sexual and reproductive health services for youth aged 16-24 years on population-level HIV outcomes in Zimbabwe: the CHIEDZA cluster randomized trial
Authors: Ferrand Rashida , Dauya Ethel , Chikwari Chido Dziva , Bandason Tsitsi 
Published: December 2024

Abstract

We conducted a cluster randomized trial of community-based services incorporating HIV testing, treatment and adherence support integrated with sexual and reproductive health services for youth (16-24years) in Zimbabwe. 24 clusters were randomized 1:1 to intervention or control (existing services only). Primary outcome was virological suppression (VS=viral load<1000copies/ml) among youth living with HIV (YLWH), ascertained through a population-level outcome survey of 17,682 youth (18-24years). Secondary outcomes corresponded to UNAIDS 90-90-90 targets. There was no difference by arm in primary outcome (mean cluster prevalence:41.3% (intervention) vs 38.3% (control); RR:1.07 (95%CI:0.88-1.30)), or in proportion of YLWH who were diagnosed. In the intervention arm, a lower proportion of diagnosed YLWH were taking treatment (RR=0.91 (95%CI:0.83-0.99)), but a higher proportion of those taking treatment had VS (RR=1.18 (95%CI:1.02-1.37)). The intervention did not impact proportion of youth with undiagnosed HIV, which explains the effect on primary outcome. Among those taking ART, the intervention improved VS.
Incident angle-dependent dynamic tuning of high-purity structural colors with an array of nanovoids on a dielectric surface
Authors: Radhakrishnan Hrudya , Basha Tummaluru Khadar , Laskar Junaid Masud , Dhara Sandip , Pandian Ramanathaswamy 
Published: December 2024

Abstract

We demonstrate incident angle-dependent dynamic tuning of visible structural colors with an array of nanovoids fabricated on the surface of silicon using focused ion beam nanolithography. Enhanced structural purity and resolution achieved by this method are manifested as sharp peaks in the experimental reflectance spectra. The linear correlation observed between reflected wavelength and changes in periodicity or incident angle demonstrates the potential for efficient tuning of structural color through manipulation of material or instrumental factors, or a combination of both. Two distinct physical phenomena, Mie resonance and light diffraction, were employed to elucidate the source of reflectance peaks and their shifts induced by incident angle or array periodicity. This analysis demonstrated that nanovoids, the fundamental components of the array, serve a dual purpose: they act as Mie-voids while simultaneously functioning as elements in a crossed-diffraction system. Our findings also show that for smaller angles of incidence (below 45°), the Mie resonance linked to individual nanovoids is the primary factor. However, when the angles exceed 45°, the structural color wavelength is predominantly influenced by the periodic arrangement of the void array and the diffraction of light, which depends on the grating constant.
Sentinel-2 enabled E. coli and Enterococcus faecal bacteria surveillance in coastal-recreational waters
Authors: Chowdhury Masuma , Laiz Irene , Calle Ignacio de la 
Published: December 2024

Abstract

Monitoring faecal indicator bacteria (FIB) such as Escherichia coli (E. coli) and Enterococcus in water bodies is critical for public health and environmental safety. While satellite data is widely used for water quality monitoring, its use to specifically map and monitor FIB represents a novel and valuable application. This study leverages Sentinel-2 satellite data to develop empirical statistical models to identify, map and monitor E. coli and Enterococcus across 13 beaches in Calvià, Mallorca, Spain. Through the integration of spectral features such as the Shortwave Infrared (SWIR1)/Coastal-Aerosol Ratio (Band11/Band1), SWIR1/SWIR2 Ratio (Band11/Band12), and the Normalized Difference SWIR1-Coastal Index (B11-B1/B11+B1), the models effectively identified and distinguished these bacteria from other key water quality indicators, including chlorophyll-a, turbidity, suspended matter, and coloured dissolved organic matter. The models achieved R2 values of 0.79 for E. coli and 0.74 for Enterococcus, with p-values of 5.37e-13 and 1.17e-11, respectively, demonstrating high accuracy and specificity. This study offers a new tool for monitoring faecal contamination, thus highlighting the potential of satellite technology to enhance environmental monitoring and ensure the safety of recreational waters.
Synthesis of Au nanoparticles by the reaction of HAuCl4·nH2O with organoaluminum compounds
Authors: Parfenova Lyudmila V. , Bikmeeva Almira Kh. , Kovyazin Pavel V. , Palatov Eldar R. , Khalilov Leonard M. , Ivanova Nina M. , Sergeev Semen N. 
Published: December 2024

Abstract

The reaction of HAuCl4.nH2O with organoaluminum compounds (HAlBui2 or AlR3, R=Me, Et, Bui) in organic solvents, followed by hydrolysis in the presence of a tertiary thiol (5-methylundecane-5-thiol), afforded gold nanoparticles (AuNPs). The proposed method enables the production of AuNPs with particle sizes ranging from 2 to 20 nm. The smallest particle sizes were observed when reducing HAuCl4 with HAlBui2. Nanoparticles have been characterized by the means of STEM, PCCS, XPS, and UV-Vis spectroscopy. The proposed method may be further utilized for the deposition of metal nanoparticles onto solid supports for applications in catalysis and other fields.
Roads imperil South American protected areas
Authors: Schauman Santiago A. , Jobbágy Esteban G. , Peñuelas Josep , Laurance William F. , Baldi Germán 
Published: December 2024

Abstract

Protected areas (PAs) in South America play a crucial role in safeguarding biodiversity and ecosystem services. However, the widespread presence of roads within PAs poses a major yet largely overlooked threat to their ecological integrity. In this study, we used the most recent and consistent global roads dataset to evaluate the extent and spatial distribution of road networks within South American PAs. Our analysis revealed approximately 150,000 km of roads—equivalent to 3.5 times the Earth’s circumference. This extensive network exacerbates habitat fragmentation, increasing the number of PA patches from 1,230 to over 43,000, with 75% of these fragments smaller than 1 km². Consequently, seven out of nine terrestrial biomes on the continent have their protected interiors, on average, less than 4 km from the nearest road or unprotected surroundings. Roads infiltrate PAs through multiple entry points (13 per PA, on average), with 36% classified as highways or primary roads facilitating rapid transit and 20% paved, further amplifying their vulnerability to potential anthropogenic stressors. Only remote regions, such as flooded grasslands and savannas, Sub-Antarctic forests, and large areas of the Amazon basin, exhibit low road presence within PAs. Immediate conservation action is essential, with a focus on transparent road monitoring and management to maintain the ecological functions of these vital landscapes and ensure the long-term conservation of nature.
L-type calcium channels regulate decision-making process during fear learning in the zebrafish
Authors: Ogawa Satoshi , Lim Gen Wen , Roy Nisa 
Published: December 2024

Abstract

L-type calcium channels (LTCCs), is a family of the high-voltage activated family of voltage-dependent calcium channel. In the central nervous system, LTCCs play variety of roles including dendritic development, neuronal survival, synaptic plasticity, cognition, and behaviour. However, the role of LTCCs in cognitive function such as learning and memory are controversial. LTCCs and their encoding genes (CACNA1s) are evolutionarily conserved, but the role of LTCCs in cognitive function in non-mammalian species remains obscure. Hence, in this study, we examined the effect of a LTCC agonist, (±)-Bay K8644 on fear-associated learning using the conditioned place avoidance paradigm in adult zebrafish. Intraperitoneal administration of Bay K8644 did not diminish conditioned avoidance learning, while the fish treated with Bay K8644 spend a longer duration in the non-conditioned compartment as compared to control. This suggests that LTCCs could a crucial role in the decision-making process, rather than fear consolidation or fear retrieval in zebrafish.
Extracellular vesicles produced in hollow fiber bioreactor as potential drug delivery systems – cell uptake tracking with label-free optical diffraction tomography
Authors: Wawrowicz Kamil , Durak-Kozica Martyna , Marzejon Marcin , Trusiak Maciej , Stępień Ewa Ł. 
Published: December 2024

Abstract

Extracellular vesicles (EVs) are emerging as one of the most promising candidates for novel drug delivery systems (DDS). Unique features, like biocompatibility, encapsulation capability and functionalization for precise targeting make them an attractive candidates for biomedical applications. However, despite the numerous benefits, progress in EVs-based DDS translation from bench to clinics remains highly challenging. One of key limitations that needs to be addressed are low production yield, limited reproducibility and poor understating of their natural, in vitro/in vivo behavior. To address these challenges, we aimed to establish a bioreactor-based system for long-term, high-yield EV production and evaluate their internalization capabilities using label-free tomography.
Hollow fiber system was implemented as bioreactor for production and pre-purification of extracellular vesicles in long time manner. The obtained vesicles were characterized by spectral flow cytometry, tunable resistive pulse sensing (tRPR) and transmission electron microscopy (TEM). Subsequently, in order to investigate their biological functions, EVs uptake by target cells was evaluated with label-free techniques, such as Optical Diffraction Tomography (ODT) and Fourier Ptychographic Microscopy (FPM).
Bioreactor enabled to performed five week long continuous production of extracellular vesicles with high homogeneity among each collected batch. This include tetraspanins expression, and more importantly, narrow size distribution with low, ~5% differences. Reconstructed tomographic images revealed that obtained extracellular vesicles can effectively internalize into the target, pancreatic, cells and were preferentially located in perinuclear area. This first stage results are highly promising for further development such approaches for high yield EVs production and its label-free in vitro tracking.
O abraço que não está na lei: O acesso aos direitos fundamentais em meio à calamidade pública instalada no Rio Grande do Sul
Authors: Bonfada Luana Carolina , Allebrandt Sérgio Luís 
Published: December 2024

O presente artigo propõe-se a debater sobre a relevância dos atores judiciais enquanto protagonistas da organização societária em situações emergenciais de calamidade pública. Busca, assim, realizar uma exposição acerca dos direitos fundamentais que podem ser acessados por meio da Justiça, e a relação do Estado para a sua satisfação e garantia até mesmo em momentos de crise. O estudo está embasado no diálogo mantido com o Promotor de Justiça Regional lotado em Lajeado, cidade localizada no Vale do Taquari, no estado do Rio Grande do Sul, uma das muitas localidades gaúchas afetadas pelas inundações ocorridas em setembro de 2023 e em maio de 2024. A partir da coleta de dados é possível verificar a necessidade de atuação extraprocessual de tais agentes, evidenciando que as necessidades do ser humano vão muito além ou, por vezes, simplesmente se resumem na espera de um abraço que não está na lei.
Evaluating the Colonization Efficiency of Probiotic Bacteria in Intestinal Milieu and Fish Growth Promotion
Authors: Bhattacharya Sabyasachi , Bhakta Jatindra Nath , Lahiri Susmita , Panigrahi Asish Kumar 
Published: December 2024

Objectives:
The objective of the present study was to select potent probiotics by evaluating
the survival and colonization properties of some probiotic bacterial strains in fish intestinal milieu
and fish growth promotion.

Methods:
The fish culture experiment was conducted in aquariums (60 l) introducing twenty fingerlings
per aquarium (L. bata, 10 fingerlings and L. rohita, 10 fingerlings) and feeding through different
supplementary feed fortified (inoculated) by eleven different probiotic strains of Lactobacillus
fermentum (As11, Cd16, Cd28, Pb8 and Pb9) and Lactobacillus reuteri (Butch14, Butch21,
Chlop24, Chlop13, Stpt9 and Stpt41). The survival of probiotic bacterial and fish growth was recorded
at regular intervals.

Results:
The higher population (1 – 61 cfu x 104/g) and colonization efficiency (CE; L. bata, 1266
to 2000%) of different probiotic strains were observed in the intestinal milieu of fish treated with
probiotics. Although all probiotic-treated fish showed a higher absolute growth rate (AGR; L. bata,
0.02 – 0.049 g/day and L. rohita, 0.2 – 0.5 g/day) compared to the control, the Butch14, As11, and
Stpt41 strains exhibited an excellent AGR than the other strains. The negative correlation between
CE and AGR (r² = -0.577 for L. bata and r² = -0.379 for L. rohita) signified that probiotic bacterial
CE is not the primary fish growth-promoting factor.

Conclusion:
It can be concluded that the employed Lac. fermentum As11 as well as Lac. reuteri
Butch14 and Stpt41 could be considered excellent probiotic candidates, and probiotic-mediated fish
growth is largely dependent upon the type of probiotic strains rather than the CE of probiotics.