bluuebunny/crossref_metadata_2025_split huggingface dataset:
Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies
Authors: Figarol Sarah , Delahaye Célia , Gence Rémi , Doussine Aurélia , Cerapio Juan Pablo , Brachais Mathylda , Tardy Claudine , Béry Nicolas , Asslan Raghda , Colinge Jacques , Villemin Jean-Philippe , Maraver Antonio , Ferrer Irene , Paz-Ares Luis , Kessler Linda , Burrows Francis , Lajoie-Mazenc Isabelle , Dongay Vincent , Morin Clara , Florent Amélie , Pagano Sandra , Taranchon-Clermont Estelle , Casanova Anne , Pradines Anne , Mazieres Julien , Favre Gilles , Calvayrac Olivier 
Published: June 2024

AbstractDrug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, the kinetics and sequence of molecular events governing this adaptive response remain poorly understood. Here, we combine real-time monitoring of the cell-cycle dynamics and single-cell RNA sequencing in a broad panel of oncogenic addiction such as EGFR-, ALK-, BRAF- and KRAS-mutant NSCLC, treated with their corresponding TT. We identify a common path of drug adaptation, which invariably involves alveolar type 1 (AT1) differentiation and Rho-associated protein kinase (ROCK)-mediated cytoskeletal remodeling. We also isolate and characterize a rare population of early escapers, which represent the earliest resistance-initiating cells that emerge in the first hours of treatment from the AT1-like population. A phenotypic drug screen identify farnesyltransferase inhibitors (FTI) such as tipifarnib as the most effective drugs in preventing relapse to TT in vitro and in vivo in several models of oncogenic addiction, which is confirmed by genetic depletion of the farnesyltransferase. These findings pave the way for the development of treatments combining TT and FTI to effectively prevent tumor relapse in oncogene-addicted NSCLC patients.
Late Cretaceous ammonoids show that drivers of diversification are regionally heterogeneous
Authors: Flannery-Sutherland Joseph T. , Crossan Cameron D. , Myers Corinne E. , Hendy Austin J. W. , Landman Neil H. , Witts James D. 
Published: June 2024

AbstractPalaeontologists have long sought to explain the diversification of individual clades to whole biotas at global scales. Advances in our understanding of the spatial distribution of the fossil record through geological time, however, has demonstrated that global trends in biodiversity were a mosaic of regionally heterogeneous diversification processes. Drivers of diversification must presumably have also displayed regional variation to produce the spatial disparities observed in past taxonomic richness. Here, we analyse the fossil record of ammonoids, pelagic shelled cephalopods, through the Late Cretaceous, characterised by some palaeontologists as an interval of biotic decline prior to their total extinction at the Cretaceous-Paleogene boundary. We regionally subdivide this record to eliminate the impacts of spatial sampling biases and infer regional origination and extinction rates corrected for temporal sampling biases using Bayesian methods. We then model these rates using biotic and abiotic drivers commonly inferred to influence diversification. Ammonoid diversification dynamics and responses to this common set of diversity drivers were regionally heterogeneous, do not support ecological decline, and demonstrate that their global diversification signal is influenced by spatial disparities in sampling effort. These results call into question the feasibility of seeking drivers of diversity at global scales in the fossil record.
Maternal transmission as a microbial symbiont sieve, and the absence of lactation in male mammals
Authors: Fagan Brennen T. , Constable George W. A. , Law Richard 
Published: June 2024

AbstractGut microbiomes of mammals carry a complex symbiotic assemblage of microorganisms. Feeding newborn infants milk from the mammary gland allows vertical transmission of the parental milk microbiome to the offspring’s gut microbiome. This has benefits, but also has hazards for the host population. Using mathematical models, we demonstrate that biparental vertical transmission enables deleterious microbial elements to invade host populations. In contrast, uniparental vertical transmission acts as a sieve, preventing these invasions. Moreover, we show that deleterious symbionts generate selection on host modifier genes that keep uniparental transmission in place. Since microbial transmission occurs during birth in placental mammals, subsequent transmission of the milk microbiome needs to be maternal to avoid the spread of deleterious elements. This paper therefore argues that viviparity and the hazards from biparental transmission of the milk microbiome, together generate selection against male lactation in placental mammals.
Superporous sponge prepared by secondary network compaction with enhanced permeability and mechanical properties for non-compressible hemostasis in pigs
Authors: Jiang Tianshen , Chen Sirong , Xu Jingwen , Zhang Yuxiao , Fu Hao , Ling Qiangjun , Xu Yan , Chu Xiangyu , Wang Ruinan , Hu Liangcong , Li Hao , Huang Weitong , Bian Liming , Zhao Pengchao , Wei Fuxin 
Published: June 2024

AbstractDeveloping superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.
Observation of discrete-light temporal refraction by moving potentials with broken Galilean invariance
Authors: Qin Chengzhi , Ye Han , Wang Shulin , Zhao Lange , Liu Menglin , Li Yinglan , Hu Xinyuan , Liu Chenyu , Wang Bing , Longhi Stefano , Lu Peixiang 
Published: June 2024

AbstractRefraction is a basic beam bending effect at two media’s interface. While traditional studies focus on stationary boundaries, moving boundaries or potentials could enable new laws of refractions. Meanwhile, media’s discretization plays a pivotal role in refraction owing to Galilean invariance breaking principle in discrete-wave mechanics, making refraction highly moving-speed dependent. Here, by harnessing a synthetic temporal lattice in a fiber-loop circuit, we observe discrete time refraction by a moving gauge-potential barrier. We unveil the selection rules for the potential moving speed, which can only take an integer v = 1 or fractional v = 1/q (odd q) value to guarantee a well-defined refraction. We observe reflectionless/reflective refractions for v = 1 and v = 1/3 speeds, transparent potentials with vanishing refraction/reflection, refraction of dynamic moving potential and refraction for relativistic Zitterbewegung effect. Our findings may feature applications in versatile time control and measurement for optical communications and signal processing.
Data-driven prediction of continuous renal replacement therapy survival
Authors: Zamanzadeh Davina , Feng Jeffrey , Petousis Panayiotis , Vepa Arvind , Sarrafzadeh Majid , Karumanchi S. Ananth , Bui Alex A. T. , Kurtz Ira 
Published: June 2024

AbstractContinuous renal replacement therapy (CRRT) is a form of dialysis prescribed to severely ill patients who cannot tolerate regular hemodialysis. However, as the patients are typically very ill to begin with, there is always uncertainty whether they will survive during or after CRRT treatment. Because of outcome uncertainty, a large percentage of patients treated with CRRT do not survive, utilizing scarce resources and raising false hope in patients and their families. To address these issues, we present a machine learning-based algorithm to predict short-term survival in patients being initiated on CRRT. We use information extracted from electronic health records from patients who were placed on CRRT at multiple institutions to train a model that predicts CRRT survival outcome; on a held-out test set, the model achieves an area under the receiver operating curve of 0.848 (CI = 0.822–0.870). Feature importance, error, and subgroup analyses provide insight into bias and relevant features for model prediction. Overall, we demonstrate the potential for predictive machine learning models to assist clinicians in alleviating the uncertainty of CRRT patient survival outcomes, with opportunities for future improvement through further data collection and advanced modeling.
NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation
Authors: Dodt Stephan , Widdershooven Noah V. , Dreisow Marie-Luise , Weiher Lisa , Steuernagel Lukas , Wunderlich F. Thomas , Brüning Jens C. , Fenselau Henning 
Published: June 2024

AbstractEfficient control of feeding behavior requires the coordinated adjustment of complex motivational and affective neurocircuits. Neuropeptides from energy-sensing hypothalamic neurons are potent feeding modulators, but how these endogenous signals shape relevant circuits remains unclear. Here, we examine how the orexigenic neuropeptide Y (NPY) adapts GABAergic inputs to the bed nucleus of the stria terminalis (BNST). We find that fasting increases synaptic connectivity between agouti-related peptide (AgRP)-expressing ‘hunger’ and BNST neurons, a circuit that promotes feeding. In contrast, GABAergic input from the central amygdala (CeA), an extended amygdala circuit that decreases feeding, is reduced. Activating NPY-expressing AgRP neurons evokes these synaptic adaptations, which are absent in NPY-deficient mice. Moreover, fasting diminishes the ability of CeA projections in the BNST to suppress food intake, and NPY-deficient mice fail to decrease anxiety in order to promote feeding. Thus, AgRP neurons drive input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation through NPY.
Spatiotemporal optical vortices with controllable radial and azimuthal quantum numbers
Authors: Liu Xin , Cao Qian , Zhang Nianjia , Chong Andy , Cai Yangjian , Zhan Qiwen 
Published: June 2024

AbstractOptical spatiotemporal vortices with transverse photon orbital angular momentum (OAM) have recently become a focal point of research. In this work we theoretically and experimentally investigate optical spatiotemporal vortices with radial and azimuthal quantum numbers, known as spatiotemporal Laguerre-Gaussian (STLG) wavepackets. These 3D wavepackets exhibit phase singularities and cylinder-shaped edge dislocations, resulting in a multi-ring topology in its spatiotemporal profile. Unlike conventional ST optical vortices, STLG wavepackets with non-zero $${{{{{\boldsymbol{p}}}}}}$$
p
and $${{{{{\boldsymbol{l}}}}}}$$
l
values carry a composite transverse OAM consisting of two directionally opposite components. We further demonstrate mode conversion between an STLG wavepacket and an ST Hermite-Gaussian (STHG) wavepacket through the application of strong spatiotemporal astigmatism. The converted STHG wavepacket is de-coupled in intensity in space-time domain that can be utilized to implement the efficient and accurate recognition of ultrafast STLG wavepackets carried various $${{{{{\boldsymbol{p}}}}}}$$
p
and $${{{{{\boldsymbol{l}}}}}}.$$
l
.
This study may offer new insights into high-dimensional quantum information, photonic topology, and nonlinear optics, while promising potential applications in other wave phenomena such as acoustics and electron waves.
Podocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury
Authors: Zhao Ying , Fan Shijie , Zhu Hong , Zhao Qingqing , Fang Zimin , Xu Diyun , Lin Wante , Lin Liming , Hu Xiang , Wu Gaojun , Min Julian , Liang Guang 
Published: June 2024

AbstractRecent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD. RNA-seq analysis indicates a significantly decreased expression of OTUD5 in HG/PA-stimulated podocytes. Podocyte-specific Otud5 knockout exacerbates podocyte injury and DKD in both type 1 and type 2 diabetic mice. Furthermore, AVV9-mediated OTUD5 overexpression in podocytes shows a therapeutic effect against DKD. Mass spectrometry and co-immunoprecipitation experiments reveal an inflammation-regulating protein, TAK1, as the substrate of OTUD5 in podocytes. Mechanistically, OTUD5 deubiquitinates K63-linked TAK1 at the K158 site through its active site C224, which subsequently prevents the phosphorylation of TAK1 and reduces downstream inflammatory responses in podocytes. Our findings show an OTUD5-TAK1 axis in podocyte inflammation and injury and highlight the potential of OTUD5 as a promising therapeutic target for DKD.
Facile fabrication of recyclable robust noncovalent porous crystals from low-symmetry helicene derivative
Authors: Zhang Guoli , Zhang Jian , Tao Yu , Gan Fuwei , Lin Geyu , Liang Juncong , Shen Chengshuo , Zhang Yuebiao , Qiu Huibin 
Published: June 2024

AbstractPorous frameworks constructed via noncovalent interactions show wide potential in molecular separation and gas adsorption. However, it remains a major challenge to prepare these materials from low-symmetry molecular building blocks. Herein, we report a facile strategy to fabricate noncovalent porous crystals through modular self-assembly of a low-symmetry helicene racemate. The P and M enantiomers in the racemate first stack into right- and left-handed triangular prisms, respectively, and subsequently the two types of prisms alternatively stack together into a hexagonal network with one-dimensional channels with a diameter of 14.5 Å. Remarkably, the framework reveals high stability upon heating to 275 °C, majorly due to the abundant π-interactions between the complementarily engaged helicene building blocks. Such porous framework can be readily prepared by fast rotary evaporation, and is easy to recycle and repeatedly reform. The refined porous structure and enriched π-conjugation also favor the selective adsorption of a series of small molecules.
T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis
Authors: Kedia Shreeya , Ji Hao , Feng Ruoqing , Androvic Peter , Spieth Lena , Liu Lu , Franz Jonas , Zdiarstek Hanna , Anderson Katrin Perez , Kaboglu Cem , Liu Qian , Mattugini Nicola , Cherif Fatma , Prtvar Danilo , Cantuti-Castelvetri Ludovico , Liesz Arthur , Schifferer Martina , Stadelmann Christine , Tahirovic Sabina , Gokce Ozgun , Simons Mikael 
Published: June 2024

AbstractAge-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer’s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer’s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8+ T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.
A significant exploration on meta-heuristic based approaches for optimization in the waste management route problems
Authors: Thakur Gauri , Pal Ashok , Mittal Nitin , Yajid Mohd Shukri Ab , Gared Fikreselam 
Published: June 2024

AbstractIn metropolitan cities, it is very complicated to govern the optimum routes for garbage collection vehicles due to high waste production and very dense population. Furthermore, wrongly designed routes are the source of wasting time, fuel and other resources in the collection of municipal trash procedure. The Vehicle Routing Problem (VRP) published between 2011 and 2023 was systematically analysed. The majority of the surveyed research compute the waste collecting problems using metaheuristic approaches. This manuscript serves two purposes: first, categorising the VRP and its variants in the field of waste collection; second, examining the role played by most of the metaheuristics in the solution of the VRP problems for a waste collection. Three case study of Asia continent has been analysed and the results show that the metaheuristic algorithms have the capability in providing good results for large-scale data. Lastly, some promising paths ranging from highlighting research gap to future scope are drawn to encourage researchers to conduct their research work in the field of waste management route problems.
Molecular modeling analysis for functionalized graphene/sodium alginate composite
Authors: Elhaes Hanan , Ibrahim Asmaa , Osman Osama , Ibrahim Medhat A. 
Published: June 2024

AbstractThis study examined the functionalization of graphene with easily ionizable elements, such as lithium, and subsequently its interaction with the biopolymer sodium alginate (SA), to highlight its potential for biomedical applications. Utilizing Density Functional Theory (DFT), the research comprehensively investigated the structural, electronic, and spectroscopic properties of these graphene-based composites. The electronic properties of functionalized graphene were investigated using DFT at the B3LYP/6-31G(d,p) level. Among the various configurations studied, graphene exhibited weak interaction with two lithium atoms, displaying the highest reactivity in terms of total dipole moment (TDM) at 5.967 Debye and a HOMO/LUMO energy gap (ΔE) of 0.748 eV. Electrostatic potential mapping revealed that graphene when enhanced with lithium and three units of SA, exhibited an augmented potential density on its surface, a finding corroborated by other investigated physical properties. Notably, the configuration of graphene/3SA/Li, with weak interaction occurring at two side carbons, demonstrated the highest reactivity with a TDM of 15.509 Debye and ΔE of 0.280 eV. Additionally, a shift in the spectral characteristics of graphene towards lower wavenumbers was observed as lithium and SA interacted with the graphene substrate. The PDOS plot for Graphene/3SA/Li, showed the highest contribution in the HOMO orbitals was equally from lithium, sodium, hydrogen, and oxygen, while the lowest contribution was from carbon. This computational analysis provides comprehensive insights into the functionalized graphene systems, aiding in their further development and optimization for practical biomedical use.
CRISPR-mediated editing of β-lactoglobulin (BLG) gene in buffalo
Authors: Tara Aseem , Singh Priyanka , Gautam Devika , Tripathi Gaurav , Uppal Chirag , Malhotra Shreya , De Sacchinandan , Singh Manoj K. , Telugu Bhanu P. , Selokar Naresh L. 
Published: June 2024

AbstractMilk is a good source of nutrition but is also a source of allergenic proteins such as α-lactalbumin, β-lactoglobulin (BLG), casein, and immunoglobulins. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas technology has the potential to edit any gene, including milk allergens. Previously, CRISPR/Cas has been successfully employed in dairy cows and goats, but buffaloes remain unexplored for any milk trait. In this study, we utilized the CRISPR/Cas9 system to edit the major milk allergen BLG gene in buffaloes. First, the editing efficiency of designed sgRNAs was tested in fibroblast cells using the T7E assay and Sanger sequencing. The most effective sgRNA was selected to generate clonal lines of BLG-edited cells. Analysis of 15 single-cell clones, through TA cloning and Sanger sequencing, revealed that 7 clones exhibited bi-allelic (−/−) heterozygous, bi-allelic (−/−) homozygous, and mono-allelic (−/+) disruptions in BLG. Bioinformatics prediction analysis confirmed that non-multiple-of-3 edited nucleotide cell clones have frame shifts and early truncation of BLG protein, while multiple-of-3 edited nucleotides resulted in slightly disoriented protein structures. Somatic cell nuclear transfer (SCNT) method was used to produce blastocyst-stage embryos that have similar developmental rates and quality with wild-type embryos. This study demonstrated the successful bi-allelic editing (−/−) of BLG in buffalo cells through CRISPR/Cas, followed by the production of BLG-edited blastocyst stage embryos using SCNT. With CRISPR and SCNT methods described herein, our long-term goal is to generate gene-edited buffaloes with BLG-free milk.
Prevalence, clinical characteristics, and long-term outcomes of new diabetes diagnosis in elderly patients undergoing percutaneous coronary intervention
Authors: Xue Zheng-Kai , Dai Xin-Ya , Ren Jia-Yi , Liu Tong , Zhang Yu-Kun , Hu Su-Tao , Wang Peng , Wu Xue , Zhang Jing-Kun , Tse Gary , Park Soohyung , Choi Cheol-Ung , Choi Byoung-Geol , Rha Seung-Woon , Chen Kang-Yin 
Published: June 2024

AbstractPrevious studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24–2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29–3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09–2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94–2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population.