bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico fragment-based discovery of CIB1-directed anti-tumor agents by FRASE-bot
Authors: An Yi , Lim Jiwoong , Glavatskikh Marta , Wang Xiaowen , Norris-Drouin Jacqueline , Hardy P. Brian , Leisner Tina M. , Pearce Kenneth H. , Kireev Dmitri 
Published: July 2024

AbstractChemical probes are an indispensable tool for translating biological discoveries into new therapies, though are increasingly difficult to identify since novel therapeutic targets are often hard-to-drug proteins. We introduce FRASE-based hit-finding robot (FRASE-bot), to expedite drug discovery for unconventional therapeutic targets. FRASE-bot mines available 3D structures of ligand-protein complexes to create a database of FRAgments in Structural Environments (FRASE). The FRASE database can be screened to identify structural environments similar to those in the target protein and seed the target structure with relevant ligand fragments. A neural network model is used to retain fragments with the highest likelihood of being native binders. The seeded fragments then inform ultra-large-scale virtual screening of commercially available compounds. We apply FRASE-bot to identify ligands for Calcium and Integrin Binding protein 1 (CIB1), a promising drug target implicated in triple negative breast cancer. FRASE-based virtual screening identifies a small-molecule CIB1 ligand (with binding confirmed in a TR-FRET assay) showing specific cell-killing activity in CIB1-dependent cancer cells, but not in CIB1-depletion-insensitive cells.
Uplift of the Tibetan Plateau driven by mantle delamination from the overriding plate
Authors: Xie Yuan , Balázs Attila , Gerya Taras , Xiong Xiong 
Published: July 2024

AbstractThe geodynamic evolution of the Tibetan Plateau remains highly debated. Any model of its evolution must explain the plateau’s growth as constrained by palaeo-altitude studies, the spatio-temporal distribution of magmatic activity, and the lithospheric mantle removal inferred from seismic velocity anomalies in the underlying mantle. Several conflicting models have been proposed, but none of these explains the first-order topographic, magmatic and seismic features self-consistently. Here we propose and test numerically an evolutionary model of the plateau that involves gradual peeling of the lithospheric mantle from the overriding plate and consequent mantle and crustal melting and uplift. We show that this model successfully reproduces the successive surface uplift of the plateau to more than 4 km above sea level and is consistent with the observed migration of magmatism and geometry of the lithosphere–asthenosphere boundary resulting from subduction of the Indian plate and delamination of the mantle lithosphere of the Eurasian plate. These comparisons indicate that mantle delamination from the overriding plate is the driving force behind the uplift of the Tibetan Plateau and, potentially, orogenic plateaus more generally.
Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping
Authors: Netskar Herman , Pfefferle Aline , Goodridge Jodie P. , Sohlberg Ebba , Dufva Olli , Teichmann Sarah A. , Brownlie Demi , Michaëlsson Jakob , Marquardt Nicole , Clancy Trevor , Horowitz Amir , Malmberg Karl-Johan 
Published: July 2024

AbstractThe functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor–ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map of healthy human blood- and tissue-derived NK cells, with temporal resolution and fate-specific expression of gene-regulatory networks defining NK cell differentiation. Transfer learning facilitated incorporation of tumor-infiltrating NK cell transcriptomes (39 datasets, 7 solid tumors, 427 patients) into the reference map to analyze tumor microenvironment (TME)-induced perturbations. Of the six functionally distinct NK cell states identified, a dysfunctional stressed CD56bright state susceptible to TME-induced immunosuppression and a cytotoxic TME-resistant effector CD56dim state were commonly enriched across tumor types, the ratio of which was predictive of patient outcome in malignant melanoma and osteosarcoma. This resource may inform the design of new NK cell therapies and can be extended through transfer learning to interrogate new datasets from experimental perturbations or disease conditions.
Benefits for children with suspected cancer from routine whole-genome sequencing
Authors: Hodder Angus , Leiter Sarah M. , Kennedy Jonathan , Addy Dilys , Ahmed Munaza , Ajithkumar Thankamma , Allinson Kieren , Ancliff Phil , Bailey Shivani , Barnard Gemma , Burke G. A. Amos , Burns Charlotte , Cano-Flanagan Julian , Chalker Jane , Coleman Nicholas , Cheng Danny , Clinch Yasmin , Dryden Caryl , Ghorashian Sara , Griffin Blanche , Horan Gail , Hubank Michael , May Phillippa , McDerra Joanna , Nagrecha Rajvi , Nicholson James , O’Connor David , Pavasovic Vesna , Quaegebeur Annelies , Rao Anupama , Roberts Thomas , Samarasinghe Sujith , Stasevich Iryna , Tadross John A. , Trayers Claire , Trotman Jamie , Vora Ajay , Watkins James , Chitty Lyn S. , Bowdin Sarah , Armstrong Ruth , Murray Matthew J. , Hook Catherine E. , Tarpey Patrick , Vedi Aditi , Bartram Jack , Behjati Sam 
Published: July 2024

AbstractClinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.
Neural representation of human experimenters in the bat hippocampus
Authors: Snyder Madeleine C. , Qi Kevin K. , Yartsev Michael M. 
Published: July 2024

AbstractHere we conducted wireless electrophysiological recording of hippocampal neurons from Egyptian fruit bats in the presence of human experimenters. In flying bats, many neurons modulated their activity depending on the identity of the human at the landing target. In stationary bats, many neurons carried significant spatial information about the position and identity of humans traversing the environment. Our results reveal that hippocampal activity is robustly modulated by the presence, movement and identity of human experimenters.
Quick methylene blue dye elimination via SDS-Ag nanoparticles catalysts
Authors: Almarashi Jamal Q. M. , Gadallah A.-S. , Shaban Mohamed , Ellabban M. A. , Hbaieb Kais , Kordy Mohamed G. M. , Zayed Mohamed , Mohamed Abdel-Aleam H. 
Published: July 2024

AbstractMethylene blue dye, being toxic, carcinogenic and non-biodegradable, poses a serious threat for human health and environmental safety. The effective and time-saving removal of such industrial dye necessitates the use of innovative technologies such as silver nanoparticle-based catalysis. Utilizing a pulsed Nd:YAG laser operating at the second harmonic generation of 532 nm with 2.6 J energy per pulse and 10 ns pulse duration, Ag nanoparticles were synthesized via an eco-friendly method with sodium dodecyl sulphate (SDS) as a capping agent. Different exposure times (15, 30, and 45 min) resulted in varying nanoparticle sizes. Characterization was achieved through UV–Vis absorption spectroscopy, scanning electron microscopy (SEM) imaging, and energy dispersive X-ray (EDX). Lorentzian fitting was used to model nanoparticle size, aligning well with SEM results. Mie’s theory was applied to evaluate the absorption, scattering, and extinction cross-sectional area spectra. EDX revealed increasing Ag and carbon content with exposure time. The SDS-caped AgNPs nanoparticles were tested as catalyst for methylene blue degradation, achieving up to 92.5% removal in just 12 min with a rate constant of 0.2626 min−1, suggesting efficient and time-saving catalyst compared to previously reported Ag-based nanocatalysts.
The association of rs17713054 with Neanderthal origin at 3p21.31 locus with the severity of COVID-19 in Iranian patients
Authors: Yaghmouri Mohammad , Safdari Lord Javad , Amini Masoumeh , Yekaninejad Mir Saeed , Izadi Pantea 
Published: July 2024

AbstractSince the COVID-19 pandemic, the diversity of clinical manifestations in patients has been a tremendous challenge. It seems that genetic variations, as one of the players, contribute to the variety of symptoms. Genome-wide association studies have demonstrated the influence of certain genomic regions on the disease prognosis. Particularly, a haplotype at 3p21.31 locus, inherited from Neanderthals, showed an association with COVID-19 severity. Despite several studies regarding this haplotype, some key variants are not sufficiently addressed. In the present study, we investigated the association of rs17713054 at 3p21.31 with COVID-19 severity. We analyzed the genotype of 251 Iranian COVID-19 patients (151 patients with asymptomatic to mild form as control and 100 patients with severe to critical symptoms without any comorbidities as case group) using the ARMS-PCR method. Results demonstrated that the A allele confers an almost twofold increased risk for COVID-19 severity (Pvalue = 0.008). The AA genotype also raises the risk by more than 11 times following the recessive model (Pvalue = 0.013). In conclusion, the A allele in rs17713054 was a risk allele in Iranian patients and was independently associated with COVID-19 severity. More studies are beneficial to confirm these findings in other populations and to develop strategies for risk assessment, prevention, and personalized medicine.
Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients
Authors: Malik Samina , Waquar Sulayman , Idrees Nimra , Malik Arif 
Published: July 2024

AbstractCancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the most common ailments worldwide, indicating the importance of developing particular techniques that could help attenuate the effects of breast cancer and related outcomes. The primary aim of the current study was to review the role of inflammatory and stress markers in the development and progression of breast cancer. Four hundred ninety-eight (n = 498) patients with breast cancer and four hundred and ninety-eight (n = 498) age- and sex-matched controls were selected for this case‒control study. Serum samples were obtained, and the levels of stress and inflammatory markers, including Matrix metalloproteases (MMPs), Interleukins (ILs), Heat shock proteins (HSPs), Malondialdehyde (MDA), Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS) and Tumour necrosis factor-alpha (TNF-α), were determined. Most (62%) patients had metastatic breast cancer (stage III or IV) with an adverse grade (65% with Grade III and 35% with Grade II). The present study showed that the levels of oxidants such as MDA, ILs, MMPs and HSPs were significantly greater, while the levels of antioxidants such as Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), vitamin A, C and D were significantly lower in breast cancer patients than in controls, suggesting their diagnostic importance and role in the pathophysiology of breast cancer. Oxidants, including IL-1, HSP27 and MMP9, which are highly specific and sensitive, may be used to develop the pathophysiological pathways of metastatic breast cancer in these patients. These pathways include cell invasion, cell migration and epithelial–mesenchymal transition. Therefore, we concluded that an increase in growth factors, e.g., Vascular Endothelial Growth Factor (VEGF), Tumour Growth Factor-beta (TGF-β) and B-cell lymphoma (Bcl2), under the influence of these variables plays a crucial role in the metastasis of breast cancer.
Salt stress amelioration and nutrient strengthening in spinach (Spinacia oleracea L.) via biochar amendment and zinc fortification: seed priming versus foliar application
Authors: Ahmad Shoaib , Khan Sehrish Adiba , Hussain Afzal , Zhang Lidan , Owdah Alomrani Sarah , Ahmad Azeem , Al-Ghanim Khalid A. , Ali Alshehri Mohammad , Ali Shafaqat , Sarker Pallab K. 
Published: July 2024

AbstractSoil salinity is a major nutritional challenge with poor agriculture production characterized by high sodium (Na+) ions in the soil. Zinc oxide nanoparticles (ZnO NPs) and biochar have received attention as a sustainable strategy to reduce biotic and abiotic stress. However, there is a lack of information regarding the incorporation of ZnO NPs with biochar to ameliorate the salinity stress (0, 50,100 mM). Therefore, the current study aimed to investigate the potentials of ZnO NPs application (priming and foliar) alone and with a combination of biochar on the growth and nutrient availability of spinach plants under salinity stress. Results demonstrated that salinity stress at a higher rate (100 mM) showed maximum growth retardation by inducing oxidative stress, resulted in reduced photosynthetic rate and nutrient availability. ZnO NPs (priming and foliar) alone enhanced growth, chlorophyll contents and gas exchange parameters by improving the antioxidant enzymes activity of spinach under salinity stress. While, a significant and more pronounced effect was observed at combined treatments of ZnO NPs with biochar amendment. More importantly, ZnO NPs foliar application with biochar significantly reduced the Na+ contents in root 57.69%, and leaves 61.27% of spinach as compared to the respective control. Furthermore, higher nutrient contents were also found at the combined treatment of ZnO NPs foliar application with biochar. Overall, ZnO NPs combined application with biochar proved to be an efficient and sustainable strategy to alleviate salinity stress and improve crop nutritional quality under salinity stress. We inferred that ZnO NPs foliar application with a combination of biochar is more effectual in improving crop nutritional status and salinity mitigation than priming treatments with a combination of biochar.
Generalized div-curl based regularization for physically constrained deformable image registration
Authors: Tzitzimpasis Paris , Ries Mario , Raaymakers Bas W. , Zachiu Cornel 
Published: July 2024

AbstractVariational image registration methods commonly employ a similarity metric and a regularization term that renders the minimization problem well-posed. However, many frequently used regularizations such as smoothness or curvature do not necessarily reflect the underlying physics that apply to anatomical deformations. This, in turn, can make the accurate estimation of complex deformations particularly challenging. Here, we present a new highly flexible regularization inspired from the physics of fluid dynamics which allows applying independent penalties on the divergence and curl of the deformations and/or their nth order derivative. The complexity of the proposed generalized div-curl regularization renders the problem particularly challenging using conventional optimization techniques. To this end, we develop a transformation model and an optimization scheme that uses the divergence and curl components of the deformation as control parameters for the registration. We demonstrate that the original unconstrained minimization problem reduces to a constrained problem for which we propose the use of the augmented Lagrangian method. Doing this, the equations of motion greatly simplify and become managable. Our experiments indicate that the proposed framework can be applied on a variety of different registration problems and produce highly accurate deformations with the desired physical properties.
Bacillaceae serine proteases and Streptomyces epsilon-poly-l-lysine synergistically inactivate Caliciviridae by inhibiting RNA genome release
Authors: Yamamoto Soh , Ogasawara Noriko , Sudo-Yokoyama Yuka , Sato Sachiko , Takata Nozomu , Yokota Nana , Nakano Tomomi , Hayashi Kyoko , Takasawa Akira , Endo Mayumi , Hinatsu Masako , Yoshida Keitaro , Sato Toyotaka , Takahashi Satoshi , Takano Kenichi , Kojima Takashi , Hiraki Jun , Yokota Shin-ich 
Published: July 2024

AbstractHuman norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-l-lysine (EPL) produced by Streptomyces—a natural antimicrobial—elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.
Mechanistic understanding of asphaltene precipitation and oil recovery enhancement using SiO2 and CaCO3 nano-inhibitors
Authors: Shadervan Ali , Jafari Arezou , Teimouri Alireza , Gharibshahi Reza , Dehaghani Amir Hossein Saeedi 
Published: July 2024

AbstractAsphaltene precipitation in oil reservoirs, well equipment, and pipelines reduces production, causing pore blockage, wettability changes, and decreased efficiency. Asphaltenes, with their unique chemical structure, self-assemble via acid–base interactions and hydrogen bonding. Nano-inhibitors prevent asphaltene aggregation at the nanoscale under reservoir conditions. This study investigates the effect of two surface-modified nanoparticles, silica, and calcium carbonate, as asphaltene inhibitors and oil production agents. The impacts of these nano-inhibitors on asphaltene content, onset point, wettability, surface tension, and oil recovery factor were determined to understand their mechanism on asphaltene precipitation and oil production. Results demonstrate that these nano-inhibitors can significantly postpone the onset point of asphaltene precipitation, with varying performance. Calcium carbonate nano-inhibitor exhibits better efficiency at low concentrations, suspending asphaltene molecules in crude oil. In contrast, silica nano-inhibitor performs better at high concentrations. Wettability alteration and IFT reduction tests reveal that each nano-inhibitor performs optimally at specific concentrations. Silica nano-inhibitors exhibit better colloidal stability and improve oil recovery more than calcium carbonate nano-inhibitors, with maximum oil recovery factors of 33% at 0.1 wt.% for silica and 25% at 0.01 wt.% for calcium carbonate nano-inhibitors.
In a rat model of bypass DuraGraft ameliorates endothelial dysfunction of arterial grafts
Authors: Lian Shuo , Loganathan Sivakkanan , Mayer Tobias , Kraft Patricia , Sayour Alex Ali , Georgevici Adrian-Iustin , Veres Gábor , Karck Matthias , Szabó Gábor , Korkmaz-Icöz Sevil 
Published: July 2024

AbstractCoronary artery bypass surgery can result in endothelial dysfunction due to ischemia/reperfusion (IR) injury. Previous studies have demonstrated that DuraGraft helps maintain endothelial integrity of saphenous vein grafts during ischemic conditions. In this study, we investigated the potential of DuraGraft to mitigate endothelial dysfunction in arterial grafts after IR injury using an aortic transplantation model. Lewis rats (n = 7–9/group) were divided in three groups. Aortic arches from the control group were prepared and rings were immediately placed in organ baths, while the aortic arches of IR and IR + DuraGraft rats were preserved in saline or DuraGraft, respectively, for 1 h before being transplanted heterotopically. After 1 h after reperfusion, the grafts were explanted, rings were prepared, and mounted in organ baths. Our results demonstrated that the maximum endothelium-dependent vasorelaxation to acetylcholine was significantly impaired in the IR group compared to the control group, but DuraGraft improved it (control: 89 ± 2%; IR: 24 ± 1%; IR + DuraGraft: 48 ± 1%, p < 0.05). Immunohistochemical analysis revealed decreased intercellular adhesion molecule-1, 4-hydroxy-2-nonenal, caspase-3 and caspase-8 expression, while endothelial cell adhesion molecule-1 immunoreactivity was increased in the IR + DuraGraft grafts compared to the IR-group. DuraGraft mitigates endothelial dysfunction following IR injury in a rat bypass model. Its protective effect may be attributed, at least in part, to its ability to reduce the inflammatory response, oxidative stress, and apoptosis.
Neutrophil percentage-to-albumin ratio is a potential marker of intravenous immunoglobulin resistance in Kawasaki disease
Authors: Deng Linfan , Wang Ting , Duan Yan , Liu Bin , Jiang Jun , Liu Dong , Li Gang 
Published: July 2024

AbstractIntravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) was associated with coronary artery lesions. Neutrophil percentage-to-albumin ratio (NPAR) is an index of mortality in several inflammatory diseases. This study focused on the association of NPAR with IVIG- resistance in KD. Clinical and laboratory data of 438 children with KD before IVIG treatment were retrospectively analyzed. Notably, high NPAR was associated with older age, high WBC, NP, ALT, total bilirubin and CRP, as well as with high the incidence of IVIG-resistance, and with low hemoglobin (Hb), PLT, ALB and sodium levels. NPAR (OR: 2.366, 95% CI: 1.46–3.897, p = 0.001) and Hb (OR: 0.967, 95% CI: 0.944–0.989, p = 0.004) were independent risk factors for IVIG-resistance. NPAR showed linear relation with IVIG-resistance (p for nonlinear = 0.711) and the nonlinear correlation was found between IVIG-resistance and Hb (p for nonlinear = 0.002). The predictive performance of NPAR was superior to Beijing model (z = 2.193, p = 0.028), and not inferior to Chongqing model (z = 0.983, p = 0.326) and the combination of NPAR and Hb (z = 1.912, p = 0.056). These findings revealed that NPAR is a reliable predictor of IVIG-resistance.