bluuebunny/crossref_metadata_2025_split huggingface dataset:
MHD flow of time-fractional Casson nanofluid using generalized Fourier and Fick's laws over an inclined channel with applications of gold nanoparticles
Authors: Shah Jamal , Ali Farhad , Khan Naveed , Ahmad Zubair , Murtaza Saqib , Khan Ilyas , Mahmoud Omar 
Published: October 2022

AbstractGold nanoparticles are commonly used as a tracer in laboratories. They are biocompatible and can transport heat energy to tumor cells via a variety of clinical techniques. As cancer cells are tiny, properly sized nanoparticles were introduced into the circulation for invasion. As a result, gold nanoparticles are highly effective. Therefore, the current research investigates the magnetohydrodynamic free convection flow of Casson nanofluid in an inclined channel. The blood is considered as a base fluid, and gold nanoparticles are assumed to be uniformly dispersed in it. The above flow regime is formulated in terms of partial differential equations. The system of derived equations with imposed boundary conditions is non-dimensionalized using appropriate dimensionless variables. Fourier's and Fick's laws are used to fractionalize the classical dimensionless model. The Laplace and Fourier sine transformations with a new transformation are used for the closed-form solutions of the considered problem. Finally, the results are expressed in terms of a specific function known as the Mittag-Leffler function. Various figures and tables present the effect of various physical parameters on the achieved results. Graphical results conclude that the fractional Casson fluid model described a more realistic aspect of the fluid velocity profile, temperature, and concentration profile than the classical Casson fluid model. The heat transfer rate and Sherwood number are calculated and presented in tabular form. It is worth noting that increasing the volume percentage of gold nanoparticles from 0 to 0.04 percent resulted in an increase of up to 3.825% in the heat transfer rate.
Discovery of small molecule inhibitors that effectively disrupt IQGAP1-Cdc42 interaction in breast cancer cells
Authors: Sayedyahossein Samar , Smith Jessica , Barnaeva Elena , Li Zhigang , Choe Jun , Ronzetti Michael , Dextras Christopher , Hu Xin , Marugan Juan , Southall Noel , Baljinnyam Bolormaa , Thines Louise , Tran Andy D. , Ferrer Marc , Sacks David B. 
Published: October 2022

AbstractThe small GTPase Cdc42 is an integral component of the cytoskeleton, and its dysregulation leads to pathophysiological conditions, such as cancer. Binding of Cdc42 to the scaffold protein IQGAP1 stabilizes Cdc42 in its active form. The interaction between Cdc42 and IQGAP1 enhances migration and invasion of cancer cells. Disrupting this association could impair neoplastic progression and metastasis; however, no effective means to achieve this has been described. Here, we screened 78,500 compounds using a homogeneous time resolved fluorescence-based assay to identify small molecules that disrupt the binding of Cdc42 to IQGAP1. From the combined results of the validation assay and counter-screens, we selected 44 potent compounds for cell-based experiments. Immunoprecipitation and cell viability analysis rendered four lead compounds, namely NCGC00131308, NCGC00098561, MLS000332963 and NCGC00138812, three of which inhibited proliferation and migration of breast carcinoma cells. Microscale thermophoresis revealed that two compounds bind directly to Cdc42. One compound reduced the amount of active Cdc42 in cells and effectively impaired filopodia formation. Docking analysis provided plausible models of the compounds binding to the hydrophobic pocket adjacent to the GTP binding site of Cdc42. In conclusion, we identified small molecules that inhibit binding between Cdc42 and IQGAP1, which could potentially yield chemotherapeutic agents.
Strength-mass scaling law governs mass distribution inside honey bee swarms
Authors: Shishkov Olga , Chen Claudia , Madonna Claire Allison , Jayaram Kaushik , Peleg Orit 
Published: October 2022

AbstractTo survive during colony reproduction, bees create dense clusters of thousands of suspended individuals. How does this swarm, which is orders of magnitude larger than the size of an individual, maintain mechanical stability? We hypothesize that the internal structure in the bulk of the swarm, about which there is little prior information, plays a key role in mechanical stability. Here, we provide the first-ever 3D reconstructions of the positions of the bees in the bulk of the swarm using x-ray computed tomography. We find that the mass of bees in a layer decreases with distance from the attachment surface. By quantifying the distribution of bees within swarms varying in size (made up of 4000–10,000 bees), we find that the same power law governs the smallest and largest swarms, with the weight supported by each layer scaling with the mass of each layer to the $$\approx 1.5$$

≈
1.5

power. This arrangement ensures that each layer exerts the same fraction of its total strength, and on average a bee supports a lower weight than its maximum grip strength. This illustrates the extension of the scaling law relating weight to strength of single organisms to the weight distribution within a superorganism made up of thousands of individuals.
Global distribution of soil fauna functional groups and their estimated litter consumption across biomes
Authors: Heděnec Petr , Jiménez Juan Jose , Moradi Jabbar , Domene Xavier , Hackenberger Davorka , Barot Sebastien , Frossard Aline , Oktaba Lidia , Filser Juliane , Kindlmann Pavel , Frouz Jan 
Published: October 2022

AbstractSoil invertebrates (i.e., soil fauna) are important drivers of many key processes in soils including soil aggregate formation, water retention, and soil organic matter transformation. Many soil fauna groups directly or indirectly participate in litter consumption. However, the quantity of litter consumed by major faunal groups across biomes remains unknown. To estimate this quantity, we reviewed > 1000 observations from 70 studies that determined the biomass of soil fauna across various biomes and 200 observations from 44 studies on litter consumption by soil fauna. To compare litter consumption with annual litterfall, we analyzed 692 observations from 24 litterfall studies and 183 observations from 28 litter stock studies. The biomass of faunal groups was highest in temperate grasslands and then decreased in the following order: boreal forest > temperate forest > tropical grassland > tundra > tropical forest > Mediterranean ecosystems > desert and semidesert. Tropical grasslands, desert biomes, and Mediterranean ecosystems were dominated by termites. Temperate grasslands were dominated by omnivores, while temperate forests were dominated by earthworms. On average, estimated litter consumption (relative to total litter input) ranged from a low of 14.9% in deserts to a high of 100.4% in temperate grassland. Litter consumption by soil fauna was greater in grasslands than in forests. This is the first study to estimate the effect of different soil fauna groups on litter consumption and related processes at global scale.
No evidence for intervention-associated DNA methylation changes in monocytes of patients with posttraumatic stress disorder
Authors: Hummel Elisabeth , Elgizouli Magdeldin , Sicorello Maurizio , Leitão Elsa , Beygo Jasmin , Schröder Christopher , Zeschnigk Michael , Müller Svenja , Herpertz Stephan , Moser Dirk , Kessler Henrik , Horsthemke Bernhard , Kumsta Robert 
Published: October 2022

AbstractDNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD.
Factors influencing patient disclosure of cancer diagnosis to the family dentist: online survey in Japan
Authors: Lee Kyunghee , Takase Kozo , Fushimi Kiyohide 
Published: October 2022

AbstractOral care during cancer treatment constitutes essential supportive care. We aimed to identify factors associated with cancer patients informing their family dentists about their cancer diagnosis. Using the generated original questionnaire, we conducted a cross-sectional questionnaire study in 500 cancer patients (gastric, colorectal, lung, breast, and prostate cancer) through the Internet from September 10 to 13, 2019. The factors influencing patients’ disclosure of their cancer diagnosis to their family dentist were identified by multivariable logistic regression analysis. Nearly half of the respondents (42.2%) informed their family dentist that they had cancer. The disclosing behavior of cancer patients was distinctively associated with their physician’s advice (odds ratio [OR] 59.3; 95% confidence interval [CI] 7.7–456.3); 8.6% of all respondents were advised to inform their dentist about their cancer diagnosis. In the group without the physician's advice, good relationship with family dentist was associated with disclosing behavior. This study indicates the need for support for cancer patients to receive appropriate oral care; patients' perceptions of the physician’s advice and communication with the family dentist should be motivators for disclosing the cancer diagnosis to dentists. Medical workers involved in cancer care should demonstrate the benefit of medical-dental collaboration in cancer care of patients.
How the Great Plains Dust Bowl drought spread heat extremes around the Northern Hemisphere
Authors: Meehl Gerald A. , Teng Haiyan , Rosenbloom Nan , Hu Aixue , Tebaldi Claudia , Walton Guy 
Published: October 2022

AbstractExtraordinary heat extremes occurred in the 1930s in areas of the Northern Hemisphere far from the record setting heat over the US associated with the Great Plains Dust Bowl drought. A climate model sensitivity experiment is used to identify a new mechanism involving a warm season circumglobal atmospheric teleconnection pattern that spread heat extremes over far-flung areas of the Northern Hemisphere arising from the intense heating over the desiccated Great Plains themselves. It has only been in the twenty-first century that human populations in these regions of the Northern Hemisphere have experienced heat extremes comparable to the 1930s. This demonstrates that humans influenced Northern Hemisphere temperature and heat extremes through disastrous and unprecedented regional land use practices over the Great Plains, and points to the possibility that future intense regional droughts could affect heat extremes on hemispheric scales.
Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis
Authors: Philpott Holly T. , Birmingham Trevor B. , Fiset Benoit , Walsh Logan A. , Coleman Mitchell C. , Séguin Cheryle A. , Appleton C. Thomas 
Published: October 2022

AbstractSynovium is critical for maintaining joint homeostasis and may contribute to mechanobiological responses during joint movement. We investigated mechanobiological responses of whole synovium from patients with late-stage knee osteoarthritis (OA). Synovium samples were collected during total knee arthroplasty and assigned to histopathology or cyclic 10% tensile strain loading, including (1) static (control); (2) low-frequency (0.3 Hz); and iii) high-frequency (1.0 Hz) for 30-min. After 6-h incubation, tissues were bisected for RNA isolation and immunostaining (3-nitrotyrosine; 3-NT). RNA sequencing was analyzed for differentially expressed genes and pathway enrichment. Cytokines and lactate were measured in conditioned media. Compared to controls, low-frequency strain induced enrichment of pathways related to interferon response, Fc-receptor signaling, and cell metabolism. High-frequency strain induced enrichment of pathways related to NOD-like receptor signaling, high metabolic demand, and redox signaling/stress. Metabolic and redox cell stress was confirmed by increased release of lactate into conditioned media and increased 3-NT formation in the synovial lining. Late-stage OA synovial tissue responses to tensile strain include frequency-dependent increases in inflammatory signaling, metabolism, and redox biology. Based on these findings, we speculate that some synovial mechanobiological responses to strain may be beneficial, but OA likely disturbs synovial homeostasis leading to aberrant responses to mechanical stimuli, which requires further validation.
Effects of lifestyle risk behaviour clustering on cardiovascular disease among UK adults: latent class analysis with distal outcomes
Authors: Tegegne Teketo Kassaw , Islam Sheikh Mohammed Shariful , Maddison Ralph 
Published: October 2022

AbstractLifestyle risk behaviours such as smoking, physical inactivity, and unhealthy diet account for a considerable disease burden globally. These risk behaviours tend to cluster within an individual, which could have detrimental health effects. In this study, we aimed to examine the clustering effect of lifestyle risk behaviours on cardiovascular disease (CVD) and CVD risk among adults in the United Kingdom (UK). We performed a latent class (LC) analysis with distal outcomes using the UK Biobank baseline (2006–2010) data. First, we estimated LC measurement models, followed by an auxiliary model conditional on LC variables. We reported continuous (mean difference—MD) and binary (odds ratio—OR) outcomes with 95% confidence intervals. We included 283,172 and 174,030 UK adults who had data on CVD and CVD risk, respectively. Multiple lifestyle risk behaviour clustering (physically inactive, poor fruit & vegetable intake, high alcohol intake, and prolonged sitting) had a 3.29 mean increase in CVD risk compared to high alcohol intake. In addition, adults with three risk behaviours (physically inactive, poor fruit & vegetable intake, and high alcohol intake) had 25.18 higher odds of having CVD than those with two risk behaviours (physically inactive, and poor fruit and vegetable intake). Social deprivation, gender and age were also associated with CVD. Individuals' LC membership with two or more lifestyle risk behaviours negatively affects CVD. Interventions targeting multiple lifestyle behaviours and social circumstances should be prioritized to reduce the CVD burden.
splitSMLM, a spectral demixing method for high-precision multi-color localization microscopy applied to nuclear pore complexes
Authors: Andronov Leonid , Genthial Rachel , Hentsch Didier , Klaholz Bruno P. 
Published: October 2022

AbstractSingle molecule localization microscopy (SMLM) with a dichroic image splitter can provide invaluable multi-color information regarding colocalization of individual molecules, but it often suffers from technical limitations. Classical demixing algorithms tend to give suboptimal results in terms of localization precision and correction of chromatic errors. Here we present an image splitter based multi-color SMLM method (splitSMLM) that offers much improved localization precision and drift correction, compensation of chromatic distortions, and optimized performance of fluorophores in a specific buffer to equalize their reactivation rates for simultaneous imaging. A novel spectral demixing algorithm, SplitViSu, fully preserves localization precision with essentially no data loss and corrects chromatic errors at the nanometer scale. Multi-color performance is further improved by using optimized fluorophore and filter combinations. Applied to three-color imaging of the nuclear pore complex (NPC), this method provides a refined positioning of the individual NPC proteins and reveals that Pom121 clusters act as NPC deposition loci, hence illustrating strength and general applicability of the method.
Noradrenergic consolidation of social recognition memory is mediated by β-arrestin–biased signaling in the mouse prefrontal cortex
Authors: Cheng Deqin , Wu Junwen , Yan Enhui , Fan Xiaocen , Wang Feifei , Ma Lan , Liu Xing 
Published: October 2022

AbstractSocial recognition memory (SRM) is critical for maintaining social relationships and increasing the survival rate. The medial prefrontal cortex (mPFC) is an important brain area associated with SRM storage. Norepinephrine (NE) release regulates mPFC neuronal intrinsic excitability and excitatory synaptic transmission, however, the roles of NE signaling in the circuitry of the locus coeruleus (LC) pathway to the mPFC during SRM storage are unknown. Here we found that LC-mPFC NE projections bidirectionally regulated SRM consolidation. Propranolol infusion and β-adrenergic receptors (β-ARs) or β-arrestin2 knockout in the mPFC disrupted SRM consolidation. When carvedilol, a β-blocker that can mildly activate β-arrestin-biased signaling, was injected, the mice showed no significant suppression of SRM consolidation. The impaired SRM consolidation caused by β1-AR or β-arrestin2 knockout in the mPFC was not rescued by activating LC-mPFC NE projections; however, the impaired SRM by inhibition of LC-mPFC NE projections or β1-AR knockout in the mPFC was restored by activating the β-arrestin signaling pathway in the mPFC. Furthermore, the activation of β-arrestin signaling improved SRM consolidation in aged mice. Our study suggests that LC-mPFC NE projections regulate SRM consolidation through β-arrestin-biased β-AR signaling.
Reconstruction of ovine axonal cytoarchitecture enables more accurate models of brain biomechanics
Authors: Bernardini Andrea , Trovatelli Marco , Kłosowski Michał M. , Pederzani Matteo , Zani Davide Danilo , Brizzola Stefano , Porter Alexandra , Rodriguez y Baena Ferdinando , Dini Daniele 
Published: October 2022

AbstractThere is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports a systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibres, namely the corpus callosum, the fornix and the corona radiata, with the specific aim to map different regions of the tissue and provide essential information for the development of accurate models of brain biomechanics. Ovine samples are imaged using scanning electron microscopy combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Focus is placed on the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. For each tract, a 3D reconstruction of relatively large volumes, including a significant number of axons, is performed and outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter are measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular axonal structures embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models using 3D volumes, either reconstructed directly from images or generated in silico using parameters extracted from the database of images, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue.
COX7A2L genetic variants determine cardiorespiratory fitness in mice and human
Authors: Benegiamo Giorgia , Bou Sleiman Maroun , Wohlwend Martin , Rodríguez-López Sandra , Goeminne Ludger J. E. , Laurila Pirkka-Pekka , Klevjer Marie , Salonen Minna K. , Lahti Jari , Jha Pooja , Cogliati Sara , Enriquez José Antonio , Brumpton Ben M. , Bye Anja , Eriksson Johan G. , Auwerx Johan 
Published: October 2022

AbstractMitochondrial respiratory complexes form superassembled structures called supercomplexes. COX7A2L is a supercomplex-specific assembly factor in mammals, although its implication for supercomplex formation and cellular metabolism remains controversial. Here we identify a role for COX7A2L for mitochondrial supercomplex formation in humans. By using human cis-expression quantitative trait loci data, we highlight genetic variants in the COX7A2L gene that affect its skeletal muscle expression specifically. The most significant cis-expression quantitative trait locus is a 10-bp insertion in the COX7A2L 3′ untranslated region that increases messenger RNA stability and expression. Human myotubes harboring this insertion have more supercomplexes and increased respiration. Notably, increased COX7A2L expression in the muscle is associated with lower body fat and improved cardiorespiratory fitness in humans. Accordingly, specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass and increased energy expenditure. Furthermore, Cox7a2l expression in mice is induced specifically in the muscle upon exercise. These findings elucidate the genetic basis of mitochondrial supercomplex formation and function in humans and show that COX7A2L plays an important role in cardiorespiratory fitness, which could have broad therapeutic implications in reducing cardiovascular mortality.
A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes
Authors: Gruber Joshua J. , Afghahi Anosheh , Timms Kirsten , DeWees Alyssa , Gross Wyatt , Aushev Vasily N. , Wu Hsin-Ta , Balcioglu Mustafa , Sethi Himanshu , Scott Danika , Foran Jessica , McMillan Alex , Ford James M. , Telli Melinda L. 
Published: October 2022

AbstractTalazoparib, a PARP inhibitor, is active in germline BRCA1 and BRCA2 (gBRCA1/2)-mutant advanced breast cancer, but its activity beyond gBRCA1/2 is poorly understood. We conducted Talazoparib Beyond BRCA (NCT02401347), an open-label phase II trial, to evaluate talazoparib in patients with pretreated advanced HER2-negative breast cancer (n = 13) or other solid tumors (n = 7) with mutations in homologous recombination (HR) pathway genes other than BRCA1 and BRCA2. In patients with breast cancer, four patients had a Response Evaluation Criteria in Solid Tumors (RECIST) partial response (overall response rate, 31%), and three additional patients had stable disease of ≥6 months (clinical benefit rate, 54%). All patients with germline mutations in PALB2(gPALB2; encoding partner and localizer of BRCA2) had treatment-associated tumor regression. Tumor or plasma circulating tumor DNA (ctDNA) HR deficiency (HRD) scores were correlated with treatment outcomes and were increased in all gPALB2 tumors. In addition, a gPALB2-associated mutational signature was associated with tumor response. Thus, talazoparib has been demonstrated to have efficacy in patients with advanced breast cancer who have gPALB2 mutations, showing activity in the context of HR pathway gene mutations beyond gBRCA1/2.